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IPF

(Idiopathic Pulmonary Fibrosis)

Diagnosis

In 2011, the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Society (ALAT) collaborated to develop a clinical practice guideline for the diagnosis and management of IPF1. The recommendations have been updated in 2018 to help clinicians make a more accurate diagnosis of IPF2.

Clinical presentation

IPF should be considered in all adult patients with unexplained chronic exertional dyspnea, cough, bibasilar inspiratory crackles, and/or digital clubbing that occur without constitutional or other symptoms that suggest a multisystem disease. The incidence of IPF increases with older age, with presentation typically consisting of insidious onset of dyspnea in the sixth and seventh decades. Patients with IPF who are younger than 50 years old are rare; such patients may subsequently manifest features of an underlying connective tissue disease (CTD) that was subclinical at the time IPF was diagnosed or may have familial IPF. More men have been reported with IPF than women, and the majority of patients have a history of past cigarette smoking2.

Diagnostic criteria

Diagnosis of IPF requires the following2:

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

The HRCT patterns of UIP are categorized as “UIP pattern”, “probable UIP pattern”, “indeterminate for UIP pattern”, and “alternative diagnosis”.

UIP pattern: “UIP pattern” is the radiologic hallmark of IPF. Honeycombing is a distinguishing feature of UIP and must be present for a definite HRCT diagnosis of UIP to be made. It can be seen with or without peripheral traction bronchiectasis or bronchiolectasis. The typical distribution of UIP is subpleural with basal predominance, although some upper lobe involvement is common; in some cases, the craniocaudal distribution of UIP may be relatively uniform.

Probable UIP pattern: Subpleural, basal-predominant reticular abnormalities with peripheral traction bronchiectasis or bronchiolectasis should be regarded as “probable UIP.” As with a UIP pattern, ground-glass opacification may be present in probable UIP, but it is not a dominant feature. Many patients with an HRCT pattern of probable UIP will be determined to have IPF once other factors such as histopathology are considered.

Indeterminate for UIP pattern: The category of “indeterminate for UIP pattern” should be assigned when HRCT demonstrates features of fibrosis but does not meet UIP or probable UIP criteria and does not explicitly suggest an alternative diagnosis. This category includes a subset of patients with very limited subpleural ground-glass opacification or reticulation without obvious CT features of fibrosis, for whom there is a suspicion that early UIP or probable UIP is present. In such cases, it should be confirmed with prone inspiratory views that the subpleural opacities do not represent dependent atelectasis.

Alternative diagnosis: “Alternative diagnosis” means that there is clinical suspicion of IPF but the HRCT pattern suggests and alternative diagnosis. Examples include bronchocentric fibrosis in the upper lobes or profuse mosaic attenuation that suggest hypersensitivity pneumonitis, posterior fibrotic retraction of the hila in sarcoidosis, or extensive ground-glass opacification with subpleural sparing in fibrotic nonspecific interstitial pneumonia (NSIP).

The histopathologic hallmark and chief diagnostic criterion of UIP is a low magnification appearance of patchy dense fibrosis that

  1. is causing remodeling of lung architecture,
  2. often results in honeycomb change, and
  3. alternates with areas of less-affected parenchyma. The histopathologic findings of biopsies are also categorized into “UIP,” “probable UIP,” “indeterminate for UIP,” and “alternative diagnosis”. “UIP” features include dense fibrosis with architectural distortion (destructive scarring and/or honeycombing), predominant subpleural and/or paraseptal distribution of fibrosis, patchy involvement of lung parenchyma by fibrosis, fibroblast foci and absence of features that suggestive of alternative diagnosis.

Patients with suspected IPF (i.e., unexplained symptomatic or asymptomatic bilateral pulmonary infiltrates on a chest radiograph or chest CT scan, bibasilar inspiratory crackles, and age older than 60 years old), unexplained dyspnea on exertion, and/or cough with evidence of ILD should be carefully evaluated for potential and/or identifiable causes of ILD, such as domestic and occupational environmental exposures, CTD, or drug toxicity. Middle-aged adults (> 40 years old and < 60 years old), especially patients with risks for familial pulmonary fibrosis, can rarely present with the otherwise same clinical scenario as the typical patient older than 60 years. If a potential cause for ILD is identified, the patient should undergo a thorough evaluation to confirm or exclude other known causes, such as hypersensitivity pneumonitis, CTD, pneumoconiosis, and iatrogenic causes (e.g., drug toxicity, irradiation). If a specific diagnosis is not made or no potential cause for ILD is identified, further evaluation is influenced by the patterns of HRCT images of the chest and supportive clinical findings surfaced in the course of multidisciplinary discussion to ascertain or exclude the diagnosis of IPF. IPF is diagnosed if the appropriate combination of HRCT patterns and histopathological patterns are present.

A multidisciplinary approach to diagnosis of IPF has been advocated the American Thoracic Society and European Respiratory Society since 2002. Studies have supported an improvement in diagnostic confidence among expert chest radiologists, pathologists and pulmonologists to review of all the clinical, radiological, and pathological information (when biopsy material is available) from patients. As a result, the guidelines recommend use of a multidisciplinary discussion in the evaluation and diagnosis of IPF. Further research is still needed to determine what other factors, such as biomarkers or quantitative imaging, might be needed to further refine the diagnostic process. Additionally, many questions remain about the composition and implementation of multidisciplinary team meetings3.

References:

  1. Raghu G, et al. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.

  2. Raghu G, et al. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68.

  3. Martinez Fj, et al. Lancet Respir Med. 2017 Jan;5(1):61-71.

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