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Determinants and outcomes of physical activity in patients with COPD: a systematic review

The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed. Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.

Methods

We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012. Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.

Results

86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both. Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence. Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low. As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence. Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.

Conclusions

Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment.

Biomarkers for predicting COPD exacerbations

This Danish prospective cohort study compared frequency of exacerbations in stable chronic obstructive pulmonary disease (COPD) patients with chronically raised inflammatory biomarkers to those with normal inflammatory biomarkers over a 5-year follow-up. It measured baseline levels of C-reactive protein (CRP), leucocytes and fibrinogen levels.

An exacerbation was defined as requiring a short course of treatment with oral corticosteroids and/or antibiotics, or requiring hospital treatment due to COPD. Frequent exacerbations were defined as having two or more per year and each being more than 4 weeks apart.

This study found that simultaneously elevated levels of CRP, fibrinogen and leucocytes positively correlated with an increased risk of frequent exacerbations in stable COPD, which was statistically significant. The relative risk remained consistent when multivariable factors, such as previous exacerbations, symptom burden, disease severity and Body Mass Index were included, indicating that inflammatory biomarkers give additional information when risk-stratifying patients.

Although this was a...

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Tuberculosis, Pulmonary Cavitation, and Matrix Metalloproteinases

Tuberculosis (TB), a chronic infectious disease of global importance, is facing the emergence of drug-resistant strains with few new drugs to treat the infection. Pulmonary cavitation, the hallmark of established disease, is associated with very high bacillary burden. Cavitation may lead to delayed sputum culture conversion, emergence of drug resistance, and transmission of the infection.

The host immunological reaction to Mycobacterium tuberculosis is implicated in driving the development of TB cavities. TB is characterized by a matrix-degrading phenotype in which the activity of proteolytic matrix metalloproteinases (MMPs) is relatively unopposed by the specific tissue inhibitors of metalloproteinases. Proteases, in particular MMPs, secreted from monocyte-derived cells, neutrophils, and stromal cells, are involved in both cell recruitment and tissue damage and may cause cavitation. MMP activity is augmented by proinflammatory chemokines and cytokines, is tightly regulated by complex signaling paths, and causes matrix destruction. MMP concentrations are elevated in human TB and are closely associated with clinical and radiological markers of lung tissue destruction. Immunomodulatory therapies targeting MMPs in preclinical and clinical trials are potential adjuncts to TB treatment.

Strategies targeting patients with cavitary TB have the potential to improve cure rates and reduce disease transmission.

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