Infectious Disease · Medical Literature
Association of asthma and COPD with pertussis risk: A systematic review and meta-analysis.
Abstract
Pertussis, caused by Bordetella pertussis, has resurged globally despite widespread childhood vaccination. With waning immunity, adolescent and adult cases have increased. Patients with asthma and chronic obstructive pulmonary disease (COPD) may be more susceptible due to chronic airway inflammation and impaired immune function, but prior findings are inconsistent. This study aims to systematically evaluate the association between asthma and COPD with the risk of pertussis infection through a meta-analysis. PubMed, Cochrane Library, Embase, Web of Science, CBM, CNKI, VIP, and Wanfang were searched from inception to August 7, 2025. Observational studies reporting adjusted effect measures (OR, RR, HR, IRR) were included. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses (DerSimonian-Laird) were performed when ≥3 studies reported comparable measures; otherwise, results were synthesized descriptively. CRD420251109793. Ten studies (7 cohort, 3 case-control) including >18.6 million participants were analyzed. Asthma was associated with increased pertussis risk (pooled OR = 2.29, 95% CI 1.94-2.69; I2 = 89%), and COPD showed a similar association (pooled OR = 2.00, 95% CI 1.53-2.62; I2 = 94%). A supplementary RR-based analysis supported the asthma association (pooled RR = 3.36, 95% CI 2.77-4.08). Leave-one-out sensitivity analyses indicated robust results. Evidence from existing observational studies suggests that asthma and chronic obstructive pulmonary disease (COPD) are associated with an increased risk of pertussis infection. The findings indicate that clinical identification and vaccination management should be strengthened to reduce preventable infections and the public health burden.
Clinical relevance
Are patients with asthma or COPD at significantly increased risk of pertussis infection compared with those without these conditions, as evaluated through a systematic review and meta-analysis of observational studies? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis of observational studies (7 cohort, 3 case-control); random-effects model (DerSimonian-Laird); descriptive synthesis where 18,600,000 participants across 10 included studies","population":"Adults and adolescents with physician-diagnosed asthma or COPD drawn from observational studies; specific age ranges, disease severity stratification, and vaccination status varied by included study","intervention":"Presence of asthma or COPD as the primary exposure of interest","comparator":"General population or individuals without asthma/COPD, depending on individual study design","primaryOutcome":"Risk of pertussis infection (reported as adjusted OR, RR, HR, or IRR across included studies)","followUp":"Varied by individual included study; aggregate follow-up duration not reported in the abstract","fundingSource":"Not reported in the abstract"}
Key findings
Ten observational studies (7 cohort, 3 case-control) comprising more than 18.6 million participants were pooled. For asthma, the random-effects meta-analysis yielded a pooled OR of 2.29 (95% CI 1.94–2.69), indicating a more than twofold increased odds of pertussis infection compared with non-asthmatic controls; I² = 89%, indicating very high statistical heterogeneity. A supplementary RR-based sensitivity analysis for the asthma association produced a pooled RR of 3.36 (95% CI 2.77–4.08), suggesting the OR-based estimate may understate the relative risk depending on pertussis incidence in the reference population. For COPD, the pooled OR was 2.00 (95% CI 1.53–2.62); I² = 94%, again reflecting very high heterogeneity. Leave-one-out sensitivity analyses were reported to indicate robust results for both associations. P-values for the primary pooled estimates, absolute risk differences, number-needed-to-harm, and data on serious adverse events or pertussis-related complications were not reported in the available abstract. No NNT/NNH can be calculated from the data provided. The magnitude of heterogeneity (I² 89–94%) is a critical quantitative concern and substantially limits confidence in the pooled point estimates.
Practice implications
This meta-analysis provides the largest pooled evidence to date that both asthma and COPD are independently associated with approximately a two- to threefold increased odds or risk of pertussis infection. The consistency of effect direction across all included study designs (cohort and case-control) and the robustness of leave-one-out sensitivity analyses strengthen the plausibility of a true association. However, several important interpretive caveats apply. First, only the abstract was available for this review; complete assessment of methodological rigor, subgroup analyses, publication bias testing, and individual study characteristics is not possible. Second, the I² values of 89% (asthma) and 94% (COPD) indicate profound statistical heterogeneity, meaning the pooled estimates should be interpreted cautiously, as they may mask meaningfully different associations across populations, healthcare systems, pertussis case definitions, or vaccination backgrounds. Third, all included studies are observational; unmeasured confounding — including differential healthcare-seeking behavior, antibiotic use, corticosteroid-related immunosuppression, and background vaccination rates — cannot be excluded as partial explanations for the observed associations. Fourth, causal directionality cannot be inferred from this design: it is biologically plausible that pre-existing airway inflammation and impaired mucociliary clearance in asthma and COPD increase susceptibility, but reverse causality (pertussis contributing to airway disease development) also exists in prior literature. Fifth, the population-level applicability of findings to specific subgroups — including patients on biologic therapy for severe asthma, those with asthma-COPD overlap, or those in low-income countries with different vaccination schedules — was not established. The supplementary RR-based estimate (pooled RR 3.36, 95% CI 2.77–4.08) for asthma diverges substantially from the OR-based estimate, warranting attention if baseline pertussis incidence is non-trivial in the reference population. Whether findings support an immediate change in Tdap booster recommendations for asthma and COPD patients specifically cannot be determined from this meta-analysis alone, as vaccine effectiveness within these populations and incremental benefit over current standard recommendations were not assessed. __LIMITATIONS__ Extremely high statistical heterogeneity (I² = 89% for asthma, 94% for COPD) substantially limits the interpretability and reliability of pooled effect estimates.,All included studies are observational; residual and unmeasured confounding — including differential access to healthcare, corticosteroid use, vaccination status, and healthcare-seeking behavior — cannot be excluded.,Pertussis case ascertainment methodology likely varied across included studies (clinical diagnosis, serological confirmation, PCR, ICD code-based claims), introducing heterogeneity in outcome definition.,The abstract was truncated, preventing full assessment of subgroup analyses, publication bias evaluation (e.g., Egger's test, funnel plots), individual study Newcastle-Ottawa Scale scores, and covariate adjustment strategies.,Funding source was not reported in the abstract; potential for industry sponsorship bias cannot be assessed.,The study does not assess pertussis-related clinical outcomes (hospitalization, complications, mortality) in asthma or COPD populations, limiting translation to clinical severity impact.,Descriptive synthesis was used for COPD when fewer than 3 comparable effect measure types were available, limiting formal quantitative inference for that condition.,Generalizability may be limited by inclusion of Chinese-language databases (CBM, CNKI, VIP, Wanfang), which may introduce geographic, epidemiological, and vaccination-program heterogeneity not applicable to other healthcare settings.,The discrepancy between pooled OR (2.29) and pooled RR (3.36) for asthma suggests that the choice of effect measure meaningfully affects the estimate, and was not fully reconciled in the abstract.,Directionality of the asthma-pertussis relationship is uncertain; prior literature supports bidirectionality, and this meta-analysis cannot resolve whether asthma precedes or follows pertussis susceptibility in individual patients. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ This large meta-analysis (>18.6 million participants, 10 observational studies) found that asthma and COPD are each associated with approximately a twofold or greater increased odds of pertussis infection, with consistent effect direction across study designs and robust sensitivity analyses. However, very high heterogeneity (I² 89–94%), reliance entirely on observational data, and inability to assess vaccine-specific benefit within these populations mean these findings are hypothesis-strengthening rather than immediately practice-changing. Clinicians should consider ensuring pertussis vaccination is current in patients with asthma or COPD, consistent with existing high-risk adult Tdap guidance, while awaiting prospective or interventional data specific to these populations.