Cystic Fibrosis Center Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands.
Pediatr Pulmonol. 2010 Jun;45(6):601-7. doi: 10.1002/ppul.21227.
Siblings with cystic fibrosis (CF) share many genetic and environmental factors but may present different phenotypes. Younger sibs are mostly earlier diagnosed with CF than their older sibs, but might be at risk for an earlier colonization with Pseudomonas aeruginosa (PA) than their older counterparts due to cross-infection within families.
To analyze the effects of birth order and age at diagnosis on lung function, PA colonization, nutritional status, and survival during the first two decades of life in siblings with CF.
A retrospective cohort study of 52 sibling pairs was performed in two Dutch CF centers. Data were analyzed both cross-sectionally and longitudinally using Kaplan-Meier curves and modified log-rank tests.
Median age at diagnosis was significantly higher in the older sib compared with the younger sib (3.0 and 0.2 years, respectively, P < 0.0001). At the age of 5, 10, and 15 years no difference in lung function was found. However, at the age of 20 years, forced expiratory volume in 1 sec (FEV(1)) in older sibs was 19.4% (95% CI: 5.9-32.9%, P = 0.007) lower than in younger sibs. In the younger sibs group, FEV(1) at age 20 years was significantly better in those who had a diagnosis before the age of 6 months (difference 22.9%, 95% CI: 0.1-45.8%, P < 0.05). In the first 10 years of life the younger sibs tended to be earlier colonized with PA than their older counterparts. No differences in nutritional status and survival were observed.
In this sibling cohort study, an early diagnosis of CF was associated with better lung function after two decades of life. Although younger siblings tended to be colonized with PA at an earlier age, they showed better lung function outcomes. This underscores the importance of early diagnosis with newborn screening and early referral to a specialized center in the prevention of long-term deleterious effects on lung function.
患有囊性纤维化 (CF) 的兄弟姐妹共享许多遗传和环境因素，但可能表现出不同的表型。与年长的兄弟姐妹相比，年幼的兄弟姐妹通常更早被诊断出 CF，但由于家庭内的交叉感染，他们可能比年长的兄弟姐妹更早定植铜绿假单胞菌 (PA)。
分析出生顺序和诊断时的年龄对 CF 兄弟姐妹在生命的头二十年期间的肺功能、PA 定植、营养状况和生存的影响。
对两个荷兰 CF 中心的 52 对兄弟姐妹进行了回顾性队列研究。使用 Kaplan-Meier 曲线和修改后的对数秩检验对数据进行了横断面和纵向分析。
年长的兄弟姐妹的中位诊断年龄明显高于年幼的兄弟姐妹（分别为 3.0 岁和 0.2 岁，P<0.0001）。在 5、10 和 15 岁时，肺功能没有差异。然而，在 20 岁时，年长的兄弟姐妹的 1 秒用力呼气量 (FEV1) 低 19.4%（95%CI：5.9-32.9%，P=0.007）。在年幼的兄弟姐妹组中，在 6 个月之前被诊断出 CF 的患者，20 岁时的 FEV1 显著更好（差异为 22.9%，95%CI：0.1-45.8%，P<0.05）。在生命的头 10 年，年幼的兄弟姐妹比年长的兄弟姐妹更早定植 PA。在营养状况和生存方面没有观察到差异。
在这项兄弟姐妹队列研究中，CF 的早期诊断与生命后二十年的更好的肺功能相关。尽管年幼的兄弟姐妹倾向于更早定植 PA，但他们的肺功能结果更好。这强调了通过新生儿筛查进行早期诊断和尽早转介到专门中心以预防对肺功能的长期有害影响的重要性。
