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Low resting inspiratory capacity (IC) and low maximal inspiratory pressure (MIP) have previously been linked to exertional dyspnea, exercise limitation, and poor survival in chronic obstructive pulmonary disease (COPD). The interaction and relative contributions of these two related variables to important clinical outcomes are unknown. The objective of the current study was to examine the interaction between resting IC and MIP (both % predicted), exertional dyspnea, exercise capacity, and long-term survival in patients with COPD. Two hundred and eighty-five patients with mild to advanced COPD completed standard lung function testing and a cycle cardiopulmonary exercise test. Multiple regression determined predictors of the exertional dyspnea-ventilation slope and peak oxygen uptake (...O2peak). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized β = -0.42, P < 0.001), whereas MIP was excluded from the regression model (P = 0.918). IC and MIP were included in the final model to predict VO2peak. However, the standardized β was greater for IC (0.43) than MIP (0.22). After adjusting for age, sex, body mass index, cardiovascular risk, airflow obstruction, and diffusing capacity, resting IC was independently associated with 10-year all-cause mortality (hazard ratio = 1.25, confidence interval5%_95% = 1.16-1.34, P < 0.001), whereas MIP was excluded from the final model (all P = 0.829). Low resting IC was consistently linked to heightened dyspnea intensity, low ...O2peak, and worse survival in COPD even after accounting for airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important physiological biomarker closely linked to key clinical outcomes in COPD. NEW & NOTEWORTHY To our knowledge, this study is the first to show an independent association between low resting inspiratory capacity (IC) and, severe exertional dyspnea, exercise limitation, and increased mortality risk, after accounting for the severity of airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important independent physiological biomarker closely linked to key clinical outcomes in COPD. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity ([V.sub.max]) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 [+ or -] 4 yr; [FEV.sub.1]/FVC = 44 [+ or -] 3%, where [FEV.sub.1] is forced expiratory volume in 1 s and FVC is forced vital capacity; means [+ or -] SE) and nine healthy age-matched controls (age 68 [+ or -] 2 yr; [FEV.sub.1]/FVC = 75 [+ or -] 2%). Compared with control, the COPD patients displayed lower (P < 0.05) [V.sub.max] (mol x kg [protein.sup.-1] x [h.sup.-1]) for cytochrome c oxidase (COX; 21.2 [+ or -] 2.0 vs. 28.7 [+ or -] 2.2) and 3-hydroxyacyl-CoA dehydrogenase (HADH; 2.54 [+ or -] 0.14 vs. 3.74 [+ or -] 0.12) but not citrate synthase (CS; 2.20 [+ or -] 0.16 vs. 3.19 [+ or -] 0.5). While no differences between groups were observed in [V.sup.max] for creatine phosphokinase, phosphorylase (PHOSPH), phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase (HEX) was elevated in COPD (P < 0.05). Enzyme activity ratios were higher (P < 0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/ HADH in COPD compared with control. It is concluded that COPD patients exhibit a reduced potential for both the electron transport system and fat oxidation and an increased potential for glucose phosphorylation while the potential for glycogenolysis and glycolysis remains normal. A comparison of enzyme ratios indicated greater potentials for glucose phosphorylation relative to the citric acid cycle and the electron transport chain and glycogenolysis and glycolysis relative to [beta]-oxidation. lung disease; skeletal muscle; enzymes; oxidative; glycolytic.

This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups (n = 11) of pregnant subjects (PG, gestational age, 36.5 [+ or -] 0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic C[O.sub.2] rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal PC[O.sub.2] increased, whereas end-tidal P[O.sub.2] was maintained at a constant hyperoxic level. The point at which ventilation ([??]E) began to rise as end-tidal PC[O.sub.2] increased was identified as the central chemoreflex ventilatory recruitment threshold for C[O.sub.2] (VRTC[O.sub.2]). [??]E levels below (basal [??]E) and above (central chemoreflex sensitivity) the VRTC[O.sub.2] were determined. The VRTC[O.sub.2], was significantly lower in the PG vs. CG (40.5 [+ or -] 0.8 vs. 45.8 [+ or -] 1.6 Tow), and both basal [??]E (14.8 [+ or -] 1.1 vs. 9.3 [+ or -] 1.6 l/min) and central chemoreflex sensitivity (5.07 [+ or -] 0.74 vs. 3.16 [+ or -] 0.29 l x [min.sup.-1] x [Torr.sup.-1]) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial PC[O.sub.2] with basal [??]E, central chemoreflex sensitivity, and the VRTC[O.sub.2]. The VRTC[O.sub.2] was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to C[O.sub.2]. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe. human gestation; hyperoxia; chemoreflex sensitivity; ventilatory recruitment threshold

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DLCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DLCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (VO2), DLCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DLCO [i.e., CO was associated with peak VO2 (P = 0.006), peak work-rate (P = 0.005), and dyspnea/VO2 slope (P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak VO2 and work rate were lower (P = 0.05) in low versus normal DLCO groups. Across all tertiles, low DLCO groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal DLCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DLCOCO. The higher dyspnea ratings and earlier exercise termination in low DLCO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DLCO) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal DLCO. [ABSTRACT FROM AUTHOR]

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (VT). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anti-cholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 ± 3%predicted; mean ± SE) inhaled tiotropium 18 μg or placebo once daily for 7–10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and VT (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 ± 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the VT response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling. [ABSTRACT FROM AUTHOR]