Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study.

BACKGROUND: There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population. AIMS: To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers. METHOD: We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA). RESULTS: The prevalence of COPD (FEV1/FVC

Exacerbation-like respiratory symptoms in individuals without chronic obstructive pulmonary disease: results from a population-based study.

RATIONALE: Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms. Chronic respiratory symptoms are common in the general population. There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD. AIMS: To determine the occurrence of 'exacerbation-like' events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts. METHOD: We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health. The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory 'exacerbation-like' events in the past year. RESULTS: Individuals without COPD had half the frequency of 'exacerbation-like' events compared with those with COPD. In the non-COPD group, the independent associations with 'exacerbations' included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health. In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001. CONCLUSIONS: Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes. They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD.

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 microg (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 (FEV(1)) 90 (7)% predicted, FEV(1)/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, FEV(1) 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.

Reliability of ventilatory parameters during cycle ergometry in multicentre trials in COPD.

We studied the distribution profiles and repeatability of key exercise performance parameters in the first large multicentre trials to include these measurements in chronic obstructive pulmonary disease (COPD). After a screening visit, 463 subjects with COPD (mean+/-SD forced expiratory volume in 1 s 43+/-13% predicted) completed two run-in visits before treatment randomisation. At the run-in visits, measurements were conducted at rest, at a standardised time near end-exercise (isotime) and at peak exercise during constant work rate (CWR) cycle tests at 75% of each individual's maximum work capacity. The intraclass correlation coefficient was used to evaluate the test-retest repeatability of measurements of endurance time (ET), inspiratory capacity (IC), ventilation and dyspnoea intensity (Borg scale) during exercise. IC, ventilation and dyspnoea ratings were normally distributed; ET showed rightward skew (median or = 0.87). Ventilation was repeatable over the same time-points (R > or = 0.92), as was dyspnoea intensity at isotime (R = 0.79) and at peak exercise (R = 0.81). In conclusion, key perceptual and ventilatory parameters can be reliably measured during CWR cycle exercise in multicentre clinical trials in moderate to very severe COPD.

Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD.

BACKGROUND: This study examined the effects of inhaled furosemide on the ventilatory and perceptual response to high-intensity constant-load cycle exercise in chronic obstructive pulmonary disease (COPD). METHODS: In a randomised, double-blind, placebo-controlled, crossover study, 20 patients with COPD (mean (SD) forced expiratory volume in 1 s 45 (15)% predicted) received either nebulised furosemide 40 mg or placebo on two separate days. Thirty minutes after each treatment, patients performed pulmonary function tests and a symptom-limited cycle exercise test at 75% of their maximum incremental work rate. Changes in spirometry, plethysmographic lung volumes, dynamic operating lung volumes, ventilation, breathing pattern, cardiovascular function, dyspnoea intensity and exercise endurance time were compared between treatments. RESULTS: Compared with placebo, treatment with furosemide resulted in a mean (SD) decrease in dyspnoea intensity at the highest equivalent exercise time (ie, isotime for each patient) of 0.9 (1.0) Borg units (p<0.01) and an increase in exercise endurance time of 1.65 (0.63) min (p<0.05). These improvements were associated with increases in dynamic inspiratory capacity, tidal volume and mean tidal expiratory flow rates at isotime (p<0.01). The eight patients whose exercise endurance time improved by >1 min had greater changes in operating lung volumes (p<0.05), submaximal oxygen pulse (p<0.05) and oxygen uptake (p = 0.05) than those in whom exercise endurance time did not improve. CONCLUSION: Alleviation of exertional dyspnoea after single-dose furosemide inhalation in COPD is multifactorial but improvements in dynamic ventilatory mechanics are contributory in some individuals.

Obesity and the lung: 5. Obesity and COPD.

Chronic obstructive pulmonary disease (COPD) and obesity are common and disabling chronic health conditions with increasing prevalence worldwide. A relationship between COPD and obesity is increasingly recognised, although the nature of this association remains unknown. This review focuses on the epidemiology of obesity in COPD and the impact of excessive fat mass on lung function, exercise capacity and prognosis. The evidence for altered adipose tissue functions in obesity--including reduced lipid storage capacity, altered expression and secretion of inflammatory factors, adipose tissue hypoxia and macrophage infiltration in adipose tissue--is also reviewed. The interrelationship between these factors and their contribution to the development of insulin resistance in obesity is considered. It is proposed that, in patients with COPD, reduced oxidative capacity and systemic hypoxia may amplify these disturbances, not only in obese patients but also in subjects with hidden loss of fat-free mass. The potential interaction between abnormal adipose tissue function, systemic inflammation and COPD may provide more insight into the pathogenesis and reversibility of systemic pathology in this disease.

Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease.

To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65 vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.

Mechanisms of exertional dyspnea in patients with cancer.

Exertional dyspnea is an important symptom in cancer patients, and, in many cases, its cause remains unexplained after careful clinical assessment. To determine mechanisms of exertional dyspnea in a variety of cancer types, we evaluated cancer outpatients with clinically important unexplained dyspnea (CD) at rest and during exercise and compared the results with age-, sex-, and cancer stage-matched control cancer (CC) patients and age- and sex-matched healthy control participants (HC). Participants (n = 20/group) were screened to exclude clinical cardiopulmonary disease and then completed dyspnea questionnaires, anthropometric measurements, muscle strength testing, pulmonary function testing, and incremental cardiopulmonary treadmill exercise testing. Dyspnea intensity was greater in the CD group at peak exercise and for a given ventilation and oxygen uptake (P < 0.05). Peak oxygen uptake was reduced in CD compared with HC (P < 0.05), and breathing pattern was more rapid and shallow in CD than in the other groups (P < 0.05). Reduced tidal volume expansion during exercise correlated with reduced inspiratory capacity, which, in turn, correlated with reduced inspiratory muscle strength. Patients with cancer had a relatively reduced diffusing capacity of the lung for carbon monoxide, reduced skeletal muscle strength, and lower ventilatory thresholds during exercise compared with HC (P < 0.05). There were no significant between-group differences in measurements of airway function, pulmonary gas exchange, or cardiovascular function during exercise. In the absence of evidence of airway obstruction or restrictive interstitial lung disease, the shallow breathing pattern suggests ventilatory muscle weakness as one possible explanation for increased dyspnea intensity at a given ventilation in CD patients.

[Dynamic lung hyperinflation and its clinical implication in COPD]. / Implications cliniques de la distension thoracique, ou quand la physiopathologie change la prise en charge thérapeutique.

Static lung hyperinflation is defined as the elevation of end- expiratory lung volume above its predicted value, with no increase in end-expiratory alveolar pressure, which remains equal to atmospheric pressure. Dynamic hyperinflation is the transient increase of this volume above the relaxation volume. In patients with COPD, dynamic hyperinflation is mainly determined by the mechanical properties of the respiratory system. Its measurement relies on plethysmography and, during exercise, inspiratory capacity. During exercise, dynamic hyperinflation attenuates expiratory flow limitation but increases the inspiratory loading and induces functional weakness of the diaphragm. It also has haemodynamic consequences and results in more rapid, shallow breathing and progressive reduction in dynamic lung compliance. These events explain exercise intolerance. Several approaches may help combat dynamic hyperinflation and its deleterious clinical effects: bronchodilators, hyperoxia, helium-oxygen mixtures, lung volume reduction surgery...

Effect of tiotropium bromide on the cardiovascular response to exercise in COPD.

INTRODUCTION: Exercise limitation and exertional dyspnea are important symptoms of chronic obstructive pulmonary disease (COPD), which may be partially relieved by tiotropium. Although the mechanism of relief is multifactorial, improved dynamic ventilatory mechanics appear to be important. It is not however known whether tiotropium may also act by improving cardiovascular function during exercise. METHODS: We conducted a randomized, placebo-controlled crossover study in 18 COPD subjects with a FEV(1) 40+/-3% predicted (mean+/-SEM). Subjects inhaled either tiotropium 18 microg or placebo once daily for 7-10 days then the other intervention for a further 7-10 days after a 35-day washout period. Subjects performed constant work rate cycle exercise at 75% of maximum after each treatment period. Heart rate, blood pressure, oxygen uptake, operating lung volumes and breathing pattern were measured. RESULTS: Heart rate was 7 beats/min lower at rest and throughout exercise with tiotropium compared to placebo (p=0.001). Oxygen uptake was unchanged throughout exercise. Oxygen pulse on exercise was greater by 7.4% (p<0.01) and systolic blood pressure was lower by 7 mmHg (p=0.03). The cardiac rate pressure product was reduced by 7.6% (p<0.01) with tiotropium. Exercise endurance tended to be greater with tiotropium. Reduction in heart rate on exercise correlated with an increase in inspiratory reserve volume (r=-0.50, p=0.04). CONCLUSION: Tiotropium may improve cardiac as well as pulmonary function during exercise in COPD. We suggest that this effect may be due, in part, to improved cardiopulmonary interaction as a result of mechanical unloading of the ventilatory muscles however further study is required.

Smoking, activity level and exercise test outcomes in a young population sample without cardiopulmonary disease.

AIM: Whether reduced activity level and exercise intolerance precede the clinical diagnosis of cardiopulmonary disorders in smokers is not known. We examined activity level and exercise test outcomes in a young population-based sample without overt cardiopulmonary disease, differentiating by smoking history. METHODS: This was a multiyear cross-sectional study using United States National Health and Nutrition Examination Survey data from 1999-2004. Self-reported activity level and incremental exercise treadmill testing were obtained on survey participants ages 20-49 years, excluding individuals with cardio-pulmonary disease. RESULTS: Three thousand seven hundred and one individuals completed exercise testing. Compared to never smokers, current smokers with >10 pack years reported significantly higher odds of little or no recreation, sport, or physical activity (adjusted OR 1.62; 95% CI 1.12-2.35). Mean perceived exertion ratings (Borg 6-20) at an estimated standardized workload were significantly greater among current smokers (18.3-18.6) compared to never (17.3) and former smokers (17.9) (p<0.05). There were no significant differences in the proportions of individuals across estimated peak oxygen uptake categories among the groups after adjusting for age and sex. Among former smokers, increasing duration of smoking abstinence was associated with significantly lower likelihood of low estimated peak oxygen uptake categorization (p<0.05). CONCLUSIONS: Among young individuals without overt cardiopulmonary disease, current smokers had reduced daily activity and higher perceived exertion ratings. Besides supporting early smoking cessation, these results set the stage for future studies that examine mechanisms of activity restriction in young smokers and the utility of measures of activity restriction in the earlier diagnosis of smoking-related diseases.

Assessment of bronchodilator efficacy in symptomatic COPD: is spirometry useful?

Bronchodilator therapy in COPD is deemed successful if it improves ventilatory mechanics to a degree where effective symptom alleviation and increased exercise capacity are achieved. A greater understanding of the pathophysiologic mechanisms of dyspnea and exercise intolerance in COPD has prompted a reevaluation of the manner in which we currently assess therapeutic efficacy. The traditional reliance on an improved postbronchodilator FEV(1) as indicative of a positive clinical response has recognized limitations. To the extent that pharmacologic volume reduction is a desirable therapeutic goal with favorable implications for dyspnea relief and increased exercise tolerance, the potential value of bronchodilator-induced changes in lung volume measurements is currently being studied. It is unlikely, however, given the multifactorial nature of dyspnea and exercise limitation in COPD, that resting spirometric measurements of maximal flows and volumes alone will be sufficiently sensitive to adequately predict a positive clinical response to bronchodilator therapy. Thus, additional direct measurements of exercise dynamic hyperinflation and exercise endurance together with reliable subjective measurements of dyspnea and quality of life are recommended in the setting of a suitable placebo-controlled design.

Breathlessness in patients with severe chronic airflow limitation. Physiologic correlations.

We wished to identify the physiologic abnormalities that distinguish severely breathless (SB) patients with chronic airflow limitation (CAL) from mildly breathless (MB) patients. Thirty-seven patients with stable, advanced CAL (FEV1 = 38 +/- 10 percent predicted, mean +/- SD) were separated into two distinct groups, SB and MB, solely on the basis of their baseline dyspnea index (BDI). BDI ratings in SB (n = 17) and MB (n = 20) patients were 2.5 +/- 1.5 and 8.5 +/- 1.5 (mean +/- SD), respectively (p less than 0.001). Groups were compared with respect to pulmonary function, breathing pattern parameters, arterial blood gases (ABGs), and responses to progressive exercise. Steady-state gas-exchange parameters were measured in a subgroup of 16 patients during exercise. There were no significant intergroup differences in dynamic flows, plethysmographic lung volumes, ABGs, resting ventilation, or breathing pattern parameters. However, the SB group had significantly lower single-breath diffusing capacities for carbon monoxide (Dco) (by an average of 50 percent, p less than 0.001), together with significantly higher resting ventilatory equivalents for carbon dioxide (VE/VCO2) (by 17 percent, p less than 0.01) and dead space to tidal volume ratios (by 11 percent, p less than 0.05). Ventilatory responses for a given metabolic load were, on average, 33 percent higher (p less than 0.05) in the SB group reflecting greater ventilation-perfusion inhomogeneity and wasted ventilation. The SB subgroup (n = 7), in contrast to the MB subgroup (n = 9), demonstrated significantly (p less than 0.01) greater O2 desaturation during exercise; PaO2 decreased in SB and MB at peak exercise by -13 +/- 7 mm Hg and -4 +/- 2 mm Hg (mean +/- SD), respectively. Stepwise regression analysis selected DCO and VE/VCO2 as the only predictors of breathlessness in this group, accounting for 52 percent of the variance in BDI (F-ratio = 18.49, p less than 0.001). Although the origin of breathlessness is multifactorial, variation in its intensity among patients with comparable levels of airflow limitation can be accounted for, in part, by underlying pathophysiologic differences. Severely breathless patients were characterized by lower resting diffusing capacities and accelerated ventilatory responses to exercise.

Mechanisms of relief of exertional breathlessness following unilateral bullectomy and lung volume reduction surgery in emphysema.

STUDY OBJECTIVE: To explore mechanisms of relief of exertional breathlessness following surgery to reduce thoracic gas volume in patients with emphysema. MATERIALS AND METHODS: We studied 8 patients with emphysema (FEV1 = 39 +/- 3% predicted; residual volume [RV] = 234 +/- 12% predicted; mean +/- SEM) who were severely breathless despite optimal pharmacotherapy and who underwent unilateral bullectomy for giant bullae (greater than one third hemithorax); 4 of these also had ipsilateral lung reduction (pneumectomy). Pulmonary function and cycle exercise performance (n = 6) were evaluated before and 13 +/- 3 weeks after surgery. Chronic breathlessness was measured with the Baseline Dyspnea Index and the Medical Research Council dyspnea scale. Exertional breathlessness was measured using Borg ratings at a standardized work rate (BorgSTD). RESULTS: FEV1, FVC, and maximal inspiratory pressures increased postsurgery by 29 +/- 7% (p < 0.05), 24 +/- 10% (p = 0.06), and 39 +/- 12% (p < 0.01), respectively. Plethysmographic total lung capacity, RV, and functional residual capacity fell by 14 +/- 2%, 30 +/- 4%, and 18 +/- 3%, respectively (p < 0.001). All measures of chronic breathlessness improved significantly (p < 0.05). During exercise at a standardized work rate, BorgSTD fell 45% (p < 0.05), end-expiratory lung volume (EELV) fell 22% (p < 0.01), and breathing frequency (F) fell 25% (p = 0.08). By multiple stepwise regression analysis, 99% (p = 0.007) of the variance in symptom relief (delta BorgSTD) was explained by the combination of decreased ratio of the end-expiratory lung volume to total lung capacity, decreased F, and diminished mechanical constraints on tidal volume (tidal volume to vital capacity ratio). CONCLUSION: Reduced exertional breathlessness at a given workload after volume reduction surgery was attributed to a combination of reduced thoracic hyperinflation, reduced F, and reduced mechanical constraints on lung volume expansion.

External mechanical loading in conscious humans: role of upper airway mechanoreceptors.

To determine whether upper airway mechanoreceptors partly subserve the ventilatory response to external mechanical loading in conscious humans, we studied 11 laryngectomized subjects. The oropharynx (OP) or tracheostomy was selectively loaded (in random order) by attaching the mouth or tracheal tube to a special pressure-generating apparatus, and steady-state ventilatory responses were recorded. Phasic negative pressure changes generated at the OP to simulate inspiratory resistive loading, expiratory resistive unloading, and elastic loading resulted in trivial prolongation of inspiratory duration by 12, 9, and 4%, respectively; other ventilatory variables were not significantly altered. Phasic positive pressure changes at the OP that simulated inspiratory resistive unloading and expiratory resistive loading had little effect on breathing pattern. When the above loads were applied via the tracheostomy, using pressures of similar magnitude, ventilatory responses were qualitatively similar and quantitatively not significantly different from those of normal healthy controls. The results suggest that the OP does not make an important contribution to ventilatory responses during external mechanical loading in conscious humans. Loading responses to conventional mechanical loads are preserved in the absence of afferent information from the upper airways.

Respiratory sensation during chest wall restriction and dead space loading in exercising men.

We mimicked important mechanical and ventilatory aspects of restrictive lung disorders by employing chest wall strapping (CWS) and dead space loading (DS) in normal subjects to gain mechanistic insights into dyspnea causation and exercise limitation. We hypothesized that thoracic restriction with increased ventilatory stimulation would evoke exertional dyspnea that was similar in nature to that experienced in such disorders. Twelve healthy young men [28 +/- 2 (SE) yr of age] completed pulmonary function tests and maximal cycle exercise tests under four conditions, in randomized order: 1) control, 2) CWS to 60% of vital capacity, 3) added DS of 600 ml, and 4) CWS + DS. Measurements during exercise included cardiorespiratory parameters, esophageal pressure, and Borg scale ratings of dyspnea. Compared with control, CWS significantly reduced the tidal volume response to exercise, increased dyspnea intensity at any given work rate or ventilation, and thus limited exercise performance. DS stimulated ventilation but had minimal effects on dyspnea and exercise performance. Adding DS to CWS further increased dyspnea by 1.7 +/- 0.6 standardized Borg units (P = 0.012) and decreased exercise performance (total work) by 21 +/- 6% (P = 0.003) over CWS alone. Across conditions, increased dyspnea intensity correlated best with decreased resting inspiratory reserve volume (r = -0.63, P < 0.0005). Dyspnea during CWS was described primarily as "inspiratory difficulty" and "unsatisfied inspiration," similar to restrictive disorders. In conclusion, severe dyspnea and exercise intolerance were provoked in healthy normal subjects when tidal volume responses were constrained in the face of increased ventilatory drive during exercise.

Qualitative aspects of exertional dyspnea in patients with interstitial lung disease.

We compared qualitative and quantitative aspects of perceived exertional dyspnea in patients with interstitial lung disease (ILD) and normal subjects and sought a physiological rationale for their differences. Twelve patients with ILD [forced vital capacity = 64 +/- 4 (SE) %predicted] and 12 age-matched normal subjects performed symptom-limited incremental cycle exercise tests with measurements of dyspnea intensity (Borg scale), ventilation, breathing pattern, operational lung volumes, and esophageal pressures (Pes). Qualitative descriptors of dyspnea were selected at exercise cessation. Both groups described increased "work and/or effort" and "heaviness" of breathing; only patients with ILD described "unsatisfied inspiratory effort" (75%), "increased inspiratory difficulty" (67%), and "rapid breathing" (58%) (P < 0.05 patients with ILD vs. normal subjects). Borg-O2 uptake (VO2) and Borg-ventilation slopes were significantly greater during exercise in patients with ILD (P < 0.01). At peak exercise, when dyspnea intensity and inspiratory effort (Pes-to-maximal inspiratory pressure ratio) were similar, the distinct qualitative perceptions of dyspnea in patients with ILD were attributed to differences in dynamic ventilatory mechancis, i.e., reduced inspiratory capacity, heightened Pes-to-tidal volume ratio, and tachypnea. Factors contributing to dyspnea intensity in both groups were also different: the best correlate of the Borg-VO2 slope in patients with ILD was the resting tidal volume-to-inspiratory capacity ratio (r = 0.58, P < 0.05) and in normal subjects was the slope of Pes-to-maximal inspiratory pressure ratio over VO2 (r = 0.60, P < 0. 05).

Ventilatory limitations in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterized by dysfunction of the small and large airways, as well as by destruction of the lung parenchyma and vasculature, in highly variable combinations. Breathlessness and exercise intolerance are the most common symptoms in COPD and progress relentlessly as the disease advances. Exercise intolerance is multifactorial, but in more severe disease, ventilatory limitation is often the proximate exercise-limiting event. Multiple factors determine ventilatory limitation and include integrated abnormalities in ventilatory mechanics and ventilatory muscle function as well as increased ventilatory demands (as a result of gas exchange abnormalities) and alterations in the neuroregulatory control of breathing. Despite its heterogeneity, the pathophysiological hallmark of COPD is expiratory flow limitation. When ventilation increases in flow-limited patients during exercise, air trapping is inevitable and causes further dynamic lung hyperinflation (DH) above the already increased resting volumes. DH causes elastic and inspiratory threshold loading of inspiratory muscles already burdened with increased resistive work. It seriously constrains tidal volume expansion during exercise. DH compromises the ability of the inspiratory muscles to generate pressure, and the positive intrathoracic pressures likely contribute to cardiac impairment during exercise. Progressive DH hastens the development of critical ventilatory constraints that limit exercise and, by causing serious neuromechanical uncoupling, contributes importantly to the quality and intensity of breathlessness. The corollary of this is that therapeutic interventions that reduce operational lung volumes during exercise, by improving lung emptying or by reducing ventilatory demand (which delays the rate of DH), result in clinically meaningful improvement of exercise endurance and symptoms in disabled COPD patients.