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Patients with chronic obstructive pulmonary disease (COPD) usually complain of symptoms such as cough, sputum, wheezing, and dyspnea. Little is known about clinical symptoms in individuals with restrictive ventilatory impairment. The aim of this study was to compare the prevalence and type of respiratory symptoms in patients with COPD to those reported by individuals with restrictive ventilatory impairment in the Proyecto Latinoamericano de Investigacion en Obstruccion Pulmonar study. Between 2002 and 2004, individuals ≥40 years of age from five cities in Latin America performed pre and post-bronchodilator spirometry and had their respiratory symptoms recorded in a standardized questionnaire. Among the 5315 individuals evaluated, 260 (5.1%) had a restrictive spirometric diagnosis (forced vital capacity (FVC) < lower limit of normal (LLN) with forced expiratory volume in the first second to forced vital capacity ratio (FEV1/FVC) ≥ LLN; American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005) and 610 (11.9%) were diagnosed with an obstructive pattern (FEV1/FVC < LLN; ATS/ERS 2005). Patients with mild restriction wheezed more ((30.8%) vs. (17.8%); p < 0.028). No difference was seen in dyspnea, cough, and sputum between the two groups after adjusting for severity stage. The health status scores for the short form 12 questionnaire were similar in restricted and obstructed patients for both physical (48.4 ± 9.4 vs. 48.3 ± 9.8) and mental (50.8 ± 10.6 vs. 50.0 ± 11.5) domains. Overall, respiratory symptoms are not frequently reported by patients with restricted and obstructed patterns as defined by spirometry. Wheezing was more frequent in patients with restricted pattern compared with those with obstructive ventilatory defect. However, the prevalence of cough, sputum production, and dyspnea are not different between the two groups when adjusted by the same severity stage., (© The Author(s) 2015.)

Background: Spirometry is the gold standard for diagnosing chronic obstructive pulmonary disease (COPD). Although there are a number of different guideline criteria for deciding who should be selected for spirometric screening, to date it is not known which criteria are the best based on sensitivity and specificity., Aims: Firstly, to evaluate the proportion of subjects in the PLATINO Study that would be recommended for spirometry testing according to Global initiative for Obstructive Lung Disease (GOLD)-modified, American College of Chest Physicians (ACCP), National Lung Health Education Program (NLHEP), GOLD and American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Secondly, we aimed to compare the sensitivity, specificity, and positive predictive and negative predictive values, of these five different criteria., Methods: Data from the PLATINO study included information on respiratory symptoms, smoking and previous spirometry testing. The GOLD-modified spirometry indication criteria are based on three positive answers out of five questions: the presence of cough, phlegm in the morning, dyspnoea, age over 40 years and smoking status., Results: Data from 5,315 subjects were reviewed. Fewer people had an indication for spirometry (41.3%) according to the GOLD-modified criteria, and more people had an indication for spirometry (80.4%) by the GOLD and ATS/ERS criteria. A low percentage had previously had spirometry performed: GOLD-modified (14.5%); ACCP (13.2%); NLHEP (12.6%); and GOLD and ATS/ERS (12.3%). The GOLD-modified criteria showed the least sensitivity (54.9) and the highest specificity (61.0) for detecting COPD, whereas GOLD and ATS/ERS criteria showed the highest sensitivity (87.9) and the least specificity (20.8)., Conclusion: There is a considerable difference in the indication for spirometry according to the five different guideline criteria. The GOLD-modified criteria recruit less people with the greatest sum of sensitivity and specificity.

Background: Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS)., Methods: The PLATINO study is a multicenter population-based survey carried out in five Latin American cities. Outcomes were self-reported exacerbations (defined by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classified in three specific groups: COPD--a postbronchodilator (post-BD) FEV₁/FVC ratio of < 0.70; asthma--presence of wheezing in the last year and a minimum post-BD increase in FEV₁ or FVC of 12% and 200 mL; and overlap COPD-asthma--the combination of the two., Results: Out of 5,044 subjects, 767 were classified as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD., Conclusions: The coexisting COPD-asthma phenotype is possibly associated with increased disease severity.

Background: The PLATINO baseline study, conducted from 2003-2005 in five Latin American cities (São Paulo, Mexico City, Montevideo, Santiago, Caracas), showed a high prevalence of chronic obstructive pulmonary disease (COPD)., Methods/design: A follow-up study was conducted in three out of the five centers (Montevideo, Santiago, and São Paulo) after a period of 5, 6 and 9years, respectively, aimed at verifying the stability of the COPD diagnosis over time, the evolution of the disease in terms of survival, morbidity and respiratory function, and the analyses of inflammatory and genetic biomarkers in the blood. Some questions were added to the original questionnaire and death certificates were obtained from the national official registries., Results: The fieldwork has been concluded in the three centers. From the original samples in the PLATINO study phasei, we were able to locate and interview 85.6% of patients in Montevideo, 84.7% in Santiago and 77.7% in São Paulo. Individuals who could not be located had higher education levels in Brazil, and were more likely to be current smokers in Santiago and São Paulo than in Montevideo. The overall quality of spirometries was ≥80% according to American Thoracic Society criteria. The number of deaths was 71 (Montevideo), 95 (Santiago) and 135 (São Paulo), with death certificates obtained from the national mortality registries for 76.1%, 88.3% and 91.8% of cases in Montevideo, Santiago and São Paulo, respectively., Conclusions: This study shows that is possible to perform population-based longitudinal studies in Latin American with high follow-up rates and high-quality spirometry data. The adequacy of national mortality registries varies among centers in Latin America., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

Introduction: Comorbidities are common in patients with chronic obstructive pulmonary disease (COPD), and have a significant impact on health status and prognosis. The PLATINO study provides data on self-reported comorbidities and perceived health status in COPD subjects., Methods: PLATINO is a population-based study on COPD prevalence in five Latin American cities. COPD diagnosis was defined by GOLD criteria (FEV1/FVC<.70 post-bronchodilator). Information was collected on the following comorbidities: heart disease, hypertension, diabetes, cerebrovascular disease, peptic ulcer and asthma. Health status was evaluated using the SF-12 questionnaire, derived from the question: «In general, would you say your health is excellent, very good, good, fair or poor?». A simple comorbidity score was calculated by adding the total number of comorbid conditions., Results: Of a total population of 5314individuals, 759 had COPD. Reported comorbidities by decreasing frequency were: any cardiovascular disease, hypertension, peptic ulcer, heart disease, diabetes, cerebrovascular disease, asthma and lung cancer. COPD patients had a higher comorbidity score and prevalence of lung cancer (P<.0001) and asthma (P<.0001), as well as a higher tendency to have hypertension (P=.0652) and cerebrovascular disease (P=.0750). Factors associated with comorbidities were age, body mass index (BMI) and female gender. The number of comorbidities increased as the health status deteriorated., Conclusions: In the PLATINO population-based study, COPD individuals had an increased number of comorbidities. Age, female gender and higher BMI were the factors associated with comorbidity in these patients. Comorbid conditions were associated with impaired health status, independently of the COPD status., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

Little information exists regarding the epidemiology of the chronic bronchitis phenotype in unselected chronic obstructive pulmonary disease (COPD) populations. We examined the prevalence of the chronic bronchitis phenotype in COPD and non-COPD subjects from the PLATINO study, and investigated how it is associated with important outcomes. Post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70 was used to define COPD. Chronic bronchitis was defined as phlegm on most days, at least 3 months per year for ≥ 2 yrs. We also analysed another definition: cough and phlegm on most days, at least 3 months per year for ≥ 2 yrs. Spirometry was performed in 5,314 subjects (759 with and 4,554 without COPD). The proportion of subjects with and without COPD with chronic bronchitis defined as phlegm on most days, at least 3 months per year for ≥ 2 yrs was 14.4 and 6.2%, respectively. Using the other definition the prevalence was lower: 7.4% with and 2.5% without COPD. Among subjects with COPD, those with chronic bronchitis had worse lung function and general health status, and had more respiratory symptoms, physical activity limitation and exacerbations. Our study helps to understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population at a particular time-point and suggests that chronic bronchitis in COPD is possibly associated with worse outcomes.

Background: Although chronic obstructive pulmonary disease (COPD) is mostly related to tobacco smoking, a variable proportion of COPD occurs in never smokers. We investigated differences between COPD in never smokers compared with smokers and subjects without COPD., Methods: PLATINO is a cross-sectional population-based study of five Latin American cities. COPD was defined as postbronchodilator FEV(1)/FVC <0.70 and FEV(1) <80% of predicted values., Results: Among 5,315 subjects studied, 2278 were never smokers and 3036 were ever smokers. COPD was observed in 3.5% of never smokers and in 7.5% of ever smokers. Never smokers with COPD were most likely older and reported a medical diagnosis of asthma or previous tuberculosis. Underdiagnosis was as common in obstructed patients who never smoked as in ever smokers., Conclusions: Never smokers comprised 26% of all individuals with airflow obstruction. Obstruction was associated with female gender, older age and a diagnosis of asthma or tuberculosis., (Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.)

There is evidence to suggest sex differences exists in chronic obstructive pulmonary disease (COPD) clinical expression. We investigated sex differences in health status perception, dyspnoea and physical activity, and factors that explain these differences using an epidemiological sample of subjects with and without COPD. PLATINO is a cross-sectional, population-based study. We defined COPD as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.70, and evaluated health status perception (Short Form (SF)-12 questionnaire) and dyspnoea (Medical Research Council scale). Among 5,314 subjects, 759 (362 females) had COPD and 4,555 (2,850 females) did not. In general, females reported more dyspnoea and physical limitation than males. 54% of females without COPD reported a dyspnoea score ≥ 2 versus 35% of males. A similar trend was observed in females with COPD (63% versus 44%). In the entire study population, female sex was a factor explaining dyspnoea (OR 1.60, 95%CI 1.40-1.84) and SF-12 physical score (OR -1.13, 95%CI -1.56- -0.71). 40% of females versus 28% of males without COPD reported their general health status as fair-to-poor. Females with COPD showed a similar trend (41% versus 34%). Distribution of COPD severity was similar between sexes, but currently smoking females had more severe COPD than currently smoking males. There are important sex differences in the impact that COPD has on the perception of dyspnoea, health status and physical activity limitation.

Background: Acute bronchodilator responsiveness is an area of discussion in COPD. No information exists regarding this aspect of the disease from an unselected COPD population. We assessed acute bronchodilator responsiveness and factors influencing it in subjects with and without airway obstruction in an epidemiologic sample., Methods: COPD was defined by GOLD criteria (post-bronchodilator FEV(1)/FVC<0.70). In this analysis, subjects with pre-bronchodilator FEV(1)/FVC <0.70 but > or =0.70 post-bronchodilator were considered to have reversible obstruction. Bronchodilator responsiveness after albuterol 200microg was assessed using three definitions: a) FVC and/or FEV(1) increment > or =12% plus > or =200mL over baseline; b) FEV(1)> or =15% increase over baseline; and c) FEV(1) increase > or =10% of predicted value., Results: There were 756 healthy respiratory subjects, 481 subjects with reversible obstruction and 759 COPD subjects. Depending on the criterion used the proportion of person with acute bronchodilator responsiveness ranged between 15.0-28.2% in COPD, 11.4-21.6% in reversible obstructed and 2.7-7.2% in respiratory healthy. FEV(1) changes were lower (110.6+/-7.40 vs. 164.7+/-11.8mL) and FVC higher (146.5+/-14.2mL vs. -131.0+/-19.6mL) in COPD subjects compared with reversible obstructed. Substantial overlap in FEV(1) and FVC changes was observed among the groups. Acute bronchodilator responsiveness in COPD persons was associated with less obstruction and never smoking., Conclusions: Over two-thirds of persons with COPD did not demonstrate acute bronchodilator responsiveness. The overall response was small and less than that considered as significant by ATS criteria. The overlap in FEV(1) and FVC changes after bronchodilator among the groups makes it difficult to determine a threshold for separating them., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Recurrent exacerbations are common in COPD patients. Limited information exists regarding exacerbation frequency in COPD patients from epidemiologic studies. We examined the frequency of self-reported exacerbations and the factors influencing exacerbation frequency among COPD patients in a population-based study conducted in Latin America., Methods: We used a post-bronchodilator FEV(1)/FVC ratio of < 0.70 to define COPD. Exacerbation was self-reported and defined by symptoms (deterioration of breathing symptoms that affected usual daily activities or caused missed work)., Results: Spirometry was performed in 5,314 subjects. There were 759 subjects with airflow limitation; of these, 18.2% reported ever having had an exacerbation, 7.9% reported having an exacerbation, and 6.2% reported having an exacerbation requiring at least a doctor visit within the past year. The proportion of individuals with an exacerbation significantly increased by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, from 4.2% in stage 1 to 28.9% in stages 3 and 4. The self-reported exacerbation rate was 0.58 exacerbations per year. The rate of exacerbations requiring at least a doctor visit and length of stay in hospital due to exacerbations also increased as COPD severity progressed. The factors associated with having an exacerbation in the past year were dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and disease severity of GOLD stages 3 and 4., Conclusions: The proportion of individuals with airflow limitation and self-reported exacerbation increases as the disease severity progresses. Dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and more severe obstruction were significantly associated with having an exacerbation in the past year.

Setting: Five Latin American cities: São Paulo, Brazil; Mexico City, Mexico; Montevideo, Uruguay; Santiago, Chile; Caracas, Venezuela., Objective: To describe the burden of chronic obstructive pulmonary disease (COPD) in Latin America., Design: This is a multicentre study. Post-bronchodilator spirometry was used and the main outcome measure was FEV(1)/FVC < 0.7 (fixed ratio criterion). Global Obstructive Lung Disease (GOLD) stages were also analysed., Results: The combined population aged > or =40 years in the five countries included in the study was approximately 85.3 million. Of these, it was estimated that 12.2 million have airflow obstruction, which corresponds to our prevalence estimate of 14.3%. The proportion of subjects in Stages II-IV of the GOLD classification was 5.6%. Risk factors presenting the highest aetiological fractions for COPD were age, current smoking, indoor exposure to coal and exposure to dust in the workplace. Smoking, the modifiable factor with the strongest aetiological fraction for COPD, affects 29.2% of adults aged > or =40 years in these cities, corresponding to approximately 25 million smokers in this age group., Conclusion: Prevention of smoking and exposure to pollutants, such as coal and dust, are the interventions most likely to succeed against COPD in Latin America. The information obtained by a collaborative study has been vast and encouraging for other similar studies.

Background: The body mass index (BMI) is a prognostic factor for chronic obstructive pulmonary disease (COPD). Despite its importance, little information is available regarding BMI alteration in COPD from a population-based study. We examined characteristics by BMI categories in the total and COPD populations in five Latin-American cities, and explored the factors influencing BMI in COPD., Methods: COPD was defined as a postbronchodilator forced expiratory volume in the first second/forced vital capacity (FEV(1)/FVC) <0.70. BMI was categorized as underweight (< 20 kg/m(2)), normal weight (20-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (> or = 30.0 kg/m(2))., Results: Interviews were completed in 5571 subjects from 6711 eligible individuals, and spirometry was performed in 5314 subjects. There were 759 subjects with COPD and 4555 without COPD. Compared with the non-COPD group, there was a higher proportion of COPD subjects in the underweight and normal weight categories, and a lower proportion in the obese category. Over one-half COPD subjects had BMI over 25 kg/m(2). No differences in BMI strata among countries were found in COPD subjects. Factors associated with lower BMI in males with COPD were aging, current smoking, and global initiative for chronic obstructive lung disease (GOLD) stages III-IV, whereas wheeze and residing in Santiago and Montevideo were associated with higher BMI. In females with COPD, current smoking, lower education, and GOLD stages II-IV were associated with lower BMI, while dyspnea and wheeze were associated with higher BMI., Conclusions: BMI alterations are common in COPD with no significant differences among countries. Current smoking, age, GOLD stages, education level, residing in Santiago and Montevideo, dyspnea and wheeze were independently associated with BMI in COPD.

Objective: PLATINO project is a population-based study designed to determine the prevalence of chronic obstructive pulmonary disease (COPD) in São Paulo, Brazil; Mexico City, Mexico; Montevideo, Uruguay; Santiago de Chile, Chile; and Caracas, Venezuela. The objective of this portion of PLATINO was to describe preventive and pharmacological treatment of COPD patients and factors associated with such treatment., Patients and Methods: Eligible subjects completed a questionnaire and underwent postbronchodilator spirometry., Results: Of the total of 5529 individuals who answered items referring to treatment, 758 had COPD (ratio of postbronchodilator forced expiratory volume in 1 second to forced vital capacity of <0.7), and 86 of them had been previously diagnosed by a physician. Among all COPD patients, only half of smokers or former smokers had been advised to quit and 24.7% had received some type of respiratory medication. Only 13.5% had used inhaled corticosteroids, and those were the patients with the most severe disease. In the group of patients who had a previous medical diagnosis of COPD, 69% of the smokers or former smokers had been advised to quit by a physician and 75.6% had received respiratory medication in the preceding year: 43% reported having used inhaled medication and 36% had used bronchodilators. Rates of vaccination against influenza and the use of mucolytic drugs and inhalers varied from one health care facility to another. All drug prescriptions were based on previous spirometry., Conclusions: Spirometry emerged not only as a diagnostic tool, but also as a factor associated with treatment, against a background of uneven use of available health care resources in these 5 Latin American cities.

The aim of this study was to describe the impact of using bronchodilators on the prevalence of Chronic Obstructive Pulmonary Disease in a population-based survey (Platino study). A cluster sampling of subjects 40 years of age or older, representative of the metropolitan areas of 5 Latin American cities (Sao Paulo, Mexico, Montevideo, Santiago and Caracas) was chosen. Spirometry according to ATS standards was done before and after inhalation of 200 micrograms of salbutamol in 5183 subjects. Prevalences of airflow obstruction were estimated using different criteria, in tests done before and after bronchodilator use, and with reference values for pre- or post-bronchodilator use. Bronchodilator testing reduced the overall prevalence of FEV(1)/FVC% < 0.70 from 21.7% to 14% (35%). In the group with FEV(1)/FVC < 0.70 after bronchodilator use, 21% were asymptomatic from the respiratory point of view, and lacked significant adverse exposures. Subjects below the 5th percentile for FEV(1)/FVC and FEV(1)/FEV(6) were fewer than those with FEV(1)/FVC < 0.70, especially among the elderly. More subjects are below the 5th percentile of FEV(1)/FVC and FEV(1)/FEV(6) using reference values for tests after bronchodilator use than using the reference values determined without bronchodilator testing. Testing after bronchodilator use reduces the prevalence of airflow obstruction from 32 to 39% depending on the definition used. In addition, the subjects who were still obstructed after bronchodilator use were the ones who showed more respiratory symptoms and exposure to tobacco and other smokes and dusts, than subjects with reversible obstruction, suggesting an increased specificity for COPD.

Background: COPD is a major worldwide problem with a rising prevalence. Despite its importance, there is a lack of information regarding underdiagnosis and misdiagnosis of COPD in different countries. As part of the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar study, we examined the relationship between prior diagnostic label and airway obstruction in the metropolitan areas of five Latin American cities (São Paulo, Santiago, Mexico City, Montevideo, and Caracas)., Methods: A two-stage sampling strategy was used in each of the five areas to obtain probability samples of adults aged >or= 40 years. Participants completed a questionnaire that included questions on prior diagnoses, and prebronchodilator and postbronchodilator spirometry. A study diagnosis of COPD was based on airway obstruction, defined as a postbronchodilator FEV(1)/FVC < 0.70., Results: Valid spirometry and prior diagnosis information was obtained for 5,303 participants; 758 subjects had a study diagnosis of COPD, of which 672 cases (88.7%) had not been previously diagnosed. The prevalence of undiagnosed COPD was 12.7%, ranging from 6.9% in Mexico City to 18.2% in Montevideo. Among 237 subjects with a prior COPD diagnosis, only 86 subjects (36.3%) had postbronchodilator FEV(1)/FVC < 0.7, while 151 subjects (63.7%) had normal spirometric values. In the same group of 237 subjects, only 34% reported ever undergoing spirometry prior to our study., Conclusions: Inaccurate diagnostic labeling of COPD represents an important health problem in Latin America. One possible explanation is the low rate of spirometry for COPD diagnosis.

Study Objective: The present study evaluated the relationship between health status (HS) and peripheral muscle histochemical characteristics in chronic obstructive pulmonary disease (COPD), and identified selected independent respiratory and extrapulmonary variables that predicted the HS of these patients., Design: Cross-sectional study., Setting: Outpatient respiratory clinic of a university hospital., Patients and Methods: We studied 29 patients (63+/-10 yrs) with a forced expiratory volume in 1s (FEV1) of 39+/-12%. All patients underwent vastus lateralis muscle biopsies for histochemical analysis. They also had spirometry, arterial blood gas analysis, body mass index (BMI), dyspnea determined with the MMRC scale and responded to the St. George's Respiratory Questionnaire (SGRQ) for HS assessment., Results: SGRQ total score correlated with fiber type distribution. A stepwise multiple regression identified three independent predictors of SGRQ total score: type I fiber proportion, BMI, and FEV1; r = 0.78 and r2 = 0.61., Conclusions: These results indicate that impaired HS in COPD is related to the peripheral muscle changes characterized by less type I fibers proportion. The findings argue in favor of an important contribution of the systemic consequences on the HS in COPD independently from the airflow limitation severity, and help to explain the observation of the poor correlation between the degree of airflow limitation and SGRQ total score.

Background: We report the performance of an ultrasound-based portable spirometer (EasyOne) used in a population-based survey of the prevalence of chronic obstructive pulmonary disease, conducted in 5 Latin American cities: São Paulo, Brazil; México City, México; Montevideo, Uruguay; Santiago, Chile; and Caracas, Venezuela (the Latin American COPD Prevalence Study [PLATINO])., Methods: During the survey period (which ranged from 3 months to 6 months in the various locations) we collected daily calibration data from the 70 EasyOne spirometers used in the 5 survey cities. The calibrations were conducted with a 3-L syringe, and the calibration data were stored in the spirometer's database., Results: Ninety-seven percent of the calibration volumes were within +/- 64 mL (2.1%) of the 3-L calibration signal. Excluding data from the first city studied (São Paulo), where one calibration syringe had to be replaced, 98% of the calibration checks were within +/- 50 mL (1.7%). The measured volume was affected only minimally by the syringe's peak flow or emptying time., Conclusion: In these 70 EasyOne spirometers neither calibration nor linearity changed during the study. Such calibration stability is a valuable feature in spirometry surveys and in the clinical setting.

In chronic obstructive pulmonary disease (COPD) the presence of systemic inflammation has been associated with peripheral muscle abnormalities and weight loss. To study whether inflammatory factors are important in these processes, the present study compared the skeletal muscle levels of nitrite, nitrate, nitrotyrosine, neuronal, endothelial and inducible nitric oxide synthases (nNOS, eNOS, and iNOS, respectively), and inflammatory markers (tumour necrosis factor (TNF)-alpha, CD154 and CD163) in 15 patients (forced expiratory volume in one second 43+/-11%) and 14 controls. All these markers were also compared between patients with normal and low body weight. Nitrite (12.5+/-2.6 versus 17.0+/-3.4 micromol.mg(-1) protein), nitrate (20.7+/-2.4 versus 24.4+/-4.5 micromol.mg(-1) protein) and eNOS (31.9+/-4.6 versus 43.6+/-7.5 ng.mg(-1) protein) were lower in COPD patients than in controls. Nitrotyrosine (25.6+/-5.4 versus 6.6+/-3.3 ng.mg(-1) protein), iNOS expression (32+/-9.5 versus 7.16+/-2.7 ng.mg(-1) protein), TNF-alpha (257+/-160 versus 48.3+/-4.4 pg.mg(-1) protein) and CD163 (6.4+/-2.1 versus 0.8+/-0.4 ng.mg(-1) protein) were higher in COPD patients than in controls. CD154 levels were 15.7+/-7.0 ng.mg(-1) protein in COPD patients and undetectable in controls. Similar levels of all these markers were observed in COPD patients with normal and low body weight. In conclusion, these findings suggest the presence of an inflammatory process in the muscle tissue of chronic obstructive pulmonary disease patients, and argue in favour of its participation in the pathogenesis of skeletal muscle abnormalities.

Objective: This study was designed to assess changes in skeletal muscle characteristics after 6 weeks' high-intensity physical training of patients with moderate to severe chronic obstructive pulmonary disease (COPD) and to determine how the changes were related to improvements in exercise tolerance and health related quality of life (HRQL)., Patients and Methods: Ten patients with a mean (SD) age of 60 (10) years and a forced expiratory volume in 1 second of 32% (9%) were enrolled. The effect of training on the 6-minute walk test, HRQL questionnaires, and skeletal muscles was examined for the 8 patients who completed the program. The structural and chemical characteristics of skeletal muscles before and after training were studied in vastus lateralis muscle biopsies., Results: Training significantly modified the 6-minute walk test (P<.01), HRQL (P<.05), and citrate synthetase activity (P<.05). Changes in distances walked during the 6-minute walk test were significantly related to changes in the mean area of fibers (r=0.81)., Conclusions: The results of this study indicate that 6 weeks of high-intensity physical training of COPD patients produces moderate changes in skeletal muscles which could partly explain improvements observed in exercise tolerance after respiratory rehabilitation.