Wadhwa Vikas, Dharmage Shyamali C, Wurzel Danielle, Sly Peter D, Svanes Cecilie, Lowe Adrian J, Idrose N Sabrina, Waidyatillake Nilakshi, Lodge Caroline, Russell Melissa
Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Pediatr Allergy Immunol. 2025 Jun;36(6):e70115. doi: 10.1111/pai.70115.
Allergic sensitization and respiratory infections commonly occur in childhood. Interplay between them in asthma development is known as the 'two-hit' hypothesis. There has been no previous investigation of this hypothesis on adult lung function.
In a birth cohort at high risk for allergic diseases, we investigated interactions between these two factors and lung function outcomes into adulthood.
Allergic sensitization was assessed at age 24 months by skin prick testing to aero and food allergens. Respiratory infection was defined as cough, rattle or wheeze measured by frequent questionnaires up to age 24 months. Regression models were utilized to identify interactions between these exposures and associations with lung function at ages 12, 18 and 25 years.
At age 25 years, those sensitized at age 2 years(n = 118) demonstrated reductions in pre-bronchodilator FEV of 0.06(95% CI: -0.12, 0.00, z-score units, p = .055) for each additional month of respiratory infections. Those not sensitized (n = 120) had increases in pre-bronchodilator FEV of 0.07 (95% CI: 0.02, 0.13, z-score units, p = .012) for each additional month of respiratory infection(p = .012). Similar findings were noted for FEV/FVC ratio(p = .011), FEF(p = .007) and absolute change in pre and post bronchodilator lung function. At 18 years, findings were similar; however, there was less evidence for interactions at 12 years.
Our study findings support the 'two-hit' hypothesis of interactions between early-life allergic sensitization and increasing respiratory infections, and impairment in lung function up to age 25 years. Early childhood respiratory infections however had different impacts on lung function depending upon the presence or absence of allergic sensitization.
过敏致敏和呼吸道感染在儿童期较为常见。它们在哮喘发展过程中的相互作用被称为“两次打击”假说。此前尚无关于该假说对成人肺功能影响的研究。
在一个有过敏性疾病高风险的出生队列中，我们研究了这两个因素之间的相互作用以及它们对成年后肺功能结果的影响。
在24个月龄时通过对空气传播和食物过敏原进行皮肤点刺试验评估过敏致敏情况。呼吸道感染定义为通过频繁问卷调查直至24个月龄时测量的咳嗽、呼噜声或喘息。使用回归模型来确定这些暴露因素之间的相互作用以及它们与12岁、18岁和25岁时肺功能的关联。
在25岁时，2岁时致敏的人群（n = 118）中，每增加一个月的呼吸道感染，支气管扩张剂使用前的第一秒用力呼气容积（FEV）降低0.06（95%可信区间：-0.12，0.00，z评分单位，p = 0.055）。未致敏的人群（n = 120）中，每增加一个月的呼吸道感染，支气管扩张剂使用前的FEV增加0.07（95%可信区间：0.02，0.13，z评分单位，p = 0.012）（p = 0.012）。对于FEV/FVC比值（p = 0.011）、用力呼气流量（FEF）（p = 0.007）以及支气管扩张剂使用前后肺功能的绝对变化，也观察到了类似的结果。在18岁时，结果相似；然而，在12岁时相互作用的证据较少。
我们的研究结果支持了早期生活过敏致敏与不断增加的呼吸道感染之间相互作用以及直至25岁时肺功能受损的“两次打击”假说。然而，儿童早期呼吸道感染对肺功能的影响因是否存在过敏致敏而有所不同。
