Inhaled corticosteroids are the cornerstone of modern asthma management. Unlike in COPD, where steroid inhalers are reserved for a specific subgroup of patients with an eosinophilic phenotype, international guidelines from the Global Initiative for Asthma recommend inhaled corticosteroids at every step of asthma severity, from mild disease treated on an as-needed basis to severe disease requiring daily maintenance therapy. That ubiquity is precisely why the question of interclass safety differences matters so much in asthma: unlike in COPD, where a concerning safety profile might prompt a clinician to simply withdraw the steroid, withdrawing inhaled corticosteroids from a patient with asthma is not a realistic therapeutic option. Any meaningful difference in pneumonia risk between drug classes would therefore have immediate and unavoidable implications for prescribing decisions worldwide.

The motivation for the study traces back to a robust body of COPD literature. Systematic reviews and meta-analyses have consistently found that budesonide/formoterol combinations are associated with fewer pneumonia events than salmeterol/fluticasone combinations, and subsequent nationwide cohort studies have reinforced the conclusion that fluticasone propionate raises pneumonia risk relative to budesonide in that population. A repeat systematic review published nine years after the first reached the same conclusion, describing a likely clinically important interclass difference. Researchers have even documented downstream economic consequences, with patients treated with fluticasone incurring higher COPD-related, pneumonia-related, and all-cause health care costs than those treated with budesonide. Whether this pharmacological divergence extended to asthma, however, remained genuinely uncertain.

The evidence in asthma was sparse and contradictory. A Swedish cohort found that fluticasone propionate was associated with increased pneumonia risk, but only when compared against patients with asthma who were not using the drug, not against budesonide users. A Canadian quasi-cohort study suggested that both budesonide and fluticasone were linked to elevated pneumonia risk in asthma. Meanwhile, analyses of randomized trial data found no increased pneumonia risk among patients with asthma taking budesonide at all. Compounding the confusion, studies comparing steroid users with non-users in asthma suffer from a fundamental design flaw: because guidelines recommend maintenance inhaled corticosteroids for all moderate to severe disease, such comparisons effectively pit patients with mild asthma against those with severe disease, confounding drug effects with underlying illness severity.

To sidestep that bias, the research team, led by Wang Chun Kwok and James Chung Man Ho of the University of Hong Kong together with colleagues at the University of South Carolina, restricted their analysis to adults with moderate to severe asthma at Global Initiative for Asthma steps 3 to 5, all of whom required regular maintenance inhaled corticosteroid combined with a long-acting beta-agonist. Drawing on the Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority, a network covering more than 90 percent of the territory’s population through 43 hospitals and 123 outpatient clinics, the investigators identified 16,170 eligible patients treated in 2018 and followed them through the end of 2023. Of these, 7,169 patients, or 44.3 percent, were prescribed budesonide; 7,853, or 48.6 percent, received fluticasone propionate; and 1,148, or 7.1 percent, received fluticasone furoate. The cohort had a mean age of 63.1 years, was 35.4 percent male, and included just over half of patients at the most severe treatment step.

The researchers evaluated pneumonia across three tiers of severity: all pneumonia events requiring emergency department visits or hospitalization, pneumonia severe enough to require admission to a medical ward, and pneumonia requiring intensive care unit admission. Over the follow-up period, 1,675 patients, or 10.4 percent of the cohort, developed pneumonia, with nearly identical proportions in the two treatment groups: 10.2 percent among budesonide users and 10.5 percent among fluticasone users. Hospitalized pneumonia affected 8.9 percent of patients overall, while only 42 patients, roughly 0.3 percent, developed pneumonia severe enough to require intensive care.

Across every analytical framework the team applied, the results pointed in the same direction. Using budesonide as the reference group, the adjusted odds ratio for all pneumonia events among fluticasone users was 0.95, with a 95 percent confidence interval of 0.85 to 1.06 and a p-value of 0.32. The adjusted incidence rate ratio was 1.05, and the adjusted hazard ratio for time to first pneumonia event was 0.94, none of which reached statistical significance. For hospitalized pneumonia, the adjusted odds ratio was 0.95 and the adjusted hazard ratio 1.03, both non-significant. Even for the rarest and most severe outcome, pneumonia requiring ICU admission, the adjusted odds ratio of 1.08 and hazard ratio of 1.06 were statistically indistinguishable between the drugs. To guard against confounding, the team also performed propensity score matching on age, sex, treatment step, comorbidity burden, steroid dose, and vaccination status for influenza and pneumococcal disease; the matched analysis reproduced the null result. Subgroup analyses isolating fluticasone furoate and fluticasone propionate individually against budesonide likewise found no significant differences.

Why would an interclass difference so prominent in COPD vanish in asthma? The authors point to fundamental differences in the two patient populations. Patients with COPD who qualify for inhaled corticosteroids tend to be older, heavy smokers with multiple comorbidities and a history of exacerbations driven by respiratory pathogens, making them intrinsically vulnerable to pneumonia. Patients with asthma, by contrast, are generally younger, more often non-smokers, and carry fewer comorbidities, and steroid initiation in asthma is dictated by disease severity rather than exacerbation history. With a baseline pneumonia incidence of only about 10 percent over five years in this asthma cohort, the researchers argue that any true interclass difference, if it exists at all, is likely too small to carry meaningful clinical weight, even in a dataset of this size and with follow-up extending across five years.

The study does carry limitations worth noting. The cohort was overwhelmingly Chinese, which may limit generalizability to other populations, although the authors observe that COPD studies of the same question have yielded consistent findings across countries. Lung function parameters and symptom burden were not directly assessed, with treatment step serving as the recognized proxy for asthma severity, and mild pneumonia cases managed entirely in outpatient settings were excluded because such events are inconsistently coded in medical records, a trade-off the investigators made to preserve diagnostic validity. The study also included only adults, leaving pediatric populations, who face distinct viral pneumonia risks, as a target for future research.

For practicing clinicians, the practical message is straightforward. In moderate to severe asthma, the choice between budesonide-based and fluticasone-based fixed-dose combinations should be guided by asthma control, device preferences, and each drug’s broader side-effect profile, not by fear of pneumonia. The shadow cast by COPD safety data, it turns out, does not extend to the asthma clinic, and patients can take some comfort in knowing that the workhorse anti-inflammatory inhalers they depend on daily differ far less in infection risk than the older literature might have suggested.

Subject of Research: Comparative pneumonia risk of budesonide versus fluticasone inhaled corticosteroids among patients with moderate to severe asthma

Article Title: Comparing Pneumonia Risks of Budesonide with Fluticasone Among Patients with Asthma in Hong Kong: A Territory-Wide Retrospective Study

Article References: Kwok, W. C., Zhou, L., Ma, T. F., Ngai, S. M., Leung, R. Y. H., Tam, T. C. C., & Ho, J. C. M. (2026). Comparing Pneumonia Risks of Budesonide with Fluticasone Among Patients with Asthma in Hong Kong: A Territory-Wide Retrospective Study. Advances in Therapy. https://doi.org/10.1007/s12325-026-03776-0

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03776-0

Keywords: asthma, inhaled corticosteroids, budesonide, fluticasone, pneumonia, COPD, Hong Kong, GINA guidelines, retrospective cohort study, respiratory medicine, drug safety, propensity score matching