Acute Exacerbations of IPF

• Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are defined as an acute (occurring within 1 month) respiratory deterioration characterized by newly developed radiologic abnormalities¹
• A diagnosis of AE-IPF requires excluding breathlessness caused by cardiac failure or fluid overload¹
• 1 in 4 patients with IPF will experience an AE-IPF event by 3 years post-diagnosis^2,3
• AE-IPF causes acute, irreversible deterioration of  lung function²
• Patients who experience AE-IPF generally have a poor prognosis^2,3 

CONSENSUS DEFINITION OF AE-IPF

In 2007, an international group of experts in IPF along with the Idiopathic Pulmonary Fibrosis Clinical Research Network developed a consensus definition of AE-IPF as well as diagnostic criteria.⁴

“Acute exacerbations are acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF”⁴

Diagnostic criteria for AE-IPF⁴

• Previous or concurrent diagnosis of IPF  
• Unexplained worsening or development of dyspnea within 30 days  
• High resolution computed tomography with new bilateral ground- glass abnormality or consolidation superimposed on a background reticular or honeycomb pattern consistent with usual interstitial pneumonia (UIP) pattern 
• No evidence of pulmonary infection by endotracheal aspirate or bronchoalveolar lavage  
• Exclusion of alternative causes, including left heart failure, pulmonary embolism, identifiable cause of acute lung injury

Patients must meet all 5 criteria to have a definite case of AE-IPF. Cases that do not meet all criteria should be termed “suspected acute exacerbation”.⁴

2016 INTERNATIONAL WORKING GROUP CLASSIFICATION OF
AE-IPF¹

In 2016, an international multidisciplinary working group redefined AE-IPF as “acute, clinically significant respiratory deterioration characterized by evidence of new, widespread alveolar abnormality”.¹

Using the International Working Group definition, diagnosis of an acute exacerbation of IPF requires¹

• Previous or concurrent diagnosis of IPF
• Acute worsening or development of dyspnea, typically within 1 month
• Appearance of new bilateral ground glass abnormality and/or consolidation superimposed on a background reticular or honeycomb pattern consistent with UIP pattern
• Deterioration explained by neither fluid overload nor cardiac failure

AE-IPF ARE RELATIVELY COMMON CLINICAL EVENTS.

• 1 out of 10 patients diagnosed with IPF will experience an AE-IPF by 1-year post-diagnosis^2,3
• 1 out of 4 patients with IPF will have at least 1 AE-IPF episode by 3 years post-diagnosis^2,3

AE-IPF OFTEN CAUSES CLINICAL DETERIORATION.

The following are common clinical signs of AE-IPF:⁴

• Cough
• Fever
• Flu-like symptoms
• Severe hypoxemia
• Respiratory failure requiring mechanical ventilation

Adapted from Raghu G, Collard HR, Egan JJ, et al.⁵

SIGNS OF AE-IPF SHOW UP ON HRCT SCANS

• HRCT scans during AE-IPF will generally demonstrate bilateral ground-glass abnormalities, with or without consolidations^6,7
• These changes will be superimposed on top of patterns that indicate UIP^6,7

The degree of CT involvement may predict survival in patients with AE-IPF.^6,7

This series of HRCT scans shows new, extensive ground-glass abnormalities overlaid on a UIP background.⁴

Reprinted with permission of the American Thoracic Society.
© 2014 American Thoracic Society.⁴

THE UPDATED CLASSIFICATION OF AE-IPF ACKNOWLEDGES IDENTIFIABLE TRIGGERS

• Acute exacerbations may be triggered by:¹
  • Infection
  • Operations/medical procedures
  • Drug toxicity
  • Aspiration
• There does not appear to be a link between AE-IPF and age or smoking history² 
  • However, men tend to experience AE-IPF more frequently than women²

AE-IPF ARE ASSOCIATED WITH A POOR PROGNOSIS

• AE-IPF often result in irreversible, accelerated disease progression²
• AE-IPF may occur with or without an identifiable triggering event¹
• AE-IPF are indicative of disease progression in patients with IPF^1,5 

In one study of 461 patients, the median survival  from onset of AE-IPF was just 2.2 months.²

AE-IPF NECESSITATING HOSPITALIZATION OFTEN RESULT IN DEATH

• 50% of patients admitted to hospital with AE-IPF do not survive²
• 80% of patients admitted to ICU with AE-IPF do not survive²
• All patients with IPF are susceptible to AE-IPF, regardless of disease severity.⁴

AE-IPF ARE CURRENTLY UNPREDICTABLE

Results from a single-center study suggest that patients with AE-IPF have different plasma biomarker profiles compared with patients with stable IPF or acute lung injury.⁸

Currently, there are no validated plasma biomarkers that can diagnose or predict AE-IPF.