Imran Satia1, Nikolaos Tsamandouras2, Kimberley Holt3, Huda Badri3, Mark Woodhead4, Kayode Ogungbenro5, Timothy W Felton1, Paul M O'Byrne3, Stephen J Fowler3, Jaclyn A Smith6. 1. Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; University Hospital of South Manchester, Manchester, United Kingdom. 2. Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom. 3. Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom. 4. Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; Central Manchester NHS Foundation Trust, Manchester, United Kingdom. 5. Central Manchester NHS Foundation Trust, Manchester, United Kingdom. 6. Centre for Respiratory Medicine and Allergy, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; University Hospital of South Manchester, Manchester, United Kingdom. Electronic address: jacky.smith@manchester.ac.uk.
Abstract
BACKGROUND: Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored. OBJECTIVES: We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses. METHODS: Capsaicin inhalational challenge was performed, and cough responses were analyzed by using nonlinear mixed-effects modeling to estimate the maximum cough response evoked by any concentration of capsaicin (Emax) and the capsaicin dose inducing half-maximal response (ED50). RESULTS: Ninety-seven patients with stable asthma (median age, 23 years [interquartile range, 21-27 years]; 60% female) and 47 healthy volunteers (median age, 38 years [interquartile range, 29-47 years]; 64% female) were recruited. Asthmatic patients had higher Emax and lower ED50 values than healthy volunteers. Emax values were 27% higher in female subjects (P = .006) and 46% higher in patients with nonatopic asthma (P = .003) compared with healthy volunteers. Also, patients with atopic asthma had a 21% lower Emax value than nonatopic asthmatic patients (P = .04). The ED50 value was 65% lower in female patients (P = .0001) and 71% lower in all asthmatic patients (P = .0008). ED50 values were also influenced by asthma control and serum IgE levels, whereas Emax values were related to 24-hour cough frequency. Age, body mass index, FEV1, PC20, fraction of exhaled nitric oxide, blood eosinophil counts, and inhaled steroid treatment did not influence cough parameters. CONCLUSION: Patients with stable asthma exhibited exaggerated capsaicin-evoked cough responses consistent with neuronal dysfunction. Nonatopic asthmatic patients had the highest cough responses, suggesting this mechanism might be most important in type 2-low asthma phenotypes.
BACKGROUND: Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored. OBJECTIVES: We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses. METHODS: Capsaicin inhalational challenge was performed, and cough responses were analyzed by using nonlinear mixed-effects modeling to estimate the maximum cough response evoked by any concentration of capsaicin (Emax) and the capsaicin dose inducing half-maximal response (ED50). RESULTS: Ninety-seven patients with stable asthma (median age, 23 years [interquartile range, 21-27 years]; 60% female) and 47 healthy volunteers (median age, 38 years [interquartile range, 29-47 years]; 64% female) were recruited. Asthmatic patients had higher Emax and lower ED50 values than healthy volunteers. Emax values were 27% higher in female subjects (P = .006) and 46% higher in patients with nonatopic asthma (P = .003) compared with healthy volunteers. Also, patients with atopic asthma had a 21% lower Emax value than nonatopic asthmatic patients (P = .04). The ED50 value was 65% lower in female patients (P = .0001) and 71% lower in all asthmatic patients (P = .0008). ED50 values were also influenced by asthma control and serum IgE levels, whereas Emax values were related to 24-hour cough frequency. Age, body mass index, FEV1, PC20, fraction of exhaled nitric oxide, blood eosinophil counts, and inhaled steroid treatment did not influence cough parameters. CONCLUSION: Patients with stable asthma exhibited exaggerated capsaicin-evoked cough responses consistent with neuronal dysfunction. Nonatopic asthmatic patients had the highest cough responses, suggesting this mechanism might be most important in type 2-low asthma phenotypes.
Authors: Kian Fan Chung; Lorcan McGarvey; Woo-Jung Song; Anne B Chang; Kefang Lai; Brendan J Canning; Surinder S Birring; Jaclyn A Smith; Stuart B Mazzone Journal: Nat Rev Dis Primers Date: 2022-06-30 Impact factor: 65.038
Authors: Andrew J Halayko; Christopher D Pascoe; Jessica D Gereige; Michael C Peters; Robyn T Cohen; Prescott G Woodruff Journal: Am J Respir Crit Care Med Date: 2021-08-15 Impact factor: 21.405
Authors: Mihai-Daniel Dumitrache; Ana Stefania Jieanu; Cristian Scheau; Ioana Anca Badarau; George Denis Alexandru Popescu; Ana Caruntu; Daniel Octavian Costache; Raluca Simona Costache; Carolina Constantin; Monica Neagu; Constantin Caruntu Journal: Exp Ther Med Date: 2021-06-29 Impact factor: 2.447
Authors: Imran Satia; Adil Adatia; Ruth P Cusack; Justina M Greene; Paul M O'Byrne; Kieran J Killian; Neil Johnston Journal: ERJ Open Res Date: 2021-05-24