{"id":{"repo_id":"queens","oai_identifier":"oai:queensu.scholaris.ca:1974/22679"},"canonical_url":"https://search.dev.ndltd.org/etd/queens/oai:queensu.scholaris.ca:1974/22679","repository":{"repo_id":"queens","name":"Queens University","base_url":"https://qspace.library.queensu.ca/server/oai/request"},"display":{"title":"Sensory-Mechanical Responses to High-Dose Methacholine Bronchoprovocation: The Modulating Effects of Deep Inspirations","abstract":"Rationale: The physiologic variables distinguishing classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough with normal airway sensitivity (COUGH) are incompletely understood. Defining the range of normal responses associated with deep inspirations (DIs) during high-dose MCh is key to understand the clinical relevance of COUGH. Purpose: To characterize responses to DI in healthy normal individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness) during high-dose MCh and compare with responses in CA, CVA and COUGH. Methods: Individuals aged 18-65 years with no history of asthma and/or chronic cough attended 2 visits. On visit 1, after baseline spirometry and body plethysmography, participants were randomized to perform either: (i) modified high-dose MCh challenge using partial and maximal expiratory flow-volume curves (PEFV/MEFV) and impulse oscillometry (IOS) or (ii) traditional high-dose MCh challenge using MEFV, at each dose to a maximum change (∆) in FEV1 of 50% from baseline (MAX). Previously published data (Wasilewski et al., 2016) was used to compare the responses of healthy individuals to individuals with CA (n=11), CVA (n=10) and COUGH (n=7). Results: 15 participants (31.4±7.3years) (Mean±SD) completed the protocol. At MAX, participants developed minor but significant cough (3.2±4.7; p=0.022), dyspnea (Borg: 0.4±0.7; p=0.016), bronchoconstriction (%∆FEV1 -14.7±7.9%; p<0.001) and gas trapping (∆IC -0.20±0.36; p=0.001), compared to baseline. At MAX, the bronchodilation effect of DIs was preserved (DI index: 0.67±0.44 and -0.14 ± 0.15 at MAX and baseline, respectively; p<0.001). Compared to healthy individuals, the COUGH group developed more cough (p=0.006), dyspnea (p=0.029) but comparable bronchoconstriction and gas trapping in response to high-dose MCh. At MAX, the bronchodilating effect was preserved in CA, CVA and healthy participants but impaired in COUGH (DI Index: 0.67±0.97 (CA); 0.51±0.73 (CVA); 0.01±0.36 (COUGH); 0.68±0.45 (healthy participants); p=0.009). Conclusion: The responses to high-dose MCh in healthy participants and participants with COUGH, CVA and CA lie on a continuum, which may reflect fundamental pathophysiological differences in terms of impairment versus preservation of the bronchodilating effect of DIs. COUGH appears to be a clinically relevant phenotype, distinct from healthy normal and CVA.","abstract_html":"Rationale: The physiologic variables distinguishing classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough with normal airway sensitivity (COUGH) are incompletely understood. Defining the range of normal responses associated with deep inspirations (DIs) during high-dose MCh is key to understand the clinical relevance of COUGH. Purpose: To characterize responses to DI in healthy normal individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness) during high-dose MCh and compare with responses in CA, CVA and COUGH. Methods: Individuals aged 18-65 years with no history of asthma and/or chronic cough attended 2 visits. On visit 1, after baseline spirometry and body plethysmography, participants were randomized to perform either: (i) modified high-dose MCh challenge using partial and maximal expiratory flow-volume curves (PEFV/MEFV) and impulse oscillometry (IOS) or (ii) traditional high-dose MCh challenge using MEFV, at each dose to a maximum change (∆) in FEV1 of 50% from baseline (MAX). Previously published data (Wasilewski et al., 2016) was used to compare the responses of healthy individuals to individuals with CA (n=11), CVA (n=10) and COUGH (n=7). Results: 15 participants (31.4±7.3years) (Mean±SD) completed the protocol. At MAX, participants developed minor but significant cough (3.2±4.7; p=0.022), dyspnea (Borg: 0.4±0.7; p=0.016), bronchoconstriction (%∆FEV1 -14.7±7.9%; p&lt;0.001) and gas trapping (∆IC -0.20±0.36; p=0.001), compared to baseline. At MAX, the bronchodilation effect of DIs was preserved (DI index: 0.67±0.44 and -0.14 ± 0.15 at MAX and baseline, respectively; p&lt;0.001). Compared to healthy individuals, the COUGH group developed more cough (p=0.006), dyspnea (p=0.029) but comparable bronchoconstriction and gas trapping in response to high-dose MCh. At MAX, the bronchodilating effect was preserved in CA, CVA and healthy participants but impaired in COUGH (DI Index: 0.67±0.97 (CA); 0.51±0.73 (CVA); 0.01±0.36 (COUGH); 0.68±0.45 (healthy participants); p=0.009). Conclusion: The responses to high-dose MCh in healthy participants and participants with COUGH, CVA and CA lie on a continuum, which may reflect fundamental pathophysiological differences in terms of impairment versus preservation of the bronchodilating effect of DIs. COUGH appears to be a clinically relevant phenotype, distinct from healthy normal and CVA.","abstract_has_math":false,"creators":["Sood, Nilita"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Biomedical and Molecular Sciences","school":null,"contributors":[],"advisors":["Lougheed, M Diane","Fisher, John"],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-27T20:35:35Z","subjects":["Methacholine","Asthma","Cough","Deep Inspirations","Bronchodilating"],"languages":["eng"],"rights":["Attribution-NonCommercial-ShareAlike 3.0 United States"],"rights_urls":["http://creativecommons.org/licenses/by-nc-sa/3.0/us/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1974/22679","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.department","label":"Department","values":["Biomedical and Molecular Sciences"]},{"key":"dc:contributor.supervisor","label":"Supervisor","values":["Lougheed, M Diane","Fisher, John"]},{"key":"dc:creator","label":"Author","values":["Sood, Nilita"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-09-09T22:59:40Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2017-09-09T22:59:40Z"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Methacholine","Asthma","Cough","Deep Inspirations","Bronchodilating"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Attribution-NonCommercial-ShareAlike 3.0 United States"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-sa/3.0/us/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1974/22679"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Rationale: The physiologic variables distinguishing classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough with normal airway sensitivity (COUGH) are incompletely understood. Defining the range of normal responses associated with deep inspirations (DIs) during high-dose MCh is key to understand the clinical relevance of COUGH. Purpose: To characterize responses to DI in healthy normal individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness) during high-dose MCh and compare with responses in CA, CVA and COUGH. Methods: Individuals aged 18-65 years with no history of asthma and/or chronic cough attended 2 visits. On visit 1, after baseline spirometry and body plethysmography, participants were randomized to perform either: (i) modified high-dose MCh challenge using partial and maximal expiratory flow-volume curves (PEFV/MEFV) and impulse oscillometry (IOS) or (ii) traditional high-dose MCh challenge using MEFV, at each dose to a maximum change (∆) in FEV1 of 50% from baseline (MAX). Previously published data (Wasilewski et al., 2016) was used to compare the responses of healthy individuals to individuals with CA (n=11), CVA (n=10) and COUGH (n=7). Results: 15 participants (31.4±7.3years) (Mean±SD) completed the protocol. At MAX, participants developed minor but significant cough (3.2±4.7; p=0.022), dyspnea (Borg: 0.4±0.7; p=0.016), bronchoconstriction (%∆FEV1 -14.7±7.9%; p<0.001) and gas trapping (∆IC -0.20±0.36; p=0.001), compared to baseline. At MAX, the bronchodilation effect of DIs was preserved (DI index: 0.67±0.44 and -0.14 ± 0.15 at MAX and baseline, respectively; p<0.001). Compared to healthy individuals, the COUGH group developed more cough (p=0.006), dyspnea (p=0.029) but comparable bronchoconstriction and gas trapping in response to high-dose MCh. At MAX, the bronchodilating effect was preserved in CA, CVA and healthy participants but impaired in COUGH (DI Index: 0.67±0.97 (CA); 0.51±0.73 (CVA); 0.01±0.36 (COUGH); 0.68±0.45 (healthy participants); p=0.009). Conclusion: The responses to high-dose MCh in healthy participants and participants with COUGH, CVA and CA lie on a continuum, which may reflect fundamental pathophysiological differences in terms of impairment versus preservation of the bronchodilating effect of DIs. COUGH appears to be a clinically relevant phenotype, distinct from healthy normal and CVA."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["M.Sc."]},{"key":"dc:title","label":"Title","values":["Sensory-Mechanical Responses to High-Dose Methacholine Bronchoprovocation: The Modulating Effects of Deep Inspirations"]}]}],"canonical_facts":{"dc:contributor.department":["Biomedical and Molecular Sciences"],"dc:contributor.supervisor":["Lougheed, M Diane","Fisher, John"],"dc:creator":["Sood, Nilita"],"dc:date.accessioned":["2017-09-09T22:59:40Z"],"dc:date.available":["2017-09-09T22:59:40Z"],"dc:description.abstract":["Rationale: The physiologic variables distinguishing classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough with normal airway sensitivity (COUGH) are incompletely understood. Defining the range of normal responses associated with deep inspirations (DIs) during high-dose MCh is key to understand the clinical relevance of COUGH. Purpose: To characterize responses to DI in healthy normal individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness) during high-dose MCh and compare with responses in CA, CVA and COUGH. Methods: Individuals aged 18-65 years with no history of asthma and/or chronic cough attended 2 visits. On visit 1, after baseline spirometry and body plethysmography, participants were randomized to perform either: (i) modified high-dose MCh challenge using partial and maximal expiratory flow-volume curves (PEFV/MEFV) and impulse oscillometry (IOS) or (ii) traditional high-dose MCh challenge using MEFV, at each dose to a maximum change (∆) in FEV1 of 50% from baseline (MAX). Previously published data (Wasilewski et al., 2016) was used to compare the responses of healthy individuals to individuals with CA (n=11), CVA (n=10) and COUGH (n=7). Results: 15 participants (31.4±7.3years) (Mean±SD) completed the protocol. At MAX, participants developed minor but significant cough (3.2±4.7; p=0.022), dyspnea (Borg: 0.4±0.7; p=0.016), bronchoconstriction (%∆FEV1 -14.7±7.9%; p<0.001) and gas trapping (∆IC -0.20±0.36; p=0.001), compared to baseline. At MAX, the bronchodilation effect of DIs was preserved (DI index: 0.67±0.44 and -0.14 ± 0.15 at MAX and baseline, respectively; p<0.001). Compared to healthy individuals, the COUGH group developed more cough (p=0.006), dyspnea (p=0.029) but comparable bronchoconstriction and gas trapping in response to high-dose MCh. At MAX, the bronchodilating effect was preserved in CA, CVA and healthy participants but impaired in COUGH (DI Index: 0.67±0.97 (CA); 0.51±0.73 (CVA); 0.01±0.36 (COUGH); 0.68±0.45 (healthy participants); p=0.009). Conclusion: The responses to high-dose MCh in healthy participants and participants with COUGH, CVA and CA lie on a continuum, which may reflect fundamental pathophysiological differences in terms of impairment versus preservation of the bronchodilating effect of DIs. COUGH appears to be a clinically relevant phenotype, distinct from healthy normal and CVA."],"dc:description.degree":["M.Sc."],"dc:identifier.uri":["http://hdl.handle.net/1974/22679"],"dc:language.iso":["eng"],"dc:rights":["Attribution-NonCommercial-ShareAlike 3.0 United States"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-sa/3.0/us/"],"dc:subject":["Methacholine","Asthma","Cough","Deep Inspirations","Bronchodilating"],"dc:title":["Sensory-Mechanical Responses to High-Dose Methacholine Bronchoprovocation: The Modulating Effects of Deep Inspirations"],"dc:type":["thesis"]},"updated_at":"2026-07-27T20:35:35Z"}