Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease resulting in the buildup of fibrosis in the pulmonary parenchyma.¹ Reported incidences of IPF vary considerably, with estimates ranging from 6.8/100,000/y to 93.7/100,000/y for North America²; however, the universal incidence between different countries is estimated to be around 10/100,000.³ The prognosis for patients with IPF is also variable, with some patients only surviving weeks whereas others survive more than a decade after initial diagnosis.² The prognosis for patients is generally poor, with median survival between 3 and 5 years.²

IPF Diagnostic Guidelines

The clinical presentation of IPF can also be quite variable, and many of the main symptoms, including exertional dyspnea and chronic cough, have overlap with several other diseases, making differential diagnosis more difficult. To aid in diagnosis, the American Thoracic Society (ATS) and European Respiratory Society (ERS) published international guidelines in 2000.⁴ The guidelines were then updated in 2011⁵ and 2018⁶ when the ATS and ERS partnered with the Japanese Respiratory Society (JRS) and Latin American Thoracic Society (ALAT) to produce and update the guidelines. The Fleischner Society also published a set of updated guidelines in 2018 that were very similar to the ATS/ERS/JRS/ALAT guidelines.⁷

The guidelines for diagnosis involve an initial clinical evaluation, physical examination, and review of medical history for patients older than age 50 years with exertional dyspnea, finger clubbing, and/or a chronic, refractory cough. A requirement of diagnosing IPF is to exclude other interstitial lung diseases and show either pattern of usual interstitial pneumonia (UIP) on high-resolution computer tomography (HRCT) or show certain patterns on HRCT scans as well as in lung biopsy histology.⁵

HRCT scans should be used to look for evidence of UIP, including clustered cystic airspaces (honeycombing), traction bronchiectasis or bronchiolectasis, reticular abnormalities, and a predominance of the features in the basilar, subpleural spaces of the lungs.⁵ In addition to these features, other anomalies that may be present on the HRCT scans may include ground-glass opacities, mediastinal lymphadenopathy, and small ossified nodules located within areas of fibrosis.⁵ According to these scans and multidisciplinary discussions, the features can be classified as having one of four patterns: UIP, probable UIP, indeterminate for UIP, or alternative diagnosis.⁵

Patients receiving a designation of the UIP pattern should be considered to have the disease whereas those patients receiving probable UIP or indeterminate for UIP designations should be considered for histopathology through tissue biopsy. The 2018 ATS/ERS/JRS/ALAT guidelines recommend the use of surgical lung biopsy to collect samples for histopathology. The guidelines did not make recommendations for the use of transbronchial lung biopsy or cryobiopsy.⁵ Histology samples should be investigated for the presence of fibrosis with architectural distortions, subpleural or paraseptal distribution, fibroblast foci, involvement of the lung parenchyma, and a lack of features that would indicate another disease. The histology features can then be used to categorize the samples as having patterns of UIP, probable UIP, indeterminate for UIP, or alternative diagnosis.⁵

Analysis of bronchoalveolar lavage fluid may also be useful for differential diagnosis of IPF compared with eosinophilic pneumonia; sarcoidosis; infection; malignancy; or lung irritants, such as asbestos or other dusts.⁸ Although some serum analyses of biomarkers such as MMP-7, SP-D, CCL-18, and KL-6 have been used in the past, the 2018 guidelines recommend against their use because of high false-positive and false-negative rates.⁵ The results of all testing should be included in the multidisciplinary discussions to arrive at a diagnosis of IPF.

IPF Treatment and Management Guidelines

In addition to diagnostic guidelines, the ATS/ERS/JRS/ALAT have also published treatment and management guidelines for IPF. The guidelines published in 2000 and 2011 included treatment information, and then a treatment-specific update was published in 2015.⁹ The 2015 guidelines gave conditional recommendations for the use of the antifibrotic medications pirfenidone and nintedanib based on clinical trial data that showed their ability to slow the decline of forced vital capacity in patients.⁹ Some results also suggested that they may reduce the risk for acute exacerbations⁹: rapid decreases in lung function that often involve hospitalization and have a high mortality rate.¹⁰ The 2011 guidelines recommended the use of corticosteroids for treatment of acute exacerbations in some patients as well.⁵

In addition, the ATS/ERS/JRS/ALAT gave conditional recommendations on the use of antacid medications, such as proton pump inhibitors and histamine-2 blocker receptor antagonists, as it is estimated that as much as 90% of patients may experience gastroesophageal reflux disease.⁹ Aspirations and microaspirations of gastric contents are hypothesized to be involved in the pathogenesis or progression of IPF.¹¹ 

The societies made recommendations against the use of several previously used medications for IPF management.⁹ These included strong recommendations against the use of warfarin, ambrisentan, imatinib, and the combination of prednisone, azathioprine, and N-acetylcysteine (NAC).⁹ Sildenafil, macitentan, bosentan, and NAC monotherapy were all given conditional recommendations against.⁹

The 2015 guideline update did not make recommendations about any nonpharmacologic treatments for IPF but the 2011 guidelines recommended the use of supplemental oxygen, lung transplantation, and pulmonary rehabilitation in the majority of patients who require it.⁵ The committee also recommended against the use of mechanical ventilation in the majority of IPF patients.⁵ The 2011 guidelines mentioned palliative care should be considered for patients but did not make a recommendation one way or the other on treatments for symptoms. Chronic opioid use for severe dyspnea and chronic cough relief was mentioned along with the possible use of corticosteroids and thalidomide to alleviate chronic cough.⁵

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.
2. Wakwaya Y, Brown KK. Idiopathic pulmonary fibrosis: Epidemiology, diagnosis and outcomes. Am J Med Sci. 2019;357(5):359-369.
3. Sauleda J, Núñez B, Sala E, Soriano JB. Idiopathic pulmonary fibrosis: Epidemiology, natural history, phenotypes. Med Sci (Basel). 2018;6(4):110.
4. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS): International consensus statement. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664.
5. 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.
6. 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;198(5):e44-e68.
7. Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018;6(2):138-153.
8. Meyer KC, Raghu G. Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful? Eur Respir J. 2011;38(4):761-769.
9. Raghu G, Rochwerg B, Zhang Y, et al. 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;192(2):e3-19.
10. Quinn C, Wisse A, Manns ST. Clinical course and management of idiopathic pulmonary fibrosis. Multidiscip Respir Med. 2019;14(1):35.
11. Spagnolo P, Tzouvelekis A, Bonella F. The management of patients with idiopathic pulmonary fibrosis. Front Med (Lausanne). 2018;5. doi:10.3389/fmed.2018.00148

Reviewed by Harshi Dhingra, MD, on 7/2/2021.

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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.