Acid reflux a gateway to multiple diseases

Gastroesophageal reflux disease (GERD) may predispose patients to developing other diseases, as reported in a study. For the most part, it puts the whammy on chronic obstructive pulmonary disorder (COPD), doubling exacerbations, and raises the risk of oesophageal adenocarcinoma (OAC).

The findings support guidelines outlining the contribution of GERD to the development of COPD and indicate that acid reflux may play an important role in the aetiology of OAC, according to the investigators. [Mayo Clin Proc 2018;93:1488-1502; Am J Respir Crit Care Med 2017;195:557-582]

That being said, controlling GERD may contribute to the control of the COPD and improve prognosis, as well as be beneficial in deterring OAC development, they added.

The investigators synthesized data from 10 systematic reviews and meta-analyses to assess the strength and validity of current evidence regarding the association between GERD and diverse diseases. These comprised a total of 92 individual studies, 14 of which were cross-sectional and 78 were case-control. The number of cases ranged from 82 to 36,503, while the number of participants varied between 198 and 254,978. [BMJ Open 2020;10:e038450]

Aside from COPD exacerbation and OAC, other diseases linked to GERD were idiopathic pulmonary fibrosis, asthma, chronic rhinosinusitis, laryngeal malignancy, Barrett’s oesophagus, nonalcoholic fatty liver disease, obstructive sleep apnea–hypopnoea syndrome, and pharyngeal cancer.

Based on GRADE approach, the certainty of evidence was high for the association between GERD and elevated risk of COPD exacerbation (odds ratio [OR], 5.37, 95 percent confidence interval [CI], 2.71–10.64) and higher prevalence of OAC (OR, 4.57, 95 percent CI, 3.89–5.36). Meanwhile, it was moderate for the association between GERD and increased chronic rhinosinusitis prevalence (OR, 2.16, 95 percent CI, 1.37–3.48).

The methodological quality, assessed using the AMSTAR 2 approach, was high for 20 percent of meta-analyses, moderate for 10 percent, low for 40 percent, and critically low for 30 percent. Eight meta-analyses reported significant heterogeneity, while another two showed evidence of publication bias.

“The oesophagus is located within the chest area and connects the throat and stomach cavities with the neighbouring nondigestive tract organs, namely the larynx, heart, and respiratory tract,” according to the investigators.

“Reflux of stomach contents (eg, pepsin, gastric acid, or bile) into the oesophagus may damage the specialized physiological structure of neighbouring organs. Therefore, GERD is a risk factor for multiple diseases,” they pointed out.

With respect to COPD and OAC, the investigators noted that proximal acidic reflux may trigger COPD exacerbations and contribute to pulmonary oxidative stress. Additionally, gastric contents (eg, bile acids, pepsin, and trypsin) stimulate interleukin-8 production from oesophageal epithelial cells, which in turn promotes epithelial cell transformation and cancer cell proliferation. [Pediatr Pulmonol 2006;41:67-73; Respir Med 2016;115:20-25; Cancer Cell Int 2019;19:64; Nihon Rinsho 2007;65:813-821]

“Further investigations using systematic reviews and meta-analyses of high methodological quality that include prospective large cohort studies and adjusted confounders are warranted,” they said.