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Small extracellular vesicles (sEVs) are a group of cell-secreted nanovesicles with a diameter up to 200 nm. A growing number of studies have indicated that sEVs can reflect the pathogenesis of human diseases and mediate intercellular communications. Recently, sEV research has drastically increased due to their drug delivery property. However, a comprehensive method of delivering exogenous small RNAs-loaded sEVs through nebulization has not been reported. The methodology is complicated by uncertainty regarding the integrity of sEVs after nebulization, the delivery efficiency of aerosolized sEVs, their deposition in the lungs/cells, etc. This study demonstrates that sEVs can be delivered to murine lungs through a vibrating mesh nebulizer (VMN). In vivo sEV tracking indicated that inhaled sEVs were distributed exclusively in the lung and localized primarily in lung macrophages and airway epithelial cells. Additionally, sEVs loaded with small RNAs were successfully delivered into the lungs. The administration of siMyd88-loaded sEVs through inhalation reduced lipopolysaccharide (LPS)-induced lung injury in mice, supporting an application of this nebulization methodology to deliver functional small RNAs. Collectively, our study proposes a novel method of sEVs-mediated small RNA delivery into the murine lung through nebulization and presents a potential sEV-based therapeutic strategy for human lung diseases.

The circadian clock is the biochemical oscillator that orchestrates the observable circadian rhythms in physiology and behavior. Disruption of the circadian clock in the lungs during chronic pulmonary diseases is considered one of the key etiological risk factors that drive pathobiology. Preclinical studies support that pharmacological manipulation of the circadian clock is a conceivable approach for the development of novel clock-based therapeutics. Despite recent advances, no effort has been undertaken to integrate novel findings for the treatment and management of chronic lung diseases. We, therefore, recognize the need to discuss the candidate clock genes that can be potentially targeted for therapeutic intervention. Here, we aim to create the first roadmap that will advance the development of circadian- clock-based therapeutics that may provide better outcomes in treating chronic pulmonary diseases.

ObjectivesTo describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.MethodsA systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.ResultsMost studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).ConclusionOur data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation. Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 10 0,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

This study investigated induction of pulmonary capillary hemorrhage (PCH) in neonatal pigs (piglets) using three different machines: a GE Venue R1 point-of-care system with C1-5 and L4-12t probes, a GE Vivid 7 Dimension with a 7L probe and a SuperSonic Imagine machine with an SL15-4 probe and shear wave elastography (SWE). Female piglets were anesthetized, and each was mounted vertically in a warm bath for scanning at two or three intercostal spaces. After aiming at an innocuous output, the power was raised for a test exposure. Hydrophone measurements were used to calculate in situ values of mechanical index (MI

Occupational lung diseases (OLDs) encompass a broad group of entities related to the inhalation of a variety of agents in the workplace. OLDs may affect the lung parenchyma, pleura, and/or airways. OLDs can pose a diagnostic challenge for radiologists due to a lack of exposure history and overlap in imaging findings with nonoccupational-related entities. For this reason, it is important for the radiologist to be familiar with the high-resolution computed tomography patterns associated with OLDs and consider OLDs when formulating a differential.

Electronic cigarettes (e-cigarettes) are battery-powered devices that use heat to aerosolize a liquid containing a variety of substances (usually nicotine and/or cannabinoids, flavorings, and glycerol or propylene glycol base) that is then inhaled. E-cigarettes are rapidly evolving over time, so the true health effects of e-cigarettes are difficult to study and remain largely unknown. We review the effects of e-cigarettes on nicotine addiction and on pulmonary disease including the effects of dual use and switching from combustible cigarettes to e-cigarettes. Studies show that e-cigarette use can increase the risk to nicotine dependence and combustible tobacco use. Studies show an association between e-cigarette use and pulmonary disease. Some studies suggest reduced harm from e-cigarette use compared with smoking, but this requires further study. Most adults who use e-cigarettes also smoke cigarettes; epidemiologic studies suggest that the combination of e-cigarettes and cigarettes is more harmful than using either product alone.

Prognostic prediction of nontuberculous mycobacteria pulmonary disease using a deep learning technique has not been attempted.Can a deep learning (DL) model using chest radiography predict the prognosis of nontuberculous mycobacteria pulmonary disease?Patients who received a diagnosis of nontuberculous mycobacteria pulmonary disease at Seoul National University Hospital (training and validation dataset) between January 2000 and December 2015 and at Seoul Metropolitan Government-Boramae Medical Center (test dataset) between January 2006 and December 2015 were included. We trained DL models to predict the 3-, 5-, and 10-year overall mortality using baseline chest radiographs at diagnosis. We tested the predictability for the corresponding mortality using only DL-driven radiographic scores and using both radiographic scores and clinical information (age, sex, BMI, and mycobacterial species).The datasets comprised 1,638 (training and validation set) and 566 (test set) chest radiographs from 1,034 and 200 patients, respectively. The Dl-driven radiographic score provided areas under the receiver operating characteristic curve (AUC) of 0.844, 0.781, and 0.792 for 10-, 5-, and 3-year mortality, respectively. The logistic regression model using both the radiographic score and clinical information provided AUCs of 0.922, 0.942, and 0.865 for the 10-, 5, and 3-year mortality, respectively.The DL model we developed could predict the mid-term to-long-term mortality of patients with nontuberculous mycobacteria pulmonary disease using a baseline radiograph at diagnosis, and the predictability increased with clinical information.

The purpose of this study is to compare the clinical characteristics and surgical outcomes of thoracotomy and video-assisted thoracoscopic surgery (VATS) in children with congenital lung malformations (CLMs) in a tertiary referring center and to report our modified biportal VATS setting.This is a single-center retrospective chart review study including children who underwent surgical resection for CLMs between January 2007 and December 2020. Patient characteristics and surgical outcomes were compared between open and thoracoscopy, as well as conventional VATS and biportal VATS. Biportal setting included an anterior utility wound and a camera trocar wound with one-lung ventilation.A total of 100 patients were identified. Twenty patients received thoracotomy, and 80 patients received VATS (67 conventional and 13 biportal VATS). The median age at operation was 0.4 months in the thoracotomy group and 4.7 months in the VATS group. More patients in the thoracotomy group had preoperative symptoms, comorbidities, and emergent operations. The patients who underwent thoracotomy had significantly longer postoperative ICU stays, chest tube durations, hospital stays, and more complications. The pathological analysis revealed 67 congenital pulmonary airway malformations, 27 pulmonary sequestration, 6 hybrid lesions, and one accompanying pleuropulmonary blastoma. Compared to conventional VATS, the ICU stay was shorter in the biportal VATS group, with comparable operative durations, hospital stay and complications.VATS for CLMs is associated with better postoperative recovery and fewer complications. Biportal VATS is also a safe and feasible approach.

In the treatment of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD), pulmonary rehabilitation (PR) has been recommended as a non-pharmacological therapy. However, no study has validated the combination of chemotherapy and PR in this context. This study investigated the effect of chemotherapy and supervised PR on health-related quality of life (HRQoL) and physical function in NTM-PD patients.This prospective cohort study included patients diagnosed with NTM-PD who had a planned hospitalization of at least 3 weeks for chemotherapy and PR. HRQoL (Leicester Cough Questionnaire [LCQ] and chronic obstructive pulmonary disease assessment test [CAT]), physical function (incremental shuttle walk distance [ISWD], quadriceps force), and C-reactive protein levels were assessed before and after treatment, and the corresponding data were analyzed in conjunction with clinical data. The adverse events of PR were also investigated.Forty-two patients who met the study criteria were included in the analysis. After treatment, all LCQ item scores, total CAT score and sub-item scores related to respiratory symptoms, ISWD, quadriceps force, and C-reactive protein levels were found to have improved significantly. In the chronic cough with excessive sputum production (CCS) group, the proportions of responders who showed improvements in LCQ and CAT scores and ISWD greater than the corresponding minimal clinically important difference were significantly greater than those in the non-CCS group. No PR-related adverse events were reported.Combined treatment with chemotherapy and PR may improve HRQoL and physical function, and supervised PR can be provided safely.

Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25-45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied. Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance. Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.

Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

Pulmonary disease in low- and middle-income countries is highly diverse and dependent on the population, background epidemiology, environmental exposures, and smoking status. Credible evaluation of lung diseases requires skilled clinicians, imaging infrastructure, microbiology, and pathologic diagnostics, including imaging-guided cytology and biopsy. When these tools are available, improvement in patient outcomes is feasible. Pathologic diagnostics of lung lesions, including histology, immunohistochemistry, and molecular testing, are critical to properly stratify patient risk and determine exact therapies for each patient. A critical focus on research and directed interventions in lung cancer treatment specifically is needed to downstage this disease and improve patient outcome.

In the emergency department, there are infrequent but essential procedures related to pulmonary diseases that emergency physicians must be able to perform. These include thoracentesis, chest tube thoracostomy, tracheostomy manipulation, and fiberoptic intubation.

Postoperative pulmonary complications (PPC) remain a main issue after cardiac surgery. The objective was to report the incidence and identify risk factors of PPC after cardiac surgery. An international multicenter prospective study (42 international centers in 9 countries). A total of 707 adult patients who underwent cardiac surgery under cardiopulmonary bypass. None MEASUREMENTS AND MAIN RESULTS: During a study period of 2 weeks, the investigators included all patients in their respective centers and screened for PPCs. PPC was defined as the occurrence of at least 1 pulmonary complication among the following: atelectasis, pleural effusion, respiratory failure, respiratory infection, pneumothorax, bronchospasm, or aspiration pneumonitis. Among 676 analyzed patients, 373 patients presented with a PPC (55%). The presence of PPC was significantly associated with a longer intensive care length of stay and hospital length of stay. One hundred ninety (64%) patients were not intraoperatively ventilated during cardiopulmonary bypass. Ventilation settings were similar regarding tidal volume, respiratory rate, inspired oxygen. In the regression model, age, the Euroscore II, chronic obstructive pulmonary disease, preoxygenation modality, intraoperative positive end-expiratory pressure, the absence of pre- cardiopulmonary bypass ventilation, the absence of lung recruitment, and the neuromuscular blockade were associated with PPC occurrence. Both individual risk factors and ventilatory settings were shown to explain the high level of PPCs. These findings require further investigations to assess a bundle strategy for optimal ventilation strategy to decrease PPC incidence.

Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH) are cystic lung diseases in which a neoplastic cell is thought to be responsible for disease pathogenesis. The neoplastic LAM cell has mutations in the TSC genes, TSC1 or TSC2, whereas the neoplastic PLCH cell may have mutations in several genes (eg, BRAF, NRAS, MAP2K1). These mutations are not specific for PLCH and have been described in multiple cancers. TSC1 or TSC2 mutations and loss of heterozygosity (LOH) have also been described in cancers.Is TSC2 LOH specific to LAM or is it also found in PLCH?We recruited patients with LAM (n = 53) and healthy volunteers (n = 22) and compared the presence of cells with TSC2 LOH with patients with PLCH (n = 12). Blood and urine samples were collected for analysis. Fluorescence-activated cell sorting (FACS) was used to identify subpopulations of cells from blood and urine samples. We isolated CD45-CD235a-, CD45-CD235a+, and CD45+CD235a- cells from blood after density gradient separation. Cells were screened for TSC2 LOH at five microsatellites markers (ie, kg8, D16S3395, D16S3024, D16S521, D16S291). We obtained four cell subpopulations from urine (ie, CD44v6+CD9+, CD44v6+CD9-, CD44v6-CD9+, CD44v6-CD9-).Using FACS, cells were isolated from blood and urine from patients with PLCH that showed TSC2 LOH. Healthy volunteers did not have cells with TSC2 LOH. As a control, cells isolated from blood and urine from patients with LAM gave results similar to those reported previously. These data show that TSC2 LOH is found in patients with cystic lung diseases with potential neoplastic characteristics, and in patients with cancer.The presence of TSC2 LOH in circulating cells is not specific for LAM. The data suggest that chromosomal abnormalities affecting the TSC2 gene are found in other diseases associated with cells having cancer-like neoplastic cells.

Retrospective performance evaluation of a computer-aided detection (CAD) system on standard posteroanterior (PA) chest radiographs (PA-CXR) in detection of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly and rib fractures compared to radiologists analyzing PA-CXR including dual-energy subtraction radiography (further termed as DESR).PA-CXR/DESR images of 197 patients were included. All patients underwent chest CT (gold standard) within a short interval (mean 28 hours). All images were evaluated by three blinded readers for the presence of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly, and rib fractures. Meanwhile PA-CXR were analyzed by a CAD software. CAD results were compared to the majority result of the three readers. Sensitivity and specificity were calculated. McNemar's test was applied to test for significant differences. Interobserver agreement was defined using Cohen's kappa (κ).Sensitivity of the CAD software was significantly higher (p0.05) for detection of infectious consolidation and pulmonary nodules (67.9% vs 26.8% and 54% vs 35.6%, respectively; p0.001) compared to radiologists analyzing DESR images. For the residual evaluated pathologies no statistical significant differences could be found. Overall, mean inter observer agreement between the three radiologists was moderate (k = 0.534). The best interobserver agreement could be reached for pneumothorax (k = 0.708) and pleural effusion (k = 0.699), while the worst was obtained for rib fractures (k = 0.412).The CAD system has the potential to improve the detection of infectious consolidation and pulmonary nodules on CXR images.

Conventional open surgery is still important beside endovascular surgery in the management of abdominal aortic aneurysms, with less reinterventions in the long-term follow-up. Incisional hernias are the major complication open surgery in the mid- and long term. The occurrence of this late complication could be due to the choice of the incision, median or transverse. The objectives of our retrospective and bicentric study were to characterize the long-term risk factors for incisional hernias after open surgery for abdominal aortic aneurysms, in particular by comparing the 2 types of laparotomy, and to determine the prevalence of the operated and not operated incisional hernias.Between January 2009 and December 2011, all the patients having elective open surgery for abdominal aortic aneurysm (AAA) by midline laparotomy at the University hospital of Besancon or by transversal laparotomy at the University Hospital of Strasbourg were included retrospectively. The demographic data, the time of diagnosis of the incisional hernia and the parietal reinterventions were collected during a 5-year postoperative follow-up. A univariate and multivariate Cox model was used for the statistical analysis to determine the long-term risk factors for the appearance of an incisional hernia.During the study period, 223 patients presenting with AAA were included, 112 of them were operated by a midline laparotomy and 111 by a transverse laparotomy. The mean age of the patients was 69 ± 8,4years and 208 (93.3%) were men. The 5-year prevalence of incisional hernias was 14.3% (32), and 20 of these hernias (9%) had to be operated. Eighteen hernias (16.1%) occurred after a midline laparotomy and 14 (12.6%) after a transverse incision (P = 0.30). In univariate analysis, obstructive chronic pulmonary disease was the only significant risk factor for incisional hernia (P = 0.01) and an age over 65 years appeared to protect against this risk (P = 0.049). These results were confirmed by multivariate analysis, which showed that obstructive chronic pulmonary disease was an independent risk factor for incisional hernia (HR = 2.35, 95% CI 1.16-4.75), and that an age over 65 years was a protective factor (HR = 0.49 95% IC 0.00-0.99).The type of laparotomy did not modify the rate of incisional hernias. We showed that only 9% of the patients had to be operated to treat an incisional hernia during the first 5 years after surgery for AAA in our bicentric study. Chronic obstructive pulmonary disease was the only independent risk factor for the occurrence of an incisional hernia.

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of recurrent episodes of diffuse alveolar hemorrhage (DAH). IPH commonly manifests with hemoptysis, radiologic chest infiltrates and anemia. The etiology of IPH is unknown, but an immunologic mechanism is widely speculated. The definitive diagnosis of IPH requires a thorough exclusion of other causes of DAH, such as infections, inflammation, malignancy, cardiac diseases, drug and toxin exposure, and medications. Due to the rarity of the disease, a diagnosis is often delayed by years. We present the case of a 49-year-old man with ischemic cardiomyopathy who presented with hemoptysis for eighteen months. Serologic workup was negative for vasculitides and autoimmune diseases. Bronchoscopy revealed DAH. A surgical lung biopsy showed 'bland pulmonary hemorrhage.' A right heart catheterization ruled out cardiac causes of DAH. The patient was diagnosed with IPH and started on systemic corticosteroids with rapid improvement of hemoptysis.

Summary Background Pediatric thoracoscopic lobectomy is a technically challenging procedure that may result in better pain control, better cosmetic results, and shorter hospital stay. However, data describing the learning curve of total thoracoscopic lobectomy (TTL) have yet to be obtained. To evaluate our learning curve for TTL in children, we reviewed the safety and efficiency of our initial experiences with TTL in pediatric patients with congenital lung malformation. Methods This was a retrospective study of all pediatric patients undergoing TTL between March 2011 and January 2017. Cumulative summation (CUSUM) analysis of operative time (OT) was used. Results One hundred patients were retrospectively analyzed and chronologically divided into three phases: the ascending (A), plateau (B), and descending (C) phases of CUSUM of OT. Phases A, B, and C comprised 35, 22, and 43 cases, respectively. OT decreased significantly from phases A to B (P = 0.035) and B to C (P = 0.019). Age and weight of patients both reduced significantly from phase A to B (p = 0.017 and p = 0.012, respectively), while the two measures did not vary from phase B to C (p = 0.987 and p = 0.874, respectively). Chest tube duration and length of hospital stay had similar trend. All complications occurred in five cases in phase A (5/35). Six cases were converted to open surgery (6%). Four conversions occurred within phase A and two in phase C (4/35 vs 2/43, p = 0.490). There were no mortalities. Conclusions Repeated standardized training plays a role in overcoming the learning curve for thoracoscopic lobectomy in children, and CUSUMOT indicates that a learning curve of approximately 57 cases is required in our institute.

Aortic dissection is a rare but well-known life-threatening disease that classically presents with tearing chest pain radiating to the back yet can have deceiving clinical presentations.A 54-year-old man with a history of hypertension presented to the emergency department with mild shortness of breath without chest pain. Point-of-care ultrasound (POCUS) detected diffuse B-lines, a dilated aortic root, aortic regurgitation, and pericardial effusion. A computed tomography angiogram confirmed a Stanford type A aortic dissection with diffuse alveolar hemorrhage (DAH), a rare complication of type A aortic dissection involving the posterior aortic wall with extension into the main pulmonary artery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Acute aortic dissection can present with a wide range of clinical manifestations with a high mortality rate for patients with an untimely diagnosis. Although an intimal flap within the aortic lumen is the characteristic finding on ultrasound, additional POCUS findings of a pericardial effusion, aortic regurgitation, and a dilated aortic root may be seen with proximal dissections. Diffuse B-lines on thoracic POCUS, although commonly associated with pulmonary edema in decompensated heart failure, can be seen in patients with DAH which has a multitude of etiologies, including aortic dissection.

Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae constitute nontuberculous mycobacteria (NTM). NTM infections are on the rise, particularly in the Western world. They cause a wide range of pulmonary and systemic manifestations. The 2 most common types are as follows: classical cavitary type, seen with preexisting lung disease, and the nonclassical bronchiectatic type, seen in elderly women without preexisting lung disease. Disseminated infections by the hematogenous route are common in immunocompromised patients including those with HIV. Imaging plays a key role in the diagnosis and monitoring of NTM infection.

The benefit of elective resection of congenital lung malformations continues to be debated. Proponents of resection endorse a decreased risk of respiratory complications as one indication for surgery. Our study aimed to compare the prevalence of respiratory infections in cases, before and after resection of congenital lung malformations, to controls without a history of congenital lung malformation.We performed a retrospective cohort study of children born from 1991 to 2007 who underwent congenital lung malformation resection. Patients were identified from Winnipeg´s Surgical Database of Outcomes and Management (WiSDOM), and a 10:1 date-of-birth matched control group was generated from a population-based administrative data repository. International Classification of Disease codes were used to assess pulmonary infection outcomes. Relative rates (RR) were calculated to compare the frequency of pneumonia, respiratory infections and influenza between cases and controls.We included 31 congenital lung malformation cases and 310 controls. Cases consisted of 14 (45.16%) congenital pulmonary airway malformations, 9 (29.03%) bronchopulmonary sequestrations and 8 (25.81%) hybrid lesions. Before resection, pneumonia was more common in cases than controls (RR 6.85; 95%CI 3.89, 11.9), while the risk of acute respiratory infections (RR 1.21; 95%CI 0.79, 1.79) and influenza (RR 0.46; 95%CI 0.01, 3.22) were similar to controls. Post-resection, the risk of pneumonia (RR 9.75; 5.06, 18.50) was still higher in cases than controls, and respiratory infections (RR 1.77; 95%CI 1.20, 2.53) and influenza (RR 3.98; 95%CI 1.48, 9.36) were more common in cases than controls.Our study demonstrated that after resection of congenital lung malformations, children experience more frequent respiratory infections compared to the general population. Resection does not eliminate the increased risk of pneumonia.

Traumatic brain injury (TBI) is a risk factor for venous thromboembolism (VTE). The risk of VTE after decompressive craniectomy (DC) and its effects on the outcomes are unknown. We assessed the incidence of VTE, associated risk factors, and effects on the outcomes.Using the National Inpatient Sample database, the hospitalizations of patients aged ≥18 years with a severe TBI diagnosis from 2004 to 2014 were extracted. The outcome was discharge status without mortality. Multivariable logistic and linear regressions were used.Of the 349,165 TBI hospitalizations, 23,813 (6.82%) had undergone DC and 14,175 (4.06%) had developed VTE. The VTE incidence was higher after DC compared with no DC (6.14% vs. 3.91%; P0.0001). DC (odds ratio [OR], 1.29; P0.005) was an independent predictor for the development of VTE. Age (OR, 1.26; P0.005), chronic lung disease (OR, 1.58; P0.05), electrolyte imbalance (OR, 1.43; P0.05), liver disease (OR, 0.10; P0.05), urinary tract infection (OR, 1.56; P0.05), pneumonia (OR, 2.03; P0.0001), and sepsis (OR, 1.57; P0.05) were significantly associated with the development of VTE. Obesity (OR, 2.09; P0.05) and spine injury (OR, 2.03; P0.05) showed a trend toward significance. VTE was associated with worse discharge outcomes (OR, 1.40; P0.05), longer lengths of stay (OR, 1.01; P0.00001), and higher costs (P0.0001).Our study showed an independent association between DC and an increased risk of VTE for patients with severe TBI. The development of VTE after DC increased the proportion of poor outcomes, prolonged the length of stay, and increased the hospitalization costs. Older patients with obesity, an electrolyte imbalance, chronic lung disease, spine injury, and infections were at a greater risk of VTE after DC. These risk factors could help in considering VTE prophylaxis for these patients.

Patients with lymphangioleiomyomatosis (LAM) frequently experience delays in diagnosis, owing partly to the delayed characterization of imaging findings. This project aimed to develop a machine learning model to distinguish LAM from other diffuse cystic lung diseases (DCLDs). Computed tomography scans from patients with confirmed DCLDs were acquired from registry datasets and a recurrent convolutional neural network was trained for their classification. The final model provided sensitivity and specificity of 85% and 92%, respectively, for LAM, similar to the historical metrics of 88% and 97%, respectively, by experts. The proof-of-concept work holds promise as a clinically useful tool to assist in recognizing LAM.

BACKGROUND Postoperative prolonged air leakage is a frequent complication after lung resection. We have developed a new sealant based on a hydrophobically modified Alaska pollock-derived gelatin (ApGltn) sealant. The purpose of this study was to evaluate the adhesive strength of the ApGltn sealant in comparison with a fibrin sealant using a new spray system in ex vivo and in vivo models. METHODS Pleural defects in ex vivo and in vivo porcine models were created, to which the ApGltn sealant or the fibrin sealant was applied. The pressure resistance was assessed with a stepwise increase in airway pressure to confirm air leakage from the sealing site. Tissue samples covered with each sealant were obtained for histologic assessment. RESULTS In the ex vivo experiment, the leak pressures of the ApGltn sealant were significantly greater than those of the fibrin sealant (102.94 ± 15.6 cm H2O and 28.37 ± 5.1 cm H2O, respectively) (P < .01). In the in vivo experiment, the leak pressures of the ApGltn sealant were also significantly greater than those of the fibrin sealant (68.82 ± 18.04 cm H2O and 43.33 ± 7.13 cm H2O, respectively) (P = .043). The histologic examination confirmed that the ApGltn sealant adhered tightly to both the pleura and the surface of the pleural defect. CONCLUSIONS The ApGltn sealant has sufficiently high adhesive quality in ex vivo and in vivo porcine lungs, which could be considered suitable and effective for use in the prevention of air leakage from the lungs.

Postoperative pulmonary complications are a common cause of postoperative morbidity in patients undergoing hepatectomy. This study aimed to identify risk factors, define severity, and evaluate the impact of postoperative pulmonary complications on postoperative morbidity after hepatectomy.We used a prospective database in identifying all hepatectomies from 2013 to 2018. The database was then augmented using extensive review of medical records. The Strasburg system was used in categorizing resections per complexity: major hepatic resection and minor hepatic resection, whereas the Clavien-Dindo system was used in defining postoperative pulmonary complications per severity. Potential confounders were controlled for on multiple regression models.A total of 702 cases were identified: major hepatic resection 413 (60%) and minor hepatic resection 289 (40%). Patients demonstrated comparable characteristics, but the postoperative pulmonary complications group was more likely to have chronic obstructive pulmonary disease (10% vs 5%; P = .02). Severe postoperative pulmonary complications among major hepatectomy was observed in 38 patients (13%). Predictors for severe postoperative pulmonary complications requiring intervention included postoperative liver failure (odds ratio = 2.8; P = .002) and biliary fistula (odds ratio = 3.5; P = .001). In addition, the occurrence of severe postoperative pulmonary complications markedly hindered recovery, increasing length of stay by 4.4-fold and readmission rates by 3-fold (P.001). On multivariable analysis, postoperative pulmonary complications significantly increase postoperative length of stay (8 vs 5 days; P.001) and readmission (odds ratio = 3.2; P = .001). Mortality was similar (1% vs 4%; P = .066).Postoperative pulmonary complications are a major cause of delayed recovery and worse outcomes after hepatectomy. Further, postoperative liver failure and biliary fistula can predict the occurrence of severe postoperative pulmonary complications among major hepatic resection and the associated need for readmission with these complications.

Objectives: The aim of this study was to determine and compare the efficacy of drugs to treat Mycobacterium kansasii (Mkn) pulmonary disease by performing minimum inhibitory concentration (MIC) determination and time–kill studies. Methods: We determined the MICs to 13 drugs against the Mkn standard laboratory strain ATCC 12478 and 20 clinical isolates and performed time–kill studies with 18 drugs from different classes using the standard laboratory strain of Mkn. The β-lactam antibiotics were tested with or without the combination of the β-lactamase inhibitor avibactam. An inhibitory sigmoid Emax model was used to describe the relationship between drug concentrations and bacterial burden. Results: Among the 13 tested drugs in the MIC experiments, the lowest MIC was recorded for bedaquiline. Among the 18 drugs used in the time–kill studies, maximum kill with cefdinir, tebipenem, clarithromycin, azithromycin, moxifloxacin, levofloxacin, tedizolid, bedaquiline, pretomanid and telacebac was greater than that for some of the drugs (isoniazid, rifampicin and ethambutol) used in standard combination therapy. Conclusion: We report preclinical data on the efficacy and potency of drugs that can potentially be repurposed to create a safe, effective and likely shorter-duration regimen for the treatment of Mkn pulmonary disease.

Background The effect of chronic sputum (CS) symptoms on health-related quality of life (HRQOL) in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been studied. The aim of this study was to clarify the differences in the clinical characteristics of NTM-PD patients with and without CS and to investigate the effect of CS on HRQOL. Methods This cross-sectional study included patients with NTM-PD who were prescribed pulmonary rehabilitation at the Fukujuji Hospital from March 2016 to June 2019. HRQOL was evaluated using the MOS 36-Item Short-Form Health Survey (SF-36). Results Of the 99 subjects studied, 71 had CS (CS+) (71.7%), and 28 (28.3%) did not have CS (CS-). Patients in the CS + group had a lower body mass index, forced vital capacity percent predicted, and forced expiratory volume in 1 s percent predicted. Regarding the radiological evaluation, the proportion of patients with the fibrocavitary form and the radiological score were significantly higher in the CS + group. The mental component summary (MCS) score of the SF-36 were significantly lower in the CS + group. Multiple regression analysis showed that the presence of CS was independently associated with a lower MCS score of the SF-36. Conclusions NTM-PD patients with CS had more severe disease, with reduced pulmonary function and severe radiological findings. CS was shown to independently affect HRQOL, especially mental status.

Background Strict isolation precautions limit formal echocardiogram use in the setting of COVID-19 infection. Information on the importance of the utilization of a hand-held focused ultrasound for cardiac evaluation in these patients is scarce. This study investigated the utility of a hand-held echocardiogram device in COVID-19 hospitalized patients in diagnosing cardiac pathologies and predicting the composite endpoint of in-hospital death, mechanical ventilation, shock, and acute decompensated heart failure. Methods From April 28th through July 27th, 2020, consecutive patients diagnosed with COVID-19 underwent evaluation using a hand-held ultrasound (Vscan Extend™ with Dual Probe; GE Healthcare) within 48-h of admission. The patients were divided into two groups: 'Normal' and 'Abnormal' (as defined by biventricular systolic dysfunction/enlargement, or moderate/severe valvular regurgitation/stenosis) echocardiogram study. Results Among 102 patients, 26 (25.5%) had an abnormal study. They were older, with more co-morbidities, and more severe presenting symptoms, as compared to the group with a normal echocardiogram. The prevalence of the composite outcome among low- and high-risk patients (oxygen saturation

Background Pulmonary artery sling (PAS) is usually associated with long-segment congenital tracheal stenosis (LSCTS). This combination of abnormalities can also be associated with lung hypoplasia abnormalities (hypoplasia, aplasia, or agenesis). This study analyzed the association of lung hypoplasia abnormalities with combined PAS and LSCTS and its influence on its surgical outcomes. Methods All patients (0 to 18 years) who underwent surgical procedures for both PAS and LSCTS from 1995 to 2019 were analyzed retrospectively for mortality, ventilation days, and intensive care unit days by dividing them into those with normal lungs (group 1) and hypoplastic lungs (group 2). Results Included were 75 patients (30 girls [40%]), who were a median age of 5.7 months (interquartile range [IQR], 2.9-13.3 months), median weight of 5.5 kg (IQR, 4.1-7.9 kg), and had a median follow-up of 99.8 months (IQR, 54.5-152.0 months); of these, 8 patients (10.7%) had hypoplastic right lung, comprising hypoplasia in 7 (87.5%), aplasia in 1 (12.5%), and agenesis in 0 (0%). There was a significant difference in mortality (group 1, 9.0%; group 2, 50%; P = .007) but no significant difference in median ventilation days (group 1, 9.0; group 2, 9.0; P = .89) or in median intensive care unit days (group 1, 14.0; group 2, 11.5; P = .44). Conclusions Lung hypoplasia associated with PAS and LSCTS is usually right-sided. As a result of severe airway obstruction and single-lung physiology, there is a high requirement of preoperative cardiorespiratory support and a significant association with adverse surgical outcomes.

Heart-lung transplantation has historically been used as a definitive treatment for children with end-stage cardiopulmonary failure, although the number performed has steadily decreased over time. In this review, we discuss current indications, preoperative risk factors, outcomes, and heart-lung transplantation in unique patient subsets, including infants, children with single-ventricle physiology, tetralogy of Fallot/major aortopulmonary collateral arteries, and prior Potts shunt palliation. We also describe the different surgical techniques utilized in pediatric heart-lung transplantation.

Noninvasive ventilation (NIV) provides respiratory support without the use of invasive ventilation with techniques that do not bypass the upper airway. NIV is particularly attractive given its associated reduced risk of complications associated with intubation. Available NIV modes include nasal cannula, simple mask, nonrebreather, high flow nasal cannula, continuous positive airway pressure (CPAP), and bilevel positive airway pressure. Acute exacerbation of COPD, cardiogenic pulmonary edema, and COVID-19 are conditions for which NIV has shown to be beneficial, whereas there is no consensus among the use of NIV in trauma patients and ARDS.

The many socioeconomic disparities in the myriad of diagnoses that make up benign lung diseases are unfortunately a global issue that was most recently highlighted by the COVID-19 pandemic of 2020. In this chapter, we will be reviewing the socioeconomic disparities in benign lung disease from both a United States perspective as well as a global perspective. We will cover the spectrum of infectious, obstructive, and restrictive lung disease and review the evidence on how social disparities affect these populations and their access to medical care.

Patients with advanced lung disease can develop pulmonary hypertension and succumb to right ventricular failure/cor pulmonale. Patients with pulmonary hypertension owing to chronic lung disease, or World Health Organization group 3 pulmonary hypertension, are more limited and carry a high risk of mortality. Adjunctive therapies remain the cornerstones of treatment. Recent evidence suggests that inhaled pulmonary vasodilator therapy can be helpful in patients with pulmonary hypertension owing to interstitial lung disease. Lung transplantation may be the only life-saving option in select patients, whereas palliative care and hospice should be sought for those who are not candidates as the disease progresses.

Background Chronic lung allograft dysfunction in lung transplant recipients (LTxRs) has 2 phenotypes: obstructive bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Our goal was to define distinct immunologic markers of exosomes from LTxRs with BOS or RAS. Methods Plasma was collected from LTxRs with BOS (n = 18), RAS (n = 13), and from stable LTxRs (n = 5). Antibodies to lung self-antigens (SAgs) were determined by ELISA. Exosomes were isolated by ultracentrifugation. Donor specific antibodies to HLA were quantified using Luminex. Exosomes were characterized for lung SAgs, transcription factors, 20S proteasome, HLA class I and II, and polymeric immunoglobulin receptor protein using western blot. Exosome miRNA was analyzed using NanoString. The exosome-induced immune response was determined in mice. Results LTxRs with RAS, but not BOS, had donor specific antibodies at diagnosis. CIITA, NFkB, polymeric immunoglobulin receptor protein, 20S proteasome, HLA-DQ, and HLA-DR were significantly higher in RAS exosomes than in BOS exosomes. RAS plasma had high levels of proinflammatory cytokines and distinct exosomal miRNA. Immunization of C57BL/6 mice with RAS exosomes showed severe inflammation and peribronchial fibrosis, whereas BOS exosomes induced patchy inflammation and fibrosis. Conclusion LTxRs with BOS or RAS had exosomes with distinct molecular and immunologic profiles. RAS samples had a higher concentration of proinflammatory factors, HLA class II, lung SAgs, and antibodies to HLA class II molecules, indicating severe allograft injury. Mice immunized with RAS exosomes developed lesions in airways, pleura, interlobular septum, and alveoli, whereas BOS exosomes induced mild to patchy inflammation with lung fibrosis.

Background Ozone effects on lung function are particularly important to understand in the context of the air pollution-health outcomes epidemiologic literature, given the complex relationships between ozone and other air pollutants with known lung function effects. Research Question What has been learned about the association between ozone exposures and lung function from epidemiology studies published from 2013 through 2020? Study Design and Methods On March 18, 2018, and September 8, 2020, PubMed was searched using the terms health AND ozone, filtering to articles in English and about humans, from 2013 or later. An additional focused review searching for ozone AND (lung function OR FEV1 OR FVC) was performed June 26, 2021. Articles were selected for this review if they reported a specific relationship between a lung function outcome and ozone exposure. Results Of 3,271 articles screened, 53 ultimately met criteria for inclusion. A systematic review with assessment of potential for bias was conducted, but a meta-analysis was not carried out because of differences in exposure duration and outcome quantification. Consistent evidence exists of small decreases in children’s lung function, even associated with very low levels of short-term ozone exposure. The effects on adult lung function from exposure to low-level, short-term ozone are less clear, although ozone-associated decrements may occur in the elderly. Finally, long-term ozone exposure decreases both lung function and lung function growth in children, although few new studies have examined long-term ozone and lung function in adults. Interpretation Much of this literature involves concentrations below the current US Environmental Protection Agency’s National Ambient Air Quality Standard of 70 parts per billion over an 8-h averaging time, suggesting that this current standard may not protect children adequately from ozone-related decrements in lung function.

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20–94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6–7·0; p1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09–0·14; p

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasingly recognized in the U.S. and worldwide as a debilitating disease that is challenging to diagnose and manage. Beyond the principle task of recognizing the protean imaging manifestations of NTM-PD, radiologists will need to appropriately communicate with pulmonology and infectious disease colleagues in multidisciplinary management discussions. This update on nontuberculous mycobacteria (NTM) species, their clinical significance, and imaging features aims to support these roles. Terminology mirrors that laid out by the American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) published guidelines on NTM-PD. 1

Background There are few clinically useful circulating biomarkers of lung function and lung disease. We hypothesized that genome-wide association studies (GWAS) of circulating proteins in conjunction with GWAS of pulmonary traits represents a clinically relevant approach to identifying causal proteins and therapeutically useful insights into mechanisms related to lung function and disease. Study Question Can an integrative genomic strategy using GWAS of plasma soluble receptor for advanced glycation end-products (sRAGE) levels in conjunction with GWAS of lung function traits identify putatively causal relations of sRAGE to lung function? Study Design and Methods Plasma sRAGE levels were measured in 6,861 Framingham Heart Study participants and GWAS of sRAGE was conducted to identify protein quantitative trait loci (pQTL), including cis-pQTL variants at the sRAGE protein-coding gene locus (AGER). We integrated sRAGE pQTL variants with variants from GWAS of lung traits. Colocalization of sRAGE pQTL variants with lung trait GWAS variants was conducted, and Mendelian randomization was performed using sRAGE cis-pQTL variants to infer causality of sRAGE for pulmonary traits. Cross-sectional and longitudinal protein-trait association analyses were conducted for sRAGE in relation to lung traits. Results Colocalization identified shared genetic signals for sRAGE with lung traits. Mendelian randomization analyses suggested protective causal relations of sRAGE to several pulmonary traits. Protein-trait association analyses demonstrated higher sRAGE levels to be cross-sectionally and longitudinally associated with preserved lung function. Interpretation sRAGE is produced by type I alveolar cells, and it acts as a decoy receptor to block the inflammatory cascade. Our integrative genomics approach provides evidence for sRAGE as a causal and protective biomarker of lung function, and the pattern of associations is suggestive of a protective role of sRAGE against restrictive lung physiology. We speculate that targeting the AGER/sRAGE axis may be therapeutically beneficial for the treatment and prevention of inflammation-related lung disease.

Objective On November 24, 2017, Organ Procurement and Transplantation Network implemented a change to lung allocation replacing donor service area with a 250 nautical mile radius around donor hospitals. We sought to evaluate the experience of a small to medium size center following implementation. Methods Patients (47 pre and 54 post) undergoing lung transplantation were identified from institutional database from January 2016 to October 2019. Detailed chart review and analysis of institutional cost data was performed. Univariate analysis was performed to compare eras. Results Similar short-term mortality and primary graft dysfunction were observed between groups. Decreased local donation (68% vs 6%, p < 0.001), increased travel distance (145 vs 235 miles, p = 0.004), travel cost ($8,626 vs $14,482, p < 0.001), and total procurement cost ($60,852 vs. $69,052, p = 0.001) were observed post implementation. We also document an increase in waitlist mortality post-implementation (6.9 vs 31.6 per 100 patient years, p < 0.001). Conclusions Following implementation of the new allocation policy in a small to medium size center, several changes were in accordance with policy intention. However, concerning shifts emerged including increased waitlist mortality and resource utilization. Continued close monitoring of transplant centers stratified by size and location are paramount to maintaining global availability of lung transplantation to all Americans regardless of geographic residence or socioeconomic status. (Word Count: 219/250)

Idiopathic pulmonary hemosiderosis (IPH) is a rare immunological disease with a genetic predisposition. It is characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH). Timely use of immunosuppressive medications has significantly improved overall outcomes, including mortality. Still, uncontrolled and frequent episodes of DAH can eventually cause pulmonary fibrosis, leading to end-stage lung disease (ESLD). The objective of the present project was to scrutinize the literature and summarize the demographic, clinical, radiological, and histopathological features, as well as the overall outcomes, in this patient population following lung transplant. The Medline database was searched using the PubMed platform. Articles published in English between 1960 and 2020 were included in the search. Different search terms were used to identify all patients who underwent lung transplantation to manage ESLD due to IPH. Only four cases of lung transplantation have been reported in the literature in patients with IPH. All but one of these underwent deceased donor lung transplant; recurrence was reported in two of these patients and suspected in the third. One patient received living donor lung transplant and had no recurrence during a five-year follow-up. Patients with IPH should not be excluded from lung transplantation because the disease may not recur in all patients, and even when it does recur it can be promptly treated by increasing immunosuppression.

Background Pulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described. Research Question What are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH? Study Design and Methods A cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an artificial intelligence method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity. Results A total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.5; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]). Interpretation Lower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed in PAH. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH., Graphical Abstract

Background The prognostic value of evaluating spirometry at a fixed time point using standardized population reference has not previously been evaluated. Our aim was to assess the association between spirometric phenotype at 12 months (Spiro 12M ), survival and incidence of chronic lung allograft dysfunction (CLAD) in bilateral lung transplant recipients. Methods We conducted a retrospective cohort study of bilateral lung transplant recipients transplanted between January 2003 and September 2012. We defined Spiro 12M as the mean of the 2 prebronchodilator FEV1 measurements 12-month post-transplant. Normal spirometry was defined as FEV1/FVC ≥0.7 and FEV1≥80% and FVC≥80% predicted population-based values for that recipient. Abnormal spirometry was defined as failure to attain normal function by 12-months. We used a Cox regression model to assess the association between Spiro 12M , survival, and CLAD. We used logistic regression to assess potential pretransplant donor and recipient factors associated with abnormal Spiro 12M Results One hundred and eleven (51%) lung transplant recipients normalized their Spiro12M. Normal Spiro12M was associated improved survival (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.41-0.88], p = 0.009. Each 10% decrement in FEV1 increased the risk of death in a stepwise fashion. Additionally, CLAD was reduced in those with normal Spiro12M (HR:0.65, 95%CI:0.46-0.92, p = 0.016). Donor smoking history (OR:2.93, 95% CI:1.21-7.09; p = 0.018) and mechanical ventilation time in hours (OR:1.03, 95% CI:1.004-1.05; p = 0.02) were identified as independent predictors of abnormal Spiro12M. Conclusions Abnormal Spiro12M is associated with increased mortality and the development of CLAD. The effect is dose dependent with increased dysfunction corresponding to increased risk. This assessment of phenotype at 12-months can easily be incorporated into standard of care.

Background Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an uncommon mycobacterial infection characterized by worsening lung function and increased health care resource utilization; however, the overall risk for hospitalization among patients with NTM-PD remains unclear. Research Question What is the hospitalization risk among older adults with NTM-PD? Study Design and Methods A retrospective, nested, case-control study was conducted by using the Medicare claims database. Cases were defined as patients with ≥ 2 NTM-PD claims ≥ 30 days apart between January 1, 2007, and December 31, 2015. The study included individuals aged ≥ 65 years with ≥ 12 months of continuous enrollment in both Parts A and B before the first NTM-PD diagnosis. Cases were matched 1:2 to Medicare beneficiaries without NTM-PD (control subjects) according to age and sex. Hospitalizations following the first NTM-PD claim were compared between case and control subjects by using univariate and multivariate analyses. Results A total of 35,444 case subjects and 65,467 matched control subjects (mean age, 76.6 years; 70% female; ≥ 87% White) were identified. Baseline comorbidities, particularly pulmonary comorbidities, were more common in case subjects than in control subjects (81.1% vs 17.7% for COPD; 44.6% vs 0.6% for bronchiectasis). All-cause hospitalization was observed in 65.7% of case subjects and 44.9% of control subjects. Unadjusted annual hospitalization rates were significantly (P < .05) greater among case subjects than control subjects. Case subjects also had a significantly shorter time to hospitalization than control subjects. The increased burden due to hospitalization was reflected in multivariate analysis adjusting for baseline comorbidities. All-cause hospitalization in patients with NTM-PD relative to control subjects was 1.2 times more likely (relative risk, 1.23; 95% CI, 1.21-1.25; P < .0001) with a 46% greater hazard (hazard ratio, 1.46; 95% CI, 1.43-1.50; P < .0001). Interpretation Patients with NTM-PD were significantly more likely to be hospitalized, had greater annualized hospitalization rates, and had shorter time to hospitalization than age- and sex-matched control subjects without NTM-PD. These findings highlight the significantly increased burden of hospitalizations among patients with NTM-PD., Graphical Abstract

Non-tuberculous mycobacterial pulmonary disease is on the rise globally. It is often missed, and causes significant morbidity and even mortality. Here, members of a clinical research network and a patient support group discuss some of the current key issues in NTM management. In addition to the need for research into epidemiology, immunology and treatment, we recommend greater use of patient and clinician networks to: (i) educate primary and secondary care clinicians to develop a high index of suspicion when investigating and treating at risk populations. (ii) promote a multidisciplinary team. (iii) promote shared patient-clinician decision making throughout care. (iv) incorporate use of patient self-report measures to assess progress and outcomes. (v) increase education of patients on their illness and its management. (vi) recruit patients into research projects and registries to improve the clinical evidence base. (vii) increase co-production of research with key stakeholders such as patients and their families, using expert patients and patient groups. (viii) understand more about the psychological, social and economic consequences of the disease.

For infants with the most severe forms of chronic lung disease, regardless of etiology, chronic mechanical ventilation can provide stability, reduce acute respiratory events, and alleviate increased work of breathing. This approach prioritizes the baby's growth and development during early life. Once breathing comfortably, these infants can tolerate developmental therapies with the goal of achieving the best neurocognitive outcomes possible.

Our purpose was to investigate the effect of automated knowledge-based planning (KBP) on real-world clinical workflow efficiency, assess whether manual refinement of KBP plans improves plan quality across multiple disease sites, and develop a data-driven method to periodically improve KBP automated planning routines.Using clinical knowledge-based automated planning routines for prostate, prostatic fossa, head and neck, and hypofractionated lung disease sites in a commercial KBP solution, workflow efficiency was compared in terms of planning time in a pre-KBP (n = 145 plans) and post-KBP (n = 503) patient cohort. Post-KBP, planning was initialized with KBP (KBP-only) and subsequently manually refined (KBP +human). Differences in planning time were tested for significance using a 2-tailed Mann-Whitney U test (P.05, null hypothesis: planning time unchanged). Post-refinement plan quality was assessed using site-specific dosimetric parameters of the original KBP-only plan versus KBP +human; 2-tailed paired t test quantified statistical significance (Bonferroni-corrected P.05, null hypothesis: no dosimetric difference after refinement). If KBP +human significantly improved plans across the cohort, optimization objectives were changed to create an updated KBP routine (KBP'). Patients were replanned with KBP' and plan quality was compared with KBP +human as described previously.KBP significantly reduced planning time in all disease sites: prostate (median: 7.6 hrs → 2.1 hrs; P.001), prostatic fossa (11.1 hrs → 3.7 hrs; P = .001), lung (9.9 hrs → 2.0 hrs; P.001), and head and neck (12.9 hrs → 3.5 hrs; P.001). In prostate, prostatic fossa, and lung disease sites, organ-at-risk dose changes in KBP +human versus KBP-only were minimal (1% prescription dose). In head and neck, KBP +human did achieve clinically relevant dose reductions in some parameters. The head and neck routine was updated (KBP'KBP increased clinical efficiency by significantly reducing planning time. On average, human refinement offered minimal dose improvements over KBP-only plans. In the single disease site where KBP +human was superior to KBP-only, differences were eliminated by adjusting optimization parameters in a revised KBP routine.