Chest
Volume 132, Issue 5, November 2007, Pages 1652-1658
Journal home page for Chest

Special Feature
Acute Exacerbation of Idiopathic Pulmonary Fibrosis

https://doi.org/10.1378/chest.07-0299Get rights and content

Background

The clinical course of patients with idiopathic pulmonary fibrosis (IPF) is generally marked by a decline in pulmonary function over time. Increasingly, patients have been recognized as having an acute, and often fatal, clinical deterioration, termed an acute exacerbation of IPF (AE-IPF).

Methods

Review of the current literature pertaining to AE-IPF.

Results

Acute exacerbations are defined by an acute onset of dyspnea (< 1 month) with worsening hypoxia and progressive infiltrates seen in the absence of heart failure or infection. New ground-glass infiltrates are seen on chest CT scans with diffuse alveolar damage superimposed on a background of usual interstitial pneumonia that is evident on histopathology. The incidence is unknown and is impeded by difficulties in eliminating infection as a cause, as well as by reporting biases contained in reported series introduced by including only biopsied patients or only deaths, or by excluding patients with advanced disease. Prognosis is poor but may be influenced by diagnostic inaccuracy. Treatment with antiinflammatory therapies, such as corticosteroids, or with anticoagulation are unproven and have not as yet been fully studied.

Conclusions

AE of IPF is a complication that demands additional careful study to clarify its relationship to the clinical course of patients with IPF.

Section snippets

Definition of AE-IPF

In 1993, Kondoh et al7 described acute clinical deterioration in three IPF patients in whom acute influenza-like symptoms, cough, fever, leukocytosis, and progressive hypoxia, developed in the absence of an identified infection. Histologic findings from open-lung biopsy specimens showed both usual interstitial pneumonia (UIP) and an organizing acute lung injury pattern. Subsequently, the following criteria have been used to identify similar patients with this AE-IPF: (1) progressive dyspnea

Incidence

The overall incidence of acute exacerbation (AE) in the IPF population remains unknown, as reported series do not contain unselected patients. A requirement for a tissue diagnosis demonstrating DAD at the time of the AE underestimates the frequency of AE-IPF, although the lack of a tissue diagnosis may lead to an overestimation. Kim et al9 reported a 1-year incidence of 8.5% in patients with biopsy-proven UIP. The incidence rate of AE-IPF in biopsied patients may differ from those in whom

Clinicopathologic Findings

Several case series8910 have characterized the clinical, radiographic, and pathologic findings seen in patients with AE-IPF. In a review of five patients who presented with dyspnea, hypoxia, and a histologic pattern that included DAD,8 four of the five patients died < 31 days after diagnosis. There was considerable heterogeneity in the degree of restriction seen on total lung capacity, the time from the diagnosis of IPF, the need for supplemental oxygen and the use of corticosteroids or

Etiology of AE-IPF

The finding of DAD on pathology suggests an acute injurious insult; nevertheless, no specific etiologies for AE-IPF have as yet been identified. The presentation of many patients with fever, flu-like symptoms, and neutrophilia found in BAL fluid specimens plausibly implicates an unrecognized infectious etiology.78910 Despite a suggested role in chronic IPF, no relationship has been made between viruses such as Epstein-Barr virus, cytomegalovirus, or human herpes virus-8 and AEs to date.22232425

Markers of AE-IPF

The longitudinal follow-up of IPF patients has shown a decline in FVC and diffusing capacity of the lung for carbon monoxide, along with arterial desaturation at rest while breathing room air and frequent hospitalization to be predictors of disease progression and ultimate death.6 The deterioration in pulmonary function is usually gradual in IPF patients. However, abrupt changes in FVC and diffusing capacity of the lung for carbon monoxide, in conjunction with new alveolar infiltrates and the

Treatment

Because of the acute decline and poor prognosis of patients with AE-IPF, various treatment strategies have been employed, including therapy with high-dose corticosteroids78910; antiinflammatory and immunosuppressive agents, such as cyclophosphamide,42 cyclosporine,4344 or pirfenidone17; and anticoagulation.45 To date, no randomized controlled trial supports a given therapy.

Pulse corticosteroid therapy (500 to 1,000 mg of methylprednisolone per day for 3 days) has been attempted, as in cases of

Suggested Approach to Diagnosis and Treatment

We believe patients with IPF in whom an acute clinical deterioration develops should undergo a high-resolution chest CT scan to document the interval development of significant ground-glass opacities, which are suggestive of AE-IPF, followed by BAL to examine the possibility of infectious etiologies. Support with supplemental oxygen should be employed to alleviate hypoxemia with a lung-protective approach utilized to minimize plateau airway pressure to < 30 cm H2O, if possible, when mechanical

Conclusion

The clinical course of IPF is difficult to predict, but AEs are increasingly recognized to play a major role in this disease. More longitudinal studies are needed to determine the incidence, establish an improved definition, and identify potential risk factors or clinical predictors. This may aid in identifying patients who may benefit from newer therapies before the onset of respiratory failure and mechanical ventilation, where current therapy has produced little success.

References (50)

  • BjorakerJA et al.

    Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis

    Am J Respir Crit Care Med

    (1998)
  • DouglasWW et al.

    Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone, or no therapy on survival

    Am J Respir Crit Care Med

    (2000)
  • SchwartzDA et al.

    Determinants of survival in idiopathic pulmonary fibrosis

    Am J Respir Crit Care Med

    (1994)
  • American Thoracic Society, European Respiratory Society

    American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias

    Am J Respir Crit Care Med

    (2002)
  • MartinezFJ et al.

    The clinical course of patients with idiopathic pulmonary fibrosis

    Ann Intern Med

    (2005)
  • AmbrosiniV et al.

    Acute exacerbation of idiopathic pulmonary fibrosis: report of a series

    Eur Respir J

    (2003)
  • KimDS et al.

    Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features

    Eur Respir J

    (2006)
  • AkiraM

    Computed tomography and pathologic findings in fulminant forms of idiopathic interstitial pneumonia

    J Thorac Imaging

    (1999)
  • AkiraM et al.

    CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis

    AJR Am J Roentgenol

    (1997)
  • JohkohT et al.

    Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients

    Radiology

    (1999)
  • RiceAJ et al.

    Terminal diffuse alveolar damage in relation to interstitial pneumonias: an autopsy study

    Am J Clin Pathol

    (2003)
  • SaydainG et al.

    Outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive care unit

    Am J Respir Crit Care Med

    (2002)
  • RaghuG et al.

    A placebo-controlled trial of interferon γ-1b in patients with idiopathic pulmonary fibrosis

    N Engl J Med

    (2004)
  • AzumaA et al.

    Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis

    Am J Respir Crit Care Med

    (2005)
  • DallariRM et al.

    Acute exacerbation of idiopathic pulmonary fibrosis

    Eur Respir J

    (2004)
  • Cited by (161)

    • Immunologic Lung Diseases

      2022, Clinical Immunology: Principles and Practice, Sixth Edition
    • Extracorporeal Artificial Organs and Therapeutic Devices

      2020, Biomaterials Science: An Introduction to Materials in Medicine
    View all citing articles on Scopus

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    View full text