Lung最新文献

Background: Fibrotic interstitial lung disease is often identified late due to non-specific symptoms, inadequate access to specialist care, and clinical unawareness precluding proper and timely treatment. Biopsy histological analysis is definitive but rarely performed due to its invasiveness. Diagnosis typically relies on high-resolution computed tomography, while disease progression is evaluated via frequent pulmonary function testing. This study tested the hypothesis that pulmonary fibrosis diagnosis and progression could be non-invasively and accurately evaluated from the hair metabolome, with the longer-term goal to minimize patient discomfort.

Methods: Hair specimens collected from pulmonary fibrosis patients (n = 56) and healthy subjects (n = 14) were processed for metabolite extraction using 2DLC/MS-MS, and data were analyzed via machine learning. Metabolomic data were used to train machine learning classification models tuned via a rigorous combination of cross validation, feature selection, and testing with a hold-out dataset to evaluate classifications of diseased vs. healthy subjects and stable vs. progressed disease.

Results: Prediction of pulmonary fibrosis vs. healthy achieved AUROC_TRAIN = 0.888 (0.794-0.982) and AUROC_TEST = 0.908, while prediction of stable vs. progressed disease achieved AUROC_TRAIN = 0.833 (0.784 - 0.882) and AUROC_TEST = 0. 799. Top metabolites for diagnosis included ornithine, 4-(methylnitrosamino)-1-3-pyridyl-N-oxide-1-butanol, Thr-Phe, desthiobiotin, and proline. Top metabolites for progression included azelaic acid, Thr-Phe, Ala-Tyr, indoleacetyl glutamic acid, and cytidine.

Conclusion: This study provides novel evidence that pulmonary fibrosis diagnosis and progression may in principle be evaluated from the hair metabolome. Longer term, this approach may facilitate non-invasive and accurate detection and monitoring of fibrotic lung diseases.

Background: The increasing incidence of encountering lung nodules necessitates an ongoing search for improved diagnostic procedures. Various bronchoscopic technologies have been introduced or are in development, but further studies are needed to define a method that fits best in clinical practice and health care systems.

Research question: How do basic bronchoscopic tools including a combination of thin (outer diameter 4.2 mm) and ultrathin bronchoscopes (outer diameter 3.0 mm), radial endobronchial ultrasound (rEBUS) and fluoroscopy perform in peripheral pulmonary lesion diagnosis?

Study design and methods: This is a retrospective review of the performance of peripheral bronchoscopy using thin and ultrathin bronchoscopy with rEBUS and 2D fluoroscopy without a navigational system for evaluating peripheral lung lesions in a single academic medical center from 11/2015 to 1/2021. We used a strict definition for diagnostic yield and assessed the impact of different variables on diagnostic yield, specifically after employment of the ultrathin bronchoscope. Logistic regression models were employed to assess the independent associations of the most impactful variables.

Results: A total of 322 patients were included in this study. The median of the long axis diameter was 2.2 cm and the median distance of the center of the lesion from the visceral pleural surface was 1.9 cm. Overall diagnostic yield was 81.3% after employment of the ultrathin bronchoscope, with more detection of concentric rEBUS views (93% vs. 78%, p < 0.001). Sensitivity for detecting malignancy also increased from 60.5% to 74.7% (p = 0.033) after incorporating the ultrathin scope into practice, while bronchus sign and peripheral location of the lesion were not found to affect diagnostic yield. Concentric rEBUS view, solid appearance, upper/middle lobe location and larger size of the nodules were found to be independent predictors of successful achievement of diagnosis at bronchoscopy.

Interpretation: This study demonstrates a high diagnostic yield of biopsy of lung lesions achieved by utilization of thin and ultrathin bronchoscopes. Direct visualization of small peripheral airways with simultaneous rEBUS confirmation increased localization rate of small lesions in a conventional bronchoscopy setting without virtual navigational planning.

Background: Pneumonia is a common lower respiratory tract infection, and early diagnosis is crucial for timely treatment and improved prognosis. Traditional diagnostic methods for pneumonia, such as chest imaging and microbiological examinations, have certain limitations. Exhaled volatile organic compounds (VOCs) detection, as an emerging non-invasive diagnostic technique, has shown potential application value in pneumonia screening.

Method: A systematic search was conducted on PubMed, Embase, Cochrane Library, and Web of Science, with the retrieval time up to March 2024. The inclusion criteria were diagnostic studies evaluating exhaled VOCs detection for the diagnosis of pneumonia, regardless of the trial design type. A meta-analysis was performed using a bivariate model for sensitivity and specificity.

Results: A total of 14 diagnostic studies were included in this meta-analysis. The pooled results demonstrated that exhaled VOCs detection had a combined sensitivity of 0.94 (95% CI: 0.92-0.95) and a combined specificity of 0.83 (95% CI: 0.81-0.84) in pneumonia screening, with an area under the summary receiver operating characteristic (SROC) curve (AUC) of 0.96. The pooled diagnostic odds ratio (DOR) was 104.37 (95% CI: 27.93-390.03), and the pooled positive and negative likelihood ratios (LR) were 8.98 (95% CI: 3.88-20.80) and 0.11 (95% CI: 0.05-0.22), indicating a high diagnostic performance.

Conclusion: This study highlights the potential of exhaled VOCs detection as an effective, non-invasive screening method for pneumonia, which could facilitate future diagnosis in pneumonia. Further high-quality, large-scale studies are required to confirm the clinical utility of exhaled VOCs detection in pneumonia screening.

Study registration: PROSPERO, Review no. CRD42024520498.

Introduction: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed.

Methods: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis.

Results: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress.

Conclusion: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe.

Trail registration: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

Purpose: We aimed to identify a safe and effective method to assist older adults with pneumonia in tolerating the prone position for a longer duration.

Methods: This was a randomized, controlled, double-blinded study performed at the Shanghai Fourth People's Hospital. Eighty patients with pneumonia aged ≥ 65 years were included. The patients were able to spontaneous breath in the prone position and were administered intravenous dexmedetomidine or an isotonic sodium chloride solution. The cumulative daily durations of prone positioning for all patients in the two groups were recorded. The primary outcome was the percentage of patients who completed ≥ 9 h/day in the prone position. The secondary outcomes included the incidence of complications in the prone position and patient outcomes.

Results: Eighty patients were included (average age: 79.6 ± 8.9 years). The percentage of patients who completed ≥ 9 h/day in the prone position was significantly higher in the dexmedetomidine group than in the placebo group (P = 0.011). The percentage of patients who completed ≥ 12 h/day in the prone position was also significantly greater in the dexmedetomidine group than in the placebo group (P = 0.008). There were no significant differences in other variables between the two groups.

Conclusions: The results of this study demonstrate that intravenous dexmedetomidine injection can significantly prolong the duration of spontaneous breathing in the prone position in elderly pneumonia patients without obvious adverse events. We provide a safe and effective method to help patients with pneumonia, especially those with delirium or cognitive impairment, who cannot tolerate the length of time needed for spontaneous breathing in the prone position to be effective.

Trial registration: The study was registered with the Chinese Clinical Trial Center (registration number: ChiCRT2300067383) on 2023-01-05.

The pulmonary lymphatic system has emerged as a critical regulator of lung homeostasis and a key contributor to the pathogenesis of respiratory diseases. As the primary conduit responsible for maintaining fluid balance and facilitating immune cell trafficking, the integrity of lymphatic vessels is essential for preserving normal pulmonary structure and function. Lymphatic abnormalities manifest across a broad spectrum of pulmonary disorders, underscoring their significance in respiratory health and disease. This review provides an overview of pulmonary lymphatic biology and delves into the involvement of lymphatics in four major lung diseases: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung transplant rejection. We examine how lymphatic abnormalities manifest in each of these conditions and investigate the mechanisms through which lymphatic remodeling and dysfunction contribute to disease progression. Furthermore, we explore the therapeutic potential of targeting the lymphatic system to ameliorate these debilitating respiratory conditions. Despite the current knowledge, several crucial questions remain unanswered, such as the spatial and temporal dynamics of lymphatic changes, the molecular crosstalk between lymphatics and the lung microenvironment, and the distinction between protective versus detrimental lymphatic phenotypes. Unraveling these mysteries holds the promise of identifying novel molecular regulators, characterizing lymphatic endothelial phenotypes, and uncovering bioactive mediators. By harnessing this knowledge, we can pave the way for the development of innovative disease-modifying therapies targeting the lymphatic highway in lung disorders.

Introduction: Azithromycin is an effective treatment for various respiratory conditions but its effect on cough is poorly understood. We synthesised data from randomised controlled trials (RCTs) and noncomparative studies (NCT) examining its effect on objective and subjective cough.

Methods: After prospective registration on PROSPERO, we searched MEDLINE, EMBASE, and CENTRAL for both RCTs and NCT trials examining the effect azithromycin on cough in respiratory disease.

Results: We identified 1240 studies of which 6 (4 RCTs and 2 NCT studies) were included in the meta-analysis, with a total of 275 patients. Azithromycin was associated with significant improvement in Leicester Cough Questionnaire scores at follow-up when compared to baseline scores (SMD = 0.62 [95% CI 0.12 to 1.12], p = 0.01). However, when only RCTs were synthesised, no significant effect was observed (SMD = 0.12 [95% CI - 0.36 to 0.60], p = 0.62). There was no significant reduction in cough severity VAS score (SMD = - 0.39 [95% CI - 0.92 to 0.14], p = 0.15). There was no significant reduction in objective cough count (SMD = - 0.41 [95% CI - 1.04 to 0.32], p = 0.09).

Conclusion: Azithromycin therapy improves cough-related quality of life in various chronic respiratory diseases; however, there was no significant effect on cough outcomes when only data from RCTs were synthesised. We believe that to accurately identify which patients whose cough would benefit from azithromycin a large-scale clinical trial of patients with a broad spectrum of respiratory diseases, with sufficiently severe cough, should be undertaken with subgroup analysis of individual disease areas.

Introduction

In sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis.

Methods

Blood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP.

Results

Differential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers.

Conclusion

Blood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood.

Trial registration: EudraCT 2019-000580-24 (17 May 2019)

Background

Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known.

Research question

Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity?

Methods

Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories.

Results

40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27 kg/m²). The presence of diabetes was independently associated with a reduction in FEV1 (− 130 ml), FVC (− 220 ml), DLCO (− 1.52 ml/min/mmHg), and VA (− 340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), p < 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI.

Conclusion

The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI.