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Correspondence |

Gastroesophageal Reflux Disease and Asthma: The Role of Proton Pump Inhibitors FREE TO VIEW

Madhav S. Menon, MD; M. Al-Hajji, MBBS; Alyn Morice, MD
Author and Funding Information

Affiliations: Castle Hill Hospital, Hull, UK,  Veterans Administration, Greater Los Angeles Healthcare System, Sepulveda, CA,  Abbott Laboratories, Abbott Park, IL,  TAP Pharmaceuticals, Inc., Lake Forest, IL

Correspondence to: Madhav S. Menon, MD, University of Hull, Respiratory Medicine, Castle Hill Hospital, Cottingham, Hull HU16 5JQ, UK; e-mail: menondr@gmail.com



Chest. 2006;129(6):1732-1733. doi:10.1378/chest.129.6.1732
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To the Editor:

We read with interest the recent study in CHEST (September 2005)1by Littner et al, who demonstrated a significant reduction in the number of exacerbations of asthma and improvement in quality of life using therapy with antireflux medication. Overall, however, there appeared to be little objective evidence of improvement in asthma. We wonder whether the generally negative findings of the study are due to the selection criteria used to define asthmatic patients with gastroesophageal reflux disease (GERD). Both asthma and GERD are common problems, and it is likely that they selected many patients with simple classic asthma and incidental coexisting acid reflux. In fact, reflux diseases related to airways symptoms are not simply defined, as in their study, by the presence of heartburn. Laryngopharyngeal reflux (LPR)2 is widely recognized as a cause of upper airways symptoms including cough and airway hyperresponsiveness. LPR differs significantly from the symptom complex in a GERD-related heartburn, and we suggest that had a more accurate clinical history of LPR been used to define reflux-related asthma, then the results of the study may have been more positive.

To illustrate the importance of a correct appreciation of reflux disease that is causally linked to asthma, we report the following example. A 31-year-old lifelong nonsmoker presented with worsening control of his asthma. He also gave a history of globus and repeated episodes of loss of voice, which suggested LPR. Heartburn was an occasional symptom. On treatment with omeprazole, 20 mg twice daily for a period of 2 months, the symptoms of LPR settled and his asthma improved. Methacholine challenge showed a provocative concentration of methacholine causing a 20% fall in FEV1 of 0.3 mg/mL on presentation, improving to 9.6 mg/mL after 2 months of twice-daily therapy with omeprazole. As the patient’s symptoms had settled, the patient discontinued therapy with omeprazole. Relapse occurred that was associated with a fall in the provocative concentration of methacholine causing a 20% fall in FEV1 to 1.31 mg/mL. Symptoms of LPR such as globus and dysphonia may be more discriminative of “asthma” responding to therapy with proton pump inhibitors.

Littner, MR, Leung, FW, Ballard, ED, et al (2005) Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptomsChest128,1128-1135. [CrossRef] [PubMed]
 
Koufman, J, Sataloff, RT, Toohill, R Laryngopharyngeal reflux: consensus conference report.J Voice1996;10,215-216. [CrossRef] [PubMed]
 
To the Editor:

The letter by Drs. Menon and Morice reporting a case of laryngopharyngeal reflux (LPR) in an asthmatic patient raises questions about the cause of the patient’s symptoms and how best to identify asthmatic patients who are likely to benefit from acid suppressive therapy. First, we suggest that the most likely cause of the patient’s symptoms was frequent intermittent reflux of acid producing exacerbations of globus, hoarseness, presumably cough, and deterioration of asthma. The most likely effect of the proton pump inhibitor (PPI) was to inhibit acid production, reduce the degree of acid reflux, and thereby improve the upper airway and asthma symptoms. This sequence of symptoms and response is consistent with the main finding of our study, which was a reduction in asthma exacerbations. The main difference was the prominence of heartburn in our study and the prominence of upper airway symptoms in the reported case. However, many patients in our study also had symptoms of globus, hoarseness, and cough, and the patient in the reported case also had heartburn.

Second, the severity of acid reflux and gastroesophageal reflux (GER) symptoms may predict a greater degree of improvement in asthmatic symptoms and pulmonary function in response to a PPI.13 Drs. Menon and Morice suggest that the symptom complex associated with LPR in asthmatics with ongoing asthma symptoms would also predict symptomatic and pulmonary function improvement with a PPI. However, atypical GER symptoms such as hoarseness compared to typical GER symptoms such as heartburn have not been obviously more successful in identifying patients whose asthma symptoms are likely to respond to a PPI.3Our study also examined cough, globus, and hoarseness and found no difference in these symptoms with a PPI.4In addition, several randomized, placebo-controlled trials57 have been inconsistent in demonstrating that a PPI resolves symptoms of LPR. These various observations indirectly suggest that LPR symptoms would not have been substantially more discriminatory than other symptoms such as heartburn in identifying patients whose asthma symptoms and pulmonary function would benefit from a PPI. However, to clarify the role of treatment of LPR to reduce asthma symptoms and improve pulmonary function, a properly performed randomized controlled trial is needed.

Our study suggested that patients with GER whose asthma is treated with an inhaled corticosteroid plus other long-term asthma control therapy such as long-acting β2-agonists are more likely to have a reduction in asthma exacerbations and improvement in asthma-specific quality of life with a PPI.4 A more recent study2 found that asthmatics receiving a long-acting β2-agonist in addition to an inhaled corticosteroid and/or a leukotriene modifier are more likely to have improvement in morning and evening peak expiratory flow. Clearly, as stated in the penultimate paragraph of our article, more work is needed to identify patients whose asthma is most likely to benefit from acid suppressive therapy.

References
Kiljander, T, Salomaa, ER, Hietanen, E, et al Asthma and gastro-oesophageal reflux: can the response to anti-reflux therapy be predicted?Respir Med2001;95,387-392. [CrossRef] [PubMed]
 
Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med 2006 (in press).
 
Harding, SM, Richter, JE, Guzzo, MR, et al Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome.Am J Med1996;100,395-405. [CrossRef] [PubMed]
 
Littner, MR, Leung, FW, Ballard, ED, II, et al Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms.Chest2005;128,1128-1135. [CrossRef] [PubMed]
 
Havas, T, Huang, S, Levy, M, et al Posterior pharyngolaryngitis: double-blind, randomised placebo-controlled trial of proton pump inhibitor therapy.Aust J Otolaryngol1999;3,243-246
 
El-Serag, HB, Lee, P, Buchner, A, et al Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial.Am J Gastroenterol2001;96,979-983. [CrossRef] [PubMed]
 
Noordzij, JP, Khidr, A, Evans, BA, et al Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo controlled, randomized, double-blind study.Laryngoscope2001;111,2147-2151. [CrossRef] [PubMed]
 

Figures

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References

Littner, MR, Leung, FW, Ballard, ED, et al (2005) Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptomsChest128,1128-1135. [CrossRef] [PubMed]
 
Koufman, J, Sataloff, RT, Toohill, R Laryngopharyngeal reflux: consensus conference report.J Voice1996;10,215-216. [CrossRef] [PubMed]
 
Kiljander, T, Salomaa, ER, Hietanen, E, et al Asthma and gastro-oesophageal reflux: can the response to anti-reflux therapy be predicted?Respir Med2001;95,387-392. [CrossRef] [PubMed]
 
Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med 2006 (in press).
 
Harding, SM, Richter, JE, Guzzo, MR, et al Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome.Am J Med1996;100,395-405. [CrossRef] [PubMed]
 
Littner, MR, Leung, FW, Ballard, ED, II, et al Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms.Chest2005;128,1128-1135. [CrossRef] [PubMed]
 
Havas, T, Huang, S, Levy, M, et al Posterior pharyngolaryngitis: double-blind, randomised placebo-controlled trial of proton pump inhibitor therapy.Aust J Otolaryngol1999;3,243-246
 
El-Serag, HB, Lee, P, Buchner, A, et al Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial.Am J Gastroenterol2001;96,979-983. [CrossRef] [PubMed]
 
Noordzij, JP, Khidr, A, Evans, BA, et al Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo controlled, randomized, double-blind study.Laryngoscope2001;111,2147-2151. [CrossRef] [PubMed]
 
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