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Mechanisms of exertional dyspnoea in symptomatic smokers without COPD
Open accessAbstract
Dyspnoea and activity limitation can occur in smokers who do not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are unknown. Detailed pulmonary function tests and sensory–mechanical relationships during incremental exercise with respiratory pressure measurements and diaphragmatic electromyography (EMG di ) were compared in 20 smokers without spirometric COPD and 20 age-matched healthy controls. Smokers (mean± sd post-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity 75±4%, mean± sd FEV 1 104±14% predicted) had greater activity-related dyspnoea, poorer health status and lower physical activity than controls. Smokers had peripheral airway dysfunction: higher phase-III nitrogen slopes (3.8±1.8 versus 2.6±1.1%·L −1 ) and airway resistance (difference between airway resistance measured at 5 Hz and 20 Hz 19±11 versus 12±7% at 5 Hz) than controls (p<0.05). Smokers had significantly (p<0.05) lower peak oxygen uptake (78±40 versus 107±45% predicted) and ventilation (61±26 versus 97±29 L·min −1 ). Exercise ventilatory requirements, operating lung volumes and cardio-circulatory responses were similar. However, submaximal dyspnoea ratings, resistive and total work of breathing were increased in smokers compared with controls (p<0.05); diaphragmatic effort (transdiaphragmatic pressure/maximumal transdiaphragmatic pressure) and fractional inspiratory neural drive to the diaphragm (EMG di /maximal EMG di ) were also increased (p<0.05) mainly reflecting the reduced denominator. Symptomatic smokers at risk for COPD had greater exertional dyspnoea and lower exercise tolerance compared with healthy controls in association with greater airways resistance, contractile diaphragmatic effort and fractional inspiratory neural drive to the diaphragm.
Overview
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TL;DR
Symptomatic smokers without spirometric COPD had greater exertional dyspnoea and lower exercise tolerance than age-matched healthy controls, despite similar ventilatory requirements and operating lung volumes. The findings link their dyspnoea to peripheral airway dysfunction, greater resistive work of breathing, higher diaphragmatic effort, and increased fractional inspiratory neural drive to the diaphragm.
Key findings
- Smokers (n=20) had post-bronchodilator FEV1/FVC 75±4% and FEV1 104±14% predicted, with greater activity-related dyspnoea, poorer health status, and lower physical activity than controls; they also showed peripheral airway dysfunction, including higher phase-III nitrogen slope (3.8±1.8 versus 2.6±1.1%·L⁻¹) and higher R5–20 (19±11 versus 12±7% at 5 Hz) (p<0.05).
- At peak exercise, smokers had lower peak oxygen uptake (78±40 versus 107±45% predicted) and ventilation (61±26 versus 97±29 L·min⁻¹), while ventilatory requirements, operating lung volumes, and cardio-circulatory responses were similar; at 80 W, dyspnoea was 1.9 Borg units higher, and dyspnoea–ventilation slopes were greater (0.108±0.05 versus 0.067±0.04 Borg units·L⁻¹·min⁻¹, p=0.008).
- Submaximal resistive and total work of breathing were increased in smokers, as were Pdi/Pdi,max and EMGdi/EMGdi,max, mainly reflecting a reduced denominator; EMGdi,max during the highest inspiratory capacity was lower in smokers (113±65 versus 165±56 µV, p=0.028).
- Dyspnoea intensity correlated with EMGdi/EMGdi,max (partial R²=0.67, p<0.0005) and inspiratory Pdi/Pdi,max (partial R²=0.61, p<0.0005), with similar relationships across groups.
Methods
- Cross-sectional study of 20 symptomatic current or ex-smokers without spirometric COPD (post-bronchodilator FEV1 >80% predicted, FEV1/FVC >0.7 and above lower limit of normal; age ≥40 years; ≥20 pack-years) and 20 age-matched healthy non-smoking controls.
- Participants completed questionnaires, pre- and post-bronchodilator pulmonary function tests, small airway tests (single-breath nitrogen washout and impulse oscillometry), and incremental cycle cardiopulmonary exercise testing with respiratory pressure measurements and diaphragmatic electromyography (EMGdi); 14 subjects per group accepted the EMGdi/pressure catheter.
- Between-group comparisons used unpaired t-tests at rest, iso-work rates, and peak exercise; multivariable linear regression evaluated dyspnoea intensity against EMGdi/EMGdi,max and inspiratory Pdi/Pdi,max, with group, interaction, and subject random effects.
Limitations
- Stated: not all subjects consented to EMGdi and respiratory pressure measurements because of invasiveness, though the n=14 subgroup was sufficient to detect differences; results cannot be generalised to asymptomatic smokers; EMGdi measured only the crural diaphragm, so ribcage and accessory muscle activity could not be assessed.
- Stated in discussion: the skeletal muscle deconditioning hypothesis for greater leg discomfort was not formally tested.
- Evident from the text: the cross-sectional design cannot establish causality, and the modest sample size (20 per group; 14 per group for EMGdi) limits broader generalisability.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fractional inspiratory neural drive to the diaphragm was increased both at rest and during exercise in smokers compared with controls (figure 3).”
§ Mechanisms of exertional dyspnoea in symptomatic smokers without COPD > Discussion
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- Rests on an assumption not shown here.
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In the paper
“There were no significant differences in resting pulmonary function and IOS measurements between active and ex-smokers (all p>0.05).”
§ Mechanisms of exertional dyspnoea in symptomatic smokers without COPD > Pulmonary function and small airway function
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Poes-derived indices of global inspiratory muscle effort (inspiratory Poes/Pi,max) and expiratory muscle activity (expiratory rise in Pga) were not significantly different between groups (figure 3, figures E1 and E3).”
§ Mechanisms of exertional dyspnoea in symptomatic smokers without COPD > Exercise responses, respiratory mechanics and diaphragmatic function
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, submaximal dyspnoea ratings, resistive and total work of breathing were increased in smokers compared with controls ( p<0.05); diaphragmatic effort (transdiaphragmatic pressure/ maximumal transdiaphragmatic pressure) and fractional inspiratory neural drive to the diaphragm (EMGdi/maximal EMGdi) were also”
- Also stated in: § Exercise responses, respiratory mechanics and diaphragmatic function · plain
“Inspiratory Pdi was similar for a given work rate and V′E, while inspiratory Pdi/Pdi,max was greater in smokers at rest and during exercise due to reduced Pdi,max (figure 3, figure E3).”
§ Mechanisms of exertional dyspnoea in symptomatic smokers without COPD > Abstract
plainstates an associationn = 20- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Exercise responses, respiratory mechanics and diaphragmatic function · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EMGdi,max during the highest inspiratory capacity was lower in smokers versus controls (113±65 versus 165±56 µV, p=0.028).”
§ Mechanisms of exertional dyspnoea in symptomatic smokers without COPD > Exercise responses, respiratory mechanics and diaphragmatic function
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Self-citation
Metadata
- Authors
- Elbehairy, A. F., Guenette, J. A., Faisal, A., Ciavaglia, C. E., Webb, K. A., Jensen, D., Ramsook, A. H., Neder, J. A., & O'Donnell, D. E.
- Affiliations
- Queen's University (CA)
- University of British Columbia (CA)
- McGill University (CA)
- ORCID
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2016-08-04
- Volume
- 48
- Issue
- 3
- Pages
- 694-705
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W2484791473
- Semantic Scholar
- 79fcd24a2c301bce450f06ef2a1b6735bee48618
- Cited by
- 99
- References
- 44
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 5 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 15 · 2017: 11 · 2016: 3
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ontario Thoracic Society
- Canadian Institutes of Health Research
- William Spear/Richard Start Endowment Fund, Queen's University, Canada
- Canadian Lung Association (CLA)/Canadian Thoracic Society
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
- Keywords
- exertional dyspnea, smokers, COPD risk, airway resistance, work of breathing, diaphragm electromyography, exercise tolerance, peak oxygen uptake, health status
- MeSH terms
- Adult, Aged, Inhalation, Cross-Sectional Studies, Diaphragm, Dyspnea, Electromyography, Exercise Test, Female, Forced Expiratory Volume, Humans, Lung, Male, Middle Aged, Oxygen, Phenotype, Respiration, Respiratory Function Tests, Risk, Smoking, Spirometry, Vital Capacity, Body Mass Index, Multivariate Analysis, Exercise Tolerance, Pulmonary Disease, Chronic Obstructive
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