Diagnostic Criteria for Idiopathic Pulmonary Fibrosis (IPF)

In 2000, IPF was defined as a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults and limited to the lungs. Usual interstitial pneumonia (UIP) is the histopathological pattern of IPF. IPF is characterized by progressive worsening of dyspnea and lung function and is associated with a poor prognosis.

Diagnostic Criteria for Idiopathic Pulmonary Fibrosis (IPF)

Diagnosis of IPF requires the following:

  1. Exclusion of other known causes of interstitial lung disease (ILD) (e.g., domestic and occupational environmental exposures, connective tissue disease (CTD), drug toxicity), and either #2 or #3:
  2. The presence of the HRCT pattern of UIP (Table 1)
  3. Specific combinations of HRCT patterns (Table 1) and histopathology patterns (Table 2) in patients subjected to lung tissue sampling

Table 1. High-Resolution Computed Tomography (HRCT) Scanning Patterns

UIP
  • Subpleural and basal predominant; distribution is often heterogeneous (Variants of distribution: occasionally diffuse, may be asymmetrical)
  • Honeycombing with or without peripheral traction bronchiectasis or bronchiolectasis (Superimposed CT features: mild ground-glass opacities, reticular pattern, pulmonary ossification)
Probable UIP
  • Subpleural and basal predominant; distribution is often heterogeneous
  • Reticular pattern with peripheral traction bronchiectasis or bronchiolectasis
  • May have mild ground-glass opacities (GGO)
Indeterminate for UIP
  • Subpleural and basal predominant
  • Subtle reticulation; may have mild ground-glass opacities or distortion (“early UIP pattern”)
  • CT features and/or distribution of lung fibrosis that do not suggest any specific etiology (“truly indeterminate for UIP”)
Alternative Diagnosis Findings suggestive of another diagnosis, including:

  • CT features:
    • Cysts
    • Marked mosaic attenuation
    • Predominant GGO
    • Profuse micronodules
    • Centrilobular nodules
    • Nodules
    • Consolidation
  • Predominant distribution:
    • Peribronchovascular
    • Perilymphatic
    • Upper or mid-lung
  • Other:
    • Pleural plaques (consider asbestosis)
    • Dilated esophagus (consider CTD)
    • Distal clavicular erosions (consider rheumatoid arthritis)
    • Extensive lymph node enlargement (consider other etiologies)
    • Pleural effusions, pleural thickening (consider CTD/drugs)

 

Table 2. Histopathology Patterns and Features

UIP
  • Dense fibrosis with architectural distortion (i.e., destructive scarring and/or honeycombing)
  • Predominant subpleural and/or loose fibrosis) paraseptal distribution of fibrosis
  • Patchy involvement of lung parenchyma by fibrosis
  • Fibroblast foci
  • Absence of features to suggest an alternate diagnosis
Probable UIP
  • Some histologic features from UIP are present but to
    an extent that precludes a definite diagnosis of UIP/IPF

And

  • Absence of features to suggest an alternative

Or

  • Honeycombing only
Indeterminate for UIP
  • Fibrosis with or without architectural distortion, with features favoring either a pattern other than UIP or features favoring UIP secondary to another cause*
  • Some histologic features from UIP, but with other features suggesting an alternative diagnosis†
Alternative Diagnosis
  • Features of other histologic patterns of idiopathic interstitial pneumonia (e.g., absence of fibroblast foci or loose fibrosis) in all biopsies
  • Histologic findings indicative of other diseases (e.g., hypersensitivity pneumonitis, Langerhans cell histiocytosis, sarcoidosis, lymphangioleiomyomatosis)

*Granulomas, hyaline membranes (other than when associated with acute exacerbation of IPF, which may be the presenting manifestation in some patients), prominent airway-centered changes, areas of interstitial inflammation lacking associated fibrosis, marked chronic fibrous pleuritis, organizing pneumonia. Such features may not be overt or easily seen to the untrained eye and often need to be specifically sought.
†Features that should raise concerns about the likelihood of an alternative diagnosis include a cellular inflammatory infiltrate away from areas of honeycombing, prominent lymphoid hyperplasia including secondary germinal centers, and a distinctly bronchiolocentric distribution that could include extensive peribronchiolar metaplasia.

 

References:

  1. Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JR, Goldin JG, Hansell DM, Inoue Y, Johkoh T, Nicholson AG, Knight SL, Raoof S, Richeldi L, Ryerson CJ, Ryu JH, Wells AU. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018 Feb;6(2):138-153. [Medline]
  2. Kalchiem-Dekel O, Galvin JR, Burke AP, Atamas SP, Todd NW. Interstitial Lung Disease and Pulmonary Fibrosis: A Practical Approach for General Medicine Physicians with Focus on the Medical History. J Clin Med. 2018 Nov 24;7(12). pii: E476. [Medline]
  3. Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018 May 10;378(19):1811-1823. [Medline]
  4. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, Flaherty KR, Wells A, Martinez FJ, Azuma A, Bice TJ, Bouros D, Brown KK, Collard HR, Duggal A, Galvin L, Inoue Y, Jenkins RG, Johkoh T, Kazerooni EA, Kitaichi M, Knight SL, Mansour G, Nicholson AG, Pipavath SNJ, Buendía-Roldán I, Selman M, Travis WD, Walsh S, Wilson KC; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and 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 Sep 1;198(5):e44-e68. [Medline]

 

 

Created May 15, 2019