situs ambiguus 与原发性纤毛运动障碍患儿的不良临床结局相关。
Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia.
机构信息
McGill University Health Centre Research Institute, Montreal Children's Hospital, Montreal, QC.
BC Children's Hospital, University of British Columbia, Vancouver, BC.
出版信息
Chest. 2024 May;165(5):1070-1081. doi: 10.1016/j.chest.2023.12.005. Epub 2023 Dec 9.
BACKGROUND
Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]).
RESEARCH QUESTION
Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT?
STUDY DESIGN AND METHODS
This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression.
RESULTS
In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA.
INTERPRETATION
Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both.
TRIAL REGISTRY
ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www.
CLINICALTRIALS
gov.
背景
原发性纤毛运动障碍（PCD）是一种罕见的运动纤毛疾病，与 situs 异常有关。至少 12%的 PCD 患者存在 situs ambiguus（SA），包括器官侧位缺陷超出正常排列（ situs solitus [SS]）或镜像反转（ situs inversus totalis [SIT]）。
研究问题
与 SS 或 SIT 相比，患有 PCD 和 SA 的患者临床结局是否更差？
研究设计和方法
本横断面、多中心研究评估了年龄在 21 岁或以下的患有 PCD 的参与者。参与者被分为存在 SA（包括异构性）或不存在 SA（SS 或 SIT）。使用广义线性模型和逻辑回归及泊松回归，在调整入组年龄和严重 CCDC39 或 CCDC40 基因型后，比较 situs 组之间的疾病严重程度标志物。
结果
在 397 名患有 PCD（平均年龄 8.4 岁；范围 0.1-21 岁）的参与者中，42 名参与者被分类为存在 SA，包括 16 名（38%）患有复杂心血管畸形或心房异构的患者、13 名（31%）患有简单心血管畸形的患者和 13 名（31%）无心血管畸形的患者。其中，15 名（36%）患者接受了心脏手术，24 名（57%）患者出现解剖性脾脏异常，7 名（17%）患者同时出现两种情况。其余 355 名参与者没有 SA，包括 152 名 SIT 和 203 名 SS。总体而言，70 名参与者（17%）携带严重的 CCDC39 或 CCDC40 基因型。与没有 SA 的参与者相比，存在 SA 的参与者的 BMI z 评分中位数较低（P=.03），FVC z 评分中位数较低（P=.01），并且在入组前 5 年期间，因急性呼吸道感染住院和接受 IV 抗生素治疗的次数更多（P<.01）。需要手术的心血管畸形或存在解剖性脾脏异常的患者与没有 SA 的患者相比，BMI z 评分中位数较低，因呼吸道疾病住院和接受 IV 治疗的次数也更多。
解释
与 SS 或 SIT 组合相比，患有 PCD 和 SA 的儿童因急性呼吸道感染住院次数更多，营养状况和肺部状况更差。患有 PCD 和 SA 的参与者的营养不良和因呼吸道感染住院次数增加与需要心脏手术的心血管畸形、脾脏异常或两者均有关。
临床试验注册
ClinicalTrials.gov；编号：NCT02389049 和 NCT00323167；网址：www.clinicaltrials.gov。
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