Content deleted Content added
Extraneous Tags: Mobile edit Mobile web edit |
m Added short description Tags: Mobile edit Mobile app edit iOS app edit App description change |
||
| (40 intermediate revisions by 23 users not shown) | |||
Line 1:
{{Short description|Scarring of the lungs for no known reason}}
{{Use dmy dates|date=August 2022}}
{{Infobox medical condition (new)
| name = Idiopathic pulmonary fibrosis
| synonyms =
| image = Ipf NIH.jpg
| caption = '''Figure A''' shows the location of the lungs and airways in the body. The inset image shows a detailed view of the lung's airways and air sacs in cross-section. <br />'''Figure B''' shows fibrosis (scarring) in the lungs. The inset image shows a detailed view of the fibrosis and how it damages the airways and air sacs.<ref name=NIH2018/>
| pronounce =
| field = [[Pulmonology]]
| symptoms = [[
| complications = [[Pulmonary hypertension]], [[heart failure]], [[pneumonia]], [[pulmonary embolism]]<ref name=NIH2018/>
| onset = Gradual<ref name=NIH2018/>
Line 23 ⟶ 25:
}}
<!-- Definition and symptoms -->
'''Idiopathic pulmonary fibrosis''' ('''IPF''') synonymous with '''cryptogenic fibrosing alveolitis'''<ref name="NICE2024">{{cite web |title=Idiopathic pulmonary fibrosis {{!}} Information for the public {{!}} Idiopathic pulmonary fibrosis in adults: diagnosis and management {{!}} Guidance {{!}} NICE |url=https://www.nice.org.uk/guidance/cg163/ifp/chapter/idiopathic-pulmonary-fibrosis |website=www.nice.org.uk |access-date=15 June 2024 |date=12 June 2013}}</ref> is a rare, progressive illness of the respiratory system, characterized by the thickening and stiffening of lung tissue, associated with the formation of scar tissue. It is a type of chronic [[
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 <!-- 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 -->
Line 32 ⟶ 36:
<!-- 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>
{{TOC limit|3}}
Line 41 ⟶ 45:
* 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 />
Line 58 ⟶ 62:
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
Familial IPF accounts for less than 5% of the total of patients with IPF and is clinically and histologically indistinguishable from sporadic IPF.<ref name=Rag2011 /> Genetic associations include mutations in [[pulmonary surfactant]] proteins A1, A2, C ([[SFTPA1]], [[SFTPA2B]]) and [[mucin]] ([[MUC5B]]).<ref name=OMIM>{{cite web|url=http://omim.org/entry/178500|title=OMIM Entry
A remarkable aspect of the MUC5B variant is its high frequency of detection, as it is found in approximately 20% of individuals with Northern and Western European ancestry and in 19% of the Framingham Heart Study population.<ref name=Mathai>{{cite journal |vauthors=Mathai S, etal | title = Genetic susceptibility and pulmonary fibrosis | journal = Current Opinion in Pulmonary Medicine| volume = 20 | issue = 5 | pages = 429–435 | year = 2014 | pmid = 25022318 | pmc = 4337021| doi = 10.1097/MCP.0000000000000074}}</ref>
Mutations in human [[telomerase]] genes are also associated with familial pulmonary fibrosis and in some patients with sporadic IPF (e.g. the [[TERT]], [[Telomerase RNA component|TERC]] genes).<ref name=OMIM /> Recently an X-linked mutation in a third telomerase-associated gene, dyskerin (DKC1), has been described in a family with IPF.<ref name=KropskiMitchell>{{cite journal |vauthors=Kropski JA, Mitchell DB, Markin C, etal | title = A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia | journal = Chest| volume = 146| issue = 1| pages = e1–7| date =
==Diagnosis==
Line 72 ⟶ 76:
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).
In the right clinical setting, it is possible to make the diagnosis of IPF by HRCT alone, obviating the need for surgical lung biopsy.<ref name=Rag2011 /><ref name="ATS/ERS">{{cite journal | vauthors = Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D |display-authors = 6| title = An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias | journal = American Journal of Respiratory and Critical Care Medicine| volume = 188 | issue = 6 | pages = 733–48 | date = September 2013 | pmid = 24032382 | pmc = 5803655 | doi = 10.1164/rccm.201308-1483ST }}</ref>
Various technologies using [[Artificial Intelligence]] have been developed to help with diagnosis. A deep learning algorithm for categorizing high-resolution CT images reported high accuracy <ref>Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JR, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018;6:138–53</ref> and a research project led by [[Nagoya University]] Graduate School of Medicine and [[Riken]] used a combination of [[Deep learning]] and [[Machine learning]] algorithm to accurately diagnose the disease.<ref>Taiki Furukawa et al. A comprehensible machine learning tool to differentially diagnose idiopathic pulmonary fibrosis from other chronic interstitial lung diseases. Respirology, 27(9) pp.739-746. First published: 13 June 2022 https://doi.org/10.1111/resp.14310</ref>
===Differential diagnosis===
Line 82 ⟶ 88:
===Classification===
[[File:Diffuse Parenchymal Lung Diseases.jpg|thumb|upright=1.4|Classification of IIPs.<ref name="ATS/ERS"/>]]
Idiopathic pulmonary fibrosis (IPF) belongs to a large group of more than 200 lung diseases known as [[interstitial lung disease]]s (ILDs), which are characterized by the involvement of the lung [[interstitium]],<ref name="ATS/ERS" /> the tissue between the air sacs of the lung. IPF is one specific presentation of [[idiopathic interstitial pneumonia]] (IIP), which is in turn a type of ILD, also known as [[diffuse parenchymal lung disease]] (DPLD).{{
The 2002 [[American Thoracic Society]]/[[European Respiratory Society]] (ATS/ERS) classification of IIPs was updated in 2013.<ref name="ATS/ERS" /> In this new classification there are three main categories of [[idiopathic]] interstitial pneumonias (IIPs): major IIPs, rare IIPs, and unclassifiable IIPs. The major IIPs are grouped into [[chronic condition|chronic]] fibrosing IPs (this includes IPF and [[non-specific interstitial pneumonia]] [NSIP]); smoking-related IPs (i.e. respiratory bronchiolitis–interstitial lung disease [RB-ILD] and [[desquamative interstitial pneumonia]] [DIP]); and acute/subacute IPs (i.e. [[cryptogenic organizing pneumonia]] [COP] and [[acute interstitial pneumonia]] [AIP]).<ref name="ATS/ERS" />
Line 89 ⟶ 95:
===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 />
Line 103 ⟶ 109:
Histologic specimens for the diagnosis of IPF must be taken at least in three different places and be large enough that the pathologist can comment on the underlying lung architecture. Small biopsies, such as those obtained via transbronchial lung [[biopsy]] (performed during bronchoscopy) are usually not sufficient for this purpose. Hence, larger biopsies obtained surgically via a [[thoracotomy]] or [[thoracoscopy]] are usually necessary.<ref name=Rag2011 /><ref name="ATS/ERS" />
Lung tissue from people with IPF usually show a characteristic histopathologic UIP pattern and is therefore the pathologic counterpart of IPF.<ref name=Rag2011 /> Although a pathologic diagnosis of UIP often corresponds to a clinical diagnosis of IPF, a UIP histologic pattern can be seen in other diseases as well, and fibrosis of known origin (rheumatic diseases for example).<ref name=NIH2018/><ref name=Rag2011 /> There are four key features of UIP including interstitial fibrosis in a 'patchwork pattern', interstitial scarring, honeycomb changes and fibroblast foci.{{
Fibroblastic foci are dense collections of myofibroblasts and scar tissue and, together with honeycombing, are the main pathological findings that allow a diagnosis of UIP.
Line 131 ⟶ 137:
===Pulmonary rehabilitation===
Fatigue and loss of muscular mass are common and disabling problems for patients with IPF. [[Pulmonary rehabilitation]] may alleviate the overt symptoms of IPF and improve functional status by stabilizing and/or reversing the extrapulmonary features of the disease.<ref name=SpagnoloTonelli /><ref name=Lee>{{cite journal | vauthors = Lee JS, McLaughlin S, Collard HR | title = Comprehensive care of the patient with idiopathic pulmonary fibrosis | journal = Current Opinion in Pulmonary Medicine | volume = 17 | issue = 5 | pages = 348–54 | date = September 2011 | pmid = 21760508 | doi = 10.1097/mcp.0b013e328349721b | s2cid = 11918582 }}</ref> The number of published studies on the role of pulmonary rehabilitation in idiopathic pulmonary fibrosis is small, but most of these studies have found significant short-term improvements in functional exercise tolerance, quality of life, and dyspnea on exertion.<ref name=KennGloeckl>{{cite journal | vauthors = Kenn K, Gloeckl R, Behr J | title = Pulmonary rehabilitation in patients with idiopathic pulmonary
===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====
Line 141 ⟶ 147:
====N-acetylcysteine and triple therapy====
[[N-Acetylcysteine|''N''-Acetylcysteine]] (NAC) is a precursor to glutathione, an [[antioxidant]]. It has been hypothesized that treatment with high doses of NAC may repair an oxidant–antioxidant imbalance that occurs in the lung tissue of patients with IPF. In the first clinical trial of 180 patients (IFIGENIA), NAC was shown in previous study to reduce the decline in VC and DLCO over 12 months of follow-up when used in combination with [[prednisone]] and [[azathioprine]] (triple therapy).<ref name=DemedtsBehr>{{cite journal |vauthors=Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M | title = High-dose acetylcysteine in idiopathic pulmonary fibrosis | journal = New England Journal of Medicine| volume = 353 | issue = 21 | pages = 2229–2242 | year = 2005 | pmid = 16306520 | doi = 10.1056/NEJMoa042976 |display-authors=etal| hdl = 2066/47718 | s2cid = 30279834 | url = https://pure.uva.nl/ws/files/3925361/45651_207328y.pdf }}</ref>
More recently, a large randomized, controlled trial (PANTHER-IPF) was undertaken by the [[National Institutes of Health]] (NIH) in the US to evaluate triple therapy and NAC monotherapy in IPF patients. This study found that the combination of prednisone, azathioprine, and NAC increased the risk of death and hospitalizations<ref name="pmid22607134">{{cite journal | vauthors = Raghu G, Anstrom KJ, King TE, Lasky JA, Martinez FJ | title = Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis | journal = New England Journal of Medicine| volume = 366 | issue = 21 | pages = 1968–77 | date = May 2012 | pmid = 22607134 | pmc = 3422642 | doi = 10.1056/NEJMoa1113354 }}</ref> and the NIH announced in 2012 that the triple-therapy arm of the PANTHER-IPF study had been terminated early.<ref name=NIHApril2013>{{cite web |url=https://www.nih.gov/news-events/news-releases/commonly-used-three-drug-regimen-idiopathic-pulmonary-fibrosis-found-harmful |title= Commonly used three-drug regimen for idiopathic pulmonary fibrosis found harmful|author=<!--Not stated--> |date=
This study also evaluated NAC alone and the results for this arm of the study were published in May 2014 in the ''[[New England Journal of Medicine]]'', concluding that "as compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to-moderate impairment in lung function".<ref name=IPFCRN>{{cite journal | author = The Idiopathic Pulmonary Fibrosis Clinical Research Network. | title = Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis | journal = New England Journal of Medicine| volume = 370 | issue = 22 | pages = 2093–2102 | year = 2014 | pmid = 24836309 | pmc = 4116664| doi = 10.1056/nejmoa1401739}}</ref>
====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
===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>
Line 158 ⟶ 164:
[[Palliative care]] focuses on reducing symptoms and improving the comfort of patients rather than treating the disease. This may include treatment of worsening symptoms with the use of chronic [[opioids]] for severe dyspnea and cough. Further, oxygen therapy may be useful for palliation of dyspnea in hypoxemic patients.
Palliative care also includes relief of physical and emotional suffering and psychosocial support for patients and caregivers.<ref name=Rag2011 /> With disease progression, patients may experience fear, anxiety and depression and psychological counseling should therefore be considered. In a recent study of outpatients with ILDs, including IPF, depression score, functional status (as assessed by walk test), as well as pulmonary function, all contributed to the severity of dyspnea.<ref name=RyersonBerkeley>{{cite journal |vauthors=Ryerson CJ, Berkeley J, Carrieri-Kohlman VL, Pantilat SZ, Landefeld CS, Collard HR | title = Depression and functional status are strongly associated with dyspnea in interstitial lung disease | journal = Chest | volume = 139 | issue = 3 | pages = 609–616 |doi=10.1378/chest.10-0608| pmid = 20688924 | year = 2011 | s2cid = 34116718 |url=http://pdfs.semanticscholar.org/a3b3/4f5c73aaf8c31f88d6b67398ac662eb64611.pdf |archive-url=https://web.archive.org/web/20200801223108/http://pdfs.semanticscholar.org/a3b3/4f5c73aaf8c31f88d6b67398ac662eb64611.pdf |url-status=dead |archive-date=1 August 2020
In selected cases of particularly severe dyspnea [[morphine]] could be considered. It can reduce dyspnea, anxiety and cough without significant decrease in oxygen saturation.<ref name=AllenRaut>{{cite journal |vauthors=Allen S, Raut S, Woollard J, Vassallo M | title = Low dose diamorphine reduces breathlessness without causing a fall in oxygen saturation in elderly patients with end-stage idiopathic pulmonary fibrosis | journal = Palliative Medicine| volume = 19 | issue = 2 | pages = 128–130 | year = 2005 | pmid = 15810751| doi = 10.1191/0269216305pm998oa| s2cid = 12999693 }}</ref>
Line 165 ⟶ 171:
IPF is often misdiagnosed, at least until physiological and/or imaging data suggest the presence of an ILD leading to delay in accessing appropriate care.<ref name=SpagnoloTonelli /> Considering that IPF is a disease with a median survival of three years after diagnosis, early referral to a center with specific expertise should therefore be considered for any patient with suspected or known ILD. On the basis of the complex differential diagnostic, multidisciplinary discussion between pulmonologists, radiologists, and pathologists experienced in the diagnosis of ILD is of the utmost importance to an accurate diagnosis.<ref name=Rag2011 />
In addition, the increasing awareness of complications and common concomitant conditions frequently associated with IPF requires a routinely evaluation of comorbidities, most of them simply reflecting concurrent diseases of aging, and medications with their interaction and side effects.
Line 175 ⟶ 181:
==Prognosis==
[[File:Comparison of the 5-year survival rate for IPF.jpg|thumb|upright=1.4|Comparison of the 5-year survival rate for IPF and common malignancies. Adapted from Bjoraker et al. 1998.<ref name=BjorakerRyu>{{cite journal |vauthors=Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP | title = Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis | journal = American Journal of Respiratory and Critical Care Medicine| volume = 157 | issue = 1 | pages = 199–203 | year = 1998 | pmid = 9445300 | doi = 10.1164/ajrccm.157.1.9704130| s2cid = 13942321 |url=http://pdfs.semanticscholar.org/9470/43dcb478d91d9f41022112d3e970c7eff750.pdf |archive-url=https://web.archive.org/web/20190227181251/http://pdfs.semanticscholar.org/9470/43dcb478d91d9f41022112d3e970c7eff750.pdf |url-status=dead |archive-date=
The clinical course of IPF can be unpredictable.<ref name=Rag2011 /><ref name=BjorakerRyu /><ref name=KimCollard>{{cite journal | vauthors = Kim DS, Collard HR, King TE | title = Classification and natural history of the idiopathic interstitial pneumonias | journal = Proceedings of the American Thoracic Society| volume = 3 | issue = 4 | pages = 285–92 | date = June 2006 | pmid = 16738191 | pmc = 2658683 | doi = 10.1513/pats.200601-005TK }}</ref> IPF progression is associated with an estimated median survival time of 2 to 5 years following diagnosis.<ref name=NIH2018/><ref name=Rag2011 />
The 5-year survival for IPF ranges between
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.
==Epidemiology==
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
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>
Line 197 ⟶ 203:
==Research==
A number of agents are currently being investigated in [[Phase II clinical trial]]s for IPF, including the monoclonal antibodies [[simtuzumab]], [[tralokinumab]], [[lebrikizumab]] and FG-3019, a [[lysophosphatidic acid]] receptor antagonist (BMS-986020). A Phase II study of STX-100 is also ongoing.<ref name=CoalitionForPF>{{Cite web |url=http://www.coalitionforpf.org/active-clinical-trials-and-investigational-research-in-ipf/ |title=Active Clinical Trials and Investigational Research in IPF |access-date=4 September 2014
[[mir-29 microRNA precursor]] investigations in mice have produced reversal of induced IPF. MRG-201 is currently being tested as-of 2016, but not in IPF patients yet, and no human trials for IPF use have been scheduled {{as of|January 2016|lc=y}}.<ref>{{cite web|title=Research Demonstrates Reversal Of Pulmonary Fibrosis With miRagen Therapeutics Synthetic microRNA-29 Mimic (promiR-29)|url=http://pulmonaryfibrosisnews.com/2014/09/23/research-demonstrates-reversal-of-pulmonary-fibrosis-with-miragen-therapeutics-synthetic-microrna-29-mimic-promir-29/|website=Pulmonaryfibrosisnews.com|access-date=8 June 2018|date=
[[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==
Line 207 ⟶ 216:
==External links==
{{Commons category|Idiopathic pulmonary fibrosis}}▼
{{Medical resources
| DiseasesDB = 4815
| ICD10 = {{ICD10|J|84|112|j|80}}
| ICD9 = {{ICD9|516.31}}
| ICDO =
| OMIM = 178500
| MedlinePlus = 000069
| eMedicineSubj = radio
| eMedicineTopic = 873
| MeshID = D011658
}}
▲{{Commons category|Idiopathic pulmonary fibrosis}}
* {{Curlie|Health/Conditions_and_Diseases/Respiratory_Disorders/Pulmonary_Fibrosis/}}
| |||