Male Sex Is Associated With Severe Pulmonary Hypertension and Worse Outcome in Chronic Obstructive Pulmonary Disease Patients Referred for Right Heart Catheterization

Syed Sardar Shah, Attiq Ur Rehman, Safa Amin, Mahnoor Nawaz, Aqdas Laiba

https://doi.org/10.1002/pul2.70317 
 

Letter

Dear Editor,
Respected Zeder et al. report an interesting retrospective analysis of chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) finding that male sex was independently associated with higher mortality risk [1]. We commend the authors for addressing not differences, but note two methodological issues that merit discussion.

Selection bias and generalizability: The cohort was limited to COPD patients referred for right heart catheterization, a highly selected population (likely enriched for advanced disease) [2]. As Avian et al. observed a referral-based COPD-PH cohort “enriched by patients with severe Pulmonary hypertension” may not represent the broader COPD population and this selection bias “may limit the generalizability of the findings” [2]. In similar pulmonary hypertension studies referral bias is a known concern. For example Pi et al. found that patients more likely to benefit from therapy tend to be referred preferentially skewing the sample [3]. In the present study it is unclear how many COPD patients were evaluated or excluded before catheterization. Without a flowchart (as recommended by reporting guidelines) or clearer sampling frame it is difficult to know whether the sex difference extends to unselected COPD-PH. We suggest the authors clarify that conclusions apply chiefly to the right heart catheterization (RHC)-referred cohort and consider providing a CONSORT/STROBE style flow diagram of patient selection. This would help readers gauge how referral patterns (e.g., only catheterizing those suspected of PH) might have influenced the observed sex disparity [2, 3]. In sum the sex effect might be exaggerated if men were referred only when PH was more severe. Stating the limits of external validity explicitly that these findings derive from a specialized referral sample would strengthen the interpretation.

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