Pulmonology · Medical Literature
Association between OLD and IBD: a systematic review and meta-analysis.
Abstract
This study aimed to systematically evaluate the bidirectional association between obstructive lung diseases (OLD) [including chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis] and inflammatory bowel disease (IBD) [including Crohn's disease (CD) and ulcerative colitis (UC)]. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search of the PubMed, Embase, and Cochrane Library databases to identify relevant observational studies published up to 30 June 2025. The included studies were cohort studies, case-control studies, and cross-sectional studies that reported relative risk (RR), hazard ratio (HR), or odds ratio (OR) with 95% confidence intervals (CIs). Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and data were analyzed using random effects or fixed effects models. HRs, RRs, and ORs were analyzed separately according to the direction of association and the disease subtype. A total of 30 observational studies were included. In the estimate-stratified analyses, IBD was associated with an increased risk of subsequent COPD, while COPD was generally associated with increased risks of subsequent CD and UC, although the COPD-to-CD and COPD-to-UC analyses showed substantial heterogeneity. For bronchiectasis, available evidence suggested a positive association with IBD; however, the pooled estimate for IBD and subsequent bronchiectasis was imprecise and should be interpreted with caution. For asthma, the association was more consistent: IBD was associated with an increased risk of subsequent asthma in both HR- and OR-based analyses, and asthma was also associated with subsequent IBD in the HR-based analysis. The bidirectional association was generally stronger and more consistent for CD than for UC. This systematic review and meta-analysis supports positive associations between OLD and IBD, particularly for COPD with the IBD subtypes and for asthma with IBD, especially CD. These associations should be interpreted according to the OLD subtype and the age context. Clinicians should be attentive to respiratory comorbidities in patients with IBD, and appropriate respiratory symptom assessment or screening may help early identification and management. https://www.crd.york.ac.uk/prospero/, identifier CRD420251169706.
Clinical relevance
Is there a statistically significant and consistent bidirectional association between obstructive lung diseases (COPD, asthma, and bronchiectasis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis), and does the direction and magnitude of these associations differ by disease subtype pairing? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis of observational studies (cohort, case-control, and cross-sectional designs), conducted per PRISMA guidelines","setting":"Multinational; affiliated institutions include Xiamen Humanity Hospital of Fujian Medical University (Xiamen, China) and The Second Hospital of Hebei Medical University (Shijiazhuang, China); studies retrieved from PubMed, Embase, and Cochrane Library databases (inception through 30 June 2025)","sampleSize":"30 observational studies included; aggregate patient-level N not reported in available abstract","population":"Adults with obstructive lung disease (COPD, asthma, bronchiectasis) or inflammatory bowel disease (Crohn's disease, ulcerative colitis); studies required to report RR, HR, or OR with 95% CI; studies excluded if both observed and control populations had comorbid conditions capable of confounding the outcome (e.g., coronary heart disease, heart failure)","intervention":"Exposure: presence of OLD (COPD, asthma, or bronchiectasis) assessed for risk of subsequent IBD; or presence of IBD assessed for risk of subsequent OLD — bidirectional framework","comparator":"General population or disease-free controls, depending on the direction of association evaluated in each included study","primaryOutcome":"Relative risk (RR), hazard ratio (HR), or odds ratio (OR) with 95% CI for the association between OLD subtypes and IBD subtypes (CD and UC), analyzed in both directions; HRs, RRs, and ORs pooled separately according to direction of association and disease subtype","followUp":"Not reported (varies by individual included study; not extractable from available abstract)","fundingSource":"Not reported in available abstract"}
Key findings
Thirty observational studies were included. In the COPD–IBD pairing, IBD was associated with an increased risk of subsequent COPD; conversely, COPD was generally associated with increased risks of subsequent Crohn's disease (CD) and ulcerative colitis (UC), although the COPD-to-CD and COPD-to-UC analyses showed substantial heterogeneity. Specific pooled effect sizes (ORs, HRs, RRs), 95% CIs, I² values, and p-values for individual disease pairings are NOT reported in the available abstract and therefore cannot be cited or reproduced here. For the bronchiectasis–IBD pairing, a positive association was suggested, but the pooled estimate for IBD predicting subsequent bronchiectasis was described as imprecise and warranting cautious interpretation. For the asthma–IBD pairing, the association was reported as more consistent: IBD was associated with an increased risk of subsequent asthma in both HR- and OR-based analyses, and asthma was associated with subsequent IBD in the HR-based analysis. Across all pairings, the bidirectional association was described as generally stronger and more consistent for CD than for UC. NNT and NNH are not calculable from the available data. No adverse event data were applicable to this observational synthesis.
Practice implications
This meta-analysis, the first to simultaneously evaluate COPD, asthma, and bronchiectasis against IBD subtypes within a unified bidirectional framework, provides aggregate observational evidence supporting a positive gut–lung axis relationship across multiple OLD–IBD pairings. The study establishes the direction and general consistency of these associations but does not establish causality, and does not quantify the magnitude of clinically actionable absolute risk increments from the available abstract. The asthma–IBD and COPD–IBD associations appear most robust; the bronchiectasis–IBD association is positive but statistically imprecise. The finding that associations are stronger and more consistent for CD than UC may have biologic significance (shared Th1/Th17 immune dysregulation) but requires confirmation. Patients with COPD or asthma who develop new gastrointestinal symptoms and vice versa may warrant earlier cross-specialty evaluation; however, this summary should not be interpreted as a recommendation for routine IBD or OLD screening in asymptomatic patients with the complementary condition without further confirmatory evidence. Limitations of the available abstract preclude reporting of specific pooled estimates, and this summary is based on abstract-level data only. __LIMITATIONS__ 1. Only the abstract is accessible; individual pooled effect sizes, I² statistics, NOS scores, and subgroup analyses by study design or geography are not reportable from available data, representing a critical limitation of this teaching summary. 2. Inherent observational study limitations across all 30 included studies: residual confounding by smoking (a major shared risk factor for COPD and CD, and potentially protective for UC), BMI, antibiotic use, and socioeconomic status cannot be excluded. 3. Substantial heterogeneity explicitly acknowledged in the COPD-to-CD and COPD-to-UC analyses; sources of heterogeneity not fully characterizable from abstract alone. 4. HRs, RRs, and ORs were pooled separately rather than combined, acknowledging methodological heterogeneity across study designs, but this approach also limits direct comparability of magnitude across pairings. 5. Bronchiectasis–IBD pooled estimate described as imprecise, likely reflecting limited number of eligible studies for this pairing. 6. Pooled analyses of cross-sectional and case-control studies cannot establish temporality. 7. Inclusion of non-English studies was excluded per stated criteria, introducing potential language bias. 8. The asthma–UC association was noted as less consistent across estimate types, raising concerns about robustness. 9. Funding source not reported, precluding assessment of potential sponsor-related bias. 10. Generalizability may be limited if most included studies originate from Western or East Asian populations with distinct IBD phenotypes, dietary patterns, and microbiome profiles. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ This 30-study meta-analysis supports a bidirectional positive association between obstructive lung diseases (particularly COPD and asthma) and inflammatory bowel disease, with the association being stronger and more consistent for Crohn's disease than ulcerative colitis. However, substantial heterogeneity in several key analyses, an imprecise bronchiectasis–IBD estimate, inability to establish causality, and unavailability of pooled effect sizes in the accessible abstract all limit immediate practice change. Clinicians managing patients with COPD, asthma, or bronchiectasis should maintain a heightened index of suspicion for comorbid IBD (and vice versa), with prompt cross-specialty referral when suggestive symptoms arise, while awaiting higher-certainty prospective or Mendelian randomization evidence before implementing systematic screening protocols.