Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring.

J Immunotoxicol. 2011 Jun 30;

Authors: Allina J, Grabowski J, Doherty-Lyons S, Fiel MI, Jackson CE, Zelikoff JT, Odin JA

Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring.

PMID: 21718087 [PubMed - as supplied by publisher]

Nitric oxide metabolism in asthma pathophysiology.

Biochim Biophys Acta. 2011 Jun 21;

Authors: Ghosh S, Erzurum SC

Asthma, a chronic inflammatory disease is typically characterized by bronchoconstriction and airway hyper-reactivity. A wealth of studies applying chemistry, molecular and cell biology to animal model systems and human asthma over the last decade has revealed that asthma is associated with increased synthesis of the gaseous molecule nitric oxide (NO). The high NO levels in the oxidative environment of the asthmatic airway lead to greater formation of reactive nitrogen species (RNS) and subsequent oxidation and nitration of proteins, which adversely affect protein functions that are biologically relevant to chronic inflammation. In contrast to the high levels of NO and nitrated products, there are lower levels of beneficial S-nitrosothiols (RSNO), which mediate bronchodilation, due to greater enzymatic catabolism of RSNO in the asthmatic airways. This review discusses the rapidly accruing data linking metabolic products of NO as critical determinants in the chronic inflammation and airway reactivity of asthma. This article is part of a Special Issue entitled Biochemistry of Asthma.

PMID: 21718755 [PubMed - as supplied by publisher]

The biochemistry of asthma.

Biochim Biophys Acta. 2011 Jun 22;

Authors: Gaston B

BACKGROUND: Asthma is not one disease. Different patients have biochemically distinct phenotypes. SCOPE OF REVIEW: Biomarker analysis was developed to identify inflammation in the asthmatic airway. It has led to a renewed interest in biochemical abnormalities in the asthmatic airway. The biochemical determinants of asthma heterogeneity are many. Examples include decreased activity of superoxide dismutases; increased activity of eosinophil peroxidase, S-nitrosoglutathione reductase, and arginases; decreased airway pH; and increased levels of asymmetric dimethyl arginine. MAJOR CONCLUSIONS: New discoveries suggest that biomarkers such as exhaled nitric oxide reflect complex airway biochemistry. This biochemistry can be informative and therapeutically relevant. GENERAL SIGNIFICANCE: Improved understanding of airway biochemistry will lead to new tests to identify unique subpopulations of patients with asthma. It will also likely lead to new, targeted treatments for these specific asthma subpopulations. This article is part of a Special Issue entitled Biochemistry of Asthma.

PMID: 21718756 [PubMed - as supplied by publisher]

Validation of a school-based written questionnaire for asthma case identification in Argentina.

Pediatr Pulmonol. 2011 Jun 30;

Authors: Busi LE, Sly PD, Restuccia S, Llancamán L

Recognition of asthma in community-based surveys can be problematic. We sought to develop and validate questionnaires that could identify elementary school-aged children likely to have asthma or who had poorly-controlled asthma. Questionnaires for parents (PQ) and students (SQ) to complete were developed using guidance on question wording from a focus group consisting of children with asthma and their parents. The gold standard for this study was a pulmonologist determination of asthma and this was used to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each question and for combinations of questions. Questionnaires were distributed to 830 children attending elementary schools in Trelew, Argentina and 96% were returned. Test-retest reliability was determined in 221 randomly selected parents and children and very good levels of agreement were seen for individual questions. Asthma was diagnosed in 92 students. Overall, the PQ was able to detect asthma better than the SQ. Optimal diagnostic ability came by combining questions from the PQ and SQ. Not surprisingly, these questionnaires had a better NPV than PPV and can be used to determine which children require further evaluation. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

PMID: 21721144 [PubMed - as supplied by publisher]