German asthma net: Nasal polyposis in patients in the severe asthma registry

Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequently comorbid diseases caused by type 2 inflammation of the airway mucosa. However, whether CRSwNP contributes to a greater asthma disease burden is unclear, and real-life studies provide contrasting results.1-5 We assessed disease parameters and underlying inflammation in patients with severe asthma and CRSwNP in the prospective, multicenter German Asthma Net (GAN, https://germanasthmanet.de/en/centers/).6, 7 CRSwNP, sinonasal surgery, treatment, comorbidities, and asthma forms were evaluated based on medical reports and patient history. Targeted treatments were prescribed for severe asthma according to recent German guidelines, with anti-immunoglobulin E (IgE) prescribed for severe allergic asthma with ≥1 perennial aeroallergen and total IgE of 30–1500 U/mL, anti-interleukin (IL)-5-(R) for severe eosinophilic asthma, and anti-IL-4-R for severe asthma with a fraction of exhaled nitric oxide (FeNO) ≥25 ppb or blood eosinophils ≥150/μL.8 Current treatment with a targeted treatment with ≥1 dose received defined patients under targeted treatment. Continuous parametric variables were assessed by univariate t-tests, nonparametric variables by Mann–Whitney U Tests, and Chi-Square tests for binary variables, as an exploratory study without adjustments for multiple testing (Data S1). Patients with severe asthma and CRSwNP (35% of n = 1746; Table 1, Figure S1) showed significantly higher levels of exhaled nitric oxide (FeNO) and blood eosinophil counts, indicating a more pronounced underlying type 2 inflammation, yet an inverse association with sensitization to perennial and seasonal allergens (p <.01). Patients with CRSwNP received significantly more targeted therapy than patients without CRSwNP, with the exception of anti-immunoglobulin E therapy due to the lower prevalence of allergic asthma forms (p <.0001, Figure S2). Mean yearly exacerbations, rates of frequent exacerbations (≥2/year), and use of systemic corticosteroids were high regardless of CRSwNP (Figure 1; Table S1). Even though rates of asthma control and health-related quality of life in patients with CRSwNP were significantly higher, the score differences were not clinically relevant (Table 2; Data S1). The effect of CRSwNP on the burden of disease was clarified when assessing only patients without targeted treatments (n = 963). Here, patients with CRSwNP experienced pronounced type 2 inflammation, significantly more often any exacerbations, frequent exacerbations, and poor quality of life than patients without CRSwNP, whereas there were no more statistically significant differences between asthma control rates in these two groups (Table 3). Differences in lung function values between patients with and without CRSwNP irrespective of targeted treatments, were statistically significant, but not clinically relevant (Figure S3). Type 2 inflammation markers were particularly high in patients with CRSwNP irrespective of Aspirin-exacerbated respiratory disease (Table S2, Figure S4). The association of coexisting severe asthma and CRSwNP with higher type 2 biomarkers was expected and corroborated by other studies;2, 5 similar to the inverse associations with allergic sensitization, which have been less elucidated in-depth outside of cluster analyses.1, 4, 5, 9 Surprisingly, we found no association of CRSwNP with high disease burden in the total cohort, in contrast to previous Italian, UK, and French real-life registry studies,1, 2, 5 which however partially corroborated our results regarding OCS therapy,4 exacerbation rates,3 lung function values,5 and asthma control.2, 5 Contrasting results are potentially a consequence of the inclusion of different type 2 inflammation levels and severities in studies that include many non-severe asthma patients, or could stem from exacerbations, poor asthma control, additionally to CRSwNP, being characteristic features of heightened underlying type 2 inflammation.1, 2 The data on CRSwNP was obtained from medical records and patient history, which did not include severity aside from surgery requirement, and conferred a possibly heightened stated rate of CRSwNP. In this study of the large, well-characterized cohort with severe asthma of the GAN, the presence of CRSwNP marked heightened underlying type 2 inflammation, with increased FeNO and blood eosinophil counts. This study assessed patients with definitionally severe disease, frequent exacerbations, high systemic corticosteroid dependency, and poor asthma control, with the use of targeted therapy in more than 50%. Here, irrespective of CRSwNP, corticosteroid maintenance therapy, and exacerbation rates were similar, and disease control, quality of life, and lung function values were clinically comparable. However, regarding only patients without targeted therapy, CRSwNP was associated with a higher rate of frequent exacerbations and poor quality of life. Relevantly, CRSwNP was highly associated with type-2 inflammatory disease irrespective of current biologic use. All authors have spoken their final approval and agree to be accountable for all aspects of the work, and have contributed substantially to the conception of the study, analysis and interpretation of data, and revising the article critically for important intellectual content. The German Asthma Net is supported by scientific grants from AstraZeneca, Chiesi, GSK, Novartis, and Sanofi. The authors would like to thank the physicians, staff, and patients at the clinical sites for their support of the registry. No specific funding was received for this study. The GAN Severe Asthma Registry is supported by the German Asthma Net e.V., a German nonprofit society, and is funded by the German Ministry for Education and Research in the CHAMP consortium (BMBF, 01GL1742D); the GAN is also receiving funding by AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, and Sanofi. CB reports speaker fees from AstraZeneca, IVEPA, OLYMPUS, Sophos Akademie, all outside the submitted work. SS received fees for lectures or consultations from AstraZeneca, all outside the submitted work. KM reports speaker fees from Astrazeneca, GSK, Novartis, Sanofi, all outside the submitted work. DS received fees for lectures or consultations from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Janssen, Novartis, Pfizer. MG reports lecture fees and honoraria for consultancy from ALK, GSK, HAL, Nestle, Novartis, Omron, Sanofi and an institutional grant from Nestle, outside the submitted work. CKR reports speaker fees from Sanofi, outside the submitted work. MJ has nothing to disclose. OS reports speaker fees from Astrazenca, GSK, Sanofi, and Boehringer all outside the submitted work. RE has nothing to disclose. CT has nothing to disclose. EH is funded by the German Ministry of Education and Reserch (BMBF) as consortional partner in CHAMP (01GL1742D) for research in severe asthma in children. RB reports grants to Mainz University and personal fees from Boehringer Ingelheim, GSK, Novartis, and Roche, as well as personal fees from AstraZeneca, Chiesi, Cipla, Sanofi, and Teva, all outside the submitted work. SK reports speaker fees from Astrazenca, GSK, Novartis, Sanofi, all outside the submitted work. MI reports lectures fees from AstraZeneca, Bayer, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, GSK, Menarini, MSD, Novartis, Roche, Sanofi, Thermofischer and advisory board fees from Alk-Pharma, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, GSK, Novartis, and Sanofi, all outside the submitted work. Research data are not shared. Figure S1. Figure S2. Figure S3. Figure S4. Data S1. Tables S1-S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.