Background: Asthma and especially severe asthma affect women more frequently than men. Since asthma severity correlates with remodeling changes in the lung, a female propensity to remodeling could be expected. We studied whether our previous observation that female mice have more pronounced airway inflammation than males is associated with more pronounced remodeling in two models of chronic allergic asthma. Methods: Male and female BALB/c mice were (1) sensitized and subsequently challenged with ovalbumin (OVA) for 4 weeks, or (2) exposed to house dust mite (HDM) for 5 weeks. In both models, allergic inflammation, remodeling, antigen-specific IgE and methacholine (MCh) responsiveness were assessed. Results: Females had higher antigen-specific serum IgE levels, higher numbers of eosinophils and were more responsive to MCh. In the OVA model, females also had higher levels of Th2 cytokines in lung tissue than males. Both sexes developed similar airway remodeling (smooth muscle layer thickness, collagen III deposition and goblet cell hyperplasia) in the two models. Conclusions: Combining results of an OVA- and a HDM-induced mouse model of allergic airway inflammation, we have shown that more severe allergic inflammation in females is not accompanied with more pronounced airway remodeling.
One third of women continue to smoke during early pregnancy, although evidence for detrimental effects of in utero smoke exposure on fetal growth and development are rising. A number of epidemiologic studies have shown that prenatal exposure to environmental smoke is an independent risk factor for poor lung function, wheezing, and the development of (possibly nonatopic) asthma. Epidemiologic data on the effect on development of allergic sensitization are inconclusive, since in most studies no clear separation is made between pre- and postnatal exposure. However, studies that included prenatal smoke exposure showed no effect on sensitization. Aberrant development of the fetal lung structure, as shown in experimental models, may underlie the increased risk for poor lung function and asthma development. Recently, we showed that maternal smoking during pregnancy decreased expression of genes that are involved in lung development in lungs of neonatal mice. In addition, maternal smoking during pregnancy increased airway remodeling in adult mice offspring. Future experimental studies may reveal whether lung developmental changes may additionally underlie susceptibility to the apparent adult-onset disease chronic obstructive pulmonary disease.
Children from smoking mothers have an increased risk of developing asthma for reasons largely unknown. The effects of maternal smoking during pregnancy on remodelling, allergic airway inflammation and hyperresponsiveness in offspring were investigated in an experimental asthma model. Mice were exposed to fresh air or cigarette smoke from 3 weeks prior to conception until birth. Offspring were exposed to house dust mite (HDM) or PBS intranasally four times per week from week 5 to week 10 after birth onwards.Maternal smoking increased airway smooth muscle layer, collagen III deposition and HDMinduced goblet cell numbers in offspring. It additionally increased methacholine responsiveness, which correlated significantly with increased airway smooth muscle layer and collagen deposition. Maternal smoking increased HDM-induced numbers of neutrophils and mast cells in lung tissue. No further effects were observed.Smoking during pregnancy induces airway remodelling in mice offspring, which may contribute to increased methacholine responsiveness. This takes place irrespective of allergen exposure but may worsen the outcome of the allergic stimulus, resulting in higher methacholine responsiveness in house dust mite-exposed offspring from smoking mothers when compared to nonsmoking mothers. The results provide a possible mechanism behind the association between maternal smoking and asthma.
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