Roff Andrea J, Davies Andrew N, Clifton Vicki L, Stark Michael J, Tai Andrew, Robinson Joshua L, Hammond Sarah J, Darby Jack R T, Meakin Ashley S, Lock Mitchell C, Wiese Michael D, Sharkey David J, Bischof Robert J, Morrison Janna L, Gatford Kathryn L
Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
School of Biomedicine, University of Adelaide, Adelaide, SA, Australia.
J Physiol. 2025 Mar;603(5):1241-1261. doi: 10.1113/JP287583. Epub 2025 Feb 6.
Asthma is the most common respiratory condition during pregnancy and increases the risks of adverse pregnancy and perinatal outcomes. Asthma symptoms change in ∼60% of pregnancies, but whether this is due to pregnancy itself is unclear. We tested the hypothesis that physiological changes during pregnancy worsen asthma severity in an ovine experimental model of allergic asthma. Three-year-old Merino ewes were randomly allocated to either control or allergic asthma groups. Asthma was induced through sensitisation and repeated airway challenge with house dust mite allergen. We compared airway function, circulating cytokine profile and airway immune response to allergen challenge throughout the study and airway structure between groups, in non-pregnant (control n = 8, asthma n = 9), singleton-pregnant (control n = 5, asthma n = 8) and twin-pregnant ewes (control n = 6, asthma n = 9). Within non-pregnant animals, transpulmonary pressure at Day 132 of the study was 37% higher in asthmatic than control ewes (P = 0.031), but not different between treatments in singleton-pregnant (P = 0.594) or twin-pregnant (P = 0.074) ewes. Between premating and Day 132, dynamic compliance decreased more in asthmatic than control ewes (P = 0.040), and this change did not differ between litter sizes (P = 0.096). Neither asthma nor pregnancy affected eosinophils in bronchoalveolar lavage or lung tissue. There was no evidence of lung airway remodelling in the cohort. The results of this study suggest that pregnancy does not increase asthma symptoms or severity of mild asthma. KEY POINTS: Asthma severity changes in ∼60% of pregnancies, but whether this is due to pregnancy itself is unclear. Using a sheep model of allergic asthma, we tested the hypothesis that physiological changes during pregnancy worsen asthma severity. Dynamic compliance decreased to a greater extent in asthmatic than control ewes over the course of the study, indicating the development of a mild asthma phenotype, and this decrease was similar in non-pregnant, singleton-pregnant and twin-pregnant ewes. Eosinophil proportions in bronchoalveolar lavage and lung tissue were not affected by either asthma or pregnancy, nor was there evidence of lung airway remodelling in this cohort. Our findings suggest that pregnancy does not increase asthma symptoms or severity of mild asthma.
哮喘是孕期最常见的呼吸道疾病，会增加不良妊娠和围产期结局的风险。约60%的孕期哮喘症状会发生变化，但这是否归因于妊娠本身尚不清楚。我们在绵羊过敏性哮喘实验模型中验证了妊娠期间的生理变化会加重哮喘严重程度这一假设。将三岁的美利奴母羊随机分为对照组或过敏性哮喘组。通过用屋尘螨过敏原致敏和反复进行气道激发来诱发哮喘。在整个研究过程中，我们比较了非妊娠（对照组n = 8，哮喘组n = 9）、单胎妊娠（对照组n = 5，哮喘组n = 8）和双胎妊娠母羊（对照组n = 6，哮喘组n = 9）之间的气道功能、循环细胞因子谱以及对过敏原激发的气道免疫反应，以及两组之间的气道结构。在非妊娠动物中，研究第132天时，哮喘母羊的跨肺压比对照母羊高37%（P = 0.031），但在单胎妊娠（P = 0.594）或双胎妊娠（P = 0.074）母羊中，不同处理之间无差异。在配种前到第132天期间，哮喘母羊的动态顺应性下降幅度比对照母羊更大（P = 0.040），且这种变化在不同产仔数之间无差异（P = 0.096）。哮喘和妊娠均未影响支气管肺泡灌洗或肺组织中的嗜酸性粒细胞。该队列中没有肺气道重塑的证据。本研究结果表明，妊娠不会增加哮喘症状或轻度哮喘的严重程度。要点：约60%的孕期哮喘严重程度会发生变化，但这是否归因于妊娠本身尚不清楚。我们使用绵羊过敏性哮喘模型验证了妊娠期间的生理变化会加重哮喘严重程度这一假设。在研究过程中，哮喘母羊的动态顺应性下降幅度比对照母羊更大，表明出现了轻度哮喘表型，且在非妊娠、单胎妊娠和双胎妊娠母羊中这种下降情况相似。支气管肺泡灌洗和肺组织中的嗜酸性粒细胞比例不受哮喘或妊娠的影响，该队列中也没有肺气道重塑的证据。我们的研究结果表明，妊娠不会增加哮喘症状或轻度哮喘的严重程度。
