Pulmonology最新文献

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: 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.

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: 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.

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 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.

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.