Major Research Findings with Direct Clinical Implication

Proton pump inhibitors do not improve asthma

Acid reflux (GER) is a common condition that is frequently reported among patients with asthma. Many physicians believed that asymptomatic GER worsened asthma, and therefore, treating patients with proton pump inhibitors would improve asthma control. In the Study of Acid Reflux and Asthma, 412 adults were randomly assigned to either receive Nexium or a placebo while over three hundred children were randomly assigned to either Lansoprazole or placebo in the Study of Acid Reflux in Childhood Asthma.

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The results of SARA and SARCA were published in the New England Journal of Medicine in 2009 and in the January 25, 2012 edition of the Journal of the American Medical Association, respectively. Both studies found that treatment with proton pump inhibitors did not improve asthma control in those with asymptomatic GER. Thus, the ACRC concluded that acid reflux without symptoms is not a likely cause of poorly controlled asthma.

Therefore, roughly 1.5 million asthma patients may be taking expensive medication unnecessarily. For people with asthma currently using a preventative asthma medication, the use of proton pump inhibitors in patients shown to actually have acid reflux instead of all patients with poorly controlled asthma could save over $1.1 billion per year in health care expenditures.

The Flu Vaccine is Safe for Asthmatics

In its first study, the Safety of Inactivated Influenza Vaccine in Asthma, the ACRC evaluated the safety of the influenza vaccine in patients with asthma. Prior to this study, less than 30% of patients with asthma were being vaccinated against influenza due to the incorrect assumption that the flu shot actually caused an asthma attack. A total of 2,032 patients with ages ranging from 3 to 64 years were randomized to receive an injection of the flu vaccine and an injection of placebo in random order with four weeks between injections. The results of the study were published in the New England Journal of Medicine in 2001 and showed that the asthma attack rate was similar between the two groups leading to a recommendation that patients with asthma should receive annual influenza vaccinations to prevent influenza related asthma attacks.

Based on these findings, flu shots are now recommended for those with asthma by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Between 2001 and 2009, the percent of people with asthma that received the flu shot increased by 20% to 47%. With this increase in the influenza vaccination rate, the number of asthma hospitalizations due to the flu each year would be expected to decrease by almost 18,000, saving over $137 million per year in health care expenditures.

Old and inexpensive drug is just as effective as newer hip drug

In its first CER trial, Effectiveness of Low Dose Theophylline as Add-On Therapy in the Treatment of Asthma, the ACRC examined whether a low dose of a relatively inexpensive asthma medication, theophylline, a drug that had fallen out of favor with doctors due to concerns over side effects, could be used as safely and effectively as an alternative to the widely used, more expensive add on asthma therapy, montelukast (Singulair). In this study, 489 participants with poorly controlled asthma (adults and children) were randomized into one of three groups: placebo, theophylline, or montelukast.

The results of this study were published in the American Journal of Respiratory and Critical Care Medicine in 2007 and found that theophylline was just as effective as montelukast in improving asthma control in patients not on inhaledcorticosteroids, a common form of asthma treatment. This finding offered an immediate clinical option for physicians treating patients unable or unwilling to use inhaled corticosteroids by providing a safe and inexpensive asthma treatment alternative to the expensive therapy option. For people with asthma at least 15 years of age not currently using a preventative asthma medication, the use of theophylline instead of montelukast could save about $800 million per year.

Less intensive treatment options for well-controlled asthmatics

In its the second CER trial, Leukotriene Modifier or Corticosteroids or Corticosteroid-Salmeterol Trial, the ACRC examined whether therapy could be decreased among well controlled asthmatics on fluticasone, a low dose inhaled corticosteroid. A treatment regimen of twice-a-day inhaled fluticasone was compared to less intensive once-a-day treatment strategies in 500 patients (adults and children) with asthma. The results of the study, published in the New England Journal of Medicine in 2007, showed that the simpler regimen of a once-a-day inhaler of fluticasone plus salmeterol (Advair) was just as effective as twice-daily treatment of inhaled fluticasone in patients with mild persistent asthma.

These results offered immediate benefits for patients by showing that a simpler treatment plan with fewer doses to take daily and fewer prescription refills – reducing the cost for medications and perhaps leading to a decrease in side effects – was just as effective in maintaining asthma control. A more convenient treatment schedule would also be expected to result in greater treatment compliance. For people with asthma at least 6 years of age currently using a preventative asthma medication, the use of once-daily fluticasone plus salmeterol instead of twice-daily fluticasone could save almost $2 billion per year.

Placebo effect in Asthmatics - A True Phenomenon

Information that a patient receives about a drug or treatment may affect that patient's expectations about the effectiveness of the drug or treatment, the so-called "placebo effect". The Trial of Asthma Patient Education enrolled 601 asthmatic patients with poor symptom control to determine the effect of expectations on physician-observed responses and patientreported responses to treatment with placebo and montelukast. Both placebo and montelukast were given under conditions in which patients were given either neutral messages about the treatment or enhanced messages about the treatment. The results of the study were published in the Journal of Allergy and Clinical Immunology in 2009. For placebo, but not montelukast, the enhanced message was associated with improvements in patient-reported asthma symptom control. Thus, the study showed both the potential and limitations of the effects of enhanced presentation of a drug to patients' experience of relief from the drug.

Use of a Questionnaire to Detect Sinonasal Disease

Sinusitis and rhinitis are very common in people with asthma and may lead to poorly controlled asthma. Guidelines recommend screening patients with asthma for sinusitis and rhinitis, yet there is no agreement on how this screening should be done and there is no simple screening test for these conditions. The ACRC commissioned a preliminary study, Sinusitis and Rhinitis in Asthma, to develop a questionnaire that would screen for these diseases. The results of the study were published in Chest in 2009 and showed that a five or six item questionnaire was effective as a screening test for chronic sinonasal disease. Therefore, it may become possible to screen asthmatic patients for chronic sinonasal disease using a simple questionnaire instead of resorting to a computerized tomography (CT) scan which is more expensive and involves multiple X rays to the head. Additional research is needed to replicate the ACRC findings in a larger number of patients with asthma.