Objective: This study aimed to delineate the clinical and genetic features of late-onset congenital central hypoventilation syndrome (LO-CCHS) in four children. Methods: Clinical data from four children with LO-CCHS, including presentations, genetic testing, and follow-up results, were collected and analyzed at the Department of Respiratory Medicine at Beijing Children’s Hospital, China, from December 2019 to December 2023. Results: Four children (two males, two females) with PHOX2B mutations and LO-CCHS diagnosis were included. Ages of disease onset were 0.75, 4.2, 10.3, and 0.4 years, corresponding diagnostic ages were 6.5, 5.8, 11.3, and 1.6 years, and diagnostic delays ranged from one to five years. All patients exhibited nocturnal bradypnea and hypercapnia. patient 1 presented with pulmonary artery hypertension (PAH) as the initial symptom. Patient 2 experienced recurrent pulmonary hemorrhage (PH) after respiratory infections and genetic testing conformed a CCHS diagnosis. patient 3 exhibited hypersomnia due to increased respiratory resistance triggered by swimming, and patient 4 experienced recurrent cyanosis and lethargy followed by convulsions a year later. Four different PHOX2B mutations were identified: three polyalanine repeat mutations (PARMs) and one non-polyalanine repeat mutation (NPARM). Two of these were de novo mutations and two were respectively inherited from asymptomatic mother. For one to three years follow-up, three of them were in stable condition with oxygen supplement while one (patient 4) dead of respiratory failure. Conclusions: PAH could be as significant phenotypes of LO-CCHS when diagnosis was delayed and PH may be as relevant manifestations of LO-CCHS in children with PHOX2B mutations.

Objectives: Primary ciliary dyskinesia (PCD) is a rare genetic disease mainly involved in lung dysfunction. PCD patient outcomes after azithromycin (AZM) treatment have rarely been reported. This study was aimed to assess AZM treatment effects on disease progression of pediatric PCD patients. Study design: This retrospective follow-up study involved PCD patients diagnosed from December 2009 to December 2020. Changes of clinical outcomes, pulmonary function, and chest computed tomography findings were compared between untreated and AZM-treated patients. Results: Of 63 enrolled patients (median follow-up duration of 3.1 years), 30 received AZM (AZM-treated group) and 33 received no AZM (AZM-untreated group). At diagnosis, no significant intergroup differences in age, sex, height, weight, respiratory infection frequency, and FEV1% and FVC% predicted values were found, although FEF25-75% predicted was lower in AZM group. Between treatment initiation and follow-up, patients in AZM-treated group had less respiratory infection frequency than that of controls (1.4 ± 0.8 VS 3.0 ± 2.1 times/year, respectively, P = 0.001) and fewer AZM-treated group patients exhibited exercise intolerance. Increases above baseline of AZM-treated group FEV1% and FVC% predicted values exceeded corresponding control increases, but intergroup differences were insignificant (FEV1% predicted: 5.3 (-13.4, 9.4) VS 1.8 (-12.1, 9.5), P = 0.477; FVC% predicted: 6.7 (-7.6, 18.8) VS 1.6 (-5.6, 7.6), P = 0·328). Conclusions: Long-term AZM treatment can reduce respiratory infection frequency and may maintain pulmonary diseases stable in pediatric PCD patients.