The analysis used data from ORESTES, a multicenter, longitudinal, retrospective observational study registered as NCT06321731. Eligible patients were aged 40 years or older, had a confirmed COPD diagnosis, initiated budesonide/glycopyrronium/formoterol fumarate dihydrate before June 2023 and had at least 12 months of clinical data before initiation. The observation period covered the 12 months before treatment and up to 12 months afterward, ending earlier if a patient discontinued therapy, was lost to follow-up or died. Patients were identified retrospectively from electronic medical records, and treatment decisions were made by physicians during routine care rather than according to a research protocol. At 12 months, 89.3% of the cohort were persistent with triple therapy; 6.6% had discontinued treatment, 3.8% had died and 0.4% were lost to follow-up.

The cohort had a mean age of 70.17 years, a mean time since COPD diagnosis of 7.32 years, and several indicators of substantial disease burden. A total of 66.4% of patients had experienced at least one exacerbation during the preceding year, 72.3% were classified as having a high-risk GesEPOC phenotype, 78.4% had modified Medical Research Council dyspnea scores of at least 2, and 50.9% were classified as GOLD E. Before triple therapy, annualized rates were 0.53 hospitalizations, 4.47 hospitalized days, 0.71 emergency room admissions, 1.89 primary care visits and 1.28 specialist visits per patient. Emergency visits were treated as a separate category and did not include episodes resulting in hospitalization. Rescue-medication use was based on prescriptions documented as actually used by patients rather than prescriptions merely issued.

After budesonide/glycopyrronium/formoterol initiation, annualized hospitalization rates declined to 0.47 per patient and hospitalized days to 4.06, corresponding to reductions of 12.9% and 9.2%. Emergency room admissions decreased to 0.62, a 12.0% reduction, while primary care visits fell to 1.80, or 4.9%. Specialist visits moved in the opposite direction, increasing 17.5% to 1.51 per patient. The investigators said this rise might partly reflect the hospital-based study design and continued follow-up in specialist respiratory clinics, but the observational records could not establish whether closer follow-up caused any of the changes in acute care. The annualized rate of actual short-acting beta-2 agonist use fell from 1.19 to 0.89 prescriptions per patient, a decrease of 25.5%.

Researchers translated these utilization measures into economic estimates from the perspective of the Spanish National Health System. Published Spanish unit costs were updated to 2026 values using the general Consumer Price Index from Spain’s National Statistics Institute. The functional unit for the estimates was one patient over 12 months, and unit costs were applied to cohort-level annualized measures of resource use. Before triple-therapy initiation, estimated healthcare resource costs averaged €2,599.46 per patient per year. Hospitalizations accounted for 88.5% of that amount, or €2,300.13, while emergency room admissions accounted for €101.57, primary care visits for €53.57 and specialist visits for €144.19. Following initiation, the overall estimate decreased by €200.11 to €2,399.35 per patient. Hospitalization costs produced a €210.59 reduction, emergency room costs a €12.14 reduction and primary care costs a €2.61 reduction, while specialist visit costs increased by €25.22.

The environmental model expressed resource use in kilograms of carbon-dioxide equivalent, combining published emission factors for hospitalizations, emergency room admissions, primary and specialist visits, patient transport and actual short-acting beta-2 agonist use. Transport-related emissions were estimated separately with Spanish travel-distance data and transport assumptions because the proxy distances used in the multinational framework were not considered sufficiently representative. Before initiation, total emissions associated with the selected care components were estimated at 245.43 kg CO2e per patient per year. Hospitalizations contributed 79.0%, or 193.96 kg CO2e, and actual rescue-medication use contributed 11.1%, or 27.27 kg CO2e. Emergency room admissions accounted for 5.2%, primary care visits 1.4% and specialist visits 3.2%. After initiation, the total fell by 25.16 kg CO2e to 220.27 kg CO2e.

Hospitalization-related emissions declined by 17.88 kg CO2e after treatment initiation, rescue-medication emissions by 6.94 kg CO2e, emergency room emissions by 1.53 kg CO2e and primary care emissions by 0.17 kg CO2e. Specialist-visit emissions increased by 1.37 kg CO2e. The emissions estimate was then tested under alternative assumptions about generic healthcare-contact factors, transport choices, vehicle electrification and travel distances. The modeled annual reduction ranged from 21.66 to 33.70 kg CO2e per patient across these scenarios, compared with the base-case estimate of 25.16 kg CO2e. Tested scenarios included varying generic healthcare-contact factors by plus or minus 25%, assuming all hospital and emergency travel used ambulances and other travel used private cars, increasing the electric-vehicle share from less than 1% to 20%, and applying the shortest and longest average travel distances reported across Spanish provinces. These sensitivity analyses supported the direction of the modeled result, although they did not remove the limitations of the observational comparison.

For system-level context, the authors multiplied the per-patient estimates by an external proprietary market estimate of 65,000 patients initiating triple therapy in Spain during 2025. This illustrative scenario implied approximately €13.0 million in annual healthcare-resource cost savings and 1,635 tons of avoided CO2e. The authors explicitly cautioned that the projection should not be interpreted as an observed national saving or emissions reduction. The economic and environmental analyses excluded maintenance inhaled therapies because complete longitudinal data for the pre-initiation period were unavailable and the previous inhaler devices could not be reliably inferred from recorded ingredients. Short-acting bronchodilator acquisition costs were omitted because their expected contribution was considered minimal. The selected resource and medication components also did not constitute a full environmental sustainability assessment of the COPD care pathway.

The results need to be interpreted within the design and scope of ORESTES. Its retrospective before-and-after comparison cannot establish that budesonide/glycopyrronium/formoterol caused the changes; regression to the mean and confounding by indication remain possible, and no paired longitudinal model, covariate adjustment, formal hypothesis testing or missing-data imputation was used. Data came from hospital-based records, potentially limiting generalizability to primary-care-led COPD services, and the analysis did not separately compare patients escalating from dual therapy with those switching from another triple regimen. It also was not a cost-effectiveness study: it included no concurrent comparator, health-utility outcome or incremental cost-effectiveness ratio. The multicenter cohort, use of routine electronic records and integration of economic and environmental estimates nevertheless provide descriptive real-world evidence that improvements in acute healthcare use after treatment optimization can coincide with lower modeled costs and emissions.

Subject of Research: Estimated healthcare costs, resource use and greenhouse gas emissions after COPD triple-therapy initiation in Spain

Article Title: Impact of Budesonide/Glycopyrronium/Formoterol Initiation on Healthcare Resource Utilization and Estimated Associated Costs and Greenhouse Gas Emissions Across COPD Care in Spain (ORESTES* Study)

Article References: Figueira-Gonçalves, J. M., Alcázar-Navarrete, B., Ancochea, A., Lastres, T., de Andrés-Nogales, F., Corregidor-García, C., Fitas, E., & Sánchez-Covisa, J. (2026). Impact of Budesonide/Glycopyrronium/Formoterol Initiation on Healthcare Resource Utilization and Estimated Associated Costs and Greenhouse Gas Emissions Across COPD Care in Spain (ORESTES* Study). Advances in Therapy. https://doi.org/10.1007/s12325-026-03817-8

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03817-8

Keywords: COPD, triple therapy, budesonide, glycopyrronium, formoterol, healthcare utilization, healthcare costs, greenhouse gas emissions, Spain, retrospective cohort, Impact, Initiation

The studies were designed to address a distinctive problem in evaluating inhaled corticosteroids. Budesonide acts locally in the airways, but the drug concentration measured in blood can represent material absorbed through the lungs as well as material swallowed during nebulization and subsequently absorbed from the gastrointestinal tract. Routine pharmacokinetic bioequivalence studies capture both routes, making it difficult to determine how much systemic exposure originated in the lungs. Activated charcoal can adsorb swallowed drug before substantial gastrointestinal uptake occurs, providing a more lung-focused view of systemic exposure without directly measuring the concentration of budesonide at its site of action.

Each study enrolled 36 healthy Chinese adults aged 18 to 65 years. Participants were assigned within each trial to one of two treatment sequences, either test-reference-test-reference or reference-test-reference-test, creating a fully replicated four-period crossover design. On each study day, subjects received a single 1 mg dose of test or reference budesonide inhalation suspension under fasting conditions. Doses were delivered with a PARI LC Jet Plus nebulizer connected to a PARI Master compressor. Participants completed standardized training, wore nasal clips, sat upright and inhaled slowly through a mouthpiece while following an audio guide. The administration continued until six minutes after sputtering was first heard, and consecutive periods were separated by a five-day washout.

The test suspension was manufactured by Sichuan Purity Pharmaceutical Co., Ltd., while Pulmicort Respules served as the reference. In the charcoal-block trial, participants received 3 g of activated charcoal suspended in 30 mL of water two minutes before nebulization, immediately after nebulization and one hour later. They were instructed to gargle before swallowing to increase adsorption of material remaining in the mouth. This protocol was intended to suppress gastrointestinal absorption, although the investigators could not directly verify that absorption had been completely blocked. Blood was sampled frequently during the first 15 hours after each dose, and a validated liquid chromatography-tandem mass spectrometry assay quantified budesonide in plasma.

Bioequivalence was evaluated with a mixed-effects model applied to natural-log-transformed pharmacokinetic values, with sequence, period and treatment treated as fixed effects and subjects nested within sequence. The primary endpoints were maximum plasma concentration, or Cmax, and two exposure measures: AUC0-t, calculated from dosing through the last measurable concentration, and AUC0-inf, calculated through infinite time. Geometric mean ratios and their 90% confidence intervals were derived using a two one-sided testing approach. All three endpoints met the acceptance criteria under both conditions. Without charcoal, the geometric mean ratios were 98.08% for Cmax, 98.36% for AUC0-t and 98.70% for AUC0-inf. Their respective confidence intervals were 91.41% to 105.24%, 93.40% to 103.57% and 93.89% to 103.77%.

With charcoal blockade, the corresponding geometric mean ratios were 93.61% for Cmax, 91.58% for AUC0-t and 91.65% for AUC0-inf. The 90% confidence intervals were 86.73% to 101.04% for Cmax, 87.59% to 95.74% for AUC0-t and 87.87% to 95.59% for AUC0-inf. These results support pharmacokinetic equivalence of the two formulations under both the conventional non-block condition and the condition designed to reduce gastrointestinal uptake. The analysis also identified significant period effects and formulation effects for some charcoal-block endpoints, but these individual analysis-of-variance results did not change the bioequivalence decision, which was based on whether all three confidence intervals met the prespecified limits.

Budesonide was absorbed rapidly in both trials, with a median time to maximum concentration of about 0.20 hours after dosing. Plasma concentrations then declined promptly, and the terminal elimination half-life was approximately three hours. Across treatment-period profiles, mean Cmax for the test formulation was 1,147.51 pg/mL without charcoal and 1,126.53 pg/mL with charcoal, compared with 1,189.55 and 1,228.52 pg/mL for the reference formulation. The corresponding test-formulation mean AUC0-inf values were 2,236.36 and 2,000.58 h·pg/mL, while those for the reference formulation were 2,288.22 and 2,155.25 h·pg/mL. These descriptive values show the overall pharmacokinetic profile but are separate from the confidence-interval analysis used to establish equivalence.

The charcoal-block and non-block conditions were assessed in different participants, so their direct comparison cannot be interpreted as a randomized estimate of the effect of charcoal. Nevertheless, an exploratory subject-level analysis associated charcoal blockade with numerically lower exposure. For the test formulation, mean AUC0-t fell from 2,135.20 ± 598.52 h·pg/mL without charcoal to 1,927.92 ± 543.73 h·pg/mL with charcoal, while AUC0-inf fell from 2,224.24 ± 613.06 to 2,000.58 ± 550.29 h·pg/mL. The nominal exploratory P values for those differences were 0.129 and 0.108, while the Cmax comparison gave 0.864. Similar nonsignificant patterns appeared for the reference formulation, with nominal P values of 0.720 for Cmax, 0.456 for AUC0-t and 0.432 for AUC0-inf. No multiplicity adjustment was applied, and the comparisons cannot establish that pulmonary absorption predominated.

Safety findings were similar across the formulations. In the non-block trial, 10 of 36 participants experienced treatment-emergent adverse events, compared with 9 of 36 in the charcoal-block trial. Most events were grade 1. One participant withdrew after a grade 2 upper respiratory tract infection that investigators judged unrelated to treatment, although completed dosing and pharmacokinetic data from that participant’s first two periods were retained without imputation. In the charcoal-block trial, one participant developed grade 2 chest tightness about two hours after the final dose and received nasal-cannula oxygen, after which the symptom resolved quickly. All adverse events had resolved by the final visit, and neither study reported serious adverse events.

The findings provide supportive evidence for evaluating generic nebulized budesonide products, but several limitations constrain their scope. The trials enrolled healthy volunteers rather than patients with asthma or chronic obstructive pulmonary disease, so airway geometry and inhalation behavior in clinical populations may differ. Only single-dose pharmacokinetics were assessed, leaving repeated-dose accumulation, steady-state exposure and long-term use unresolved. Charcoal effectiveness depended on participants following standardized administration and gargling instructions, and complete suppression of gastrointestinal absorption was not demonstrated. Lung deposition may also vary with nebulizer performance and inhalation technique, limiting extrapolation to other devices. The replicated crossover design, standardized dosing procedure, intensive early sampling and dedicated charcoal-block study strengthen the within-trial equivalence analysis, but the mechanistic comparison remains exploratory rather than causal.

Subject of Research: Pharmacokinetic bioequivalence of two nebulized budesonide inhalation suspensions in healthy Chinese adults with and without activated-charcoal blockade.

Article Title: Bioequivalence of budesonide inhalation suspension with and without activated charcoal in healthy Chinese subjects: two randomized four-period crossover trials

Article References: Li, Y., Qi, L., Fan, R., Zhang, Q., Liu, J., Cheng, X., & Wang, X. (2026). Bioequivalence of budesonide inhalation suspension with and without activated charcoal in healthy Chinese subjects: two randomized four-period crossover trials. Journal of Pharmacy & Pharmaceutical Sciences, 29, Article 17048. https://doi.org/10.3389/jpps.2026.17048

Image Credits: AI Generated

DOI: 10.3389/jpps.2026.17048

Keywords: budesonide, bioequivalence, activated charcoal, nebulized corticosteroids, pharmacokinetics, pulmonary absorption, drug development, healthy volunteers, inhalation, suspension, without, activated

Thunderstorm asthma lacks a universally standardized definition, but it is widely understood as a sudden cluster of asthma attacks or bronchospasm symptoms, including coughing and dyspnea, that follows a thunderstorm and results from the interaction between storm conditions and airborne allergens. The first documented outbreak occurred in Birmingham, United Kingdom, in 1983, affecting 106 individuals. Since then, incidents have been reported across Australia, Europe, the Middle East, and China. The most severe event took place in Melbourne, Australia, on November 21, 2016, when more than 1,000 people flooded into emergency rooms and roughly 500 required hospitalization. Although individual outbreaks are rare and often overlooked, a large-scale event can overwhelm healthcare systems with unpredictable consequences and impose a substantial socioeconomic burden, making thunderstorm asthma a genuine public health threat rather than a meteorological curiosity.

The Shanxi study enrolled all 39 patients who presented on the night of the outbreak, drawing clinical data from electronic medical records and subsequent telephone follow-up, and analyzed the findings with descriptive statistics. The demographic picture was strikingly consistent with international precedents. Men accounted for a slightly higher proportion of cases than women, with 20 male and 19 female patients, a pattern echoed in previous reports, one of which found that males made up as much as 58 percent of cases. The mean age of the cohort was 31.62 plus or minus 12.86 years, a figure that the authors note was remarkably close to the mean age of patients during the 2016 Melbourne event. The researchers suggest that this age concentration may reflect a relatively active immune system in young adults, rendering them more susceptible to the allergic airway inflammation that thunderstorm asthma triggers.

Perhaps the most consequential clinical finding concerned allergy history. A review of the patients’ medical histories revealed that 94.87 percent, or 37 of the 39 individuals, had allergic rhinitis, a figure that closely matches earlier research by Nur-Shirin Harun and colleagues, who found that over 90 percent of thunderstorm asthma patients had the condition. This convergence underscores a central risk factor: people with pollen-sensitized airways, even those who have never experienced a full asthma attack, are the primary targets of these epidemics. Laboratory data, though limited, reinforced the allergic picture. Blood tests were performed on only 8 patients, and 5 of them, or 62.5 percent, showed elevated peripheral blood eosinophil counts above 0.52 times 10 to the ninth per liter, a hallmark of type 2 allergic inflammation. The authors acknowledge that the small number of tested patients represents a gap, and they call for future research to identify specific diagnostic biomarkers that could aid clinicians in diagnosis and prognostic evaluation.

The mechanism behind thunderstorm asthma is a story of atmospheric physics colliding with immunology. During a thunderstorm, strong winds carry allergenic pollen grains into the humid cloud layer, where they absorb moisture and rupture, releasing allergen-carrying particles ranging from 0.03 to 4 micrometers in size. These micro-particles are then driven back to ground level by downdrafts, creating a high concentration of respirable allergens exactly where sensitized people are breathing. Studies have confirmed a significant increase in these fragmented pollen particles after thunderstorms. The high concentration of positive ions in the air during storms may also interact with negatively charged pollen grains, potentially facilitating their rupture and further increasing airborne allergen loads. In northern China, early autumn is the peak season for Artemisia pollen, which interacts with thunderstorm conditions to form the respirable particles that set off the attacks. A separate outbreak reported in Hohhot on September 1, consistent with the timing of the Shanxi event, reinforces the conclusion that these epidemics in northern China cluster in early autumn and center on Artemisia species.

Once the microscopic particles are inhaled, the immune cascade unfolds with textbook precision. Particles smaller than 10 micrometers can reach the bronchi, where dendritic cells act as antigen-presenting cells, phagocytosing the pollen proteins and processing them into fragments recognizable by T cells. These antigens are presented to CD4-positive T cells via MHC Class II molecules, activating them to differentiate into T-helper 2 cells. The activated Th2 cells release cytokines including IL-4, IL-5, and IL-13. IL-4 stimulates goblet cells in the airways to produce excess mucus and promotes B cell differentiation and the production of IgE antibodies, which bind to receptors on mast cells, eosinophils, and airway smooth muscle cells. Upon re-exposure, the allergen cross-links the bound IgE, triggering these cells to release mediators that cause airway smooth muscle contraction and further mucus secretion, culminating in the irritating cough and dyspnea that brought the Shanxi patients to the hospital. The initial exposure to Artemisia pollen particles may sensitize the immune system and form a memory response, so the storm essentially delivers a massive re-exposure dose to a population already primed for reaction.

On the treatment side, the emergency department activated its contingency plan, recalling off-duty first-line medical staff to manage the rapid surge of patients presenting with chest tightness, cough, wheezing, and dyspnea. Life-threatening cases would have required immediate resuscitation, but fortunately none of the 39 patients developed life-threatening conditions. The pharmacological backbone of care consisted of nebulized medications: budesonide inhalation suspension, an inhaled corticosteroid that suppresses the activation of inflammatory cells and the release of allergic mediators, thereby reducing airway hyperresponsiveness; terbutaline sulfate inhalation solution, a short-acting beta-2 adrenergic agonist that selectively stimulates beta-2 adrenoceptors on airway smooth muscle, inducing bronchial relaxation and rapidly relieving acute bronchospasm; and ipratropium bromide inhalation solution, a short-acting muscarinic antagonist that competitively blocks airway muscarinic receptors, attenuating vagally mediated bronchoconstriction and reducing mucus hypersecretion.

The medication distribution revealed the practical logic of the response. The most common regimen, combining budesonide inhalation suspension with terbutaline sulfate inhalation solution, was administered to 23 patients, or 58.97 percent of the cohort, while 10 patients, or 25.64 percent, received budesonide combined with ipratropium bromide. Four patients received budesonide alone and four received formoterol. For more severe cases, methylprednisolone sodium succinate for injection was used in 2 patients. Notably, 32 patients, or 82.05 percent, received oral montelukast sodium therapy, a leukotriene receptor antagonist. The authors point out that pharmacological management of thunderstorm asthma still shows considerable heterogeneity in clinical practice, and that exploration and consensus regarding standardized preventive medication strategies remain inadequate and require further supplementation. Combined application of inhaled medications, they note, may help alleviate acute symptoms and reduce the persistence of acute exacerbations.

One month after the event, telephone follow-up found that the patients reported no recurrence-related discomfort after discharge and had gained an understanding of the disease and its preventive measures. The authors were strongly advising patients to seek immediate medical help if breathing difficulties persisted. Beyond individual care, the study draws a lesson from Australia: after the 2016 Melbourne epidemic, the country established an environmental monitoring system with a multi-level public alert system disseminated via media, allowing sensitized individuals to take preventive measures such as staying indoors and using bronchodilators while alerting healthcare systems to prepare. The Shanxi team recommends that health authorities develop integrated early warning systems combining environmental monitoring and public communication, and suggests that monitoring instruments targeting allergen concentrations could be engineered to forecast ambient allergen loads and generate early alerts, enabling patients to implement appropriate preventive strategies.

The broader message from Taiyuan is that thunderstorm asthma is no longer a phenomenon confined to Melbourne’s grass pollen springs. Northern China’s early autumn Artemisia season, coinciding with late-summer thunderstorms, creates a recurring window of risk that health systems must now anticipate. The authors argue that hospitals must develop specific thunderstorm asthma emergency response plans, with adequate material reserves as the foundation, supported by robust training on standardized management protocols and workflows. They also call for enhanced health education and public science promotion during the early autumn season to prevent future outbreaks. As climate change alters pollen seasons and storm frequency, as Beggs argued in JAMA in 2024, the intersection of violent weather and airborne allergens may become less rare, making the Shanxi episode both a warning and a template for emergency departments across the region.

Subject of Research: Epidemic thunderstorm asthma outbreak linked to Artemisia pollen in Shanxi, China

Article Title: Episode of epidemic thunderstorm asthma in Shanxi China September 2025: epidemiological characteristics, mechanisms, and emergency management strategies

Article References: Shen, T., Guo, G., Li, H., Wang, J., Wang, H., & Mi, J. (2026). Episode of epidemic thunderstorm asthma in Shanxi China September 2025: epidemiological characteristics, mechanisms, and emergency management strategies. Frontiers in Medicine, 13, Article 1953484. https://doi.org/10.3389/fmed.2026.1953484

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1953484

Keywords: thunderstorm asthma, Artemisia pollen, allergic rhinitis, IgE-mediated inflammation, eosinophils, emergency department, budesonide, terbutaline, ipratropium bromide, montelukast, early warning systems, northern China

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