Clinical bottom line
Inhaled monoclonal antibodies (mAbs) represent a promising but still investigational approach to preventing viral-induced exacerbations in chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Early-phase studies and mechanistic insights suggest potential benefits in targeting respiratory viruses directly at the airway mucosa, potentially reducing viral load and subsequent inflammation. However, clinical evidence remains limited, and inhaled mAbs have not yet been established as standard prophylactic therapy. Current management of viral exacerbations continues to rely primarily on bronchodilators, corticosteroids, and supportive care (Beeh et al., 2016; Lee et al., 2025). Further rigorous clinical trials are needed to define efficacy, safety, optimal delivery methods, and patient populations most likely to benefit.
What the evidence shows
Respiratory viral infections are well-recognized triggers of exacerbations in chronic respiratory diseases, contributing substantially to morbidity (Role of Respiratory Viral Infection at Exacerbation, 2008). Traditional pharmacologic prevention strategies focus on bronchodilators and inhaled corticosteroids, which reduce exacerbation frequency but do not specifically target viral pathogens (Beeh et al., 2016; Lee et al., 2025). Monoclonal antibodies have emerged as targeted antiviral agents, with systemic mAbs approved for prevention of respiratory syncytial virus (RSV) in high-risk infants, demonstrating proof of concept for antibody-mediated viral prophylaxis (Boonyaratanakornkit et al., 2022).
Inhaled delivery of mAbs offers theoretical advantages by concentrating the agent at the site of viral entry and replication, potentially improving efficacy and reducing systemic exposure. Preclinical and early clinical studies have explored inhaled mAbs against RSV and other respiratory viruses, showing promising antiviral activity and tolerability (Boonyaratanakornkit et al., 2022; Langedijk et al., 2020). Viral sequence analysis has informed mAb design to enhance neutralization breadth and reduce resistance risk (Langedijk et al., 2020).
However, clinical data specifically evaluating inhaled mAbs for preventing viral exacerbations in COPD or asthma remain sparse. Most evidence derives from systemic mAbs or inhaled corticosteroid/long-acting β2-agonist combinations, which reduce exacerbations but do not directly neutralize viruses (Beeh et al., 2016; Lee et al., 2025; Efficacy of inhaled corticosteroids/long-acting β2-agonist combinations, 2007). Barriers to inhaled medication adherence and delivery in COPD patients may also impact real-world effectiveness (Craddock et al., 2023).
Caveats and uncertainty
The inhaled mAb approach is still largely hypothesis-generating. Key uncertainties include optimal dosing, delivery devices, durability of protection, and cost-effectiveness. Viral diversity and mutation rates pose challenges for sustained efficacy, necessitating ongoing viral surveillance and mAb redesign (Langedijk et al., 2020). The safety profile of inhaled mAbs requires further characterization, particularly regarding local airway immune responses and potential hypersensitivity.
Patient selection criteria remain undefined; it is unclear which chronic respiratory disease phenotypes or exacerbation risk profiles would derive the greatest benefit. Additionally, inhaled mAbs would likely complement rather than replace existing therapies, necessitating studies on combination regimens.
Finally, logistical and economic considerations, including manufacturing complexity and inhaler device compatibility, may limit widespread adoption in the near term.
How this may change practice
If ongoing and future clinical trials demonstrate clear efficacy and safety, inhaled monoclonal antibodies could become a novel prophylactic option to reduce viral-triggered exacerbations in chronic respiratory diseases. This would represent a shift toward precision antiviral prophylaxis targeting the initial trigger rather than downstream inflammation alone.
Clinicians may eventually integrate inhaled mAbs into exacerbation prevention strategies, particularly for patients with frequent viral exacerbations refractory to standard therapies. This approach could reduce hospitalizations, improve quality of life, and decrease healthcare costs associated with exacerbation management.
Until robust evidence emerges, clinicians should continue optimizing established pharmacologic and non-pharmacologic interventions while monitoring developments in inhaled antiviral biologics.