Lung最新文献

Background: Free fatty acids (FFAs) are established risk factors for various cardiovascular and metabolic disorders. Elevated FFAs can trigger inflammatory response, which may be associated with the occurrence of acute respiratory distress syndrome (ARDS) in cardiac surgery. In this prospective study, we aimed to investigate the association between circulating FFA and the incidence of ARDS, as well as the length of ICU stay, in patients undergoing off-pump coronary artery bypass grafting (CABG).

Methods: We conducted a single-center, prospective, observational study among patients undergoing off-pump CABG. The primary endpoint was the occurrence of ARDS within 6 days after off-pump CABG. Serum FFA were measured at baseline and 24 h post-procedure, and the difference (Δ-FFA) was calculated.

Results: A total of 180 patients were included in the primary analysis. The median FFA was 2.3 mmol/L (quartile 1 [Q1]-Q3, 1.4-3.2) at baseline and 1.5 mmol/L (Q1-Q3, 0.9-2.3) 24 h after CABG, with a Δ-FFA of 0.6 mmol/L (Q1-Q3, -0.1 to 1.6). Patients with elevated Δ-FFA levels had a significantly higher ARDS occurrence (55.6% vs. 22.2%; P < 0.001). Elevated Δ-FFA after off-pump CABG correlated with a significantly lower PaO₂/FiO₂ ratio, prolonged mechanical ventilation, and extended length of ICU stay. The area under the curve (AUC) of Δ-FFA for predicting ARDS (AUC, 0.758; 95% confidence interval, 0.686-0.831) significantly exceeded the AUC of postoperative FFA (AUC, 0.708; 95% CI 0.628-0.788; P < 0.001).

Conclusions: Elevated Δ-FFA levels correlated with ARDS following off-pump CABG. Monitoring FFA may assist in identifying high-risk patients for ARDS, facilitating timely interventions to improve clinical outcomes.

Purpose: Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic.

Methods: Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed.

Results: A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination.

Conclusion: Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.

Purpose: Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT).

Methods: Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported.

Results: 1347 individuals underwent lung cancer screening, with a median age of 51 years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible.

Conclusion: Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.

Background: Inhaled corticosteroids (ICS) are effective in managing asthma and chronic obstructive pulmonary disease (COPD) but increase the risk of pneumonia. Benzodiazepines (BZD), commonly prescribed for comorbid psychiatric disorders in asthma or COPD patients, are also associated with pneumonia. This study investigates the risk of pneumonia associated with the concomitant use of ICS and BZD.

Methods: Data from the FDA Adverse Event Reporting System from Q4 2013 to Q3 2023 were extracted. Reports involving asthma or COPD patients were included. Disproportionality analysis and logistic regression analysis were performed to assess the risk of pneumonia associated with the combined use of ICS and BZD. Additive and multiplicative models were used to further confirm the results. Additionally, subgroup analyses were conducted based on gender, age, and disease type.

Results: A total of 238,411 reports were included. The combined use of ICS and BZD was associated with a higher reporting of pneumonia (ROR: 2.41, 95% CI 2.25-2.58). Using additive and multiplicative methods, the results remained significant. The strongest risk signals were observed in specific drug combinations, such as mometasone with clonazepam, budesonide with temazepam, and mometasone with zopiclone. Subgroup analyses showed higher pneumonia risks in females, patients over 60 years old, and those with asthma.

Conclusion: Our findings identified a significantly elevated pneumonia risk with the combined use of ICS and BZD. These results highlighted the necessity for cautious co-prescription of ICS and BZD and suggested the need for more comprehensive clinical studies to assess this interaction.

Purpose: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients.

Methods: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO.

Results: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence.

Conclusions: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

Purpose: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy.

Methods: The 52-gene risk signature was implemented to classify patients as being at "high risk" or "low risk" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature.

Results: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort.

Conclusions: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality.

Objectives: Readability of patient-facing information of oral antibiotics detailed in the WHO all oral short (6 months, 9 months) has not been described to date. The aim of this study was therefore to examine (i) how readable patient-facing TB antibiotic information is compared to readability reference standards and (ii) if there are differences in readability between high-incidence countries versus low-incidence countries.

Methods: Ten antibiotics, including bedaquiline, clofazimine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, pretomanid, pyrazinamide, were investigated. TB antibiotic information sources were examined, consisting of 85 Patient Information Leaflets (PILs) and 40 antibiotic web resouces. Of these 85 PILs, 72 were taken from the National Medicines Regulator from six countries (3 TB high-incidence [Rwanda, Malaysia, South Africa] + 3 TB low-incidence [UK, Ireland, Malta] countries). Readability data was grouped into three categories, including (i) high TB-incidence countries (n = 33 information sources), (ii) low TB-incidence countries (n = 39 information sources) and (iii) web information (n = 53). Readability was calculated using Readable software, to obtain four readability scores [(i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index], as well as two text metrics [words/sentence, syllables/word].

Results: Mean readability scores of patient-facing TB antibiotic information for FRE and FKGL, were 47.4 ± 12.6 (sd) (target ≥ 60) and 9.2 ± 2.0 (target ≤ 8.0), respectively. There was no significant difference in readability between low incidence countries and web resources, but there was significantly poorer readability associated with PILs from high incidence countries versus low incidence countries (FRE; p = 0.0056: FKGL; p = 0.0095).

Conclusions: Readability of TB antibiotic PILs is poor. Improving readability of PILs should be an important objective when preparing patient-facing written materials, thereby improving patient health/treatment literacy.

Purpose: We determined the cough counts and their variability in subjects with persistent cough for 30 days.

Methods: The Hyfe cough tracker app uses the mobile phone microphone to monitor sounds and recognizes cough with artificial intelligence-enabled algorithms. We analyzed the daily cough counts including the daily predictability rates of 97 individuals who monitored their coughs over 30 days and had a daily cough rate of at least 5 coughs per hour.

Results: The mean (median) daily cough rates varied from 6.5 to 182 (6.2 to 160) coughs per hour, with standard deviations (interquartile ranges) varying from 0.99 to 124 (1.30 to 207) coughs per hour among all subjects. There was a positive association between cough rate and variability, as subjects with higher mean cough rates (OLS) have larger standard deviations. The accuracy of any given day for predicting all 30 days is the One Day Predictability for that day, defined as the percentage of days when cough frequencies fall within that day's 95% confidence interval. Overall Predictability was the mean of the 30-One Day Predictability percentages and ranged from 95% (best predictability) to 30% (least predictability).

Conclusion: There is substantial within-day and day-to-day variability for each subject with persistent cough recorded over 30 days. If confirmed in future studies, the clinical significance and the impact on the use of cough counts as a primary end-point of cough interventions of this variability need to be assessed.

Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function.

Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent.

Results: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV_0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways.

Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.

Objectives: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks.

Methods: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group.

Results: (1) Gestational age, 5 min Apgar, Max FiO₂ during NIV, and FiO₂ fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts.

Conclusion: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.