Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

Changing prevalence of obesity in a rural community between 1977 and 2003: a multiple cross-sectional study.

OBJECTIVE: To determine the changes in the prevalence of obesity in a rural community between 1977 and 2003. STUDY DESIGN: A multiple cross-sectional study. METHODS: The analysis was based on data from four cross-sectional surveys of adults aged 25-59 years, conducted in the town of Humboldt, Saskatchewan in 1977, 1983, 1993 and 2003. People with a body mass index (BMI) > or =30 kg/m(2) were considered to be obese. RESULTS: Average body weight increased by 8 kg for both men and women during the study period. The increase in BMI was greater in adults aged 25-39 years compared with older age groups. The prevalence of obesity increased from 24% in 1977 to 38% in 2003 for men, and from 16% to 32% for women. The change was more pronounced from 1993 to 2003 than from 1977 to 1993, especially among younger adults. Standardized to the 2003 study population by sex, age and smoking status, the prevalence of obesity was 16.8% in 1977, 22.7% in 1983, 24.7% in 1993 and 34.5% in 2003, and was much higher than the Canadian national average (16% in 2003). CONCLUSION: There was a dramatic increase in the prevalence of obesity in rural adults, and this was greater in younger adults. Changes in cigarette smoking did not explain the increase. There is an urgent need to identify and implement effective interventions to slow if not reverse the trend, particularly in rural populations.

In vitro production of tumor necrosis factor-alpha by human monocytes stimulated with lipopolysaccharide is positively correlated with increased blood monocytes after exposure to a swine barn.

Recently there has been interest in the air quality in and around intensive livestock production facilities, such as modern swine production barns, where agricultural workers and surrounding residents may be exposed to elevated levels of organic dusts. The health effects of these exposures are not completely understood. The study that is reported here is a component of a larger investigation of the relationships among the acute effects of high-concentration endotoxin exposure (swine barn dust), polymorphisms in the TLR4 gene, and respiratory outcomes following exposure to swine confinement buildings. The relationships among a mediator of acute lung inflammation, tumor necrosis factor alpha (TNF-alpha), and clinical responses to acute swine barn exposure were characterized. Analysis of the results showed that in vitro stimulation of human monocytes with as little as 1 ng/ml of lipopolysaccharide (LPS) produced a significant increase in the monocytes that produced TNF-alpha. Although the proportion of TNF-alpha-positive monocytes after in vitro stimulation with 1 ng/ml of LPS was not associated with gender or TLR4 genotype, it was positively associated with the concentration of monocytes in blood after barn exposure. Thus, these two responses to different forms of LPS exposure are significantly correlated, and more responsive monocytes in vitro indicate a forthcoming relative monocytosis, post barn exposure, which may initiate a cascade of chronic inflammation.

Prevention of agricultural injuries: an evaluation of an education-based intervention.

OBJECTIVE: To evaluate the effectiveness of an agricultural health and safety program in reducing risks of injury. DESIGN: Cross-sectional survey. SETTING: 50 rural municipalities in the Province of Saskatchewan, Canada. INTERVENTION: The Agricultural Health and Safety Network (AHSN), a mainly educational program that administered 112 farm safety interventions over 19 years. SUBJECTS: 5292 farm people associated with 2392 Saskatchewan farms. Farms and associated farm people were categorized into three groups according to years of participation in the AHSN. IMPACT: self-reported prevalence of: (1) farm safety practices; (2) physical farm hazards. OUTCOME: (1) self-reported agricultural injuries. RESULTS: After adjustment for group imbalances and clustering at the rural municipality level, the prevalence of all impact and outcome measures was not significantly different on farms grouped according to years of AHSN participation. To illustrate, the adjusted relative risk of reporting no rollover protection on tractors among farms with none (0 years) versus high (>8 years) levels of AHSN participation was 0.95 (95% CI 0.69 to 1.30). The adjusted relative risk for agricultural injuries (all types) reported for the year before the survey was 0.99 (95% CI 0.74 to 1.32). CONCLUSIONS: Educational interventions delivered via the AHSN program were not associated with observable differences in farm safety practices, physical farm hazards, or farm-related injury outcomes. There is a need for the agricultural sector to extend the scope of its injury prevention initiatives to include the full public health model of education, engineering, and regulation.

The development of the Canadian Rural Health Research Society: creating capacity through connection.

CONTEXT: The organization of rural health research in Canada has been a recent development. Over the past 8 years, rural and remote researchers from more than 15 universities and agencies across Canada have engaged in a process of research capacity building through the development of a network, the Canadian Rural Health Research Society (CRHRS) among the scientifically and geographically diverse researchers and their community partners. The purpose of this article is to discuss the development of the CRHRS as well as the challenges and lessons learned about creating networks and building capacity among rural and remote health researchers. ISSUE: Key elements of network development have included identifying and developing multidisciplinary research groupings, maintaining ongoing connections among researchers, and promoting the sharing of expertise and resources for research training. The focus has been on supporting research excellence among networks of researchers in smaller centres. Activities include a national annual scientific meeting, the informal formation of several regional and national research networks in specific areas, and the development of training opportunities. Challenges have included the issues of sustaining communication, addressing a range of networking and capacity-enhancement needs, cooperating in an environment that rewards competition, obtaining resources to support a secretariat and research activities, and balancing the demands to foster research excellence with the needs to create infrastructure and advocate for adequate research funding. LESSONS LEARNED: The CRHRS has learned how to begin to support researchers with diverse interests and needs across sectors and wide geographical areas, specifically by: (1) focusing on research development through creating and supporting trusting connections among researchers; (2) building the science first, followed by infrastructure development; (3) making individual researchers the nodes in the network; (4) being inclusive by accommodating a wide variety of researchers and researcher strengths; (5) emphasizing social exchange, knowledge exchange, and mentoring in annual scientific meetings; (6) taking opportunities to develop separate projects while finding ways to link them; (7) finding a balance between advancing the science and advocating for adequate funding and appropriate peer review; (8) developing a network organizational structure that is both stable and flexible; and (9) maintaining sustained visionary leadership.

Total dust and endotoxin in poultry operations: comparison between cage and floor housing and respiratory effects in workers.

OBJECTIVE: The objective of this study was to assess respiratory outcomes and environmental exposure levels of workers in cage-housed and floor-housed poultry operations. METHODS: Poultry operations were evaluated for total dust, endotoxin, and ammonia, and respiratory symptoms and lung function tests of workers were conducted. RESULTS: Workers in floor-housed poultry operations had significantly greater exposures to total dust and ammonia, whereas workers from cage-housed poultry operations reported greater frequency of current and chronic symptoms overall and significantly greater current and chronic phlegm (39% vs 18% and 40% vs 11%, respectively). Endotoxin concentration (EU/mg) was a significant predictor (P = 0.05) of chronic phlegm for all poultry workers. CONCLUSIONS: Greater endotoxin concentration in the presence of significantly lower total dust, in conjunction with greater respiratory symptoms in workers from cage-housed poultry operations, as compared with workers from floor-housed poultry operations, appears to indicate that differences in environmental exposures may impact respiratory outcomes of workers.

Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.

Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.

Evidence for major genetic control of wheeze in relation to history of respiratory allergy: Humboldt family study.

We report the results of segregation analyses for wheeze before and after a history of respiratory allergy was taken into consideration. The analyses were based on data from 309 nuclear families with 1,053 individuals living in the town of Humboldt, Saskatchewan in 1993, and were performed by using the REGD program of the SAGE package. For adults, information on wheeze and history of respiratory allergy was provided by themselves, and for children, by their parents. Segregation analyses were first conducted before adjustment for history of respiratory allergy. Other covariates were adjusted including sex, current smoking, household exposure to tobacco smoke, and type of house. A single locus model with residual familial effects fit the data well, but none of the Mendelian models (recessive, dominant, and codominant) could be distinguished. The no-parent-offspring-transmission hypothesis was rejected. However, when the variable of respiratory allergy was included in the models as a covariate, both Mendelian and environmental hypotheses were rejected. The Mendelian model had a relatively lower value of Akaike's Information Criterion than did the environmental model (1095.56 versus 1111.24). The data suggest that a single locus gene explains a portion of wheeze that is related to respiratory allergy, and that common environmental factors and/or polygenes also account for a certain familial aggregation of wheeze.

Segregation analyses of asthma and respiratory allergy: the Humboldt family study.

We performed segregation analyses of asthma and respiratory allergy based on data from 309 nuclear families comprising 1,053 individuals living in the town of Humboldt, Saskatchewan, in 1993, using the REGD program of the S.A.G.E. program package. For adults, information on asthma and history of respiratory allergy was provided by the subjects themselves, and for children by their parents. When asthma was considered as the trait in segregation analysis, models of no major effect, with or without familial effects, were rejected, but they were not rejected after adjusting for history of respiratory allergy. The major gene hypothesis was not rejected before adjusting for history of respiratory allergy. When respiratory allergy was analyzed as the trait, both major gene and multifactorial models fitted the data well, regardless of whether there was adjustment for asthma or not. Other covariates adjusted for in the segregation analyses were age, sex, number of household smokers, current smoking, number of household members, generation, and house type. The data suggest that a major gene related to respiratory allergy may explain the familial aggregation of asthma.

Men, women and primary lung cancer--a Saskatchewan personal interview study.

In a previous study conducted by mail questionnaire and with a large proportion of surrogate responders, we found differences in smoking habits, age at diagnosis, tumour cell type distribution and occupational exposures between men and women who developed primary lung cancer. This study was designed to confirm those findings by conducting personal case interviews and extend them by examining the impact of certain biological factors. We have investigated demographic, smoking, occupational and medical history sex differences in cases with primary lung cancer by interviewing 273 male and 103 female cases diagnosed between November 1983 and July 1986. The females were significantly younger at diagnosis, a pattern consistent for all cell types. Squamous cell (40%), small cell anaplastic (20%) and adenocarcinomas (16%) were the most prevalent cell types in men. In women, similar frequencies of adenocarcinomas (32%) and squamous cell carcinomas (29%) occurred. Despite a higher prevalence of physician diagnosed allergy and asthma among women, minimal sex differences in the prevalence of atopy as measured by prick skin test were found. Female cases were more likely to be lifetime non-smokers (15% vs 3%), to have started smoking on average 3 years older and to smoke 6 fewer cigarettes per day. The mean pack years of female cases was significantly lower than males' for squamous, adenocarcinoma and small cell anaplastic tumours. The majority of these women had not been occupationally exposed to any substance known to be carcinogenic or to damage the lung. However, in a small subset of cases pulmonary function variables were as depressed in women as in men with significantly higher mean pack years.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased airways responsiveness in swine farmers.

A respiratory questionnaire, pulmonary function tests, and an examination of airways responsiveness were conducted on 20 swine farmers and 20 control subjects. The swine farmers represented almost the complete work force from 13 Hutterite colonies and had worked in confinement buildings with more than 2,000 swine (3,270 +/- 1,221 swine) for at least four hours (6.6 +/- 1.8 hours) per day for more than two years (10.5 +/- 7.5 years). The control subjects were randomly selected from outdoor city workers from the city of Saskatoon and were matched for gender, age (+/- 2 years), and smoking status. Eleven swine farmers (55 percent) had chronic cough, compared with three (15 percent) of the control subjects (p less than 0.01). Eight (40 percent) of the swine farmers had symptoms of wheezing, compared with three (15 percent) of the control subjects (p less than 0.05). The FEV1 was significantly lower in swine farmers (97.2 +/- 11.5 percent predicted) than in control subjects (106.0 +/- 12.0 percent of predicted) (p less than 0.05). Airways responsiveness was measured by methacholine challenge with doubling concentrations ranging from 0.25 to 256 mg/ml. The provocation concentrations resulting in a reduction of 10 percent (PC10) and 20 percent (PC20) in FEV1 were lower in swine farmers than in control subjects (PC10, 77.2 +/- 78.8 mg/ml vs 180.8 +/- 96.5 mg/ml; p less than 0.01; and PC20, 154.5 +/- 99.9 mg/ml vs 229.6 +/- 66.8 mg/ml; p less than 0.05). Twelve swine farmers (60 percent) had PC20 of less than 256 mg/ml, compared with three (15 percent) of the control workers (p less than 0.01). Fewer swine farmers demonstrated atopy as measured by skin prick tests than did control workers (21 percent vs 56 percent; p less than 0.05). These findings suggested that occupational exposure in swine confinement buildings is associated with mild increases of nonspecific, nonatopic airways responsiveness in swine farmers.

Peripheral airways function and nonspecific airways reactivity in cigarette smokers.

Increasing concentrations of inhaled aerosolized histamine acid phosphate were administered to 31 heavy cigarette smokers from a smoking cessation clinic. Nineteen of 31 smokers (mean age +/- ISD: 39.6 +/- 11.5 yrs; pack years 25.5 +/- 13.5) failed to reduce forced expired volume in one second (FEV1) while inhaling histamine and were labelled nonresponders. In 12 of 31 smokers (age 38.4 +/- 9.4 yrs; pack years 23.0 +/- 10.5), extrapolated provocation concentration of inhaled histamine required to reduce forced expired volume in one second (FEV1) by 10 percent (PC10) could be determined and these smokers were labelled responders. We also measured maximum expiratory flow volume curves with air and also a mixture of 80 percent helium and 20 percent oxygen (HeO2) to determine the percentage of increase in maximal flow at 50 percent vital capacity breathing HeO2 as compared to air (delta Vmax50), and the slope of phase III of the single breath oxygen test (delta N2/L). In the responders, PC10 ranged from 1.4 mg/ml to 10.2 mg/ml (mean 5.5 +/- 3.3 mg/ml) and delta Vmax50 ranged from 7.1 percent to 68.4 percent (mean 39.6 +/- 18.3 percent). There was a significant positive correlation between PC10 and delta Vmax50 (r = 0.77, p less than 0.01), and a significant negative correlation between PC20 and delta N2/L (r = -.61, p less than 0.01). There was no difference between responders and nonresponders in mean values for lung function tests, allergy skin tests, or symptoms. These results suggest that there may be two fundamentally different groups of smokers with peripheral airways dysfunction: one group in which dysfunction is associated with, or related to, airways reactivity, and one group in which dysfunction is related to other factors.

Airway responsiveness to inhaled histamine in chronic obstructive airways disease. Chronic bronchitis vs emphysema.

Airway responsiveness to inhaled histamine was examined in two groups of carefully selected patients with nonasthmatic chronic obstructive airways disease (COAD). Twelve patients with chronic bronchitis and airflow obstruction but little emphysema and 13 with predominantly emphysema and airflow obstruction but little bronchitis were selected based on history, chest roentgenogram, and diffusing capacity for carbon monoxide (Dsb). Emphysema patients had less cough, less sputum, less chronic bronchitis, lower Dsb, and more radiographic evidence of vascular deficiency. There was no difference in anthropometric features, smoking history, atopic skin sensitivity, hemoglobin, blood eosinophilia, PaO2, PaCO2, ECG, lung volumes, or expiratory flow rates. The two groups had similar airway responsiveness to inhaled histamine; the geometric mean provocation concentrations producing a 20 percent FEV1 fall (PC20) was 0.56 mg/ml for the bronchitis patients and 0.28 mg/ml for the emphysema patients (p greater than 0.20). Regression of log histamine PC20 vs percent predicted FEV1 showed a high correlation in both groups (r = 0.73, p less than 0.01 in bronchitis and r = 0.79, p less than 0.001 in emphysema). The regression lines were almost identical. These data suggest that in COAD bronchial responsiveness to inhaled histamine is mainly due to the altered airway geometry, and that there is no difference in histamine responsiveness between patients with emphysematous COAD and nonemphysematous COAD with chronic bronchitis.

Risk factors for reduced pulmonary function in women. A possible relationship between Pi phenotype, number of children, and pulmonary function.

Smoking and severe deficiency of protease inhibitor (Pi Z phenotype) both contribute significantly to the development of chronic obstructive pulmonary disease (COPD). The role of moderate Pi deficiency (Pi MZ phenotype) remains controversial. During a community-wide study of respiratory health which included 1,633 individuals, of whom 897 were women, we measured forced vital capacity (FVC), forced expired flow in 1 s (FEV1), midmaximum expired flow rate (MMFR), flow rate at 50 percent of FVC (Vmax50%) and flow rate at 25 percent of FVC above residual volume (Vmax25%). We carried out Pi phenotyping on 544 of these women, including 22 who were Pi MZ or FZ phenotypes. There were no statistically significant differences in mean pulmonary function (pf) values between the Pi MZ and Pi M women. Examination of residual pf values (difference between observed and expected) by means of multiple multivariate regression analysis revealed that in Pi MZ women, FEV1/FVC%, MMFR, Vmax50%, and Vmax25% had significantly greater values with increasing numbers of children, whereas there was no relationship in the Pi M women. These results suggest that some factors may interact differently in individuals with Pi M and MZ phenotypes. In addition, the results suggest that pregnancy or pregnancy-induced increased Pi levels may have significant effects on the pulmonary health of Pi MZ women.

Characteristics of patients with primary lung cancer diagnosed at age of 50 years or younger.

We examined the extrinsic and intrinsic characteristics of patients with primary lung cancer diagnosed at early ages and compared them with those of older patients. Significant differences in gender distribution and histologic cell type were present. Cigarette smoking was an important etiologic factor in both groups.

Fatal cases of farmer's lung in a Canadian family. Probable new antigens, Penicillium brevicompactum and P olivicolor.

Three Canadian farmers, including a married couple and another close relative, died from progressive pulmonary fibrosis. Their histories and investigations were compatible with chronic farmer's lung (FL). Our environmental and immunologic studies indicate Penicillium brevicompactum and P olivicolor as probable new antigens of FL in a cool and dry climate.

Determinants of cell type in patients with cancer of the lungs.

In order to evaluate the determinants of cell type in patients with primary lung cancer, we compared smoking characteristics in 1,939 patients (1,474 men and 465 women). Patients with squamous cell carcinomas, adenocarcinomas, or small-cell carcinomas were eligible. This study did not consider smoking as a risk factor for lung cancer, as all subjects had a confirmed diagnosis. We were interested in smoking history and the pattern of smoking among those whose risk was 100 percent. Among these patients, we confirmed that a larger subset of nonsmoking individuals developed adenocarcinomas than squamous cell or small-cell carcinomas; however, the duration and intensity of cigarette smoking, as measured by pack-years, were not determinants of tumor cell type in male patients. Small-cell carcinomas in women were more strongly associated with cigarette smoking than either squamous cell carcinomas or adenocarcinomas. More than 3,500 different substances have been measured in tobacco smoke, including tumor initiators, promoters, and those involved in tumor progression. These data confirm the hypothesis that factors other than cigarette smoking are more likely to be involved in the initiation of adenocarcinomas than other cell types. Endogenous and exogenous factors related to gender may be more important than the duration or intensity of cigarette smoking.

Pulmonary function in Pi M and MZ grainworkers.

Twenty-eight men with the Pi MZ phenotype who have been employed in the Saskatchewan country grain elevators and thus regularly exposed to high levels of grain dust, were case matched for age, years of employment, employment status, smoking status, and smoking history with grainworkers of type Pi M. Individuals answered a questionnaire, had a chest roentgenogram, skin tests, and performed a battery of pulmonary function tests. There were no differences between the two groups in prevalence of symptoms or atopy. Although not statistically significant, the MZ group had three times as many individuals with abnormal roentgenograms suggestive of COPD as the M group. The Pi MZ grainworkers had consistently poorer mean results for the pulmonary function tests with significantly lower mean values for FEV1, FEV1/FVC, MMFR, and Vmax50, leading us to suggest that Pi MZ individuals may be at higher risk of COPD than Pi M individuals, but only in the presence of other risk factors such as grain dust exposure.

Lower prevalence of positive atopic skin tests in lung cancer patients.

Allergy prick skin testing was performed on 137 newly diagnosed patients with primary lung cancer and 137 age-(+/- 3 years) and sex-matched randomly selected control subjects. We also compared 38 patients with lung cancer and 38 of their closest in age, same-sex siblings. Demographic data, personal, medical, smoking and occupational histories were obtained by personal interview. We skin tested these individuals with a standard battery of seven common allergens and a diluent control. Fewer patients (35.8 percent) than control subjects (58.4 percent) responded with one or more positive skin reactions (p less than .005). There was no significant difference between patients (27.8 percent) and control subjects (37.2 percent) responding to more than one allergen. Fewer of the 38 sibling-matched patients had one or more positive skin tests (23.7 percent) than did their siblings (55.3 percent) (p less than .01). There were fewer patients with greater than one positive skin test (15.8 percent) than sibling control subjects (42.1 percent) (p less than .025). There were no differences in smoking pack-years between patients and siblings. Historic evidence of allergy was greater in both control groups compared to their matched cancer groups; p less than .05 for community controls, p less than .005 for sibling control subjects. These findings raise the possibility that atopy, by either immunologic or nonimmunologic means, protects against development of lung cancer, or alternately, that lung cancer affects immunologic status as gauged by (type 1) skin sensitivity.

Increased bronchial reactivity to inhaled histamine in nonsmoking grain workers with normal lung function.

We measured nonspecific bronchial reactivity to inhaled histamine in 26 lifetime nonsmoking grain handlers and 29 lifetime nonsmoking unexposed control subjects matched for age, sex and specific conductance. Routine lung function tests revealed a total lung capacity that was higher in control subjects than in workers (P less than 0.05) with no difference in other subdivisions of lung volume, or expiratory flow rates between the two groups. An index of allergy was significantly greater in the control subjects than in the grain workers (P less than 0.01). None of the grain handlers was sensitive to grain dust by history or by skin tests. Respiratory symptoms (cough, sputum, dyspnea, or wheezing) were more prevalent in the grain workers than in controls (P less than 0.05). The mean concentration of histamine required to reduce the specific conductance by 35 percent was 4.5 +/- 2.0 mg/ml in grain workers and 5.9 +/- 3.0 mg/ml in controls (P less than 0.05). Chronic exposure to grain dust in nonallergic individuals appears to be associated with both increased prevalence of respiratory symptoms and increased nonspecific bronchial reactivity when compared to nonexposed control subjects.