Scientific Knowledge on the Subject: Despite observational studies suggesting that COPD exacerbation can be detected using a combination of symptoms and physiological measures, such as pulse and oxygen saturation, larger randomized controlled trials have not shown any effect of telemonitoring on time to first hospital admission (TTFH), hospitalization and quality of life. Tested tele-monitoring programs had a negligible impact on healthcare costs, and, in some cases, resulted in an increased healthcare utilisation. What This Study Adds to the Field:This randomized controlled trial of 312 COPD patients is the first using only objective lung function data measured daily by the forced oscillation technique to prompt early intervention. Despite being feasible and well accepted by patients, this approach did not affect TTFH and quality of life. However, it significantly reduced healthcare costs, mostly due to a reduction in duration and frequency of subsequent hospitalisations, which was greatest in patients hospitalised the year before recruitment.This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org 3 AbstractRationale Early detection of COPD exacerbations using tele-monitoring of physiological variables might reduce the frequency of hospitalisation.Objectives To evaluate the efficacy of home monitoring of lung mechanics by the forced oscillation technique (FOT) and cardiac parameters in older COPD patients with co-morbidities.Methods This multicentre, randomized clinical trial recruited 312 GOLD grade II-IV COPD patients (median age 71 years [IQR:66-76], 49.6% grade II, 50.4% grade III-IV), with a history of exacerbation in the previous year and at least one non-pulmonary co-morbidity. Patients were randomised to usual care (n=158) or tele-monitoring (n=154) and followed for 9 months. All telemonitoring patients self-assessed lung mechanics daily and in a subgroup with congestive heart failure (n=37) cardiac parameters were monitored. An algorithm identified deterioration, triggering a telephone contact to determine appropriate interventions. Measurements and Main resultsPrimary outcomes were time to first hospitalisation (TTFH) and change in EQ-5D utility index score. Secondary outcomes included: rate of antibiotic/corticosteroid prescriptions, hospitalisation, CAT, PHQ-9 and MLHF questionnaire scores, quality-adjusted life years and healthcare costs. Tele-monitoring did not affect TTFH, EQ-5D utility index score, antibiotic prescriptions, hospitalization rate and questionnaire scores. Tele-medicine was associated with fewer repeat hospitalizations (-54%, p=0.017). Previously hospitalised patients showed the greatest reduction in hospitalization rate (-53%, p=0.017) with large potential for cost savings (-3736€/patient/year, p=0.010). ConclusionsIn older COPD patients with co-morbidities remote monitoring of lung function by FOT and cardiac parameters did not change TTFH and EQ-5D. However patients at risk of hospitalisation may benefit fr...

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The purpose of this study was to determine whether other cellular sources than neutrophils can express matrix metalloproteinase (MMP)-8 protein and mRNA in bronchiectatic (BE) lung. The molecular forms of MMP-8 in the BE bronchoalveolar lavage fluid (BALF) and healthy control BALF were analysed by western immunoblotting. MMP-8 expression was demonstrated by immunohistochemistry and in situ hybridization in BE lung tissue and by immunohistochemistry in control lung tissue. In the BE BALF, different MMP-8 species were detected: 70-80 kD MMP-8 apparently of polymorphonuclear leukocyte (PMN) origin and also 40-60 kD MMP-8 from non-PMN cellular sources, such as bronchial epithelial cells, glandular cells or monocytes/macrophages. Both of these MMP-8 species were elevated and converted to a significant extent to activated forms in BE BALF compared with healthy control BALF. The levels of high molecular weight (>80 kD) MMP-8 complexes, evidently representing MMP-8 trapped by endogenous MMP inhibitors and/or MMP-8 dimers, were significantly elevated in BE BALF compared with healthy control BALF. In BE lung tissue, the MMP-8 protein and mRNA expression was found in bronchial ciliated epithelial cells, glandular cells, neutrophils, and monocytes/macrophages infiltrating the bronchial epithelial area. Minimal MMP-8 expression was observed in neutrophils, monocytes/macrophages, and epithelial cells in control lung tissues. In this study, new potential cellular sources have been demonstrated for MMP-8 in the inflamed lung. MMP-8 from multiple cellular sources, including inflamed lung epithelium, was activated to a significant extent in the BE BALF, indicating a major role for MMP-8 in the destruction of lung and bronchial tissues.

The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis.The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MMP-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement.Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9.Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.

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