Search Our Scientific Publications & Authors

Am J Ind Med 2019 Feb 18. Epub 2019 Feb 18.

Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland.

Introduction: This study examined the association of spirometry-defined airflow obstruction and self-reported COPD defined as self-reported doctor diagnosed chronic bronchitis or emphysema, with occupational exposure among ever-employed US adults.

Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 to 2011-2012, a nationally representative study of the non-institutionalized civilian US population. Reported current and/or longest held job were used to create prevalence estimates and prevalence odds ratios (PORs) (adjusted for age, gender, race, and smoking status) for airflow obstruction and self-reported COPD by occupational exposure, determined using both NHANES participants' self-reported exposures and eight categories of COPD job exposure matrix (JEM) assigned exposures. Read More

Am J Ind Med 2019 Feb 18. Epub 2019 Feb 18.

Respiratory Health Division, National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention (CDC), Morgantown, West Virginia.

Background: Non-malignant respiratory disease (NMRD) cases have occurred among rubber manufacturing workers. We examined exposure to rubber manufacturing emissions as a risk factor for NMRD.

Methods: From a systematic literature review, we identified case reports and assessed cross-sectional and mortality studies for strength of evidence of positive association (strong, intermediate, non-significant positive association, none) between exposure to rubber manufacturing emissions and NMRD-related morbidity and mortality, and conducted two meta-analyses. Read More

Chronic Obstr Pulm Dis 2019 Jan 25;6(1):118-125. Epub 2019 Jan 25.

Denver, Colorado.

Chronic Obstr Pulm Dis 2018 Nov 28;6(1):100-114. Epub 2018 Nov 28.

Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville.

Alpha-1 antitrypsin deficiency (AATD) is a largely monogenetic disorder associated with a high risk for the development of chronic obstructive pulmonary disease (COPD) and cirrhosis. Intravenous alpha-1 antitrypsin (AAT) therapy has been available for the treatment of individuals with AATD and COPD since the late 1980s. Initial Food and Drug Administration (FDA) approval was granted based on biochemical efficacy. Read More

Chronic Obstr Pulm Dis 2018 Dec 11;6(1):51-63. Epub 2018 Dec 11.

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Patients with severe emphysema have limited treatment options. Little is known about patients' willingness to accept risks for new treatments that offer meaningful benefits. We determined treatment preferences of patients with severe emphysema using a web-based discrete-choice experiment survey. Read More

Chronic Obstr Pulm Dis 2018 Oct 12;6(1):40-50. Epub 2018 Oct 12.

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

Long-term effects of lung volume reduction surgery (LVRS) on respiratory muscle strength and effects of age, sex, and emphysema pattern on these changes are unknown. Therefore, we aimed to determine the long-term effect of LVRS on respiratory muscle strength changes in severe emphysema. The National Emphysema Treatment Trial was a prospective controlled multicentered trial, comparing LVRS to optimal medical treatment on survival and maximal exercise capacity. Read More

ERJ Open Res 2019 Feb 11;5(1). Epub 2019 Feb 11.

Medical Sciences, School of Life Sciences, Faculty of Science, University of Technology, Sydney, Australia.

http://ow.ly/wZ5P30ng8bU. Read More

Beijing Da Xue Xue Bao Yi Xue Ban 2019 Feb;51(1):171-176

Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.

Objective: To evaluate the efficacy and safety of submucosal tunneling endoscopic resection (STER) and endoscopic submucosal excavation (ESE) for upper gastroenterology submucosal tumors (SMT) originating from the muscularis propria (MP) layer.

Methods: Clinicopathological and endoscopic data of 42 cases with upper gastroenterology tumors originating from the MP layer who were treated with STER (n=28) or ESE (n=14) between April 2013 and December 2016 in Peking University Third Hospital were retrospectively analyzed. The treatment and complications of the two groups were compared. Read More

J Thorac Cardiovasc Surg 2018 Nov 24. Epub 2018 Nov 24.

Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, Miss. Electronic address:

Objective: Chest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization. Read More

Int J Surg Case Rep 2019 Feb 10;55:213-217. Epub 2019 Feb 10.

Department of Acute Care Surgery, Shimane University, Faculty of Medicine, Shimane, Japan.

Introduction: Mediastinal and subcutaneous emphysema usually result from spontaneous rupture of the alveolar wall. We present an extremely rare case of massive mediastinal, retroperitoneal, and subcutaneous emphysema due to the penetration of the colon into the mesentery.

Presentation Of Case: A 57-year-old man presented to our institution with a history of chest pain. Read More

Clin Exp Rheumatol 2019 Feb 11. Epub 2019 Feb 11.

Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Objectives: To investigate the clinical characteristics of patients positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, and to analyse the potential pathogenesis of anti-MDA5 antibodies.

Methods: The clinical manifestations, serological tests, imaging features, treatments, and prognoses of 32 anti-MDA5 antibody-positive patients diagnosed in the Rheumatology and Immunology Department of the Second Affiliated Hospital of Chongqing Medical University from September 2015 to August 2018 were analysed.

Results: Of the 32 anti-MDA5 antibody-positive patients, eleven patients were clinically diagnosed with interstitial pneumonia with autoimmune features (IPAF), ten patients were diagnosed with clinically amyopathic dermatomyositis (CADM), six patients were diagnosed with dermatomyositis (DM) and five patients were diagnosed with anti-synthetase syndrome (ASS). Read More

BMJ Case Rep 2019 Feb 13;12(2). Epub 2019 Feb 13.

Department of Paediatrics, Luton and Dunstable University Hospital NHS Foundation Trust, Luton, Bedfordshire, UK.

Spontaneous subcutaneous emphysema and pneumomediastinum in children without any predisposing factors is a rare entity. We present a case of an adolescent boy with spontaneous pneumomediastinum. He is a 14-year-old boy brought to the hospital with an odd feeling in the neck and chest. Read More

Food Chem Toxicol 2019 Feb 11. Epub 2019 Feb 11.

PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000, Neuchâtel, Switzerland. Electronic address:

Smoking is one of the major modifiable risk factors in the development and progression of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Modified-risk tobacco products (MRTP) are being developed to provide substitute products for smokers who are unable or unwilling to quit, to lessen the smoking-related health risks. In this study, the ApoE mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F, or aerosol from two potential MRTPs based on the heat-not-burn principle, carbon-heated tobacco product 1. Read More

Life Sci 2019 Feb 11. Epub 2019 Feb 11.

State Key Laboratory of Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, PR China; Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona, Tucson, AZ 85721-0202, USA; Department of Laboratory Medicine, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, PR China. Electronic address:

Aims: A rat model of emphysema was established that mimics the features of the human emphysema subtype and explores the effects of demethylation on lung function and blood tests.

Materials And Methods: Rats were randomly assigned to NO, NO + 5-Azacytidine, and normal air groups based on a emphysema rat model induced by chronic NO exposure. This study estimates the characteristics of emphysema by conducting an analysis for IL-6 and TNF-α levels in bronchoalveolar lavage fluids (BALF) and plasma. Read More

J Appl Physiol (1985) 2019 Feb 14. Epub 2019 Feb 14.

Respiratory Medicine, Woolcock Institute, University of Sydney, Australia.

Respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) is theoretically and experimentally related to lung volume. In chronic obstructive pulmonary disease (COPD), the absolute volume measured by body plethysmography includes a proportion which is inaccessible to pressure oscillations applied via the mouth - that is, a 'non-communicating' lung volume. We hypothesized that, in COPD, the presence of non-communicating lung would disrupt the expected Xrs-volume relationship when compared to plethysmographic functional residual capacity (FRC). Read More

Medicine (Baltimore) 2019 Feb;98(7):e14450

Diagnostic Department, Division of Radiology.

To compare 2 incompatible generations of iterative reconstructions from the same raw dataset based on automatic emphysema quantification and noise reduction: a hybrid algorithm called sinogram affirmed iterative reconstruction (SAFIRE) versus a model-based algorithm called advanced modeled iterative reconstruction (ADMIRE).Raw datasets of 40 non-contrast thoracic computed tomography scanners obtained from a single acquisition on a SOMATOM Definition Flash unit (Siemens Healthcare, Forchheim) were reconstructed with 3 levels of SAFIRE and ADMIRE algorithms resulting in a total of 240 datasets. Emphysema index (EI) and image noise were compared using repeated analysis of variance (ANOVA) analysis with a P value <. Read More

Medicine (Baltimore) 2019 Feb;98(7):e14438

Department of Radiology, Affiliated Zhongshan Hospital of Dalian University, Da Lian.

A new method of quantitative computed tomography (CT) measurements of pulmonary vessels are applicable to morphological studies and may be helpful in defining the progression of emphysema in smokers. However, limited data are available on the relationship between the smoking status and pulmonary vessels alteration established in longitudinal observations. Therefore, we investigated the change of pulmonary vessels on CTs in a longitudinal cohort of smokers. Read More

Expert Rev Respir Med 2019 Feb 14. Epub 2019 Feb 14.

b Department of Respiratory Medicine , Maastricht University Medical Center , Maastricht , The Netherlands.

Introduction: Distinct pathologies can cause chronic obstructive pulmonary disease (COPD). Emphysema is a COPD-phenotype characterized by destruction of lung parenchyma. Alpha-1 antitrypsin deficiency (AATD) is a genetic cause of emphysema, whereas smoking is the most important risk factor of non-AATD emphysema. Read More

J Gastrointest Surg 2019 Feb 13. Epub 2019 Feb 13.

Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Background: Endoscopic submucosal dissection (ESD) of superficial esophageal cancer has been used increasingly as an alternative to surgery because it is minimally invasive and has a high rate of en bloc resection. We previously reported that the double endoscopic intraluminal operation (DEILO) is a useful technique for ESD of early esophageal cancers. In the current study, we showed comparable short-term data between DEILO and conventional ESD groups to demonstrate the further advanced use of DEILO. Read More

Am J Case Rep 2019 Jan 30;20:125-130. Epub 2019 Jan 30.

Department of Anesthesiology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China (mainland).

BACKGROUND One-lung ventilation under general anesthesia is necessary for most thoracic surgical procedures. However, adverse effects may derive from mechanical ventilation in emphysema patients. At present, lung volume reduction surgery under spontaneous ventilation may attenuate these adverse effects. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S266-S272

1 Division of Pulmonary and Critical Care Medicine and.

The mechanisms underlying the pathogenesis of chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis, remain incompletely understood. Mitochondria are vital cellular organelles crucial for energy generation, the maintenance of cellular metabolism, calcium homeostasis, intracellular signaling, and the regulation of cell death programs. Emerging evidence suggests that mitochondrial dysfunction plays a cardinal role in the initiation and progression of many human diseases, including chronic lung diseases. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S291-S292

1 Vanderbilt University Medical Center, Nashville, Tennessee.

Rationale: Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States. COPD and associated emphysematous loss of tissue structure often is exacerbated by vasculopathy, which substantially worsens prognosis and limits survival. Vasculopathy is characterized by remodeling and loss of microvessels. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S227-S233

Program in Translational Lung Research and Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.

The pathogenesis of chronic obstructive pulmonary disease remains elusive; investigators in the field have struggled to decipher the cellular and molecular processes underlying chronic bronchitis and emphysema. Studies in the past 20 years have underscored that the tissue destruction, notably in emphysema, involves a multitude of injurious stresses, with progressive engagement of endogenous destructive processes triggered by decades of exposure to cigarette smoke and/or pollutants. These lead to an aged lung, with evidence of macromolecular damage that is unlikely to repair. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S285

2 Brigham and Women's Hospital, Boston Massachusetts.

Chronic obstructive pulmonary disease (COPD) is a syndrome that comprises several lung pathologies, but subphenotyping the various disease subtypes has not been successful. We found that a single-nucleotide polymorphism (SNP) within the proline-rich domain of transformation-related protein 53 (TP53) that modifies Pro72 to Arg is associated with twofold increased risk for chronic bronchitis in the Lovelace Smokers and COPDGene cohorts. This association is pronounced for those who report either wood smoke, dust, or fumes exposure. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S243-S248

Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan.

Despite being a major cause of morbidity and mortality, chronic obstructive pulmonary disease (COPD) is frequently undiagnosed. Yet the burden of disease among the undiagnosed is significant, as these individuals experience symptoms, exacerbations, and excess mortality compared to those without COPD. The U. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S249-S252

National Jewish Health and University of Colorado, Denver, Colorado.

A better understanding of the pathogenesis of distinct chronic obstructive pulmonary disease (COPD) phenotypes will improve diagnostic and therapeutic options for this common disease. We present evidence that sphingolipids such as ceramides are involved in the emphysema pathogenesis. Whereas distinct ceramide species cause cell death by apoptosis and necroptosis, cell adaptation leads to accumulation of other sphingolipid metabolites that extend cell survival by triggering autophagy. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S278-S281

Justus Liebig University Giessen, Excellence Cluster Cardio-Pulmonary System (ECCPS), Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; and member of the German Center for Lung Research (DZL), Germany.

Chronic obstructive pulmonary disease (COPD) is one of the most important causes of death worldwide, and in addition to its impact on the patient's health, it poses a major socioeconomic burden. Tobacco smoke, indoor cooking, and air pollution are major triggers of the disease. This article summarizes evidence for the concept that lung microvascular molecular alterations can be a driver of lung emphysema. Read More

Ann Am Thorac Soc 2018 Dec;15(Supplement_4):S292-S293

1 Department of Anatomy and Cell Biology and.

Rationale: The most prevalent genetic cause of chronic obstructive pulmonary disease is alpha-1 antitrypsin (A1AT) deficiency, a disorder that has yet to be widely modeled in animals because of species-specific differences between rodents and humans.

Objectives: To address these challenges, we engineered two A1AT ferret models using zygote gene editing to test the hypothesis that unopposed protease activity within the lung leads to emphysema and bronchitis.

Methods: Guide RNAs targeting exon 2 (for knockout) and exon 5 (for Z-allele mutation, Pi*Z) of the ferret A1AT gene were injected into ferret zygotes with Cas9 mRNA. Read More

Am J Respir Crit Care Med 2019 Feb 13. Epub 2019 Feb 13.

Brigham and Women's Hospital, Radiology, Boston, Massachusetts, United States.

Background: Cor pulmonale (right ventricular dilation) and cor pulmonale parvus (right ventricular shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes. Here, we explored the relationship between CT measures of emphysema and distal pulmonary arterial morphology with RV volume, as well as their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study. Read More

Eur J Case Rep Intern Med 2018 25;5(5):000823. Epub 2018 May 25.

Medical Intensive Care Unit, Farhat Hached Hospital, Sousse, Tunisia.

Introduction: Pulmonary interstitial emphysema is a rare finding defined as abnormal air collection inside the lung interstitial tissues. Described more frequently in ventilated new-borns, pulmonary interstitial emphysema is an uncommon barotrauma-related complication in adults. Management and clinical sequelae are poorly described. Read More

Lancet Respir Med 2019 Feb 7. Epub 2019 Feb 7.

Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Lung Imaging Core and UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Lancet Respir Med 2019 Feb 7. Epub 2019 Feb 7.

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital, London, UK; National Heart & Lung Institute, Imperial College, London, UK; Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. Electronic address:

Background: Severe emphysema is a debilitating condition with few treatment options. Lung volume reduction procedures in the treatment of severe emphysema have shown excellent results in selected patients but their exact role remains unclear with studies reporting a wide variation in outcomes. We therefore aimed to evaluate the effects of volume reduction. Read More

J Pediatr Rehabil Med 2018 ;11(4):243-254

Human Engineering Research Laboratories, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.

Purpose: To describe pulmonary function and determine the impact of neurological level, scoliosis, and obesity on pulmonary function in people with spina bifida (SB).

Methods: Participants with SB (N= 29) (15 females; age, 30 ± 12 years) completed spirometry and body plethysmographic lung volume testing. Univariate and multivariate regression analyses were used to describe the factors associated with pulmonary function in people with SB. Read More

Genet Epidemiol 2019 Feb 11. Epub 2019 Feb 11.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Genetic association studies have increasingly recognized variant effects on multiple phenotypes. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with environmental and genetic causes. Multiple genetic variants have been associated with COPD, many of which show significant associations to additional phenotypes. Read More

Clin Sci (Lond) 2019 02 7. Epub 2019 Feb 7.

School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia

Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiate and drive the long-term progression of disease. Read More

BMJ Case Rep 2019 Feb 6;12(2). Epub 2019 Feb 6.

General Intensive Care Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Pneumomediastinum (PNMD) entails the presence of air or other gas in the mediastinum and is also known as mediastinal emphysema. PNMD may cause a wide variety of signs and symptoms, as well as ECG abnormality, including ST segment changes. We present a 56-year-old man admitted to our hospital after a trauma. Read More

Thromb Res 2019 Jan 17;175:90-94. Epub 2019 Jan 17.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.

Introduction: Mean platelet volume (MPV) is a measure of platelet size and activity. We conducted a population study with National Health and Nutrition Examination Survey (NHANES) data to understand the relationship of MPV with health and diseases.

Materials And Methods: The NHANES is a cross-sectional survey of non-institutionalized adult population, administered every 2 years by the Centers for Disease Control and Prevention. Read More

Ophthalmic Plast Reconstr Surg 2019 Jan 25. Epub 2019 Jan 25.

Department of Ophthalmology, New York University School of Medicine, New York, New York, U.S.A.

The authors describe the case of a 19-year-old female who suffered posttraumatic emphysema of the optic nerve sheath. She suffered massive head trauma requiring emergent neurosurgery and was incidentally found to have air in her optic nerve sheath on CT scan. At 6 weeks follow up, her visual acuity (20/25 uncorrected) and color perception in the affected eye were excellent. Read More

Pulm Circ 2019 Feb 7:2045894019832214. Epub 2019 Feb 7.

Medizinische Universitat Graz.

Eur Respir J 2019 Feb 6. Epub 2019 Feb 6.

Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA

The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model, and emphysema in patients with COPD.A transgenic mouse model of chronic type 2 pulmonary inflammation ( ) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Read More

J Bras Pneumol 2018 Nov-Dec;44(6):486-490

. Departamento de Cirurgia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista - UNESP - Botucatu (SP) Brasil.

Objective: To evaluate the efficacy of mitomycin C (MMC) in the endoscopic treatment of tracheal stenosis.

Methods: Patients with laryngotracheal, tracheal, or tracheobronchial stenosis were treated with dilation and topical MMC. The inclusion criteria were as follows: being ineligible for surgery (for medical reasons) at the time of evaluation; membranous stenosis responding well to dilation; and postoperative stenosis at the anastomosis site. Read More

Chronic Obstr Pulm Dis 2018 Oct 8;5(4):277-288. Epub 2018 Oct 8.

Respiratory Division, Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Quebec Canada.

Antioxidants represent an attractive therapeutic avenue for individuals with chronic obstructive pulmonary disease (COPD). Cigarette smoke, the major cause of COPD, contains very high concentrations of gaseous and soluble oxidants that can directly induce cell injury and death. Furthermore, particulate matter in cigarette smoke activates lung macrophages that subsequently attract neutrophils. Read More

Chronic Obstr Pulm Dis 2018 Sep 19;5(4):267-276. Epub 2018 Sep 19.

Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. Read More

Chronic Obstr Pulm Dis 2018 Sep 15;5(4):258-266. Epub 2018 Sep 15.

Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.

PIZZ alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disease affecting approximately 100,000 individuals in the United States and one of the most common hereditary causes of liver disease. The most common form of the disease results from a single base pair mutation (Glu342Lys), known as the "Z" mutation, that encodes a mutant protein (Z alpha-1 antritypsin [AAT]) that is prone to misfolding and is retained in the endoplasmic reticulum (ER) rather than appropriately secreted. Some of the retained mutant protein attains an unusual aggregated or conformation. Read More

Chronic Obstr Pulm Dis 2018 Aug 17;5(4):244-257. Epub 2018 Aug 17.

Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.

Alpha-1 antitrypsin deficiency (AATD) manifests primarily as early-onset emphysema caused by the destruction of the lung by neutrophil elastase due to low amounts of the serine protease inhibitor alpha-1 antitrypsin (AAT). The current therapy involves weekly intravenous infusions of AAT-derived from pooled human plasma that is efficacious, yet costly. Gene therapy applications designed to provide constant levels of the AAT protein are currently under development. Read More

Chronic Obstr Pulm Dis 2018 Aug 6;5(4):233-243. Epub 2018 Aug 6.

UCL Respiratory, Division of Medicine, University College London, United Kingdom.

Alpha-1antitrypsin deficiency (AATD) results from the intracellular polymerization and retention of mutant alpha-1antitrypsin (AAT) within the endoplasmic reticulum of hepatocytes. This causes cirrhosis whilst the deficiency of circulating AAT predisposes to early onset emphysema. This is an exciting time for researchers in the field with the development of novel therapies based on understanding the pathobiology of disease. Read More

Thorax 2019 Feb 5. Epub 2019 Feb 5.

General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.

Purpose: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial.

Methods: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Read More

JCI Insight 2019 Feb 5. Epub 2019 Feb 5.

Airway mucin secretion is necessary for ciliary clearance of inhaled particles and pathogens, but can be detrimental in pathologies such as asthma and cystic fibrosis. Exocytosis in mammals requires a Munc18 scaffolding protein, and airway secretory cells express all three Munc18 isoforms. Using conditional airway epithelial deletant mice, we found that Munc18a has the major role in baseline mucin secretion, Munc18b has the major role in stimulated mucin secretion, and Munc18c does not function in mucin secretion. Read More