PPIs and Uncontrolled Asthma
PPIs and Uncontrolled Asthma
Abstract & commentary
By Malcolm Robinson, MD, FACP, FACG, AGAF, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson reports no financial relationship to this field of study.
Synopsis: Despite a clear-cut association between asthma and gastroesophageal reflux, aggressive PPI treatment had no clinical effect on poorly controlled asthma.
Source: American Lung Association Asthma Clinical Research Centers; Mastronarde JG, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med 2009;360:1487-1499.
Gastroesophageal reflux and asthma are both common, and they often occur concomitantly. Asthma is frequently associated with asymptomatic gastroesophageal reflux (GER). Esophageal pH monitoring confirms the presence of pathological GER in up to 84% of asthmatics. Some previous studies suggest that the treatment of GER might be beneficial in asthma management, and many gastroenterologists have been taught to recommend aggressive proton-pump inhibitor (PPI) therapy in poorly controlled asthmatics who have been shown to have reflux by pH monitoring. Acid definitely can lead to bronchoconstriction, either by microaspiration or via esophagobronchial reflexes. Asthma and some of its medications can cause GER mechanically and otherwise. PPIs, especially in double doses, can dramatically decrease acid production and thus lessen GER. This study at 9 clinical research sites enrolled 412 patients with poorly controlled and well-documented asthma who did not have symptomatic GER (i.e., < 2 episodes of heartburn per week). Patients completed a panoply of recurring questionnaires, and they underwent 24-hour esophageal pH monitoring to document the presence or absence of pathological acid reflux. Asthma exacerbations were carefully documented. Patients received either esomeprazole 20 mg bid or a matching placebo. Each group reported over 84% compliance with study drug self-administration throughout the 6-month trial. Overall, the participants had persistent, poorly controlled symptoms of asthma. Approximately 42%-61% of study patients experienced an episode of poor asthma control, depending on whether increased beta-agonist use wasn't or was one of the criteria. Eighteen percent of patients needed urgent care or a course of prednisone. Annualized poor asthma control by any criteria was similar between esomeprazole and placebo treatment groups. Asthma-related nocturnal awakenings were recorded on 1 or more occasions in approximately half of the patients, and rates were not different between the 2 groups. The presence of documented GER by pH monitoring did not differentiate esomeprazole responders from nonresponders, nor was there any difference in response to PPI vs placebo with the presence or absence of GER symptoms.
Commentary
Previous clinical studies have suggested that there might be some asthma-related benefit associated with effective acid control in asthmatic patients who had exhibited symptomatic GER. Although patients with 2 or more episodes of heartburn weekly were excluded from this study, there were patients who had some heartburn symptoms. Such mildly symptomatic individuals had no better asthma control with esomeprazole bid than placebo recipients. An accompanying editorial correctly pointed out that non-acid reflux wasn't evaluated in this study nor do PPIs necessarily eliminate the reflux of such potentially injurious material. Although there has been some evidence that fundoplication may benefit asthma control in patients with documented GER, such data are not yet compelling. Meanwhile, until different information becomes available, the routine prescription of PPIs to poorly controlled asthmatics (even those with well-documented GER) cannot be justified. Gastroenterologic evaluation of asthmatic patients and any treatment derived from such evaluation dramatically increases the cost of asthma management. Unless the patient requires such evaluation for suspected concomitant esophageal disease, routine GI consultation is not warranted in the routine management of poorly controlled asthma and PPIs will not lead to better asthmatic control in such patients. I might add that endoscopy is almost always useless in the evaluation of suspected extraesophageal manifestations of GER, such as chest pain or laryngitis, since endoscopy is virtually never positive in such cases. The same is true in asthma, and the routine use of endoscopy to evaluate asthmatics unresponsive to routine asthma therapy (unless they have concomitant esophageal symptoms) is to be deplored.
Despite a clear-cut association between asthma and gastroesophageal reflux, aggressive PPI treatment had no clinical effect on poorly controlled asthma.Subscribe Now for Access
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