ANTIBODIES TO SACCHAROMYCES CEREVISIAE and ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES IN INFLAMMATORY BOWEL DISEASE: ASSESSMENT and RELEVANCE IN AN AUSTRALIAN POPULATION USING TWO DIFFERENT ASCA ASSAY KITS

A number of North American and European studies have elucidated a relationship between antibodies to the yeast Saccharomyces cerevisiae (ASCA) and Crohn's disease (CD).
Aims  (1) To ascertain whether this relationship is relevant to Australian patients; (2) To compare the results with two different commercial ASCA kits; (3) To examine the usefulness of this test in combination with perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) for distinguishing Crohn's disease from ulcerative colitis (UC).
Methods  Serum samples were obtained from 28 patients with CD, 27 patients with UC and 22 non-IBD patients presenting for investigation of other gastroenterological illnesses. ASCA IgG and IgA were determined by enzyme immunoassay using the two test kits. pANCA was detected by indirect immunofluorescence.
Results  Using the Medizym test kit, the presence of either IgG or IgA ASCA was 50% sensitive and 93% specific for CD. The QUANTA Lite kit yielded a higher sensitivity of 79% but specificity of 74%. The sensitivity of pANCA for UC was 48% but was 100% specific. Used in combination, ASCA+ve/pANCA–ve was only 50% sensitive but 100% specific for CD using the Medizym kit compared with 79% sensitivity and 93% specificity using QUANTA Lite. The combination of ASCA–ve/pANCA+ve was 41% sensitive and 100% specific for ulcerative colitis using the Medizym kit compared with 30% sensitive and 100% specific using QUANTA Lite.
Conclusions  At least 50% of Australian patients with CD have ASCA detectable in serum, confirming the results of overseas studies. Sensitivity was greater with the QUANTA Lite kit whereas the Medizym kit was slightly more specific. ASCA may aid in the diagnosis of CD. When used in combination with pANCA it may also help distinguish CD from UC in difficult cases.     

Posttransplant Bronchiolitis Obliterans Syndrome Is Associated with Bronchial Epithelial to Mesenchymal Transition

Bronchiolitis obliterans syndrome (BOS) compromises lung transplant outcomes and is characterised by airway epithelial damage and fibrosis. The process whereby the normal epithelial configuration is replaced by fibroblastic scar tissue is poorly understood, but recent studies have implicated epithelial mesenchymal transition (EMT). The primary aim of this study was to assess the utility of flow cytometry in detecting and quantifying EMT in bronchial epithelial cells.
Large airway brushings were obtained at 33 bronchoscopies in 16 BOS-free and 6 BOS grade 1–3 patients at 2–120 months posttransplant. Flow cytometry was used to assess expression of the mesenchymal markers αSMA, S100A4 and ED-A FN and HLA-DR. TGF β1 and HGF were measured in Bronchoalveolar lavage (BAL). Expression of all three mesenchymal markers was increased in BOS, as was HLA-DR. BAL HGF, but not TGF β1 was increased in BOS. Longitudinal investigation of one patient revealed a 100% increase in EMT markers concurrent with a 6-fold increase in BAL TGF β1 and the diagnosis of BOS at 17 months posttransplant.
Flow cytometric evaluation of bronchial epithelium may provide a novel and rapid means to assess lung allografts at risk of BOS.     

Exposure to grain dust and changes in lung function

Respiratory symptoms and lung function were assessed in 41 seasonal grain handlers and related to duration of employment and level of exposure to grain dust. Ten public works department employees, not exposed to grain dust, were examined during the same period. Respiratory symptoms, forced expired volume in one second (FEV1), and bronchial responsiveness (dose of methacholine provoking a 20% fall in FEV1-PD20) were assessed before starting work and at weekly intervals during a period of employment lasting up to four weeks. Two atopic grainhandlers with pronounced bronchial hyperresponsiveness (PD20 less than 1 mumol) and a history of asthma withdrew from the study within two weeks because they developed severe asthma. Respiratory symptoms were more frequent and more often attributed to work in the grainhandlers than in the non-exposed subjects. In the grainhandlers the FEV1 decreased by a mean (95% confidence intervals) of 321 ml (198-444) (p less than 0.05) and the mean (95% confidence interval) PD20 decreased from 20.6 mumol (10.3-41.2) to 6.0 mumol (2.8-12.5) (p less than 0.05) after one week of work. Over the next three weeks the mean FEV1 returned towards the prestudy values. The mean PD20, however, remained significantly lower than the initial value. The mean FEV1 and PD20 did not change significantly in the non-exposed subjects. The frequency of symptoms and decreases in FEV1 were greater in grainhandlers when working in jobs where total exposure to dust was greater than 20 mg/m3 than when working in jobs where it was less than 10 mg/m3. The results indicate that occupational exposure to grain dust results in respiratory symptoms and changes in lung function, including increased airway responsiveness, within the first week of exposure to grain dust at work. These changes appear to be determined by the degree of dust exposure and suggest a direct effect of grain dust on the lung in these subjects.     

Atopy, non-allergic bronchial reactivity, and past history as determinants of work related symptoms in seasonal grain handlers

One hundred and five young subjects with little or no previous exposure to grain dust were studied before and after a seven week period of grain handling work to determine if there was an association between symptoms experienced at work and pre-employment respiratory symptoms, allergy skin test responses, and non-allergic bronchial reactivity. The incidence of work related symptoms was cough 18%, wheeze 13%, and dyspnoea 14%. The results showed that pre-employment history of respiratory symptoms, positive allergy skin test responses, and a high level of non-allergic bronchial reactivity were significantly associated with these symptoms. These measurements may be useful to predict symptoms associated with exposure to grain dust in new employees and the results suggest that these work related symptoms may be due to allergen induced asthma.     

Prevalence of radiographic asbestosis in crocidolite miners and millers at Wittenoom, Western Australia.

An estimate has been made of the prevalence of unrecognised pneumoconiosis in former crocidolite workers from Wittenoom, Western Australia. All plain chest radiographs relating to a one in six random sample (1025 men) of all former Wittenoom workers who had never entered a compensation claim to the Pneumoconiosis Medical Board of Western Australia were sought from Perth teaching hospitals and from the Perth Chest Clinic where compulsory examination of all workers in the mining industry takes place. Radiographs were recovered for 83% of the men and read independently by two observers. By means of logistic regression analysis a current prevalence of parenchymal abnormality (defined as a radiographic profusion of small opacities of category 1/0 or greater on the ILO classification) of nearly 20% was calculated after adjustment for age, time since first exposure, and cumulative exposure level. One hundred men randomly selected from those known to be alive in the sample were invited to attend for a new radiographic examination. Seventy four men attended and the predicted prevalence was confirmed. It is estimated from these data that there were between 450 and 900 former Wittenoom workers in Australia at the end of 1980 who had radiographic abnormality consistent with pneumoconiosis but had not claimed compensation or had asbestosis diagnosed. The data are consistent with there being no threshold dose of crocidolite exposure for the development of radiographic abnormality in this group.     

Familial aggregation and heritability of adult lung function: results from the Busselton Health Study.

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated. Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25-60 yrs of age) when the subject was as close to age 45 yrs as possible. Multivariate analysis suggested that FEV1 and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1 levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1%). FVC levels had an h2N of 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1 or FVC levels. The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.     

Trends in mortality from malignant mesothelioma of the pleura, and production and use of asbestos in Australia

Annual mortality from malignant mesothelioma of the pleura (MMP) in Australia (as represented by ICD8 codes 163.0 and 212.4, and ICD9 codes 163 and 212.4) increased in men aged 30 years and older from about 0.5/100 000 in 1968-1970 to 2.1/100 000 in 1983. Corresponding rates in women varied from 0.1/100 000 to 0.2/100 000 between 1968 and 1980, then rose to 0.3/100 000 in 1983. The rise in MMP mortality in men probably corresponds to the increasing use of asbestos, particularly amosite, in Australia during and after World War II. That production and importation of amosite and crocidolite in Australia reached a peak in 1958 may mean that peak mortality from MMP will not be reached until the 1990s (allowing a 35-year lag period). Substantial increases in importation and later production, of chrysotile in the 1950s, 1960s and 1970s may lead to increases in the incidence of other asbestos-related cancers, not reflected in trends in the incidence of MMP.     

Cancer mortality in relation to measures of occupational exposure to crocidolite at Wittenoom Gorge in Western Australia

The separate and combined effects of duration and intensity of exposure to crocidolite on mortality from lung cancer, malignant mesothelioma, and stomach cancer were examined in 6506 male former crocidolite miners and millers at Wittenoom Gorge, Western Australia. Each subject who had died from lung cancer (92), mesothelioma (31), or stomach cancer (17) was matched with up to 20 control subjects of the same age who were not known to have died before the index subject. Relations of dose and time of exposure to crocidolite to risk of death were modelled by conditional logistic regression. For lung cancer, the best fitting multiplicative model was one which estimated a relative risk (RR) of 1.12 (95% CI 1.04-1.20) per year of exposure and 1.01 (95% CI 1.00-1.01) per fibre/ml. This was statistically indistinguishable from an additive model showing an increase in RR of 0.01045 (95% CI 0.008-0.020) per f/ml year. For mesothelioma the best fitting model appeared to be one estimating a RR of 24.9 (95% CI 3.51-1.77) per log year since first exposed and a RR of 10.5 (95% CI 3.12-35.1) if exposed for longer than six months. This was not distinguishable statistically from a model that showed mortality increasing as the fourth power of time since first exposed less the fourth power of time since last exposed. The effect of intensity of exposure on the RR for mesothelioma was only slight. There was no consistent effect of any measure of exposure to crocidolite on death from stomach cancer.