Correspondence
Esomeprazole for Asthma
N Engl J Med 2009; 361:206-208July 9, 2009
- Article
To the Editor:
In their article on the use of esomeprazole in patients with poorly controlled asthma (April 9 issue),1 Mastronarde et al. conclude that treatment with proton-pump inhibitors does not improve asthma control in such patients. They also state that despite a high prevalence of asymptomatic gastroesophageal reflux in these patients, the condition is not a likely cause of poorly controlled asthma. In clinical practice, esophageal reflux is usually confirmed by ambulatory pH monitoring with the use of an instrument that assesses reflux episodes in patients with acid reflux but not in those with nonacid reflux.2,3 In addition, acid-reflux events that are identified by pH monitoring probably represent a subgroup of reflux events, and pH monitoring during treatment has been considered to be a low-yield measurement.4 The data reported by Mastronarde et al. show only that acid reflux is not a likely cause of poorly controlled asthma. In the subgroup analyses, no significant interaction was found between gastroesophageal reflux and factors that are known to be associated with risk, including body-mass index, older age, sex, and former smoking status.5 Thus, other possibilities should be explored to explain the high prevalence of asymptomatic gastroesophageal reflux in these patients.
5 ReferencesChing-Sheng Hsu, M.D.
Buddhist Tzu Chi General Hospital, Taipei 231, TaiwanJia-Horng Kao, M.D., Ph.D.
National Taiwan University Hospital, Taipei 100, Taiwan
kaojh@ntu.edu. tw 1
The American Lung Association Asthma Clinical Research Centers
Full Text | Web of Science | Medline2
Canning BJ ,Mazzone SB . Reflex mechanisms in gastroesophageal reflux disease and asthma. Am J Med 2003;115:Suppl 3A:45S-48S
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Kahrilas PJ ,Sifrim D . High-resolution manometry and impedance-pH/manometry: valuable tools in clinical and investigational esophagology. Gastroenterology 2008;135:756-769
CrossRef | Web of Science | Medline4
Poelmans J ,Tack J . Extraoesophageal manifestations of gastro-oesophageal reflux. Gut 2005;54:1492-1499
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Corley DA ,Kubo A ,Zhao W . Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms. Gut 2007;56:756-762
CrossRef | Web of Science | Medline
To the Editor:
Mastronarde et al. conclude that asymptomatic gastroesophageal reflux may not be a frequent cause of poor asthma control. We disagree, because although the use of proton-pump inhibitors diminishes the acidity of the refluxate, it does not reduce either the number or proximal extent of reflux events.1 Microaspiration and esophageal reflexes may still contribute to airway inflammation in patients with asthma who are receiving a high-dose proton-pump inhibitor. Only trials that include a study group undergoing effective reflux control could possibly support the conclusion cited above. As the authors point out, asymptomatic reflux may be responsible for adverse health effects that are unrelated to asthma. Endoscopy with biopsy specimens obtained from the squamocolumnar junction or segments of columnar-lined esophagus would be a more useful approach than pH monitoring for identifying asymptomatic patients who require treatment for gastroesophageal reflux disease (GERD) or surveillance.2
2 ReferencesJohannes Lenglinger, M.D.
Martin Riegler, M.D.
Medical University Vienna, 1090 Vienna, Austria
johannes.lenglinger@meduniwien. ac. at 1
Hemmink GJ ,Bredenoord AJ ,Weusten BL ,Monkelbaan JF ,Timmer R ,Smout AJ . Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: `on' or `off' proton pump inhibitor? Am J Gastroenterol 2008;103:2446-2453
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Lenglinger J ,Eisler M ,Wrba F , et al. Update: histopathology-based definition of gastroesophageal reflux disease and Barrett's esophagus. Eur Surg 2006;40:165-175
CrossRef | Web of Science
To the Editor:
Mastronarde et al. report that esomeprazole had no benefit in patients with poorly controlled asthma and asymptomatic gastroesophageal reflux. An alternative explanation for the lack of efficacy is related to bacterial overgrowth in the stomach, promoted by acid suppression. A gastric pH of more than 4 favors the growth of predominantly gram-negative bacteria in the stomach.1,2 Although proton-pump inhibitors reduce both the volume and acidity of gastric contents, they do not prevent pulmonary microaspiration. In large population studies, the use of acid-suppressing drugs has been associated with the development of community-acquired pneumonia.3,4 We suggest that recurrent microaspiration of bacteria-enriched gastric contents might not have been sufficient to overwhelm pulmonary defense mechanisms but might have sustained lung inflammation in the group of patients with poorly controlled asthma evaluated by Mastronarde et al.
4 ReferencesMatt P. Wise, D.Phil.
Anton G. Saayman, M.B., Ch.B.
Paul J. Frost, M.B., Ch.B.
University Hospital of Wales, Cardiff CF14 4XW, United Kingdom
mattwise@doctors.org. uk 1
Thorens J ,Froehlich F ,Schwizer W , et al. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut 1996;39:54-59
CrossRef | Web of Science | Medline2
Wang K ,Lin HJ ,Tseng GY , et al. The effect of H2-receptor antagonist and proton pump inhibitor on microbial proliferation in the stomach. Hepatogastroenterology 2004;51:1540-1543
Web of Science | Medline3
Laheij RJ ,Sturkenboom MC ,Hassing RJ ,Dieleman J ,Stricker BH ,Jansen JB . Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004;292:1955-1960
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Gulmez SE ,Holm A ,Frederiksen H ,Jensen TG ,Pedersen C ,Hallas J . Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch Intern Med 2007;167:950-955
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Author/Editor Response
Both Hsu and Kao and Lenglinger and Riegler make the valid point that therapy with proton-pump inhibitors is effective only in reducing acid-reflux events. We agree that our study has not ruled out the possibility that nonacid reflux may contribute to asthma events. However, we know of no evidence that nonacid reflux can cause reflex bronchoconstriction in the same way as acid instillation into the esophagus or airways.
We do not address the question of whether body-mass index, age, smoking status, and sex differed in patients with reflux and in those without reflux. We report only that there was no difference in treatment effect in these subgroups. We speculate that the high prevalence of reflux in patients with asthma is a consequence of the underlying disordered lung mechanics, since a similarly high prevalence of acid reflux is also found among patients with cystic fibrosis, those with chronic obstructive pulmonary disease, and those with interstitial fibrosis.1-3
Both the question of whether it is appropriate to screen asymptomatic patients who are at risk for GERD with endoscopy and biopsy and the question of whether asymptomatic patients with Barrett's esophagus should be treated with proton-pump inhibitors, as implied by Lenglinger and Riegler, are beyond the scope of our work and have been addressed by statements from other expert groups.4,5
Wise and colleagues present the interesting hypothesis that bacterial colonization of the gastric contents and microaspiration in patients who are receiving proton-pump inhibitors might lead to worsening asthma. We did not find any convincing evidence that the use of proton-pump inhibitors leads to an increase in the rate of pneumonia or worsening of asthma. However, it is possible that there was a balanced trade-off between beneficial effects and harmful effects of acid suppression.
Robert A. Wise, M.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21224
rwise@jhmi.edu for the Writing Committee of the American Lung Association Asthma Clinical Research Centers
Since publication of this article, Dr. Wise reports receiving consulting fees from Genentech. No further potential conflict of interest relevant to this letter was reported.
5 References1
Button BM ,Roberts S ,Kotsimbos TC , et al. Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation. J Heart Lung Transplant 2005;24:1522-1529
CrossRef | Web of Science | Medline2
Kempainen RR ,Savik K ,Whelan TP ,Dunitz JM ,Herrington CS ,Billings JL . High prevalence of proximal and distal gastroesophageal reflux disease in advanced COPD. Chest 2007;131:1666-1671
CrossRef | Web of Science | Medline3
Raghu G ,Freudenberger TD ,Yang S , et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J 2006;27:136-142
CrossRef | Web of Science | Medline4
Wang KK, Sampliner RE Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol 2008;103:788-797
CrossRef | Web of Science | Medline5
Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology 2008;135(4):1383-91, 1391.e1-1391.e5.
- Citing Articles (1)
Citing Articles
1
SHOAIB FARUQI, IAN D. MOLYNEUX, HOSNIEH FATHI, CAROLINE WRIGHT, RACHAEL THOMPSON, ALYN H. MORICE. (2011) Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study. Respirology 16:7, 1150-1156
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