|
1
|
Huang J, Xie S, Gao Y, Lin Z, Xu Z, Lin J, He L, Chen G, Zheng Z, Xu Z, Chen J, Guo J, Wu Z, Duan A, Luo W, Song X, Li S. Phenotypic heterogeneity in mortality and prognosis of pulmonary alveolar proteinosis: a large-scale, global pooled analysis of individual-level data. Orphanet J Rare Dis 2025; 20:102. [PMID: 40038784 PMCID: PMC11881271 DOI: 10.1186/s13023-025-03617-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 02/17/2025] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Pulmonary Alveolar Proteinosis (PAP) is a rare interstitial lung disease with diverse clinical manifestations and outcomes. However, there are limited data on the heterogeneity of PAP, as well as its prognosis, cause of death and genetic mechanisms. This study aims to elucidate mortality, prognostic features, and genetic mechanisms in patients with PAP. METHODS The individual patient data of clinical and mortality were obtained by summarizing the published cases series. Patients with PAP were classified using K-means clustering, and logistic regression identified prognostic factors affecting outcomes. Inheritance and related mechanism of PAP were described by summarizing PAP related genes and enrichment analysis. FINDINGS Our analysis included 3278 patients from 295 reports, with 88.6% diagnosed with idiopathic PAP (IPAP). Twelve major categories of cause were counted from 312 deaths (mortality: 9.5%), the most common of which were respiratory failure (45.8%) and lung infections (18.3%). Three symptom-related clusters were identified, and patients with multiple symptoms appeared to have worse mortality than those with single or no symptoms (p < 0.05). Non-secondary patterns (OR 2.87, p = 0.003), whole lung lavage (OR 0.15, p < 0.001), and effective GM-CSF therapy (OR 0.08, p < 0.001) are prognostic factors associated with decreased mortality. Additionally, 134 significant genes related to PAP development were identified, highlighting the roles of immune response and lipid metabolism. INTERPRETATION This study comprehensively describes the clinical characteristics cause of death, prognosis and associated factors based on the global PAP population. The significant phenotype heterogeneity highlighting the importance of long-term prognosis and individualized management for patients with PAP.
Collapse
Affiliation(s)
- Junfeng Huang
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Shuojia Xie
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yuewen Gao
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zikai Lin
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhe Xu
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jinsheng Lin
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Linzhi He
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Gengjia Chen
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Ziwen Zheng
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhixing Xu
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jingyan Chen
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jiaming Guo
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhile Wu
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Ailing Duan
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Weizhan Luo
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xinyu Song
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
| | - Shiyue Li
- Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
| |
Collapse
|
|
2
|
Lyu TW, Yung K, Chien YC, Tsai XCH, Hou HA. Primary myelofibrosis as the etiology of pulmonary alveolar proteinosis: a rare clinical scenario. Leuk Lymphoma 2025; 66:150-154. [PMID: 39329179 DOI: 10.1080/10428194.2024.2408363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 09/13/2024] [Accepted: 09/19/2024] [Indexed: 09/28/2024]
Affiliation(s)
- Ting-Wei Lyu
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Kenneth Yung
- Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Pulmonology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Ying-Chun Chien
- Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Xavier Cheng-Hong Tsai
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Education and Research, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Hsin-An Hou
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
3
|
Yanagisawa A, Konaka H, Tanaka M, Ihara S, Tachibana I. Pulmonary Alveolar Proteinosis During Intensive Immunosuppressive Treatment for Acute Exacerbation of Interstitial Pneumonia: A Case Report and Literature Review. Cureus 2024; 16:e74669. [PMID: 39734970 PMCID: PMC11681919 DOI: 10.7759/cureus.74669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2024] [Indexed: 12/31/2024] Open
Abstract
Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactants in the alveoli. It has been suggested that immunosuppressants contribute to the development and exacerbation of PAP. Here, we report the case of a 73-year-old man who developed secondary PAP after intensive immunosuppressive treatment for acute exacerbation of interstitial pneumonia (IP). In this case, despite the improvement of the inflammatory response after immunosuppressive treatment, Krebs von den Lungen-6 (KL-6) continued to increase, leading to the diagnosis of PAP. De-escalation of immunosuppressive treatment improved the PAP, allowing him to be discharged from the hospital. Although KL-6 is a useful marker of IP, when IP appears to be refractory and KL-6 increases despite the improvement of other inflammatory markers, physicians should consider the development of PAP and perform proactive bronchoscopic evaluation.
Collapse
Affiliation(s)
- Atsushi Yanagisawa
- Department of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, JPN
- Department of Respiratory Medicine and Clinical Immunology, Osaka University, Osaka, JPN
| | - Hachiro Konaka
- Department of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, JPN
| | - Masaki Tanaka
- Department of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, JPN
| | - Shoichi Ihara
- Department of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, JPN
| | - Isao Tachibana
- Department of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, JPN
| |
Collapse
|
|
4
|
Shimaya M, Inagaki Y, Arai T, Kawakami M, Takeuchi N, Sumikawa H, Shimizu S, Takimoto T, Inoue Y. Autoimmune Pulmonary Alveolar Proteinosis Complicated by Myelodysplastic Syndrome. Intern Med 2024; 63:1451-1457. [PMID: 37839886 PMCID: PMC11157314 DOI: 10.2169/internalmedicine.1982-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 09/01/2023] [Indexed: 10/17/2023] Open
Abstract
Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal surfactant accumulation in peripheral air spaces. Autoimmune PAP (APAP) results from macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, and the presence of antibodies more than the cutoff value is specific for APAP. In contrast, secondary PAP (SPAP) does not require anti-GM-CSF autoantibodies and is complicated by other diseases, including myelodysplastic syndrome (MDS). A 73-year-old man with anemia and thrombocytopenia was diagnosed with APAP and MDS simultaneously. The measurement of serum anti-GM-CSF autoantibodies is important for the correct diagnosis and management of PAP, even with an established diagnosis of underlying SPAP-suggestive disease.
Collapse
Affiliation(s)
- Minako Shimaya
- Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Japan
| | - Yuji Inagaki
- Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Japan
| | - Toru Arai
- Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Japan
| | - Mayu Kawakami
- Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Japan
| | - Naoko Takeuchi
- Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Japan
| | | | - Shigeki Shimizu
- Department of Pathology, NHO Kinki Chuo Chest Medical Center, Japan
| | - Takayuki Takimoto
- Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Japan
| | - Yoshikazu Inoue
- Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Japan
| |
Collapse
|
|
5
|
Neehus AL, Carey B, Landekic M, Panikulam P, Deutsch G, Ogishi M, Arango-Franco CA, Philippot Q, Modaresi M, Mohammadzadeh I, Corcini Berndt M, Rinchai D, Le Voyer T, Rosain J, Momenilandi M, Martin-Fernandez M, Khan T, Bohlen J, Han JE, Deslys A, Bernard M, Gajardo-Carrasco T, Soudée C, Le Floc'h C, Migaud M, Seeleuthner Y, Jang MS, Nikolouli E, Seyedpour S, Begueret H, Emile JF, Le Guen P, Tavazzi G, Colombo CNJ, Marzani FC, Angelini M, Trespidi F, Ghirardello S, Alipour N, Molitor A, Carapito R, Mazloomrezaei M, Rokni-Zadeh H, Changi-Ashtiani M, Brouzes C, Vargas P, Borghesi A, Lachmann N, Bahram S, Crestani B, Fayon M, Galode F, Pahari S, Schlesinger LS, Marr N, Bogunovic D, Boisson-Dupuis S, Béziat V, Abel L, Borie R, Young LR, Deterding R, Shahrooei M, Rezaei N, Parvaneh N, Craven D, Gros P, Malo D, Sepulveda FE, Nogee LM, Aladjidi N, Trapnell BC, Casanova JL, Bustamante J. Human inherited CCR2 deficiency underlies progressive polycystic lung disease. Cell 2024; 187:390-408.e23. [PMID: 38157855 PMCID: PMC10842692 DOI: 10.1016/j.cell.2023.11.036] [Citation(s) in RCA: 27] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 09/26/2023] [Accepted: 11/29/2023] [Indexed: 01/03/2024]
Abstract
We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.
Collapse
Affiliation(s)
- Anna-Lena Neehus
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France.
| | - Brenna Carey
- Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA
| | - Marija Landekic
- Department of Medicine, McGill University, Montreal, QC H3G 0B1, Canada
| | - Patricia Panikulam
- Molecular Basis of Altered Immune Homeostasis, INSERM U1163, Paris Cité University, Imagine Institute, Paris 75015, France
| | - Gail Deutsch
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
| | - Masato Ogishi
- St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
| | - Carlos A Arango-Franco
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Quentin Philippot
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Mohammadreza Modaresi
- Pediatric Pulmonary and Sleep Medicine Department, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran; Pediatric Pulmonary Disease and Sleep Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Science, Tehran, Iran
| | - Iraj Mohammadzadeh
- Non-communicable Pediatric Diseases Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; USERN Office, Babol University of Medical Sciences, Babol, Iran
| | - Melissa Corcini Berndt
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Darawan Rinchai
- St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
| | - Tom Le Voyer
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Jérémie Rosain
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris 75015, France
| | - Mana Momenilandi
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Marta Martin-Fernandez
- Center for Inborn Errors of Immunity, Icahn School, New York, NY 10029, USA; Precision Immunology Institute, Icahn School, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School, New York, NY 10029, USA; Department of Pediatrics, Icahn School, New York, NY 10029, USA; Department of Microbiology, Icahn School, New York, NY 10029, USA
| | - Taushif Khan
- The Jackson Laboratory, Farmington, CT 06032, USA
| | - Jonathan Bohlen
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Ji Eun Han
- St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
| | - Alexandre Deslys
- Leukomotion Laboratory, Paris Cité University, INSERM UMR-S1151, CNRS UMR-S8253, Necker Hospital for Sick Children, Paris 75015, France
| | - Mathilde Bernard
- Leukomotion Laboratory, Paris Cité University, INSERM UMR-S1151, CNRS UMR-S8253, Necker Hospital for Sick Children, Paris 75015, France; Curie Institute, PSL Research University, CNRS, UMR144, Paris 75248, France; Pierre-Gilles de Gennes Institute, PSL Research University, Paris 75005, France
| | - Tania Gajardo-Carrasco
- Molecular Basis of Altered Immune Homeostasis, INSERM U1163, Paris Cité University, Imagine Institute, Paris 75015, France
| | - Camille Soudée
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Corentin Le Floc'h
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Mélanie Migaud
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Yoann Seeleuthner
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France
| | - Mi-Sun Jang
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover 30625, Germany
| | - Eirini Nikolouli
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover 30625, Germany
| | - Simin Seyedpour
- Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran; Nanomedicine Research Association (NRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Hugues Begueret
- Department of Pathology, Haut-Lévèque Hospital, CHU Bordeaux, Pessac 33604, France
| | | | - Pierre Le Guen
- Pulmonology Service, Bichat Hospital, AP-HP and Paris Cité University, INSERM U1152, PHERE, Paris 75018, France
| | - Guido Tavazzi
- Department of Surgical, Pediatric, and Diagnostic Sciences, University of Pavia, Pavia 27100, Italy; Anesthesia and Intensive Care, San Matteo Research Hospital, Pavia 27100, Italy
| | - Costanza Natalia Julia Colombo
- Anesthesia and Intensive Care, San Matteo Research Hospital, Pavia 27100, Italy; Experimental Medicine, University of Pavia, Pavia 27100, Italy
| | | | - Micol Angelini
- Neonatal Intensive Care Unit, San Matteo Research Hospital, Pavia 27100, Italy
| | - Francesca Trespidi
- Neonatal Intensive Care Unit, San Matteo Research Hospital, Pavia 27100, Italy
| | - Stefano Ghirardello
- Neonatal Intensive Care Unit, San Matteo Research Hospital, Pavia 27100, Italy
| | - Nasrin Alipour
- Molecular Immuno-Rheumatology Laboratory, INSERM UMR_S1109, GENOMAX Platform, Faculty of Medicine, OMICARE University Hospital Federation, Immunology and Hematology Research Center, Research Center in Biomedicine of Strasbourg (CRBS), Federation of Translational Medicine of Strasbourg (FMTS), University of Strasbourg, Strasbourg 67081, France; Interdisciplinary Thematic Institute (ITI) of Precision Medicine of Strasbourg, University of Strasbourg, Strasbourg 67081, France
| | - Anne Molitor
- Molecular Immuno-Rheumatology Laboratory, INSERM UMR_S1109, GENOMAX Platform, Faculty of Medicine, OMICARE University Hospital Federation, Immunology and Hematology Research Center, Research Center in Biomedicine of Strasbourg (CRBS), Federation of Translational Medicine of Strasbourg (FMTS), University of Strasbourg, Strasbourg 67081, France; Interdisciplinary Thematic Institute (ITI) of Precision Medicine of Strasbourg, University of Strasbourg, Strasbourg 67081, France
| | - Raphael Carapito
- Molecular Immuno-Rheumatology Laboratory, INSERM UMR_S1109, GENOMAX Platform, Faculty of Medicine, OMICARE University Hospital Federation, Immunology and Hematology Research Center, Research Center in Biomedicine of Strasbourg (CRBS), Federation of Translational Medicine of Strasbourg (FMTS), University of Strasbourg, Strasbourg 67081, France; Interdisciplinary Thematic Institute (ITI) of Precision Medicine of Strasbourg, University of Strasbourg, Strasbourg 67081, France; Immunology Laboratory, Biology Technical Platform, Biology Pole, New Civil Hospital, Strasbourg 67091, France
| | | | - Hassan Rokni-Zadeh
- Department of Medical Biotechnology, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran
| | - Majid Changi-Ashtiani
- School of Mathematics, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
| | - Chantal Brouzes
- Laboratory of Onco-Hematology, Necker Hospital for Sick Children, Paris 75015, France
| | - Pablo Vargas
- Leukomotion Laboratory, Paris Cité University, INSERM UMR-S1151, CNRS UMR-S8253, Necker Hospital for Sick Children, Paris 75015, France; Curie Institute, PSL Research University, CNRS, UMR144, Paris 75248, France; Pierre-Gilles de Gennes Institute, PSL Research University, Paris 75005, France
| | - Alessandro Borghesi
- Neonatal Intensive Care Unit, San Matteo Research Hospital, Pavia 27100, Italy; School of Life Sciences, Swiss Federal Institute of Technology, Lausanne 1015, Switzerland
| | - Nico Lachmann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover 30625, Germany; REBIRTH - Research Center for Translational Regenerative Medicine, Hannover 30625, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover 30625, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover 30625, Germany
| | - Seiamak Bahram
- Molecular Immuno-Rheumatology Laboratory, INSERM UMR_S1109, GENOMAX Platform, Faculty of Medicine, OMICARE University Hospital Federation, Immunology and Hematology Research Center, Research Center in Biomedicine of Strasbourg (CRBS), Federation of Translational Medicine of Strasbourg (FMTS), University of Strasbourg, Strasbourg 67081, France; Interdisciplinary Thematic Institute (ITI) of Precision Medicine of Strasbourg, University of Strasbourg, Strasbourg 67081, France; Immunology Laboratory, Biology Technical Platform, Biology Pole, New Civil Hospital, Strasbourg 67091, France
| | - Bruno Crestani
- Pulmonology Service, Bichat Hospital, AP-HP and Paris Cité University, INSERM U1152, PHERE, Paris 75018, France
| | - Michael Fayon
- Department of Pediatrics, Bordeaux Hospital, University of Bordeaux, 33000 Bordeaux, France; Cardiothoracic Research Center, U1045 INSERM, 33000 Bordeaux, France
| | - François Galode
- Department of Pediatrics, Bordeaux Hospital, University of Bordeaux, 33000 Bordeaux, France; Cardiothoracic Research Center, U1045 INSERM, 33000 Bordeaux, France
| | - Susanta Pahari
- Host-Pathogen Interactions and Population Health programs, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Larry S Schlesinger
- Host-Pathogen Interactions and Population Health programs, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Nico Marr
- Department of Human Immunology, Sidra Medicine, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Institute of Translational Immunology, Brandenburg Medical School, Brandenburg 14770, Germany
| | - Dusan Bogunovic
- Center for Inborn Errors of Immunity, Icahn School, New York, NY 10029, USA; Precision Immunology Institute, Icahn School, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School, New York, NY 10029, USA; Department of Pediatrics, Icahn School, New York, NY 10029, USA; Department of Microbiology, Icahn School, New York, NY 10029, USA
| | - Stéphanie Boisson-Dupuis
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
| | - Vivien Béziat
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
| | - Laurent Abel
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA
| | - Raphael Borie
- Pulmonology Service, Bichat Hospital, AP-HP and Paris Cité University, INSERM U1152, PHERE, Paris 75018, France
| | - Lisa R Young
- Division of Pulmonary and Sleep Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Robin Deterding
- Pediatric Pulmonary Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA
| | - Mohammad Shahrooei
- Dr. Shahrooei Laboratory, 22 Bahman St., Ashrafi Esfahani Blvd, Tehran, Iran; Clinical and Diagnostic Immunology, KU Leuven, Leuven 3000, Belgium
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity to Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Parvaneh
- Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
| | - Daniel Craven
- Division of Pediatric Pulmonology, Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA
| | - Philippe Gros
- Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 2B4, Canada
| | - Danielle Malo
- Department of Medicine, McGill University, Montreal, QC H3G 0B1, Canada; Department of Human Genetics, McGill University, Montreal, QC H3G 0B1, Canada
| | - Fernando E Sepulveda
- Molecular Basis of Altered Immune Homeostasis, INSERM U1163, Paris Cité University, Imagine Institute, Paris 75015, France
| | - Lawrence M Nogee
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Nathalie Aladjidi
- Pediatric Oncology Hematology Unit, Clinical Investigation Center (CIC), Multi-theme-CIC (CICP), University Hospital Bordeaux, Bordeaux 33000, France
| | - Bruce C Trapnell
- Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Departments of Medicine and Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
| | - Jean-Laurent Casanova
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, New York, NY 10065, USA; Department of Pediatrics, Necker Hospital for Sick Children, Paris 75015, France.
| | - Jacinta Bustamante
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France; Paris Cité University, Imagine Institute, Paris 75015, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris 75015, France.
| |
Collapse
|
|
6
|
Sato Y, Fukatsu M, Suzuki T, Sasajima T, Gunji N, Yoshida S, Asano N, Fukuchi K, Mori H, Takano M, Hayashi K, Takahashi H, Shirado-Harada K, Kimura S, Koyama D, Migita K, Ikezoe T. Successful allogeneic hematopoietic stem cell transplantation for myelodysplastic neoplasms complicated with secondary pulmonary alveolar proteinosis and Behçet's disease harboring GATA2 mutation. Int J Hematol 2023; 118:642-646. [PMID: 37084069 DOI: 10.1007/s12185-023-03603-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 04/22/2023]
Abstract
Myelodysplastic neoplasms (MDS) are defined by cytopenia and morphologic dysplasia originating from clonal hematopoiesis. They are also frequently complicated with diseases caused by immune dysfunction, such as Behçet's disease (BD) and secondary pulmonary alveolar proteinosis (sPAP). MDS with both BD and sPAP is extremely rare, and their prognosis is poor. In addition, haploinsufficiency of the hematopoietic transcription factor gene GATA2 is recognized as a cause of familial MDS and is frequently complicated by sPAP. Herein, we report a case of MDS combined with both BD and sPAP in association with GATA2 deficiency in a Japanese woman. Because she developed progressive leukopenia and macrocytic anemia during BD treatment at the age of 61, she underwent a bone-marrow examination and was diagnosed with MDS. She subsequently developed sPAP. At the age of 63, she underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since allo-HSCT, she has maintained complete remission of MDS as well as the symptoms of BD and sPAP. Furthermore, we performed whole exome sequencing and identified the GATA2 Ala164Thr germline mutation. These findings suggest that patients with MDS, BD and sPAP should be considered for early allo-HSCT.
Collapse
Affiliation(s)
- Yuki Sato
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Masahiko Fukatsu
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Tomohiro Suzuki
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Fukushima, 973-8403, Japan
| | - Tomomi Sasajima
- Department of Rheumatology, Fukushima Rosai Hospital, Iwaki, Fukushima, 973-8403, Japan
| | - Naohiko Gunji
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Shuhei Yoshida
- Department of Rheumatology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Naomi Asano
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Koichiro Fukuchi
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Hirotaka Mori
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Motoki Takano
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Kiyohito Hayashi
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Hiroshi Takahashi
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Kayo Shirado-Harada
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Satoshi Kimura
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Daisuke Koyama
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan.
| | - Kiyoshi Migita
- Department of Rheumatology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| | - Takayuki Ikezoe
- Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, 960-1295, Japan
| |
Collapse
|
|
7
|
Rossi A, Basilicata S, Borrelli M, Ferreira CR, Blau N, Santamaria F. Clinical and biochemical footprints of inherited metabolic diseases. XIII. Respiratory manifestations. Mol Genet Metab 2023; 140:107655. [PMID: 37517329 PMCID: PMC11753447 DOI: 10.1016/j.ymgme.2023.107655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/17/2023] [Accepted: 07/17/2023] [Indexed: 08/01/2023]
Abstract
At any age, respiratory manifestations are a major cause of increased morbidity and mortality of inherited metabolic diseases (IMDs). Type and severity are extremely variable, this depending on the type of the underlying disorder. Symptoms and signs originating from upper or lower airways and/or thoracic wall and/or respiratory muscles involvement can occur either at presentation or in the late clinical course. Acute respiratory symptoms can trigger metabolic decompensation which, in turn, makes airway symptoms worse, creating a vicious circle. We have identified 181 IMDs associated with various types of respiratory symptoms which were classified into seven groups according to the type of clinical manifestations affecting the respiratory system: (i) respiratory failure, (ii) restrictive lung disease, (iii) interstitial lung disease, (iv) lower airway disease, (v) upper airway obstruction, (vi) apnea, and (vii) other. We also provided a list of investigations to be performed based on the respiratory phenotypes and indicated the therapeutic strategies currently available for IMD-associated airway disease. This represents the thirteenth issue in a series of educational summaries providing a comprehensive and updated list of metabolic differential diagnoses according to system involvement.
Collapse
Affiliation(s)
- Alessandro Rossi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Simona Basilicata
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Melissa Borrelli
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Carlos R Ferreira
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
| | - Nenad Blau
- Division of Metabolism, University Children's Hospital, Zürich, Switzerland.
| | - Francesca Santamaria
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
| |
Collapse
|
|
8
|
Chuang CH, Cheng CH, Tsai YC, Tsai MJ, Sheu CC, Chong IW. Pulmonary alveolar proteinosis in Taiwan. J Formos Med Assoc 2023; 122:1061-1068. [PMID: 37105870 DOI: 10.1016/j.jfma.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/13/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND/PURPOSE Pulmonary alveolar proteinosis (PAP) is rare disease manifested as alveolar macrophage dysfunction and abnormal accumulation of surfactant protein in the alveoli. In this nationwide, population-based study, we investigated the epidemiology of PAP in Taiwan, and discovered the comorbidities and prognostic factors of PAP. METHODS From the National Health Insurance Research Database (NHIRD), we obtained comprehensive information about all patients of PAP in Taiwan between 1995 and 2013. The incidence, baseline characteristics comorbidities, and prognostic factors of PAP were investigated. RESULTS The annual incidence rate of PAP was around 0.79 (range: 0.49-1.17) patients per million people after 2000, and the prevalence rate was 7.96 patients per million people by the end of 2013. In total, 276 patients of PAP were identified, including 177 (64%) and 99 (36%) patients with primary and secondary PAP, respectively. The median age of diagnosis was 53.8 years. The median survival was 9.6 years after the initial PAP diagnosis, and the 5-year survival rate was 65.96%. Twenty (7%) patients received whole lung lavage (WLL) within three months after the diagnosis had significantly better survival compared to the others. Multivariable Cox regression analyses showed that elder age, secondary PAP, and malignancy were associated with poorer survival, while WLL within 3 months of diagnosis might greatly improve the survival. CONCLUSION We demonstrated the epidemiology of PAP in Taiwan, showing several poor prognostic factors and the potential effectiveness of WLL. Further prospective studies based on registry are warranted to improve the diagnosis and treatment of PAP.
Collapse
Affiliation(s)
- Cheng-Hao Chuang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Hung Cheng
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Yu-Chen Tsai
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Ming-Ju Tsai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chau-Chyun Sheu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Inn-Wen Chong
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| |
Collapse
|
|
9
|
Buschulte K, Cottin V, Wijsenbeek M, Kreuter M, Diesler R. The world of rare interstitial lung diseases. Eur Respir Rev 2023; 32:32/167/220161. [PMID: 36754433 PMCID: PMC9910344 DOI: 10.1183/16000617.0161-2022] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 12/21/2022] [Indexed: 02/10/2023] Open
Abstract
The world of rare interstitial lung diseases (ILDs) is diverse and complex. Diagnosis and therapy usually pose challenges. This review describes a selection of rare and ultrarare ILDs including pulmonary alveolar proteinosis, pulmonary alveolar microlithiasis and pleuroparenchymal fibroelastosis. In addition, monogenic ILDs or ILDs in congenital syndromes and various multiple cystic lung diseases will be discussed. All these conditions are part of the scope of the European Reference Network on rare respiratory diseases (ERN-LUNG). Epidemiology, pathogenesis, diagnostics and treatment of each disease are presented.
Collapse
Affiliation(s)
- Katharina Buschulte
- Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of Heidelberg, German Center for Lung Research (DZL), ERN-LUNG, Heidelberg, Germany
| | - Vincent Cottin
- National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, UMR 754, Claude Bernard University Lyon 1, ERN-LUNG, Lyon, France
| | - Marlies Wijsenbeek
- Center for Interstitial Lung Diseases and Sarcoidosis, Department of Respiratory Medicine, Erasmus MC-University Medical Center, ERN-LUNG, Rotterdam, The Netherlands
| | - Michael Kreuter
- Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of Heidelberg, German Center for Lung Research (DZL), ERN-LUNG, Heidelberg, Germany
| | - Rémi Diesler
- National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, UMR 754, Claude Bernard University Lyon 1, ERN-LUNG, Lyon, France
| |
Collapse
|
|
10
|
Fan G, Huang Y, Xue F, He B. Complete remission of pulmonary alveolar proteinosis after anti-tuberculous chemotherapy: a case report. J Int Med Res 2022; 50:3000605221113785. [PMID: 35899929 PMCID: PMC9340953 DOI: 10.1177/03000605221113785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Pulmonary alveolar proteinosis (PAP) is a rare respiratory system disorder. Patients with PAP are at risk for a wide variety of secondary infections. This current case report describes a patient with PAP complicated by tuberculosis. A 48-year-old male patient with multiple follow-up chest computed tomography scans that showed predominant diffuse ground glass opacity in both lung fields, presented a few years later with new calcified lesions and pleural effusion. At this point, the associated auxiliary examination indicated the possibility of PAP combined with tuberculosis infection. The patient achieved complete remission after anti-tuberculosis treatment. PAP is an easily overlooked clinical syndrome due to its low prevalence and lack of specific clinical manifestations, especially when combined with other pulmonary lesions. Therefore, clinicians should consider this rare disease in patients presenting with pulmonary disease and plan for its co-morbidity with other secondary outcomes, such as opportunistic infections, which are a common and life-threatening complication in patients with PAP. This case indicates the possibility that anti-tuberculosis therapy can improve alveolar proteinosis in patients with PAP and secondary Mycobacterium tuberculosis infection.
Collapse
Affiliation(s)
- Guangtao Fan
- Department of Imaging, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Yilong Huang
- Department of Imaging, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Fenglin Xue
- Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Bo He
- Department of Imaging, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| |
Collapse
|
|
11
|
McCarthy C, Carey BC, Trapnell BC. Autoimmune Pulmonary Alveolar Proteinosis. Am J Respir Crit Care Med 2022; 205:1016-1035. [PMID: 35227171 PMCID: PMC9851473 DOI: 10.1164/rccm.202112-2742so] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 02/24/2022] [Indexed: 01/23/2023] Open
Abstract
Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease characterized by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation, and innate immune deficiency. It has a prevalence of 7-10 per million; occurs in individuals of all races, geographic regions, sex, and socioeconomic status; and accounts for 90% of all patients with PAP syndrome. The most common presentation is dyspnea of insidious onset with or without cough, production of scant white and frothy sputum, and diffuse radiographic infiltrates in a previously healthy adult, but it can also occur in children as young as 3 years. Digital clubbing, fever, and hemoptysis are not typical, and the latter two indicate that intercurrent infection may be present. Low prevalence and nonspecific clinical, radiological, and laboratory findings commonly lead to misdiagnosis as pneumonia and substantially delay an accurate diagnosis. The clinical course, although variable, usually includes progressive hypoxemic respiratory insufficiency and, in some patients, secondary infections, pulmonary fibrosis, respiratory failure, and death. Two decades of research have raised autoimmune PAP from obscurity to a paradigm of molecular pathogenesis-based diagnostic and therapeutic development. Pathogenesis is driven by GM-CSF (granulocyte/macrophage colony-stimulating factor) autoantibodies, which are present at high concentrations in blood and tissues and form the basis of an accurate, commercially available diagnostic blood test with sensitivity and specificity of 100%. Although whole-lung lavage remains the first-line therapy, inhaled GM-CSF is a promising pharmacotherapeutic approach demonstrated in well-controlled trials to be safe, well tolerated, and efficacious. Research has established GM-CSF as a pulmonary regulatory molecule critical to surfactant homeostasis, alveolar stability, lung function, and host defense.
Collapse
Affiliation(s)
- Cormac McCarthy
- Department of Respiratory Medicine, St. Vincent’s University Hospital, Dublin, Ireland
- University College Dublin, Dublin, Ireland
| | - Brenna C. Carey
- Translational Pulmonary Science Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; and
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Bruce C. Trapnell
- Translational Pulmonary Science Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; and
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| |
Collapse
|
|
12
|
Shimizu H, Sato S, Suzuki T, Sasajima T, Takahata Y, Shinohara N, Hideshima K, Yokokawa Y, Matsuhashi N, Ichii O, Tai M, Ejiri Y, Yano K, Ikezoe T, Ohira H, Migita K. Intestinal Behçet's disease complicated by myelodysplastic syndrome and secondary pulmonary alveolar proteinosis: a case report. BMC Gastroenterol 2021; 21:488. [PMID: 34930121 PMCID: PMC8686569 DOI: 10.1186/s12876-021-02065-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 12/08/2021] [Indexed: 11/23/2022] Open
Abstract
Background Gastrointestinal lesions, which sometimes develop in Behçet’s disease (BD), are referred to as intestinal BD. Although rare, intestinal BD can be accompanied by myelodysplastic syndrome (MDS) with abnormal karyotype trisomy 8, which is refractory to immunosuppressive therapy. Pulmonary alveolar proteinosis is a rare lung complication of BD and MDS. Herein, we present an extremely rare case of intestinal BD presenting with MDS and several chromosomal abnormalities, followed by secondary pulmonary proteinosis. Case presentation A 58-year-old Japanese woman with a 3-year history of genital ulcers and oral aphthae was admitted to our hospital. The patient developed abdominal pain and persistent diarrhea. Colonoscopy revealed multiple, round, punched-out ulcers from the terminal ileum to the descending colon. Intestinal BD was diagnosed and the patient was treated with colchicine, prednisolone, and adalimumab. However, her symptoms were unstable. Bone marrow examination to investigate the persistent macrocytic anemia revealed the presence of trisomy 8, trisomy 9, and X chromosome abnormalities (48, + 8, + 9, X, i(X) (q10) in 12 out of the examined 20 cells). Based on her hypoplastic bone marrow, the patient was diagnosed with low-risk MDS (refractory anemia). At the age of 61, the patient developed pneumonia with fever and diffuse ground-glass opacities on the lung computed tomography (CT). Chest high-resolution CT and histopathology via transbronchial lung biopsy revealed the presence of pulmonary alveolar proteinosis (PAP). These findings combined with the underlying disease led to the diagnosis of secondary PAP. Conclusions Secondary pulmonary proteinosis may accompany intestinal BD with MDS and several chromosomal abnormalities. Physicians should pay attention to lung complications, such as PAP, in patients with intestinal BD complicated by MDS. Genetic abnormalities may be associated with the development of such diseases.
Collapse
Affiliation(s)
- Hiroshi Shimizu
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan.,Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Shuzo Sato
- Department of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
| | - Tomohiro Suzuki
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan.
| | - Tomomi Sasajima
- Department of Rheumatology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Yosuke Takahata
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Nobuhiko Shinohara
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Kosuke Hideshima
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Yuko Yokokawa
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Nobuo Matsuhashi
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Osamu Ichii
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Mayumi Tai
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Yutaka Ejiri
- Department of Gastroenterology, Fukushima Rosai Hospital, Uchigo, Iwaki, Fukushima, 973-8403, Japan
| | - Kiori Yano
- Department of Rheumatology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Takayuki Ikezoe
- Department of Hematology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Kiyoshi Migita
- Department of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan
| |
Collapse
|
|
13
|
Salvator H, Tcherakian C, Maillard N, Milin S, Bergeron A, Bondeelle L, Meignin V, Guyen SN, Souchet L, Guenounou S, Evrard SM, Rubio MT, Robin M, Sestili S, Brissot E, Fajac A, Catherinot E, Givel C, Chabrol A, Goyard C, Longchampt E, Chabi-Charvillat ML, Bernaudin JF, Couderc LJ. Pulmonary Alveolar Proteinosis After Allogeneic Hematopoietic Stem-Cell Transplantation in Adults: A French Société Francophone de Greffe de Moelle et Thérapie Cellulaire Survey. Chest 2021; 160:1783-1788. [PMID: 34102143 DOI: 10.1016/j.chest.2021.05.056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 05/10/2021] [Accepted: 05/25/2021] [Indexed: 10/21/2022] Open
Affiliation(s)
- Helene Salvator
- Service de Pneumologie, Hôpital Foch, Suresnes, France; Laboratoire de Recherche en Pharmacologie Respiratoire, INSERM V2I UMR 1173, Université Paris Saclay, Suresnes, France; Faculté Simone Veil des Sciences de la Santé Université Paris-Saclay, Montigny-le-Bretonneux, France.
| | | | | | - Serge Milin
- d'Anatomopathologie, CHU de Poitiers, France
| | | | | | | | - Stephanie N Guyen
- Service d'Hématologie, Hôpital Pitié-Salpétrière, APHP Paris, France; Société Francophone de Greffe de Moelle et Thérapie Cellulaire
| | - Laetitia Souchet
- Service d'Hématologie, Hôpital Pitié-Salpétrière, APHP Paris, France
| | - Sarah Guenounou
- Service d'Hématologie, Institut universitaire du Cancer de Toulouse-Oncopole, CHU Toulouse, Toulouse, France
| | - Solène M Evrard
- Département d'Anatomie et Cytologie pathologiques, Institut universitaire du Cancer de Toulouse-Oncopole, CHU Toulouse, Toulouse, France
| | - Marie-Therese Rubio
- Service d'Hématologie, CHRU Nancy Hôpital Brabois, Vandoeuvre les Nancy, France; Société Francophone de Greffe de Moelle et Thérapie Cellulaire
| | - Marie Robin
- Société Francophone de Greffe de Moelle et Thérapie Cellulaire
| | - Simona Sestili
- Service d'Hématologie et thérapie cellulaire, Hôpital Saint Antoine, APHP, Paris, France
| | - Eolia Brissot
- Service d'Hématologie et thérapie cellulaire, Hôpital Saint Antoine, APHP, Paris, France; Sorbonne Université, INSERM CRSA UMR_S 938, Paris, France
| | - Anne Fajac
- Service d'Anatomopathologie, Hôpital Tenon, APHP, Paris, France
| | | | - Claire Givel
- Service de Pneumologie, Hôpital Foch, Suresnes, France
| | | | - Céline Goyard
- Service de Pneumologie, Hôpital Foch, Suresnes, France
| | | | | | | | - Louis-Jean Couderc
- Service de Pneumologie, Hôpital Foch, Suresnes, France; Laboratoire de Recherche en Pharmacologie Respiratoire, INSERM V2I UMR 1173, Université Paris Saclay, Suresnes, France; Faculté Simone Veil des Sciences de la Santé Université Paris-Saclay, Montigny-le-Bretonneux, France
| |
Collapse
|
|
14
|
Chen C, Huang XL, Gao DQ, Li YW, Qian SX. Chronic myelomonocytic leukemia-associated pulmonary alveolar proteinosis: A case report and review of literature. World J Clin Cases 2021; 9:1156-1167. [PMID: 33644180 PMCID: PMC7896663 DOI: 10.12998/wjcc.v9.i5.1156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/06/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pulmonary alveolar proteinosis (PAP) is a rare condition that can cause progressive symptoms including dyspnea, cough and respiratory insufficiency. Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia (CMML). To the best of our knowledge, this is the first reported case of PAP occurring secondary to CMML.
CASE SUMMARY We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever. Based upon clinical symptoms, computed tomography findings, bone marrow aspiration, flow cytometry studies and cytogenetic analyses, the patient was diagnosed with PAP secondary to CMML. He underwent whole lung lavage in March 2016 to alleviate his dyspnea, after which he began combined chemotherapeutic treatment with decitabine and cytarabine. The patient died in January 2020 as a consequence of severe pulmonary infection.
CONCLUSION This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.
Collapse
Affiliation(s)
- Can Chen
- Department of Hematology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Xi-Lian Huang
- Department of Hematology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Da-Quan Gao
- Department of Hematology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Wei Li
- Department of Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Shen-Xian Qian
- Department of Hematology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| |
Collapse
|
|
15
|
Sugiura H, Nishimori H, Nishii K, Toji T, Fujii K, Fujii N, Matsuoka KI, Nakata K, Kiura K, Maeda Y. Secondary Pulmonary Alveolar Proteinosis Associated with Primary Myelofibrosis and Ruxolitinib Treatment: An Autopsy Case. Intern Med 2020; 59:2023-2028. [PMID: 32448830 PMCID: PMC7492123 DOI: 10.2169/internalmedicine.4082-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Pulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. We confirmed a diagnosis of PAP with complications based on the pathological findings at the autopsy. Notably, this case might suggest an association between ruxolitinib treatment and PAP occurrence.
Collapse
Affiliation(s)
- Hiroyuki Sugiura
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| | - Hisakazu Nishimori
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| | - Kazuya Nishii
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| | - Tomohiro Toji
- Department of Pathology, Okayama University Hospital, Japan
| | - Keiko Fujii
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| | - Nobuharu Fujii
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| | - Ken-Ichi Matsuoka
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| | - Koh Nakata
- Department of Bioscience Medical Research Center, Niigata University Medical & Dental Hospital, Japan
| | - Katsuyuki Kiura
- Department of Allergy and Respiratory Medicine, Okayama University Hospital, Japan
| | - Yoshinobu Maeda
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
| |
Collapse
|
|
16
|
Lawi D, Dubruc E, Gonzalez M, Aubert JD, Soccal PM, Janssens JP. Secondary pulmonary alveolar proteinosis treated by lung transplant: A case report. Respir Med Case Rep 2020; 30:101108. [PMID: 32528843 PMCID: PMC7276430 DOI: 10.1016/j.rmcr.2020.101108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 05/26/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Pulmonary alveolar proteinosis (PAP) is a pulmonary disease characterized by disruption of surfactant homeostasis resulting in its accumulation in the alveoli. PAP is classically classified into three categories (Table 1): 1/primary (or autoimmune) with antibodies targeting the GM-CSF pathway, 2/secondary to another disease, typically a hematologic malignancy, and 3/genetic. CASE-REPORT A 30 year-old woman received an allogenic hematopoietic stem cell transplantation (HSCT) after treatment for acute myeloid leukemia (AML). Within the first 6 months post HSCT, she developed an ocular, oral, digestive and hepatic graft-versus-host disease associated with a mixed ventilatory defect with a very severe obstructive syndrome and a severe CO diffusion impairment. High resolution computed tomography showed a classical "crazy paving" pattern. Aspect and differential cell count of BAL were normal. All microbiological samples remained culture negative. Histo-pathological analysis of transbronchial biopsies was unremarkable. Because of the severity of the respiratory insufficiency, open-lung biopsy (OBL) could not be performed. Despite multiple immunosuppressive therapies, lung function deteriorated rapidly; the patient also developed an excavated fungal lesion unresponsive to treatment. She underwent a bilateral lung transplant 48 months after HSCT. Histo-pathological analysis of explanted lungs showed obliterative bronchiolitis (OB), diffuse PAP and invasive cavitary pulmonary aspergillosis. CONCLUSIONS This case illustrates the simultaneous occurrence of OB, PAP and a fungal infection in a 30-year old female patient who underwent HSCT for acute myeloid leukemia (AML). To our knowledge this is the only documented case of PAP associated with OB treated by lung transplantation.
Collapse
Key Words
- AML, Acute myeloid leukemia
- BAL, Bronchoalveolar lavage
- BLT, Bilateral Lung Transplant
- GVHd, Graft-versus-host disease
- HRCT, High Resolution Computed Tomography
- HSCT, Hematopoietic Stem Cell Transplantation
- Invasive pulmonary aspergillosis
- Lung transplantation
- OB, Obliterative Bronchiolitis
- OLB, Open-lung biopsy
- Obliterative bronchiolitis
- PAP, Pulmonary Alveolar Proteinosis
- PFT, Pulmonary Function Tests
- Secondary pulmonary alveolar proteinosis
- TBB, Transbronchial Biopsy
Collapse
Affiliation(s)
- David Lawi
- Division of Pulmonology, Geneva University Hospitals, 1211, Geneva, Switzerland
| | - Estelle Dubruc
- Division of Pathology, Lausanne University Hospital, 1011, Lausanne, Switzerland
| | - Michel Gonzalez
- Division of Thoracic Surgery, Lausanne University Hospital, 1011, Lausanne, Switzerland
| | - John-David Aubert
- Division of Pulmonology, Lausanne University Hospital, 1011, Lausanne, Switzerland.,Faculty of Medicine, University of Lausanne, Lausanne, Switzerland
| | - Paola M Soccal
- Division of Pulmonology, Geneva University Hospitals, 1211, Geneva, Switzerland.,Faculty of Medicine, University of Geneva, 1211, Geneva, Switzerland
| | - Jean-Paul Janssens
- Division of Pulmonology, Geneva University Hospitals, 1211, Geneva, Switzerland.,Faculty of Medicine, University of Geneva, 1211, Geneva, Switzerland
| |
Collapse
|
|
17
|
Hashimoto M, Itonaga H, Nannya Y, Taniguchi H, Fukuda Y, Furumoto T, Fujioka M, Kasai S, Taguchi M, Taniguchi H, Sato S, Sawayama Y, Atogami S, Iwasaki K, Hata T, Soda H, Moriuchi Y, Nakata K, Ogawa S, Miyazaki Y. Secondary Pulmonary Alveolar Proteinosis Following Treatment with Azacitidine for Myelodysplastic Syndrome. Intern Med 2020; 59:1081-1086. [PMID: 31875636 PMCID: PMC7205539 DOI: 10.2169/internalmedicine.3770-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Secondary pulmonary alveolar proteinosis (sPAP) is a complication of myelodysplastic syndrome (MDS). A 60-year-old woman was diagnosed with MDS with excess blasts-1. Fifty-four months after the initial diagnosis, treatment with azacitidine was initiated. Seventy-three months after the diagnosis, a bone marrow examination revealed increased myeloblasts, at which time computed tomography showed diffuse ground-glass opacities and interlobular septal thickening in the bilateral lower lung fields. A lung biopsy revealed the presence of PAP; therefore, the clinical diagnosis of MDS/sPAP was confirmed. Careful attention should be paid to the development of sPAP in MDS patients with pulmonary lesions during azacitidine treatment.
Collapse
Affiliation(s)
- Miki Hashimoto
- Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Hidehiro Itonaga
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Japan
| | - Yasuhito Nannya
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Japan
| | - Hirokazu Taniguchi
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Yuichi Fukuda
- Department of Respiratory Medicine, Sasebo City General Hospital, Japan
| | | | - Machiko Fujioka
- Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Japan
- Department of Hematology, Nagasaki University Hospital, Japan
| | - Sachie Kasai
- Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | | | | | - Shinya Sato
- Department of Hematology, Nagasaki University Hospital, Japan
| | | | - Sunao Atogami
- Department of Clinical Laboratory, Sasebo City General Hospital, Japan
| | - Keisuke Iwasaki
- Department of Pathology, Sasebo City General Hospital, Japan
| | - Tomoko Hata
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Japan
| | - Hiroshi Soda
- Department of Respiratory Medicine, Sasebo City General Hospital, Japan
| | | | - Koh Nakata
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Japan
| | - Seishi Ogawa
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Japan
| | - Yasushi Miyazaki
- Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Japan
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Japan
- Department of Hematology, Nagasaki University Hospital, Japan
| |
Collapse
|
|
18
|
Affiliation(s)
- Haruyuki Ishii
- Department of Respiratory Medicine, Kyorin University School of Medicine, Japan
| |
Collapse
|
|
19
|
Zhang F, Weng D, Su Y, Yin C, Shen L, Zhang Y, Zhou Y, Li Q, Hu Y, Li H. Therapeutic effect of subcutaneous injection of low dose recombinant human granulocyte-macrophage colony-stimulating factor on pulmonary alveolar proteinosis. Respir Res 2020; 21:1. [PMID: 31898493 PMCID: PMC6941258 DOI: 10.1186/s12931-019-1261-1] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 12/12/2019] [Indexed: 01/15/2023] Open
Abstract
Objective To observe the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for pulmonary alveolar proteinosis (PAP). Materials and methods A total of 55 patients with PAP were screened at Shanghai Pulmonary Hospital between May 2014 and May 2018. Among these, 42 were diagnosed with idiopathic PAP, 24 were included in this study, 20 were treated for 6 months, and 17 were followed up for additional 6 months. All patients received a subcutaneous injection of 75μg/d GM-CSF qd for 1 month. The therapeutic dose was adjusted according to the changes in the lesions of chest CT. If the lesions were absorbed, subcutaneous injections of 75μg/d GM- CSF qd and 75μg/d GM-CSF qod were given for 2 and 3 months, otherwise, the dose was increased to 150μg/d GM-CSF qd and 150μg/d qod for 2 and 3 months, respectively. All cases were treated once a day in the first 3 months and once every other day in the last 3 months. The total course of treatment was 6 months. After withdrawal, the patients were followed up for another 6 months. The deadline of follow up was September 30, 2019. Results Twenty patients completed the treatment and efficacy evaluation. One patient was completely cured, 16 cases improved, three cases were noneffective. After 1-month evaluation, 12 patients received an increased dose (150μg) from the second month of treatment. Seventeen patients completed the 12-month follow-up, among which fourteen improved. CT showed the lesions were slightly increased in three cases. Economic burden was the following: RMB 7324–15,190 Yuan were required for the 6-month treatment course, which is significantly lower compared to other treatment methods. Conclusion Subcutaneous injection of rhGM-CSF at low dose (75μg-150μg /d) is effective treatment for patients with idiopathic PAP. Trial registration NCT01983657. Registered 16 April 2013.
Collapse
Affiliation(s)
- Fen Zhang
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Dong Weng
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Yiliang Su
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Chengsheng Yin
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Li Shen
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Yuan Zhang
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Ying Zhou
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Qiuhong Li
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Yang Hu
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China
| | - Huiping Li
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China.
| |
Collapse
|
|
20
|
Zhang FZ, Yuan JX, Qin L, Tang LF. Pulmonary Alveolar Proteinosis Due to Pneumocystis carinii in Type 1 Hyper-IgM Syndrome: A Case Report. Front Pediatr 2020; 8:264. [PMID: 32596190 PMCID: PMC7301693 DOI: 10.3389/fped.2020.00264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 04/27/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease. Reports of rare cases of PAP due to Pneumocystis jirovecii (P. jirovecii) exist in infants with immunodeficiency diseases, but no cases have been reported to date in pediatric patients with type 1 hyper-IgM syndrome (HIGM1). Case Presentation: Herein, we present a case of PAP secondary to P. jirovecii on an infant with HIGM1. He was admitted to our unit because of cough and tachypnea. Lung biopsy confirmed the diagnosis of PAP, whereas hexamine-silver staining of the bronchoalveolar lavage fluid identified P. jirovecii infection. No other probable cause of PAP was observed. Whole exome sequencing indicated a novel c.511dupA (p.I171N*30) hemizygous mutation in the CD40 ligand (CD40LG) gene. He was cured with bronchoalveolar lavage and compound sulfamethoxazole tablets. Conclusions: To our knowledge, this is the first reported case of P. jirovecii infection as a reversible cause of PAP in an infant with HIGM1.
Collapse
Affiliation(s)
- Fei Zhou Zhang
- Department of Pneumology, Zhejiang University School of Medicine of Children's Hospital, Hangzhou, China
| | - Jie Xin Yuan
- Department of Pneumology, Zhejiang University School of Medicine of Children's Hospital, Hangzhou, China
| | - Lu Qin
- Department of Pneumology, Zhejiang University School of Medicine of Children's Hospital, Hangzhou, China
| | - Lan Fang Tang
- Department of Pneumology, Zhejiang University School of Medicine of Children's Hospital, Hangzhou, China
| |
Collapse
|
|
21
|
Inoue D, Marumo S, Ishii H, Fukui M. Secondary pulmonary alveolar proteinosis during corticosteroid therapy for organising pneumonia associated with myelodysplastic syndrome. BMJ Case Rep 2019; 12:12/9/e231055. [PMID: 31537595 DOI: 10.1136/bcr-2019-231055] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Myelodysplastic syndrome (MDS) is frequently complicated by pulmonary disease. Here, we describe secondary pulmonary alveolar proteinosis (sPAP) that developed during corticosteroid therapy for organising pneumonia (OP) associated with MDS. A 75-year-old woman with MDS complained of cough for 2 weeks. Chest CT showed bilateral patchy consolidations with reversed halo sign. Bronchoalveolar lavage (BAL) examination showed remarkably increased cell density with an increased lymphocyte proportion. Abnormal radiological findings improved rapidly on administration of systemic corticosteroid under the diagnosis of OP; however, they relapsed a few weeks later. Transbronchial lung biopsy showed periodic acid-Schiff stain-positive amorphous materials. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum and BAL fluid (BALF) were both negative, while GM-CSF level in BALF was elevated. The patient was diagnosed with sPAP. When chest radiological findings show exacerbation during corticosteroid therapy for OP in a patient with MDS, physicians should consider sPAP complication as a differential diagnosis.
Collapse
Affiliation(s)
- Daiki Inoue
- Respiratory Disease Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Satoshi Marumo
- Respiratory Disease Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Haruyuki Ishii
- Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Motonari Fukui
- Respiratory Disease Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| |
Collapse
|
|
22
|
McCarthy C, Kokosi M, Bonella F. Shaping the future of an ultra-rare disease: unmet needs in the diagnosis and treatment of pulmonary alveolar proteinosis. Curr Opin Pulm Med 2019; 25:450-458. [PMID: 31365379 DOI: 10.1097/mcp.0000000000000601] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Pulmonary alveolar proteinosis (PAP) can be considered the archetype of ultra-rare diseases with a prevalence of under 10 cases per million. We discuss the classification of PAP, the current diagnostic practice and the supplementary role of genetic testing and granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in the diagnosis of congenital and hereditary PAP. We report on novel therapeutic approaches such as GM-CSF substitution, stem cell transplantation, pioglitazone, statins and immunomodulation. RECENT FINDINGS The discovery of new genetic mutations underlying this syndrome raises the question whether the classification should be radically revised in the future. Serum GM-CSF autoantibody is the best diagnostic marker for autoimmune PAP, the most common form, but does not correlate with disease severity. Several circulating biomarkers have been investigated to assess disease activity and predict outcome. Imaging techniques have also enormously evolved and offer new tools to quantify disease burden and possibly drive therapeutic decisions. Promising clinical trials are ongoing and will generate new treatment strategies besides or in addition to whole lung lavage in the next future. SUMMARY Despite impressive advances in understanding pathogenesis, PAP remains a rare syndrome with several unanswered questions impacting diagnosis, management and treatment, and, as a result, patients' quality of life.
Collapse
Affiliation(s)
- Cormac McCarthy
- Department of Respiratory Medicine, Rare Lung Disease Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland
| | - Maria Kokosi
- Interstitial Lung Disease Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK
| | - Francesco Bonella
- Department of Pneumology, Centre for Interstitial and Rare Lung Disease, Ruhrlandklinik, University Hospital Essen, Essen, Germany
| |
Collapse
|
|
23
|
Can somatic GATA2 mutation mimic germ line GATA2 mutation? Blood Adv 2019; 2:904-908. [PMID: 29669757 DOI: 10.1182/bloodadvances.2017012617] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 03/18/2018] [Indexed: 02/07/2023] Open
Abstract
Key Points
Somatic GATA2 mutation is associated with immunodeficiency and pulmonary alveolar proteinosis in a patient with myeloproliferative neoplasm.
Collapse
|
|
24
|
Trapnell BC, Nakata K, Bonella F, Campo I, Griese M, Hamilton J, Wang T, Morgan C, Cottin V, McCarthy C. Pulmonary alveolar proteinosis. Nat Rev Dis Primers 2019; 5:16. [PMID: 30846703 DOI: 10.1038/s41572-019-0066-3] [Citation(s) in RCA: 227] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by the accumulation of alveolar surfactant and dysfunction of alveolar macrophages. PAP results in progressive dyspnoea of insidious onset, hypoxaemic respiratory failure, secondary infections and pulmonary fibrosis. PAP can be classified into different types on the basis of the pathogenetic mechanism: primary PAP is characterized by the disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling and can be autoimmune (caused by elevated levels of GM-CSF autoantibodies) or hereditary (due to mutations in CSF2RA or CSF2RB, encoding GM-CSF receptor subunits); secondary PAP results from various underlying conditions; and congenital PAP is caused by mutations in genes involved in surfactant production. In most patients, pathogenesis is driven by reduced GM-CSF-dependent cholesterol clearance in alveolar macrophages, which impairs alveolar surfactant clearance. PAP has a prevalence of at least 7 cases per million individuals in large population studies and affects men, women and children of all ages, ethnicities and geographical locations irrespective of socioeconomic status, although it is more-prevalent in smokers. Autoimmune PAP accounts for >90% of all cases. Management aims at improving symptoms and quality of life; whole-lung lavage effectively removes excessive surfactant. Novel pathogenesis-based therapies are in development, targeting GM-CSF signalling, immune modulation and cholesterol homeostasis.
Collapse
Affiliation(s)
- Bruce C Trapnell
- Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
| | - Koh Nakata
- Bioscience Medical Research Center, Niigata University, Niigata, Japan
| | - Francesco Bonella
- Interstitial and Rare Lung Disease Unit, Pneumology Department, Ruhrlandklinik University Hospital, University of Essen, Essen, Germany
| | - Ilaria Campo
- Pneumology Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Matthias Griese
- Pediatric Pneumology, University of Munich, German Center for Lung Research (DZL), Munich, Germany
| | - John Hamilton
- University of Melbourne, Parkville, Victoria, Australia
| | - Tisha Wang
- Department of Medicine, University of California, Los Angeles, CA, USA
| | - Cliff Morgan
- Department of Critical Care and Anaesthesia, Royal Brompton Hospital, London, UK
| | - Vincent Cottin
- National Reference Center for Rare Pulmonary Diseases, University of Lyon, Lyon, France
| | - Cormac McCarthy
- Department of Medicine, St. Vincent's University Hospital and University College Dublin, Dublin, Ireland
| |
Collapse
|
|
25
|
Hosoda C, Saito K, Fujimoto S, Yamanaka Y, Watanabe N, Miyagawa H, Kurita Y, Seki Y, Kinoshita A, Endo Y, Kuwano K. Pulmonary alveolar proteinosis developing during steroid treatment in a patient with organizing pneumonia in association with atypical chronic myeloid leukemia. Clin Case Rep 2019; 7:477-481. [PMID: 30899476 PMCID: PMC6406221 DOI: 10.1002/ccr3.2014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/20/2018] [Accepted: 01/04/2019] [Indexed: 11/09/2022] Open
Abstract
Organizing pneumonia (OP) and pulmonary alveolar proteinosis (PAP) are rare complications in patients with hematologic disorders. We herein report a case of PAP that developed during steroid treatment for OP in a patient with atypical chronic myeloid leukemia. Physicians should pay close attention to these complications in patients with hematologic malignancies.
Collapse
Affiliation(s)
- Chiaki Hosoda
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Keisuke Saito
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Shota Fujimoto
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Yumie Yamanaka
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Naoaki Watanabe
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Hanae Miyagawa
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Yusuke Kurita
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Yoshitaka Seki
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Akira Kinoshita
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University Daisan HospitalTokyoJapan
| | - Yasuhiko Endo
- Department of PathologyThe Jikei University School of MedicineTokyoJapan
| | - Kazuyoshi Kuwano
- Department of Internal Medicine, Division of Respiratory MedicineThe Jikei University School of MedicineTokyoJapan
| |
Collapse
|
|
26
|
Kumar A, Abdelmalak B, Inoue Y, Culver DA. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. THE LANCET RESPIRATORY MEDICINE 2018; 6:554-565. [PMID: 29397349 DOI: 10.1016/s2213-2600(18)30043-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 11/16/2017] [Accepted: 11/23/2017] [Indexed: 12/24/2022]
Abstract
Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages due to abnormal surfactant homoeostasis. Identification of the granulocyte-macrophage colony-stimulating factor (GM-CSF) as an indispensable mediator of macrophage maturation and surfactant catabolism was the key discovery leading to the current understanding of the pathogenesis of most forms of PAP. Impaired GM-CSF bioavailability due to anti-GM-CSF autoimmunity is the cause of approximately 90% of adult PAP cases. Abnormal macrophage function due to endogenous or exogenous triggers, GM-CSF receptor defects, and other genetic abnormalities of surfactant production account for the remainder of causes. The usual physiological consequence of PAP is impairment of gas exchange, which can lead to dyspnoea, hypoxaemia, or even respiratory failure and death. Pulmonary fibrosis occurs occasionally in patients with PAP. For patients with moderate to severe disease, whole lung lavage is still the first-line treatment of choice. Supplemental GM-CSF is also useful, but details about indications, choice of agent, and dosing remain unclear. Other therapies, including rituximab, plasmapheresis, and lung transplantation have been described but should be reserved for refractory cases.
Collapse
Affiliation(s)
- Anupam Kumar
- Division of Pulmonary & Critical Care Medicine, Spectrum Health-Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
| | - Basem Abdelmalak
- Departments of General Anesthesiology and Outcomes Research, Anesthesiology Institute, Cleveland, OH, USA
| | - Yoshikazu Inoue
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan
| | - Daniel A Culver
- Department of Pulmonary Medicine, Respiratory Institute, and Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| |
Collapse
|
|
27
|
Zhang D, Tian X, Feng R, Guo X, Wang P, Situ Y, Xiao Y, Xu KF. Secondary pulmonary alveolar proteinosis: a single-center retrospective study (a case series and literature review). BMC Pulm Med 2018; 18:15. [PMID: 29368649 PMCID: PMC5784666 DOI: 10.1186/s12890-018-0590-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Accepted: 01/15/2018] [Indexed: 02/07/2023] Open
Abstract
Background Secondary pulmonary alveolar proteinosis (sPAP) is an extremely rare disease. The clinical features of sPAP patients remain to be summarizeds. Methods Patients pathologically diagnosed with PAP and with negative results for anti-granulocyte macrophage colony stimulating factor (GM-CSF) autoantibodies from Peking Union Medical College Hospital between January 2000 and July 2016 were retrospectively studied. The PubMed database was also searched for literature to collect published cases. Results In our center, nine patients were diagnosed as sPAP with a median age of 37 years. Hematological disorders, including myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and pulmonary tuberculosis (TB) infection were the underlying diseases. Cases secondary to MDS had very poor prognosis as all of them survived less than 2 years after their diagnosis, while those secondary to TB had favorable prognosis. Only 33.3% of cases showed interlobular septal thickening in our sPAP group. Through literature review, 164 sPAP cases were collected. The age at diagnosis was 45.0 ± 14.8 years old and the gender radio was 1.20:1 (M:F). 61.9% of cases were diagnosed by bronchoscopy. MDS and CML were common underlying diseases in 34.1% and 15.2% of patients, respectively. Patients with sPAP secondary to hematological diseases had a short survival time and half of them died within 14.95 months after diagnosis. Conclusions MDS and TB infection were the most frequent underlying causes of sPAP in this single-center research in China, with cases secondary to MDS having a poor survival rate. sPAP was more likely to be secondary to hematological disorders, especially MDS and CML and had a fairly poor prognosis in published cases. sPAP should be suspected in PAP patients whose CT scan presents only ground-glass opacities without interlobular septal thickening. Electronic supplementary material The online version of this article (10.1186/s12890-018-0590-z) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Dongmei Zhang
- Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Present address: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xinlun Tian
- Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Ruie Feng
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaobei Guo
- Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Peng Wang
- Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yusen Situ
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Yi Xiao
- Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Kai-Feng Xu
- Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| |
Collapse
|
|
28
|
Pulmonary Alveolar Proteinosis in Setting of Inhaled Toxin Exposure and Chronic Substance Abuse. Case Rep Pulmonol 2018; 2018:5202173. [PMID: 29607238 PMCID: PMC5828087 DOI: 10.1155/2018/5202173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Revised: 08/15/2017] [Accepted: 09/20/2017] [Indexed: 11/17/2022] Open
Abstract
Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which defects in alveolar macrophage maturation or function lead to the accumulation of proteinaceous surfactant in alveolar space, resulting in impaired gas exchange and hypoxemia. PAP is categorized into three types: hereditary, autoimmune, and secondary. We report a case of secondary PAP in a 47-year-old man, whose risk factors include occupational exposure to inhaled toxins, especially aluminum dust, the use of anabolic steroids, and alcohol abuse, which in mice leads to alveolar macrophage dysfunction through a zinc-dependent mechanism that inhibits granulocyte macrophage-colony stimulating factor (GM-CSF) receptor signalling. Although the rarity and vague clinical presentation of PAP can pose diagnostic challenges, clinician awareness of PAP risk factors may facilitate the diagnostic process and lead to more prompt treatment.
Collapse
|
|
29
|
Favorable evolution of lung interstitial disease in a patient with chronic myelomonocytic leukemia treated with azacitidine. Ann Hematol 2017; 97:541-542. [DOI: 10.1007/s00277-017-3190-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 11/17/2017] [Indexed: 11/26/2022]
|
|
30
|
Liu Y, Chen LL, Qiu YY, Xiao YL, Cai HR. Clinical features of secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome: Two case reports. Medicine (Baltimore) 2017; 96:e8481. [PMID: 29095306 PMCID: PMC5682825 DOI: 10.1097/md.0000000000008481] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
RATIONALE Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by the abnormal accumulation of alveolar surfactant protein in alveolar spaces. Secondary PAP can result from myelodysplastic syndrome (MDS). PATIENT CONCERNS But most reports described a single case; here we reported 2 cases of PAP secondary to MDS. One case developed secondary PAP at the same time as MDS, and the other developed during the course of MDS. DIAGNOSES The diagnosis of PAP was made by bronchoalveolar lavage and based on the identification of periodic acid-Schiff-positive proteinaceous material. Chest high resolution CT (HRCT) scans showed variable distribution of ground glass opacities, but crazy-paving appearance was not seen in our 2 cases. INTERVENTIONS Because the patients' general conditions were poor, whole lung lavage was not used in the 2 cases. OUTCOMES And the 2 cases' prognoses were poor. LESSONS In conclusion, pulmonary physicians should suspect the possibility of secondary PAP when they encounter unexplained pulmonary infiltrates with some hematologic or infectious disease that shows diffuse bilateral GGO on an HRCT scan.
Collapse
|
|
31
|
Huaringa AJ, Francis WH. Pulmonary alveolar proteinosis: a case report and world literature review. Respirol Case Rep 2016; 4:e00201. [PMID: 28031836 PMCID: PMC5167286 DOI: 10.1002/rcr2.201] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 09/10/2016] [Accepted: 09/25/2016] [Indexed: 11/11/2022] Open
Abstract
Pulmonary alveolar proteinosis (PAP) is a lung disorder which was first described in 1958 by Rosen et al. and is indeed rare disease with a prevalence of 0.1 per 100,000 individuals. PAP is characterized by abnormal accumulation of pulmonary surfactant in the alveolar space, which impairs gas exchange leading to a severe hypoxemia. Pulmonary surfactant is an insoluble proteinaceous material that is rich in lipids and stains positive with periodic acid-Schiff (PAS). The most common type of PAP is the so-called autoimmune or idiopathic type. It has been hypothesized that deficiency in granulocyte macrophage-colony stimulating factor (GM-CSF), as a result of the anti-GM-CSF antibody production, is strongly related to impaired surfactant recycling that leads to the accumulation of surfactant in the alveolar space. Its clinical course is variable from spontaneous remission in the best case scenario, going through the entire spectrum of disease severity, towards fatal respiratory failure. Whole lung lavage has been the gold standard therapy in PAP until the advent of GM-CSF. Although the first case was reported to be idiopathic, subsequent analysis revealed that Pneumocystis jirovecii, silica, and other inhalational toxins were able to trigger this reaction. In this study, we report the case of a 52-year-old man who developed PAP syndrome after a 2-year exposure to silica dust. Our review of the world literature that includes 363 cases reported until now, reflects the evolution of science and technology in determining different aetiologies and diagnostic tests that lead to an improved perspective in the life of these patients.
Collapse
Affiliation(s)
- Armando J Huaringa
- Pulmonary and Critical Care Medicine Section Mountain Home Veterans Administration Medical Center and East Tennessee James H. Quillen College of Medicine Johnson City TN USA; Department of Medicine White Memorial Medical Center Los Angeles CA USA; Department of Medicine Loma Linda University School of Medicine Los Angeles CA USA
| | - Wassem H Francis
- Department of Medicine White Memorial Medical Center Los Angeles CA USA
| |
Collapse
|
|
32
|
Ballerie A, Nimubona S, Meunier C, Gutierrez FL, Desrues B, Delaval P, Jouneau S. Association of pulmonary alveolar proteinosis and fibrosis: patient with GATA2 deficiency. Eur Respir J 2016; 48:1510-1514. [PMID: 27799394 DOI: 10.1183/13993003.00252-2016] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 08/09/2016] [Indexed: 02/01/2023]
Affiliation(s)
- Alice Ballerie
- Service de pneumologie, centre de compétences des maladies pulmonaires rares de Bretagne, hôpital Pontchaillou, Rennes, France
| | | | | | | | - Benoît Desrues
- Service de pneumologie, centre de compétences des maladies pulmonaires rares de Bretagne, hôpital Pontchaillou, Rennes, France.,Université de Rennes 1, Rennes, France
| | - Philippe Delaval
- Service de pneumologie, centre de compétences des maladies pulmonaires rares de Bretagne, hôpital Pontchaillou, Rennes, France.,IRSET UMR 1085, Université de Rennes 1, Rennes, France
| | - Stéphane Jouneau
- Service de pneumologie, centre de compétences des maladies pulmonaires rares de Bretagne, hôpital Pontchaillou, Rennes, France.,IRSET UMR 1085, Université de Rennes 1, Rennes, France
| |
Collapse
|
|
33
|
Takaki M, Tanaka T, Komohara Y, Tsuchihashi Y, Mori D, Hayashi K, Fukuoka J, Yamasaki N, Nagayasu T, Ariyoshi K, Morimoto K, Nakata K. Recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation in a patient with a nonsense mutation in CSF2RB. Respir Med Case Rep 2016; 19:89-93. [PMID: 27595063 PMCID: PMC4995526 DOI: 10.1016/j.rmcr.2016.06.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 06/23/2016] [Accepted: 06/27/2016] [Indexed: 01/27/2023] Open
Abstract
Hereditary pulmonary alveolar proteinosis (PAP) caused by mutations in CSF2RA or CSF2RB, which encode GM-CSF receptor α and β respectively, is a rare disease. Although some experimental therapeutic strategies have been proposed, no clinical evidence has yet been reported. We herein describe the clinical course and recurrence of hereditary PAP after lung transplantation. A 36-year-old woman developed PAP of unknown etiology. She underwent bilateral lung transplantation from living donors at the age of 42 years because of severe respiratory failure complicated by pulmonary fibrosis. However, PAP recurred after 9 months, and we found that donor-origin alveolar macrophages had been almost completely replaced with recipient-origin macrophages. We performed a genetic analysis and identified a point deletion in the CSF2RB gene that caused a GM-CSF receptor-mediated signaling defect. PAP progressed with fibrosis in both transplanted lungs, and the patient died of respiratory failure 5 years after the lung transplantation. Distinct from recent reports on pulmonary macrophage transplantation in mice, this case suggests that human alveolar macrophages might not maintain their population only by self-renewal but may depend on a supply of precursor cells from the circulation. Bone marrow transplantation should be considered for treatment of severe PAP with GM-CSF receptor gene deficiency.
Collapse
Affiliation(s)
- Masahiro Takaki
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
| | - Takeshi Tanaka
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
| | - Yoshihiro Komohara
- Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoshiko Tsuchihashi
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
| | - Daisuke Mori
- Department of Pathology, Saga-ken Medical Centre Koseikan, Saga, Japan
| | - Kentaro Hayashi
- Department of Pathology, Nagasaki University, Nagasaki, Japan
| | - Junya Fukuoka
- Department of Pathology, Nagasaki University, Nagasaki, Japan
| | - Naoya Yamasaki
- Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takeshi Nagayasu
- Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Koya Ariyoshi
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
| | - Konosuke Morimoto
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan
| | - Koh Nakata
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan
| |
Collapse
|
|
34
|
Abstract
Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by the accumulation of surfactant in alveoli and terminal airways resulting in respiratory failure. PAP comprises part of a spectrum of disorders of surfactant homeostasis (clearance and production). The surfactant production disorders are caused by mutations in genes required for normal surfactant production. The PAP syndrome is identified based on history, radiologic, and bronchoalveolar lavage and/or histopathologic findings. The diagnosis of PAP-causing diseases in secondary PAP requires further studies. Whole-lung lavage is the current standard therapy and promising new pharmacologic therapies are in development.
Collapse
Affiliation(s)
- Takuji Suzuki
- Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, MLC7029, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
| | - Bruce C Trapnell
- Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, MLC7029, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
| |
Collapse
|
|
35
|
Imura Y, Yukawa N, Handa T, Nakashima R, Murakami K, Yoshifuji H, Ohmura K, Ishii H, Nakata K, Mimori T. Two cases of autoimmune and secondary pulmonary alveolar proteinosis during immunosuppressive therapy in dermatomyositis with interstitial lung disease. Mod Rheumatol 2016; 28:724-729. [PMID: 26872621 DOI: 10.3109/14397595.2016.1153443] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Interstitial lung disease (ILD) with dermatomyositis often requires intensive immunosuppressive therapy. Here, we report two cases of pulmonary alveolar proteinosis (PAP) in dermatomyositis with ILD. One case was secondary PAP, and the other was autoimmune PAP positive for the anti-granulocyte macrophage-colony-stimulating factor antibody. PAP arose during immunosuppressive therapy and symptoms ceased by attenuating immunosuppression. Exacerbation of pulmonary lesions during intensive immunosuppressive therapy may distinguish PAP from worsening ILD and attenuating immunosuppression should be considered.
Collapse
Affiliation(s)
| | | | - Tomohiro Handa
- b Department of Respiratory Medicine Graduate School of Medicine , Kyoto University , Sakyo-ku, Kyoto , Japan
| | - Ran Nakashima
- a Department of Rheumatology and Clinical Immunology
| | | | | | | | - Haruyuki Ishii
- c Department of Respiratory Medicine , Kyorin University School of Medicine , Mitaka , Japan , and
| | - Koh Nakata
- d Bioscience Medical Research Center , Niigata University , Chuoku, Niigata , Japan
| | | |
Collapse
|
|
36
|
Vece TJ, Young LR. Update on Diffuse Lung Disease in Children. Chest 2016; 149:836-45. [PMID: 26502226 DOI: 10.1378/chest.15-1986] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 09/22/2015] [Accepted: 10/04/2015] [Indexed: 12/31/2022] Open
Abstract
Diffuse lung diseases in children, also called children's interstitial lung disease, are a diverse group of rare disorders that cause disturbances of gas exchange in the lungs. Although individually rare, there are many different forms of diffuse lung disease in children, and collectively these disorders are associated with significant morbidity and mortality, as well as health-care resource utilization. Over the past several years, there have been many significant advances in the field, including genetic discoveries and the development of clinical practice guidelines. This review summarizes recent advances in the understanding, diagnosis, and treatment of diffuse lung diseases in children.
Collapse
Affiliation(s)
- Timothy J Vece
- Section of Pulmonology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
| | - Lisa R Young
- Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN; Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| |
Collapse
|
|
37
|
Akasaka K, Tanaka T, Kitamura N, Ohkouchi S, Tazawa R, Takada T, Ichiwata T, Yamaguchi E, Hirose M, Arai T, Nakano K, Nei T, Ishii H, Handa T, Inoue Y, Nakata K. Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study. BMC Pulm Med 2015; 15:88. [PMID: 26264717 PMCID: PMC4534060 DOI: 10.1186/s12890-015-0085-0] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 07/28/2015] [Indexed: 02/03/2023] Open
Abstract
Background Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections. Methods For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications. Results DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (>18.9 mg/day, n = 16) than treated with low-dose prednisolone (≤18.9 mg/day, n = 15) divided by median daily dose (p < 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p < 0.05). Median serum granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study. Conclusion The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections. Electronic supplementary material The online version of this article (doi:10.1186/s12890-015-0085-0) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Keiichi Akasaka
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan. .,Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
| | - Takahiro Tanaka
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan.
| | - Nobutaka Kitamura
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan.
| | - Shinya Ohkouchi
- Department of Respiratory Medicine, Tohoku University Graduate school of Medicine, Miyagi, Japan.
| | - Ryushi Tazawa
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan.
| | - Toshinori Takada
- Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
| | - Toshio Ichiwata
- Department of Pulmonary Medicine, Tokyo Medical School, Tokyo, Japan.
| | - Etsuro Yamaguchi
- Department of Respiratory and Allergy Medicine, Aichi Medical School, Aichi, Japan.
| | - Masaki Hirose
- Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan.
| | - Toru Arai
- Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan.
| | - Kentaro Nakano
- Department of Respiratory Medicine, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan.
| | - Takahito Nei
- Department of Respiratory Medicine, Nippon Medical University of Medicine, Tokyo, Japan.
| | - Haruyuki Ishii
- Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
| | - Tomohiro Handa
- Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan.
| | - Yoshikazu Inoue
- Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan.
| | - Koh Nakata
- Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan.
| |
Collapse
|
|
38
|
Griese M, Zarbock R, Costabel U, Hildebrandt J, Theegarten D, Albert M, Thiel A, Schams A, Lange J, Krenke K, Wesselak T, Schön C, Kappler M, Blum H, Krebs S, Jung A, Kröner C, Klein C, Campo I, Luisetti M, Bonella F. GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. BMC Pulm Med 2015; 15:87. [PMID: 26264606 PMCID: PMC4542098 DOI: 10.1186/s12890-015-0083-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 07/28/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases. Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders. METHODS Of 21 patients with GM-CSF-autoantibody negative PAP, 13 had no other organ involvement and 8 had some form of hematologic disorder. The latter were sequenced for GATA2. RESULTS Age at start of PAP ranged from 0.3 to 64 years, 4 patients were children. In half of the subjects GATA2-sequence variations were found, two of which were considered disease causing. Those two patients had the typical phenotype of GATA2 deficiency, one of whom additionally showed a previously undescribed feature - a cholesterol pneumonia. Hematologic disorders included chronic myeloic leukemia, juvenile myelo-monocytic leukemia, lymphoblastic leukemia, sideroblastic anemia and two cases of myelodysplastic syndrome (MDS). A 4 year old child with MDS and DiGeorge Syndrome Type 2 was rescued with repetitive whole lung lavages and her PAP was cured with heterologous stem cell transplant. CONCLUSIONS In children and adults with severe GM-CSF negative PAP a close cooperation between pneumologists and hemato-oncologists is needed to diagnose the underlying diseases, some of which are caused by mutations of transcription factor GATA2. Treatment with whole lung lavages as well as stem cell transplant may be successful.
Collapse
Affiliation(s)
- Matthias Griese
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Ralf Zarbock
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Ulrich Costabel
- Interstitial and Rare Lung Disease Unit, Ruhrland Hospital, University of Duisburg-Essen, Essen, Germany.
| | - Jenna Hildebrandt
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Dirk Theegarten
- Institute for Pathology and Neuropathology, University Hospital Essen, Essen, Germany.
| | - Michael Albert
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Antonia Thiel
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Andrea Schams
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Joanna Lange
- Department of Pediatric Pneumology and Allergy, University Hospital, University of Warsaw, Warsaw, Poland.
| | - Katazyrna Krenke
- Department of Pediatric Pneumology and Allergy, University Hospital, University of Warsaw, Warsaw, Poland.
| | - Traudl Wesselak
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Carola Schön
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Matthias Kappler
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Helmut Blum
- LAFUGA Genomics, Gene center, Ludwig-Maximilians University Munich, Munich, Germany.
| | - Stefan Krebs
- LAFUGA Genomics, Gene center, Ludwig-Maximilians University Munich, Munich, Germany.
| | - Andreas Jung
- Institute of Pathology, Ludwig-Maximilians University, Munich, Germany.
| | - Carolin Kröner
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Christoph Klein
- Hauner Children's University Hospital, Ludwig-Maximilians University, Member of the German Center for Lung Research, Lindwurmstr. 4, 80337, Munich, Germany.
| | - Ilaria Campo
- Department of Molecular Medicine, Pneumology Unit, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
| | - Maurizio Luisetti
- Department of Molecular Medicine, Pneumology Unit, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
| | - Francesco Bonella
- Interstitial and Rare Lung Disease Unit, Ruhrland Hospital, University of Duisburg-Essen, Essen, Germany.
| |
Collapse
|
|
39
|
Borie R, Danel C, Lainé C, Kannengiesser C, Crestani B. [Treatment of alveolar proteinosis by intrapulmonary transplantation of macrophages]. Med Sci (Paris) 2015; 31:241-4. [PMID: 25855273 DOI: 10.1051/medsci/20153103005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Raphael Borie
- APHP, hôpital Bichat, DHU Fire, service de pneumologie A, centre de compétence des maladies pulmonaires rares, 46, rue Henri Huchard, 75018 Paris, France - Inserm unité 1152, Paris, France - Université Paris Diderot, Paris, France
| | - Claire Danel
- Université Paris Diderot, Paris, France - APHP, hôpital Bichat, service d'anatomopathologie, 46, rue Henri Huchard, 75018 Paris, France
| | - Catherine Lainé
- service d'immunologie-thérapie cellulaire et hématopoïèse, centre hospitalo-universitaire Pontchaillou, Rennes, France
| | - Caroline Kannengiesser
- Université Paris Diderot, Paris, France - APHP, hôpital Bichat, service de génétique, 46, rue Henri Huchard, 75018 Paris, France
| | - Bruno Crestani
- APHP, hôpital Bichat, DHU Fire, service de pneumologie A, centre de compétence des maladies pulmonaires rares, 46, rue Henri Huchard, 75018 Paris, France - Inserm unité 1152, Paris, France - Université Paris Diderot, Paris, France
| |
Collapse
|
|
40
|
Jouneau S, Kerjouan M, Briens E, Lenormand JP, Meunier C, Letheulle J, Chiforeanu D, Lainé-Caroff C, Desrues B, Delaval P. La protéinose alvéolaire pulmonaire. Rev Mal Respir 2014; 31:975-91. [DOI: 10.1016/j.rmr.2014.08.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 08/20/2014] [Indexed: 01/30/2023]
|