Featured, In the News / Politics:

Idiopathic Pulmonary Fibrosis: Treating a Mystery

By: Svetlana Akbasheva, Section Editor

Idiopathic pulmonary fibrosis (IPF) is a devastating condition in which the lungs become thick and tough with scar tissue and progressively lose their ability to efficiently deliver oxygen to the blood.1 That the disease has no established cause can make diagnosis difficult. However, the 2011 ATS/ERS/JRS/ALAT guidelines2 provide three criteria to establish a diagnosis of IPF. First, all other causes of interstitial lung disease must be excluded. These include environmental exposures, certain medications, and connective tissue diseases.2 While there is no standardized or validated approach to conduct such a diagnosis of exclusion, a thorough physical assessment and patient history are essential.2 Physicians also need to perform a multitude of diagnostic tests to evaluate the extent of lung damage and rule out other diseases like cancer and tuberculosis.1 The second diagnostic criterion set out by the guidelines is the presence of a usual interstitial lung disease pattern, or UIP, on high-resolution computed tomography (HRCT). Thirdly, if a lung biopsy is performed, the combined findings of the biopsy and HRCT should have a pattern consistent with IPF.2

The worldwide prevalence of IPF is estimated to be between 13 and 20 cases per 100,000 people.3 It is usually diagnosed in the older population—largely people in their 60s and 70s—and affects men more than women.1 Although the cause of IPF is unknown, several risk factors are suspected based on the characteristics of patients who present with the disease. Cigarette smoking is thought to be one of the biggest risk factors; others include environmental exposures and microbes.2 Since many patients with IPF have comorbid GERD, it is hypothesized that aspiration of acid droplets into the lungs may prompt lung damage in this manner.1 In addition, less than 5% of patients with IPF have a close family member with the disease, suggesting that some cases may involve a genetic component.2 So far two genes have been potentially implicated in the pathology of this disease, known as TERC and TERT, which are involved in making the telomerase enzyme. Although more research is needed, it is hypothesized that genetics may predispose certain people to IPF but environmental factors are necessary to ultimately precipitate the disease.3

Generally, patients with IPF first present with shortness of breath and a dry, hacking cough. Signs and symptoms can also include fatigue, unintended weight loss, shallow breathing, and clubbing of the fingers and toes.1 Without treatment, pulmonary function gradually deteriorates and patients usually survive for no more than five years after diagnosis. The majority of patients die from respiratory failure or disease complications such as pulmonary hypertension, pulmonary embolism, heart failure, or pneumonia.1 There is no cure for IPF, and until recently there were no effective pharmacological treatments available for this condition.1,2,4,5

The 2011 IPF treatment guidelines were written before the approval of two medications for IPF in 2014. In the absence of effective treatment for IPF, the recommendations for drug therapy were strongly against the use of agents such as corticosteroid monotherapy, colchicine, and cyclosporine A, while weakly supportive of the use of an acetylcysteine/ azathioprine/ prednisone combination, acetylcysteine monotherapy, anticoagulants, and pirfenidone. These were international guidelines, and pirfenidone had not yet been approved in the United States. The only strong recommendations made by the guidelines were for long-term oxygen therapy and lung transplantation in appropriate patients.2 Although lung transplantation prolongs survival in advanced disease, only about 44% of IPF patients survive for five years after the procedure.6 Pulmonary rehabilitation can be used as adjunctive therapy in all stages of IPF; it educates patients about managing their disease by teaching them techniques to conserve energy and improve breathing. Providing access to counseling or support groups is also encouraged.1

On October 15, 2014, the FDA approved nintedanib (Ofev®), and pirfenidone (Esbriet®), the first two medications indicated exclusively for IPF.4,5 Based on the findings of clinical trials, these agents have been proven to slow IPF progression.4,5 While nintedanib works through the inhibition of tyrosine kinases,7 the mechanism of action of pirfenidone is unknown.8 Both are oral medications, although pirfenidone has a higher pill burden (three capsules three times a day)8 than nintedanib (one capsule twice daily).7 In addition, both have warnings regarding the elevation of liver enzymes.7,8 It will be interesting to see long-term safety and efficacy data for these two medications in the future, as well as changes in the guidelines in response to the availability of these agents.



  1. Idiopathic pulmonary fibrosis. National Heart, Lung, and Blood Institute. http://www.nhlbi.nih.gov/health/health-topics/topics/ipf. Updated 09/20/11. Accessed 05/15/15.
  2. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824.
  3. Idiopathic pulmonary fibrosis. Genetics Home Reference. http://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis. Updated April 2015. Accessed September 20, 2015.
  4. FDA approves Ofev to treat idiopathic pulmonary fibrosis. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418994.htm. Updated October 16, 2014. Accessed May 15, 2015.
  5. FDA approves Esbriet to treat idiopathic pulmonary fibrosis. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418991.htm. Updated October 16, 2014. Accessed May 15, 2015.
  6. King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. The Lancet. 2011; 378(9807):1949-61.
  7. Ofev (nintedanib) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; October 2014.
  8. Esbriet (pirfenidone) [package insert]. Brisbane, CA: Intermune, Inc.; October 2014.


Published by Rho Chi Post
Both comments and trackbacks are currently closed.