The role of γδ T cells in airway epithelial injury and bronchial responsiveness after chlorine gas exposure in mice

BACKGROUND: Acute exposure to chlorine (Cl(2)) gas causes epithelial injury and airway dysfunction. γδ T cells are present in the mucosal surface of the airways and may contribute to the injury/repair response of the epithelium. METHODS: C57Bl/6J (wild type) and TCR-δ(-/- )mice exposed to Cl(2 )(400 ppm) for 5 minutes underwent measurements of airway responses to i.v. methacholine (MCh) at 1, 3, and 5 days after exposure. Bronchoalveolar lavage was performed to determine epithelial and leukocyte counts, and protein content. Tissue repair was assessed by proliferating cell nuclear antigen (PCNA) immunoreactivity and by expression of keratinocyte growth factor (KGF) mRNA by real-time PCR. RESULTS: Wild type mice developed a greater degree of airway hyperresponsiveness to MCh at 1 day post exposure to Cl(2 )compared with TCR-δ(-/- )mice. Epithelial cell counts in BAL after Cl(2 )exposure were greater in TCR-δ(-/- )mice, but macrophages showed a later peak and granulocyte numbers were lower in TCR-δ(-/- )than in wild type mice. Both groups had increased levels of total protein content in BAL after Cl(2 )exposure that resolved after 3 and 5 days, respectively. Epithelial proliferating cell nuclear antigen staining was increased at 1 and 3 days post exposure and was similar in the two groups. KGF mRNA was constitutively expressed in both groups and did not increase significantly after Cl(2 )but expression was lower in TCR-δ(-/- )mice. CONCLUSION: The severity of airway epithelial injury after Cl(2 )is greater in TCR-δ(-/- )mice but the inflammatory response and the change in airway responsiveness to methacholine are reduced. The rates of epithelial regeneration are comparable in both groups

Utjecaj izloženosti 1,6-heksametilen diizocijanatu (HDI) na vršni ekspiratorni protok u autolakirera u Iranu

The aim of this study was to investigate the effects of occupational exposure to 1,6-hexamethylene diisocyanate (HDI) on peak flowmetry in automobile body paint shop workers in Iran. We studied a population of 43 car painters exposed to HDI at their workplaces. Peak expiratory fl ow was tested for one working week, from the start to the end of each shift. Air was sampled and HDI analysed in parallel, according to the OSHA 42 method. Daily and weekly HDI exposure averages were (0.42±0.1) mg m-3 and (0.13±0.05) mg m-3, respectively. On painting days, 72 % of workers showed more than a 10 % variation in peak expiratory fl ow. Inhalation exposure exceeded the threshold limit value (TLV) ten times over. This strongly suggests that HDI affected the peak fl owmetry in the studied workers.Cilj je ovog ispitivanja bio utvrditi vršni protok u 43 iranska autolakirera profesionalno izložena 1,6-heksametilen diizocijanatu (HDI). Vršni ekspiratorni protok testiran je tjedan dana na početku i kraju svake smjene. Uzorkovanje i mjerenje HDI-ja u zraku radilo se istodobno s testiranjem vršnoga protoka, prema metodi OSHA 42. Prosječna dnevna izloženost radnika HDI-ju iznosila je (0.42±0.1) mg m-3, a tjedna (0.13±0.05) mg m-3. U 72 % radnika vršni ekspiratorni protok tijekom dana varirao je više od 10 %. Radnici su udisali deset puta više razine HDI-ja od graničnih te je moguće da je HDI utjecao na mjerenja plućne funkcije

Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts

BACKGROUND: An imbalance in matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to chronic obstructive pulmonary disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking. METHODS: We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n=1152). RESULTS: MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development. CONCLUSIONS: We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population

Methyl methacrylate and respiratory sensitization: A Critical review

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer

The precision of longitudinal lung function measurements: monitoring and interpretation

Background: The efficacy of decision making based on longitudinal spirometric measurements depends critically on the precision of the available data, which is determined by the magnitude of the within-person variation. Aims: Firstly, to describe and investigate two statistical methods—a pairwise estimate of within-person standard deviation s(p) and the reliability coefficient G—for use in the monitoring of precision of longitudinal measurements of forced expiratory volume in one second (FEV1). Secondly, to investigate the effect of longitudinal data precision on the detectable excess rate of decline in FEV1. Methods: The authors "monitored" retrospectively on a yearly basis the magnitude of the within-person variation s(p) and the coefficient G in 11 workplace based spirometric monitoring programmes conducted from 1987 to 2001 on 12 729 workers in various industrial plants. Results: The plant-specific mean values [Image: see text] (p) (range 122–166 ml) and [Image: see text] (range 0.88–0.95), averaged over all years of follow up, correlated well with the plant-specific within-person standard deviation s(r) (range 130–177 ml) estimated from all longitudinal data. The correlations were 0.90 for [Image: see text] (p) and 0.68 for [Image: see text]. The average precision of the longitudinal FEV1 measurements affected the duration of follow up needed to identify a "true" excess rate of decline in FEV1 in an individual. Conclusions: The results show that monitoring of longitudinal spirometry data precision (1) allows that data precision can be improved or maintained at levels that allow individuals with a rapid decline to be identified at an earlier age; and (2) attaches a measure of precision to the data on which decision making is based