Blacquière M J, Timens W, Melgert B N, Geerlings M, Postma D S, Hylkema M N
Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eur Respir J. 2009 May;33(5):1133-40. doi: 10.1183/09031936.00129608. Epub 2009 Jan 7.
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 HDM-induced 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.
母亲吸烟的孩子患哮喘的风险增加,其原因很大程度上尚不清楚。在一个实验性哮喘模型中,研究了孕期母亲吸烟对后代气道重塑、过敏性气道炎症和高反应性的影响。从受孕前3周直到出生,将小鼠暴露于新鲜空气或香烟烟雾中。从出生后第5周开始至第10周,每周4次经鼻给后代注射屋尘螨(HDM)或磷酸盐缓冲盐水(PBS)。母亲吸烟会增加后代气道平滑肌层、III型胶原蛋白沉积以及HDM诱导的杯状细胞数量。此外,它还会增加乙酰甲胆碱反应性,这与气道平滑肌层增加和胶原蛋白沉积显著相关。母亲吸烟会增加HDM诱导的肺组织中嗜中性粒细胞和肥大细胞的数量。未观察到进一步的影响。孕期吸烟会诱导小鼠后代气道重塑,这可能导致乙酰甲胆碱反应性增加。这一情况与是否接触过敏原无关,但可能会使过敏刺激的结果恶化,导致与非吸烟母亲相比,吸烟母亲的后代在接触屋尘螨时乙酰甲胆碱反应性更高。这些结果为母亲吸烟与哮喘之间的关联提供了一种可能的机制。