Short-term effects of air pollution and weather on physical activity in patients with chronic obstructive pulmonary disease (COPD).

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) accumulate low levels of physical activity. How environmental factors affect their physical activity in the short-term is uncertain. AIM: to assess the short-term effects of air pollution and weather on physical activity levels in COPD patients. METHODS: This multi-center panel study assessed 408 COPD patients from Catalonia (Spain). Daily physical activity (i.e., steps, time in moderate-to-vigorous physical activity (MVPA), locomotion intensity, and sedentary time) was recorded in two 7-day periods, one year apart, using the Dynaport MoveMonitor. Air pollution (nitrogen dioxide (NO2), particulate matter below 10 µm (PM10) and a marker of black carbon (absorbance of PM2.5: PM2.5ABS), and weather (average and maximum temperature, and rainfall) were estimated the same day (lag zero) and up to 5 days prior to each assessment (lags 1-5). Mixed-effect distributed lag linear regression models were adjusted for age, sex, weekday, public holidays, greenness, season, and social class, with patient and city as random effects. RESULTS: Patients (85% male) were on average (mean ± SD) 68 ± 9 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 ± 18% predicted. Higher NO2, PM10 and PM2.5ABS levels at lag four were associated with fewer steps, less time in MVPA, reduced locomotion intensity, and longer sedentary time (e.g., coefficient (95% CI) of -60 (-105, -15) steps per 10 µg/m3 increase in NO2). Higher average and maximum temperatures at lag zero were related to more steps and time in MVPA, and less sedentary time (e.g., +85 (15, 154) steps per degree Celsius). Higher rainfall at lag zero was related to fewer steps and more sedentary time. CONCLUSION: Air pollution affects the amount and intensity of physical activity performed on the following days in COPD patients, whereas weather affects the amount of physical activity performed on the same day.

Urban environment and physical activity and capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity and exercise capacity are key prognostic factors in chronic obstructive pulmonary disease (COPD) but their environmental determinants are unknown. OBJECTIVES: To test the association between urban environment and objective physical activity, physical activity experience and exercise capacity in COPD. METHODS: We studied 404 patients with mild-to-very severe COPD from a multi-city study in Catalonia, Spain. We measured objective physical activity (step count and sedentary time) by the Dynaport MoveMonitor, physical activity experience (difficulty with physical activity) by the Clinical visit-PROactive (C-PPAC) instrument, and exercise capacity by the 6-min walk distance (6MWD). We estimated individually (geocoded to the residential address) population density, pedestrian street length, slope of terrain, and long-term (i.e., annual) exposure to road traffic noise, nitrogen dioxide (NO2) and particulate matter (PM2.5). We built single- and multi-exposure mixed-effects linear regressions with a random intercept for city, adjusting for confounders. RESULTS: Patients were 85% male, had mean (SD) age 69 (9) years and walked 7524 (4045) steps/day. In multi-exposure models, higher population density was associated with fewer steps, more sedentary time and worse exercise capacity (-507 [95% CI: 1135, 121] steps, +0.2 [0.0, 0.4] h/day and -13 [-25, 0] m per IQR). Pedestrian street length related with more steps and less sedentary time (156 [9, 304] steps and -0.1 [-0.1, 0.0] h/day per IQR). Steeper slope was associated with better exercise capacity (15 [3, 27] m per IQR). Higher NO2 levels related with more sedentary time and more difficulty in physical activity. PM2.5 and noise were not associated with physical activity or exercise capacity. DISCUSSION: Population density, pedestrian street length, slope and NO2 exposure relate to physical activity and capacity of COPD patients living in highly populated areas. These findings support the consideration of neighbourhood environmental factors during COPD management and the attention to patients with chronic diseases when developing urban and transport planning policies.

Roles of the physical environment in health-related quality of life in patients with chronic obstructive pulmonary disease.

RATIONALE: Many clinical and psychological factors are known to influence the health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). However, research on whether environmental factors, such as air pollution, noise, temperature, and blue/green spaces also influence HRQL in COPD has not been systematically investigated. OBJECTIVE: To assess the relationship between air pollution, road traffic noise, temperature, and distance to blue/green spaces and respiratory-specific HRQL in COPD. METHODS: We used cross-sectional data from a multicenter study in 407 stable mild-to-very severe COPD patients from Barcelona (Catalonia). Patients answered the COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ). Individual residential exposure to air pollutants (nitrogen dioxide [NO2] and particulate matters of varying aerodynamic diameters [PM2.5, PM10, and PM2.5absorbance]), road traffic noise (Lden), and land surface temperature were estimated using long-term averages from land-use regression models, 24-h noise maps, and land surface temperature maps, respectively. We measured residential distances to blue/green spaces from the Urban Atlas. We used mixed-effect negative binomial (for CAT) and linear (for CCQ) regression models, adjusted for potential confounders, with a random effect by center. RESULTS: Of those patients, 85 % were male and had a mean (SD) age of 69 (9) years, CAT score of 12 (7), CCQ-total score of 1.4 (1.0), and post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 (18) %predicted. We found that NO2 and PM2.5absorbance were associated with worsened CAT and CCQ-mental scores, e.g., 0.15-unit change in CAT score [regression coefficient (ß) = 0.15; 95 % confidence interval (CI) = 0.03, 0.26] per interquartile range in NO2 [13.7 µg/m3]. Greater distances to blue/green spaces were associated with worsened CCQ-mental scores [0.08; 0.002, 0.15]. CONCLUSIONS: Our study showed that increased air pollution, particularly NO2 and PM2.5absorbance and greater distances to blue/green spaces negatively influence HRQL in COPD patients. These findings have important implications for the WHO promotion to develop healthy cities for our future.

The dyspnoea-inactivity vicious circle in COPD: development and external validation of a conceptual model.

The vicious circle of dyspnoea-inactivity has been proposed, but never validated empirically, to explain the clinical course of chronic obstructive pulmonary disease (COPD). We aimed to develop and validate externally a comprehensive vicious circle model.We utilised two methods. 1) Identification and validation of all published vicious circle models by a systematic literature search and fitting structural equation models to longitudinal data from the Spanish PAC-COPD (Phenotype and Course of COPD) cohort (n=210, mean age 68 years, mean forced expiratory volume in 1 s (FEV1) 54% predicted), testing both the hypothesised relationships between variables in the model ("paths") and model fit. 2) Development of a new model and external validation using longitudinal data from the Swiss and Dutch ICE COLD ERIC (International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts) cohort (n=226, mean age 66 years, mean FEV1 57% predicted).We identified nine vicious circle models for which structural equation models confirmed most hypothesised paths but showed inappropriate fit. In the new model, airflow limitation, hyperinflation, dyspnoea, physical activity, exercise capacity and COPD exacerbations remained related to other variables and model fit was appropriate. Fitting it to ICE COLD ERIC, all paths were replicated and model fit was appropriate.Previously published vicious circle models do not fully explain the vicious circle concept. We developed and externally validated a new comprehensive model that gives a more relevant role to exercise capacity and COPD exacerbations.

Long-term efficacy and effectiveness of a behavioural and community-based exercise intervention (Urban Training) to increase physical activity in patients with COPD: a randomised controlled trial.

There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD). We assessed 12-month efficacy and effectiveness of the Urban Training intervention on physical activity in COPD patients.This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202). Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number). The primary outcome was 12-month change in steps·day-1 measured by accelerometer.Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184-1731) steps·day-1 between Urban Training and usual care. Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups. Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events.Urban Training, combining behavioural strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns. However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.

Socio-environmental correlates of physical activity in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Study of the causes of the reduced levels of physical activity in patients with COPD has been scarce and limited to biological factors. AIM: To assess the relationship between novel socio-environmental factors, namely dog walking, grandparenting, neighbourhood deprivation, residential surrounding greenness and residential proximity to green or blue spaces, and amount and intensity of physical activity in COPD patients. METHODS: This cross-sectional study recruited 410 COPD patients from five Catalan municipalities. Dog walking and grandparenting were assessed by questionnaire. Neighbourhood deprivation was assessed using the census Urban Vulnerability Index, residential surrounding greenness by the satellite-derived Normalized Difference Vegetation Index, and residential proximity to green or blue spaces as living within 300 m of such a space. Physical activity was measured during 1 week by accelerometer to assess time spent on moderate-to-vigorous physical activity (MVPA) and vector magnitude units (VMU) per minute. FINDINGS: Patients were 85% male, had a mean (SD) age of 69 (9) years, and post-bronchodilator FEV1 of 56 (17) %pred. After adjusting for age, sex, socio-economic status, dyspnoea, exercise capacity and anxiety in a linear regression model, both dog walking and grandparenting were significantly associated with an increase both in time in MVPA (18 min/day (p<0.01) and 9 min/day (p<0.05), respectively) and in physical activity intensity (76 VMU/min (p=0.05) and 59 VMUs/min (p<0.05), respectively). Neighbourhood deprivation, surrounding greenness and proximity to green or blue spaces were not associated with physical activity. CONCLUSIONS: Dog walking and grandparenting are associated with a higher amount and intensity of physical activity in COPD patients. TRIAL REGISTRATION NUMBER: Pre-results, NCT01897298.

Multi-level differential network analysis of COPD exacerbations.

Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation (ECOPD) that impact negatively the course of their disease. ECOPD are heterogeneous events of unclear pathobiology and non-specific diagnosis. Network analysis is a novel research approach that can help unravelling complex biological systems. We hypothesised that the comparison of multi-level (i.e., clinical, physiological, biological, imaging and microbiological) correlation networks determined during ECOPD and convalescence can yield novel patho-biologic information.In this proof-of-concept study we included 86 patients hospitalised because of ECOPD in a multicentre study in Spain. Patients were extensively characterised both during the first 72 h of hospitalisation and during clinical stability, at least 3 months after hospital discharge.We found that 1) episodes of ECOPD are characterised by disruption of the network correlation observed during convalescence; and 2) a panel of biomarkers that include increased levels of dyspnoea, circulating neutrophils and C-reactive protein (CRP) has a high predictive value for ECOPD diagnosis (AUC 0.97).We conclude that ECOPD 1) are characterised by disruption of network homeokinesis that exists during convalescence; and 2) can be identified objectively by using a panel of three biomarkers (dyspnoea, circulating neutrophils and CRP levels) frequently determined in clinical practice.

Inspiratory capacity-to-total lung capacity ratio and dyspnoea predict exercise capacity decline in COPD.

BACKGROUND AND OBJECTIVE: Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD. METHODS: We measured IC/TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6-min walk distance (6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline. RESULTS: Mean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/TLC had greater 6MWD decline (-27.4 ± 42.5, -24.9 ± 36.5 and -13.4 ± 39.9 m/year in the first, second and third tertile of IC/TLC, respectively; P-for-trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C-reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/TLC (ß = 0.7 m/year per each percentage unit of IC/TLC; P = 0.007) and dyspnoea (mMRC ≥ 2) (ß = -14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change. CONCLUSION: IC/TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions.

Benefits of physical activity on COPD hospitalisation depend on intensity.

The present study aims to disentangle the independent effects of the quantity and the intensity of physical activity on the risk reduction of chronic obstructive pulmonary disease (COPD) hospitalisations.177 patients from the Phenotype Characterization and Course of COPD (PAC-COPD) cohort (mean±sd age 71±8 years, forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro 2 Armband accelerometer (BodyMedia, Pittsburgh, PA, USA) for eight consecutive days, providing data on quantity (steps per day, physically active days and daily active time) and intensity (average metabolic equivalent tasks) of physical activity. Information on COPD hospitalisations during follow-up (2.5±0.8 years) was obtained from validated centralised datasets. During follow-up 67 (38%) patients were hospitalised. There was an interaction between quantity and intensity of physical activity in their effects on COPD hospitalisation risk. After adjusting for potential confounders in the Cox regression model, the risk of COPD hospitalisation was reduced by 20% (hazard ratio (HR) 0.79, 95% CI 0.67-0.93; p=0.005) for every additional 1000 daily steps at low average intensity. A greater quantity of daily steps at high average intensity did not influence the risk of COPD hospitalisations (HR 1.01, p=0.919). Similar results were found for the other measures of quantity of physical activity. Greater quantity of low-intensity physical activity reduces the risk of COPD hospitalisation, but high-intensity physical activity does not produce any risk reduction.

Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress of the disease is available. OBJECTIVES: To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in development of lung emphysema and pulmonary hypertension (PH) and to test whether the sGC-cGMP axis is a treatment target for these conditions. METHODS: Investigations were performed in human lung tissue from patients with COPD, healthy donors, mice, and guinea pigs. Mice were exposed to cigarette smoke (CS) for 6 hours per day, 5 days per week for up to 6 months and treated with BAY 63-2521. Guinea pigs were exposed to CS from six cigarettes per day for 3 months, 5 days per week and treated with BAY 41-2272. Both BAY compounds are sGC stimulators. Gene and protein expression analysis were performed by quantitative real-time polymerase chain reaction and Western blotting. Lung compliance, hemodynamics, right ventricular heart mass alterations, and alveolar and vascular morphometry were performed, as well as inflammatory cell infiltrate assessment. In vitro assays of cell adhesion, proliferation, and apoptosis have been done. MEASUREMENTS AND MAIN RESULTS: The functionally essential sGC ß1-subunit was down-regulated in patients with COPD and in CS-exposed mice. sGC stimulators prevented the development of PH and emphysema in the two different CS-exposed animal models. sGC stimulation prevented peroxynitrite-induced apoptosis of alveolar and endothelial cells, reduced CS-induced inflammatory cell infiltrate in lung parenchyma, and inhibited adhesion of CS-stimulated neutrophils. CONCLUSIONS: The sGC-cGMP axis is perturbed by chronic exposure to CS. Treatment of COPD animal models with sGC stimulators can prevent CS-induced PH and emphysema.

Characterisation and prognosis of undiagnosed chronic obstructive pulmonary disease patients at their first hospitalisation.

BACKGROUND: Under-diagnosis of COPD is an important unmet medical need. We investigated the characteristics and prognosis of hospitalised patients with undiagnosed COPD. METHODS: The PAC-COPD cohort included 342 COPD patients hospitalised for the first time for an exacerbation of COPD (2004-2006). Patients were extensively characterised using sociodemographic, clinical and functional variables, and the cohort was followed-up through 2008. We defined "undiagnosed COPD" by the absence of any self-reported respiratory disease and regular use of any pharmacological respiratory treatment. RESULTS: Undiagnosed COPD was present in 34% of patients. They were younger (mean age 66 vs. 68 years, p = 0.03), reported fewer symptoms (mMRC dyspnoea score, 2.1 vs. 2.6, p < 0.01), and had a better health status (SGRQ total score, 29 vs. 40, p < 0.01), milder airflow limitation (FEV1% ref., 59% vs. 49%, p < 0.01), and fewer comorbidities (two or more, 40% vs. 56%, p < 0.01) when compared with patients with an established COPD diagnosis. Three months after hospital discharge, 16% of the undiagnosed COPD patients had stopped smoking (vs. 5%, p = 0.019). During follow-up, annual hospitalisation rates were lower in undiagnosed COPD patients (0.14 vs. 0.25, p < 0.01); however, this difference disappeared after adjustment for severity. Mortality was similar in both groups. CONCLUSIONS: Undiagnosed COPD patients have less severe disease and lower risk of re-hospitalisation when compared with hospitalised patients with known COPD.

Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients.

The origin(s) of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the impact of exposure to ambient air pollution on systemic biomarkers of inflammation (C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-6, IL-8 and fibrinogen) and tissue repair (hepatocyte growth factor (HGF)) in 242 clinically stable COPD patients (mean age 67.8 years and forced expiratory volume in 1 s 71.3% predicted) in Barcelona, Spain, in 2004-2006. A spatiotemporal exposure assessment framework was applied to predict ambient nitrogen dioxide (NO2) and levels of particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5) at each participant's home address during 10 periods of 24 h (lags 1-10) and 1 year prior to the blood sampling date. We used linear regression models to estimate associations between biomarkers and exposure levels. An interquartile range (IQR) increase in NO2 exposure in lag 5 was associated with 51%, 10% and 9% increases in CRP, fibrinogen and HGF levels respectively. We also observed 12% and 8% increases in IL-8 associated with an IQR increase in NO2 exposure in lag 3 and over the year before sampling, respectively. These increases were larger in former smokers. The results for PM2.5 were not conclusive. These results show that exposure to ambient NO2 increases systemic inflammation in COPD patients, especially in former smokers.

Hospital admissions and exercise capacity decline in patients with COPD.

Exercise capacity declines with time and is an important determinant of health status and prognosis in patients with chronic obstructive pulmonary disease (COPD). We hypothesised that hospital admissions are associated with exercise capacity decline in these patients. Clinical and functional variables were collected for 342 clinically stable COPD patients. The 6-min walk distance (6MWD) was determined at baseline and after a mean±sd of 1.7±0.3 years. Information on hospitalisations during follow-up was obtained from centralised administrative databases. Linear regression was used to model changes in exercise capacity. Patients were mostly male (92%), with mean±sd age 67.9±8.6 years, post-bronchodilator forced expiratory volume in 1 s 54±17% predicted and baseline 6MWD 433±93 m. During follow-up, 6MWD decreased by 21.9±51.0 m·year(-1) and 153 (45%) patients were hospitalised at least once. Among patients admitted only for COPD-related causes (50% of those ever admitted), the proportion presenting a clinically significant loss of 6MWD was higher than in patients admitted for only nonrespiratory conditions (53% versus 29%, p=0.040). After adjusting for confounders, annual 6MWD decline was greater (26 m·year(-1), 95% CI 13-38 m·year(-1); p<0.001) in patients with more than one all-cause hospitalisation per year, as compared with those with no hospitalisations. Hospitalisations are related to a greater decline in exercise capacity in COPD.

Endurance exercise training improves heart rate recovery in patients with COPD.

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.

Real-world walking cadence in people with COPD.

Introduction: The clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence. Methods: We assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days' accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries. Results: Participants were mostly male (80%) and had mean±sd age of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57±19% predicted and walked 6880±3926 steps·day-1. Mean walking cadence was 88±9 steps·min-1, followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90-0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1, 6-min walk distance, physical activity (steps·day-1, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min-1, 95% CI 0.91-0.99, p=0.009). Conclusions: Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome.

FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts.

Since the publication of the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal for the assessment of chronic obstructive lung disease (COPD), four studies have used existing cohorts to explore the characteristics, temporal variability and/or relationship with outcomes of the four resulting patient categories (A, B, C and D). Here, we compare their results and address a number of frequently asked questions (FAQs) on the topic. The most salient findings were that: 1) the prevalence of these four groups depends on the specific population studied, C being the least prevalent; 2) comorbidities are particularly prevalent in the two "high-symptom" groups (B and D); 3) patients classifiedZ as A or D tend to remain in the same group over time, whereas those classified as B or C change substantially during follow-up; 4) mortality at 3 years was lowest in A and worst in D but surprisingly similar (and intermediate) in B and C; and 5) the incidence of exacerbations during follow-up increases progressively from A to D but that of hospitalisations behave similarly to mortality. These results identify several strengths and shortcomings of the new GOLD assessment proposal, particularly that group B is associated with more morbidity and high mortality.

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.

Salbutamol but not ipratropium abolishes leukotriene D4-induced gas exchange abnormalities in asthma.

PURPOSE: Leukotriene D(4) (LTD(4)) is a central mediator in asthma inducing bronchoconstriction and profound disturbances in pulmonary gas exchange in asthmatic subjects. The aim of the study was to compare, for the first time, the influence of the bronchodilators salbutamol (400 µg) and ipratropium (80 µg) on lung function changes induced by inhaled LTD(4). METHODS: Treatments were evaluated in a randomized, three-period, double-blind, placebo-controlled, cross-over study where spirometric and pulmonary gas exchange indices were followed in 12 subjects with mild asthma before and after LTD(4) challenge. RESULTS: Compared with placebo, salbutamol provided significant protection against the fall in FEV(1) (forced expiratory volume in 1 s) after LTD(4) challenge. Salbutamol also abolished the LTD(4)-induced gas exchange disturbances [decreased arterial oxygen tension (PaO(2)) and increased alveolar-arterial oxygen tension difference (AaPO(2))]. Ipratropium provided significant but less marked attenuation of the changes in FEV(1) and arterial oxygenation induced by LTD(4). CONCLUSION: Despite the equal bronchodilatory effects of salbutamol and ipratropium before the challenge with LTD(4), salbutamol was superior to ipratropium in preventing spirometric and gas exchange abnormalities. This result indicates a broader action of salbutamol on several of the disturbances that contribute to airway obstruction including, for example, exudation of plasma in the airway mucosa. The clinical implication of this new finding is that in this model of acute asthmatic airway obstruction, salbutamol was more effective than ipratropium.

Physical activity and cardiac autonomic dysfunction in patients with chronic obstructive pulmonary disease: A cross-sectional analysis.

BACKGROUND: The cardiac autonomic function in patients with chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVES: We aimed to 1) describe the cardiac autonomic function assessed by heart rate recovery (HRR) and chronotropic response (CR) during a 6-min walk test (6MWT) and afterward and 2) estimate the association of physical activity with HRR and CR in COPD patients. METHODS: This cross-sectional analysis included 320 patients with mild to very severe COPD. Physical activity (steps, time in any/moderate-to-vigorous/vigorous physical activity, intensity and sedentary time) was measured during 1 week by accelerometer. CR and HRR were measured during a 6MWT and 5min after, respectively, and their association with physical activity parameters was estimated by multivariable linear regression models. RESULTS: Patients were 82% male and had a mean (SD) age 68 (8) years, post-bronchodilator FEV1 57 (18) % predicted, and walked a mean of 7716 (4139) steps/day. HRR was slow until 5min after the 6MWT; the mean (SD) HRR was 15 (10), 22 (11), 25 (12), 25 (12) and 27 (12) bpm after 1, 2, 3, 4 and 5min, respectively. The mean (SD) CR was 35% (16). After adjusting for relevant confounders, time in vigorous physical activity was significantly associated with a fast decrease in HRR (p=0.044) and an increase in CR (p=0.021). We found no independent association for other physical activity parameters. CONCLUSION: A cardiac autonomic dysfunction is present in patients with mild to very severe COPD and is inversely related to the practice of vigorous physical activity. Trial registration ClinicalTrials.gov NCT01897298.

Similar gene expression profiles in smokers and patients with moderate COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by multiple cellular and structural changes affecting the airways, lung parenchyma and vasculature, some of which are also identified in smokers without COPD. The molecular mechanisms underlying these changes remain poorly understood. With the aim of identifying mediators potentially implicated in the pathogenic processes that occur in COPD and their potential relationship with cigarette smoking, we evaluated the mRNA expression of genes involved in inflammation, tissue remodeling and vessel maintenance. Lung tissue samples were obtained from 60 patients who underwent lung resection (nonsmokers, n=12; smokers, n=12; and moderate COPD, n=21) or lung transplant (severe-to-very severe COPD, n=15). PCR arrays containing 42 genes coding for growth factors/receptors, cytokines, metalloproteinases, adhesion molecules, and vessel maintenance mediators were used. Smoking-induced changes include the up-regulation of inflammatory genes (IL-1ß, IL-6, IL-8, CCL2, and CCL8) and the decreased expression of growth factor/receptor genes (BMPR2, CTGF, FGF1, KDR and TEK) and genes coding for vessel maintenance factors (EDNRB). All these genes exhibited a similar profile in moderate COPD patients. The up-regulation of MMP1 and MMP9 was the main change associated with COPD. Inflammatory genes as well as the endothelial selectin gene (SELE) were down-regulated in patients with more severe COPD. Clustering analysis revealed a closer relationship between moderate COPD and smokers than between both subsets of COPD patients for this selected set of genes. The study reveals striking similarities between smokers and COPD patients with moderate disease emphasizing the crucial role of cigarette smoking in the genesis of these changes, and provides additional evidence of the involvement of the matrix metalloproteinase's in the remodeling process of the lung in COPD.