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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
2Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research
3Dept 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.
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)
doi: 10.18176/jiaci.0850

Background: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit negative BDR test.
Aim: To describe frequency of positive and negative BDR in patients with severe asthma and associations with phenotypic characteristics.
Methods: Positive BDR was defined as FEV1 increase > 200 ml AND > 12% upon testing with a short-acting beta-agonist (SABA).
Results: Out of 2013 patients included in the German Asthma Net (GAN) severe asthma registry, 793 had data on BDR. Hereof, 250 (31.5%) had a positive and 543 (68.5%) had a negative BDR test. Comorbidities significantly associated with negative BDR were gastro-esophageal reflux (GERD) (28.0% vs 40.0%, p<0.01) and EGPA (0.4% vs 3.0%; p<0.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and COPD comorbidity (5.2% vs 7.2%) were similar in both groups. Patients with positive BDR had worse asthma control (median ACQ-5 3.4 vs 3.0, p<0.05), reported dyspnea at rest (26.8% vs 16.4%, p<0.001) and chest tightness (36.4% vs 26.2%, p<0.001) more frequently, had more severe airway obstruction at baseline (FEV1% pred: 56 vs 64, p<0.001) and higher FeNO levels (41 vs 33 ppb, p<0.05), while diffusion capacity did not differ (DLCO-SB % pred. 70% vs 71%). Multivariate linear regression analysis identified association of lower baseline FEV1% (p<0.001) and chest tightness (p<0.05) with positive, and GERD (p<0.05) with negative BDR.
Conclusion: In this real-life setting the majority of patients with severe asthma exhibited negative BDR. 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  

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