BACKGROUND: Anti-T2 biological therapies have proven to effectively reduce acute exacerbations and daily doses of oral steroids in severe eosinophilic asthma. Despite the remarkable clinical efficacy, there are usually only moderate improvements in airflow limitation, suggesting that other measures of lung function like small airway dysfunction (SAD) might better reflect the clinical response. We aimed to investigate if measures of small airway function would predict and correlate with the clinical response to anti-T2 therapy. METHODS: We studied data of patients who were previously included in the German prospective longitudinal All Age Asthma Cohort (ALLIANCE) that recruits asthma patients of all severity grades and inflammatory phenotypes. The selection criteria for this analysis were adult patients with severe eosinophilic asthma under treatment with anti-T2 biological agents. Asthma control was assessed by asthma control test (ACT) and number of severe exacerbations. Small airway function was assessed by the frequency dependence of resistance (FDR, R5-20)) derived from impulse oscillometry (IOS) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75)). We also studied air trapping (RV and RV/TLC), blood eosinophils and FeNO. Patients were classified into responders and partial or non-responders. Clinical response was defined as at least 50% reduction in annualized severe exacerbations and daily oral steroid doses accompanied with a minimum increase of 3 points in the ACT score. We used a Receiver Operator Characteristic (ROC) to study the capacity of FDR in predicting clinical response compared to other clinical variable like blood eosinophils. We studied the correlation between FDR measures and clinical response, represented by the ACT score and number of exacerbations, using linear regressions. RESULTS: 20 patients were included (mean age, 59 ± 9 years; 60% female; mean body mass index (BMI), 27.6 ± 5.4 kg/m(2); mean absolute blood eosinophils, 570 ± 389/µl; mean number of severe exacerbations 12 months prior to initiating the biological therapy, 5.0 ± 3; mean predicted FEV1, 76 ± 21%; mean predicted FDR, 224 ± 140%; mean daily prednisolone dose, 6.4 ± 4.9 mg; mean ACT score, 15 ± 5). Responders had significantly higher baseline FDR compared to partial or non-responders but similar FEV1, FEF(25-75,) RV and RV/TLC. ROC analysis showed that the combination of FDR and blood eosinophils had the best predictive capacity of the clinical response among all tested clinical markers (FeNO, FEV1, FDR, blood eosinophils) with an AUC of 85% [67-100%], (CI = 0.95, p = 0.01). Linear regressions indicated better associations between improvements in FDR and ACT score (R(2) = 0.42, p = 0.001) than with FEV1 and ACT score (R(2) = 0.25, p = 0.013). Likewise, we observed better associations between improvements in FDR and reduction of exacerbations (R(2) = 0.41, p = 0.001) than with FEV1 (R(2) = 0.20, p = 0.025). CONCLUSION: Our data suggest that severe SAD may represent a distinct phenotype of eosinophilic asthma that substantially improves under anti-T2 biological therapy. Measures of small airway function might be useful in selecting appropriate patients qualifying for anti-T2 biological therapy in addition to blood eosinophil count.
- Abdo, M.
- Watz, H.
- Veith, V.
- Kirsten, A. M.
- Biller, H.
- Pedersen, F.
- von Mutius, E.
- Kopp, M. V.
- Hansen, G.
- Waschki, B.
- Rabe, K. F.
- Trinkmann, F.
- Bahmer, T.
Keywords
- Anti-T2 biologics
- Asthma control
- Fev1
- Small airways dysfunction
- his employer from AstraZeneca, Boehringer Ingelheim, BerlinChemie, Chiesi, Novartis,
- GSK, and Sanofi outside the submitted work. VV reports no conflict of interest. AMK
- reports personal fees and study honoraria of her employer from AstraZeneca,
- Boehringer Ingelheim, BerlinChemie, Chiesi, Novartis, GSK, and Sanofi outside the
- submitted work. HB reports no conflict of interest. FP reports no conflict of
- interest. During the 36 months prior to publication, EvM Mutius reports to have
- received personal fees from Pharmaventures, from OM Pharma S. A., from
- Springer-Verlag GmbH, from Elsevier GmbH and Elsevier Ltd., from Peptinnovate Ltd.,
- from Turun Yliopisto, from Tampereen Yliopisto, from Helsingin Yliopisto, from
- European Respiratory Society, from Deutsche Pharmazeutische Gesellschaft e. V., from
- Massachusetts Medical Society, from Chinese University of Hongkong, from European
- Commission, from Böhringer Ingelheim International GmbH, from Universiteit Utrecht,
- Faculteit Diergeneeskunde, from Universität Salzburg, from Georg Thieme Verlag, from
- Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI), outside the
- submitted work
- In addition, Dr. von Mutius has a patent LU101064—Barn dust extract
- for the prevention and treatment of diseases pending, a patent EP2361632: Specific
- environmental bacteria for the protection from and/or the treatment of allergic,
- chronic inflammatory and/or autoimmune disorders with royalties paid to ProtectImmun
- GmbH, a patent Publication number EP 1411977: Composition containing bacterial
- antigens used for the prophylaxis and the treatment of allergic diseases, licensed
- to ProtectImmun GmbH, a patent Publication number EP1637147: Stable dust extract for
- allergy protection licensed to ProtectImmun GmbH, and a patent Publication number EP
- 1964570: Pharmaceutical compound to protect against allergies and inflammatory
- diseases licensed to ProtectImmun GmbH. MVK reports no conflict of interest. GH
- reports no conflict of interest. BW reports no conflict of interest. KFR reports
- personal fees from AstraZeneca, Boehringer Ingelheim, BerlinChemie, Chiesi,
- Novartis, GSK, and Sanofi outside the submitted work. FT received travel support
- from Actelion, Berlin Chemie, Boehringer Ingelheim, Chiesi, Novartis, Mundipharma
- and TEVA as well as speaker or consultation fees from AstraZeneca, Berlin Chemie,
- Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, GlaxoSmithKline, Novartis and
- Roche, Sanofi aventis, all outside the submitted work. TB reports personal fees from
- AstraZeneca, Boehringer Ingelheim, BerlinChemie, Chiesi, Novartis, GSK, and Sanofi
- outside the submitted work.
