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{{Short description|Scarring of the lungs for no known reason}}
{{Use dmy dates|date=August 2022}}
{{Infobox medical condition (new)
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<!-- Definition and symptoms -->
'''Idiopathic pulmonary fibrosis''' ('''IPF''')
The tissue in the lungs becomes thick and stiff, which affects the tissue that surrounds the air sacs in the lungs.<ref>{{Cite web|title=Idiopathic Pulmonary Fibrosis | work = NHLBI, NIH|url= https://www.nhlbi.nih.gov/health-topics/idiopathic-pulmonary-fibrosis |access-date=5 December 2020 }}</ref> Symptoms typically include gradual onset of [[dypsnea|shortness of breath]] and a dry [[cough]].<ref name=NIH2018>{{cite web|title=Idiopathic Pulmonary Fibrosis|url=http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/|website=NHLBI|access-date=21 January 2018}}</ref> Other changes may include feeling tired, and [[nail clubbing|clubbing]] abnormally large and dome shaped finger and toenails <!-- Cause and diagnosis -->
The cause is unknown, hence the term [[Idiopathic disease|idiopathic]].<ref name=ATS2015>{{cite journal | vauthors = Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, Brozek JL, Collard HR, Cunningham W, Homma S, Johkoh T, Martinez FJ, Myers J, Protzko SL, Richeldi L, Rind D, Selman M, Theodore A, Wells AU, Hoogsteden H, Schünemann HJ | display-authors = 6 | title = An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline | journal = American Journal of Respiratory and Critical Care Medicine | volume = 192 | issue = 2 | pages = e3–19 | date = July 2015 | pmid = 26177183 | doi = 10.1164/rccm.201506-1063ST }}</ref> Risk factors include [[cigarette smoking]], [[Gastroesophageal reflux disease|acid reflux disease (GERD)]], certain [[viral infection]]s, and genetic predisposition.<ref name=NIH2018/> The underlying mechanism involves [[pulmonary fibrosis|scarring of the lungs]].<ref name=NIH2018/> Diagnosis requires ruling out other potential causes.<ref name=Rag2011 /> It may be supported by a [[High-resolution computed tomography|
<!-- Treatment -->
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<!-- Epidemiology and prognosis -->
About 5 million people are affected globally.<ref name=Melt2008>{{cite journal |vauthors=Meltzer EB, Noble PW | title = Idiopathic pulmonary fibrosis | journal = Orphanet Journal of Rare Diseases| volume = 3 | issue = 1 | pages = 8| year = 2008 | pmid = 18366757 | pmc = 2330030 | doi = 10.1186/1750-1172-3-8 | doi-access = free }}</ref> The disease newly occurs in about 12 per 100,000 people per year.<ref name=Fer2018/> Those in their 60s and 70s are most commonly affected.<ref name=Fer2018/> Males are affected more often than females.<ref name=Fer2018/> Average [[life expectancy]] following diagnosis is about four years.<ref name=NIH2018/> Updated international guidelines were published in 2022, which some simplification in diagnosis and the removal of antacids as a possible adjunct therapy.<ref>{{Cite journal |last1=Raghu |first1=Ganesh |last2=Remy-Jardin |first2=Martine |last3=Richeldi |first3=Luca |last4=Thomson |first4=Carey C. |last5=Inoue |first5=Yoshikazu |last6=Johkoh |first6=Takeshi |last7=Kreuter |first7=Michael |last8=Lynch |first8=David A. |last9=Maher |first9=Toby M. |last10=Martinez |first10=Fernando J. |last11=Molina-Molina |first11=Maria |last12=Myers |first12=Jeffrey L. |last13=Nicholson |first13=Andrew G. |last14=Ryerson |first14=Christopher J. |last15=Strek |first15=Mary E. |date=2022-05-01 |title=Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline |journal=American Journal of Respiratory and Critical Care Medicine |volume=205 |issue=9 |pages=e18–e47 |doi=10.1164/rccm.202202-0399ST |pmid=35486072 |pmc=9851481 |s2cid=248432749 |issn=1073-449X}}</ref>
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* Dry, non-productive cough on exertion
* Progressive exertional dyspnea (shortness of breath with exercise)
* Dry, inspiratory
* [[nail clubbing|Clubbing of the digits]], a disfigurement of the finger tips or toes (see image)
* Abnormal [[pulmonary function test]] results, with evidence of restriction and impaired [[gas exchange]].
Some of these features are due to chronic [[hypoxemia]] (oxygen deficiency in the blood), and are not specific for IPF,
Assessment of
If bilateral fine crackles are present throughout the inspiratory time and are persisting after several deep breaths, and if remaining present on several occasions several weeks apart in a subject aged ≥60 years, this should raise the suspicion of IPF and lead to consideration of an HRCT scan of the chest which is more sensitive than a [[chest X-ray]].<ref name=CottinCordier /> As crackles are not specific for IPF, they must prompt a thorough diagnostic process.<ref name=Rag2011 />
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Despite extensive investigation, the cause of IPF remains unknown.<ref name=Rag2011 /> The [[fibrosis]] in IPF has been linked to cigarette smoking, environmental factors (e.g. occupational exposure to gases, smoke, chemicals or dusts), other medical conditions including [[gastroesophageal reflux disease]] (GERD), or to genetic predisposition (familial IPF). However, none of these is present in all people with IPF and therefore do not provide a completely satisfactory explanation for the disease.<ref name=Rag2011 /><ref name=GarciaBuendia>{{cite journal | vauthors = García-Sancho C, Buendía-Roldán I, Fernández-Plata MR, Navarro C, Pérez-Padilla R, Vargas MH, Loyd JE, Selman M | display-authors = 6 | title = Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis | journal = Respiratory Medicine | volume = 105 | issue = 12 | pages = 1902–7 | date = December 2011 | pmid = 21917441 | doi = 10.1016/j.rmed.2011.08.022 | doi-access = free }}{{medrs|date=June 2019}}</ref>
IPF is believed to be the result of an aberrant wound healing process including/involving abnormal and excessive deposition of [[collagen]] (fibrosis) in the [[pulmonary interstitium]] with minimal associated [[inflammation]].<ref name=HarariCaminati>{{cite journal |vauthors=Harari S, Caminati A | title = IPF: new insight on pathogenesis and treatment | journal = Allergy| volume = 65 | issue = 5 | pages = 537–553 | year = 2010 | pmid = 20121758 | doi = 10.1111/j.1398-9995.2009.02305.x| s2cid = 21633787 | doi-access = free }}</ref> [[Cellular senescence]] is suspected to be a central contributing cause, a belief which is supported by benefits seen in patients given [[senolytic]] therapy.<ref name="pmid30616998">{{cite journal | vauthors = Justice JN, Nambiar AM, Tchkonia T, Kirkland JL | title = Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study | journal = [[EBioMedicine]] | volume = 40 | pages = 554–563 | date=2019 | url= | doi = 10.1016/j.ebiom.2018.12.052 | pmc=6412088 | pmid = 30616998}}</ref><ref name="pmid31451866">{{cite journal | vauthors = Palmer AK, Gustafson B, Kirkland JL, Smith U | title = Cellular senescence: at the nexus between ageing and diabetes | journal = [[Diabetologia]] | volume = 62 | issue=10 | pages = 1835–1841 | date=2019 | url= | doi = 10.1007/s00125-019-4934-x | pmc=6731336 | pmid = 31451866}}</ref><ref name="pmid32686219">{{cite journal | vauthors = Kirkland JL, Tchkonia T| title = Senolytic Drugs: From Discovery to Translation | journal = [[Journal of Internal Medicine]] | date=2020 | volume = 288 | issue = 5 | pages = 518–536 | doi = 10.1111/joim.13141 | pmid = 32686219| pmc = 7405395 | doi-access = free }}</ref>
It is hypothesized that the initial or repetitive injury in IPF occurs to the lung
In the past, it was thought that [[inflammation]] was the first event in initiating lung tissue scarring. Later findings showed that the development of fibroblastic foci precedes the accumulation of inflammatory cells and the consequent deposition of collagen.<ref name="PardoSelman">{{cite journal |vauthors=Pardo A, Selman M | title = Idiopathic pulmonary fibrosis: new insights in its pathogenesis | journal = The International Journal of Biochemistry & Cell Biology| volume = 34 | issue = 12 | pages = 1534–1538 | year = 2002 | pmid = 12379275| doi = 10.1016/s1357-2725(02)00091-2}}</ref> This pathogenetic model is indirectly supported by the clinical features of IPF, including an insidious onset over several years, relatively infrequent acute exacerbations, and failure to respond to [[immunosuppressive therapy]].<ref name="HarariCaminati" /><ref name="SelmanKing">{{cite journal |vauthors=Selman M, King TE, Pardo A | title = Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy | journal = Annals of Internal Medicine| volume = 134 | issue = 2 | pages = 136–151 | year = 2001 | pmid = 11177318 | doi = 10.7326/0003-4819-134-2-200101160-00015| s2cid = 10955241 }}</ref> However, it is the belief of some researchers that the disease is a multi-mechanistic one, wherein the trigger for the disease may stem from abnormalities in any number of wound healing pathways, including the inflammatory response.<ref name=":0" /> Such abnormalities could occur in any number of the nine implicated pathways (clotting cascade, antioxidant pathways, apoptosis, inflammatory cytokines, angiogenesis and vascular remodelling, growth factors, surfactant and matrix regulatory factors),<ref name=":0" /> and that through further investigation into all nine, novel therapies and approaches could be proposed on a unique or case-by-case basis should attempts at treating or circumventing complications in any one pathway prove unsuccessful. A number of therapies that target fibroblast activation or the synthesis of extracellular matrix are currently in early testing or are being considered for development.{{citation needed|date=November 2020}}
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A Multidisciplinary Consensus Statement on the Idiopathic Interstitial Pneumonias published by the [[American Thoracic Society]] (ATS) and the [[European Respiratory Society]] (ERS) in 2000 proposed specific major and minor criteria for establishing the diagnosis of IPF.<ref name=Rag2011 /> However, in 2011, new simplified and updated criteria for the diagnosis and management of IPF were published by the ATS, ERS, together with the Japanese Respiratory Society (JRS) and Latin American Thoracic Association (ALAT).<ref name=Rag2011 /> Currently, a diagnosis of IPF requires:
* Exclusion of known causes of [[interstitial lung disease]] (ILD), e.g., domestic and occupational environmental exposures, connective tissue disorders, or drug exposure/toxicity
* The presence of a typical radiological pattern of [[usual interstitial pneumonia]] (UIP) on [[high-resolution computed tomography]] (HRCT).
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===Radiology===
[[Chest X-rays]] are useful in the follow
Typical HRCT of the chest of IPF demonstrates fibrotic changes in both lungs, with a predilection for the bases and the periphery. According to the joint ATS/ERS/JRS/ALAT 2011 guidelines, HRCT is an essential component of the diagnostic pathway in IPF which can identify UIP by the presence of:<ref name=Rag2011 />
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===Medications===
A number of treatments have been investigated in the past for IPF, including [[Interferon beta 1a|interferon gamma-1β]],<ref name=KingAlberaBradford>{{cite journal | vauthors = King TE, Albera C, Bradford WZ, Costabel U, Hormel P, Lancaster L, Noble PW, Sahn SA, Szwarcberg J, Thomeer M, Valeyre D, du Bois RM | display-authors = 6 | title = Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial | journal = Lancet | volume = 374 | issue = 9685 | pages = 222–8 | date = July 2009 | pmid = 19570573 | doi = 10.1016/S0140-6736(09)60551-1 | hdl = 1942/31878 | s2cid = 2432490 | hdl-access = free }}</ref> [[bosentan]],<ref name=KingBrown>{{cite journal | vauthors = King TE, Brown KK, Raghu G, du Bois RM, Lynch DA, Martinez F, Valeyre D, Leconte I, Morganti A, Roux S, Behr J | display-authors = 6 | title = BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 184 | issue = 1 | pages = 92–9 | date = July 2011 | pmid = 21474646 | doi = 10.1164/rccm.201011-1874OC | s2cid = 3190634
====Pirfenidone====
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====Nintedanib====
[[Nintedanib]] is a triple [[angiokinase inhibitor]] that targets [[receptor tyrosine kinase]]s involved in the regulation of [[angiogenesis]]: [[fibroblast growth factor receptor]] (FGFR), [[platelet-derived growth factor receptor]] (PDGFR), and [[vascular endothelial growth factor receptor]] (VEGFR),<ref name=BIBF>{{cite web|title=BIBF 1120 Fact Sheet|access-date=8 April 2014|url=http://dl.groovygecko.net/anon.groovy/clients/broadview/shirehealth/04/Vargatef_backgrounder.pdf|website=Dl.groovygecko.net|archive-date=3 March 2016|archive-url=https://web.archive.org/web/20160303194214/http://dl.groovygecko.net/anon.groovy/clients/broadview/shirehealth/04/Vargatef_backgrounder.pdf|url-status=dead}}</ref> which have also been implicated in the pathogenesis of fibrosis and IPF. In both phase III trials, nintedanib reduced the decline in lung function by approximately 50% over one year.<ref name=RicheldiduBois/> It was approved by the US FDA in October 2014<ref>{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000Approv.pdf|title=FDA Approval Package for Nintedanib|website=www.accessdata.fda.gov|access-date=7 January 2019}}</ref> and authorised in Europe in January 2015.<ref>{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/ofev#authorisation-details-section|title=Ofev {{!}} European Medicines Agency|website=www.ema.europa.eu|access-date=7 January 2019|date=17 September 2018}}</ref>
===Lung transplantation===
[[Lung transplantation]] may be suitable for those patients physically eligible to undergo a major transplant operation. In IPF patients, lung transplant has been shown to reduce the risk of death by 75% as compared with patients who remain on the waiting list.<ref name=RussoIribarne>{{cite journal |vauthors=Russo MJ, Iribarne A, Hong KN, Davies RR, Xydas S, Takayama H, Ibrahimiye A, Gelijns AC, Bacchetta MD, D'Ovidio F, Arcasoy S, Sonett JR | title = High lung allocation score is associated with increased morbidity and mortality following transplantation | journal = Chest| volume = 137 | issue = 3 | pages = 651–657 | year = 2010 | pmid = 19820072| pmc = 2832864| doi = 10.1378/chest.09-0319}}</ref> Since the introduction of the [[lung allocation score]] (LAS), which prioritizes transplant candidates based on survival probability, IPF has become the most common indication for lung transplantation in the USA.<ref name=SpagnoloTonelli>{{cite journal |vauthors=Spagnolo P, Tonelli R, Cocconcelli E, Stefani A, Richeldi L | title = Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges | journal = Multidisciplinary Respiratory Medicine| volume = 7 | issue = 1 | page = 42 | year = 2012 | pmid = 23146172| pmc = 3537555| doi = 10.1186/2049-6958-7-42 | doi-access = free }}</ref>
Symptomatic patients with IPF younger than 65 years of age and with a body mass index (BMI) ≤26 kg/m<sup>2</sup> should be referred for lung transplantation, but there are no clear data to guide the precise timing for LTx. Although controversial, the most recent data suggest that bilateral lung transplantation is superior to single lung transplantation in patients with IPF.<ref name=GeorgeArnaoutakis>{{cite journal |vauthors=George TJ, Arnaoutakis GJ, Shah AS | title = Lung transplantation for idiopathic pulmonary fibrosis | journal = The Annals of Thoracic Surgery| volume = 84 | issue = 4 | pages = 1121–1128 | year = 2007 | pmid = 17888957 | doi = 10.1016/j.athoracsur.2007.04.096}}</ref> Five-year survival rates after lung transplantation in IPF are estimated at between 50 and 56%.<ref name=Rag2011 /><ref name=MasonBrizzio>{{cite journal |vauthors=Mason DP, Brizzio ME, Alster JM, McNeill AM, Murthy SC, Budev MM, Mehta AC, Minai OA | title = Lung transplant in idiopathic pulmonary fibrosis | journal = Archives of Surgery| volume = 146 | issue = 10 | pages = 1204–1209 | year = 2011 | pmid = 22006881| doi = 10.1001/archsurg.2011.239|display-authors=etal| doi-access = free }}</ref><ref name=KeatingLevvey>{{cite journal |vauthors=Keating D, Levvey B, Kotsimbos T, Whitford H, Westall G, Williams T, Snell G | title = Lung transplantation in pulmonary fibrosis challenging early outcomes counter balanced by surprisingly good outcomes beyond 15 years | journal = Transplantation Proceedings| volume = 41 | issue = 1 | pages = 289–291 | year = 2009 | pmid = 19249537 | doi = 10.1016/j.transproceed.2008.10.042 }}</ref>
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The 5-year survival for IPF ranges between 20 and 40%,<ref name=KimCollard /> a mortality rate higher than that of a number of malignancies, including colon cancer, multiple myeloma and bladder cancer.<ref name=BjorakerRyu /><ref name=KimCollard />
Recently a multidimensional index and staging system has been proposed to predict mortality in IPF.<ref name=LeyRyerson>{{cite journal |vauthors=Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, ((King TE Jr)), Collard HR | title = A multidimensional index and staging system for idiopathic pulmonary fibrosis | journal = Annals of Internal Medicine| volume = 156 | issue = 10 | pages = 684–691 | pmid = 22586007| doi = 10.7326/0003-4819-156-10-201205150-00004| year = 2012 | citeseerx = 10.1.1.691.4472 | s2cid = 207536377 }}</ref> The name of the index is GAP and is based on gender [G], age [A], and two lung physiology variables [P] (FVC and DL<small>CO</small>) that are commonly measured in clinical practice to predict mortality in IPF. The highest stage of GAP (stage III) has been found to be associated with a 39% risk of mortality at 1 year.<ref name=LeyRyerson /> This model has also been evaluated in IPF and other ILDs and shown good performance in predicting mortality in all main ILD subtypes. A modified ILD-GAP Index has been developed for application across ILD subtypes to provide disease-specific survival estimates.<ref name=RyersonVittinghoff>{{cite journal |vauthors=Ryerson CJ, Vittinghoff E, Ley B, Lee JS, Mooney JJ, Jones KD, Elicker BM, Wolters PJ | title = Predicting Survival Across Chronic Interstitial Lung Disease: The ILD-GAP Model | journal = Chest| volume = 145 | issue = 4 | pages = 723–728 | year= 2014 | pmid = 24114524 | doi = 10.1378/chest.13-1474|display-authors=etal}}</ref> In IPF patients, the overall mortality at 5 years rate is high but the annual rate of all-cause mortality in patients with mild to moderate lung impairment is relatively low. This is the reason why change in lung function (FVC) is usually measured in 1-year clinical trials of IPF treatments rather than survival.<ref name=KingAlbera>{{cite journal | vauthors = King TE, Albera C, Bradford WZ, Costabel U, du Bois RM, Leff JA, Nathan SD, Sahn SA, Valeyre D, Noble PW | title = All-cause mortality rate in patients with idiopathic pulmonary fibrosis. Implications for the design and execution of clinical trials | journal = American Journal of Respiratory and Critical Care Medicine| volume = 189 | issue = 7 | pages = 825–31 | date = April 2014 | pmid = 24476390 | doi = 10.1164/rccm.201311-1951OC | hdl = 2318/156709 | hdl-access = free }}</ref>
In addition to clinical and physiological parameters to predict how rapidly patients with IPF might progress, genetic and molecular features are also associated with IPF mortality. For example, it has been shown that IPF patients who have a specific genotype in the mucin MUC5B gene polymorphism (see above) experience slower decline in FVC and significantly improved survival.<ref name=PeljtoZhang>{{cite journal |vauthors=Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JG, Richards TJ, Silveira LJ, Lindell KO | title = Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis | journal = JAMA| volume = 309| issue = 21 | pages = 2232–2239 | year=2013 | pmid = 23695349 | pmc = 4545271| doi = 10.1001/jama.2013.5827|display-authors=etal}}</ref><ref name=StockSato>{{cite journal |vauthors=Stock CJ, Sato H, Fonseca C, Banya WA, Molyneaux PL, Adamali H, Russell AM, Denton CP | title = Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis | journal = Thorax| volume = 68 | issue = 5 | pages = 436–441 | year=2013 | pmid = 23321605 | doi = 10.1136/thoraxjnl-2012-201786|display-authors=etal| url = http://thorax.bmj.com/cgi/content/short/68/5/436 | doi-access = free }}</ref> Even if such data are interesting from a scientific point of view, the application in the clinical routine of a prognostic model based on specific genotypes is still not possible.
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Although rare, IPF is the most common form of IIP.<ref name="ATS/ERS" /> The prevalence of IPF has been estimated between 14.0 and 42.7 per 100,000 persons based on a USA analysis of healthcare claims data, with variation depending on the case definitions used in this analyses.<ref name=RaghuWeycker /><ref name=PulmonaryFibrosis>Pulmonary Fibrosis Foundation. "Prevalence and Incidence". Pulmonaryfibrosis.org. Retrieved 11 April 2013</ref> IPF is more common in men than in women and is usually diagnosed in people over 50 years of age.<ref name=Rag2011 />
The [[incidence (epidemiology)|incidence]] of IPF is difficult to determine as uniform diagnostic criteria have not been applied consistently.<ref name=Rag2011 /><ref name=RaghuWeycker /> A recent study from the
A recent single-centre, retrospective, observational cohort study including incident patients diagnosed with ILD at [[Aarhus University Hospital]] (Denmark) between 2003 and 2009 revealed an incidence of 4.1 per 100,000 inhabitants/year for ILD. IPF was the most common diagnosis (28%) followed by connective tissue disease-related ILD (14%), hypersensitivity pneumonitis (7%) and non-specific interstitial pneumonia (NSIP) (7%). IPF incidence was 1.3 per 100,000 inhabitants/year.<ref name=HyldgaardHilberg>{{cite journal |vauthors=Hyldgaard C, Hilberg O, Muller A, Bendstrup E | title = A cohort study of interstitial lung diseases in central Denmark | journal = Respiratory Medicine| volume = 108 | issue = 5 | pages = 793–799 | year = 2014 | pmid = 24636811| doi = 10.1016/j.rmed.2013.09.002| doi-access = free }}</ref>
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[[Stem cell therapy|Stem cell therapies]] for IPF are an area of research.<ref>{{cite journal | vauthors = Liu M, Ren D, Wu D, Zheng J, Tu W | title = Stem Cell and Idiopathic Pulmonary Fibrosis: Mechanisms and Treatment | journal = Current Stem Cell Research & Therapy | volume = 10 | issue = 6 | pages = 466–76 | year = 2015 | pmid = 25986617 | doi = 10.2174/1574888X10666150519092639 }}</ref><ref>{{cite web|title=Stem cell therapy for lung fibrosis conditions |url= https://www.sciencedaily.com/releases/2017/08/170803091928.htm |website=Sciencedaily.com |access-date=8 June 2018}}</ref>
A [[machine learning]] algorithm has been proposed that discovers subtle patterns in individual history of medical encounters to reliably estimate the risk of a future IPF diagnosis, up to four years before current medical practice.<ref name=onishenko2022>{{cite journal | vauthors=Onishchenko D, Marlowe RJ, Ngufor, Faust LJ, Limper AH, Hunninghake GM, Martinez FJ, Chattopadhyay I | title = Screening for idiopathic pulmonary fibrosis using comorbidity signatures in electronic health records. | journal = Nature Medicine | year = 2022 | volume = 28 | issue = 10 | pages = 2107–2116 | pmid = 36175678 | doi = 10.1038/s41591-022-02010-y | s2cid = 252622515 | doi-access = free }}</ref> The algorithm outputs a score (ZCoR) using medical history on file with no new tests, and might be deployable as a universal IPF screening tool in primary care. ZCoR has been trained and validated on nearly 3 million patients across multiple databases, achieving high predictive performance in out-of-sample data (positive likelihood ratio > 30 with 99% specificity). The authors conclude that past respiratory disorders maximally contribute to IPF risk, followed by known IPF comorbidities, metabolic diseases, cardiovascular abnormalities, and diseases of the eye, with the overall pattern of the importance ranking substantially invariant across the sexes.
==References==
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