Sensory-Mechanical Responses to High-Dose Methacholine Bronchoprovocation: The Modulating Effects of Deep Inspirations

dc.contributor.authorSood, Nilitaen
dc.contributor.departmentBiomedical and Molecular Sciencesen
dc.contributor.supervisorLougheed, M Dianeen
dc.contributor.supervisorFisher, Johnen's University at Kingstonen
dc.description.abstractRationale: 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.en
dc.embargo.termsIntention to seek publication, based on the results of the research performeden
dc.relation.ispartofseriesCanadian thesesen
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United Statesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectDeep Inspirationsen
dc.titleSensory-Mechanical Responses to High-Dose Methacholine Bronchoprovocation: The Modulating Effects of Deep Inspirationsen
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
3.45 MB
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
2.6 KB
Item-specific license agreed upon to submission