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Biomedical subjects

M Saetta

Publications and source records attributed to M Saetta.

At least 19 recordsLinked to original sources
PubMed2003

Predominant emphysema phenotype in chronic obstructive pulmonary.

Patients with fixed airflow limitation are grouped under the heading of chronic obstructive pulmonary disease (COPD). The authors investigated whether COPD patients have distinct functional, radiological and sputum cells characteristics depending on the presence or absence of emphysema. Twenty-four COPD outpatients, 12 with and 12 without emphysema on high-resolution computed tomography scan of the chest, were examined. Patients underwent chest radiography, pulmonary function tests and sputum induction and analysis. Subjects with documented emphysema had lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio, and lower carbon monoxide diffusion constant (K(CO)), compared with subjects without emphysema. Chest radiograph score of emphysema was higher, chest radiograph score of chronic bronchitis was lower, and the number of sputum lymphocytes was increased in patients with emphysema, who also showed a negative correlation between K(CO) and pack-yrs. Chronic obstructive pulmonary disease patients with emphysema, documented by high-resolution computed tomography scan, have a different disease phenotype compared with patients without emphysema. Identification of chronic obstructive pulmonary disease-related phenotypes may improve understanding of the natural history and treatment of the disease.

Aged↗
PubMed2003

Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients.

Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The current study examined the expression of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric oxide synthase (iNOS) respectively, in patients with severe COPD and control smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was quantified in peripheral lung. HO-1+ alveolar macrophages were decreased in severe COPD compared to control smokers, whereas no difference was observed in iNOS+ macrophages. In contrast, severe patients had significantly higher numbers of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2 pneumocytes and their number was inversely related to HO-1+ macrophages. There were no significant differences in N-Tyr immunostaining between the two groups. However, the rate of protein nitration in lung tissue was directly related to iNOS expression and associated with lower values of forced expiratory volume in one second/forced vital capacity. HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD. In conclusion, the results suggest that the enzymes involved in the oxidative stress response may have a different role in the lung defence and that imbalance between haem oxygenase-1 and inducible nitric oxide synthase may be associated with the development of severe impairment in chronic obstructive pulmonary disease patients.

Aged↗
PubMed2002

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers.

BACKGROUND: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. METHODS: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. RESULTS: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9-5.8) and 1.4 (1.07-3.4) respectively); glands (33.3 (18.2-43.8) and 16.2 (11.5-22.2), respectively); and bronchial vessels (54.2 (48.7-56.8) and 40.0 (36-40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. CONCLUSIONS: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD.

Aged↗
PubMed2001

Remodeling in response to infection and injury. Airway inflammation and hypersecretion of mucus in smoking subjects with chronic obstructive pulmonary disease.

Airway epithelium represents the first line of defense against toxic inhalants. In some subjects, cigarette smoking causes airway inflammation, hypersecretion of mucus, and poorly reversible airflow limitation through mechanisms that are still largely unknown. Likewise, it is unclear why only some smokers develop chronic obstructive pulmonary disease (COPD). Two cell types consistently result in relation to chronic airflow limitation in COPD: neutrophils and CD8(+) cells. Neutrophils are compartmentalized in the mucosal surface of the airways and air spaces, that is, the epithelium and lumen, whereas CD8(+) cells exhibit a more extensive distribution along the subepithelial zone of the airways and lung parenchyma, including alveolar walls and arteries. This pattern of inflammatory cell distribution is observed in mild or moderate COPD, and in patients who have developed COPD, it is not modified by smoking cessation. The number of neutrophils further increases in the submucosa of patients with severe COPD, suggesting a role for these cells in the progression of the disease. Hypersecretion of mucus is a major manifestation in COPD. Mucus is produced by bronchial glands and goblet cells lining the airway epithelium. Unlike mucous gland enlargement, greater mucosal inflammation is associated with sputum production. Whereas neutrophil infiltration of submucosal glands occurs only in smokers with COPD, goblet cell hyperplasia in peripheral airways occurs both in smokers with or without COPD, suggesting that the major determinant of goblet cell hyperplasia is cigarette smoke itself.

Biopsy↗
PubMed2001

Increased expression of heme oxygenase (HO)-1 in alveolar spaces and HO-2 in alveolar walls of smokers.

It has been suggested that oxidative stress protein heme oxygenase (HO)-1 plays a role in chronic airway diseases including chronic obstructive pulmonary disease (COPD). The inducible isoform HO-1 and the constitutive HO-2 catalyze the same reaction. Their distribution in situ was studied in lungs of 10 nonsmoking subjects, 6 healthy smokers, and 10 smokers with COPD. Paraffin-embedded sections of surgical lung specimens were immunostained with antibodies against HO-1 and HO-2. HO-1 immunoreactivity was observed mainly in alveolar macrophages. HO-1-positive macrophages were increased in smokers with COPD (median: 36%) as compared with nonsmoking subjects (13%; p < 0.02), whereas no differences were observed between patients with COPD and healthy smokers (34%). HO-2 had a more widespread distribution in cells of the alveolar wall, in adventitia of pulmonary arteries and bronchioles, and in vascular smooth muscle. Lower percentages of alveolar macrophages exhibited positive staining for HO-2 without significant differences between the three groups. HO-2(+) cells in the alveolar wall were increased in smokers with (15/mm) and without COPD (12/mm) as compared with nonsmokers (8/mm, p < 0.01). In conclusion, inducible HO-1 and constitutive HO-2 are detectable in human lung tissue and their expression is increased in smokers, suggesting that oxidative stress due to cigarette smoke may increase lung cells expressing HO-1 and HO-2.

Aged↗
PubMed2001

Exacerbations of Bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants.

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted = 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV(1) % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.

Adult↗
PubMed2001

Bronchiolitis obliterans organizing pneumonia (BOOP) in a child with mild-to-moderate asthma: evidence of mast cell and eosinophil recruitment in lung specimens.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is rarely described in children and little is known about its pathogenesis. This paper reports on an 11-year-old patient suffering from mild-to-moderate asthma. He presented with a retrocardiac density at chest computed tomography scan that was slow to resolve and failed to respond to antibiotic therapy. Open lung biopsy revealed a histological picture with buds of granulation tissue in respiratory bronchioles and alveolar ducts, with organized extensions into the alveoli. The use of monoclonal antibodies on biopsy specimens demonstrated the presence of an inflammatory process affecting not only the thickened alveolar walls, but also the remaining lung parenchyma, the pulmonary arteries, and the bronchioles. The inflammatory infiltrate consisted mainly of mast cells and eosinophils. The clinical condition improved with steroid therapy. To the best of the authors' knowledge, this is the first report of BOOP in an asthmatic child with recruitment of mast cells and eosinophils documented by using monoclonal antibodies.

Asthma↗
PubMed2001

Pathogenesis and pathology of COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Since flow is the result of a driving pressure that promotes flow and of an opposing resistance that contradicts it, the reduction in flow observed in COPD has two main components: increased resistance, which is due to airway obstruction, and a loss of the elastic recoil pressure of the lung, which is due to parenchymal destruction. Although it has long been known that the major site of increased resistance in COPD is the peripheral airways, recent studies have shown that central airways are involved in the disease as well. The purpose of this review is to describe the major structural and cellular changes present in peripheral airways, central airways and lung parenchyma of patients with COPD, and to underline the possible mechanisms contributing to airflow limitation in these subjects.

Bronchitis↗
PubMed2001

Airway pathology in asthma.

This review focuses on the major cellular and structural changes present in the airways and lung parenchyma in asthma in comparison with chronic obstructive pulmonary disease (COPD) in an attempt to underline the possible mechanisms contributing to airflow limitation in these two diseases. Both asthma and COPD are characterized by a thickening of the airway wall and by the presence of an inflammatory process, but the inflammatory cells infiltrating the airway wall differ between the two diseases. In asthma, the most striking feature is the eosinophilic infiltration, whereas, in COPD, it is the CD8 T-lymphocytic infiltration of the airway wall. In the lung parenchyma, both diseases are characterized by an inflammatory process, whereas destruction and fibrosis of the alveolar walls occur in COPD but not in asthma. These cellular and structural changes may contribute to the development of airflow limitation (that characterizes both asthma and chronic obstructive pulmonary disease) by inducing either an increase in resistance or a decrease in driving pressure.

Airway Obstruction↗
PubMed2000

The distribution of neurokinin-1 and neurokinin-2 receptors in human central airways.

The precise locations of neurokinin (NK)-1 and NK-2 receptors in human airways, and their role in airway inflammatory diseases, have not been carefully examined. To determine the distribution of NK-1 and NK-2 receptors in human central airways, and to determine whether their distribution was different in smokers, we examined surgical specimens from patients undergoing lung resection for limited lung lesions. We mapped NK-1 and NK-2 receptors in four groups of subjects: four asymptomatic nonsmokers, seven asymptomatic smokers, seven symptomatic smokers with normal lung function, and eight symptomatic smokers with chronic airflow limitation. Tissues were immunostained with anti-NK-1- and anti-NK-2-receptor antibodies. Expression of NK-1 and NK-2 receptors was quantified through light microscopy and image analysis. Both NK-1 and NK-2 receptors were found in bronchial glands, bronchial vessels, and bronchial smooth muscle. Although no receptors were observed in the epithelium, receptors were occasionally found in nerves (NK-1) and in inflammatory cells (NK-2) such as T lymphocytes, macrophages, and mast cells. The distribution of both NK-1 and NK-2 receptors was similar in all the tissues examined in the four groups of subjects. These data show that NK-1 and NK-2 receptors are present in human central airways and that their expression is not modified by cigarette smoking.

Adult↗
PubMed2000

Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation.

To quantify the number of goblet cells and inflammatory cells in the epithelium of peripheral airways in smokers with both symptoms of chronic bronchitis and chronic airflow limitation, we examined surgical specimens obtained from 25 subjects undergoing lung resection for localized pulmonary lesions: 10 smokers with symptoms of chronic bronchitis and chronic airflow limitation, six asymptomatic smokers with normal lung function, and nine nonsmoking control subjects. Peripheral airways were examined with histochemical methods to identify goblet cells and with immunohistochemical methods to identify total leukocytes (CD45(+) cells), neutrophils, macrophages, CD4(+) and CD8(+) cells in the epithelium. When compared with nonsmokers, smokers with both symptoms of chronic bronchitis and chronic airflow limitation had an increased number of goblet cells (p < 0.01), CD45(+) cells (p < 0. 01), macrophages (p < 0.05), and CD8(+) cells (p < 0.01) in the epithelium of peripheral airways. When all the smokers were grouped together, they showed an increased number of neutrophils (p < 0.05) along with an increased number of goblet cells, CD45(+) cells, macrophages and CD8(+) cells (p < 0.05) compared with nonsmokers. In conclusion, smokers with both symptoms of chronic bronchitis and chronic airflow limitation have an increased number of goblet cells and inflammatory cells in the epithelium of peripheral airways.

Aged↗
PubMed2000

Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease.

We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.

Administration, Inhalation↗
PubMed2000

Modification of serum proteins in guinea pigs immunized and challenged with toluene diisocyanate.

OBJECTIVES: Guinea pigs were used to determine whether immunization and challenge by toluene diisocyanate (TDI) induce changes in the serum protein concentrations of the "acute-phase response" and whether TDI can form adducts with serum proteins. METHODS: Guinea pigs were immunized by weekly intradermal injections of TDI and challenged with TDI 7 days after the 3rd injection. The animals were killed 6 hours after the challenge, and serum was analyzed for protein characterization by gel electrophoresis and for specific antibodies to TDI by enzyme-linked immunosorbent assay (ELISA) and Western blotting. RESULTS: The total serum protein concentration of the immunized TDI-challenged guinea pigs increased in comparison with that of nonimmunized animals [75 (SE 0.7) versus 47.4 (SE 2.3) mg/ml; ]. Albumin and alpha, and alpha2 globulins increased significantly [respectively: 65.8 (SE 0.2)%, 2.1 (SE 0.1)% and 7.2 (SE 0.1)% versus 59 (SE 1.3)%, 1.3 (SE 0.1)% and 3.7 (SE 0.1)%], whereas beta1 and beta2 globulins decreased in the immunized TDI-challenged guinea pigs [7.8 (SE 0.2)% and 0.8 (SE 0.2)% versus 15.8 (SE 0.7)% and 4.8 (SE 0.2)%]. The gamma globulin concentrations did not change significantly. In the immunized TDI-challenged animals, albumin was modified by TDI and ran faster on agarose gel electrophoresis than did albumin from nonimmunized guinea pigs. In the ELISA, only immunized animals had high titers of TDI-specific antibodies (IgG and IgG1); by blotting, the antibodies reacted against TDI, the TDI-BSA-conjugate and several TDI-conjugated guinea pig serum proteins, but they did not react against any native or denaturated serum protein when unconjugated with TDI. CONCLUSIONS: These findings indicate that, in guinea pigs, immunization and challenge with TDI induces changes in serum proteins of the "acute phase response" and TDI is adducted to serum proteins with different molecular weights (eg, albumin).

Animals↗
PubMed2000

Structural basis for airflow limitation in chronic obstructive pulmonary disease.

The airflow limitation that characterises chronic obstructive pulmonary disease (COPD) has two main components: an increased resistance, which is due to airway obstruction, and a loss of the elastic recoil pressure of the lung, which is due to parenchymal destruction. Although it has long been known that the major site of increased resistance in COPD is the peripheral airways, recent studies have shown that central airways are involved in the disease as well. The purpose of this review is to describe the major structural and cellular changes present in peripheral airways, central airways and lung parenchyma of patients with COPD, and to underline the possible mechanisms contributing to airflow limitation in these subjects.

Airway Resistance↗
PubMed1999

Integrin expression on neutrophils and mononuclear cells in blood and induced sputum in stable asthma.

BACKGROUND: We speculated that the expression of integrins in the airway lumen of asthmatic subjects might be altered compared with normal subjects during cell recruitment from circulation. METHODS: To test this hypothesis, we investigated the expression of integrin alpha-chains (CD11a, CD11b, and CD11c) in hypertonic saline-induced sputum and peripheral blood leukocytes in mild to moderate stable asthmatic and control subjects. Immunoreactivity for integrin alpha-chains was assessed by immunocytology on cytospin preparations of sputum and blood. RESULTS: In comparison of the percentages of CD11a+, CD11b+ and CD11c+ mononuclear cells in sputum with their blood counterparts, no significant differences were observed in control subjects, whereas CD11a and CD11b in asthmatic subjects were less expressed on sputum cells. In both control and asthmatic subjects, sputum neutrophils tended to decrease their expression of integrin alpha-chains compared with circulating neutrophils. CONCLUSIONS: We showed that the sputum of asthmatics, unlike normal subjects, is characterized by decreased expression of integrins on mononuclear cells compared with their blood counterparts. The results suggest that downregulation of integrins occurs in asthmatic airways after cell recruitment from circulation.

Adult↗
PubMed1999

CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease.

Previous studies have shown an increased number of inflammatory cells and, in particular, CD8+ve cells in the airways of smokers with chronic obstructive pulmonary disease (COPD). In this study we investigated whether a similar inflammatory process is also present in the lungs, and particularly in lung parenchyma and pulmonary arteries. We examined surgical specimens from three groups of subjects undergoing lung resection for localized pulmonary lesions: nonsmokers (n = 8), asymptomatic smokers with normal lung function (n = 6), and smokers with COPD (n = 10). Alveolar walls and pulmonary arteries were examined with immunohistochemical methods to identify neutrophils, eosinophils, mast cells, macrophages, and CD4+ve and CD8+ve cells. Smokers with COPD had an increased number of CD8+ve cells in both lung parenchyma (p < 0.05) and pulmonary arteries (p < 0.001) as compared with nonsmokers. CD8+ve cells were also increased in pulmonary arteries of smokers with COPD as compared with smokers with normal lung function (p < 0.01). Other inflammatory cells were no different among the three groups. The number of CD8+ve cells in both lung parenchyma and pulmonary arteries was significantly correlated with the degree of airflow limitation in smokers. These results show that an inflammatory process similar to that present in the conducting airways is also present in lung parenchyma and pulmonary arteries of smokers with COPD.

Airway Resistance↗