Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule.

BACKGROUND: sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. METHODS: thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. RESULTS: both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. CONCLUSIONS: our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy.

Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule

Background: sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. Methods: thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. Results: both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. Conclusions: our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy (AU)

Antecedentes: la inmunoterapia sublingual ha sido reconocida como segura y eficaz pero está aún pobremente documentada sobre alergia al polen de árboles. La alergia al aliso, abedul y avellano es importante en los países del norte de Europa, pero su relevancia clínica está aumentando en el sur de Europa. Métodos: 30 pacientes seleccionados y observados a lo largo de una época de polinización, fueron aleatorizados para recibir placebo (15 pacientes) o tratamiento activo (15 pacientes). Completaron el primer año 27 pacientes y 24 de ellos fueron tratados con inmunoterapia activa durante el segundo año del estudio, comparándose con un grupo paralelo tratado solamente con medicamentos. El registro de síntomas y medicamentos durante cada época de polinización, IgE específica al aliso, cambios en la reactividad de la piel, cambio en la prueba de provocación nasal específica y el recuento diario de pólenes de los árboles relevantes fueron considerados para evaluar la eficacia del tratamiento. Resultados: tanto el grupo activo como el placebo mostraron una mejora estadísticamente significativa en los registros, en comparación al año anterior, bajo una menor presión alergénica. La mejoría fue mayor en el grupo activo (76,04 por ciento de reducción de medicamentos) que en el placebo (37,05 por ciento de reducción). En la fase abierta del estudio, los pacientes tratados mostraron una puntuación significativamente mejor que el grupo control. No se registraron cambios significativos en la reactividad de la piel, IgE específica y prueba de provocación nasal específica. La tolerancia del SLIT fue muy buena.Conclusiones: nuestra información muestra un mejor, que no estadísticamente significativo, resultado clínico, en los pacientes tratados con el tratamiento SLIT activo, pero el efecto placebo y la variabilidad de año en año de la carga ambiental alergénica en nuestro pequeño ensayo piloto, no permiten realizar una afirmación concluyente sobre la eficacia de este tipo de terapia (AU)

Preventive symptomatic immunotherapy versus placebo in seasonal rhinitis due to grasses in children and to Parietaria in adult patients.

BACKGROUND: EPD is the only preventive symptomatic immunotherapy available on the market and approved by competent bodies. Recent double-blind placebo controlled (DBPC) studies have demonstrated its efficacy in seasonal and perennial rhinitis. The aim of the study was to confirm the efficacy and safety of a single dose of immunotherapy administered six-eight weeks before the pollen season. METHODS: Two simultaneous DBPC trials were carried out. The first consisted of 20 children with grass-pollen seasonal rhinitis (Bollate-Milano, Italy) and the second included 30 adult patients with Parietaria-pollen seasonal rhinitis (Genova, Italy). EPD was administered only to the active groups. RESULTS: A significant difference in favour of the active treatment groups was seen in oral antihistamine use (p < 0.05) during the peak pollen seasons. Throughout the pollen seasons, rhinoconjunctivitis scores for the two groups in both studies presented no significant difference, even if the values were lower in the active groups. CONCLUSIONS: The oral antihistamine reduction, observed in the active groups during the seasonal period, supports the efficacy of this treatment, although a significant improvement in the rhinoconjunctivitis symptoms was not observed, probably due to the use of oral antihistamine in the placebo groups. The overall profile of the EPD was good. It could be particularly suited for short term therapy to prevent seasonal symptoms in allergic patients.

A novel zinc finger gene is fused to EWS in small round cell tumor.

Ewing sarcoma family of tumors share recurrent translocations that fuse EWS from 22q12 to five different members of transcription factors namely FLI-1, ERG, ETV1, E1AF and FEV. Different classes of DNA binding proteins, ATF1, WT1 and CHOP are fused to EWS generating distinct tumor phenotypes: clear cell sarcoma, desmoplastic small round cell tumor, and myxoid liposarcoma, respectively. We have cloned a novel gene located at 22q12 fused to EWS by a submicroscopic inversion of 22q in a small round cell sarcoma showing a translocation (t(1;22)(p36.1;q12). The gene, designated ZSG (Zinc finger Sarcoma Gene), is a putative Cys2-His2 zinc finger protein which contains a POZ transcriptional repressor-like domain at the N-terminus. The rearrangement involves intron 8 of EWS and exon 1 of ZSG creating a chimeric sequence containing the transactivation domain of EWS fused to zinc finger domain of ZSG. This product lacks the transcriptional repressor domain at the N-terminus of ZSG. A rearrangement of the second ZSG allele was also found in tumor cells. This is the first example of an intra-chromosomal rearrangement of chromosome 22, undetectable by cytogenetics, activating EWS in soft tissue sarcoma.

Apolipoprotein E and intronic polymorphism of presenilin 1 and alpha-1-antichymotrypsin in Alzheimer's disease and vascular dementia.

Apolipoprotein E (ApoE) genotypes, presenilin 1 (PS-1) and alpha(1)-antichymotrypsin (ACT) polymorphism and the association of the genotypes were examined in patients with Alzheimer's disease (AD, n = 121) or vascular dementia (VD, n = 68) in comparison with elderly controls (n = 125). The frequency of the ApoE epsilon 4 allele was significantly increased both in late-onset AD (0.35) and in VD (0.17); the frequency of ApoE epsilon 2 was significantly reduced in AD, but it was similar in VD and controls. The presence of the allele 1 of PS-1 intronic polymorphism was not associated with AD or VD and was not influenced by the ApoE genotypes. Also, the frequency of allele A of the intronic polymorphism of ACT was similar in AD, VD and controls and it was not altered by ApoE or PS-1 genotypes. The results confirm the association between ApoE epsilon 4 and AD and indicate an increase in ApoE epsilon 4 in Vd, too. A potential protective role of ApoE epsilon 2 is also suggested for late-onset AD but not for VD. No association was shown between ACT allele A and PS-1 allele 1 in AD or VD.

Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway.

Cerebral deposits of beta-amyloid (betaA) are a major feature in Alzheimer's disease. betaA is derived from amyloid precursor protein (APP). APP is subject to N- and O-glycosylation and undergoes a series of proteolytic cleavages that lead to the release of betaA or of a non-amyloidogenic secreted form of APP (APPs). We used primary neuronal and glial cultures to investigate how cholesterol affects the production and secretion of APPs. Exposure to cholesterol for 2 h did not change the neuronal release of APPs; after 6 h APPs release was slightly lower, whereas 24 h of exposure decreased APPs in the medium by approx. 60%. The time courses were similar in astrocytes and microglia preparations. To verify whether the effect of cholesterol was a consequence of membrane rigidification we tested the activity of ganglioside GM1 and prion protein fragment PrP 106-126, which affect membrane fluidity similarly to cholesterol, on APPs secretion. Neither altered the production of APPs. APP mRNA and the total amount of APP in the cells were slightly decreased by cholesterol after 2 and 24 h respectively. Immunoblot analysis of APP associated with neuronal cells and astrocytes indicated that cholesterol progressively decreased the glycosylated forms of the protein; a similar tendency was noted in cells treated with brefeldin A and monensin, two substances that interfere with protein glycosylation. The cell-surface biotinylation method showed that in cholesterol-treated cells APP reached the plasma membrane. Our results indicate that cholesterol decreases the secretion of APPs by interfering with APP maturation and inhibiting glycosylation of the protein; although APP is inserted in the membrane it is not cleaved by alpha-secretase.

Prevalence rates of respiratory symptoms and diseases in general population samples of North and Central Italy.

SETTING: Four cross-sectional general population surveys in Italy: northern rural Po Delta area (1980-1982, n = 3284; 1988-1991, n = 2841), and central urban Pisa area (1985-1988, n = 3865; 1991-1993, n = 2841). OBJECTIVE: To analyse changes in prevalence rates of respiratory symptoms and diseases. DESIGN: Prospective epidemiological studies by standardised interviewer-administered questionnaire. RESULTS: Prevalence rates of respiratory symptoms and diseases tended to be higher in males (except for dyspnea and pleuritis), in the urban area (more polluted), and in the second surveys; moreover, they increased with age. Asthma peaked in those aged under 25 years and over 64 years. The highest prevalence rates were shown by current smokers of both sexes for all respiratory symptoms and by ex-smoker males for all respiratory diseases, while female current smokers reported chronic bronchitis, emphysema and asthma more frequently. The most clear-cut trend towards increase between the two surveys within each area was exhibited by wheeze and asthma. CONCLUSIONS: These findings highlight the relevance of sex, age and smoking habit, as well as the possible effects of air pollution, in relation to respiratory symptoms. They also indicate a trend towards an increase in asthma symptoms in Italian general population samples in the 1990s, and an under-estimate of medically diagnosed chronic respiratory diseases.

Management of patients at risk for adverse reactions to local anesthetics: analysis of 386 cases.

Local anesthetics are among the most used drugs in clinical practice. Various types of reactions have been reported and many patients are told that they are allergic to caines or are at risk of allergic reactions. We report our experience with 386 patients using skin test and progressive subcutaneous challenge in order to select a local anesthetic that could be safely used. The patients underwent specific protocol including clinical history, prick and intradermal tests, and subcutaneous incremental challenge with a local anesthetic from the amide group which was free of preservatives and vasoconstrictors. Thirteen patients showed a positive skin test: 10 with positive prick test underwent the subsequent challenge with no reactions; the three who were also positive by the intradermal route were carefully evaluated with a different drug. Eight of the patients with negative skin tests complained of various clinical symptoms after the challenge. All the patients found the local anesthetic to be well tolerated and nobody reported reactions after the clinical use. These results show that skin tests and subcutaneous challenge are safe and sufficient to reliably identify a local anesthetic that patients with a prior history of adverse reaction or at higher risk could tolerate.

The Po River Delta Respiratory Epidemiological Survey: an analysis of factors related to level of total serum IgE.

The purpose of the present study was to analyse whether sex, age, skin test reactivity, cigarette smoking and occupational exposure were related to the total serum immunoglobulin (Ig)E concentrations (kU x L[-1]), in a general population sample. We studied 1,905 subjects (915 males, 990 females) of a general population sample (n=2,841, 8-73 yrs) participating in the second cross-sectional respiratory epidemiological survey in the rural Po Delta area (near Venice, North Italy). Distribution of total serum IgE concentrations was skewed, thus a log-transformation was performed to obtain a Gaussian shape. Significantly higher values of IgE were found in males compared to females. In general, a peak of IgE concentration was found at 8-14 yrs. IgE values tended to be lower in older than younger adults. Significantly higher serum IgE levels were shown in subjects with a positive skin-prick test index (ST+) than in those with a negative skin-prick test index (ST-). There was a significant relationship of total IgE levels with skin reactivity to pollens and house-dust mites. In both sexes higher values of IgE were found in current smokers than in ex-nonsmokers, regardless of skin-test reactivity. There was no significant difference in IgE values between ex- and nonsmokers. Passive smoking and occupational exposure were significantly related to increased IgE values. Our results confirm that in a general population sample immunoglobulin E concentrations are related not only to skin-prick test reactivity to common aeroallergens, but also to other risk factors for chronic obstructive lung diseases, such as sex, active/ passive smoking and occupational exposure.

Serum immunoglobulins E are related to menstrual cycle.

During a cross sectional epidemiological survey on a general population sample, 596 fertile women underwent total serum IgE determination. They completed an interviewer-administered standardized questionnaire and were categorized according to their menstrual period. They were divided into two groups: those from days 10 to 20, who were considered to be in the periovulatory phase, and those in the other phases. IgE mean values were significantly different (p = 0.01) in the two groups: particularly, lower IgE values were found in those in periovulatory phase, after accounting for smoking habit and atopic status. By multiple regression analysis, taking into account the independent effects of menstrual period, age, smoking habit, hours of fast, skin prick test reactivity and presence of cough, significantly lower IgE values in the periovulatory phase were found. We hypothesize the possibility that a decrease of IgE concentration occurs during midcycle: a reduced immune response might facilitate the ovuli implantation. Further studies are necessary to longitudinally investigate the trend of IgE in the same women, as well as the distributions and the trends of other immunoglobulins.

Skin prick test reactivity to common aeroallergens in relation to total IgE, respiratory symptoms, and smoking in a general population sample of northern Italy.

Skin prick test (SPT) reactivity to common airborne allergens and its relationships to sex, age, smoking habits, and respiratory symptoms/diseases were evaluated in a general population sample (n = 2841, 8-75 years of age) living in the Po delta area (northern Italy). Subjects completed a standardized questionnaire and underwent prick tests (12 local allergens, a negative and a positive control) and determination of total serum IgE. Atopy was evaluated by measuring the maximal diameter for each allergen, after subtracting that of the negative control. Thirty-one percent of subjects showed a positive skin response at a 3-mm threshold. Pollens, Dermatophagoides pteronyssinus, and D. farinae caused the highest frequencies of reactions. Young people and those who had never smoked had higher prevalence rates of SPT reactivity. Asthma, asthma symptoms, and rhinitis were significantly associated with SPT reactivity in both sexes (cough only in females) and with the number of positive reactions. IgE values were also significantly associated with SPT reactivity. In conclusion, our findings indicate that almost one-third of the general population of an Italian rural area is skin test positive, emphasizing the importance of assessing atopy in respiratory epidemiologic surveys.

CD4+ Th0 cell clones, isolated from a metastatic lymph node of a melanoma patient, possess cytolytic function.

In the present study T lymphocytes isolated from a metastatic lymph node (T-LNL) of a melanoma patient have been cloned. In the attempt to verify whether T-LNL may acquire in vitro functional activities in the absence of tumour-associated antigens, they were cloned utilizing allogenic lymphocytes as feeder cells. Nineteen clones generated from T-LNL proved to be CD4+ and, among these, five were able to kill autologous and allogeneic human melanoma cells in HLA-class-II-restricted way. On the basis of their cytokine production, these CD4+ cytolytic T-LNL clones were shown to belong to the Th0 subset and three of them expressed the V beta 17 chain of the T cell receptor. These results suggest the presence of melanoma-specific but functionally inactive lymphocytes with T cell receptor oligoclonality in the lymph node environment. These specific T cells may acquire in vitro the capacity to kill autologous and allogeneic tumours without any induction by autologous melanoma cells.

Distribution of bronchial responsiveness in a general population: effect of sex, age, smoking, and level of pulmonary function.

Bronchial responsiveness (BR) was assessed by the methacholine challenge test in 1,694 subjects from a sample of the general population (aged 8 to 73 yr) enrolled in a prospective epidemiologic study on the natural history of chronic obstructive pulmonary disease (COPD). Information on respiratory symptoms and risk factors for COPD were obtained with a standardized questionnaire. The provocative dose causing a 10%, 15%, and 20% decrease in FEV1 was reached in 939 (55%), 658 (39%), and 447 (26%) subjects, respectively, after the last cumulative dose of methacholine (i.e., 4.8 mg). The slope of the dose-response curve was also computed in order to attribute a parameter to subjects who did not reach the provocative dose. After natural log transformation, the slope (Ln Slope) of the curve showed a significant association with the degree of airway obstruction, as assessed by FEV1% predicted, FEV1/VC%, and FEV1/FVC%. Therefore, relationships between BR, sex, age, and smoking were evaluated after adjustments for the initial airway caliber (FEV1, FEV1 adjusted for height, and FEV1/VC%). Females showed significantly higher values of Ln Slope than did males after adjustments were made for baseline lung function. In males, higher BR was observed in childhood-adolescence age groups and at older ages, while in females a higher level of BR was observed during childhood. Significantly higher Ln Slope values were found for females who currently smoked than for non- and ex-smokers. No difference was observed in males in relation to smoking habit. (ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for chronic obstructive pulmonary disease in a north Italian rural area.

To assess the role of risk factors for chronic obstructive lung disease (COPD) by multiple logistic models, the data of the first cross-sectional epidemiological survey in the unpolluted rural area of the Po River Delta were analyzed (n = 2382; 20-64 years). Each subject filled out a standardized questionnaire; 94% of the subjects were also able to perform forced expirograms. Dependent variables were chronic respiratory symptoms, asthma, abnormal parameters of flow-volume curve (ABNFVC), and a complex characterized by chronic phlegm, and/or any wheeze and/or dyspnea grade 2+ and/or diagnosis of asthma and/or an FEV1/FVC ratio less than 60% (ANYABN). Independent variables were: age, ever cigarette smoking (SMK) and lifetime cigarette consumption expressed as pack-years, childhood respiratory infections (CRI), adolescence-adulthood respiratory infections (ARI), familial history for COPD (FCOPD) or for asthma/allergies (FASTHMA), work exposure to dusts/chemicals (EXPO), low socio-economic conditions (SES). A significant relationship with almost all dependent variables was shown by pack-years, ARI and age in both sexes. In males, FCOPD was related to chronic mucus hypersecretion and to ABNFVC, FASTHMA was associated with wheeze and ANYABN. EXPO was related to dyspnea and asthmatic symptoms in both sexes and also to bronchitic symptoms in males. CRI was a significant contributor for asthma symptoms in males, for ANYABN in females. SES had no significant association. In conclusion, our findings show that, beside lifetime cigarette smoking, other host--or environment--related conditions are important risk factors for COPD, suggesting the need for a more thorough strategy for prevention.

Prevalence rates of diagnosis of asthma in general population samples of northern and central Italy.

In order to assess the distribution of asthma in Italy in the 1980s, we have compared the findings of three general population surveys carried out in the North and the Centre of the country. Two cross-sectional investigations were performed in the Po Delta area (North Italy), 6 yrs apart: 1) 3,285 subjects, aged 8-64 yrs, in 1980-1982 (PD1); and 2) 2,841 subjects, aged 8-73 yrs, in 1988-1991 (PD2). One cross-sectional survey was carried out in Pisa (Central Italy): 3,866 subjects, aged 5-90 yrs, in 1985-1988 (PI1). For this analysis we have used data from the standardized questionnaires of those subjects between 18-64 yrs, who were currently employed. The prevalence rate of ever asthma was 3.3-5.5%, that of current asthma 1.3-2.9%; almost all of the diagnoses were confirmed by a doctor. Taking into account only doctor-confirmed asthma, the age of onset of manifestations was most frequently over 18 yrs (41-79%). It also occurred more frequently after the onset of employment. As regards smoking, whilst most asthmatic males were current or former smokers (70-86%), most asthmatic females were nonsmokers. However, the situation changed in PD2, where females showed the same pattern as males. Considering asthmatic subjects with skin-prick test reactivity (data available only in PD2), the vast majority (67% in males, 75% in females) had an age of disease onset under 18 yrs. In conclusion, the prevalence of asthma in Italy in the 1980s was similar to that in other European countries and was affected by atopy and smoking differently in the two sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial reactivity in a general population of north Italy: relationships with occupational exposure.

Two thousand eight hundred and forty one subjects, aged 8-73 yrs, took part in the second cross-sectional survey in the Po River Delta area: among them, a subsample of currently employed people, aged 14-71 yrs, was chosen to establish the relationship between occupational exposure to dusts, chemicals or gases and respiratory symptoms, lung function and bronchial reactivity. Each subject filled out the Italian National Research Council (CNR) standardized questionnaire concerning respiratory symptoms, diseases and risk factors. A variable proportion of subjects performed acceptable forced and slow vital capacity manoeuvres, diffusing capacity of carbon monoxide and bronchial challenge test to methacholine. Occupational exposure appeared to be related to prevalence rate of respiratory symptoms (wheeze, dyspnoea, presence of at least one respiratory symptom) and bronchial asthma. Consistent effects on lung function were not evident. With respect to the bronchial challenge test, using the measurement of the provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) a significantly higher percentage of hyperreactive subjects was found among ex-smoker exposed men; a borderline higher percentage of hyperreactive subjects was also found in non-smoker exposed women. The study findings support the suggestion that occupational exposure may play a role in the development of airway obstructive diseases.

CO diffusing capacity in a general population sample: relationships with cigarette smoking and airflow obstruction.

The single-breath carbon monoxide diffusing capacity (DLCOsb) was measured together with ventilatory lung function tests as part of a survey of a general population sample living in Northern Italy (n = 2,481). Based on answers to an interviewer-administered questionnaire, subjects free of respiratory symptoms or diseases were identified. Data from subjects who had never regularly smoked cigarettes were used to derive reference equations for the test indexes, and data from the remaining subjects who had smoked were used to derive regression equations incorporating a term expressing cigarette consumption (cube root of pack-years) and a term indicating current smoking decrement, in order to obtain expected DLCOsb percent predicted. Neither number of cigarettes smoked daily or duration of smoking, in smokers, nor duration of smoking or years since quitting smoking, in ex-smokers, entered significantly the multiple-regression model. The mean values of DLCOsb were only slightly affected by the increasing degree of airway obstruction. When subjects with confirmed asthma were analyzed, after stratifying for different levels of FEV1/FVC ratio, increased mean value of DLCOsb (over 100%) was found in those with an FEV1/FVC ratio between 75 and 65%. This cross-sectional analysis suggests that there is a decrease in DLCOsb with cumulative cigarette consumption even in healthy subjects. Further, it confirms the clinical observations of high DLCOsb values in asthmatic patients, at least in those with an initial degree of chronic airflow obstruction.

Residual volume in a general population. Effects of body size, age, cigarette smoking, and respiratory symptoms.

Residual volume (RV) was obtained by subtracting vital capacity from total lung capacity determined by the single breath helium dilution (TLCsb) to measure CO diffusing capacity in 2,680 subjects (8 to 64 years old) of a general population sample. There were 712 normal subjects (243 male and 469 female subjects) selected to evaluate the pattern of RV by age and to derive reference values for internal comparisons. From 8 to 20 years old, RV showed an increase because of the cross-sectional body size effect; after 20 to 30 years, RV was still increasing, however, at a lower level. Age and height coefficients were significantly related to RV in younger and older ages, both in male and female subjects. The RV percent predicted and RV/TLC percent were higher in smokers when compared to nonsmokers and exsmokers (the difference was significant in male subjects). A dose-response effect was observed between RV percent predicted, RV/TLC percent, and pack-years. The RV percent predicted and RV/TLC percent were significantly higher in smokers and nonsmokers with FEV1 percent predicted below the normal limit (the difference was significant in male subjects). Moreover, higher values of RV percent predicted and RV/TLC percent were observed in subjects with wheezy symptoms in male smokers and nonsmokers. A negative significant correlation was observed between RV/TLC percent and the diffusing capacity adjusted for lung volume (DL/VA) in smokers, exsmokers and nonsmokers of both sexes, confirming the hypothesis that the decrease in DL/VA may be ascribed to the enlargement of terminal air spaces. In conclusion, determination of RV by the single breath helium dilution method is suitable in epidemiology, and it allows additional important information for understanding the physiopathologic mechanisms related to the pathogenesis of chronic obstructive lung disease.

Effects of the home environment on respiratory symptoms of a general population sample in middle Italy.

The effects of home environment characteristics were evaluated in a multistage, stratified, cluster sample (N = 3,866) of the general population who lived in the district of Pisa (middle Italy). Each subject completed a standardized interviewer-administered questionnaire that contained questions about respiratory symptoms/diseases and risk factors (e.g., type of heating, fuels used for cooking and heating). Cough and asthma were significantly more frequent in men who did not smoke and who did not use natural gas for cooking and heating. Attacks of shortness of breath accompanied by wheeze, dyspnea, and cardiovascular conditions in female nonsmokers were associated with use of a stove or forced-air circulation for heating; the type of fuel used did not affect this result. Multiple logistic models, which accounted for independent effects of age, smoking status, pack-years, childhood respiratory illness, education, zone of residence, and work exposure to dusts, chemicals, or fumes, showed significantly increased odds ratios for (a) cough and phlegm in males (associated with bottled gas for cooking), (b) wheeze and shortness of breath with wheeze in females (associated with the use of a stove or forced-air circulation). These results, which confirm our previous observations in an unpolluted rural area of north Italy, indicate that characteristics of the home environment, as assessed by questionnaire, may be linked to mild adverse health effects, i.e., respiratory symptoms, in the general population. The results also identify the need to better characterize the dose-response relationship in indoor air pollution monitoring studies that include subsamples of this population.