Demographic,Physiologic and Radiographic Characteristics of COPD Patients Taking Chronic Systemic Corticosteroids

Abstract

Long-term therapy with systemic corticosteroids is not recommended in the treatment of chronic obstructive pulmonary disease (COPD). However, experience demonstrates that some patients receive low dose therapy. Our objective was to describe the demographic, physiologic and radiologic characteristics of COPD patients treated with chronic systemic corticosteroids. We analyzed COPD subjects with GOLD I-IV disease in the COPDGene® study. Subjects were divided into 2 groups based on whether they reported using chronic oral steroids or not; 1264 subjects were included. Fifty-eight (4.5%) reported chronic systemic corticosteroid use. There were no differences in age, race, co-morbid conditions (other than asthma), or body mass index between the groups. There was a greater proportion of GOLD III (41% vs. 26%) and IV (41% vs. 13%) subjects in the group using chronic systemic corticosteroids. This group used more respiratory medications, required more oxygen (2.31 ± 0.21 vs. 0.59 ± 0.05 L/min; p < 0.0001), and walked less distance (245.4 ± 17.4 vs. 367.2 ± 3.9 meters; p < 0.0001). They reported more total (1.7 ± 0.16 vs. 0.62 ± 0.03; p < 0.0001) and severe exacerbations per year (0.41 ± 0.05 vs. 0.18 ± 0.01; p < 0.0001). BODE (5.0 ± 0.3 vs. 2.6 ± 0.1; p < 0.0001), MMRC (3.31 ± 0.19 vs. 1.90 ± 0.04; p < 0.0001) and SGRQ scores (54.9 ± 2.9 vs 53.3 ± 0.6; p < 0.0001) were higher. They also had a higher percentage of emphysema (22.4 ± 1.9 vs. 14.0 ± 0.4;%, p = <0.0001) on CT scan. COPD patients that report using chronic systemic corticosteroids have more severe clinical, physiologic, and radiographic disease.     

Diffusing Capacity for Carbon Monoxide is Linked to Ventilatory Demand in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (VD/VT) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P_CO2 allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43–80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological VD/VT ratios (r = ?0.55, p = 0.0015 and r = ?0.40, p = 0.032; respectively). The peak physiological VD/VT ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted V˙O2) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological VD/VT at peak exercise, respectively. The non-invasive measurement of transcutaneous P_CO2 both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO₂ measurement.     

Evidence of reduced respiratory muscle endurance in patients with heart failure

Objectives. We sought to investigate whether reduced respiratory muscle endurance contributes to increased dyspnea and decreased exercise capacity in patients with chronic heart failure.Background. In patients with heart failure, the sensation of dyspnea may be related to abnormalities of respiratory muscle function, such as diminished strength or endurance, or both.Methods. Respiratory muscle endurance was assessed by measuring maximal sustainable ventilatory capacity in 15 patients with congestive heart failure and 8 normal subjects using progressive isocapnic hyperpnea. Near-infrared spectroscopy of an accessory respiratory muscle, Borg scale recordings of perceived dyspnea, time in inspiration, time per breath and minute ventilation were measured. Exercise testing with measurement of oxygen consumption was also performed.Results. Maximal voluntary ventilation (normal subjects 167 ± 40, heart failure group 89 ± 31 liters/min) and maximal sustainable ventilatory capacity (normal subjects 90 ± 23, heart failure group 53 ± 22 liters/min) were significantly reduced in patients with heart failure (both p < 0.05). No significant accessory respiratory muscle deoxygenation was observed in either group. Borg scale recordings at maximal sustainable ventilatory capacity were comparable in both groups. At rest, the inspiratory duty cycle (i.e., time in inspiration divided by the time per breath) was comparable in the two groups (normal subjects 0.34 ± 0.09, heart failure group 0.37 ± 0.12, p = NS). However at maximal sustainable ventilatory capacity, only normal subjects had a significant increase in the inspiratory duty cycle (normal subjects 0.49 ± 0.04, heart failure group 0.36 ± 0.10, p < 0.05). This finding suggests obstruction to airflow in patients with congestive heart failure. Values for peak exercise minute ventilation did not differ significantly from values in maximal sustainable ventilatory capacity in either group and were significantly correlated (r = 0.84, p < 0.0001).Conclusion. Respiratory muscle endurance as assessed by maximal sustainable ventiiatory capacity is reduced in patients with heart failure.     

Is The CAT Questionnaire Sensitive To Changes In Health Status In Patients With Severe COPD Exacerbations?

Abstract

The COPD Assessment Test (CAT) was validated in English showing good psychometric properties. The objective of this study is to assess the capacity of the CAT to detect changes in health status in patients experiencing COPD exacerbations (ECOPD) and to further explore the validity of the Spanish version. An observational study was conducted in 49 Spanish centres. Patients hospitalised because of ECOPD (n = 224) completed the CAT, the St. George's Respiratory Questionnaire-adapted for COPD (SGRQ-C) and the London Chest Activities of Daily Living (LCADL) questionnaire during the first 48 hours of admission and 4 ± 1 weeks after discharge. Stable patients (n = 153) also completed these at recruitment and 4 ± 1 weeks later. Over 90% of patients were male. The CAT discriminated between stable and ECOPD patients (15.8 vs 22.4, p < 0.01), as well as between patients with different levels of airflow limitation and dyspnea (MRC scale). The CAT proved sensitive to change; change in mean score was 8.9 points (effect size (ES), 0.90) in ECOPD patients reporting their health state as “much better” after discharge, 4.8 points in those reporting “quite a lot better” (ES = 0.63), and 4.6 points in those reporting “slightly better” (ES = 0.59). Cronbach's alpha and Intraclass Correlation Coefficient were 0.86 and 0.83, respectively. It correlated with both the SGRQ (r = 0.82; p < 0.01) and the LCADL (r = 0.63; p < 0.01). Change in CAT correlated well with Δ SGRQ (r = 0.63; p < 0.01). The CAT showed to be sensitive to the change in health status associated with ECOPD. We also provide evidence of the validity of the Spanish version.     

Diffusing capacity for carbon monoxide is linked to ventilatory demand in patients with chronic obstructive pulmonary disease

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (V(D)/V(T)) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P(CO2) allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43-80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological V(D)/V(T) ratios (r = -0.55, p = 0.0015 and r = -0.40, p = 0.032; respectively). The peak physiological V(D)/V(T) ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted VO(2)) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological V(D)/V(T) at peak exercise, respectively. The non-invasive measurement of transcutaneous P(CO2) both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO(2) measurement.     

A Simplified Approach to Select Exercise Endurance Intensity for Interventional Studies in COPD

ABSTRACT

Time to exercise limitation (Tlim) in response to constant work rate (CWR) is sensitive to interventions in chronic obstructive pulmonary disease (COPD). This is particularly true when the pre-intervention test lasts between 3 and 8 min (Tlim_3′–8′). There is, however, no simple method to select a work rate which is consistently associated with Tlim_3′–8′ across the spectrum of COPD severity.

We assessed 59 GOLD stages II–IV patients who initially cycled to Tlim at 75% peak. In case of short (<3 min, low-endurance) or long (>8 min, high-endurance) tests, patients exercised after 60 min at 50% or 90%, respectively (CWR_50%?75%?90%).

Critical mechanical constraints and limiting dyspnea at 75% were reached within the desired timeframe in 27 “mid-endurance” patients (46%). Increasing work rate intensity to 90% hastened the mechanical-ventilatory responses leading to Tlim_3′–8′ in 23/26 (88%) “high-endurance” patients; conversely, decreasing exercise intensity to 50% slowed those responses leading to Tlim_3′–8′ in 5/6 (83%) “high-endurance” patients. Repeating the tests at higher (60%) or lower (80%) intensities fail to consistently produce Tlim_3′–8′ in “low-” and “high-endurance”, respectively (p > 0.05). Compared to a fixed work rate at 75%, CWR_50%?75%?90% significantly decreased Tlim's coefficient of variation; consequently, the required N to detect 100 s or 33% improvement in Tlim decreased from 82 to 26 and 41 to 14, respectively.

This simplified approach to individualized work rate adjustment (CWR_50%?75%?90%) might allow greater sensitivity in evaluating interventional efficacy in improving respiratory mechanics and exercise tolerance while simultaneously reducing sample size requirements in patients with COPD.     

稳定期慢性阻塞性肺疾病患者的气道阻力与运动相关呼吸困难肺功能参数的关系

目的观察稳定期慢性阻塞性肺疾病(COPD)患者的各项气道阻力(Raw)参数与运动相关呼吸困难肺功能参数的相关关系。方法前瞻性纳入上海交通大学附属胸科医院和第一人民医院门诊稳定期COPD患者180例,根据慢性阻塞性肺疾病全球倡议(GOLD 2017版)制订的肺功能诊断标准分为Ⅰ-Ⅳ级4组,受试前8 h内均未应用支气管舒张剂。所有患者在吸入沙丁胺醇400μg后接受常规肺功能和气道阻力测试。同期选择42例成年健康体检者作为对照组。结果Ⅱ级以上COPD患者的第1秒用力呼气容积和呼出50%肺活量时流量均显著低于健康成年人和Ⅰ级COPD患者,总气道阻力、有效气道阻力、吸气阻力和呼气阻力则呈进行性增高。Ⅲ-Ⅳ级COPD患者的深吸气量占预计值百分比(IC%pred)<80%,同时改良英国医学研究委员会呼吸困难量表评分超过2分;7例Ⅲ级(13.2%)和14例Ⅳ级COPD患者(33.3%)的吸气分数(IC/TLC)≤25%,而仅有1例Ⅱ级COPD患者的IC/TLC≤25%(1.9%)。结论稳定期中重度COPD患者呼出气流受限趋于加重,Raw各项参数中呼气阻力增高尤为显著。Ⅲ-Ⅳ级COPD患者更易出现运动相关呼吸困难症状,且IC/TLC≤25%。     

Walking with Non-Invasive Ventilation Does Not Prevent Exercise-Induced Hypoxaemia in Stable Hypercapnic COPD Patients

Background: Non-invasive positive pressure ventilation (NPPV) in addition to supplemental oxygen improves arterial oxygenation, walking distance and dyspnea when applied during exercise in stable hypercapnic COPD patients. The aim of the current study was to investigate whether NPPV without supplemental oxygen is capable of preventing severe exercise-induced hypoxemia in these patients when applied during walking. Methods and Results: 15 stable hypercapnic COPD patients (FEV1 29.9 ± 15.9%) performed two 6-minute walk tests (6MWT) with a rollator in a randomized cross-over design: using either supplemental oxygen

(2.4 ± 0.7 L/min) or NPPV (inspiratory/expiratory positive airway pressure of 28.2 ± 2.8 / 5.5 ± 1.5 mbar) without supplemental oxygen. Results: 10 patients were able to complete both 6MWT. 6MWT with supplemental oxygen resulted in no changes for PO2 (pre: 67.3 ± 11.2 mmHg vs. post: 65.6 ± 12.0 mmHg, p = 0.72) whereas PCO2 increased (pre: 50.9 ± 8.1 mmHg vs. post: 54.3 ± 10.0 mmHg (p < 0.03). During 6MWT with NPPV PO2 significantly decreased from 66.8 ± 7.2 mmHg to 55.5 ± 10.6 mmHg (p < 0.02) whereas no changes occurred in PCO2 (pre: 50.6 ± 7.5 mmHg vs. post: 53.0 ± 7.1 mmHg; p = 0.17). Walking distance tended to be lower in 6MWT with NPPV compared to 6MWT with supplemental oxygen alone (318 ± 160 m vs. 377 ± 108 m; p = 0.08). Conclusion: The use of NPPV during walking without the application of supplemental oxygen does not prevent exercise-induced hypoxemia in patients with stable hypercapnic COPD.     

Distal Leg Muscle Function in Patients with COPD

Abstract

Quadriceps muscle weakness and increased fatigability are well described in patients with chronic obstructive pulmonary disease (COPD). Whether these functional alterations also exist in distal leg muscles in patients with COPD is uncertain. Fifteen patients with COPD and 15 aged-matched healthy controls performed a 12-minute standardized treadmill exercise during which a fixed total expense of 40 Kcal was reached. The strength of i) dorsiflexors, ii) plantar flexors and iii) quadriceps was assessed at rest and after exercise using maximal voluntary contraction (MVC) and potentiated twitch force (Tw_pot). Resting MVC and Tw_pot were significantly lower in patients with COPD when compared with controls respectively for i) dorsiflexors (24.9 ± 8.4 vs. 31.2 ± 8.5 Nm, p < 0.05 and 4.3 ± 1.3 vs. 5.7 ± 1.8 Nm, p < 0.05), ii) plantar flexors (49.5 ± 11.8 vs. 62.1 ± 19.6 Nm, p < 0.05 and 10.8 ± 3.5 vs. 13.4 ± 2.7 Nm, p < 0.05), and iii) quadriceps muscles. There was a greater force loss in the distal leg muscles 15 minutes post-exercise in patients with COPD, while the strength of the quadriceps muscle remained stable in both groups. Patients with COPD had weaker dorsiflexor and plantar flexor muscles when compared to age-matched healthy controls. In addition, when exposed to the same absolute walking task, the fatigability of the distal leg muscles was higher in patients with COPD.     

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow thereby contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at 20% and 80% peak work rate were performed by overlap (FEV₁ = 56.9 ± 15.9% predicted, ejection fraction = 32.5 ± 6.9%; N = 16), FEV₁-matched COPD (N = 16), ejection fraction-matched heart failure patients (N = 15) and controls (N = 12). Differences (Δ) in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (ΔO₂ uptake). Overlap patients had approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). ΔBlood flow was closely proportional to Δcardiac output in all groups (r = 0.89–0.98; p < 0.01). Overlap showed the largest impairments in Δcardiac output/ΔO₂ uptake and Δblood flow/ΔO₂ uptake (p < 0.05). Systemic arterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion was related to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively; p < 0.05). ΔBlood flow/ΔO₂ uptake was related to time to exercise intolerance only in overlap and heart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output and skeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategies that increase muscle O₂ delivery and/or decrease O₂ demand may be particularly helpful to improve exercise tolerance in COPD patients presenting heart failure as co-morbidity.     

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 (D_LCO) 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 D_LCO% predicted (r = 0.487, p < 0.0005) and RV/TLC% (r = ?0.389, p = 0.002). D_LCO% 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.     

Exercise intolerance in patients with chronic left heart failure: Relation to oxygen transport and ventilatory abnormalities

Circulatory, metabolic, and ventilatory responses to maximal and submaximal symptom-limited exercise were studied in 13 patients with chronic stable heart failure. Maximal exercise was sustained 6.5 ± 0.6 minutes (mean ± standard error of the mean) and increased minute oxygen consumption (VO₂) to 940 ± 65 ml/min, whereas submaximal exercise was sustained for 15.4 ± 2.3 minutes and increased VO₂ to 825 ± 49 ml/min (both p < 0.01 compared with maximal exercise). Both exercise protocols were terminated because of fatigue and both were associated with reduced cardiac output relative to VO₂, marked systemic oxygen extraction (80 ± 2% maximal versus 78 ± 2% submaximal) and similarly elevated blood lactate concentrations (37 ± 4 mg/dl maximal versus 36 ± 4 mg/dl submaximal), suggesting inadequate oxygen delivery to working muscle. Minute ventilation during both types of exercise was also more than twice normal relative to carbon dioxide production. However, during submaximal exercise, dyspnea was noted in only 3 patients despite these ventilatory abnormalities. During maximal exercise, dyspnea was noted in 11 patients but did not force termination of exercise or preclude achievement of marked systemic oxygen extraction and lactate production. These data suggest that patients with chronic stable cardiac failure are limited during both maximal and submaximal exercise primarily by inadequate oxygen transport to working muscle.     

Bi-level Positive Airway Pressure (BiPAP) with Standard Exhalation Valve Does Not Improve Maximum Exercise Capacity in Patients with COPD

Background: Although BiPAP has been used as an adjunct to exercise, little is know about its effect on exercise in COPD. We aimed to evaluate the acute effect of BiPAP delivered with a standard valve (Vision, Respironics), compared to no assist, on exercise capacity in individuals with COPD. Methods: Peak exercise workload (WL_peak), dyspnea (Borg), end-expiratory lung volume (EELV), tidal volume (V_T), minute ventilation (V_E), O₂ uptake (VO₂), and CO₂ production (VCO₂) were assessed in 10 COPD patients (FEV₁ 53 ± 22% pred) during three symptom-limited bicycle exercise tests while breathing i) without a ventilator (noPS), ii) with a pressure support (PS) of 0 cm H₂O (PS0; IPAP & EPAP 4 cm H₂O) and iii) PS of 10 cm H₂O (PS10; IPAP 14 & EPAP 4 cm H₂O) on separate days using a randomized crossover design. Results: WL_peak was significantly lower with PS10 (33 ± 16) and PS0 (30.5 ± 13) than noPS (43 ± 19) (p < 0.001). Dyspnea at peak exercise was similar with noPS, PS0 and PS10; at isoload it was lower with noPS compared to PS10 and PS0 (p < 0.01). V_T and V_E were highest with PS10 and lowest with noPS both at peak exercise and isoload (p < 0.001). EELV was similar at peak exercise with all three conditions. VO₂ and VCO₂ were greater with PS10 and PS0 than noPS (p < 0.001), both at peak exercise and isoload. Conclusion: Use of BiPAP with a standard exhalation valve during exercise increases V_T and V_E at the expense of augmenting VCO₂ and dyspnea, which in turns reduces WL_peak in COPD patients.     

Systemic impairment in relation to disease burden in patients with moderate COPD eligible for a lifestyle program. Findings from the INTERCOM trial

Introduction

In contrast with the frequency distribution of chronic obstructive pulmonary disease (COPD) stages in the population, in which the majority of the patients is classified as GOLD 2, much less information is available on the prevalence and implications of systemic manifestations in less severe patients relative to GOLD 3 and 4.

Aim

To characterize local and systemic impairment in relation to disease burden in a group of GOLD 2 COPD patients (n = 127, forced expiratory volume in one second (SD): 67 (11)% pred) that were eligible for the Interdisciplinary Community-based COPD management (INTERCOM) trial.

Methods

Patients were included for this lifestyle program based on a peak exercise capacity (Wmax) <70% of predicted. Metabolic and ventilatory response to incremental cycle ergometry, 6 minute walking distance (6MWD), constant work rate test (CWR), lung function, maximal inspiratory pressure (Pimax), quadriceps force (QF), quadriceps average power (QP) (isokinetic dynamometry), handgrip force (HGF) and body composition were measured. Quality of life (QoL) was assessed by the St. George’s Respiratory Questionnaire (SGRQ) and dyspnea by the modified Medical Research Council (MRC) dyspnea scale. Exacerbations and COPD-associated hospital admissions in 12 months prior to the start of the study were recorded. Burden of disease was defined in terms of exercise capacity, QoL, hospitalization, and exacerbation frequency. GOLD 2 patients were compared with reference values and with GOLD 3 patients who were also included in the trial.

Results

HGF (77.7 (18.8) % pred) and Pimax (67.1 (22.5)% pred) were impaired in GOLD 2, while QF (93.5 (22.5)% pred) was only modestly decreased. Depletion of FFM was present in 15% of weight stable GOLD 2 patients while only 2% had experienced recent involuntary weight loss. In contrast to Wmax, submaximal exercise capacity, muscle function, and body composition were not significantly different between GOLD 2 and 3 subgroups. Body mass index and fat-free mass index were significantly lower in smokers compared to ex-smokers. In multivariate analysis, QF and diffusing capacity (DLco) were independently associated with Wmax and 6 MWD in GOLD 2 while only 6 MWD was identified as an independent determinant of health-related QoL. HGF was an independent predictor of hospitalization.

Conclusions

This study shows that also in patients with moderate COPD, eligible for a lifestyle program based on a decreased exercise capacity, systemic impairment is an important determinant of disease burden and that smoking affects body composition.     

Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease

Patients with severe chronic obstructive pulmonary disease (COPD) develop dynamic lung hyperinflation (DH) during symptom-limited incremental and constant work exercise with cycle ergometer and treadmill. The increase in end-expiratory lung volume seems to be the best predictor of dyspnea. Quantification of DH is based on the relatively complex use of on-line measurement of inspiratory capacity (IC) from flow volume loops. We reasoned that DH could occur during daily activities such as walking, and that it could be simply measured using the spirometrically determined IC. We studied 72 men with COPD (FEV(1) = 45 +/- 13.3% predicted). IC was measured at rest and after a 6-min walk test. Exertional dyspnea was evaluated using the Borg scale and dyspnea during daily activities with the modified Medical Research Council (MRC) scale. IC decreased significantly from 28.9 +/- 6.7% TLC at rest to 24.1 +/- 6.8% TLC after exercise (p < 0.001). Exertional dyspnea correlated with DeltaIC (r = -0.49, p < 0.00001) and baseline MRC (r = 0.59, p < 0.00001). In many patients with COPD, walking leads to DH that can be easily determined with simple spirometric testing. DH helps explain exercise capacity limitation and breathlessness during simple daily activities.     

Exercise Ventilatory Inefficiency Adds to Lung Function in Predicting Mortality in COPD

Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO₂ output (VCO₂) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO₂ nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan–Meier analyses showed that survival time was particularly reduced when ventilation/VCO₂ nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease.     

Impaired Carbon Monoxide Diffusing Capacity is the Strongest Predictor of Exercise Intolerance in COPD

Abstract

Background: Exercise intolerance is a hallmark of chronic obstructive pulmonary disease (COPD) and forced expiratory volume in one second (FEV₁) is the traditional metric used to define the severity of COPD. However, there is dissociation between FEV₁ and exercise capacity in a large proportion of subjects with COPD. The aim of this study was to investigate whether other lung function parameters have an additive, predictive value for exercise capacity and whether this differs according to the COPD stage. Methods: Spirometry, body plethysmography and diffusing capacity for carbon monoxide (DLCO) were performed on 88 patients with COPD GOLD stages II-IV. Exercise capacity (EC) was determined in all subjects by symptom-limited, incremental cycle ergometer testing. Results: Significant relationships were found between EC and the majority of lung function parameters. DLCO, FEV₁ and inspiratory capacity (IC) were found to be the best predictors of EC in a stepwise regression analysis explaining 72% of EC. These lung function parameters explained 76% of EC in GOLD II, 72% in GOLD III and 40% in GOLD IV. DLCO alone was the best predictor of exercise capacity in all GOLD stages. Conclusions: Diffusing capacity was the strongest predictor of exercise capacity in all subjects. In addition to FEV₁, DLCO and IC provided a significantly higher predictive value regarding exercise capacity in COPD patients. This suggests that it is beneficial to add measurements of diffusing capacity and inspiratory capacity when clinically monitoring COPD patients.     

Is static hyperinflation a limiting factor during exercise in adolescents with cystic fibrosis?

Increased work of breathing is considered to be a limiting factor in patients with cystic fibrosis (CF) performing aerobic exercise. We hypothesized that adolescents with CF and with static hyperinflation are more prone to a ventilatorily limited exercise capacity than non‐static hyperinflated adolescents with CF. Exercise data of 119 adolescents with CF [range 12–18 years], stratified for static hyperinflation, defined as ratio of residual volume to total lung capacity (RV/TLC) > 30%, were obtained during a progressive bicycle ergometer test with gas analysis and analyzed for ventilatory limitation. Static hyperinflation showed a significant, though weak association (Φ 0.38; P < 0.001) with a ventilatorily limited exercise capacity (breathing reserve index at maximal effort >0.70; FEV₁ < 80% predicted and reduced exercise capacity, defined as VO_2peak < 85% predicted). Analysis of association for increasing degrees of hyperinflation showed an increase to Φ 0.49 (P < 0.001) for RV/TLC > 50%. In adolescents with static hyperinflation, peak work rate (W_peak; 3.1 ± 0.7 W/kg (75.1 ± 17.3% of predicted), peak oxygen uptake (VO_2peak/kg (ml/min/kg); 39.2 ± 9.2 ml/min/kg (91.0 ± 20.3% of predicted), peak heart rate (HR_peak; 176 ± 19 beats/min) were significantly (P < 0.05) decreased when compared with non‐static hyperinflated adolescents (W_peak 3.5 ± 0.5 W/kg (81.4 ± 10.0% of predicted)); VO_2peak/kg (ml/min/kg); 43.1 ± 7.5 ml/min/kg (98.0 ± 15.1% of predicted); and HR_peak 185 ± 14 beats/min). Additionally, no difference was found in the degree of association of FEV₁ (%) and RV/TLC (%) with VO_2peak/kg_pred and W_peak/kg_Pred, but we found the RV/TLC (%) to be a slightly stronger predictor of VO_2peak/kg_pred and W_peak/kg_Pred than FEV₁ (%). These results indicate that the presence of static hyperinflation in adolescents with CF by itself does not strongly influence ventilatory constraints during exercise and that static hyperinflation is only a slightly stronger predictor of W_peak/kg_Pred and VO_2peak/kg_Pred than airflow obstruction (FEV₁ (%)). Pediatr. Pulmonol. 2011; 46:119–124. © 2011 Wiley‐Liss, Inc.     

Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure

Objectives. This study sought to establish the chemosensitivity of patients with chronic heart failure.Background. The ventilatory response to exercise is often increased in patients with chronic heart failure, as characterized by the steeper regression slope relating minute ventilation to carbon dioxide output. We hypothesized that the sensitivity of chemoreceptors may be reset and may in part mediate the exercise hyperpnea seen in this condition.Methods. Hypoxic and peripheral hypercapnic chemosensitivity were studied in 38 patients with chronic heart failure (35 men, 3 women; mean [±SE] age 60.2 ± 1.3 years; radionuclide left ventricular ejection fraction 25.7 ± 2.3%) and 15 healthy control subjects (11 mean, 4 women; mean age 54.9 ± 3.0 years) using transient inhalations of pure nitrogen and single breaths of 13% carbon dioxide, respectively. The change in chemosensitivity during mild exercise (25 W) was assessed in the first 15 patients and all control subjects. Central hypercapnic chemosensitivity was also characterized in 25 patients and 10 control subjects by the rebreathing of 7% carbon dioxide in 93% oxygen. Cardiopulmonary exercise testing was performed in all subjects.Results. Maximal oxygen consumption was 16.6 ± 0.9 versus 29.7 ± 2.2 ml/kg per min (p < 0.0001), and the ventilation-carbon dioxide output regression slope was 37.2 ± 1.5 versus 26.5 ± 1.4 (p < 0.0001) in patients and control subjects, respectively. Hypoxic and central hypercapnic chemosensitivity were enhanced in patients (0.707 ± 0.076 vs. 0.293 ± 0.056 liters/min per % arterial oxygen saturation [Sao₂], p = 0.0001 and 3.15 ± 0.41 vs. 2.02 ± 0.25 liters/min per mm Hg, p = 0.025, respectively) and correlated significantly with the ventilatory response to exercise. Hypoxic chemosensitivity was augmented during exercise in patients and in control subjects but remained higher in the former (1.530 ± 0.27 vs. 0.685 ± 0.12 liters/min per %Sao₂, p = 0.01). The peripheral hypercapnic chemosensitivity of patients at rest and during exercise was similar to that in control subjects, consistent with its lesser contribution to overall carbon dioxide chemosensitivity.Conclusions. Enhanced hypoxic and central hypercapnic chemosensitivity may play a role in mediating the increased ventilatory response to exercise in chronic heart failure.