Patients with idiopathic pulmonary fibrosis (IPF) experience progressive dyspnea and functional decline over time. The median survival time has been estimated to be 2-5 years from the time of diagnosis, and most patients will die from their disease.[21]Meltzer EB, Noble PW. Idiopathic pulmonary fibrosis. Orphanet J Rare Dis. 2008 Mar 26;3:8.
https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-8
http://www.ncbi.nlm.nih.gov/pubmed/18366757?tool=bestpractice.com
[57]American Thoracic Society; European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):646-64.
https://www.atsjournals.org/doi/full/10.1164/ajrccm.161.2.ats3-00
http://www.ncbi.nlm.nih.gov/pubmed/10673212?tool=bestpractice.com
[64]Martinez FJ, Safrin S, Weycker D, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. 2005 Jun 21;142(12 Pt 1):963-7.
http://www.ncbi.nlm.nih.gov/pubmed/15968010?tool=bestpractice.com
[118]Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun;3(4):285-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658683
http://www.ncbi.nlm.nih.gov/pubmed/16738191?tool=bestpractice.com
However, the course of the clinical decline differs among patients, with some progressing rapidly, others progressing slowly, and others declining only during acute exacerbations.
Factors associated with a good prognosis:[119]Flaherty KR, Thwaite EL, Kazerooni EA, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax. 2003 Feb;58(2):143-8.
https://thorax.bmj.com/content/58/2/143.long
http://www.ncbi.nlm.nih.gov/pubmed/12554898?tool=bestpractice.com
[120]Collard HR, King TE Jr, Bartelson BB, et al. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003 Sep 1;168(5):538-42.
https://www.atsjournals.org/doi/full/10.1164/rccm.200211-1311OC#.UmERpNglgZk
http://www.ncbi.nlm.nih.gov/pubmed/12773325?tool=bestpractice.com
[121]Latsi PI, du Bois RM, Nicholson AG, et al. Fibrotic idiopathic interstitial pneumonia. The prognostic value of longitudinal functional trends. Am J Respir Crit Care Med. 2003 Sep 1;168(5):531-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.200210-1245OC#.UmERetglgZk
http://www.ncbi.nlm.nih.gov/pubmed/12791580?tool=bestpractice.com
[122]Flaherty KR, Mumford JA, Murray S, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003 Sep 1;168(5):543-8.
https://www.atsjournals.org/doi/full/10.1164/rccm.200209-1112OC#.UmERTNglgZk
http://www.ncbi.nlm.nih.gov/pubmed/12773329?tool=bestpractice.com
[123]King TE Jr, Tooze JA, Schwarz MI, et al. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001 Oct 1;164(7):1171-81.
https://www.atsjournals.org/doi/full/10.1164/ajrccm.164.7.2003140#.UmEQ-9glgZk
http://www.ncbi.nlm.nih.gov/pubmed/11673205?tool=bestpractice.com
"Atypical" high-resolution CT pattern for IPF
Stability or improvement in FVC, and/or lung diffusion capacity test over the first 6 months after diagnosis
Paradoxically, current cigarette smoking
The effect of smoking may be related to differences in disease severity at presentation among current smokers.[124]Antoniou KM, Hansell DM, Rubens MB, et al. Idiopathic pulmonary fibrosis: outcome in relation to smoking status. Am J Resp Crit Care Med. 2008 Jan 15;177(2):190-4.
http://www.ncbi.nlm.nih.gov/pubmed/17962635?tool=bestpractice.com
Factors associated with a poor prognosis:[12]Gupta R, Morgan AD, George PM, et al. Incidence, prevalence and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study. Thorax. 2024 Jun 14;79(7):624-31.
http://www.ncbi.nlm.nih.gov/pubmed/38688708?tool=bestpractice.com
[15]Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis. an international working group report. Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75.
https://www.atsjournals.org/doi/10.1164/rccm.201604-0801CI?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/27299520?tool=bestpractice.com
[118]Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun;3(4):285-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658683
http://www.ncbi.nlm.nih.gov/pubmed/16738191?tool=bestpractice.com
[120]Collard HR, King TE Jr, Bartelson BB, et al. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003 Sep 1;168(5):538-42.
https://www.atsjournals.org/doi/full/10.1164/rccm.200211-1311OC#.UmERpNglgZk
http://www.ncbi.nlm.nih.gov/pubmed/12773325?tool=bestpractice.com
[122]Flaherty KR, Mumford JA, Murray S, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003 Sep 1;168(5):543-8.
https://www.atsjournals.org/doi/full/10.1164/rccm.200209-1112OC#.UmERTNglgZk
http://www.ncbi.nlm.nih.gov/pubmed/12773329?tool=bestpractice.com
[125]Song JW, Hong SB, Lim CM, et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors, and outcome. Eur Respir J. 2011 Feb;37(2):356-63.
http://www.ncbi.nlm.nih.gov/pubmed/20595144?tool=bestpractice.com
[126]Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis.
Eur Respir J. 2010 Apr;35(4):830-6.
http://www.ncbi.nlm.nih.gov/pubmed/19840957?tool=bestpractice.com
[127]Swigris JJ, Swick J, Wamboldt FS, et al. Heart rate recovery after 6-min walk test predicts survival in patients with idiopathic pulmonary fibrosis. Chest. 2009 Sep;136(3):841-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775995
http://www.ncbi.nlm.nih.gov/pubmed/19395579?tool=bestpractice.com
[128]Lama VN, Flaherty KR, Toews GB, et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003 Nov 1;168(9):1084-90.
https://www.atsjournals.org/doi/full/10.1164/rccm.200302-219OC#.UmESG9glgZk
http://www.ncbi.nlm.nih.gov/pubmed/12917227?tool=bestpractice.com
[129]Scholand MB, Coon H, Wolff R, et al. Use of a genealogical database demonstrates heritability of pulmonary fibrosis. Lung. 2013 Oct;191(5):475-81.
https://link.springer.com/article/10.1007/s00408-013-9484-2
http://www.ncbi.nlm.nih.gov/pubmed/23867963?tool=bestpractice.com
[130]Atkins CP, Loke YK, Wilson AM. Outcomes in idiopathic pulmonary fibrosis: a meta-analysis from placebo controlled trials. Respir Med. 2014 Feb;108(2):376-87.
https://www.resmedjournal.com/article/S0954-6111(13)00448-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/24440032?tool=bestpractice.com
Advanced age
Male sex
Severity of FVC impairment
Severity of DLCO abnormalities
FVC decline in the initial 6-12 months after diagnosis
Increased number of fibroblastic foci on lung biopsy
Oxyhemoglobin desaturation during an initial 6-minute walk test
Failure of the heart rate to recover normally after exercise
Acute exacerbations
In one UK cohort study, mortality due to IPF increased by 53% between 2008 and 2018 from 5.2 to 7.9 per 100,000 person-years and was consistently higher for males than females (8.7 vs. 5.3 per 100,000 person-years).[12]Gupta R, Morgan AD, George PM, et al. Incidence, prevalence and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study. Thorax. 2024 Jun 14;79(7):624-31.
http://www.ncbi.nlm.nih.gov/pubmed/38688708?tool=bestpractice.com
One meta-analysis of placebo controlled trials reported that mortality is lower among patients with mild-moderate disease (78.6 deaths per 1000 patient/years) compared with those with severe disease (188.6 deaths per 1000 patient/years).[130]Atkins CP, Loke YK, Wilson AM. Outcomes in idiopathic pulmonary fibrosis: a meta-analysis from placebo controlled trials. Respir Med. 2014 Feb;108(2):376-87.
https://www.resmedjournal.com/article/S0954-6111(13)00448-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/24440032?tool=bestpractice.com
Acute exacerbations pose a significantly increased mortality risk, preceding up to 46% of IPF-related deaths because of the association with rapid deterioration.[15]Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis. an international working group report. Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75.
https://www.atsjournals.org/doi/10.1164/rccm.201604-0801CI?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/27299520?tool=bestpractice.com
[125]Song JW, Hong SB, Lim CM, et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors, and outcome. Eur Respir J. 2011 Feb;37(2):356-63.
http://www.ncbi.nlm.nih.gov/pubmed/20595144?tool=bestpractice.com
The risk of death is increased 4.7-fold when pulmonary fibrosis is present in first-degree relatives.[129]Scholand MB, Coon H, Wolff R, et al. Use of a genealogical database demonstrates heritability of pulmonary fibrosis. Lung. 2013 Oct;191(5):475-81.
https://link.springer.com/article/10.1007/s00408-013-9484-2
http://www.ncbi.nlm.nih.gov/pubmed/23867963?tool=bestpractice.com
Multiple prognostic biomarkers have been identified; the clinical utility of these biomarkers is not yet clear.[131]Peljto AL, Zhang Y, Fingerlin TE, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA. 2013 Jun 5;309(21):2232-9.
http://www.ncbi.nlm.nih.gov/pubmed/23695349?tool=bestpractice.com
[132]Song JW, Do KH, Jang SJ, et al. Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. Chest. 2013 May;143(5):1422-9.
http://www.ncbi.nlm.nih.gov/pubmed/23715088?tool=bestpractice.com
[133]Nathan SD, Reffett T, Brown AW, et al. The red cell distribution width as a prognostic indicator in idiopathic pulmonary fibrosis. Chest. 2013 Jun;143(6):1692-8.
http://www.ncbi.nlm.nih.gov/pubmed/23238641?tool=bestpractice.com
[134]Kahloon RA, Xue J, Bhargava A, et al. Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med. 2013 Apr 1;187(7):768-75.
http://www.ncbi.nlm.nih.gov/pubmed/23262513?tool=bestpractice.com
Prognostic models
The Gender-Age-Physiology (GAP) staging system is an easy-to-calculate and validated prediction tool that can estimate mortality risk in untreated patients.[135]Ley B, Ryerson CJ, Vittinghoff E, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012 May 15;156(10):684-91.
http://www.ncbi.nlm.nih.gov/pubmed/22586007?tool=bestpractice.com
[136]Ryerson CJ, Vittinghoff E, Ley B, et al. Predicting survival across chronic interstitial lung disease: the ILD-GAP model. Chest. 2014 Apr;145(4):723-8.
http://www.ncbi.nlm.nih.gov/pubmed/24114524?tool=bestpractice.com
[137]Zhang X, Ren Y, Xie B, et al. External validation of the GAP model in Chinese patients with idiopathic pulmonary fibrosis. Clin Respir J. 2023 Sep;17(9):831-40.
https://onlinelibrary.wiley.com/doi/10.1111/crj.13564
http://www.ncbi.nlm.nih.gov/pubmed/36437511?tool=bestpractice.com
Its validity in treated patients is being evaluated.[138]Lacedonia D, De Pace CC, Rea G, et al. Machine learning and BMI improve the prognostic value of GAP index in treated IPF patients. Bioengineering (Basel). 2023 Feb 14;10(2):251.
https://www.mdpi.com/2306-5354/10/2/251
http://www.ncbi.nlm.nih.gov/pubmed/36829744?tool=bestpractice.com
[139]Bocchino M, Bruzzese D, Scioscia G, et al. Disease stage-related survival in idiopathic pulmonary fibrosis patients treated with nintedanib and pirfenidone: An exploratory study. Respir Med Res. 2023 Nov;84:101013.
https://www.sciencedirect.com/science/article/pii/S2590041223000259?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/37302161?tool=bestpractice.com
The GAP staging system classifies patients into three stages at the time of diagnosis based on:
sex (female = 0 vs. male = 1),
age (≤60 years = 0; 61-65 years = 1; >65 years = 2),
percent predicted forced vital capacity (>75% = 0; 50% to 75% = 1; <50% = 2),
percent predicted diffusing lung capacity of carbon monoxide (>55% = 0; 36% to 55% = 1; ≤35% = 2; cannot perform = 3).
The final score estimates the average risk of mortality at 1, 2, and 3 years by disease stage (i.e., score 0-3 = stage 1; score 4-5 = stage 2; score 6-8 = stage 3). Mortality increases with increasing stage and varies depending on the cohort in which the GAP index was validated.