The immunopathology of asthma is complex. Although classic type 2 helper T-cell (Th2) immune responses are one major mechanism underlying asthma, other contributing mechanisms include activation of IL-17–mediated neutrophilic inflammation and innate Toll-like receptor responses to pathogens. These pathways are important to normal host response to pathogens and may potentially benefit patients with asthma. Greater mast cell degranulation and release of mediators, such as tumor necrosis factor-a and IL-6, may benefit outcomes of infections through enhanced neutrophil influx and killing of bacteria (1). Parasitic worms, which drive Th2 polarization, enhance clearance of Klebsiella in a septic peritonitis murine model and improve survival (2). In humans, circulating Th2 levels are higher among survivors as compared with matched patients who died after Staphylococcus aureus infection in a case–control study (3). Non-Th2 pathways also likely benefit patients with asthma. Toll-like receptors are linked to asthma and are primary sensors of invading pathogens (4–6). Heightened innate responses would enable faster pathogen clearance. Cecal puncture–induced sepsis in mice deficient in IL-17 receptor leads to less neutrophil recruitment into the peritoneal cavity, greater spread of infection, greater inflammatory response, and increased mortality as compared with wild-type mice (7). We hypothesized that individuals with asthma, characterized by activation of proinflammatory pathways, have a lower incidence of sepsis and/or sepsis-related mortality. We investigated this using the 2012 Healthcare Cost and Utilization Project–National Inpatient Sample (NIS), and validated results with additional data sources: 2007, 2008, and 2011 NIS and Cleveland Clinic Health System (CCHS) admissions between 2010 and 2014 for patients hospitalized with pneumonia, urinary tract infection (UTI), or skin and soft tissue infection (SSTI). The NIS is the largest all-payer inpatient database available in the United States and an important component of the Healthcare Cost and Utilization Project. In accordance with data use agreement, we analyzed a 20% weighted sample of US hospital discharges, constituting more than 7 million discharges in each year. Deidentified data of patients hospitalized at the Cleveland Clinic from 2010 through 2014 were extracted using eResearch (Cleveland Clinic Enterprise Data Center, Cleveland, OH). The study was approved by the Cleveland Clinic Institution Review Board.

The impact of asthma on rates of septicemia, sepsis, severe sepsis, and septic shock was determined among patients hospitalized for any of three common infections, that is, pneumonia, UTI, and SSTI. Adjusted effects in models account for patient’s age, sex, race, median household income quartiles for ZIP code, hospital location, and the modified Elixhauser comorbidity index, which summarizes disease burden and predicts hospital mortality (8). In 2008, the Centers for Disease Control and Prevention (CDC) recommended pneumococcal vaccination of patients with asthma and who are 65 years of age and younger, which could introduce endogeneity bias, that is, through change in clinical practice. Thus we analyzed data sets from before (2007), during (2008), and after (2011, 2012) the CDC recommendation. The NIS contains up to 25 diagnoses recorded according