Comorbid COPD as a major independent predictor of post-discharge morbidity in adults hospitalized for sickle cell acute chest syndrome: A national propensity-matched analysis

Abstract Introduction Patients with sickle cell disease (SCD) experience a state of endothelial dysfunction and hypercoagulability, which elevates their risk for cardiovascular complications, including acute chest syndrome (ACS). The presentation of ACS in this population is associated with significant morbidity and mortality. Chronic obstructive pulmonary disease (COPD), a common comorbidity, shares underlying inflammatory pathways and may worsen outcomes by compounding cardiopulmonary stress. However, the specific impact of comorbid COPD on post-ACS outcomes within the SCD population has not been extensively studied on a national level. A clear understanding of this relationship is critical for risk stratification and the development of targeted management strategies. We hypothesized that among patients with SCD hospitalized for ACS, the presence of comorbid COPD is associated with an increased risk of adverse in-hospital outcomes and subsequent readmissions. Methods We conducted a retrospective cohort study utilizing the Nationwide Readmissions Database (NRD) from 2018 to 2022. The NRD is the largest all-payer inpatient database in the United States, enabling a robust analysis of national readmission patterns. We identified all adult hospitalizations with a principal diagnosis of acute chest syndrome (ACS) and a concurrent diagnosis of sickle cell disease (SCD) using International Classification of Diseases, Tenth Revision (ICD-10) codes. The primary exposure was a co-existing diagnosis of COPD. To mitigate selection bias and control for confounding variables, we performed 1:1 propensity score matching (PSM) with a caliper of 0.2. The model included a comprehensive set of covariates: patient demographics (age, sex), hospital characteristics (teaching status, bed size), and markers of illness severity (APR-DRG severity score). After matching, we assessed covariate balance using standardized mean differences. The primary outcomes were rates of all-cause, all-payer hospital readmission at 30-, 60-, and 90-day post-discharge. Secondary outcomes included in-hospital mortality, total length of stay (LOS), and total hospital charges. We employed survey-weighted Cox proportional hazards models to analyze the time to readmission. We used survey-weighted generalized linear models (logit for mortality, gamma with a log link for length of stay and charges) to evaluate in-hospital outcomes in the matched cohort, accounting for the complex survey design of the NRD. All statistical analyses were conducted using Stata 19.5. Results Our initial analysis identified 19,064 hospitalizations for ACS in adult patients with SCD, of which 5,115 (26.8%) had a concurrent diagnosis of COPD. Propensity score matching successfully created a well-balanced cohort of 5,115 patient pairs. In the matched analysis, a diagnosis of COPD was not associated with a statistically significant difference in in-hospital mortality (adjusted Odds Ratio [aOR]: 0.85, 95% CI: 0.62-1.15, p = 0.280). However, COPD was a significant and independent predictor of greater resource utilization, including a longer length of stay (adjusted Rate Ratio [aRR]: 1.09, 95% CI: 1.04-1.13, p < 0.001) and higher total hospital charges (aRR: 1.07, 95% CI: 1.00-1.15, p = 0.050), which reached statistical significance. Notably, the presence of COPD was a significant predictor of post-discharge readmission. Patients with COPD had a significantly higher hazard of 30-day readmission (adjusted Hazard Ratio [aHR]: 1.26, 95% CI: 1.04-1.52, p=0.018), 60-day readmission (aHR: 1.33, 95% CI: 1.14-1.55, p<0.001), and 90-day readmission (aHR: 1.35, 95% CI: 1.19-1.53, p<0.001). Conclusion In this extensive, nationwide analysis of adults with SCD hospitalized for ACS, although comorbid COPD did not increase the risk of dying in the hospital, it was significantly associated withincreased length of stay, higher costs, and a markedly higher hazard of readmission within 90 days of discharge. These findings highlight a critical interaction between SCD and COPD that leads to a significant clinical and economic burden. The results underscore the need for heightened surveillance and targeted interventions for this high-risk subgroup. Future strategies should focus on optimizing cardiopulmonary care during index admission and implementing enhanced post-discharge management, such as multidisciplinary follow-up and care coordination, to mitigate readmission risk and improve long-term outcomes for these vulnerable patients.