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Evaluation of acute bronchodilator reversibility in patients with symptoms of GOLD stage I COPD

Background: Patients with symptoms of GOLD stage I chronic obstructive pulmonary disease (COPD) can have significant abnormalities of ventilatory mechanics with greater exertional symptoms and exercise limitation than age-matched healthy subjects. In such patients the impact of bronchodilator therapy remains unknown and is difficult to evaluate. Methods: The acute effects of nebulised ipratropium bromide 500 μg (IB) on resting pulmonary function and on dyspnoea and ventilatory parameters during symptom-limited constant work rate cycle exercise were measured. In a randomised double-blind crossover study, 16 patients with COPD (mean (SD) post-bronchodilator forced expiratory volume in 1 s (FEV1) 90 (7)% predicted, FEV1/forced vital capacity (FVC) 59 (7)%) with a significant smoking history (mean (SD) 44 (16) pack-years) inhaled either IB or placebo on each of two separate visits. Pulmonary function tests and cycle exercise at 80–85% of each subject’s maximal work capacity were performed 2 h after dosing. Results: Compared with placebo, FEV1 increased 5 (9)% predicted, residual volume decreased 12 (20)% predicted and specific airway resistance decreased 81 (93)% predicted (all p<0.05) after IB. At a standardised time during exercise, dynamic inspiratory capacity and tidal volume significantly increased in tandem by 0.12 and 0.16 litres, respectively (each p<0.05), dyspnoea fell by 0.9 (1.8) Borg units (p = 0.07) and dyspnoea/ventilation ratios fell significantly (p<0.05). The fall in dyspnoea intensity at higher submaximal ventilations correlated with the concurrent decrease in end-expiratory lung volume (p<0.05). Conclusion: In patients with symptoms of GOLD stage I COPD, IB treatment is associated with modest but consistent improvements in airway function, operating lung volumes and dyspnoea intensity during exercise. These results provide a physiological rationale for a trial of bronchodilator therapy in selected patients with milder but symptomatic COPD.

Lung Hyperinflation and Its Reversibility in Patients with Airway Obstruction of Varying Severity

ABSTRACT The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a post-bronchodilator FEV1/FVC <0.70. We examined relationships between indices of airway obstruction and lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV1 decreased, while VC and IC decreased linearly. Regardless of baseline FEV1, the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.

Sex differences in the perceived intensity of breathlessness during exercise with advancing age

The prevalence of activity-related breathlessness increases with age, particularly in women, but the specific underlying mechanisms have not been studied. This novel cross-sectional study was undertaken to examine the effects of age and sex, and their interaction, on the perceptual and ventilatory responses to incremental treadmill exercise in 73 healthy participants (age range 40-80 yr old) with normal pulmonary function. Age-related changes at a standardized oxygen uptake (Vo(2)) during exercise included significant increases in breathlessness ratings (Borg scale), ventilation (Ve), ventilatory equivalent for carbon dioxide, and the ratio of tidal volume (Vt) to dynamic inspiratory capacity (IC) (all P < 0.05). These changes were quantitatively similar in women (n = 39) and in men (n = 34). For the group as a whole, exertional breathlessness ratings increased as resting static inspiratory muscle strength diminished (P = 0.05), as exercise ventilation increased relative to capacity (P = 0.013) and as the Vt/IC ratio increased (P = 0.003) during exercise. Older women (60-80 yr old, n = 23) reported greater (P < 0.05) intensity of exertional breathlessness at a standardized Vo(2) and Ve than age-matched men (n = 16), despite similar age-related changes in ventilatory demand and dynamic ventilatory mechanics. These increases in breathlessness ratings in older women disappeared when sex differences in baseline maximal ventilatory capacity were accounted for. In conclusion, although increased exertional breathlessness with advancing age is multifactorial, contributory factors included higher ventilatory requirements during exercise, progressive inspiratory muscle weakness, and restrictive mechanical constraints on Vt expansion related to reduced IC. The sensory consequences of this age-related respiratory impairment were more pronounced in women, who, by nature, have relatively reduced maximal ventilatory reserve.

Sex differences in exertional dyspnea in patients with mild COPD: Physiological mechanisms

The purpose of this study was to evaluate the physiological basis for sex-differences in exercise-induced dyspnea in patients with mild COPD. We compared operating lung volumes, breathing pattern and dyspnea during incremental cycling in 32 men (FEV(1)=86±10% predicted) and women (FEV(1)=86±12% predicted) with mild COPD and 32 age-matched controls. There were no sex differences in dyspnea in the control group at any work-rate or ventilation (V(E)). Women with COPD had significantly greater dyspnea than men at 60 and 80 W. At 80 W, dyspnea ratings were 5.7±2.3 and 3.3±2.5 Borg units (P<0.05) and the V(E) to maximal ventilatory capacity ratio was 72% and 55% in women and men, respectively (P<0.05). Comparable increases in dynamic hyperinflation were seen in both male and female COPD groups at symptom limitation but women reached tidal volume constraints at a lower work rate and V(E) than men. Superimposing mild COPD on the normal aging effects had greater sensory consequences in women because of their naturally reduced ventilatory reserve.