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Biomedical subjects

L M Fabbri

Publications and source records attributed to L M Fabbri.

At least 37 records · Page 2Linked to original sources
PubMed2004

Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis.

Vasoactive intestinal peptide (VIP) is a neuropeptide involved in the regulation of airway mucus secretion. The biological functions of VIP are mediated through two receptors, the vasoactive intestinal peptide receptor type 1 (VPAC1R) and type 2 (VPAC2R). The aim of this study was to quantify the expression of both VPAC1R and VPAC2R in the central airways of smokers with chronic bronchitis. Surgical specimens were obtained from 33 smokers undergoing thoracotomy for localised pulmonary lesions: 23 smokers with symptoms of chronic bronchitis and 10 asymptomatic smokers with normal lung function. By using immunohistochemical and microscopic analysis, an increased expression of VPAC1R, but not VPAC2R, was found in bronchial epithelium, bronchial glands and vessels of smokers with symptoms of chronic bronchitis compared with asymptomatic smokers. Smokers with symptoms of chronic bronchitis also had an increased number of mononuclear cells positive for both VPAC1R and VPAC2R in the bronchial submucosa. In conclusion, the expression of type 1 and type 2 vasoactive intestinal peptide receptors is increased in the central airways of smokers with chronic bronchitis, suggesting their possible involvement in the pathogenesis of chronic bronchitis.

Adult↗
PubMed2003

Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations.

BACKGROUND: Exacerbations represent an important feature of the clinical manifestation and natural history of chronic obstructive pulmonary disease (COPD). Nuclear localisation of p65 is a signal of nuclear factor-kappaB (NF-kappaB) activation. A study was undertaken to evaluate whether NF-kappaB activation is modified in sputum cells during COPD exacerbations. METHODS: Total and nuclear p65 immunoreactivity was measured by immunocytochemistry in the sputum cells of 11 smokers with moderate COPD during an exacerbation and after 6-8 weeks of clinical stability. RESULTS: Total sputum cell count was significantly increased during exacerbations from a median (IQR) of 880 (510-1865) to 1914.5 (1065-3205) x 10(3)/ml (p<0.05). The main inflammatory cells in the sputum were neutrophils (83.2 (75.4-92.3)%) and macrophages (14.7 (2.6-21.6)%) and their relative proportion did not change during exacerbations. Nuclear staining for p65 was absent in sputum neutrophils, both during exacerbations and in the stable phase. In contrast, the percentage of macrophages expressing nuclear p65 increased significantly during exacerbations from a median (IQR) of 16 (7-24)% to 41.4 (6-69)% (p<0.05). CONCLUSIONS: NF-kappaB appears to be activated in sputum macrophages but not in sputum neutrophils during exacerbations of COPD

Aged↗
PubMed2003

Interleukin-13 and -4 expression in the central airways of smokers with chronic bronchitis.

The aim of this study was to determine whether the T-helper 2-type cytokines interleukin (IL)-13 and -4 are involved in mucus hypersecretion, the hallmark of chronic bronchitis (CB). Surgical specimens were examined from 33 subjects undergoing lung resection for localised peripheral malignant pulmonary lesions: 21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers with normal lung function. The number of IL-4 and -13 positive (+) cells in the central airways was quantified. To better assess the cytokine profile, a count was also made of IL-5+ and interferon (IFN)-gamma+ cells. Compared to AS, the CB group had an increased number of IL-13+ and -4+ cells in the bronchial submucosa, while the number of IL-5+ and IFN-gamma+ cells were similar in all the groups. No significant associations were found between the number of cells expressing IL-13 or -4 and the number of inflammatory cells. Double labelling showed that 13.2 and 12.9% of IL-13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL-4+ cells were CD8+ and CD4+, respectively. In conclusion, T-helper-2 and -1 protein expression is present in the central airways of smokers and interleukin-4 and -13 could contribute to mucus hypersecretion in chronic bronchitis.

Adult↗
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

Macrolides for chronic asthma.

BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role. The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae). Macrolides are antibiotics with both antimicrobial and anti-inflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function. OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma. SEARCH STRATEGY: We searched MEDLINE, EMBASE and CINAHL up to May 2001. This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors. All languages were included in the initial search. SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. Two reviewers reviewed the full text of any potentially relevant article independently. MAIN RESULTS: The initial search retrieved 95 studies. Preliminary evaluation identified 20 studies that were potentially eligible. Five (357 patients) met the entry criteria. The entry criteria for the primary trials differed, but all recruited a specific subgroup of patients (eg severe oral steroid dependent, aspirin intolerant or evidence of Chlamydia pnuemoniae infection). There was a positive effect on symptoms (Standardised Mean Difference -1.25, 95% Confidence Intervals (CI) -1.80, -0.70) and markers of eosinophilic inflammation; eg sputum eosinophils Weighted Mean difference -78.5, 95%CI -90.8, -66.1). Tests of oral corticosteroid-sparing effects have not yet been performed on the newer agents such as roxithromycin and clarithromycin. REVIEWER'S CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Anti-Bacterial Agents↗
PubMed2002

Actions other than smooth muscle relaxation may play a role in the protective effects of formoterol on the allergen-induced late asthmatic reaction.

Long-acting beta(2)-adrenoceptor agonists attenuate the allergen-induced late asthmatic reaction. We evaluated whether other mechanisms in addition to airway smooth muscle relaxation may be implicated in this protective effect. The effects of formoterol (Foradil Aerolizer(TM), 24 microg dry powder) on the late asthmatic reaction were assessed by a randomised crossover factorial study in 24 patients with asthma. Four challenge/treatment combinations were tested: (A) saline/placebo, (B) saline/formoterol, (C) allergen/placebo, (D) allergen/formoterol. Formoterol and placebo were administered double blind after the last inhalation of the allergen or saline. FEV(1) was measured up to 32 h. The bronchodilator effect of formoterol was estimated as (B-A) and the overall protective effect as (D-C). The effect not due to bronchodilation was estimated as [(D-C)-(B-A)]/2. The bronchodilator effect of formoterol was statistically significant up to 5h (all P< or =0.015). Formoterol significantly attenuated the late asthmatic reaction between 3 and 32 h after allergen inhalation (all P< or =0.0012). The difference between this protective effect and the bronchodilator effect was statistically significant at 5 h and between 7 and 28 h after allergen inhalation (all P< or =0.035). Our results suggest that functional antagonism may not be the sole mechanism by which formoterol attenuates the allergen-induced late asthmatic reaction.

Adolescent↗
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↗
PubMed2002

Clinical use of Levofloxacin in the long-term treatment of drug resistant tuberculosis.

Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. IN VITRO ACTIVITY ON MYCOBACTERIA: The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. CLINICAL EXPERIENCE: Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. CONCLUSION: We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.

Adult↗
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

Low domestic exposure to house dust mite allergens (Der p 1) is associated with a reduced non-specific bronchial hyper-responsiveness in mite-sensitized asthmatic subjects under optimal drug treatment.

BACKGROUND: Airway inflammation in asthma causes symptoms, airflow limitation and bronchial hyper-responsiveness. The strategy of asthma management is to reduce airway inflammation by drug treatment and avoidance of triggers, including allergens. OBJECTIVE: We determined the effect of exposure to house dust mite (HDM) allergens on bronchial responsiveness in asthmatics sensitive to mites while under optimal drug treatment. METHODS: We studied 71 mild to moderate HDM-sensitive asthmatics. Drug treatment sufficient to keep asthma under control was administered to each patient for 1 year. Subjects were divided into two groups, according to the amount of Der p 1 in their bedrooms measured after standard HDM reduction measures: low Der p 1 exposure (0.64 +/- 0.5 microg/g dust) (Group 1, n = 34) and high Der p 1 exposure (12.5 +/- 11.4 microg/g) (Group 2, n = 37). Bronchial responsiveness to methacholine (PD20FEV1) was determined at the beginning and end of the study. RESULTS: In Group 1, PD20FEV1 increased 2.15-fold at the end of the study from 57 to 123 microg (P < 0.05), whereas in Group 2 no significant changes were observed. The subjects in Group 2 tended to increase the use of inhaled steroids and bronchodilators in the autumn months compared with subjects in Group 1, but the difference was not significant. CONCLUSION: This long-term study shows that exposure to lower levels of mite allergens in the bedroom is associated with a decrease of bronchial hyper-responsiveness in sensitized asthmatic subjects under optimal drug treatment.

Adolescent↗
PubMed2001

Serum-mediated relaxant response to toluene diisocyanate (TDI) in isolated guinea-pig bronchi.

The present study was designed to evaluate whether pre-incubation with serum, obtained from both control and toluene diisocyanate (TDI)-immunized guinea-pigs, modified the contractile response to TDI in isolated guinea-pig bronchial rings. Guinea-pigs were anaesthetized and the main bronchi dissected in two rings. Bronchial rings were incubated with normal or immune serum (100 microl ml(-1) for 2 h) and dose-response curves to TDI (0.03-1000 microM) were studied isometrically. Before serum incubation, in eight bronchial rings, epithelium was removed by rubbing the luminal surface gently with a gauze. In control rings, TDI produced a concentration-dependent contraction, whereas in rings pre-incubated with either normal or TDI-immune serum, it produced a concentration-dependent relaxation. Relaxation was 101.4 (SEM 17.4)% and 94.9 (SEM 21)% of the relaxation induced by isoproterenol (1 mM) respectively with normal and TDI-immune serum. Similarly to the pre-incubation with serum, pre-incubation with albumin produced a concentration-dependent relaxation to TDI. Serum-induced relaxant response to TDI was not affected by capsaicin desensitization, it was only partially inhibited by an NK1-tachykinin antagonist, whereas it was blocked by indomethacin. In bronchial rings without epithelium, pre-incubated with serum, TDI caused contraction at highest doses, while it still induced relaxation at the lowest doses. This study shows that one or more components of the serum modify the contractile response to TDI in isolated guinea-pig bronchi. In bronchial rings without epithelium serum was able to inhibit the contration induced by low doses of TDI.

Albumins↗