Idiopathic pulmonary fibrosis

General Information (adopted from Orphanet):

Synonyms, Signs: FIBROSING ALVEOLITIS, CRYPTOGENIC
IDIOPATHIC PULMONARY FIBROSIS, FAMILIAL
INTERSTITIAL PNEUMONITIS, USUAL
FIBROCYSTIC PULMONARY DYSPLASIA
UIP HAMMAN-RICH DISEASE, INCLUDED
IPF
UIP
Cryptogenic fibrosing alveolitis
familial interstitial pneumonia
Usual interstitial pneumonia
Number of Symptoms 54
OrphanetNr: 2032
OMIM Id: 178500
ICD-10: J84.1
UMLs:
MeSH: D054990
MedDRA: 10021240
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 11.5 of 100 000
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Idiopathic interstitial pneumonia
 -Rare respiratory disease

Comment:

IPF is a chronic, progressive, fibrotic lung disease of unknown cause with an extremely poor prognosis (PMID:25551350). Prevalence of idiopathic pulmonary fibrosis (IPF) ranges from 0.8 to 64.7 individuals in 100,000 (PMID:16809633). Genes associated with idiopathic pulmonary fibrosis or familial interstitial pneumonia, include ABCA3, surfactant-related proteins, SFTPC and SFTPA2, MUC5B and genes linked to telomere functioning, TERT, TERC, DKC1, TINF2 and RTEL1 (PMID:21992127, 25837031). LRP5 expression levels are significantly elevated in patients with IPF (PMID:24921217) indicating that IPF is linked to the Wnt/β-catenin signaling pathway. Up to one in five patients with IPF have a family history of interstitial lung disease (PMID:25607374). For diagnosis of IPF exclusion of other known causes of interstitial lung disease, e.g. domestic and occupational environmental exposures, connective tissue disease, and drug toxicity is necessary (PMID:21471066). Features that best differentiated IPF from chronic hypersensitivity pneumonitis are basal predominance of honeycombing, absence of relative sub pleural sparing, and absence centrilobular nodules (PMID:18096541).

Symptom Information: Sort by abundance 

1
 (HPO:0002360) Sleep disturbance 10673212 IBIS 113 / 7739
2
 (HPO:0012378) Fatigue Occasional [IBIS] 7.6% (n=132) 23432171 IBIS 50 / 7739
3
 (HPO:0010535) Sleep apnea 21471066 IBIS 24 / 7739
4
 (HPO:0100760) Clubbing of toes 23133780 IBIS 24 / 7739
5
 (HPO:0100749) Chest pain Occasional [IBIS] 8.3% (n=132) 23432171 IBIS 92 / 7739
6
 (HPO:0100759) Clubbing of fingers 50 % [HPO] Frequent [IBIS] 53.3% (n=132) 23432171 IBIS 40 / 7739
7
 (HPO:0001217) Clubbing Frequent [IBIS] 25984423 IBIS 39 / 7739
8
 (HPO:0001394) Cirrhosis 22853774 IBIS 102 / 7739
9
 (HPO:0002020) Gastroesophageal reflux 21471066 IBIS 101 / 7739
10
 (HPO:0001513) Obesity 21471066 IBIS 172 / 7739
11
 (HPO:0001824) Weight loss 10673212 IBIS 42 / 7739
12
 (HPO:0000961) Cyanosis Occasional [IBIS] 6.8% (n=132) 23432171 IBIS 60 / 7739
13
 (HPO:0000988) Skin rash 24504062 IBIS 98 / 7739
14
 (HPO:0002092) Pulmonary hypertension Occasional [IBIS] 29% (n=210) 24824247 IBIS 109 / 7739
15
 (HPO:0001648) Cor pulmonale 18366757 IBIS 16 / 7739
16
 (HPO:0010702) Increased antibody level in blood 14338292 IBIS 29 / 7739
17
 (HPO:0011991) Abnormal neutrophil cell number Frequent [IBIS] 10673212 IBIS 3 / 7739
18
 (HPO:0001945) Fever Occasional [IBIS] 4.5% (n=132) 23432171 IBIS 218 / 7739
19
 (HPO:0012398) Peripheral edema 10673212 IBIS 12 / 7739
20
 (HPO:0002113) Pulmonary infiltrates 10673212 IBIS 36 / 7739
21
 (HPO:0002097) Emphysema Frequent [IBIS] 42% (n=210) 24824247 IBIS 40 / 7739
22
 (HPO:0002206) Pulmonary fibrosis Very frequent [IBIS] 10673212 IBIS 51 / 7739
23
 (HPO:0002093) Respiratory insufficiency 10673212 IBIS 410 / 7739
24
 (HPO:0002109) Abnormality of the bronchi 10936140 IBIS 6 / 7739
25
 (HPO:0002795) Functional respiratory abnormality Frequent [IBIS] 23432171 IBIS 13 / 7739
26
 (HPO:0002094) Dyspnea Frequent [IBIS] 68.2% (n=132) 23432171 IBIS 132 / 7739
27
 (HPO:0002875) Exertional dyspnea 16809633 IBIS 29 / 7739
28
 (HPO:0006530) Interstitial pulmonary disease Very frequent [IBIS] 24424167 IBIS 26 / 7739
29
 (HPO:0002110) Bronchiectasis 10673212 IBIS 73 / 7739
30
 (HPO:0002789) Tachypnea 10673212 IBIS 48 / 7739
31
 (HPO:0002792) Reduced vital capacity 10673212 IBIS 17 / 7739
32
 (HPO:0002111) Restrictive deficit on pulmonary function testing Frequent [IBIS] 58.3% (n=132) 23432171 IBIS 25 / 7739
33
 (HPO:0002207) Diffuse reticular or finely nodular infiltrations 10673212 IBIS 11 / 7739
34
 (HPO:0012418) Hypoxemia 10673212 IBIS 18 / 7739
35
 (HPO:0012415) Abnormal blood gas level 23937857 IBIS 9 / 7739
36
 (HPO:0003493) Antinuclear antibody positivity Occasional [IBIS] 10673212 IBIS 15 / 7739
37
 (HPO:0002923) Rheumatoid factor positive Occasional [IBIS] 10673212 IBIS 5 / 7739
38
 (MedDRA:10017507) Functional residual capacity decreased 24424167 IBIS 1 / 7739
39
 (MedDRA:10064780) Breath sounds abnormal 23432171 IBIS 3 / 7739
40
 (OMIM) Reduced diffusion capacity 23937857 IBIS 8 / 7739
41
 (MedDRA:10037833) Rales Frequent [IBIS] 85.6% (n=132) 23432171 IBIS 4 / 7739
42
 (MedDRA:10062049) Lymphocytic infiltration 23576879 IBIS 9 / 7739
43
 (MedDRA:10001889) Alveolitis 10936140 IBIS 3 / 7739
44
 (MedDRA:10062759) Congenital dyskeratosis 24504062 IBIS 1 / 7739
45
 (MedDRA:10065906) Carbon monoxide diffusing capacity decreased 23937857 IBIS 8 / 7739
46
 (OMIM) Radiograph shows ground glass appearance 25672832 IBIS 7 / 7739
47
 (MedDRA:10070955) Right ventricular heave 10673212 IBIS 1 / 7739
48
 (OMIM) Honeycomb fibrosis, varying in age and location Frequent [IBIS] 10673212 IBIS 6 / 7739
49
 (MedDRA:10021240) Idiopathic pulmonary fibrosis Very frequent [IBIS] 24424167 IBIS 1 / 7739
50
 (HPO:0012735) Cough Frequent [IBIS] 60.6% (n=132) 23432171; 25984423 IBIS 24 / 7739
51
 (OMIM) Pulmonary fibrosis with fibroblast foci on histology Very frequent [IBIS] 21642472; 19287097 IBIS 3 / 7739
52
 (MedDRA:10016987) Forced expiratory volume decreased 23776595 IBIS 2 / 7739
53
 (MedDRA:10067182) Bronchial wall thickening Occasional [IBIS] 18.8 % (n=16) 24998369 IBIS 5 / 7739
54
 (OMIM) Reduced forced vital capacity 25984423 IBIS 3 / 7739

Associated genes:

SFTPC; SFTPA2; ABCA3; TERT; TERC; DKC1; TINF2; RTEL1; MUC5B

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM McKusick and Fisher (1958) described 3 cases. Donohue et al. (1959) reported a Canadian family with 8 cases in 4 generations, and Rezek and Talbert (1962) reported father and daughter.

Jacox et al. (1964) described a ...
Molecular genetics OMIM - Mutation in the SFTPA2 Gene

In a 4-generation family segregating autosomal dominant IPF with or without lung cancer mapping to chromosome 10, Wang et al. (2009) sequenced the candidate genes SFTPA1 (178630) and SFTPA2 (178642) ...
Population genetics OMIM Hunninghake et al. (2013) examined chest CT scans of 2,633 individuals enrolled in the Framingham Heart Study and found that 177 of them (7%) had interstitial lung abnormalities, and that 47 (27%) of those could be classified as ...