Trends in Sepsis-Associated Respiratory Disease Mortality in the United States,1999 to 2023

Abstract

Background

Sepsis-associated respiratory disease, often linked to conditions like pneumonia and acute respiratory distress syndrome (ARDS), is a major contributor to mortality in the United States. Despite its significant impact, national trends and demographic disparities in sepsis-related respiratory deaths, particularly with the influence of the COVID-19 pandemic, remain underexplored.

Study Design and Methods

This retrospective cohort study analyzed CDC WONDER mortality data (1999-2023) for adults aged ≥24 years with death records listing both respiratory disease (ICD-10: J00–J98) and sepsis (ICD-10: A02.1, A22.7, A26.7, A32.7, A40.0–A41.9, A42.7, B37.7) as causes. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Joinpoint regression estimated annual percent changes (APCs) and average annual percent changes (AAPCs) to identify temporal trends, stratified by sex, race/ethnicity, age, region, state, and place of death.

Results

Of 2,090,242 combined respiratory and sepsis deaths, 51.49% were male. AAMRs increased from 29.83 in 1999 to 41.12 in 2023 (AAPC=1.69%, 95% CI: 0.30-3.10; P = .017), with a rise from 1999–2018 (APC=1.86%), a surge from 2018–2021 (APC=11.47%), and a decline from 2021–2023 (APC=-12.82%). Males, American Indian or Alaska Native populations, middle-aged adults (45-64 years), and Western/Southern states showed the largest increases. Most deaths (88.16%) occurred in medical facilities.

Conclusion

Sepsis-associated respiratory mortality rose over 25 years, with a pronounced COVID-19-driven surge (2018-2021) and partial post-2021 decline. Persistent disparities by sex, race, age, and region highlight the need for targeted interventions, improved screening, and equity-focused policies to address systemic vulnerabilities.