Tag Archives: Health

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

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Sleep disordered breathing

Often allergy patients have sleep disordered breathing and want to know if allergies contribute.  Most of the time, interruptions in your sleep due to allergy consist of congestion, snoring, sneezing, and possibly apnea.  Anything other than those symptoms should be evaluated for alternative causes.  Specialists dealing with sleep disorders are allergists, ENT (otolaryngologists) and pulmonologists.  There is a board-certification for sleep medicine, so you might want to check for this on listed credentials.  Good night! 

Sweet Dreams!

Sleep disordered breathing  (click to review slides; e-mail me if you need a password) —> lwiens@cox.net

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?

What is the Best Method for Testing Allergy to Drugs?

I must have a drug allergy….what is the best method for testing?  Countless times I have reviewed skin biopsy results that state evidence of a drug allergy.  Obviously, this is not a very specific method of diagnosis, so what does work?  I’ll copy the entire abstract for you and make some comments below.  In the meantime, if you’re interested in what doctors learn about drug allergy, this is a lecture from University of Texas–Southwestern designed for allergy fellowship training.  It’s a little long unless you’re a doctor, but have at it!  And yes, I trained at Children’s Mercy Hospital with Dr. Portnoy. 

L.M. Heinzerling; D. Tomsitz; M.D. Anliker  The British Journal of Dermatology. 2012;166(1):107-114. 

Is Drug Allergy Less Prevalent than Previously Assumed?

Background Rashes are a frequent conundrum in clinical practice as they may be reactive, drug induced or disease specific. Identification of the culprit drug is important as re-exposure may be harmful or even life-threatening and unnecessary avoidance of ‘innocent’ drugs leads to limitations of treatment options.
Objective To objectify the cause of suspected cutaneous drug reactions in a large patient population.
Method Over 5 years (2006–10), 612 patients with suspected cutaneous drug reactions were evaluated. Histology was assessed. About 200 patients were invited for complete work-up with skin tests (prick/intracutaneous testing and scratch/patch as indicated) and, if necessary, lymphocyte transformation tests (LTT). In special cases, drug provocation tests were conducted.
Results A total number of 141 cases with suspected drug reaction underwent full work-up (age 6–86 years; 75% female, 25% male). In 107 cases (76%) a drug was identified whereas 34 (24%) were reactive rashes or had other causes. Mostly, cutaneous drug reactions were maculopapular rashes, urticaria/angio-oedema; less frequently, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, systemic drug-related intertriginous and flexural exanthema, toxic epidermal necrolysis and fixed drug eruptions were present. Of all the cutaneous drug reactions investigated, 39·8% were caused by antibiotics, 21·2% by anti-inflammatories, 7·6% by contrast media and 31·4% by others (oral antidiabetics, antimycotics, antipsychotics, antiepileptics and others).
Conclusion Clinical assessment overestimates the role of drug allergies in cutaneous reactions. Assessment of suspected drug reactions can be greatly improved by thorough evaluation including dermatological and allergological work-up with skin testing and assays such as LTT.

Out of a total of 612 patients, 141 cases with suspected drug allergy were fully evaluated with allergy testing. Interestingly, out of the tested subjects with suspected drug reaction one-quarter could not be confirmed by objective testing, and skin changes were tracked to another trigger. This agrees with data from other studies which also found that not all the suspected drug reactions were finally confirmed.

Thus, depending on prescreening, the role of drugs in sudden exanthema is overestimated. In plain English, all of these  cases would have been FALSELY attributed as drug reactions had it not been for the testing and work-up.

However, only rigorous testing (and provocation) can rule out or confirm the drug reaction and finally identify the culprit drug. Interestingly, it was by means of a lymphocyte transformation test (LTT) that one-fifth of the cases were identified, which thus represents an important tool shown to have a sensitivity of 78%, even though this methodology is often considered experimental.

Further studies are needed to specify the sensitivity and specificity of LTT in comparison with skin tests for each substance.

Ouch! my tonsils are hurting me!

All that wheezes isn’t asthma!  Ever heard that before?  A common finding in our clinic is “wheezing” or difficulty breathing not due to asthma, but as a result of large tonsils/adenoids.  A typical history is as follows:

  • Snoring at night
  • He wheezes–(it’s not really wheezing, but loud noises coming from the lungs is often labeled as such)
  • I can never breathe through my nose
  • Examination reveals no wheezing in the chest, but coarse rhonchi transmitted to the chest from the upper airway
  • Look at these tonsils that are almost completely obstructing the back of the throat–

ENT doctors are the surgeons that perform T & A’s as they are popularly called.  (tonsillectomy/adenoidectomy)  The enthusiasm for removing tonsils in young children as a “routine” procedure as decreased because of intraoperative complications, but if it’s needed, the risks outweigh the benefits.  

Complementary medicine to treat Asthma?

I have a story for you….but first, “traditional” medicine is trying very hard to work with other methods for treating asthma.  The web page below reviews treatment of asthma using something other than “inhalers“.  Now on to the story….

I am a member of the Complementary Medicine Committee of the American Academy of Allergy, Asthma, & Immunology (that’s a mouthful).  We met last month to discuss better ways to “integrate” traditional health care with Chinese medicine for instance.  Another member of the group had studied accupressure in China before coming to the United States 20 years ago.  When she first arrived, while on rounds she intervened using accupressure with a parent experiencing asthma.  The “attack” stopped immediately.  Later on that day, her attending physician who happened to be the chairman of Pediatrics, called her in his office and let her know that further intervention using accupressure would not be tolerated and she would be dismissed from the training program if this ever happened again. 

I’m glad times have changed and this type of intimidation is rare; what are your thoughts about integration of traditional and other forms of complementary medicine?  The government is putting together a great effort to see this happen.  See below.

Complementary treatment & asthma

Breathing Retraining in Asthma Management–I told you so!

Many asthma patients or patients who can’t breathe are found to have problems with their breathing technique.  In medical terms, I use Vocal Cord Dysfunction, Spasmodic Dysphonia, Irritable Larnyx Syndrome just to name a few.  Some health care providers, including doctors, aren’t always familiar with the concept that vocal cord problems can cause difficulty breathing, but this 40+ page review should convince you otherwise. This is an informative video about problems that affect many asthma patients & isn’t directly related to the lungs at all–

Now I’m not condoning the use of “breathing exercises” to treat asthma, but remember that up to 40% of asthma patients have problems with their vocal cords.  What does this translate to:

  •  Underdiagnosis of vocal cord problems
  • Lack of follow-up when inhalers don’t completely resolve asthma symptoms

 Thanks to Dr Burgess & colleagues, I am beginning to see extensive medical reviews on breathing exercises for asthma that will most likely apply to vocal cord problems as well.  Burgess, et al.  Published in Expert Rev Resp Med. 2011;5(6):789-807)

In asthma management, complementary and alternative medicine is enjoying a growing popularity worldwide. This review synthesizes the literature on complementary and alternative medicine techniques that utilize breathing retraining as their primary component and compares evidence from controlled trials with before-and-after trials. Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library electronic databases were searched.  Breathing retraining, a popular form of complementary and alternative medicine (CAM), is the subject of this review.  You can read the entire article if you would like–don’t count on staying awake for the entire article! 

What do breathing modification techniques do for asthma:

  • Demonstrate a significant decrease in β2-agonist use
  • Improvement in quality of life
  • Decrease in inhaled corticosteroid use
  •  No between-group differences in forced expiratory volume  (FEV1) or provocation dose needed to cause a 20% fall in FEV1 for methacholine  (PD20)

 It is reasonable for clinicians to offer qualified support to patients with asthma undertaking these breathing retraining techniques.

What are these techniques?

  • Diaphragmatic breathing
  • Inspiratory/expiratory muscle trainer–see this very good video: 
  • The Buteyko technique
  • There was some evidence that beneficial effects declined with time if breathing techniques were not maintained.

Weiner et al., in three separate controlled trials, found that specific inspiratory muscle training using either an externally weighted device or a purpose-designed threshold inspiratory muscle trainer (HealthScan; NJ, USA) compared with ‘sham’ muscle training significantly increased inspiratory muscle strength as measured by maximal inspiratory mouth pressure at residual volume (PImax at residual volume). Whew what a mouthful!

The most recent of these studies that compared female to male asthmatics found that using the same training method to allow females to attain a PImax equal to that of males resulted in a significant and highly correlated decrease in both dyspnea score and medication use in the active intervention group only.  

Here’s a video on some very simple breathing exercises one can do for VCD:

VCD training

I am now beginning to use “The Breather” for both inspiratory/expiratory muscle training in patients with “Irritable Larnyx” syndrome who also have asthma.  Early success only means it warrants further examination of this technique by well-designed clinical studies–any volunteers? 

These techniques will not replace asthma medication or a carefully designed asthma plan, but their use should not be dismissed out of hand, especially in patients with throat problems along with their asthma.  Further well-designed trials of these techniques are needed to properly evaluate their place in asthma management.

Graphic cigarette labeling ruled illegal–what do you think?

Because smoking has such an impact on respiratory health, I’m always interested in your feedback on articles that appear in USA Today on health.  What do you think about graphic advertising discouraging the use of cigarettes?

Too graphic?

Should scare people more?

It really doesn’t change behavior?

The full article is listed here:  gory details

The Teen Who Can’t Swallow–What To Do?

The Evaluation of a Patient With Suspected EoE

Our series is on eosinophilic esophagitis (EoE) and I’ve covered how you present with this condition and a little bit about what the heck this condition really is! The website reference is http://www.medscape.com/viewarticle/754206?src=mp&spon=38

Patients with suspected EoE should be evaluated by both an allergist and a gastroenterologist.

  • A careful history should include screening for the presence of reflux/GERD, growth delay, feeding/swallowing difficulty, and a past history of allergic disease. 
  • Symptoms of interest include history of weight loss or poor weight gain, dysphagia or odynophagia, multiple emergency department visits for impacted food, altered eating habits such as food aversions, overcutting or overchewing one’s food or eating very deliberately and requiring lots of fluids to wash down each bite.
  • A family history of similar symptoms or atopy can also be a clue.
  • EGD with multilevel biopsy is needed to make the tissue based diagnosis. Careful attention should be paid to gross features when performing the procedure. Dilation may frequently be performed in conjunction with the biopsy.

Allergen testing should be performed only in patients with biopsy proven EoE, because the tests do not have good positive predictive value without established disease.  Unfortunately, skin testing can be positive AND negative in biopsy proven EoE, which leads to much confusion from a diagnostic standpoint. 

Testing is guided by foods reported to cause symptoms, but should include 13 common foods with established predictive values for EoE.   What are those foods? I’m glad you asked.  Milk, egg, soy, wheat, corn, beef, chicken, apple, rice, potato, peanut, oat, barley. This means BOTH skin testing and patch tests to the above list.  Patch testing is a bit different in that I make a “paste” with the food and place it in a Finn chamber on the back for 48 hours.  Keeping it on can be a challenge, but good results.   

Patch test applied to skin
Loading a Finn chamber for patch testing

Inhalants should also be tested given aeroallergy can play a role.  Food atopy patch testing assesses for a cellular-mediated mechanism, and should be placed for food items not positive on initial testing, and read at a minimum of 48 hours after placement. Both prick and patch tests have independent positive and negative predictive values, as well as combined values. Foods positive on either test are generally recommended to be removed from the diet. There is no established role for ImmunoCAP® testing or other allergy blood tests in diagnosing EoE. 

  • So there you have it…find out if EoE is even present before testing for foods.
  • Use both skin tests and patch testing to identify suspected foods that will need to be eliminated.
  • And in case you’re wondering, here’s what a positive patch test looks like…..

    Positive patch test for EoE.