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Study Objectives: Congenital central hypoventilation syndrome (CCHS) is caused by the paired-like homeobox 2B (PHOX2B) mutation and predominantly diagnosed during the neonatal period. Although late-onset CCHS and PHOX2B mutation carriers have been reported, the features of these disease states in adults remain uncertain. This study aimed to identify the characteristics of adult-onset CCHS and PHOX2B-mutation carriers in adult. Methods: We mainly searched the PubMed/Medline and Cochrane Databases and classified our target patients into 2 groups: group A, symptomatically diagnosed with late-onset CCHS in adulthood; group B, adult PHOX2B-mutation carriers. Then, clinical characteristics, including the onset, treatment, long-term course, and pattern of the PHOX2B mutation in both groups were analyzed. Additionally, a new adult-case of late-onset CCHS was added to the analysis. Results: Group A was comprised of 12 patients. The onset triggers of illness included a history of respiratory compromise following general anesthesia and respiratory tract infections. All patients in group A had 20/25 polyalanine repeat mutations and required some chronic ventilatory support at least during sleep, including portable positive pressure ventilator via tracheostomy or noninvasive positive pressure ventilation. In these patients with ventilatory support during sleep, sudden death or poor prognosis was not reported. Group B was comprised of 33 adults from 24 families with PHOX2B mutations. Nine patients in group B were confirmed with the diagnosis of CCHS. Although polyalanine repeat mutations 20/25 represented the most common gene mutation, diverse mutations, including mosaicism, were observed. Hypoventilation of several cases in group B were underdiagnosed by overnight polysomnography without monitoring for CO 2 . Conclusion: Alveolar hypoventilation with unknown origin can be caused by the PHOX2B mutation even in adult cases. Both the identification of the PHOX2B mutation and the incorporation of capnography in polysomnography are important for adult cases with unexplained alveolar hypoventilation or asymptomatic mutation carriers.

Background Interstitial pneumonia (IP) is a poor prognostic comorbidity in patients with non-small cell lung cancer (NSCLC) and is also a risk factor for pneumonitis. The TORG1936/AMBITIOUS trial, the first known phase II study of atezolizumab in patients with NSCLC with comorbid IP, was terminated early because of the high incidence of severe pneumonitis. Methods This study included patients with idiopathic chronic fibrotic IP, with a predicted forced vital capacity (%FVC) of >70%, with or without honeycomb lung, who had previously been treated for NSCLC. The patients received atezolizumab every 3 weeks. The primary endpoint was the 1-year survival rate. Results A total of 17 patients were registered; the median %FVC was 85.4%, and 41.2% had honeycomb lungs. The 1-year survival rate was 53.3% (95% CI, 25.9-74.6). The median overall and progression-free survival times were 15.3 months (95% CI, 3.1-not reached) and 3.2 months (95% CI, 1.2-7.4), respectively. The incidence of pneumonitis was 29.4% for all grades, and 23.5% for grade ≥3. Tumor mutational burden and any of the detected somatic mutations were not associated with efficacy or risk of pneumonitis. Conclusion Atezolizumab may be one of the treatment options for patients with NSCLC with comorbid IP, despite the high risk of developing pneumonitis. This clinical trial was retrospectively registered in the Japan Registry of Clinical Trials on August 26, 2019, (registry number: jRCTs031190084, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084).

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