The role of collagenase in emphysema

The extracellular matrix is essential for the integrity of the lung and when disrupted can lead to the architectural changes seen in emphysema. The etiology of emphysema is believed to be due to an imbalance in the proteases and antiproteases within the lung. Studies have focused on elastolytic enzymes as the primary agents in disease pathogenesis, however, recent data suggest that collagenases may also be involved in the destruction of lung tissue in emphysema. It is hoped that this expanded understanding of the pathophysiology of emphysema will lead to improved therapy in the treatment of the disease

Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Culture & Childhood Obesity: Investigating maternal experiences

<p>(A) Perivascular and (B) bronchial inflammation was recorded in mice exposed to cigarette smoke and RSV for 6 months and their corresponding controls. (C) Matrix accumulation was assessed with trichrome staining in each mouse group and quantified by the Ashcroft fibrosis score. Representative images of mice lungs from each group are presented here (scale bar = 20 µM; left panels). Fibrosis and inflammation scores were calculated for each treatment group (right panels where n = 12 animals/group). Each graph is represented as mean ± S.E.M. where each measurement was performed on 12 animals/group. p values shown, comparing both treatments connected by a line.</p

Nonmalignant Respiratory Effects of Chronic Arsenic Exposure from Drinking Water among Never-Smokers in Bangladesh

BACKGROUND: Arsenic from drinking water has been associated with malignant and nonmalignant respiratory illnesses. The association with nonmalignant respiratory illnesses has not been well established because the assessments of respiratory symptoms may be influenced by recall bias or interviewer bias because participants had visible skin lesions. OBJECTIVES: We examined the relationship of the serum level of Clara cell protein CC 16-a novel biomarker for respiratory illnesses-with well As, total urinary As, and urinary As methylation indices. METHODS: We conducted a cross-sectional study in nonsmoking individuals (n = 241) selected from a large cohort with a wide range of As exposure (0.1-761 mu g/L) from drinking water in Bangladesh. Total urinary As, urinary As metabolites, and serum CC16 were measured in urine and serum samples collected at baseline of the parent cohort study. RESULTS: We observed an inverse association between urinary As and serum CC 16 among persons with skin lesions (beta = -0. 13, p = 0.01). We also observed a positive association between secondary methylation index in urinary As and CC16 levels (beta = 0. 12,,P = 0.05) in the overall study population; the association was stronger among people without skin lesions (beta = 0. 18, p = 0.04), indicating that increased methylation capability may be protective against As-induced respiratory damage. In a subsample of study participants undergoing spirometric measures (n = 3 1), we observed inverse associations between urinary As and predictive FEV1 (forced expiratory volume measured in 1 sec) (r = -0.37; FEV1/forced vital capacity ratio and primary methylation index (r = -0.42, p = 0.01). CONCLUSIONS: The findings suggest that serum CC 16 may be a useful biomarker of epithelial lung damage in individuals with arsenical skin lesions. Also, we observed the deleterious respiratory effects of As exposure at concentrations lower than reported in earlier studies

VII Scandinavian Copd Research Symposium, Holmenkollen, Oslo 18th-19th November 2016

Peer reviewe

The Potential for Resident Lung Mesenchymal Stem Cells to Promote Functional Tissue Regeneration: Understanding Microenvironmental Cues

Tissue resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs) and endothelial progenitor cells (EPC) are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH), pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD)/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases