Chest
Special FeatureAcute Exacerbation of Idiopathic Pulmonary Fibrosis
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.
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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.