Effect of Six-Minute Walk Test and Incremental Exercise on Inspiratory Capacity, Ventilatory Constraints, Breathlessness and Exercise Performance in Sedentary Male Smokers without Airway Obstruction

We investigated physiological responses and exercise capacity in sedentary young smokers during sub-maximal and maximal test and its impact on dyspnea and exercise intolerance. Fifty sedentary male smokers and non-smokers (age: 24 ± 1 years., weight: 71 ± 9 kg, height: 177.3 ± 4.8 cm, body mass index: 22.6 ± 2.5 kg/m2) underwent two visits with pulmonary function tests, breathing pattern, and inspiratory capacity measurement at rest and during sub-maximal and maximal exercise. Smokers show reduced exercise capacity during six minutes walk test (6-MWT) with decreased walked distance (p < 0.001) and inspiratory capacity (p < 0.05). During cardiopulmonary exercise test (CPET), smokers had higher minute ventilation VE for a given submaximal intensity (p < 0.05) and lower minute ventilation at maximal exercise (p < 0.001). End expiratory lung volume was significantly lower in sedentary smokers at rest (p < 0.05), at ventilatory threshold during exercise (p < 0.05), but not during peak exercise. End inspiratory lung volume was significantly lower in smokers at rest (p < 0.05) and ventilatory threshold (p < 0.05). Cigarette smoking alters lung function during submaximal and maximal exercise. This alteration is manifested by the development of dynamic hyperinflation contributing to exercise capacity limitation.

Exercise Capacity, Ventilatory Response, and Gas Exchange in COPD Patients With Mild to Severe Obstruction Residing at High Altitude

BackgroundExercise intolerance, desaturation, and dyspnea are common features in patients with chronic obstructive pulmonary disease (COPD). At altitude, the barometric pressure (BP) decreases, and therefore the inspired oxygen pressure and the partial pressure of arterial oxygen (PaO2) also decrease in healthy subjects and even more in patients with COPD. Most of the studies evaluating ventilation and arterial blood gas (ABG) during exercise in COPD patients have been conducted at sea level and in small populations of people ascending to high altitudes. Our objective was to compare exercise capacity, gas exchange, ventilatory alterations, and symptoms in COPD patients at the altitude of Bogotá (2,640 m), of all degrees of severity.MethodsMeasurement during a cardiopulmonary exercise test of oxygen consumption (VO2), minute ventilation (VE), tidal volume (VT), heart rate (HR), ventilatory equivalents of CO2 (VE/VCO2), inspiratory capacity (IC), end-tidal carbon dioxide tension (PETCO2), and ABG. For the comparison of the variables between the control subjects and the patients according to the GOLD stages, the non-parametric Kruskal–Wallis test or the one-way analysis of variance test was used.ResultsEighty-one controls and 525 patients with COPD aged 67.5 ± 9.1 years were included. Compared with controls, COPD patients had lower VO2 and VE (p &lt; 0.001) and higher VE/VCO2 (p = 0.001), A-aPO2, and VD/VT (p &lt; 0.001). In COPD patients, PaO2 and saturation decreased, and delta IC (p = 0.004) and VT/IC increased (p = 0.002). These alterations were also seen in mild COPD and progressed with increasing severity of the obstruction.ConclusionThe main findings of this study in COPD patients residing at high altitude were a progressive decrease in exercise capacity, increased dyspnea, dynamic hyperinflation, restrictive mechanical constraints, and gas exchange abnormalities during exercise, across GOLD stages 1–4. In patients with mild COPD, there were also lower exercise capacity and gas exchange alterations, with significant differences from controls. Compared with studies at sea level, because of the lower inspired oxygen pressure and the compensatory increase in ventilation, hypoxemia at rest and during exercise was more severe; PaCO2 and PETCO2 were lower; and VE/VO2 was higher.

Pulmonary function with expiratory resistive loading in healthy volunteers

Expiratory flow limitation is a key characteristic in obstructive pulmonary diseases. To study abnormal lung mechanics isolated from heterogeneities of obstructive disease, we measured pulmonary function in healthy adults with expiratory loading. Thirty-seven volunteers (25±5 yr) completed spirometry and body plethysmography under control and threshold expiratory loading of 7, 11 cmH2O, and a subset at 20 cmH2O (n = 11). We analyzed the shape of the flow-volume relationship with rectangular area ratio (RAR; Ma et al., Respir Med 2010). Airway resistance was increased (p<0.0001) with 7 and 11 cmH2O loading vs control (9.20±1.02 and 11.76±1.68 vs. 2.53± 0.80 cmH2O/L/s). RAR was reduced (p = 0.0319) in loading vs control (0.45±0.07 and 0.47±0.09L vs. 0.48±0.08). FEV1 was reduced (p<0.0001) in loading vs control (3.24±0.81 and 3.23±0.80 vs. 4.04±1.05 L). FVC was reduced (p<0.0001) in loading vs control (4.11±1.01 and 4.14±1.03 vs. 5.03±1.34 L). Peak expiratory flow (PEF) was reduced (p<0.0001) in loading vs control (6.03±1.67 and 6.02±1.84 vs. 8.50±2.81 L/s). FEV1/FVC (p<0.0068) was not clinically significant and FRC (p = 0.4) was not different in loading vs control. Supra-physiologic loading at 20 cmH2O did not result in further limitation. Expiratory loading reduced FEV1, FVC, PEF, but there were no clinically meaningful differences in FEV1/FVC, FRC, or RAR. Imposed expiratory loading likely leads to high airway pressures that resist dynamic airway compression. Thus, a concave expiratory flow-volume relationship was consistently absent–a key limitation for model comparison with pulmonary function in COPD. Threshold loading may be a useful strategy to increase work of breathing or induce dynamic hyperinflation.

Effect of portable non-invasive ventilation on thoracoabdominal volumes in recovery from intermittent exercise in patients with COPD

Background: We previously showed that use of portable non-invasive ventilation (pNIV) during recovery periods within intermittent exercise improved breathlessness and exercise tolerance in COPD patients compared to pursed-lip breathing (PLB). However, in a minority of patients recovery from dynamic hyperinflation (DH) was better with PLB, based on inspiratory capacity. We further explored this using Optoelectronic Plethysmography to assess total and compartmental thoracoabdominal volumes. Methods: Fourteen COPD patients (mean±SD) (FEV1: 55±22% predicted) underwent, in a balanced order sequence, two intermittent exercise protocols on the cycle ergometer consisting of five repeated 2-min exercise bouts at 80% peak capacity, separated by 2-min recovery periods, with application of pNIV or PLB in the first minute of recovery.Results: Our findings identified 7 patients showing clinically meaningful recovery in DH with pNIV (DH responders) while 7 showed similar or better recovery in DH with PLB. When pNIV was applied, DH responders compared to DH non-responders exhibited greater tidal volume (by 0.8±0.3 L, p=0.015), inspiratory flow rate (by 0.6±0.5 L/sec, p=0.049), prolonged expiratory time (by 0.6±0.5 sec, p=0.006) and duty cycle (by 0.7±0.6 sec, p=0.007). DH responders showed a clinically meaningful reduction in end-expiratory thoracoabdominal DH (by 265±633 ml) predominantly driven by reduction in the abdominal compartment (by 210±494 ml); this effectively offset end-inspiratory rib-cage DH. Compared to DH non-responders, DH responders had significantly greater BMI by 8.4±3.2, p=0.022 and tended towards less severe resting hyperinflation by 0.3±0.3 L.Conclusion: COPD patients who mitigate end-expiratory rib-cage DH by expiratory abdominal muscle recruitment benefit from pNIV application.

Targeting dynamic hyperinflation in moderate to severe asthma – a randomised controlled trial

BackgroundDynamic hyperinflation (DH) is highly prevalent in moderate to severe asthma, which may significantly impede activities of daily life. We hypothesised that DH in asthma is due to inflammation of large and small airways and can be reduced by systemic anti-inflammatory treatment. Therefore, we investigated the effect of systemic glucocorticoids on DH in moderate to severe asthma patients and explored the relationships between inflammatory markers and changes in DH.MethodsIn this randomised placebo-controlled trial we included 32 asthma patients on inhaled glucocorticoid therapy showing DH, defined by a ≥10% reduction in inspiratory capacity measured by standardised metronome-paced tachypnea test. Patients received either triamcinolone (80 mg) or placebo intramuscularly. Before and 2 weeks after treatment, patients completed respiratory health questionnaires, had blood eosinophils and exhaled nitric oxide levels measured and underwent lung function and DH testing.ResultsAfter adjustment for potential confounders, DH was significantly reduced by 28.1% in the triamcinolone group, and increased by 9.4% in the placebo group (p=0.027). In the triamcinolone-treated patients, the reduction in DH was greater in patients with higher blood eosinophils at baseline (r=−0.592, p=0.020) and tended to be associated with a reduction in blood eosinophils (r=0.412, p=0.127) and exhaled nitric oxide (r=0.442, p=0.099).ConclusionsThis exploratory study suggests that dynamic hyperinflation in asthma can be reduced by systemic anti-inflammatory treatment, particularly in patients with elevated blood eosinophils. This supports the hypothesis that dynamic hyperinflation in asthma is due to airway inflammation and should be considered an important target for treatment.

The Effect of Long-Acting Dual Bronchodilator Therapy on Exercise Tolerance, Dynamic Hyperinflation and Dead Space during Constant Work Rate Exercise in COPD

Purpose: We investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere®) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (VD/VT) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in COPD. Methods: 48 COPD patients (62.9±7.6yrs; 33 male; GOLD spirometry stage 1/2/3/4, n=2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak work rate. Transcutaneous PCO2(TcPCO2) measurement was used for VD/VTestimation. Results: Baseline post-albuterol FEV1was 1.86±0.58L (63.6%±13.9 predicted). GFF increased FEV1by 0.18±0.21L relative to PL (P<0.001). CWRET endurance time was greater after GFF vs. PL (383±184s vs 328±115s; difference 55±125s; P=0.013; C.I. 20-90s), a 17% increase. IC on GFF was above placebo IC at all time points and fell less with GFF vs. PL (P≤0.0001). Isotime tidal volume (1.54±0.50 vs. 1.47±0.45L; P=0.022) and ventilation (52.9±19.9 vs. 51.0±18.9 L/min; P=0.011) were greater, and respiratory rate was unchanged (34.9±9.2 vs. 35.1±8.0 br/min, P=0.865). Isotime VD/VTdid not differ between groups (GFF 0.28±0.08 vs. PL 0.27±0.09; P=0.926). Conclusions: GFF increased exercise tolerance in COPD patients and the increase was accompanied by attenuated dynamic hyperinflation without altering VD/VT. ClinicalTrials.Gov Identifier: NCT03081156