Diego A. Rodríguez

Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity

Chronic obstructive pulmonary disease (COPD) is characterized by a decline in forced expiratory volume in 1 s (FEV(1)) and, in many advanced patients, by arterial hypoxemia with or without hypercapnia. Spirometric and gas exchange abnormalities have not been found to relate closely, but this may reflect a narrow range of severity in patients studied. Therefore, we assessed the relationship between pulmonary gas exchange and airflow limitation in patients with COPD across the severity spectrum. Ventilation-perfusion (V(A)/Q) mismatch was measured using the multiple inert gas elimination technique in 150 patients from previous studies. The distribution of patients according to the GOLD stage of COPD was: 15 with stage 1; 40 with stage 2; 32 with stage 3; and 63 with stage 4. In GOLD stage 1, AaPo(2) and V(A)/Q mismatch were clearly abnormal; thereafter, hypoxemia, AaPo(2), and V(A)/Q imbalance increased, but the changes from GOLD stages 1-4 were modest. Postbronchodilator FEV(1) was related to Pa(O(2)) (r = 0.62) and Pa(CO(2)) (r = -0.59) and to overall V(A)/Q heterogeneity (r = -0.48) (P < 0.001 each). Pulmonary gas exchange abnormalities in COPD are related to FEV(1) across the spectrum of severity. V(A)/Q imbalance, predominantly perfusion heterogeneity, is disproportionately greater than airflow limitation in GOLD stage 1, suggesting that COPD initially involves the smallest airways, parenchyma, and pulmonary vessels with minimal spirometric disturbances. That progression of V(A)/Q inequality with spirometric severity is modest may reflect pathogenic processes that reduce both local ventilation and blood flow in the same regions through airway and alveolar disease and capillary involvement.

Physical Activity and Clinical and Functional Status in COPD

BACKGROUND The mechanisms underlying the benefits of regular physical activity in the evolution of COPD have not been established. Our objective was to assess the relationship between regular physical activity and the clinical and functional characteristics of COPD. METHODS Three hundred forty-one patients were hospitalized for the first time because of a COPD exacerbation in nine teaching hospitals in Spain. COPD diagnosis was confirmed by spirometry under stable conditions. Physical activity before the first COPD hospitalization was measured using the Yale questionnaire. The following outcome variables were studied under stable conditions: dyspnea, nutritional status, complete lung function tests, respiratory and peripheral muscle strength, bronchial colonization, and systemic inflammation. RESULTS The mean age was 68 years (SD, 9 years), 93% were men, 43% were current smokers, and the mean postbronchodilator FEV(1) was 52% predicted (SD, 16% predicted). Multivariate linear regression models were built separately for each outcome variable and adjusted for potential confounders (including remaining outcomes if appropriate). When patients with the lowest quartile of physical activity were compared to patients in the other quartiles, physical activity was associated with significantly higher diffusing capacity of the lung for carbon monoxide (Dlco) [change in the second, third, and fourth quartiles of physical activity, compared with first quartile (+ 6%, + 6%, and + 9% predicted, respectively; p = 0.012 [for trend])], expiratory muscle strength (maximal expiratory pressure [Pemax]) [+ 7%, + 5%, and + 9% predicted, respectively; p = 0.081], 6-min walking distance (6MWD) [+ 40, + 41, and + 45 m, respectively; p = 0.006 (for trend)], and maximal oxygen uptake (Vo(2)peak) [+ 55, + 185, and + 81 mL/min, respectively; p = 0.110 (for trend)]. Similarly, physical activity reduced the risk of having high levels of circulating tumor necrosis factor alpha (odds ratio, 0.78, 0.61, and 0.36, respectively; p = 0.011) and C-reactive protein (0.70, 0.51, and 0.52, respectively; p = 0.036) in multivariate logistic regression. CONCLUSIONS More physically active COPD patients show better functional status in terms of Dlco, Pemax, 6MWD, Vo(2)peak, and systemic inflammation.

Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial

Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease (COPD) that currently has no established pharmacological treatment. This study aimed to assess whether concomitant treatment with sildenafil would enhance the results of pulmonary rehabilitation in patients with COPD and increased pulmonary arterial pressure (PAP). In this double-blind, randomised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months. The primary end-point was the gain in the cycle endurance time at a constant work-rate. Secondary end-points included performance in the incremental exercise test, 6-min walk distance and quality of life. 63 patients with severe COPD and moderately increased PAP were randomised. Cycle endurance time increased by 149 s (95% CI 26–518 s) in the sildenafil group and by 169 s (95% CI 0–768 s) in the placebo group (median change difference -7 s, 95% CI -540–244 s; p=0.77). Gains in the incremental exercise test, 6-min walk distance and quality of life at the end of the study did not differ between groups. Measurements of arterial oxygenation and adverse events were similar in both groups. In patients with severe COPD and moderately increased PAP, concomitant treatment with sildenafil does not improve the results of pulmonary rehabilitation in exercise tolerance. Sildenafil did not improve respiratory rehabilitation outcomes in patients with severe COPD and moderately increased PAP http://ow.ly/lh7cb

Muscle and blood redox status after exercise training in severe COPD patients.

Beneficial effects of exercise training in patients with chronic obstructive pulmonary disease (COPD) are acknowledged. However, high-intensity exercise may enhance muscle oxidative stress in severe COPD patients. We hypothesized that high-intensity exercise training of long duration does not deteriorate muscle redox status. In the vastus lateralis and blood of 18 severe COPD patients and 12 controls, before and after an 8-week training program, protein oxidation and nitration, antioxidant systems, and inflammatory cytokines were examined. At baseline, COPD patients showed greater muscle oxidative stress and superoxide dismutase activity and circulating inflammatory cytokines than controls. Among COPD patients, muscle and blood protein carbonylation levels were correlated. Both groups showed training-induced increase in VO(2) peak and decreased blood lactate levels. After training, among the COPD patients, blood protein nitration levels were significantly reduced and muscle protein oxidation and nitration levels did not cause impairment. Muscle and blood levels of inflammatory cytokines were not modified by training in either patients or controls. We conclude that in severe COPD patients, high-intensity exercise training of long duration improves exercise capacity while preventing the enhancement of systemic and muscle oxidative stress. In addition, in these patients, resting protein oxidation levels correlate between skeletal muscle and blood compartments.

Physical activity in COPD patients: patterns and bouts

The present study aims to describe the pattern of physical activity and the frequency, duration and intensity of physical activity bouts in patients with chronic obstructive pulmonary disease (COPD), to assess how these patterns differ according to COPD severity, and to explore whether these patients meet the general guidelines for physical activity for older adults. 177 patients (94% male, mean±sd age 71±8 years and forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro2 Armband accelerometer for eight consecutive days. Physical activity bouts were defined as periods of ≥10 min above 1.5 metabolic equivalent tasks and classified according to their median intensity. Patients engaged in activity a median of 153 min·day−1 and 57% of that time was spent in bouts. Median frequencies of bouts per day were four and three for all and moderate-to-vigorous intensities, respectively. With increasing COPD severity, time in physical activity, proportion of time in bouts and frequency of bouts decreased. 61% of patients fulfilled the recommended physical activity guidelines. In conclusion, COPD patients of all spirometric severity stages engage in physical activity bouts of moderate-to-vigorous intensities. Patients with severe and very severe COPD perform their daily activities in fewer and shorter bouts than those in mild and moderate stages. Patients with severe COPD perform their daily activities in fewer, shorter bouts than those in mild and moderate stages http://ow.ly/nug7k

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

Clinical assessment of peripheral muscle function in patients with chronic obstructive pulmonary disease.

Vilaro J, Rabinovich R, Gonzalez-deSuso JM, Troosters T, Rodríguez D, Barberà JA, and Roca J: Clinical assessment of peripheral muscle function in patients with chronic obstructive pulmonary disease. Am J Phys Med Rehabil 2009;88:39–46. Objective:Correlation of muscle function, muscle mass and endurance, and exercise tolerance in chronic obstructive pulmonary disease (COPD). Design:Sixteen COPD patients (forced expiratory volume during the first second 38 ± 15% predicted) and 6 controls underwent magnetic resonance imaging of the thigh, muscle strength and endurance, and exercise tolerance assessments. Results:Thigh mass distribution was bimodal (cutoff 19.0 kg m−2). Six COPD patients (16 ± 2.5 kg m−2) (P < 0.05) presented reduced thigh mass (COPDLQ), whereas 10 patients with normal quadriceps mass (COPDNQ) and all controls had identical mass distribution (22 ± 2.4 kg m−2). COPDLQ patients had lower muscle function and lower exercise tolerance than both COPDNQ and controls (P < 0.05 each), but muscle strength corrected by mass was similar between COPD patients (COPDLQ 0.59 ± 0.12 and COPDNQ 0.55 ± 0.10 Nm kg−1 m−2) and controls (0.62 ± 0.04 Nm Kg−1 m−2). In contrast, endurance to muscle mass ratio was lower in COPD (COPDLQ and COPDNQ 0.91 ± 0.15 and 0.89 ± 0.15 J kg−1 m−2) than in controls (1.07 ± 0.11 J kg−1 m−2) (P < 0.05). Half-time phosphocreatine recovery (COPDLQ 66 ± 14 and COPDNQ 55 ± 9 secs, not significant) was also slower than in controls (43 ± 10 secs) (P < 0.01). Conclusions:Impaired muscle strength was explained by reduced muscle mass, but it did not account for abnormal muscle endurance. The latter seems associated to impaired O2 transport/O2 utilization, resulting in altered muscle bioenergetics.

Effects and barriers to deployment of telehealth wellness programs for chronic patients across 3 European countries

BACKGROUND Benefits of cardiopulmonary rehabilitation (CPR) in patients with chronic obstructive pulmonary disease (COPD) are well established, but long-term sustainability of training-induced effects and its translation into healthy lifestyles are unsolved issues. It is hypothesized that Integrated Care Services supported by Information and Communication Technologies (ICS-ICT) can overcome such limitations. In the current study, we explored 3 ICS-ICT deployment experiences conducted in Barcelona, Trondheim and Athens. METHODS In the 3 sites, a total of 154 patients completed an 8-week supervised CPR program. Thereafter, they were allocated either to an ICS-ICT group or to usual care (CPR + UC) during a follow-up period of at least 12 months with assessment of 6-min walking test (6MWT) as main outcome variable at all time points in the 3 sites. Because real deployment was prioritized, the interventions were adapted to site heterogeneities. RESULTS In the ICS-ICT group from Barcelona (n = 77), the use of the personal health folder (PHF) was the cornerstone technological tool to empower COPD patients for self-management showing high applicability and user-acceptance. Long-term sustainability of training-induced increase in exercise capacity was observed in ICS-ICT compared to the control group (p = 0.01). Likewise, ICS-ICT enhanced the activities domain of the SGRQ (p < 0.01) and daily physical activity (p = 0.03), not seen in controls. No effects of ICS-ICT were observed in Trondheim (n = 37), nor in Athens (n = 40), due to technological and/or organizational limitations. CONCLUSIONS The study results suggest the potential of the ICS-ICT Barcelonas approach to enhance COPD management. Moreover, it allowed identification of the factors limiting transferability to the other sites. The research prompts the need for large multicenter trials specifically designed to assess effectiveness, efficiencies and transferability of this type of intervention.

Endurance Exercise Training Improves Heart Rate Recovery in Patients with COPD

Abstract Background: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease. The effect of the exercise training in heart rate recovery (HRR) has not been established in patients with COPD. Objective: To assess the effects of 8-weeks’ endurance training program on parasympathetic nervous system response measured as heart rate recovery in a sample of moderate-to-severe COPD patients. Methods: We recruited a consecutive sample of patients with COPD candidates to participate in a pulmonary rehabilitation program from respiratory outpatient clinics of a tertiary hospital. HRR was calculated, before and after training, as the difference in heart rate between end-exercise and one minute thereafter (HRR1) in a constant-work rate protocol. Results: A total of 73 COPD patients were included: mean (SD) age 66 (8) years, median (P25-P75) post-bronchodilator FEV1 39 (29–53)%. The prevalence of slow HRR1 (≤12 beats) at baseline was 63%, and was associated with spirometric severity (mean FEV1 35% in slow HRR1 vs 53 in normal HRR1, p < 0.001). After 8-weeks training, HRR1 improved from mean (SD) 10 (7) to 12 (7) beats (p = 0.0127). Multivariate linear regression models showed that the only variable related to post-training HRR1 was pre-training HRR1 (p < 0.001). Conclusions: These results suggest that training enhances HRR in patients with moderate-to-severe COPD. HRR is an easy tool to evaluate ANS such that it may be a useful clinical marker of parasympathetic nervous system response in patients with COPD.

Inspiratory and expiratory muscle training in subacute stroke: A randomized clinical trial.

Objective: To assess the effectiveness, feasibility, and safety of short-term inspiratory and expiratory muscle training (IEMT) in subacute stroke patients. Methods: Within 2 weeks of stroke onset, 109 patients with a first ischemic stroke event were randomly assigned to the IEMT (n = 56) or sham IEMT (n = 53) study group. The IEMT consisted of 5 sets of 10 repetitions, twice a day, 5 days per week for 3 weeks, at a training workload equivalent to 30% of maximal respiratory pressures. Patients and researchers assessing outcome variables were blinded to the assigned study group. The main outcome was respiratory muscle strength assessed by maximal inspiratory and expiratory pressures (PImax, PEmax). Respiratory complications at 6 months were also recorded. Results: Both groups improved respiratory muscle strength during the study. IEMT was associated with significantly improved %PImax and %PEmax: effect size d = 0.74 (95% confidence interval [CI] 0.28–1.20) and d = 0.56 (95% CI 0.11–1.02), respectively. No significant training effect was observed for peripheral muscle strength. Respiratory complications at 6 months occurred more frequently in the sham group (8 vs 2, p = 0.042), with an absolute risk reduction of 14%. The number needed to treat to prevent one lung infection event over a follow-up of 6 months was 7. No major adverse events or side effects were observed. Conclusion: IEMT induces significant improvement in inspiratory and expiratory muscle strength and could potentially offer an additional therapeutic tool aimed to reduce respiratory complications at 6 months in stroke patients. Classification of evidence: This study provides Class II evidence that short-term training may have the potential to improve respiratory muscle strength in patients with subacute stroke.