Diagnostic Criteria and Algorithm

An early and accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is critical. Early diagnosis of IPF allows for appropriate management of symptoms and quality-of-life issues in patients with this disease.^1-3 It’s essential for timely referral to a lung transplant center for patients with advanced disease.⁴

CURRENT DIAGNOSTIC CRITERIA FOR IPF

According to the 2018 ATS/ERS/JRS/ALAT guideline criteria, diagnosing IPF requires the following:⁵

DIAGNOSTIC ALGORITHM⁶

Reprinted with permission of the American Thoracic Society. Copyright © 2022 American Thoracic Society. All rights reserved. Raghu G et al. 2022. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 205(9):e18-e47. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.

^*Patients with a radiological pattern of probable usual interstitial pneumonia (UIP) can receive a diagnosis of IPF after multidisciplinary discussion (MDD) without confirmation by lung biopsy in the appropriate clinical setting (e.g., 60 yr old, male, smoker). BAL may be appropriate in some patients with a probable UIP pattern.

^†BAL may be performed before MDD in some patients evaluated in experienced centers.

^‡Transbronchial lung cryobiopsy (TBLC) may be preferred to surgical lung biopsy (SLB) in centers with appropriate expertise and/or in some patient populations, as described in the text. A subsequent SLB may be justified in some patients with nondiagnostic findings on TBLC.

When you suspect a patient has ILD, the first things to do are:^5-8

• Perform a physical exam
• Take a complete history, including exposures
• Evaluate pulmonary function through pulmonary function tests (PFTs)

POSSIBLE CLINICAL FEATURES IN PATIENTS SUSPECTED OF HAVING ILD

Physical Exam⁵

• Typically affects adults >60 years of age
• Chronic exertional dyspnea
• Dry, nonproductive cough
• Crackles or rales on auscultation
• May show signs of digital clubbing

History⁵

• Current or former smoker
• Exposure to any number of dusts (e.g., stone, silica, wood)
• Agriculture and/or bird exposures
• Viral exposures (e.g., Hepatitis C)
• Family history of pulmonary fibrosis

PFT results^9,10

• Restrictive physiology
• Reduced TLC
• Increased FEV₁/FVC ratio
• Reduced DL_CO
• Reduced predicted FVC
• Desaturation on exertion

IDENTIFIABLE CAUSES AND ASSOCIATED CONDITIONS

Many ILDs have identifiable causes:¹¹

• Hypersensitivity pneumonitis
• Asbestosis
• Silicosis
• Post-infectious ILD
• Drug-induced ILD

If there are obvious causes of ILD based on patient history, continue with further evaluation in pursuit of a specific diagnosis. If no specific diagnosis can be reached, proceed to HRCT testing (below).^5,6

If there are no obvious causes of ILD based on patient history, you should continue to suspect IPF.^5,6

CONNECTIVE TISSUE DISORDER (CTD)

The next step is to consider performing serologic testing to evaluate for CTD.^5-7

• Screens include: Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), antinuclear antibody (ANA)

These tests should be paired with clinical signs of CTD (e.g., arthralgia/synovitis, proximal muscle weakness, Raynaud’s phenomenon).^5-7

If there are no elevations in CTD markers, you should continue to suspect IPF.^5,6

HRCT

Next, patients should have an HRCT performed.^5,6

• The positive predictive value of a definite UIP pattern on HRCT is 90%-100%^12-17
• UIP pattern on HRCT should be paired with an exclusion of other causes of ILD before reaching a diagnosis of IPF^5,6

HRCT: UIP PATTERN^5,6,18

Image courtesy of and used with permission from Sudhakar Pipavath, MD.

A UIP pattern on HRCT, paired with a lack of identifiable cause, is sufficient to diagnose IPF.^5,6,18

HRCT: PROBABLE UIP PATTERN^5,6,18

HRCT: INDETERMINATE FOR UIP^5,6,18

HRCT: ALTERNATIVE DIAGNOSIS^5,6,18

MDD

Cases of probable UIP pattern on HRCT can be given a diagnosis of IPF after multidisciplinary discussion (MDD) without a lung biopsy to confirm.⁶ BAL may be considered in select patients with a probable UIP pattern.⁶

Cases of indeterminate or alternative diagnosis on HRCT should undergo biopsy (when possible) and MDD to ensure a more accurate diagnosis.^5,6,17

HISTOPATHOLOGY: UIP PATTERN^5,6,18

MDD

An MDD provides a sounding board to evaluate all evidence to come up with a consensus diagnosis, whether that is IPF or another ILD.^5,6,18

In select patients and/or expert medical centers, transbronchial lung cryobiopsy (TBLC) may be an acceptable alternative to SLB.⁶ However, tissue obtained via TBLC is more likely to show a probable UIP pattern than a definite UIP pattern, compared to SLB, due to the limited capabilities of TBLC to acquire subpleural lung samples.⁶ By combining UIP and probable UIP patterns in the setting of a MDD, diagnostic agreement for SLB and TBLC in IPF patients was seen to be comparable.⁶

DESIGNATING THE HRCT AND HISTOPATHOLOGY PATTERN

Reprinted with permission of the American Thoracic Society. Copyright © 2022 American Thoracic Society. All rights reserved. Raghu G et al. 2022. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 205(9):e18-e47. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society

^*“Clinically suspected of having IPF” is defined as unexplained patterns of bilateral pulmonary fibrosis on chest radiography or chest computed tomography, bibasilar inspiratory crackles, and age > 60 years. Middle-aged adults (>40 and <60 yr old) can rarely present with otherwise similar clinical features, especially in patients with features suggesting familial pulmonary fibrosis.

^†Diagnostic confidence may need to be downgraded if histopathological assessment is based on transbronchial lung cryobiopsy given the smaller biopsy size and greater potential for sampling error compared with surgical lung biopsy.

^‡IPF is the likely diagnosis when any of the following features are present: 1) moderate to severe traction bronchiectasis and/or bronchiolectasis (defined as mild traction bronchiectasis and/or bronchiolectasis in four or more lobes, including the lingula as a lobe, or moderate to severe traction bronchiectasis in two or more lobes) in a man >50 years old or in a woman >60 yr old, 2) extensive (>30%) reticulation on HRCT and age > 70 yr, 3) increased neutrophils and/or absence of lymphocytosis in BAL fluid, and 4) multidisciplinary discussion produces a confident diagnosis of IPF.

^§Indeterminate for IPF 1) without an adequate biopsy remains indeterminate and 2) with an adequate biopsy may be reclassified to a more specific diagnosis after multidisciplinary discussion and/or additional consultation.