Person:

Milton, Donald

Bioaerosol concentrations in office environments and their roles in causing building-related symptoms have drawn much attention in recent years. Most bioaerosol studies have been cross-sectional. We conducted a longitudinal study to examine the characteristics of airborne fungal populations and correlations with other environmental parameters in office environments. We investigated four office buildings in Boston, Massachusetts, during 1 year beginning May 1997, recruiting 21 offices with open workstations. We conducted intensive bioaerosol sampling every 6 weeks resulting in 10 sets of measurement events at each workstation, and recorded relative humidity, temperature, and CO2 concentrations continuously. We used principal component analysis (PCA) to identify groups of culturable fungal taxa that covaried in air. Four major groupings (PCA factors) were derived where the fungal taxa in the same groupings shared similar ecological requirements. Total airborne fungal concentrations varied significantly by season (highest in summer, lowest in winter) and were positively correlated with relative humidity and negatively related to CO2 concentrations. The first and second PCA factors had similar correlations with environmental variables compared with total fungi. The results of this study provide essential information on the variability within airborne fungal populations in office environments over time. These data also provide background against which cross-sectional data can be compared to facilitate interpretation. More studies are needed to correlate airborne fungi and occupants' health, controlling for seasonal effects and other important environmental factors.

Endotoxin exposure has been proposed as an environmental determinant of allergen responses in children. To better understand the implications of using a single measurement of house dust endotoxin to characterize exposure in the first year of life, we evaluated room-specific within-home and between-home variability in dust endotoxin obtained from 470 households in Boston, Massachusetts. Homes were sampled up to two times over 5–11 months. We analyzed 1,287 dust samples from the kitchen, family room, and baby’s bedroom for endotoxin. We fit a mixed-effects model to estimate mean levels and the variation of endotoxin between homes, between rooms, and between sampling times. Endotoxin ranged from 2 to 1,945 units per milligram of dust. Levels were highest during summer and lowest in the winter. Mean endotoxin levels varied significantly from room to room. Cross-sectionally, endotoxin was moderately correlated between family room and bedroom floor (r = 0.30), between family room and kitchen (r = 0.32), and between kitchen and bedroom (r = 0.42). Adjusting for season, the correlation of endotoxin levels within homes over time was 0.65 for both the bedroom and kitchen and 0.54 for the family room. The temporal within-home variance of endotoxin was lowest for bedroom floor samples and highest for kitchen samples. Between-home variance was lowest in the family room and highest for kitchen samples. Adjusting for season, within-home variation was less than between-home variation for all three rooms. These results suggest that room-to-room and home-to-home differences in endotoxin influence the total variability more than factors affecting endotoxin levels within a room over time.

Exposure to elevated levels of endotoxin in family-room dust was previously observed to be significantly associated with increased wheeze in the first year of life among a cohort of 404 children in the Boston, Massachusetts, metropolitan area. However, it is likely that family-room dust endotoxin was a surrogate for airborne endotoxin exposure. Therefore, a related substudy characterized the relationship between levels of airborne household endotoxin and the level of endotoxin present in house dust, in addition to identifying other significant predictors of airborne endotoxin in the home. We now reexamine the relationship between endotoxin exposure and wheeze under the assumption that the level of airborne endotoxin in the home is the exposure of interest and that the amount of endotoxin in household dust is a surrogate for this exposure. We applied a measurement error correction technique, using all available data to estimate the effect of endotoxin exposure in terms of airborne concentration and accounting for the measurement error induced by using house-dust endotoxin as a surrogate measure in the portion of the data in which airborne endotoxin could not be directly measured. After adjusting for confounding by lower respiratory infection status and race/ethnicity, endotoxin exposure was found to be significantly associated with a nearly 6-fold increase in prevalence of wheeze for a one interquartile range increase in airborne endotoxin (95% confidence interval, 1.2–26) among the 360 children in households with dust endotoxin levels between the 5th and 95th percentiles.

Background: A growing body of epidemiologic evidence suggests an association between exposure to cleaning products with asthma and other respiratory disorders. Thus far, these studies have conducted only limited quantitative exposure assessments. Exposures from cleaning products are difficult to measure because they are complex mixtures of chemicals with a range of physicochemical properties, thus requiring multiple measurement techniques. We conducted a pilot exposure assessment study to identify methods for assessing short term, task-based airborne exposures and to quantitatively evaluate airborne exposures associated with cleaning tasks simulated under controlled work environment conditions. Methods: Sink, mirror, and toilet bowl cleaning tasks were simulated in a large ventilated bathroom and a small unventilated bathroom using a general purpose, a glass, and a bathroom cleaner. All tasks were performed for 10 minutes. Airborne total volatile organic compounds (TVOC) generated during the tasks were measured using a direct reading instrument (DRI) with a photo ionization detector. Volatile organic ingredients of the cleaning mixtures were assessed utilizing an integrated sampling and analytic method, EPA TO-17. Ammonia air concentrations were also measured with an electrochemical sensor embedded in the DRI. Results: Average TVOC concentrations calculated for 10 minute tasks ranged 0.02 - 6.49 ppm and the highest peak concentrations observed ranged 0.14-11 ppm. TVOC time concentration profiles indicated that exposures above background level remained present for about 20 minutes after cessation of the tasks. Among several targeted VOC compounds from cleaning mixtures, only 2-BE was detectable with the EPA method. The ten minute average 2- BE concentrations ranged 0.30 -21 ppm between tasks. The DRI underestimated 2-BE exposures compared to the results from the integrated method. The highest concentration of ammonia of 2.8 ppm occurred during mirror cleaning. Conclusions: Our results indicate that airborne exposures from short-term cleaning tasks can remain in the air even after tasks' cessation, suggesting potential exposures to anyone entering the room shortly after cleaning. Additionally, 2-BE concentrations from cleaning could approach occupational exposure limits and warrant further investigation. Measurement methods applied in this study can be useful for workplace assessment of airborne exposures during cleaning, if the limitations identified here are addressed.

Background: Collection of exhaled breath samples for the analysis of inflammatory biomarkers is an important area of research aimed at improving our ability to diagnose, treat and understand the mechanisms of chronic pulmonary disease. Current collection methods based on condensation of water vapor from exhaled breath yield biomarker levels at or near the detection limits of immunoassays contributing to problems with reproducibility and validity of biomarker measurements. In this study, we compare the collection efficiency of two aerosol-to-liquid sampling devices to a filter-based collection method for recovery of dilute laboratory generated aerosols of human cytokines so as to identify potential alternatives to exhaled breath condensate collection. Methodology/Principal Findings: Two aerosol-to-liquid sampling devices, the SKC® Biosampler and Omni 3000™, as well as Teflon® filters were used to collect aerosols of human cytokines generated using a HEART nebulizer and single-pass aerosol chamber setup in order to compare the collection efficiencies of these sampling methods. Additionally, methods for the use of Teflon® filters to collect and measure cytokines recovered from aerosols were developed and evaluated through use of a high-sensitivity multiplex immunoassay. Our results show successful collection of cytokines from pg/m3 aerosol concentrations using Teflon® filters and measurement of cytokine levels in the sub-picogram/mL concentration range using a multiplex immunoassay with sampling times less than 30 minutes. Significant degradation of cytokines was observed due to storage of cytokines in concentrated filter extract solutions as compared to storage of dry filters. Conclusions: Use of filter collection methods resulted in significantly higher efficiency of collection than the two aerosol-to-liquid samplers evaluated in our study. The results of this study provide the foundation for a potential new technique to evaluate biomarkers of inflammation in exhaled breath samples.

The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.

The CDC recommends that healthcare settings provide influenza patients with facemasks as a means of reducing transmission to staff and other patients, and a recent report suggested that surgical masks can capture influenza virus in large droplet spray. However, there is minimal data on influenza virus aerosol shedding, the infectiousness of exhaled aerosols, and none on the impact of facemasks on viral aerosol shedding from patients with seasonal influenza. We collected samples of exhaled particles (one with and one without a facemask) in two size fractions (“coarse”>5 µm, “fine”≤5 µm) from 37 volunteers within 5 days of seasonal influenza onset, measured viral copy number using quantitative RT-PCR, and tested the fine-particle fraction for culturable virus. Fine particles contained 8.8 (95% CI 4.1 to 19) fold more viral copies than did coarse particles. Surgical masks reduced viral copy numbers in the fine fraction by 2.8 fold (95% CI 1.5 to 5.2) and in the coarse fraction by 25 fold (95% CI 3.5 to 180). Overall, masks produced a 3.4 fold (95% CI 1.8 to 6.3) reduction in viral aerosol shedding. Correlations between nasopharyngeal swab and the aerosol fraction copy numbers were weak (r = 0.17, coarse; r = 0.29, fine fraction). Copy numbers in exhaled breath declined rapidly with day after onset of illness. Two subjects with the highest copy numbers gave culture positive fine particle samples. Surgical masks worn by patients reduce aerosols shedding of virus. The abundance of viral copies in fine particle aerosols and evidence for their infectiousness suggests an important role in seasonal influenza transmission. Monitoring exhaled virus aerosols will be important for validation of experimental transmission studies in humans.

Background: Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children. Methods: In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6. Results: We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele. Conclusion: Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.

Background: The Greek-Cypriot (G/C) and Turkish-Cypriot (T/C) communities have lived apart since 1974, with the former presumably adopting a more westernized way of life. We estimated the prevalence of asthma and allergies among children in the two communities and investigated differences in socio-demographic and lifestyle risk factors. Methods: The ISAAC questionnaire was completed by 10156 children aged 7–8 and 13–14 years. Relative differences in asthma and allergic symptoms between the two communities were expressed as odds ratios (OR), estimated in multivariable logistic regression models before and after adjusting for participants’ risk characteristics. Results: In contrast to our original speculation, consistently lower prevalence rates were observed for respiratory outcomes (but not eczema) among G/C compared to T/C children in both age-groups. For instance, the prevalence of current wheeze among 7–8 year-olds was 8.7% vs 11.4% (OR = 0.74, 95%, CI: 0.61, 0.90) and of current rhinoconjuctivitis 2.6% vs 4.9% (OR = 0.52, 95% CI: 0.37, 0.71). Surprisingly, the proportion reporting family history of allergy was almost double in the G/C community. With the exception of early life nursery attendance, several protective factors were more prevalent amongst T/C, such as bedroom sharing, less urbanized environment and exposure to farm animals. In contrast, exposure to tobacco smoke was more frequent in the T/C community. Controlling for risk factors did not account for the observed lower prevalence of current wheeze (in the younger age-group) and rhinoconjuctivitis (in both age-groups) among G/C children while differences in the prevalence of eczema between the two communities were no longer statistically significant. Conclusions: A mixed picture of potential risk factors was observed in the two communities of Cyprus, not consistently favoring one over the other community since, for example, bedroom sharing and rural living but also exposure to tobacco smoke were more common among T/C children. Investigated risk factors do not fully account for the lower prevalence of asthma and allergies among G/C children, especially against a background of higher family history of allergy in this community.