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Idiopathic pulmonary fibrosis

Background

Overview

Definition
IPF is a chronic, progressive fibrosing interstitial pneumonia of idiopathic origin, occurring primarily in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia.
1
Pathophysiology
IPF is a disease of unknown cause. Cigarette smoking, older age, male sex, air pollution, occupational exposures, viral infection, obstructive sleep apnea, gastroesophageal reflux, and genetic polymorphisms are potential risk factors.
1
2
Epidemiology
The incidence of IPF is estimated at 5.8 cases per 100,000 person-years in the US.
3
Disease course
In patients with IPF, secretion of profibrotic mediators lead to matrix deposition by myofibroblasts, with a progressive decline in pulmonary function, respiratory failure, and eventual death.
2
Prognosis and risk of recurrence
The prognosis for IPF is poor, with a median survival of 3.8 years in adults ≥ 65 years of age in the US.
2

Guidelines

Key sources

The following summarized guidelines for the evaluation and management of idiopathic pulmonary fibrosis are prepared by our editorial team based on guidelines from the European Respiratory Society (ERS 2022), the European Society of Cardiology (ESC/ERS 2022), the Latin American Thoracic Association (ALAT/ERS/JRS/ATS 2022,2018,2015,2011), the American College of Chest Physicians (ACCP 2018), the Japanese Respiratory Society (JRS 2018), the French Society ...
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Screening and diagnosis

Diagnosis
As per SPLF 2017 guidelines:
Consider establishing the diagnosis of IPF based on a HRCT pattern of definite usual interstitial pneumonia, including honeycombing, after ruling out other causes of usual interstitial pneumonia (secondary forms).
E
Integrate all the data available for the definitive diagnosis of IPF during a multidisciplinary discussion involving pulmonologists, radiologists and pathologists experienced in the field of ILD.
E
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Classification and risk stratification

Prognosis: as per SPLF 2017 guidelines, consider assessing the prognosis in patients with IPF:
at the time of diagnosis, depending on the severity of dyspnea pulmonary function test (FVC and CO diffusing capacity), percutaneous oxygen saturation at the end of a 6-minute walk test, the extent of honeycombing on high-resolution chest CT, the existence of signs of pulmonary hypertension on echocardiography, and using a score such as the GAP score
during the follow-up, depending on the evolution of symptoms, FVC and CO diffusing capacity, and possibly the existence of signs of pulmonary hypertension on echocardiography and fibrosis on chest CT.
E

Diagnostic investigations

History and physical examination: as per ALAT/ATS/ERS/JRS 2018 guidelines, elicit a detailed history of both medication use and environmental exposures at home, work, and other places the patient frequently visits to exclude potential causes of ILD.
B

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  • Laboratory testing

  • Pulmonary function testing

  • Exercise testing

  • CT

  • Evaluation for pulmonary hypertension

  • Genetic testing

Diagnostic procedures

BAL fluid analysis
As per ALAT/ATS/ERS/JRS 2018 guidelines:
Avoid performing cellular analysis of bronchoalveolar lavage fluid in patients with definite usual interstitial pneumonia on HRCT.
D
Consider performing cellular analysis of bronchoalveolar lavage fluid in patients probable usual interstitial pneumonia, indeterminate usual interstitial pneumonia, or alternative diagnosis on HRCT.
C

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  • Lung biopsy

Respiratory support

Supplemental oxygen: as per JRS 2018 guidelines, administer oxygen in patients with IPF in the chronic phase with hypoxemia.
B

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  • Mechanical ventilation

Medical management

General principles: as per ALAT/ATS/ERS/JRS 2018 guidelines, consider ensuring a multidisciplinary discussion for diagnostic decision-making in patients with IPF.
C

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  • Pirfenidone

  • Nintedanib

  • Interferon gamma-1 beta

  • Corticosteroids

  • Immunosuppressive agents

  • N-acetylcysteine

  • PDE5 inhibitors

  • Endothelin receptor antagonists

  • TKIs

  • Anticoagulation therapy

  • Acid-reducing therapy

  • Recombinant thrombomodulin

  • Neutrophil elastase inhibitors

  • Polymyxin B-immobilized fiber column

  • Management of pulmonary hypertension

Nonpharmacologic interventions

Smoking cessation: as per BTS/ITS/TSANZ 2008 guidelines, offer opportunistic smoking cessation advice from healthcare professionals, recorded in the clinical notes, in current smoker patients with ILD. Offer specialist support and nicotine replacement therapy or bupropion.
B

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  • Pulmonary rehabilitation

Surgical interventions

Lung transplantation
As per ISHLT 2015 guidelines:
Refer patients meeting any of the following criteria for the evaluation of lung transplantation:
histopathologic or radiographic evidence of usual interstitial pneumonitis or fibrosing non-specific interstitial pneumonitis, regardless of lung function
FVC < 80% of predicted or DLCO < 40% of predicted
any dyspnea or functional limitation attributable to lung disease
any oxygen requirement, even if only during exertion
failure to improve dyspnea, oxygen requirement, and/or lung function after a clinically indicated trial of medical therapy (in patients with inflammatory lung diseases)
List patients for lung transplantation if any of the following criteria is met:
decline in FVC ≥ 10% during 6 months of follow-up (recognize that a 5% decline is associated with a poorer prognosis and may warrant listing)
decline in DLCO ≥ 15% during 6 months of follow-up
desaturation to < 88% or distance < 250 m on 6-minute-walk test or > 50 m decline in 6-minute-walk distance over a 6-month period
pulmonary hypertension on right heart catheterization or 2D echocardiography
hospitalization because of respiratory decline, pneumothorax, or acute exacerbation

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  • Antireflux surgery

Specific circumstances

Patients with lung cancer: as per JRS 2018 guidelines, consider performing surgery in patients with lung cancer with comorbid IPF or other interstitial pneumonias.
C
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Follow-up and surveillance

Follow-up
As per SPLF 2017 guidelines:
Perform clinical examination and obtain pulmonary function testing with FVC measurement every 3-6 months in patients with a confirmed diagnosis of IPF.
E
Consider obtaining diffusing capacity of CO measurement every 3-6 months in patients with a confirmed diagnosis of IPF.
E