Mechanisms of exertional dyspnoea in symptomatic smokers without COPD

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.