Chronic Cough Due to Gastroesophageal Reflux Disease: Treatment

Chronic Cough Due to Gastroesophageal Reflux Disease: TreatmentFor patients with chronic cough, the following tests are not routinely recommended to link cough with GERD: (a) assessing for lipidladen macrophages in BAL fluid and induced sputum, because this test has not been studied in patients with chronic cough and because a positive test result is not specific for aspiration; (b) exhaled nitric oxide measurements, because they do not appear to be helpful in diagnosing cough due to GERD; (c) a Bernstein test, because a negative Bernstein test result cannot be used to exclude the diagnosis of cough due to GERD; and (d) inhaled tussigenic challenges with capsaicin, because they are not specific for coughs due to GERD and because the test result can be positive in patients with GERD without cough. Level of evidence, low; benefit, conflicting; grade of recommendation, I Here

Based on the apparent heterogeneity of patient populations with differing pathogenetic mechanisms and differing risk factors that can adversely affect GERD, it is not likely that all patients will theoretically respond to the same treatment. A review of the literature on the treatment of cough due to GERD, which is summarized in Table 2, supports this statement. The review suggests the following: that when medical therapy is effective, some patients with cough due to GERD will favorably respond to acid suppression therapy alone>; that proton pump inhibition may be effective when H2-antagonism has been ineffective; that prokinetic therapy and diet, when added to proton pump inhibition, may be effective when proton pump inhibition alone has been ineffective; that while medial therapy may eliminate cough within 8 weeks in some patients, it may still lead to a favorable outcome despite taking months before it starts to work>; and that cough in other patients will only improve or be eliminated with antireflux surgery, after cough in these patients has failed to improve with maximal medical therapy that includes an intensive antireflux diet, maximum acid suppression, and prokinetic therapy. These findings have come from prospective and retrospective before-and-after intervention trials, and from two imperfectly designed (see Table 2), prospective, double-blind, randomized placebo-controlled trials, that have compared the effects of omeprazole with placebo.

Table 2—Evidence for the Treatment of Chronic Cough Due to GERD

Treatment Dosing Study ID Patients,No. Age Results
Diet + LS, antacids, cimetidine qid300 mg hs Prospective, before/after intervention, uncontrolled, unblinded 5 67.2 yr Cough cured 100%
Diet + LS, metoclopramide and/ or H£-blockers Not stated Not stated Prospective, before/after intervention, uncontrolled, unblinded 9 52 ± 11 yr Cough cured 100%; time to cure, 161 ± 74 d
Diet + LS, metoclopramide and/ or H2-blockers Not stated Not stated Prospective, before/after intervention, uncontrolled, unblinded 28 56 ± 12 yr Cough cured 100%; time to cure, 179 ± 205 d
Diet + LS, antacids, metoclopramide, cimetidine, surgery Not stated, 10 mg tid300, mg qid Retrospective, before/after intervention, uncontrolled, unblinded 20 Adult Cough cured 90%; 70% cured with medication in 3 mo, 20% with surgery
Diet + LS, omeprazole or surgery 20-40 mg/d Prospective, before/after intervention, uncontrolled, unblinded 25 Adult Cough or hoarseness improved in 80%; only patients without heartburn had full resolution of cough
Cisapride,!domperidone 0.2 mg/kg tid 0.2 mg/kg tid Prospective, before/after intervention, uncontrolled, unblinded 55 Infants Cough improved 64.5%; no significant difference between drugs
Domperidone 2 mg/kg/d divided qid Prospective, before/after intervention, uncontrolled, unblinded 18 1 mo to 12.7 yr Cough improved 100% (p < 0.05)
Diet Prokinetic and/or H2-blockers Not stated Not stated Prospective, before/after intervention, uncontrolled, unblinded 20 yr17±

8

5

Cough cured in 97%; productive coughs in all patients
Surgery Prospective, before/after intervention, uncontrolled, unblinded 17 Adult 100% cure if esophageal motility was normal
Surgery Prospective, before/after intervention, uncontrolled, unblinded 5 Adult 100% cured in highly selected patients who were thought to be aspirators; only 5/100 patients were suitable
Surgery Prospective, before/after intervention, uncontrolled, unblinded 13 Adult Cough cured in 84.6%; only 13/140 patients considered suitable
Diet, prokinetics and/or PPIs Cisapride or metoclopra-pramide 10 mg qid, omeprazole up to 40 mg and lansoprazole, 30 mg bid Retrospective, before/after intervention, uncontrolled, unblinded 56 57 yr Cough cured or improved in 86%; 17/56 had not responded to H2-blockers; 5/56 required up to 8 weeks to improve, and 1/55 up to 12 weeks; 24/56 only required PPIs, 18/56 required PPIs plus prokinetics
Omeprazole Omeprazole, 40 mg/d, or placebo for 8 wk Prospective, double-blind, randomized, placebo-controlled, cross-over trial 29 Adults Cough improved (p = 0.02) with omeprazole compared to placebo; proper statistics were not utilized to analyze crossover design
Omeprazole Omeprazole, 40 mg bid, or placebo for 12 wk Prospective, double-blind, randomized, placebo-controlled trial 23 Adults Of 17 patients with abnormal findings of 24-h esophageal pH monitoring studies, 6 significantly improved after drug therapy compared to placebo; it is not known whether the remaining patients also had GERD because no further testing was performed and treatment was not intensified
Surgery Prospective, before/after intervention, uncontrolled, unblinded 119 Adults Of 119 patients with inadequate control of respiratory symptoms with medical therapy, 42 had chronic cough as chief complaint; surgery cured or improved cough in 85% at 6 mo after surgery
Surgery Prospective before/after intervention, uncontrolled, unblinded 35 Adults Of 35 patients with chronic cough, cough improved or was cured in 56% at 12 mo; patients did not appear to have been selected based upon lack of response to medical treatment
Surgery Prospective before/after intervention, uncontrolled, unblinded 21 Adults At 1 yr following surgery, cough had significantly improved (p < 0.01); improvement was reported by 86% of patients, with complete resolution in 62%; prior to surgery, cough had failed to improve with intensive medical therapy
Surgery Prospective before/after intervention, uncontrolled, unblinded 8 54.2 ± 10.8 yr At 1 yr following surgery, cough had significantly improved (p < 0.001); all patients reported improvement in cough; prior to surgery, patients had failed to respond to maximal medical therapy even though there was total/near-total elimination of esophageal acid

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