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PubMed2006

Diaphragmatic function in advanced Duchenne muscular dystrophy.

The aim of this study was to assess diaphragm electrical activation and diaphragm strength in patients with advanced Duchenne muscular dystrophy during resting conditions. Eight patients with advanced Duchenne muscular dystrophy (age of 25 +/- 2 years) were studied during tidal breathing, maximal inspiratory capacity, maximal sniff inhalations, and magnetic stimulation of the phrenic nerves. Six patients were prescribed home mechanical ventilation (five non-invasive and one tracheotomy). Transdiaphragmatic pressure and diaphragm electrical activation were measured using an esophageal catheter. During tidal breathing (tidal volume 198 +/- 83 ml, breathing frequency 25 +/- 7), inspiratory diaphragm electrical activation was clearly detectable in seven out of eight patients and was 12 +/- 7 times above the noise level, and represented 45 +/- 19% of the maximum diaphragm electrical activation. Mean inspiratory transdiaphragmatic pressure during tidal breathing was 1.5 +/- 1.2 cmH2O, and during maximal sniff was 7.6 +/- 3.6 cmH2O. Twitch transdiaphragmatic pressure deflections could not be detected. This study shows that despite near complete loss of diaphragm strength in advanced Duchenne muscular dystrophy, diaphragm electrical activation measured with an esophageal electrode array remains clearly detectable in all but one patient.

Action Potentials↗
PubMed2026

Impact of neoprene wetsuits on lung volumes and work of breathing: implications for military diver safety and performance.

INTRODUCTION: Neoprene wetsuits may impose mechanical constraints on the chest wall, potentially altering respiratory function. This study investigated the impact of neoprene wetsuits on lung volumes, airway mechanics, and work of breathing (WOB) in healthy male divers. METHODS: A randomised crossover trial was conducted with 31 male divers at the Royal Netherlands Navy Diving Medical Centre. Participants underwent pulmonary function testing, including spirometry, body plethysmography, the forced oscillation technique (FOT), and diffusion capacity measurements, both with and without a hoodless standardised 5 mm neoprene full body wetsuit with a neoprene neck seal. Primary outcomes included changes in forced vital capacity (FVC), functional residual capacity (FRC), airway resistance (Raw), reactance (Xrs), and WOB. RESULTS: Wearing a neoprene wetsuit led to statistically significant reductions in FVC (2.8%, P < 0.05), forced expiration in one second (2.9%, P < 0.05), FRC (4.0%, P < 0.05), and expiratory reserve volume (10.9%, P < 0.05), alongside increases in inspiratory capacity and tidal volume. Raw increased significantly (P < 0.05), while the FOT revealed altered airway mechanics, evidenced by increased Xrs at multiple frequencies (P < 0.05). Diffusion capacity remained unchanged, suggesting preserved alveolar-capillary function. CONCLUSIONS: Neoprene wetsuits induce mechanically restrictive effects on the chest wall, reducing static and dynamic lung volumes and increasing WOB. While these changes may not be clinically relevant at rest, their impact needs to be determined during strenuous or prolonged dives, particularly when combined with other equipment that limits thorax excursions. Future research should explore the effects of the military 5 mm wetsuit under immersed conditions to better understand their operational impact on diver performance and safety.

Male↗
PubMed1979

Lung function in healthy British women.

The forces expiratory volume, total lung capacity, transfer factor (diffusing capacity), and their subdivisions have been measured in 113 healthy British women aged 27 to 74 years of whom 47 were current smokers and 66 were lifetime non-smokers. The results have been analysed in terms of age, stature, mass, body fat, and smoking. In addition to their relation to stature and to age, the inspiratory capacity was positively correlated with indices of body muscle while the residual volume, expiratory reserve volume, and total lung capacity were inversely correlated with the percentage of body mass that is fat or with mass divided by the square of stature. The inverse correlation between total lung capacity and age was apparently due to the quantity of body fat increasing with age. The transfer factor and its subdivisions were inversely correlated with smoking. In this study the forced expiratory volume and vital capacity were independent of both fat and smoking; the transfer factor was independent of the physiological response to exercise. The results provide reference values for lung function in British women.

Adipose Tissue↗
PubMed1993

Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation.

There is considerable intersubject variability in the perceived intensity of breathlessness for a given level of activity among patients with chronic airflow limitation (CAL). To examine possible factors contributing to this variability we compared breathing pattern parameters, dynamic operational lung volumes, and Borg dyspnea ratings in 23 patients with severe CAL and in 10 healthy age-matched normal subjects during cycle ergometry to symptom-limitation. Patients with CAL had significantly (p < 0.01) higher levels of ventilation (% maximal voluntary ventilation) for a given work rate (slope of VE(%MVV)/WR(% pred max) = 1.51 +/- 0.18 versus 0.63 +/- 0.10; mean +/- SEM) and greater dynamic lung hyperinflation (DH) (change [delta] in end-expiratory lung volume [EELVdyn] = +0.31 +/- 0.11 L versus -0.16 +/- 0.22 L). Compared with normal subjects at a standardized VE (30 L/min), the CAL group was more breathless Borg = 4 +/- 1 versus 2 +/- 1, p < 0.01) and hyperinflated (EELVdyn = 75 +/- 3 versus 46 +/- 6% TLC, p < 0.001; end-inspiratory lung volume [EILVdyn] = 85 +/- 3 versus 67 +/- 5% TLC, p < 0.01). Within the CAL group, change in Borg ratings correlated with delta VE(%MVV) (r = 0.77, p < 0.001) and with slope of VE(%MVV)/WR(% pred max) (r = 0.48, p < 0.01). Regression analysis selected delta EILVdyn (or delta inspiratory reserve volume [delta IRVdyn]) from various dynamic ventilatory parameters as the strongest predictor of delta Borg (r = 0.63, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Functional and morphologic changes in the lungs after a single intratracheal instillation of silica.

The functional and morphologic consequences in the lungs of a single intratracheal instillation of silica dust were evaluated over 6 months. Male Fischer-344 rats were subjected to pulmonary function tests that measured lung volumes, forced expiratory flows, and carbon monoxide diffusing capacity (DLCO). Then saline (0.7 ml, n = 10) or saline containing either 10 mg (n = 9) or 40 mg (n = 14) of silica dust was instilled in the trachea, and each animal was tested 3, 12, and 24 wk later. Morphologic studies were performed on 27 rats similarly treated (3/group/time). By 3 wk after instillation, the inspiratory capacity, forced vital capacity, and DLCO diminished significantly (p less than 0.01) in the high-dose group. After 3 wk, the response tended to level off. Forced expiratory flows were not significantly affected. By contrast, biochemical analysis of lung collagen content indicated a linear accumulation throughout the experimental period. Microscopic evaluation revealed intra-alveolar accumulation of lipoproteinaceous material (alveolar proteinosis) by 3 wk in both dose groups, which persisted through the 24-wk experimental period. A few fibrotic nodules were seen as early as 3 wk in the 40-mg silica group, and their numbers increased with time, whereas they were relatively sparse in the 10-mg silica group throughout the experimental period, despite the diminished functional measurements. These data suggest a closer temporal correlation of the functional decrements observed to the evolution of the alveolar changes than they do to the development of fibrosis. We conclude that the development of nodular fibrosis was not the major contributing factor to the observed functional changes.

Animals↗
PubMed2002

Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest.

BACKGROUND: A study was undertaken to investigate whether bronchodilators are associated with less breathlessness at rest and during light exercise in patients with moderate to severe chronic obstructive pulmonary disease (COPD) with resting tidal expiratory flow limitation (EFL; flow limited (FL)) compared with those without EFL (non-flow limited (NFL)). METHODS: Twenty subjects (13 men) of mean (SD) age 65 (8) years (range 43-77) suffering from COPD with forced expiratory volume in 1 second (FEV(1)) 47 (18)% predicted were studied before and after inhalation of salbutamol (400 microg). Routine pulmonary function tests were performed in the seated position at rest. EFL was assessed by the negative expiratory pressure (NEP) method and changes in end expiratory lung volume (EELV) were inferred from variations in inspiratory capacity (IC). Dyspnoea was measured using the Borg scale at rest and at the end of a 6 minute steady state exercise test at 33% of the maximal predicted workload. RESULTS: EFL occurred in 11 patients. Following salbutamol IC did not change in NFL patients but increased by 24% (95% CI 15 to 33) in FL patients (p<0.001). Maximal inspiratory pressure (PImax) improved at EELV from 45 (95% CI 26 to 63) to 55 (95% CI 31 to 79) cm H(2)O (p<0.05) in FL patients after salbutamol but remained unchanged in NFL patients. The workload performed during exercise amounted to 34 (95% CI 27 to 41) and 31 (95% CI 21 to 40) watts (NS) for patients without and with EFL, respectively. After salbutamol, dyspnoea did not change either at rest or during exercise in the NFL patients, but decreased from 0.3 (95% CI -0.1 to 0.8) to 0.1 (95% CI -0.1 to 0.4) at rest (NS) and from 3.7 (95% CI 1.7 to 5.7) to 2.6 (95% CI 1.1 to 4.0) at the end of exercise (p<0.01) in FL patients. CONCLUSIONS: Patients with COPD with EFL may experience less breathlessness after a bronchodilator, at least during light exercise, than those without EFL. This beneficial effect, which is closely related to an increase in IC at rest, occurs even in the absence of a significant improvement in FEV(1) and is associated with a greater PImax.

Administration, Inhalation↗
PubMed1981

The effects of intermittent positive pressure breathing on patients with respiratory muscle weakness.

Marked reductions in pulmonary compliance have been noted in patients with respiratory muscle weakness, which greatly contribute to the losses of lung volume. In an attempt to reverse this abnormality and to decrease the work of breathing, we evaluated the effects of a 15-min period of positive pressure, mechanical hyperinflation of the lungs in 10 patients with generalized neuromuscular disorders and long-standing involvement of the respiratory muscles. The vital capacity was 46, and the static expiratory lung compliance was 59% of control values. The recoil pressure of the lung at full inflation was 19 cm H2O. Using positive pressure breathing devices, we inflated the lungs either with inflation pressures ranging between 20 and 40 cm H2O or with volume that were at least twofold larger than the patients' natural inspiratory capacity. Lung volumes, including functional residual capacity, and static pulmonary compliance were not modified by these procedures. Maintaining 10 cm H2O of positive end-expiratory pressure did not alter the results. These findings suggest that (1) alveolar collapse, rather than a simple decrease in the compliance of the surface film of the lung, is the major cause of the low pulmonary compliance in patients with chronic respiratory muscle weakness; (2) these patients do not acutely benefit from intermittent positive breathing treatment.

Adolescent↗
PubMed2003

Factors associated with improvement in breathing capacity during exercise in patients with chronic obstructive pulmonary disease.

OBJECTIVES: The aim of this study was to explore the relationship between resting pulmonary function indices and the ratio of minute ventilation at peak exercise to the maximal voluntary ventilation (VEmax/MVV) and to determine whether an improvement in breathing capacity during exercise (i.e. VEmax/MVV > 1) is associated with greater exercise capacity in patients with COPD. METHODOLOGY: The results of pulmonary function tests and incremental, symptom-limited cardiopulmonary exercise testing in 84 patients with predominantly moderate to severe COPD were reviewed. Multiple linear regression analysis was applied to determine the relationship of VEmax/MVV with selected independent variables at rest. Multiple logistic regression was used to determine significant predictors of VEmax/MVV </= or > 1. RESULTS: FEV1/FVC and inspiratory capacity (IC) were the only variables among resting pulmonary function indices that were significant independent determinants of VEmax/MVV and the stepwise analysis generated the following equation: VEmax/MVV = (-1.05E-02 x FEV1/FVC) + (0.15 x IC) + 1.28; r= 0.701, P < 0.001. Using multiple logistic regression with VEmax/MVV </= or > 1 as a dependent categorical variable, FEV1/FVC was the only significant predictor among resting pulmonary indices of a VEmax/MVV ratio of > 1 (Odds ratio 0.93, 95%CI 0.89, 0.97). There was a significant association between VEmax/MVV and peak oxygen uptake (VO2max) after adjusting for FEV1 (r = 0.66, P < 0.001). If the categorical variable of VEmax/MVV (</= or > 1) was used instead of a continuous variable, a significant association with VO2max remained after adjusting for FEV1 (r = 0.60, P < 0.001). CONCLUSIONS: Among resting pulmonary function indices, the FEV1/FVC ratio is the best determinant of an improvement in breathing capacity during exercise in COPD patients. After adjusting for FEV1, an improvement in breathing capacity during exercise is associated with significantly higher exercise capacity.

Aged↗
PubMed1985

Ventilation during steady-state exercise in patients with chronic obstructive pulmonary disease. A preliminary study.

In this preliminary study 20 patients with chronic obstructive pulmonary disease (COPD) walked on the treadmill until symptoms limited further exercise. When minute volume exceeded 60% of the predicted maximum breathing capacity the arterial carbon dioxide partial pressure was frequently low, thus indicating hyperventilation; the arterial oxygen partial pressure also declined on exercise. In only 2 patients was there alveolar hypoventilation. Although other factors may be operative, the hyperventilation in some patients with COPD may be induced by an exertional decline in alveolar oxygen partial pressure. In 4 patients the exercise tidal volume exceeded the resting inspiratory capacity, indicating a decline in functional residual capacity and increased work of breathing. It is concluded that there is a need further to assess patients with COPD in respect of the association between exertional dyspnoea, alveolar ventilation and lung mechanics.

Aged↗
PubMed1990

Adaptation of the inert gas FRC technique for use in heavy exercise.

We automated the inert gas rebreathe technique for measurement of end-expiratory lung volume (EELV) during heavy exercise. We also assessed the use of two gas tracers (He and N2) vs. a single gas tracer (He) for measurement of this lung volume and compared the two-tracer EELV to changes in the inspiratory capacity (defined with transpulmonary pressure) and shifts in the end-expiratory pressure from rest through heavy exercise. A computer program switched a pneumatic valve when flow crossed zero at end expiration and defined points in the He and N2 traces for calculation of EELV. An inherent delay of the rebreathing valve (50 ms) caused virtually no error at rest and during light exercise and an error of 74 +/- 9 ml in the EELV at peak inspiratory flow rates of 4 l/s. The measurement of EELV by the two gas tracers was closely correlated to the single-gas tracer measurement (r = 0.97) but was consistently higher (120 +/- 10 ml) than when He was used alone. This difference was accentuated with increased work rates (2-5% error in the EELV, rest to heavy exercise) and as rebreathe time increased (2-7% error in the EELV with rebreathe times of 5-20 s for all work loads combined). The double-gas tracer measurement of EELV agreed quite well with the thoracic gas volume at rest (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and exercise in emphysema.

Endobronchial valve placement improves pulmonary function in some patients with chronic obstructive pulmonary disease, but its effects on exercise physiology have not been investigated. In 19 patients with a mean (SD) FEV(1) of 28.4 (11.9)% predicted, studied before and 4 weeks after unilateral valve insertion, functional residual capacity decreased from 7.1 (1.5) to 6.6 (1.7) L (p = 0.03) and diffusing capacity rose from 3.3 (1.1) to 3.7 (1.2) mmol . minute(-1) . kPa(-1) (p = 0.03). Cycle endurance time at 80% of peak workload increased from 227 (129) to 315 (195) seconds (p = 0.03). This was associated with a reduction in end-expiratory lung volume at peak exercise from 7.6 (1.6) to 7.2 (1.7) L (p = 0.03). Using stepwise logistic regression analysis, a model containing changes in transfer factor and resting inspiratory capacity explained 81% of the variation in change in exercise time (p < 0.0001). The same variables were retained if the five patients with radiologic atelectasis were excluded from analysis. In a subgroup of patients in whom invasive measurements were performed, improvement in exercise capacity was associated with a reduction in lung compliance (r(2) = 0.43; p = 0.03) and isotime esophageal pressure-time product (r(2) = 0.47; p = 0.03). Endobronchial valve placement can improve lung volumes and gas transfer in patients with chronic obstructive pulmonary disease and prolong exercise time by reducing dynamic hyperinflation.

Bronchoscopy↗
PubMed2005

The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. OBJECTIVE AND METHODS: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 mug once daily or placebo for 12 weeks. RESULTS: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 +/- 0.08 liters) and 84 (0.20 +/- 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 +/- 0.07 liters) and 84 (0.15 +/- 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 +/- 12 (day 42) and 36 +/- 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George's Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. CONCLUSION: Tiotropium 18 mug once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.

Adult↗
PubMed2003

Cardiorespiratory responses to submaximal incremental exercise are not affected by one night's sleep deprivation during the follicular and luteal phases of the menstrual cycle.

The purpose of the study was to investigate the effects of one night's sleep deprivation on the cardiorespiratory responses to exercise during the follicular and luteal phases of the menstrual cycle. We have studied nine, healthy females aged 24-35 years with regular menstrual cycles. Each subject performed spirometric tests at rest and then an incremental exercise testing during 11-13 days of follicular phase and 22-24 days of luteal phase following one normal night's sleep or one night's sleep loss. Compared with resting values exercise produced significant increases in cardiorespiratory variables including oxygen uptake (VO2), carbon dioxide production (VCO2), tidal volume (VT), respiratory rate (RR), minute ventilation (VE), systolic blood pressure, heart rate (HR) and respiratory quotient (R). However, it did not alter significantly diastolic blood pressure, end-tidal PO2 (PETO2), end-tidal PCO2 (PETCO2) and arterial oxygen saturation (SaO2). Spirometric variables which include forced vital capacity (FVC), forced expiratory volume in one s (FEV1), FEV1/FVC%, forced expiratory volume in three s (FEV3), forced expired flow from 25-75% of FVC (FEF 25-75%), forced expired flow at 25% of FVC (FEF 25%), forced expired flow at 50% of FVC (FEF 50%), forced expired flow at 75% of FVC (FEF 75%), forced expired flow from 75-85% of FVC (FEF 75-85%), peak expiratory flow (PEF), expiratory reserve volume (ERV), inspiratory capacity (IC) and maximal voluntary ventilation (MVV) and cardiorespiratory variables were not different between the cycle phases after one normal night's sleep or one night's sleep deprivation. Neither menstrual cycle phase nor sleep deprivation affected spirometric and cardiorespiratory parameters. We suggest that one night's sleep deprivation does not produce alterations in spirometric parameters and cardiorespiratory responses to submaximal incremental exercise during the follicular and luteal phases.

Adult↗
PubMedDate not supplied

Role of the mechanical impairment on the ventilatory response to CO2 in chronic airway obstruction.

The purpose of this study was to assess the relationship between the breathing pattern response to CO2 and the severity of mechanical impairment in twenty patients with COLD. The CO2 response was compared to that of a control group of twelve normal subjects. All patients had airway obstruction (FEV1 = 40 +/- 14% of predicted; means +/- SD) and hyperinflation (FRC = 154 +/- 23% of predicted). Tidal volume (VT), inspiratory and total cycle duration (TI, TT), occlusion pressure (P0.1) and endtidal PCO2 were measured at rest and during hyperoxic CO2 rebreathing. On the same day, in all patients, arterial blood gas analysis, spirometric and plethysmographic measurements were made. The slope (S) of the P0.1 response (SP 0.1) to increasing endtidal PCO2 was negatively correlated with airway resistance (r = -0.59; p less than 0.01). Although the flow response, S(VT/TI), was positively and closely correlated with SP 0.1 (r = 0.88; p less than 0.001), it also appeared to be independently influenced by obstruction (p less than 0.01). The tidal volume response, SVT, was principally correlated with inspiratory capacity (r = 0.90; p less than 0.001) and also, independently, with Vmax50 (p less than 0.01). SVT was diminished in seventeen patients, ten of whom only had a decreased S(VT/TI). The shortening in TI during hypercapnia was most marked in patients with the greatest S(P0.1), who did not have arterial hypercapnia at rest. These results suggest: that the poor VT response to CO2 in COLD patients is principally caused by a limitation in inspiratory volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗
PubMed1990

The breathing patterns in Chinese and Indian adult males in the supine posture.

The breathing patterns in the supine posture during inspiration from functional residual capacity (simulating the "liver palpation" manoeuvre) were studied in two groups of young adult male Chinese and Indians with each group comprising 30 subjects. Both groups were matched for age, height and weight. Although the findings did not reach a statistically significant level, Indian subjects were found to breathe more with their abdomen compared to the Chinese during the manoeuvre. The two groups behaved similarly when they breathed with increasing amplitude from their resting tidal volume to full inspiratory capacity. There was also no difference between the two groups when they performed the total lung capacity manoeuvre.

Adult↗
PubMed1995

Determining the role of exercise in patients with chronic pulmonary disease.

Chronic pulmonary diseases are common in the community and their pathophysiology is complex. The principal symptoms are dyspnea and limited exercise capacity. Some, but not all, patients have true ventilatory limitation where the maximal exercise ventilation (VEmax) equals the measured maximal ventilatory volume (MVV). Those with obstructive disease have impeded expiration requiring an obligatory expiratory time for adequate lung emptying (i.e., a timing constraint). In these patients, increased breathing frequency during exercise tends to lead to hyperinflation and smaller tidal volumes, circumstances that predictably worsen breathing efficiency (i.e., result in high VD/VT). Those with restrictive disease characteristically have limited inspiratory capacity but unimpeded or even accelerated expiration (i.e. tidal volume constraint). These patients characteristically exhibit rapid respiratory rates (e.g., > 50.min-1) at end exercise.

Chronic Disease↗
PubMedDate not supplied

Sitting height, fat-free mass and body fat as reference variables for lung function in healthy British children: comparison with stature.

The ventilatory capacity, total lung capacity and transfer factor with their respective subdivisions have been measured on 254 healthy British boy and girl twins aged 8-16 yrs. The logarithmic regression relationships of lung function on stature have been compared with those on sitting height and on stature plus indices of body muscle and fat. The regressions on stature and on sitting height describe the results with similar precision, but stature is marginally better; either index may be used as the reference variable. For the description of inspiratory capacity and of all indices which include this volume (e.g. vital capacity, total lung capacity and transfer factor), additional precision is secured by adding to the regression equation on stature a term for fat-free mass or body mass divided by the square of the stature; for the description of functional residual capacity, the inclusion of a term for % body fat similarly reduces the variance about the regression equation. The difference in lung function between boys and girls is smaller when the function is related to stature than to sitting height. It is further reduced when fat-free mass/sature and % body fat are also included in the prediction equations. The equations may be used to obtain reference values for indices of lung function in similar subjects.

Adipose Tissue↗
PubMed2006

Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD.

STUDY OBJECTIVE: To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group study. PATIENTS: Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal. INTERVENTIONS: Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50. RESULTS: A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50. CONCLUSION: We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.

Adrenergic beta-Agonists↗