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!

#asthma, #omalizumab, #regeneron

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.

#asthma

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

#asthma, #battle-of-the-bulge, #combination-therapy, #long-acting-beta-adrenoceptor-agonist

Practice Makes Perfect!

I had the privilege this week of watching my favorite sport….10 players dribbling an inflated ball up & down a court, trying to throw it through a steel hoop more times than the opposing team.  Yeah, it’s my passion.  The Thunder vs Bobcats and Oral Roberts University vs the Sooners of Oklahoma.  (little in state rivalry) What impressed me about the current state of basketball is how fast any human 6 ft 8 inches tall can get up and down the court!  As a devout Kansas Jayhawk fan growing up, we (of course I’m part of the team!) had some good exhibits, but never with the agility, speed, and shooting accuracy seen today.  Regardless of better nutrition, year round practice schedules, and the 3-point shot, we all practice to get better. I didn’t realize that despite many alternatives to oral steroids, our use of a “quick fix” is increasing.  Is that why we call this the “practice of medicine?”

I report here a study published barely one month ago on the use of steroids for treating many medical conditions.  Our approach to steroids (by mouth) is to use them when necessary, but substitute with inhaled steroids or other alternatives whenever possible.  Why?  Side effects.  In fact, did you know that based on systemic absorption, a 5 day “burst” of oral steroids is equal to 20 years of the inhaled route?  Based on this poster presentation, it would seem that we need more practice in reducing the use of steroids, especially in children!  My recommendations:

  1. As noted below, emergency rooms and urgent care clinics often don’t know how many times in one year a patient has been on steroids.  Patients often don’t go to the same clinic, and the doctor in that case has no way of monitoring overall steroid use and exposure.  The fix: communicate to ANY provider how many times you have used oral steroids.  You’ll be pleasantly surprised at the results!
  2. Inhaled steroids, allergy shots, avoidance of pets are all designed to reduce your need for bursts of oral steroids.  I agree, avoiding dust and animal dander can be a hassle, but you’ll have better control of asthma if you do and less of a need for oral steroids.  The fix:  take preventive medications as prescribed, avoid all known triggers of asthma (perfume included), and measure your peak flow reading at the first sign of coughing or wheezing. 
  3. Who gets tired of repeating the same list of medications every time you go to the doctor?  Oh, yes, I get tired of writing them down!  There is a reason for the madness….your arthritis doctor, allergist, and ER doctor all prescribe prednisone for different conditions, and unless each prescription is written down and recorded, it’s easy to get an overdose.   The fix: try to remember “in-between” medicine that you have received from one doctor visit to the next.  This is especially important to review with your “primary care doctor”. 

American College of Allergy, Asthma & Immunology (ACAAI) 2012 Annual Scientific Meeting: Abstract P313. Presented November 11, 2012.

English: Ball-and-stick model of the immunosup...

English: Ball-and-stick model of the immunosuppressant drug prednisone (Photo credit: Wikipedia)

The number of prescriptions for prednisone has been increasing steadily since 2000 in the United States, and not all prescriptions are appropriate, researchers reported in a poster session here at the American College of Allergy, Asthma & Immunology 2012 Annual Scientific Meeting.

“I have been in residency for the past 3 and a half years, and was surprised at the amount of steroids being prescribed and the diseases they were being prescribed for,” Tricia Lee, MD, 2012 chief resident in internal medicine and pediatrics at the University of Louisville in Kentucky, told Medscape Medical News.

“This impressed me because we are taught in medical school about all of the significant side effects of systemic steroids, which include weight gain, thinning of skin, psychiatric changes, and adrenal suppression. I wanted to see if we, as physicians, were truly prescribing more prednisone now than we were a few years ago,” Dr. Lee explained.

She and her group examined data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey databases, which were collected by the Centers for Disease Control and Prevention, from 2000 to 2009.

During that time, 11 billion visits were recorded in the 2 databases. Prednisone was prescribed in 178,655,280 visits for any diagnosis — an increase of 17% for all ages.

For adults, prednisone was prescribed 13% more frequently in 2009 than it was in 2000; for children, it was prescribed 38% more frequently, Dr. Lee said.

Diagnoses Associated With Prednisone Prescription

More than 1000 different primary diagnoses were associated with a prescription for prednisone. Asthma, allergy, bronchitis, rheumatoid arthritis, urticaria, contact dermatitis, acute upper respiratory infections, and pneumonia accounted for the majority of prescriptions.

For allergic rhinitis, prednisone prescriptions increased from 1.9% in 2000 to 2.2% in 2009, Dr. Lee noted.

“The worry is that a patient will go to one doctor to get a prescription for prednisone for his rheumatoid arthritis, go to another to get prednisone for a pain in his shoulder, go to another to get a prescription for his asthma, and so on, until he is taking a dangerous amount of prednisone, without all of his doctors being aware,” Dr. Lee said.

“The danger to the patient is that, in the span of a few months, they may be exposed to steroids for a chronic period,” she said.

Emergency Department Implicated

John Oppenheimer, MD, clinical professor of medicine at the New Jersey Medical School in Newark, was asked by Medscape Medical News to comment on the study. “This abstract highlights a significant rise in the use of prednisone, specifically in the emergency department setting,” he said.

He added that “in the case of allergic respiratory illness, this is overall the most effective therapy; however, as pointed out by Dr. Lee and her colleagues, it is not without side effects.”

Dr. Oppenheimer called this increase in the use of prednisone “alarming.”

“The authors postulate that this is the result of a lack of appreciation of potential side effects. However, one may also argue that this is the sequel to the undertreatment in a proactive approach of the underlying illness.”

 

#american-college-of-allergy-asthma-immunology, #asthma, #medical-prescription, #prednisone

Happy Thanksgiving message

If you’re anything like me, waking up on Thanksgiving morning brings to mind a flood of memories to truly appreciate.  Maybe its the intoxicating smell of turkey (and the tryptophan will make you want a nap)  mixed with pumpkin pie, or the anticipation of Christmas that entices us to slow down and reflect on what is truly important in our hectic lives.  For me, of course, my delightful family is always a “sweet spot” when I come home from work each day. 

All 5 to be thankful for!

Healthcare on the other hand, has come under criticism for many reasons, and my position is no exception.  Despite all of the challenges facing health providers, I still love the challenge of caring for patients with respiratory illness!  Despite all of the changes proposed by the “powers that be” to make health care better, the following principles remain:

  1.   If you understand the WHY about your condition, you’ll be better prepared to implement the HOW do I feel better!
  2.  Feeling better is a cooperative effort between patients, health care providers, support systems, the right diagnosis and the right treatment.  Solutions are never usually simple, easy, or a quick fix.
  3.  I’m reminded of a middle-aged woman who was frequently hospitalized for her asthma.  She was frequently on steroids (oral) for wheezing and almost died several times.  She made a decision to stop smoking, clean her environment, and took her medications on a regular basis.  She also attended classes on asthma and taught herself about what made her asthma so severe in the first place.  Was she successful?  I never hear from her anymore if that tells you something about her progress. 

Enjoy your holiday….and by the way if you get heartburn, I wrote last year about the inevitable!  Click on the link below. 

http://wp.me/p1O8HY-3a

#asthma, #pumpkin-pie, #respiratory-disease, #respiratory-disorders, #thanksgiving

Don’t ask….don’t tell!

If patients don’t think you as a doctor are open to discussion about complementary medicine, guess what? 

Ask your doctor about complementary medicine–don’t be silent any longer!

They won’t talk!  This web site is to prove that the Federal Government is interested in “bridging the gap” between traditional medicine and the complementary approach.  I would advise you to visit with your doctor about complementary medicines and treatment for allergies & asthma. 

NCCAM website

#alternative, #alternative-medicine, #asthma, #health, #medicine, #national-center-for-complementary-and-alternative-medicine, #physician, #united-states

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)

#allergy, #asthma, #dyspnea, #spirometry

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

#asthma, #budesonideformoterol, #conditions-and-diseases, #fda, #health, #journal-of-allergy-and-clinical-immunology, #mometasoneformoterol, #respiratory-disorders

The More You Know, the Less You Know

The practice of medicine is just that….I advise the recommended treatment based on the information available at the time.  If I look back to the time during my fellowship in the early 90’s, much of what we thought was true and now 20 years later, been disproven.  As an example, the following study from a respected medical journal cautions against the use of PPI medication for reflux in children.  It’s worth your attention, but first some background information.

Children have a high prevalence of asthma and gastroesophageal reflux (GER). Children with asthma often report symptoms of GER and also have a high prevalence of asymptomatic GER.  We call this “silent reflux”. 

Some experts have suggested that untreated GER may cause persistent asthma control problems in children refractory to treatment with inhaled corticosteroids. However, whether treatment with proton pump inhibitors (PPIs) improves asthma control has not previously been determined. The objective of this study by Holbrook and colleagues was to determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.  (ie, Prevacid for “silent reflux”)

Study Synopsis and Perspective

Use of PPIs in children with poorly controlled asthma who were using inhaled corticosteroids and who had no symptoms of GER was not found to improve asthma control and was, in fact, associated with an increase in adverse effects, according to results of a study published in the January 25 issue of JAMA. (PPIs Produce Negative Outcomes in Children With Poor Asthma Control)

PPIs “are often prescribed for poorly controlled asthma regardless of reflux symptoms, and there have been large increases in the use of PPIs among children between 2000 and 2005…. Hence, it is of clinical importance to determine whether antireflux therapy, the most common of which are PPIs, improves control of asthma in children,” write Janet T. Holbrook, MPH, PhD, from the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers.

The goal of this placebo-controlled, double-masked, randomized study was to determine whether the PPI lansoprazole was effective in controlling asthma symptoms in children with asthma, but no overt GER. The researchers also investigated whether pH testing would identify children with GER who responded to PPI therapy.

The children were randomly assigned to receive either lansoprazole (15 mg/day for those weighing <30 kg; 30 mg/day for those weighing ≥30 kg; n = 149) or a matching placebo (n = 157). The researchers found that the mean difference in the Asthma Control Questionnaire (ACQ) score between the 2 groups was 0.2 units (95% confidence interval [CI], 0.0 – 0.3 units), which was not statistically significant (P = .12).

There also was no significant difference in the forced expiratory volume in the first second (FEV1; 0.0 L; 95% CI, −0.1 to 0.1 L), and no change in the rate of episodes of poor asthma control (relative risk [RR], 1.2; 95% CI, 0.9 – 1.5) or asthma-related quality of life (−0.1; 95% CI, −0.3 to 0.1). In addition, children treated with lansoprazole developed more respiratory infections (RR, 1.3; 95% CI, 1.1 – 1.6; P = .02) than those in the placebo group.

A subgroup of children in the study (n = 115) underwent esophageal pH studies before randomization; the prevalence of GER among this group was found to be 43%. In those children with a positive pH study, there was no positive treatment effect with lansoprazole vs placebo for any asthma outcome.

The most common adverse event reported among both groups was asthma exacerbation.

  • This is the exact opposite of what I would expect!

A higher prevalence of upper respiratory tract infections, sore throats, and episodes of bronchitis was noted among patients in the lansoprazole group. The study authors speculate that this may be a result of loss of host defense against bacterial colonization as a result of higher gastric pH levels.

“The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airway reactivity, or quality of life,” write the authors. The results also “indicate that PPI therapy for poorly controlled asthma is not warranted.”

In an accompanying editorial, Fernando Martinez, MD, from the Arizona Respiratory Center, University of Arizona, Tucson, notes that although it is not a statistically significant difference, the increase in activity-related bone fractures in the lansoprazole group also raises concerns. This potential complication has prompted an advisory from the US Food and Drug Administration about the risk for fractures in adults receiving chronic PPI therapy.

Overall, however, Dr. Martinez praises the work of Dr. Holbrook and colleagues and concludes that “[g]iven their potential adverse effects, these medications should thus be used with great restraint for treatment of GER/[gastroesophageal reflux disease] during childhood. The substantial increase in use of PPIs in children during the last decade is worrisome and unwarranted.”

Support for this study was provided by the American Lung Association Asthma Clinical Research Centers Infrastructure Award and National Institutes of Health/National Heart, Lung, and Blood Institute grants. Dr. Holbrook and colleagues have disclosed no relevant financial relationships. Dr. Martinez has served as a consultant to MedImmune and has presented at an Abbott-sponsored seminar.

JAMA. 2012;307:373-381, 406-407.

Study Highlights

  • The Study of Acid Reflux in Children With Asthma was a randomized, masked, placebo-controlled, parallel clinical trial comparing lansoprazole vs placebo in children without overt GER but with poor asthma control despite treatment with inhaled corticosteroids.
  • Lung function measures, such as FEV1, asthma-related quality of life, and episodes of poor asthma control, were secondary endpoints.
  • In the subgroup with a positive pH study result, there was no apparent treatment effect for lansoprazole vs placebo for any asthma outcome, including asthma-related quality of life or lung function.
  • Lansoprazole was also ineffective in subgroups defined by markers of asthma severity (either FEV1 at baseline or oral corticosteroid use in the past year).
  • At least 1 serious adverse event occurred in 10 participants in the lansoprazole group and 9 in the placebo group.
  • Asthma exacerbation was the most common serious adverse event in both groups (15 of 25 reports).
  • The investigators concluded that in children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole did not reduce symptoms or improve lung function but was associated with increased adverse events.
  • The findings do not support routine esophageal pH testing to identify children who respond to PPIs, nor do they support trials of PPIs for poorly controlled asthma.
  • An accompanying editorial notes that the overuse of PPIs in childhood asthma is an example of “therapeutic creep,” or extending the use of a treatment with real or suggestive therapeutic effects in selected patients to other patients in whom the efficacy of that treatment has never been demonstrated.
  • The editorial also notes that therapeutic creep increases the risk for potential adverse effects without any added advantage for patients and may have significantly added to the marked increase in asthma drug costs.

Clinical Implications

  • Findings of a randomized, placebo-controlled trial suggest that PPI treatment of children with poorly controlled asthma but without symptomatic GER is not effective in reducing asthma symptoms or improving lung function.
  • In this randomized, placebo-controlled trial, the addition of lansoprazole was associated with increased adverse events, particularly respiratory tract infections. There may be significant safety concerns for long-term PPI use in children, meriting further research
  • I personally wonder if more aggressive use of Vitamin D replacement would be helpful for the increase in risk of fractures for the patients taking PPI medication.  Yes indeed, further research is warranted. 

Full reference on the dangers of PPI medications

#asthma, #conditions-and-diseases, #health, #holbrook, #johns-hopkins-bloomberg-school-of-public-health, #medimmune, #respiratory-disorders, #spirometry

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?

#asthma, #centers-for-disease-control-and-prevention, #health, #pediatric, #pregnancy