Clinical bottom line
Inhaled anti-IL-5 therapies represent a putative adjunctive treatment for chronic eosinophilic pneumonia (CEP), a rare eosinophilic lung disease characterized by pulmonary infiltrates and eosinophilic inflammation. While systemic corticosteroids remain the mainstay of therapy, their long-term use is limited by adverse effects and frequent relapses. Emerging evidence suggests that targeting IL-5, a key cytokine in eosinophil survival and activation, via inhaled delivery may offer a localized, steroid-sparing approach. However, current data are largely limited to case reports and extrapolations from related eosinophilic conditions, underscoring the need for cautious interpretation and further validation.
What the evidence shows
Chronic eosinophilic pneumonia is traditionally managed with systemic corticosteroids, which induce rapid clinical and radiographic improvement but are associated with high relapse rates upon tapering (Chan et al., 2016). Adjunctive inhaled corticosteroids have been explored to maintain remission and reduce systemic steroid exposure. Lavandier et al. (1994) reported that high-dose inhaled corticosteroids could be effective in maintaining remission in CEP, though evidence remains limited and primarily observational. Minakuchi et al. (2003) similarly described inhaled corticosteroids as a potential adjunct in CEP management, highlighting their role in reducing systemic steroid doses.
The role of anti-IL-5 therapies, such as mepolizumab and benralizumab, has been established in eosinophilic asthma and hypereosinophilic syndromes but remains largely unexplored in CEP. Angelopoulos et al. (2023) discuss anti-IL-5 therapies in eosinophilic fasciitis, an eosinophil-driven disease, suggesting a mechanistic rationale for their use in other eosinophilic conditions. Although direct clinical trial data in CEP are lacking, the pathophysiological role of IL-5 in eosinophil recruitment and survival provides a theoretical basis for anti-IL-5 agents as targeted therapy.
Chan et al. (2017) reported adjunctive inhaled steroids in CEP cases with favorable outcomes, but these did not specifically involve anti-IL-5 biologics. Khazar et al. (2023) describe complex cases involving eosinophilic lung disease and comorbid conditions, illustrating the challenges in managing refractory eosinophilic inflammation and the potential need for novel therapies.
Radiological and clinical diagnostic criteria for CEP are well characterized (Knipe et al., 2015; Lawler et al., 2025), facilitating patient identification for potential targeted interventions. However, no randomized controlled trials have yet evaluated inhaled anti-IL-5 therapies in CEP, and current evidence is hypothesis-generating rather than confirmatory.
Caveats and uncertainty
The evidence supporting inhaled anti-IL-5 therapy in CEP is preliminary and indirect. Most clinical experience derives from systemic anti-IL-5 use in eosinophilic asthma or hypereosinophilic syndromes, which may not fully extrapolate to CEP’s unique pulmonary pathology. Inhaled delivery of anti-IL-5 agents is an emerging concept without robust clinical trial data, raising questions about optimal dosing, delivery mechanisms, and long-term safety.
CEP’s rarity and heterogeneous clinical course complicate study design and patient recruitment for definitive trials. Additionally, the natural history of CEP includes spontaneous remission in some cases, which may confound assessment of therapeutic efficacy. The potential for inhaled anti-IL-5 therapies to reduce systemic corticosteroid exposure and relapse frequency remains speculative without controlled evidence.
Moreover, the cost and accessibility of biologic therapies, as well as patient selection criteria, require clarification. Safety profiles specific to inhaled anti-IL-5 agents in CEP have not been established, necessitating vigilance for adverse effects and immunogenicity.
How this may change practice
Pending further evidence, inhaled anti-IL-5 therapies could emerge as a targeted, steroid-sparing option for patients with CEP who experience frequent relapses or corticosteroid-related toxicity. Clinicians should remain aware of the evolving landscape of eosinophilic lung disease management and consider enrollment of eligible patients into clinical trials investigating these agents.
In the interim, adjunctive inhaled corticosteroids remain a pragmatic option to maintain remission and reduce systemic steroid burden, as supported by historical observational studies (Lavandier et al., 1994; Chan et al., 2016). Multidisciplinary collaboration and careful phenotyping of eosinophilic lung diseases will be essential to tailor emerging biologic therapies appropriately.
Ultimately, the integration of inhaled anti-IL-5 therapies into CEP management will depend on rigorously designed clinical trials to define efficacy, safety, dosing, and patient selection. Until such data are available, their use should be considered experimental and reserved for refractory cases under specialist guidance.