Limited evidence for acute exacerbations in IPF

Management of acute exacerbations in idiopathic pulmonary fibrosis (IPF) is still guided by limited evidence despite its high mortality rate, the Respiratory Insights Forum was told.

Up to 46% of IPF deaths are preceded by an acute exacerbation with in-hospital mortality above 50%1.

Dr Lauren Troy, a respiratory specialist at the Royal Prince Alfred Hospital and Chris O’Brien Lifehouse in Sydney, told the meeting there was no treatment protocol and no proven effective therapy.

However first steps involved imaging and attempting to identify a trigger for the exacerbation.

She said hallmark features of acute exacerbations of IPF typically involved diffuse alveolar damage, for example acute ground glass changes, superimposed on usual interstitial pneumonia (UIP).

A 2014 review2 of 52 deaths revealed almost 30% of patients had a fungal, viral or bacterial infection.

More recently, INPULSIS trial data3 showed a clear increase in acute exacerbations in the northern hemisphere winter suggesting that viral respiratory infections may contribute to risk.

As well as common respiratory viruses such as parainfluenza, rhinovirus and coronavirus, herpes simplex, Epstein-Barr and the torque teno virus have also been detected in acute exacerbations4.

“Infections appear to have a major impact on patient stability and functionality,” Dr Troy said.

She recommended broad-spectrum antibiotics with cotrimoxazole if there was concern about Pneumocystis jirovecii pneumonia.

“Broad-spectrum antibiotics are a little controversial in the era of antibiotic stewardship but are a low-risk strategy for this patient group.”

She said patients were commonly treated with high-dose steroids but 2011 guidelines5 acknowledged the evidence was slim.

“It’s a very tricky situation – to consider giving corticosteroids to patients when there is very limited evidence but sometimes it’s a case of what else to do.”

She suggested IV methylprednisolone 1g for three days and oral prednisolone 50mg/day then slowly weaned.

Dr Troy said patients required supportive, ward-based care unless they were candidates for lung transplant. Intubation should be avoided.

The introduction of opiates, benzodiazepines and other palliative care measures should be considered.

“It’s good to start to introduce these with a lot of discussion with patients and their families and in preparation for negative outcomes.”

More evidence needed

Dr Troy said studies on immunosuppressive therapies including cyclosporine, tacrolimus, cyclophosphamide and thrombomodulin were needed.

“This is an area hugely bereft of data and with room to move ahead.”

She said thrombomodulin was currently being tested in a randomised clinical trial.

There was some emerging evidence for polymyxin B-immobilised fibre haemoperfusion column therapy, a form of dialysis used in Japan in the sepsis setting including in IPF patients.

Rituximab plus plasma exchange and intravenous immunoglobulin (IVIG) in a small trial of critically ill patients had shown a one-year survival advantage compared to historical controls6 but was not yet recommended.

Nintedanib and pirfenidone appear to reduce the risk of acute exacerbations but have little role in their management.


  1. Collard HR et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. AJRCCM. 2016;194(3).
  2. Oda K et al. Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis. Respiratory Research. 2014;15:109.
  3. Collard HR et al. Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis. Eur Respir J 2017;49: 1601339.
  4. Wootton SC et al. Viral Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011;183:1698–02.
  5. Raghu G et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. AJCCRM. 2011;183(6): 788–824.
  6. Donohoe M et al. Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis. PLOS ONE. 2015;10(6):e0127771.

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