Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals.

OBJECTIVE: To determine cardiorespiratory fitness and neuromuscular function of people with CFS and FMS compared to healthy individuals. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Medline, CINAHL, AMED, Cochrane Central Register of Controlled Trials (CENTRAL), and PEDro from inception to June 2022. ELIGIBLE CRITERIA FOR SELECTING STUDIES: Studies were included if presenting baseline data on cardiorespiratory fitness and/or neuromuscular function from observational or interventional studies of patients diagnosed with FMS or CFS. Participants were aged 18 years or older, with results also provided for healthy controls. Risk of bias assessment was conducted using the Quality Assessment Tool for Quantitative Studies (EPHPP). RESULTS: 99 studies including 9853 participants (5808 patients; 4405 healthy controls) met our eligibility criteria. Random effects meta-analysis showed lower cardiorespiratory fitness (VO2max, anaerobic threshold, peak lactate) and neuromuscular function (MVC, fatigability, voluntary activation, muscle volume, muscle mass, rate of perceived exertion) in CFS and FMS compared to controls: all with moderate to high effect sizes. DISCUSSION: Our results demonstrate lower cardiorespiratory fitness and muscle function in those living with FMS or CFS when compared to controls. There were indications of dysregulated neuro-muscular interactions including heightened perceptions of effort, reduced ability to activate the available musculature during exercise and reduced tolerance of exercise. TRAIL REGISTRATION: PROSPERO registration number: (CRD42020184108).

Effects of nociceptive and mechanosensitive afferents sensitization on central and peripheral hemodynamics following exercise-induced muscle damage.

This study aims to test the separated and combined effects of mechanoreflex activation and nociception through exercise-induced muscle damage (EIMD) on central and peripheral hemodynamics before and during single passive leg movement (sPLM). Eight healthy young males undertook four experimental sessions, in which a sPLM was performed on the dominant limb while in each specific session the contralateral was: 1) in a resting condition (CTRL), 2) stretched (ST), 3) resting after EIMD called delayed onset muscle soreness (DOMS) condition, or 4) stretched after EIMD (DOMS + ST). EIMD was used to induce DOMS in the following 24-48 h. Femoral blood flow (FBF) was assessed using Doppler ultrasound whereas central hemodynamics were assessed via finger photoplethysmography. Leg vascular conductance (LVC) was calculated as FBF/mean arterial pressure (MAP). RR-intervals were analyzed in the time (root mean squared of successive intervals; RMSSD) and frequency domain [low frequency (LF)/high frequency (HF)]. Blood samples were collected before each condition and gene expression analysis showed increased fold changes for P2X4 and IL1ß in DOMS and DOMS + ST compared with baseline. Resting FBF and LVC were decreased only in the DOMS + ST condition (-26 mL/min and -50 mL/mmHg/min respectively) with decreased RMSSD and increased LF/HF ratio. MAP, HR, CO, and SV were increased in ST and DOMS + ST compared with CTRL. Marked decreases of Δpeaks and AUC were observed for FBF (Δ: -146 mL/min and -265 mL respectively) and LVC (Δ: -8.66 mL/mmHg/min and ±1.7 mL/mmHg/min respectively) all P < 0.05. These results suggest that the combination of mechanoreflex and nociception resulted in decreased vagal tone and concomitant rise in sympathetic drive that led to increases in resting central hemodynamics with reduced limb blood flow before and during sPLM.NEW & NOTEWORTHY Exercise-induced muscle damage (EIMD) is a well-known model to study mechanical hyperalgesia and muscle peripheral nerve sensitizations. The combination of static stretching protocol on the damaged limb extensively increases resting central hemodynamics with reduction in resting limb blood flow and passive leg movement-induced hyperemia. The mechanism underlining these results may be linked to reduction of vagal tone with concomitant increase in sympathetic activity following mechano- and nociceptive activation.

Effect of nitrate supplementation on skeletal muscle motor unit activity during isometric blood flow restriction exercise.

BACKGROUND: Nitrate (NO3-) supplementation has been reported to lower motor unit (MU) firing rate (MUFR) during dynamic resistance exercise; however, its impact on MU activity during isometric and ischemic exercise is unknown. PURPOSE: To assess the effect of NO3- supplementation on knee extensor MU activities during brief isometric contractions and a 3 min sustained contraction with blood flow restriction (BFR). METHODS: Sixteen healthy active young adults (six females) completed two trials in a randomized, double-blind, crossover design. Trials were preceded by 5 days of either NO3- (NIT) or placebo (PLA) supplementation. Intramuscular electromyography was used to determine the M. vastus lateralis MU potential (MUP) size, MUFR and near fibre (NF) jiggle (a measure of neuromuscular stability) during brief (20 s) isometric contractions at 25% maximal strength and throughout a 3 min sustained BFR isometric contraction. RESULTS: Plasma nitrite (NO2-) concentration was elevated after NIT compared to PLA (475 ± 93 vs. 198 ± 46 nmol L-1, p < 0.001). While changes in MUP area, NF jiggle and MUFR were similar between NIT and PLA trials (all p > 0.05), MUP duration was shorter with NIT compared to PLA during brief isometric contractions and the sustained ischemic contraction (p < 0.01). In addition, mean MUP duration, MUP area and NF jiggle increased, and MUFR decreased over the 3 min sustained BFR isometric contraction for both conditions (all p < 0.05). CONCLUSIONS: These findings provide insight into the effect of NO3- supplementation on MUP properties and reveal faster MUP duration after short-term NO3- supplementation which may have positive implications for skeletal muscle contractile performance.

The association of elevated blood pressure during ischaemic exercise with sport performance in Master athletes with and without morbidity.

BACKGROUND: An exaggerated exercise blood pressure (BP) is associated with a reduced exercise capacity. However, its connection to physical performance during competition is unknown. AIM: To examine BP responses to ischaemic handgrip exercise in Master athletes (MA) with and without underlying morbidities and to assess their association with athletic performance during the World Master Track Cycling Championships 2019. METHODS: Forty-eight Master cyclists [age 59 ± 13yrs; weekly training volume 10.4 ± 4.1 h/week; handgrip maximum voluntary contraction (MVC) 46.3 ± 11.5 kg] divided into 2 matched groups (24 healthy MA and 24 MA with morbidity) and 10 healthy middle-aged non-athlete controls (age 48.3 ± 8.3 years; MVC 40.4 ± 14.8 kg) performed 5 min of forearm occlusion including 1 min handgrip isometric contraction (40%MVC) followed by 5 min recovery. Continuous beat-by-beat BP was recorded using finger plethysmography. Age-graded performance (AGP) was calculated to compare race performances among MA. Healthy Master cyclists were further grouped into middle-age (age 46.2 ± 6.4 years; N:12) and old-age (age 65.0 ± 7.7 years; N:12) for comparison with middle-aged non-athlete controls. RESULTS: Healthy and morbidity MA groups showed similar BP responses during forearm occlusion and AGP (90.1 ± 4.3% and 91.0 ± 5.3%, p > 0.05, respectively). Healthy and morbidity MA showed modest correlation between the BP rising slope for 40%MVC ischaemic exercise and AGP (r = 0.5, p < 0.05). MA showed accelerated SBP recovery after cessation of ischaemic handgrip exercise compared to healthy non-athlete controls. CONCLUSION: Our findings associate long-term athletic training with improved BP recovery following ischaemic exercise regardless of age or reported morbidity. Exaggerated BP in Master cyclists during ischaemic exercise was associated with lower AGP during the World Master Cycling Championships.

Reduced skeletal muscle endurance and ventilatory efficiency during exercise in adult smokers without airflow obstruction.

Smokers without airflow obstruction have reduced exercise capacity, but the underlying physiological mechanisms are not fully understood. We aimed to compare quadriceps function assessed using nonvolitional measures and ventilatory requirements during exercise, between smokers without airway obstruction and never-smoker controls. Adult smokers (n = 20) and never-smoker controls (n = 16) aged 25-50 yr with normal spirometry, underwent incremental cycle cardiopulmonary exercise testing to exhaustion with measurement of symptoms and dynamic lung volumes. Quadriceps strength and endurance were assessed nonvolitionally using single and repetitive magnetic stimulation. Quadriceps bulk was assessed using ultrasound, as rectus-femoris cross-sectional area. Physical activity level was quantified using the SenseWear armband worn for 5 days. Smokers had lower peak exercise workload, peak oxygen consumption, and anaerobic threshold than controls (170 ± 46 vs. 256 ± 57 W, 2.20 ± 0.56 vs. 3.18 ± 0.72 L/min, 1.38 ± 0.33 vs. 2.09 ± 0.7 L/min, respectively; P < 0.01 for all). Quadriceps endurance was lower in smokers (Δforce-time integral 54.9% ± 14.7% vs. 40.4% ± 14.7%; P = 0.007), but physical activity, quadriceps strength, and bulk were similar between groups. Smokers displayed higher ventilation (120 W: 52.6 ± 11.8 vs. 40.7 ± 6.0 L/min; P < 0.001), decreased ventilatory efficiency (higher V̇e/V̇co2), and were more breathless with greater leg fatigue at iso-workloads and iso-ventilation levels compared with never-smoker controls. Smokers showed no mechanical constraints on tidal volume expansion during exercise or ventilatory limitation at peak exercise. Adult smokers without airflow obstruction have reduced skeletal muscle endurance and ventilatory efficiency compared with never-smoker controls, despite similar daily physical activity levels, which contributed to reduced peak exercise capacity.NEW & NOTEWORTHY In adult smokers without airflow obstruction, the contributions of pulmonary and skeletal muscle functions to reduced exercise capacity are unclear. We found that non-COPD smokers had decreased exercise capacity and muscle endurance although strength was preserved compared with never-smoking controls. Exercise endurance was associated with quadriceps endurance and CO transfer factor. Despite similar physical activity levels, smokers developed leg fatigue, breathlessness, and displayed increased ventilation with reduced ventilatory efficiency at lower workloads, without exhibiting ventilatory constraint.

Mechanisms of orthopnoea in patients with advanced COPD.

Many patients with severe chronic obstructive pulmonary disease (COPD) report an unpleasant respiratory sensation at rest, which is further amplified by adoption of a supine position (orthopnoea). The mechanisms of this acute symptomatic deterioration are poorly understood.Sixteen patients with advanced COPD and a history of orthopnoea and 16 age- and sex-matched healthy controls underwent pulmonary function tests (PFTs) and detailed sensory-mechanical measurements including inspiratory neural drive (IND) assessed by diaphragm electromyography (EMGdi), oesophageal pressure (P es) and gastric pressure (P ga), in both sitting and supine positions.Patients had severe airflow obstruction (forced expiratory volume in 1 s (FEV1): 40±18% pred) and lung hyperinflation. Regardless of the position, patients had lower inspiratory capacity (IC) and higher IND for a given tidal volume (V T) (i.e. greater neuromechanical dissociation (NMD)), higher intensity of breathing discomfort, higher minute ventilation (V'E) and higher breathing frequency (f B) compared with controls (all p<0.05). For controls in a supine position, IC increased by 0.48 L versus sitting erect, with a small drop in V'E, mainly due to reduced f B (all p<0.05). By contrast, IC remained unaltered in patients with COPD, but dynamic lung compliance (C Ldyn) decreased (p<0.05) in the supine position. Breathing discomfort, inspiratory work of breathing (WOB), inspiratory effort, IND, NMD and neuroventilatory uncoupling all increased in COPD patients in the supine position (p<0.05), but not in the healthy controls. Orthopnoea was associated with acute changes in IND (r=0.65, p=0.01), neuroventilatory uncoupling (r=0.76, p=0.001) and NMD (r=0.73, p=0.002).In COPD, onset of orthopnoea coincided with an abrupt increase in elastic loading of the inspiratory muscles in recumbency, in association with increased IND and greater NMD of the respiratory system.

Inspiratory muscle training reduces diaphragm activation and dyspnea during exercise in COPD.

Among patients with chronic obstructive pulmonary disease (COPD), those with the lowest maximal inspiratory pressures experience greater breathing discomfort (dyspnea) during exercise. In such individuals, inspiratory muscle training (IMT) may be associated with improvement of dyspnea, but the mechanisms for this are poorly understood. Therefore, we aimed to identify physiological mechanisms of improvement in dyspnea and exercise endurance following inspiratory muscle training (IMT) in patients with COPD and low maximal inspiratory pressure (Pimax). The effects of 8 wk of controlled IMT on respiratory muscle function, dyspnea, respiratory mechanics, and diaphragm electromyography (EMGdi) during constant work rate cycle exercise were evaluated in patients with activity-related dyspnea (baseline dyspnea index <9). Subjects were randomized to either IMT or a sham training control group ( n = 10 each). Twenty subjects (FEV1 = 47 ± 19% predicted; Pimax = -59 ± 14 cmH2O; cycle ergometer peak work rate = 47 ± 21% predicted) completed the study; groups had comparable baseline lung function, respiratory muscle strength, activity-related dyspnea, and exercise capacity. IMT, compared with control, was associated with greater increases in inspiratory muscle strength and endurance, with attendant improvements in exertional dyspnea and exercise endurance time (all P < 0.05). After IMT, EMGdi expressed relative to its maximum (EMGdi/EMGdimax) decreased ( P < 0.05) with no significant change in ventilation, tidal inspiratory pressures, breathing pattern, or operating lung volumes during exercise. In conclusion, IMT improved inspiratory muscle strength and endurance in mechanically compromised patients with COPD and low Pimax. The attendant reduction in EMGdi/EMGdimax helped explain the decrease in perceived respiratory discomfort despite sustained high ventilation and intrinsic mechanical loading over a longer exercise duration. NEW & NOTEWORTHY In patients with COPD and low maximal inspiratory pressures, inspiratory muscle training (IMT) may be associated with improvement of dyspnea, but the mechanisms for this are poorly understood. This study showed that 8 wk of home-based, partially supervised IMT improved respiratory muscle strength and endurance, dyspnea, and exercise endurance. Dyspnea relief occurred in conjunction with a reduced activation of the diaphragm relative to maximum in the absence of significant changes in ventilation, breathing pattern, and operating lung volumes.

Sensory-mechanical effects of a dual bronchodilator and its anticholinergic component in COPD.

This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14±0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): "unpleasantness of breathing" fell 0.8±1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise.

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an augmented tidal volume and a rise in minute ventilation.

Resting Physiological Correlates of Reduced Exercise Capacity in Smokers with Mild Airway Obstruction.

Smokers with minor spirometric abnormalities can experience persistent activity-related dyspnea and exercise intolerance. Additional resting tests can expose heterogeneous physiological abnormalities, but their relevance and association with clinical outcomes remain uncertain. Subjects included sixty-two smokers (≥20 pack-years), with cough and/or dyspnea and minor airway obstruction [forced expiratory volume in one-second (FEV1) ≥80% predicted and >5th percentile lower limit of normal (LLN) (i.e., z-score >-1.64) using the 2012-Global Lung Function Initiative equations]. They underwent spirometry, plethysmography, oscillometry, single-breath nitrogen washout, and symptom-limited incremental cycle exercise tests. Thirty-two age-matched nonsmoking controls were also studied. Thirty-three (53%) of smokers had chronic obstructive pulmonary disease by LLN criteria. In smokers [n = 62; age 65 ± 11 years; smoking history 43 ± 19 pack-years; post-bronchodilator FEV1 z-score -0.60 ± 0.72 and FEV1/FVC z-score -1.56 ± 0.87 (mean ± SD)] versus controls, peak oxygen uptake (̇VO2) was 21 ± 7 vs. 32 ± 9 ml/kg/min, and dyspnea/̇VO2 slopes were elevated (both p < 0.0001). Smokers had evidence of peripheral airway dysfunction and maldistribution of ventilation when compared to controls. In smokers versus controls: lung diffusing capacity for carbon monoxide (DLCO) was 85 ± 22 vs. 105 ± 17% predicted, and residual volume (RV)/total lung capacity (TLC) was 36 ± 8 vs. 31 ± 6% (both p < 0.01). The strongest correlates of peak ̇VO2 were DLCO% predicted (r = 0.487, p < 0.0005) and RV/TLC% (r = -0.389, p = 0.002). DLCO% predicted was also the strongest correlate of dyspnea/̇VO2 slope (r = -0.352, p = 0.005). In smokers with mild airway obstruction, associations between resting tests of mechanics and pulmonary gas exchange and exercise performance parameters were weak, albeit consistent. Among these, DLCO showed the strongest association with important outcomes such as dyspnea and exercise intolerance measured during standardized incremental exercise tests.

Exertional dyspnoea in COPD: the clinical utility of cardiopulmonary exercise testing.

Activity-related dyspnoea is often the most distressing symptom experienced by patients with chronic obstructive pulmonary disease (COPD) and can persist despite comprehensive medical management. It is now clear that dyspnoea during physical activity occurs across the spectrum of disease severity, even in those with mild airway obstruction. Our understanding of the nature and source of dyspnoea is incomplete, but current aetiological concepts emphasise the importance of increased central neural drive to breathe in the setting of a reduced ability of the respiratory system to appropriately respond. Since dyspnoea is provoked or aggravated by physical activity, its concurrent measurement during standardised laboratory exercise testing is clearly important. Combining measurement of perceptual and physiological responses during exercise can provide valuable insights into symptom severity and its pathophysiological underpinnings. This review summarises the abnormal physiological responses to exercise in COPD, as these form the basis for modern constructs of the neurobiology of exertional dyspnoea. The main objectives are: 1) to examine the role of cardiopulmonary exercise testing (CPET) in uncovering the physiological mechanisms of exertional dyspnoea in patients with mild-to-moderate COPD; 2) to examine the escalating negative sensory consequences of progressive respiratory impairment with disease advancement; and 3) to build a physiological rationale for individualised treatment optimisation based on CPET.

Mechanisms of exertional dyspnoea in symptomatic smokers without COPD.

Dyspnoea and activity limitation can occur in smokers who do not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are unknown.Detailed pulmonary function tests and sensory-mechanical relationships during incremental exercise with respiratory pressure measurements and diaphragmatic electromyography (EMGdi) were compared in 20 smokers without spirometric COPD and 20 age-matched healthy controls.Smokers (mean±sd post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity 75±4%, mean±sd FEV1 104±14% predicted) had greater activity-related dyspnoea, poorer health status and lower physical activity than controls. Smokers had peripheral airway dysfunction: higher phase-III nitrogen slopes (3.8±1.8 versus 2.6±1.1%·L(-1)) and airway resistance (difference between airway resistance measured at 5 Hz and 20 Hz 19±11 versus 12±7% at 5 Hz) than controls (p<0.05). Smokers had significantly (p<0.05) lower peak oxygen uptake (78±40 versus 107±45% predicted) and ventilation (61±26 versus 97±29 L·min(-1)). Exercise ventilatory requirements, operating lung volumes and cardio-circulatory responses were similar. However, submaximal dyspnoea ratings, resistive and total work of breathing were increased in smokers compared with controls (p<0.05); diaphragmatic effort (transdiaphragmatic pressure/maximumal transdiaphragmatic pressure) and fractional inspiratory neural drive to the diaphragm (EMGdi/maximal EMGdi) were also increased (p<0.05) mainly reflecting the reduced denominator.Symptomatic smokers at risk for COPD had greater exertional dyspnoea and lower exercise tolerance compared with healthy controls in association with greater airways resistance, contractile diaphragmatic effort and fractional inspiratory neural drive to the diaphragm.

Common Mechanisms of Dyspnea in Chronic Interstitial and Obstructive Lung Disorders.

RATIONALE: The mechanisms underlying dyspnea in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are unknown. OBJECTIVES: To examine whether the relationship between inspiratory neural drive to the diaphragm and exertional dyspnea intensity is different in ILD and COPD, given the marked differences in static respiratory mechanics between these conditions. METHODS: We compared sensory-mechanical relationships in patients with ILD, patients with COPD, and healthy control subjects (n = 16 each) during incremental cycle exercise with diaphragmatic electromyography (EMGdi) and respiratory pressure measurements. MEASUREMENTS AND MAIN RESULTS: In patients with mild to moderate ILD or COPD with similarly reduced inspiratory capacity, the peak oxygen uptake, work rate, and ventilation were lower (P < 0.05) than in healthy control subjects. EMGdi expressed as a percentage of the maximum (EMGdi/EMGdi,max), respiratory effort (esophageal pressure expressed as percentage of the maximum), and ventilation were higher (P < 0.05) at rest and during exercise in both patients with ILD and patients with COPD than in control subjects. Each of these measurements was similar in the ILD and COPD groups. A Vt inflection and critically reduced inspiratory reserve volume occurred at a lower (P < 0.05) ventilation in the ILD and COPD groups than in control subjects. Patients with ILD had greater diaphragmatic activity, whereas patients with COPD had greater expiratory muscle activity. The relationship between dyspnea intensity and EMGdi/EMGdi,max during exercise was similar in all three groups. In ILD and COPD, descriptors alluding to inspiratory difficulty were selected more frequently, with a greater disparity between EMGdi/EMGdi,max and Vt. CONCLUSIONS: Disease-specific differences in mechanics and respiratory muscle activity did not influence the key association between dyspnea intensity and inspiratory neural drive to the diaphragm.

Effective Bronchoscopic Lung Volume Reduction Accelerates Exercise Oxygen Uptake Kinetics in Emphysema.

BACKGROUND: The impact of bronchoscopic lung volume reduction (BLVR) on physiologic responses to exercise in patients with advanced emphysema remains incompletely understood. We hypothesized that effective BLVR (e-BLVR), defined as a reduction in residual volume > 350 mL, would improve cardiovascular responses to exercise and accelerate oxygen uptake (Vo2) kinetics. METHODS: Thirty-one patients (FEV1, 36% ± 9% predicted; residual volume, 219% ± 57% predicted) underwent a constant intensity exercise test at 70% peak work rate to the limit of tolerance before and after treatment bronchoscopy (n = 24) or sham bronchoscopy (n = 7). Physiologic responses in patients who had e-BLVR (n = 16) were compared with control subjects (ineffective BLVR or sham bronchoscopy; n = 15). RESULTS: e-BLVR reduced residual volume (-1.1 ± 0.5 L, P = .001), improved lung diffusing capacity by 12% ± 13% (P = .001), and increased exercise tolerance by 181 ± 214 s (P = .004). Vo2 kinetics were accelerated in the e-BLVR group but remained unchanged in control subjects (Δ mean response time, -20% ± 29% vs 1% ± 25%, P = .04). Acceleration of Vo2 kinetics was associated with reductions in heart rate and oxygen pulse response half-times by 8% (84 ± 14 to 76 ± 15 s, P = .04) and 20% (49 ± 16 to 34 ± 16 s, P = .01), respectively. There were also increases in heart rate and oxygen pulse amplitudes during the cardiodynamic phase post e-BLVR. Faster Vo2 kinetics in the e-BLVR group were significantly correlated with reductions in residual volume (r = 0.66, P = .005) and improvements in inspiratory reserve volume (r = 0.56, P = .024) and exercise tolerance (r = 0.63, P = .008). CONCLUSIONS: Lung deflation induced by e-BLVR accelerated exercise Vo2 kinetics in patients with emphysema. This beneficial effect appears to be related mechanistically to an enhanced cardiovascular response to exercise, which may contribute to improved functional capacity.

Effect of age-related ventilatory inefficiency on respiratory sensation during exercise.

To examine the effect of age-related respiratory function impairment on exertional dyspnea, we compared ventilatory and perceptual responses to incremental exercise under control (CTRL) and added dead space (DS) loading conditions in healthy fit older (55-79 years) and younger (20-39 years) men. Older individuals had higher ventilatory equivalents for CO2 throughout exercise (p<0.05) suggesting greater ventilatory inefficiency but operating lung volumes were similar compared to younger individuals. With added DS compared to CTRL, both groups similarly increased tidal volume (by 0.3-0.6 L) and ventilation (by 8-13 L/min) at submaximal work rates (each p<0.05). At peak exercise with DS, both groups failed to further increase ventilation and had small reductions in peak work rate (p<0.05). Increases in dyspnea intensity ratings with the addition of DS were similar at standardized submaximal work rates in older and younger groups. We conclude that, despite differences in ventilatory efficiency, the respiratory-mechanical and sensory responses to added chemostimulation during exercise were similar in fit older and younger individuals.

On the method of fitting cardiac output kinetics in severe exercise.

The kinetic responses of oxygen uptake (VO2) and cardiac output (Q) describe the rate at which these physiological variables approach the required steady state value with work rate transitions. In this issue of the Journal, Adami and colleagues examined the kinetic responses during the transition to severe intensity exercise (metabolic demands exceeding maximal VO2). Two methods were described for fitting VO2 kinetics: one was an exponential model that referenced the time course of VO2 relative to an apparent plateau while the second examined the rate of change with respect to the value predicted to be 120% of maximal VO2. The rate of change of the primary adaptive component described by the time constant (tau2) was considerably slower when referenced to the predicted VO2 (62.5 s) than when fit by the exponential model (20.3 s). For the description of Q kinetics Adami and colleagues fitted only the exponential model. We investigated the impact of fitting the kinetics of Q relative to a predicted value for this severe work rate as was done for VO2. The time course for Q was reconstructed from their group mean fitting parameters then referenced to values for the required Q based on the literature. The estimate for the time constant (tau2) exceeded the value determined from the exponential model in which the curve fit was referenced to an apparent plateau by more than sixfold (86.4 s vs. 13.5 s). This outcome suggests that future investigations should explore further the dynamic interactions of metabolic regulatory factors and the limitations of the O2 supply system when describing the system kinetics.