Obstructive sleep apnea (OSA) causes many systemic disorders via mechanisms related to sympathetic nerve activation, systemic inflammation, and oxidative stress. OSA typically shows repeated sleep apnea followed by hyperventilation, which results in intermittent hypoxia (IH). IH is associated with an increase in sympathetic activity, which is a well-known pathophysiological mechanism in hypertension and insulin resistance. In this review, we show the basic and clinical significance of IH from the viewpoint of not only systemic regulatory mechanisms focusing on pulmonary circulation, but also cellular mechanisms causing lifestyle-related diseases. First, we demonstrate how IH influences pulmonary circulation to cause pulmonary hypertension during sleep in association with sleep state-specific change in OSA. We also clarify how nocturnal IH activates circulating monocytes to accelerate the infiltration ability to vascular wall in OSA. Finally, the effects of IH on insulin secretion and insulin resistance are elucidated by using an in vitro chamber system that can mimic and manipulate IH. The obtained data implies that glucose-induced insulin secretion (GIS) in pancreatic β cells is significantly attenuated by IH, and that IH increases selenoprotein P, which is one of the hepatokines, as well as TNF-α, CCL-2, and resistin, members of adipokines, to induce insulin resistance via direct cellular mechanisms. Clinical and experimental findings concerning IH give us productive new knowledge of how lifestyle-related diseases and pulmonary hypertension develop during sleep.

Background Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines was reported in studies in several countries, data is limited from Asian countries, especially against the Delta (B.1.617.2) variant. Methods We conducted a multicenter test-negative case-control study in patients aged 16 visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from July 1 to September 30, 2021, when the Delta variant was dominant (90% of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16 to 64 was also assessed. Results We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving two doses 14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8–93.9) among patients aged 16 to 64 and 90.3% (95% CI, 73.6–96.4) among patients aged 65. Among patients aged 16 to 64, vaccine effectiveness within one to three months after full vaccination was 91.8% (95% CI, 80.3–96.6), and was 86.4% (95% CI, 56.9–95.7) within four to six months. Conclusions mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July 1 to September 30, 2021, when the Delta variant was dominant nationwide.

IntroductionThere is no established clinical prediction model for in-hospital death among patients with pneumonic chronic obstructive pulmonary disease (COPD) exacerbation. We aimed to externally validate BAP-65 and CURB-65 and to develop a new model based on the eXtreme Gradient Boosting (XGBoost) algorithm.MethodsThis multicentre cohort study included patients aged ≥40 years with pneumonic COPD exacerbation. The input data were age, sex, activities of daily living, mental status, systolic and diastolic blood pressure, respiratory rate, heart rate, peripheral blood eosinophil count, and blood urea nitrogen. The primary outcome was in-hospital death. BAP-65 and CURB-65 underwent external validation using the area under the receiver operating characteristic curve (AUROC) in the whole dataset. We used XGBoost to develop a new prediction model. We compared the AUROCs of XGBoost with that of BAP-65 and CURB-65 in the test dataset using bootstrap sampling.ResultsWe included 1190 patients with pneumonic COPD exacerbation. The in-hospital mortality was 7% (88/1190). In the external validation of BAP-65 and CURB-65, the AUROCs (95% confidence interval [CI]) of BAP-65 and CURB-65 were 0.69 (0.66–0.72, and 0.69 (0.66–0.72), respectively. XGBoost showed an AUROC of 0.71 (0.62–0.81) in the test dataset. There was no significant difference in the AUROCs of XGBoost versus BAP-65 (absolute difference, 0.054; 95% CI, −0.057–0.16) or versus CURB-65 (absolute difference, 0.0021; 95% CI, −0.091–0.088).ConclusionBAP-65, CURB-65, and XGBoost showed low predictive performance for in-hospital death in pneumonic COPD exacerbation. Further large-scale studies including more variables are warranted.

Background Chronic pulmonary aspergillosis (CPA) develops in various underlying pulmonary conditions. There is scarce data evaluating interstitial lung disease (ILD)/abnormalities (ILA) as such conditions, and it has not been explored much whether non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a prognostic factor for mortality in CPA patients. Few reports had investigated prognostic factors of CPA including underlying pulmonary conditions. Objectives To explore prognostic factors of CPA including pulmonary conditions. Methods We conducted a retrospective cohort study of 264 CPA patients from a center for pulmonary aspergillosis in Japan. Results Survival rates were 78.7%, 61.0%, and 47.4% at 1, 3, and 5 years, respectively. Of 264 patients, 53 (20.1%) and 87 (33.1%) were complicated with ILA and NTM-PD. Several independent prognostic factors were identified by multivariate Cox proportional analysis: ILA (HR 1.76, 95%CI 1.06–2.92, p = 0.029), age (1.05, 1.02–1.08, p<0.001), male sex (2.48, 1.34–4.59, p = 0.004), body mass index of <18.5 kg/m2 (1,87, 1.20–2.90, p = 0.005), presence of aspergilloma (1.59, 1.04–2.45, p = 0.033), and lower serum albumin (0.56, 0.38–0.83, p = 0.004). NTM-PD was not associated with higher mortality (0.85, 0.52–1.38, p = 0.51). Conclusions The poor prognosis of CPA and several prognostic factors were revealed. Early diagnosis and intervention is required with reference to such factors.

<b><i>Background:</i></b> There is no study on the predictive factors of recurrent haemoptysis after bronchial artery embolization (BAE) with the long-term outcomes in patients with bronchiectasis (BE). <b><i>Objectives:</i></b> To evaluate the long-term outcomes of BAE in BE patients without accompanying refractory active infection of mycobacteriosis and aspergillosis with analysis for the predictive factors of recurrent haemoptysis. <b><i>Methods:</i></b> Data of 106 patients with BE who underwent BAE using coils between January 2011 and December 2018 were retrospectively reviewed. The cumulative haemoptysis control rate was estimated using Kaplan-Meier methods with log-rank tests to analyze differences in recurrence-free rate between groups based on technical success and failure, bacterial colonization status, number of BE lesions, and vessels embolized to bronchial arteries (BAs) or BAs + non-bronchial systemic arteries (NBSAs). <b><i>Results:</i></b> Bacterial colonization was detected in approximately 60% of patients. Computed tomography showed bronchiectatic lesions with 2.9 ± 1.4 lobes. In the first series of BAE, embolization was performed in the BAs alone and BAs + NBSAs in 65.1 and 34.9% of patients, respectively, with 2.4 ± 1.4 embolized vessels in total. The median follow-up period was 1,000 (7–2,790) days. The cumulative haemoptysis control rates were 91.3, 84.2, 81.5, and 78.9% at 1, 2, 3, and 5 years, respectively. The haemoptysis control rates were higher in the technical success group than in the technical failure group (<i>p</i> = 0.029). <b><i>Conclusions:</i></b> High haemoptysis control rates for long-term periods were obtained by embolization for all visualized abnormal arteries, regardless of the colonization status, number of bronchiectatic lobes, and target vessels, irrespective of NBSAs.