KL-6 levels in the connective tissue disease population: typical values and potential confounders–a retrospective, real-world study

BackgroundKrebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation.MethodsFrom the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD.ResultsUnivariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the β were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients.ConclusionKL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account

Clinical implications of trichomonads detected in bronchoalveolar fluid by metagenomic next-generation sequencing: a multicenter retrospective study

BackgroundPulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS).MethodsThis multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients.ResultsA total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered.ConclusionmNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors

Extracellular Vesicle MicroRNA Transfer in Lung Diseases

MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that ate involved in the transcriptional and post-transcriptional regulation of gene expression. Recently, miRNAs were demonstrated to be effectively delivered to a target cell or tissue from a host cell via extracellular vesicles (EVs). These EVs can be detected in blood, urine, exhaled breath condensates, bronchoalveolar lavage fluid (BALF), and other fluids. miRNAs are generated by donor cells and then packaged into EVs and delivered with intact functionality. After being delivered to the target cells, they regulate the translation of their target genes and the function of the target cells. Thus, EV transported miRNAs have become a new method for intercellular communication. EV miRNA transfer is well-documented in various pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary hypertension, and acute lung injury (ALI). In this review, we summarize the novel findings of EV miRNA transfer, focusing on the roles of miR-210, miR-200, miR-17, miR-146a, miR-155, and other miRNAs that are transported from primary human bronchial epithelial cells (HBECs), BALF, mesenchymal stem cells, and dendritic cells

Gut Microbiome-Based Therapeutics in Critically Ill Adult Patients—A Narrative Review

The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc

A prediction model for acute respiratory distress syndrome among patients with severe acute pancreatitis: a retrospective analysis

Background: Acute respiratory distress syndrome (ARDS) is a severe complication among patients with severe acute pancreatitis (SAP), which may be associated with increased mortality in hospitalized patients. Thus, an effective model to predict ARDS in patients with SAP is urgently required. Methods: We retrospectively analyzed the data from the patients with SAP who recruited in Xiangya Hospital between April 2017 and May 2021. Patients meeting the Berlin definition of ARDS were categorized into the ARDS group. Logistic regression models and a nomogram were utilized in the study. Descriptive statistics, logistic regression models, and a nomogram were used in the current study. Results: Comorbidity of ARDS occurred in 109 (46.58%) of 234 patients with SAP. The SAP patients with ARDS group had a higher 60-day mortality rate, an increased demand for invasive mechanical ventilation, and a longer intensive care unit (ICU) stay than those without ARDS ( p  250 U/L, creatinine >111 mg/dL, and procalcitonin >0.5 ng/mL were independent risk variables for development of ARDS in SAP patients. The area under the curve for the model was 0.814, and the model fit was acceptable [ p  = .355 (Hosmer–Lemeshow)]. Incorporating these 5 factors, a nomogram was established with sufficient discriminatory power (C-index 0.814). Calibration curve indicated the proper discrimination and good calibration in the predicting nomogram model. Conclusion: The prediction nomogram for ARDS in patients with SAP can be applied using clinical common variables after the diagnosis of SAP. Future studies would be warranted to verify the potential clinical benefits of this model

Association of air pollution, genetic risk, and lifestyle with incident adult-onset asthma: A prospective cohort study

Background: Numerous studies have explored the association of air pollution with asthma but have yielded conflicting results. The exact role of air pollution in the incidence of adult-onset asthma and whether this effect is modified by genetic risk, lifestyle, or their interaction remain uncertain. Methods: We conducted a prospective cohort study on 298,738 participants (aged 37–73 years) registered in the UK Biobank. Cox proportional hazard models were used to evaluate the association of air pollution, including particulate matter (PM2.5, PMcoarse, and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with asthma incidence. We constructed genetic risk and lifestyle scores, assessed whether the impact of air pollution on adult-onset asthma risk was modified by genetic susceptibility or lifestyle factors, and evaluated the identified interactions. Results: We found that each interquartile range increase in annual concentrations of PM2.5, NO2, and NOx was related to 1.04 (95% confidence interval [CI]: 1.01, 1.08), 1.04 (95% CI: 1.00, 1.08), and 1.03 (95% CI: 1.00, 1.06) times the risk of adult-onset asthma, respectively. The size of the effect of air pollution was greater among subpopulations with low genetic risk or unfavorable lifestyles. We also identified an additive interaction effect of air pollution with lifestyle factors, but not with genetic risk, on the risk of adult-onset asthma. Conclusion: Our analyses show that air pollution increases the risk of adult-onset asthma, but that the size of the effect is modified by lifestyle and genetic risk. These findings emphasize the need for integrated interventions for environmental pollution by the government as well as adherence to healthy lifestyles to prevent adult-onset asthma

Association of Coffee and Tea Consumption with the Risk of Asthma: A Prospective Cohort Study from the UK Biobank

Background: Previous observational studies investigated the relationship between coffee and tea intake and the risk of asthma, however, the conclusions were inconsistent. Further, the combined effect of coffee and tea consumption on asthma has rarely been studied. Methods: We examined associations between the self-reported intake of tea and coffee and the risk of incident asthma in a total of 424,725 participants aged from 39 to 73 years old from the UK Biobank. Cox proportional hazards models were used to estimate the associations between coffee/tea consumption and incident adult-onset asthma, adjusting for age, sex, race, smoking status, body mass index (BMI), education, and Townsend deprivation index. Results: Cox models with penalized splines showed J-shaped associations of coffee, tea, caffeinated coffee, and caffeine intake from coffee and tea with the risk of adult-onset asthma (p for nonlinear <0.01). Coffee intake of 2 to 3 cups/d (hazard ratio [HR] 0.877, 95% confidence interval [CI] 0.826–0.931) or tea intake of 0.5 to 1 cups/d (HR 0.889, 95% CI 0.816–0.968) or caffeinated coffee intake of 2 to 3 cups/d (HR 0.858, 95% CI 0.806–0.915) or combination caffeine intake from tea and coffee of 160.0 to 235.0 mg per day (HR 0.899, 95% CI 0.842–0.961) were linked with the lowest hazard ratio of incident asthma after adjustment for age, sex, race, smoking status, BMI, qualification, and Townsend deprivation index. Conclusions: Collectively, the study showed light-to-moderate coffee and tea consumption was associated with a reduced risk of adult-onset asthma and controlling total caffeine intake from coffee and tea for a moderate caffeine dose of 160.0 to 305.0 mg/day may be protective against adult-onset asthma. Further investigation on the possible preventive role of caffeine in asthma is warranted

sj-docx-2-tar-10.1177_17534666231214134 – Supplemental material for Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study

Supplemental material, sj-docx-2-tar-10.1177_17534666231214134 for Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study by Rongli Lu, Ying Li, Chengping Hu, Pinhua Pan, Qiaohong Zhao and Ruoxi He in Therapeutic Advances in Respiratory Disease</p

Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9

The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner