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BackgroundThis study aims to investigate the clinical outcome between high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) therapy in mild to moderate hypoxemic patients on the first ICU day and to develop a predictive model of 48-h intubation.MethodsThe study included adult patients from the MIMIC III and IV databases who first initiated HFNC or NIV therapy due to mild to moderate hypoxemia (100

BackgroundAmbroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance.MethodsThis study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population.ResultsBetween 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: −0.29; 95% CI: −0.53 to −0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: −0.18; 95% CI: −0.34 to −0.03; p = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported.DiscussionIn hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo.Clinical trial registration[https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].

IntroductionBecause of persistent airflow limitation in chronic obstructive pulmonary disease (COPD), patients with COPD often have complications of dyspnea. However, as a leading symptom of COPD, dyspnea in COPD deserves special consideration regarding treatment in this fragile population for pre-clinical health management in COPD. Methods: Based on the above, this paper proposes a multi-modal data combination strategy by combining the local and global features for dyspnea identification in COPD based on the multi-layer perceptron (MLP) classifier.MethodsFirst, lung region images are automatically segmented from chest HRCT images for extracting the original 1,316 lung radiomics (OLR, 1,316) and 13,824 3D CNN features (O3C, 13,824). Second, the local features, including five selected pulmonary function test (PFT) parameters (SLF, 5), 28 selected lung radiomics (SLR, 28), and 22 selected 3D CNN features (S3C, 22), are respectively selected from the original 11 PFT parameters (OLF, 11), 1,316 OLR, and 13,824 O3C by the least absolute shrinkage and selection operator (Lasso) algorithm. Meantime, the global features, including two fused PFT parameters (FLF, 2), six fused lung radiomics (FLR, 6), and 34 fused 3D CNN features (F3C, 34), are respectively fused by 11 OLF, 1,316 OLR, and 13,824 O3C using the principal component analysis (PCA) algorithm. Finally, we combine all the local and global features (SLF + FLF + SLR + FLR + S3C + F3C, 5+ 2 + 28 + 6 + 22 + 34) for dyspnea identification in COPD based on the MLP classifier.ResultsOur proposed method comprehensively improves classification performance. The MLP classifier with all the local and global features achieves the best classification performance at 87.7% of accuracy, 87.7% of precision, 87.7% of recall, 87.7% of F1-scorel, and 89.3% of AUC, respectively.DiscussionCompared with single-modal data, the proposed strategy effectively improves the classification performance for dyspnea identification in COPD, providing an objective and effective tool for COPD management.

IntroductionPositive airway pressure (PAP) therapy is currently the first-line respiratory support technique for acute respiratory failure (ARF) due to acute cardiogenic pulmonary edema (ACPE), but the accompanied adverse events and patient's intolerance with treatment in some cases limited its use in clinical practice. Some recent trials indicated that high-flow nasal cannula oxygen (HFNO) is a promising alternative to PAP therapy. In order to choose the optimum treatment for patients with ACPE, this network meta-analysis will firstly compares the efficacy of HFNO, PAP, and conventional oxygen therapy (COT).Methods and analysisThe Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement and its extension for network meta-analysis will be followed in the conduct of this investigation. We will examine these databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. The ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform Search Portal will be used to search ongoing trials. Only randomized controlled trials meeting the eligibility criteria will be included. Through the Cochrane Collaboration's tool, the included studies' risk of bias will be assessed. The pairwise meta-analysis will be performed with RevMan 5.4.1 software. A Bayesian network meta-analysis will use random-effects models to derive odds ratios for the treatment effects of all interventions compared to each other using R software (version 3.6.1), and the rjags and gemtc packages. The Q statistic and I2 index will be used for investigating the heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence.

BackgroundJAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors and the optimum thereof for COVID-19 have not been adequately defined.MethodsDatabases were searched from their inception dates to 17 June 2022. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. The primary outcome was the coefficient of mortality.ResultsTwenty-eight studies of 8,206 patients were included and assessed qualitatively (modified Jadad and Newcastle–Ottawa Scale scores). A pairwise meta-analysis revealed that JAK inhibitors effectively reduced the mortality (OR = 0.54; 95% CI: 0.46–0.63; P < 0.00001; I2 = 32%) without increasing the risk of adverse events (OR = 1.02; 95% CI: 0.88–1.18; P = 0.79; I2 = 12%). In a network meta-analysis, clinical efficacy benefits were seen among different types of JAK inhibitors (baricitinib, ruxolitinib, and tofacitinib) without the observation of a declined incidence of adverse events. The assessment of rank probabilities indicated that ruxolitinib presented the greatest likelihood of benefits regarding mortality and adverse events.ConclusionJAK inhibitors appear to be a promising treatment for COVID-19 concerning reducing mortality, and they do not increase the risk of adverse events vs. standard of care. A network meta-analysis suggests that mortality benefits are associated with specific JAK inhibitors, and among these, ruxolitinib presents the greatest likelihood of having benefits for mortality and adverse events.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42022343338].

BackgroundChronic obstructive pulmonary disease (COPD), a preventable lung disease, has the highest prevalence in the elderly and deserves special consideration regarding earlier warnings in this fragile population. The impact of age on COPD is well known, but the COPD risk of the aging process in the lungs remains unclear. Therefore, it is necessary to understand the COPD risk of the aging process in the lungs, providing an early COPD risk decision for adults.MethodsCOPD risk is evaluated for adults to make an early COPD risk decision from the perspective of lung radiomics features. First, the subjects are divided into four groups according to the COPD stages. Their ages are divided into eight equal age intervals in each group. Second, four survival Cox models are established based on the lung radiomics features to evaluate the risk probability from COPD stage 0 to suffering COPD and COPD stages. Finally, four risk ranks are defined by equally dividing the COPD risk probability from 0 to 1. Subsequently, the COPD risk at different stages is evaluated with varying age intervals to provide an early COPD risk decision.ResultsThe evaluation metrics area under the curve (AUC)/C index of four survival Cox models are 0.87/0.94, 0.84/0.83, 0.94/0.89, and 0.97/0.86, respectively, showing the effectiveness of the models. The risk rank levels up every 5 years for the subjects who had suffered COPD after 60. For the subjects with COPD stage 0, the risk rank of suffering COPD stage I levels up every 5 years after the age of 65 years, and the risk rank of suffering COPD stages II and III & IV levels up every 5 years after the age of 70 years.ConclusionOnce the age is above 60 years, the patients with COPD need to take action to prevent the progress and deterioration of COPD. Once the age is above 65 years, the patients with COPD stage 0 need to take precautions against COPD.

BackgroundThe AtyPical Asthma in China (APAC) cohort is a multi-center prospective, observational cohort set-up to investigate the clinical, pathophysiological features, prognosis, and mechanisms of cough variant asthma (CVA).ObjectivesTo present the characteristics of newly physician-diagnosed adults with CVA (n = 328) compared to mild-moderate classic asthma (CA, n = 206).Methods and Main ResultsCVA subjects showed a higher proportion of female (67.1 vs. 55.3%, P = 0.0084), abnormal laryngopharyngeal sensations (71 vs. 51%, p < 0.0001) than CA, but presented with near normal spirometry and higher methacholine PD20-FEV1 values [4.2 (1, 8.6) vs. 0.8 (0.4, 4.7), P < 0.0001]. Lower fractional exhaled nitric oxide (FENO) levels [38.5 (19.8, 72.5) vs. 53. (28.5, 92.2), P = 0.0019], blood eosinophil counts [0.2 (0.1, 0.4) vs. 0.3 (0.2, 0.5), P = 0.0014], and sputum eosinophils [2.3 (0.3, 8.0) vs. 12.2 (2, 34.5), p < 0.0001] were found in CVA. Despite lower total serum IgE levels in CVA, there was similar proportion of atopy in both groups. The prevalence of cough in CA was 86.4%, while CVA reported more severe cough on Visual Analog Scale, Cough Evaluation Test, and Leicester Cough Questionnaire, similar anxiety and depression scores but better asthma control scores as reflected by Asthma Control Test compared to CA. No correlation was found between cough assessment outcomes and sputum eosinophil count, blood eosinophil count, FENO, spirometry variables, or PD20-FEV1.ConclusionCough variant asthma is distinctive from classic asthma in regard to clinical features, lung function, and airway inflammation. Quality of life is badly impaired as well in spite of better asthma control scores.

This study explored the epidemiology, risk factors, and prognosis of invasive fungal disease (IFD) in Chinese lung transplant recipients (LTRs). This retrospective cohort study included patients who received lung transplants at four hospitals in South China between January 2015 and June 2019. The participants were divided into IFD and non-IFD (NIFD) groups. The final analysis included 226 LTRs (83.2% males) aged 55.0 ± 14.2 years old. Eighty-two LTRs (36.3%) developed IFD (proven or probable diagnosis). The most common pathogens were Aspergillus (57.3%), Candida (19.5%), and Pneumocystis jiroveci (13.4%). Multivariate logistic regression revealed that anastomotic disease [odds ratio (OR): 11.86; 95% confidence interval (95%CI): 4.76–29.54; P < 0.001], cytomegalovirus (CMV) pneumonia (OR: 3.85; 95%CI: 1.88–7.91; P = 0.018), and pre-transplantation IFD (OR: 7.65; 95%CI: 2.55–22.96; P < 0.001) were associated with higher odds of IFD, while double-lung transplantation (OR: 0.40; 95%CI: 0.19–0.79; P = 0.009) was associated with lower odds of IFD. Logistic regression analysis showed that anastomotic disease was associated with higher odds of death (OR: 5.01; 95%CI: 1.24–20.20; P = 0.02) and that PJP prophylaxis was associated with lower odds of death (OR: 0.01; 95%CI: 0.001–0.11; P < 0.001). Invasive fungal disease is prevalent among LTRs in southern China, with Aspergillus the most common pathogen. Prophylaxis should be optimized based on likely pathogens.

Introduction: Noninvasive ventilation (NIV) has been used to alleviate hypoxemia and dyspnea, but there is no consensus on the application of NIV in patients with coronavirus disease 2019 (COVID-19). Some staff use NIV as the rescue therapy which might lead to the adverse outcomes. This study was to identify early factors associated with intubation to help the medical staff select appropriate patients for receiving NIV treatment.Methods: Patients with laboratory-confirmed COVID-19 who were treated with NIV in emergency department or ICU of the Third People's Hospital (the only designated hospital for treating COVID-19 in Shenzhen) between January 1 and August 31, 2020, were retrospectively analyzed.Results: Thirty-nine patients with COVID-19 treated with NIV were included; of them, 16 (41%) received endotracheal intubation and 3 (8%) died. Significant differences were observed between intubated and non-intubated patients in PaO2/FiO2 before NIV initiation, hospitalization duration, NIV as the rescue therapy, and PaO2/FiO2 of ≤200 mmHg after 1–2 h of NIV initiation. Notably, 1–2 h after NIV initiation, a PaO2/FiO2 of ≤200 mmHg (odds ratio [OR], 9.35; 95% confidence interval [CI], 1.84–47.62; P = 0.007) and NIV as the rescue therapy (OR, 5.43; 95% CI, 1.09–27.12; P = 0.039) were the risk factors for intubation.Conclusions: In patients with COVID-19-related acute hypoxemic respiratory failure receiving NIV, close attention should be paid to PaO2/FiO2 after 1–2 h of NIV initiation. Also, using NIV as rescue therapy should draw our awareness that it might delay escalation of respiratory support and lead to adverse outcomes.