Pharmacological and surgical interventions for the treatment of gastro-oesophageal reflux in adults and children with asthma

Background Asthma and gastro-oesophageal reflux disease (GORD) are common medical conditions that frequently co-exist. GORD has been postulated as a trigger for asthma; however, evidence remains conflicting. Proposed mechanisms by which GORD causes asthma include direct airway irritation from micro-aspiration and vagally mediated oesophagobronchial reflux. Furthermore, asthma might precipitate GORD. Thus a temporal association between the two does not establish that GORD triggers asthma. Objectives To evaluate the eHectiveness of GORD treatment in adults and children with asthma, in terms of its benefits for asthma. Search methods The Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and online clinical trial databases were searched. The most recent search was conducted on 23 June 2020. Selection criteria We included randomised controlled trials comparing treatment of GORD in adults and children with a diagnosis of both asthma and GORD versus no treatment or placebo. Data collection and analysis A combination of two independent review authors extracted study data and assessed trial quality. The primary outcome of interest for this review was acute asthma exacerbation as reported by trialists. Main results The systematic search yielded a total of 3354 citations; 23 studies (n = 2872 participants) were suitable for inclusion. Included studies reported data from participants in 25 different countries across Europe, North and South America, Asia, Australia, and the Middle East. Participants included in this review had moderate to severe asthma and a diagnosis of GORD and were predominantly adults presenting to a clinic for treatment. Only two studies assessed effects of intervention on children, and two assessed the impact of surgical intervention. The remainder were concerned with medical intervention using a variety of dosing protocols. There was an uncertain reduction in the number of participants experiencing one or more moderate/severe asthma exacerbations with medical treatment for GORD (odds ratio 0.53, 95% confidence interval (CI) 0.17 to 1.63; 1168 participants, 2 studies; low-certainty evidence). None of the included studies reported data related to the other primary outcomes for this review: hospital admissions, emergency department visits, and unscheduled doctor visits. Medical treatment for GORD probably improved forced expiratory volume in one second (FEV1) by a small amount (mean difference (MD) 0.10 L, 95% CI 0.05 to 0.15; 1333 participants, 7 studies; moderate-certainty evidence) as well as use of rescue medications (MD -0.71 puffs per day, 95% CI -1.20 to -0.22; 239 participants, 2 studies; moderate-certainty evidence). However, the benefit of GORD treatment for morning peak expiratory flow rate was uncertain (MD 6.02 L/min, 95% CI 0.56 to 11.47; 1262 participants, 5 studies). It is important to note that these mean improvements did not reach clinical importance. The benefit of GORD treatment for outcomes synthesised narratively including benefits of treatment for asthma symptoms, quality of life, and treatment preference was likewise uncertain. Data related to adverse events with intervention were generally underreported by the included studies, and those that were available indicated similar rates regardless of allocation to treatment or placebo. Authors' conclusions Effects of GORD treatment on the primary outcomes of number of people experiencing one or more exacerbations and hospital utilisation remain uncertain. Medical treatment for GORD in people with asthma may provide small benefit for a number of secondary outcomes related to asthma management. This review determined with moderate certainty that with treatment, lung function measures improved slightly, and use of rescue medications for asthma control was reduced. Further, evidence is insufficient to assess results in children, or to compare surgery versus medical therapy.