Pulmonary Fibrosis Week

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General Information

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Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia comprising about 20% of specific interstitial lung diseases in the United States (1).  IPF is a chronic, progressive fibrotic interstitial lung disease that is characterized by the progressive accumulation of scar tissue within the lung, loss of alveolar architecture and eventually loss of lung function due to respiratory insufficiency.  As the name implies, the cause of the disease is unknown.  It is often diagnosed following a careful examination of the patients exposure history, characteristic imaging obtained by HRCT scans (bilateral reticulation and honeycombing that is peripheral and predominant in the lower lobes) or histology (pathologic diagnosis of usual interstitial pneumonia) seen on biopsy specimens when a patient presents with unexplained shortness of breath, chronic cough and/or Velcro-like crackles on physical examination (2).  The disease is also more common in adults over 50 years of age and affects men more than women.  Sadly, IPF carries a poor prognosis and for patients that are over the age of 65, the median survival is only 3.8 years (1).  This mortality rate is far worse than most cancers.


The disease occurs worldwide and the prevalence is 10-60 cases per 100,000, but some studies report even higher incidence (3).  Patients with IPF are often misdiagnosed which is problematic because recent studies have shown that immunosuppressive therapies are potentially harmful in these patients (4) and currently available therapies are likely to be more effective if initiated early (5,6).


The pathobiology of IPF is still poorly understood but current hypotheses suggest the disease is initiated by repetitive, subclinical injury of the alveolar epithelium.  This repetitive stress to the epithelium may lead to a premature “aging” of the tissue, release of profibrotic factors and dysregulated repair.  Chronic innate immune inflammation is also a feature of the disease along with the accumulation of apoptosis-resistant myofibroblasts that promote contraction of the tissue and deposition of extracellular matrix (reviewed in (1).   There is a growing interest in how innate immunity and alterations to the lung microbiota might contribute to disease pathogenesis (7-9).  Patients can experience variability in disease course with some patients experiencing a steady rate of respiratory decline, while others may experience episodes known as “acute exacerbations” (10) which often result in precipitous decline.  Patients with IPF are also at risk for poor outcomes from pneumonias due to respiratory infections with viruses or bacteria.
Treatments for the disease remain sub-optimal.  Supplemental oxygen is strongly recommended for patients with IPF and pulmonary rehabilitation can also be beneficial.  Two new drugs were approved by the FDA in 2014 (nintedanib and pirfenidone) and both were shown in placebo-controlled trials to slow the rate of decline in forced vital capacity by approximately 50% (11,12) over the course of a year.  However, the drugs are not a cure and the costs for each are estimated at over $100,000 annually (1).  Lung transplantation is the only known cure for IPF, but this procedure carries significant morbidity and mortality as well and not all patients are candidates for the procedure.  Thus, a better understanding of the pathogenesis and heterogeneity of the disease is needed to inform new therapies and there is also an urgent need to identify relevant biomarkers of disease activity to better assess efficacy in clinical trials of new investigational therapies.

References

  1. Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. The New England journal of medicine2018; 378:1811-1823

  2. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE, Jr., Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. American journal of respiratory and critical care medicine2011; 183:788-824

  3. Raghu G, Chen SY, Yeh WS, Maroni B, Li Q, Lee YC, Collard HR. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001-11. The Lancet Respiratory medicine2014; 2:566-572

  4. Raghu G, Anstrom KJ, King TE, Jr., Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. The New England journal of medicine2012; 366:1968-1977

  5. Albera C, Costabel U, Fagan EA, Glassberg MK, Gorina E, Lancaster L, Lederer DJ, Nathan SD, Spirig D, Swigris JJ. Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function. The European respiratory journal2016; 48:843-851

  6. Kolb M, Richeldi L, Behr J, Maher TM, Tang W, Stowasser S, Hallmann C, du Bois RM. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax2017; 72:340-346

  7. Han MK, Zhou Y, Murray S, Tayob N, Noth I, Lama VN, Moore BB, White ES, Flaherty KR, Huffnagle GB, Martinez FJ. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. The Lancet Respiratory medicine2014; 2:548-556

  8. Huang Y, Ma SF, Espindola MS, Vij R, Oldham JM, Huffnagle GB, Erb-Downward JR, Flaherty KR, Moore BB, White ES, Zhou T, Li J, Lussier YA, Han MK, Kaminski N, Garcia JGN, Hogaboam CM, Martinez FJ, Noth I. Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis. American journal of respiratory and critical care medicine2017; 196:208-219

  9. Molyneaux PL, Willis-Owen SAG, Cox MJ, James P, Cowman S, Loebinger M, Blanchard A, Edwards LM, Stock C, Daccord C, Renzoni EA, Wells AU, Moffatt MF, Cookson WOC, Maher TM. Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis. American journal of respiratory and critical care medicine2017; 195:1640-1650

  10. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE, Jr., Lasky JA, Loyd JE, Noth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Muller-Quernheim J, Myers JL, Nicholson AG, Selman M, Toews GB, Wells AU, Martinez FJ. Acute exacerbations of idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine2007; 176:636-643

  11. King TE, Jr., Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. The New England journal of medicine2014; 370:2083-2092

  12. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. The New England journal of medicine2014; 370:2071-208

 


 

Important Facts About Pulmonary Fibrosis

  1. Pulmonary Fibrosis (PF) is scarring in the lungs, which progressively builds up over time, making it hard for oxygen to get into your blood. Symptoms of PF include: shortness of breath, dry, hacking cough, fatigue, and weakness.
  2. There are five main categories of identifiable PF: drug induced, radiation induced, environmental, autoimmune (connective tissue disesase related), and occupational.
  3. Idiopathic Pulmonary Fibrosis (IPF) is a type of PF which the cause is not known. Although IPF is still considered to be a disease of unknown cause, we do know some factors that increase the risk of getting IPF, including aging (IPF is rare before age 50), smoking, and having certain genetic predispositions.
  4. Treatment options for PF include: supplemental oxygen, pulmonary rehabilitation, lung transplantation, medications.