A new tool to screen patients with severe obstructive sleep apnea in the primary care setting: a prospective multicenter study

Background The coordination between different levels of care is essential for the management of obstructive sleep apnea (OSA). The objective of this multicenter project was to develop a screening model for OSA in the primary care setting. Methods Anthropometric data, clinical history, and symptoms of OSA were recorded in randomly selected primary care patients, who also underwent a home sleep apnea test (HSAT). Respiratory polygraphy or polysomnography were performed at the sleep unit to establish definite indication for continuous positive airway pressure (CPAP). By means of cross-validation, a logistic regression model (CPAP yes/no) was designed, and with the clinical variables included in the model, a scoring system was established using the β coefficients (PASHOS Test). In a second stage, results of HSAT were added, and the final accuracy of the model was assessed. Results 194 patients completed the study. The clinical test included the body mass index, neck circumference and observed apneas during sleep (AUC 0.824, 95% CI 0.763–0.886, P < 0.001). In a second stage, the oxygen desaturation index (ODI) of 3% (ODI3% ≥ 15%) from the HSAT was added (AUC 0.911, 95% CI 0.863–0.960, P < 0.001), with a sensitivity of 85.5% (95% CI 74.7–92.1) and specificity of 67.8% (95% CI 55.1–78.3). Conclusions The use of this model would prevent referral to the sleep unit for 55.1% of the patients. The two-stage PASHOS model is a useful and practical screening tool for OSA in primary care for detecting candidates for CPAP treatment. Clinical Trial Registration Registry: ClinicalTrials.gov; Name: PASHOS Project: Advanced Platform for Sleep Apnea Syndrome Assessment; URL: https://clinicaltrials.gov/ct2/show/NCT02591979; Identifier: NCT02591979. Date of registration: October 30, 2015.

A randomised controlled trial on roles of prostaglandin E1 nebulization among patients undergoing one lung ventilation

Background Prostaglandin E1 (PGE1) has been reported to maintain adequate oxygenation among patients under 60% FiO2 one-lung ventilation (OLV). This research aimed to explore whether PGE1 is safe in pulmonary shunt and oxygenation under 40% FiO2 OLV and provide a reference concentration of PGE1. Methods Totally 90 esophageal cancer patients treated with thoracotomy were enrolled in this study, randomly divided into three groups (n = 30/group): Group A (60% FiO2 and 0.1 µg/kg PGE1), Group B (40% FiO2 and 0.1 µg/kg PGE1), and Group C (40% FiO2, 0.2 µg/kg PGE1). Primary outcomes were oxygenation and pulmonary shunt during OLV. Secondary outcomes included oxidative stress after OLV. Results During OLV, patients in Group C and B had lower levels of PaO2, SaO2, SpO2, MAP, and Qs/Qt than those in Group A (P < 0.05). At T2 (OLV 10 min), patients in Group C and B exhibited a lower level of PaO2/FiO2 than those in Group A, without any statistical difference at other time points. The IL-6 levels of patients in different groups were different at T8 (F = 3.431, P = 0.038), with IL-6 in Group C being lower than that in Group B and A. MDA levels among the three groups differed at T5 (F = 4.692, P = 0.012) and T7 (F = 5.906, P = 0.004), with the MDA level of Group C being lower than that of Group B and A at T5, and the MDA level of Group C and B being lower than that of Group A at T7. In terms of TNF-α level, patients in Group C had a lower level than those in Group B and A at T8 (F = 3.598, P = 0.033). Compared with patients who did not use PGE1, patients in Group C had comparable complications and lung infection scores. Conclusion The concentration of FiO2 could be reduced from 60 to 40% to maintain oxygenation. 40% FiO2 + 0.2 µg/kg PGE1 is recommended as a better combination on account of its effects on the inflammatory factors. Trial registration: Chictr.org.cn identifier: ChiCTR1800018288, 09/09/2018.

GLP2-GLP2R signal affects the viability and EGFR-TKIs sensitivity of PC9 and HCC827 cells

Background The resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs) therapy is currently the major clinical challenge in the treatment of lung cancer. This study aims to reveal the role of glucagon-like peptide (GLP) 2 and GLP-2 receptor (GLP2R) signaling on the EGFR-TKIs and cisplatin resistance of lung cancer cells. Methods The common differentially expressed genes in PC9 and HCC827 cells that were individually resistant to one of the three EGFR-TKIs (dacomitinib, osimertinib and afatinib) were screened. The data were from GSE168043 and GSE163913. The expression of GLP2R in drug-resistant cells was detected by western blot. The effect of GLP2R expression down- or up-regulation on resistance to dacomitinib, osimertinib, afatinib or cisplatin was measured by CCK-8 and flow cytometry assays. The long-acting analog of GLP-2, teduglutide, treated the parental cells. Results A total of 143 common differentially expressed genes were identified. Compared with the parent cells, the GLP2R expression in drug-resistant cell lines was significantly up-regulated. The exogenous expression of GLP2R in parental cells enhanced cell viability, while knockdown of GLP2R levels in drug-resistant cell lines inhibited cell viability. In addition, teduglutide treatment also enhanced the viability of lung cancer cells. Conclusion GLP2-GLP2R signal may change the sensitivity of cells to EGFR-TKIs and cisplatin. The development of GLP-2 or GLP2R inhibitors may be beneficial to the clinical treatment of lung cancer.

Pulmonary involvement of ANCA-associated vasculitis in adult Chinese patients

Objective The aim of this study was to clarify the clinical characteristics and long-term outcomes of ANCA-associated vasculitis (AAV) patients with pulmonary involvement from a single Chinese cohort. Methods Newly diagnosed AAV patients with pulmonary involvement, as defined by CT, were recruited from January 2010 to June 2020. Clinical data and CT images were collected retrospectively. Baseline CTs were evaluated and re-classified into four categories: interstitial lung disease (ILD), airway involvement (AI), alveolar hemorrhage (AH), and pulmonary granuloma (PG). Results A total of 719 patients were newly diagnosed with AAV, 366 (50.9%) of whom combined with pulmonary involvement at baseline. Among the AAV cases with pulmonary involvement, 55.7% (204/366) had ILD, 16.7% (61/366) had AI alone, 14.8% (54/366) had PG, and 12.8% (47/366) had AH alone. During follow-up of a median duration of 42.0 months, 66/366 (18.0%) patients died, mainly died from infections. Survival, relapse, and infection were all significantly different based on the radiological features. Specifically, the ILD group tends to have a poor long-term prognosis, the PG group is prone to relapse, and the AI group is apt to infection. The AH group has a high risk of both early infection and relapse, thus a poor short-term prognosis. Conclusion AAV patients with diverse radiological features have different clinical characteristics and outcomes. Therefore, the intensity of immunosuppressive therapy must be carefully valued by considering the baseline CT findings among AAV patients with pulmonary involvement.

The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study

Background Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience exacerbations more frequently than those with asthma or COPD alone. Since low diffusing capacity of the lung for carbon monoxide (DLCO) is known as a strong risk factor for severe exacerbation in COPD, DLCO or a transfer coefficient of the lung for carbon monoxide (KCO) is speculated to also be associated with the risk of exacerbations in ACO. Methods This study was conducted as an observational cohort survey at the National Hospital Organization Fukuoka National Hospital. DLCO and KCO were measured in 94 patients aged ≥ 40 years with a confirmed diagnosis of ACO. Multivariable-adjusted hazard ratios (HRs) for the exacerbation-free rate over one year were estimated and compared across the levels of DLCO and KCO. Results Within one year, 33.3% of the cohort experienced exacerbations. After adjustment for potential confounders, low KCO (< 80% per predicted) was positively associated with the incidence of exacerbation (multivariable-adjusted HR = 3.71 (95% confidence interval 1.32–10.4)). The association between low DLCO (< 80% per predicted) and exacerbations showed similar trends, although it failed to reach statistical significance (multivariable-adjusted HR = 1.31 (95% confidence interval 0.55–3.11)). Conclusions Low KCO was a significant risk factor for exacerbations among patients with ACO. Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory.

Comprehensive risk assessment for hospital-acquired pneumonia: sociodemographic, clinical, and hospital environmental factors associated with the incidence of hospital-acquired pneumonia

Background Social and hospital environmental factors that may be associated with hospital-acquired pneumonia (HAP) have not been evaluated. Comprehensive risk assessment for the incidence of HAP including sociodemographic, clinical, and hospital environmental factors was conducted using national health insurance claims data. Methods This is a population-based retrospective cohort study of adult patients who were hospitalized for more than 3 days from the Health Insurance Review and Assessment Service-National Inpatient Sample data between January 1, 2016 and December 31, 2018 in South Korea. Multivariable logistic regression analyses were conducted to identify the factors associated with the incidence of HAP. Results Among the 512,278 hospitalizations, we identified 25,369 (5.0%) HAP cases. In multivariable analysis, well-known risk factors associated with HAP such as older age (over 70 vs. 20–29; adjusted odds ratio [aOR], 3.66; 95% confidence interval [CI] 3.36–3.99), male sex (aOR, 1.35; 95% CI 1.32–1.39), pre-existing lung diseases (asthma [aOR, 1.73; 95% CI 1.66–1.80]; chronic obstructive pulmonary disease [aOR, 1.62; 95% CI 1.53–1.71]; chronic lower airway disease [aOR, 1.79; 95% CI 1.73–1.85]), tube feeding (aOR, 3.32; 95% CI 3.16–3.50), suctioning (aOR, 2.34; 95% CI 2.23–2.47), positioning (aOR, 1.63; 95% CI 1.55–1.72), use of mechanical ventilation (aOR, 2.31; 95% CI 2.15–2.47), and intensive care unit admission (aOR, 1.29; 95% CI 1.22–1.36) were associated with the incidence of HAP. In addition, poverty (aOR, 1.08; 95% CI 1.04–1.13), general hospitals (aOR, 1.54; 95% CI 1.39–1.70), higher bed-to-nurse ratio (Grade ≥ 5; aOR, 1.45; 95% CI 1.32–1.59), higher number of beds per hospital room (6 beds; aOR, 3.08; 95% CI 2.77–3.42), and ward with caregiver (aOR, 1.19; 95% CI 1.12–1.26) were related to the incidence of HAP. Conclusions The incidence of HAP was associated with various sociodemographic, clinical, and hospital environmental factors. Thus, taking a comprehensive approach to prevent and treat HAP is important.

A prediction rule for severe adverse events in all inpatients with community-acquired pneumonia: a multicenter observational study

Background Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. Methods Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. Results The ALL-COP SCORE rule included albumin (< 2 g/dL, 2 points; 2–3 g/dL, 1 point), white blood cell (< 4000 cells/μL, 3 points), chronic lung disease (1 point), confusion (2 points), PaO2/FIO2 ratio (< 200 mmHg, 3 points; 200–300 mmHg, 1 point), potassium (≥ 5.0 mEq/L, 2 points), arterial pH (< 7.35, 2 points), systolic blood pressure (< 90 mmHg, 2 points), PaCO2 (> 45 mmHg, 2 points), HCO3− (< 20 mmol/L, 1 point), respiratory rate (≥ 30 breaths/min, 1 point), pleural effusion (1 point), and extent of chest radiographical infiltration in unilateral lung (> 2/3, 2 points; 1/2–2/3, 1 point). Patients with 4–5, 6–7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. Conclusions ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. Trial registration This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.

Association of healthy lifestyle with risk of obstructive sleep apnea: a cross-sectional study

Background No studies investigated the whole effect of modifiable lifestyle factors on OSA risk. This study aimed to examine the individual and combined effects of lifestyle factors on OSA risk among Chinese adults. Methods This cross-sectional study included 9733 participants aged 35 to 74 years from the baseline survey of Guangzhou Heart Study. OSA was evaluated by Berlin Questionnaire. The healthy lifestyle score (HLS), representing the overall effect of lifestyles, was derived from seven lifestyle factors: active smoking, passive smoking, alcohol, diet, waist-hip ratio, leisure-time physical activity, and mental status. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model. Results 8107 participants were divided into the non-OSA group and 1626 participants into the OSA group. No passive smoking (OR 0.83, 95% CI 0.74–0.94), healthy waist-hip ratio (OR 0.67, 95% CI 0.58–0.77) and healthy mental status (OR 0.45, 95% CI 0. 29–0.73) were associated with a reduced risk of OSA after adjusting for confounders, while others not. Participants with higher HLS were negatively associated with OSA risk (P-trend < 0.001). In comparison to the participants with 0–3 HLS, the OR for participants with 4, 5, 6, and 7 HLS was 0.68 (95% CI 0.56–0.84), 0.71 (95% CI 0.59–0.86), 0.62 (95% CI 0.51–0.76) and 0.49 (95% CI 0.37–0.65) after adjusting for confounders. Every 1-score increment of HLS was associated with a 13% lower risk of OSA. Conclusions The results suggest that HLS reflecting the combined effect of multiple-dimensional lifestyle factors was inversely associated with OSA risk. Preventive strategies integrating multiple lifestyle factors may provide a more feasible approach for OSA prevention.

Cost-effectiveness of the anti-fibrotics for the treatment of idiopathic pulmonary fibrosis in the United States

Background The anti-fibrotic medications nintedanib and pirfenidone were approved in the United States for use in patients with idiopathic pulmonary fibrosis several years ago. While there is a growing body of evidence surrounding their clinical effectiveness, these medications are quite expensive and no prior cost-effectiveness analysis has been performed in the United States. Methods A previously published Markov model performed in the United Kingdom was replicated using United States data to project the lifetime costs and health benefits of treating idiopathic pulmonary fibrosis with: (1) symptom management; (2) pirfenidone; or (3) nintedanib. For the cost-effectiveness analysis, strategies were ranked by increasing costs and then checked for dominating treatment strategies. Then an incremental cost-effectiveness ratio was calculated for the dominant therapy. Results The anti-fibrotic medications were found to cost more than $110,000 per year compared to $12,291 annually for symptom management. While pirfenidone was slightly more expensive than nintedanib and provided the same amount of benefit, neither medication was found to be cost-effective in this U.S.-based analysis, with an average cost of $1.6 million to gain one additional quality-adjusted life year over symptom management. Conclusions Though the anti-fibrotics remain the only effective treatment option for patients with idiopathic pulmonary fibrosis and the data surrounding their clinical effectiveness continues to grow, they are not considered cost-effective treatment strategies in the United States due to their high price.

Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies

Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients. Conclusions ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.