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Autoimmune pulmonary alveolar proteinosis

MedGen UID:
410079
Concept ID:
C1970472
Disease or Syndrome
Synonyms: PAP acquired; Pulmonary alveolar lipoproteinosis acquired; Pulmonary alveolar proteinosis acquired
SNOMED CT: Autoimmune pulmonary alveolar proteinosis (707443007)
Modes of inheritance:
Non-Mendelian inheritance
MedGen UID:
109109
Concept ID:
C0600599
Genetic Function
Source: Orphanet
A mode of inheritance that depends on genetic determinants in more than one gene.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Monarch Initiative: MONDO:0012579
OMIM®: 610910
Orphanet: ORPHA747

Definition

Pulmonary alveolar proteinosis is a pathologic entity characterized by intraalveolar surfactant accumulation. There are 3 clinically distinct forms: hereditary (usually congenital), secondary, and acquired. The acquired form of pulmonary alveolar proteinosis is the most common form, accounting for approximately 90% of cases. The mean age at diagnosis is 39 years and it is associated with smoking in 72% of cases. The estimated incidence and prevalence are 0.36 and 3.70 cases per million, respectively (Trapnell et al., 2003; Seymour and Presneill, 2002). Secondary pulmonary alveolar proteinosis develops in association with conditions involving functional impairment or reduced numbers of alveolar macrophages. Such conditions include some hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust or toxic fumes, and certain infections. Congenital pulmonary alveolar proteinosis is a rare, severe, often fatal disorder of newborns associated with pulmonary surfactant metabolism dysfunction caused by mutations in genes involved in surfactant metabolism (see, e.g., SMDP1, 265120) (Trapnell et al., 2003). See 300770 for information on congenital PAP due to CSF2RA (306250) deficiency. [from OMIM]

Clinical features

From HPO
Chest pain
MedGen UID:
2992
Concept ID:
C0008031
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the chest.
Clubbing
MedGen UID:
57692
Concept ID:
C0149651
Anatomical Abnormality
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Hemoptysis
MedGen UID:
5502
Concept ID:
C0019079
Sign or Symptom
Coughing up (expectoration) of blood or blood-streaked sputum from the larynx, trachea, bronchi, or lungs.
Inspiratory crackles
MedGen UID:
661427
Concept ID:
C0577961
Finding
Crackles that are heard during the inspiratory phase.
Hypoxemia
MedGen UID:
152145
Concept ID:
C0700292
Finding
An abnormally low level of blood oxygen.
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Decreased DLCO
MedGen UID:
892993
Concept ID:
C4073175
Finding
Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test.
Pulmonary alveolar proteinosis
MedGen UID:
1763046
Concept ID:
C5400698
Finding
Accumulation of amorphous PAS-positive material in the space between alveolar macrophages, sometimes as condensed form (oval bodies) are typically found in alveolar proteinosis.
Brain abscess
MedGen UID:
2335
Concept ID:
C0006105
Disease or Syndrome
A collection of pus, immune cells, and other material in the brain.
Lung abscess
MedGen UID:
7397
Concept ID:
C0024110
Disease or Syndrome
A circumscribed area of pus or necrotic debris in lung parenchyma, which leads to a cavity, and after formation of bronchopulmonary fistula, can manifest as an air-fluid level inside the cavity.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Anti-granulocyte-macrophage colony stimulating factor antibody positivity
MedGen UID:
1640956
Concept ID:
C4703382
Finding
The presence of autoantibodies in the serum that react against granulocyte-macrophage colony stimulating factor.
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutoimmune pulmonary alveolar proteinosis
Follow this link to review classifications for Autoimmune pulmonary alveolar proteinosis in Orphanet.

Professional guidelines

PubMed

Grutters LA, Smith EC, Casteleijn CW, van Dongen EP, Ruven HJ, van der Vis JJ, Veltkamp M
J Bronchology Interv Pulmonol 2021 Jul 1;28(3):215-220. doi: 10.1097/LBR.0000000000000741. PMID: 34151899Free PMC Article
Ben-Dov I, Segel MJ
Autoimmun Rev 2014 Apr-May;13(4-5):513-7. Epub 2014 Jan 11 doi: 10.1016/j.autrev.2014.01.046. PMID: 24424195
Leth S, Bendstrup E, Vestergaard H, Hilberg O
Respirology 2013 Jan;18(1):82-91. doi: 10.1111/j.1440-1843.2012.02274.x. PMID: 23036113

Recent clinical studies

Etiology

Mabo A, Borie R, Wemeau-Stervinou L, Uzunhan Y, Gomez E, Prevot G, Reynaud-Gaubert M, Traclet J, Bergot E, Cadranel J, Marchand-Adam S, Bergeron A, Blanchard E, Bondue B, Bonniaud P, Bourdin A, Burgel PR, Hirschi S, Marquette CH, Quétant S, Nunes H, Chenivesse C, Crestani B, Guirriec Y, Monnier D, Ménard C, Tattevin P, Cottin V, Luque Paz D, Jouneau S; OrphaLung Network
Thorax 2023 Dec 15;79(1):68-74. doi: 10.1136/thorax-2023-220040. PMID: 37758458
Campo I, Meloni F, Gahlemann M, Sauter W, Ittrich C, Schoelch C, Trapnell BC, Gupta A
Sci Rep 2022 May 24;12(1):8708. doi: 10.1038/s41598-022-11446-8. PMID: 35610268Free PMC Article
Trapnell BC, Inoue Y, Bonella F, Morgan C, Jouneau S, Bendstrup E, Campo I, Papiris SA, Yamaguchi E, Cetinkaya E, Ilkovich MM, Kramer MR, Veltkamp M, Kreuter M, Baba T, Ganslandt C, Tarnow I, Waterer G, Jouhikainen T; IMPALA Trial Investigators
N Engl J Med 2020 Oct 22;383(17):1635-1644. Epub 2020 Sep 7 doi: 10.1056/NEJMoa1913590. PMID: 32897035Free PMC Article
Tazawa R, Ueda T, Abe M, Tatsumi K, Eda R, Kondoh S, Morimoto K, Tanaka T, Yamaguchi E, Takahashi A, Oda M, Ishii H, Izumi S, Sugiyama H, Nakagawa A, Tomii K, Suzuki M, Konno S, Ohkouchi S, Tode N, Handa T, Hirai T, Inoue Y, Arai T, Asakawa K, Sakagami T, Hashimoto A, Tanaka T, Takada T, Mikami A, Kitamura N, Nakata K
N Engl J Med 2019 Sep 5;381(10):923-932. doi: 10.1056/NEJMoa1816216. PMID: 31483963
Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED
Expert Rev Respir Med 2015 Jun;9(3):337-49. Epub 2015 Apr 12 doi: 10.1586/17476348.2015.1035259. PMID: 25864717

Diagnosis

Mabo A, Borie R, Wemeau-Stervinou L, Uzunhan Y, Gomez E, Prevot G, Reynaud-Gaubert M, Traclet J, Bergot E, Cadranel J, Marchand-Adam S, Bergeron A, Blanchard E, Bondue B, Bonniaud P, Bourdin A, Burgel PR, Hirschi S, Marquette CH, Quétant S, Nunes H, Chenivesse C, Crestani B, Guirriec Y, Monnier D, Ménard C, Tattevin P, Cottin V, Luque Paz D, Jouneau S; OrphaLung Network
Thorax 2023 Dec 15;79(1):68-74. doi: 10.1136/thorax-2023-220040. PMID: 37758458
Goda M, Takigawa Y, Fujiwara K, Shinno Y
Intern Med 2023 May 15;62(10):1569-1570. Epub 2022 Oct 12 doi: 10.2169/internalmedicine.0226-22. PMID: 36223923Free PMC Article
Carey B, Chalk C, Stock J, Toth A, Klingler M, Greenberg H, Uchida K, Arumugam P, Trapnell BC
J Immunol Methods 2022 Dec;511:113366. Epub 2022 Oct 2 doi: 10.1016/j.jim.2022.113366. PMID: 36198356Free PMC Article
McCarthy C, Carey BC, Trapnell BC
Am J Respir Crit Care Med 2022 May 1;205(9):1016-1035. doi: 10.1164/rccm.202112-2742SO. PMID: 35227171Free PMC Article
Ben-Dov I, Segel MJ
Autoimmun Rev 2014 Apr-May;13(4-5):513-7. Epub 2014 Jan 11 doi: 10.1016/j.autrev.2014.01.046. PMID: 24424195

Therapy

McCarthy C, Carey BC, Trapnell BC
Am J Respir Crit Care Med 2022 May 1;205(9):1016-1035. doi: 10.1164/rccm.202112-2742SO. PMID: 35227171Free PMC Article
Trapnell BC, Inoue Y, Bonella F, Morgan C, Jouneau S, Bendstrup E, Campo I, Papiris SA, Yamaguchi E, Cetinkaya E, Ilkovich MM, Kramer MR, Veltkamp M, Kreuter M, Baba T, Ganslandt C, Tarnow I, Waterer G, Jouhikainen T; IMPALA Trial Investigators
N Engl J Med 2020 Oct 22;383(17):1635-1644. Epub 2020 Sep 7 doi: 10.1056/NEJMoa1913590. PMID: 32897035Free PMC Article
Tazawa R, Ueda T, Abe M, Tatsumi K, Eda R, Kondoh S, Morimoto K, Tanaka T, Yamaguchi E, Takahashi A, Oda M, Ishii H, Izumi S, Sugiyama H, Nakagawa A, Tomii K, Suzuki M, Konno S, Ohkouchi S, Tode N, Handa T, Hirai T, Inoue Y, Arai T, Asakawa K, Sakagami T, Hashimoto A, Tanaka T, Takada T, Mikami A, Kitamura N, Nakata K
N Engl J Med 2019 Sep 5;381(10):923-932. doi: 10.1056/NEJMoa1816216. PMID: 31483963
Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED
Expert Rev Respir Med 2015 Jun;9(3):337-49. Epub 2015 Apr 12 doi: 10.1586/17476348.2015.1035259. PMID: 25864717
Ben-Dov I, Segel MJ
Autoimmun Rev 2014 Apr-May;13(4-5):513-7. Epub 2014 Jan 11 doi: 10.1016/j.autrev.2014.01.046. PMID: 24424195

Prognosis

Munsif M, Sweeney D, Leong TL, Stirling RG
Eur Respir Rev 2023 Dec 31;32(170) Epub 2023 Nov 22 doi: 10.1183/16000617.0080-2023. PMID: 37993127Free PMC Article
Mariani F, Salvaterra E, Lettieri S, De Silvestri A, Corino A, Bosio M, Fraolini E, Piloni D, Rodi G, Corsico AG, Campo I
Respir Res 2022 Mar 17;23(1):60. doi: 10.1186/s12931-022-01982-2. PMID: 35300687Free PMC Article
McCarthy C, Carey BC, Trapnell BC
Am J Respir Crit Care Med 2022 May 1;205(9):1016-1035. doi: 10.1164/rccm.202112-2742SO. PMID: 35227171Free PMC Article
Fukushima K, Tsujino K, Futami S, Kida H
Int J Mol Sci 2020 Feb 8;21(3) doi: 10.3390/ijms21031138. PMID: 32046322Free PMC Article
Ben-Dov I, Segel MJ
Autoimmun Rev 2014 Apr-May;13(4-5):513-7. Epub 2014 Jan 11 doi: 10.1016/j.autrev.2014.01.046. PMID: 24424195

Clinical prediction guides

Munsif M, Sweeney D, Leong TL, Stirling RG
Eur Respir Rev 2023 Dec 31;32(170) Epub 2023 Nov 22 doi: 10.1183/16000617.0080-2023. PMID: 37993127Free PMC Article
Campo I, Meloni F, Gahlemann M, Sauter W, Ittrich C, Schoelch C, Trapnell BC, Gupta A
Sci Rep 2022 May 24;12(1):8708. doi: 10.1038/s41598-022-11446-8. PMID: 35610268Free PMC Article
Mariani F, Salvaterra E, Lettieri S, De Silvestri A, Corino A, Bosio M, Fraolini E, Piloni D, Rodi G, Corsico AG, Campo I
Respir Res 2022 Mar 17;23(1):60. doi: 10.1186/s12931-022-01982-2. PMID: 35300687Free PMC Article
Trapnell BC, Inoue Y, Bonella F, Morgan C, Jouneau S, Bendstrup E, Campo I, Papiris SA, Yamaguchi E, Cetinkaya E, Ilkovich MM, Kramer MR, Veltkamp M, Kreuter M, Baba T, Ganslandt C, Tarnow I, Waterer G, Jouhikainen T; IMPALA Trial Investigators
N Engl J Med 2020 Oct 22;383(17):1635-1644. Epub 2020 Sep 7 doi: 10.1056/NEJMoa1913590. PMID: 32897035Free PMC Article
Manali ED, Papadaki G, Konstantonis D, Tsangaris I, Papaioannou AI, Kolilekas L, Schams A, Kagouridis K, Karakatsani A, Orfanos S, Griese M, Papiris SA
Expert Rev Respir Med 2016 Feb;10(2):235-40. Epub 2015 Nov 27 doi: 10.1586/17476348.2016.1116389. PMID: 26558331

Recent systematic reviews

Munsif M, Sweeney D, Leong TL, Stirling RG
Eur Respir Rev 2023 Dec 31;32(170) Epub 2023 Nov 22 doi: 10.1183/16000617.0080-2023. PMID: 37993127Free PMC Article
Lazarus HM, Ragsdale CE, Gale RP, Lyman GH
Front Immunol 2021;12:706186. Epub 2021 Aug 17 doi: 10.3389/fimmu.2021.706186. PMID: 34484202Free PMC Article

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