BMC Pulmonary Medicine最新文献

Background: Lung phenotypes have been extensively utilized to assess lung injury and guide precise treatment. However, current phenotypic evaluation methods rely on CT scans and other techniques. Although lung ultrasound (LUS) is widely employed in critically ill patients, there is a lack of comprehensive and systematic identification of LUS phenotypes based on clinical data and assessment of their clinical value.

Methods: Our study was based on a retrospective database. A total of 821 patients were included from September 2019 to October 2020. 1902 LUS examinations were performed in this period. Using a dataset of 55 LUS examinations focused on lung injuries, a group of experts developed an algorithm for classifying LUS phenotypes based on clinical practice, expert experience, and lecture review. This algorithm underwent validation and refinement with an additional 140 LUS images, leading to five iterative revisions and the generation of 1902 distinct LUS phenotypes. Subsequently, a validated machine learning algorithm was applied to these phenotypes. To assess the algorithm's effectiveness, experts manually verified 30% of the phenotypes, confirming its efficacy. Using K-means cluster analysis and expert image selection from the 1902 LUS examinations, we established seven distinct LUS phenotypes. To further explore the diagnostic value of these phenotypes for clinical diagnosis, we investigated their auxiliary diagnostic capabilities.

Results: A total of 1902 LUS phenotypes were tested by randomly selecting 30% to verify the phenotypic accuracy. With the 1902 LUS phenotypes, seven lung ultrasound phenotypes were established through statistical K-means cluster analysis and expert screening. The acute respiratory distress syndrome (ARDS) exhibited gravity-dependent phenotypes, while the cardiogenic pulmonary edema exhibited nongravity phenotypes. The baseline characteristics of the 821 patients included age (66.14 ± 11.76), sex (560/321), heart rate (96.99 ± 23.75), mean arterial pressure (86.5 ± 13.57), Acute Physiology and Chronic Health Evaluation II (APACHE II)score (20.49 ± 8.60), and duration of ICU stay (24.50 ± 26.22); among the 821 patients, 78.8% were cured. In severe pneumonia patients, the gravity-dependent phenotype accounted for 42% of the cases, whereas the nongravity-dependent phenotype constituted 58%. These findings highlight the value of applying different LUS phenotypes in various diagnoses.

Conclusions: Seven sets of LUS phenotypes were established through machine learning analysis of retrospective data; these phenotypes could represent the typical characteristics of patients with different types of critical illness.

Objective: Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges.

Methods: Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups.

Results: Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years.

Conclusions: This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.

Background: Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear.

Case presentation: A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV₁)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25-75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV₁ coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25-75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively.

Conclusions: This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV₁. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.

Background: Health-related quality of life (HRQoL) assessments and estimates of prognosis are needed for comprehensive care and planning of subsequent treatment in patients with idiopathic pulmonary fibrosis (IPF). We investigated HRQoL and its association with survival using a disease-specific tool in patients with IPF.

Methods: The patients were recruited from the real-life FinnishIPF study in 2015. HRQoL was assessed with the King's Brief Interstitial Lung Disease (K-BILD) questionnaire every six months for 2.5 years. Dyspnoea was assessed with the modified Medical Research Council (mMRC) dyspnoea scale. Survival was registered until 31 December 2022. Patient survival according to the K-BILD total score was evaluated using the Kaplan‒Meier method. The Friedman test was used to compare the K-BILD total scores longitudinally, and the Mann‒Whitney U test was used to compare the mMRC groups. P values < 0.05 were considered statistically significant.

Results: The median K-BILD total score (n = 245) was 51.6. At baseline, patients in the highest HRQoL quartile (K-BILD scores 58.9-100) had a longer median survival time (5.3 years) than did those with scores of 51.7-58.8 (3.1 years), 45.7-51.6 (2.3 years), and 0.0-45.6 (1.8 years). A decrease in the K-BILD total score of ≥ 5 units in the preceding 12 or 24 months showed a trend towards poorer survival, although statistical significance was not reached. Ninety-four patients survived more than 2.5 years and had available K-BILD data at all time points. The K-BILD total score remained higher in patients with a baseline mMRC of 0-1 than in those with a mMRC of 2-4, and the total score decreased only modestly in both groups (median of 3.3 and 4.8 units in patients with mMRC scores of 0-1 and 2-4, respectively).

Conclusions: In IPF, a reduced HRQoL is associated with impaired survival. A K-BILD total score less than approximately 50 units is associated with a median survival of approximately two years. In addition to assessing the treatment needs of patients with IPF using K-BILD, a decreased score may be useful for facilitating advance care planning and transplantation assessment.

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition frequently encountered in critically ill patients, including those with advanced non-small cell lung cancer (NSCLC). Almonertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has shown promise as a first-line treatment for NSCLC with classical EGFR mutations. However, its efficacy in NSCLC patients suffering from ARDS has not been well-documented.

Case presentation: We report the case of a 63-year-old Chinese Han female with severe NSCLC complicated by ARDS. Upon hospital admission, the patient exhibited progressive dyspnea and required intubation to maintain oxygenation. Pathological analysis of bronchoalveolar lavage fluid sediment confirmed lung adenocarcinoma, and genetic testing of blood identified an EGFR E19 mutation. The patient was treated with almonertinib, resulting in significant clinical improvement and successful extubation after nine days. Radiographic imaging showed substantial reduction in pulmonary lesions, highlighting the efficacy of almonertinib.

Conclusion: This case represents the first documented successful treatment of ARDS induced by EGFR E19 mutated NSCLC using almonertinib. The favorable clinical response observed in this critically ill patient suggests that almonertinib may be a viable therapeutic option for managing severe complications in NSCLC. Further research is necessary to corroborate these findings and optimize dosage and toxicity management strategies for broader clinical application.

Background: Evaluation of indeterminate pulmonary nodules (IPNs) often creates a diagnostic conundrum which may delay the early detection of lung cancer. Rare circulating genetically abnormal cells (CGAC) have previously demonstrated utility as a biomarker for discriminating benign from malignant small IPNs in the LungLB assay. CGAC are identified using a unique 4-color fluorescence in-situ hybridization (FISH) assay and are thought to reflect early cell-based events in lung cancer pathogenesis and the anti-tumor immune response. LungLB is a prognostic tool that combines the CGAC biomarker and clinical features to aid in IPN evaluation by improving the stratification of patient risk of malignancy.

Methods: Herein we describe the analytical performance of the LungLB blood test. Analytical validation was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines with adaptations for rare cell-based assays. Multiple operators, reagent lots, and assay runs were tested to examine accuracy, precision, reproducibility, and interfering factors.

Results: The FISH probes used in the LungLB assay demonstrate 100% sensitivity and specificity for their intended chromosomal loci (3q29, 3p22.1, 10q22.3 and 10cen). LungLB demonstrates analytical sensitivity of 10 CGAC per 10,000 lymphocytes analyzed, 100% analytical specificity, and high linearity (R² = 0.9971). Within run measurements across 100 samples demonstrated 96% reproducibility. Interfering factors normally found in blood (lipemia, biotin) and exposure to adverse temperatures (-20ºC or 37ºC) did not interfere with results. Sample stability was validated to 96 hours.

Conclusion: The analytical performance of LungLB in this validation study successfully demonstrates it is robust and suitable for everyday clinical use.

Objective: Pulmonary infection is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). It is sometimes difficult to differentiate pulmonary infection from pulmonary involvement of vasculitis in AAV patients. Fiberoptic bronchoscopy and bronchoalveolar lavage fluid (BALF) assays are useful diagnostic methods. In addition to conventional microbiological tests (CMTs), metagenomic next-generation sequencing (mNGS) facilitates rapid and sensitive detection of various pathogens. The current study aimed to evaluate the advantages of additional BALF mNGS in the management of pulmonary infection in AAV patients.

Methods: 27 patients with active AAV and suspected pulmonary infection whose BALF samples were tested by mNGS and CMTs and 17 active AAV patients whose BALF were tested by CMTs alone were retrospectively recruited. The results of microbiological tests, and adjustments of treatment following BALF mNGS, were described. The durations of antimicrobial treatment and in-hospital mortality in patients were compared.

Results: Among the 27 patients whose BALF samples were tested by mNGS, 25.9% of patients did not have evidence of pathogenic microorganism in their BALF samples, 55.6% had polymicrobial infections, including bacteria, fungi and viruses. Of these 27 patients, 40.7% did not have evidence of pathogenic microorganism in their BALF or serum samples according to CMTs. Patients in the BALF mNGS/CMT group received a significantly shorter duration of antibacterial and total antimicrobial treatment than patients in the CMT alone group (17.3 ± 14.7 vs. 27.9 ± 19.0 days, P = 0.044; 18.9 ± 15.0 vs. 29.5 ± 17.7 days, P = 0.040, respectively). Fewer patients in the BALF mNGS/CMT group died than in the CMT alone group (4/27 vs. 7/17, P = 0.049).

Conclusion: Compared with CMT alone, additional mNGS tests may shorten the duration of antimicrobial treatment and possibly decrease death from severe infection by providing precise and quick diagnosis of infection.

Background: Chlamydia abortus, as a pathogen of atypical pneumonia, is rare in humans, especially in HIV infection patients.

Case presentation: We present the case of a 48-year-old man with a history of HIV infection who started high fever and developed pneumonia. The pathogen-targeted next-generation sequencing (ptNGS) results of bronchial lavage fluid showed Chlamydia abortus infection.

Conclusion: This is the first report of Chlamydia abortus infection presented as atypical pneumonia in an AIDS patient.

Background: The expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in lung cancer has been validated in numerous studies. However, the prognostic value of OAS1 expression in lung adenocarcinoma (LUAD) still remains unclear. This study aimed to reveal the prognostic value and associated molecular mechanisms of OAS1 expression in LUAD.

Methods: Gene expression data of LUAD were extracted from online databases. Gene and protein expression levels of OAS1 in LUAD and normal samples were revealed, followed by prognostic analysis of OAS1. Next, we conducted a thorough bioinformatics analysis to examine the enrichment of key functional and biological signaling pathways and their correlation with the abundance of immune cells. The independent prognoses, drug responses, and PPI networks associated with OAS1 were analyzed. OAS1 expression was evaluated in LUAD tissues and cell lines. OAS1 was knocked down by siRNA transfection, followed by CCK8, colony formation, and wound-healing assays.

Results: Gene and protein expression levels of OAS1 in LUAD samples were significantly higher than those in normal samples (all P < 0.05). OAS1 stimulation were correlated with poor prognosis, lymph node metastasis, advanced tumor stage, immune cells, and immunomodulators. The prognostic value of OAS1 in LUAD was determined via univariate regression analysis. In total, 10 OAS1-associated genes were revealed via PPI analysis of OAS1, which were primarily enriched in functions, such as the negative regulation of viral genome replication. Transcriptional analysis revealed several OAS1-related interactions, including STAT3-miR-21-OAS1. STAT3 was overexpressed and miR-21 was expressed in LUAD cells. Upregulation of OAS1 protein was determined in LUAD tissues and cell lines. OAS1 knockdown significantly reduced proliferation and migration of LUAD cells.

Conclusions: OAS1 overexpression influenced survival and immune cell infiltration in patients with LUAD, which might be a potential prognostic gene for LUAD. Moreover, OAS1 contributed to LUAD progression by participating in STAT3-miR-21-OAS1 axis.

Background: The mitochondria are essential organelles not only providing cellular energy in the form of ATP, but also regulating the inflammatory response and the cell death program. Mitochondrial dysfunction has been associated with various human diseases, including metabolic syndromes as well as inflammatory and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by uncontrolled alveolar inflammation, apoptotic lung epithelial/endothelial cells, and pulmonary edema. Despite the high mortality of ARDS, an effective pharmacotherapy to treat this disease has not been established yet. Therefore, identifying a novel targeted therapy for ARDS is important. Recently, exogenous mitochondrial transplantation was reported to be beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transplantation on ARDS in vitro and in vivo.

Methods: Mitochondria were isolated from human stem cells. For in vitro efficacy of mitochondrial transplantation on the inflammation and cell death, murine alveolar macrophages MH-S and human pulmonary microvascular endothelial cells HPMECs were exposed to LPS, respectively. The ARDS mice model established by a single intratracheal instillation of LPS was used for in vivo efficacy of intravenously treated mitochondria.

Results: Our results showed that the mitochondria isolated from human stem cells exhibited an anti-inflammatory effect against alveolar macrophages and an anti-apoptotic effect against the alveolar epithelial cells. Furthermore, intravenous mitochondrial treatment was associated with the attenuation of lung injury in the LPS-induced ARDS mice.

Conclusion: Dual effects of mitochondria on anti-inflammation and anti-apoptosis support the potential of mitochondrial transplantation as a novel therapeutic strategy for ARDS.