New Evidence on Biologics in Severe Asthma with Normal Lung Function

While biologic therapies present a treatment option for severe asthma (SA), many randomized controlled trials (RCTs) restrict enrollment to patients with reduced lung function—typically defined as a pre-bronchodilator (pre-BD) FEV₁ <80% of predicted normal. However, several studies have found that approximately one third of patients with SA have normal lung function (pre-BD FEV1 ≥80% predicted normal).  

So, how effective are biologics in patients with SA and normal lung function? A newly published correspondence by Panettieri et al. in Respiratory Research in January 2026 provides the first real-world look into this question using data from the CHRONICLE study (NCT03373045), a prospective observational cohort of U.S. adults with SA treated by subspecialists.

The analysis included 233 patients with severe asthma who initiated biologic therapy between February 2018 and November 2023 and had no prior biologic use in the preceding year. 29% of these patients (n=67) had normal lung function at baseline (pre-BD FEV₁ ≥80% of predicted). Although these patients met criteria for SA independent of spirometry, their normal lung function (pre-BD FEV₁ ≥80% predicted) would have rendered them ineligible for some biologic RCTs. Demographically, the normal-lung-function group were younger, were more often female, and had a more recent asthma diagnosis than those with reduced lung function.

Comparable Effectiveness Across Lung Function Strata

Biologic therapy yielded meaningful reductions in exacerbation rates in both subgroups:

• Normal lung function: 50% reduction (from 1.19 to 0.60 events/year; p<0.0001)
• Reduced lung function: 59% reduction (from 1.42 to 0.58 events/year; p<0.0001)

Emergency department (ED) visits followed a similar trend:

• Normal lung function: 44% reduction (from 0.18 to 0.10 visits/year; p=0.03)
• Reduced lung function: 63% reduction (from 0.38 to 0.14 visits/year; p<0.0001).

Implications for Eligibility Criteria and Access

In some healthcare systems, reimbursement criteria require evidence of reduced lung function for biologic eligibility. However, this study challenges lung function-based eligibility thresholds by demonstrating clinically meaningful biologic effectiveness in patients with SA and normal spirometry. Given that approximately 30% of patients with SA in this cohort had normal lung function yet experienced significant benefit from biologic therapy, exclusion based on spirometry alone may deny timely access to effective treatment.

Approximately one-third of patients with SA in both the Wessex Severe Asthma cohort and the International Severe Asthma Registry also had normal lung function at baseline, mirroring CHRONICLE’s findings and reinforcing the need for policy reconsideration.

Study Limitations

The authors acknowledge that the analysis was descriptive and did not adjust for baseline differences between patients with normal and reduced lung function. The objective was not to evaluate lung function as an independent predictor of treatment response, but rather to report real-world outcomes as they occur in routine clinical practice.

As with all observational studies, potential confounding factors may influence results, and findings may not be broadly generalizable beyond subspecialist-treated adults in the U.S.

Looking Ahead

Patients with SA and normal lung function demonstrated clinically meaningful reductions in exacerbations and ED visits following biologic initiation. These findings support broader inclusion criteria in future clinical trials and reinforce the need to validate these real-world outcomes in larger, more diverse populations.

Reference

Panettieri RA Jr, Mohan A, Lugogo NL, Ledford DK, Carstens DD, Ambrose CS. Outcomes after biologic initiation among patients with severe asthma and normal lung function in the CHRONICLE study. Respir Res. 2026;27(1):5. Published 2026 Jan 7. doi:10.1186/s12931-025-03439-8