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.

Background: Lymphatic plastic bronchitis (PB) most commonly occurs in children with congenital heart disease as a result of secondary pulmonary lymphatic flow disorder (PLFD). However, PB caused by primary PLFD is rare. We made a retrospective analysis of two children diagnosed with PB due to primary PLFD, in order to contribute to further understanding of these disorders. Results: Patient 1, an eight-year-old boy, presented with chronic productive cough and expectorated milky-white mucous plugs accompanied by intermitted wheezing for one year. Patient 2, a nine-month-old girl, presented with episodes of acute respiratory distress with expectoration of milky-white bronchial casts for four months. There was no obvious evidence of infection in either child. Bronchoscopy showed massive milky-white casts blocking the airway in patient 2; no casts were observed in patient 1. Bilateral thickening of bronchovascular bundles and interlobular septal, as well as multiple patchy ground-glass opacities were seen on chest computed tomography (CT) in both patients. Lymphangioscintigraphy demonstrated pulmonary lymph reflux in both patients and slowed lymphatic drainage of the lower limbs in patient 1. Primary PLFD was considered for both patients, and a diagnosis of yellow nail syndrome was made in patient 1. Both patients received lymphatic interventional treatment, but all experienced recurrence following the procedure. Conclusions: Primary PLFD is a rare but significant cause of PB in children. Chest CT findings have highly suggestive significance for the diagnosis. The lymphatic interventional procedure may be effective for short-term resolution of symptoms, but prone to recurrence.

there are several advantages to the use of transbronchial lung cryobiopsy (TBLC), including less trauma, fewer complications, large and high-quality specimens, and lower cost. This procedure is mainly used for the etiological diagnosis of diffuse parenchymal lung diseases (DPLD) [2] and its most common complications, including bleeding and pneumothorax. Virtual bronchoscopy navigation (VBN) can assist bronchoscopists in pinpointing the target area in the lung and designing an appropriate navigation pathway to accurately reach the target lesion [3]. Thus, VBN improves the rate of diagnosis and reduces the risk of bleeding and pneumothorax. In this report, which we believe to be the first of its kind, we performed TBLC guided by VBN.