Airway microbial communities, smoking and asthma in a general population sample.

BACKGROUND: Normal airway microbial communities play a central role in respiratory health but are poorly characterized. Cigarette smoking is the dominant global environmental influence on lung function, and asthma has become the most prevalent chronic respiratory disease worldwide. Both conditions have major microbial components that are incompletely defined. METHODS: We investigated airway bacterial communities in a general population sample of 529 Australian adults. Posterior oropharyngeal swabs were analyzed by sequencing of the 16S rRNA gene. The microbiota were characterized according to their prevalence, abundance and network memberships. FINDINGS: The microbiota were similar across the general population, and were strongly organized into co-abundance networks. Smoking was associated with diversity loss, negative effects on abundant taxa, profound alterations to network structure and expansion of Streptococcus spp. By contrast, the asthmatic microbiota were selectively affected by an increase in Neisseria spp. and by reduced numbers of low abundance but prevalent organisms. INTERPRETATION: Our study shows that the healthy airway microbiota in this population were contained within a highly structured ecosystem, suggesting balanced relationships between the microbiome and human host factors. The marked abnormalities in smokers may contribute to chronic obstructive pulmonary disease (COPD) and lung cancer. The narrow spectrum of abnormalities in asthmatics encourages investigation of damaging and protective effects of specific bacteria. FUNDING: The study was funded by the Asmarley Trust and a Wellcome Joint Senior Investigator Award to WOCC and MFM (WT096964MA and WT097117MA). The Busselton Healthy Ageing Study is supported by the Government of Western Australia (Office of Science, Department of Health) the City of Busselton, and private donations.

Pleurodesis outcome in malignant pleural mesothelioma.

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.

Postmortem findings of malignant pleural mesothelioma: a two-center study of 318 patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an incurable cancer with a rising incidence. MPM is often perceived as a locally invasive cancer, and the exact cause of death is poorly understood.This two-center study describes the anatomic features of patients with MPM at postmortem. METHODS: The Western Australia Mesothelioma Registry (Australia) and Coroner's Office reports from the Avon region (England) were interrogated for the postmortem records of confirmed mesothelioma cases. RESULTS: Postmortem records of 318 patients with pleural mesothelioma (169 from Western Australia and 149 from Avon) were identified. Most patients (91.5%) were men (mean age, 68.4 ± 11.5 years), and MPM was right-sided in 55.3%. Extrapleural dissemination of tumor was found in 87.7% of cases and lymph node involvement in 53.3%. Tumor dissemination in extra thoracicsites was common (55.4% of patients), and almost all organs were involved, including liver(31.9%), spleen (10.8%), thyroid (6.9%), and the brain (3.0%). Pulmonary emboli were found in 6% of cases and considered as directly contributing to death in 13 patients (4.1%). The precise cause of death could only be determined in 63 (19.8%) cases even after postmortem. The BMI was significantly lower in cases that had no identifiable anatomic cause of death at postmortem(18.8 ± 4.3 vs 21.0 ± 4.7, P = .034). CONCLUSIONS: In this largest, to our knowledge, postmortem series on MPM, extrathoracic dissemination of mesothelioma was common and often under recognized. No anatomic cause of death was identified in the majority of patients even at autopsy, raising the possibility of physiologic and metabolic causes of death.

Early prediction of response to chemotherapy and survival in malignant pleural mesothelioma using a novel semiautomated 3-dimensional volume-based analysis of serial 18F-FDG PET scans.

UNLABELLED: The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival. Measuring response using CT is challenging because of the circumferential tumor growth pattern. This study aims to evaluate the role of serial (18)F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma. METHODS: Patients were prospectively recruited and underwent both (18)F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy. Quantitative volume-based (18)F-FDG PET analysis was performed to obtain the total glycolytic volume (TGV) of the tumor. Survival outcomes were measured. RESULTS: Twenty-three patients were suitable for both radiological and (18)F-FDG PET analysis, of whom 20 had CT measurable disease. After 1 cycle of chemotherapy, 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In the 7 patients with radiological partial response, the median TGV on quantitative PET analysis fell to 30% of baseline (range, 11%-71%). After 1 cycle of chemotherapy, Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival (P = 0.015). Neither a reduction in the maximum standardized uptake value (P = 0.097) nor CT (P = 0.131) demonstrated a statistically significant association with patient survival. CONCLUSION: Semiquantitative (18)F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment. Therefore, metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients. This technology may also be useful in the assessment of new systemic treatments for mesothelioma.

Asbestos-induced and smoking-related disease: apportioning pulmonary function deficit by using thin-section CT.

PURPOSE: To retrospectively correlate the extent of individual diseases seen at thin-section computed tomography (CT) with pulmonary function in an initial group of patients with asbestos-related parenchymal disease (asbestosis) and to test these findings in a subsequent group of patients whose CT scans were retrospectively identified. MATERIALS AND METHODS: This retrospective study had Institutional Review Board approval; informed consent was not required. The study included 133 individuals who had been exposed to asbestos. In the initial study group (81 patients; 79 men, two women; median age, 67 years), two observers used a CT scoring system to quantify the extent of pulmonary fibrosis, diffuse pleural thickening, small-airways disease, and emphysema. Multivariate equations were formulated by using independent CT variables to predict changes in total lung capacity (TLC) and carbon monoxide diffusing capacity (Dlco). The validity of these equations was then tested in a subsequent group of patients (52 patients; all men; median age, 60 years). RESULTS: At thin-section CT, the extent of asbestos-induced pleuropulmonary disease and emphysema correlated significantly with physiologic impairment (P<.001). Combined CT variables predicted 58% and 57% of the variability in TLC and Dlco, respectively, despite considerable variation in the proportion of coexisting pathologic conditions. When predictive equations with CT variables derived from the initial study group were applied to the subsequent study group, predicted TLC (rho=0.75, P<.001) and Dlco (rho=0.64, P<.001) correlated strongly with measured values. CONCLUSION: The proposed CT system provides a semiquantitative method for assessing the relative contribution of asbestos-induced pleuropulmonary disease and smoking-related emphysema to functional impairment.

Plasma retinol, carotene and vitamin E concentrations and lung function in a crocidolite-exposed cohort from Wittenoom, Western Australia: a cohort study.

BACKGROUND: Increased rates of death from asbestos related diseases have been reported for people previously employed in the mining and milling operations at Wittenoom (Western Australia), and people who lived in the nearby town, where they were environmentally exposed to crocidolite. METHODS: Annual measurements of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and plasma concentrations of retinol, carotene and vitamin E have been made since 1992. Mixed effects models were used to examine the associations between lung function and the plasma vitamin levels of retinol, carotene and vitamin E. RESULTS: After adjusting for potential confounders, higher plasma retinol and carotene concentrations were significantly associated with higher levels of lung function at entry into the study, while vitamin E concentrations were associated with lower entry lung function. Retinol was associated with a less steep decline of lung function over time, while carotene concentrations were associated with an increased decline of lung function over time and vitamin E levels were not associated with changes of lung function over time. CONCLUSION: These results support a beneficial relationship between plasma concentrations of retinol on the levels and rates of change of lung function, while showing no such consistent beneficial effect for plasma levels of beta-carotene or vitamin E.

Decline in lung function in the Busselton Health Study: the effects of asthma and cigarette smoking.

Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Smoking and asthma had additive but not multiplicative effects on decline. Thus, asthma is associated with reduced lung function at the beginning of adult life as well as an increased rate of decline during adult life.

Epidemiology of malignant mesothelioma in Australia.

In Australia, consumption of asbestos peaked in about 1975 at around 70,000t per year--the majority being used for asbestos cement manufacture. Chrysotile, amphibole and crocidolite have all been mined in Australia and employment records from the single company which mined most of the crocidolite deposits at Wittenoom have formed the basis of an ongoing cohort mortality study of the workforce.

The diagnosis and attribution of asbestos-related diseases in an Australian context: report of the Adelaide Workshop on Asbestos-Related Diseases. October 6-7, 2000.

Predictions of future cases of mesothelioma in Australia to the year 2020 are in the order of a total of 10,000 new cases. Compensation claims are testing the attribution in a particular case between occupational asbestos exposure and lung cancer. The cost of the problem necessitates clarifying and standardizing the criteria for a confident diagnosis of asbestos-related disease. The possibility of differences in criteria that determine attribution of asbestos to a disease prompted a consensus meeting of pathologists, epidemiologists, physicians, oncologists, radiologists, and others to define current thinking and to agree on an Australian document based on the scientific evidence for establishing diagnoses and attribution data of asbestos-related diseases in Australia. The participants' findings are reported.

Mesothelin-family proteins and diagnosis of mesothelioma.

BACKGROUND: Mesothelioma is a highly aggressive tumour for which there are no reliable serum tumour markers. Identification of such a marker would be useful in diagnosis of mesothelioma and for monitoring responses to treatment and screening at-risk individuals. METHODS: We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases. FINDINGS: 37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma. INTERPRETATION: Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma.

Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features.

PURPOSE: To identify differences, if any, in thin-section computed tomographic (CT) features between asbestosis and idiopathic pulmonary fibrosis (IPF) and to test the findings in a subset of histopathologically proved cases of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Consecutive patients with a diagnosis of IPF (n = 212) or asbestosis (n = 74) were included. The relationships derived from the initial comparison were tested in a separate group of biopsy-proved UIP (n = 30) and NSIP (n = 23) cases. Two observers independently scored thin-section CT images for extent, distribution, and coarseness of fibrosis; proportion of ground-glass opacification; severity of traction bronchiectasis; and extent of emphysema. RESULTS: After controlling for extent of fibrosis, patients with asbestosis had coarser fibrosis than those with IPF (odds ratio, 1.52; 95% CI: 1.25, 1.84; P <.001). Compared with the biopsy-proved cases, the asbestosis cases involved coarser fibrosis (after controlling for disease extent) than the NSIP cases (odds ratio, 2.48; 95% CI: 1.49, 4.11; P <.001) but fibrosis similar to that in the UIP cases. A basal and subpleural distribution of disease was usual in all subgroups but significantly more prevalent (P, <.01 to.001) with asbestosis than with UIP or NSIP. CONCLUSION: The thin-section CT pattern of asbestosis closely resembles that of biopsy-proved UIP and differs markedly from that of biopsy-proved NSIP.

The reliability of ten-year dietary recall: implications for cancer research.

Remote dietary intakes may be more important than recent diet in the etiology of cancer because of the long latency in cancer development. We examined the reliability of remote dietary recall over 10 y. Subjects were 56 adults participating in a cancer prevention trial in Western Australia. All subjects completed a 28-d diet record (DR) in 1991. A food-frequency questionnaire (FFQ) modified to ask respondents about their diet 10 y earlier was sent to each subject for completion in 2001. Remote intakes recalled from 10 y earlier using the FFQ were compared with the DR using the limits of agreement (LOA) method and Pearson correlation coefficients. Mean intakes of most nutrients did not differ between dietary methods. The LOA indicated that the FFQ could under- or overestimate DR estimates by >/=50%. For many nutrients, agreement between methods depended on the magnitude of intake. Pearson's correlation coefficients ranged from 0.02 for retinol to 0.66 for alcohol. These findings are similar to those of other studies that examined the reliability of recent and remote dietary intakes. They also show that using this FFQ, remote diet recalled from 10 y earlier may be as reliable as recent dietary recall.

Benign asbestos pleural diseases.

The global incidence of asbestos-related lung diseases is expected to continue to rise. Although much attention is devoted to malignant diseases induced by asbestos, benign asbestos pleural diseases (pleural plaques, benign asbestos-related pleural effusion, diffuse pleural thickening, and rounded atelectasis) are common in clinical practice and often produce diagnostic difficulties. The authors describe the clinical features of benign asbestos-related pleural disease, before focusing on recent advances in radiology and on controversies surrounding the pathogenesis of asbestos-induced pleural injury. Advances in computed tomography have assisted the understanding and diagnosis of these diseases, and increasing evidence suggests radiologic appearances on computed tomography can predict impairment in pulmonary function tests. The pathogenesis of asbestos-induced pleural diseases has also been subject to extensive investigation. Asbestos fibers can provoke pleural inflammation from direct toxicity to mesothelial cells. Inhaled asbestos fibers can also elicit pleural injury indirectly via the release of growth factors and inflammatory cytokines from within the lung. Although progress has been made in the understanding of the mechanisms of asbestos pleural injury, many important questions remain unanswered. The role of genetic factors and possible environmental cofactors (eg, simian virus 40) in the pathogenesis of benign asbestos pleural diseases requires further research.

Respiratory symptoms and lung-function changes with exposure to five substances in aluminium smelters.

OBJECTIVES: To determine whether exposure to five different occupational substances contributes to respiratory symptoms in aluminium smelter workers. METHODS: A cross-sectional survey of 1,615 male employees of two Australian aluminium smelters was conducted in 1995. Subjects underwent spirometry and were asked about respiratory symptoms and the relationship of those symptoms to work. Their job histories were combined with a task exposure matrix to produce individual quantitative measures of cumulative exposure to fluoride, sulphur dioxide, inspirable dust, the benzene-soluble fraction of coal tar pitch volatiles (BSF), and oil mist. RESULTS: After adjusting for smoking and age, we found that subjects with the highest cumulative exposure to fluoride (>0.16 mg/m(3) years) and inspirable dust (>2.9 mg/m(3) years) were two to four times more likely to report work-related wheeze and chest tightness than were unexposed subjects. Lower prevalence ratios for the same symptoms were seen with sulphur dioxide and BSF. Levels of lung function decreased slightly with exposure to oil mist, but not with cumulative exposure to other substances. CONCLUSIONS: This study suggests that the relevant causative agents for respiratory symptoms in aluminium smelters are fluoride and inspirable dust.

Respiratory morbidity and lung function in two Aboriginal communities in Western Australia.

OBJECTIVE: To examine differences in the rates of respiratory symptoms, asthma and levels of lung function in two remote Aboriginal communities. METHODOLOGY: Respiratory symptoms, smoking history, skin prick test responses to common allergens, serum IgE, lung function, airway responsiveness to methacholine and white blood cell counts were compared in two Aboriginal communities, one from the central desert (n = 84) and another from the tropical north (n = 209) of Western Australia. RESULTS: Compared with the tropical community, chest tightness and dyspnoea were more frequent and forced expiratory volume in 1 s and forced vital capacity were lower in the desert community, despite similar levels of wheeze, doctor-diagnosed asthma and skin prick test responses and lower levels of airway responsiveness and smoking. The total white cell and neutrophil counts were greater in the desert community. Serum IgE was very high and similar in both communities. CONCLUSIONS: Our findings show a low prevalence of asthma in children, a high prevalence of respiratory symptoms and low levels of lung function in remote Aboriginal communities. The greater prevalence of respiratory morbidity in the desert community was not explained by diagnosed asthma, airway hyperresponsiveness or cigarette smoking. The role of infection requires further investigation. The results suggest that the lower lung function observed in Aboriginal communities (compared with non-Aboriginal communities) results at least partly from environmental factors.