Question: I have a patient with IPF whose condition has worsened over the past few weeks. I believe that "acute exacerbations of IPF" describes my patient well; she has a rapid deterioration of PFTs and quality of life and is requiring higher concentration of oxygen. What can be done to help her or slow the decline?

Answer: Patients in all stages (early, moderate, advanced) of IPF are at risk of developing acute decompensation of their clinical condition. They may present with progressive dyspnea, cough, and/or low grade fever.

Deterioration in function may be caused by opportunistic infection (viral, bacterial, or fungal); ischemia/congestive heart failure; thromboembolism; aspiration; barotrauma or acute exacerbation of IPF. This last term is reserved for a decline in function over a short period, usually weeks, associated with well-defined diagnostic criteria:

  1. Increasing dyspnea or cough within one month in patient with IPF
  2. Newly developed pulmonary opacities on chest x-ray or ground glass densities on HRCT superimposed on findings consistent with a UIP pattern
  3. Increasing oxygen requirements: decrease in PO2 (> 10 mm Hg) or saturation under similar conditions
  4. Exclusion of other causes of respiratory distress: CHF, cardiac ischemia, thromboembolism, barotrauma, aspiration, conditions that may lead to ARDS (pancreatitis, sepsis), infection
  5. Some authors also include a significant decline in FVC (> 10 % absolute decrease)

Thus, a systematic approach should be taken with a patient with IPF and worsening respiratory status. The evaluation should include thorough history, ABGs/saturation, PFTs, HRCT (CT angio when possible), echocardiogram, serologic studies for viruses or atypical organisms, sputum cultures and if safe, BAL.

The incidence of acute exacerbation is not well established but it has been estimated to occur in about 5-19% of patients with IPF.1 It may be the presenting manifestation or occur at any stage of disease and is independent of degree of physiological impairment. In patients undergoing surgical biopsy, the predominant histologic finding is diffuse alveolar damage superimposed on UIP. The morbidity and mortality of this complication is high. It was initially described in patients with acute respiratory failure, where mortality was over 90% at 60 days. A recent systematic review estimates the mortality to be 60% at 1 month and 67% at 3 months.2

An effective treatment for acute exacerbation does not exist. Recognition of acute exacerbation at an early stage has allowed for interventions geared toward avoiding respiratory failure. Responses to pulsed corticosteroids, immunosuppressants (cyclosporine, cytoxan), antifibrotics (pirfenidone), and anticoagulants in combination with or after antibiotics have been reported. Survivors of an acute exacerbation may be left with further decrement in their functional ability and with greater physiologic impairment.

The unpredictability of acute exacerbations, the dismal prognosis and the adverse impact on the course of IPF make it imperative to be vigilant for this complication, to treat infection rapidly, and to intervene promptly. Evaluation for lung transplantation is recommended prior to the onset of an acute exacerbation.

  1. Hyzy R, Huang S, Myers J, Flaherty K, Martinez F. Acute exacerbation of idiopathic pulmonary fibrosis. Chest. 2007:132:1652-1658.
  2. Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med. 2008;19:227-235.