RERF Report No.2-13

Published in Radiation Research§“Radiation Exposure and the Risk of Mortality from Noncancer Respiratory
Diseases in the Life Span Study, 1950–2005”
Truong-Minh Pham, Ritsu Sakata, Eric J. Grant, Yukiko Shimizu, Kyoji Furukawa, Ikuno
Takahashi, Hiromi Sugiyama, Fumiyoshi Kasagi, Midori Soda, Akihiko Suyama, Roy E. Shore,
Kotaro Ozasa.
Radiat Res 2013 (November); 180(5): 539–45 (doi: 10.1667/RR13421.1)
Study Rationale
The Life Span Study (LSS) has found that exposure to A-bomb radiation is associated withmortality from noncancer respiratory diseases (hereinafter, simply called respiratory diseases).
However, this relationship may be a secondary association caused by the fact that respiratory
diseases that can develop at the terminal stage of illnesses such as cancer and circulatory
diseases, which have already been linked to radiation exposure, are designated as the cause ofdeath. Considering that the biological mechanisms behind the association between radiation
exposure and respiratory diseases are unclear, further examination was necessary before
reaching any conclusion about whether the association between radiation exposure andnoncancer respiratory disease mortality was genuine or an artifact disease misclassification.
Explanation
1. Objectives
While the LSS has clarified the association between A-bomb radiation exposure andcancer, attention has also recently been paid to noncancer diseases. The two purposes of thestudy were (1) to examine the associations of radiation dose with the main subclasses of deaths
coded as respiratory diseases on the death certificates; and (2) to determine the degree to which
the associations between radiation exposure and respiratory diseases were genuine or werecaused by biases due to lifestyle and sociodemographic factors or disease misclassification.
2. Methods
The subjects of the present study were 86,611 people with estimated lung doses fromamong the 120,321 members of the LSS, which was established on the basis of the Japan 1950
National Census. Based on the International Classification of Diseases, respiratory diseases
recorded as causes of death of these subjects were classified into acute respiratory infection,
pneumonia/influenza, chronic obstructive lung disease, bronchial asthma, and other respiratory
diseases. The present study was based on a follow-up conducted from 1950 through 2005. To
determine the degree of association of radiation exposure with mortality from these diseases,
excess relative risks (ERR) were estimated using Cox regression analyses.
3. Results(1) Association between radiation exposure and respiratory diseases
During the study period, 5,515 deaths due to respiratory diseases occurred. The ERR per
Gy for all noncancer respiratory diseases was significantly elevated, being 0.17 (95%
confidence interval [CI]: 0.08, 0.27). (The ERR of 0.17 here indicates a 17% increase in therisk at 1 Gy of exposure as compared with unexposed subjects, but with a range of uncertainty
from 8% to 27%.) The ERR for each of the respective diseases varied, being 0.20 (95% CI:0.09, 0.34) for pneumonia/influenza, 0.08 (95% CI: –0.14, 0.37) for chronic obstructive lungdisease, 0.16 (95% CI: –0.10, 0.52) for bronchial asthma, and –0.16 (95% CI: <0, 0.40) for
acute respiratory infection. Adjustments for lifestyle and socioeconomic factors had virtuallyno impact on the risk estimates. When the study period was divided into shorter intervals(1950–1964, 1965–1979, and 1980–2005), the association between radiation exposure andrespiratory diseases was observed to be stronger in the period 1980–2005. Until the 1970s,
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most respiratory disease deaths in Japan were from acute infections, but in the 1980s
respiratory disease deaths started to be observed primarily as diseases accompanying theterminal stages of cancer and circulatory diseases among the elderly. It was thus plausible thatthe suggestive association between radiation exposure and respiratory diseases might reflect
cancer and circulatory disease in this later period.
(2) Effects of cause-of-death misclassification
Because in the present study information on cause of death was obtained from deathcertificates, it is important that the underlying cause of death recorded on death certificates beaccurate in order to correctly estimate risks. Many patients with cancer or circulatory diseasedie of respiratory diseases at the terminal stage of such illnesses. Thus, there is a concern that
although the actual underlying cause of death is cancer or circulatory diseases, respiratory
diseases may be mistakenly recorded as the cause of death. With this in mind, analysis wasconducted after excluding subjects with a history of cancer or circulatory diseases from among
deaths due to respiratory diseases. As a result, the ERRs decreased by about 35%, and except
for pneumonia/influenza, no statistically significant association between radiation exposureand mortality from respiratory diseases was observed.
Care should be taken in interpreting the results of the present study because the study could
only partially correct for other causes of death. Some study subjects did not live in Hiroshima
or Nagasaki prefectures where our tumor registries could have identified associated cancers,
and death certificates often list only one “cause” of death, rather than identifying the important
accompanying causes as well, such as cancer or cardiovascular disease. Thus, the apparent
associations of radiation with respiratory diseases may have been reduced even more if we hadcomplete ascertainment of the alternative underlying causes. However, the present study
indicates that at least part of the apparent association of radiation exposure with noncancer
respiratory disease deaths is likely due to reporting artifacts on the death certificates, but notdue to sociodemographic or lifestyle biases.

The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring inHiroshima and Nagasaki for more than 60 years. RERF’s research achievements are considered theprincipal scientific basis for radiation risk assessment by the United Nations Scientific Committee on theEffects of Atomic Radiation (UNSCEAR) and for recommendations regarding radiation protection
standards by the International Commission on Radiological Protection (ICRP). RERF expresses its
profound gratitude to the A-bomb survivors and survivors’ offspring for their cooperation in our studies.
§Radiation Research, which is an official monthly journal of the Radiation Research Society, publishes
original, peer-reviewed papers and review articles on radiation effects and related issues in the fields ofphysics, chemistry, biology, and medicine. (Impact factor in 2012: 2.698)

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