Enhanced Respiratory Frequency Response to Lower Limb Mechanoreceptors Activation in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Purpose 

To investigate the mechanoreflex control of respiration and circulation in patients with chronic obstructive pulmonary disease (COPD).

Methods 

Twenty-eight patients with moderate-to-severe COPD (mean ± SD: 67.0 ± 7.9 yr, 10 women) and 14 age- and sex-matched controls (67.9 ± 2.6 yr, 7 women) participated in the study. Their dominant knee was passively moved to stimulate mechanoreceptors, whereas vastus lateralis surface electrical activity checked active contractions. A differential pressure flowmeter, an electrocardiogram, and a servo-controlled finger photoplethysmograph acquired cardiorespiratory data. To gain insight into the mechanoreflex arc, we further analyzed reduced/oxidized glutathione ratio and mechanoreceptor-related gene expression in a vastus lateralis biopsy of additional nine patients (63.9 ± 8.1 yr, 33% women) and eight controls (62.9 ± 9.1 yr, 38% women).

Results 

Patients with COPD had a greater peak respiratory frequency response (COPD: Δ = 3.2 ± 2.3 vs Controls: 1.8 ± 1.2 cycles per minute, P = 0.036) and a smaller peak tidal volume response to passive knee movement than controls. Ventilation, heart rate, stroke volume, and cardiac output peak responses, and total peripheral resistance nadir response, were unaltered by COPD. In addition, patients had a diminished glutathione ratio (COPD: 13.3 ± 3.8 vs controls: 20.0 ± 5.5 a.u., P = 0.015) and an augmented brain-derived neurotrophic factor expression (COPD: 2.0 ± 0.7 vs controls: 1.1 ± 0.4 a.u., P = 0.002) than controls. Prostaglandin E receptor 4, cyclooxygenase 2, and Piezo1 expression were similar between groups.

Conclusions 

Respiratory frequency response to mechanoreceptors activation is increased in patients with COPD. This abnormality is possibly linked to glutathione redox imbalance and augmented brain-derived neurotrophic factor expression within locomotor muscles, which could increase mechanically sensitive afferents’ stimulation and sensitivity.