The findings of our systematic review support a significant association between GORD and asthma. The pooled prevalence values indicate that the prevalence of symptoms of GORD among individuals with asthma is substantially higher (1.6‐fold) than in controls. Similarly, although to a lesser degree, the average prevalence of asthma in individuals with GORD is also higher than in controls (1.2‐fold). The average prevalence of reflux symptoms in adults with asthma was 59%, and the prevalence of erosive oesophagitis was 37%. The average prevalence of GORD diagnosed by pH monitoring was 51%. These values in individuals with asthma are substantially higher than those reported in the general population (10–20% for GORD symptoms, 7–16% for erosive oesophagitis11,14,15,85
). None of the studies reporting the prevalence of GORD in asthma were population based, however, and some of this difference may be because the subjects came from selected primary and secondary care populations.
Although there appears to be a strong association between GORD and asthma, most of the studies included in our analysis were cross‐sectional or case–control in design, and therefore could not give a clear indication of the temporal sequence of these conditions, an important criterion for causal associations. The temporal sequence between GORD and asthma was explored in only two studies. The single study that assessed whether primary care patients with asthma were at an increased risk of subsequently developing GORD found a significantly increased incidence of GORD among those patients compared with controls. That and another study reported the likelihood of GORD preceding asthma, with inconsistent findings. Similarly, the severity–response relationship, another criterion for a causal association, was reported in a minority of studies. Results were again inconsistent, but tended towards a positive correlation when the increasing severity of GORD (based on either increasing symptom frequency or the increasing severity of oesophagitis) was associated with an increase in the prevalence of asthma. In several studies, increasingly severe asthma was associated with an increased prevalence of symptoms of GORD or severity of GORD. As a result, the available evidence does not yet clearly indicate whether GORD precedes asthma, or asthma triggers GORD. The recently published Montreal definition of GORD concludes that GORD can be an “aggravating cofactor” in asthma.1
In addition to statistical association and temporal and severity–response relationships, the controlled introduction or removal of stimuli related to one condition (such as GORD) and the corresponding response (such as the effect on asthma symptoms or pulmonary function) have been used to examine the potential for a causal relationship between the two conditions. This has been investigated using oesophageal acid perfusion testing, but no consistent effect has been found.86
GORD treatment in patients with asthma has also had mixed results. A recent systematic review showed minimal improvement of asthma symptoms with GORD therapy, but no improvement in objective pulmonary function indices.87
Antireflux therapy does, however, allow a reduction in asthma medication use.4
This difference in effect may be related to the fact that pharmacological treatments for GORD change the composition of refluxate without preventing reflux itself, whereas antireflux surgery reduces the number of reflux events. It may be that only some patients are sensitive to acid reflux, or that GORD may affect asthma symptoms but not the pulmonary function measures used in those studies.4,9
For example, increased respiratory effort could be a result of the pain of heartburn causing increased minute ventilation rather than triggering bronchospasm. Even if asthma is GORD related, in some cases there may be resistance to GORD treatment through chronic or irreversible changes.
Our systematic review has both strengths and limitations. We present the most comprehensive systematic review of the epidemiological and clinical literature in this area. In particular, consistent definitions of GORD and asthma provide as true a representation of the prevalence of these diseases as possible. The results of our statistical funnel plot testing argue against the presence of publication bias. We have attempted to minimise selection bias by excluding studies in which investigated asthma patients were referred on the basis of a suspicion of underlying GORD. Most of the studies included in our review were, however, based in secondary and tertiary referral centres and thus have limited generalisability because they are subject to selection bias. In particular, the results from endoscopic and oesophageal pH monitoring studies may have limited generalisability because a large proportion of eligible patients will not give consent for these invasive and sometimes uncomfortable procedures, especially if the procedure is for the purpose of research only. Most studies had no internal controls and this aspect may have led to an overestimation of the association between GORD and asthma, as patients with difficult‐to‐control disease or suspicion of another causative factor may be overrepresented in these populations. Although we did not employ formal scoring of the studies in this review based on quality, we did perform a secondary analysis of studies with greater generalisability including only those that were population based and included internal controls. Six studies measuring the prevalence of asthma in individuals with GORD met these generalisability criteria, and the pooled odds ratios from those studies were indicative of a significant positive association between GORD symptoms and asthma.
Although there are a great many studies reporting the prevalence of GORD in individuals with asthma, and vice versa, we found very few population‐based studies, and very few studies that considered the temporal sequence relationship between the two diseases. This type of epidemiological research would add to our understanding of the link between GORD and asthma. Prospective studies of individuals with GORD that include long‐term follow‐up and systematic testing for the incidence of asthma, and vice versa, would be the most valuable strategy. Further studies should also evaluate the severity–response relationship between the two diseases. Ideally, studies should include internal controls and adequate numbers of patients to avoid type 2 errors. They should also document, using validated and reproducible measures, the severity of asthma, GORD and oesophagitis. Age is an important factor in relation to the onset of asthma. Most asthma diagnoses are made in childhood, whereas most ‘difficult to control' asthma is thought to originate in adult life.88
It would be interesting to investigate whether age plays a role in GORD‐related asthma.
In conclusion, this systematic review quantifies the prevalence of GORD in individuals with asthma, and asthma in GORD, and so contributes to our understanding of the association between these two diseases. It also highlights that, despite the enormous volume of literature that exists on the subject, there is a shortage of high‐quality data. We have identified a clear paucity of data on the direction of the temporal sequence association. Addressing this should be a focus for future epidemiological research in this area.