Bronchodilator Reversibility Phenotypes: Characteristics, Future Asthma Exacerbations

Woman using a bronchodilator, inhaler
Woman using a bronchodilator, inahler
Is reduced bronchodilator reversibility in asthma patients predictive of future asthma exacerbations?

The bronchodilator reversibility (BDR)-low phenotype was associated with future asthma exacerbations and non-type 2 high asthma, according to study findings published recently in Respiratory Medicine.

Studies have found that high BDR “is associated with worse asthma symptom control at baseline” and that “reduced BDR could be used as a surrogate marker for airway remodeling in asthma,” said investigators for the current study. Moreover, it has been unclear whether reduced BDR could be predictive of asthma exacerbations, they added.

The definition for BDR varies in the literature, noted investigators for the current study; Global Initiative for Asthma (GINA) guidelines2 define the BDRhigh phenotype as a >12% and >200 mL improvement in the FEV1 from baseline, whereas Ward et al.3 has defined the BDRhigh phenotype as a >8% improvement in the predicted FEV1. Moreover, the guideline-based definition of BDR takes into account age, sex, and BMI, whereas the Ward-based definition does not.

For the current study, researchers from the Asthma Clinic of West China Hospital, in Sichuan, China, sought to identify characteristics of BDRhigh/low phenotypes as well as the associations between BDRhigh/low phenotypes and future asthma exacerbations, taking into account both guideline- and Ward-based BDR criteria. Investigators conducted a 2-part study from October 2015 to October 2018. The first part (n=456) was a 12-month prospective observational cohort study to identify the clinical characteristics of BDRhigh/low phenotypes and associations with future AEs in (n = 456); the second part, a post hoc analysis of the first part of the study, assessed the association between BDRhigh/low phenotypes and treatment responsiveness (n = 360).

On the basis of baseline assessments, the researchers divided patients into cohorts for BDRhigh (n=200) and BDRlow (n=256) phenotypes. Through analysis, researchers found that the BDRlow phenotype was associated with better baseline of asthma management and that this phenotype was negatively associated with type 2 (T2) high asthma. Patients with BDRlow phenotype also had greater risk of severe asthma exacerbations during the 12-month follow-up period (guideline-based criterion: RRadj = 2.24; 95% CI, 1.25-3.68; Ward criterion: RRadj = 2.46; 95% CI, 1.40-4.00), and moderate-to-severe asthma exacerbations in the following year (guideline-based criterion: RRadj = 1.83; 95% CI, 1.22-2.56; Ward criterion: RRadj = 1.94; 95% CI, 1.32-2.68) as per regression models.

The post-hoc analysis found that BDRlow phenotype was a risk factor for insensitive response to anti-asthma treatment (guideline-based criterion: ORadj = 1.96; 95% CI, 1.05-3.65; Ward’s criterion: ORadj = 2.01; 95% CI, 1.12-3.58).

Study limitations include measurement bias, treatment responsiveness not evaluated at all levels of dose treatment, and the relationship between airway remodeling and BDRhigh/low phenotypes not examined.

Researchers concluded that, “BDRlow phenotype was associated with non-T2 high asthma and future AEs,” which is significant for future asthma control. “BDRlow phenotype is a distinctive pathophysiological characteristic of asthma, which can potentially have clinically relevant implications for asthma management,” they added.


  1. Liu L, Zhang X, Zhang L, et al. Reduced bronchodilator reversibility correlates with non-type 2 high asthma and future exacerbations: A prospective cohort study. Respir Med. Published online June 23, 2022. doi:10.1016/j.rmed.2022.106924
  2. GINA At-A-Glance Asthma Management Reference. Updated 2014. Accessed July 20, 2022.
  3. Ward H, Cooper BG, Miller MR. Improved criterion for assessing lung function reversibility. Chest. 2015;148(4):877-886. doi: 10.1378/chest.14-2413. PMID: 25879725