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Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019
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Image courtesy of author's practice database.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
A 71-year-old man comes to the office with complaints of shortness of breath and a dry cough for the last 8 months. His cough has not improved with antibiotics or albuterol inhalers. His other main symptom is fatigue. He reports no significant past medical history, takes no medications, and has no known allergies. He denies recreational drug use. He is a social drinker with no history of smoking. His initial pulmonary examination reveals fine bibasilar crackles. Jugular veins are not distended, and no leg edema is present. His ejection fraction is 60% on echocardiography.
What is the radiologic description of this patient's chest radiograph (shown)?
Image courtesy of Radiopaedia.org.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: The patient's chest radiograph shows bilateral reticular (a fine network or netlike) opacities.
What is the most appropriate next step in the workup?
Images courtesy of Radiopaedia.org (left) and author's practice database (right).
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: The most appropriate next step is to obtain a high-resolution computed tomography (HRCT) scan of the lungs.
Accordingly, the patient undergoes HRCT, which yields the scans shown in the slide. What do these scans reveal?
Images courtesy of Radiopaedia.org.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: The HRCT scan shows basal and peripheral reticular opacities with honeycombing and traction bronchiectasis.
What are the signal features of honeycombing on pathologic analysis and HRCT?
Images courtesy of Radiopaedia.org.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: Pathologically, honeycombing includes cystic spaces that are air-filled, are lined by bronchiolar epithelium, and have thick walls composed of dense fibrous tissue. On HRCT, honeycombing includes cystic spaces a few millimeters to a few centimeters in diameter that are air-filled and have clear definable walls ranging from 1 to 3 mm in thickness.[1] Adjacent honeycomb cysts share the same walls.
Honeycombing is differentiated from intralobular interstitial thickening on the basis of the material in the cyst-shaped spaces. In honeycombing, the contents of the cystic spaces appear black (air), but in intralobular interstitial thickening, the contents of the spaces appear gray (lung parenchyma). Honeycombing is due to pulmonary fibrosis, and pathologically, it is a terminal process.
What is the main histopathologic feature of IPF?
Image courtesy of Wikimedia Commons.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: Fibroblastic foci. Usual interstitial pneumonia (UIP) is the pathologic finding in IPF, and fibroblastic foci and honeycombing are the characteristic histopathologic features of UIP.[2] A fibroblastic focus includes clusters of fibroblasts and myofibroblasts.
Does IPF progress? And if yes, how fast?
Image courtesy of Latsi PI et al.[4]
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: The rate of decline in forced vital capacity (FVC) is around 150-200 ml annually.[3]
Among other changes seen in pulmonary function testing is a decline in the diffusing capacity of the lung for carbon monoxide (DLCO), which has prognostic significance.
A DLCO of less than 35% is associated with a worse prognosis.[4]
What are the most important risk factors for IPF?
Table adapted from Raghu et al.[5]
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Although IPF is, by definition, a disease of unknown etiology, a number of potential risk factors have been described, including smoking, environmental exposure, infection, gastroesophageal reflux, familial IPF, and genetic factors.[5,6]
Image courtesy of Wikimedia Commons | Table adapted from Bjoraker JA et al.[7]
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
IPF should be considered in all adult patients with unexplained chronic exertional dyspnea. Common presenting symptoms include cough, bibasilar inspiratory crackles, and finger clubbing (25-50%). Prevalence estimates for IPF have ranged from 2 to 29 cases per 100,000 in the general population. Patients most often present in the sixth and seventh decades of life, and there is a slight male preponderance. Only 20-30% of patients are still alive after 5 years. The median survival is in the range of 2.5-3.5 years.[5]
What are the treatment options for IPF?
Image courtesy of Medscape.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: Current treatment options for IPF are as follows:
Supportive care and nonspecific therapies, including oxygen supplementation, pulmonary rehabilitation, vaccinations for influenza, and pneumococcal vaccines
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: In an IPF exacerbation (which occurs in 10-57% of patients with IPF), acute or subacute worsening of respiratory symptoms develops with no clear identifiable cause.[8,9] No viral or bacterial infection is apparent, and no heart failure is detected. The HRCT scan in the slide shows areas of honeycombing with new ground-glass opacities or consolidation. Heart failure or volume overload do not explain the worsening of the patient's condition.[10]
What are the treatment options for acute exacerbations of IPF?
Image courtesy of Wikimedia Commons.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Answer: Treatment options for acute IPF exacerbations include the following[11]:
Maintaining oxygen saturation of 88% or greater by administration of oxygen supplementation or high-flow oxygen.
Palliative care strategies to improve dyspnea.
Anti-acid therapy, based on a hypothesis that acid reflux may contribute to the acute exacerbations.
Broad-spectrum antibiotics.
Pirfenidone and nintedanib. They can be continued during the course of acute exacerbations. For new patients, they can be started after improvement of acute exacerbation.
Possibly, cytotoxic agents and mechanical ventilation.
The mortality exceeds 70%.
What, if any, specific medical therapies are available for IPF?
Image courtesy of Medscape.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Although no curative therapies for IPF are available, two medications have been approved by the US Food and Drug Administration (FDA) for treatment of this condition. One of these agents is the tyrosine kinase receptor blocker nintedanib, which reduces the fibrogenesis and slows down the decline in lung function[12,13]; in addition, it may increase the time to first exacerbation.[13] The dosage is 150 mg twice daily with food. Liver function test (LFT) results should be checked both before the initiation of nintedanib therapy and during treatment. In clinical trials, diarrhea was reported in 62% of patients taking nintedanib, compared with 18% of those taking placebo; nausea was observed in 24% of those taking nintedanib, compared with 7% of those taking placebo.
Image courtesy of Sam Shlomo Spaeth / Medscape.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
The second medication approved by the FDA for the treatment of IPF is pirfenidone, an antifibrotic agent that slows down the lung function decline.[14] It is more effective in a subset of patients with mild-to-moderate disease.[15,16] Recommended dosing for pirfenidone is as follows:
Days 1-7: 267 mg (one capsule) orally q8hr with food
Days 8-14: 534 mg (two capsules) orally q8hr with food
Day 15 and thereafter: 801 mg (three capsules) orally q8hr with food
LFT results should be checked both before and during treatment with pirfenidone. In clinical trials, nausea was observed in 36% of patients taking pirfenidone, compared with 16% of those taking placebo; diarrhea was reported in 26% of those taking pirfenidone, compared with 20% of those taking placebo. Rash and photosensitivity are common; accordingly, patients must use sunscreen and avoid direct sun exposure.
The 2015 update of the 2011 ATS/ERS/JRS/ALAT clinical practice guideline included a conditional recommendation for the use of pirfenidone to treat IPF.[17] The 2015 guideline also contained conditional recommendations against the use of macitentan, bosentan, or sildenafil, as well as strong recommendations against the use of warfarin, imatinib, ambrisentan, or prednisone + azathioprine + N-acetylcysteine.
Surgical treatment (ie, lung transplant) may be an option for some, but not all, IPF patients. What are the indications for lung transplant in the setting of IPF?
Image courtesy of Wikimedia Commons.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
With regard to an IPF patient's candidacy for a lung transplant, the criteria for referral differ from the criteria for placement on the transplant list.[18] For the referral, the DLCO should be less than 40% of the predicted value, and the functional vital capacity (FVC) should be less than 80% of the predicted value. Oxygen saturation at baseline or during an exacerbation should be less than 89%. Many people get worse and die while on the transplant waiting list.
Palliative care and end-of-life discussions should be started when the FVC is reduced to less than 50% of the predicted value. The adequacy of end-of-life management in IPF is deserving of further study.[19,20]
Image courtesy of Wikipedia.
Idiopathic Pulmonary Fibrosis: Killer Without a Cause
Mehran Farid-Moayer, MD; Mark P Brady, PA-C | May 1, 2019 | Contributor Information
Herazo-Maya from Yale University and collaborators from six academic centers recruited 425 participants and carried out analysis of a 52-gene signature in mononuclear cells from the blood of IPF patients.[21] They were able to predict transplant-free survival on the basis of changes in the gene profile, and they demonstrated changes in the gene profile after the initiation of antifibrotic therapy. This approach may eventually play a role in prioritization of transplant or in stratification of patients in drug studies.
Traumatic brain injury (TBI) is a common global public health problem with potentially catastrophic consequences. Early recognition and prompt treatment are essential to minimizing morbidity and mortality. Learn more about 7 TBIs that may have devastating effects.Slideshows, March 2019
Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, primarily occurring in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP).Diseases/Conditions, October 2018
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Contributor Information
Mehran Farid-Moayer, MD
Adjunct Clinical Associate Professor
Department of Psychiatry and Behavioral Sciences
Stanford University Medical School
Palo Alto, CA
Pulmonary, Critical Care, and Sleep Medicine
Mills-Peninsula Medical Center
Burlingame, CA
Disclosure: Mehran Farid-Moayer, MD, has disclosed no relevant financial relationships.
Mark P Brady, PA-C
Department of Emergency Medicine
Cambridge Health Alliance
Cambridge, MA
Disclosure: Mark P Brady, PA-C, has disclosed no relevant financial relationships.
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References
Webb WR, Muller NL, Naidich DP. High-Resolution CT of the Lung. 5th ed. Philadelphia: Wolters Kluwer; 2014.
Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med. 2001 Aug 16;345(7):517-25. [PMID: 11519507].
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. [PMID: 15968010].
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. [PMID: 12791580].
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. [PMID: 21471066].
Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68. [PMID: 30168753]
Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;157(1):199-203. [PMID: 9445300].
Collard HR, Moore BB, Flaherty KR, et al; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007 Oct 1;176(7):636-43. [PMID: 17585107].
Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011 Feb;37(2):356-63. [PMID: 20595144].
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. [PMID: 27299520]
Kim DS, Park JH, Park BK, Lee JS, Nicholson AG, Colby T. Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J. 2006 Jan;27(1):143-50. [PMID: 16387947].
Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. [PMID: 21992121].
Richeldi L, du Bois RM, Raghu G, et al; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82. [PMID: 24836310].
King TE Jr, Bradford WZ, Castro-Bernardini S, et al; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. [PMID: 24836312].
Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2005 May 1;171(9):1040-7. [PMID: 15665326]
Noble PW, Albera C, Bradford WZ, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J. 2016 Jan;47(1):243-53. [PMID: 26647432]
Raghu G, Rochwerg B, Zhang Y, et al; ATS, ERS, JRS, and ALAT. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015 Jul 15;192(2):e3-e19. [PMID: 26177183].
Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015 Jan;34(1):1-15. [PMID: 25085497].
Lindell KO, Liang Z, Hoffman LA, et al. Palliative care and location of death in decedents with idiopathic pulmonary fibrosis. Chest. 2015 Feb;147(2):423-9. [PMID: 25187973]
Ahmadi Z, Wysham NG, Lundström S, Janson C, Currow DC, Ekström M. End-of-life care in oxygen-dependent ILD compared with lung cancer: a national population-based study. Thorax. 2016 Jun;71(6):510-6. [PMID: 26865603]
Herazo-Maya JD, Sun J, Molyneaux PL, et al. Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study. Lancet Respir Med. 2017 Nov;5(11):857-68. [PMID: 28942086]
Slide 7: Image source: 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. [PMID: 12791580].
Slide 8: Table source: Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. 2011 Mar 15. 183(6):788-824.
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