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Summary: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. Methods: A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV1, 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PImax), and expiratory (PEmax) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. Results: Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV1 (PEmax, OR = 6.8, p < 0.01; PImax, OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV1, was associated with current acute exacerbations. Conclusions: Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction [Copyright &y& Elsevier]

Summary: Background: The potential role of decreased respiratory muscle mass, if any, in mediating the susceptibility to exacerbation in COPD patients has not been determined. We hypothesized that a decrease in respiratory muscle mass is associated with increased risk of multiple hospital admissions due to acute exacerbations of the disease. Methods: Eligible cases and controls (n =20) were identified from records of our department''s pulmonary clinic. Ten subjects diagnosed with COPD (males, 66±7yr, Body Mass Index (BMI)=26±4kg/m2) were identified as fragile patients. Fragility was defined as four or more admissions in the previous year due to severe exacerbations of the disease. Fragile patients were matched with 10 non-fragile controls, defined as COPD patients who had required only one admission due to exacerbation of the disease. Criteria for 1:1 matching included ethnicity, gender, age, BMI, degree of airflow obstruction (i.e., FEV1), comorbidity and chronic treatment. Multiple computed tomography (CT) scan slices were obtained to assess area and attenuation coefficients of multiple upper limb, thorax, abdomen and lower limb muscles. Results: CSA of intercostal and abdominal muscles was significantly decreased in fragile COPD patients (right side intercostals, mean relative difference (MRD)=−14%, p =0.010; OR (95% CI)=2.2 (1.1–4.8), p =0.021; left side, MRD=−13%, p =0.007; OR=2.2 (1.1–4.5), p =0.027). CSA and attenuation coefficients of all other muscle compartments showed no statistical differences between the two study groups but showed the same trend. Strength of the inspiratory and expiratory muscles did not differ between the two study groups. Conclusions: This study shows that the risk for multiple admissions due to a COPD exacerbation associates with a marked decrease in the CSA of the intercostal muscle compartment. [Copyright &y& Elsevier]

We conducted a 15-year retrospective cohort study to determine the prevalence of restrictive lung disease before allogeneic hematopoietic cell transplantation (HCT), and to assess whether this was a risk factor for poor outcomes. A total of 2545 patients were eligible for the analysis. Restrictive lung disease was defined as a total lung capacity (TLC) < 80% of predicted normal. Chest x-rays and /or computed tomography (CT) scans were reviewed for all restricted patients to determine whether lung parenchymal abnormalities were unlikely or highly likely to cause restriction. Multivariate Cox proportional hazard and sensitivity analyses were performed to assess the relationship between restriction and early respiratory failure and nonrelapse mortality. Restrictive lung disease was present in 194 subjects (7.6%) before HCT. Among these cases, radiographically apparent abnormalities were unlikely to be the cause of the restriction in 149 subjects (77%). In unadjusted and adjusted analyses, the presence of pulmonary restriction was significantly associated with a 2-fold increase in risk for early respiratory failure and nonrelapse mortality, suggesting that these outcomes occurring in the absence of radiographically apparent abnormalities may be related to respiratory muscle weakness. These findings suggest that pulmonary restriction should be considered a risk factor for poor outcomes after transplantation. [Copyright &y& Elsevier]

It is unknown if diminished pulmonary function early after allogeneic hematopoietic transplant is associated with poor long-term outcomes. The objective of this study was to determine if posttransplant lung function is associated with 5-year nonrelapse mortality (NRM) and the development of chronic graft-versus-host disease (cGVHD). Retrospective analysis was done for 2158 patients who had routine pulmonary function testing 60-120 days after transplant between 1992 and 2004. Cox regression was used to assess the hazard ratio for 5-year NRM. A second analysis assessed the hazard ratio for the development of cGVHD. Lung function score was the primary exposure, and was calculated according to forced expiratory volume in 1 second (FEV1) and carbon monoxide diffusion capapcity (DLCO). Individual pulmonary function parameters were secondary exposures. The primary outcomes were 5-year NRM and the development of cGVHD. Most patients had normal lung function following transplant. A higher lung function score, signifying greater impairment, was associated with an increased risk of mortality (category 1 hazard ratio [HR] 1.47 [1.17-1.85]; category 2 HR 3.38 [2.53-4.53]; category 3 HR 7.80 [4.15-14.68]). A similar association was observed for all individual pulmonary function parameters. Low FEV1 was associated with the subsequent development of cGVHD (FEV1 70%-79% HR 1.26 [1.01-1.57]; 60%-69% HR 1.48 [1.10-2.01]; <60% HR 2.02 [1.34-3.05]). Models using either lung function score or individual pulmonary function parameters performed about equally well as judged by the C-statistic. Impaired lung function at day 80 posttransplant was associated with a higher risk of NRM. A low FEV1 following transplant was associated with developing cGVHD within 1 year. [Copyright &y& Elsevier]

Summary: Background: This study describes the characteristics of a large sample of patients hospitalised for the first time for a chronic obstructive pulmonary disease (COPD) exacerbation. Methods: All subjects first admitted for a COPD exacerbation to nine teaching Spanish hospitals during January 2004–March 2006, were eligible. COPD diagnosis was confirmed by spirometry under stability. At admission, sociodemographic data, lifestyle, previous treatment and diagnosis of respiratory disease, lung function and Charlson index of co-morbidity were collected. A comprehensive assessment, including dyspnea, lung function, six-minute walking test, and St. George’s Respiratory Questionnaire (SGRQ), was completed 3months after admission, during a clinically stable disease period. Results: Three-hundred and forty-two patients (57% of the eligible) participated in the study: 93% males, mean (SD) age 68 (9) years, 42% current smokers, 50% two or more co-morbidities, 54% mild-to-moderate dyspnea, post-bronchodilator FEV1 52 (16)% of predicted (54% mild-to-moderate COPD in ATS/ERS stages), 6-min walking distance 440m, total SGRQ score 37 (18), and 36% not report respiratory disease. The absence of a previous COPD diagnosis, positive bronchodilator test, female gender, older age, higher DLco and higher BMI were independently associated with less severe COPD. Conclusions: We show that the patients admitted after presenting with their first COPD exacerbation have a wide range of severity, with a large proportion of patients in the less advanced COPD stages. [Copyright &y& Elsevier]

Summary: The most common symptoms in chronic obstructive pulmonary disease (COPD) patients are breathlessness and exercise limitation. Although both general and inspiratory muscle training have shown clinical benefits, the effects of specific expiratory muscle training remain controversial. Objective: To investigate the effects of expiratory training on lung function, exercise tolerance, symptoms and health-related quality of life in severe COPD patients. Methods: Sixteen patients (FEV1, 28±8% pred.) were randomised to either expiratory muscle or sham training groups, both completing a 5-week programme (30min sessions breathing through an expiratory threshold valve 3 times per week) (50% of their maximal expiratory pressure (MEP) vs. placebo, respectively). Lung function, exercise capacity (bicycle ergometry and walking test), and clinical outcomes (dyspnoea and quality of life (St. George Respiratory Questionnaire (SGRQ)) were evaluated both at baseline and following the training period. Results: Although lung function remained roughly unchanged after training, exercise capacity, symptoms and quality of life significantly improved. The improvement in both walking distance and the SGRQ score significantly correlated with changes in MEP. Conclusion: Our results confirm that a short outpatient programme of expiratory training can improve symptoms and quality of life in severe COPD patients. These effects could be partially explained by changes in expiratory muscle strength. [Copyright &y& Elsevier]

Abstract: Oxidative stress is involved in the sarcopenia of aging muscles. On the grounds that ventilatory muscles are permanently active, and their activity may even increase with aging, we hypothesized that the levels of oxidative stress would probably be increased in the external intercostals of elderly healthy individuals. We conducted a case–control study in which reactive carbonyl groups, malondialdehyde–protein adducts, 3-nitrotyrosine immunoreactivity, Mn-superoxide dismutase (Mn-SOD), and catalase were detected using immunoblotting in external intercostals and quadriceps (open muscle biopsies) obtained from 12 healthy elderly and 12 young individuals of both sexes. In elderly subjects, reactive carbonyls, malondialdehyde–protein adducts, 3-nitrotyrosine, Mn-SOD, and catalase were significantly greater in the external intercostals than in the young controls. A post hoc analysis, in which men and women from both groups were analyzed separately, revealed that the external intercostals of elderly women, but not those of elderly men, showed significantly increased levels of reactive carbonyls, malondialdehyde–protein adducts, 3-nitrotyrosine, and Mn-SOD compared to those of control females. This study suggests that differences in muscle activity might explain the differential pattern of oxidative stress observed in human respiratory and limb muscles with aging as well as the likely existence of a sex-related regulation of this phenomenon in these muscles. [Copyright &y& Elsevier]