Brian P. Leaderer

Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium

BACKGROUND Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). METHODS We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. FINDINGS The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083). INTERPRETATION Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.

Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2205 pregnancies.

OBJECTIVE To prospectively examine in pregnant women whether asthma or asthma therapy influenced preterm delivery, intrauterine grown restriction (IUGR), or birthweight. METHODS We enrolled 873 pregnant women with a history of asthma, of whom 778 experienced asthma symptoms or took medication, and 1333 women with no asthma history, including 884 women with neither asthma diagnosis nor symptoms and 449 with symptoms but no diagnosis. Asthma symptoms, medication, and severity were classified according to 2002 Global Initiative for Asthma guidelines. RESULTS Preterm delivery was not associated with asthma diagnosis, severity, or symptoms but was associated with use of controller medications, independent of symptoms, specifically oral steroids and theophylline. Gestation was reduced by 2.22 weeks in women using oral steroids daily (P =.001) and 1.11 weeks after theophylline (P =.002). We observed a 24% (5-47%) increased risk for IUGR with each increased symptom step, which increased further in symptomatic women with no asthma diagnosis (31%, 4-65%) compared with women with neither asthma nor symptoms. CONCLUSIONS We found no effect of asthma symptoms or severity on preterm delivery but observed increased risks associated with use of oral steroid and theophylline. Intrauterine growth restriction was associated with asthma severity, which possibly reflects a hypoxic fetal effect. Women with asthma symptoms but no diagnosis were at particular risk of undermedication and delivering IUGR infants. These observations support guidelines that advocate active management of pregnant patients with mild or moderate asthma with beta(2) agonists, with oral steroids added only if severity increases. Symptomatic patients without an asthma diagnosis might need to be equally managed.

The relation between fungal propagules in indoor air and home characteristics

Background: Questionnaires are commonly used in epidemiologic studies to obtain information about house characteristics in order to predict the household aeroallergen exposure levels. However, the reliability of the predictions made with the questionnaires has not been evaluated. To address this issue, we compared objectively measured fungal propagules including the most frequently isolated mold genera (i.e., Alternaria, Aspergillus, Cladosporium, Penicillium, etc.) in a large sample of homes and compared these measured values to the questionnaire‐determined household characteristics.

Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in connecticut United States women

AbstractObjective: To further investigate the role of prior medical conditions and medication use in the etiology of non-Hodgkin lymphoma (NHL), we analyzed the data from a population-based case–control study of NHL in Connecticut women. Methods: A total of 601 histologically confirmed incident cases of NHL and 717 population-based controls were included in this study. In-person interviews were administered using standardized, structured questionnaires to collect information on medical conditions and medication use. Results: An increased risk was found among women who had a history of autoimmune disorders (such as rheumatoid arthritis, lupus erythematosus, Sjogrens syndrome, and multiple sclerosis), anemia, eczema, or psoriasis. An increased risk was also observed among women who had used steroidal anti-inflammatory drugs and tranquilizers. A reduced risk was found for women who had scarlet fever or who had used estrogen replacement therapy, aspirin, medications for non-insulin dependent diabetes, HMG-CoA reductase inhibitors, or beta-adrenergic blocking agents. Risk associated with past medical history appeared to vary based on NHL subtypes, but the results were based on small number of exposed subjects. Conclusion: A relationship between certain prior medical conditions and medication use and risk of NHL was observed in this study. Further studies are warranted to confirm our findings.

Comparisons of seasonal fungal prevalence in indoor and outdoor air and in house dusts of dwellings in one Northeast American county.

Fungi cause allergies and many other adverse health effects. In this study, we characterized the nature and seasonal variation of fungi inside and outside homes in the Greater New Haven, Connecticut area. Three indoor air samples (in the living room, bedroom, and basement) and one outdoor sample were collected by the Burkard portable air sampler. House dust samples were collected in the living room by a vacuum cleaner. The mold concentrations varied widely from house to house in both indoor and outdoor air. No significant difference (p>0.05) in concentration and type of fungi between living room and bedroom or by season was observed. Both concentration and type of fungi were significantly higher (p<0.05) in the basement than other indoor areas and outdoor air in winter. The type of fungi in living room, bedroom, and outdoor air were found to have significant changes among seasons, but there was no significant difference for the basement among seasons. Cladosporium spp. was dominant in both indoor and outdoor air in summer. Penicillium and Aspergillus were dominant in indoor air in winter, but neither was dominant in any season in outdoor air. The type of fungi and their concentrations in house dust samples were not representative of those isolated in indoor air. In dust samples, more Mucor, Wallemia, and Alternaria species, but less Aspergillus, Cladosporium, and Penicillium species were found in all seasons. Air sampling in spring or fall in every suspected house is suggested for year-round fungal exposure assessment.

Prenatal Exposure to Fine Particulate Matter and Birth Weight: Variations by Particulate Constituents and Sources

Background: Exposure to fine particles (PM2.5) during pregnancy has been linked to lower birth weight; however, the chemical composition of PM2.5 varies widely. The health effects of PM2.5 constituents are unknown. Methods: We investigated whether PM2.5 mass, constituents, and sources are associated with birth weight for term births. PM2.5 filters collected in 3 Connecticut counties and 1 Massachusetts county from August 2000 through February 2004 were analyzed for more than 50 elements. Source apportionment was used to estimate daily contributions of PM2.5 sources, including traffic, road dust/crustal, oil combustion, salt, and regional (sulfur) sources. Gestational and trimester exposure to PM2.5 mass, constituents, and source contributions were examined in relation to birth weight and risk of small-at-term birth (term birth <2500 g) for 76,788 infants. Results: Road dust and related constituents such as silicon and aluminum were associated with lower birth weight, as were the motor-vehicle-related species such as elemental carbon and zinc, and the oil-combustion-associated elements vanadium and nickel. An interquartile range increase in exposure was associated with low birthweight for zinc (12% increase in risk), elemental carbon (13%), silicon (10%), aluminum (11%), vanadium (8%), and nickel (11%). Analysis by trimester showed effects of third-trimester exposure to elemental carbon, nickel, vanadium, and oil-combustion PM2.5. Conclusions: Exposures of pregnant women to higher levels of certain PM2.5 chemical constituents originating from specific sources are associated with lower birth weight.

Symptoms and Medication Use in Children with Asthma and Traffic-Related Sources of Fine Particle Pollution

Background Exposure to ambient fine particles [particulate matter ≤ 2.5 μm diameter (PM2.5)] is a potential factor in the exacerbation of asthma. National air quality particle standards consider total mass, not composition or sources, and may not protect against health impacts related to specific components. Objective We examined associations between daily exposure to fine particle components and sources, and symptoms and medication use in children with asthma. Methods Children with asthma (n = 149) 4–12 years of age were enrolled in a year-long study. We analyzed particle samples for trace elements (X-ray fluorescence) and elemental carbon (light reflectance). Using factor analysis/source apportionment, we identified particle sources (e.g., motor vehicle emissions) and quantified daily contributions. Symptoms and medication use were recorded on study diaries. Repeated measures logistic regression models examined associations between health outcomes and particle exposures as elemental concentrations and source contributions. Results More than half of mean PM2.5 was attributed to traffic-related sources motor vehicles (42%) and road dust (12%). Increased likelihood of symptoms and inhaler use was largest for 3-day averaged exposures to traffic-related sources or their elemental constituents and ranged from a 10% increased likelihood of wheeze for each 5-μg/m3 increase in particles from motor vehicles to a 28% increased likelihood of shortness of breath for increases in road dust. Neither the other sources identified nor PM2.5 alone was associated with increased health outcome risks. Conclusions Linking respiratory health effects to specific particle pollution composition or sources is critical to efforts to protect public health. We associated increased risk of symptoms and inhaler use in children with asthma with exposure to traffic-related fine particles.

Collection and analysis of nicotine as a marker for environmental tobacco smoke

Abstract Nicotine is a potential marker for environmental tobacco smoke (ETS) because it is unique to tobacco smoke and is a major constituent of the smoke. An air sampling method is presented which efficiently collects both particulate and vapor phase nicotine. Two filters are assembled in tandem in a personal sampling cassette. The first filter collects total or size fractional particules and the second is treated with sodium bisulfate to collect vapor phase nicotine and nicotine which has volatilized from the paniculate material collected on the first filler. The nicotine is then desorbed from the filters and analyzed by gas chromatography with nitrogen sensitive detection. The sampling method was evaluated in an environmental chamber under controlled conditions of temperature, humidity, ventilation and smoking rate. It was then employed in a field study of particulate exposures of railroad office workers and railroad mechanics to determine the portion of the particulate exposure attributable to environmental tobacco smoke. The method was found to be efficient and sensitive for the determination of nicotine levels in air.

Ventilation requirements in buildings—I. Control of occupancy odor and tobacco smoke odor

Abstract Psychophysical measurements of odor, supplemented with certain physical measurements, were taken to examine ventilation requirements during smoking and nonsmoking occupancy in an environmental chamber. The facility provided the means to compare impressions of visitors (persons who inhaled air from the chamber only briefly) with impressions of occupants. For nonsmoking occupancy, 47 combinations of temperature, humidity, ventilation rate and occupancy density were examined. Odor level depended entirely on ventilation rate per person irrespective of the number of persons in the chamber. The ventilation necessary to satisfy 75 % of visitors equalled only about 4 l s −1 per person. Occupants, however, were satisfied with far less. In an array of 38 conditions of smoking occupancy, the ventilation deemed necessary to satisfy 75 % of visitors under customary conditions of occupancy equalled 17.5 l s −1 per person. For both smoking and nonsmoking conditions, a combination of high temperature (25.5°C) and humidity (r.h. > 70 %) exacerbated the odor problem. During smoking, carbon monoxide rarely reached dangerous levels, but suspended particulate matter often reached levels considered unacceptable outdoors. The results highlight the energy penalty incurred in ventilation for smoking occupancy.

Heterogeneity in assessing self-reports of caffeine exposure: Implications for studies of health effects

Background. Coffee and its metabolite caffeine are widely studied for their health effects but with inconclusive results. Caffeine is particularly difficult to assess, and therefore we explore heterogeneity of caffeine exposure. Methods. We categorized caffeine exposure among 2,478 pregnant women in southern New England during 1996–2000 by the traditional laboratory-based methods of M. Bunker and M. McWilliams. A subsample was examined to ascertain caffeine levels of brewed or purchased beverages actually consumed. Results. More than half (56.6%) of women drank coffee since becoming pregnant. Serving sizes ranged from 2 to 32 oz and are considerably larger than laboratory standards, which are typically 8–10 oz, as compared with the standard of 5 to 6 oz. Conversely, caffeine content per serving of coffee was one-third the laboratory standard, eg, 100 mg caffeine compared with 300 mg for a 10-oz cup. Tea brewed more than 3 minutes contained 42 mg caffeine as compared with the standard of 94 mg. When the amount of caffeine actually consumed was measured, one-quarter (24.8%) of subjects traditionally classified as consuming 300+ gm caffeine daily were reclassified as consuming 150–299 mg. Conclusion. Misclassification of caffeine consumption increases difficulty in identifying health effects from caffeine. Some combination of more precise consumption data and a biomarker such as paraxanthine may more precisely estimate exposure.