Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that involves the buildup of fibrotic tissue in the pulmonary parenchyma.¹  IPF primarily occurs in older patients (60 and above) with a median survival of 3-4 years after diagnosis.² There is considerable variability in incidence and prevalence estimates, especially between countries, but the universal incidence is estimated to be around 10 cases per 100,000 people per year.² A study of patients in the US over age 65 receiving Medicare found an overall incidence rate of 93.7 cases per 100,000 people and a prevalence of 494.5 cases per 100,000 people in 2011.³ 

History of IPF

The earliest reports of patients with symptoms consistent with IPF were by German physicians in the late 1800s and early 1900s. The disease became much more widely known after English-language publications from Hamman and Rich in 1933, 1935, and 1944 provided detailed descriptions of the disease, which they referred to as “acute diffuse interstitial fibrosis of the lungs.” Based on the descriptions provided by Hamman and Rich, several other cases were reported in the literature around the world, and research has continued into the causes and treatments for the disease.⁴

Symptoms of IPF

The most commonly reported symptom of patients with IPF is dyspnea. Chronic, unproductive cough is also a common symptom, especially in patients without a history of smoking or those with more severe forms of the disease. Other symptoms may include “clubbed fingers” (distal phalanges become hypertrophied and enlarged), fine crackles in the lower posterior lung fields on lung auscultation, and symptoms of connective tissue disease such as sicca and arthralgia.⁵ 

Read more about IPF symptoms.

IPF Causes and Risk Factors

As the name suggests, the exact cause of IPF is unknown, although several factors have been identified that may contribute to the disease. Environmental, genetic, and epigenetic factors may all be involved in the pathogenesis of IPF.¹ Environmental exposure to cigarette smoke, agricultural compounds, and dust from wood, stone, sand, and silica have been correlated with IPF. Exposure to pulmonary microbial agents, as well as more systemic infections, may increase the risk of IPF. 

A number of genetic mutations have also been linked to an increased risk of IPF. These mutations are involved in a variety of biological processes including surfactant protein production and secretion for alveolar stability, telomere maintenance related to cell senescence, production of mucus and human leukocyte antigens related to host defense, and the production of cell-cell adhesion molecules critical for lung epithelial layer integrity.⁶ Epigenetic modulation through DNA methylation and changes in levels of regulatory microRNAs may also contribute to the development of IPF.¹ The 2 main effectors of epigenetic alterations appear to be smoking and aging.¹

Diagnosis

Diagnosis begins with a thorough review of the medical history and a clinical examination to rule out similar diseases. Patient age, environmental exposures, family history, and extrapulmonary symptoms should all be considered when making a diagnosis.⁷ High-resolution computed tomography (HRCT) scans are the next step in diagnosis and are used to look for specific features including “honeycombing,” traction bronchiectasis/bronchiolectasis, and “ground-glass opacification” that can be used to categorize the patterns of usual interstitial pneumonia (UIP) based on the 2018 guidelines from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society.⁸ Additional testing including serum biomarker analysis and lung biopsy may be performed, although the 2018 guidelines recommend against biomarker analysis due to lack of evidence and advise lung biopsy only be performed in certain circumstances based on the results of clinical examination and HRCT scans.

Read more about PAH diagnosis.

Progression, Management, and Treatment of IPF

IPF progression can be highly variable, with some patients experiencing rapid deterioration in lung function while others experience much slower progression, and some experiencing periods of stability punctuated by acute, sometimes fatal, exacerbations.²

There is currently no cure for IPF, although 2 anti-fibrotic drugs have been approved for use in IPF by the US Food and Drug Administration (FDA). These 2 drugs, nintedanib and pirfenidone, do not cure the disease but slow the progression.¹ In addition, the treatments do not affect fibrosis that has already occurred and do not improve symptoms, necessitating the need for palliative care.¹ 

Read more about IPF treatment.

Management of symptoms may include long-term oxygen therapy, respiratory rehabilitation, and treatment of chronic cough triggers or comorbidities such as gastroesophageal reflux disease (GERD), angiotensin-converting enzyme (ACE) inhibitor use, infections, or obstructive sleep apnea.¹ Palliative care can also help patients with depression and anxiety.⁹

Lung transplantation has been shown to prolong the survival of patients, however, it is not a viable option for many patients due to their advanced age and comorbidities such as cardiovascular disease.¹⁰ 

References

1. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32. doi:10.1186/s12931-018-0730-2
2. Sauleda J, Núñez B, Sala E, Soriano JB. Idiopathic pulmonary fibrosis: epidemiology, natural history, phenotypes. Med Sci (Basel). 2018;6(4):110. doi:10.3390/medsci6040110
3. Raghu G, Chen SY, Yeh WS, et al. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001-11. Lancet Respir Med. 2014;2(7):566-572. doi:10.1016/S2213-2600(14)70101-8
4. Homolka J. Idiopathic pulmonary fibrosis: a historical review. CMAJ. 1987;137(11):1003-1005.
5. Nakamura Y, Suda T. Idiopathic pulmonary fibrosis: diagnosis and clinical manifestations. Clin Med Insights Circ Respir Pulm Med. 2016;9(Suppl 1):163-171. doi:10.4137/CCRPM.S39897
6. Kaur A, Mathai SK, Schwartz DA. Genetics in idiopathic pulmonary fibrosis pathogenesis, prognosis, and treatment. Front Med (Lausanne). 2017;4:154. doi:10.3389/fmed.2017.00154
7. Martinez FJ, Chisholm A, Collard HR, et al. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Respir Med. 2017;5(1):61-71. doi:10.1016/S2213-2600(16)30325-3
8. Raghu G, Remy-Jardin M, Myers JL, et al.; American Thoracic Society; European Respiratory Society; Japanese Respiratory Society; Latin American Thoracic Society. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68. doi:10.1164/rccm.201807-1255ST
9. Zou RH, Kass DJ, Gibson KF, Lindell KO. The role of palliative care in reducing symptoms and improving quality of life for patients with idiopathic pulmonary fibrosis: a review. Pulm Ther. 2020;6(1):35-46. doi:10.1007/s41030-019-00108-2
10. Quinn C, Wisse A, Manns ST. Clinical course and management of idiopathic pulmonary fibrosis. Multidiscip Respir Med. 2019;14:35. doi:10.1186/s40248-019-0197-0

Reviewed by Harshi Dhingra, MD, on 7/1/2021.

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Brian Murphy, PhD

Brian Murphy, PhD, is a medical/science writer and educator who has written over 300 resource articles about rare diseases. He holds a BS from Georgia Institute of Technology and a PhD from Case Western Reserve University, both in Biomedical Engineering. After graduation, Brian worked as a clinical neural engineer to help restore movement in spinal cord injured patients by reconnecting their brain to their paralyzed muscles using experimental medical devices. In addition to resource pages, Brian has also authored/co-authored several research articles in journals including The Lancet, Journal of Neural Engineering, and PLOS ONE.