Pulmonary Rehabilitation Reduces Type 2 Inflammation in High Inflammation Asthma

Pulmonary rehabilitation (PR) significantly reduced fractional exhaled nitric oxide (FeNO) levels in people with asthma with high baseline FeNO, supporting the role of PR as a complementary strategy to manage asthma.1

“The role of FeNO in monitoring non-pharmacological interventions like PR remains unclear. Since PR may reduce airway inflammation through mechanisms independent of corticosteroids, FeNO could help assess these effects. Therefore, the aim of this study was to evaluate FeNO changes during a PR program in patients with asthma and different levels of airway inflammation,” study investigator Rainer Gloeckl, PhD, Philipps-Universität Marburg, Marburg, Germany, and colleagues wrote.1

Gloeckl and colleagues evaluated PR in a prospective, single-center study that enrolled 62 people with asthma undergoing a comprehensive 3-week inpatient PR program. The 15-day observation period included thrice-daily FeNO measurements, with patients stratified into 3 baseline FeNO categories: low (<25 ppb), intermediate (25–50 ppb), and high (>50 ppb). a FeNO is a biomarker of type 2 airway inflammation.

A significant FeNO reduction was observed only in the high-FeNO subgroup (n = 22), with levels decreasing by 40% from 93 ± 29 ppb to 56 ± 27 ppb (P <.001), independent of changes in medication. FeNO values remained stable in the low (17 ± 8 ppb to 16 ± 10 ppb) and intermediate groups (39 ± 12 ppb to 30 ± 10 ppb). Asthma control and exercise capacity improved across all subgroups, with the most pronounced improvements seen in patients with initially high FeNO. No meaningful changes in FeNO were seen in the low or intermediate FeNO groups.

“Our findings align with previous studies demonstrating the beneficial effects of PR on asthma control and exercise performance while providing novel insights into its impact on airway inflammation. To our knowledge, this is the first study to show that PR exerts an anti-inflammatory effect in asthma patients with high baseline FeNO levels, independent of medication changes. These results highlight the potential role of PR as a complementary strategy in asthma management, particularly for patients with persistent airway inflammation despite optimized pharmacological therapy,” Gloeckl and colleagues said.1

In other recent news in asthma treatment, new findings from the WAYFINDER phase 3 trial demonstrated that almost all patients with oral corticosteroid (OCS)-dependent severe, uncontrolled asthma achieved a maintenance OCS dose of 5 mg per day or less and more than half completely discontinued OCS while maintaining asthma control after 52 weeks of open-label tezepelumab treatment.2

Participants in WAYFINDER had a mean baseline maintenance OCS dose of 10.8 mg per day (SD, 6.5). Investigators found that the proportion of participants who had a maintenance OCS dose of 5 mg per day or less without loss of asthma control was 88.9% (n = 265; 95% CI, 84.8–92.3) at week 28 and 89.9% (n = 268; 95% CI, 85.9–93.1) at week 52. Furthermore, 32.2% of participants (n = 96; 95% CI, 26.9–37.8) were able to discontinue OCS without loss of asthma control by week 28, increasing to 50.3% (n = 150; 95% CI, 44.5–56.2) by week 52.2

Paola Rogliani, MD, and Luigino Calzetta, PhD, both from University of Rome “Tor Vergata” in Italy, took the findings with a grain of salt with their related editorial.3

“In conclusion, although WAYFINDER4 provides suggestive evidence that tezepelumab might reduce OCS dependence in severe asthma, methodological limitations, baseline imbalances, and the influence of the placebo effect indicate that these findings are not definitive; well-designed randomized, placebo-controlled trials or high-quality pooled analyses are needed to confirm the OCS-sparing effect of tezepelumab,” Rogliani and Calzetta wrote.3

References

1. Gloeckl R, Kroll D, Abdulleyev G, et al. Pulmonary Rehabilitation Reduces Airway Inflammation in Asthma Patients with High FeNO Levels. J Asth Aller. 2025; Volume 18:1651-1660. doi: 10.2147/jaa.s555317

2. ‌Johnson V. Tezepelumab Drastically Reduces OCS Use for Asthma in Open-Label Trial. Article. HCPLive. November 28, 2025. https://www.hcplive.com/view/tezepelumab-drastically-reduces-ocs-use-asthma-open-label-trial

3. Rogliani P, Luigino Calzetta. Efficacy of tezepelumab in reducing oral corticosteroid use in severe asthma. Lancet Resp Med. Published online November 1, 2025. doi: 10.1016/s2213-2600(25)00395-9