Asthma with bronchial hypersecretion: expression of mucins and toll-like receptors in sputum and blood

Astrid Crespo-Lessmann,1 Eder Mateus,1,2 Montserrat Torrejón,1 Alicia Belda,1 Jordi Giner,1 Silvia Vidal,2 Oriol Sibila,1 Vicente Plaza,1 1Service of Pneumology, Hospital de la Santa Ceu i Sant Pau, Institute of Sant Pau Biomedical Research (IBB Sant Pau), Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), 2Department of Immunology, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomédica Sant Pau, Barcelona, Spain Abstract: Asthma with bronchial hypersecretion is a type of asthma that is poorly studied. Its pathogenesis is not well understood, but is probably related to innate impaired immunity, particularly with toll-like receptors (TLRs) and secretory mucins (MUC). Objectives: 1) Define the clinical and inflammatory phenotype of asthma with bronchial hypersecretion of mucus. 2) Compare the type of mucin present in induced sputum (IS) of patients with and without bronchial hypersecretion. 3) Determine the expression of TLRs in IS and blood of asthmatics with and without bronchial hypersecretion. Materials and methods: Cross-sectional study which included 43 non-smoking asthmatic patients without bronchiectasis, 19 with bronchiectasis, and 24 without bronchial hypersecretion. All patients underwent the following: IS, spirometry, fractional exhaled nitric oxide, prick test, total immunoglobulin E (IgE), and blood albumin. Analysis of mucins was determined by ELISA and expression of TLR2 and TLR4 by flow cytometry. The level of asthma control was determined by the Asthma Control Test (ACT) questionnaire and quality of life was assessed by the reduced version of the Asthma Quality of Life Questionnaire (mini-AQLQ). Results: Asthmatics with bronchial hypersecretion were significantly older (62.6 years vs 48.5 years; p=0.02); had greater severity (persistent severe asthma 94.7% vs 29.2%; p=0.000); a higher proportion of nasal polyposis (36.8% vs 8.3%; p=0.022); less control of asthma (73.7% vs 8.3%; p=0,000); a higher proportion of asthma with negative prick test (68.4% vs 16.6%; p=0.001), and lower levels of IgE (113.4 IU/mL vs 448 IU/mL; p=0.007), compared with asthmatics without bronchial hypersecretion. Significant differences were observed neither in the expression of  TLRs 2 and 4 in inflammatory cells of IS or peripheral blood, nor in the expression of mucins between both groups. Conclusion: Asthma patients with bronchial hypersecretion have more severe and uncontrolled disease, with poor quality of life as well as a non-allergic inflammatory phenotype. Within the mechanisms involving these differences, it does not appear that mucins and TLRs play an important role. Keywords: asthma, mucins, inflammation, induced sputum, toll-like recepto