Reading Room

Article Summary
Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features

Kim DS, Park JH, Park BK, Lee JS, Nicholson AG, Colby T. Eur Respir J. 2006;27:143-150.

Discussion

• Acute exacerbations (AE) of IPF remain a poorly defined entity. Areas that require a better understanding include its incidence, risk factors, etiology, and management.
• The present study was designed to assess the incidence and outcomes of acute exacerbations among 147 patients with biopsy-proven IPF.
• Depending on the definition, acute exacerbations had a 1-year frequency of 8.5-15.4% and a 2-year frequency of 9.6-18%.
• Outcomes are very poor, with a 3-month mortality of 81.8%.

Study Design:

• Retrospective review of 147 patients with biopsy-proven IPF
• Criteria for an acute exacerbation included all of the following:¹
  • Worsening of dyspnea within 1 month
  • Hypoxemia with a PaO₂/FiO₂ ratio < 225
  • Newly developed pulmonary infiltrates
  • Absence of infection or heart disease
• All clinical, laboratory, pulmonary function tests, bronchoalveolar lavage (BAL), and surgical biopsy (SLB) pathology data were collected retrospectively from medical records.

Results:

• Using the above criteria, 8.5% (n = 11) patients were characterized as having an acute exacerbation at 1 year and 9.6% at 2 years. Using a less-stringent definition, the incidence was 15.4% at 1 year and 18% at 2 years.²
• Time to diagnosis of AE: In 5/11 patients the onset occurred 13.3 +/-11.7 months after the diagnosis of IPF
• 3/11 patients developed the AE after a diagnostic procedure (1 BAL, 2 SLB).
• 3/11 presented with an AE without a prior diagnosis of IPF.
• Average time from symptom onset to admission was 13 +/- 10 (range: 2-30) days.
• In addition to rapidly progressive dyspnea (100%), other symptoms included cough (55%), "scanty" sputum (46%), and mild fever (9%).
• All microbiologic studies were negative at the time of the acute exacerbation.
• Radiologic findings: All patients had new ground-glass opacities (GGO) at the time of the acute exacerbation. The distribution of the GGO included multifocal (n = 7), peripheral (n = 3), and diffuse (n = 1) patterns.
• Pathologic features: SLB was performed at the time of the AE in 4/11 patients. All 4 cases had evidence of UIP with superimposed diffuse alveolar damage (DAD).
• Treatment: All the patients were treated with broad-spectrum antibiotics and corticosteroids; 6 also received pulsed methylprednisolone (1 gram daily IV x 3).
• Outcomes: 9/11 patients required mechanical ventilation and the hospital mortality of this group was 78%. The overall 3-month mortality was 81.8%. The cause of death was attributed to progression of disease except in 1 patient. Only 1/3 of patients died from the group in which the AE was related to a procedure. The distribution of the GGO on HRCT also appeared to have prognostic implications; all 3 patients with the peripheral distribution but only 1 with the multifocal pattern survived their initial episodes.

Implications/Recommendations:

• AEs are unpredictable and carry a bleak prognosis.
• AEs can occur in any patient with IPF and might herald the onset of the disease in patients without a prior diagnosis.
• There is likely a spectrum of severity of AEs. Standardized definitions and possibly a grading system incorporating rapidity of onset, nature and extent of infiltrates, and severity of gas impairment are needed. This will provide a framework to better define the natural history, prognosis, risk factors and, hopefully, treatment for this devastating complication.

Reference

1. Kondoh Y, Taniguchi H, Kawabata Y, Yokoi T, Suzuki K, Takagi K. Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest. 1993;103:1808-1812.
2. Akira M, Hamada H, Sakatani M, Kobayashi C, Nishioka M, Yamamoto S. CT findings during phase of accelerated deterioration in patients with idiopathic pumonary fibrosis. AJR Am J Roentgenol. 1997;168:79-83.

Article link

Click here for a direct link to the article abstract.