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Biomedical subjects

L M Fabbri

Publications and source records attributed to L M Fabbri.

At least 73 records · Page 4Linked to original sources
PubMed1998

What can we learn from late-onset and occupational asthma?

Late-onset asthma and occupational asthma may provide interesting models of human asthma to compare with the most frequent type of atopic early-onset asthma. The discovery of similarities and discrepancies in the aetiology and pathogenesis of these different diseases might provide new insights on different mechanisms producing the same phenotype and, thus, by recognizing the different underlying mechanisms of the different forms of asthma, may allow better targeting of prevention and treatment. Occupational asthma, in addition to being a late-onset asthma, provides the unique opportunity to study the development of asthma under measurable exposure conditions, and consequently to examine the effect of cessation of exposure which, at variance with allergen avoidance, is possible in most of the cases.

Adult↗
PubMed1998

CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease.

To investigate whether the inflammatory process in peripheral airways is different in smokers who develop symptoms of chronic bronchitis and chronic airflow limitation and in asymptomatic smokers who do not develop chronic airflow limitation, we examined surgical specimens obtained from 16 smokers undergoing lung resection for localized pulmonary lesions. Nine had symptoms of chronic bronchitis and chronic airflow limitation and seven were asymptomatic with normal lung function. In peripheral airways, immunohistochemical methods were performed to identify neutrophils, macrophages, CD4+ and CD8+ T-lymphocytes infiltrating the airway wall, and morphometric methods were used to measure the internal perimeter, the airway wall area, and the smooth muscle area. The number of CD8+ T-lymphocytes and the smooth muscle area were increased in smokers with symptoms of chronic bronchitis and chronic airflow limitation as compared with asymptomatic smokers with normal lung function, while the number of neutrophils, macrophages, and CD4+ T-lymphocytes were similar in the two groups of subjects examined. We concluded that smokers who develop symptoms of chronic bronchitis and chronic airflow limitation have an increased number of CD8+ T-lymphocytes and an increased smooth muscle area in the peripheral airways as compared with asymptomatic smokers with normal lung function, supporting the important role of CD8+ T-lymphocytes and airway remodeling in the pathogenesis of chronic obstructive pulmonary disease.

Aged↗
PubMed1998

Immunization and challenge with toluene diisocyanate decrease tachykinin and calcitonin gene-related peptide immunoreactivity in guinea pig central airways.

Toluene diisocyanate (TDI) is a potent sensitizer that causes occupational asthma in a significant proportion of subjects exposed. We used an animal model to investigate whether neuropeptide changes occur in the airways of immunized and TDI-challenged guinea pigs. Animals were immunized by weekly intradermal injections, challenged with TDI (5 to 20 ppb) after the third injection, and killed 6 h after exposure. Control guinea pigs received injections of saline. Lung tissue was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene- related peptide (CGRP). We also quantified the inflammatory infiltrate in the submucosa of central airways, and we measured the serum level of specific IgG and IgG1. Specific antibodies against TDI were present only in immunized animals. Immunized as compared with nonimmunized animals had a significant increase in eosinophils in the submucosa of central airways, and a further increase was observed 6 h after TDI challenge. Immunization and TDI challenge did not modify the number of mononuclear cells in the submucosa of central airways in both nonimmunized and immunized animals. TDI exposure did not change the overall innervation in both nonimmunized and immunized animals, but the density of PGP 9.5-positive nerves was significantly different between nonimmunized and immunized TDI-challenged animals. The density of SP-, and CGRP-immunostained nerves was significantly lower in immunized TDI-challenged than in nonimmunized animals. TDI exposure significantly decreased the density of SP-positive nerves in nonimmunized animals. A negative relationship was found between the presence of airway inflammation, as indexed by eosinophil cell infiltration, and the density of PGP 9.5-, SP-, and CGRP-immunostained nerves. In conclusion, TDI produces airway inflammation and neuropeptides changes in the central airways of immunized guinea pigs 6 h after TDI challenge. These findings support an interaction between tachykinins, inflammatory (i.e., eosinophils) and possibly immune cells.

Animals↗
PubMed1998

Severity of airflow limitation is associated with severity of airway inflammation in smokers.

To investigate the relationship between airflow limitation and airway inflammation in smokers, we examined paraffin-embedded bronchial biopsies obtained from 30 smokers: 10 with severe airflow limitation, eight with mild/moderate airflow limitation, and 12 control smokers with normal lung function. Histochemical and immunohistochemical methods were performed to assess the number of inflammatory cells in the subepithelium and the expression of CC chemokines macrophage inflammatory protein (MIP)-1alpha and -1beta in the bronchial mucosa. Compared with control smokers, smokers with severe airflow limitation had an increased number of neutrophils (p < 0.02), macrophages (p < 0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased number of MIP-1alpha+ epithelial cells (p < 0.02). When all smokers were considered together, the value of FEV1 was inversely correlated with the number of neutrophils (r = -0.59, p < 0.002), macrophages (r = -047, p < 0. 012), NK-lymphocytes (r = -0.51, p < 0.006) in the subepithelium, and with the number of MIP-1alpha+ epithelial cells (r = -0.61, p < 0.003). We conclude that in smokers the severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitation is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha+ cells in the bronchial mucosa.

Aged↗
PubMed1997

CD4-positive T-lymphocytes infiltrate the bronchial mucosa of patients with Sjögren's syndrome.

To investigate the degree and the type of inflammation in the bronchial mucosa in patients with Sjögren's syndrome, we examined lobar bronchial biopsies obtained from 10 patients with Sjögren's syndrome (six with primary and four with secondary) and eight control subjects. Histochemistry with hematoxylin-eosin was performed both to identify the number of mononuclear cells and eosinophils and to measure the thickness of the basement membrane. Immunohistochemistry was performed to identify neutrophils (neutrophil-elastase), macrophages (CD68), and T-lymphocyte subpopulations (CD4 and CD8) in the submucosa. Subjects with Sjögren's syndrome presented a greater number of CD4-positive T-lymphocytes than did the normal control subjects (p = 0.0129). Instead, eosinophils, neutrophils, macrophages, CD8 positive T-lymphocytes, and basement membrane thickness were similar in the two groups. There were no differences in cell counts between patients with primary and those with secondary Sjögren's syndrome and between symptomatic and asymptomatic patients. No correlation was found between cell counts, symptoms, lung volumes, and disease duration. This study has shown that patients with Sjögren's syndrome have an increased number of CD4 positive T-lymphocytes in the bronchial mucosa outside of the bronchial glands, supporting the concept that, in the airways. Sjögren's syndrome involves also extraglandular tissues.

Adult↗
PubMed1997

Human leukocyte antigen associations in occupational asthma induced by isocyanates.

Exposure to diisocyanates is recognized as a leading cause of occupational asthma. Occupational asthma induced by isocyanates shares many characteristics with immunoglobulin E (IgE)-mediated asthma: in both, the responsible agent is known, and the clinical presentation, response to inhalation challenge in the laboratory, and response to antiasthma drugs are similar. Although asthma mediated by an IgE mechanism occurs in atopic subjects, occupational asthma induced by isocyanates occurs mostly in nonatopic asthmatics, and an IgE-mediated mechanism has not been consistently demonstrated. However, activated T lymphocytes, methacromatic cells, and eosinophils are increased in the bronchial mucosa of allergic and nonallergic asthmatics and subjects with occupational asthma induced by isocyanates, suggesting similar, probably immunologically mediated mechanisms for both nonoccupational and occupational asthma. Occupational asthma occurs in up to 5-10% of the exposed subjects. Evaluation of major histocompatibility complex (MHC) class II genes in exposed subjects who develop toluene diisocyanate (TDI) asthma has shown a negative association with HLA-DQB1*0501 and a positive association with HLA-DQB1*0503 alleles. In addition, a high proportion of TDI asthmatics express the HLA-DQB1*0503-associated aspartic acid at residue 57, suggesting that HLA-DQ may have a key role in conferring susceptibility. Thus, asthma induced by the low-molecular-weight agent TDI may result from an immunologic reaction due to the interaction of genetic susceptibility with exposure in the workplace.

Antibodies↗
PubMed1997

Inflammatory cells in the bronchial glands of smokers with chronic bronchitis.

To characterize the inflammatory process in the bronchial glands of smokers with chronic sputum production, we examined lobar bronchi from 18 subjects undergoing lung resection for localized pulmonary lesions, all with a history of cigarette smoking. Nine of the subjects had symptoms of chronic bronchitis and chronic airflow obstruction, and nine were asymptomatic, with normal lung function. The number of neutrophils, eosinophils, mast cells, macrophages, CD4+ and CD8+ T-lymphocytes, and the ratio of CD4+ to CD8+ cells were assessed in the bronchial glands, epithelium, and submucosa. Cells were identified through immunohistochemistry. Smokers with symptoms of chronic bronchitis had an increased number of neutrophils (p = 0.01) and macrophages (p = 0.03) and a decreased CD4+/CD8+ ratio (p = 0.01) in the bronchial glands as compared with asymptomatic smokers. Chronic bronchitic smokers also had an increased number of epithelial neutrophils (p = 0.04), whereas the numbers of macrophages and CD4+ and CD8+ T-lymphocytes in the epithelium and submucosa were similar in the two groups of smokers. No differences in numbers of eosinophils or mast cells were observed between bronchitic and asymptomatic smokers in any of the compartments examined. In conclusion, smokers with chronic sputum production have an increased infiltration of neutrophils and macrophages and an increased proportion of CD8+ T-lymphocytes in their bronchial glands, supporting the important role of bronchial-gland inflammation in the pathogenesis of chronic bronchitis.

Aged↗
PubMed1997

Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI).

BACKGROUND: TDI-induced asthma exhibits clinical, functional and morphological similarities with allergen-induced asthma, suggesting that an immunological mechanism is involved in the sensitization to TDI. In vitro studies using the technique of cloning lymphocytes demonstrated that a great proportion of T-cell clones derived from bronchial mucosa of subjects with TDI-induced asthma produced IL-5 and interferon-gamma, but not IL-4, upon in vitro stimulation. OBJECTIVES: To investigate in vivo the role of IL-4 and IL-5 on the inflammatory response of the bronchial mucosa to TDI in sensitized subjects, we performed a quantitative analysis of bronchial biopsies. METHODS: We obtained bronchial biopsies from six subjects with TDI asthma 48 h after an asthmatic reaction induced by TDI challenge (challenged group), in six subjects with TDI asthma 1-4 weeks after the last exposure to TDI (chronic group), and in six non-asthmatic controls. The number of eosinophils, mast cells, T-lymphocytes, and IL-4 and IL-5 protein positive cells was determined by immunohistochemistry in the area 100 microm beneath the epithelial basement membrane. RESULTS: The characteristic increase of submucosal eosinophils, but not of mast cells and T-lymphocytes, was observed in the subjects with TDI-induced asthma when compared with controls. No differences were detected between the two groups of asthmatics. In the subjects with TDI-induced asthma, cell immunoreactivity for IL-5 was increased when compared with normal controls. There was no difference in the expression of IL-5 protein between challenged and chronic asthmatics. In contrast, the expression of IL-4 protein was increased only in the asthmatic subjects tested after recent exposure to TDI. CONCLUSIONS: We demonstrated that TDI asthma 48 h after specific bronchial challenge was associated with increased numbers of cells expressing IL-4 and IL-5, whereas chronic TDI asthma was associated with increased expression of IL-5, but not of IL-4. The results suggest that subjects who developed TDI asthma exhibit increased production of IL-5 even in the absence of a recent trigger by the exogenous sensitizer and that production of TH2-like cytokines in TDI-induced asthma may not always be co-ordinately regulated in vivo.

Adult↗
PubMed1997

Subcutaneous emphysema of the chest wall: a case with unusual presentation.

Subcutaneous emphysema (SE) is the presence of air or other gas in the subcutaneous tissue and is generally associated with pneumothorax and/or pneumomediastinum. We describe an unusual presentation of SE of the chest wall without radiological evidence of pneumothorax or pneumomediastinum, which aetiopathogenesis remains open to several hypotheses in spite of an accurate clinical study.

Adult↗
PubMed1996

Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a serious respiratory pathology characterized by irreversible limitation of expiratory flow and includes chronic obstructive bronchitis, chronic airflow limitation, and emphysema. To determine whether xanthine oxidase activity increased in the airspaces of COPD patients, we examined bronchoalveolar lavage fluid (BAL) from COPD patients recruited during a 2-year clinical study. Filtered BAL supernatant from COPD patients and healthy nonsmoking controls was examined by fluorometric analysis of DNA unwinding (FADU) and spectrophotometric assays (cytochrome c reduction kinetics and uric acid kinetics). Compared to controls, filtered BAL supernatant of subjects with COPD exhibited a detectable clastogenic activity probably related to superoxide production. The method of BAL preparation as an acellular system strongly suggests that superoxide production may be due to xanthine oxidase activity.

Adult↗
PubMed1996

Controlled-release theophylline inhibits early morning airway obstruction and hyperresponsiveness in asthmatic subjects.

BACKGROUND: Nocturnal asthma reflects the severity of the disease, and thus its pharmacologic prevention represents one on the main goals of asthma management. SUBJECTS AND METHODS: To determine whether controlled-release theophylline inhibits the development of airway obstruction and/or airway hyperresponsiveness early in the morning, we examined 18 subjects reporting recurrent nocturnal asthma. In each subject, after five days' treatment with an 8 PM increasing dose of oral controlled-release theophylline, up to 10 +/- 1 mg/kg or placebo the night before the study day, we measured serum theophylline, FEV1 and PC20FEV1 at 6 AM, 2 PM and 10 PM. RESULTS: At 6 AM, both FEV1 and PC20FEV1 were significantly higher on theophylline than on placebo (3.52 +/- 0.22 versus 3.17 +/- 0.25 L; P < .005 and 2.76 divided by 3.61 versus 1.55 divided by 3.73 mg/mL; P < .05, respectively). At 2 PM and 10 PM FEV1, but not PC20FEV1, was higher on theophylline than on placebo (3.73 +/- 0.21 versus 3.54 +/- 0.25 L; P < .05 and 3.40 +/- 0.22 versus 3.24 +/- 0.24 L; P < .05). Serum theophylline was 12.8 +/- 1.1 micrograms/ml, 8.9 +/- 0.77 and 9.5 +/- 0.85 at 6 AM, 2 PM and 10 PM, respectively. CONCLUSIONS: We conclude that an evening dose of controlled-release theophyl line inhibits early morning airway obstruction and hyperresponsiveness, and that it may be helpful in the prevention of nocturnal asthma.

Administration, Inhalation↗
PubMed1996

Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.

Acetylcholine↗
PubMed1996

Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils.

BACKGROUND: Smoking may cause inflammation of the airways and impairment of lung function. To determine the relationship between the type and degree of airways inflammation and the decline in lung function, leucocytes in the sputum of smokers and ex-smokers were examined. METHODS: Forty six smokers and ex-smokers of median age 64 years (25%; 75% percentiles 62;66) with a smoking history of 40.1 (31.7;53) pack years were studied with lung function tests and a questionnaire at the end of a 15 year follow up period. Sputum was induced by inhalation of hypertonic saline and differential leucocyte counts were performed on cytospin preparations. RESULTS: Adequate sputum samples were obtained in 38 subjects (78%). The ratio of forced expiratory volume in one second (FEV1) to vital capacity (VC) was 67.1 (60; 72)% and the annual decline in FEV1 was 19.4 (12;30) ml/year. Subjects with airways obstruction (FEV1/VC < 63%) had more neutrophils (77 (50;86)%) than those without airways obstruction (60 (43;73)%). The percentage of neutrophils was also significantly greater (77 (62;85)%) in those with chronic expectoration than in those without expectoration (57 (45;75)%. Increased levels of neutrophils in the sputum were correlated with a rapid decline in FEV1 over the 15 year follow up period. CONCLUSIONS: Airways obstruction and chronic expectoration, as well as accelerated decline in lung function, are associated with increased numbers of neutrophils in the sputum of smokers and ex-smokers which suggests that neutrophilic inflammation of the airways may be involved in the pathogenesis of chronic obstructive pulmonary disease.

Cough↗
PubMed1996

Airflow limitation in chronic bronchitis is associated with T-lymphocyte and macrophage infiltration of the bronchial mucosa.

To investigate whether the airway inflammatory process is different in patients with chronic bronchitis with airflow limitation and those with chronic bronchitis without airflow limitation, we obtained bronchial biopsies from 14 subjects with chronic sputum production and fixed airway obstruction, and from 10 subjects with chronic sputum production and normal FEV1, all with a history of cigarette smoking. Paraffin-embedded and frozen bronchial biopsies were examined by immunohistochemistry to identify the number of neutrophils (neutrophil-elastase), eosinophils (antieosinophil cationic protein [EG-2]), mast cells (tryptase), T-lymphocytes (CD3), T-lymphocyte subpopulations (CD4 and CD8), B-lymphocytes, and macrophages (CD68) in the submucosa. Subjects with chronic bronchitis with airflow limitation had a greater number of T-lymphocytes (p < 0.01) and macrophages (p < 0.05) than subjects with chronic bronchitis without airflow limitation, whereas the T-lymphocyte subpopulations and the numbers of B-lymphocytes, neutrophils, eosinophils, and mast cells were similar in the two groups. When all the subjects were considered together, the number of T-lymphocytes correlated inversely with the values of FEV1 (r = 0.46, p < 0.02). In conclusion, airflow limitation in subjects with chronic bronchitis is associated with an increased number of T-lymphocytes and macrophages in the bronchial mucosa.

Adult↗