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Biomedical subjects

G Marcer

Publications and source records attributed to G Marcer.

At least 19 recordsLinked to original sources

Effect of natural grass pollen exposure on exhaled nitric oxide in asthmatic children.

Exhaled nitiric oxide (NO) is increased in exhaled breath of asthmatic patients. The aim of this study was to investigate the longitudinal changes of exhaled NO outside and during the pollen season in pollen-allergic asthmatic children. Twenty-one children (age 6 to 16 yr), with a seasonal allergic asthma sensitive to grass pollen, underwent measurements of exhaled NO and pulmonary function before (March), during (May), and after (November) the pollen season. Exhaled NO was measured by a tidal breathing method with a chemiluminescence analyzer and NO steady-state levels were recorded. The timing of the measurements during the pollen season was based on the atmospheric pollen count. Exhaled NO values of asthmatic children were compared with those of 21 sex- and age-matched healthy children. Pulmonary function and symptoms of asthma were also evaluated at each visit. The mean value of exhaled NO before the grass season was 12.7 +/- 5.1 ppb (mean +/- SD), significantly higher when compared with controls (7.8 +/- 2.7 ppb, p < 0.001). In the pollen season there was a significant (p < 0.001) twofold increase in exhaled NO (21.4 +/- 7.6 ppb) that, after the season, returned to values similar (12.8 +/- 5.8 ppb, p = NS) to those found before the season. There were no significant changes in FEV1 before and during the season (98.6% predicted versus 101% predicted, p = NS). We conclude that natural allergen exposure is related to an increase of exhaled NO in asthmatic grass pollen-allergic children even in absence of significant changes in airways function. We speculate that measurement of exhaled NO could be a sensitive noninvasive marker of asthma disease activity.

Adolescent

Prevalence of sensitization to Alternaria in allergic patients in Italy.

BACKGROUND: The actual prevalence of sensitization to Alternaria is not known, partly due to the unreliability of diagnostic extracts. OBJECTIVE: To assess skin positivity to extracts of Alternaria in a wide population of Italian patients suffering from respiratory symptoms using a biologically standardized extract. METHODS: A total of 2942 patients were skin prick tested with Alternaria, and a panel of common inhalant allergens. Blood samples for specific IgE quantitation were taken both from patients positive and from patients negative (control group) to Alternaria extract. RESULTS: Three hundred six patients (10.4%, ranging from 1.8% in Turin to 29.3% in Cagliari) were positive to Alternaria; 37 were sensitized to only this mold, while the remaining 269 were sensitized to at least one other allergen. Of the Alternaria-positive patients, 79.7% suffered from rhinitis and 53.3% from asthma, either alone or associated with other symptoms. CONCLUSIONS: We suggest that, at least in Italy and in countries with similar climatic and environmental situations, standardized Alternaria extract should be included in the panel commonly used in investigating the allergen responsible in patients suffering from respiratory allergy.

Adolescent

Selection of T lymphocytes bearing limited TCR-Vbeta regions in the lung of hypersensitivity pneumonitis and sarcoidosis.

Hypersensitivity pneumonitis (HP) and sarcoidosis are interstitial lung disorders (ILD) characterized by a lymphocytic alveolitis that, in the active phase of the disease, is sustained by different T-cell subsets, i.e., CD8+ cells in HP and CD4+ lymphocytes in sarcoid patients. To address the question of whether a bias in T-cell selection occurs in the lung of patients with HP and sarcoidosis, we analyzed the T-cell receptor beta chain variable region (TCR-Vbeta) repertoire by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 14 HP and 25 sarcoid patients. To verify whether these cells can be activated in vitro through the TCR, blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins, including SEA, SEB, SEC1, SEC2, SED, and SEE. Flow cytometry and PCR analyses demonstrated an overexpression of cells bearing Vbeta2, Vbeta3, Vbeta5, Vbeta6, and Vbeta8 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments were overrepresented in the lung rather than in the blood. Both in HP and sarcoid patients almost all T cells bearing the dominant Vbeta segment belonged to the T-cell subset that sustains the alveolitis, i.e., CD8 in HP patients and CD4 in sarcoid subjects. Follow-up studies demonstrated that the recovery of the alveolitis was characterized by the disappearance of cells bearing a limited T-cell repertoire. Interestingly, T-lymphocyte response to different superantigens demonstrated that the proliferation elicited by different staphylococcal toxins was more pronounced in the lung than in the blood. Taken together, our findings indicate a compartmentalization of cells bearing discrete Vbeta gene products in the pulmonary microenvironment and suggest that the expansion of specific Vbeta region subsets occurring in the lung might result from triggering by a specific antigen. In fact, the removal from exposure in HP patients or specific treatment in sarcoidosis resulted in the decrease of the overrepresented cell population accounting for the lymphocytic alveolitis.

Adult

Allergic and Irritant Glove-related Diseases in Health Care Workers and Their Prevention.

Because the widespread use of gloves by health care workers has induced an increase of both irritant and type I or type IV allergic glove-related diseases, the Italian Society of Preventive Medicine for Health Care Workers set up a working group to collect information about glove composition and to standardize procedures for the diagnosis and prevention of glove-related disease and job-fitness evaluation of employees who will be wearing gloves. In addition, the group made recommendations for educational programs focusing not only on users but also on purchasers, who presently favor glove selection for economic reasons. The group's recommendations are summarized in a consensus document, but cannot be considered definitive. More research is needed to achieve answers to questions raised by the working group, indicated in the consensus document. In particular, diagnostic criteria must be standardized to plan multicenter studies to verify the real extent of the problem, and further studies are needed to verify whether limit values for substances contained in the gloves (e.g., latex proteins, residual chemicals) can be established.

Journal Article

Reduced lung cancer mortality in dairy farmers: is endotoxin exposure the key factor?

From two areas in the Province of Padova, we selected 2,283 male farmers who worked either in cattle raising or in crop/orchard cultivation. There were 422 cohort deaths from 1970 to 1992. Using the regional population as a reference, the standardized mortality ratio (SMR) was calculated, with 95% confidence intervals (CI) based on the Poisson distribution. Cancer mortality was significantly reduced among the 1,561 dairy farmers (SMR = 0.65; CI = 0.53-0.81); there was a significant decrease in lung cancer (SMR = 0.49; CI = 0.31-0.74), whereas a significant increase from brain tumors was found (SMR = 2.83; CI = 1.04-6.17). Neither overall cancer mortality nor the lung cancer SMR deviated significantly from unity for the 722 crop/orchard farmers. Among dairy farmers, moreover, lung cancer SMRs showed a significant downward trend across the quartiles of increasing length of work, 0.96 in the first quartile, and 0.48, 0.40, and 0.25 in the second, third, and fourth quartiles, respectively. Moreover, lung cancer risk decreased with increasing farm land area, with SMRs in the quartiles of 0.89, 0.37, 0.41 and 0.19. This decrease cannot be attributed to either a selection (healthy worker effect) or a confounding (lower percentage of smokers) bias. Nor was it due to an artifact introduced by differences in age distribution among the quartiles. Dairy farmers are known to be exposed to higher airborne endotoxin concentrations; reasonably, this cumulative exposure increases further with years of work and area of farm. Endotoxins may have protected the dairy farmers against lung cancer through the tumor necrosis factor produced by alveolar macrophages.

Adolescent

Preliminary study on the effect of broxaterol on bronchial hyperresponsiveness in asthmatic children: influence of allergen exposure.

Increased bronchial hyperresponsiveness (BHR) has been reported in adult asthmatic patients after regular treatment with beta 2-agonists. In this study we evaluated the effect of a 4-weeks treatment period with broxaterol, a new beta 2-agonist, on BHR in asthmatic children living in two different environmental conditions. Two groups of patients, 24 domiciled at sea level, allergen exposed (group 1), and 24 resident at high altitude (Misurina, 1,756 m) in an allergen-free environment (group 2), have been tested. Children were randomly treated with broxaterol 400 micrograms q.i.d. or sodium chromoglycate 10 mg q.i.d. (as control treatment) by the metered dose inhaler for 4 weeks. Pulmonary function tests and methacholine challenge were performed at the beginning and at the end of the study. Throughout the study period a diary card was completed and peak expiratory flow rate (PEFR) was measured three times daily. Forty-two of the patients admitted concluded the study. No significant change was observed in the methacholine PC20 throughout the study period regardless of the type of treatment and/or environment. The amplitude percentage mean of diurnal changes in PEFR during the study period showed no statistically significant differences between treatments or centres, or in the interaction of treatment with centre, time with treatment, time with centre, time with centre and treatment (p > 0.05). Therefore in this pilot study regular treatment with broxaterol for 4 weeks did not cause an increase in BHR in asthmatic children both in conditions of allergen exposure and in an environment free of offending allergens.

Adolescent

Pulmonary impairment in workers exposed to silicon carbide.

Two hundred and sixty seven workers employed in the manufacture of silicon carbide (SiC) were examined to determine the effects of exposure to contaminants (SiC, quartz, and SO2) in the workplace on pulmonary function. No exposure concentrations exceeded the current permissible limits. Ten subjects (3.7%) showed rounded opacities (profusion greater than or equal to 1/0). Two subjects employed only in the final stages of the production process and not exposed to crystalline silica showed opacities (profusion q1/0 and q2/1) on x ray film suggesting a role of SiC in the genesis of interstitial lung disease. Chest abnormalities on x ray film were correlated with cumulative exposure to dust and pulmonary function was affected by cumulative dust exposure, profusion of opacities, and smoking. It is concluded that the current standards do not provide adequate protection against pneumoconiosis and chronic pulmonary disease in this industry.

Carbon

Longitudinal study of alveolitis in hypersensitivity pneumonitis patients: an immunologic evaluation.

Cells recovered from bronchoalveolar lavage were studied, both from a phenotypic and functional point of view, in 18 patients with hypersensitivity pneumonitis (HP) during a prolonged follow-up. A series of monoclonal antibodies against different lymphocyte subpopulations, including T cells, T cell subsets, and natural killer (NK) cells have been used. In some cases, an immunohistologic analysis of lung tissue sections has also been performed. The NK activity has been evaluated with regard to the in vitro function. At the time of the first evaluation, a high number of CD8+ cells with an imbalance of CD4/CD8 ratio had been demonstrated in patients with HP. Consecutive bronchoalveolar lavage evaluations demonstrated a persistent increase of CD8+ cells and a reversal of CD4/CD8 ratio in patients who continued to be regularly exposed to etiologic antigens at work (W+). In the same cases, a persistent increase of NK cells was demonstrated. Cytotoxic cells demonstrated a persistently enhanced in vitro lytic function during the follow-up, even though there appeared to be a trend toward the normal range. Patients who continued to live in agricultural environments but were not further exposed to specific antigens at work (W-) exhibited a recovery of CD4+ cells, a decrease in CD8+ cells, and an increase of CD4/CD8 ratio to the normal range 6 months after the first observation. Immunohistologic analysis, performed at the time of the first evaluation, demonstrated a diffuse infiltration of lung parenchyma by CD8+ cells, both in W+ and W- patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic

Different types of cytotoxic lymphocytes recovered from the lungs of patients with hypersensitivity pneumonitis.

To better characterize the cytotoxic lymphocytes present in the lung of patients with hypersensitivity pneumonitis (HP), we studied cells recovered from bronchoalveolar lavage (BAL) of 5 subjects with farmer's lung disease. Specifically, this cytotoxic activity was evaluated: (1) in resting conditions and after boosting with interleukin-2 (IL-2) against NK-sensitive, NK-insensitive target cell lines, and against specific antigen-sensitized (Micropolyspora faenl) autologous monocytes; (2) after removal of NK-related populations; (3) in blocking experiments with CD3 and CD2 monoclonal antibodies. It has been demonstrated that lung lymphocytes from patients with HP in resting conditions are able to lyse both NK-susceptible and NK-resistant targets and that IL-2 is able to induce BAL cells to generate lymphokine-activated killer (LAK) cell activity. Neither resting nor activated HP lung lymphocytes were capable of specific lysis of autologous monocytes previously sensitized with specific antigen. Removal of HNK-1+ or CD16+ cells reduces, but does not completely eliminate the cytotoxic function, whereas blocking with anti-CD3 monoclonal antibody almost completely abolishes the cytotoxicity. All these data taken together suggest that different types of cytotoxic cells are recovered from the BAL of patients with HP, i.e., NK cells and non-MHC-restricted cytotoxic lymphocytes, including LAK cells.

Adult

Pulmonary alveolar macrophages in patients with sarcoidosis and hypersensitivity pneumonitis: characterization by monoclonal antibodies.

Using a panel of monoclonal antibodies (MoAbs), the frequency of cells bearing Class I and Class II major histocompatibility complex (MHC) determinants, transferrin receptor (TR) sites, and interleukin-2 receptors (IL-2R) has been evaluated on pulmonary alveolar macrophages (PAM) recovered from the bronchoalveolar lavage (BAL) fluid of 21 patients with pulmonary sarcoidosis (including 11 cases with active sarcoidosis and 10 cases with inactive disease), 8 patients with hypersensitivity pneumonitis (HP), and 6 normal non-smoking volunteers. When the frequency of Class II DR-positive cells was considered, 64.3% of control PAM expressed HLA-DR products. No statistically significant differences were observed between controls and sarcoid patients, while HP patients showed an enhanced proportion of DR+ PAM with respect to normal PAM (P less than 0.05). On the contrary, the frequency of PAM expressing HLA-DQ molecules was higher in both active sarcoidosis and HP patients with respect to patients with inactive sarcoidosis and normal subjects (P less than 0.001). A statistically significant increase in Class I antigen-positive PAM has been demonstrated in HP patients as compared to controls (P less than 0.05). Active sarcoid patients showed a higher number of PAM-bearing TR sites than controls and other groups of patients considered (P less than 0.001). An increase in the percentage of IL-2R-positive PAM has been demonstrated in active sarcoidosis (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic

Occupational asthma due to ebony wood (Diospyros crassiflora) dust.

A 47-year-old man developed a specific late asthmatic reaction after occupational-type exposure to ebony wood dust. Intradermal skin test to an aqueous extract of ebony wood did not give any immediate or late response. The challenge with ebony wood dust was therefore the only method of confirming the cause of asthma. The mechanism underlying this asthmatic reaction remains unknown.

Asthma

Modification of bronchial hyperreactivity during pollen season in children allergic to grass.

Ten children, sensitive to grass pollens with seasonal rhinitis and mild asthma, underwent bronchial challenge with carbachol in the pre-seasonal, seasonal, and post-seasonal period. According to pollen count, we observed significant differences between pre-seasonal, seasonal, and post-seasonal values. Also basal FEV1 values varied in the same fashion. Seven of the ten children also participated in a previous similar study in 1984, at which time they did not demonstrate significant variations to bronchial challenge. We wish to emphasize the importance of pollen concentration in the atmosphere as well as the existence of a threshold value of grass pollen necessary for a significant modification in bronchial reactivity to occur.

Asthma

Lung T cells in hypersensitivity pneumonitis: phenotypic and functional analyses.

Cells recovered from bronchoalveolar lavage (BAL) and tissue sections from transbronchial lung biopsies were studied in 16 patients with symptomatic hypersensitivity pneumonitis (HP) and in six subjects with a similar history of exposure but without features of disease by using a series of monoclonal antibodies (MoAb) detecting different lymphocyte subpopulations, including T and T subsets, B lymphocytes, and natural killer (NK) cells. Their functional activities in cytotoxic and suppressor assays and the microenvironment in the lung by using immunohistological techniques were also evaluated. It has been demonstrated that the majority of cells recovered from BAL of HP patients are represented by T8 lymphocytes, with a relevant imbalance of the T4/T8 ratio (p less than 0.001). HNK-1+ cells were markedly increased (p less than 0.001), whereas the frequency of cells bearing other NK-related markers (NK-15, VEP 13, Ab8.28, T10, M1, and Fc gamma R) were not significantly increased with respect to controls. Immunohistological study confirmed that the majority of cells infiltrating lung parenchyma are T8+ lymphocytes. The number of HNK-1+ cells detected on lung biopsies was very low in all cases, even in patients with the highest values on BAL suspensions. The evidence of cells bearing the proliferation-associated markers (Tac and T9 antigens) seems to support the hypothesis of a local proliferation in the lung. In terms of phenotypic analysis, the results observed in the group of asymptomatic individuals are qualitatively superimposable on those observed in the HP group, but the magnitude of the phenomenon is less prominent and therefore the data are not as statistically significant as that produced by the comparison between HP patients and the same controls. Functional analysis of BAL T cells from both HP patients and asymptomatic individuals showed suppressor activity in vitro, as determined by the ability to influence a pokeweed mitogen (PWM)-driven B cell differentiation assay. BAL cells from HP patients were also able to display a definite cytotoxic function in vitro, whereas BAL lymphocytes from asymptomatic subjects did not. Taken together, these data demonstrated that cells responsible for the alveolitis in patients with HP are characterized by the expansion of T cells with the phenotype and functions of both suppressor and/or cytotoxic lymphocytes. This expansion is likely to be related to a local immunologic response to the antigenic stimulus and may provide new insights into the pathogenetic mechanisms of this disease, its pathological pattern, and its management.

Adult

Peripheral blood NK cells in patients with extrinsic allergic alveolitis: phenotype and function.

Peripheral blood mononuclear cells obtained from patients with extrinsic allergic alveolitis were tested with a series of monoclonal antibodies against natural killer cells, including HNK-1, NK-15, Ab8.28, OKM1 reagents. An NK in vitro functional evaluation of these cells was associated to the phenotypic analysis. Our data demonstrated an increase, with respect to controls, of the percentage and absolute number of HNK-1 positive cells in the blood of these patients. This increase was consistent with an enhanced cytotoxic in vitro activity. These findings provide evidence that in patients with extrinsic allergic alveolitis, the exposition to antigenic stimuli triggers the NK system. Possible immunopathogenetic mechanisms, especially in comparison with other interstitial lung disorders, are discussed.

Adolescent

Influence of aeroallergens on bronchial reactivity in children sensitized to grass pollens.

Nine children, sensitized to grass pollens, with seasonal rhinitis and mild asthma underwent bronchial challenge with carbachol and EIA test repeatedly either during a pre-seasonal or in seasonal period. We failed to find any significant difference between pre-seasonal and seasonal values in both tests. We believe that atmospheric conditions are an important determinant of our results. It is our hypothesis that a threshold concentration in atmospheric pollen may exist which must be reached before an allergic reaction is evident.

Air Pollution

Bronchoalveolar lavage and lung histology. Comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

Adolescent