Medline ® Abstracts for References 48,61
of 'Reactive airways dysfunction syndrome and irritant-induced asthma'
AEOL10150: a novel therapeutic for rescue treatment after toxic gas lung injury.
McGovern T, Day BJ, White CW, Powell WS, Martin JG
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.
Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H2X 2P2, Canada.
Occupational lower airway disease in relation to World Trade Center inhalation exposure.
de la Hoz RE
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.
Departments of Preventive Medicine and Medicine, Mount Sinai School of Medicine, New York, New York, USA. Rafael.delaHoz@mssm.edu