The ventilatory response pattern to exercise across the age-span in healthy adults

Healthy aging is associated with a progressive decline in respiratory function and altered ventilatory mechanics, typically characterized on static physiological measurements. We aimed to evaluate the ventilatory response to exhaustive exercise across the age-span and hypothesized that aging would be associated with inefficient alterations that may be relevant in the etiology of breathlessness. We analyzed ventilatory data obtained from cardiopulmonary exercise tests performed in 526 healthy adults (aged 20-91 years; 52% female) from the COmPLETE cohort. Sample Entropy (SampEn) was used to quantify the irregularity of minute ventilation (V̇_E), breathing frequency (Bf), and tidal volume (V_T) time series. Age versus entropy relationships were assessed using penalized cubic splines, adjusting for sex, BMI, peak oxygen uptake, and FEV₁. As a result, older age was associated with a progressive decline in peak oxygen uptake, V̇_E, Bf, and V_T (all p < 0.001). Ventilatory efficiency also decreased across the age span, evidenced by an increased V_E/VCO₂ nadir, and older adults demonstrated a tachypneic breathing pattern, with a higher Bf to V̇_E ratio (p < 0.001). Contrary to our hypothesis, ventilatory SampEn remained stable through early adulthood but increased after the sixth decade (SampEn Bf p = 0.023; SampEn V_T: p = 0.004; SampEn V̇_E: p = 0.001). In conclusion, older age is accompanied by a shift in the ventilatory response to exercise, characterized by a mechanically constrained, frequency-dominant breathing pattern and diminished ventilatory efficiency. This is associated with increases in ventilatory irregularity that become most apparent after the sixth decade. Further work is needed to determine how these alterations relate to exertional breathlessness.