Background
People with asthma are three times more likely to have reflux (where acid from the stomach comes back up the oesophagus) than healthy people. Reflux may be a trigger for asthma, or alternatively, asthma may trigger reflux. Treatments that can help reflux include drugs that reduce stomach acids or improve stomach emptying. Research studies have found inconsistent benefit for improvement in asthma symptoms or lung function. Although asthma may be improved in some people, it was not possible to predict who might benefit.
Review question
This review aimed to investigate if treatment for gastro-oesophageal reflux disease (GORD) would benefit adults and children with asthma.
Study characteristics
To answer this question, we looked for all randomised controlled trials (RCTs) comparing GORD treatment (medical and/or surgical intervention) to placebo or no treatment in adults or children who had been diagnosed as having both asthma and GORD.
Key results
We found 23 studies for inclusion in this review. These studies focused mostly on adults, with a total of 2872 participants involved. Only two studies assessed the effects of treating GORD in children, and two investigated the benefits of using surgery for GORD to improve asthma control. According to evidence presented in this review, using medication to treat GORD in people with asthma probably reduces the amount of rescue medication needed to control asthma symptoms and also probably improves lung function to a small degree. It is important to note that these benefits may be too small to make an impact on the daily life of someone with asthma.
Based on available evidence, this review is not able to show if there was clear benefit of treatment for asthma symptoms for quality of life, or how many flare-ups are experienced by a person with asthma. Because researchers used many different approaches to treating people who participated in their studies, it is also difficult to suggest whether a specific type of medication regimen would be best. Not many of the included studies mentioned negative effects of being involved in the research. Those that did reported that any negative effects during the research period happened equally in both treatment and placebo/no treatment groups.
We did not find any data in the included studies related to hospital admissions nor to emergency room or unscheduled doctor visits.
Certainty of evidence
Overall certainty of the evidence was assessed as moderate to low. This is mainly because the studies that were included in this review were very different in the way they approached the research, which produced variable results.
Bottom line
Moderate-certainty evidence (as some of the included studies were poorly described) shows that with medical treatment for GORD, people with asthma may experience a small improvement in their lung function and may be able to reduce their need to use rescue medications. However, the impact of treatment for GORD on events such as asthma flare-ups, symptoms, or the need to go to the hospital or consult a doctor is uncertain. Additionally, there was not enough evidence, with only two studies reporting on each, to assess surgical treatment or the effectiveness of GORD treatment in children.
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.
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.
To evaluate the effectiveness of GORD treatment in adults and children with asthma, in terms of its benefits for asthma.
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.
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.
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.
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.