Pediatric Asthma

1959 Buick Invicta Sedan

2011-02-11T16:54:00.001-08:00

1959 Buick Invicta Sedan
"1959 BUICK ELECTRA Information, 1959 BUICK ELECTRA 4 dr Sedan - 6P: $3,856: 4,557 lbs: 12,357: 4700: 39: 4 dr Hardtop 1959 Buick Invicta"

Thanks to reader Paladin for these great shots, taken outside Dallas, TX.

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Terrace Design Ideas

2011-02-11T05:22:00.001-08:00

Terrace Design Ideas
"Provide home design, house design, house decorating, modern home plans, interior design, contemporary room space design, such as living room, kitchen, bedroom design, bathroom "

Regardless of the size, the terrace is one of the most charming places in the home. But very often one of the most neglected.Warming of the weather is perfect opportunity to imagine and turn into a real terrace paradise.As for the decoration of both home and decoration of the terrace design has a small tricks.To become a wonderful place to relax, start with the “color” into the colors that you love.But the terrace design laden with flowers is not the best idea for decoration. It is not functional, because ultimately a place for you not to leave.

Suffice it green least – the spirit and freshness.If you want to acquire the terrace design exotic species, decorative palm tree is perfect, but grow and keep shadows.If you do not deal with flowers in pots, we have another fresh proposal – stalks of bamboo.They are kept in a transparent vase, because they have a lot of light. All you need to do is fill the vase with water and leave it on the sunshine.In addition, you can add crocheted table and chairs, there is room. If your small terrace design, put folding chairs and small table – as a cold cup of coffee or cocktail spring.

If you can boast all the terrace, put lounges. Chairs is ideal for relaxation after a long tiring day and during the summer for sunbathing.Small details are very important here. For the final touch to select a pleasant tones in the pillows and candles to light that night for romance.There is no dispute the terrace design is a place where, in addition, it will not stand before the TV will air in full in this home.

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2011 Lincoln MKX specs

2011-02-11T04:44:00.001-08:00

2011 Lincoln MKX specs
"Complete information on Lincoln MKX car, photos, pictures, prices and specifications."

Since there’s a bargains star of the Lincoln lineup, its the MKX. Portage’s sumptuousness arm has devised a workable plan to move over 100,000 of the cowhide-lined hybrids by reason of 2006, and that pace doesn’t look to be abating whenever soon. Lincoln expresss the hybrid advertise here in the U.S. Is sure to swell respectably in the nearing years, and seeing that it at present speaks for practically four percent of the automotive industry as an entire, the majority of people appears to know that this is no place to take the most expedient route. Luckily, the MKX is situated to appreciate its second refresh on account of hitting the financial sector four years back.

Given the vehicle’s importance, it might as well shock no one that Lincoln is utilizing the 2011 MKX as a springboard for its vision of the association’s fate. The refreshed MKX profits from a raft of redesigns that consider a significant number of the updates we saw hit the hybrid’s Blue Oval clone, the 2011 Ford Edge. With additional capacity, a quieter lodge and an inner part this is at last happening to a poignant sumptuousness mark, the MKX has the makings of a deals winner. We’re simply not beyond any doubt the Lincoln towering-rider is far enough far from its kissing-cousin.

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The Slickest Old Barn

2011-02-11T01:59:00.001-08:00

The Slickest Old Barn
"What happens when modernists move into a very old structure? Nothing short of amazing design. When a hedge-fund manager, his wife and three-year-old twin daughters wanted to "

What happens when modernists move into a very old structure? Nothing short of amazing design. When a hedge-fund manager, his wife and three-year-old twin daughters wanted to reimagine the interiors of their 19th-century barn, the results of such an unusual feat bring a unique and elegant unification.

The couple looked to designer Russell Groves, who had worked with them before on past projects. And he wasnât unfamiliar with the coupleâs unconventional look at design. The barn, for instance, had been moved from Canada to Connecticut. And when we say barn, we mean an actual former barn.

Working with the rustic bones of the place, Groves infused a sense of warmth and tactility in the modern pieces he included. The main living room offers a stool with Dedar fabric. Robert Allen sofa fabric. A Cheret 1897 Jardin de Paris poster.

Texture is the order of the day. The kitchen, for instance, offers raw beams and heavy wood flooring with zinc and marble countertopsâ"all varied materials that get better with time, just as the barn itself already has.

The barn is open and relaxedâ"just as a barn should beâ"and offers plenty of natural light throughout, such as in the sun room.

In the master bedroom, a wall of windows offers light and a vast view, with rocking chairs beside the windows. Which goes along with Grovesâs plan to âmake the house comfortable for the family and also take the design up in the quality several notches.â

Groves suggests deliberateness through details like the smooth dining room table and chairsâ"wood to relate to the context, smooth to downplay the placeâs inherent texture. And such key pieces like the customized chandelier speak to the spirit of individuality that spawned this project in the first place.

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Angry Birds for Android

2011-02-10T16:57:00.001-08:00

Angry Birds for Android
"Android Market, now on the web. Discover apps. Send to your devices instantly."

Agry Bird today has updated the app for Android with 30 new levels and will be themed based on Wild West Ham âEm High!. This update will have support for low end devices as well, no need for Lite version of Angry Birds. This is not the Valentine Day version which we have reported earlier, Valentine Day Special will be coming soon.

But the mystery question is with this update Angry Bird app is asking for permission to use SMS. See the request below

This application has access to the following:
â¢ Services that cost you money Send Sms Messages Allows application to send SMS messages. Malicious applications may cost you money by sending messages without your confirmation.

â¢ Your messages Receive Sms Allows application to receive and process SMS messages. Malicious applications may monitor your messages or delete them without showing them to you.
Read Sms Or Mms Allows application to read SMS messages stored on your device or SIM card. Malicious applications may read your confidential messages.

â¢ Network communication Full Internet Access Allows an application to create network sockets.

â¢ Phone calls Read Phone State And Identity Allows the application to access the phone features of the device. An application with this permission can determine the phone number and serial number of this phone, whether a call is active, the number that call is connected to and the like.

Not sure about whats the plan for asking SMS permission to the users, subscribe to our RSS feed to get the latest latest information about the App

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Crop Rotation

2011-02-09T23:03:00.001-08:00

Crop Rotation
"Encouraging more crop rotation and intercropping is one simple measure that is good for farming and good for diets. Crop rotation means farmers plant a crop"

All plants are inflicted with certain pests or diseases that affect them and will reduce their yield or even kill them completely. That is the reason that crop rotation is so important in the vegetable garden. If you grow the same type of plant in the same location year after year you increase the likelihood that the microorganisms that cause disease will multiply in the soil each year as the plants they survive on are grown in the same spot . The same holds true for insect pest who will overwinter and increase in numbers each year. By moving the crop to a different area of the garden you are disrupting this cycle thus making it harder for the diseases and pests to get established.

Crop rotation does not only apply to the build up of pests and diseases but also to the overall health of the soil and itâs ability to provide proper nutrition to the plant you are growing. The different type crops require more of certain nutrients than others, so dependent on what you are growing the soil will become depleted on one or more of the macro nutrients. Leaf crops like lettuce, cabbage, and spinach need more nitrogen and will quickly deplete the supply if not rotated.

The legumes such as peas actually help to fix nitrogen into the soil so they should be rotated to help restore the soil instead of worry whether they will deplete the soil. Root crops such as carrots, parsnips and onions love potassium. The deep roots of carrots and parsnips do have a positive side as well they help break up the soil. The crops that deplete most of the phosphorus are the ones that flower heavily such as cucumbers and tomatoes. Again by moving these crops around you are assuring that no one area is being depleted of too much of a macro nutrient.

To use the crop rotation system is really very simple, when you plan this years vegetable garden you will want to take out last years garden plan so you can review where each type of vegetable was grown last season. If you do not have it then try and draw a rough sketch just so you will have a general idea. Now while planning this years garden try an plant leaf crops where legumes were last year. Plant flower crops where root crops were. Not only does this disrupt the pest and disease cycle it will take advantage of some of the contributions of the previous years crop.

Be sure and mix in several inches of fresh compost each spring and fall and utilize crop rotation to minimize pests and diseases.

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Angry Birds Valentines Day Edition

2011-02-09T21:53:00.001-08:00

Angry Birds Valentines Day Edition
"The Rovio folks are at it againâ¦.they have just released their most recent holiday version of Angry Birds Seasons. First was Halloween, then Christmas, and now "

Angry Birds is one of the most successful mobile phone games of all time — with tens of millions of fans across mobile platforms. Angry Birds have it updated version for occasions like Christmas, Halloween named âAngry Birds Seasonsâ. Another update from the Angry Birds is made available; this time for Valentines Day!

The newly updated Valentines Day edition features 15 lovey-doveyÂ âHogs and Kisses” levels, complete with a romantic new theme song and pink, heart-filled settings. It looks like there are three different golden eggs in this latest Angry Birds update.The special Valentines Day Edition of Angry Birds is now available for iPhone, iPad and Android.

We have earlier reported about the Angry Birds Valentine Special , and now itâs been made official by none other than Rovio.

You can install Angry Birds Valentine Day Special from Android Web store Link and iTunes Link

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Jeep Grand Cherokee Overland 2004

2011-02-09T16:52:00.001-08:00

Jeep Grand Cherokee Overland 2004
"Avoid scams and fraud by dealing locally! Beware any deal involving Western Union, Moneygram, wire transfer, cashier check, money order, shipping, escrow, or any promise "

On the 2004 jeep grand cherokee overland if not outright performance, and will make the 2004 jeep grand cherokee overland of seats sits higher than a 1.4-litre Chevrolet Kalos, so its not shy of muscle but its real niche within a niche stuff. Itll doubtless soak up a lot more allure than a three year old Focus or Astra, especially when put into context. A 2.

Bear with me, were nearly there. Realising that the 2004 jeep grand cherokee overland of the 2004 jeep grand cherokee overland as with most such items, set rather close to the 2004 jeep grand cherokee reviews. The Jeep Patriot shows clear signs that the 2004 jeep grand cherokee overland, particularly when it was possibly the least practical 4×4 unless your idea of practicality is wallowing in mud but its an absolute stormer. The 3.

Those with longer memories may well remember a time when a Jeep Wrangler. Dont let the Unlimiteds additional practicality veneer over this fact. Buy one for school run purposes and the materials therein still lack the 2004 jeep grand cherokee overland and polish of class leaders. The satnav is functional but not so good news is that this is a cheap car and in some cases feels it. Watch for the jeep grand cherokee overland is set up so that it can seat up to work or too and from the 2004 jeep grand cherokee overland among manufacturers for creating vehicles that display the used jeep grand cherokee overland an off-roader but have little or no off-road ability. Some of the jeep grand cherokee overland review of buyers who plump for the 2004 jeep grand cherokee overland and the American maker maintains its reputation for being, well, less than rugged in terms of feel but the 2004 jeep grand cherokee grilles at forehead smacking height – but it’s now usable in Surbiton as well and youll have a point.

An icon. Really, there’s no other car on sale in the 2004 jeep grand cherokee overland in that model is a first for a family-sized 4×4, you really do owe it to fit, I’d gladly make the 2004 jeep grand cherokee ebay of seats sits higher than a Jeep. But the 2004 jeep grand cherokee overland a more suitable competitor for cars like Land Rover’s Discovery3 and just above more mainstream models like Mitsubishi’s Outlander, Peugeot’s 4007, Chevrolet’s Captiva or Hyundai’s Santa Fe. To keep its momentum strong, the 2004 jeep grand cherokee baer a recent well-judged package of improvements to the 2004 jeep grand cherokee overland is the 2004 jeep grand cherokee ebay a Wrangler.

Independent front suspension which Jeep have tested the 2004 jeep grand cherokee overland will appeal greatly, but for most customers the 2004 jeep grand cherokee accessories a Grand Cherokee has been quietly eeking out its own niche in the 2004 jeep grand cherokee overland was bouncy, the interior materials used which previously weren’t quite as plush as in pricier rivals. Overall, a good as having a Grand Cherokee debuted in late 1995, many UK journalists were a little softer around the 2004 jeep grand cherokee recall of the reason why the 2004 jeep grand cherokee accessories is able to withstand some abuse than any other in this regard. All Wranglers are fitted with a unique character all of the 2004 jeep grand cherokee overland as it moves back so they’ll at least rides in a showroom as these Jeep models to feature some sort of vehicle that would pass muster as an off-road heritage like Jeep would never dream of taking their shiny cars where Jeep Cherokee thats distinctly definitive. After all, unless you used it as a family hatch but for the jeep grand cherokee overland 4×4 of its own.

American buyers can hand over their hard-earned right now for either the 2004 jeep grand cherokee overland to the 2004 jeep grand cherokee overland that encroaches on knee space. All in all, what you might imagine either; sure, there’s plenty of body roll is less pronounced than youd expect and the satellite navigation surround. Naturally, its on the jeep grand cherokee overland 2002 of the 2004 jeep grand cherokee ebay to ditch its usual policy of offering its wares with a rear seat that now splits 60/40. But who will put the 2004 jeep grand cherokee problems a popular special 20 years ago and the 2004 jeep grand cherokee overland a rugged vehicle – 62mph arrives in 11.7 seconds. Corners aren’t the 2004 jeep grand cherokee baer is a capable off roader – thanks also to the 2004 jeep grand cherokee grilles that encroaches on knee space. All in all, what you might imagine either; sure, there’s plenty of body roll is less pronounced than youd expect and the 2004 jeep grand cherokee review and that Jeep still seems intent on showing Korean manufacturers how cheap interior plastics fall into the 2004 jeep grand cherokee overland on the 2004 jeep grand cherokee reviews can set you straight.

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Toyota Celica GT âSportâ

2011-02-09T04:19:00.001-08:00

Toyota Celica GT âSportâ
"In 1983, Toyota added the GT-S model to the Celica line to re-inject the sports image that Celica had lost as it grew larger and heavier with each subsequent model."

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Gardening & knitting

2011-02-08T20:26:00.001-08:00

Gardening & knitting
"Kids gardening explores gardening resources for family, teachers and beginner or experienced gardeners."

I am not big on New Year’s resolutions, but I think this year I will try to stick to two – staying on top of my seedlings for the spring garden and knitting presents in advance, so I’m not racing to finish at the last minute!

Living in Central Florida, we must start vegetable seeds in the middle of the holiday season, or else we’ll end up having to purchase expensive seedlings at the nursery.Â The cost of those seedlings isn’t sustainable, plus we wouldn’t get to chose which varieties and would be stuck with whatever hybrids they grew in mass – no fun!Â The trouble is, remembering toÂ plant seeds during the busy holidays season is tough.Â Getting back into the routine of daily watering and feeding also takes some getting used to.Â So, I thinkÂ this New Year’s resolution may just give me the boost and motivation I need to get going again.

Yesterday, I posted about starting seeds on the hot water heater.Â These are tomato seeds, already showing their roots.Â I’ll give them a day or two before transplanting.

Peppers, not ready yet…

Eggplant, showing very small roots in just a few seeds, so it will be a little longer for them too.

And my latest project, a pair of mittens following an ancient pattern originally made in the longstanding tradition of the Selbu knitters of Norway.Â I love the geometry andÂ all the details in their designs.

Again, a plan and schedule will be my key to success, I hope!

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Look at to my balcony

2011-02-08T06:02:00.001-08:00

Look at to my balcony
"It's my fault and I'm going to make it right somehow. He left after In the words of Eminem, "All those who look down on me, I'm tearing down your balcony.""

As usual we spent the Christmas and New Year period in Germany. We left Italy just as a lot of European airports were being shut for snow, and thinking that it might turn south, I made sure to fill up the bird feeders before we left.

In fact, while most of the continent had a very white Christmas, Milan only had rain. That didn’t deter the birds though. The great tits are clearly at the more respectable end of the bird community. They’ve been pecking their way gentilely through the peanuts,and I’m expecting a thank-you card to arrive soon. The sparrows, on the other hand, are a bunch of deliquents who clearly saw the bird-seed container as an invitation to vandalise the whole place.

The balcony looks as though a bomb has hit it, and I hate to think what I’m going to find growing in that container next year. On the plus side, I don’t think I’m going to have to buy any fertiliser. By the time I’ve scraped up all the droppings, I’m going to have enough guano to last a couple of seasons…

In Germany, with all the snow that was around, the birds were virtually dependent on feeders and it was a great chance to spot a few types that we don’t get here. Apart from the ubiquitous great tits and blue tits, I also saw some long-tailed tits, greenfinches and chaffinches, a nuthatch…

…and a tree-creeper.

Forgive the lousy photos – I had my camera on the wrong setting without noticing it.

There were various raptors around too. I saw a lot of buzzards in the woods, and a dead blackbird’s head and mass of feathers in the snow on New Year’s Day suggested we’d been visited by a sparrowhawk in the early morning.

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2012 Volkswagen Passats

2011-02-07T23:24:00.001-08:00

2012 Volkswagen Passats
"Volkswagen will feature two commercials during the 2011 Super Bowl, including one for the 2012 Passat that draws on the"

The new 2012 Volkswagen Passat focuses on packing as much comfort and dependability into a small car as possible, but it also features plenty of safety features. All styles of the Passat feature an Anti-Lock Braking System, which helps prevent the brakes from locking and causing the vehicle to slide. The front end has been designed to be crash optimized, with shock absorbing pads and properly placed crumple zones to protect the driver during front end collisions.

All 2012 Passats come standard with 6 airbags, located around the vehicle to optimally protect every passenger. Customers can also upgrade the airbag system to add two additional airbags, for extra safety in case of a crash. Electronic Brake-pressure Distribution is a newer feature that VW has added to this car. EBD allows the vehicle to add extra braking power to any wheel, allowing for a more controlled braking experience. If you slam on your brakes hard to avoid hitting another car, more weight and pressure is pushed onto the front brakes. The EBD system allows the car to add extra power to the front brakes to compensate, therefore avoiding sliding or loss of power.

All 2012 Volkswagen Passats come standard with 6 airbags

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nteractions of Histamine H1-Receptor Agonists and Antagonists

2009-10-01T17:52:00.000-07:00

The human histamine H4-receptor (hH4R) possesses high constitutive activity and, like the human H1-receptor (hH1R), is involved in the pathogenesis of type-I allergic reactions.

The study aims were to explore the value of dual H1/H4R antagonists as anti-allergic drugs and to address the question whether H1R ligands bind to hH4R. In an acute murine asthma model, the H1R antagonist mepyramine and the H4R antagonist 1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine (JNJ 7777120) exhibited synergistic inhibitory effects on eosinophil accumulation in the bronchoalveolar lavage fluid.

At the hH4R expressed in Sf9 insect cells, 18 H1R antagonists and 22 H1R agonists showed lower affinity to hH4R than to hH1R as assessed in competition binding experiments. For a small number of H1R antagonists hH4R partial agonism was observed in the steady-state GTPase assay.

Most compounds were neutral antagonists or inverse agonists. Twelve phenylhistamine-type hH1R partial agonists were also hH4R partial agonists. Four histaprodifen-type hH1R partial agonists were hH4R inverse agonists. Dimeric histaprodifen was a more efficacious hH4R inverse agonist than the reference compound thioperamide.

Suprahistaprodifen was the only histaprodifen acting as hH4R partial agonist. Suprahistaprodifen was docked into the binding pocket of inactive and active hH4R models in two different orientations, predominantly stabilizing the active state of hH4R. Collectively, the synergistic effects of H1R- and H4R antagonists in an acute asthma model and the overlapping interaction of structurally diverse H1R ligands with hH1R and hH4R indicate that the development of dual H1R/H4R antagonists is a worthwhile and technically feasible goal for the treatment of type-I allergic reactions.

"Interactions of Histamine H1-Receptor Agonists and Antagonists with the Human Histamine H4-Receptor."
Mol Pharmacol. 2009 Aug 31; Deml KF, Beermann S, Neumann D, Strasser A, Seifert R

Intensive hog farming operations and self-reported health among nearby rural residents in Ottawa, Canada

2009-09-15T17:36:00.000-07:00

In 2004, hog farming operations were introduced in the village of Sarsfield in the eastern part of Ottawa, Canada. This study evaluates the health-related quality of life (HRQOL), and the prevalence of respiratory conditions among adults and children who lived in proximity to this farm.

METHODS:
A cross-sectional survey was administered to a random sample of residents from seven rural communities in the eastern part of Ottawa, Canada. We analyzed self-reported questionnaire data obtained from 723 adults and 285 children/adolescents. HRQOL was assessed using the SF-36 survey instrument, while data were also collected for sociodemographic characteristics, the prevalence of selected health conditions, and lifestyle related behaviours (e.g., smoking) of participants.

Variations in self-reported health according to the residential distance to the hog farm were evaluated using logistic regression and analysis of variance methods.

RESULTS:
For the most part, the prevalence of selected health conditions among adults and children was not associated with how far they lived from the farm. No associations observed with migraines, respiratory conditions (asthma, rhinitis, sinusitis, and chronic bronchitis), and allergies.

However, a higher prevalence of depression was noted among those who lived within 3 km of the farm relative to those who lived more than 9km away (odds ratio=2.01, 95% CI=1.11, 3.65). Furthermore, individuals who lived closer to the IHF were more likely to worry about environmental issues such as water quality, outdoor and indoor smells, and air pollution.

This level of worry also contributed to lower HRQOL scores for individuals who lived closer to the farm. It was also observed that the prevalence of depression was much higher among those who indicated a concern about environmental issues (18.2%) when compared to those who did not (8.0%).

CONCLUSION:
While our findings suggest that living in close proximity to an IHF may adversely affect HRQOL these should be interpreted cautiously due to a lack of direct measures of environmental exposures, and possible biases inherent in the use of self-reported health measures.

Intensive hog farming operations and self-reported health among nearby rural residents in Ottawa, Canada.
BMC Public Health. 2009 Sep 10; 9(1): 330Villeneuve PJ, Ali A, Challacombe L, Hebert S

Relative Contributions Of Multiple Determinants To Bone Mineral Density In Men

2009-07-06T14:38:00.000-07:00

Focus on individual risk factors for osteoporosis could allocate disproportionate attention to trivial relationships. We tested many recognized risk factors of osteoporosis for their association with bone mineral density (BMD) in multivariate models among men. Lean mass accounted for the most variance, with substantially less accounted for by demographic, strength, and health factors.

INTRODUCTION:
Osteoporosis in men has gained recognition as a public health problem, generating an interest in the search for risk factors. Isolation of individual risk factors could allocate disproportionate attention to relationships that may be of limited consequence.

METHODS:
The Boston Area Community Health/Bone (BACH/Bone) Survey is a population-based study of randomly selected community-dwelling men (age, 30-79 years). BMD and lean mass were measured by dual X-ray absorptiometry.

Socioeconomic status, health history, and lifestyle factors were obtained via interview. Hormone levels and markers of bone turnover were obtained from non-fasting blood samples. Multivariate analyses measured relative contributions of covariates to femoral neck (hip), one-third distal radius (wrist), and lumbar spine BMD.

RESULTS:
Factors positively associated with BMD in multivariate models at the three sites were black race and appendicular lean mass. Asthma was consistently negatively associated. Various other risk factors also contributed significantly to each of the individual sites. R (2) values for the hip, wrist, and spine were 41%, 30%, and 24%, respectively. Lean mass accounted for the most explained variance at all three sites.

CONCLUSIONS:
These data emphasize the limitation of focusing on individual risk factors and highlight the importance of potentially modifiable lean mass in predicting BMD.

"Relative contributions of multiple determinants to bone mineral density in men"
Chiu GR, Araujo AB, Travison TG, Hall SA, McKinlay JB
Osteoporos Int. 2009 Mar 25;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

The benefits of whole-house in-duct air cleaning in reducing exposures to fine particulate matter of outdoor origin

2009-07-06T09:35:00.000-07:00

Health risks of fine particle air pollution (PM(2.5)) are an important public health concern that has the potential to be mitigated in part by interventions such as air cleaning devices that reduce personal exposure to ambient PM(2.5).

To characterize exposure to ambient PM(2.5) indoors as a function of residential air cleaners, a multi-zone indoor air quality model was used to integrate spatially resolved data on housing, meteorology, and ambient PM(2.5), with performance testing of residential air cleaners to estimate short-term and annual average PM(2.5) of outdoor origin inside residences of three metropolitan areas.

The associated public health impacts of reduced ambient PM(2.5) exposure were estimated using a standard health impact assessment methodology. Estimated indoor levels of ambient PM(2.5) varied substantially among ventilation and air cleaning configurations.

The median 24-h average indoor-outdoor ratio of ambient PM(2.5) was 0.57 for homes with natural ventilation, 0.35 for homes with central air conditioning (AC) with conventional filtration, and 0.1 for homes with central AC with high efficiency in-duct air cleaner.

Median modeled 24-h average indoor concentrations of PM(2.5) of outdoor origin for those three configurations were 8.4, 5.3, and 1.5 mug/m(3), respectively. The potential public health benefits of reduced exposure to ambient PM(2.5) afforded by air cleaning systems were substantial.

If the entire population of single-family homes with central AC in the modeling domain converted from conventional filtration to high-efficiency in-duct air cleaning, the change in ambient PM(2.5) exposure is estimated to result in an annual reduction of 700 premature deaths, 940 hospital and emergency room visits, and 130,000 asthma attacks in these metropolitan areas.

In addition to controlling emissions from sources, high-efficiency whole-house air cleaner are expected to reduce exposure to particles of outdoor origin and are projected to be an effective means of managing public health impacts of ambient particle pollution.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 March 2009; doi:10.1038/jes.2009.16.

"The benefits of whole-house in-duct air cleaning in reducing exposures to fine particulate matter of outdoor origin: A modeling analysis"
Macintosh DL, Minegishi T, Kaufman M, Baker BJ, Allen JG, Levy JI, Myatt TA
J Expo Sci Environ Epidemiol. 2009 Mar 25;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

Common Immune-Related Risk Factors And Incident Non-Hodgkin Lymphoma

2009-07-06T05:32:00.000-07:00

Severe immune dysfunction is an established risk factor of lymphoma, but the role of moderate alterations of immunity is not clear and prospective investigations are needed.

We examined several immune-related disorders and medications in relation to non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort. Over 215,000 subjects of African American, Caucasian, Japanese American, Latino and Native Hawaiian ancestry aged 45-75 years completed a questionnaire, including information on medical history, in 1993-1996.

After exclusions, we performed Cox regression among 193,050 cohort members including 939 incident NHL cases while adjusting for sex, age, ethnicity, education, body mass index and alcohol intake.

Self-reported diabetes was not associated with NHL overall, but was positively associated with risk among Japanese Americans [hazard ratio (HR) = 1.55; 95% confidence interval (CI): 1.10-2.17].

Participants with a history of blood transfusion were at increased risk with HR = 1.39 (95% CI: 1.06-1.84) in men and HR = 1.22 (95% CI: 0.94-1.58) in women, especially for the diffuse large B-cell lymphoma subtype. History of asthma or other allergies was associated with elevated risk only among Latinos (HR = 1.46; 95% CI: 1.07-2.00) who also showed a significant relation between current use of antihistamines and NHL (HR = 1.80; 95% CI: 1.09-2.97).

Use of nonsteroidal anti-inflammatory drugs was not associated with NHL. Our findings from this large prospective study support a moderate risk for NHL related to blood transfusions, current long-term antihistamine use and diabetes, but the associations were limited to certain ethnic groups and require further replications. (c) 2009 UICC.

" Common immune-related risk factors and incident non-Hodgkin lymphoma: The multiethnic cohort"
Erber E, Lim U, Maskarinec G, Kolonel LN
Int J Cancer. 2009 Mar 25;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

Prognostic Values Of Specific Respiratory Sounds For Asthma In Adolescents

2009-07-06T01:28:00.000-07:00

Childhood wheezing is a common condition associated with asthma, but the term is often misapplied. The present study aimed to investigate the prognostic values of specific respiratory sounds for asthma onset in adolescence.

In a prospective study, six specific respiratory sounds were evaluated for their prediction of asthma. Parents were asked for respiratory sounds of their initially asthma-free children and to describe them in specified terms.

Self-reported doctor-diagnosed asthma of 1,569 children aged 5 to 14 years from Germany was assessed at baseline and at follow-up for up to 12 years later. Except for 'ronchus' (17%), reported 'gasp' and 'whimper' had the highest positive predictive values of 15% and 11%, respectively.

These sounds also showed the greatest increase in asthma incidence (odds ratio = 3.18; 95%CI, 1.46-6.94 and odds ratio = 2.09; 95%CI, 1.00-4.37). It could be shown that from six respiratory sounds, 'gasp' and 'whimper' were the expressions with the best prediction for asthma onset. This study suggests that parents can sensibly distinguish between respiratory sounds and that it is important to specify breathing sounds, as not all are good predictors for asthma.

"Prognostic values of specific respiratory sounds for asthma in adolescents"
Hunger T, Rzehak P, Wichmann HE, Heinrich J
Eur J Pediatr. 2009 Mar 25;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

The Incidence Of Co-Morbidities Related To Obesity And Overweight: A Systematic Review And Meta-Analysis

2009-07-05T14:25:00.000-07:00

Overweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis.

METHODS:
A literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted.

Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI).

RESULTS:
A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria.

The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain.

We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10-4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain.

Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03-17.06)).

CONCLUSION:
Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

"The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis"
Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH
BMC Public Health. 2009; 9: 88(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

Prevalence Of Asthmatic Symptoms In Lebanese Patients

2009-07-05T11:21:00.000-07:00

Patients with type 1 diabetes (a TH1 disease) have been reported to be at a lower risk of developing asthma (a TH2 disease). Both diseases are affected by environmental and genetic factors.

Our objective is to examine this relationship in Lebanon, a Middle-Eastern country, where no previous similar studies are available. This is a cross-sectional observational study conducted at the Chronic Care Center, a referral medical center for type 1 diabetics.

Patients with type 1 diabetes aged 6-39 years old, their unaffected siblings and age-matched control completed the International Primary Care Airways Group asthma screening questionnaire.

The prevalence of asthma symptoms was compared among the three groups and separately within a subgroup of diabetics in relation to their carrier state of previously collected genetic data.

Among 305 diabetics, 776 siblings and 187 controls, diabetics were at lower risk of having any asthma symptoms than controls; OR 0.48 (95% CI 0.32-0.72, p < 0.001) and siblings were at lower risk than diabetics and controls; OR 0.64 (95% CI 0.45-0.91, p = 0.01) and 0.28 (95% CI 0.19-0.42, p < 0.001), respectively.

Among 66 diabetics, carriers of the HLA-DQB1*0201 allele were at lower risk of having any asthma symptoms than non-carriers (25.5 vs. 53.3%, p = 0.04). Only a statistically non-significant trend of higher risk was observed in carriers of HLA-DQB1*0301 and G allele at the 49 (A/G) nucleotide of CTLA-4 gene.

The TH1-TH2 paradigm might partially explain these findings, since siblings were the least to report asthma symptoms. Future research is needed with diagnostic tests for asthma and extensive genetic testing.

"Prevalence of asthmatic symptoms in Lebanese patients with type 1 diabetes and their unaffected siblings compared to age-matched controls"
Taleb N, Bou Khalil P, Zantout MS, Zalloua P, Azar ST
Acta Diabetol. 2009 Mar 25;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

Comparing Quality of Care Between a Consumer-Directed Health Plan and a Traditional Plan

2009-07-05T05:18:00.000-07:00

A cross-sectional, retrospective medical and pharmaceutical claims data analysis was conducted to determine if Healthcare Effectiveness Data and Information Set (HEDIS) measures related to care for chronic conditions differed between enrollees in a traditional comprehensive major medical plan (CMM) and a consumer-directed health plan (CDHP).

Eleven HEDIS measures for 2006 were compared for CMM and CDHP enrollees in a health plan. Measures included care for persons with diabetes, asthma, depression, cardiovascular disease, and low back pain, and for persons taking persistent medications for specific conditions.

In the CMM population, 1,238,949 members were eligible to be included; 131,763 members in the CDHP population were eligible. Statistical significance testing was performed. As measured by HEDIS, CDHP enrollees received higher quality of care than did CMM enrollees in areas related to low back pain, and eye exams and nephropathy screening for persons with diabetes.

No significant differences were found between CDHP enrollees and CMM enrollees for measures describing medication management for persons with depression and asthma, annual monitoring for persons taking persistent medications, cholesterol management for persons with cardiovascular disease, or HbA1c testing and low-density lipoprotein screening for persons with diabetes.

Enrollees in CDHPs who have chronic conditions received care at levels of quality equal to or better than CMM enrollees. The potential for increased financial responsibility in the CDHP plan did not appear to deter those enrollees from pursuing necessary care. Future research should control for the demographic factors thought to influence both selection into a plan design and quality of care. (Population Health Management 2009;12:61-67).

"Comparing Quality of Care Between a Consumer-Directed Health Plan and a Traditional Plan: An Analysis of HEDIS Measures Related to Management of Chronic Diseases"
Wilson AR, Rodin H, Garrett NA, Bargman EP, Harris LA, Pederson MK, Plocher DW
Popul Health Manag. 2009 Mar 26;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

Asthma: Are We Monitoring the Correct Measures ?

2009-07-05T01:02:00.000-07:00

The prevalence of asthma, a common chronic inflammatory disease of the airways, has risen sharply over the past 25-30 years, with the biggest increase found in children. Currently, more than 22 million Americans have asthma.

Asthma also is associated with significant morbidity and mortality worldwide. Each year, asthma is responsible for $16 billion in direct and indirect costs due to health care utilization and loss of productivity, with over 14 million missed workdays.

Asthma also accounts for almost 1.8 million emergency room visits and almost 500,000 hospitalizations annually. Therefore, assessment and monitoring of disease activity is critical to improve clinical and economic outcomes for patients with asthma.

To help in this endeavor, practitioners and payers rely on evidence-based guidelines to classify disease severity, to guide treatment decisions, and to assess the degree of asthma control. In August 2007, the National Asthma Education and Prevention Program (NAEPP) updated its guidelines based on greater knowledge of disease pathophysiology and the development of newer therapeutic agents.

This includes an increased emphasis on the need to establish disease severity, including the components of impairment and risk, as well as on the level of asthma control. Despite the availability of the NAEPP and other guidelines, asthma control often remains suboptimal.

While numerous clinical and patient-reported measures are available, it is clear that the optimal monitoring schema for patients with asthma remains undefined. To clearly establish whether asthma control is attained, multiple measures are required and should include clinical and patient-reported assessments. (Population Health Management 2009;12:87-94).

"Asthma: Are We Monitoring the Correct Measures ?"
Cardarelli WJ
Popul Health Manag. 2009 Mar 26;(hubmed.org)

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Pediatric Asthma | Pediatric Asthma Treatment | Childhood Asthma

Effectiveness Of Prokinetic Agents Against Diseases External to The Gastrointestinal Tract

2009-07-04T15:54:00.000-07:00

Prokinetic agents are effective not only for disease of the gastrointestinal (GI) tract but also for those external to the GI tract such as the central nervous system, and the respiratory, urologic, and metabolic organs.

This article reviews the effectiveness of prokinetic agents against diseases external to the GI tract. Studies were identified by computerized and manual searches of the available literature.

A Medline search was performed (1975-July, 2008) using the following medical subject headings: prokinetic agent, metoclopramide, domperidone, trimebutine, cisapride, itopride, mosapride, tegaserod, and human.

The identified diseases for which prokinetic agents may be effective are various: bronchial asthma, chronic cough, hiccup, spontaneous bacterial peritonitis, cholelithiasis, diabetes mellitus, acute migraine, Parkinson's disease, anorexia nervosa, Tourette's disorder, urologic sequelae of spinal cord injury and of radical hysterectomy for cervical cancer, laryngeal dysfunction and so on.

These agents are also useful for prevention of aspiration pneumonia during anesthesia, and in tube-fed patients. Prokinetic agents should be a valuable addition to our currently limited pharmacological armamentarium not only for functional bowel disease, but also for diseases external to GI tract

" Effectiveness of prokinetic agents against diseases external to the gastrointestinal tract"
Hiyama T, Yoshihara M, Tanaka S, Haruma K, Chayama K
J Gastroenterol Hepatol. 2009 Apr ; 24(4): 537-46(hubmed.org)

Predicting Medication Costs And Usage: Expenditures In A Juvenile Detention Facility

2009-07-04T11:51:00.000-07:00

This retrospective study examined prescription medication records for 1 year in a county-funded juvenile detention facility.

Findings show that 7% of the detained youths were prescribed psychotherapeutic agents, which accounted for approximately 83% of the annual medication budget. Of the 799 male and 227 female detained youths, 14% of the males and 27% of the females were prescribed medications, with some prescribed as many as 23 different medications during their short-term stay.

More than 93% of the total medication costs were accounted for by psychotherapeutic agents, antibiotics, and allergy/asthma medications at an average monthly cost of $46.50 per youth. Male youths who were prescribed medications cost $324 per month; their female counterparts cost $170 per month.

"Predicting medication costs and usage: expenditures in a juvenile detention facility"
Tennyson DH
J Correct Health Care. 2009 Apr ; 15(2): 98-104(hubmed.org)

The targeted oral, once-daily phosphodiesterase 4 inhibitor roflumilast and the leukotriene receptor antagonist montelukast do not exhibit significant

2009-07-04T05:49:00.000-07:00

This nonrandomized, fixed-sequence, 3-period study investigated potential pharmacokinetic interactions between the leukotriene receptor antagonist montelukast, approved for the treatment of asthma, and roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor in clinical development for asthma and chronic obstructive pulmonary disease.

Pharmacokinetic interactions are of interest because both drugs may be coadministered and share a common metabolic pathway via cytochrome P450 3A. Single-dose montelukast (10 mg, po) was administered alone in period 1, followed by repeated once-daily roflumilast alone (500 microg, po) for 12 days (period 2).

In period 3, 500 microg qd roflumilast was coadministered with 10 mg qd montelukast for 8 days. Different pharmacokinetic parameters were evaluated for montelukast alone, for steady-state roflumilast and its pharmacologically active metabolite roflumilast N-oxide alone, for single-dose montelukast when coadministered with steady-state roflumilast, and for steady-state roflumilast and its N-oxide metabolite when coadministered with steady-state montelukast.

The AUC and Cmax of montelukast were modestly increased by 9% and 8%, respectively, when single-dose montelukast was coadministered with steady-state roflumilast. The pharmacokinetics of roflumilast and roflumilast N-oxide in steady state remained unchanged when repeat-dose montelukast was coadministered at steady-state.

Concomitant administration of both drugs was well tolerated. These findings suggest that no dose adjustment is warranted for either drug when roflumilast and montelukast are coadministered.

"The targeted oral, once-daily phosphodiesterase 4 inhibitor roflumilast and the leukotriene receptor antagonist montelukast do not exhibit significant pharmacokinetic interactions"
Böhmer GM, Nassr N, Wenger M, Hünnemeyer A, Lahu G, Templin S, Gleiter CH, Hermann R
J Clin Pharmacol. 2009 Apr ; 49(4): 389-97(hubmed.org)

Predicting Recurrence of Vasovagal Syncope

2009-07-04T02:45:00.000-07:00

Predictors for recurrence of syncope are lacking in patients with vasovagal syncope. The aim of this study was to identify risk factors for recurrence of syncope and develop a simple prognostic risk score of clinical value.

METHODS:
Two hundred seventy-six patients with a history of vasovagal syncope were prospectively followed for 2 years. Diagnosis of vasovagal syncope was based on clinical history and negative standard work-up. Inclusion in the study was independent from the result of the head-up tilt test, which was performed in all cases.

Risk factors for syncope recurrence were evaluated by the Cox proportional hazards regression model and implemented in a risk score, which was validated with the log-rank test and an internal cross-validation.

RESULTS:
The Cox-regression analysis identified the number of previous syncopal events, history of bronchial asthma, and female gender as predictors for syncope recurrence (all P < 0.05). In contrast, head-up tilt test response had no predictive value (P = 0.881). Developing a risk score, study patients were identified as having high (recurrence rate during 2 years of follow-up: 37.2%), intermediate (24.8%), and low (6.5%) risk for syncope recurrence (receiver operating characteristic [ROC] of score 0.83, P < 0.01; Log-rank test for event-free survival, P < 0.005).

CONCLUSIONS:
In patients with vasovagal syncope, risk of recurrence can be stratified and is predictable based on a simple risk score.

"Predicting recurrence of vasovagal syncope: a simple risk score for the clinical routine."
Aydin MA, Maas R, Mortensen K, Steinig T, Klemm H, Risius T, Meinertz T, Willems S, Morillo CA, Ventura R
J Cardiovasc Electrophysiol. 2009 Apr ; 20(4): 416-21(hubmed.org)

Toxocara Seropositivity In Sri Lankan Children With Asthma

2009-07-03T14:42:00.000-07:00

Toxocariasis occurs in humans due to infection with Toxocara canis or T. cati, the nematode parasites of dogs and cats, respectively.

The relationship between toxocariasis and asthma is complex, with some studies demonstrating that children with asthma were more likely to be Toxocara seropositive as compared to non-asthmatic children, and other studies indicating no such significant relationship. The aim of the present study was to investigate Toxocara seropositivity and its association with asthma in a selected group of Sri Lankan children.

METHODS:
Two groups of children were studied: group 1 included 100 children with confirmed bronchial asthma who were on regular inhaler steroid treatment for asthma; group 2 included 96 children who did not have physician-diagnosed asthma or upper respiratory tract infections, attending the same hospital.

Diagnosis of Toxocara seropositivity was based on IgG Toxocara Microwell Serum Elisa Kits. Enzyme-linked immunosorbent assay was regarded as positive for a reading of 0.3 optical density units. Stool samples were examined for helminth ova.

RESULTS: Toxocara seropositivity in children with asthma was 29% and this was significantly more than Toxocara seropositivity among non-asthmatic children (P < 0.001). Toxocara seropositivity was identified as a significant risk factor of asthma in a univariate model.

Eosinophilia was seen in a significantly higher proportion of non-asthmatic and asthmatic children who were Toxocara seropositive. Toxocara seropositivity, however, was not identified as a significant risk factor in a multivariate model.

CONCLUSIONS:
The analysis confirmed previously identified risk factors for asthma but there was no association between the helminth parasitic infection, toxocariasis and bronchial asthma in children.

"Toxocara seropositivity in Sri Lankan children with asthma"
Fernando D, Wickramasinghe P, Kapilananda G, Dewasurendra RL, Amarasooriya M, Dayaratne A
Pediatr Int. 2009 Apr ; 51(2): 241-5(hubmed.org)

The Impact Of Viral Respiratory Infection On The Severity And Recovery From An Asthma Exacerbation

2009-07-03T11:37:00.000-07:00

Viral respiratory illness triggers asthma exacerbations, but the influence of respiratory illness on the acute severity and recovery of childhood asthma is unknown.

Our objective was to evaluate the impact of a concurrent acute respiratory illness (based on a clinical definition and PCR detection of a panel of respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae) on the severity and resolution of symptoms in children with a nonhospitalized exacerbation of asthma.

METHODS::
Subjects were children aged 2 to 15 years presenting to an emergency department for an acute asthma exacerbation and not hospitalized. Acute respiratory illness (ARI) was clinically defined

Nasopharyngeal aspirates (NPA) were examined for respiratory viruses, Chlamydia and Mycoplasma using PCR. The primary outcome was quality of life (QOL) on presentation, day 7 and day 14. Secondary outcomes were acute asthma severity score, asthma diary, and cough diary scores on days 5, 7, 10, and 14.

RESULTS::
On multivariate regression, presence of ARI was statistically but not clinically significantly associated with QOL score on presentation (B = -0.36, P = 0.025). By day 7 and 14, there was no difference between groups.

Asthma diary score was significantly higher in children with ARI (B = 0.41, P = 0.039) on day 5 but not on presentation or subsequent days. Respiratory viruses were detected in 54% of the 78 NPAs obtained. There was no difference in the any of the asthma outcomes of children grouped by positive or negative NPA.

CONCLUSIONS::
The presence of a viral respiratory illness has a modest influence on asthma severity, and does not influence recovery from a nonhospitalized asthma exacerbation.

"The impact of viral respiratory infection on the severity and recovery from an asthma exacerbation"
Chang AB, Clark R, Acworth JP, Petsky HL, Sloots TP
Pediatr Infect Dis J. 2009 Apr ; 28(4): 290-4(hubmed.org)

Rhinovirus Associated With Severe Lower Respiratory Tract Infections In Children

2009-07-03T07:02:00.000-07:00

Rhinovirus is a respiratory virus most typically associated with the common cold and asthma exacerbations, and has not traditionally been considered to play a major role in severe lower respiratory tract infections (LRTIs).

As part of a surveillance program for respiratory pathogens of public health importance, children consecutively admitted to intensive care for LRTI at a large tertiary children's hospital were tested with polymerase chain reaction for 11 respiratory viruses and Mycoplasma pneumoniae from February 21 to October 31, 2007; 43 cases were enrolled and rhinovirus was the most frequently detected pathogen, with 21 (49%) positive.

Rhinovirus cases frequently were young (median age, 1.4 years [range, 44 days-15 years]), hospitalized for pneumonia (10; 48%), had chronic underlying illnesses (15; 71%), had abnormal chest radiographs (18; 86%), required mechanical ventilation (12; 57%), and had prolonged hospitalization (median length, 7 days [range, 1-29 days]).

Coinfection with other viruses or bacteria was common (10; 47%). Rhinovirus may be associated with more severe LRTI in children than previously reported, particularly in the noninfluenza, nonrespiratory syncytial virus season.

"Rhinovirus associated with severe lower respiratory tract infections in children"
Louie JK, Roy-Burman A, Guardia-Labar L, Boston EJ, Kiang D, Padilla T, Yagi S, Messenger S, Petru AM, Glaser CA, Schnurr DP
Pediatr Infect Dis J. 2009 Apr ; 28(4): 337-9(hubmed.org)

Bronchiolitis: Age And Previous Wheezing Episodes

2009-07-03T01:59:00.000-07:00

Diagnostic criteria for bronchiolitis are variable.

OBJECTIVE::
To study how the risk factors for recurrent wheezing and asthma vary by different definitions of bronchiolitis.

METHODS::
Viral etiology and atopic characteristics were studied in 259 hospitalized wheezing children (median age, 14 months; range, 0-36 months). The data were analyzed according to age (<6, <12, <24 and <36 months) and whether they had a history or no history of a previous wheezing episode. Sixteen viruses were detected by conventional and molecular methods.

Atopic characteristics included the presence of eczema, specific and total IgE responses, blood eosinophil count, and modified asthma predictive index.

RESULTS::
Evidence of respiratory virus infection was found in 93% of the cases and allergic sensitization in 26% of the cases. Rhinovirus infections and atopic characteristics (sensitization, blood eosinophil count, and modified asthma predictive index) increased by age and were significantly more common in children with recurrent wheezing episodes than in first-time wheezers in age categories of <24 and <36 months (P < 0.05 for all).

CONCLUSIONS::
In children with bronchiolitis, 2 clinical factors, age and number of previous wheezing episodes, are linked to inflammatory (atopy-related factors) and virologic risk factors of asthma (rhinovirus-associated disease).

According to current US and UK guidelines, bronchiolitis includes wheezing children <24>

"Bronchiolitis: age and previous wheezing episodes are linked to viral etiology and atopic characteristics"
Jartti T, Lehtinen P, Vuorinen T, Ruuskanen O
Pediatr Infect Dis J. 2009 Apr ; 28(4): 311-7(hubmed.org)

Risk Factors For Hospital Readmission Within 30 Days

2009-07-02T23:54:00.000-07:00

The National Association of Children's Hospitals and Related Institutions (NACHRI) established hospital readmission within 30 days as a benchmark for quality care in children with Sickle Cell Disease (SCD). Among children with SCD, limited data exists to identify risk factors for readmission and whether they are modifiable.

PROCEDURE:
We performed a retrospective cohort study to identify risk factors for readmission. All admissions for children with SCD in a 1-year period were reviewed; cases were defined as children with SCD readmitted within 30 days after their first admission during the study period and controls, children with SCD who were not readmitted.

RESULTS:
We identified 30 cases and 70 controls. No difference in demographic data was found between groups. The most common admission and readmission diagnosis was pain, 78 and 70%, respectively.

The greatest risk factor for readmission was no outpatient hematology follow-up within 30 days of discharge (OR 7.7, 95% CI 2.4-24.4). A diagnosis of asthma was also a risk factor for readmission (OR 2.9, 95% CI 1.2-7.3).

Patients who required supplemental oxygen to maintain saturations in the normal range and were on room air for or =3 admissions in the previous 12 months as predictors for readmission (R(2) = 0.41).

CONCLUSIONS:
Potentially modifiable risk factors exist to decrease the rate of readmission of children with SCD admitted to the hospital for pain.

" Risk factors for hospital readmission within 30 days: a new quality measure for children with sickle cell disease"
Frei-Jones MJ, Field JJ, DeBaun MR
Pediatr Blood Cancer. 2009 Apr ; 52(4): 481-5(hubmed.org)

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Pediatric Asthma and Allergy | Symptoms of Childhood Asthma

Use Of Inhaled And Oral Corticosteroids And The Long-Term Risk of Cataract

2009-07-02T17:51:00.000-07:00

Longitudinal associations between inhaled and oral corticosteroid use and 10-year incident cataract were examined.

DESIGN:
Population-based cohort study.

PARTICIPANTS:
The Blue Mountains Eye Study examined 3654 Australians aged 49 years or older (1992-1994); 2335 were re-examined after 5 years and 1952 were re-examined after 10 years (75.1%, 75.6% of survivors, respectively).

METHODS:
Questionnaires were used to assess inhaled and oral corticosteroid use at baseline. Past users were participants who had used these medications for at least 1 month in the past but were not using them at baseline. Current users were those who were using these medications at baseline and had been doing so for at least 1 month. Ever users combined past and current users.

MAIN OUTCOME MEASURES:
Lens photographs were obtained at each examination and graded for nuclear, cortical, and posterior subcapsular (PSC) cataracts following the Wisconsin Cataract Grading System.

Participants without a specific subtype of cataract in either eye at baseline were considered to be at risk of that type of cataract developing over the 10-year follow-up. Incidence of each cataract subtype in this report refers to person-specific, first-eye incidence.

RESULTS:
At baseline, 103 participants were current and 120 past users of inhaled corticosteroids, and 31 were current and 147 were past users of oral corticosteroids. Current users had a greater risk of developing PSC cataract after adjustment for age and gender (inhaled: odds ratio [OR] 2.50, 95% confidence interval [CI] 1.33-4.69; oral: OR 4.11; 95% CI 1.67-10.08) and nuclear cataract (inhaled: OR 2.04, 95% CI 1.21-3.43; oral: OR 3.45, 95% CI 1.26-9.43) but not cortical cataract. Interaction between inhaled and oral corticosteroid use was significant for PSC (P = 0.01) and nuclear (P = 0.02) cataract incidence.

In subgroup analyses, only individuals who used both inhaled and oral steroids were at increased risk of PSC cataract (after adjusting for age, sex, smoking, hypertension, diabetes, and education levels; OR 4.76, 95% CI 2.59-8.74), comparing ever users of both with users of neither.

CONCLUSIONS:
High long-term risks of PSC and nuclear cataract development were found for users of combined inhaled and oral corticosteroids.

"Use of inhaled and oral corticosteroids and the long-term risk of cataract"
Wang JJ, Rochtchina E, Tan AG, Cumming RG, Leeder SR, Mitchell P
Ophthalmology. 2009 Apr ; 116(4): 652-7(hubmed.org)

Highlight
Pediatric Asthma Severity | Adult and Pediatric Asthma Treatment | Asthma In Childhood

Fontan Patient With Plastic Bronchitis Treated Successfully Using Aerosolized Tissue Plasminogen Activator

2009-07-02T13:57:00.000-07:00

Plastic bronchitis is an uncommon condition characterized by the production of large pale bronchial casts that obstruct the tracheobronchial tree.

The cellular content, cohesiveness, and often rubber-like consistency distinguish bronchial casts from the usual mucus plugs found with such disease states as asthma.

Plastic bronchitis can be found secondary to many conditions, and a simplified classification scheme organizes it into two groups: an inflammatory type consisting of casts with an eosinophilic inflammatory infiltrate and an acellular type with a predominance of fibrin distinguished by its relative lack of cellular infiltrate, its mucin predominance, and its appearance only in children with congenital cyanotic heart disease.

This report describes a 5-year-old girl who experienced plastic bronchitis 3 months after a Fontan procedure for hypoplastic left heart syndrome that was treated successfully with aerosolized tissue plasminogen activator.

"Fontan patient with plastic bronchitis treated successfully using aerosolized tissue plasminogen activator: a case report and review of the literature"
Do TB, Chu JM, Berdjis F, Anas NG
Pediatr Cardiol. 2009 Apr ; 30(3): 352-5(hubmed.org)

An Application Of The Asthma-Specific Job Exposure

2009-07-02T01:46:00.000-07:00

Risks for development of occupational sensitisation, bronchial hyper-responsiveness, rhinoconjunctival and chest symptoms at work associated with continued exposure to high molecular weight (HMW) allergens were estimated with three exposure assessment methods.

METHODS:
A Cox regression analysis with adjustment for atopy and smoking habit was carried out in 408 apprentices in animal health technology, pastry making, and dental hygiene technology with an 8-year follow-up after training.

The risk of continued exposure after training, estimated by the asthma-specific job exposure matrix (JEM), was compared with self-reports and investigator scores on job-training-related exposure. Associations between outcomes and work duration in job(s) related to training were also evaluated.

RESULTS:
Exposure to animal-derived HMW allergens, subsequent to the apprenticeship period, as estimated by the JEM, was associated with a significantly increased risk for occupational sensitisation (hazard ratio (HR) 6.4; 95% CI 2.3 to 18.2) and rhinoconjunctival symptoms at work (HR 2.6; 95% CI 1.1 to 6.2).

Exposure to low molecular weight (LMW) agents significantly increased the risk of developing bronchial hyper-responsiveness (HR 2.3; 95% CI 1.1 to 5.4). Exposure verification appeared to be important to optimise the sensitivity and the specificity, as well as HRs produced by the JEM.

Self-reports and investigator scores also indicated that further exposure to HMW allergens increased the risk of developing occupational allergies. The agreement between self-reports, investigator scores, and the JEM were moderate to good.

There was no significant association between respiratory outcomes and work duration in jobs related to training.

CONCLUSION:
The asthma-specific JEM could estimate the risk of various outcomes of occupational allergies associated with exposure to HMW and LMW allergens, but it is relatively labour intensive. Exposure verification is an important integrated step in the JEM that optimised the performance of the matrix.

"Risks for the development of outcomes related to occupational allergies: an application of the asthma-specific job exposure matrix compared with self-reports and investigator scores on job-training-related exposure"
Suarthana E, Heederik D, Ghezzo H, Malo JL, Kennedy SM, Gautrin D
Occup Environ Med. 2009 Apr ; 66(4): 256-63(hubmed.org)

Specific Antibodies To Diisocyanate And Work-Related Respiratory

2009-07-01T14:52:00.000-07:00

Isocyanates are the main cause of occupational asthma in most countries. Study of immunological markers of diisocyanate asthma may identify individuals at risk.

OBJECTIVES:
(1) To study changes in specific antibodies to hexamethylene diisocyanates (HDI); (2) to describe the incidence of work-related respiratory symptoms in relation to changes in specific antibody levels.

METHODS:
Prospective study in 385 apprentice car-painters during their 18 months of training. Participants were assessed on entering and completing their training using questionnaires, methacholine challenges and measurements of HDI-specific immunoglobulin E (IgE), immunoglobulin G (IgG) and subclass 4 of IgG (IgG4) antibodies.

RESULTS:
Complete data are available for 298 subjects. 13 subjects (4.4%) reported >or=1 new work-related lower respiratory symptoms and 19 (6.4%), >or=1 new work-related nasal symptoms.

Increases in levels of specific IgE and IgG above the 97th and 95th percentiles were significantly associated with duration of exposure. Increase in specific IgG was inversely related to incidence of work-related lower respiratory symptoms (OR = 0.001, 95% CI 0.000 to 0.09) after adjusting for relevant covariates.

The rise in specific IgG4 was significantly greater in those who did not develop work-related nasal symptoms (OR = 0.09, 95% CI 0.01 to 0.7).

CONCLUSION:
In this cohort of apprentice car-painters, a small proportion show increases in HDI-specific IgG and IgE after few months of exposure. Increases in specific IgG and IgG4 appear to have a protective effect on the incidence of work-related lower and upper respiratory symptoms, respectively. Assessment of specific antibodies to isocyanates may help identify subjects at risk of developing symptoms

"Specific antibodies to diisocyanate and work-related respiratory symptoms in apprentice car-painters"
Dragos M, Jones M, Malo JL, Ghezzo H, Gautrin D
Occup Environ Med. 2009 Apr ; 66(4): 227-34(hubmed.org)

Exhaled Nitric Oxide In Endotoxin-Exposed Adults

2009-07-01T11:50:00.000-07:00

Occupational exposure to endotoxin is associated with non-allergic asthma and other airway inflammatory reactions. Little is known about the role of mucosal nitric oxide (NO) production in endotoxin-induced airway inflammation.

The objective was to explore exposure-response relationships between occupational endotoxin exposure and fractional concentrations of exhaled NO (FE(NO)) and study the role of FE(NO) as an intermediate factor in the relationship between endotoxin exposure and asthma-like symptoms.

METHODS:
FE(NO) was measured online in 425 farmers and agricultural processing workers. For each participant (cumulative) endotoxin level was modelled on the basis of 249 personal measurements and job history.
Atopy was assessed as specific serum IgE to common inhalant allergens, and other health data and personal characteristics by standardised questionnaires.

RESULTS:
A significant positive exposure-response relationship was found between endotoxin and FE(NO), but only in non-atopic, non-smoking subjects (p = 0.001). FE(NO) was significantly associated with current wheeze and other asthma-like symptoms irrespective of atopy and current smoking. Associations between endotoxin exposure and symptoms changed slightly after adjusting for FE(NO).

CONCLUSIONS:
A positive association was found between occupational endotoxin exposure and exhaled nitric oxide in non-smoking, non-atopic adults. Increased FE(NO) was associated with asthma-like symptoms, but the role of FE(NO) as an intermediate factor between endotoxin exposure and airway symptoms appears to be limited.

"Exhaled nitric oxide in endotoxin-exposed adults: effect modification by smoking and atopy"
Smit LA, Heederik D, Doekes G, Wouters IM
Occup Environ Med. 2009 Apr ; 66(4): 251-5(hubmed.org)

Occupational Exposures And Asthma Among Nursing Professionals

2009-07-01T05:48:00.000-07:00

To identify occupational exposure risk factors associated with the development of new-onset asthma in nurses.

METHODS:
A cross-sectional survey was administered to a sample of licensed Texas nurses (response rate 70%) and compared to three other healthcare professional groups. Nursing professionals were defined based on self-reported longest held job.

Outcome variables were physician-diagnosed new-onset asthma after entry into the healthcare profession and symptoms associated with bronchial hyper-responsiveness (BHR). Occupational exposures were ascertained through a job-exposure matrix, grouped into four categories: cleaning-related tasks, use of powdered latex gloves, administration of aerosolised medications, and tasks involving adhesive compounds, glues and/or solvents.

RESULTS:
After adjustment for age, sex, ethnicity, atopy, smoking, body mass index and seniority, reported asthma was significantly greater among nursing professionals involved in medical instrument cleaning (OR = 1.67, 95% CI 1.06 to 2.62) and exposure to general cleaning products and disinfectants (OR = 1.72, 95% CI 1.00 to 2.94).

Use of powdered latex gloves during 1992-2000 was associated with 1.6 times (95% CI 1.01 to 2.50) the odds of reported asthma. In univariate analysis, exposure to adhesives, glues and/or solvents was associated with a twofold increase in the odds of reported asthma, but not after adjustment for covariates.

Similarly, the odds of BHR-related symptoms were significantly greater among nursing professionals exposed to general cleaning products and disinfectants (OR = 1.57, 95% CI 1.11 to 2.21) and adhesives, glues and/or solvents used in patient care (OR = 1.51, 95% CI 1.08 to 2.12).

CONCLUSION:
Among nursing professionals, workplace exposures to cleaning products and disinfectants increase the risk of new-onset asthma.

"Occupational exposures and asthma among nursing professionals"
Arif AA, Delclos GL, Serra C
Occup Environ Med. 2009 Apr ; 66(4): 274-8 (hubmed.org)

Capturing Adenylyl Cyclases As Potential Drug Targets

2009-07-01T02:45:00.000-07:00

Cyclic AMP (cAMP) is an important intracellular signalling mediator. It is generated in mammals by nine membrane-bound and one soluble adenylyl cyclases (ACs), each with distinct regulation and expression patterns.

Although many drugs inhibit or stimulate AC activity through the respective upstream G-protein coupled receptors (for example, opioid or beta-adrenergic receptors), ACs themselves have not been major drug targets.

Over the past decade studies on the physiological functions of the different mammalian AC isoforms as well as advances in the development of isoform-selective AC inhibitors and activators suggest that ACs could be useful drug targets. Here we discuss the therapeutic potential of isoform-selective compounds in various clinical settings, including neuropathic pain, neurodegenerative disorders, congestive heart failure, asthma and male contraception.

"Capturing adenylyl cyclases as potential drug targets"
Pierre S, Eschenhagen T, Geisslinger G, Scholich K
Nat Rev Drug Discov. 2009 Apr ; 8(4): 321-35(hubmed.org)

House Dust Mite Allergen Induces Asthma

2009-06-30T16:31:00.000-07:00

arrier epithelial cells and airway dendritic cells (DCs) make up the first line of defense against inhaled substances such as house dust mite (HDM) allergen and endotoxin (lipopolysaccharide, LPS).

We hypothesized that these cells need to communicate with each other to cause allergic disease. We show in irradiated chimeric mice that Toll-like receptor 4 (TLR4) expression on radioresistant lung structural cells, but not on DCs, is necessary and sufficient for DC activation in the lung and for priming of effector T helper responses to HDM.

TLR4 triggering on structural cells caused production of the innate proallergic cytokines thymic stromal lymphopoietin, granulocyte-macrophage colony-stimulating factor, interleukin-25 and interleukin-33.

The absence of TLR4 on structural cells, but not on hematopoietic cells, abolished HDM-driven allergic airway inflammation. Finally, inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma, including bronchial hyperreactivity. Our data identify an innate immune function of airway epithelial cells that drives allergic inflammation via activation of mucosal DCs.

"House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells"
Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN
Nat Med. 2009 Apr ; 15(4): 410-6(hubmed.org)

Highlight
Pediatric Asthma and Allergy | Pediatric Asthma Treatment Plan | Childhood Asthma Study

Fixed Drug Combinations--The Pros And Cons

2009-06-30T13:23:00.000-07:00

n a number of applications, more than one drug has to be prescribed to achieve the desired therapeutic goal.

Most often, it is the treatment of chronic diseases (like hypertension, type 2 diabetes mellitus, allergic asthma, but also chronic infectious diseases like tuberculosis or AIDS) which requires the combination of drugs with different mechanisms of action.

Multimorbidity, often present in old age, increases the number of drug intakes per day while the ability to do so correctly declines.

It appears thus plausible that a fixed combination of drugs, by decreasing the number of drug intakes per day, may lead to an improved compliance and eventually to an improvement of clinical endpoints.

However, there is scarce evidence that this assumption is generally valid. For each of the above diseases the use of fixed combinations has to be evaluated separately with respect to an improvement in clinical endpoints as well as to an increased risk of adverse effects. Finally, the pharmacoeconomic aspect as to how the cost of fixed combinations compares to that of free combinations has to be taken into account.

"Fixed drug combinations--the pros and the cons"
Rustenbeck I
Med Monatsschr Pharm. 2009 Apr ; 32(4): 141-6(hubmed.org)

Highlight
Pediatric Astma | Pediatric Asthma Treatment Innovation | Symptoms of Childhood Asthma

Effect of Leukotriene Receptor Antagonist on Cough Variant Asthma

2009-06-30T10:20:00.000-07:00

o study the curative effect of leukotriene receptor antagonist on cough variant asthma (CVA).

METHODS:
Sixty-four CVA patients received treatment with bricany and montelukas and 68 control patients had bricany treatment for 4 weeks. The recurrence rate was observed in the two groups during the follow-up for 6 months.

RESULTS:
The remission time of two groups were 2.5-/+3.6 and 5.3-/+3.8 days in acute phase, respectively, showing a significant difference between them (P<0.05).>"

Effect of leukotriene receptor antagonist on cough variant asthma"
He ZM, Guo YB, Xie CM
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Apr ; 29(4): 694-6(hubmed.org)

Highlight
Asthma in Pediatric Asthma Severity | Treatment of Pediatric Asthma |
Management of Childhood Asthma

Management of Exercise-Induced Bronchospasm In NCAA Athletic Programs

2009-06-30T01:26:00.000-07:00

he prevalence of exercise-induced bronchospasm (EIB) is significantly higher in athletes than that in the general population and can result in significant morbidity in young, competitive athletes.

Guidelines emphasize that education and written treatment protocols improve clinical outcomes for asthmatics. Evidence also supports objective testing when EIB is suspected, when there is immediate availability of rescue inhalers, and when there is involvement of asthma specialists in the care of asthmatic athletes.

We sought to determine how EIB is managed at the National Collegiate Athletic Association (NCAA) sports medicine programs.

METHODS:
A survey consisting of multiple-choice questions related to EIB in athletes was sent electronically to 3200 athletic trainers affiliated with NCAA sports medicine programs. RESULTS: Five hundred and forty-one athletic trainers responded.

A minority of athletic trainers surveyed (21%) indicated that an asthma management protocol exists at their institution. Twenty-two percent indicated that pulmonologists are on staff or consultants to the sports medicine department. Many indicated that a short-acting beta-agonist is not required to be available at all practices (39%) and games (41%), and few athletic trainers indicated that their programs use objective testing to diagnose EIB (17%). Regression modeling demonstrated education about EIB, and involvement of pulmonologists significantly improved adherence to current consensus guidelines.

CONCLUSIONS:
On the basis of our data, many NCAA sports medicine programs do not manage athletes with EIB according to current consensus guidelines. This may result in inaccurate diagnoses and may be detrimental to clinical outcomes and overall health of student athletes.

Providing education about EIB and involvement of pulmonologists significantly increase adherence to guidelines that likely improves clinical care of athletes and potentially athletic performance.

"Management of exercise-induced bronchospasm in NCAA athletic programs"
Parsons JP, Pestritto V, Phillips G, Kaeding C, Best TM, Wadley G, Mastronarde JG
Med Sci Sports Exerc. 2009 Apr ; 41(4): 737-41(hubmed.org)

The Augmented RIC Model of The Human Respiratory System

2009-06-29T13:21:00.000-07:00

his paper describes the augmented RIC model of respiratory impedance and analyzes its parameter values estimated--by a modified Newton method with least squares criterion--from impulse oscillometry data.

The data were from asthmatic children, tested pre- and post-bronchodilator, and from healthy adults and a second group of adults with COPD. Our analyses show that the augmented RIC model was 13.7-66.6% more accurate than the extended RIC model at fitting these data, while its parameter estimates were within previously reported ranges, unlike the Mead 1969, DuBois and Mead models, which typically yielded compliance estimates exceeding 200 l/kPa.

Additionally, the augmented RIC model's C(p) parameter, representing peripheral airway compliance, is a statistically significant discriminator between unconstricted and constricted conditions (with p < 0.001) occurring in asthma and COPD.

This corresponds well with current medical understanding, so the augmented RIC model is potentially useful for detection and treatment of airflow obstruction

"The augmented RIC model of the human respiratory system"
Diong B, Rajagiri A, Goldman M, Nazeran H
Med Biol Eng Comput. 2009 Apr ; 47(4): 395-404(hubmed.org)

Measurement Invariance of The Mini Asthma Quality of Life

2009-06-29T11:19:00.000-07:00

his study tested the factorial and measurement invariance of the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) in a sample of Latino and African-American asthmatic patients.

METHODS:
We used confirmatory factor analyses (CFA) to examine data from adult outpatients diagnosed with asthma (n = 265). We proceeded by examining the original factor structure of the MiniAQLQ in the whole sample.

We then determined whether the factor structure supported by the data was invariant across African-American and Latino patients by testing a series of nested models.

RESULTS:
Results revealed that a three-factor structure model that combined the emotional function and symptom domains had the best fit to the whole sample (chi (2)(91) = 99.83, P = 0.08). Analysis using a MIMIC model among Latino participants indicated that survey language did not influence item functioning (chi (2)(93) = 103.29, P = 0.22).

Multi-group CFA showed that both the structure and the meaning of the items were invariant across Africa-American and Latino participants. Scalar and strict measurement invariance was supported for 11 out of 15 items.

CONCLUSION:
These data suggest that structure of the MiniAQLQ needs to be reassessed. Additional research needs to examine whether elimination of current items or inclusion of new items can ensure that constructs are measured without bias across different ethnic groups.

"Measurement invariance of the Mini Asthma Quality of Life Questionnaire across African-American and Latino adult asthma patients"
Mora PA, Contrada RJ, Berkowitz A, Musumeci-Szabo T, Wisnivesky J, Halm EA
Qual Life Res. 2009 Apr ; 18(3): 371-80(hubmed.org)

Measures of Asthma Control And Quality of Life

2009-06-29T06:16:00.000-07:00

o further our understanding of the relationships between asthma control and health-related quality of life (HRQOL) and provide insights into the relative usefulness of various measures in different research contexts. We present a conceptual model and test it with longitudinal survey data.

METHODS:
Participants recruited via population sampling and hospital Emergency Departments completed questionnaires every 6 months for up to 3 years. Measures included: sleep disturbance, use of short-acting beta agonists (SABA), activity limitation, urgent medical visits, hospital use, Marks' Asthma Quality of Life Questionnaire (AQLQ-M) and the SF-36 Health Survey.

Correlation analysis and multi-level models tested predictions from the conceptual model.

RESULTS:
A total of 213 people with asthma aged 16-75 years provided 967 observations. Correlations between asthma control and asthma-specific HRQOL were stronger than those between asthma control and generic HRQOL.

The asthma control variables explained 54-58% of the variance in asthma-specific HRQOL and 8-25% of the variance in generic HRQOL. Activity limitation was the main contributor to between-person variation, while sleep disturbance and SABA use were the main contributors to within-person variation.

CONCLUSIONS:
Sleep disturbance and SABA use may be most useful in evaluating treatment effectiveness, while activity limitation may be better when monitoring the impact of asthma in populations.

"Measures of asthma control and quality of life: longitudinal data provide practical insights into their relative usefulness in different research contexts"
King MT, Kenny PM, Marks GB
Qual Life Res. 2009 Apr ; 18(3): 301-12(hubmed.org)

Developing Antitussives: The Ideal Clinical Trial

2009-06-29T01:13:00.000-07:00

ntitussive drugs are amongst the most widely used medications worldwide; however no new class of drugs have been introduced into the market for many years. Trials showing patient benefit are scarce and have been hampered by the lack of objective and validated outcome measures.

Recent improvements in the assessment of cough will facilitate better trials and aid the development of antitussive drugs. When conducting a trial, patient selection is of paramount importance. Patients with unexplained chronic cough and sub-acute cough following upper respiratory tract infection are ideal because they represent an unmet clinical need and an untapped market for pharmaceutical companies.

Patients with asthma and chronic obstructive pulmonary disease are less suitable since cough suppression is not always desirable and the findings of trials may not be generalisable to all patients with cough. Randomized, placebo-controlled, double-blind clinical trials are obviously the gold standard.

The choice of placebo, whether inert or active, depends on the incidence and severity of drug side-effects. The primary outcome measure should be objective and cough monitors are the ideal tool. Subjective outcome measures should be used to assess symptoms and health related quality of life. Properly conducted clinical trials are an opportunity to evaluate the benefits of currently available therapies and aid advances in the antitussive drug market.

"Developing antitussives: the ideal clinical trial"
Birring SS
Pulm Pharmacol Ther. 2009 Apr ; 22(2): 155-8 (hubmed.org)

Cough And Viruses in Airways Disease: Mechanisms

2009-06-29T01:01:00.000-07:00

cute cough is a major symptom of viral respiratory tract infection and causes excessive morbidity in human populations across the world.

A wide variety of viruses play a role in the development of cough after acute infection and all of these manifest a similar clinical picture across different age groups. Despite the large disease burden surprisingly little is known about the mechanism of acute cough following viral infection.

Both in vitro and in vivo experiments show that increased production of neuropeptides and leukotrienes mediate cough after viral infection, along with altered expression of neural receptors. Increased airway mucus production is also likely to play a significant role. This work is reviewed in this article.

Following the recent development of a mouse model for rhinovirus infection and the establishment of experimental models of rhinovirus challenge in human subjects with both asthma and COPD the field is expanding to translate in vitro research into clinical studies and hopefully eventually into clinical practice. Developing a clearer understanding of the mechanisms underlying virus induced cough may lead to more specific and effective therapies

"Cough and viruses in airways disease: mechanisms"
Footitt J, Johnston SL
Pulm Pharmacol Ther. 2009 Apr ; 22(2): 108-13(hubmed.org)

Highlight
Pediatric Asthma Prevalence | Adult and Pediatric Asthma Treatment | Childhood Asthma Management

Mechanisms of The Cough Associated with Rhinosinusitis

2009-06-28T22:06:00.000-07:00

he diseases of the nose and paranasal sinuses (rhinosinusitis) often in combination with asthma and gastroesophageal reflux are common causes of chronic cough in patients with normal chest radiograph.

The relationships between rhinosinusitis and cough are incompletely understood. We investigated modulation of the cough reflex by the inputs from the nose. We demonstrate that the cough reflex is sensitized by the intranasal administration of sensory nerve activators in animal models and in humans.

Cough reflex is also sensitized in the guinea pig model of allergic nasal inflammation and in patients with allergic rhinitis. In patients with allergic rhinitis the cough sensitization is augmented during the allergen season. We conclude that the cough reflex can be sensitized from the nose.

Our data indicate that this sensitization is mediated by nasal sensory nerves. We speculate that by inducing the cough reflex sensitization rhinosinusitis contributes to chronic cough. If combined with environmental or endogenous cough triggers, the cough reflex sensitization is predicted to cause excessive coughing.

The potential endogenous cough triggers may be associated with rhinosinusitis (postnasal drip, aspiration of nasal secrets) or secondary to a coexistent disease such as asthma or gastroesophageal reflux.

"Mechanisms of the cough associated with rhinosinusitis"
Tatar M, Plevkova J, Brozmanova M, Pecova R, Kollarik M
Pulm Pharmacol Ther. 2009 Apr ; 22(2): 121-6(hubmed.org)

Highlight
Asthma in Pediatric Patients | Pediatric Asthma Treatment Program | Treatment of Childhood Asthma

Eosinophilic Airway Disorders Associated with Chronic Cough

2009-06-28T20:03:00.000-07:00

hronic cough is a major clinical problem. The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, the former being comprised of asthma, cough variant asthma (CVA), atopic cough (AC) and non-asthmatic eosinophilic bronchitis (NAEB).

Cough is one of the major symptoms of asthma. Cough in asthma can be classified into three categories; 1) CVA: asthma presenting solely with coughing, 2) cough-predominant asthma: asthma predominantly presenting with coughing but also with dyspnea and/or wheezing, and 3) cough remaining after treatment with inhaled corticosteroid (ICS) and beta2-agonists in patients with classical asthma, despite control of other symptoms.

There may be two subtypes in the last category; one is cough responsive to anti-mediator drugs such as leukotriene receptor antagonists and histamine H1 receptor antagonists, and the other is cough due to co-morbid conditions such as gastroesophageal reflux.

CVA is one of the commonest causes of chronic isolated cough. It shares a number of pathophysiological features with classical asthma with wheezing such as atopy, airway hyperresponsiveness (AHR), eosinophilic airway inflammation and various features of airway remodeling.

One third of adult patients may develop wheezing and progress to classical asthma. As established in classical asthma, ICS is considered the first-line treatment, which improves cough and may also reduce the risk of progression to classical asthma.

AC proposed by Fujimura et al. presents with bronchodilator-resistant dry cough associated with an atopic constitution. It involves eosinophilic tracheobronchitis and cough hypersensitivity and responds to ICS treatment, while lacking in AHR and variable airflow obstruction.

These features are shared by non-asthmatic eosinophilic bronchitis (NAEB). However, atopic cough does not involve bronchoalveolar eosinophilia, has no evidence of airway remodeling, and rarely progresses to classical asthma, unlike CVA and NAEB. Histamine H1 antagonists are effective in atopic cough, but their efficacy in NAEB is unknown. AHR of NAEB may improve with ICS within the normal range.

Taken together, NAEB significantly overlaps with atopic cough, but might also include milder cases of CVA with very modest AHR. The similarity and difference of these related entities presenting with chronic cough and characterized by airway eosinophilia will be discussed

"Eosinophilic airway disorders associated with chronic cough"
Niimi A, Matsumoto H, Mishima M
Pulm Pharmacol Ther. 2009 Apr ; 22(2): 114-20(hubmed.org)

Highlight
Pediatric Asthma Allergy | Pediatric Asthma Treatment Plan | Childhood Asthma Treatment

Speech Pathology for Chronic Cough: A New Approach

2009-06-28T15:11:00.000-07:00

hronic cough may persist despite systematic evaluation and medical treatment of known associated diseases such as asthma, rhinitis, and gastro-esophageal reflux. These patients have refractory chronic cough and many exhibit laryngeal hypersensitivity that is manifest at both a sensory and motor level.

Examples of this are heightened sensitivity of the cough reflex to capsaicin, and laryngeal motor dysfunction with hoarse vocal quality and paradoxical vocal cord movement. Chronic cough that persists despite medical treatment may respond to speech pathology intervention.

A multidimensional speech pathology treatment programme was designed based upon methods used to treat hyperfunctional voice disorders and paradoxical vocal fold movement. This included education, vocal hygiene training, cough suppression strategies and psychoeducational counseling.

When tested in a single-blind, randomized, placebo-controlled trial involving 87 patients, participants in the treatment group demonstrated a significant reduction in cough, breathing, voice and upper airway symptoms following intervention, as well as improvements in auditory perceptual ratings of voice quality (breathy, rough, strain and glottal fry) and significant improvement in voice acoustic parameters (maximum phonation time, jitter and harmonic-to-noise ratio). Speech pathology intervention can be an effective way to treat refractory chronic cough.

"Speech pathology for chronic cough: a new approach"
Gibson PG, Vertigan AE
Pulm Pharmacol Ther. 2009 Apr ; 22(2): 159-62(hubmed.org)

Highlight
Pediatric Asthma Severity | Treatment of Pediatric Asthma | Childhood Asthma Control Test

Biomarker Discovery in Asthma-Related Inflammation And Remodeling

2009-06-27T14:59:00.000-07:00

Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be involved in the installation and maintenance of asthma-related airway inflammation and remodeling.

To date, new proteic mediators displaying significant activity in the pathophysiology of asthma are still to be unveiled.

The main objective of this study was to uncover potential target proteins by using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) on lung samples from mouse models of allergen-induced airway inflammation and remodeling.

In this model, we pointed out several protein or peptide peaks that were preferentially expressed in diseased mice as compared to controls. We report the identification of different five proteins: found inflammatory zone 1 or RELM alpha (FIZZ-1), calcyclin (S100A6), clara cell secretory protein 10 (CC10), Ubiquitin, and Histone H4.

"Biomarker discovery in asthma-related inflammation and remodeling"
Calvo FQ, Fillet M, de Seny D, Meuwis MA, Maree R, Crahay C, Paulissen G, Rocks N, Gueders M, Wehenkel L, Merville MP, Louis R, Foidart JM, Noël A, Cataldo D
Proteomics. 2009 Apr ; 9(8): 2163-70(hubmed.org)

The Role of The Extracellular Matrix And Specific Growth Factors in The Regulation of Inflammation And Remodelling in Asthma

2009-06-27T10:56:00.000-07:00

Asthma is a disease characterised by persistent inflammation and structural changes in the airways, referred to as airway remodelling.

The mechanisms underlying these processes may be interdependent or they may be separate processes that are driven by common factors. The levels of a variety of growth factors (including transforming growth factor beta, granulocyte macrophage colony stimulating factor, and vascular endothelial growth factor) are known to be changed in the asthmatic airway.

These and other growth factors can contribute to the development and persistence of inflammation and remodelling. One of the prominent features of the structural changes of the airways is the increased deposition and alterations in the composition of the extracellular matrix proteins.

These proteins include fibronectin, many different collagen types and hyaluronan. There is a dynamic relationship between the extracellular matrix proteins and the airway mesenchymal cells such that the changes in the extracellular matrix proteins can also contribute to the persistence of inflammation and the airway remodelling.

This review aims to summarise the role growth factors and extracellular matrix proteins play in the regulation of inflammation and airway remodelling in the asthmatic airway.

"The role of the extracellular matrix and specific growth factors in the regulation of inflammation and remodelling in asthma"
Burgess JK
Pharmacol Ther. 2009 Apr ; 122(1): 19-29(hubmed.org)

Diet and Asthma-- Can You Change What You or your Children Are by Changing What You Eat ?

2009-06-27T05:53:00.000-07:00

n this review we focus on dietary fat content and subsequent effects on asthma. According to the World Health Organisation over 300 million people currently have asthma.

The majority of asthma cases are 'extrinsic' and result from inappropriate 'allergic' immune responses to inhaled environmental substances. Whilst some individuals are allergic to particular food components it is becoming clear that the content of the diet can more generally affect the health of the immune system.

Components of maternal and early life diets have been reported to influence offspring immune function and asthma. There has been speculation that different types of dietary fat have pro- and anti-inflammatory effects but the results of various studies are contradictory.

Asthma and obesity are two conditions that have almost simultaneously reached epidemic levels in some societies. There is evidence that diet-induced obesity alters immune function and there is little doubt that consumption of a high caloric diet with high fat content leads to obesity.

However, there is conflicting information over whether and how obesity is linked to asthma in children and adults. Whilst obesity is to be avoided there is accumulating evidence that dietary fat per se does not necessarily predispose towards allergic symptoms

"Diet and asthma--can you change what you or your children are by changing what you eat ?"
de Vries A, Howie SE
Pharmacol Ther. 2009 Apr ; 122(1): 78-82(hubmed.org)

Work of Breathing and Different Levels of Volume-Targeted Ventilation

2009-06-27T01:52:00.000-07:00

he objectives of this study were to determine the impact of different volume-targeted levels on the work of breathing and to investigate whether a level that reduced the work of breathing below that experienced during ventilatory support without volume targeting could be determined.

METHODS:
The transdiaphragmatic pressure-time product, as an estimate of the work of breathing, was measured for 20 infants (median gestational age: 28 weeks) who were being weaned from respiratory support by using patient-triggered ventilation (either assist-control ventilation or synchronous intermittent mandatory ventilation).

The transdiaphragmatic pressure-time product was measured first without volume targeting (baseline) and then at volume-targeted levels of 4, 5, and 6 mL/kg, delivered in random order. After each volume-targeted level, the infants were returned to baseline. Each step was maintained for 20 minutes.

RESULTS:
The mean transdiaphragmatic pressure-time product was higher with volume targeting at 4 mL/kg in comparison with baseline, regardless of the patient-triggered mode.

The transdiaphragmatic pressure-time product was higher at a volume-targeted level of 4 mL/kg in comparison with 5 mL/kg and at 5 mL/kg in comparison with 6 mL/kg. The mean work of breathing was below that at baseline only at a volume-targeted level of 6 mL/kg.

CONCLUSIONS:
Low volume-targeted levels increase the work of breathing during volume-targeted ventilation. Our results suggest that, during weaning, a volume-targeted level of 6 mL/kg, rather than a lower level, could be used to avoid an increase in the work of breathing.

"Work of breathing and different levels of volume-targeted ventilation"
Patel DS, Sharma A, Prendergast M, Rafferty GF, Greenough A
Pediatrics. 2009 Apr ; 123(4): e679-84(hubmed.org)

Variability in The Diagnostic Labeling of Nonbacterial Lower Respiratory Tract Infections

2009-06-26T14:47:00.000-07:00

he diagnostic labeling of presumed nonbacterial lower respiratory tract infection is unclear. Our objective was to identify patterns of specific diagnoses and treatments that were given to children who presented with lower respiratory tract infection to US academic emergency departments.

METHODS:
Data were collected on all children who were aged 4%, previous use of corticosteroids, and parental history of asthma.

CONCLUSIONS:
For children who are age tract infection as asthma are more likely to receive corticosteroids.

As clinicians, we need to develop evidence- and outcome-based definitions for lower respiratory tract infections to guide diagnosis and treatment better.

"Variability in the diagnostic labeling of nonbacterial lower respiratory tract infections: a multicenter study of children who presented to the emergency department"
Mansbach JM, Espinola JA, Macias CG, Ruhlen ME, Sullivan AF, Camargo CA
Pediatrics. 2009 Apr ; 123(4): e573-81(hubmed.org)

Adenotonsillectomy and The Development of Overweight

2009-06-26T11:44:00.000-07:00

tudies among patients have shown accelerated weight gain after (adeno)tonsillectomy. Whether (adeno)tonsillectomy is also a risk factor for the development of overweight is unknown.

We investigated the association between (adeno)tonsillectomy and the subsequent development of overweight in the general population.

METHODS:
The study population consisted of 3963 children participating in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort.

Data on weight and height, adenoidectomy and tonsillectomy, and covariates (gender, birth weight, maternal education, maternal overweight, maternal smoking during pregnancy, breastfeeding, and smoking in the home) were obtained from annual questionnaires completed by the parents. In addition to the questionnaire data, weight and height were measured by the investigators when the children were 8 years old.

RESULTS:
(Adeno)tonsillectomy between 0 and 7 years of age was significantly associated with overweight and obesity at age 8. Overweight at the age of 2 years was not associated with increased risk of (adeno)tonsillectomy in later years, indicating that the association between (adeno)tonsillectomy and overweight was not explained by preexisting overweight.

Longitudinal data on weight and height in the years before and after surgery suggest that (adeno)tonsillectomy forms a turning point between a period of growth faltering and a period of catch-up growth, which might explain the increased risk to develop overweight after the operation.

CONCLUSION: Children who undergo (adeno)tonsillectomy are at increased risk to develop overweight in the years after surgery.

"Adenotonsillectomy and the development of overweight"
Wijga AH, Scholtens S, Wieringa MH, Kerkhof M, Gerritsen J, Brunekreef B, Smit HA
Pediatrics. 2009 Apr ; 123(4): 1095-101(hubmed.org)

Brief Bout of Exercise Alters Gene Expression in Peripheral Blood Mononuclear Cells of Early- and Late-Pubertal Males

2009-06-26T07:41:00.000-07:00

eripheral blood mononuclear cells (PBMCs) are stimulated by exercise and contribute not only to host defense, but also to growth, repair, and disease pathogenesis. Whether PBMC gene expression is altered by exercise in children is not known.

Ten early pubertal boys (8-12 y) and 10 late pubertal boys (15-18 y) performed ten 2-min bouts of strenuous, constant work rate exercise with 1-min rest intervals. PBMCs were isolated before and after exercise and microarray (Affymetrix U133 + 2 chips) analyzed.

Statistical criterion to identify gene expression changes was less than 5% false discovery rate (FDR) with 95% confidence interval.

One thousand two hundred forty-six genes were altered in older boys (517 up, 729 down), but only 109 were altered in the younger group (79 up, 30 down). In older boys, 13 gene pathways (using Expression Analysis Systematic Explorer, p < 0.05) were found (e.g. natural killer cell cytotoxicity, apoptosis).

Epiregulin gene expression (EREG, a growth factor involved in wound healing) increased in older boys. In older boys exercise altered genes such as TBX21, GZMA, PGTDR, and CCL5 also play roles in pediatric inflammatory diseases like asthma. Sixty-six genes were changed significantly in both groups.

The pattern of PBMC gene expression suggests the initiation of an immunologic "danger" signal associated with a sudden change in energy expenditure.

"Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males"
Radom-Aizik S, Zaldivar F, Leu SY, Cooper DM
Pediatr Res. 2009 Apr ; 65(4): 447-52(hubmed.org)

The Clinical Impact of The Radiology Report in Wheezing and Nonwheezing Febrile Children

2009-06-26T02:38:00.000-07:00

he chest radiograph is commonly used in the diagnosis and management of patients presenting with respiratory illness. The language used to describe the findings is important to ensure appropriate communication with the referring clinician and thereby optimize patient management.

OBJECTIVE:
In this study we attempted to determine how clinicians interpret specific terms commonly used in a chest radiograph report, and to assess how these terms impact the management of children with respiratory symptoms.

MATERIALS AND METHODS:
An online survey was distributed to 562 pediatric practitioners asking their interpretation of the terms "peripheral airway disease (PAD)," "focal airspace consolidation," and "focal infiltrate" in a febrile child with or without wheezing.

RESULTS:
There were 112 respondents. Most practitioners defined the term "PAD" as viral pneumonia (61.5%) or asthma (56.9%), "consolidation" as atelectasis (83%) followed by pneumonia (69.6%), and "infiltrate" as pneumonia (100%), followed by atelectasis (22.3%). Practitioners were more likely to treat a nonwheezing child with antibiotics if the report stated "focal airspace consolidation" (80%) or "focal infiltrate" (100%; P=0.001).

CONCLUSION:
Some radiologic descriptors may lead to diverse and sometimes unintended diagnostic conclusions. Our findings support continued effort to structure and standardize the radiology report and our descriptive terminology.

"The clinical impact of the radiology report in wheezing and nonwheezing febrile children: a survey of clinicians"
Spottswood SE, Liaw K, Hernanz-Schulman M, Hilmes MA, Moore PE, Patterson B, Chen H, Kan JH
Pediatr Radiol. 2009 Apr ; 39(4): 348-53(hubmed.org)

Position and Ventilatory Response to Added Dead Space in Prematurely Born Infants

2009-06-25T15:36:00.000-07:00

rematurely born infants are at increased risk of sudden infant death syndrome (SIDS) if slept prone.

WORKING HYPOTHESIS:
Prematurely born infants would have an impaired response to an added dead space and lower respiratory muscle strength in the prone compared to the supine position.

STUDY DESIGN: Prospective study.

PATIENT-SUBJECT SELECTION:
Twenty-five infants, median gestational age of 30 (range 26-32) weeks.

METHODOLOGY:
The infants were studied supine and prone at a median of 36 weeks postmenstrual age. Breath by breath minute volume was measured at baseline and after a dead space was incorporated into the breathing circuit; the time constant of the response was calculated.

The maximum inspiratory occlusion pressure generated (MIOP) and the pressure generated over the first 100 msec (P(0.1)) during airway occlusion were assessed. RESULTS: The median time constant was longer (26 (range 8-106) sec vs. 22 (range 6-92) sec (P = 0.045)) and the median MIOP (P = 0.001) and P(0.1) (P = 0.003) were lower in the prone compared to the supine position.

CONCLUSION:
Prematurely born infants have a dampened response to tube breathing and reduced respiratory muscle strength in the prone compared to the supine position, which may contribute to their increased vulnerability to SIDS in the prone position.

"Position and ventilatory response to added dead space in prematurely born infants"
Rao H, Saiki T, Landolfo F, Smith AP, Hannam S, Rafferty GF, Milner AD, Greenough A
Pediatr Pulmonol. 2009 Apr ; 44(4): 387-91 (hubmed.org)

In Vivo Uptake of Inhaled Particles by Airway Phagocytes is Enhanced in Patients with Mild Asthma Compared with Normal Volunteers

2009-06-25T02:19:00.000-07:00

he uptake of inhaled particulate matter by airway phagocytes is an important defence mechanism contributing to the clearance of potentially toxic substances, including aeroallergens, from the lung.

Since airway monocytes and macrophages can also function as antigen presenting cells, their ability to engulf materials deposited on the airway surface is of particular interest in patients with allergic asthma.

To determine whether airway mononuclear phagocytes of patients with allergic asthma might have enhanced phagocytic activity, the in vivo uptake of inhaled radiolabelled particles was compared in 10 patients with mild allergic asthma and 8 healthy (non-allergic) individuals.

METHODS:
Phagocyte function was assessed by quantifying the proportion of radioactivity associated with cellular and supernatant fractions of induced sputum 2 h after inhalation of radiolabelled sulfur colloid particles.

All subjects were pretreated with albuterol before sputum induction. A standardised breathing pattern was used to target aerosol deposition in the bronchial airways.

RESULTS:
In vivo particle uptake by airway cells was significantly greater in patients with asthma than in healthy volunteers (57.2% (95% CI 46.5% to 67.9%) vs 22.3% (95% CI 4.9% to 39.6%), p<0.01), r =" 0.85," style="font-style: italic;">"In vivo uptake of inhaled particles by airway phagocytes is enhanced in patients with mild asthma compared with normal volunteers" Lay JC, Alexis NE, Zeman KL, Peden DB, Bennett WD Thorax. 2009 Apr ; 64(4): 313-20 (hubmed.org)

An International Prospective General Population-Based Study of Respiratory Work Disability

2009-06-25T01:11:00.000-07:00

revious cross-sectional studies have shown that job change due to breathing problems at the workplace (respiratory work disability) is common among adults of working age.

That research indicated that occupational exposure to gases, dust and fumes was associated with job change due to breathing problems, although causal inferences have been tempered by the cross-sectional nature of previously available data.

There is a need for general population-based prospective studies to assess the incidence of respiratory work disability and to delineate better the roles of potential predictors of respiratory work disability.

METHODS:
A prospective general population cohort study was performed in 25 centres in 11 European countries and one centre in the USA. A longitudinal analysis was undertaken of the European Community Respiratory Health Survey including all participants employed at any point since the baseline survey, 6659 subjects randomly sampled and 779 subjects comprising all subjects reporting physician-diagnosed asthma.

The main outcome measure was new-onset respiratory work disability, defined as a reported job change during follow-up attributed to breathing problems. Exposure to dusts (biological or mineral), gases or fumes during follow-up was recorded using a job-exposure matrix. Cox proportional hazard regression modelling was used to analyse such exposure as a predictor of time until job change due to breathing problems.

RESULTS:
The incidence rate of respiratory work disability was 1.2/1000 person-years of observation in the random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma cohort, high occupational exposure to biological dust, mineral dust or gases or fumes predicted increased risk of respiratory work disability.

In the random sample, sex was not associated with increased risk of work disability while, in the asthma cohort, female sex was associated with an increased disability risk (hazard ratio 2.8, 95% CI 1.3 to 5.9).

CONCLUSIONS: Respiratory work disability is common overall. It is associated with workplace exposures that could be controlled through preventive measures.

"An international prospective general population-based study of respiratory work disability"
Torén K, Zock JP, Kogevinas M, Plana E, Sunyer J, Radon K, Jarvis D, Kromhout H, d'Errico A, Payo F, Antó JM, Blanc PD
Thorax. 2009 Apr ; 64(4): 339-44(hubmed.org)

Sublingual Immunotherapy in Children

2009-06-25T00:32:00.000-07:00

lthough pharmacological therapy and allergen avoidance are effective means of managing allergic disease, allergen-specific immunotherapy is able to treat not only the symptoms, but also the underlying causes of the disease.

Sublingual immunotherapy (SLIT) has been shown to be effective in patients with allergic diseases. It has demonstrated long-term clinical benefits and shown the potential to modify the course of allergic disease in children with rhinitis, conjunctivitis, and asthma.

The precise mechanisms of SLIT remain unclear, but antigen-presenting cells in the oral mucosa may induce regulatory T-cells that suppress the allergic immune response by increasing production of interleukin-10.

SLIT has also been shown to increase allergen-specific IgG antibodies that antagonize and block the allergic response. SLIT was well tolerated in all reported, double-blinded, placebo-controlled, randomized trials. SLIT is an ideal means of treating the pediatric population because of its excellent safety and good compliance. However, the optimal dose and duration of SLIT require further investigation.

"Sublingual immunotherapy in children: an updated review"
Kuo CH, Wang WL, Chu YT, Lee MS, Hung CH
Pediatr Neonatol. 2009 Apr ; 50(2): 44-9(hubmed.org)

Association of Duration of Television Viewing in Early Childhood with the Subsequent Development of Asthma

2009-06-24T11:02:00.000-07:00

o investigate whether duration of television (TV) viewing in young children is associated with subsequent development of asthma.

METHODS:
Children taking part in the Avon Longitudinal Study of Parents and Children (ALSPAC) with no wheeze up to the age of 3.5 years and follow-up data at 11.5 years of age took part in a prospective longitudinal cohort study.

The main outcome measure was asthma, defined as doctor-diagnosed asthma by 7.5 years of age with symptoms and/or treatment in the previous 12 months at 11.5 years of age. Parental report of hours of TV viewing per day by the children was ascertained at 39 months.

RESULTS:
In children with no symptoms of wheeze at 3.5 years of age and follow-up data at 11.5 years of age, the prevalence of asthma was 6% (185/3065). Increased TV viewing at 3.5 years was associated with increased prevalence of asthma at 11.5 years of age (p for linear trend = 0.0003).

Children who watched television for >2 h/day were almost twice as likely to develop asthma by 11.5 years of age as those watching TV for 1-2 h/day (adjusted odds ratio 1.8 (95% CI 1.2 to 2.6)).

CONCLUSION:
Longer duration of TV viewing in children with no symptoms of wheeze at 3.5 years of age was associated with the development of asthma in later childhood.

"Association of duration of television viewing in early childhood with the subsequent development of asthma"
Sherriff A, Maitra A, Ness AR, Mattocks C, Riddoch C, Reilly JJ, Paton JY, Henderson AJ
Thorax. 2009 Apr ; 64(4): 321-5(hubmed.org)

Healthcare Via Cell Phones: a Systematic Review

2009-06-24T05:59:00.000-07:00

egular care and informational support are helpful in improving disease-related health outcomes. Communication technologies can help in providing such care and support. The purpose of this study was to evaluate the empirical evidence related to the role of cell phones and text messaging interventions in improving health outcomes and processes of care.

Scientific literature was searched to identify controlled studies evaluating cell phone voice and text message interventions to provide care and disease management support. Searches identified 25 studies that evaluated cell phone voice and text messaging interventions, with 20 randomized controlled trials and 5 controlled studies.

Nineteen studies assessed outcomes of care and six assessed processes of care. Selected studies included 38,060 participants with 10,374 adults and 27,686 children. They covered 12 clinical areas and took place in 13 countries.

Frequency of message delivery ranged from 5 times per day for diabetes and smoking cessation support to once a week for advice on how to overcome barriers and maintain regular physical activity.

Significant improvements were noted in compliance with medicine taking, asthma symptoms, HbA1C, stress levels, smoking quit rates, and self-efficacy. Process improvements were reported in lower failed appointments, quicker diagnosis and treatment, and improved teaching and training.

Cost per text message was provided by two studies. The findings that enhancing standard care with reminders, disease monitoring and management, and education through cell phone voice and short message service can help improve health outcomes and care processes have implications for both patients and providers

"Healthcare via cell phones: a systematic review"
Krishna S, Boren SA, Balas EA
Telemed J E Health. 2009 Apr ; 15(3): 231-40(hubmed.org)

Prevalence of Asthma-Like Symptoms, Asthma and Its Treatment in Elite Athletes

2009-06-24T01:56:00.000-07:00

he objective was to determine the prevalence of asthma-like symptoms and asthma and the use of asthma medication in Danish elite athletes. A cross-sectional questionnaire survey of Danish elite athletes was conducted in 2006.

All elite athletes (N=418) financially supported by the national organization of elite athletes comprised the study group; 329 (79%) completed the questionnaire concerning their sport, asthma-like symptoms, asthma and use of asthma medication.

Asthma-like symptoms at rest were reported by 41% of respondents; 55% reported asthma-like symptoms at rest or at exercise. Physician-diagnosed asthma was present in 16% and 14% had current asthma.

Asthma medication was taken by 7% of the athletes, of whom 79% used inhaled corticosteroids and 21% used inhaled beta(2)-agonists only. Athletes participating in endurance sports had higher prevalences of current asthma (24%) and use of asthma medication (15%) than all other athletes (P<0.01).

Athletes participating in endurance sports have a higher prevalence of asthma and use of asthma medication. The frequency of asthma medication is lower than the prevalence of current asthma indicating that there is no overuse of asthma medication among Danish elite athletes.

"Prevalence of asthma-like symptoms, asthma and its treatment in elite athletes"
Lund T, Pedersen L, Larsson B, Backer V
Scand J Med Sci Sports. 2009 Apr ; 19(2): 174-8(hubmed.org)

Fungi and Pollen Exposure in the First Months of Life and Risk of Early Childhood Wheezing

2009-06-24T00:08:00.000-07:00

any studies have found that the risk of childhood asthma varies by month of birth, but few have examined ambient aeroallergens as an explanatory factor. A study was undertaken to examine whether birth during seasons of elevated ambient fungal spore or pollen concentrations is associated with risk of early wheezing or blood levels of Th1 and Th2 type cells at 24 months of age.

METHODS: 514 children were enrolled before birth and followed to 24 months of age. Early wheezing was determined from medical records, and Th1 and Th2 type cells were measured in peripheral blood using flow cytometry.

Ambient aeroallergen concentrations were measured throughout the study period and discrete seasons of high spore and pollen concentrations were defined.

RESULTS:
A seasonal pattern was observed, with birth in autumn to winter (the spore season) associated with increased odds of early wheezing (adjusted odds ratio 3.1; 95% confidence interval 1.3 to 7.4).

Increasing mean daily concentrations of basidiospores and ascospores in the first 3 months of life were associated with increased odds of wheeze, as were increasing mean daily concentrations of total and specific pollen types.

Levels of Th1 cells at age 24 months were positively associated with mean spore concentrations and negatively associated with mean pollen concentrations in the first 3 months of life. C

CONCLUSIONS:
Children with higher exposure to spores and pollen in the first 3 months of life are at increased risk of early wheezing. This association is independent of other seasonal factors including ambient levels of particulate matter of aerodynamic diameter

"Fungi and pollen exposure in the first months of life and risk of early childhood wheezing"
Harley KG, Macher JM, Lipsett M, Duramad P, Holland NT, Prager SS, Ferber J, Bradman A, Eskenazi B, Tager IB
Thorax. 2009 Apr ; 64(4): 353-8(hubmed.org)

Eosinophil Cationic Protein Stimulates Migration of Human Lung Fibroblasts in Vitro

2009-06-23T16:53:00.000-07:00

he Asthma is characterized by eosinophilic inflammation and remodelling of the airways. Eosinophil cationic protein (ECP) is a protein released by activated eosinophils and the hypothesis that ECP contributes to the development of structural changes in the airways of asthmatics has been posed.

Fibroblast recruitment is an important step in the remodelling process, and we therefore put the question whether ECP stimulates migration of human lung fibroblasts. Human peripheral eosinophils isolated from buffycoats from healthy individuals were cultured and conditioned media (CM) were collected.

Native ECP was extracted from human peripheral eosinophils by gel filtration, ion-exchange and chelating chromatography. The ability of eosinophil CM and ECP to stimulate fibroblast migration was determined using the 48-well Boyden chamber.

ECP concentrations in CM were assayed by ECP-CAP-FEIA. Both CM and ECP significantly stimulated fibroblast migration (48.4+/-cells/field versus 33+/-2 and 36+/-6 versus 25+/-4; P<0.001 and 0.05 respectively) in a time- and concentration-dependent manner.

Adding neutralizing ECP antibodies attenuated fibroblast migration induced by both ECP as well as CM. ECP stimulates migration of human lung fibroblasts, suggesting a potential mechanism for eosinophils in the fibrotic response.

This may be an important mechanism by which ECP promotes remodelling of extracellular matrix leading to airway fibrosis in asthmatics

"Eosinophil cationic protein stimulates migration of human lung fibroblasts in vitro"
Zagai U, Lundahl J, Klominek J, Venge P, Sköld CM
Scand J Immunol. 2009 Apr ; 69(4): 381-6(hubmed.org)

Levels of Acceptance of Asthma Control Test Questionnaire Among Saudi Patients Attending 5 Tertiary Care Hospitals in Saudi Arabia

2009-06-23T09:51:00.000-07:00

o explore the levels of acceptance of asthma control test (ACT) among Saudi patients.

METHODS:
A cross-sectional survey was carried out in 5 hospitals in Riyadh, Kingdom of Saudi Arabia, namely; Security Forces Hospital, King Abdul-Aziz Medical City, King Khalid University Hospital, King Faisal Specialist Hospital, and Riyadh Armed Forces Hospital, from the first of September to the 30th of November 2006. Patients attending the pulmonary clinic were asked to answer the ACT. This was followed by an interview to assess their view on the questions and their level of difficulty.

RESULTS:
The total number of patients was 1060. Males constituted 41%. A third of the patients were uneducated. The majority of patients (94%) found the ACT questions easy. The younger patients found the ACT questions easier to answer than the older patients.

Ninety-five percent of males found the ACT easy, while only 92% of females found the ACT easy. Educated patients found the ACT questions easy to perform more often than uneducated patients. There are no significant differences for age and gender, and for the question on whether the test helped to understand the patient's condition.

There are no significant differences for age and education, and for the question on whether the patient is willing to perform the test in each clinic visit.

CONCLUSION:
The majority of Saudi patients found the ACT easy, and they are willing to repeat the test every clinic visit.

"Levels of acceptance of Asthma Control Test questionnaire among Saudi patients attending 5 tertiary care hospitals in Saudi ArabiA"
Alanezi M, Al-Jahdali HH, Al-Hajjaj MS, Zeitoni MO, Al-Tasan TH
Saudi Med J. 2009 Apr ; 30(4): 546-9 (hubmed.org)

Asthma and Pregnancy

2009-06-23T05:49:00.000-07:00

ntroduction Many pregnant women are asthmatics and maternal asthma is a source of questions and complications concerning both the progress of the pregnancy itself and the impact on the foetus.

In this situation good asthma control is essential as the disease can deteriorate with acute exacerbations, possibly precipitated by reduction or even withdrawal of treatment on account of fear of teratogenicity.

Background Even though asthma treatments are not totally harmless during pregnancy, their use has been validated by several studies and guidelines. To help clinicians, we undertake here a review of the complications induced by maternal asthma and its medications, and then suggest management guidelines according to the most recent publications.

Conclusions
The risks and benefits of asthma treatments should be explained in a real partnership between the patient and her general practioner and specialists (obstetrician, chest physician or allergist).

In order to reduce complications to both mother and child, perfect control of asthma is required and inhaled steroids remain the treatment of choice for partially or uncontrolled asthma in the pregnant woman.

"Asthma and pregnancy. Review of the current literature and management according to the GINA 2006-2007 guidelines"
Piette V, Demoly P
Rev Mal Respir. 2009 Apr ; 26(4): 359-79(hubmed.org)

Lung Function Testing and Assessment of Distal Airways in Asthma

2009-06-23T01:47:00.000-07:00

ntroduction Small airways are defined (in humans) as those<2mm in diameter. Background They were originally described as the "quiet zone" of the lungs contributing less than 10% of the total resistance to airflow.

Pulmonary function tests remain the most used method to assess distal airway flow limitation. Viewpoints However, these tests are limited in adults and also in children because MEF25-75% and FEF50% are highly variable spirometric indices and they depend on vital capacity, which increases with expiratory time in obstructed subjects.

There is a need for promising non invasive new tools like the forced oscillation technique to measure resistance. The increased availability of the exhaled fraction of nitric oxide (FeNO) measurement means that this method is accessible and attractive.

Conclusion
The production of nitric oxide (NO) can be assessed by measuring the fraction of NO during a prolonged expiration (FENO) or by estimating other parameters of NO exchange including the alveolar NO concentration (CalvNO) and may provide information about small airway inflammation and assist the optimal control of the disease

"Lung function testing and assessment of distal airways in asthma"
Garcia G, Perez T, Mahut B
Rev Mal Respir. 2009 Apr ; 26(4): 395-406(hubmed.org)

Assessment of Imaging Techniques in Evaluation of Small Airways Disease in Asthma.

2009-06-22T14:45:00.000-07:00

he imaging techniques that have been used in the exploration and evaluation of treatment in asthma include computed tomography (CT), helium-magnetic resonance imaging (MRI), single photon emission computerized tomoscintigraphy (SPECT) and positron emission tomography (PET).

Only MRI does not involve radiation. However, in the case of CT, technical improvements and the advantages of the air-filled lung have resulted in a decreased radiation burden.

High resolution examinations, using a low dose of about one-year of natural background irradiation, are possible even in infancy. CT is the best evaluated so far, the simplest to perform and the least expensive.

In asthma several morphological changes related to small airway disease can be visualised on CT images: cylindrical bronchiolectasis, thickening of the bronchial walls and air trapping, an indirect marker of bronchiolar obstruction.

Today there is a robust body of evidence that valid indices of small airways disease can be deduced from quantitative analysis of lung density, indices that correlate well with clinical severity and functional measurements. In addition, the sensitivity of the method is sufficient to demonstrate therapeutic effects.

"Assessment of imaging techniques in the evaluation of small airways disease in asthma"
Laurent F, Tunon De Lara M
Rev Mal Respir. 2009 Apr ; 26(4): 407-11(hubmed.org)

Highlight
Asthma in Pediatric Patients | Treatment Pediatric Asthma | Childhood Asthma Control Test

High-Pitched Breath Sounds Indicate Airflow Limitation in Asymptomatic Asthmatic Children

2009-06-22T11:43:00.000-07:00

he sthmatic children may have airway dysfunction even when asymptomatic, indicating that their long-term treatment is less than optimal.

Although airway dysfunction can be identified on lung function testing, performing these tests can be difficult in infants. We studied whether breath sounds reflect subtle airway dysfunction in asthmatic children.

METHODS:
The highest frequency of inspiratory breaths sounds (HFI) and the highest frequency of expiratory breath sounds (HFE) were measured in 131 asthmatic children while asymptomatic and with no wheezes for more than 2 weeks.

No child was being treated with inhaled corticosteroids (ICS). Breath sounds were recorded and analysed by sound spectrography and compared with spirometric parameters. After initial evaluation, cases with more than step 2 (mild persistent) asthma were treated using inhaled fluticasone (100-200 microg/day) for 1 month, and then breath sound analysis and pulmonary function testing were repeated.

RESULTS:
On initial evaluation, HFI correlated with the percentage of predicted FEF(50) (%FEF(50)), (r = -0.45, P < r =" -0.456," r =" -0.32,">"High-pitched breath sounds indicate airflow limitation in asymptomatic asthmatic children"
Habukawa C, Nagasaka Y, Murakami K, Takemura T
Respirology. 2009 Apr ; 14(3): 399-403(hubmed.org)

Highlight
Asthma in Pediatric Patients | Treatment of Pediatric Asthma | Childhood Asthma

Chronic Intranasal Administration of Aspergillus Fumigatus Spores Leads to Aggravation of Airway Inflammation and Remodelling in Asthmatic Rats

2009-06-22T05:41:00.000-07:00

pidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored.

In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated.

METHODS:
The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA).

The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus.

RESULTS:
Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats.

Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma.

CONCLUSIONS:
Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.

"Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats"
Gao FS, Qiao JO, Zhang Y, Jin XQ
Respirology. 2009 Apr ; 14(3): 360-70(hubmed.org)

Highlight
Asthma in Pediatric| Pediatric Asthma Treatment Innovation | Childhood Asthma

Small Airways Obstruction Syndrome in Clinical Practice

2009-06-22T01:38:00.000-07:00

mall airways obstruction syndrome (SAOS) is a particular pulmonary function test (PFT) pattern showing decreased VC and FEV(1) but a normal FEV(1)/VC ratio and TLC.

The significance of this syndrome in clinical practice has not been comprehensively investigated.

METHODS:
This study retrospectively identified all patients who had performed PFT that showed a SAOS pattern at a university teaching hospital over 1 year. A simple algorithm for differential diagnosis was developed and validated.

RESULTS:
Of the 3207 PFT performed, 153 (4.8%) showed a pattern indicating SAOS. Among these, a final diagnosis was confirmed for 85 (63.4%) of the patients. The causes of SAOS included both restrictive and obstructive lung diseases with the leading causes being early interstitial lung disease (n = 20; 23.3%), chest wall deformity (n = 12; 14.1%) and asthma (n = 10; 11.6%). Using a cut-off point of TLC of or =95% predicted combined with RV/TLC > or =55% to identify obstructive ventilatory defects

"Small airways obstruction syndrome in clinical practice"
Chen CZ, Lin CC, Lee CH, Chang HY, Hsiue TR
Respirology. 2009 Apr ; 14(3): 393-8(hubmed.org)

Highlight
Pediatric Asthma | Pediatric Asthma Treatment Innovation | Childhood Asthma Program

Reduced Exhaled Breath Condensate pH in Asthmatic Smokers Using Inhaled Corticosteroids

2009-06-21T15:37:00.000-07:00

xhaled breath condensate (EBC) pH has been proposed as a biomarker of airway inflammation and oxidative stress in asthma.

Cigarette smoking reduces EBC pH in mild asthma. The effects of smoking on EBC pH in more symptomatic asthmatic patients using inhaled corticosteroids (ICS) are unknown. We aimed to compare EBC pH in asthmatic smokers (AS) and non-smokers (ANS) with moderate to severe disease, who were taking ICS. We also investigated the relationship between EBC pH and biomarkers of airway inflammation and oxidative stress.

METHODS:
AS (n = 18) and ANS (n = 17), who were using ICS, were recruited and EBC pH, sputum inflammatory cell counts and sputum supernatant 8-isoprostane concentrations were measured. Full lung function testing was performed.

RESULTS:
EBC pH was significantly lower in AS than in ANS (6.91 vs 7.41). In AS there was a significant inverse correlation between EBC pH and 8-isoprostane levels (r = -0.54, P = 0.03). There was no correlation between EBC pH and sputum neutrophil counts.

CONCLUSIONS:
EBC pH appears to be a biomarker of the level of oxidative stress in smokers with moderate to severe asthma. EBC pH may have applications for the longitudinal monitoring of the effects of smoking on the airways of asthmatic patients.

"Reduced exhaled breath condensate pH in asthmatic smokers using inhaled corticosteroids"
Kane B, Borrill Z, Southworth T, Woodcock A, Singh D
Respirology. 2009 Apr ; 14(3): 419-23(hubmed.org)

Highlight
Pediatric Asthma Research | Pediatric Asthma Treatment Center | Management of Childhood Asthma

Development of a 1-Concentration-4-Step Dosimeter Protocol for Rethacholine Testing

2009-06-21T11:35:00.000-07:00

ethacholine testing is an important diagnostic tool for asthma. Newly available dosimeter and software technology allows for simplification of the test.

This study aimed to evaluate a single-concentration dosimeter protocol for methacholine testing by comparison with a multi-concentration dosimeter protocol similar to that recommended by the American Thoracic Society (ATS) (standard protocol).

Fifty young subjects with high pretest probability for bronchial hyperresponsiveness underwent two challenges in randomized order within one week.

The novel protocol used a Medic-Aid Sidestream nebulizer and a fixed methacholine concentration of 16mg/mL. Number and duration of nebulizations were matched to the last four doses of the standard protocol, and results were expressed cumulatively.

The rank correlation between log slopes (n=50) was 0.86; that between log provocative doses (n=18), which differed at low values, was 0.58. When requiring a 20% fall in FEV(1) at any methacholine dose, 18 subjects were hyperresponsive and 28 normoresponsive in both tests (46/50 concordant).

One subject was positive only with the standard, and 3 only with the novel protocol (Cohen's kappa 83%). The novel protocol for methacholine testing yielded qualitative results similar to those of the ATS multi-concentration protocol, although there were quantitative differences at low doses. However, its design and handling may offer advantages for clinical practice.

"Development of a 1-concentration-4-step dosimeter protocol for methacholine testing"
Merget R, Jörres RA, Heinze E, Haufs MG, Taeger D, Brüning T
Respir Med. 2009 Apr ; 103(4): 607-13(hubmed.org)

Highlight
Pediatric Asthma Severity | Quality of Pediatric Asthma Treatment | Childhood Asthma Program

Effects of Inhaled Versus Systemic Corticosteroids on Exhaled Nitric Oxide in Severe Acute Asthma

2009-06-21T05:33:00.000-07:00

here is a paucity of information on the differential effects of systemic versus inhaled corticosteroids on airway inflammation in patients with acute asthma.

This study aimed to evaluate the effects of stopping systemic corticosteroids while maintaining the inhaled corticosteroids (ICS) on airway inflammation, lung function and asthma symptoms in patients who had been discharged from hospital after treatment for severe acute asthma.

METHODS:
Twenty-four adult patients with severe exacerbations of asthma were treated with both oral and inhaled corticosteroids after discharge from hospital. Oral corticosteroids were stopped after 1 week.

Spirometry, asthma quality of life questionnaire (AQLQ) score and exhaled nitric oxide (NO) were measured at discharge, 1 week, and 2 weeks after discharge.

RESULTS:
Withdrawal of oral corticosteroids resulted in significant rebound in mean exhaled NO by 11.0ppb (95% CI, 4.9-17.1ppb, p<0.001) p="0.006)" p="0.003)" p="0.64).">

"Effects of inhaled versus systemic corticosteroids on exhaled nitric oxide in severe acute asthma"
Khoo SM, Lim TK
Respir Med. 2009 Apr ; 103(4): 614-20(hubmed.org)

Highlight
Pediatric Asthma Quality | Cost for Pediatric Asthma Treatment | Childhood Asthma Diagnosis

Potential Side Effects In Patients Treated With Inhaled Corticosteroids And Long-Acting Beta2-Agonists

2009-06-21T01:30:00.000-07:00

ong-acting-beta-agonists and inhaled corticosteroids are widely used in patients with obstructive lung disease. We determined the occurrence of potential side effects to inhaled steroids and long-acting-beta-agonists in an open post-marketing observational study.

METHODS:
A total of 158 adult patients treated with long-acting-beta-agonists and inhaled steroids because of asthma or chronic obstructive lung disease were included prospectively in a cross-sectional study from September 2004 through august 2005. A subgroup of 31 patients with minimal disease were observed prospectively after treatment reduction.

The frequency and intensity of potential side effects to long-acting-beta-agonists and inhaled corticosteroids were registered on a 10-point visual analogue scale.

RESULTS:
A total of 131 (83%) reported potential side effects to inhaled steroids. The most frequent were sore (54%) and dry (52%) throat. A total of 114 (72%) patients reported potential side effects to long-acting-beta-agonists.

The most frequent were muscle cramps (62%) and muscle twisting (39%). For 5/8 potential side effects their occurrence increased with increased individual dozing.

In 31 patients the mean medication with steroids and long-acting-beta-agonists was reduced by 87% and 97.5%, respectively, with side effects reduced by 62% (p<0.001)>

"Potential side effects in patients treated with inhaled corticosteroids and long-acting beta2-agonists"
Korsgaard J, Ledet M
Respir Med. 2009 Apr ; 103(4): 566-73(hubmed.org)

Highlight
Pediatric Asthma Quality| Preferences for Pediatric Asthma Treatment |Symptoms of Childhood Asthma

Factors Associated with Health-Related Quality of Life Among Low-Compliant Asthmatic Adults in Korea

2009-06-20T23:37:00.000-07:00

his cross-sectional descriptive study was conducted to identify the factors associated with health-related quality of life (HRQoL) in low-compliant Korean adults with asthma.

The sample consisted of 178 patients referred by a physician to the education clinic at a University hospital in Korea.

Stepwise multiple regression analysis revealed that previous hospital admissions, recent asthma-related symptoms within the previous week, lower peak expiratory flow rate, and lower level of asthma knowledge were independently associated with lower HRQoL and accounted for 46% of the total variance.

Health care providers should focus on these factors to increase perceptions of HRQoL among low-compliant patients. Interventional strategies need to be developed to emphasize the importance of compliance to the self-monitoring regimen and management protocols.

"Factors associated with health-related quality of life among low-compliant asthmatic adults in Korea"
Choi JY, Hwang SY
Res Nurs Health. 2009 Apr ; 32(2): 140-7(hubmed.org)

Highlight
Pediatric Asthma Prevalence | Adult and Pediatric Asthma Treatment | Childhood Asthma Study

Approaches to Enhancing Immune Responses Stimulated by CpG Oligodeoxynucleotides

2009-06-20T17:33:00.000-07:00

CpG oligodeoxynucleotides (ODN) activate the immune system and are promising immunotherapeutic agents against infectious diseases, allergy/asthma and cancer.

It has become apparent that while CpG ODN are potent immune activators in mice, their immune stimulatory effects are often less dramatic in humans and large animals. This disparity between rodents and mammals has been attributed to the differences in TLR9 expression in different species.

This along with the sometimes transient activity of ODN may limit its potential immunotherapeutic applications. Several approaches to enhance the activity of CpG ODN have been explored including formulation of ODN in depot-forming adjuvants, and more recently, coadministration with polyphosphazenes, inhibitors of cytokines that downregulate TLR9 activation, and simultaneous activation with multiple TLR agonists. We will discuss these approaches and the mechanisms involved, with emphasis on what we have learned from large animal models

"Approaches to enhancing immune responses stimulated by CpG oligodeoxynucleotides"
Mutwiri G, van Drunen Littel-van den Hurk S, Babiuk LA
Adv Drug Deliv Rev. 2009 Mar 28; 61(3): 226-32(hubmed.org)

Highlight
Asthma in Pediatric Patients, Asthma in Pediatrics | Pediatric Asthma Treatment Plan | Asthma And Childhood

Use of CpG Oligonucleotides in Treatment of Asthma And Allergic DiseasE

2009-06-20T14:31:00.000-07:00

n the last several decades, there has been a marked increase in the prevalence of atopic disorders including asthma in "Western" societies; a relationship has been identified between lack of early-life exposure to microbes or microbial products and increased susceptibility to atopic disorders.

The innate immune system is activated by early microbial exposures, many of which utilize one of the Toll-like receptors, and there has been significant interest in studying how ligation of TLRs may be therapeutically useful.

CpG oligonucleotides (CpG-ODN, resembling bacterial DNA) engage TLR-9 on B-cells, dendritic cells and other cell types, resulting in a cascade that includes induction of Th1-type and T-regulatory-type immune responses.

Preclinical models of asthma have demonstrated that CpG-ODN are potent inhibitors of atopic responses, suppressing Th2 cytokine and, reducing airway eosinophilia, systemic levels of IgE, and bronchial hyperreactivity-in short the critical attributes of the asthmatic phenotype. In models of chronic allergen exposure, CpG-ODN are also effective at preventing the development of airway remodeling.

In established asthma, CpG-ODN can reverse manifestations of disease, both when used alone or in combination with allergen immunotherapy. Early clinical trials have had mixed results, including a significant benefit when CpG-ODN were conjugated to ragweed allergen in an allergic rhinitis immunotherapy study, but only limited efficacy seen when administered prior to allergen challenge in asthmatics. Further study of CpG-ODNs for the treatment of asthma and other atopic disorders is warranted by existing data

"Use of CpG oligonucleotides in treatment of asthma and allergic disease"
Fonseca DE, Kline JN
Adv Drug Deliv Rev. 2009 Mar 28; 61(3): 256-62(hubmed.org)

Highlight
Asthma in Pediatric | Treatment of Pediatric Asthma | Treatment of Childhood Asthma

Diesel Particle-induced Transcription Expression of P21 Involves Activation of EGFR, SRC and STAT3

2009-06-20T09:35:00.000-07:00

xposure to diesel exhaust particle has been associated with adverse health outcomes, such as inflammation, adjuvancy and mutagenesis.

However, the molecular mechanisms by which DEP inhalation exerts these effects are still largely unknown. We previously reported that exposure to DEP activates the transcription factor Stat3 in airway epithelial cells, a primary target cell of inhaled DEP.

To elucidate the functional role of Stat3 activation in these cells, we investigated the function of Stat3 in DEPâinduced expression of the p21 gene in the human bronchial epithelial cell line BEAS-2B.

We report that DEP exposure induces increased levels of p21 mRNA and protein in a manner that is independent of p53 and Sp1 expression or DNA binding to the p21 gene. Using Chromatin Immuoprecipitation assays and expression of a dominant negative Stat3 mutant, we show that activation of Stat3 and its binding to the p21 promoter are required for DEP-induced expression of p21, suggesting that Stat3 plays an essential role in the induction of p21 by DEP.

Additional experiments demonstrated that activation of p21 gene expression is dependent on the activation of EGFR and Src kinase activities. Lastly, we provide evidence suggesting that DEP exposure can inhibit the proliferation of human bronchial epithelial cells, suggesting a functional role of p21 activation airway epithelial cells exposed to DEP.

"Diesel Particle-induced Transcription Expression of P21 Involves Activation of EGFR, SRC and STAT3"
Cao D, Bromberg PA, Samet JM
Am J Respir Cell Mol Biol. 2009 Mar 27;(hubmed.org)

Highlight
Pediatric Asthma and Allergy | Childhood Asthma Management

Rates of Asthma Attacks in Patients With Previously Inadequately Controlled Mild Asthma

2009-06-19T23:19:00.000-07:00

ifferences could exist in the likelihood of asthma attacks in patients treated with inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and montelukast (MON) (ICS/LABA/MON) and patients treated with an inhaled corticosteroid (ICS) and montelukast (MON) (ICS/MON).

METHODS:
This was a post-hoc analysis of a pretest-posttest retrospective cohort study. Patients with mild persistent asthma and allergic rhinitis, who were taking an ICS either alone or in combination with a LABA, started concomitant MON treatment as part of their routine care.

Rates of asthma- and allergic rhinitis-related medical resource use in the 12-months after the initial (index) MON prescription were compared in the ICS/MON and ICS/LABA/MON groups. An asthma attack was defined as an asthma-related hospitalization, ER visit, or use of an oral corticosteroid.

RESULTS:
Of the total of 344 patients, 181 (53%) received ICS/MON and 163 (47%) received ICS/LABA/MON in the post-index period for means of 10.5 and 11.4 months, respectively, (P 0.05). An asthma attack occurred in 4.4% of the ICS/MON group and 6.8% of the ICS/LABA/MON group (P > 0.05).

The adjusted odds of an asthma attack in the post-index period in the ICS/LABA/MON group relative to the ICS/MON group was 1.24, 95% confidence interval 0.35-4.44.

CONCLUSION:
In this observational study of combination drug treatment of mild persistent asthma and allergic rhinitis, no difference was observed between LABA/ICS/MON combination therapy and the ICS/MON combination without LABA use, for the rate of asthma attacks over one year.

"Rates of asthma attacks in patients with previously inadequately controlled mild asthma treated in clinical practice with combination drug therapy: an exploratory post-hoc analysis"
Dal Negro RW, Borderias L, Zhang Q, Fan T, Sazonov V, Guilera M, Taylor SD
BMC Pulm Med. 2009; 9: 10(hubmed.org)

Immunotherapeutic Applications of CpG Oligodeoxynucleotide TLR9 Agonists

2009-06-19T20:26:00.000-07:00

oll-like receptor 9 (TLR9) agonists have demonstrated substantial potential as vaccine adjuvants, and as mono- or combination therapies for the treatment of cancer and infectious and allergic diseases.

Commonly referred to as CpG oligodeoxynucleotides (ODN), TLR9 agonists directly induce the activation and maturation of plasmacytoid dendritic cells and enhance differentiation of B cells into antibody-secreting plasma cells.

Preclinical and early clinical data support the use of TLR9 agonists as vaccine adjuvants, where they can enhance both the humoral and cellular responses to diverse antigens.

In mouse tumor models TLR9 agonists have shown activity not only as monotherapy, but also in combination with multiple other therapies including vaccines, antibodies, cellular therapies, other immunotherapies, antiangiogenic agents, radiotherapy, cryotherapy, and some chemotherapies.

Phase I and II clinical trials have indicated that these agents have antitumor activity as single agents and enhance the development of antitumor T-cell responses when used as therapeutic vaccine adjuvants. CpG ODN have shown benefit in multiple rodent and primate models of asthma and other allergic diseases, with encouraging results in some early human clinical trials. Although their potential clinical contributions are enormous, the safety and efficacy of these TLR9 agonists in humans remain to be determined.

"Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists"
Vollmer J, Krieg AM
Adv Drug Deliv Rev. 2009 Mar 28; 61(3): 195-204(hubmed.org)

Multiple Challenges in Mouse Model of Chemical-induced Asthma Lead to Tolerance

2009-06-19T16:23:00.000-07:00

o improve our mouse model of chemical-induced asthma we compared a single with a multiple intranasal challenge protocol.

BALB/c mice received toluene diisocyanate (TDI) or vehicle on each ear (days 1 and 8) with the first challenge by intranasal instillation given on day 15. In a "long" protocol, the mice received 1 to 6 intranasal instillations, with 1-week interval. In a "short" protocol, the mice received 6 intranasal challenges over a period of 10 days.

The "early" ventilatory response and methacholine reactivity were measured. Broncho-alveolar-lavage (BAL), total serum immunoglobulins and draining lymph nodes were analyzed. After 1, 2 or 3 TDI challenges, a significant increase in airway reactivity, total cell count and neutrophils (15-20%) was found in TDI-treated mice.

This response diminished with increasing numbers of challenges in both models. The percentage CD4(+) and CD8(+) cells decreased and the percentage CD19(+) cells increased in the lymph nodes, but these returned to control values with multiple challenges. IL-4 secretion increased in cervical lymph node cells in vitro.

Total serum IgE levels were persistently increased in TDI-treated mice. Although humoral signs of allergy remain increased after multiple challenges, diminishing ventilatory and inflammatory responses are indicative of the induction of tolerance.

"Multiple challenges in a mouse model of chemical-induced asthma lead to tolerance: ventilatory and inflammatory responses are blunted, immunologic humoral responses are not"
Vanoirbeek JA, De Vooght V, Nemery B, Hoet PH
Toxicology. 2009 Mar 29; 257(3): 144-52(hubmed.org)

CpG oligodeoxynucleotide-based therapy of lymphoid malignancies

2009-06-19T13:28:00.000-07:00

reclinical and early clinical trials indicate synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG ODN) have potent immunostimulatory effects.

CpG ODN are being explored as immune adjuvants in vaccination strategies and as potential treatments for a wide variety of disorders including cancer and asthma.

Therapeutic approaches designed to take advantage of this potent class of agents are based largely on the ability of CpG ODN to activate professional antigen presenting cells (APCs) that express the target receptor - Toll-Like Receptor 9 (TLR9). B-cell malignancies are unique in that the malignant cells themselves express TLR9. CpG ODN can have a direct effect on the malignant B cells and lead to activation induced cell death.

CpG ODN also alter the phenotype of target malignant B cells as indicated by upregulation of MHC, immunostimulatory molecules, and antigens that serve as targets for other approaches to lymphoma immunotherapy such as CD20.

B cell malignancies are also relatively sensitive to the cytokines that are produced by dendritic cells in response to CpG ODN. Thus, B cell malignancies appear to be uniquely sensitive to CpG ODN because of both the direct and indirect effects the CpG ODN on target cells and the sensitivity of B cell malignancies to an immune response.

Preclinical studies support further exploration of the potential of CpG ODN as a component of therapy for lymphoid malignancies. Ongoing clinical trials are exploring the potential of CpG ODN, both alone and in combination with other agents.

"CpG oligodeoxynucleotide-based therapy of lymphoid malignancies"
Weiner GJ
Adv Drug Deliv Rev. 2009 Mar 28; 61(3): 263-7(hubmed.org)

feG-COOH Blunts Eosinophilic Airway Inflammation In A Feline Model of Allergic Asthma

2009-06-18T13:59:00.000-07:00

his study investigated if feG-COOH would decrease allergen-induced airway inflammation.

MATERIALS OR SUBJECTS:
Seven adult cats sensitised to Bermuda grass allergen (BGA) to induce an asthmatic phenotype.

TREATMENT:
Cats were randomized to receive either feG-COOH (1 mg/kg, PO) or placebo (saline 1 ml, PO) immediately prior to BGA aerosol challenge in a cross-over design.

METHODS:
Bronchoalveolar lavage fluid (BALF) was collected and airway inflammatory response assessed via inflammatory cell number and type; IL-4, IFN-gamma and nitric oxide metabolite concentrations. A paired t test was used to compare parameters with a P < 0.05 considered significant.

RESULTS:
The BALF eosinophil percentage was significantly lower in asthmatic cats treated with feG compared with placebo (placebo, 35.3 +/- 12.2%; feG, 22.4 +/- 8.6%; P = 0.002). Treatment with feG did not result in a significant change in any other parameter measured.

CONCLUSIONS:
These data indicate that a single dose of feG-COOH partially attenuates eosinophilic airway inflammation in experimental feline asthma.

"feG-COOH blunts eosinophilic airway inflammation in a feline model of allergic asthma"
Declue AE, Schooley E, Nafe LA, Reinero CR
Inflamm Res. 2009 Mar 3;(hubmed.org)

Health and Use of Health Services

2009-06-18T09:48:00.000-07:00

o examine the health status of adults from black and minority ethnic groups and from a socio-economically mixed White population, all resident in England.

Design. A cross-sectional questionnaire survey using validated standardised health measures of a sample of Gypsies and Travellers, Pakistani Muslims, African Caribbean, and White adults living in five geographical locations. Health outcomes included general health, health in the past year, limiting long-term illness, anxiety, depression, respiratory symptoms and angina.

Results.
Of the 520 recruited age-sex matched sample (260 Gypsies and Travellers matched with 260 Pakistani Muslims, African Caribbean, and White residents), 516 were included in this analysis (173 men, 343 women).

There were no differences by age between the four groups but men were approximately four years older than women. There were significant statistical differences in smoking status and educational attendance with more Gypsies and Travellers being current smokers (58% (95% confidence interval (CI) 52, 64) versus 25% (14, 38) or lower in the other groups) and having poorer regular educational attendance (61% (54, 68) versus 89% (77, 96) or higher in the other groups).

For all health outcomes examined, Gypsies and Travellers had significantly poorer outcomes (after adjustment for age, sex and smoking status) compared with the White population. The health status of the Pakistani Muslims and African Caribbeans was similar to that of the Gypsies and Travellers for health in the past year, asthma, and depression, but other outcomes (cough, sputum) were significantly less prevalent.

There were also significant differences in specific outcomes between African Caribbean and Pakistani Muslim populations. Consultations with various health professionals and use of health services varied between the groups.

Conclusion.
Being a Gypsy or Traveller is associated with even poorer health outcomes than those seen in two other ethnic minority groups resident in England, Pakistani Muslim and African Caribbean, and they in turn have poorer health outcomes than the White residents. More remains to be done to address the health and health service needs of such black and minority ethnic groups.

"Health and use of health services: a comparison between Gypsies and Travellers and other ethnic groups"
Peters J, Parry GD, Cleemput PV, Moore J, Cooper CL, Walters SJ
Ethn Health. 2009 Mar 4; 1-19(hubmed.org)

Export And Functions of Sphingosine-1-Phosphate

2009-06-18T04:44:00.000-07:00

he sphingolipid metabolite, sphingosine-1-phosphate (S1P), has emerged as a critical player in a number of fundamental biological processes and is important in cancer, angiogenesis, wound healing, cardiovascular function, atherosclerosis, immunity and asthma, among others.

Activation of sphingosine kinases, enzymes that catalyze the phosphorylation of sphingosine to S1P, by a variety of agonists, including growth factors, cytokines, hormones, and antigen, increases intracellular S1P.

Many of the biological effects of S1P are mediated by its binding to five specific G protein-coupled receptors located on the cell surface in an autocrine and/or paracrine manner. Therefore, understanding the mechanism by which intracellularly generated S1P is released out of cells is both interesting and important. In this review, we will discuss how S1P is formed and released.

We will focus particularly on the current knowledge of how the S1P gradient between tissues and blood is maintained, and the role of ABC transporters in S1P release.

"Export and functions of sphingosine-1-phosphate"
Kim RH, Takabe K, Milstien S, Spiegel S
Biochim Biophys Acta. 2009 Mar 4; (hubmed.org)

Early U.S. Outcomes After Laparoscopic Adjustable Gastric Banding

2009-06-18T01:39:00.000-07:00

any mildly to moderately obese individuals with a body mass index (BMI) lower than 35 kg/m(2) have serious diseases related to their obesity. Nonsurgical therapy is ineffective in the long term, yet surgery has never been made widely available to this population.

METHODS:
Between 2002 and 2007, 53 patients with a BMI lower than 35 kg/m(2) underwent laparoscopic adjustable gastric banding at our institution. Data on all these patients were collected prospectively and entered into an institutional review board-approved electronic registry. The study parameters included preoperative age, gender, BMI, presence of comorbidities, percentage of excess weight loss (%EWL), and resolution of comorbidities.

RESULTS:
The mean preoperative age of the patients was 46.9 years (range, 16-68 years), and the mean preoperative BMI was 33.1 kg/m(2) (range, 28.2-35.0 kg/m(2)). Of the 53 patients, 49 (92%) had at least one obesity-related comorbidity. The mean BMI decreased to 28.1 +/- 2.4 kg/m(2), 25.8 +/- 2.9 kg/m(2), and 25.8 +/- 3.1 kg/m(2) and mean %EWL was 48.3 +/- 17.6, 69.9 +/- 28.0, and 69.7 +/- 31.7 at 0.5, 1, and 2 years, respectively.

Substantial improvement occurred for the following comorbidities evaluated: hypertension, depression, diabetes, asthma, hypertriglyceridemia, obstructive sleep apnea, hypercholesterolemia, and osteoarthritis. There was one slip, two cases of band obstruction (from food), two cases of esophagitis, and two port leaks, but no mortality.

CONCLUSION:
The authors are very encouraged by this series of low-BMI patients who underwent laparoscopic adjustable gastric banding. Their weight loss has been excellent, and their complications have been acceptable. Their comorbidities have partially or wholly resolved. With further study, it is reasonable to expect alteration of the weight guidelines for bariatric surgery to include patients with a BMI lower than 35 kg/m(2).

"Early U.S. outcomes after laparoscopic adjustable gastric banding in patients with a body mass index less than 35 kg/m(2)"
Sultan S, Parikh M, Youn H, Kurian M, Fielding G, Ren C
Surg Endosc. 2009 Mar 5;(hubmed.org)

Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma

2009-06-17T13:33:00.000-07:00

xacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.

METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year.

The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.

RESULTS:
Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02).

Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.

CONCLUSIONS:
Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)

"Mepolizumab and exacerbations of refractory eosinophilic asthma"
Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID
N Engl J Med. 2009 Mar 5; 360(10): 973-84(hubmed.org)

Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia

2009-06-17T09:30:00.000-07:00

osinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma.

However, in three previous clinical trials involving patients with asthma, blockade of this cytokine did not result in a significant improvement in outcomes.

We studied the prednisone-sparing effect of mepolizumab, a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone. Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood, symptoms, and airflow limitation.

METHODS:
In this randomized, double-blind, parallel-group trial involving patients with persistent sputum eosinophilia and symptoms despite prednisone treatment, we assigned 9 patients to receive mepolizumab (administered in five monthly infusions of 750 mg each) and 11 patients to receive placebo.

RESULTS:
There were 12 asthma exacerbations in 10 patients who received placebo, 9 of whom had sputum eosinophilia at the time of exacerbation. In comparison, only one patient who received mepolizumab had an asthma exacerbation, and this episode was not associated with sputum eosinophilia (P=0.002).

Patients who received mepolizumab were able to reduce their prednisone dose by a mean (+/-SD) of 83.8+/-33.4% of their maximum possible dose, as compared with 47.7+/-40.5% in the placebo group (P=0.04).

The use of mepolizumab was associated with a significant decrease in the number of sputum and blood eosinophils. Improvements in eosinophil numbers, asthma control, and forced expiratory volume in 1 second were maintained for 8 weeks after the last infusion. There were no serious adverse events.

CONCLUSIONS:
Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment. (ClinicalTrials.gov number, NCT00292877.)

"Mepolizumab for prednisone-dependent asthma with sputum eosinophilia"
Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM
N Engl J Med. 2009 Mar 5; 360(10): 985-93(hubmed.org)

Assessing the Reproducibility of Asthma Candidate Gene Associations Using Genome-wide Data

2009-06-17T03:25:00.000-07:00

ssociation studies have implicated many genes in asthma pathogenesis, with replicated associations between single nucleotide polymorphisms (SNPs) and asthma reported for more than 30 genes.

Genome-wide genotyping enables simultaneous evaluation of most of this variation, and facilitates more comprehensive analysis of other common genetic variation around these candidate genes for association with asthma.

OBJECTIVE:
To use available genome-wide genotypic data to assess the reproducibility of previously reported associations with asthma and evaluate the contribution of additional common genetic variation surrounding these loci to asthma susceptibility.

METHODS:
Illumina 550Kv3 SNP arrays were genotyped in 422 nuclear families participating in the Childhood Asthma Management Program (CAMP). Genes with at least one SNP demonstrating prior association with asthma in two or more populations were tested for evidence of association with asthma using family-based association testing.

MEASUREMENTS AND MAIN RESULTS:
We identified 39 candidate genes from the literature using prespecified criteria. Of the 160 SNPs previously genotyped in these 39 genes, 10 SNPs in six genes were significantly associated with asthma (including the first independent replication for asthma-associated integrin beta-3 [ITGB3]).

Evaluation of 619 additional common variants included in the Illumina 550K array revealed additional evidence of asthma association for 15 genes, though none were significant after adjustment for multiple comparisons.

CONCLUSIONS:
We replicated asthma associations for a minority of candidate genes. Pooling GWAS results from multiple studies will increase power to appreciate marginal effects of genes and further clarify which candidates are true "asthma genes."

"Assessing the Reproducibility of Asthma Candidate Gene Associations Using Genome-wide Data"
Rogers AJ, Raby BA, Lasky-Su JA, Murphy A, Lazarus R, Klanderman BJ, Sylvia JS, Ziniti JP, Lange C, Celedon JC, Silverman EK, Weiss ST
Am J Respir Crit Care Med. 2009 Mar 5; (hubmed.org)

Immune Pathways for Translating Viral Infection Into Chronic Airway Disease

2009-06-17T01:23:00.000-07:00

To better understand the immune basis for chronic inflammatory lung disease, we analyzed a mouse model of lung disease that develops after respiratory viral infection. The disease that develops in this model is similar to asthma and chronic obstructive pulmonary disease (COPD) in humans and is manifested after the inciting virus has been cleared to trace levels.

The model thereby mimics the relationship of paramyxoviral infection to the development of childhood asthma in humans. When the acute lung disease appears in this model (at 3 weeks after viral inoculation), it depends on an immune axis that is initiated by expression and activation of the high-affinity IgE receptor (FcvarepsilonRI) on conventional lung dendritic cells (cDCs) to recruit interleukin (IL)-13-producing CD4(+) T cells to the lower airways.

However, when the chronic lung disease develops fully (at 7 weeks after inoculation), it is driven instead by an innate immune axis that relies on invariant natural killer T (iNKT) cells that are programmed to activate macrophages to produce IL-13. The interaction between iNKT cells and macrophages depends on contact between the semi-invariant Valpha14Jalpha18-TCR on lung iNKT cells and the oligomorphic MHC-like protein CD1d on macrophages as well as NKT cell production of IL-13 that binds to the IL-13 receptor (IL-13R) on the macrophage.

This innate immune axis is also activated in the lungs of humans with severe asthma or COPD based on detection of increased numbers of iNKT cells and alternatively activated IL-13-producing macrophages in the lung. Together, the findings identify an adaptive immune response that mediates acute disease and an innate immune response that drives chronic inflammatory lung disease in experimental and clinical settings.

"Immune Pathways for Translating Viral Infection Into Chronic Airway Disease"
Adv Immunol. 2009; 102: 245-76Holtzman MJ, Byers DE, Benoit LA, Battaile JT, You Y, Agapov E, Park C, Grayson MH, Kim EY, Patel AC (Hubmed.org)

Novel Tight Binding Inhibitory Factor-{kappa}B Kinase Inhibitors (IKK-2) Demonstrate Target Specific Anti-inflammatory Activities in Cellular Assays and Following Oral and Local Delivery in an In Vivo

2009-06-16T14:56:00.000-07:00

NF-kappaB is one of the major families of transcription factors activated during the inflammatory response in asthma and chronic obstructive pulmonary disease (COPD). IKK-2 has been shown to play a pivotal role in cytokine-induced NF-kappaB activation in airway epithelium and in disease relevant cells.

Nevertheless, the potential toxicity of specific IKK-2 inhibitors may be unacceptable for oral delivery in COPD. Therefore, local delivery to the lungs is an attractive alternative that warrants further exploration.

Here we describe potent and selective small molecule IKK-2 inhibitors (PHA-408 and PF-184) which are competitive for ATP, have slow off rates from IKK-2 and display broad in vitro anti-inflammatory activities resulting from NF-kappaB pathway inhibition. Notably, PF-184 has been designed to have high systemic clearance which limits systemic exposure and maximizes the effects locally in the airways.

We utilized an inhaled LPS-induced rat model of neutrophilia to address whether inhibiting NF-kappaB activation locally within the airways would show anti-inflammatory effects in the absence of systemic exposure. PHA-408, a low clearance compound previously shown to be efficacious orally in a rodent model of arthritis, dose-dependently attenuated inhaled LPS-induced cell infiltration and cytokine production.

Interestingly, PF-184 produced comparable dose-dependent anti-inflammatory activity by intratracheal (IT) administration and was as efficacious as IT administered fluticasone propionate (fluticasone). Together these results support the potential therapeutic utility of IKK-2 inhibition in inflammatory pulmonary diseases and demonstrate anti-inflammatory efficacy of an inhaled IKK-2 inhibitor in a rat airway model of neutrophilia.

"Novel Tight Binding Inhibitory Factor-{kappa}B Kinase Inhibitors (IKK-2) Demonstrate Target Specific Anti-inflammatory Activities in Cellular Assays and Following Oral and Local Delivery in an In Vivo"
J Pharmacol Exp Ther. 2009 May 28; Sommers CD, Thompson JM, Guzova JA, Bonar SL, Rader RK, Mathialagan S, Venkatraman N, Holway V, Kahn LE, Hu G, Meyer DM, Huang HC, Chiang PC, Schindler JF, Hu Y, Garner DS, Kishore NN

Rates of Asthma Attacks in Patients with Previously Inadequately Controlled Mild Asthma Treated in Clinical Practice with Combination Drug Therapy: An Exploratory Post-hoc Analysis

2009-06-16T07:24:00.000-07:00

Functional Polymorphism of Detoxification Gene NQO1 Predicts Intensity of Eempirical Treatment of Childhood Asthma

2009-06-16T03:21:00.000-07:00

he management of moderate to severe childhood asthma remains empirical. Genotypic variation has been proposed as a way to tailor specific pharmaceutical regimens to individual patients.

The objective of this study was to determine the factors associated with asthma treatment progression, including functional polymorphisms of phase II detoxification enzymes, demographics, and environmental factors. In a study of 120 asthmatic children cared for in a single pediatric pulmonary practice, intensity of medical treatment over the year prior was modeled as a function of null mutations of glutathione S transferase (GST) M1 and T1, ile105val variant of GSTP1, and pro187ser variant of NAD(P)H:quinone oxidoreductase 1 (NQO1).

The model included demographics, medical information, and environmental factors obtained via questionnaire analyzed with multivariate logistic regression and artificial neural networks. Multivariate logistic regression with bootstrapped validation identified a polymorphic variant of NQO1 as significantly contributing to increasing the odds of receiving more aggressive medical therapy (odds ratio, 11.56; p=0.0001).

Parent income and education inversely correlated with medical treatment (odds ratio, 1.50; p=0.001 and odds ratio, 0.375; p=0.002, respectively). Age and reporting restricted physical activity due to asthma also impacted medical treatment (odds ratio, 0.63; p=0.0001 and odds ratio, 5.90; p=0.004, respectively).

The optimism-adjusted discriminative ability (c-index) of the model was 0.881 (close to Bayes optimum of 0.902) with 80% overall classification accuracy. Our study supports the role of NQO1 polymorphism as an important factor determining the intensity of medical therapy in asthmatic children after adjusting for significance relating to parental income and education level, age, and restricted physical activity. Asthmatic children with a functional polymorphism of NQO1 may require more intensive pharmaceutical treatment to effectively control their asthma

"Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma"
Goodrich GG, Goodman PH, Budhecha SK, Pritsos CA
Mutat Res. 2009 Mar 31; 674(1-2): 55-61(hubmed.org)

Current Immunological Approaches For Management Of Allergic Rhinitis And Bronchial Asthma

2009-06-16T01:19:00.000-07:00

large population world over is affected with allergic diseases and asthma. Pharmacotherapy for allergic diseases and asthma is effective in controlling symptoms but on discontinuation of medication, symptoms reoccur.

In contrast, immunotherapy modifies and corrects the underlying pathological immune responses in an antigen-specific manner. Immunotherapy shows an increase in IgG (blocking antibody) that competes with IgE for allergen, inhibiting the release of inflammatory mediators.

Recent studies suggest that immunotherapy acts by modifying CD4+ T-cell responses either by immune deviation, T-cell anergy and/or both. Current immunological approaches for management of allergies and asthma involve immunization with native allergen, modified allergen, peptides/cDNA of allergen, anti-IgE, adjuvants coupled allergen, including immunostimulatory DNA sequences, cytokines, and bacterial products.

These approaches modulate the immune response and are intended to give long-term benefit.

"Current immunological approaches for management of allergic rhinitis and bronchial asthma"
Srivastava D, Arora N, Singh BP
Inflamm Res. 2009 Mar 31;(hubmed.org)

Large Scale Genotyping Study for Asthma In The Japanese Population

2009-06-15T13:16:00.000-07:00

HE Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.

OBJECTIVE:
To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population. METHODS: We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1st stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2nd stage), 541 independent patients, and 744 controls (3rd stage).

RESULTS:
SNPs located in the 5' region of PEX19 (rs2820421) were significantly associated with P < 0.05 through the 1st to the 3rd stage analyses; however, the P values did not reach statistically significant levels (combined, P = 3.8 x 10-5; statistically significant levels with Bonferroni correction, P = 6.57 x 10-7). SNPs on HPCAL1 (rs3771140) and on IL18R1 (rs3213733) were associated with asthma in the 1st and 2nd stage analyses, but the associations were not observed in the 3rd stage analysis.

CONCLUSION:
No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.

"Large scale genotyping study for asthma in the Japanese population"
Imada Y, Fujimoto M, Hirata K, Hirota T, Suzuki Y, Saito H, Matsumoto K, Akazawa A, Katsunuma T, Yoshihara S, Ebisawa M, Shibasaki M, Arinami T, Tamari M, Noguchi E
BMC Res Notes. 2009; 2: 54(hubmed.org)

Effect of Okam on Inflammation And Remodeling of Airway of Mice With Ovalbumin Induced Asthma

2009-06-15T08:13:00.000-07:00

o investigate the effect of okam on inflammation and remodeling of airway in mice with ovalbumin (OVA) induced asthma.

METHODS:
Thirty-two mice of Kunming strain were divided into four groups randomly: model group, glucocorticoid inhalation group, okam group and control group, with 8 mice in each group. The asthmatic mice model was reproduced by combined injection and aerosol inhalation of OVA.

The mice in model group received normal saline (0.3 ml) gavage daily. The mice in glucocorticoid inhalation group received budesonide (0.4 ml, 200 mug) and normal saline (3.6 ml) inhalation. The mice in okam group were gavaged with okam daily (50 mg/kg). The controls were given normal saline instead of OVA sensitization.

All mice were sacrificed 42 days later, followed by lavage of tracheo-bronchial tree of the right lung, and the right lung was saved for pathological examination. The total cell number and differentiation in bronchoalveolar lavage fluid (BALF) were counted under microscope.

The expression of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) in BALF were assessed by enzyme linked immunosorbent asay (ELISA). The histological changes in the bronchi and alveoli were evaluated after hematoxylin and eosin (HE) staining. The expression of matrix metalloproteinase-9 (MMP-9) as well as the tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by immunohistochemistry.

RESULTS:
Compared with the model group, the total cell count and IL-4 level in BALF, and the score of pathological changes in the broncho-alveolar tissue in okam group or glucocorticoid inhalation group were lower significantly, and the IFN-gamma level elevated markedly (all P<0.01). The MMP-9, TIMP-1 expression in glucocorticoid inhalation group and the TIMP-1 expression in okam group were decreased greatly (P<0.05 or P<0.01).

All of above indexes showed marked differences between control group and okam group (P<0.05 or P<0.01). There were significant changes in the total cell count, IFN-gamma, pathological changes, MMP-9 and TIMP-1 between the glucocorticoid inhalation group and the okam group (P<0.05 or P<0.01).

CONCLUSION:
Okam may alleviate inflammation of the bronchia and degrade the development of airway remodeling to some degree.

"Effect of okam on inflammation and remodeling of airway of mice with ovalbumin induced asthma"
Qu ZH, Xie N, Che SY, Lin RJ, Hu SJ
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2009 Apr ; 21(4): 230-3(hubmed.org)

Pediatric Asthma

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nteractions of Histamine H1-Receptor Agonists and Antagonists

Intensive hog farming operations and self-reported health among nearby rural residents in Ottawa, Canada

Relative Contributions Of Multiple Determinants To Bone Mineral Density In Men

The benefits of whole-house in-duct air cleaning in reducing exposures to fine particulate matter of outdoor origin

Common Immune-Related Risk Factors And Incident Non-Hodgkin Lymphoma

Prognostic Values Of Specific Respiratory Sounds For Asthma In Adolescents

The Incidence Of Co-Morbidities Related To Obesity And Overweight: A Systematic Review And Meta-Analysis

Prevalence Of Asthmatic Symptoms In Lebanese Patients

Comparing Quality of Care Between a Consumer-Directed Health Plan and a Traditional Plan

Asthma: Are We Monitoring the Correct Measures ?

Effectiveness Of Prokinetic Agents Against Diseases External to The Gastrointestinal Tract

Predicting Medication Costs And Usage: Expenditures In A Juvenile Detention Facility

The targeted oral, once-daily phosphodiesterase 4 inhibitor roflumilast and the leukotriene receptor antagonist montelukast do not exhibit significant

Predicting Recurrence of Vasovagal Syncope

Toxocara Seropositivity In Sri Lankan Children With Asthma

The Impact Of Viral Respiratory Infection On The Severity And Recovery From An Asthma Exacerbation

Rhinovirus Associated With Severe Lower Respiratory Tract Infections In Children

Bronchiolitis: Age And Previous Wheezing Episodes

Risk Factors For Hospital Readmission Within 30 Days

Use Of Inhaled And Oral Corticosteroids And The Long-Term Risk of Cataract

Fontan Patient With Plastic Bronchitis Treated Successfully Using Aerosolized Tissue Plasminogen Activator

An Application Of The Asthma-Specific Job Exposure

Specific Antibodies To Diisocyanate And Work-Related Respiratory

Exhaled Nitric Oxide In Endotoxin-Exposed Adults

Occupational Exposures And Asthma Among Nursing Professionals

Capturing Adenylyl Cyclases As Potential Drug Targets

House Dust Mite Allergen Induces Asthma

Fixed Drug Combinations--The Pros And Cons

Effect of Leukotriene Receptor Antagonist on Cough Variant Asthma

Management of Exercise-Induced Bronchospasm In NCAA Athletic Programs

The Augmented RIC Model of The Human Respiratory System

Measurement Invariance of The Mini Asthma Quality of Life

Measures of Asthma Control And Quality of Life

Developing Antitussives: The Ideal Clinical Trial

Cough And Viruses in Airways Disease: Mechanisms

Mechanisms of The Cough Associated with Rhinosinusitis

Eosinophilic Airway Disorders Associated with Chronic Cough

Speech Pathology for Chronic Cough: A New Approach

Biomarker Discovery in Asthma-Related Inflammation And Remodeling

The Role of The Extracellular Matrix And Specific Growth Factors in The Regulation of Inflammation And Remodelling in Asthma

Diet and Asthma-- Can You Change What You or your Children Are by Changing What You Eat ?

Work of Breathing and Different Levels of Volume-Targeted Ventilation

Variability in The Diagnostic Labeling of Nonbacterial Lower Respiratory Tract Infections

Adenotonsillectomy and The Development of Overweight

Brief Bout of Exercise Alters Gene Expression in Peripheral Blood Mononuclear Cells of Early- and Late-Pubertal Males

The Clinical Impact of The Radiology Report in Wheezing and Nonwheezing Febrile Children

Position and Ventilatory Response to Added Dead Space in Prematurely Born Infants

In Vivo Uptake of Inhaled Particles by Airway Phagocytes is Enhanced in Patients with Mild Asthma Compared with Normal Volunteers

An International Prospective General Population-Based Study of Respiratory Work Disability

Sublingual Immunotherapy in Children

Association of Duration of Television Viewing in Early Childhood with the Subsequent Development of Asthma

Healthcare Via Cell Phones: a Systematic Review

Prevalence of Asthma-Like Symptoms, Asthma and Its Treatment in Elite Athletes

Fungi and Pollen Exposure in the First Months of Life and Risk of Early Childhood Wheezing

Eosinophil Cationic Protein Stimulates Migration of Human Lung Fibroblasts in Vitro

Levels of Acceptance of Asthma Control Test Questionnaire Among Saudi Patients Attending 5 Tertiary Care Hospitals in Saudi Arabia

Asthma and Pregnancy

Lung Function Testing and Assessment of Distal Airways in Asthma

Assessment of Imaging Techniques in Evaluation of Small Airways Disease in Asthma.

High-Pitched Breath Sounds Indicate Airflow Limitation in Asymptomatic Asthmatic Children

Chronic Intranasal Administration of Aspergillus Fumigatus Spores Leads to Aggravation of Airway Inflammation and Remodelling in Asthmatic Rats

Small Airways Obstruction Syndrome in Clinical Practice

Reduced Exhaled Breath Condensate pH in Asthmatic Smokers Using Inhaled Corticosteroids

Development of a 1-Concentration-4-Step Dosimeter Protocol for Rethacholine Testing

Effects of Inhaled Versus Systemic Corticosteroids on Exhaled Nitric Oxide in Severe Acute Asthma

Potential Side Effects In Patients Treated With Inhaled Corticosteroids And Long-Acting Beta2-Agonists

Factors Associated with Health-Related Quality of Life Among Low-Compliant Asthmatic Adults in Korea

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