Guido Marcer

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.

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.

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<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<0.001). A statistically significant increase in Class I antigen-positive PAM has been demonstrated in HP patients as compared to controls (P<0.05). Active sarcoid patients showed a higher number of PAM-bearing TR sites than controls and other groups of patients considered (P<0.001). An increase in the percentage of IL-2R-positive PAM has been demonstrated in active sarcoidosis (P<0.001). Our data suggest that (1) PAM of patients with the above-considered interstitial lung diseases are in a state of activation and exhibit structures which play a crucial role in antigenic recognition by T lymphocytes, such as HLA-DQ molecules; (2) the presence of TR in PAM of patients with active sarcoidosis could be related to a more advanced differentiation stage of these cells and/or to particular functional properties; and (3) a direct role of the IL-2/IL-2R system in the interaction between T cells and monocytes in sarcoid lung is crucial. Besides representing an additional parameter which differentiates BAL features of sarcoidosis from those of HP patients, these results could represent a useful tool in the evaluation of the macrophagic component of alveolitis by the BAL.

Airborne allergenic pollens in Padua: 1991–1996

Graminaceae, Urticaceae, Compositae, Betulaceae, Corylaceae and Oleaceae are the most representative allergenic taxa in Italy. In this paper the airborne pollen counts of the main allergenic families collected for a six-year period (1991–1996) in Paduas area were analysed. We observed a significant variability for all allergenic pollen types considered.

Study of immunological parameters in Farmer's lung

A cross‐sectional epidemiological study was carried out on 2932 farmers (response rate 92%) living in Northern Italy. A questionnaire on respiratory symptoms was supplied, chest X‐ray taken and simple spirometry tests made. Thirty‐nine subjects reported attacks of breathlessness associated with fever after exposure to mouldy hay; thirty‐six had a clinical history of Farmers lung and X‐ray and/or respiratory function changes indicative of chronic Farmers lung; 113 were classified as having bronchial asthma. These 118 subjects and a random sample of 131 non‐symptomatic subjects were examined by intracutaneous skin tests and double diffusion precipitation tests with antigens associated with Farmers lung. All sera positive by precipitation were examined by immunoelectrophoresis, counterimmunoelectrophoresis, and C1q binding test, and Bovine conglutinin test in solid phase for the detection of circulating immunocomplexes. 27.8% cases of chronic Farmers lung, 4.4% of cases of bronchial asthma and 2.3% of non‐symptomatic subjects showed precipitating antibodies against Farmers lung antigens. Of the precipitin‐positive subjects, the majority had precipitating antibodies against Micropolyspora faeni. No differences in immunoelectrophoregrams in number and pattern of precipitation arcs for M. faeni were found between chronic Farmers lung and bronchial asthma subjects. Circulating immune complexes were present in 50% of chronic Farmers lung patients, 40% of those with bronchial asthma and 33.3% of non‐symptomatic subjects. Three Farmers lung subjects (9.3%) showed immediate skin‐test reactions to rural environmental allergens.

Efficacy of venom immunotherapy given every 3 or 4 months: a prospective comparison with the conventional regimen

BACKGROUND Standard venom immunotherapy involves the administration of the maintenance dose every 4 to 6 weeks. This regimen may have adherence problems, especially in the long term; thus, extended intervals have been proposed. OBJECTIVE We prospectively compared the efficacy of 3- or 4-month extended maintenance dose vs the conventional regimen. METHODS Patients receiving immunotherapy with a single venom were offered the extended maintenance dose (EMD) and were then followed up for field re-stings. Only the re-stings by the insect for which the patients received immunotherapy were considered. A comparable group of patients receiving the conventional maintenance dose (CMD) was used for comparison by logistic regression analysis. RESULTS Seventy-six patients (60 male; mean age, 48 years) receiving the EMD were re-stung on 247 occasions by the insect for which they were receiving immunotherapy. The group receiving CMD included 110 patients (82 male; mean age, 44 years) certainly re-stung on 167 occasions by the specific insect. The percentage of re-sting without reaction was 93.5% in the EMD group and 81.5% in the CMD group, with a significant difference in favor of the former (P=.001). At logistic regression analysis, only age, but not maintenance dose protocol, was predictive of subsequent systemic reactions. CONCLUSION The EMD is as effective and safe as the CMD. An increased maintenance seems to be the best option in term of convenience and economic savings.

T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a clonal manner

Hypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by CD8+ T lymphocytes showing a limited expression of the T cell receptor (TCR). We previously demonstrated that a bias in T cell selection occurs in the lower respiratory tract of patients with HP, with a compartmentalization in the lung of CD8+ T cells bearing (TCR)‐β variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene segments. We herein characterized the clonal T cell populations present in the lung and in the blood of patients with HP. Heteroduplex analyses, cloning, and sequencing T cells bearing TCR indicate oligoclonal expansions of T cells expressing homologous or identical complementary‐determining region 3. Furthermore, T cell clones isolated from the two compartments expressed similar, sometimes identical, junctional regions. Removal from antigenic exposure led to the disappearance of T cell clones. Our findings indicate that expansions of T lymphocytes bearing clonal TCRBV region gene segments take place in the lung of patients with HP during exposure. The evidence that identical T cell clones are present in the lung and the blood of the same patient suggests that the immune reaction occurring at lung level gives rise to a systemic reaction.

Airborne pollen in Padua (NE-Italy): A comparison between two pollen samplers

During recent years a gradual decrease inallergenic airborne pollen concentration hasbeen observed in the monitoring station ofPadua (Italy). Because technical checks of thesampler were not able to explain this trend,the results obtained from two twinpollen-samplers (Lanzoni VPPS 2000), placed twometres apart, were compared.An eight-week sampling was carried out duringthe year 2000 from July to September.Subsequent analysis revealed no statisticallysignificant difference between the dataobtained with the two instruments. On the otherhand, both samplers captured high levels offungal spores. We conclude that the observednegative trend in pollen count is real and notrelated to technical biases.

Phenological and aerobiological monitoring of allergenic flora in padua (Italy). Preliminary data

A phenological study on allergenic plants was carried out in Padua during 1995 in order to identify spontaneous and cultivated allergenic species in an urban area and their distribution, and to evaluate the relationship between anthesis length and airborne pollen concentrations. In some cases, there was no temporal overlap between phenological and aerobiological data, in particular forCorylaceae, Betulaceae, Chenopodiaceae, Amaranthaceae, Polygonaceae and Fagaceae.

Biological effects of contaminated silicon carbide particles from a workstation in a plant producing abrasives

A sample of silicon carbide dust taken in the field from a plant producing abrasives was studied in vitro. The SiC particles (part unmilled and part milled) were able to disturb the structure of erythrocyte membranes and to lead to blood red-cell lysis; they also either interfered with complement and activated the alternate pathway, or interacted with biological media and polymorphonuclear leucocyte membranes, thus eliciting reactive oxygen species production. These in vitro properties were detected both in original large particles and unmilled particles, over 40% of which were of respirable size. The ability of these SiC particles to produce complement activation in vitro lends support to the previous hypothesis, that the radiographic opacities found in two workers employed in the same area of the plant from which the dust tested was taken are due to a reaction by pulmonary interstitial structures to SiC particle inhalation. It is speculated that SiC particles could act like asbestos, the ability of which to activate complement through the alternate pathway is considered to be one of the mechanisms by which the initial asbestotic lesions and subsequent fibrotic inflammatory infiltrates are generated in the lung.