Remodeling of bronchial and pulmonary muscular arteries in mild/moderate COPD

Pulmonary hypertension is well documented in severe COPD but little is known about vascular remodeling in mild/moderate patients. Aim:To investigate bronchial and pulmonary muscular arteries morphology and the expression of elastic fibers (EF) and collagen I in the lungs of mild/moderate COPD patients. Methods:Lung tissue of 18 COPD subject (FEV1:67\ub115%pred), 14 non-obstructed smokers(NOS) (FEV1:95\ub110%pred) and 11 never-smoking controls(CTRL) (FEV1:108\ub115%pred) was used to analyze the morphology of bronchial and pulmonary muscular arteries and the expression of EF and collagen I in the tunica intima, media and adventitia, using immune- and histochemistry and image analysis. Values (mean\ub1SD) were expressed as (stained) area\u2044vessel outer perimeter (\u3bcm2\u2044\u3bcm) and as staining density (collagen I). Results:The intimal areas of pulmonary (CTRL=8.87\ub14.3, COPD=14.7\ub15, p=0.04) and the adventitia of bronchial arteries (CTRL=27.7\ub111.4, COPD=50.6\ub123.7, p=0.007) were larger in COPD patients than in CTRL. Higher EF expression was observed in adventitia of bronchial arteries of NOS group (8.8\ub113.2) than CTRL (3.1\ub11.3, p=0.04). The CTRL group had higher collagen I staining density in the adventitia of bronchial (CTRL=81.6\ub135.8; NOS=32.8\ub115; COPD=40.9\ub125.4, p=0.002) and pulmonary (CTRL=96.5\ub123.2; NOS=54.8\ub124; COPD=69.6\ub119.1, p=0.0005) arteries than NOS and COPD. Within COPD group, negative correlations were observed between the intimal area of pulmonary arteries and FEV1 (R=-0.57, p=0.04) and FEV1\u2044FVC (R=-0.56, p=0.04). Conclusions:Remodeling of bronchial and pulmonary muscular arteries occurs in mild\u2044moderate COPD, is associated with impaired lung function and it might contribute to the development of pulmonary hypertension

Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice

Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of Sao Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 mu L of saline (CTRL) or PM2.5 at 5 or 15 mu g in 30 mu L of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical impedance and inflammation than CTRL, but lower inflammation and oxidative stress than P15. In conclusion, acute exposure to low doses of fine PM induced lung inflammation, oxidative stress and worsened lung impedance and histology in a dose-dependent pattern in mice.The Centers of Excellence Program (PRONEX-MCT/FAPERJ)The Brazilian Council for Scientific and Technological Development (MCT/CNPq)The Carlos Chagas Filho Rio de Janeiro State Research Supporting Foundation (FAPERJ

Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction

Stress amplifies lung tissue mechanics, inflammation and oxidative stress induced by chronic inflammation

Background: Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. Objective: We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea pigs (GP) with chronic pulmonary inflammation. Methods: the GP were exposed to ovalbumin or saline aerosols (2x/wk/4wks, OVA, and SAL). Twenty-four hours after the 4th inhalation, the GP were submitted to the FS protocol (5x/wk/2wks, SAL-S, and OVA-S). Seventy-two hours after the 7th inhalation, lung strips were cut and tissue resistance (Rt) and elastance (Et) were obtained (at baseline and after OVA and Ach challenge). Strips were submitted to histopathological evaluation. Results: the adrenals' weight, the serum cortisol, and the catecholamines were measured. There was an increase in IL-2, IL-5, IL-13, IFN-gamma, iNOS, 8-iso-PGF2 alpha, and in %Rt and %Et after Ach challenge in the SAL-S group compared to the SAL one. the OVA-S group has had an increase in %Rt and %Et after the OVA challenge, in %Et after the Ach and in IL-4, 8-iso-PGF2 alpha, and actin compared to the OVA. Adrenal weight and cortisol serum were increased in stressed animals compared to nonstressed ones, and the catecholamines were unaltered. Conclusion & clinical relevance: Repeated stress has increased distal lung constriction, which was associated with an increase of actin, IL-4, and 8-iso-PGF2 alpha levels. Stress has also induced an activation of iNOS, cytokines, and oxidative stress pathways.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)LIM-20-FMUSPUniv São Paulo, Sch Med, Med Dept LIM 20, BR-01246903 São Paulo, BrazilUniv São Paulo, Sch Med, Pathol Dept LIM 5, BR-01246903 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, BrazilUniv Mogi das Cruzes, Mogi Das Cruzes, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, BrazilWeb of Scienc