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Introduction: Congenital lung anomalies (CLA) are a group of anomalies, including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestrations (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts (BC). The prevalence of these rare anomalies has risen in recent years, according to various population-based studies due to advances in fetal ultrasound technology., Method: This retrospective study examines the diagnosis of CLA, and was conducted on 72 patients between March 2014 and March 2024 at Taleghani Pediatric Hospital in Gorgan, Iran., Result: The average age was 18.8 ± 30.3 months, with the majority being boys (62.5%). Most participants had CCAM (41.7%), followed by CLE (18.1%), BPS (16.7%), pulmonary hypoplasia (9.7%), BC (8.3%), and hybrid lesion (5.6%). The majority of patients were Fars (62.5%), and the average hospitalization days was 9.4 ± 4.5 days. Cardiac anomalies were observed in 19.4% of the patients. 62 patients (86.1%) exhibited respiratory symptoms, and prenatal screening during pregnancy led to the diagnosis in 51 patients (70.8%). Most patients had left lung anomalies (43; 59.7%), and the majority (90.3%) survived. There is a statistically significant relation between needed for surgical treatment and patients' type of pulmonary lesions (p-value: 0.02). In addition, there was a significant relation between the Fars ethnicity and the presence of cardiac anomalies (p-value: 0.04)., Conclusion: Some CLAs remain undiagnosed or untreated due to the rare nature of congenital lung anomalies. Nevertheless, improvements in ultrasound and other imaging methods will make diagnosing and managing these anomalies during the prenatal period more prevalent, resulting in enhanced understanding., (© 2024. The Author(s).)

Spontaneous pneumomediastinum is an uncommon condition described in veterinary medicine with concurrent respiratory disease. It can be caused by the Macklin effect, which is when gas leaks from the alveoli into the surrounding interstitial lung tissue. Pulmonary interstitial emphysema (PIE) is the presence of gas within the pulmonary vascular sheaths and indicates the presence of the Macklin effect. In the authors' experience, spontaneous pneumomediastinum and PIE are more prevalent in sighthound dogs than in other breeds and are often considered incidental findings. This retrospective, observational, cross-sectional study compared the prevalence of PIE and subsequent pneumomediastinum in sighthound with other purebred dogs. It characterized the appearance of PIE in CT and analyzed a possible association with concomitant pulmonary pathologies or with the use of general anesthesia. Medical records and thoracic CTs of sighthounds and nonsighthound dogs from two institutions were reviewed. A total of 256 dogs, comprising 127 sighthounds and 129 other purebred dogs, were included. The prevalence of PIE and pneumomediastinum was statistically higher in sighthound (14.2%) compared with other nonsighthound dogs (2.2%). There was no statistical association between the presence of PIE and pneumomediastinum with different age and weight groups or with sex. There was no statistical difference in the prevalence of PIE and pneumomediastinum between dogs with and without pulmonary pathology or in dogs undergoing CT with sedation or general anesthesia. Spontaneous pneumomediastinum in sighthounds is more prevalent than in other breeds, and its prevalence is not associated with the presence of pulmonary pathology or the use of general anesthesia., (© 2024 American College of Veterinary Radiology.)

Purpose: We determine and compare the prevalence, subtypes, severity, and risk factors for emphysema assessed by low-dose CT(LDCT) in Chinese and Dutch general populations., Methods: This cross-sectional study included LDCT scans of 1143 participants between May and October 2017 from a Chinese Cohort study and 1200 participants with same age range and different smoking status between May and October 2019 from a Dutch population-based study. An experienced radiologist visually assessed the scans for emphysema presence (≥trace), subtype, and severity. Logistic regression analyses, overall and stratified by smoking status, were performed and adjusted for fume exposure, demographic and smoking data., Results: The Chinese population had a comparable proportion of women to the Dutch population (54.9 % vs 58.9 %), was older (61.7 ± 6.3 vs 59.8 ± 8.1), included more never smokers (66.4 % vs 38.3 %), had a higher emphysema prevalence ([58.8 % vs 39.7 %], adjusted odds ratio, aOR = 2.06, 95 %CI = 1.68-2.53), and more often had centrilobular emphysema (54.8 % vs 32.8 %, p < 0.001), but no differences in emphysema severity. After stratification, only in never smokers an increased odds of emphysema was observed in the Chinese compared to the Dutch (aOR = 2.55, 95 %CI = 1.95-3.35). Never smokers in both populations shared older age (aOR = 1.59, 95 %CI = 1.25-2.02 vs 1.26, 95 %CI = 0.97-1.64) and male sex (aOR = 1.50, 95 %CI = 1.02-2.22 vs 1.93, 95 %CI = 1.26-2.96) as risk factors for emphysema., Conclusions: Only never smokers had a higher prevalence of mainly centrilobular emphysema in the Chinese general population compared to the Dutch after adjusting for confounders, indicating that factors other than smoking, age and sex contribute to presence of CT-defined emphysema., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Patients with advanced emphysema eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV) are characterized by severe static lung hyperinflation, which can be considered a treatable trait. Other treatable traits (TTs), which are assumed to be present in this highly selected patient group, have not been studied in detail nor how they may affect health-related quality of life (HRQL)., Aims: We aimed to evaluate a spectrum of TTs in COPD patients eligible for EBV treatment and their association with HRQL., Methods: The SoLVE study (NCT03474471) was a prospective multicenter randomized controlled trial to examine the impact of pulmonary rehabilitation in COPD patients receiving EBV. The presence/absence of 16 TTs was based on pre-defined thresholds. HRQL was assessed with the St. George's Respiratory Questionnaire (SGRQ). Subjects were stratified into two groups, using the median split method, into higher or lower SGRQ total score. Logistic regression assessed the odds ratio (OR) of having a higher SGRQ total score per TT., Results: Ninety-seven subjects were included, the mean number of TTs per patient was 8.1 ± 2.5. Low physical activity (95%), poor exercise capacity (94%) and severe fatigue (75%) were the most prevalent TTs. The sum of TTs present in a subject was associated with the SGRQ total score (r = 0.53; p < 0.001). Severe fatigue, depression, and anxiety were predictors of having a higher SGRQ total score., Conclusions: A high prevalence and co-occurrence of multiple TTs were identified in emphysema patients eligible for EBV. Patients with a higher number of TTs were more likely to have worse HRQL., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA)., Methods: We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis., Results: A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65-4.76; CPFE: adjusted HR 2.01; 95% CI 1.24-3.23)., Conclusions: RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: S. Mori received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Boehringer Ingelheim Japan, and Taisho Pharma Co., Ltd. and received research funds from AbbVie GK, Asahikasei Pharma Corp, and Chugai Pharmaceutical Co., Ltd. Y. Ueki received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahikasei Pharma Corp., Astellas Pharma Inc., Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., and Takeda Pharmaceutical Co., Ltd. T. Hidaka received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahi Kasei Pharma Corp., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., and Eisai Co. K. Nakamura received honoraria for lectures from AstraZeneca K.K. The other authors had no financial relationships that could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Mori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Although pulmonary involvement due to alpha-1 antitrypsin (AAT) deficiency has been widely described, most studies focus on the genotypes causing severe deficiency (<60 mg/dL)., Objective: The aim of this study was to analyze the prevalence of the different AAT gene variants that do not cause severe deficiency in patients with pulmonary emphysema diagnosed by thoracic computed tomography (CT). Furthermore, we assessed the risk associated with a non-severe decrease in AAT values in the pathogenesis of emphysema., Methods: Case-control study design that included patients who had a CT scan available of the entire thorax. In total, 176 patients with emphysema (cases) and 100 control subjects without emphysema were analyzed., Results: The prevalence of variants was higher among cases (25.6%; 45/176) than controls (22%; 22/100), although the difference was not statistically significant (P=0.504) when analyzed globally. In the control group, all the variants detected were MS. Excluding this variant, statistically significant differences were observed in the remaining variants (MZ, SS and SZ). Only 18% of the controls (all MS) presented values below our limit of normality, and all had values very close to the reference value (90 mg/dL). In contrast, 76% of patients with the other variants presented pathological levels. In a logistic regression model, both smoking and a non-severe reduction in AAT (60 to 90 mg/dL) increased the probability of emphysema., Conclusion: Our study confirms an association between certain variants in the alpha-1 antitrypsin gene that do not cause severe deficiency and the presence of pulmonary emphysema. This association with variants that are associated with reductions in serum AAT values is statistically significant and independent of smoking habit., Competing Interests: José Luis Izquierdo received professional fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Grifols, Menarini, Novartis, Orion, Pfizer, Sandoz, Teva, and Zambon. He is also the director of the Chair of Inflammatory Diseases of the Airways, University of Alcalá, during the conduct of the study. José Miguel Rodríguez received professional fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Grifols, Menarini, Novartis, Orion, Pfizer and Teva. The authors report no other conflicts of interest in this work., (© 2024 Laviña et al.)

Introduction: The Global Initiative for Obstructive Lung Disease (GOLD) recommends lung cancer screening for patients with Chronic Obstructive Pulmonary Disease (COPD), but data is lacking regarding results of screening in this high-risk population. The main goal of the present work is to explore if lung cancer screening with Low Dose Chest Tomography (LDCT) in people with COPD, allows lung cancer (LC) diagnosis in early stages with survival compatible with curative state., Methods: This is a post hoc exploratory analysis. Pamplona International Early Lung Cancer Action Program (P-IELCAP) participants with a GOLD defined obstructive pattern (post bronchodilator FEV 1 /FVC<0.70) were selected for analysis. The characteristics of those who developed LC and their survival are described. A Cox proportional analysis explored the factors associated with LC diagnosis., Results: Eight hundred and sixty-five patients (77% male, 93% in spirometric GOLD stage 1+2) were followed for 102±63 months. LC prevalence was 2.6% at baseline, with an annual LC diagnosis rate of 0.68%. Early-stage tumors predominated (74%) with a median survival (25-75th percentiles) of 139 (76-185) months. Cumulative tobacco exposure, FEV 1 %, and emphysema were the main predictors of an LC diagnosis. Eight (11%) patients with COPD had a second LC, most of them in early stage (92%), and 6 (8%) had recurrence. Median survival (25-75th percentiles) in these patients was 168 (108-191) months., Conclusions: Lung cancer screening of selected high-risk participants with COPD allowed the LC diagnosis in early stages with survival compatible with curative state., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To explore whether small airway disease and emphysema were affected by the interaction between smoking and aging on chest computed tomography (CT) images of asymptomatic healthy men analysed using a quantitative imaging tool parametric response mapping (PRM)., Materials and Methods: In this retrospective study, 95 asymptomatic healthy men underwent biphasic chest CT. The PRM classifies lung as a percentage of normal (PRM Normal %), functional small airway disease (PRM fSAD %), and emphysema (PRM Emph %). The patients were divided into groups based on their age and smoking status. Multiple linear regression analysis was applied to explore the factors influencing lung injury. Simple effects analysis was performed to explore the interaction between different age groups and smoking status., Results: The interaction between aging and smoking significantly affected PRM fSAD % and PRM Emph % (p<0.001). The age range 60-69 and smoking were associated with increased PRM fSAD % and PRM Emph % (p<0.05). Futher stratification into different age subgroups showed that smoking was associated with increased PRM fSAD % and PRM Emph % in the 50-59 year age group. Besides, smoking in the 50-59 and 60-69 years group was associated with decreased PRM Normal %, while smoking in the 60-69 years group did not significantly influence the prevalence of PRM fSAD % and PRM Emph % (p>0.05)., Conclusions: PRM reveals the interplay between smoking and aging in the development of lung injury in asymptomatic healthy men. Aging and smoking are important factors of emphysema and small airway disease in the 50-69 years group. In the 60-69 years group, aging poses a greater risk of lung injury compared to smoking., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality., Methods: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography-mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini-Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst., Results: We found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways., Conclusions: Metabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers., (© 2023. The Author(s).)

While variation in emphysema severity between patients with chronic obstructive pulmonary disease (COPD) is well-recognized, clinically applicable definitions of the emphysema-predominant disease (EPD) and non-emphysema-predominant disease (NEPD) subtypes have not been established. To study the clinical relevance of the EPD and NEPD subtypes, we tested the association of these subtypes with prospective decline in forced expiratory volume in 1 second (FEV1) and mortality among 3,427 subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grade 2-4 COPD at baseline in the Genetic Epidemiology of COPD (COPDGene) Study, an ongoing national multicenter study that started in 2007. NEPD was defined as airflow obstruction with less than 5% computed tomography (CT) quantitative densitometric emphysema at -950 Hounsfield units, and EPD was defined as airflow obstruction with 10% or greater CT emphysema. Mixed-effects models for FEV1 demonstrated larger average annual FEV1 loss in EPD subjects than in NEPD subjects (-10.2 mL/year; P < 0.001), and subtype-specific associations with FEV1 decline were identified. Cox proportional hazards models showed higher risk of mortality among EPD patients versus NEPD patients (hazard ratio = 1.46, 95% confidence interval: 1.34, 1.60; P < 0.001). To determine whether the NEPD/EPD dichotomy is captured by previously described COPDGene subtypes, we used logistic regression and receiver operating characteristic (ROC) curve analysis to predict NEPD/EPD membership using these previous subtype definitions. The analysis generally showed excellent discrimination, with areas under the ROC curve greater than 0.9. The NEPD and EPD COPD subtypes capture important aspects of COPD heterogeneity and are associated with different rates of disease progression and mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Since early in the HIV epidemic, emphysema has been identified among people with HIV (PWH) and has been associated with increased mortality. Smoking cessation is key to risk reduction. Health maintenance for PWH and emphysema should ensure appropriate vaccination and lung cancer screening. Treatment should adhere to inhaler guidelines for the general population, but inhaled corticosteroid (ICS) should be used with caution. Frontiers in treatment include targeted therapeutics. Major knowledge gaps exist in the epidemiology of and optimal care for PWH and emphysema, particularly in low and middle-income countries (LMIC)., Areas Covered: Topics addressed include risk factors, pathogenesis, current treatment and prevention strategies, and frontiers in research., Expert Opinion: There are limited data on the epidemiology of emphysema in LMIC, where more than 90% of deaths from COPD occur and where the morbidity of HIV is most heavily concentrated. The population of PWH is aging, and age-related co-morbidities such as emphysema will only increase in salience. Over the next 5 years, the authors anticipate novel trials of targeted therapy for emphysema specific to PWH, and we anticipate a growing body of evidence to inform optimal clinical care for lung health among PWH in LMIC.

Background and Aim: Pulmonary hypertension (PH) is a common complication of combined pulmonary fibrosis and emphysema (CPFE). Whether the incidence of PH is increased in CPFE compared with pure pulmonary fibrosis or emphysema remains unclear. This meta-analysis aimed to evaluate the risk of PH in patients with CPFE compared to those with IPF or COPD/emphysema., Methods: We searched the PubMed, Embase, Cochrane Library, and CNKI databases for relevant studies focusing on the incidence of PH in patients with CPFE and IPF or emphysema. Pooled odds ratios (ORs) and standard mean differences (SMD) with 95% confidence intervals (95% CIs) were used to evaluate the differences in the clinical characteristics presence and severity of PH between patients with CPFE, IPF, or emphysema. The survival impact of PH in patients with CPFE was assessed using hazard ratios (HRs)., Results: A total of 13 eligible studies were included in the meta-analysis, involving 560, 720, and 316 patients with CPFE, IPF, and emphysema, respectively. Patients with CPFE had an increased PH risk with a higher frequency of pulmonary hypertension and higher estimated systolic pulmonary artery pressure (esPAP), compared with those with IPF (OR: 2.66; 95% CI: 1.55-4.57; P < 0.01; SMD: 0.86; 95% CI: 0.52-1.19; P < 0.01) or emphysema (OR: 3.19; 95% CI: 1.42-7.14; P < 0.01; SMD: 0.73; 95% CI: 0.50-0.96; P < 0.01). In addition, the patients with CPFE combined with PH had a poor prognosis than patients with CPFE without PH (HR: 6.16; 95% CI: 2.53-15.03; P < 0.01)., Conclusions: Our meta-analysis showed that patients with CPFE were associated with a significantly higher risk of PH compared with those with IPF or emphysema alone. The presence of PH was a poor predictor of mortality., (© 2023. The Author(s).)

Background: Although the endobronchial valves (EBV) were successfully developed as treatment for severe emphysema, its main complication, pneumothorax, remained an important concern., Objective: To assess whether the placement of Zephyr© endobronchial valves throughout 2 procedures instead of 1 minor the frequency of pneumothorax without lowering the benefits of such treatment., Methods: This retrospective study was conducted in 15 pulmonology department in France. All the patients met the inclusion criteria of the recommendation set by the expert panel on the Endoscopic Lung Volume Reduction (ELVR) updated in 2019. As recommended, all the scan were analyzed with the StratX© (PulmonX Corporation, Redwood city, CA) protocol, and completed by a Chartis© (PulmonX Corporation, Redwood city, CA) in case of questionable fissure. During the first procedure, all but the most proximal sub-segment of the targeted lobe were occluded. One month after, EBV were placed in the bronchus of the last subsegment. All patients were evaluated before and 3 months after the second procedure., Results: Between March 2019 and December 2020, 96 patients received EBV treatment. 12 patients (12.5%) presented a pneumothorax (3 after the 1st step and 9 after the 2nd procedure). Beside pneumothorax, the main adverse event was exacerbation (10.4%) and pneumonia (4.1%). No death were reported. Significant improvement were found for FEV1 (14.6 ± 25.3%), RV (- 0.69 ± 2.1 L), 6MWT (34.8 ± 45.9 m), BODE Score (-1.41 ± 1.41pts), and mMRC scale (-0.85 ± 0.7pts). These results are compared not only to the results previously published using the usual approach but also to our previous publication evaluating the 2-step approach. Some patients presented authentic segmental atelectasis despite infralobar treatment., Conclusion: Placing EBV during 2 procedures instead of one led to a significant decrease of post treatment pneumothoraces without increasing the rate of other complications. It does not seem to alter the benefits of such therapy for severe emphysema. These results must be confirmed by launching a multicenter, prospective, randomized, controlled study to compare the frequency of pneumothorax and the efficacy of this new approach with the usual one-time procedure., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: COPD patients living in Tibet are exposed to specific environments and different risk factors and probably have different characteristics of COPD from those living in flatlands. We aimed to describe the distinction between stable COPD patients permanently residing at the Tibet plateau and those in flatlands., Methods: We conducted an observational cross-sectional study that enrolled stable COPD patients from Tibet Autonomous Region People's Hospital (Plateau Group) and Peking University Third Hospital (Flatland Group), respectively. Their demographic information, clinical features, spirometry test, blood routine and high-resolution chest CT were collected and evaluated., Results: A total of 182 stable COPD patients (82 from plateau and 100 from flatland) were consecutively enrolled. Compared to those in flatlands, patients in plateau had a higher proportion of females, more biomass fuel use and less tobacco exposure. CAT score and frequency of exacerbation in the past year were higher in plateau patients. The blood eosinophil count was lower in plateau patients, with fewer patients having an eosinophil count ≥300/μL. On CT examination, the proportions of previous pulmonary tuberculosis and bronchiectasis were higher in plateau patients, but emphysema was less common and milder. The ratio of diameters of pulmonary artery to aorta ≥1 was more often in plateau patients., Conclusion: Patients with COPD living at Tibet Plateau had a heavier respiratory burden, lower blood eosinophil count, less emphysema but more bronchiectasis and pulmonary hypertension. Biomass exposure and previous tuberculosis were more common in these patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Jiang et al.)

Background: Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population., Methods: We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB., Results: NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p<0.05), but there was no significant difference in lung function. Never-smokers with NOCB had higher rates of emphysema than those without NOCB, but airway resistance was similar. Ever-smokers with NOCB had greater airway resistance than those without NOCB, but emphysema rates were similar. During 1-year follow-up, participants with NOCB had a significantly increased risk of acute respiratory events compared with participants who did not have NOCB, after adjustment for confounders (risk ratio 2.10, 95% CI 1.32 to 3.33; p=0.002). These results were robust in never-smokers and ever-smokers., Conclusions: Never-smokers and ever-smokers with NOCB had more chronic obstructive pulmonary disease-related risk factors, evidence of airway disease and greater risk of acute respiratory events than those without NOCB. Our findings support expanding the criteria defining pre-COPD to include NOCB., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lung cancer is one of the primary causes of death with poor life expectancy after diagnosis. History of past respiratory diseases such as asthma, chronic obstructive lung disease (COPD), emphysema, and chronic bronchitis can increase the risk of lung cancer. Very few studies are available to simultaneously assess multiple respiratory diseases and lung cancer. The objective of this study was to investigate correlations between asthma, emphysema, chronic bronchitis, and chronic obstructive lung disease with lung cancer in the US adult population. This was a cross-sectional study using data from a total of 23,523 adult participants from the National Health Examination and Nutrition Survey (NHANES) datasets for seven cycles ranging from 2003-2004 to 2015-2016. To analyze the data, specialized weighted complex survey logit regressions were conducted. Linear logit regression models using only main-effects were constructed first to assess the correlation between the selected demographic and lifestyle variables and asthma, emphysema, chronic bronchitis, and COPD. A second set of linear, main-effects logit regression models were constructed to examine the correlation between lung cancer and asthma, emphysema, chronic bronchitis, COPD when corrected for the selected covariates. The study identified positive correlations between emphysema, chronic bronchitis, COPD, and lung cancer. No correlation between asthma and lung cancer was established. Of the covariates studied, race/ethnicity, marital status, highest educational level, age, family income to poverty ratio, and lifetime smoking were also found to be correlated with the presence of lung cancer. Correlations between the covariates gender, body mass index, alcohol consumption, and country of birth and lung cancer were not found. The study established statistically significant correlations between lung cancer and the lung diseases emphysema, chronic bronchitis, and COPD. The lack of association between asthma and lung cancer may arise from the timeline of diagnosis asthma or type of lung cancer. The study also established significant correlations between lung cancer and several of the covariates included in the analysis. It also established correlations between the covariates and the lung diseases asthma, emphysema, chronic bronchitis, and COPD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To estimate the prevalence of treatments used for the management of chronic obstructive pulmonary disease (COPD) in the Brazilian adult population., Methods: A population-based cross-sectional study with data from the 2013 Brazilian National Survey of Health, including individuals aged 40 years or older, with a self-reported medical diagnosis of COPD, chronic bronchitis and/or emphysema, who were asked about treatments used for disease management., Results: A total of 60,202 adults were interviewed, of which 636 were 40 years of age or older and had reported a medical diagnosis of COPD, emphysema, or chronic bronchitis. Less than half (49.4%) of the diagnosed population reported using some type of treatment, with differences regarding the macro-region of the country (South 53.8% - Northeast 41.2%, p = 0.007). Pharmacological treatment was the most reported, and emphysema patients had the highest proportion of those undergoing more than one type of treatment. Among the individuals who reported having only chronic bronchitis, 55.1% (95%CI: 48.7-61.4) used medication, 4.7% (95%CI: 2.6-8.3) underwent physical therapy, and 6.0% (95%CI: 3.6-9.9) oxygen therapy. On the other hand, among the emphysema patients, 44.1% (95%CI: 36.8-51.7) underwent drug treatment, 8.8% (95%CI: 5.4-14.2) physical therapy, and 10.0% (95%CI: 6.3-15.6) oxygen therapy., Conclusion: The prevalence of treatments for COPD management was below ideal in 2013. The pharmacological treatment was the main type of treatment, followed by oxygen therapy and physical therapy.

Background: Physiological and prognostic associations of centrilobular emphysema (CLE) and paraseptal emphysema (PSE) in smokers with and without chronic obstructive pulmonary disease (COPD) have been increasingly recognized, but the associations with extrapulmonary abnormalities, such as muscle wasting, osteoporosis, and cardiovascular diseases, remain unestablished., Objectives: The aim of the study was to investigate whether CLE was associated with extrapulmonary abnormalities independent of concomitant PSE in smokers without airflow limitation., Methods: This retrospective study consecutively enrolled current smokers without airflow limitation who underwent lung cancer screening with computed tomography and spirometry. CLE and PSE were visually identified based on the Fleischner Society classification system. Cross-sectional areas of pectoralis muscles (PM) and adjacent subcutaneous adipose tissue (SAT), bone mineral density (BMD), and coronary artery calcification (CAC) were evaluated., Results: Of 310 current smokers without airflow limitation, 83 (26.8%) had CLE. The PSE prevalence was higher (67.5% vs. 23.3%), and PM area, SAT area, and BMD were lower in smokers with CLE than in those without (PM area (mean), 34.5 versus 38.6 cm2; SAT area (mean), 29.3 versus 36.8 cm2; BMD (mean), 158.3 versus 178.4 Hounsfield unit), while CAC presence did not differ. In multivariable models, CLE was associated with lower PM area but not with SAT area or BMD, after adjusting for PSE presence, demographics, and forced expiratory volume in 1 s., Conclusions: The observed association between CLE and lower PM area suggests that susceptibility to skeletal muscle loss could be high in smokers with CLE even without COPD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history., Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022., Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%)., Conclusions: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www., Clinicaltrials: gov (ID: NCT04180319)., (© 2022. The Author(s).)

Objectives: This study aimed to evaluate the association between visual emphysema and the presence of lung nodules, and Lung-RADS category with low-dose CT (LDCT)., Methods: Baseline LDCT scans of 1162 participants from a lung cancer screening study (Nelcin-B3) performed in a Chinese general population were included. The presence, subtypes, and severity of emphysema (at least trace) were visually assessed by one radiologist. The presence, size, and classification of non-calcified lung nodules (≥ 30 mm 3 ) and Lung-RADS category were independently assessed by another two radiologists. Multivariable logistic regression and stratified analyses were performed to estimate the association between emphysema and lung nodules, Lung-RADS category, after adjusting for age, sex, BMI, smoking status, pack-years, and passive smoking., Results: Emphysema and lung nodules were observed in 674 (58.0%) and 424 (36.5%) participants, respectively. Participants with emphysema had a 71% increased risk of having lung nodules (adjusted odds ratios, aOR: 1.71, 95% CI: 1.26-2.31) and 70% increased risk of positive Lung-RADS category (aOR: 1.70, 95% CI: 1.09-2.66) than those without emphysema. Participants with paraseptal emphysema (n = 47, 4.0%) were at a higher risk for lung nodules than those with centrilobular emphysema (CLE) (aOR: 2.43, 95% CI: 1.32-4.50 and aOR: 1.60, 95% CI: 1.23-2.09, respectively). Only CLE was associated with positive Lung-RADS category (p = 0.02). CLE severity was related to a higher risk of lung nodules (ranges aOR: 1.44-2.61, overall p < 0.01)., Conclusion: In a Chinese general population, visual emphysema based on LDCT is independently related to the presence of lung nodules (≥ 30 mm 3 ) and specifically CLE subtype is related to positive Lung-RADS category. The risk of lung nodules increases with CLE severity., Key Points: • Participants with emphysema had an increased risk of having lung nodules, especially smokers. • Participants with PSE were at a higher risk for lung nodules than those with CLE, but nodules in participants with CLE had a higher risk of positive Lung-RADS category. • The risk of lung nodules increases with CLE severity., (© 2022. The Author(s).)

Background: There is no universally accepted criterion for assessing exercise-induced desaturation (EID). The purpose of this study is to compare the two methods regularly used for determining EID in COPD patients, as well as to explore the risk factors and predictors related to EID., Methods: The 6MWT was performed with continuous SpO 2 monitoring on patients with stable COPD. Using two methods (method A: "SpO 2rest -SpO 2min  ≥ 4% and/or SpO 2min  < 90%", method B: "SpO 2rest -SpO 2end  ≥ 4% and/or SpO 2end  < 90%") as EID determination criteria to assess the incidence of EID. The differences and consistency of the two methods are compared. Moreover, we collected data through the pulmonary function test, mMRC dyspnea score, COPD assessment test, BODE index and CT-defined emphysema. Univariate and multivariate logistic regression analyses were used to identify factors affecting the EID. For the parameters that predict EID in 6MWT, a receiver operating characteristic (ROC) curve analysis was employed., Results: The analysis included 124 patients. The overall incidence of EID was 62.1% by using method A as the criterion and 51.6% by method B. All of the EID patients found by method B were included in the EID patients identified by method A, as well as 13 new-EID patients. The difference in diagnostic outcomes between the two approaches was not statistically significant (P > 0.05), but they were in excellent agreement (Kappa = 0.807, P = 0.001). Logistic regression analyses found that D L CO SB% pred, D L CO/VA% pred, CAT score, mean density, PD15, emphysema volume and %LAA were significant determinants of the EID. For predicting EID, the ROC analysis produced AUC and cutoffs of 0.689 and 50.45% (D L CO SB% pred), 0.707 and 75.0% (D L CO/VA% pred), 0.727 and 15 points (CAT score), 0.691 and - 955.00HU (PD15), 0.671 and - 856.46HU (mean density), 0.668 and 338.14 ml (emphysema volume) and 0.656 and 7.63% (%LAA), respectively., Conclusions: Two methods evaluating EID in this research are in a good agreement, method A can find more EID patients by focusing on SpO 2min. When conditions are constrained, it is also sufficient to assess EID in COPD patients by method B. In terms of the predictors of EID, D L CO SB% pred, D L CO/VA% pred, CAT score and CT-defined emphysema are all statistically significant test variables to determine EID., (© 2022. The Author(s).)

Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits., Methods: A longitudinal study of PiZZ individuals (n=1595) from the Swedish National AATD Register, and controls (n=5999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within 5 years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analysed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease., Results: The median follow-up time was 17 years (interquartile range 11 years) for the whole study population. The incidence rates of hepatic and non-hepatic cancer per 1000 person-years were 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0), respectively, for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1), respectively, for the controls. The adjusted hazard ratios for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5), respectively, in the PiZZ individuals compared with the controls., Conclusion: These results suggest that individuals with severe AATD may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population., Competing Interests: Conflict of interest: A. Lindberg reports lecture honoraria from Boehringer Ingelheim and Novartis; personal fees for advisory board participation with AstraZeneca, GlaxoSmithKline, Novartis and Boehringer Ingelheim; outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Pulmonary emphysema and liver disease are the clinical expressions of alpha 1-antitrypsin deficiency, an autosomal recessive genetic disease., State of the Art: Alpha 1-antitrypsin deficiency is usually associated with the homozygous Z variant of the SERPINA1 gene. Its clinical expression always consists in a substantial reduction of alpha 1-antitrypsin serum concentration and its variants are analyzed by isoelectric focalization or molecular techniques. Assessed by CO transfer alteration and CT scan, risk of pulmonary emphysema is increased by tobacco consumption. Assessed by transient elastography and liver ultrasound, risk of liver disease is increased by alcohol consumption or obesity. Treatment of COPD-associated alpha 1-antitrypsin deficiency does not differ from that of other forms of COPD. In patients presenting with severe deficiency, augmentation therapy with plasma-derived alpha 1-antitrypsin reduces the progression of emphysema, as shown in terms of CT-based lung density metrics. Patients with alpha 1-antitrypsin deficiency with a ZZ genotype should refrain from alcohol or tobacco consumption, and watch their weight; so should their close relatives., Perspectives: Modulation of alpha 1-antitrypsin liver production offers an interesting new therapeutic perspective., Conclusion: Homozygous (Z) variants of the SERPINA1 gene confer an increased risk of pulmonary emphysema and liver disease, particularly among smokers, drinkers and obese persons., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Unlike the well-documented effects of tobacco smoke on the lung, the effects of cannabis smoke remain controversial, the main bias consisting in co-consumption of tobacco. That said, the composition of joint smoke is close to that of cigarettes, containing many compounds that are carcinogenic and/or alter the respiratory epithelium. Confirmed respiratory effects in chronic cannabis smokers include aggravated chronic bronchitis symptoms, a cumulative effect with tobacco on COPD and emphysema occurrence, an increased risk of bullous emphysema, and pneumothorax with heightened risk of recurrence after pleural symphysis. Recent prospective studies have shown a negative impact on lung function, with not only damage to the airways, but also DLCO alteration and an accelerated drop in FEV1. Finally, cannabis smoking is very common among young patients with lung cancer. Its consumption could lead to a different lung cancer profile, potentially more undifferentiated and less accessible to targeted therapy. Questioning about cannabis consumption must be systematic and targeted medical care should be offered., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Recently, it has been shown and validated that presence and severity of emphysema on computed tomography could be estimated by a novel spirometry based index, the emphysema severity index (ESI). However, the clinical relevance of the index has not been established. We conducted cox-regression analyses with adjustment for age, smoking, sex, forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) to study whether ESI was associated with all-cause, respiratory and non-respiratory 10-year mortality. Study population was all participants with acceptable spirometry from the Gott Åldrande i Skåne study, a Swedish general population aged 65-102 years old. ESI is expressed as a continuous numeric parameter on a scale ranging from 0 to 10. Out of the 4453 participants in the main study, 3974 was included in the final analysis. Higher age, higher ESI, lower FEV 1 and male sex increased hazard of respiratory death. ESI was significantly correlated to respiratory death but not non-respiratory death, while high age, male sex and low FEV 1 was associated with non-respiratory as well as respiratory death. Current smoking habits increased the hazard of respiratory death but did not reach significance (p 0.066) One unit increase in ESI increased hazard of all-cause death by 20% (p 0.0002) and hazard of respiratory death by 57% (p < 0.0001). The ESI is a novel clinical marker of emphysema severity that is associated with respiratory death specifically. Since it can be derived from standard spirometry there are potential benefits for clinical practice in terms of more individualised prognosis and treatment alternatives., Competing Interests: Declaration of competing interest Dr. Occhipinti reports grants from Fondazione Menarini, personal fees from Novartis, outside the submitted work; Dr. Wollmer reports grants from Swedish Heart and Lung Foundation, grants from Lund University, grants from Skåne Region, during the conduct of the study; personal fees from Chiesi Pharma, outside the submitted work; In addition, Dr. Wollmer has a patent Device and method for pulmonary function measurement issued.. Dr. Luoto reports grants from Skåne County, during the conduct of the study., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Computed tomography (CT) imaging complements spirometry and may provide insight into racial disparities in respiratory health., Objective: To determine the difference in emphysema prevalence between Black and White adults with different measures of normal spirometry results., Design: Observational study using clinical data and spirometry from the CARDIA (Coronary Artery Risk Development in Young Adults) study obtained in 2015 to 2016 and CT scans done in 2010 to 2011., Setting: 4 U.S. centers., Participants: Population-based sample of Black and White adults., Measurements: Self-identified race and visually identified emphysema on CT in participants with different measures of "normal" spirometry results, calculated using standard race-specific and race-neutral reference equations., Results: A total of 2674 participants (485 Black men, 762 Black women, 659 White men, and 768 White women) had both a CT scan and spirometry available for analysis. Among participants with a race-specific FEV 1 between 80% and 99% of predicted, 6.5% had emphysema. In this group, emphysema prevalence was 3.9-fold (95% CI, 2.1- to 7.1-fold; 15.5% vs. 4.0%) higher among Black men than White men and 1.9-fold (CI, 1.0- to 3.8-fold; 6.6% vs. 3.4%) higher among Black women than White women. Among participants with a race-specific FEV 1 between 100% and 120% of predicted, 4.0% had emphysema. In this category, Black men had a 6.4-fold (CI, 2.2- to 18.7-fold; 13.9% vs. 2.2%) higher prevalence of emphysema than White men, whereas Black and White women had a similar prevalence of emphysema (2.6% and 2.0%, respectively). The use of race-neutral equations to identify participants with an FEV 1 percent predicted between 80% and 120% attenuated racial differences in emphysema prevalence among men and eliminated racial differences among women., Limitation: No CT scans were obtained during the most recent study visit (2015 to 2016) when spirometry was done., Conclusion: Emphysema is often present before spirometry findings become abnormal, particularly among Black men. Reliance on spirometry alone to differentiate lung health from lung disease may result in the underrecognition of impaired respiratory health and exacerbate racial disparities., Primary Funding Source: National Institutes of Health.

Purpose: Metal and chemical exposure can cause acute and chronic respiratory diseases in humans. The purpose of this analysis was to analyze 14 types of urinary metals including mercury, uranium, tin, lead, antimony, barium, cadmium, cobalt, cesium, molybdenum, manganese, strontium, thallium, tungsten, six types of speciated arsenic, total arsenic and seven forms of polycyclic aromatic hydrocarbons (PAHs), and the link with self-reported emphysema in the US adult population., Methods: A cross-sectional analysis using the 2011-2012, 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey datasets was conducted. A specialized weighted complex survey design analysis package was used in analyzing the data. Multivariate logistic regression models were used to assess the association between urinary metals, arsenic, and PAHs and self-reported emphysema among all participants and among non-smokers only. Models were adjusted for lifestyle and demographic factors., Results: A total of 4,181 adults were analyzed. 1-Hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxypyrene, and 2 & 3-hydroxyphenanthrene were positively associated with self-reported emphysema. Positive associations were also observed in cadmium and cesium with self-reported emphysema. Among non-smokers, quantiles among 2-hydroxynaphthalene, arsenocholine, total urinary arsenic, cesium, and tin were associated with increased odds of self-reported emphysema. Quantiles among 1-hydroxyphenanthrene, cadmium, manganese, lead, antimony, thallium, and tungsten were associated with an inverse relationship with self-reported emphysema in non-smokers., Conclusion: The study determined that six types of urinary PAHs, cadmium, and cesium are positively associated with self-reported emphysema. Certain quantiles of 2-hydroxynaphthalene, arsenocholine, total urinary arsenic, cesium, and tin are positively associated with self-reported emphysema among non-smokers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic obstructive pulmonary disease (COPD) is a major comorbid disease of Mycobacterium avium complex pulmonary disease (MAC-PD). Emphysema is one of the main pathological findings in COPD, a risk factor for chronic pulmonary aspergillosis (CPA), and is associated with poor prognosis. We aimed to clarify the effect of emphysema on mortality in MAC-PD., Methods: We retrospectively analyzed 203 patients with MAC-PD at The Jikei Daisan Hospital between January 2014 and December 2018. We investigated the mortality and CPA development rates after MAC-PD diagnosis in patients with or without emphysema., Results: Multivariate Cox proportional hazards regression analysis showed the following negative prognostic factors in patients with MAC-PD: emphysema (hazard ratio [HR]: 11.46; 95% confidence interval [CI]: 1.30-100.90; P = 0.028); cavities (HR: 3.12; 95% CI: 1.22-7.94; P = 0.017); and low body mass index (<18.5 kg/m 2 ) (HR: 4.62; 95% CI: 1.63-13.11; P = 0.004). The mortality and occurrence of CPA were higher in MAC-PD patients with than without emphysema (log-rank test, P < 0.0001 and P < 0.0001)., Conclusion: Our study findings showed that emphysema detected by computed tomography was associated with an increased risk of CPA development and mortality in MAC-PD., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy., Objectives: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy., Method: 238 subjects were submitted to molecular analysis of the SERPINA1 gene, and data on anthropometric variables, smoking habits, number of packs per year, AAT serum concentration, and clinical manifestations were recorded and presented as mean ± SD or median values (1st quartile; 3rd quartile)., Results: The results show a distribution of genetic AATD of 4.1% of the screened population in the area encompassing the city of Parma. PI*MS and PI*MZ were the most common genotypes at 40.9% and 28.2% of the population with genetic AATD, and asthma and emphysema were the most represented clinical manifestations., Conclusion: Our study allowed to increase the knowledge of the distribution of genetic AATD in Northern Italy providing information regarding frequencies of genotypes and clinical manifestations of the disorder., (© 2022 S. Karger AG, Basel.)

Background: Small Airways Disease (SAD) is a recognised part of the pathology in Chronic Obstructive Pulmonary Disease (COPD) and contributes to the symptom burden in the disease. Upper airway symptoms in COPD is an emerging field of study, and in this study, we sought to examine the co-existence of SAD and upper airways symptoms in a cohort of COPD patients METHODS: We investigated a cohort of patients with COPD for the presence of SAD with three different modalities. We performed High-Resolution CT (HRCT) with Parametric Response Mapping (PRM) analysis and recorded distribution of emphysema (PRM Emph ) and functional Small Airways Disease (PRM fSAD ). We measured central and peripheral lung resistance using Impulse Oscillometry (IOS) and recorded R5Hz, R20Hz, R5-R20Hz, X5, Fres and Ax. Static lung function parameters were obtained using Body Plethysmography. Data on upper and lower airway symptoms were evaluated using the Upper Airway subdomain of the 22 items Sino Nasal Outcome Test (SNOT22 nasal ) and the COPD Assessment Test (CAT), respectively., Findings: We recruited a total of 112 patients. (female sex: 58%, Age 68 (±8) years, FEV1%predicted: 53% (±16%), GOLD stage: A: 23%, B: 55%, C:1% D: 21%). Forty-five (40%) were classified as having high upper airway symptoms (UAS), defined as SNOT22 nasal ≥6. Eighty-seven per cent showed signs of SAD using IOS (R5-R20Hz > 0.07 kPa/L/s). No significant differences were found between UAS groups in IOS, PRM or Body Plethysmography parameters., Conclusion: In patients with COPD, the prevalence of small airways disease was very high, but no association between upper airway symptoms and small airways disease was demonstrated., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the clinical management of patients with combined pulmonary fibrosis and emphysema (CPFE), early recognition and appropriate treatment is essential. This study was designed to develop an accurate prognostic nomogram model to predict the presence of CPFE., Methods: We retrospectively enrolled 85 patients with CPFE and 128 patients with idiopathic pulmonary fibrosis (IPF) between January 2015 and January 2020. Clinical characteristics were compared between groups. A multivariable logistic regression analysis was performed to identify risk factors for CPFE. Then, and a nomogram to predict the presence of CPFE was constructed for clinical use. Concordance index (C-index), area under the receiver operating characteristic curve (AUC), and calibration plot was used to evaluate the efficiency of the nomogram., Results: Compared to the IPF group, the proportion of patients with male, smoking and allergies were significantly higher in the CPFE group. In terms of pulmonary function tests, patients with CPFE had lower FEV1/FVC%, DLCO/VA% pred, and higher RV, RV%pred, VC, VC%pred, TLC%pred, VA, TLC, TLC%pred, FVC, FVC%pred and FEV1 with significant difference than the other group. Positive correlation was found between DLCO and VA%, RV%, TLC% in patients with IPF but not in patients with CPFE. By multivariate analysis, male, smoking, allergies, FEV1/FVC% and DLCO/VA%pred were identified as independent predictors of the presence of CPFE. The nomogram was then developed using these five variables. After 1000 internal validations of bootstrap resampling, the C-index of the nomogram was 0.863 (95% CI 0.795-0.931) and the AUC was 0.839 (95% CI 0.764-0.913). Moreover, the calibration plot showed good concordance of incidence of CPFE between nomogram prediction and actual observation (Hosmer-Lemeshow test: P = 0.307)., Conclusions: Patients of CPFE have a characteristic lung function profile including relatively preserved lung volumes and ventilating function, contrasting with a disproportionate reduction of carbon monoxide transfer. By incorporating clinical risk factors, we created a nomogram to predict the presence of CPFE, which may serve as a potential tool to guide personalized treatment., (© 2021. The Author(s).)

Background: Patients with chronic obstructive pulmonary disease (COPD) commonly have comorbidities which may impact both symptoms and prognosis. Endoscopic lung volume reduction (ELVR) with endobronchial valves (EBV) is an innovative, effective and safe treatment for patients with severe emphysema who remain symptomatic despite optimal medical therapy., Objectives: To evaluate medical comorbidities associated with increased risk of complications after EBV procedure., Method: This was a retrospective cohort review of patients with severe, heterogeneous emphysema who underwent Zephyr® EBV installation for ELVR. Demographics, baseline comorbidities, dyspnea scores, data regarding procedure, pulmonary function test, minimal clinically important difference and post-EBV complications were recorded., Results: Of a total 82 participants, 24 were identified as having a post procedure complication. There was a significant difference in the incidence of type 2 diabetes mellitus (T2DM) at baseline (25%) in complication group compared with non-complication group (5.1%) (p value = 0.01). There was also a significant difference between baseline coronary artery disease (CAD) in those with (58.3%) or without (29.3%) complication (p = 0.01). Multivariate analysis of other covariables, identified associations of both CAD and T2DM with a heightened risk of complication (adjusted OR 4.19 CI: 1.23-14.2, p value = 0.02 and adjusted OR of 6.1 CI: 1.3-26.1, p value = 0.02 respectively)., Conclusions: Our study found that patients with severe, heterogeneous emphysema who undergo ELVR utilizing Zephyr® EBV and suffer complications during post-procedure period are more likely to have CAD or T2DM as baseline comorbidity. These data suggest that baseline CAD and T2DM might be predictive of increased risk of complications following ELVR with EBV., (© 2021 John Wiley & Sons Ltd.)

Purpose: Chronic Obstructive Pulmonary Disease (COPD) includes chronic bronchitis, small airways disease, and emphysema. Diagnosis of COPD requires spirometric evidence and may be normal even when small airways disease or emphysema is present. Emphysema increases the risk of exacerbations, and is associated with all-cause mortality and increased risk of lung cancer. We evaluated the prevalence of emphysema in participants with and without a prior history of COPD., Methods: We reviewed a prospective cohort of 52,726 subjects who underwent baseline low dose CT screening for lung cancer from 2003 to 2016 in the International Early Lung Cancer Action Program., Results: Of 52,726 participants, 23.8%(12,542) had CT evidence of emphysema. Of these 12,542 participants with emphysema, 76.5%(9595/12,542) had no prior COPD diagnosis even though 23.6% (2258/9595) had moderate or severe emphysema. Among 12,542 participants, significant predictors of no prior COPD diagnosis were: male (OR = 1.47, p < 0.0001), younger age (OR age10  = 0.72, p < 0.0001), lower pack-years of smoking (OR 10pack-years  = 0.90, p < 0.0001), completed college or higher (OR = 1.54, p < 0.0001), no family history of lung cancer (OR = 1.12, p = 0.04), no self-reported cardiac disease (OR = 0.76, p = 0.0003) or hypertension (OR = 0.74, p < 0.0001). The severity of emphysema was significantly lower among the 9595 participants with no prior COPD diagnosis, the OR for moderate emphysema was OR moderate  = 0.58(p = 0.0007) and for severe emphysema, it was OR severe  = 0.23(p < 0.0001)., Conclusion: Emphysema was identified in 23.8% participants undergoing LDCT and was unsuspected in 76.5%. LDCT provides an opportunity to identify emphysema, and recommend smoking cessation., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Despite significant advances in surgical techniques, including thoracoscopic approaches and perioperative care, the morbidity rate remains high after lung resection. This study focused on a low attenuation cluster analysis, which represented the size distribution of pulmonary emphysema and assessed its utility for predicting postoperative pulmonary complications after thoracoscopic lobectomy., Methods: From April 2013 to September 2018, lung cancer patients who received spirometry and computed tomography (CT) before surgery and underwent thoracoscopic lobectomy were included. The cumulative size distribution of the low attenuation area (LAA, defined as ≤-950 Hounsfield unit on CT) clusters followed a power-law characterized by an exponent D-value, a measure of the complexity of the alveolar structure. D-value and LAA% (LAA/total lung volume) were calculated using preoperative 3-dimensional CT software. The relationship between pulmonary complications and patient characteristics, including D-value and LAA%, was investigated., Results: Among 471 patients, there were 61 respiratory complication cases (12.9%). Receiver operation characteristic curve analysis revealed that the best predictive cut-off value of D-value and LAA% for pulmonary complications was 2.27 and 16.5, respectively, with an area under the curve of 0.72 and 0.58, respectively. D-value was significantly correlated with % forced expiratory volume in 1 s. Per univariate analysis, gender, smoking history, forced expiratory volume in 1 s/forced vital capacity, LAA% and D-value were risk factors for predicting postoperative pulmonary complications. In the multivariate analysis, D-value remained a significant predictive factor., Conclusion: Preoperative assessment of emphysema cluster analysis may represent the vulnerability of the operated lung and could be the novel predictor for pulmonary complications after thoracoscopic lobectomy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Lung emphysema is an important phenotype of chronic obstructive pulmonary disease (COPD), and CT scanning is strongly recommended to establish the diagnosis. This study aimed to identify criteria by which physicians with limited technical resources can improve the diagnosis of emphysema., Methods: We studied 436 COPD patients with prospective CT scans from the COSYCONET cohort. All items of the COPD Assessment Test (CAT) and the St George's Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale, as well as data from spirometry and CO diffusing capacity, were used to construct binary decision trees. The importance of parameters was checked by the Random Forest and AdaBoost machine learning algorithms., Results: When relying on questionnaires only, items CAT 1 & 7 and SGRQ 8 & 12 sub-item 3 were most important for the emphysema- versus airway-dominated phenotype, and among the spirometric measures FEV 1 /FVC. The combination of CAT item 1 (≤ 2) with mMRC (> 1) and FEV 1 /FVC, could raise the odds for emphysema by factor 7.7. About 50% of patients showed combinations of values that did not markedly alter the likelihood for the phenotypes, and these could be easily identified in the trees. Inclusion of CO diffusing capacity revealed the transfer coefficient as dominant measure. The results of machine learning were consistent with those of the single trees., Conclusions: Selected items (cough, sleep, breathlessness, chest condition, slow walking) from comprehensive COPD questionnaires in combination with FEV 1 /FVC could raise or lower the likelihood for lung emphysema in patients with COPD. The simple, parsimonious approach proposed by us might help if diagnostic resources regarding respiratory diseases are limited. Trial registration ClinicalTrials.gov, Identifier: NCT01245933, registered 18 November 2010, https://clinicaltrials.gov/ct2/show/record/NCT01245933 ., (© 2021. The Author(s).)

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10 -8 ), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10 -6 ) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10 -6 ) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema., (© 2021. The Author(s).)

Background: Disease heterogeneity in idiopathic pulmonary fibrosis (IPF) often complicates the systematic study of disease, management of patients and clinical investigations., Objective: To describe combined pulmonary fibrosis emphysema (CPFE) phenotype in a rural Appalachian IPF cohort with the highest smoking rates in the United States., Methods: CPFE patients (n = 60) in a developed IPF cohort (n = 153) were characterized. Groups (CPFE vs IPF without emphysema) were categorized based on the predominant HRCT patterns of UIP (n = 109). Demographics, clinical variables, and treatment details were recorded. Kaplan-Meier survival and multivariate logistic regression analysis were performed., Results: The prevalence of CPFE in our IPF cohort was 45% (n = 49). The CPFE group was younger (73.9 vs 78.2), had a more extensive smoking history (93.9% vs 53.3%) with greater mean smoking pack years (49.09 vs 15.39) and had lower percentage predicted DL CO on presentation (38.35 vs 51.09) compared to IPF without emphysema group. Both groups shared equivalent higher burden of comorbidities, including pulmonary hypertension (PH) (46.9% vs 33.3%). One-fifth of patients were prescribed antifibrotics and only a subset (5%) of patients underwent lung transplantation. There was a non-significant trend towards reduced survival in CPFE (p = 0.076). Smoking status and DL CO predicted CPFE in our cohort. Body mass index (BMI), PH, and pirfenidone use were significant predictors of mortality., Conclusion: CPFE was highly prevalent in our rural IPF cohort. In contrast to previous studies, CPFE group was older and had higher female (approx. 30%) occurrence. A greater exposure to cigarette smoke and reduced DL CO at diagnosis predicted CPFE. Lower BMI and PH predicted higher mortality whereas use of pirfenidone improved survival in our cohort. This study highlights a complex interaction of cigarette smoking, advanced fibrosis of UIP, PH and potential utility of antifibrotic agents in CPFE phenotype. Substantial burden of comorbidities, older age, and the limited utilization of advanced therapeutics in the cohort emphasize the challenges faced by rural Appalachian patients., Competing Interests: The authors report no relevant conflict of interests in relation to this work., (© 2021 Sangani et al.)

Background: The prevalence of abdominal aortic aneurysm is high in chronic obstructive pulmonary disease (COPD) population. Emphysema involves proteolytic destruction of elastic fibers. Therefore, emphysema may also contribute to thoracic aorta dilatation. This study assessed aorta dilation in smokers stratified by presence of COPD, emphysema and airway thickening., Methods: Aorta diameters were measured on 3D magnetic resonance angiography in smokers recruited from the Multi-Ethnic Study of Atherosclerosis (MESA), the Emphysema and Cancer Action Project (EMCAP), and the local community. COPD was defined by standard spirometric criteria; emphysema was measured quantitatively on computed tomography and bronchitis was determined from medical history., Results: Participants (n = 315, age 58-79) included 150 with COPD and 165 without COPD, of whom 56% and 19%, respectively, had emphysema. Subjects in the most severe quartile of emphysematous change showed the largest diameter at all four aorta locations compared to those in the least severe quartiles (all p < 0.001). Comparing subjects with and without COPD, aorta diameters were larger in participants with severe COPD in ascending and arch (both p < 0.001), and abdominal aorta (p = 0.001). Chronic bronchitis and bronchial wall thickness did not correlate with aorta diameter. In subjects with emphysema, subjects with coexistence of COPD showed larger aorta than those without COPD in ascending (p = 0.003), arch (p = 0.002), and abdominal aorta (p = 0.04)., Conclusions: This study showed larger aorta diameter in subjects with COPD and severe emphysema compared to COPD related to chronic bronchitis or bronchial wall thickening., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the association between the degree of emphysema on computed tomography (CT) images and disease severity, in order to predict the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD)., Study Design: Cross-sectional, observational study., Place and Duration of Study: University of Health Sciences, Diskapi Training and Research Hospital, Ankara, Turkey between January 2016 and January 2017. The analysis of the medical records of patients was performed in December 2020., Methodology: Clinically diagnosed COPD patients were included in this study. Based on emphysema severity on CT, the patients were classified into three groups as group I (n=59), group II (n=37), and group III (n=20), and emphysema was not present in the remaining 15 patients. The associations between emphysema severity and the GOLD stage, mMRC dyspnea score and exacerbation frequency were analysed with Chi-square test., Results: In 131 patients, the severity and presence of emphysema was found to be significantly associated with smoking history (p=0.034). However, no significant differences were observed between emphysema severity and exacerbation frequency (p=0.512) and mMRC dyspnea scores (p=0.110). The severity of emphysema was related with the GOLD stage (p=0.001). There was also a significant association between BMI and severity of emphysema, with the severe emphysema cases tending to be underweight (p=0.001)., Conclusion: CT-emphysema severity can be used to classify COPD to assist in the clinical characterisation of patients. This type of classification is important to determine the underlying pathophysiology and genomic profile of COPD.     Key Words: Chronic obstructive pulmonary disease, Computed tomography, Emphysema.

Background: People living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH., Methods: We included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under -950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75 th percentile., Results: Of 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001)., Conclusion: Two markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking., Clinical Trial Registration: clinicaltrials.gov, identifier NCT02382822., Competing Interests: RT: reports a grant from Rigshospitalet Research Council. TB: reports grants from Pfizer, grants from Novo Nordisk Foundation, grants from Lundbeck Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, outside the submitted work. AM: has received travel support, honoraria and consultancy fees from ViiV, Gilead and Eiland and Bonnin PC. JV: reports honoraria from consulting/presenting from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, Novartis and Sanofi and a grant from Boehringer-Ingelheim, outside the submitted work. SN: unrestricted research grants from Novo Nordisk Foundation and Rigshospitalet Research Council. Advisory board activity for Gilead and GSK/ViiV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Thudium, Ringheim, Ronit, Hoel, Benfield, Mocroft, Gerstoft, Trøseid, Borges, Ostrowski, Vestbo and Nielsen.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients., Objective: Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE., Methods: We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data., Results: Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers., Conclusion: CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Hage et al.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting., Methods: We conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE., Results: Among 228 patients with CPFE, 89 had fibrosis affecting < 5% of their lungs, 54 had 5 to < 10% fibrosis, and 85 had ≥ 10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p < 0.001). In particular, among those with < 5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥ 10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥ 10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to < 10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis., Conclusions: Less severe (< 5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed. Trial Registration Retrospectively registered.

Background: Tracheobronchial foreign body (TFB) aspiration is a significant cause of respiratory problems in children. The timely diagnosis of TFB is important to decrease the mortality rate and the incidence of complications. Advances in radiology have led multi-slice spiral computed tomography (MSCT) to become the best technique for diagnosing TFB., Methods: We performed a retrospective study over 5 years from July 2008 to June 2013. We collected information on children who were diagnosed with a TFB by bronchoscopy, and analyzed age, sex, location, type of foreign body, and various MSCT manifestations., Results: A total of 382 children were included and 68.6% of them were aged 1 to <2 years. The majority (95.8%) of aspirated foreign bodies were vegetation items, and nearly half (47.6%) of them were peanut kernels, followed by sunflower seeds (26.2%). A total of 4.7% of TFBs were in the trachea, 51.0% were in the left main bronchus, and 44.2% were in the right main bronchus. Among the TFBs, 359 (95.5%) showed a high-density shadow in the tracheal / bronchial lumen using MSCT, which could establish the presence of a foreign body directly. Emphysema, localized obstruction and pneumonia were more commonly detected in the 7-21 days and ≥21 days group compared with those in the <7 days group (all P < 0.01). Bronchiectasis was found in two children who were diagnosed at least 21 days after aspiration., Conclusions: Multi-slice spiral computed tomography is very sensitive to TFBs. Timely diagnosis and treatment of TFB is important to prevent long-term sequelae in children., (© 2020 Japan Pediatric Society.)

Purpose: Idiopathic Pulmonary Fibrosis is a progressive and fatal interstitial lung disease (ILD) characterized by a typical radiographic or histologic usual interstitial pneumonia (UIP) pattern. In 2018, diagnostic categories of UIP based on computed tomography patterns were revised by the Fleischner Society. The study aimed to describe differences in comorbidities and spirometry in ILD patients that were characterized by high-resolution computed tomography (HRCT) images as having a typical, probable, indeterminate, and alternative diagnosis of UIP., Methods: We retrospectively studied 80 ILD patients from 2017 to 2019. Typical UIP was defined using the Fleischner Society diagnostic criteria for IPF. Atypical UIP was reached by consensus after a multidisciplinary clinical-radiological-pathological review of patient data. Baseline characteristics, comorbidities, and spirometry were compared among the four subgroups., Results: Among 80 patients, 59% were male, 61% had a history of smoking, and the mean age was 67.7 ± 10 years (SD). A typical UIP pattern was more frequently observed among patients with chronic obstructive pulmonary disease (COPD) (p < 0.001) and pulmonary hypertension (p = 0.03). Of 30 patients with COPD, 14 had emphysema, while 10 had IPF. After adjusting for forced expiratory volume in one second (FEV 1 ) in liters, change of FEV 1 % from baseline to 6-12 months, age, and sex, only COPD remained significantly associated with typical UIP (p = 0.018). Tobacco use was not significantly associated with any radiographic type (p = 0.199)., Conclusion: Typical UIP was prevalent among COPD/emphysema patients. Although smoking has a strong association with IPF, we did not find a significant association with smoking and typical UIP in our cohort.

Purpose: The prevalence of chronic obstructive pulmonary disease (COPD) in females has increased, changing the concept of COPD as a disease mostly limited to males. In this study, the clinical characteristics of COPD in females were investigated., Patients and Methods: The study was based on a multicenter cohort of COPD patients recruited from 54 medical centers in South Korea. Sex-based differences in general characteristics, exposure risk factors, depression scores, results of pulmonary function tests, COPD exacerbation, symptom scores, and radiologic findings were evaluated. Sex-related differences in the annual FEV 1 change over 5 years were analyzed in a linear mixed model., Results: Of the 2515 patients enrolled in this study, 8.1% were female. Female patients who had a higher BMI and a lower level of education were less likely to be smokers, were more exposed to passive smoking/biomass, and were more depressed compared to males. The rates of bronchiectasis, previous childhood respiratory infection, and asthma were higher in females. Female patients also had more symptoms and a poorer exercise capacity than males, but no significant differences were observed in terms of exacerbations. Radiologic findings revealed that male patients had worse emphysema, and female patients had worse bronchiectasis, as determined based on chest X-ray and computed tomography findings. On pulmonary function tests, female patients had less obstruction and less annual FEV 1 loss over 5 years., Conclusion: This study revealed differences in the clinical parameters between male and female patients with COPD, including general characteristics, disease characteristics, and clinical outcomes., Competing Interests: The authors have no conflicts of interest., (© 2020 Choi et al.)

Background The clinical significance of visually evident emphysema on CT images in individuals without spirometric evidence of chronic obstructive pulmonary disease (COPD) by current diagnostic criteria is, to the knowledge of the authors, unknown. Purpose To evaluate whether participants with visually evident emphysema at CT were more likely to have progressive disease and increased mortality at 5 years compared with those without visual emphysema. Materials and Methods This secondary analysis of the prospective Genetic Epidemiology of COPD study evaluated current or former smokers enrolled between 2008 and 2011 who did not meet current criteria for COPD (defined as Global Initiative for Obstructive Lung Disease stage 0). Statistical analysis was performed by using linear mixed models to estimate mean physiologic, imaging, and clinical outcomes for those with and without visual emphysema. Hazard ratios for mortality were calculated by using Cox regression models with emphysema as the main predictor. Results Of the 4095 participants, 48.3% (1979 participants; 1096 men and 883 women; mean age, 57 years ± 8 [standard deviation]) had trace or greater visual emphysema at CT and 51.7% (2116 participants; 1068 men and 1048 women; mean age, 56 years ± 8) had no emphysema at CT. At 5 years, participants with visual emphysema at CT demonstrated progressive airflow obstruction with lower values of ratio of forced expiratory volume in 1 second (FEV 1 )-to-functional vital capacity (FVC) ratio (-1.7 vs -0.7) and greater progression in quantitative emphysema measured by 15th percentile lung density (-3.3 vs -0.3 HU), adjusted lung density (-3.1 vs -0.2 g/L), and percentage of lung voxels with CT attenuation less than -950 HU (0.17 vs -0.20) than participants without emphysema ( P < .001 for each). The rate of quantitative emphysema progression increased with greater grades of emphysema severity within the emphysema group. Conclusion The presence of visual emphysema at CT in current and former Global Initiative for Obstructive Lung Disease stage 0 smokers predicted structural and physiologic disease progression. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.