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Basis of Acute Exacerbation of Idiopathic Pulmonary Fibrosis in Japanese Patients

A pulmonary perspective by Dr. Collard and colleagues focused on acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), trying to establish a worldwide consensus about acutely progressive respiratory failure during the course of IPF (1). Awareness of this serious phenomenon as a distinct pattern of IPF is extremely important, and helps clinicians worldwide to share the same background information on the diagnosis and management of AE. However, Japanese patients with IPF seem to suffer from AE much more frequently than patients of other ethnic backgrounds. AE is often triggered by infections, drugs, radiotherapy, anticancer agents, and surgery. Epidemiological data suggest that Japanese more frequently suffer from diffuse alveolar damage (DAD) due to various causes such as drugs (2). These observations strongly suggest that genetic factor(s) predispose Japanese to DAD. Reports on AE-IPF are frequent from Japan (3, 4). A large-scale study showed that 5.8% of Japanese patients on gefitinib therapy developed interstitial lung disease, a frequency 10- to 100-fold higher than for patients of other genetic backgrounds (2).

Ethnic differences in the incidence of pulmonary disease have been observed before. For example, most Japanese clinicians have never seen ₁-antitrypsin deficiency or cystic fibrosis, because these diseases are extremely rare in the Japanese population. Population genetics indicates that a founder gene may predominate in a genetically isolated population through the bottleneck effect or random genetic drift (5).

Homo sapiens emerged in Africa around 200,000 years ago and reached Japan about 30,000 years ago, at the end of the Ice Age when the sea level was low and Japan was joined to the Eurasian continent. Subsequent elevation of the sea has genetically isolated Japan, so that the Japanese population may share disease genes that are not found or rarely found in other ethnic groups.

Although there is more movement of people in modern society, the world is still a mosaic of ethnic groups with different diseases. We believe that AE-IPF is actually a collection of diseases with different causes, among which a cause specific to Japanese patients accounts for many cases in Japan. Elucidation of the responsible genetic factor(s) would be important for public health in the world, as well as for understanding pulmonary physiology.

Arata Azuma

Nippon Medical School
Tokyo, Japan

Koichi Hagiwara

Saitama Medical School
Moroyama, Saitama, Japan

Shoji Kudoh

Nippon Medical School
Tokyo, Japan

FOOTNOTES

Conflict of Interest Statement: A.A. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. K.H. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.K. received 220,000 Japanese yen from AstraZeneca for advisory board activities.

REFERENCES

1. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, et al.; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2007;176:636–643.[Abstract/Free Full Text]
2. Azuma A, Kudoh S. High prevalence of drug-induced pneumonia in Japan. Japan Med Assoc J 2007;50:405–411.
3. 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.[CrossRef][Medline]
4. Akira M, Hamada H, Sakatani M, Kobayashi C, Nishioka M, Yamamoto S. CT findings during the phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis. AJR Am J Roentgenol 1997;168:79–83.[Abstract/Free Full Text]
5. Nagel RL. Epistasis and the genetics of human diseases. C R Biol 2005;328:606–615.[Medline]

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