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Background and objective: Traditionally, the diagnosis of acute rejection (AR) relies on invasive transbronchial biopsies (TBBs) to obtain histopathological samples. We aimed to evaluate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) as a complementary and non-invasive tool for ACR screening, comparing its results with those obtained from TBBs.

Methods: Between January 2015 and April 2022, we conducted a retrospective study of all lung transplant recipients aged over 18 years at Toulouse University Hospital (France). All patients who underwent bronchoscopies with both TBBs and pCLE imaging were included. Two experienced interpreters (TV and MS) reviewed the pCLE images independently, blinded to all clinical information and pathology results.

Results: From 120 procedures in 85 patients, 34 abnormal histological samples were identified. Probe-based confocal laser endomicroscopy revealed significant associations between both alveolar (ALC) and perivascular (PVC) cellularities and abnormal histological samples (p<0.0001 and 0.003 respectively). Alveolar cellularity demonstrated a sensitivity (Se) of 85.3 %, specificity (Spe) of 43 %, positive predictive value (PPV) of 37.2 % and negative predictive value (NPV) of 88.1 %. For PVC, Se was 70.6 %, Spe 80.2 %, PPV 58.5 % and NPV 87.3 %. Intra-interpreter correlation (TV) was 88.3 % for the number of vessels (+/-1), 98.3 % for ALC and 90 % for PVC. Inter-interpreter correlation (TV and MS) was 80 % for vessels (+/-1), 97.5 % for ALC and 83.3 % for PVC.

Conclusion: Our study demonstrates the feasibility of incorporating pCLE into clinical practice, demonstrating good diagnostic yield and reproducible outcomes in the screening of AR in lung transplant recipients.

Background: Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM.

Aim: To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis.

Methods: MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale.

Results: From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132-3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197‑3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574-5p; no miRNA was found associated to LC prognosis.

Conclusion: Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.

Background: The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support.

Methods: In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area.

Results: One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity).

Conclusions: The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.

Age-related lung function decline is associated with small airway closure and gas trapping. The mechanisms which cause these changes are not fully understood. It has been suggested that COPD is caused by accelerated ageing. We have investigated pathological changes in the small airways during ageing, and evaluated whether the same or different processes exist in COPD. Histopathology and immunohistochemistry were used to examine small airway remodelling in healthy ageing, and then compare to age matched COPD patients. Ageing was associated with reduced alveolar attachment numbers (rho= -0.4 p = 0.049), increased epithelial area (rho = 0.5 p = 0.01), greater luminal narrowing due to epithelial expansion (rho = 0.5 p = 0.04) and increased alveolar septal neutrophils (rho = 0.6 p = 0.005). Compared to age matched controls, COPD small airways had 31% less alveolar attachments per airway (p = 0.02) and significantly more alveoalr septal neutrophils (p = 0.0007). Increased airway wall thickness was a feature of COPD but was not related to ageing in non-smokers. Alveolar attachment loss, accompanied by alveolar septum neutrophilic inflammation, and increased luminal narrowing due to epithelial expansion are major features of small airway remodelling during ageing. These features can explain the increased small airway narrowing and closure during ageing. Alveolar attachment loss is accelerated in COPD, likely due to increased neutrophilic inflammation.

Introduction and objectives: The fractional exhaled fraction of nitric oxide (FeNO) is used in clinical practice for asthma diagnosis, phenotyping, and therapeutic management. Therefore, accurate thresholds are crucial. The normal FeNO values over lifespan in a respiratory healthy population and the factors related to them remain unclear.

Materials and methods: We determined FeNO levels in 2,251 respiratory healthy, non-atopic, and non-smoking participants from the Lung, hEart, sociAl, boDy (LEAD) cohort, a general population, observational cohort study of participants aged 6-82 years in Austria.

Results: The median FeNO value in the total study population was 13.0 [interquartile range: 9.0, 20.0] ppb, increases with age, and, except in young participants (<18 years: 9.0 [7.0, 12.0], ≥18 years: 15.0 [11.0, 22.0]), it was significantly lower in females versus males. Multiple regression analyses showed that body height and blood eosinophil counts were associated with higher FeNO levels, both in children/adolescents and adults. In children/adolescents, FeNO values were positively associated with total IgE levels, FEV1/FVC ratio, and urban living. In adults, FeNO was positively associated with age and negatively associated with the presence of cardiovascular and ischaemic vascular disease.

Conclusions: We identified the normal FeNO ranges within a respiratory healthy population at different age ranges and associated factors. Collectively, they serve as a reference to frame FeNO values in clinical practice.

Rhinitis is a common comorbidity in patients with asthma. However, the frequency of underreported rhinitis in asthma is not known. In this study, we aimed to assess the characteristics of patients with self-reported asthma and no self-reported rhinitis, as well as the extent of the underreporting of rhinitis. We performed a cross-sectional study of all MASK-air^Ⓡ users (2015-2022, 27 countries), comparing reported symptoms and medication use in patients with (i) self-reported asthma without rhinitis ("asthma alone"), (ii) self-reported rhinitis+asthma and (iii) self-reported rhinitis without asthma ("rhinitis alone"). In patients reporting asthma alone and providing MASK-air^Ⓡ data in at least three different months, a cluster analysis was performed to potentially identify groups of patients underreporting rhinitis and/or undertreated for rhinitis. We assessed 35,251 users (529,751 days): 671 (1.9%) reporting asthma alone 25,882 (73.4%) reporting rhinitis alone and 8698 (24.7%) reporting rhinitis+asthma. Overall, 27% of the patients reporting asthma alone were treated with rhinitis medications. Patients reporting asthma alone displayed a lower frequency of days under rhinitis medication and less severe nasal symptoms than those reporting rhinitis+asthma. Among patients reporting asthma alone, three clusters of patients were identified: (A; 22.2%) severe rhinitis symptoms and low frequency of rhinitis medication use, (B, 41.0%) moderate rhinitis symptoms and high frequency of rhinitis medication use (41.0%), and (C, 36.8%) mild or no rhinitis symptoms and almost no rhinitis medication use. This study suggests that, among patients with self-reported asthma, the underreporting or undertreatment of rhinitis may be common.

Background: Previous studies have shown that patients with chronic obstructive pulmonary disease (COPD) of severe or very severe airflow limitation have a reduced pectoralis muscle area (PMA), which is associated with mortality. However, whether patients with COPD of mild or moderate airflow limitation also have a reduced PMA remains unclear. Additionally, limited evidence is available regarding the associations between PMA and respiratory symptoms, lung function, computed tomography (CT) imaging, lung function decline, and exacerbations. Therefore, we conducted this study to evaluate the presence of PMA reduction in COPD and to clarify its associations with the referred variables.

Methods: This study was based on the subjects enrolled from July 2019 to December 2020 in the Early Chronic Obstructive Pulmonary Disease (ECOPD) study. Data including questionnaire, lung function, and CT imaging were collected. The PMA was quantified on full-inspiratory CT at the aortic arch level using predefined -50 and 90 Hounsfield unit attenuation ranges. Multivariate linear regression analyses were performed to assess the association between the PMA and airflow limitation severity, respiratory symptoms, lung function, emphysema, air trapping, and the annual decline in lung function. Cox proportional hazards analysis and Poisson regression analysis were used to evaluate the PMA and exacerbations after adjustment.

Results: We included 1352 subjects at baseline (667 with normal spirometry, 685 with spirometry-defined COPD). The PMA was monotonically lower with progressive airflow limitation severity of COPD after adjusting for confounders (vs. normal spirometry; Global Initiative for Chronic Obstructive Lung Disease [GOLD] 1: β=-1.27, P=0.028; GOLD 2: β=-2.29, P<0.001; GOLD 3: β=-4.88, P<0.001; GOLD 4: β=-6.47, P=0.014). The PMA was negatively associated with the modified British Medical Research Council dyspnea scale (β=-0.005, P=0.026), COPD Assessment Test score (β=-0.06, P=0.001), emphysema (β=-0.07, P<0.001), and air trapping (β=-0.24, P<0.001) after adjustment. The PMA was positively associated with lung function (all P<0.05). Similar associations were discovered for the pectoralis major muscle area and pectoralis minor muscle area. After the 1-year follow-up, the PMA was associated with the annual decline in the post-bronchodilator forced expiratory volume in 1 s percent of predicted value (β=0.022, P=0.002) but not with the annual rate of exacerbations or the time to first exacerbation.

Conclusion: Patients with mild or moderate airflow limitation exhibit a reduced PMA. The PMA is associated with airflow limitation severity, respiratory symptoms, lung function, emphysema, and air trapping, suggesting that PMA measurement can assist with COPD assessment.

Introduction: Low physical activity (PA) levels have a negative impact on the health status of patients with Chronic Obstructive Pulmonary Disease (COPD). Smartphone applications (apps) focused on PA promotion may mitigate this problem; however, their effectiveness depends on patient adherence, which can be influenced by the technological features of the apps. This systematic review identified the technological features of smartphone apps aiming to promote PA in patients with COPD.

Methods: A literature search was performed in the databases ACM Digital Library, IEEE Xplore, PubMed, Scopus and Web of Science. Papers including the description of a smartphone app for PA promotion in patients with COPD were included. Two researchers independently selected studies and scored the apps features based on a previously developed framework (38 possible features).

Results: Twenty-three studies were included and 19 apps identified, with an average of 10 technological features implemented. Eight apps could be connected to wearables to collect data. The categories 'Measuring and monitoring' and 'Support and Feedback' were present in all apps. Overall, the most implemented features were 'progress in visual format' (n = 13), 'advice on PA' (n = 14) and 'data in visual format' (n = 10). Only three apps included social features, and two included a web-based version of the app.

Conclusions: The existing smartphone apps include a relatively small number of features to promote PA, which are mostly related to monitoring and providing feedback. Further research is warranted to explore the relationship between the presence/absence of specific features and the impact of interventions on patients' PA levels.

Introduction and aims: Workplace exposures are widely known to cause specific occupational diseases such as silicosis and asbestosis, but they also can contribute substantially to causation of common respiratory diseases. In 2019, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) published a joint statement on the occupational burden of respiratory diseases. Our aim on this narrative review is to summarise the most recent evidence published after the ATS/ERS statement as well as to provide information on traditional occupational lung diseases that can be useful for clinicians and researchers.

Results: Newer publications confirm the findings of the ATS/ERS statement on the role of workplace exposure in contributing to the aetiology of the respiratory diseases considered in this review (asthma, COPD, chronic bronchitis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, infectious pneumonia). Except for COPD, chronic bronchitis and infectious pneumonia, the number of publications in the last 5 years for the other diseases is limited. For traditional occupational lung diseases such as silicosis and asbestosis, there are old as well as novel sources of exposure and their burden continues to be relevant, especially in developing countries.

Conclusions: Occupational exposure remains an important risk factor for airways and interstitial lung diseases, causing occupational lung diseases and contributing substantially in the aetiology of common respiratory diseases. This information is critical for public health professionals formulating effective preventive strategies but also for clinicians in patient care. Effective action requires shared knowledge among clinicians, researchers, public health professionals, and policy makers.