Exposure to ozone (O 3 ) impairs lung function, induces airway inflammation and alters epithelial permeability. Whilst impaired lung function and neutrophilia have been observed at relatively low concentrations, altered lung epithelial permeability is only seen after high-dose challenges. The appearance of Clara cell protein (CC16) in serum has been proposed as a sensitive marker of lung epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated under a controlled exposure to O 3 and the relationship between this marker of lung injury and early lung function decrements was investigated.Subjects (n=22) were exposed on two separate occasions to 0.2 parts per million O 3 and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h preexposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure.O 3 increased CC16 serum concentrations at 2 h (12.0¡4.5 versus 8.4¡3.1 mg?L -1 ) and 4 h postexposure (11.7¡5.0 versus 7.9¡2.6 mg?L -1 ) compared with air concentrations. Archived samples from O 3 studies utilising the same design indicated that this increase was sustained for up to 6 h postexposure (9.1¡2.6 versus 7.1¡1.7 mg?L -1 ) with concentrations returning to baseline by 18 h (7.7¡2.9 versus 6.6¡1.7 mg?L -1 ). In these studies, the increased plasma CC16 concentration was noted in the absence of increases in traditional markers of epithelial permeability. No association was observed between increased CC16 concentrations and lung function changes.To conclude, Clara cell protein represents a sensitive and noninvasive biomarker for ozone-induced lung epithelial damage that may have important uses in assessing the health effects of air pollutants in future epidemiological and field studies. Eur Respir J 2003; 22: 883-888.

In this investigation the effects of repeated exposure to 1-5 ppm NO2 on immune competent cells in bronchoalveolar lavage (BAL) fluid was studied. Special attention was focused on effects on lymphocyte subpopulations. Eight healthy subjects were exposed to 1 5 ppm NO2 every second day on six occasions. Bronchoalveolar lavage fluid was collected at least three weeks before the exposure series as reference and 24 hours after the last exposure. The results obtained were analysed using a non-parametric test for paired observations, with each subject as his own control. Significant reductions were found in the total number and percentage of T cytotoxic-suppressor cells in BAL fluid; this caused an increase in the ratio of T helper-inducer: cytotoxic-suppressor cells.

ObjectiveMaternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method.MethodsIn a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period).ResultsWomen whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78±SD4.79 years, 18–37 vs 29.79±SD6 years, 18–42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95thCI 1.08–4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95thCI 0.18–0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95th CI1.20–10.02, p = 0.01).ConclusionsWe demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age.

Objectives-'Persistent cloaca' is a severe malformation affecting females in which the urinary, genital and alimentary tracts share a single conduit. Previously, a Uroplakin IIIA (UPIIIA) mutation was reported in one individual with persistent cloaca, and UPIIIA, Sonic Hedgehog (SHH), Ephrin B2 (EFNB2) and Hepatocyte Nuclear Factor 1β (HNF1β) are expressed during the normal development of organs that are affected in this condition. HNF1β mutations have been associated with uterine malformations in humans, and mutations of genes homologous to human SHH or EFNB2 cause persistent cloaca in mice.Patients and Methods-We sought mutations of coding regions of UPIIIA, SHH, EFNB2 and HNF1β genes by direct sequencing in a group of 20 patients with persistent cloaca. Most had associated malformations of the upper renal tract and over half had impaired renal excretory function. The majority of patients had congenital anomalies outside the renal/genital tracts and two had the VACTERL association.Results-Apart from a previously described index case, we failed to find UPIIIA mutations, and no patient had a SHH, EFNB2 or HNF1β mutation.Conclusion-Persistent cloaca is only rarely associated with UPIIIA mutation. Despite the fact that SHH and EFNB2 are appealing candidate genes, based on their expression patterns and mutant mice phenotypes, they were not mutated in these humans with persistent cloaca. Although HNF1β mutations can perturb paramesonephric duct fusion in humans, HNF1β was not mutated in persistent cloaca.

A cohort of 1455 sea pilots and boatmen employed after 1921 was established. Those identified and alive in 1951 (n = 1323) were linked to the Swedish cause of death register 1951-84. In 21 352 person-years 383 deaths were observed among sea pilots compared with 379 3 expected (SMR = 101; 95% CI between 99 and 112) and in 12 127 person-years the observed number of deaths among boatmen was 136, expected 135-9 (SMR = 100) when Swedish men were used as a reference population. For ischaemic heart disease (IHD) (ICD-8: 410-414) the SMR was equal to 96 (obs = 131, exp = 137-2) for sea pilots and 91 (obs = 44, exp = 48-4) for boatmen. No trend over time or geographical differences could be observed. A healthy worker effect could not explain why there was no excess mortality from IHD.In 1984 a suspicion arose among sea pilots in northern Sweden that too many of their fellow workers died from ischaemic heart disease (IHD). This did not seem unreasonable, as studies of workers with a similar type of work, such as channel pilots in West Germany and the United Kingdom, had indicated an excess mortality from circulatory diseases, especially IHD, in middle aged workers.'2 Further, Kilbom showed, in a physiological study of six Swedish sea pilots, recording heart rate with a portable ECG tape recorder parallel with time studies, that psychological stress during periods of heavy sea pilot working produced an increased heart rate and thereby increased load on the heart and boarding and leaving a ship in certain circumstances produced high heart rate which, among older sea pilots, implied that they used almost all their physical capacity.'