A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

The efficacy of hydrogen/oxygen therapy favored the recovery of omicron SARS-CoV-2 variant infection: results of a multicenter, randomized, controlled trial.

Clinical studies had found that hydrogen/oxygen mixed inhalation was beneficial to ameliorate the respiratory symptoms in the adjuvant treatment of patients with COVID-19. We aimed to explore the efficacy of hydrogen/oxygen therapy in favoring the recovery of Omicron SARS-CoV-2 variant infection. There were 64 patients who randomly assigned to receive hydrogen/oxygen inhalation (32 patients) and oxygen inhalation (32 patients). The average shedding duration of Omicron in hydrogen/oxygen group was shorter than oxygen group. The trend of cumulative negative conversion rate of Omicron increased gradually after the third day. The IL-6 levels in hydrogen/oxygen group decreased by 22.8% compared with the baseline. After hydrogen/oxygen mixed gas inhalation, the lymphocyte count increased to 61.1% of the baseline on the 3rd day in the hydrogen/oxygen group. More patients in the hydrogen/oxygen group had resolution of pulmonary lesions. Our study showed the beneficial trends of molecular hydrogen in treating patients with COVID-19, which may offer a prospective solution to adjuvant therapy for COVID-19 Patients.

A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With Bronchiectasis With Pseudomonas aeruginosa Infection.

BACKGROUND: Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. RESEARCH QUESTION: Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection? STUDY DESIGN AND METHODS: This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29. RESULTS: The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35; P < .001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P < .001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. INTERPRETATION: TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection. TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT03715322; URL: www. CLINICALTRIALS: gov.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Research advances and clinical management of bronchiectasis: Chinese perspective.

Bronchiectasis is a debilitating chronic suppurative airway disease that confers a substantial burden globally. Despite the notable prevalence, research on bronchiectasis in mainland China remains in its infancy. Nevertheless, there has been a significant leap in the quantity and quality of research, which has contributed to the ever-improving clinical practice. A nationwide collaborative platform has been established to foster multicentre studies, which will help increase the level of evidence further. Here, we summarise the status quo of clinical management and consider the research priorities for bronchiectasis that have been published previously. We also highlight the efforts of the Chinese medical communities to outline the core tasks that need to be addressed within the next decade.

The Controversy About the Effects of Different Doses of Corticosteroid Treatment on Clinical Outcomes for Acute Respiratory Distress Syndrome Patients: An Observational Study.

Background: Corticosteroid usage in acute respiratory distress syndrome (ARDS) remains controversial. We aim to explore the correlation between the different doses of corticosteroid administration and the prognosis of ARDS. Methods: All patients were diagnosed with ARDS on initial hospital admission and received systemic corticosteroid treatment for ARDS. The main outcomes were the effects of corticosteroid treatment on clinical parameters and the mortality of ARDS patients. Secondary outcomes were factors associated with the mortality of ARDS patients. Results: 105 ARDS patients were included in this study. Corticosteroid treatment markedly decreased serum interleukin-18 (IL-18) level (424.0 ± 32.19 vs. 290.2 ± 17.14; p = 0.0003) and improved arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (174.10 ± 65.28 vs. 255.42 ± 92.49; p < 0.0001). The acute physiology and chronic health evaluation (APACHE II) score (16.15 ± 4.41 vs. 14.88 ± 4.57, p = 0.042) decreased significantly on the seventh day after systemic corticosteroid treatment. Interestingly, the serum IL-18 decreased significantly (304.52 ± 286.00 vs. 85.85 ± 97.22, p < 0.0001), whereas the improvement of PaO2/FiO2 (24.78 ± 35.03 vs. 97.17 ± 44.82, p < 0.001) was inconspicuous after systemic corticosteroid treatment for non-survival patients, compared with survival patients. Furthermore, the receiver operating characteristic (ROC) model revealed, when equivalent methylprednisolone usage was 146.5 mg/d, it had the best sensitivity and specificity to predict the death of ARDS. Survival analysis by Kaplan-Meier curves presented the higher 45-day mortality in high-dose corticosteroid treatment group (logrank test p < 0.0001). Multivariate Cox regression analyses demonstrated that serum IL-18 level, APACHE II score, D-dimer, and high-dose corticosteroid treatment were associated with the death of ARDS. Conclusion: Appropriate dose of corticosteroids may be beneficial for ARDS patients through improving the oxygenation and moderately inhibiting inflammatory response. The benefits and risks should be carefully weighed when using high-dose corticosteroid for ARDS. Trial registration: This work was registered in ClinicalTrials.gov. Name of the registry: Corticosteroid Treatment for Acute Respiratory Distress Syndrome. Trial registration number: NCT02819453. URL of trial registry record: https://register.clinicaltrials.gov.

Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial.

BACKGROUND: To investigate whether the administration of hydrogen/oxygen mixture was superior to oxygen in improving symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: This prospective, randomized, double-blind, controlled clinical trial in 10 centres enrolled patient with AECOPD and a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 6 points. Eligible patients were randomly assigned (in a 1:1 ratio) to receive either hydrogen/oxygen mixture or oxygen therapy. Primary endpoint was the change from baseline in BCSS score at day 7. Adverse events (AEs) were recorded to evaluate safety. RESULTS: Change of BCSS score in Hydrogen/oxygen group was larger than that in Oxygen group (- 5.3 vs. - 2.4 point; difference: - 2.75 [95% CI - 3.27 to - 2.22], meeting criteria for superiority). Similar results were observed in other time points from day 2 through day 6. There was a significant reduction of Cough Assessment Test score in Hydrogen/oxygen group compared to control (- 11.00 vs. - 6.00, p < 0.001). Changes in pulmonary function, arterial blood gas and noninvasive oxygen saturation did not differ significantly between groups as well as other endpoints. AEs were reported in 34 (63.0%) patients in Hydrogen/oxygen group and 42 (77.8%) in Oxygen group. No death and equipment defects were reported during study period. CONCLUSIONS: The trial demonstrated that hydrogen/oxygen therapy is superior to oxygen therapy in patient with AECOPD with acceptable safety and tolerability profile. TRIAL REGISTRATION: Name of the registry: U.S National Library of Medicine Clinical Trials; Trial registration number: NCT04000451; Date of registration: June 27, 2019-Retrospectively registered; URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/study/NCT04000451?term=04000451&draw=2&rank=1 .

Stool-based Xpert MTB/RIF Ultra assay as a tool for detecting pulmonary tuberculosis in children with abnormal chest imaging: A prospective cohort study.

OBJECTIVES: To evaluate the diagnostic efficacy of stool-based Xpert MTB/RIF Ultra assay versus other assays for the detection of paediatric pulmonary tuberculosis (PTB). METHODS: A prospective head-to-head comparative study was conducted from Dec 2017 to May 2019 in Shanghai Public Health Clinical Centre. Samples were collected from children (< 15 years) with abnormal chest imaging (X-ray or CT scan) results for the following tests: Ultra on stool sample (Ultra-Stool), Ultra on respiratory tract sample (Ultra-RTS), Xpert MTB/RIF assay (Xpert) on RTS (Xpert-RTS), acid-fast bacilli smear on RTS (AFB-RTS), and Mycobacterium tuberculosis (Mtb) culture on RTS (Culture-RTS). The results were compared with a composite reference standard. RESULTS: A total of 126 cases with paired results were analysed. Against a composite reference standard, Ultra-RTS demonstrated the highest sensitivity (52%) and specificity (100%). Ultra-Stool showed 84.1% concordance with Ultra-RTS, demonstrating 45.5% sensitivity and 94.7% specificity (kappa = 0.65, 95% CI= 0.51-0.79). The sensitivity of Ultra-Stool was similar to Mtb culture (45.5%, p = 1.000) and higher than AFB-RTS (27.3%, p < 0.05). Assay positivity was associated with age and infiltration range in chest imaging. CONCLUSIONS: When RTS is difficult to obtain, stool sample-based Ultra is a comparable alternative.

Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression.

Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.

Development and validation of nomogram estimating post-surgery hospital stay of lung cancer patients: relevance for predictive, preventive, and personalized healthcare strategies.

OBJECTIVE: In the era of fast track surgery, early and accurately estimating whether postoperative length of stay (p-LOS) will be prolonged after lung cancer surgery is very important, both for patient's discharge planning and hospital bed management. Pulmonary function tests (PFTs) are very valuable routine examinations which should not be underutilized before lung cancer surgery. Thus, this study aimed to establish an accurate but simple prediction tool, based on PFTs, for achieving a personalized prediction of prolonged p-LOS in patients following lung resection. METHODS: The medical information of 1257 patients undergoing lung cancer surgery were retrospectively reviewed and served as the training set. p-LOS exceeding the third quartile value was considered prolonged. Using logistic regression analyses, potential predictors of prolonged p-LOS were identified among various preoperative factors containing PFTs and intraoperative factors. A nomogram was constructed and subjected to internal and external validation. RESULTS: Five independent risk factors for prolonged p-LOS were identified, including older age, being male, and ratio of residual volume to total lung capacity (RV/TLC) ≥ 45.0% which is the only modifiable risk factor, more invasive surgical approach, and surgical type. The nomogram comprised of these five predictors exhibited sufficient predictive accuracy, with the area under the receiver operating characteristic curve (AUC) of 0.76 [95% confidence interval (CI) 0.73-0.79] in the internal validation. Also its predictive performance remained fine in the external validation, with the AUC of 0.70 (95% CI 0.60-0.79). The calibration curves showed satisfactory agreements between the model predicted probability and the actually observed probability. CONCLUSIONS: Preoperative amelioration of RV/TLC may prevent lung cancer patients from unnecessary prolonged p-LOS. The integrated nomogram we developed could provide personalized risk prediction of prolonged p-LOS. This prediction tool may help patients perceive expected hospital stays and enable clinicians to achieve better bed management after lung cancer surgery.

Lactate dehydrogenase as a prognostic marker of renal transplant recipients with severe community-acquired pneumonia: a 10-year retrospective study.

BACKGROUND: Lactate dehydrogenase (LDH) is an easily accessible biological marker that has been associated with several pulmonary disorders. The aim of this study was to investigate the prognostic value of serum LDH in renal transplant recipients with severe community-acquired pneumonia (CAP). METHODS: A total of 77 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility in this retrospective study. Patient characteristics and laboratory tests, such as LDH on day 1 (LDHday 1) and day 3 (LDHday 3) were recorded. Cox regression models were used to assess the performance of LDH to predict 90-day mortality. RESULTS: Median LDH level was higher on day 1 in 90-day nonsurvivors (440 U/L, IQR, 362-1,055 U/L) than in survivors (334 U/L, IQR, 265-432 U/L; P<0.001); median LDH level on day 3 in nonsurvivors was 522.5 U/L (IQR, 457.5-1,058.5 U/L) and in survivors 290 U/L (IQR, 223-387.5 U/L; P<0.001). Analysis of LDH kinetics from day 1 to day 3 showed an increase in nonsurvivors and a decrease in survivors. Moreover, Multivariate Cox analysis showed that LDHday 1 (increase per 100 U/L), LDHday 3 (increase per 100 U/L) and LDH kinetics (increase per 10%) were independently associated with 90-day mortality. CONCLUSIONS: Serum LDH levels and LDH kinetics early were independently associated with 90-day mortality in renal transplant recipients with severe CAP. In future, the prognostic role of LDH needs to be warranted.

Prevalence of and risk factors for presenting initial respiratory symptoms in patients undergoing surgery for lung cancer.

Background: Patients with early stage lung cancer seldom present initial respiratory symptoms, causing a delayed diagnosis and missed opportunity to receive operation. This study aimed to investigate the prevalence of initial respiratory symptoms and identity what factors would predispose lung cancer patients to present initial respiratory symptoms in patients undergoing lung cancer surgery. Methods: A retrospective chart review was conducted on 3,203 patients undergoing surgery for primary lung cancer. The prevalence of initial respiratory symptoms was investigated and the comparisons of clinicopathological parameters were performed between patients with and without initial respiratory symptoms or between patients with single and multiple initial respiratory symptoms. Independent risk factors for presenting initial respiratory symptoms or multiple initial respiratory symptoms were identified using a logistic regression. Results: A total of 1,474 (46.0%) patients with lung cancer were admitted to hospital due to present initial respiratory symptoms. Symptom clusters of cough or sputum (33.1%) and bloody sputum or hemoptysis (16.7%) presented as the two major chief complaints for medical consultation while chest pain (6.9%) and chest distress or dyspnea (5.6%) remained relatively unusual. Multiple analyses found that coexisting chronic obstructive pulmonary disease (OR=1.70, 95% CI=1.41-2.05), tumor size >3 cm (OR=2.27, 95% CI=1.93-2.67), squamous cell carcinoma (OR=2.22, 95% CI=1.86-2.65), tumor located in left lower lung (OR=1.39, 95% CI=1.10-1.74) and advanced tumor stage (OR=1.27, 95% CI=1.06-1.52) were independent risk factors for presenting initial respiratory symptoms. Furthermore, current smoking (OR=1.36, 95% CI=1.07-1.73), tumor size >3 cm (OR=1.53, 95% CI=1.21-1.93) and squamous cell carcinoma (OR=1.68, 95% CI=1.32-2.15) were demonstrated to be independent risk factors for presenting multiple initial respiratory symptoms. Conclusions: Presenting initial respiratory symptoms was the common cause for medical consultation in patients undergoing lung cancer surgery. Patients with lung cancer in larger tumor size or squamous cell carcinoma more likely presented initial and even multiple initial respiratory symptoms.

Status of coexisting chronic obstructive pulmonary disease and its clinicopathological features in patients undergoing lung cancer surgery: a cross-sectional study of 3,006 cases.

BACKGROUND: Lung cancer is often complicated with chronic obstructive pulmonary disease (COPD). Coexistence of COPD has significant impacts on the decision-making process for lung cancer surgery as well as the postoperative effects. This study aimed to investigate the status of coexisting COPD and analyze its clinicopathological characteristics in lung cancer patients undergoing surgical resection. METHODS: Clinical data of 3,006 patients with resected primary lung cancer from January 2008 to April 2014 were analyzed. Status of coexisting COPD was evaluated according to patient's lung function. Differences of clinicopathological characteristics between the COPD group and the non-COPD group were compared. RESULTS: A total of 643 patients (21.4%) were complicated with COPD. The average age of patients with COPD (64.9±8.5 years) was significantly older than those without COPD (59.4±9.9 years). The percentage of males (85.7% vs. 54.0%) and current smokers (43.4% vs. 22.5%) were both higher in the COPD group than the non-COPD group (P<0.05). The percentage of patients with initial symptoms was higher in the COPD group than the non-COPD group (63.9% vs. 44.5%, P<0.05). The average white blood cell count was higher in the COPD group than the non-COPD group [(6.72±2.28 vs. 6.28±2.24) ×109/L, P<0.05]. The percentage of tumor size more than 3 cm was higher in the COPD group than the non-COPD group (53.2% vs. 38.0%, P<0.05). Squamous cell carcinoma accounted for 47.6% in the COPD group while adenocarcinoma accounted for 72.4% in the non-COPD group (P<0.05). A higher percentage of lung cancer with poor differentiation was found in the COPD group than the non-COPD group (53.2% vs. 43.6%, P<0.05). The median total and postoperative length of hospital stay were significantly longer in the COPD group than the non-COPD group (13 vs. 11 days, 8 vs. 7 days, respectively, P<0.05). CONCLUSIONS: COPD is a common comorbidity of early stage lung cancer. Lung cancer patients with coexistence of COPD have obviously different clinicopathological features compared to patients without COPD, which requires special attention and management during the perioperative period of lung cancer.

Characteristics of circular RNA expression in lung tissues from mice with hypoxia­induced pulmonary hypertension.

Pulmonary hypertension (PH) is a life­threatening lung disease, characterized by an increase in pulmonary arterial pressure caused by vasoconstriction and vascular remodeling. The pathogenesis of PH is not fully understood, and there is a lack of potential biomarkers for the diagnosis and treatment of patients with PH. Non­coding RNAs with a characteristic covalently closed loop structure, termed circular RNAs (circRNAs), are present in a number of pulmonary diseases. To the best of our knowledge, the present study is the first to use microarray analysis to determine the expression profile of circRNAs in lung tissues from mice with hypoxia­induced PH. In total, 23 significantly upregulated and 41 significantly downregulated circRNAs were identified. Of these, 12 differentially expressed circRNAs were selected for further validation using reverse transcription­quantitative polymerase chain reaction. Putative microRNAs (miRNAs) that bind to the dysregulated circRNAs were predicted. Subsequently, bioinformatics tools were used to construct circRNA­miRNA­mRNA networks for the two most promising circRNAs, namely mmu_circRNA_004592 and mmu_circRNA_018351. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target genes of the dysregulated circRNAs revealed that these dysregulated circRNAs may serve an important role in the pathogenesis of hypoxia­induced PH. Therefore, these dysregulated circRNAs are candidate diagnostic biomarkers and potential therapeutic targets for PH.

Impaired self-healing capacity in airway epithelia lacking aquaporin-3.

In this study, we utilized AQP3-knockout mice as the in vivo model and AQP3-knockdown human bronchial epithelial cells (HBECs) as the in vitro model. Airway injury was experimentally induced by intra-tracheal injection of naphthalene. HE staining, transmission and scanning electron microscope were performed to evaluate self-healing capacity in vivo. Transwell and wound-healing assays were performed to evaluate epithelial cell migration in vitro. We found that both the airway epithelial cells of AQP3-knockout mice and AQP3-knockdown HBECs exhibited an obviously impaired self-healing capacity with defective epithelial cell migration through AQP3-facilitated glycerol transport. In addition, glycerol supplementation could largely correct defective injury healing and epithelial cell migration. For the first time, we found evidence for distinct defects in AQP3-deficient airway epithelial cell migration. Mechanistic analysis showed AQP3-facillitated glycerol transport plays a role in airway epithelial self-healing after injury.

Role of a serum-based biomarker panel in the early diagnosis of lung cancer for a cohort of high-risk patients.

BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China.