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Milton, Donald

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Milton

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Milton, Donald
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    Prevalence of asthma and allergies in children from the Greek-Cypriot and Turkish-Cypriot communities in Cyprus: a bi-communal cross-sectional study
    (BioMed Central, 2013) Lamnisos, Demetris; Moustaki, Maria; Kolokotroni, Ourania; Koksoy, Huseyin; Faiz, Muharrem; Arifoglu, Kenan; Milton, Donald; Middleton, Nicos; Yiallouros, Panayiotis K
    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.
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    Influenza Virus Aerosols in Human Exhaled Breath: Particle Size, Culturability, and Effect of Surgical Masks
    (Public Library of Science, 2013) Milton, Donald; Fabian, Maria; Cowling, Benjamin J.; Grantham, Michael L.; McDevitt, James
    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.
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    What was the primary mode of smallpox transmission? Implications for biodefense
    (Frontiers Media S.A., 2012) Milton, Donald
    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.
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    Collection of Aerosolized Human Cytokines Using Teflon® Filters
    (Public Library of Science, 2012) McKenzie, Jennifer Helen; McDevitt, James; Fabian, Maria; Hwang, Grace M.; Milton, Donald
    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.
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    Effects of Endotoxin Exposure on Childhood Asthma Risk are Modified by a Genetic Polymorphism in ACAA1
    (BioMed Central, 2011) Sordillo, Joanne; Sharma, Sunita; Poon, Audrey; Lasky-Su, Jessica; Belanger, Kathleen; Milton, Donald; Bracken, Michael B; Triche, Elizabeth W; Leaderer, Brian P; Gold, Diane; Litonjua, Augusto A.
    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.
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    A Longitudinal Study of Adult-Onset Asthma Incidence among HMO Members
    (BioMed Central, 2003) Sama, Susan R; Hunt, Phillip R; Cirillo, CIH Priscilla; Marx, Arminda; Rosiello, Richard A; Henneberger, Paul K; Milton, Donald
    Background: HMO databases offer an opportunity for community based epidemiologic studies of asthma incidence, etiology and treatment. The incidence of asthma in HMO populations and the utility of HMO data, including use of computerized algorithms and manual review of medical charts for determining etiologic factors has not been fully explored. Methods: We identified adult-onset asthma, using computerized record searches in a New England HMO. Monthly, our software applied exclusion and inclusion criteria to identify an "at-risk"; population and "potential cases". Electronic and paper medical records from the past year were then reviewed for each potential case. Persons with other respiratory diseases or insignificant treatment for asthma were excluded. Confirmed adult-onset asthma (AOA) cases were defined as those potential cases with either new-onset asthma or reactivated mild intermittent asthma that had been quiescent for at least one year. We validated the methods by reviewing charts of selected subjects rejected by the algorithm. Results: The algorithm was 93 to 99.3% sensitive and 99.6% specific. Sixty-three percent (n = 469) of potential cases were confirmed as AOA. Two thirds of confirmed cases were women with an average age of 34.8 (SD 11.8), and 45% had no evidence of previous asthma diagnosis. The annualized monthly rate of AOA ranged from 4.1 to 11.4 per 1000 at-risk members. Physicians most commonly attribute asthma to infection (59%) and allergy (14%). New-onset cases were more likely attributed to infection, while reactivated cases were more associated with allergies. Medical charts included a discussion of work exposures in relation to asthma in only 32 (7%) cases. Twenty-three of these (72%) indicated there was an association between asthma and workplace exposures for an overall rate of work-related asthma of 4.9%. Conclusion: Computerized HMO records can be successfully used to identify AOA. Manual review of these records is important to confirm case status and is useful in evaluation of provider consideration of etiologies. We demonstrated that clinicians attribute most AOA to infection and tend to ignore the contribution of environmental and occupational exposures.
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    Inactivation of Poxviruses by Upper-Room UVC Light in a Simulated Hospital Room Environment
    (Public Library of Science, 2008) McDevitt, James; Milton, Donald; Rudnick, Stephen; First, Melvin
    In the event of a smallpox outbreak due to bioterrorism, delays in vaccination programs may lead to significant secondary transmission. In the early phases of such an outbreak, transmission of smallpox will take place especially in locations where infected persons may congregate, such as hospital emergency rooms. Air disinfection using upper-room 254 nm (UVC) light can lower the airborne concentrations of infective viruses in the lower part of the room, and thereby control the spread of airborne infections among room occupants without exposing occupants to a significant amount of UVC. Using vaccinia virus aerosols as a surrogate for smallpox we report on the effectiveness of air disinfection, via upper-room UVC light, under simulated real world conditions including the effects of convection, mechanical mixing, temperature and relative humidity. In decay experiments, upper-room UVC fixtures used with mixing by a conventional ceiling fan produced decreases in airborne virus concentrations that would require additional ventilation of more than 87 air changes per hour. Under steady state conditions the effective air changes per hour associated with upper-room UVC ranged from 18 to 1000. The surprisingly high end of the observed range resulted from the extreme susceptibility of vaccinia virus to UVC at low relative humidity and use of 4 UVC fixtures in a small room with efficient air mixing. Increasing the number of UVC fixtures or mechanical ventilation rates resulted in greater fractional reduction in virus aerosol and UVC effectiveness was higher in winter compared to summer for each scenario tested. These data demonstrate that upper-room UVC has the potential to greatly reduce exposure to susceptible viral aerosols. The greater survival at baseline and greater UVC susceptibility of vaccinia under winter conditions suggest that while risk from an aerosol attack with smallpox would be greatest in winter, protective measures using UVC may also be most efficient at this time. These data may also be relevant to influenza, which also has improved aerosol survival at low RH and somewhat similar sensitivity to UVC.
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    Influenza Virus in Human Exhaled Breath: An Observational Study
    (Public Library of Science, 2008) Fabian, Patricia; McDevitt, James; DeHaan, Wesley H.; Fung, Rita O. P.; Cowling, Benjamin J.; Chan, Kwok Hung; Leung, Gabriel M.; Milton, Donald; Fouchier, Ron A. M.
    Background: Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection. Methodology/Principal Findings: We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects–three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 µm in diameter. Conclusions: These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission.
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    A Study of Indoor Carbon Dioxide Levels and Sick Leave among Office Workers
    (BioMed Central, 2002) Myatt, Theodore A; Staudenmayer, John; Adams, Kate; Walters, Michael D.; Rudnick, Stephen; Milton, Donald
    Background: A previous observational study detected a strong positive relationship between sick leave absences and carbon dioxide (CO2) concentrations in office buildings in the Boston area. The authors speculated that the observed association was due to a causal effect associated with low dilution ventilation, perhaps increased airborne transmission of respiratory infections. This study was undertaken to explore this association. Methods: We conducted an intervention study of indoor CO2 levels and sick leave among hourly office workers employed by a large corporation. Outdoor air supply rates were adjusted periodically to increase the range of CO2 concentrations. We recorded indoor CO2 concentrations every 10 minutes and calculated a CO2 concentration differential as a measure of outdoor air supply per person by subtracting the 1–3 a.m. average CO2 concentration from the same-day 9 a.m. – 5 a.m. average concentration. The metric of CO2 differential was used as a surrogate for the concentration of exhaled breath and for potential exposure to human source airborne respiratory pathogens. Results: The weekly mean, workday, CO2 concentration differential ranged from 37 to 250 ppm with a peak CO2 concentration above background of 312 ppm as compared with the American Society of Heating, Refrigeration and Air-conditioning Engineers (ASHRAE) recommended maximum differential of 700 ppm. We determined the frequency of sick leave among 294 hourly workers scheduled to work approximately 49,804.2 days in the study areas using company records. We found no association between sick leave and CO2 differential. Conclusions: The CO2 differential was in the range of very low values, as compared with the ASHRAE recommended maximum differential of 700 ppm. Although no effect was found, this study was unable to test whether higher CO2 differentials may be associated with increased sick leave.
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    Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria
    (National Institue of Environmental Health Sciences, 2005) Beckett, William; Kallay, Michael; Sood, Akshay; Zuo, Zhengfa; Milton, Donald
    A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace.