医学最新文献

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.

Introduction and objectives: Assessment of breathlessness requires a combination of imaging and lung function testing. Dynamic digital radiography (DDR) of the thorax is an imaging technique that allows physiological and anatomical information to be gathered at the time of chest X-ray and has the potential to significantly streamline diagnostic pathways. The aims of this study were to investigate the acceptability of DDR to patients and explore the correlation between DDR-derived measurements with lung volumes measured using full pulmonary function tests (PFT).

Materials and methods: We conducted a single-centre, prospective, pilot study of patients with confirmed asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) or post-COVID-19 infection. Participants underwent DDR and paired PFT between March 2021 and August 2022. Dynamic digital radiography acceptability was measured using a 10-cm visual analogue scale (VAS). Point estimates and exact confidence intervals were used to evaluate participant preference. Digital dynamic radiography would be considered acceptable if the lower bound of the 95% confidence interval (exact) is greater than 50%. Pearson correlation (r) was used to explore associations between DDR measurements and PFT parameters.

Results: 40 participants (asthma, n = 11; COPD, n = 9; ILD, n = 11; post-COVID, n = 9) had DDR with adequate image acquisition and PFT. Mean age of participants was 63.38 years (standard deviation 14.89) and 63% were male (25/40). The lower 95% confidence interval threshold for VAS acceptability was 92% for all groups combined and considered acceptable. The projected lung area at end inspiration (PLA_insp) closely correlated with total lung capacity across all disease cohorts (r = 0.80, p < 0.001) and projected lung area at end expiration (PLA_exp) was strongly correlated with residual volume in airways disease (COPD: r = 0.87, p = 0.003; asthma: r = 0.85, p = 0.002).

Conclusion: Dynamic digital radiography is an acceptable investigation for respiratory patients. DDR-derived measurements correlate with lung volumes obtained from PFTs. Larger studies are required to validate DDR as a possible method to identify and monitor air trapping in airways disease, allowing early detection and assessment of treatment effectiveness.

Spirometry is used to determine what is "unusual" lung function compared with what is "usual" for healthy non-smokers. This study aimed to investigate regional variation in the forced vital capacity (FVC) and in the forced expiratory volume in one second to FVC ratio (FEV₁/FVC) using cross-sectional data from all 41 sites of the multinational Burden of Obstructive Lung Disease study. Participants (5,368 men; 9,649 women), aged ≥40 years, had performed spirometry, had never smoked and reported no respiratory symptoms or diagnoses. To identify regions with similar FVC, we conducted a principal component analysis (PCA) on FVC with age, age² and height², separately for men and women. We regressed FVC against age, age² and height², and FEV₁/FVC against age and height², for each sex and site, stratified by region. Mean age was 54 years (both sexes), and mean height was 1.69 m (men) and 1.61 m (women). The PCA suggested four regions: 1) Europe and richer countries; 2) the Near East; 3) Africa; and 4) the Far East. For the FVC, there was little variation in the coefficients for age, or age², but considerable variation in the constant (men: 2.97 L in the Far East to 4.08 L in Europe; women: 2.44 L in the Far East to 3.24 L in Europe) and the coefficient for height². Regional differences in the constant and coefficients for FEV₁/FVC were minimal (<1%). The relation of FVC with age, sex and height varies across and within regions. The same is not true for the FEV₁/FVC ratio.

Introduction and objectives: Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether SERPINA1 genetic variants and reduced AAT protein levels are associated with asthma exacerbations.

Materials and methods: In the discovery analysis, SERPINA1 Pi*S and Pi*Z variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (Open Targets Genetics) were analyzed. The associations between SERPINA1 Pi*S and Pi*Z variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates.

Results: In the discovery, a significant association with asthma exacerbations was found for both Pi*S (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, p-value=0.001) and Pi*Z (OR=3.49, 95%CI=1.55-7.85, p-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, p-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, p-value=0.005). The Pi*Z association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, p-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, p-value=0.007).

Conclusions: AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.

Introduction: The prediction rules of acute pulmonary embolism(PE) before imaging tests recommended by the commonly used guidelines have low diagnostic efficiency if not combined with D-dimer, therefore it is necessary to seek for a prediction rule with higher diagnostic efficiency.

Methods: We designed a new score named Legend by synthesizing the scores of Wells, PERC, and Geneva, as well as D-dimer with patients in the development group(n = 2112), and then validated it in patients of validation group(n = 388). Diagnostic efficiency was also compared between Legend score and Wells+D-dimer (DD), PERC+DD, Geneva+DD, and YEARS+DD(YEAR algorithm).

Results: The Legend score comprised active cancer, D-dimer≥1000 ng/mL, DVT symptoms and/or signs, previous venous thromboembolism (VTE) history, and surgery, trauma, or immobilization in the past month. The sensitivity, specificity, Youden index, and area under the curve(AUC) were 0.985, 0.744, 0.729, and (0.861[0.796-0.925], P<0.001), respectively, for original Legend score, whereas were 0.982, 0.778, 0.760, and (0.871[0.823-0.920], P<0.001), respectively, for simplified Legend score. The Kappa coefficient and P value of McNemar test were 0.988 and 1.000, respectively, between the original and simplified Legend scores. In the validation group, the sensitivity, specificity, Youden index, and C-index were 0.971, 0.749, 0.720, and (0.838[0.781-0.896], P<0.001), respectively, for the original Legend score, whereas were 0.986, 0.715, 0.701, and (0.816[0.750-0.880], P = 0.001) respectively, for the simplified Legend score. The Kappa coefficient and P value of McNemar test between original Legend score and Wells+DD, PERC+DD, Geneva+DD, and YEARS+DD were (0.563, 0.001), (0.139, <0.001), (0.631, 0.006), and (0.732, 0.029), respectively. The Kappa coefficient and P value of McNemar test between simplified Legend score and aforementioned scores were (0.675, 0.009), (0.172, <0.001), (0.747, 0.001), and (0.883, 0.012), respectively.

Discussion: In view of the fact the Legend score reserves the efficient predictors and eliminates the inefficient ones in Wells, PERC, and revised Geneva scores, and incorporates D-dimer into it, a more efficient, modified, and user-friendly one has replaced the original ones.

Conclusions: The Legend score yields excellent diagnostic efficiency with good safety in the pretest prediction of acute PE prior to imaging tests. It also avoids more unnecessary imaging tests than Wells+DD, PERC+DD, Geneva+DD, or YEARS+DD.

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.