Improvements in Lung Diffusion Capacity following Pulmonary Rehabilitation in COPD with and without Ventilation Inhomogeneity.

BACKGROUND: Lung diffusing capacity (DLCO) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify DLCO parameters is unknown. OBJECTIVES: To investigate changes in DLCO and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD. METHODS: This was a prospective, observational, multicentric study. Patients were evaluated before and after a standardized 3-week PR program. Functional assessment included body plethysmography, DLCO, transfer factor (KCO) and alveolar volume (VA), gas exchange, the 6-min walking test (6MWT) and exercise-related dyspnea. Patients were categorized according to the severity of airflow limitation and presence of ventilation inhomogeneity, identified by a VA/TLC <0.8. RESULTS: Two hundred and fifty patients completed the study. Baseline forced expiratory volume in 1 s (FEV1) % predicted (mean ± SD) was 50.5 ± 20.1 (76% males); 137 patients had a severe disease. General study population showed improvements in 6MWT (38 ± 55 m; p < 0.01), DLCO (0.12 ± 0.63 mmol × min-1 kPa-1; p < 0.01), lung function and dyspnea. Comparable improvements in DLCO were observed regardless of the severity of disease and the presence of ventilation inhomogeneity. While patients with VA/TLC <0.8 improved the DLCO increasing their VA (177 ± 69 ml; p < 0.01), patients with VA/TLC >0.8 improved their KCO (8.1 ± 2.8%; p = 0.019). The latter had also better baseline lung function and higher improvements in 6MWT (14.6 ± 6.7 vs. 9.0 ± 1.8%; p = 0.015). Lower DLCO at baseline was associated with lower improvements in 6MWT, the greatest difference being between subjects with very severe and mild DLCO impairment (2.7 ± 7.4 vs. 14 ± 2%; p = 0.049). CONCLUSIONS: In COPD patients undergoing a PR program, different pathophysiological mechanisms may drive improvements in DLCO, while ventilation inhomogeneity may limit improvements in exercise tolerance.

Diagnostic decision support of heart rate turbulence in sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated upper-airway obstruction during sleep. It is diagnosed by polysomnographic studies, scoring OSAS severity by an apneas/hypopneas index associated to worse prognosis, mainly for an increased cardiovascular morbidity. Cardiac autonomic impairments involved in the development of cardiovascular disease in OSAS can be assessed by heart rate turbulence (HRT) analysis and aim of the paper is to show the increased medical decision support by HRT evaluation in OSAS patients. HRT has been assessed in 274 polysomnographic recordings of mild-to-severe OSAS patients and an overall cardiorespiratory risk scoring (CRRIS) index has been proposed on the base of both OSAS severity and HRT assessment. Results showed that, while the only polysomnografic analysis would have equally ranked OSAS patients within their mild-to-severe classification, CRRIS index allows to identify a 19% of severe-OSAS patients at very high risk of sudden cardiac death, a 13% of moderate-OSAS patients with a risk level comparable to those of severe, and a 17% of mild-OSAS patients with evidence of an autonomic impairment. CRRIS index, detecting patients at greater probability of worsening could give to the physician a very useful medical decision support in the follow up of this particular chronic disease.

Severe respiratory and skeletal muscles involvement in a carrier of dysferlinopathy with chronic obstructive pulmonary disease.

The natural course of progressive neuromuscular diseases can be complicated by respiratory muscle involvement. In muscular dystrophies such as Duchenne muscular dystrophy and myotonic dystrophy, respiratory muscle involvement is common. In others such as Becker, limb-girdle, and facioscapulo-humeral dystrophies, respiratory muscle involvement is infrequent and generally occurs in the more severe cases. Recently, it was reported that a mutation in the dysferlin gene and/or dysferlin deficiency causes proximal and distal forms of muscular dystrophy, which are known by the term dysferlinopathy. We describe a case of severe weakness of both limb-girdle and respiratory muscles in a patient who was carrier of the dysferlin gene mutation and who also had COPD. We suggest that the systemic inflammatory response of COPD and the dysferlin deficit interact and are responsible for both the skeletal and respiratory muscle impairment.

Pulmonary rehabilitation improves exercise capacity in subjects with kyphoscoliosis and severe respiratory impairment.

BACKGROUND: Patients with kyphoscoliosis and severe respiratory impairment frequently experience reduction in exercise tolerance, limitation in daily life activities, and deterioration in health-related quality of life (HRQOL). Noninvasive ventilation (NIV) as an add-on treatment to long-term oxygen therapy (LTOT) was shown to improve symptoms and HRQOL in these patients. Pulmonary rehabilitation can increase exercise capacity and HRQOL in patients with COPD, but its role in patients with restrictive thoracic disease, such as kyphoscoliosis, is uncertain. The aim of this study was to analyze the effects of combining pulmonary rehabilitation with LTOT and NIV treatments on arterial blood gases and the 6-min walk test (6MWT) in a homogeneous group of subjects with kyphoscoliosis. METHODS: Twenty-three subjects with kyphoscoliosis and respiratory failure who were being treated with both LTOT and NIV and who had been referred to a pulmonary rehabilitation program were retrospectively analyzed. Eighteen subjects were included, and there was no control group. Pulmonary rehabilitation involved educational and physical training sessions and was carried out daily for 4-6 weeks. Exercise intensity was personalized based on individual tolerance, physiologic parameters, or physiotherapist judgment. RESULTS: Upon completion of pulmonary rehabilitation, a significant improvement in 6-min walk distance was observed (P = .04). The dyspnea score at the end of the 6MWT improved as well, although the improvement did not reach statistical significance (P = .06). These changes were not confirmed at a 12-month follow-up visit. No significant effects of pulmonary rehabilitation on arterial blood gases were observed. CONCLUSIONS: A combined intervention including a tailored pulmonary rehabilitation program together with LTOT and NIV seems to be of short-term benefit in subjects with kyphoscoliosis and severe respiratory impairment.

INDACO project: COPD and link between comorbidities, lung function and inhalation therapy.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by respiratory and extrarespiratory components referring both to systemic complications of COPD, like skeletal muscle myopathy, weight loss and others, and frequently associated comorbidities, interesting various organs and systems (cardiovascular diseases, malignancies, osteoporosis, diabetes, etc.). These comorbidities may increase the rate of hospitalization of COPD patients and have a huge effect on the outcomes of the respiratory disease. Inhalation therapy of COPD with bronchodilators and steroid is primary driven by airflow obstruction, symptoms like dyspnoea, and acute exacerbations. INDACO project has been developed in 2013 to assess the prevalence and type of comorbidities in COPD patients referred to the outpatient wards of some hospitals in Central and South Italy and a preliminary report has recently been published. In the present study, after widening that database, we evaluate the prevalence of comorbidities and the relationships between comorbidities and sex, age, symptoms, lung function and inhalation therapy in COPD patients. METHODS: In each enrolled patient, anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for Chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI) were recorded. RESULTS: We collected data of 569 patients (395 males and 174 females, mean age 73 ± 8.5 yrs). The prevalence of patients with comorbidities was 81.2%. Overall number of comorbidities was not related to airflow obstruction and age, but to acute exacerbation of COPD, dyspnoea measured with MRC scale, and male gender. A subgroup analysis revealed that ischaemic heart disease was predominant in males, whereas mood disorders in females. The use of a more complex (multi-drug) inhalation therapy was related with bronchial obstruction measured by FEV1/FVC (p for trend = 0.003) and number of comorbidities (p for trend = 0.001). In multivariate analysis, only airflow obstruction and number of comorbidities were determinant of complexity of therapy, but not MRC and acute exacerbation of COPD. However, the statistical model reached an extreme low degree of significance (r^2 = 0.07). CONCLUSIONS: Our study showed a high prevalence of comorbidities in COPD, with some differences related to gender. Number of comorbidities and airflow obstruction represent the determinant of inhalation therapy prescription. Dyspnoea and acute exacerbation of COPD, unlikely suggested by guidelines, are not significant drivers of therapy in the real life setting of our study.

Histopathology and exercise: a winning combination in pulmonary fibrosis: a case report.

The diffuse parenchymal lung diseases form a heterogeneous group of disorders characterized by varying degrees of inflammation and fibrosis involving the space between epithelial and endothelial basement membranes. Among the diffuse parenchymal lung diseases of unknown etiology, one of the most common is usual interstitial pneumonia/idiopathic pulmonary fibrosis, which carries the worst prognosis. In contrast, nonspecific interstitial pneumonia, which belongs to the same diffuse parenchymal lung disease group, has a more favorable prognosis. Based on the relative amount of inflammation and fibrosis observed on lung biopsies, at least 2 nonspecific interstitial pneumonia patterns have been suggested: cellular and fibrosing. The long-term prognosis is excellent for patients with nonspecific interstitial pneumonia with a cellular pattern, as compared to patients with a fibrosing pattern. We describe here a patient with nonspecific interstitial pneumonia with a fibrosing pattern in a highly practiced runner, showing an unexpectedly long-term favorable course, and consider the possible role of exercise in the diagnosis and clinical course of the disease. This case reinforces the evidence that exercise training, which is a principal component of pulmonary rehabilitation, may have clinically important effects on functional exercise capacity, especially if it is delivered early in the course of the disease.

Airway bacterial colonization: the missing link between COPD and cardiovascular events?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and, according to the World Health Organization, its prevalence will double by 2020. COPD is a chronic inflammatory disease of the lung characterized by poorly reversible airflow limitation and, frequently, by extrapulmonary manifestations. In particular, the cardiovascular manifestations are responsible for high morbidity and mortality. METHODS AND RESULTS: A systematic literature search was performed of studies published in Medline until December 2010, using the key-words: COPD, bacterial colonization, COPD exacerbation, atherosclerosis, systemic inflammation, cardiovascular event and risk factors. In addition to the studies identified in the primary search, reference lists of included articles were analyzed for additional papers related to the topic. The pathogenetic mechanisms underlying atherosclerosis - namely inflammation, oxidative stress and endothelial dysfunction - are in common with COPD. Moreover, they are increased in the presence of COPD, especially in patients who present airway bacterial colonization, increased rate of exacerbations and elevated levels of both airway and systemic inflammation. CONCLUSION: COPD is associated with an increased burden of atherosclerotic disease. Systemic inflammation and oxidative stress play key roles in this association. COPD patients with airway bacterial colonization, as compared to patients without airway colonization, generally present more frequent exacerbations and higher levels of both airway and systemic inflammation. This COPD subgroup should be considered at particularly increased risk of developing cardiovascular complications and receive more attention concerning diagnosis, treatment, prevention and research.