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Bronchodilator Reversibility in the GAN Severe Asthma Cohort

Milger K1,2, Skowasch D3, Hamelmann E4, Mümmler C1,2, Idzko M5, Gappa M6, Jandl M7, Körner-Rettberg C8, Ehmann R9, Schmidt O10, Taube C11, Holtdirk A12, Timmermann H13, Buhl R14, Korn S15,16

1Department of Medicine V, University Hospital, LMU Munich, Munich, Germany
2Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany
3Department of Internal Medicine II - Pneumology/Cardiology, University Hospital Bonn, Bonn, Germany
4University Hospital for Pediatrics and Adolescent Medicine, Children's Center Bethel, University of Bielefeld, Bielefeld, Germany
5Department of Pulmonary Medicine, Medical University of Vienna, Vienna, Austria
6Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany
7Hamburger Institut für Therapieforschung, Hamburg, Germany
8Marienhospital Wesel, Wesel, Germany
9Ambulante Pneumologie Stuttgart, Stuttgart, Germany
10Pneumologische Gemeinschaftspraxis Koblenz, Koblenz, Germany
11Department of Pulmonary Medicine, University Hospital - Ruhrlandklinik, Essen, Germany
12CRO Kottmann, Hamm, Germany
13Allergopraxis Hamburg, Hamburg, Germany
14Pulmonary Department, Mainz University Hospital, Mainz, Germany
15IKF Pneumologie Mainz, Mainz, Germany
16Thoraxklinik Heidelberg, Heidelberg, Germany

J Investig Allergol Clin Immunol 2023; Vol 33(6) : 446-456
doi: 10.18176/jiaci.0850

Background: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response.
Aim: To describe the frequency of positive and negative BDR response in patients with severe asthma and study associations with phenotypic characteristics.
Methods: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist.
Results: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a negative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05).
Conclusion: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.

Key words: Bronchodilator responsiveness, Severe asthma, Real-life cohort, GERD. FeNO