U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Interstitial lung disease 2(ILD2)

MedGen UID:
1794136
Concept ID:
C5561926
Disease or Syndrome
Synonyms: Familial idiopathic pulmonary fibrosis; Familial Pulmonary Fibrosis; Fibrocystic pulmonary dysplasia; Fibrosing alveolitis, cryptogenic; ILD2
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.
 
Genes (locations): MUC5B (11p15.5); SFTPA2 (10q22.3); SFTPC (8p21.3); TERT (5p15.33)
 
Monarch Initiative: MONDO:0800029
OMIM®: 178500
Orphanet: ORPHA2032

Definition

Interstitial lung disease (ILD) comprises a heterogeneous group of rare diseases affecting the distal part of the lung and characterized by a progressive remodeling of the alveolar interstitium. The manifestations form a spectrum ranging from idiopathic interstitial pneumonia (IIP) or pneumonitis to the more severe idiopathic pulmonary fibrosis (IPF). IPF is associated with an increased risk of developing lung cancer, which occurs in a subset of patients with ILD. Clinical features of ILD include dyspnea, clubbing of the fingers, and restrictive lung capacity. Imaging typically shows ground glass opacities and inter- and intraseptal thickening, while histologic studies usually show a pattern consistent with 'usual interstitial pneumonia' (UIP) (review by Gross and Hunninghake, 2001; summary by Legendre et al., 2020). Idiopathic pulmonary fibrosis is one of a family of idiopathic pneumonias sharing clinical features of shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees in inflammation, fibrosis, or both on lung biopsy. In some cases, the disorder can be rapidly progressive and characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Although older studies included several forms of interstitial pneumonia under the term 'idiopathic pulmonary fibrosis,' the clinical label of 'idiopathic pulmonary fibrosis' should be reserved for patients with a specific form of fibrosing interstitial pneumonia referred to as usual interstitial pneumonia (Gross and Hunninghake, 2001). It is estimated that 0.5 to 2.2% of cases of idiopathic pulmonary fibrosis are familial (Marshall et al., 2000). Gross and Hunninghake (2001) reviewed idiopathic pulmonary fibrosis, emphasizing definition, pathogenesis, diagnosis, natural history, and therapy. Antoniou et al. (2004) provided a 'top ten list' of references pertaining to etiopathogenesis, prognosis, diagnosis, therapy, and other aspects of idiopathic pulmonary fibrosis. For a discussion of genetic heterogeneity of ILD, see ILD1 (619611). Pulmonary fibrosis can also be a feature in patients with mutations in the TERT (187270) or the TERC (602322) gene; see PFBMFT1 (614742) and PFBMFT2 (614743). Some patients with surfactant protein C deficiency (610913) who survive to adulthood manifest features of pulmonary fibrosis. [from OMIM]

Clinical features

From HPO
Minimally invasive lung adenocarcinoma
MedGen UID:
2871
Concept ID:
C0007120
Neoplastic Process
Adenocarcinoma of the Bronchus.
Clubbing of fingers
MedGen UID:
3129
Concept ID:
C0009080
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
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.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Exertional dyspnea
MedGen UID:
68549
Concept ID:
C0231807
Sign or Symptom
Perceived difficulty to breathe that occurs with exercise or exertion and improves with rest.
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.
Usual interstitial pneumonia
MedGen UID:
1662563
Concept ID:
C4721509
Disease or Syndrome
Temporal and spatial heterogeneity in lungs based on presence of fibrosis and honeycombing.
Elevated bronchoalveolar lavage fluid neutrophil proportion
MedGen UID:
1710230
Concept ID:
C5397969
Finding
Usually, Neutrophils make up less than 3% of all cells found in the broncho-alveloar lavage fluid. In children, standard value of neutrophils is higher depending on their age (children under the age of 5 show a maximum value of 10%). This elevated cell proportion is a sign for acute and chronic infections (HP:0012387, HP:0006538) and can be associated to specific diseases.
Increased circulating antibody level
MedGen UID:
1713383
Concept ID:
C5397581
Finding
An increased level of gamma globulin (immunoglobulin) in the blood.

Professional guidelines

PubMed

Swain SM, Nishino M, Lancaster LH, Li BT, Nicholson AG, Bartholmai BJ, Naidoo J, Schumacher-Wulf E, Shitara K, Tsurutani J, Conte P, Kato T, Andre F, Powell CA
Cancer Treat Rev 2022 May;106:102378. Epub 2022 Mar 12 doi: 10.1016/j.ctrv.2022.102378. PMID: 35430509
Aveyard P, Gao M, Lindson N, Hartmann-Boyce J, Watkinson P, Young D, Coupland CAC, Tan PS, Clift AK, Harrison D, Gould DW, Pavord ID, Hippisley-Cox J
Lancet Respir Med 2021 Aug;9(8):909-923. Epub 2021 Apr 1 doi: 10.1016/S2213-2600(21)00095-3. PMID: 33812494Free PMC Article
Soares RV, Forsythe A, Hogarth K, Sweiss NJ, Noth I, Patti MG
Arq Gastroenterol 2011 Apr-Jun;48(2):91-7. doi: 10.1590/s0004-28032011000200002. PMID: 21709948

Recent clinical studies

Etiology

Strykowski R, Adegunsoye A
Immunol Allergy Clin North Am 2023 May;43(2):209-228. Epub 2023 Mar 3 doi: 10.1016/j.iac.2023.01.010. PMID: 37055085
Conte P, Ascierto PA, Patelli G, Danesi R, Vanzulli A, Sandomenico F, Tarsia P, Cattelan A, Comes A, De Laurentiis M, Falcone A, Regge D, Richeldi L, Siena S
ESMO Open 2022 Apr;7(2):100404. Epub 2022 Feb 24 doi: 10.1016/j.esmoop.2022.100404. PMID: 35219244Free PMC Article
Luppi F, Sebastiani M, Salvarani C, Bendstrup E, Manfredi A
Nat Rev Rheumatol 2022 Feb;18(2):85-96. Epub 2021 Dec 7 doi: 10.1038/s41584-021-00721-z. PMID: 34876670
Roofeh D, Lescoat A, Khanna D
Curr Opin Rheumatol 2021 May 1;33(3):240-248. doi: 10.1097/BOR.0000000000000795. PMID: 33741803Free PMC Article
Antoniou KM, Margaritopoulos GA, Tomassetti S, Bonella F, Costabel U, Poletti V
Eur Respir Rev 2014 Mar 1;23(131):40-54. doi: 10.1183/09059180.00009113. PMID: 24591661Free PMC Article

Diagnosis

Strykowski R, Adegunsoye A
Immunol Allergy Clin North Am 2023 May;43(2):209-228. Epub 2023 Mar 3 doi: 10.1016/j.iac.2023.01.010. PMID: 37055085
McCarthy C, Keane MP
Respirology 2022 Jul;27(7):539-548. Epub 2022 May 5 doi: 10.1111/resp.14278. PMID: 35513341Free PMC Article
Conte P, Ascierto PA, Patelli G, Danesi R, Vanzulli A, Sandomenico F, Tarsia P, Cattelan A, Comes A, De Laurentiis M, Falcone A, Regge D, Richeldi L, Siena S
ESMO Open 2022 Apr;7(2):100404. Epub 2022 Feb 24 doi: 10.1016/j.esmoop.2022.100404. PMID: 35219244Free PMC Article
Luppi F, Sebastiani M, Salvarani C, Bendstrup E, Manfredi A
Nat Rev Rheumatol 2022 Feb;18(2):85-96. Epub 2021 Dec 7 doi: 10.1038/s41584-021-00721-z. PMID: 34876670
Antoniou KM, Margaritopoulos GA, Tomassetti S, Bonella F, Costabel U, Poletti V
Eur Respir Rev 2014 Mar 1;23(131):40-54. doi: 10.1183/09059180.00009113. PMID: 24591661Free PMC Article

Therapy

Rahaghi FF, Hsu VM, Kaner RJ, Mayes MD, Rosas IO, Saggar R, Steen VD, Strek ME, Bernstein EJ, Bhatt N, Castelino FV, Chung L, Domsic RT, Flaherty KR, Gupta N, Kahaleh B, Martinez FJ, Morrow LE, Moua T, Patel N, Shlobin OA, Southern BD, Volkmann ER, Khanna D
Respir Res 2023 Jan 9;24(1):6. doi: 10.1186/s12931-022-02292-3. PMID: 36624431Free PMC Article
Roofeh D, Lescoat A, Khanna D
Curr Opin Rheumatol 2021 May 1;33(3):240-248. doi: 10.1097/BOR.0000000000000795. PMID: 33741803Free PMC Article
Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, Raghu G, Sauter W, Girard M, Alves M, Clerisme-Beaty E, Stowasser S, Tetzlaff K, Kuwana M, Maher TM; SENSCIS Trial Investigators
N Engl J Med 2019 Jun 27;380(26):2518-2528. Epub 2019 May 20 doi: 10.1056/NEJMoa1903076. PMID: 31112379
Graney BA, Fischer A
Ann Am Thorac Soc 2019 May;16(5):525-533. doi: 10.1513/AnnalsATS.201808-565CME. PMID: 30695649Free PMC Article
Barnes H, Holland AE, Westall GP, Goh NS, Glaspole IN
Cochrane Database Syst Rev 2018 Jan 3;1(1):CD010908. doi: 10.1002/14651858.CD010908.pub2. PMID: 29297205Free PMC Article

Prognosis

McCarthy C, Keane MP
Respirology 2022 Jul;27(7):539-548. Epub 2022 May 5 doi: 10.1111/resp.14278. PMID: 35513341Free PMC Article
Conte P, Ascierto PA, Patelli G, Danesi R, Vanzulli A, Sandomenico F, Tarsia P, Cattelan A, Comes A, De Laurentiis M, Falcone A, Regge D, Richeldi L, Siena S
ESMO Open 2022 Apr;7(2):100404. Epub 2022 Feb 24 doi: 10.1016/j.esmoop.2022.100404. PMID: 35219244Free PMC Article
Nasser M, Larrieu S, Si-Mohamed S, Ahmad K, Boussel L, Brevet M, Chalabreysse L, Fabre C, Marque S, Revel D, Thivolet-Bejui F, Traclet J, Zeghmar S, Maucort-Boulch D, Cottin V
Eur Respir J 2021 Feb;57(2) Epub 2021 Feb 11 doi: 10.1183/13993003.02718-2020. PMID: 32943410Free PMC Article
Rivera-Ortega P, Molina-Molina M
Ann Glob Health 2019 Jan 22;85(1) doi: 10.5334/aogh.2414. PMID: 30741505Free PMC Article
Antoniou KM, Margaritopoulos GA, Tomassetti S, Bonella F, Costabel U, Poletti V
Eur Respir Rev 2014 Mar 1;23(131):40-54. doi: 10.1183/09059180.00009113. PMID: 24591661Free PMC Article

Clinical prediction guides

Lee KS, Han J, Wada N, Hata A, Lee HY, Yi C, Hino T, Doyle TJ, Franquet T, Hatabu H
AJR Am J Roentgenol 2024 Feb;222(2):e2329119. Epub 2023 Apr 12 doi: 10.2214/AJR.23.29119. PMID: 37095673
Roofeh D, Lin CJF, Goldin J, Kim GH, Furst DE, Denton CP, Huang S, Khanna D; focuSSced Investigators
Arthritis Rheumatol 2021 Jul;73(7):1301-1310. Epub 2021 May 25 doi: 10.1002/art.41668. PMID: 33538094Free PMC Article
Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, Preston R, Thillai M, Dewar A, Molyneaux PL, West AG
Ann Am Thorac Soc 2021 May;18(5):799-806. doi: 10.1513/AnnalsATS.202008-1002OC. PMID: 33433263Free PMC Article
Nasser M, Larrieu S, Si-Mohamed S, Ahmad K, Boussel L, Brevet M, Chalabreysse L, Fabre C, Marque S, Revel D, Thivolet-Bejui F, Traclet J, Zeghmar S, Maucort-Boulch D, Cottin V
Eur Respir J 2021 Feb;57(2) Epub 2021 Feb 11 doi: 10.1183/13993003.02718-2020. PMID: 32943410Free PMC Article
Antoniou KM, Margaritopoulos GA, Tomassetti S, Bonella F, Costabel U, Poletti V
Eur Respir Rev 2014 Mar 1;23(131):40-54. doi: 10.1183/09059180.00009113. PMID: 24591661Free PMC Article

Recent systematic reviews

Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D
Ann Rheum Dis 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764. PMID: 36927642
Paik JJ, Lubin G, Gromatzky A, Mudd PN Jr, Ponda MP, Christopher-Stine L
Clin Exp Rheumatol 2023 Mar;41(2):348-358. Epub 2022 Jun 28 doi: 10.55563/clinexprheumatol/hxin6o. PMID: 35766013Free PMC Article
Kondoh Y, Makino S, Ogura T, Suda T, Tomioka H, Amano H, Anraku M, Enomoto N, Fujii T, Fujisawa T, Gono T, Harigai M, Ichiyasu H, Inoue Y, Johkoh T, Kameda H, Kataoka K, Katsumata Y, Kawaguchi Y, Kawakami A, Kitamura H, Kitamura N, Koga T, Kurasawa K, Nakamura Y, Nakashima R, Nishioka Y, Nishiyama O, Okamoto M, Sakai F, Sakamoto S, Sato S, Shimizu T, Takayanagi N, Takei R, Takemura T, Takeuchi T, Toyoda Y, Yamada H, Yamakawa H, Yamano Y, Yamasaki Y, Kuwana M; joint committee of Japanese Respiratory Society and Japan College of Rheumatology
Respir Investig 2021 Nov;59(6):709-740. Epub 2021 Oct 1 doi: 10.1016/j.resinv.2021.04.011. PMID: 34602377
Dowman L, Hill CJ, May A, Holland AE
Cochrane Database Syst Rev 2021 Feb 1;2(2):CD006322. doi: 10.1002/14651858.CD006322.pub4. PMID: 34559419Free PMC Article
Barnes H, Holland AE, Westall GP, Goh NS, Glaspole IN
Cochrane Database Syst Rev 2018 Jan 3;1(1):CD010908. doi: 10.1002/14651858.CD010908.pub2. PMID: 29297205Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...