Thermal desorption effects on fragment ion production from multi-photon ionized uridine and selected analogues.

Experiments on neutral gas-phase nucleosides are often complicated by thermal lability. Previous mass spectrometry studies of nucleosides have identified enhanced relative production of nucleobase ions (e.g. uracil+ from uridine) as a function of desorption temperature to be the critical indicator of thermal decomposition. On this basis, the present multi-photon ionization (MPI) experiments demonstrate that laser-based thermal desorption is effective for producing uridine, 5-methyluridine, and 2'-deoxyuridine targets without thermal decomposition. Our experiments also revealed one notable thermal dependence: the relative production of the sugar ion C5H9O4 + from intact uridine increased substantially with the desorption laser power and this only occurred at MPI wavelengths below 250 nm (full range studied 222-265 nm). We argue that this effect can only be rationalized plausibly in terms of changing populations of different isomers, tautomers, or conformers in the target as a function of the thermal desorption conditions. Furthermore, the wavelength threshold behavior of this thermally-sensitive MPI channel indicates a critical dependence on neutral excited state dynamics between the absorption of the first and second photons. The experimental results are complemented by density functional theory (DFT) optimizations of the lowest-energy structure of uridine and two further conformers distinguished by different orientations of the hydroxymethyl group on the sugar part of the molecule. The energies of the transitions states between these three conformers are low compared with the energy required for decomposition.

An observational study of PM10 and hospital admissions for acute exacerbations of chronic respiratory disease in Tasmania, Australia 1992-2002.

OBJECTIVE: Particulate matter with a diameter below 10 µ (PM10) has been a major concern in the Tamar Valley, Launceston, where wood heaters are extensively used. We examined the relationship between PM10 levels, meteorological variables, respiratory medications and hospital admissions for respiratory disease over the decade 1992-2002. METHODS: PM10 levels were provided by the Department of Primary Industry Water, Parks and Environment, and meteorological variables from the Bureau of Meteorology. We obtained hospital discharge codes for the Launceston General Hospital. Poisson regression was used for statistical analyses. RESULTS: Mean daily PM10 levels declined from 50.7 to 16.5 µg/m(3). Hospitalisations for asthma decreased from 29 to 21 per month, whereas chronic obstructive pulmonary disease (COPD) increased and bronchitis/bronchiolitis remained unchanged. We found a 10 µg/m(3) increase in PM10 to be associated with a 4% increase in admissions for acute bronchitis/bronchiolitis (p0.05), but no association with asthma or COPD was found. All respiratory diseases showed seasonal patterns of hospitalisation. CONCLUSIONS: This is the first long-term study in Australia to demonstrate an association between PM10 levels and respiratory diseases. Reducing exposure to PM10 may decrease hospital admissions for respiratory diseases. IMPLICATION: Better preventive measures, including sustained public health initiatives to combat air pollution, are required to reduce respiratory morbidity.

Adult serum cytokine concentrations and the persistence of asthma.

BACKGROUND: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. METHODS: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. RESULTS: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. CONCLUSION: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.

Ambient wood smoke exposure and respiratory symptoms in Tasmania, Australia.

Wood smoke exposure has been associated with adverse respiratory health outcomes, with much of the current research focused on wood smoke from domestic heating and cooking. This study examined the association between respiratory symptoms and outdoor wood smoke in Launceston, Tasmania, where ~30% of homes use wood burners for domestic heating. This ecological study examined data from participants of the 2004 Tasmanian Longitudinal Health Study postal survey and compared the prevalence of respiratory symptoms in Launceston (n=601) with that in Hobart (n=1071), a larger Tasmanian city with much less wood smoke. Multivariate logistic regression models were used to investigate the associations of interest while adjusting for gender, atopy, history of allergic disease and current smoking status. There were no significant differences in symptom prevalence between Launceston and Hobart. Two subgroup analyses, which examined participants with pre-existing chronic respiratory disease, and those who reported actively using a wood burner in their home, also did not find significant differences. Any impact of wood smoke on non-specific respiratory symptoms might have been overshadowed by other important determinants of respiratory health, such as vehicle exhaust and tobacco smoking, or were too small to have been detected. However, the lack of detectable differences in symptom prevalence might also reflect the success of regulatory action by local governments to reduce wood smoke emissions in Launceston. The results of other epidemiological studies support an association between ambient wood smoke exposure and adverse respiratory health. Further investigations of wood smoke exposure in Australian settings are needed to investigate the lack of significant associations found in this study, especially studies of indoor air quality and health impacts in children and elderly populations.

Poor lung function and tonsillectomy in childhood are associated with mortality from age 18 to 44.

BACKGROUND: The aim of this analysis was to examine associations between lung health in childhood and mortality between ages 18 and 44 years in the Tasmanian Longitudinal Health Study (TAHS). METHODS: The 1961 Tasmanian birth cohort who attended school in 1968 (n=8583) were linked to the Australian National Death Index (NDI) to identify deaths. Additional deaths were notified by families through a 37 year follow-up postal questionnaire. Information on lung health at age 7 years and on potential confounders was obtained from the original 1968 TAHS survey and school medical records. Cox proportional hazards modelling was used to assess determinants of mortality. RESULTS: A total of 264 (3%) deaths were identified. The principal causes of death were external injury (56.1%, n=97) and cancer (17.9%, n=31). Males were more likely than females to have died (p=<0.1). Only two (1.1%) participants had died from respiratory conditions. Having an FEV(1)<80% predicted at 7 years of age was associated with a 2-fold increased incidence of death. Tonsillectomy before age 7 years was associated with a 1.5-fold increase in mortality (p=0.05); being male with a 3.6-fold increase in mortality (p=0.0001); and repeated chest illnesses at age 7 years causing >30 days confinement in the last year, was associated with a 2.2-fold increase in mortality (p=0.03). CONCLUSIONS: Childhood lung health appears to be associated with increased mortality in adulthood, perhaps by affecting the ability to survive trauma, major illnesses and other physical stresses.

Adherence to asthma management guidelines by middle-aged adults with current asthma.

BACKGROUND: With the increasing burden of asthma worldwide, much effort has been given to developing and updating management guidelines. Using data from the Tasmanian Longitudinal Health Study (TAHS), the adequacy of asthma management for middle-aged adults with asthma was investigated. METHODS: Information about spirometry, medication history and current asthma status was collected by the most recent TAHS when participants were in their mid 40s. Only those who reported ever having asthma were eligible for analysis. RESULTS: Of the 702 participants who reported ever having asthma, 50% had current asthma (n = 351) of whom 71% were categorised as having persistent asthma (n = 98 mild, n = 92 moderate, n = 58 severe). The majority (85.2%) of participants with current asthma had used some form of asthma medication in the past 12 months, but the proportion of the use of minimally adequate preventer medication was low (26%). Post-bronchodilator airflow obstruction increased progressively from mild to severe persistent asthma for those inadequately managed, but not for those on adequate therapy. CONCLUSION: Appropriate use of asthma medication by this middle-aged group of adults with current asthma was inadequate, especially for those with adult-onset moderate or severe persistent disease and without a family history of asthma. These results suggest that proper use of preventer medication could protect against the progressive decline in lung function associated with increasing severity. This has implications not just for poor quality of life, but also for the development of fixed airflow obstruction.