Idiopathic Pulmonary Fibrosis (IPF)

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Idiopathic pulmonary fibrosis (IPF) is a rare, progressive lung disease that is often fatal. The median survival is estimated at 3-5 years after diagnosis.1 The disease is more common in middle-aged and elderly patients, with estimates of incidence varying between 6.8 and 93.7 cases per 100,000 people per year in North America.2 Patients typically experience non-distinct symptoms that overlap with many other diseases, such as dyspnea and chronic cough, making diagnosis difficult.

Dyspnea

The most frequent initial symptom of patients with IPF is dyspnea, especially exertional dyspnea.3 The dyspnea is often insidious and progresses over a period of months or years before patient consultation with their primary care physician. Since IPF is rare, exertional dyspnea related to the disease is commonly misdiagnosed initially as heart failure or chronic obstructive pulmonary disease.4 The full mechanism causing dyspnea in patients with IPF is not fully understood but is believed to be related to loss of lung volume, reduced elasticity and increased surface tension in alveoli, and impaired gas exchange due to progressive interstitial fibrosis. The interplay between these factors, along with an imbalance between respiratory drive and the response of the respiratory musculature, may contribute to the feeling of unsatisfied inspiration in patients, especially during exertion.5

Cough

A chronic, nonproductive cough is another major presenting symptom of patients with IPF. As many as 80% of patients with IPF experience chronic cough. Chronic cough usually lasts at least 8 weeks and is often refractory to antitussive therapies. The cough is characterized as being dry and nonproductive, and patients fail to relieve the urge to cough. IPF-related chronic cough appears to be more common in patients with advanced forms of the disease as well as in non-smokers, although the reason for this is unknown. The pathophysiology of chronic cough is also unknown in patients with IPF, but it may be related to increased reflex sensitivity to stimuli such as smoke, perfume, laughing, and temperature changes caused by heightened nerve sensitivity due to mechanical distortions of the lungs or increased levels of neurotrophins.6

Inspiratory Crackles

Fine crackles on lung auscultation is another fairly common symptom among patients with IPF. These crackles, also known as rales in the US and crepitations in the UK, can be heard in the basilar portions of the lungs where IPF commonly initiates before moving higher. Fine crackles are usually heard during the inspiratory portion of deep breaths, and the sound is described to be similar to velcro being separated.7 The exact cause of the crackles is not known but is believed to be caused by the sudden opening of distal airways that have collapsed during expiration due to fibrotic tissue causing dilation and exerting retractile forces on these airways. The presence of fine crackles has been found to correlate with radiologic features of IPF on high resolution computed tomography (HRCT), including reticulation, honeycombing, ground glass opacities, and traction bronchiectasis.8 Inspiratory crackles are not limited to patients with IPF and can be shared with a number of other disorders including asbestosis, congestive heart failure, and pneumonia. Because of this overlap, differential diagnosis should be pursued, although the “velcro” crackles of IPF are often distinct from the crackle sounds of other disorders.7

Finger Clubbing

Finger clubbing has also been reported in variable numbers of patients with IPF. No agreed-upon methods for measuring and diagnosing finger clubbing exist which has led to varying estimates of prevalence, ranging from 7% to 52%. Finger clubbing is swollen and spongy distal portions of the phalanges that lead to deformation of the nail base and a loss of the nail-fold angle. As clubbing progresses, it may become painful for patients. The exact etiology of clubbing is unknown, although one hypothesis involves the collection of megakaryocytes, which are normally broken down into platelets in the pulmonary capillaries, in the distal phalanges. These megakaryocytes release growth factors which result in vascular growth, increased permeability, edema, changes in connective tissues, and proliferation of osteoblasts and fibroblasts, leading to the increased size of the tissue at the distal phalanges.9

Acute Exacerbations

The progression of IPF can vary considerably from patient to patient, with some experiencing a rapid decline while others have a much slower progression that may be punctuated by acute respiratory exacerbations.10 These exacerbations can be life-threatening and usually require hospitalization. A sudden worsening of dyspnea, increased need for supplemental oxygen, and radiological changes that develop over 30 days are all characteristics of these acute exacerbations. The annual incidence of acute exacerbations is estimated to be between 4% and 20%.10 The exact cause of acute exacerbations is unknown but may be related to respiratory viral infections, aspiration, or a reaction to certain medications or surgeries such as biopsies.11

References

  1. 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
  2. Wakwaya Y, Brown KK. Idiopathic pulmonary fibrosis: epidemiology, diagnosis andoutcomes. Am J Med Sci. 2019;357(5):359-369. doi:10.1016/j.amjms.2019.02.013
  3. 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
  4. 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
  5. Bonini M, Fiorenzano G. Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing. Eur Respir Rev. 2017;26(143):160099. doi:10.1183/16000617.0099-2016
  6. van Manen MJG, Birring SS, Vancheri C, et al. Cough in idiopathic pulmonary fibrosis. Eur Respir Rev. 2016;25(141):278-286. doi:10.1183/16000617.0090-2015
  7. Cottin V, Cordier JF. Velcro crackles: the key for early diagnosis of idiopathic pulmonary fibrosis? Eur Respir J. 2012;40(3):519-521. doi:10.1183/09031936.00001612
  8. Sgalla G, Walsh SLF, Sverzellati N, et al. “Velcro-type” crackles predict specific radiologic features of fibrotic interstitial lung disease. BMC Pulm Med. 2018;18(1):103. doi:10.1186/s12890-018-0670-0
  9. van Manen MJG, Vermeer LC, Moor CC, et al. Clubbing in patients with fibrotic interstitial lung diseases. Respir Med. 2017;132:226-231. doi:10.1016/j.rmed.2017.10.021
  10. Rozenberg D, Sitzer N, Porter S, et al. Idiopathic pulmonary fibrosis: a review of disease, pharmacological, and nonpharmacological strategies with a focus on symptoms, function, and health-related quality of life. J Pain Symptom Manage. 2020;59(6):1362-1378. doi:10.1016/j.jpainsymman.2019.12.364
  11. 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;194(3):265-275. doi:10.1164/rccm.201604-0801CI

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

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