Sex differences in exercise-induced diaphragmatic fatigue in endurance-trained athletes

There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 ± 1.9 ml·kg–1·min–1) and women (n = 19; maximal aerobic capacity = 57.1 ± 1.5 ml·kg–1·min–1). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a 15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 ± 2.3, 20.7 ± 3.2, and 13.3 ± 4.5%, respectively, whereas results in women (n = 8) were 21.0 ± 2.1, 11.6 ± 2.9, and 9.7 ± 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts

Pathogenesis of hyperinflation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease

Respiratory mechanics during exercise in endurance trained men and women

A number of recent studies have shown that young healthy women may be susceptible to pulmonary system limitations during exercise including expiratory flow limitation (EFL). Several sex based differences in the anatomy and function of the pulmonary system have been reported as possible mechanisms. For example, women consistently have smaller lung volumes, smaller diameter airways, and a decreased diffusion surface area relative to height matched men. These anatomical differences may also have implications in terms of breathing mechanics, particularly at maximal exercise. However, there have been no studies that have systematically compared the mechanics of breathing in men and women. Accordingly, the purpose of the present study was to provide a comprehensive assessment of breathing mechanics including the measurement of EFL, end expiratory lung volume (EELV), end inspiratory lung volume (EILV), and the work of breathing (Wb) in endurance trained men and women. It was hypothesized that women would develop EFL more frequently than men and that women would have greater relative increases in EELV and EILV at maximal exercise. It was also hypothesized that women would have a higher Wb across a range of ventilations. EFL was assessed by applying a negative expiratory pressure (NEP) at the mouth and comparing the resultant flow volume curve with that of the preceding control breath. If the NEP increased expiratory flow rate, the subject was considered non flow limited. Conversely, if application of the NEP did not illicit an increase in expiratory flow, the subject was considered flow limited. Operational lung volumes (i.e., EELV and EILV) were determined at various stages of exercise by having subjects perform inspiratory capacity manoeuvres. Flow, volume, oesophageal and airway opening pressure were continuously monitored throughout exercise. Trans-pulmonary pressure (Ptp) was taken as the difference between oesophageal and airway opening pressure which was then plotted against volume. The integral of the Ptp-volume loop was multiplied by breathing frequency to determine the Wb. A total of 18 endurance trained male (n=8) and female (n=10) athletes volunteered to participate in this study. Males had a higher absolute (mean ± SD; 5.30 ± 0.7 vs. 3.8 ± 0.4 L min⁻¹) and relative (69.5 ± 7.8 vs. 59.8 ± 4.8 mL-kg-¹.min-¹) VOE₂MAX and a higher maximal minute ventilation (161 ± 25 vs. 120 ± 18 L.min-¹) compared to females (P<0.01). Due to an abnormal response to the NEP in one male subject, EFL data was obtained in 7 of the 8 males. EFL occurred in 9 females (90%) and 4 males (57%) during the final stage of exercise. However, 8 (6F, 2M) of these subjects were later able to overcome EFL during the final stage of exercise through an alteration in breathing pattern. Females had a higher relative EELV (42±8 vs. 35±5 %FVC) and EILV (88±5v s. 82±7 %FVC) compared to males at maximal exercise (P<0.05). Women also had a higher Wb compared to men across a range of ventilations. On average, women had a Wb that was twice that of men at ventilatioℓ̨̨ns above 90 L.rninw’. This data suggests that EFL may be more common in females and that they experience greater relative increases in EELV and EILV at maximal exercise compared to males. The higher Wb in women is likely attributed to their smaller lung volumes and smaller diameter airways. Collectively, these findings suggest that women utilize the majority of their ventilatory reserve compared to men but the associated cost may have physiological and performance based implications.Education, Faculty ofKinesiology, School ofGraduat

New Insights into the Pathophysiology of Mild Chronic Obstructive Pulmonary Disease

The classification of mild chronic obstructive pulmonary disease (COPD) requires a postbronchodilator forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio <0.7 and an FEV1 ≥80% predicted. Given their relatively well-preserved spirometry, some have argued that respiratory symptoms in patients with mild COPD are unlikely to be related to pulmonary function abnormalities and that early detection of COPD is a ‘waste of resources’. Despite this viewpoint, there is emerging clinical and physiological evidence of peripheral airway dysfunction, diminished quality of life and reduced physical activity levels, and increased mortality, hospitalizations, dyspnea and exercise intolerance in patients with mild COPD compared with healthy controls. The purpose of the present focused review was to summarize recent research regarding the pathophysiology and treatment of mild COPD

The role of pharmacotherapy in mild to moderate chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and most of those afflicted have mild to moderate disease as measured by spirometry. There is mounting evidence that even mild airway obstruction is associated with activity-related dyspnea, exercise limitation, impaired quality of life, increased hospitalization and mortality. As our understanding of the complex, heterogeneous pathophysiology and clinical consequences of milder COPD continues to grow, there is increasing interest in the potential impact of therapeutic interventions beyond smoking cessation. Unfortunately, few clinical trials have included patients with mild to moderate disease and the evidence base for pharmacological treatment in this subpopulation is currently lacking. Recent short-term mechanistic studies confirm that reversal of airway smooth muscle cholinergic tone consistently improves respiratory mechanics during rest and exercise in mild COPD but long-term clinical benefits remain to be evaluated. Secondary analysis of large, prospective studies designed to evaluate the efficacy of long-acting bronchodilators, inhaled corticosteroids and combination therapy indicate that patients with moderate COPD achieve comparable benefits to those with advanced disease. In the absence of evidence-based guidelines for the management of milder COPD, treatment choices are driven mainly by clinical presentation: for those with persistent and troublesome activity-related dyspnea a trial of inhaled bronchodilator therapy is justified; for those with a propensity for recurrent infective exacerbations, consideration of additional anti-inflammatory treatment seems reasonable. In this paper, we review the current knowledge base and emerging paradigm for the pharmacological treatment of mild to moderate COPD

Therapeutic Advances in Respiratory Disease The role of pharmacotherapy in mild to moderate chronic obstructive pulmonary disease The role of pharmacotherapy in mild to moderate chronic obstructive pulmonary disease

Abstract: Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and most of those afflicted have mild to moderate disease as measured by spirometry. There is mounting evidence that even mild airway obstruction is associated with activity-related dyspnea, exercise limitation, impaired quality of life, increased hospitalization and mortality. As our understanding of the complex, heterogeneous pathophysiology and clinical consequences of milder COPD continues to grow, there is increasing interest in the potential impact of therapeutic interventions beyond smoking cessation. Unfortunately, few clinical trials have included patients with mild to moderate disease and the evidence base for pharmacological treatment in this subpopulation is currently lacking. Recent short-term mechanistic studies confirm that reversal of airway smooth muscle cholinergic tone consistently improves respiratory mechanics during rest and exercise in mild COPD but long-term clinical benefits remain to be evaluated. Secondary analysis of large, prospective studies designed to evaluate the efficacy of long-acting bronchodilators, inhaled corticosteroids and combination therapy indicate that patients with moderate COPD achieve comparable benefits to those with advanced disease. In the absence of evidence-based guidelines for the management of milder COPD, treatment choices are driven mainly by clinical presentation: for those with persistent and troublesome activity-related dyspnea a trial of inhaled bronchodilator therapy is justified; for those with a propensity for recurrent infective exacerbations, consideration of additional antiinflammatory treatment seems reasonable. In this paper, we review the current knowledge base and emerging paradigm for the pharmacological treatment of mild to moderate COPD

Respiratory Consequences of Mild-to-Moderate Obesity: Impact on Exercise Performance in Health and in Chronic Obstructive Pulmonary Disease

In many parts of the world, the prevalence of obesity is increasing at an alarming rate. The association between obesity, multiple comorbidities, and increased mortality is now firmly established in many epidemiological studies. However, the link between obesity and exercise intolerance is less well studied and is the focus of this paper. Although exercise limitation is likely to be multifactorial in obesity, it is widely believed that the respiratory mechanical constraints and the attendant dyspnea are important contributors. In this paper, we examined the evidence that critical ventilatory constraint is a proximate source of exercise limitation in individuals with mild-to-moderate obesity. We first reviewed existing information on exercise performance, including ventilatory and perceptual response patterns, in obese individuals who are otherwise healthy. We then considered the impact of obesity in patients with preexisting respiratory mechanical abnormalities due to chronic obstructive pulmonary disease (COPD), with particular reference to the effect on dyspnea and exercise performance. Our main conclusion, based on the existing and rather sparse literature on the subject, is that abnormalities of dynamic respiratory mechanics are not likely to be the dominant source of dyspnea and exercise intolerance in otherwise healthy individuals or in patients with COPD with mild-to-moderate obesity