Occupational asthma: a review.

Occupational asthma is the most common form of occupational lung disease in the developed world at the present time. In this review, the epidemiology, pathogenesis/mechanisms, clinical presentations, management, and prevention of occupational asthma are discussed. The population attributable risk of asthma due to occupational exposures is considerable. Current understanding of the mechanisms by which many agents cause occupational asthma is limited, especially for low-molecular-weight sensitizers and irritants. The diagnosis of occupational asthma is generally established on the basis of a suggestive history of a temporal association between exposure and the onset of symptoms and objective evidence that these symptoms are related to airflow limitation. Early diagnosis, elimination of exposure to the responsible agent, and early use of inhaled steroids may play important roles in the prevention of long-term persistence of asthma. Persistent occupational asthma is often associated with substantial disability and consequent impacts on income and quality of life. Prevention of new cases is the best approach to reducing the burden of asthma attributable to occupational exposures. Future research needs are identified

Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma

Background: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. Methods: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. Results: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4–77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5–19.2) vs histology 11.1 (4.8–19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. Conclusions: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

Introduction: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. Methods: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 μg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. Results: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. Discussion: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry

Rationale, design and methods for a community-based study of clustering and cumulative effects on chronic disease process and their effects on ageing: the Busselton healthy ageing study

Background: The global trend of increased life expectancy and increased prevalence of chronic and degenerative diseases will impact on health systems. To identify effective intervention and prevention strategies, greater understanding of the risk factors for and cumulative effects of chronic disease processes and their effects on function and quality of life is needed. The Busselton Healthy Ageing Study aims to enhance understanding of ageing by relating the clustering and interactions of common chronic conditions in adults to function. Longitudinal (3–5 yearly) follow-up is planned. Methods/design: Phase I (recruitment) is a cross-sectional community-based prospective cohort study involving up to 4,000 ‘Baby Boomers’ (born from 1946 to 1964) living in the Busselton Shire, Western Australia. The study protocol involves a detailed, self-administered health and risk factor questionnaire and a range of physical assessments including body composition and bone density measurements, cardiovascular profiling (blood pressure, ECG and brachial pulse wave velocity), retinal photography, tonometry, auto-refraction, spirometry and bronchodilator responsiveness, skin allergy prick tests, sleep apnoea screening, tympanometry and audiometry, grip strength, mobility, balance and leg extensor strength. Cognitive function and reserve, semantic memory, and pre-morbid intelligence are assessed. Participants provide a fasting blood sample for assessment of lipids, blood glucose, C-reactive protein and renal and liver function, and RNA, DNA and serum are stored. Clinically relevant results are provided to all participants. The prevalence of risk factors, symptoms and diagnosed illness will be calculated and the burden of illness will be estimated based on the observed relationships and clustering of symptoms and illness within individuals. Risk factors for combinations of illness will be compared with those for single illnesses and the relation of combinations of illness and symptoms to cognitive and physical function will be estimated. Discussion: This study will enable a thorough characterization of multiple disease processes and their risk factors within a community-based sample of individuals to determine their singular, interactive and cumulative effects on ageing. The project will provide novel cross-sectional data and establish a cohort that will be used for longitudinal analyses of the genetic, lifestyle and environmental factors that determine whether an individual ages well or with impairment

The effect of chemotherapy on health-related quality of life in mesothelioma: Results from the SWAMP trial

© 2015 Cancer Research UK. All rights reserved. Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage

Exposure of bakery and pastry apprentices to airborne flour dust using PM2.5 and PM10 personal samplers

<p>Abstract</p> <p>Background</p> <p>This study describes exposure levels of bakery and pastry apprentices to flour dust, a known risk factor of occupational asthma.</p> <p>Methods</p> <p>Questionnaires on work activity were completed by 286 students. Among them, 34 performed a series of two personal exposure measurements using a PM_2.5and PM₁₀personal sampler during a complete work shift, one during a cold ("winter") period, and the other during a hot ("summer") period.</p> <p>Results</p> <p>Bakery apprentices experience greater average PM_2.5and PM₁₀exposures than pastry apprentices (p < 0.006). Exposure values for both particulate fractions are greater in winter (average PM₁₀values among bakers = 1.10 mg.m^-3[standard deviation: 0.83]) than in summer (0.63 mg.m^-3[0.36]). While complying with current European occupational limit values, these exposures exceed the ACGIH recommendations set to prevent sensitization to flour dust (0.5 mg.m^-3). Over half the facilities had no ventilation system.</p> <p>Conclusion</p> <p>Young bakery apprentices incur substantial exposure to known airways allergens, a situation that might elicit early induction of airways inflammation.</p

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis. OBJECTIVE: To investigate genetic susceptibility to PA. METHODS: Eight hundred and fifty cases and 926 hyper-controls and >7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. Meta-analysis of two phenotypes (PA and food allergy) was conducted using 7 studies from the Canadian, American (2), Australian, German and Dutch (2) populations. RESULTS: A SNP near ITGA6 reached genome-wide significance with PA (p=1.80×10(-8)), while SNPs associated with SKAP1, MMP12/MMP13, CTNNA3, ARHGAP24, ANGPT4, c11orf30 (EMSY), and EXOC4 reached a threshold suggestive of association (p≤1.49×10(-6)). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, c11orf30 and EXOC4 were significant (p≤1.49×10(-6)). When a phenotype of any food allergy was used for meta-analysis, the c11orf30 locus reached genome-wide significance (p=7.50×10(-11)), while SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, EXOC4 and additional c11orf30 SNPs were suggestive (p≤1.49×10(-6)). Functional annotation indicated SKAP1 regulates expression of CBX1, which co-localizes with the EMSY protein coded by c11orf30. CONCLUSION: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes c11orf30 as a risk locus for both peanut and food allergy. Multiple genes (c11orf30/EMSY, SKAP1 and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression