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Interstitial lung disease 1(ILD1)

MedGen UID:
1794231
Concept ID:
C5562021
Disease or Syndrome
Synonyms: ILD1; INTERSTITIAL LUNG DISEASE 1
 
Gene (location): SFTPA1 (10q22.3)
 
Monarch Initiative: MONDO:0030608
OMIM®: 619611

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) (summary by Nathan et al., 2016, Doubkova et al., 2019). Genetic Heterogeneity of Interstitial Lung Disease See also ILD2 (178500), caused by mutation in the SFTPA2 gene (178642) on chromosome 10q22. [from OMIM]

Clinical features

From HPO
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.
Crackles
MedGen UID:
11118
Concept ID:
C0034642
Finding
Crackles are discontinuous, explosive, and nonmusical adventitious lung sounds normally heard in inspiration and sometimes during expiration. Crackles are usually classified as fine and coarse crackles based on their duration, loudness, pitch, timing in the respiratory cycle, and relationship to coughing and changing body position.
Non-specific interstitial pneumonia
MedGen UID:
220936
Concept ID:
C1290344
Disease or Syndrome
Temporally uniform (all lesions are in the same stage of evolution) pattern of diffuse inflammatory interstitial process, mostly symmetric over the entire lung, involving mainly the alveolar septa.
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.
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.
Elevated bronchoalveolar lavage fluid eosinophil proportion
MedGen UID:
1718571
Concept ID:
C5397979
Finding
Usually, eosinophils make up less than 0.5% of all cells found in the broncho-alveloar lavage fluid. But in eosinophilic lung disease, the eosinophil cell proportion typically represents more than 25%. Comment
Ground-glass opacification
MedGen UID:
1779663
Concept ID:
C5539411
Finding
On chest radiographs, ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. On CT scans, it appears as hazy increased opacity of lung, with preservation of bronchial and vascular margins. It is caused by partial filling of airspaces, interstitial thickening (due to fluid, cells, and/or fibrosis), partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air. Ground-glass opacity is less opaque than consolidation, in which bronchovascular margins are obscured.
Interlobular septal thickening
MedGen UID:
1779791
Concept ID:
C5539418
Finding
Presence of thickening of the interlobular septa of the lungs as seen on a CT scan.
Intralobular septal thickening
MedGen UID:
1779605
Concept ID:
C5539736
Finding
Intralobular septal thickening is a computed tomography finding of increased width of the walls (septa) within a pulmonary lobule. Secondary pulmonary lobules represent a cluster of up to 30 acini 9 supplied by a common distal pulmonary artery and bronchiole. These clustered acini are bounded by interstitial fibrous septa (interlobular septa) which outline an irregular polyhedron of varying size between 1 and 2.5 cm. Interlobular septal thickening is seen on chest radiographs as thin linear opacities at right angles to and in contact with the lateral pleural surfaces near the lung bases. In contrast, intralobular septal thickening are visible as fine linear opacities in a lobule when the intralobular interstitial tissue is abnormally thickened. When numerous, they may appear as a fine reticular pattern.

Professional guidelines

PubMed

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
Glinjongol C, Pengpol W
J Med Assoc Thai 2005 Jun;88(6):734-42. PMID: 16083211

Recent clinical studies

Etiology

Singh S, Lum J, Majeed A
Transplant Proc 2023 Nov;55(9):2197-2202. Epub 2023 Sep 26 doi: 10.1016/j.transproceed.2023.08.005. PMID: 37758562
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
Kam JK, Charan N, Leong RW, Loh ZW, Thong BY
Lupus 2021 Feb;30(2):248-255. Epub 2020 Dec 1 doi: 10.1177/0961203320976932. PMID: 33259751
du Plessis AM, Andronikou S, Zar HJ
Paediatr Respir Rev 2021 Jun;38:16-23. Epub 2020 Sep 26 doi: 10.1016/j.prrv.2020.06.022. PMID: 33139219
Casoni GL, Tomassetti S, Cavazza A, Colby TV, Dubini A, Ryu JH, Carretta E, Tantalocco P, Piciucchi S, Ravaglia C, Gurioli C, Romagnoli M, Gurioli C, Chilosi M, Poletti V
PLoS One 2014;9(2):e86716. Epub 2014 Feb 28 doi: 10.1371/journal.pone.0086716. PMID: 24586252Free PMC Article

Diagnosis

Singh S, Lum J, Majeed A
Transplant Proc 2023 Nov;55(9):2197-2202. Epub 2023 Sep 26 doi: 10.1016/j.transproceed.2023.08.005. PMID: 37758562
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
du Plessis AM, Andronikou S, Zar HJ
Paediatr Respir Rev 2021 Jun;38:16-23. Epub 2020 Sep 26 doi: 10.1016/j.prrv.2020.06.022. PMID: 33139219
Casoni GL, Tomassetti S, Cavazza A, Colby TV, Dubini A, Ryu JH, Carretta E, Tantalocco P, Piciucchi S, Ravaglia C, Gurioli C, Romagnoli M, Gurioli C, Chilosi M, Poletti V
PLoS One 2014;9(2):e86716. Epub 2014 Feb 28 doi: 10.1371/journal.pone.0086716. PMID: 24586252Free PMC Article
Strollo D, Goldin J
Curr Rheumatol Rep 2010 Apr;12(2):156-61. doi: 10.1007/s11926-010-0095-0. PMID: 20425026Free PMC Article

Therapy

Long W, Luo J, Ma L, Wei J, Xiang H, Hong L, Luo M
Medicine (Baltimore) 2024 Jul 12;103(28):e38269. doi: 10.1097/MD.0000000000038269. PMID: 38996169Free PMC Article
Singh S, Lum J, Majeed A
Transplant Proc 2023 Nov;55(9):2197-2202. Epub 2023 Sep 26 doi: 10.1016/j.transproceed.2023.08.005. PMID: 37758562
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
Kam JK, Charan N, Leong RW, Loh ZW, Thong BY
Lupus 2021 Feb;30(2):248-255. Epub 2020 Dec 1 doi: 10.1177/0961203320976932. PMID: 33259751
Solomon JJ, Danoff SK, Goldberg HJ, Woodhead F, Kolb M, Chambers DC, DiFranco D, Spino C, Haynes-Harp S, Hurwitz S, Peters EB, Dellaripa PF, Rosas IO; Trail Network
Adv Ther 2019 Nov;36(11):3279-3287. Epub 2019 Sep 12 doi: 10.1007/s12325-019-01086-2. PMID: 31515704

Prognosis

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
du Plessis AM, Andronikou S, Zar HJ
Paediatr Respir Rev 2021 Jun;38:16-23. Epub 2020 Sep 26 doi: 10.1016/j.prrv.2020.06.022. PMID: 33139219
Solomon JJ, Danoff SK, Goldberg HJ, Woodhead F, Kolb M, Chambers DC, DiFranco D, Spino C, Haynes-Harp S, Hurwitz S, Peters EB, Dellaripa PF, Rosas IO; Trail Network
Adv Ther 2019 Nov;36(11):3279-3287. Epub 2019 Sep 12 doi: 10.1007/s12325-019-01086-2. PMID: 31515704
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
Alam SM, Kidwai AA, Jafri SR, Qureshi BM, Sami A, Qureshi HH, Mirza H
J Pak Med Assoc 2011 Feb;61(2):123-6. PMID: 21375157

Clinical prediction guides

Long W, Luo J, Ma L, Wei J, Xiang H, Hong L, Luo M
Medicine (Baltimore) 2024 Jul 12;103(28):e38269. doi: 10.1097/MD.0000000000038269. PMID: 38996169Free PMC Article
Dal Santo T, Rice D, Carrier ME, Virgili-Gervais G, Levis B, Kwakkenbos L, Bartlett SJ, Gietzen A, Gottesman K, Guillot G, Hudson M, Hummers LK, Malcarne V, Mayes M, Mouthon L, Richard M, Sauve M, Wojeck R, Geoffroy MC, Benedetti A, Thombs B; SPIN investigators
RMD Open 2024 Feb 29;10(1) doi: 10.1136/rmdopen-2023-003876. PMID: 38428973Free PMC Article
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
Solomon JJ, Danoff SK, Goldberg HJ, Woodhead F, Kolb M, Chambers DC, DiFranco D, Spino C, Haynes-Harp S, Hurwitz S, Peters EB, Dellaripa PF, Rosas IO; Trail Network
Adv Ther 2019 Nov;36(11):3279-3287. Epub 2019 Sep 12 doi: 10.1007/s12325-019-01086-2. PMID: 31515704
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

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