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Rationale: Knowledge regarding the prevalence and shared and unique characteristics of the restrictive spirometric pattern (RSP) and preserved ratio impaired spirometry (PRISm) is lacking for a general population investigated with post-bronchodilator spirometry and computed tomography of the lungs. Objectives: To investigate shared and unique features for RSP and PRISm. Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population sample of 28,555 people aged 50-64 years (including 14,558 never-smokers) was assessed. The participants answered a questionnaire and underwent computed tomography of the lungs, post-bronchodilator spirometry, and coronary artery calcification score. Odds ratios with 95% confidence intervals (CIs) were calculated using adjusted logistic regression. RSP was defined as forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) ≥0.70 and FVC <80%. PRISm was defined as FEV 1 /FVC ≥0.70 and FEV 1 <80%. A local reference equation was applied. Results: The prevalence of RSP and PRISm were 5.1% (95% CI, 4.9-5.4) and 5.1% (95% CI, 4.8-5.3), respectively, with similar values seen in never-smokers. For RSP and PRISm, shared features were current smoking, dyspnea, chronic bronchitis, rheumatic disease, diabetes, ischemic heart disease, bronchial wall thickening, interstitial lung abnormalities, and bronchiectasis. Emphysema was uniquely linked to PRISm (odds ratio, 1.69; 95% CI, 1.36-2.10) versus 1.10 (95% CI, 0.84-1.43) for RSP. Coronary artery calcification score ≥300 was related to PRISm, but not among never-smokers. Conclusions: PRISm and RSP have respiratory, cardiovascular, and metabolic conditions as shared features. Emphysema is only associated with PRISm. Coronary atherosclerosis may be associated with PRISm. Our results indicate that RSP and PRISm may share more features than not.

Background: Giant bullous emphysema is characterized by large bullae occupying at least one-third of the hemithorax and leading to compression of the surrounding lung parenchyma. Overdiagnosis can occur because of the atypical appearance of hyperplastic type II pneumocytes, which may be mistaken for malignant cells., Case Presentation: A 48-year-old male with a history of smoking and occupational exposure presented with dyspnea and drowsiness. Initial chest X-ray revealed a tension pneumothorax, and subsequent chest CT revealed extensive bullous emphysema and lung cancer in the right middle lobe (RML). Pathologic examination initially indicated resected bullae to metastatic adenocarcinoma, but upon review, it was determined that the reactive alveolar cells were misdiagnosed as malignant., Conclusions: This case emphasizes the need for thorough histopathological assessment and prudent interpretation of atypical cellular morphology., (© 2024. The Author(s).)

The presence of comorbidities (CM) in congenital lobar emphysema (CLE) has been previously described with varying rates. However, the clinical implication of CM on the clinical presentation and patient outcome in CLE is unclear. This was a retrospective cohort study between 2000 and 2022 in a single institution. The study included pediatric patients diagnosed with CLE. During the study period, 36 patients were identified with CLE. The presence of respiratory symptoms at diagnosis was documented in 69% (24/35) of the patients with 48% admitted to intensive care units. The presence of CM was documented in 14/36 (39%) of the patients, with cardiovascular anomalies as the most common (22%), followed by genitourinary anomalies (11%) and large airway anomalies (8%). When comparing the CM group (n = 14) vs the non-CM group (N = 22), there was no significant difference regarding gender, term birth, age of diagnosis, and the location of the lesion. The CM group had significantly higher rates of intensive care unit (ICU) admissions (75% vs 33%, p = 0.02), longer duration of admission (median 46 days vs 9, p = 0.02), and need for pre-operative non-invasive respiratory support (50% vs 5%, p = 0.002).Conclusion: The presence of CM in CLE was associated with a more severe presentation as reflected with significantly higher rates of ICU admissions, prolonged admissions, and higher need for non-invasive respiratory support. Screening for CM, mostly for cardiac anomalies, is recommended at time of CLE diagnosis. What is Known: • Congenital lobar emphysema (CLE) is a developmental lung anomaly generally associated with other comorbidities; however, their clinical implication on presentation is unclear • The prevalence of comorbidities in CLE was previously reported around 15-20%, with cardiovascular anomalies as the most common What is New: • Comorbidities are very common (39%) in CLE, and their presence is related to a more severe clinical presentation and need for respiratory support • Screening for comorbidities is recommended in CLE, specifically for cardiovascular and genitourinary anomalies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost., Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DL NO and DL CO via a single-breath (sDL NO and sDL CO )., Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDL NO , sDL CO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC)., Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV 1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDL CO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDL CO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R 2 ), RV coupled with sDL CO or Vc proved the best predictors of emphysema., Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDL NO , sDL CO and Vc do enhance the predictive power of current spirometric measures substantially. sDL NO , sDL CO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Dal Negro et al.)

Endoscopic lung volume reduction (ELVR) is an established treatment option for patients with severe emphysema. Not all patients are candidates for this type of intervention, and in the context of significant airway secretions, they may be excluded from treatment. Bronchial Rheoplasty (BR) was developed to treat mucus hypersecretion by delivering nonthermal pulsed electric fields to the airway epithelium and submucosa. The literature to date demonstrates that patients treated with BR in clinical studies have a reduction in airway goblet cell hyperplasia as well as substantive clinical improvement in the setting of chronic bronchitis (CB). In this case series, we present four patients treated at three different institutions who had previously undergone ELVR with beneficial outcome. However, over time, these patients subsequently developed worsening clinical issues, including complaints of increased and thickened mucus, along with exacerbations in the setting of a loss of some ELVR-associated benefits. These patients then underwent exploratory treatment with BR with the intent of reducing their secretion burden and potentially restoring the efficacy associated with the initial placement of the airway valves. All BR procedures were well tolerated, and three of the four patients showed substantial improvement in their symptom burden. Airway examinations during the second of the two BR procedures also revealed what appeared to be less airway mucosal inflammation and a decrease in the quantity of airway secretions. Therefore, treatment with BR may have the potential to improve and restore the initial benefits associated with ELVR, thus enhancing long-term outcomes. Further clinical studies with sufficient follow-up are warranted to assess this in a larger cohort of patients, and to determine whether treatment with BR prior to ELVR may make more patients eligible for this treatment through reduction in their secretions and/or symptoms., Competing Interests: Dr Michael Perch reports personal fees from AstraZeneca, personal fees from PulmonX, grants from PulmonX, grants from Therakos, personal fees from Takeda, personal fees from Zambon, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Jensen et al.)

Background: The role of obesity on dyspnea in chronic obstructive pulmonary disease (COPD) patients remains unclear. We aimed to provide an assessment of dyspnea in COPD patients according to their Body Mass Index (BMI) and to investigate the impact of obesity on dyspnea according to COPD severity., Methods: One hundred and twenty seven COPD patients with BMI ≥ 18.5 kg/m² (63% male, median (interquartile range) post bronchodilator forced expiratory volume of 1 second (post BD FEV 1 ) at 51 (34-66) % pred) were consecutively included. Dyspnea was assessed by mMRC (Modified medical research council) scale. Lung function tests were recorded, and emphysema was quantified on CT-scan (computed tomography-scan)., Results: Twenty-five percent of the patients were obese (BMI ≥ 30kg/m²), 66% of patients experienced disabling dyspnea (mMRC ≥ 2). mMRC scores did not differ depending on BMI categories (2 (1-3) for normal weight, 2 (1-3) 1 for overweight and 2 (1-3) for obese patients; p = 0.71). Increased mMRC scores (0-1 versus 2-3 versus 4) were associated with decreased post BD-FEV 1 (p < 0.01), higher static lung hyperinflation (inspiratory capacity/total lung capacity (IC/TLC), p < 0.01), reduced DLCO (p < 0.01) and higher emphysema scores (p < 0.01). Obese patients had reduced static lung hyperinflation (IC/TLC p < 0.01) and lower emphysema scores (p < 0.01) than non-obese patients. mMRC score increased with GOLD grades (1-2 versus 3-4) in non-obese patients but not in obese patients, in association with a trend towards reduced static lung hyperinflation and lower emphysema scores., Conclusion: By contrast with non-obese patients, dyspnea did not increase with spirometric GOLD grades in obese patients. This might be explained by a reduced lung hyperinflation related to the mechanical effects of obesity and a less severe emphysema in severe COPD patients with obesity., Competing Interests: GD reports personal fees from Chiesi, GSK and AstraZeneca outside the submitted work. SD reports personal fees from Boehringer Ingelheim and Sanofi-Aventis outside the submitted work. J.M. Perotin reports lecture honoraria from AstraZeneca and support for attending meetings from AstraZeneca and Chiesi; outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Dupuis et al.)

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).)

There has been an increased recognition of a subset of congenital lobar emphysema (CLE), termed congenital sublobar hyperinflation (CSLH), which may affect only a segment of lung as opposed to an entire lobe. This is an uncommon variant for which there is a paucity of information in published literature. The majority of CLE are managed surgically. Current literature suggests non-operative management for CSLH. However, there has been slow adoption of non-operative management and there is not a well-established observation pathway. A retrospective review of all pediatric patients diagnosed with CSLH at a single institution was performed from 2017 to 2023 to determine if this variant may be safely managed with observation. A total of 10 patients were identified. Of these, three patients had consolidation on cross-sectional imaging; therefore, operative intervention was undertaken given diagnostic uncertainty. All patients managed observationally remained asymptomatic. This case series validates non-operative management for patients with asymptomatic CSLH., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

Research on the condition of the lungs in senile people is an urgent task. This is due to the fact that degenerative or age-associated changes in the respiratory system play an important role in the formation of senile asthenia syndrome and a decrease in the age-related viability of the body as a whole. CT-scans of patients aged 80-90 years were analyzed (n=31). Age-associated changes were evaluated: the presence of linear fibrosis, increased pulmonary pattern by the type of reticular (reticular) changes, the presence of gross fibrous reticular changes with cystic cavities and air bullae (by the type of «cellular lung»), as well as the presence of pulmonary emphysema. Most naturally, senile people show changes characteristic of linear pulmonary fibrosis and emphysema. The progression of the process leads to diffuse reticular changes in the interalveolar and intersegmental septa and, in adverse cases, to the formation of gross changes in the type of «cellular lung». Fibro-emphysematous changes are significantly more common in men. A microbiological study of the microbiota of the lower respiratory tract in elderly people was also carried out (n=16). When studying the microbiocenosis of the lower respiratory tract in elderly people, the following data were obtained: resident microflora was found in 71% and clinically significant microorganisms were found in 29%.

Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.

COPD is a highly prevalent, chronic and irreversible obstructive airway disease without curative treatment. Standard therapeutic strategies, both non-pharmacological and pharmacological, have only limited effects on lung function parameters of patients with severe disease. Despite optimal pharmacological treatment, many patients with severe COPD still have a high burden of dyspnoea and a poor quality of life. If these patients have severe lung emphysema, with hyperinflation as the driver of symptoms and exercise intolerance, lung volume reduction may be an effective treatment with a significant impact on lung function, exercise capacity and quality of life. Currently, different lung volume reduction approaches, both surgical and bronchoscopic, have shown encouraging results and have been implemented in COPD treatment recommendations. Nevertheless, choosing the optimal lung volume reduction strategy for an individual patient remains challenging. Moreover, there is still room for improving durability of effect and safety in all available procedures. Ongoing and innovative research is essential to push this field forwards. This review provides an overview of results and limitations of the current lung volume reduction options for patients with severe lung emphysema and hyperinflation., Competing Interests: Conflict of interest: S. Everaerts, C.M. Vandervelde and P. Shah have no conflicts of interest related to the content of the manuscript. D-J. Slebos reports grants or contracts, study material, registration fees and travel costs, and participation on a Data and Safety Monitoring Board for Pulmonx, Corp., BTG/PneumRx Inc, FreeFlowMedical, Nuvaira, PulmAir, GALA, CSA Medical and Apreo, most of them paid to his institution. L.J. Ceulemans received an unrestricted university chair from Medtronic and a philanthropic grant from Gunze., (Copyright ©The authors 2023.)

Augmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress.Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient., Competing Interests: Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols; and research grants from Grifols. A. Anzueto has received consultant fees from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Verona Pharma, TEVA and Mylan/Theravance. M. Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK and Boehringer Ingelheim; and consulting fees from GSK, Novartis, CSL Behring and Boehringer Ingelheim., (Copyright ©The authors 2023.)

Combined pulmonary fibrosis and emphysema (CPFE) syndrome refers to co-occurrence of two disease processes in the lung that can be difficult to diagnose but is associated with high morbidity and mortality burden. Diagnosis of CPFE is challenging because the two diseases can counterbalance respective impairments resulting in deceivingly normal-appearing chest radiography and spirometry in a dyspneic patient. Although an international committee published the terminology and definitions of CPFE in 2022, consensus on exact diagnostic criteria and optimal management strategy is yet to be determined. Herein, we provide a narrative review summarizing the literature on CPFE from 1990 to 2022, including historical background, epidemiology, pathogenesis, clinical features, imaging and pulmonary function findings, diagnosis, prognosis, complications, and treatment. Although CPFE was initially conceived as a variant presentation of idiopathic pulmonary fibrosis, it has been recognized to occur in patients with a wide variety of interstitial lung diseases, including connective tissue disease-associated interstitial lung diseases, and hypersensitivity pneumonitis. The affected patients have a heightened risk for pulmonary hypertension and lung cancer. Clinicians need to recognize the characteristic presenting features of CPFE along with prognostic implications of this entity., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1 gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZ homozygous status and is favored by smoking. Liver fibrosis is due to the ZZ homozygous status and is favored by obesity and excessive chronic alcohol intake, with a risk of liver cancer. Diagnosis is based on serum level and either isoelectric focusing determination of the biochemical phenotype or PCR detection of some variants. SERPINA1 gene sequencing is necessary in case of discrepancies between the results of these tests. No treatment is available for the liver disease in AATD. Although no specific trial has been performed, COPD in AATD should be treated as per COPD recommendations. Based on a randomized clinical trial, augmentation therapy is indicated in non-smoking adults less than 70 years of age with emphysema at chest CT, confirmed homozygous AATD, and FEV1 between 35% and 70% of predicted. In contrast Z heterozygosis (MZ or SZ) brings a risk of lung or liver disease only in association with further risk factors. Early detection, in all patients with COPD and chronic liver disease, is critical for the correct information of Z variant carriers. News ways of correcting the liver production of alpha1-antitrypsin will modify the care of AATD patients., Competing Interests: Declaration of Competing Interest The authors have not supplied their declaration of competing interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

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: 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.)

Purpose: Up to 41% of patients with endobronchial valve implantation need revision bronchoscopies and valve replacements most likely due to valve dysfunction or lack of benefit. So far, no data is available whether valve replacements lead to the desired lobar volume reduction and therapy benefit., Patients and Methods: We conducted a single-center retrospective analysis of patients with endobronchial valve implantation and at least one valve replacement. Indications and number of revision bronchoscopies and valve replacements were evaluated. Therapy benefit regarding lung function and exercise capacity as well as development of complete lobar atelectasis was investigated and possible predictors identified., Results: We identified 73 patients with 1-12 revision bronchoscopies and 1-5 valve replacements. The main indication for revision bronchoscopy in this group was lack of therapy benefit (44.2%). Lung function and exercise capacity showed improvements in about one-third of patients even years after the initial implantation. A total of 26% of all patients showed a complete lobar atelectasis at the end of the observation period, 56.2% had developed lung volume reduction. The logistic regression revealed the development of a previous complete lobar atelectasis as predictor for a complete lobar atelectasis at final follow-up. Oral cortisone long-term therapy was also shown as predictive factor. The probability for a final complete lobar atelectasis was 69.2% if a lobar atelectasis had developed before., Conclusion: Valve replacements are more likely to be beneficial in patients who develop a re-aeration of a previous lobar atelectasis following valve implantation. Every decision for revision bronchoscopy must be taken carefully., Competing Interests: Judith Brock has received honoraria and consultation fees from Boehringer Ingelheim, Astra Zeneca, streamed up!, Intuitive Surgical Inc, Berlin Chemie, outside the submitted work. Paul Ulrich Schuster, Felix Böhmker, and Nicola Benjamin have no conflicts of interest to report for this work. Prof. Dr. Ralf Eberhardt reports honoraria or payment for lectures and presentations from Broncus, Olympus, Pentax, Pulmonx, Astra Zeneca. He joins the data safety monitoring board for Intuitive Surgical Inc, outside the submitted work. Prof. Dr. Daniela Gompelmann reports fees for lectures and travel from Pulmonx, Chiesi, Boehringer Ingelheim, Astra Zeneca, Berlin Chemie, Erbe, Novartis, Olympus, outside the submitted work. Konstantina Kontogianni has received honoraria for lectures from Berlin-Chemie, Astra Zeneca and Boston Scientific, outside the submitted work. Franziska Trudzinski has received honoraria for lectures from Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Novartis, CSL Behring. She participates in an Advisory Board for CSL Behring, GlaxoSmithKline and Boehringer Ingelheim, outside the submitted work. Felix Herth reports Research Support from Olympus Medical, Pulmonx, Broncus, Uptake Medical, Roche Diagnostics, BMBF, DFG, EU, Klaus-Tschira Stiftung, BMG; Lecturing honoraria from Pulmonx, Uptake Medical, Roche Diagnostics, Astra Zeneca, Boehringer Ingelheim, Novartis, Berlin Chemie, Chiesi, Medupdate, Erbe, GSK and consulting activities for Olympus Medical, Pulmonx, Broncus – Uptake Medical, Roche Diagnostics, Astra Zeneca, J&J, Karger, LÄK, Boston Scientific, Dinova, Nanovation, Free Flow Medical, Erbe, outside the submitted work., (© 2023 Brock et al.)

Introduction: Surgical (OP) management for symptomatic congenital lobar emphysema (CLE) is the standard of care with nonoperative (NOP) approach applied for asymptomatic cases. The aim of this study is to report the outcomes for NOP approach to the care of symptomatic CLE infants., Methods: A retrospective study of CLE patients treated 2000-2021 at a single institution. Patients with CLE and respiratory symptoms were included., Results: Overall, 23 children had symptomatic CLE, and 12 had NOP management. The median age at diagnosis was 38.5 days (50) in the NOP group versus 25 days (20) in the OP group (p = 0.31). There was no significant difference in the location of the involved lobe, term birth, postnatal diagnosis and gender, and both groups required noninvasive support in 33% of the cases. There was a trend towards higher frequency of oxygen support in the OP group preoperatively (89% vs. 42%, p = 0.07). The median length of stay was 14 days in the NOP group compared to a median postsurgery stay of 7.5 days in the OP group. In follow-up, there was no significant difference in respiratory readmission in first year of life, growth delay, treatment with asthma medication or body mass index in the NOP versus OP group. None of the children in the NOP group required surgery during follow-up., Conclusions: A NOP approach for symptomatic CLE infants can have favorable long-term outcomes. Further studies will be required to identify markers to aid in clinical decision-making., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Bronchoscopic lung volume reduction is as a safe and effective therapy for patients with advanced emphysema, suffering from breathlessness despite optimal medical therapy. By reducing hyperinflation, it improves lung function, exercise capacity and quality of life. The technique includes one-way endobronchial valves, thermal vapor ablation and endobronchial coils. Patient selection is the key to a successful therapy; hence the indication should be evaluated in a multidisciplinary emphysema team meeting. The procedure can lead to a potentially life-threatening complication. Therefore, an adequate post-procedural patient management is crucial., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einem/den Sponsor(en) dieser Fortbildungseinheit; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einem/den Sponsor(en) dieser Fortbildungseinheit; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen K. Darwiche: Mitgliedschaft in DGP, WDGP, DKG, ERS, ECBIP, WABIP, BDI, (Thieme. All rights reserved.)

COPD and α-1 antitrypsin deficiency emphysema remain one of the major indications for lung transplantation. If all other treatment possibilities are exhausted or not possible (including rehabilitation, oxygen therapy, noninvasive ventilation, lung volume reduction), patients may qualify for lung transplantation. Strict selection criteria are implemented with a lot of relative and absolute contraindications. Because of an ongoing donor shortage, only a minority of endstage COPD patients will finally get transplanted. The procedure may involve a single or a double lung transplantation, dependent on the experience of the centre, the waiting list, the availability of donor lungs and the patient's risk-benefit ratio. In general, the life expectancy as well as the health-related quality of life after lung transplantation for COPD are usually increased, and may be somewhat better after double compared with single lung transplantation. Several specific complications can be encountered, such as the development of solid organ cancer and chronic lung allograft dysfunction, which develops in up to 50% of patients within 5 years of their transplant and has a major impact on long-term survival, because of the current inefficient treatment modalities., Competing Interests: Conflict of interest: the authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Both COPD and interstitial lung abnormalities (ILAs) are conditions associated with smoking and age. The impact of coexistent ILAs on the manifestations and outcomes of COPD or emphysema awaits evaluation., Methods: We searched PubMed and Embase using Medical Subject Headings terms in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Eleven studies were included in the review. The sample size of the studies ranged from 30 to 9579. ILAs were reported in 6.5% to 25.7% of the patients with COPD/emphysema, higher than that reported in the general populations. COPD/emphysema patients with ILAs were older, mostly male, and had a higher smoking index than those without ILAs. Hospital admission and mortality were increased in COPD patients with ILAs compared to those without ILAs, whereas the frequency of COPD exacerbations was discrepant in 2 of the studies. The FEV 1 and FEV 1 % predicted tended to be higher in the group with ILAs, but not significantly in most of the studies., Conclusion: ILAs were more frequent in subjects with COPD/emphysema than in the general population. ILAs may have a negative impact on hospital admission and mortality of COPD/emphysema. The impact of ILAs on lung functions and exacerbations of COPD/emphysema was discrepant in these studies. Further prospective studies are warranted to provide high-quality evidence of the association and interaction between COPD/emphysema and ILAs., Competing Interests: The authors report no conflicts of interst in this work., (© 2023 Liu et al.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a distinct clinical entity that can progress to end-stage lung disease. Patients with CPFE may develop pulmonary hypertension and face a predicted 1-year mortality of 60%. Lung transplantation is the only curative therapeutic option for CPFE. This report describes our experience after lung transplantation in patients with CPFE., Methods: This retrospective, single-center study describes short- and long-term outcomes for adult patients who underwent lung transplant for CPFE., Results: The study included 19 patients with explant pathology-proven diagnosis of CPFE. The patients were transplanted between July 2005 and December 2018. Sixteen recipients (84%) had pulmonary hypertension before transplant. Of the 19 patients, 7 (37%) had primary graft dysfunction at 72 hours post-transplant. 1-, 3-, and 5-year freedom from bronchiolitis obliterans syndrome was 100%, 91% (95% CI, 75%-100%), and 82% (95% CI, 62%-100%), respectively. One-, 3-, and 5-year survival was 94% (95% CI, 84%-100%), 82% (95% CI, 65%-100%), and 74% (95% CI, 54%-100%), respectively., Conclusion: Our experience demonstrates the safety and feasibility of lung transplant for patients with CPFE. Significant morbidity and mortality without lung transplant coupled with favorable post-transplant outcomes merit prioritization of CPFE in the Lung Allocation Score algorithm for lung transplant candidacy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.)

Purpose: We investigated the effect of pulmonary rehabilitation (PR) on airway resistance in chronic obstructive pulmonary disease (COPD) patients with severe airway obstruction and hyperinflation., Patients and Methods: This retrospective cohort study was conducted with data from severe COPD cases with those who underwent an 8-week PR program. Main inclusion criteria were having severe airflow obstruction (defined as a forced expiratory volume in one second (FEV 1 ) <50%) and plethysmographic evaluation findings being compatible with hyperinflation supporting the diagnosis of emphysema (presence of hyperinflation defined as functional residual capacity ratio of residual volume to total lung capacity (RV/TLC) >120%). Primary outcomes were airway resistance (R aw ) and airway conductance (G aw ) which were measured by body plethysmography, and other measurements were performed, including 6-minute walk test (6-MWT), modified Medical Research Council dyspnea scale (mMRC) and COPD assessment test (CAT)., Results: Twenty-six severe and very severe COPD patients (FEV 1, 35.0 ± 13.1%; RV/TLC, 163.5 ± 29.4) were included in the analyses, mean age 62.6 ± 5.8 years and 88.5% males. Following rehabilitation, significant improvements in total specific airway resistance percentage (sR awtot %, p = 0.040) and total specific airway conductance percentage (sG awtot %; p = 0.010) were observed. The post-rehabilitation mMRC scores and CAT values were significantly decreased compared to baseline results (p < 0.001 and p < 0.001, respectively). Although there were significant improvements in 6-MWT value (p < 0.001), exercise desaturation (ΔSaO 2 , p = 0.026), the changes in measured lung capacity and volume values were not significant., Conclusion: We concluded that PR may have a positive effect on airway resistance and airway conductance in COPD patients with severe airflow obstruction., Competing Interests: The authors report no conflicts of interest in this study., (© 2023 Kiliç et al.)

We summarized the available data on therapeutic, surgical and endoscopic treatment of chronic obstructive pulmonary disease and emphysema that may be used like a bridge to lung transplantation. Treatment of chronic obstructive pulmonary disease and emphysema is expensive. Certain limitations in lung transplantation make to create new methods of treatment of severe emphysema. However, one should be ready for possible complications and carefully select patients for certain treatment to avoid false negative results. Reducing costs or developing cheaper treatments is important for the future and availability of care. The risks and complications associated with surgical treatment of emphysema can make endoscopic surgery preferable for these patients, and this undoubtedly requires further research.

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).)

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.)

Background: Alpha-1 Antitrypsin (AAT) deficiency (AATD), the most common genetic cause of emphysema presents with unexplained phenotypic heterogeneity in affected subjects. Our objectives to identify unique and shared AATD plasma biomarkers with chronic obstructive pulmonary disease (COPD) may explain AATD phenotypic heterogeneity., Methods: The plasma or serum of 5,924 subjects from four AATD and COPD cohorts were analyzed on SomaScan V4.0 platform. Using multivariable linear regression, inverse variance random-effects meta-analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression we tested the association between 4,720 individual proteins or combined in a protein score with emphysema measured by 15th percentile lung density (PD15) or diffusion capacity (DLCO) in distinct AATD genotypes (Pi*ZZ, Pi*SZ, Pi*MZ) and non-AATD, PiMM COPD subjects. AAT SOMAmer accuracy for identifying AATD was tested using receiver operating characteristic curve analysis., Findings: In PiZZ AATD subjects, 2 unique proteins were associated with PD15 and 98 proteins with DLCO. Of those, 68 were also associated with DLCO in COPD also and enriched for three cellular component pathways: insulin-like growth factor, lipid droplet, and myosin complex. PiMZ AATD subjects shared similar proteins associated with DLCO as COPD subjects. Our emphysema protein score included 262 SOMAmers and predicted emphysema in AATD and COPD subjects. SOMAmer AAT level <7.99 relative fluorescence unit (RFU) had 100% sensitivity and specificity for identifying Pi*ZZ, but it was lower for other AATD genotypes., Interpretation: Using SomaScan, we identified unique and shared plasma biomarkers between AATD and COPD subjects and generated a protein score that strongly associates with emphysema in COPD and AATD. Furthermore, we discovered unique biomarkers associated with DLCO and emphysema in PiZZ AATD., Funding: This work was supported by a grant from the Alpha-1 Foundation to RPB. COPDGene was supported by Award U01 HL089897 and U01 HL089856 from the National Heart, Lung, and Blood Institute. Proteomics for COPDGene was supported by NIH 1R01HL137995. GRADS was supported by Award U01HL112707, U01 HL112695 from the National Heart, Lung, and Blood Institute, and UL1TRR002535 to CCTSI; QUANTUM-1 was supported by the National Heart Lung and Blood Institute, the Office of Rare Diseases through the Rare Lung Disease Clinical Research Network (1 U54 RR019498-01, Trapnell PI), and the Alpha-1 Foundation. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion., Competing Interests: Declaration of interests KAS serves on Alpha-1 Foundation Grant Advisory Committee, Alpha-1 Foundation Medical Advisory and Scientific Committee, ATS - RCMB Website Committee, National Jewish Health IBC committee (all unpaid); KAP does not report any potential conflict of interest; CS reports grants or contracts from Adverum, Arrowhead, AstraZeneca, CSA Medical, Grifols, Nuvaira, Takeda, Vertex; consulting fees from AstraZenca, Dicerna, Glaxo Smith Kline, Inhibrx, Morair, UpToDate, Vertex; has received honoraria for presentations from the American Thoracic Society; has received support for travel from CSL Behring; serves as the Medical Director for AlphaNet; RAS reports grants or contracts from Vertex, NIH/NCATS, Alpha-1 Foundation, consulting fees from Grifols, CSL Behring, Vertex, Intellia, Inhibrx, Takeda, Evolve Biologics, has received travel support from CSL Behring; has served on the Advisory Board of Arrowhead Pharmaceuticals, and serves as the Medical Director for AlphaNet and on the board of directors for Global Implementation Solutions, Osteogenesis Imperfecta Foundation, Alpha-1 Foundation, and AlphaNet; AMT reports grants or contracts from Vertex, Grifols, and CSl Behring; has received consulting fees from CSL Behring, Inhibrix, Z-factor, and Takeda, has received honoraria for lectures from Glaxo Smith Kline and AstraZeneca; TB does not report any potential conflict of interest; DAS does not report any potential conflict of interest; LM does not report any potential conflict of interest; NH does not report any potential conflict of interest; EKS reports grants or contracts from Glaxo Smith Kline, Bayer; BDH does not report any potential conflict of interest; CPH reports grants or contracts from Alpha-1 Foundation, Bayer, Boehringer-Ingelheim, and Vertex, consulting fees from AstraZeneca and Takeda; DLD has received honoraria for lectures from Novartis and financial support from Bayer towards the institution; MHC reports grants or contracts from Glaxo Smith Kline, Bayer, consulting fees from AstraZeneca and Genentech, honoraria for presentations from Illumina, RPB does not report any potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Idiopathic Giant Bullous Emphysema (or Vanishing Lung Syndrome) is a rare condition which is usually associated with male gender, active smoking and underlying emphysematous disease. We present an unusual case of a giant bulla occurring in the absence of these risk factors., Case Presentation: A 54-year-old woman presented to the respiratory outpatient clinic with gradually worsening left sided chest discomfort, which was most marked during a recent flight. She had no significant dyspnoea or other symptoms. She had a remote 5-pack-year smoking history. Chest X-Ray revealed a large hyperlucent area in the left upper lobe. CT Thorax found this to be an isolated bulla occupying more than one-third of the hemithorax. The remaining lung parenchyma was normal. A diagnosis of Idiopathic Giant Bullous Emphysema was made. The patient was referred for VATS (Video-assisted thoracoscopic surgery) bullectomy which was carried out without complication. Her symptoms resolved completely following the operation., Conclusions: This is an unusual case of a solitary giant bulla occurring without major risk factors or underlying lung disease. VATS bullectomy was shown to be an effective therapeutic option, allowing re-expansion of compressed lung tissue and complete resolution of symptoms., (© 2022. The Author(s).)

Sestrins (Sesns) are a family of highly conserved stress-inducible proteins and various stresses have been shown to strongly up-regulate them. Sestrin 2 (Sesn2) deficiency has been shown to partially suppress pulmonary emphysema. The aim of this study was to evaluate Sesn2 levels in COPD patients and its possible associations with the presence of emphysema and blood eosinophils. All patients underwent lung function testing and high-resolution computed tomography (HRCT) of the chest. The presence of emphysematous lesions in >15% of the pulmonary parenchyma was considered as significant emphysema. Sixty-seven patients were included in the study. 40/67 patients were characterized as having significant emphysema. Patients with significant emphysema had higher levels of Sesn2 (ng/ml) [median (IQR) 6.7 (2.7,10.3 vs 1.09 (0.9,1.9), p<0.001)] and significantly lower % and absolute blood eosinophil counts (cells/μL) compared to patients without emphysema [1 (0, 2) vs 4 (2, 4) p<0.001 and 62 (0, 110) vs 248 (180, 300), p<0.001 respectively]. Sesn2 presented a significant positive correlation to the score of emphysema in HRCT (rs = 0.87, p<0.001) and similar positive but weaker correlation to FRC (rs = 0.27, p = 0.024). Negative correlations were observed between Sesn2 and either the % of blood eosinophils and/or the absolute blood eosinophil count (rs = -0.79, p<0.001, and rs = -0.78, p<0.001 respectively). Sesn2 levels above 1.87 ng/ml showed a high diagnostic performance for the presence of significant emphysema in HRCT with an AUC 0.93, 95% CI (0.85,0.98), p<0.001. Sesn2 could serve as a potential biomarker of emphysema., Competing Interests: The authors have declared that no competing interests exist.

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: Oxidative stress is known to activate tumor suppressor p53, which inhibits cell cycle progression and induces apoptosis. Levels of p53 in lung tissues from patients with chronic obstructive pulmonary disease (COPD) are increased compared with levels in nonsmokers or smokers without emphysema. A polymorphism in p53 codon 72 (rs1042522) is associated with emphysematous changes in patients with COPD. However, whether oxidative stress in the serum is associated with the p53 polymorphism and disease severity in COPD patients is unclear., Patients and Methods: A total of 251 patients with a history of smoking more than 10 pack-years were enrolled in this study, and serum levels of derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and d-ROMs/BAP ratio (oxidative stress index; OSI) were measured. The percent low-attenuation area (LAA%) and cross-sectional area of the erector spinae muscles (ESM CSA ) at the Th 12 level were calculated from chest high-resolution computed tomography images. p53 codon 72 C/G genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis., Results: In patients carrying the p53 GG genotype, LAA% was significantly higher than in those carrying the CC genotype. d-ROM levels and OSI were associated with COPD severity and correlated with airflow limitation and markers of muscle atrophy (ESM CSA and creatinine/cystatin C ratio). Associations between markers of oxidative stress and COPD severity were observed primarily in patients carrying the p53 codon 72 GG genotype., Conclusion: Susceptibility to pulmonary emphysema and responses to oxidative stress may be affected by the p53 gene polymorphism., Competing Interests: The authors report no conflicts of interest in this work. The authors confirm that the data supporting the findings of this study are available within the article., (© 2022 Yamamura et al.)

Background: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism., Objective: To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD., Methods: GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed., Results: Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3 + GARP + Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3 + GARP - Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood., Conclusion: Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage., (© 2022. The Author(s).)

Aims and Objectives: Many patients with chronic obstructive lung disease suffer from emphysema. Valve implantation may be a reasonable method in patients presenting advanced emphysema and absent interlobar collateral ventilation (CV). However, other clinical parameters influencing the effectiveness of endoscopic lung volume reduction (ELVR) are not well known., Methods: COPD patients with advanced emphysema who received valve implantation in 2016 were retrospectively analyzed. The following characteristics were collected prior to valve implantation: age, sex, body mass index, presence of allergies, use of inhaled corticosteroids (ICS), lung function parameters, diffusion capacity, 6-minute walk distance (6-MWD), blood gases, COHb, smoking history, and emphysema index (quantitative multi-detector computed tomography). Three months following valve implantation, lung function parameters, diffusion capacity, 6-MWD and blood gases were measured. In this analysis, we evaluated the impact of these variables on an increase in FEV 1 and 6-MWT as well as a decrease in RV three months after valve implantation., Results: Overall, 77 COPD patients (57% male, mean age 66, mean FEV 1 32%, mean RV 259%) who underwent valve therapy were enrolled. At 3-month follow-up, patients experienced a mean FEV 1 increase of 0.09 ± 0.21 L, a mean RV decrease of 0.42 ± 1.80 L and a mean improvement of 8.3 ± 57 m in the 6-MWT. Overall, ICS, sex and emphysema index had an impact on the outcome following ELVR: ICS medication was associated with inferior FEV 1 outcome. The higher the emphysema index, the less the RV reduction. Sex was a predictor for change of FEV 1 (%), RV (L), and 6-MWT: male patients seem to benefit less than female patients from valve implantation., Conclusion: These findings suggest that ICS, emphysema index and sex are clinical parameters that may be associated with inferior outcome following ELVR. Further studies have to confirm these results to improve patient selection and clinical outcome of ELVR., Competing Interests: Prof. Dr. Ralf Eberhardt reports personal fees from Olympus and Pulmonx, outside the submitted work. Prof. Dr. Daniela Gompelmann reports personal fees from Pulmonx, Olympus, Böhringer Ingelheim, Novartis, Chiesi, Astra Zeneca, Berlin Chemie, and Grifols, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Polke et al.)

Background: Idiopathic lobar emphysema (ILE) and bronchopulmonary sequestration (BPS) are two of the well-characterized pulmonary malformations. Case report: An antenatally detected case of a left bronchopulmonary malformation (BPM) was clinicoradiologically diagnosed to be a left upper lobar emphysema with isolated dextrocardia in the neonatal period. Besides the emphysematous left upper lobe, an accessory lobe akin to an extra lobar BPS was an operative surprise. Histopathological examination of both excised lobes led to a revised diagnosis of a 'hybrid' malformation comprising lobar emphysema and extra lobar BPS. The postoperative recovery was uneventful. Discussion/conclusion: The observations suggest that BPS and ILE may be interim entities in a continuum of abnormal embryogenesis. Such a hybrid malformation has not been hitherto reported.

Introduction: Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue hydrolysis and lack specificity for those fibres undergoing breakdown. To address this limitation, free (nonpeptide-bound) DID content in unhydrolyzed tissues was evaluated as a more accurate biomarker in an animal model of pulmonary emphysema., Methods: Hamsters were treated with either cigarette smoke and lipopolysaccharide (LPS), room air and LPS, or room air alone (controls). Free DID levels in fresh and formalin-fixed lungs were measured by LC-MS/MS and correlated with the mean linear intercept (MLI) measure of airspace size., Results: There was no significant difference in free DID between fresh and formalin-fixed lungs. Animals treated with smoke and LPS had significantly higher levels of free DID than the LPS only group (359 vs. 93.1 ng/g wet lung, respectively; p  = 0.0012) and room air controls (undetectable levels; p  = 0.0002). There was a significant positive correlation between free DID and MLI ( p  < 0.0001)., Conclusions: The results support the hypothesis that free lung DID is a sensitive indicator of alveolar wall injury that may be used to study the development of pulmonary emphysema in both animal models and post-mortem human lung tissue.

Background: Alpha1-antitrypsin deficiency (AATD) is a genetic-based risk condition, mainly affecting the lungs and liver. Despite its wide distribution, it is largely underdiagnosed, thus being considered a rare disease, and is consequently managed in ad-hoc reference centers. Unfortunately, an easy-to-use algorithm for managing such a complex disease is still lacking., Methods: An expert consensus meeting was conducted among experts in the management of AATD to build a comprehensive algorithm, including diagnosis, monitoring, AAT therapy, rehabilitation and lung transplantation, and liver disease, that could serve as a guide for physicians and treating centers. A panel of AATD specialists evaluated the results of their work., Results: Diagnosis is the most delicate phase, and awareness about this condition should be raised among GPs. A set of recommendations has been written about the most suitable follow-up visits. Augmentation therapy with AAT may be useful to reduce the progression of emphysema and lung function decline in selected patients. Exercise capacity may be improved by pulmonary rehabilitation and, in selected cases, by lung volume reduction or lung transplantation. Support therapies are needed for those who develop liver disease, and, in selected cases, liver transplantation may be considered. Patients should be carefully educated about their lifestyle, including smoking cessation, body weight control, and reduced alcohol intake., Conclusions: The proposed algorithm obtained the endorsement of the Italian Society of Pneumology (SIP). However, further studies and additional clinical data are required to confirm the validity of these recommendations.

Background: The combination of pulmonary fibrosis and emphysema (CPFE) has been recently defined as a syndrome, it is radiologically recognized and is characterized by the simultaneous coexistence of emphysema of superior pulmonary location and fibrosis predominantly in lower lobes., Case Presentation: We present three patients with CPFE, who underwent right cardiac catheterization for pulmonary hemodynamic assessment, finding mean pulmonary artery pressure (mPAP) between 37-52 mm Hg (mean 45 mm Hg), who received treatment with specific vasodilators for pulmonary arterial hypertension (PAH)., Discussion and Conclusions: The three patients had higher mPAP than expected for Group III (Pulmonary hypertension due to lung disease and/or hypoxia) of the classification of pulmonary hypertension (PH) by the World Health Organization (WHO), in whom the use of Sildenafil was justified by the presence of progressive dyspnea, and no symptoms suggestive of infectious exacerbation associated with right ventricular failure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate the association between different smoking statuses and survival and emphysema in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)., Methods: This retrospective study included patients admitted from October 2014 to September 2017. Demographic, clinical, laboratory, imaging, impulse oscillometry, and traditional pulmonary function data were collected. The relationship between smoking and EI was analyzed via binary logistic regression after adjusting for other factors. Survival was analyzed using the Kaplan-Meier method and the log rank test., Results: The patients with AECOPD (357 cases) were identified (and stratified into three groups: never smoked (NS; n=83), former smokers (FS, n=118), and current smokers (CS; n=156). Compared with CS, NS were older and predominantly female. No differences were observed in respiratory symptoms and acute exacerbation between CS and NS. NS had higher resistance and reaction in the central and peripheral airways, while CS exhibited more severe diffuse dysfunction. CS demonstrated more severe and extensive emphysema. Smoking was an independent risk factor for emphysema after adjusting for age, forced expiratory volume in the first second over predicted value, BMI, leukocyte count, and carbon monoxide transfer coefficient. No difference in 5-year survival rates between NS and CS was established., Conclusion: CS has the worst pulmonary function, suggesting a more important destruction of the lung parenchyma, while AECOPD without smoking risk factors mostly affects the airways. Impulse oscillometry can be used for imaging airway-dominant AECOPD. There was no difference in the 5-year survival rate., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Ding et al.)

Congenital pulmonary malformations comprise a heterogenous group of rare developmental diseases. The most common malformations are the tracheal bronchus, bronchial atresia, bronchogenic cyst, pulmonary sequestration, congenital lobar emphysema, and congenital pulmonary airway malformation. Due to their space-consuming effect, patients suffer early postnatal respiratory distress which generally requires immediate surgical resection. The management of asymptomatic lesions remains subject to debate, but early elective surgery is generally recommended to avoid respiratory and infectious complications at a later time point.We here provide a comprehensive review in which we present causes, clinical presentation and therapeutic options for the most prominent congenital malformations of the airways and lung parenchyma., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: There is a strong need for biomarkers to better characterize individuals with COPD and to take into account the heterogeneity of COPD. The blood protein sRAGE has been put forward as promising biomarker for COPD in general and emphysema in particular. Here, we measured plasma sRAGE levels using quantitative LC-MS and assessed whether the plasma sRAGE levels associate with (changes in) lung function, radiological emphysema parameters, and radiological subtypes of emphysema., Methods: Three hundred and twenty-four COPD patients (mean FEV 1 : 63%predicted) and 185 healthy controls from the COPDGene study were selected. Plasma sRAGE was measured by immunoprecipitation in 96-well plate methodology to enrich sRAGE, followed by targeted quantitative liquid chromatography-mass spectrometry. Spirometry and HRCT scans (inspiration and expiration) with a 5-year follow-up were used; both subjected to high quality control standards., Results: Lower sRAGE values significantly associated with the presence of COPD, the severity of airflow obstruction, the severity of emphysema on HRCT, the heterogeneous distribution of emphysema, centrilobular emphysema, and 5-year progression of emphysema. However, sRAGE values did not associate with airway wall thickness or paraseptal emphysema., Conclusions: Rather than being a general COPD biomarker, sRAGE is especially a promising biomarker for centrilobular emphysema. Follow-up studies should elucidate whether sRAGE can be used as a biomarker for other COPD phenotypes as well., (© 2022. The Author(s).)