Idiopathic pulmonary fibrosis—results from a Japanese nationwide epidemiological survey using individual clinical records

Idiopathic interstitial pneumonias (IIP) were internationally classified into seven types in 2002.1 In Japan, the fourth revision of clinical diagnostic criteria for IIP was prepared in 2003, and IIP were classified in accordance with the international classification.2 Since the Specific Disease/Pulmonary Fibrosis Survey/Study Group of the Ministry of Health and Welfare (currently, Study Group on Diffuse Pulmonary Disorders, Scientific Research/Refractory Disease-Overcoming Research Business, Ministry of Health, Labor and Welfare) was established in 1974, epidemiological studies of IIP were made using a questionnaire3 or in specific areas4,5. Currently, a nationwide epidemiological study may be of significance, as the disease entity has now been well established. Among patients with IIP, the subjects were those to whom a certificate of medical benefits was delivered in 2005. As medical benefits for IIP are examined in each prefecture, clinical personal records are collected and submitted to the Disease Strategy Section, Health Bureau, Ministry of Health, Labor and Welfare and then stored in a database in the Ministry. Using this database, we analysed the age at onset, smoking history, dust inhalation, diagnostic methods, disease type, classification of severity, main symptoms, respiratory dysfunction, imaging findings, serum markers and drug therapy in the new patients, and disease type, classification of severity and drug therapy in the updated patients. In Japan, the severity of IIP was classified by resting PaO2 and desaturation during exercise: stage I: PaO2 ≥ 80 Torr; stage II: 70 ≤ PaO2 < 80 Torr; stage III: 60 ≤ PaO2 < 70 Torr; stage IV: PaO2 < 60 Torr. If SpO2 was below 90% during 6-minute walking test, stage II or III was up to III or IV, respectively.2 In 2005, medical benefits were delivered to 4396 patients with IIP. Based on a population of 127 756 815 persons, the prevalence was 3.44 per 100 000 persons. Of the 4396 patients, clinical personal records were collected and available for 1543 (35.1%) patients; new and updated patients were 658 and 885, respectively. Concerning disease type, a total of 1322 (85.7%) patients had IPF (Table 1): 545 new patients and 777 updated patients; 878 were men. The following analysis was performed in the IPF. Pathological diagnosis was made only in 67 (12%) patients. Concerning disease severity, stage I/II/III/IV were 32/28/177/287 in the new patients and 73/64/229/318 in the updated patients. The mean age at disease onset was 64.5 ± 10.5 years (men: 64.8 ± 9.3 years, women: 64.0 ± 12.4 years). There was no gender difference. Overall, 59% had a history of smoking (men: 79%, women: 13%). In addition, 13% had a history of dust inhalation (men: 17%, women: 2%). The prevalence was significantly higher in men. The main symptoms of fine crackles, dry cough, dyspnoea on exertion and finger clubbing were observed in 98%, 94%, 98% and 53%, respectively. Concerning respiratory function, restrictive impairment, reduced diffusion capacity, hypoxemia, an increase in A-aDO2 and a desaturation after a 6-minute walking test were noted in 86%, 92%, 90%, 80% and 91%, respectively. There was a significantly negative correlation between %VC or %DLco and disease severity. CXR showed bilateral diffuse shadows, predominant lower lung fields and lung volume loss in 99%, 93% and 83%, respectively. HRCT revealed bilateral basal shadow, honeycombing, traction bronchiectasis, ground glass opacities and consolidation in 97%, 91%, 85%, 82% and 43%, respectively. Serological testing showed increases in KL-6, SP-A, SP-D and LDH in 95%, 89%, 86% and 71%, respectively. There was no correlation between serum markers and disease severity. Drug therapy was performed in 246 (45%) of the 545 new patients and in 505 (65%) of the 777 updated patients. Corticosteroids alone were most frequently administered (Fig. 1). With respect to severity of IPF, the proportion of patients undergoing drug therapy increased with severity among the new patients, whereas in the updated patients, there was a negative correlation. There were no differences in drug therapy among patients with differing severities. Drug treatment in new and updated patients with IPF. () Corticosteroid; () corticosteroid + immunosuppressant; () immunosuppressant. The present epidemiological study is the first nationwide report in Japan to utilize clinical personal records. Previous epidemiological studies were conducted using a questionnaire or health check-up in the specific prefectures. In Hokkaido, the prevalence of IIP is 3.4 per 100 000 persons4. Based on the results of health check-up in residents over 50 years in Niigata, the prevalence was 2.9 to 4.9 per 100 000 persons5. Thus, the prevalence of IIP in Japan has been reported to be approximately five per 100 000 persons. In the present study, the prevalence was estimated to be 3.44 per 100 000, which was consistent with the values previously reported. However, IIP conditions for which medical benefits were delivered corresponded to IPF severity level of III or IV. Therefore, patients with other IIP or mild IPF were not included, and the true prevalence may be higher. In epidemiological studies of IPF in various countries, the prevalence in England,6 in the USA7 and in Finland8 were 3–6, 13–20 and 16–18 per 100 000 persons, respectively. Recently, these prevalence numbers have risen further.9,10 The clinical personal records were collected for about 35% of the 4396 patients in our survey. The conditions of most patients with IIP corresponded to stage III or IV IPF. Our subjects showed typical clinical findings, because most patients were diagnosed as having IPF based on clinical findings. Furthermore, a high proportion of patients were positive for three new serum markers, KL-6, SP-A and SP-D, which suggests that they may be useful in the diagnosis of IPF. In the present study, severe IPF patients predominated, which could raise various concerns. Initially, most patients were diagnosed based on clinical findings, suggesting fibrotic NSIP might be commingled in IPF. Regarding treatment, drug therapy was performed in 65% of our updated patients, reflecting medical treatment might be aimed to prevent disease progression even in stage I or II patients in clinical practice, despite its low efficacy. However, most regimens consisted of corticosteroids alone; combination therapy with immunosuppressants, as recommended in the guidelines,1,2 was not commonly used. N-acetylcysteine and interferon are not approved for use in the Japanese health system. This study was based on the data collected in 2005. Future continuous analysis may facilitate the understanding of various features of IIP, especially IPF.