Long-term night shift work, genetic predisposition, and risk of incident asthma: a prospective cohort study.

BACKGROUND: Evidence about a potential link between current and lifetime night shift work and risk of incident asthma is insufficient. AIM: To investigate the association of current and lifetime night shift work with risk of incident asthma, and the modified effect of genetic susceptibility on this association. DESIGN AND METHODS: We included 253,773 individuals with complete night shift work information in the UK biobank. We calculated the standard polygenetic risk score (PRS) for asthma. The Cox proportional hazard models were conducted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: After multivariable adjustments, we found that current night shift work was associated with an increased risk of incident asthma in a dose-response fashion (P for trend<0.001). Compared with day workers, those working usual/permanent night shifts had a 17% (95% CI: 1.04-1.33) higher risk of asthma incidence. In addition, we observed significant dose-dependent relationships of longer lifetime duration or frequency of night shift work with elevated risk of asthma incidence (all P for trend<0.05). Compared with never night shift workers, those with a duration (≥5 years) or frequency (≥8 nights/month) of night shift work exhibited a 20% (95% CI: 1.03-1.39) or 22% (95% CI: 1.03-1.44) higher risk of incident asthma, respectively. Moreover, the elevated risk of incident asthma related to current and lifetime night shift work exposure was strengthened by high PRS, although no significant shift work-PRS interactions were detected. CONCLUSION: Both current and lifetime night shift work may increase the risk of incident asthma, regardless of genetic predisposition to asthma.

Whole-genome microRNA sequencing analysis in patients with pulmonary hypertension.

Pulmonary hypertension (PH) is a pathological disorder with multiple clinical manifestations that lead to cardiovascular and respiratory diseases in most patients. Recent studies have revealed that microRNAs (miRNAs) play important roles as upstream signaling molecules in several diseases, including PH. However, miRNAs that can be used as diagnostic or prognostic biomarkers for PH have not been identified. Thus, in this study, peripheral blood samples obtained from patients with PH and healthy individuals were subjected to genome-wide miRNA sequencing and transcriptome analysis. We screened 136 differentially expressed miRNAs in patients with PH and verified that four differentially expressed miRNAs, namely, hsa-miR-1304-3p, hsa-miR-490-3p, hsa-miR-11400, and hsa-miR-31-5p, could be used as clinical diagnostic biomarkers for pulmonary arterial hypertension. Our findings provide a basis for further in-depth investigations of the specific mechanisms of miRNAs in PH.

A Prediction Model for In-Hospital Mortality of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Patients Based on Red Cell Distribution Width-to-Platelet Ratio.

Purpose: To explore the association between red cell distribution width (RDW)-to-platelet ratio (RPR) and in-hospital mortality of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients and establish a prediction model based on RPR and other predictors. Material and Methods: This cohort study included 1922 AECOPD patients aged ≥18 years in the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV as well as 1738 AECOPD patients from eICU Collaborative Research Database (eICU-CRD). Possible confounding factors were screened out by univariate logistic regression, and multivariable logistic regression was applied to evaluate the association between RPR and in-hospital mortality of AECOPD patients. The area under the curve (AUC), calibration curve and decision curve analysis (DCA) curve were plotted to evaluate the predictive value of the model. The median follow-up time was 3.14 (1.87, 6.25) day. Results: At the end of follow-up, there were 1660 patients survived and 262 subjects died. After adjusting for confounders, we found that Log (RPR×1000) was linked with elevated risk of in-hospital mortality of AECOPD patients [odds ratio (OR)=1.36, 95% confidence interval (CI): 1.01-1.84]. The prediction model was constructed using predictors including Log (RPR×1000), age, malignant cancer, atrial fibrillation, ventilation, renal failure, diastolic blood pressure (DBP), temperature, Glasgow Coma Scale (GCS) score, white blood cell (WBC), creatinine, blood urea nitrogen (BUN), hemoglobin, infectious diseases and anion gap. The AUC of the prediction model was 0.785 (95% CI: 0.751-0.820) in the training set, 0.721 (95% CI: 0.662-0.780) in the testing set, and 0.795 (95% CI: 0.762-0.827) in the validation set. Conclusion: RPR was associated with the in-hospital mortality of AECOPD patients. The prediction model for the in-hospital mortality of AECOPD patients based on RPR and other predictors presented good predictive performance, which might help the clinicians to quickly identify AECOPD patients at high risk of in-hospital mortality.

Total White Blood Cell Count is Associated with Arterial Stiffness Among Hypertensive Patients.

The association between white blood cell (WBC) count and arterial stiffness in patients with hypertension is not well-documented. We aimed to examine the relationships of total WBC count with arterial stiffness and risk of macrovascular damage in hypertensive patients. A total of 631 hypertensive adults (mean age: 65.6 years) were included in the present study. Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). Macrovascular damage was defined as baPWV >1.8 m/s or ABI <.9. The dose-response associations were assessed by multivariate linear or logistic regression models. After multivariate adjustments, we observed a dose-response relationship between increasing total WBC count and arterial stiffness. Participants in the highest tertile of total WBC count showed a significantly elevated baPWV (ß = .088; 95% CI: .021, .154; Ptrend = .010) and reduced ABI (ß = -.027; 95% CI: -.046, -.008; Ptrend = .005), as compared with those in the first tertile. The association was similar in different subgroups. In addition, elevated total WBC count was related to a greater risk of macrovascular damage, as indicated by baPWV >1.8 m/s (OR = 1.86; 95% CI: 1.15, 2.99, comparing the extreme tertiles). Our data suggest that elevated total WBC count was related to arterial stiffness among individuals with hypertension.

The earlier, the better? A review of neoadjuvant immunotherapy in resectable non-small-cell lung cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up.

OBJECTIVE: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function. METHODS AND MATERIAL: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020. RESULTS: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (D LCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO. Pulmonary interstitial damage may be associated with abnormal D LCO. CONCLUSION: Pulmonary function, particularly D LCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO.