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Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8-21 years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation ([rho] = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV.sub.1 ([greater than or equal to] 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV.sub.1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV.sub.1., Author(s): Ajay S. Kasi [sup.1] [sup.2], Choo Phei Wee [sup.1], Thomas G. Keens [sup.1], Danieli B. Salinas [sup.1] Author Affiliations: (1) grid.42505.36, 0000 0001 2156 6853, Division of Pediatric Pulmonology, [...]

In preschool children with cystic fibrosis (CF), lung clearance index (LCI) is a sensitive test to detect early lung disease. Some children with CF screen positive, inconclusive diagnosis (CFSPID) may in time develop clinical features of CF. LCI has not been studied in CFSPID children. LCI and spirometry were performed in preschool age children with CF, CFSPID, and non-CF healthy controls (HCs) during two visits. Fifty-four preschool age children (HC n = 18, CFSPID n = 17, and CF n = 19) were tested. Mean LCI from the CFSPID group was not statistically different from HC (p = 0.49), but significantly different when compared to CF (p = 0.04). LCI was abnormal in 2 CFSPID children who carried potentially deleterious CFTR variants. Mean forced expiratory volume in 1 s (FEV.sub.1) was not statistically different between CFSPID and CF (p = 0.26). LCI can potentially detect early lung disease in CFSPID individuals as part of assessing their risk for reclassification to CF diagnosis., Author(s): Ajay S. Kasi [sup.1] [sup.2] , Choo Phei Wee [sup.1] , Thomas G. Keens [sup.1] , Danieli B. Salinas [sup.1] Author Affiliations: (1) grid.42505.36, 0000 0001 2156 6853, Division [...]

Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation. Nonpolyalanine repeat mutations are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and neural crest tumors; however, our patient had a relatively milder respiratory phenotype requiring sleep-only assisted ventilation without tracheostomy. Although alveolar hypoventilation is the hallmark of CCHS, our patient lacked hypoventilation. Bilevel positive airway pressure could be considered in some infants with CCHS requiring sleep-only assisted ventilation for tracheostomy avoidance. Our case demonstrates the expanding phenotypic spectrum in CCHS and the importance of formulating an individualized care plan., Citation: Fain ME, Raghunandan S, Pencheva B, Leu RM, Kasi AS. Images: atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea. J Clin Sleep Med . 2024;20(3):478-481., (© 2024 American Academy of Sleep Medicine.)

Study Objectives: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by impaired control of breathing caused by paired-like homeobox 2B ( PHOX2B ) gene variants, necessitating lifelong assisted ventilation (AV). This study aimed to assess sleep quality in patients with CCHS and their parents using sleep questionnaires., Methods: Parents of patients with CCHS completed the Pittsburgh Sleep Quality Index (PSQI) regarding their sleep and the Sleep Disturbance Scale for Children (SDSC) regarding their child's sleep., Results: Twenty participants completed the questionnaires. The median (interquartile range) ages of the parents and patients were 41.5 (38.5-51.5) and 11.5 (7.4-16.7) years, respectively. The median (interquartile range) PSQI and SDSC scores were elevated at 6.5 (4-10) and 41.5 (34-51.5), respectively, suggesting that parents and patients with CCHS can experience sleep disturbances and poor sleep quality. There were no significant differences in SDSC ( P = 1.0) and PSQI ( P = .76) scores for AV with or without tracheostomy. Similarly, there were no significant differences in SDSC ( P = .22) and PSQI ( P = .34) scores based on PHOX2B genotypes. There was a moderately strong, significant, and positive correlation between the CCHS SDSC scores and parental PSQI scores ( r = .48, P = .03), suggesting that sleep disturbances in patients with CCHS were associated with poor parental sleep quality. There was no difference in the median parental sleep duration between those with and without nighttime home nursing ( P = .09)., Conclusions: Patients with CCHS and their parents are at risk for sleep disturbances regardless of their AV modality and PHOX2B genotype. In addition to AV management, patients with CCHS and their parents should be assessed for sleep disturbances., Citation: Finch CE, Leu RM, Harford K-L, Westbrook AL, Kasi AS. Sleep disturbances in parental caregivers and patients with congenital central hypoventilation syndrome. J Clin Sleep Med . 2023;19(3):549-554., (© 2023 American Academy of Sleep Medicine.)

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and potentially lethal disorder of respiratory control, autonomic, and hypothalamic dysfunction of unknown etiology. We report a 15-year-old girl with ROHHAD who developed hyperphagia and rapid weight gain of 16 kg between 2.5 and 4 years of age and cardiorespiratory arrest at 4 years. Initial polysomnography showed central sleep apnea and severe oxygen desaturations without hypoventilation. Mild obstructive sleep apnea and intermittent hypoxemia were identified at 4.5 years, following which nocturnal bilevel positive airway pressure therapy was initiated. At 6 years, she developed sleep-related hypoventilation, and subsequent polysomnograms continued to show obstructive sleep apnea and hypoventilation requiring bilevel positive airway pressure. Clinicians interpreting polysomnograms should become familiar with the evolution of sleep-disordered breathing in ROHHAD and that hypoventilation may develop over time. Our case highlights the importance of serial polysomnography in patients with ROHHAD and optimal ventilatory management., Citation: Ghosh R, Malik M, Daley TC, Kasi AS. Images: Sleep-disordered breathing and hypoventilation in a child with obesity and hypothalamic dysfunction. J Clin Sleep Med . 2022;18(1):339-342., (© 2022 American Academy of Sleep Medicine.)

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with failure of central control of breathing and of the autonomic nervous system function due to a mutation in the paired-like homeobox 2B (PHOX2B) gene. Affected patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxemia, and they do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis of CCHS must be confirmed with PHOX2B gene mutation. Generally, the PHOX2B mutation genotype can aid in anticipating the severity of the phenotype. They require ventilatory support for life. Home assisted ventilation options include positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and diaphragm pacing via phrenic nerve stimulation, but each strategy has its associated limitations and challenges. Since all the clinical manifestations of CCHS may not manifest at birth, periodic monitoring and early intervention are necessary to prevent complications and improve outcome. Life-threatening arrhythmias can manifest at different ages and a normal cardiac monitoring study does not exclude future occurrences leading to the dilemma of timing and frequency of cardiac rhythm monitoring and treatment. Given the rare incidence of CCHS, most health care professionals are not experienced with managing CCHS patients, particularly those with diaphragm pacers. With early diagnosis and advances in home mechanical ventilation and monitoring strategies, many CCHS children are surviving into adulthood presenting new challenges in their care., Competing Interests: Disclosure The authors report no conflicts of interest in this work.