Acute exacerbation of IPF: The concept was proposed in Japan, but why was it not recognized in western countries?

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrosing disease. Acute exacerbation of IPF (AE-IPF) is an abrupt and rapid deterioration by unidentifiable causes which occurs during chronic clinical course of IPF. The estimated incidence is 5-15 % per year in IPF patients. Moreover, AE-IPF is not only associated with a very high mortality rate (over 70 %), but it is also an important determinant of overall prognosis in patients with IPF. Pathologically, AE-IPF is characterized by acute diffuse alveolar damage (DAD) lesion that develops close to the chronic progressive usual interstitial pneumonia (UIP) lesion. Because DAD is also a common pathological feature observed in acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), and AE-IPF, it is possible to regard AE-IPF as ARDS developed due to IPF. Although the trigger factors for AE-IPF are often unclear, sometimes the triggers such as surgery, corticosteroid dose reduction, or viral infection are evident. Evidence-based and effective therapies are lacking for AE-IPF, with the current management guidelines recommending only supportive care and corticosteroid use. Novel treatments for AE-IPF that have been investigated in small-scale studies, including the use of polymyxin B-immobilized fiber column (PMX) hemoperfusion, may be promising. When AE with DAD pathology develops once, treatment is extremely difficult; therefore, development of effective prevention methods is required. To this date, there is emerging evidence from clinical trials of investigational treatments for chronic phase of IPF which may reduce the incidence of AE-IPF.