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Medline ® Abstracts for References 41,43,44,57-60

of 'Reactive airways dysfunction syndrome and irritant-induced asthma'

41
TI
Effects of dexamethasone on functional and pathological changes in rat bronchi caused by high acute exposure to chlorine.
AU
Demnati R, Fraser R, Martin JG, Plaa G, Malo JL
SO
Toxicol Sci. 1998;45(2):242.
 
We assessed the effects of dexamethasone on functional and histological changes after acute exposure to a high level of chlorine gas in an animal model of reactive airways dysfunction syndrome (RADS). Sprague-Dawley male rats were exposed to 1500 ppm of chlorine for 5 min and treated with either dexamethasone (dex; 300 micrograms/kg/day) or saline intraperitoneally for 7 days. Lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), airway wall morphometric measurements, and bronchoalveolar lavage (BAL) cells were assessed over a 2-week period after exposure. Dex administration significantly attenuated both chlorine-induced increased RL and chlorine-induced increased responsiveness to methacholine compared with saline: -2.7 +/- 6.8% vs 102.3 +/- 36.6% change from baseline RL (P<0.01) and 2.5 +/- 0.6 mg/ml vs 1.2 +/- 0.7 mg/ml in the MCh concentration required to double the RL from baseline (P<0.01). There was a tendency, albeit nonsignificant, for improvement in some indices of epithelial injury. Dex significantly attenuated the postexposure neutrophilic cellular response in BAL 1 day after exposure (15.8 +/- 4.9% neutrophils in the dex group vs 49.8 +/- 2.7% neutrophils in the saline group) (P<or = 0.001). Our results show that dex administration helps maintain pulmonary function, reduces BAL inflammatory cell number, and tends to improve some morphometric airway wall structure parameters in rats exposed to chlorine.
AD
Department of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, Quebec, Canada.
PMID
43
TI
Neutrophils mediate airway hyperresponsiveness after chlorine-induced airway injury in the mouse.
AU
McGovern TK, Goldberger M, Allard B, Farahnak S, Hamamoto Y, O'Sullivan M, Hirota N, Martel G, Rousseau S, Martin JG
SO
Am J Respir Cell Mol Biol. 2015 Apr;52(4):513-22.
 
Chlorine gas (Cl2) inhalation causes oxidative stress, airway epithelial damage, airway hyperresponsiveness (AHR), and neutrophilia. We evaluated the effect of neutrophil depletion on Cl2-induced AHR and its effect on the endogenous antioxidant response, and if eosinophils or macrophages influence Cl2-induced AHR. We exposed male Balb/C mice to 100 ppm Cl2 for 5 minutes. We quantified inflammatory cell populations in bronchoalveolar lavage (BAL), the antioxidant response in lung tissue by quantitative PCR, and nuclear factor (erythroid-derived 2)-like 2 (NRF2) nuclear translocation by immunofluorescence. In vitro, NRF2 nuclear translocation in response to exogenous hypochlorite was assessed using a luciferase assay. Anti-granulocyte receptor-1 antibody or anti-Ly6G was used to deplete neutrophils. The effects of neutrophil depletion on IL-13 and IL-17 were measured by ELISA. Eosinophils and macrophages were depleted using TRFK5 or clodronate-loaded liposomes, respectively. AHR was evaluated with the constant-phase model in response to inhaled aerosolized methacholine. Our results show that Cl2 exposure induced neutrophilia and increased expression of NRF2 mRNA, superoxide dismutase-1, and heme-oxygenase 1. Neutrophil depletion abolished Cl2-induced AHR in large conducting airways and prevented increases inantioxidant gene expression and NRF2 nuclear translocation. Exogenous hypochlorite administration resulted in increased NRF2 nuclear translocation in vitro. After Cl2 exposure, neutrophils occupied 22±7% of the luminal space in large airways. IL-17 in BAL was increased after Cl2, although this effect was not prevented by neutrophil depletion. Neither depletion of eosinophils nor macrophages prevented Cl2-induced AHR. Our data suggest the ability of neutrophils to promote Cl2-induced AHR is dependent on increases in oxidative stress and occupation of luminal space in large airways.
AD
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada.
PMID
44
TI
AEOL10150: a novel therapeutic for rescue treatment after toxic gas lung injury.
AU
McGovern T, Day BJ, White CW, Powell WS, Martin JG
SO
Free Radic Biol Med. 2011 Mar;50(5):602-8. Epub 2010 Dec 13.
 
New therapeutics designed as rescue treatments after toxic gas injury such as from chlorine (Cl(2)) are an emerging area of interest. We tested the effects of the metalloporphyrin catalytic antioxidant AEOL10150, a compound that scavenges peroxynitrite, inhibits lipid peroxidation, and has SOD and catalase-like activities, on Cl(2)-induced airway injury. Balb/C mice received 100ppm Cl(2) gas for 5 min. Four groups were studied: Cl(2) only, Cl(2) followed by AEOL10150 1 and 9 h after exposure, AEOL10150 only, and control. Twenty-four hours after Cl(2) gas exposure airway responsiveness to aerosolized methacholine (6.25-50mg/ml) was measured using a small-animal ventilator. Bronchoalveolar lavage (BAL) was performed to assess airway inflammation and protein. Whole lung tissue was assayed for 4-hydroxynonenal. In separate groups, lungs were collected at 72 h after Cl(2) injury to evaluate epithelial cell proliferation. Mice exposed to Cl(2) showed a significantly higher airway resistance compared to control, Cl(2)/AEOL10150, or AEOL10150-only treated animals in response to methacholine challenge. Eosinophils, neutrophils, and macrophages were elevated in BAL of Cl(2)-exposed mice. AEOL10150 attenuated the increases in neutrophils and macrophages. AEOL10150 prevented Cl(2)-induced increase in BAL fluid protein. Chlorine induced an increase in the number of proliferating airwayepithelial cells, an effect AEOL10150 attenuated. 4-Hydroxynonenal levels in the lung were increased after Cl(2) and this effect was prevented with AEOL10150. AEOL10150 is an effective rescue treatment for Cl(2)-induced airway hyperresponsiveness, airway inflammation, injury-induced airway epithelial cell regeneration, and oxidative stress.
AD
Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H2X 2P2, Canada.
PMID
57
TI
Occupational lower airway disease in relation to World Trade Center inhalation exposure.
AU
de la Hoz RE
SO
Curr Opin Allergy Clin Immunol. 2011;11(2):97.
 
PURPOSE OF REVIEW: To summarize the knowledge about the occupational lower airway diseases that seem related to exposures at the World Trade Center disaster site.
RECENT FINDINGS: Those diseases have been characterized as irritant-induced asthma, chronic nonspecific bronchitis, chronic bronchiolitis/small airway disease, and aggravated preexistent chronic obstructive lung disease (most frequently chronic obstructive pulmonary disease, but also asthma), with the expected overlapping features among them. One remarkable characteristic of the irritant-induced asthma observed among these workers was the slow onset of symptoms and long delay in clinical diagnoses.
SUMMARY: Longitudinal studies suggest that both the incidence and the associated functional decline of these predominantly obstructive lung diseases stabilized several years ago, but longer follow-up is clearly necessary.
AD
Departments of Preventive Medicine and Medicine, Mount Sinai School of Medicine, New York, New York, USA. Rafael.delaHoz@mssm.edu
PMID
58
TI
Can reactive airways dysfunction syndrome (RADS) transform into occupational asthma due to "sensitisation" to isocyanates?
AU
Leroyer C, Perfetti L, Cartier A, Malo JL
SO
Thorax. 1998;53(2):152.
 
The case history is described of a worker who presented with a history suggestive of reactive airways dysfunction syndrome which occurred after an acute high level inhalation of diphenylmethane diisocyanate. Further exposure at work, at a time when concentrations of isocyanates were no longer "irritant", suggested occupational asthma; this diagnosis was confirmed by a specific inhalation challenge test.
AD
DEpartment of Chest Medicine, Hôpital du Sacré-Coeur, Gouin, Montréal Canada.
PMID
59
TI
Air trapping detected on end-expiratory high-resolution computed tomography in symptomatic World Trade Center rescue and recovery workers.
AU
Mendelson DS, Roggeveen M, Levin SM, Herbert R, de la Hoz RE
SO
J Occup Environ Med. 2007;49(8):840.
 
OBJECTIVES: We utilized end-expiratory chest computed tomography (CT) to investigate air trapping (AT) in symptomatic former World Trade Center (WTC) workers, and correlated the findings with clinical, physiological, and exposure-related characteristics.
METHODS: Twenty-nine WTC workers with lower respiratory symptoms were evaluated. Clinical data included symptom inventories, quantitative respiratory symptom scores, WTC dust exposure duration, pulmonary function tests, and inspiratory and end-expiratory high-resolution chest CT scans. The latter were scored quantitatively for AT (by two methods) and interstitial changes, and those scores were correlated with the clinical data.
RESULTS: The two AT scoring methods yielded highly correlated results. AT was demonstrated in 25 of 29 patients, with scores ranging from 0 to 24 (mean, 10.6). There was a statistically significant correlation between AT and the duration of dust exposure. AT scores were significantly higher in patients with restrictive lung function data, and in lifetime nonsmokers.
CONCLUSIONS: Our data suggest that AT from small airways disease may account for some of the reported clinical and pulmonary functional abnormalities in WTC dust-exposed workers, and support the use of high-resolution CT scans in the investigation and characterization of the pulmonary ailments of selected workers.
AD
Department of Radiology, The Mount Sinai School of Medicine, New York, New York 10029, USA.
PMID
60
TI
Asthma characteristics in cleaning workers, workers in other risk jobs and office workers.
AU
Zock JP, Kogevinas M, Sunyer J, Jarvis D, Torén K, AntóJM, European Community Respiratory Health Survey
SO
Eur Respir J. 2002;20(3):679.
 
Several studies have demonstrated an excess risk for asthma among cleaning workers. The aim of this analysis was to compare clinical, immunological and functional characteristics associated with asthma in cleaners and other occupational groups. Cleaners, workers exposed to high molecular weight (MW) agents, workers exposed to low MW agents, and office workers were identified from an international community-based epidemiological study. Influence of sex, smoking, age and atopy on the relationships with asthma was investigated. Rates of respiratory symptoms, bronchial hyperresponsiveness, atopic sensitisation and lung function were compared between asthmatics from the four groups (case-case analysis). The risk for asthma in workers exposed to low MW agents was higher among nonatopics than among atopics. Case-case analysis showed no major differences in asthma characteristics between cleaners and workers exposed to high or low MW agents. Asthmatic cleaners had less atopy, more chronic bronchitis and a lower lung function as compared to office workers. Asthma in cleaning workers showed many similarities with that in workers known to be at risk for occupational asthma. Atopic sensitisation did not seem to play an important role in cleaning-related asthma.
AD
Respiratory and Environmental Health Research Unit, Institut Municipal d'lnvestigacióMèdica, Barcelona, Spain. jpzock@imim.es
PMID