Exhaled nitric oxide (NO) is elevated in untreated patients with asthma but not in patients treated with inhaled glucocorticoids. This may reflect an inhibitory effect of glucocorticoids on the induction of the enzyme NO synthase in the respiratory tract. We have now studied the effect of an inhaled glucocorticoid (budesonide 800 micrograms twice daily via a dry powder delivery system for 3 wk) on exhaled NO in 11 patients with mild asthma in a double-blind crossover randomized-order placebo-controlled study. Exhaled NO was reduced from a baseline value of 203 +/- 29 parts per billion (ppb) to 120 +/- 26 ppb after 3 wk of treatment (p < 0.01), whereas there was no change after a matched placebo (169 +/- 20 at baseline compared with 184 +/- 16 ppb after 3 wk). A significant and progressive fall in exhaled NO was found from 1 to 3 wk. There was no significant change in FEV1 after inhaled steroids (although mean FEV1 was 92% predicted normal at baseline), although there was a reduction in airway responsiveness to methacholine (approximately 2.5 doubling dilutions). These results add further support to the view that the elevated levels of exhaled NO in asthma may derive from induction of an inducible isoform of NO synthase and indicate that exhaled NO may be a useful way of monitoring the anti-inflammatory effects of glucocorticoids and other anti-inflammatory treatments in asthma.

The effect of inhaled recombinant human tumor necrosis factor-alpha (rhTNF alpha) on airway responsiveness and the cellular composition of sputum was studied in eight normal subjects using a placebo-controlled study design. Spirometric data and bronchial responsiveness (BR) to methacholine were studied, and an estimate of pulmonary-cell infiltration was made using the technique of induced sputum. A single dose of rhTNF alpha (60 ng) caused an increase in BR, with a leftward shift in the concentration-based response to methacholine at all time points after inhalation, as compared with a saline control challenge. Likewise, there was a decrease in the log provocative concentration of methacholine causing a 15% decrease in FEV1, which reached a maximum at 24 h (1.37 +/- 0.22 versus 1.87 +/- 0.24, rhTNF alpha and control, respectively; p < 0.05). No change was observed in baseline spirometric measures at any of the time points. A significant increase in the percentage of neutrophils occurred in the induced sputum, reaching a maximum at 24 h (44.2 +/- 9.9% versus 16.6 +/- 7.1%, rhTNF alpha and control, respectively; p < 0.05). We conclude that TNF alpha can induce an increase in airway responsiveness in normal subjects, and is associated with a neutrophil infiltration, thus making it a candidate cytokine for the induction of airway inflammation and hyperresponsiveness.

I In nc cr re ea as se ed d n ni it tr ri ic c o ox xi id de e i in n e ex xh ha al le ed d a ai ir r o of f n no or rm ma al l h hu um ma an n s su ub bj je ec ct ts s w wi it th h u up pp pe er r r re es sp pi ir ra at to or ry y t tr ra ac ct t i in nf fe ec ct ti io on ns s We have studied the levels of exhaled NO in 18 normal subjects during symptomatic upper respiratory tract infections and during recovery 3 weeks later. Exhaled NO was measured using a modified chemiluminescence analyser.At the time of symptoms of upper respiratory tract infection, the peak exhaled NO values were 315±57 ppb (mean±SEM) and decreased to 87±9 ppb during recovery. Recovery values of exhaled NO were similar to those reported in age-matched normal control subjects (88±3 ppb, n=72).These findings suggest that symptomatic upper respiratory tract infections markedly increase the concentration of NO in exhaled air. This may reflect the induction of nitric oxide synthase (NOS) in upper and lower respiratory tract, and may be relevant to viral exacerbations of asthma.

Malignant mesothelioma is an uncommon tumour usually attributable to asbestos exBackground -Malignant mesothelioma is posure, which is rising in incidence in the UK.1 a rare pleural tumour associated with asClinical and pathological features of malignant bestos exposure. The proportion of maligmesothelioma have been previously well denant mesothelioma unrelated to asbestos scribed. [2][3][4] In many published series, however, exposure, and any differentiating features numbers are small and complete clinical, ocbetween exposed and unexposed cases, are cupational, and pathological details have been not well described. This study describes oc-difficult to obtain. The proportion of tumours cupational, clinical, and pathological fea-not related to asbestos, survival with different tures in a large cohort of cases of malignant tumour subtypes, and features of non-asbestos mesothelioma from south east England.related tumours are also uncertain. This report Methods -All 272 cases from this region provides complete documentation of 272 cases were studied, either in life or after death where mesothelioma was the cause of death when necropsy examination suggested within a defined geographical area in the south malignant mesothelioma. Detailed in-east of England for the calendar year 1987. formation was gathered regarding the ocIn the UK a system of compensation for cupational history, clinical course, and occupational lung disease has existed since mode of death. Necropsies were performed 1931, 5 and a regional network of Pneumoin 98% of cases. Lung tissue was examined coniosis Panels (now called Medical Boarding Centres (MBCs)) assesses live and posthumous histologically to confirm the diagnosis, claims. The London MBC area covers all of subtype of tumour, presence or absence of the industrial south east. asbestosis and asbestos bodies.In England all deaths suspected of being due Results -Exposure to asbestos was docuto industrial disease must be reported to the mented in 87% of cases, while in the recoroner and a necropsy performed. Until April mainder, no asbestos exposure was found 1988 it was mandatory for coroners to refer all nor were asbestos bodies seen; 94.5% were cases of malignant mesothelioma to MBCs for pleural, 5.1% peritoneal, and 0.4% peri-special examination of the lungs. A report by cardial. Right sided tumours were more specialist physicians as to cause of death and common than left sided tumours (ratio presence or absence of an occupational lung 1.6:1). Patients usually presented with disease was then made to the coroner. breathlessness and chest pain, but 33%Although only cases where there was any presented with pleural effusion in the ab-suspicion of industrial causation were legally sence of chest pain. The mean (SD) time required to be reported to the coroner, in pracfrom first exposure to asbestos to sympMedical Boarding tice -because of compensation issues -almost features do not differentiate between as-causation had arisen.

IntroductionArtificial stone is an increasingly popular material used to fabricate kitchen and bathroom benchtops. Cutting and grinding artificial stone is associated with generation of very high levels of respirable crystalline silica, and the frequency of cases of severe silicosis associated with this exposure is rapidly increasing.AimTo report the characteristics of a clinical series of Australian workers with artificial stone-associated silicosis.MethodsRespiratory physicians voluntarily reported cases of artificial stone-associated silicosis identified in their clinical practices. Physicians provided information including occupational histories, respiratory function tests, chest radiology and histopathology reports, when available.ResultsSeven male patients were identified with a median age of 44 years (range 26–61). All were employed in small kitchen and bathroom benchtop fabrication businesses with an average of eight employees (range 2–20). All workplaces primarily used artificial stone, and dust control measures were poor. All patients were involved in dry cutting artificial stone. The median duration of exposure prior to symptoms was 7 years (range 4–10). Six patients demonstrated radiological features of progressive massive fibrosis. These individuals followed up over a median follow-up period of 16 months (IQR 21 months) demonstrated rapid decline in prebronchodilator forced expiratory volume in 1 s of 386 mL/year (SD 204 mL) and forced vital capacity of 448 mL/year (SD 312 mL).ConclusionsThis series of silicosis in Australian workers further demonstrates the risk-associated high-silica content artificial stone. Effective dust control and health surveillance measures need to be stringently implemented and enforced in this industry.

In clinical disease, markers of inflammation and oxidative stress are easily measurable in EBC using standard laboratory techniques and EBC is readily obtained. However, EBC and BAL markers do not correlate.

Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity.20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case-control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction.10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases.Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.

There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment.The present article details the more important biomarkers, their potential applications and the evidence supporting their use.