Category Archives: Asthma

Health Care Changes Will Affect Your Asthma Regimen

 

Europe and the United States differ on many things including how we look at war and how often we pick our noses…yes it’s true about rhinotillexomania (nose picking).  Perhaps this is why Europeans will reach for a nose spray FIRST to treat allergies and then go for antihistamines.  Yes, there’s even a Dr Oz video on the subject: http://www.oprah.com/oprahshow/Dr-Oz-on-Health-and-Hygiene

So what is the point of all this nonsense?  Treatment of asthma also differs between the United States and Europe.

The Misuse of Asthma Drugs

Gene L Colice Expert Rev Resp Med. 2013;7(3):307-320. 

There are three major problems with asthma care in the USA today and misuse of asthma drugs contributes to each.

This is where the information comes from!
This is where the information comes from!

First, multiple sources document that symptom control of most Americans with asthma in the general population does not meet standards established in the National Asthma Education and Prevention Program Expert Panel Report III (EPR3). In the CHOICE survey, 1000 patients with asthma randomly chosen across the USA were asked about their care and burden of disease.  Almost half of these patients (49%) reported that they did not use asthma controller medications, although 79% had evidence of persistent disease. Of the 51% of the patients reporting the use of asthma controller medications in this survey, 85.7% had not well controlled or very poorly controlled disease. Numerous previous surveys of asthma patients in the USA and Europe, using either telephone interviews or questionnaires, have reported similarly high levels of uncontrolled disease. In the Exercise-Induced Bronchospasm Landmark Survey, 78.8% of the children with asthma and 83% of adults with asthma described respiratory symptoms with exercise. Children and adults with asthma commonly described being limited in their ability to perform sports and outdoor activities by their disease in this survey. 

I know most patients would like to stop their asthma medications ASAP, but it comes at the cost of losing asthma control.  I’ve previously discussed when to stop asthma medications…I’d like to know what you think?  Are doctors prescribing unneccesary medications?

 Second, in addition to difficulties with symptom control on a daily basis, patients with asthma in the USA frequently suffer exacerbations.

Grandpa can't breathe! --that's what exacerbation means
Grandpa can’t breathe! –that’s what exacerbation means

In the CHOICE survey, 5% of the patients reported being hospitalized and 14.4% described either an emergency department (ED) or urgent outpatient visit for an asthma exacerbation in the past year. Patients interviewed in this survey with more severe, persistent or uncontrolled asthma were more likely to have suffered asthma exacerbations. Previous surveys have reported similarly high rates of asthma exacerbations resulting in ED visits and hospitalizations. Data from the US CDC confirm that nationwide rates of ED visits and hospitalizations for asthma exacerbations remain unacceptably high.

So what are parents to do?  The choice between giving your child steroids and having to rush to the emergency room for an asthma flare can be a “no win” proposition. 

 Third, asthma is an expensive disease.

If only!
If only!

The CDC has recently estimated that asthma costs the US economy approximately US$56 billion annually. On average, an asthma patient has been calculated to generate approximately US$2000–$4000 more in healthcare costs per year than a nonasthma control patient. Indirect costs due to work loss, school absenteeism, reduced productivity and so on, further contribute to the economic impact of asthma. Healthcare costs of asthma increase in patients with more severe disease. In patients with moderate and severe persistent asthma, exacerbations will further substantially increase healthcare costs.

I know the most common reason that patients stop their medication is simple: medications are too expensive.  Here are some tips to reduce the cost of your prescribed medications for asthma:

  1. Make sure the medications you are picking up at your pharmacy are needed year round.  Some patients need asthma inhalers only during the cold winter months.
  2. Educate yourself…know your triggers for asthma attacks to keep you out of the ER and better yet to use inhalers as prevention! (I have links to the American College of Allergy and the American Academy of Allergy, Asthma, and Immunology)
  3. Monitor your symptoms with a peak flow meter and pay attention to how much exercise you can do, and how well you sleep.  Both of these indicators will tell you several days in advance if your asthma is flaring.
  4. Use coupons for your inhalers.  In years past, pharmacy reps would leave samples for us to hand out to get patients started on asthma prevention.  This is no longer the case because of health care reform.  But….coupons are available for a similar value.  Just don’t forget to take the coupon in to your pharmacist when you pick up your inhaler. 

  In summary, having reviewed the data, the EPR3 predisposes to under treatment of asthma. The tendency is for healthcare providers to underestimate asthma severity and to correspondingly undertreat the disease. In most asthma patients, the result will be persistent asthma symptoms. In important subsets of asthma patients, particularly smokers, the efficacy of ICS seems impaired. For a given categorization of asthma severity (even if accurately calculated by the healthcare provider), the corresponding recommended treatment with ICS in the EPR3 might be insufficient in smoking and obese asthma patients. Again, the consequence will be persistent asthma symptoms.  Asthma tragedies occur all the time…let’s make sure it doesn’t happen to someone you know!

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Why Does Vitamin D work?

Asthma sufferers may benefit more from inhaling vitamin D than the steroids usually prescribed for the condition.  And besides, aren’t we all concerned with side effects from steroids? A new study from the U.K. identifies a mechanism through which the vitamin can significantly reduce asthma symptoms and suggests it may offer a new method of treatment. Continue reading Why Does Vitamin D work?

You’ll Be the Hit of the Party!

Oh, if I only knew of a more interesting subject for MY next cocktail party.  When kids’ drama, and the latest neighborhood gossip just won’t do, try your luck at the newest asthma mediation! 

A special thanks to Reuters for their excellent reporting…my comments will be in RED.

Medscape Medical News from the American Thoracic Society (ATS) 2013 International Conference

Regeneron, Sanofi Asthma Drug Seen as Potential Game Changer

By Ransdell Pierson

(Reuters) – A new type of asthma drug meant to attack the underlying causes of the respiratory disease slashed episodes by 87% in a mid-stage trial, making it a potential game changer for patients with moderate to severe disease, researchers said on Tuesday.

Slashing episodes by 50% is pretty dramatic, much less results of 87%.  Too good to be true always lurks in the background with medical studies.  Am I cynical?  Unfortunately, I’ve been burned by too many drugs, gadgets, and the next best nutritional supplement to accept this news without a grain of salt.

“Overall, these are the most exciting data we’ve seen in asthma in 20 years,” said Dr. Sally Wenzel, lead investigator for the 104-patient study of dupilumab, an injectable treatment being developed by Regeneron Pharmaceuticals Inc and French drugmaker Sanofi.

The drug also met all its secondary goals, such as improving symptoms and lung function and reducing the need for standard drugs called beta agonists.

Although far larger trials will be needed to confirm findings from the “proof of concept” study, researchers expressed optimism. They noted that dupilumab has also shown the ability to tame atopic dermatitis or severe eczema.

The medicine, if approved, could hold promise for patients with moderate to severe persistent asthma that is not well controlled by standard drugs.

“We have been treating asthma with sort of Band-Aid therapies that didn’t get at the underlying causes,” Dr. Wenzel said in an interview, adding that dupilumab could be an important step in going to the root of the problem. 

The Holy Grail in more ways than one!
The Holy Grail in more ways than one!

The drug works by simultaneously blocking proteins that have been linked to inflammation, interleukin-4 (IL-4) and interleukin-13 (IL-13).

Dr. Wenzel, director of the Asthma Institute at the University of Pittsburgh, said other drugmakers have tested medicines that block one or both of the proteins, but without success.

The trial recruited patients with high levels of eosinophils. Such patients were deemed likely to benefit from treatment.

This new form of medication, called monoclonal antibodies, targets single molecules to avoid the side effects of steroids.  Our prototype for asthma is Omalizumab or Xolair which just celebrated its 10th year out in the market.  Other than Xolair, I’m limited to using steroids for severe asthma.  😦

All patients initially stayed on their standard asthma treatments, meaning medium-to-high doses of inhaled glucocorticoids, as well as long-acting beta agonists. But patients gradually tapered off on those drugs and were no longer taking either of them after nine weeks.

Throughout the Phase IIa trial, half the patients also received weekly injections of dupilumab, while half received placebo injections.

After the ninth week, about 25% of those on placebos had experienced exacerbations, i.e., the need to take a beta agonist, a decrease in lung function, the need for an oral or inhaled corticosteroid, or admission to the hospital or emergency room for worsening asthma.

“By end of the trial, after 12 weeks, 44% of those in the placebo group had exacerbations, compared with 5% of those on dupilumab,” Dr. Wenzel said.

That represented an overall 87% reduction in exacerbations, which Dr. Wenzel said was highly statistically significant.

She said dupilumab was well tolerated, with side effects similar to placebo. But she cautioned that longer trials are needed to fully assess the drug.

Regeneron and Sanofi said standard drugs are unable to control asthma well in 10% to 20% of patients. They estimate that inflammation caused by Th2 cells – the type of inflammation among patients they tested – plays a role in half of those moderate to severe cases and affects as many as 2.5 million people in the United States and up to 30 million worldwide.

Dupilumab has also shown strong hints of safety and effectiveness in two early-stage trials that involved 67 patients with atopic dermatitis. Larger studies are slated to begin later this year.

Atopic dermatitis is inherited and involves patches of highly itchy skin on any part of the body. Patients, many of whom also have asthma and hay fever, have compared the sensation to having unending poison ivy.

“This asthma data and the data we already have in atopic dermatitis really raises the possibility the scientific community has finally hit upon the key pathway across all these allergic diseases,” George Yancopoulos, Regeneron’s research chief, said in an interview.

And there you have it….next time don’t be stuck with boring conversation about the weather, talk about Dupilumab!

American College of Allergy news tidbit…

One over-active gene has been implicated in 20-30 percent of patients with childhood asthma, according to a study in Science Translational Medicine. The gene, according to authors, interrupts the synthesis of lipid molecules sphingolipids, which are part of cell membranes found throughout the body. Reduced sphingolipids was clearly linked to bronchial hyper-reactivity, unrelated to allergens or inflammation, according to the researchers, from New York-Presbyterian Hospital/Weill Cornell Medical Center, Columbia University Medical Center and SUNY Downstate Medical Center.

Here is the full citation—>Sci Transl Med. 2013 May 22;5(186):186ra67. doi: 10.1126/scitranslmed.3005765.

Impaired sphingolipid synthesis in the respiratory tract induces airway
hyperreactivity.

Worgall TS, Veerappan A, Sung B, Kim BI, Weiner E, Bholah R, Silver RB, Jiang XC,
Worgall S.

Department of Pathology and Cell Biology, Columbia University, New York, NY
10032, USA.

Asthma is a clinically heterogeneous genetic disease, and its pathogenesis is
incompletely understood. Genome-wide association studies link orosomucoid-like 3
(ORMDL3), a member of the ORM gene family, to nonallergic childhood-onset asthma.
Orm proteins negatively regulate sphingolipid (SL) synthesis by acting as
homeostatic regulators of serine palmitoyl-CoA transferase (SPT), the
rate-limiting enzyme of de novo SL synthesis, but it is not known how SPT
activity or SL synthesis is related to asthma. The present study analyzes the
effect of decreased de novo SL synthesis in the lung on airway reactivity after
administration of myriocin, an inhibitor of SPT, and in SPT heterozygous knockout
mice. We show that, in both models, decreased de novo SL synthesis increases
bronchial reactivity in the absence of inflammation. Decreased SPT activity
affected intracellular magnesium homeostasis and altered the bronchial
sensitivity to magnesium. This functionally links decreased de novo SL synthesis
to asthma and so identifies this metabolic pathway as a potential target for
therapeutic interventions.

When Can I Stop My Medicine?

“The following story uses fictional names to comply with HIPPA regulations and is not intended to offer medical advice.  If you have specific questions regarding your asthma, please contact my office or call your regular doctor. ”

 “And what medications are you taking now?”  This wasn’t my usual style to get right to the point, but I was running behind schedule. 

“Oh, the ones that are in my chart”, replied Mr. Williams with a broad grin that always let me know he was glad to see me.  Continue reading When Can I Stop My Medicine?

What’s important about Asthma?

If you’re like me, your schedule can’t take another committment–how can you add one more task for asthma?  Don’t neglect treatment for your asthma as proper attention now will save you time & money in the end.  Anyone remember the Fram oil filter commercial….”you can pay me now or pay me later?”  We’ll help you focus on what needs to be done everyday and which tasks are to be used just when needed. 

But first, how does asthma really work and why do I have it?  Review this link for “real time” photos!

 What is my hope for you by using these techniques?

1.  More activity without wheezing, coughing, or becoming short of breath

2.  No unscheduled office visits or Urgent care/emergency room visits for asthma flares

3.  Preserve your lung function for your retirement…we all love being active with our grandkids!

4.  Get you on the cheapest medicines available to prevent asthma.

So what’s most important in treatment of your asthma to avoid the top box?

1.  Get a written Asthma Action Plan…if we don’t bring it up, ask.

2.  Review your inhaler use like you would an oil change–every 3 months.  Which medicines are “everyday” and which ones are just “as needed?”

3.  Peak flow meter.  Use for 1-2 weeks as a baseline and thereafter like a thermometer for your asthma. 

Need extra help:  Click on the link to the American Academy of Allergy (AAAAI)

Are We Overreacting?

The Journal of Allergy and Clinical Immunology
Volume 129, Issue 5 , Pages 1280-1281, May 2012

Thanks Dr Pedersen for your insight!  The bottom line: maybe combination Advair, Symbicort, or Dulera aren’t as bad as they are put out to be. 

Over the last decade, the aims of asthma management have altered to focus on achieving and maintaining good asthma control and reducing future risks, such as decrease in lung function, asthma exacerbations, hospitalizations, death, and adverse effects from treatment.  The benefits of good asthma control include a variety of asthma outcomes that are important to both patients and society.

These include:

  • No restriction in lifestyle
  • Better physical fitness and quality of life
  • Reductions in patients’ perception of the asthma burden, health care resource use, and lower risk of exacerbations, hospitalizations, and death.

Inhaled corticosteroids (ICSs) or combination therapy with an ICS and a long-acting β2-agonist (LABA) have become established as cornerstones in guideline-recommended asthma treatment because these therapies have been the most successful in achieving asthma control and reducing future risks in the vast majority of patients with asthma. 

Changes in the goals of asthma management, as well as treatment recommendations, have revolutionized management from both the patient’s perspective and a societal perspective. The main question that remains is whether the clinical benefits balance or outweigh the risks of the treatments?

When regular ICS treatment was introduced 4 decades ago, safety concerns were common, and initially, the treatment was reserved for patients with severe disease. The concerns were based on fears generated by the side effects of oral corticosteroids rather than data generated by using ICSs, but with increasing knowledge and experience, the concerns decreased, and ICSs became a first-line therapy for asthma because the benefits of the treatment clearly outweighed the risks.  Fast foward to 2012 and our concern is overuse of combination therapy with LABAs/ICS as a risk factor for severe, albeit rare, severe asthma exacerbations. 

In this issue of the Journal of Allergy and Clinical Immunology, Wells et al add to the paucity of real-world data by reporting the findings from a large, population-based, real-world observational study comparing the effects of ICSs and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population of 1828 patients with a total of 3791 person years of follow-up. Data were obtained longitudinally from a managed care organization, and LABA exposure was estimated from pharmacy data. It was found that ICS/LABA combination therapy had an overall protective effect on asthma exacerbations that was as good as or better than that for ICSs alone. The protective effects of ICS/LABA combination therapy seemed particularly marked in patients older than 18 years, male subjects, patients with moderate and severe asthma at baseline, and reassuringly, African Americans (who have been suggested to be at greater risk).

Although the study is well executed, carefully analyzed, and uses sound methodology, it was not of a sufficient size to make any firm conclusions about severe but rare asthma-related events, such as intubations, death, or both. Yet it is an important contribution to the literature on the perceived risk of serious adverse effects of LABAs. It is reassuring that the results from a carefully executed observational study, mimicking real-world study conditions, are in such good agreement with the findings in the randomized, controlled efficacy trials comparing ICS use alone with a fixed LABA/ICS combination.  In addition to significant improvements in asthma control, such studies consistently report reductions in asthma exacerbations, need for oral steroid bursts, and asthma-related emergency department visits compared with ICS treatment alone. Because such events normally precede more serious outcomes, such as intubations, death, or both, these findings make it unlikely (but do not prove) that treatment with fixed LABA/ICS combinations per se should be associated with an increased risk of these serious outcomes.

The US Food and Drug Administration has requested a series of very large postmarketing clinical trials to evaluate LABA/ICS combination safety, (see reference below) but the most serious asthma outcomes are so rare that even these studies might not be able to provide a definite conclusion. Moreover, the results from these studies will not be available until 2017 at the earliest. What should clinicians do in the meantime?

It would be a disservice to our patients if we, in the fear of doing harm to our patients, waited for the perfect. The study by Wells et al supports that a better option would be to follow the recommendations of the asthma guidelines, which unanimously have taken the stand that there is no convincing evidence that LABA/ICS combinations administered in a single inhaler are associated with serious adverse effects. Their benefits on asthma control and reduction of asthma exacerbations outweigh their risk, and we should be careful not to let the perfect become the enemy of the good.

Chowdhury BA, Seymour SM, Michele TM, Durmowicz AG, Liu D, Rosebraugh CJ. The risks and benefits of indacaterol—the FDA’s review. N Engl J Med. 2011;365:2247–2249

I usually don’t trash talk, but….

 You should be concerned about the effects of asthma medication on the developing fetus; fortunately, birth defects are rare and often overstated, but you always have to maintain vigilance for new developments.
 
Why the concern about atresia? 
 

Maternal Asthma Medication Use May Cause Certain Birth Defects

Approximately 4% to 12% of pregnant women have asthma. Current clinical guidelines recommend that women with asthma maintain asthma therapy use during pregnancy. These medications act in 2 ways: as bronchodilators or anti-inflammatories. Few studies have examined the effects of maternal asthma medication use on birth defects.

The aim of this study by Lin and colleagues was to examine whether maternal asthma medication use during early pregnancy increases the risk for selected birth defects.  (Pediatrics. Published online January 16, 2012)

Study Synopsis and Perspective

A recent study found a statistically significant increase in the risk for isolated esophageal atresia, isolated anorectal atresia, and omphalocele in infants whose mothers used asthma medications within the month before conception or during the first 3 months of pregnancy.

Shao Lin, PhD, from the Center for Environmental Health, New York State Department of Health, Troy, and colleagues reported their study results in an article published online January 16 in Pediatrics.

The researchers used data collected for the National Birth Defects Prevention Study, an ongoing, multicenter, population-based, case-control study of the causes of birth defects that has been collecting data from 10 states in the United States since 1997 by conducting interviews with mothers and analyzing DNA obtained from cheek swabs from family members. That study includes both infants with 1 or more specified birth defects (diaphragmatic hernia, esophageal atresia, small intestinal atresia, anorectal atresia, neural tube defects, omphalocele, or limb deficiencies) and control infants without those birth defects.

For this study, the researchers analyzed data from a case group consisting of 2853 live births, stillbirths, or elective terminations with estimated dates of delivery from October 1, 1997, through December 31, 2005, and with 1 or more of the identified birth defects. The control group comprised 6726 infants born alive and without birth defects during the same period, randomly selected from birth hospital information or birth certificates.

Dr. Lin’s team concentrated on periconceptional use of anti-inflammatory medications, bronchodilators, or both. They defined exposure as use of asthma medication once or more from 1 month before conception through the third month of gestation. Mothers who described their medication use as only “as needed” and who could not provide an exact time frame for use were excluded from the study.  (This is a good study design to exclude these patients…doesn’t give you biased results for minimal exposure)

The study found a statistically significant association between isolated esophageal atresia and bronchodilator use only (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.23 – 4.66). The aORs for esophageal atresia and anti-inflammatory use only (aOR, 1.61; 95% CI, 0.69 – 3.76) and for use of both bronchodilators and anti-inflammatory medications (aOR, 2.93; 95% CI, 0.88 – 9.75) were elevated, but were not statistically significant.

There was a statistically significant increase in the risk for isolated anorectal atresia associated with anti-inflammatory use only (aOR, 2.12; 95% CI, 1.09 – 4.12).

Use of both bronchodilators and anti-inflammatory medications was associated with a statistically significant increase in the risk for isolated omphalocele (aOR, 4.13; 95% CI, 1.43 – 11.95).

The results are not all bad however.  The medications studied were not significantly associated with 6 other birth defects studied (neural tube defects, anencephaly, spina bifida, small intestinal atresia, limb deficiency, and diaphragmatic hernia).

The researchers performed a stratified analysis by time of medication use, using the periconceptional period and the period from the fourth through ninth month of gestation. The positive associations were found only in infants of women who took the medications during the periconceptional period, and not in infants whose mothers took the medications only in the fourth through ninth months of pregnancy. 

My comment—>by the time you know you’re pregnant, you’ve had the exposure!

The authors write that from 60% to 67% of mothers of infants with esophageal atresia, anorectal atresia, and omphalocele used bronchodilators during their entire pregnancy, although these data were not shown.

This is a key point–“With the interview information available for analysis, we were unable to distinguish between the effects of asthma and those of asthma medications; however, we did observe that mothers with possible indicators of uncontrolled asthma or severe asthma episodes (eg, use of multiple bronchodilators) were at higher risk for delivering a child with 1 of the defects studied than those who used 1 bronchodilator,” the authors write.

“When regular use of bronchodilators is required, an activated inflammatory process is implied; thus, use of bronchodilators throughout pregnancy might indicate that these mothers had frequent or ongoing inflammatory exacerbations during pregnancy,” they add.

Noting the importance of controlling asthma during pregnancy, the authors write, “The current clinical guidelines and specific recommendations for aggressive asthma management during pregnancy should remain unchanged.”

“Given the low baseline prevalence of these defects, if the observed association proved to be causal, the absolute risks of asthma medications on these rare defects would be small,” they conclude.

The study was supported by the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

Clinical Implications

  • Clinical guidelines recommend that women with asthma maintain asthma medication use during pregnancy.
  • In the current study, positive associations were observed for anorectal atresia, esophageal atresia, and omphalocele and maternal periconceptional use of asthma medications, but not for other birth defects studied.

You must want to know how to treat esophageal atresia?

To Use or Not To Use FeNO (exhaled nitric oxide)

 

Whether exhaled NO helps to identify a specific phenotype of asthmatic patients remains debated. Not everyone would agree with Dr. Boggs in this video–what do you think?

In conclusion, FENO0.05 is independently linked to two pathophysiological characteristics of asthma (ICS-dependant inflammation and bronchomotor tone) but does not help to identify a clinically relevant phenotype of asthmatic children.

For the Usefulness of FeNO complete study click here:  (let me know if you need a password)

Steroids in Young Children–too Much of a Good Thing?

 Intermittent budesonide therapy for children with recurrent wheezing 

Here’s the issue:  my doctor prescribes budesonide (or Pulmicort™) for my child’s asthma and tells me to use it EVERYDAY.  Is this really necessary?  Conventional wisdom says to use inhaled steroids or anti-inflammatory medications for asthma everyday or they don’t work well.  That attitude may now be challenged with this new study from the prestigious New England Journal of Medicine. 

That's a mouthful

This summary appears in the February issue of Journal of Clinical Allergy & Immunology.  Wow–that’s a mouthful!

Concerns over adherence and growth suppression in children with wheeze who are regularly treated with inhaled corticosteroids have prompted re-examination of some clinical guidelines by the National Heart, Lung, and Blood Institute‘s Childhood Asthma Research and Education Network. Zeiger et al (N Engl J Med 2011;365:1990-2001) compared low-dose, daily inhaled budesonide with intermittent budesonide therapy initiated at the beginning of respiratory tract infection and continued for 1 week in 278 children between the ages of 12 and 53 months with frequent, episodic wheezing at risk for asthma exacerbation.

The authors found that daily low-dose budesonide therapy did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations. Although the difference in growth measures was not statistically significant between the 2 groups, they noted that the mean exposure to budesonide was greater in those undergoing the daily low-dose regimen.

Budesonide is given by nebulization as shown here

Zeiger et al commented that their findings of lack of superiority of daily low-dose budesonide to high-dose intermittent budesonide might be an important consideration in future clinical guidelines.

Lead author, Robert Zeiger, MD, PhD, at Kaiser Permanente and University of California, San Diego, gave us this comment: “Our study offers a treatment option for wheezing preschoolers. . .while the study may benefit many preschoolers who wheeze during respiratory illnesses, it did not evaluate children who have more severe disease or persistent symptoms.

Bottom line?  Maybe doctors can treat preschoolers who wheeze with intermittent inhaled steroids and avoid year-round use of budesonide.  Stay tuned.