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Pulmonary Perspective: Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Collard HR, Moore BB, Flaherty KR, et al. Am J Respir Crit Care Med, June 21, 2007.

Introduction:

• The natural history of idiopathic pulmonary fibrosis (IPF) may not be chronic slowly progressive impairment of lung function, but rather, may be characterized by periods of accelerated deterioration without apparent cause.
• Acute exacerbations are likely to be important in IPF and better characterization of this poorly understood process is needed.
• This article summarizes the current understanding of acute exacerbations of IPF and proposes future directions in research.

Findings:

• This consensus statement regarding acute exacerbation of IPF is most noteworthy for emphasizing the lack of coherent understanding of this clinical process or its pathogenesis. Due to the present lack of knowledge and the absence of a clear and specific definition, estimates of the incidence of acute exacerbations vary widely, ranging from 5% to 50% of patients with IPF.
• The authors suggest diagnostic criteria that include:
  • Unexplained worsening dyspnea within a 30 day period
  • High-resolution CT scan with new bilateral ground glass abnormality
  • No evidence of inciting processes, such as infection, heart failure, pulmonary embolism, or any other cause of acute lung injury
• The risk factors for acute exacerbations are not clear but may include surgical lung biopsy itself.
• When available, the pathology reveals diffuse alveolar damage superimposed on underlying usual interstitial pneumonia.
• There is no proven treatment for acute exacerbation, although high-dose corticosteroids are often employed. Other potential interventions include cyclosporine A, anticoagulation, and antifibrotic therapy.
• The etiology of acute exacerbation of IPF is not known. It may be a manifestation of IPF itself, or represent lung injury consequent to infection or esophageal reflux and aspiration. Although poorly understood, the pathogenesis of acute exacerbations may involve loss of epithelial cell integrity and injury, increased pulmonary fibrocyte recruitment, and/or abnormalities related to cellular inflammation, cytokines, matrix metalloproteinases, and coagulation components. Further complicating the understanding of the pathobiology of this process is the interaction of this complex microenvironment and specific patient genetic variability (polymorphism), which may explain why only a subset of IPF patients appear to develop acute exacerbations.

Expert Opinion:

What is the clinician’s response to an IPF patient with a possible acute exacerbation? Nothing can be more difficult than developing an approach to the diagnosis and therapy of an entity that is so poorly understood, yet as potentially lethal as acute exacerbation of IPF.

The most important message from this paper is that patients with the potential for acute exacerbation should be systematically assessed by employing the proposed diagnostic scheme. Further, there should be a registry for clinical data and biological samples collected from such patients with acute exacerbations. Having patients enrolled in specific IPF drug trials would facilitate such data collection.

Presently, patients should be made aware of the potential for such acute declines and instructed to contact their physician. As for risk factors of acute exacerbation, in the later stages of disease, probably a surgical lung biopsy should be avoided. In terms of avoiding lung injury that might incite acute exacerbations, some centers would consider esophageal wrap to eliminate aspiration following appropriate esophageal assessment.

For the individual patient with deterioration and possible acute exacerbation, specific processes should be ruled out, including infection, pulmonary emboli, heart failure, and/or pulmonary hypertension. Given the importance of excluding infection, bronchoalveolar lavage should be performed for routine organisms, including viruses as well as opportunistic infections like pneumocystis jiroveci, especially in patients on immunosuppressive therapy.

Although there are no guidelines or evidence upon which to base therapeutic decisions, steroids seem reasonable. Anticoagulation may be a consideration given the presence of the disordered coagulation and fibrinolysis implicated in acute lung injury.

Finally, it should be remembered that with the new lung allocation scoring system, IPF patients with acute worsening may still be candidates for lung transplantation, given the shorter waiting time for organs. Also, with the newly appreciated unpredictability of the natural history of IPF and the risk of acute exacerbation, it is reasonable to have newly diagnosed IPF patients undergo complete lung transplant evaluation.

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