IPF Disease Progression

According to the 2011 evidence-based guidelines for diagnosis and management of IPF, published by the American Thoracic Society (ATS), the European Respiratory Society (ERS), the Japanese Respiratory Society (JRS), and the Latin American Thoracic Association (ALAT), in the absence of an additional identifiable cause, changes in any of the following parameters are consistent with IPF disease progression123456:

  • Progressive dyspnea, assessed objectively
  • Progressive, sustained decrease of at least 10% from baseline in absolute forced vital capacity (FVC)
  • Progressive, sustained decrease of at least 15% from baseline in absolute diffusing capacity of the lung for carbon monoxide (DLCO), corrected for hemoglobin
  • Progression of fibrosis from baseline, as visualized by high-resolution computed tomography (HRCT)
  • Acute exacerbation of IPF (AE-IPF)

It is recommended that patients with IPF be monitored over 3- to 6-month periods, but changes in symptoms, physiology, and radiology may identify disease progression within shorter periods of time.1

An important distinction is to define which of these parameters are clinically useful in individual patients, and which provide prognostic information in the setting of IPF clinical trials.7 Unfortunately, no agreed upon evidence-based surrogate endpoints for all-cause mortality exist for IPF.7 Surrogate endpoints for all-cause mortality (e.g. ventilator-free days in intensive care medicine or 6-minute walk (6MWT) distance for idiopathic pulmonary hypertension) are pervasive in clinical trials and allow for smaller samples size to show benefit. Additionally, evidence-based patient reported outcome measures of symptoms have not been shown to be prognostic as they are for other respiratory diseases.7 Despite this, it is important to realize that a change in an individual patient's symptoms (such as with AE-IPF) or physiology (desaturation during 6MWT or decrease in FVC) does correlate with a worsened IPF prognosis.8910 While certain parameters appear to be clinically useful, there is still significant debate as to which endpoints are appropriate for patients with IPF.

Clinical assessment should focus on physiologic and/or symptomatic changes that portend a poor outcome; this aids in facilitating more detailed discussions with the patient regarding lung transplantation, supplemental oxygen therapy, and/or palliative care/hospice referral if appropriate.1 Clinical variables that are monitored and associated with poor prognosis in IPF include:

  • Decrease in FVC (10% threshold recommended by ATS/ERS/JRS/ALAT)11112
  • Decrease in DLCO (15% threshold recommended by ATS/ERS/JRS/ALAT)13513
  • Desaturation during 6MWT10
  • AE-IPF (defined as worsening dyspnea within 30 days not explained by other causes)89

If disease progression is observed, consideration of lung transplant and timely referral to a lung transplant center is recommended in appropriate patients.1

Questionnaires focused on patient symptoms are often used to define disease progression in clinical trials, though their utility in clinical practice is not established.14 Though HRCT worsening has been correlated with increased mortality,115161718 use of routine HRCT scans for monitoring in patients with a firmly established diagnosis of IPF is of unclear and of uncertain benefit when used in concert with physiologic variables.1 However, if worsening breathlessness arises, HRCT is helpful to confirm disease progression or AE-IPF as well as exclude other causes of dyspnea (e.g. pneumonia, pneumothorax).19

Examples of individual clinical variables will be reviewed here in the context of the advantages and potential challenges for use in clinical practice.

Content contributed by:
Ryan Hadley, MD
University of Michigan