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Systemic corticosteroids remain the backbone of treatment for acute exacerbations of asthma and COPD, yet up to 30% of exacerbations respond inadequately. A commentary in the September 2026 issue of CHEST by Mario Cazzola of the University of Rome Tor Vergata and Maria Gabriella Matera of the University of Campania examines whether biologic therapies developed for prevention have a role during the acute episode itself, and concludes that the rationale is sound while the evidence is thin.
The authors begin with a definitional problem. "Exacerbation" covers biologically diverse events and is defined variously by symptom worsening, lung function decline, corticosteroid use, or healthcare utilization. Eosinophilic inflammation accounts for roughly 30% of COPD exacerbations and up to half of asthma exacerbations, and the type 2 pathway driven by IL-4, IL-5, and IL-13 promotes mucus hypersecretion, smooth muscle contraction, and mast cell degranulation, processes that corticosteroids do not reliably suppress. That gap is the conceptual opening for agents that act upstream.
The evidence base, however, consists largely of case reports and retrospective series. A systematic review of monoclonal antibodies used as rescue therapy in critical care found 14 studies covering just 17 patients, nearly all with near-fatal asthma, and no studies of biologics for COPD exacerbations in the ICU. The strongest data come from the phase 2 ABRA trial, in which a single 100 mg dose of benralizumab, alone or with prednisolone, cut 90-day treatment failure by about 74% compared with prednisolone alone in patients with an eosinophilic endotype, with a number needed to treat of 4. The authors note that ABRA was small, weighted toward asthma, excluded ventilated patients, and enrolled people likely to respond, and that the optimal acute dose for COPD is unknown.
Pharmacokinetics complicate the picture. Subcutaneous antibodies absorb slowly, with half-lives of 12 to 26 days and peak concentrations reached over days, which limits immediate effect in critically ill patients. Intravenous delivery is faster but does not guarantee lung exposure, and the authors flag inhaled formulations as a direction worth developing.
Their position is that biologics are not emergency drugs and must not displace bronchodilators or corticosteroids. Their primary role stays preventive. In severe, corticosteroid-refractory cases, earlier initiation during hospitalization may make sense given the slow onset. Biomarker-guided patient selection using blood eosinophils, IgE, FeNO, or molecular signatures could limit unnecessary exposure and cost, and the authors argue that high upfront drug cost should be weighed against the larger burden of hospitalization, ICU care, and recurrent treatment failure, with randomized trials needed to establish both clinical role and economic value. They anticipate a shift from one-size-fits-all corticosteroid treatment toward endotype-directed care as exacerbation triggers are better classified and additional targeted agents, including antiviral strategies, emerge.
