Gastroesophageal reflux

The prevalence of gastroesophageal reflux disease (GERD) in patients with asthma has been shown to be between 30% and 80% in different studies. (1) GERD has been implicated in a number of respiratory illnesses besides asthma, such as bronchitis, bronchiectasis, pneumonia, idiopathic pulmonary fibrosis, and, most recently, COPD. (2,3) It is not entirely clear whether GERD contributes to the pathophysiology of asthma, occurs as a result of it, or perhaps is entirely incidental to the asthma symptoms. Nevertheless, many studies have identified the presence of GERD as an important factor in the poor control of asthma, and the treatment of GERD may improve respiratory symptoms. (4)

In this issue of CHEST (see page 1159), Leggett et al evaluated the effects of GERD treatment on patients whose asthma was "difficult-to-control." Detailed evaluations were conducted to identify the treatable causes of poor control that included 24-h dual-probe ambulatory esophageal pH probe monitoring in 52 subjects. All subjects received maximal therapy for their asthma, and those with reflux were treated with omeprazole, 40 mg daily. At the end of 12 months, subjects were designated as being therapy-resistant, if their condition had failed to improve, or therapy-responsive, if good asthma control had been achieved. This study found that the presence of GERD in the evaluation phase of the study was similar in the therapy-resistant and therapy-responsive groups (57.1% and 55%, respectively). The authors concluded that the identification and treatment of GERD does not result in the improvement of asthma control in patients with difficult asthma.

It is clearly evident from the study by Leggett et al that the prevalence of GERD in patients with difficult asthma is > 50%. It is somewhat more difficult to agree with the authors that their results point to a failure of anti-GERD therapy in asthmatic patients, especially given the absence of a control group that did not receive proton-pump inhibitor (PPI) therapy. Instead, it would appear that approximately 50% of patients with evidence of GERD found by a pH probe study showed improvement in their difficult-to-control asthma symptoms when they were treated with a PPI.

Asthma is a complex disease with many possible extrinsic and intrinsic triggers, which may contribute differently to symptoms in any individual patient. The prevalence of GERD in the general population is 30 to 40%, and while in some patients asthma and GERD may be present coincidentally, this does not discount the finding in multiple studies (5,6) that a subset of asthmatic patients clearly responds to antireflux therapy. This subset of patients has ranged anywhere from 35 to 73%, and an improved understanding of not only of asthma, but also of GERD will be necessary before we can clearly identify these patients. (5,6)

Leggett et al are correct in pointing out that the majority of patients (78 to 85%) receiving PPI therapy obtain symptom relief and evidence of healing of their esophagitis by endoscopy. (7) However, this clearly does not occur in a proportion of patients, and a recent study (8) found that 50% of patients with GERD, when treated with a PPI in a real-life scenario, continued to have abnormal intraesophageal pH levels, despite achieving adequate symptom control. A possible solution may be to frequently monitor intraesophageal pH and to adjust the dose of the PPI, as was done in the study by Harding et al. (6) This has its practical limitations, but it may be pointed out that Harding et al (6) found improvement in asthma scores in 73% of the patients thus studied. It is plausible that individual patients with asthma related to GERD may require a higher dose of PPI to sufficiently suppress acid reflux, and inadequate treatment of reflux (despite adequate symptom control) may result in a poor outcome.

Keeping in mind that medical therapy for GERD may not provide effective control of reflux, so as to prevent or reduce asthma symptoms, it is interesting to note a study by Sontag et al (9) that looked at the effects of medical vs surgical treatment for GERD in asthmatic patients. Improvement of asthma was noted in 74.9% of patients who received Nissen fundoplication, with only 9.1% of the medically treated group showing improvement. The mean improvement in asthma scores was 43% in the former group vs only 10% in the latter group. Other studies (10,11) have shown similar results. It may be that reducing the contact time of acid (ie, pH, < 4.0) with esophageal mucosa to below a threshold of 4.8% is simply not enough and only the complete cessation of all reflux has a significant effect on asthma symptoms.

Some reports using the novel technique of multi-channel intraluminal impedance technology to assess acid and nonacid reflux may also help our understanding of why the conditions of some asthmatic patients with GERD fail to improve with PPI therapy. It is increasingly evident that nonacid reflux is as prevalent as acid reflux and that the addition of PPI therapy to patients with GERD does not eliminate the former. (12,13) The presence of nonacid reflux, as elicited by impedance recordings, has been recently shown (14) to influence persistent respiratory symptoms in a pediatric population. If this is indeed the case, promotility agents or medications directed at increasing the lower esophageal sphincter tone may need to be added to the antiacid therapy that we give to our asthmatic patients.

In conclusion, the study by Leggett et al is useful in that it points out the limitations of current medical therapy for GERD in improving asthma symptoms. The possible reasons for this failure to improve are several, as pointed out above. It remains to be seen whether a greater understanding of the potential mechanisms by which GERD causes/worsens asthma symptoms will allow us to change the outcomes in patients with asthma, and perhaps in patients with other respiratory illnesses.

REFERENCES

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(12) Tamhankar AP, Peters JH, Portale G, et al. Omeprazole does not reduce gastroesophageal reflux: new insights using multichannel intraluminal impedance technology. J Gastrointest Surg 2004; 8:888-896

(13) Vela MF, Camacho-Lobato L, Srinivasan R, et al. Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole. Gastroenterology 2001; 120:1599-1606

(14) Rosen R, Nurko S. The importance of multichannel intraluminal impedance in the evaluation of children with persistent respiratory symptoms. Am J Gastroenterol 2004; 99:2452-2458

Subin Jain, MBBS, FCCP

Louisville, KY

Dr. Jain is Assistant Professor of Medicine and Director Adult Cystic Fibrosis Program University of Louisville Health Sciences Center.

Dr. Iain has worked for the Speakers Bureau at Pfizer and Glaxo Smith Kline Beecham and has received clinical trial funding from Pfizer.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Subin Jain, MBBS, FCCP, Section of Pulmonary Medicine, Veterans Affairs Medical Center, 800 Zorn Ave, Mail Code 111-i, Louisville, ICY 40206; e-mail: subin.jain@ Louisville.edu

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