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AE-IPF (Acute Exacerbations of IPF)

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Acute exacerbations of IPF

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 criteria1
 
“Acute exacerbations are acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF.”1

AE-IPF, acute exacerbations of idiopathic pulmonary fibrosis

1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.

Diagnostic criteria for AE-IPF

  • Previous or concurrent diagnosis of IPF
  • Unexplained worsening or development of dyspnea within 30 days
  • HRCT with new bilateral ground-glass abnormality or consolidation superimposed on a background reticular or honeycomb pattern consistent with 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”

1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.

2016 International Working Group Classification of AE-IPF

In 2016, an international multidisciplinary working group redefined AE-IPF to reflect the current state 
of knowledge2

“Acute, clinically significant respiratory deterioration characterized by evidence of 
new, widespread alveolar abnormality”2


2. Collard HR et al. Am J Respir Crit Care Med. 2016;194(3):265-275.

2016 International Working Group Classification of AE-IPF

Acute respiratory deterioration (typically <1 month)
Adapted from Collard HR et al. 2016.1 

Extraparenchymal cause identified?

New, bilateral GGO/consolidation on CT?

Acute Exacerbation of IPF
•Triggered AE
(eg, infection, post-procedural/post-operative, drug toxicity, aspiration)
 
•Idiopathic AE
(no trigger identified)

 
2. Collard HR et al. Am J Respir Crit Care Med 2016;194(3):265-275.

2016 International Working Group diagnostic criteria for AE-IPF

Using the International Working Group definition, diagnosis of an acute exacerbation of IPF requires2:
  • 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

2. Collard HR et al. Am J Respir Crit Care Med. 2016;194(3):265-275.

AE-IPF are relatively common clinical events

1 in 10
Number of patients diagnosed with IPF who will experience an AE-IPF by 1 year post-diagnosis3,4
 
1 in 4
Number of patients with IPF who will have at least 1 AE-IPF episode by 3 years post-diagnosis3,4

3. Song JW et al. Eur Respir J 2011;37:356-363.;
4. Kondoh Y et al. Sarcoidosis Vasc Diffuse Lung Dis 2010;27:103-110.

AE-IPF often causes clinical deterioration

The following are common clinical signs of AE-IPF1:
  • Cough
  • Fever
  • Flu-like symptoms
  • Severe hypoxemia
  • Respiratory failure requiring mechanical ventilation
 
1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.
5. Raghu G et al. Am J Respir Crit Care Med. 2011;183:788-824.

Signs of AE-IPF show up on HRCT scans

HRCT scans during AE-IPF will generally demonstrate bilateral ground-glass abnormalities, with or 
without consolidation6,7

These changes will be superimposed on top of patterns that indicate UIP6,7

The degree of CT involvement may predict survival in patients with AE-IPF1


6. Ambrosini V et al. Eur Respir J. 2003;22(5):821-826.
7. Kim DS et al. Eur Respir J. 2006;27(1):143-150.

Signs of AE-IPF show up on HRCT scans (cont.)

This series of HRCT scans shows new, extensive ground-glass abnormalities overlaid on a UIP background.1

Reprinted with permission of the American Thoracic Society. © 2014 American Thoracic Society. Collard HR et al. Am J Respir Crit Care Med 2007; 176:636-643.

1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.

The updated classification of AE-IPF acknowledges identifiable triggers

  • Acute exacerbations may be triggered by2:
    • Infection
    • Operations/medical procedures
    • Drug toxicity
    • Aspiration
  • There does not appear to be a link between AE-IPF and age or smoking history1
    • However, men tend to experience AE-IPF more frequently than women1

1. Collard HR et al. Am J Respir Crit Care Med. 2007;176(7):636-643.
2. Collard HR et al. Am J Respir Crit Care Med. 2016;194(3):265-275.

AE-IPF are associated with a poor prognosis

  • AE-IPF often result in irreversible, accelerated disease progression3 
  • AE-IPF often occur without an identifiable triggering event2
  • In the absence of another identifiable cause, AE-IPF are indicative of disease progression in patients with IPF2,5
In one study of 461 patients, the median survival from onset of AE-IPF was just 2.2 months.3
 
2. Collard HR et al. Am J Respir Crit Care Med. 2016;194(3):265-275.
3. Song JW et al. Eur Respir J. 2011;37(2):356-363.
5. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

AE-IPF necessitating hospitalization often result in death

50%
Patients admitted to hospital with AE-IPF who do not survive3

80%
Patients admitted to ICU with AE-IPF who do not survive3

All patients with IPF are susceptible to AE-IPF, regardless of disease severity.1

1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.
3. Song JW et al. Eur Respir J 2011;37:356-363.

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 injury8
Currently, there are no validated plasma biomarkers that can diagnose or predict AE-IPF

8. Collard HR et al. Am J Physiol Lung Cell Mol Physiol 2010;299:L3-L7.

Summary

  • AE-IPF are defined as an acute* respiratory deterioration characterized by newly developed radiologic abnormalities2
  • A diagnosis of AE-IPF requires excluding breathlessness caused by cardiac failure or fluid overload2
  • 1 in 4 patients with IPF will experience an AE-IPF event by 3 years post-diagnosis3,4
  • AE-IPF causes acute, irreversible deterioration of lung function3
    Patients who experience AE-IPF generally have a poor prognosis3,4
*Defined as occurring within 1 month

1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.
3. Song JW et al. Eur Respir J 2011;37:356-363.
4. Kondoh Y et al. Sarcoidosis Vasc Diffuse Lung Dis 2010;27:103-110.

References

  1. Collard HR et al. Am J Respir Crit Care Med 2007;176:636-643.
  2. Collard HR et al. Am J Respir Crit Care Med 2016;194(3):265-275.
  3. Song JW et al. Eur Respir J 2011;37:356-363.
  4. Kondoh Y et al. Sarcoidosis Vasc Diffuse Lung Dis 2010;27:103-110.
  5. Raghu G et al. Am J Respir Crit Care Med. 2011;183:788-824.
  6. Ambrosini V et al. Eur Respir J. 2003;22(5):821-826.
  7. Kim DS et al. Eur Respir J. 2006;27(1):143-150.
  8. Collard HR et al. Am J Physiol Lung Cell Mol Physiol 2010;299:L3-L7.