Lung最新文献

Purpose: Our group has proposed that aspiration of gastric contents leads to exposure of normally sequestered lung self-antigens (SAgs), specifically collagen-V (Col-V) and K-α-1-tubulin (Kα1T), which elicits an immune response characterized by increasing concentrations of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. We sought to establish the point prevalence of abnormally elevated concentrations of SAbs among patients with pathological gastroesophageal reflux disease (GERD) and/or hiatal hernia undergoing antireflux surgery (ARS).

Methods: For this cross-sectional study, we retrieved a plasma aliquot from the Norton Thoracic Institute BioBank from blood samples that were taken preoperatively from patients who underwent ARS between November 2019 and August 2022. Enzyme-linked immunosorbent assays were employed to detect and quantify anti-Col-V and anti-Kα1T.

Results: Samples from 43 patients (females, n = 34 [79.1%]; mean age, 62 ± 12 years; and mean BMI, 30.5 ± 7  kg/m²) were analyzed. Before ARS, 28 (65.1%, CI95: 50.3-80.0%) patients had abnormally elevated concentrations of anti-Col-V and 19 (44.2%, CI95: 28.7-59.7%) had elevated concentrations of circulating anti-Kα1T. Overall, 13 patients (30.2%) had low (i.e., normal) concentrations of both SAbs, 13 (30.2%) were positive only for one, and 17 (39.5%) were positive for both SAbs.

Conclusion: A relative high point prevalence of abnormally elevated circulating SAbs (i.e., anti-Col-V and/or anti-Kα1T) before ARS was found. This result suggests clinically unsuspected pulmonary parenchymal injury secondary to GERD-related aspiration. Further studies are required to confirm this hypothesis and to identify alternative non-invasive early biomarkers of GERD-related lung damage.

Purpose: We measured corticosteroid medication adherence (CMA) in sarcoidosis patients and analyzed if demographic and clinical factors, beliefs about medications, corticosteroid side-effects, psychosocial status, and the doctor-patient relationship were associated with corticosteroid adherence.

Methods: Sarcoidosis patients receiving corticosteroids were eligible to participate. CMA was measured using the Medication Adherence Response Scale-10 (MARS-10), a validated patient reported outcome measure (PRO). Data collection included patient demographics and clinical variables to assess their sarcoidosis phenotype. The patients were administered additional PROs concerning their psychosocial status, beliefs about medication use, corticosteroid side-effects and the strength of their doctor-patient relationship.

Results: 132 patients were enrolled. Their mean prednisone dose was 9.9 ± 7.5 mg/day. 75% (99/132) were adherent with corticosteroids (MARS-10 ≥ 6) and 25% (33/132) were nonadherent (MARS-10 < 6). All demographic features, education level, and annual family income were not associated with CMA. Most clinical variables including spirometry, use of additional sarcoidosis drugs, number of organs involved with sarcoidosis were not associated with CMA. Almost all PROs including a better attitude toward medication use, less psychological issues, less corticosteroid side-effects, and a stronger doctor-patient relationship were associated with better CMA. A multi-logistic regression found that patient-doctor communication and the patient's intrinsic beliefs about the use of medications remained associated with CMA.

Conclusion: We found no significant relationship between demographic or socioeconomic factors and CMA. Few clinical factors were associated with CMA. In a univariate analysis, CMA was associated with physician-doctor communication, beliefs about medication use, psychological/emotional issues, and corticosteroid side-effects. Only the first two of these factors remained associated with CMA in a multi-logistic analysis. These data suggest that CMA is heavily influenced by sarcoidosis patient beliefs about medications, and less so by patient demographics.

Purpose: Poor functional status is associated with pediatric lung transplant (LTx) waitlist mortality. We investigate how pre-transplant functional status affects post-LTx survival.

Methods: A retrospective analysis was performed using The United Network for Organ Sharing (UNOS) Registry data. Pediatric first-time lung transplant candidates between ages 1 and 18 years with reported Lansky Play-Performance Scores (LPPS) at the time of waitlist and/or transplant were included from 2005 and 2021. Functional status by the LPPS scores is defined as severe limitation for LPPS score 10-40, mild limitation for LPPS score 50-70, and normal activity for LPPS score 80-100. Univariate analyses, multivariable Cox regression, and Kaplan-Meier plots were used to assess the impact of functional status on 1-year post-LTx survival.

Results: There were 913 and 610 patients at the time of LTx listing and transplant with LPPS scores, respectively. Poor functional status as determined by the LPPS score at the time of LTx, but not at the time of waitlist, was associated with worse 1-year post-LTx outcome (p value 0.0025 vs. 0.071). Multivariable survival analysis using Cox proportional hazards regression identified that a severely limited functional status at the time of LTx was the most profound risk factor for worse 1-year post-LTx survival outcomes when compared to a normal functional status (HR 2.16; 95% CI 1.15-4.07, p value 0.017).

Conclusions: Children with severely limited functional status at the time of LTx have worse 1-year post-LTx outcome. It is important to develop strategies to optimize the functional status of children for improved post-LTx outcomes.

Objectives: This study explored the expression and diagnostic value of differentially expressed miR-3591-5p in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH).

Methods: A total of 110 CHD patients were divided into four groups based on their mean pulmonary artery pressure (PAPm). The plasma miR-3591-5p expression was determined by reverse transcription polymerase chain reaction. The correlation between the miR-3591-5p expression and various clinical indices, as well as its diagnostic value for CHD-PAH patients, were analyzed.

Results: The plasma levels of miR-3591-5p were significantly higher in the patients in the no PAH group, mild PAH group, and moderate to severe PAH group than in the control group, and they were significantly higher in the moderate to severe PAH group than in the no PAH group. Correlation analysis revealed that the miR-3591-5p expression level was significantly positively correlated with various clinical indicators, including the PAPm, pulmonary artery systolic pressure, brain natriuretic peptide, pulmonary vascular resistance, red blood cell distribution width, uric acid, Na + , systolic blood pressure, left atrial internal dimension, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension. Univariate and multivariate regression analyses identified the plasma miR-3591-5p level as an independent risk factor for CHD-PAH. Receiver operating characteristic curve analysis demonstrated that the plasma miR-3591-5p level had a moderate diagnostic value for CHD-PAH, which was further improved when combined with a B-type natriuretic peptide.

Conclusion: This study identified the expression profiles of differentially expressed plasma miRNAs in patients with CHD-PAH, focusing on the upregulation of miR-3591-5p. Bioinformatics analysis suggested that miR-3591-5p is involved in the pathogenesis of CHD-PAH and may serve as a circulating biomarker that may have diagnostic and prognostic value in CHD-PAH.

Introduction: Fibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m).

Methods: A retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered.

Results: Baseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan-Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival.

Conclusion: 6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs.

Background: Lymphangioleiomyomatosis (LAM) is a rare (twenty-one per million female inhabitants) neoplastic cystic lung disease that impairs health-related quality of life (HRQoL). However, the factors associated with impaired quality of life in patients with LAM are poorly understood.

Objective: To assess the clinical, psychosocial, and functional characteristics associated with impaired quality of life in patients with LAM.

Methods: This was a cross-sectional study performed on two nonconsecutive days. HRQoL (SF-36 and CRQ), lung function tests, anxiety and depression symptoms (HADS), maximal (CPET and ISWT), and submaximal exercise capacity (6MWT) were assessed. Linear associations among outcomes were assessed using Pearson's correlation and multivariate tests.

Results: Forty-five women with LAM (46 ± 10.years; FEV_1,74%pred) were evaluated. The lowest SF-36 scores were observed for general health and vitality and the highest for the physical and social domains. The lowest CRQ scores were observed for dyspnea and fatigue, and the highest were for the emotional function and self-control domains. Sixteen (35%) women had anxiety, and 8 (17%) had depression symptoms. Most of the SF-36 and CRQ domains were associated with anxiety and depression symptoms (from r = 0.4 to r = 0.7; p < 0.05) and exercise capacity (from r = 0.3 to r = 0.5; p < 0.05). Lung function parameters were weakly or not associated with quality of life domains. After multiple linear regression, HRQoL was independently associated with depression symptoms and physical capacity but not with lung function.

Conclusion: Our results show that aerobic capacity and depression symptoms are the main factors, rather than lung function, related to quality of life in patients with LAM.

Purpose: Tripartite motif-containing protein 13 (TRIM13) directly or indirectly participates in autophagy and apoptosis. However, it remains unclear whether TRIM13 participates in chronic obstructive pulmonary disease (COPD) progression. This study aimed to reveal the molecular mechanisms through which TRIM13 regulates alveolar epithelial cell injury in COPD to provide new molecular targets for COPD treatment.

Methods: The TRIM13 expression levels were determined in clinical COPD patients and a rat emphysema model. A cigarette smoke-induced model of endoplasmic reticulum stress (ERS) and endoplasmic reticulum autophagy (ER-phagy) was developed using A549 cells, and the effects of TRIM13 gene overexpression/knockdown on ERS, ER-phagy, and cell apoptosis were assessed in these cells.

Results: TRIM13 expression was significantly decreased in the lung tissues of COPD patients and rats with emphysema. Moreover, the apoptosis level was significantly increased in the lung tissues of rats with emphysema. TRIM13 gene overexpression reduced the expression levels of ERS-related molecules (GRP78, GRP94, XBP-1, and eIF2a) in the COPD model; it also lowered the ER-phagy level, as evidenced by decreased number of autolysosomes observed by transmission electron microscopy, improved endoplasmic reticulum structure, reduced LC3-II/LC3-I and Beclin1 expression levels, and increased expression level of the autophagy inhibitory molecule Bcl-2. TRIM13 gene knockdown, however, led to opposite results.

Conclusion: TRIM13 expression attenuated alveolar epithelial cell injury in COPD by inhibiting ERS-induced ER-phagy.

Background: Asthma is associated with accelerated rate of FEV₁ decline.

Objective: To determine predictive factors associated with accelerated FEV₁ decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline.

Methods: We recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV₁ decline > 0.85% pred.y^-1) and others. Predictive factors were highlighted with linear regression analysis. Sputum EGF, VEGF, FGF, IL5, IL8, TGF-β, and IgE levels were measured in 58 of these patients at both visits by Human XL cytokine Luminex Performance assay and Elisa.

Results: Post-BD FEV₁ decline was 0.06 ± 2.44% pred.y^-1 in the overall population. Median (IQR) time between visits was 66 (62 - 86) months. The multivariable analysis showed that an increase in blood eosinophils over time (Δ BEC) (Reg. Coef. (95%CI): 0.002 (0.001 to 0.004), p = 0.005)) and onset of asthma (0.04 (0.003 to 0.07), p = 0.036) were independently associated with FEV₁ decline. IL8 levels measured at baseline were higher (499 (408-603) pg/ml, p = 0.0040) in patients with accelerated decline compared to others (143 (88-308) pg/ml).

Conclusion: In this study, we have confirmed that an increase in blood eosinophil counts over a follow-up of at least 5 years and later onset of asthma are associated with accelerated annual FEV₁ decline. Moreover, high sputum IL8 levels could be a risk factor for accelerated decline in asthma patients.

Purpose: In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV₁ of 10-14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI_2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population.

Methods: We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12 months. They were grouped according to the 12-month change in FEV₁ into two groups: Individuals who experienced a change in FEV₁ ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI_2.5 were estimated using generalized estimating equations.

Results: The study included 129 pwCF who initiated ETI at our center (Age Range: 12-36 years). In 20 subjects (15.5%), the FEV₁ change was < MCID. These individuals had better baseline pulmonary function than those with FEV₁ changes ≥ MCID (Median FEV₁: 102.5 vs 87.0%), with the majority (90%) having FEV₁ values ≥ 90%. Mean changes in LCI_2.5 at 12-month follow-up visit were - 1.44 units (95% CI: - 2.12; - 0.75) in individuals with changes in FEV₁ < MCID and - 2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID.

Conclusion: LCI_2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV₁ change following treatment initiation.