Sixty seven cases with pulmonary atypical mycobacteriosis (2 by M. kansasii, 62 by M. intracellulare, 2 by M. fortuitum and 1 by a possible new pathogen of group III mycobacteria) died in 9 Japanese ...national sanatoria up to October 1976. Of these 67 cases, 40 died of atypical mycobacterial disease, and the remaining 27 cases died of other diseases. Roentgenological aggravation was found in 44 cases (1 by M. kansasii, 1 by M. fortuitum and 42 by M. intracellulare). There were various types of roentgenological aggravation. Spread of non-cavitary foci, infiltrate and pneumonia were found most frequently (40/44, 90.9%). Enlargement of cavity was found in 12 cases (27.2%), appearance of pleural effusion in 5 cases (11.4%), and spontaneous pneumothorax in 3 cases. Infection of bulla was found in 11 out of 22 cases with bullae as the underlying disease. The first roentgenological aggravation was found in 20 (45.5%) out of 44 cases within 12 months; 13 cases (29.5%) between 13 to 24 months; and 11 cases (25%) over 2 years after the discovery of the disease. From the results mentioned above, in the fatal cases, progression of the disease was predicted by the appearance of the roentgenological aggravation within 2 years after the discovery of the disease. There were various courses of the progression of the lesions as shown in Figures 2a and 2b. One of the typical course of the progression was devided into the following 5 stages: The first stage: localized cavitary lesion. The second stage: spread of foci around cavity. The third stage: spread of foci in contralateral lung. The fourth stage: enlargement of cavity (appearance of giant cavity). The fifth stage: extensive pneumonia in the lower lung field. Another typical course of the progression was the repeated infections of bullae. Roentgenological aggravation found in patients with atypical mycobacterial disease was not rarely due to the mixed infection with various organisms (gram-negative bacilli, fungi and also human type tubercle bacilli). The majority of the patients with underlying pulmonary disease (extensive emphysema, chronic bronchitis and bronchiectasis) died of pulmonary insufficiency in the relatively early stage of atypical mycobacteriosis. The patients with the mixed infection have died, in spite of the negative conversion or the dicrease of the excretion of atypical mycobacteria. There were two cases (M. intracellulare infection) complicated with pulmonary tuberculosis.
Frequency and kind of species of atypical mycobacteria isolated from patients hospitalized in thirteen participating hospitals in June, September, and December 1977, and March 1978 were studied using ...p-nitrobenzoic acid-Ogawa egg medium as a screening medium. Data were taken from the results of monthly sputum examinations in the above months. Futhermore, patients with lung disease due to atypical mycobacteria hospitalized in the study year, April 1977 to March 1978, were the sub jects of the present study. 1) Atypical mycobacteria were found at a rate of 9.5% among all mycobacteria including M. tuberculosis (Table 1). The kind of species of the atypical mycobacteria isolated are shown in Table 2. 2) A total of 159 patients with lung disease due to atipical mycobacteria were found in the study year (Table 4). Frequency of the patients were considered to be high in the Tokyo, Kanagawa, and Kinki (Osaka) hospitals (Table 5). 3) Frequency of isolation of atypical mycobacteria from sputum specimens of the patients in the participating hospitals has appeared to be increasing (Table 7). However, no significant changes were found in the kind of the species of atypical mycobacteria isolated in various years (Table 8). 4) In contrast to that the number of tuberculous patients is decreasing, the number of patients with lung disease due to atypical mycobacteria is increasing (Table 9). The kinds of species of atypical mycobacteria which cause the diseases in patients were similar in various study years (Table 10).
The incidence of lung disease due to mycobacteria other than Mycobacterium tuberculosis (atypical mycobacteria) in Japan was estimated to be 0.9-1.9 per 10⁵ population per year in 1971-1979. Although ...the incidence of lung tuberculosis is steadily decreasing, the incidence of lung disease due to atypical mycobacteria has remained at almost the same level. The number of patients newly infected per year in recent years was calculated to be ∼2,000. The ratio of the number of patients with lung disease due to atypical mycobacteria to the number of patients with lung disease due to all species of mycobacteria was highest in hospitals on the southwest coast of the Pacific. The atypical mycobacteria that caused disease most frequently belonged to the Mycobacterium avium-intracellulare complex. Of the 537 cases of disease due to atypical mycobacteria, 491 (89.6%) were due to these organisms; 43 (8.0%), to Mycobacterium kansasii; and 7 (1.3%), to Mycobacterium fortuitum. The disease due to M. kansasii appeared most frequently in hospitals in the Tokyo and Kanagawa prefectures. Patients with lung tuberculosis had a high risk of lung infection due to M. avium-intracellulare. The incidence of such disease in tuberculous patients was estimated to be 18.7 per 10⁵ population per year, a rate that is ∼10 times that found in the general population.
It was reported previously by the present group (1-3) that the frequency of isolation of my cobacteria other than tubercle bacilli (‘atypical’ mycobacteria) and the incidence of mycobacterioses due ...to these mycobacteria are higher in the hospitals locating in the South coast of the Honshu island. It was shown also that more than 90% of the mycobacterioses in this country were due to M. avium-intracellulare complex and that the lung disease due to M. kansasii was found only in the Tokyo area and its neighbourhood. In the present study, the prevalence rate of the “atypical” mycobacterioses was compared among the hospitals locating in various places of this country. A morning sputum specimen was added with an equal volume of a 4% NaOH solution and dissolved by shaking at room temperature for 15 to 20 minutes. The sputum was inoculated to the Ogawa egg medium. Growing organisms were screened for ‘atypical’ mycobacteria by the use of the PNB medium (4) or the salicylate medium (5). The acid-fastness and the photochromogenicity were also tested in individual hospitals. The organisms that grew on the PNB or salicylate medium were sent to the Chubu hospital and were identified according to the methods previously described (2). ‘Atypical’ mycobacterioses were defined by the following conditions: (a) The excretion of ‘atypical’ mycobacteria more than three times in the period of the first 6 months after hospitalization; (b) presence of lung lesion in the chest X-ray picture; (c) coincidence of the excretion of ‘atypical’ mycobacteria and clinical symptoms. The location of the 13 participating hospitals are shown in Fig. 1. The prevalence rate was the highest in five hospitals, Tokyo, Chubu, Kinki, Tenryuso, and Kochi, which are located in the Southern Pacific coast of Japan (Table 1). The species of mycobacteria other than tubercle bacilli which caused lung disease in patients are shown in Table 2. Furthermore, it was shown that tuberculous patients who were hospitalized for long time were infected with ‘atypical’ mycobacteria (Table 3). All causative organisms which caused ‘secondary’ infection belonged to M. aviurnintracellulare complex.
A co-operative study was carried out by 11 national chest hospitals in various places of Japan, using the same technique of screening for ‘atypical’ mycobacteria (mycobacteria other than tubercle ...bacilli). The screening by ‘salicylate medium’ (Tsukamura, M.: Amer. Rev. Resp. Dis., 86: 81-83, 1962) or ‘p-nitrobenzpate medium’ (Tsukamura, M.& Tsukamura, S.: Tubercle, 45: 64-65, 1964) was made on mycobacterial cultures isolated from all patients hospitalized in the months, June, September and December 1971 and March 1972. All strains obtained by the screening were identified according to the schedule described previously (Tsukamura, M.: Tubercle, 48: 311-338, 1967; Tubercle, 50: 51-60, 1969). The following useful tests were also used: Tween hydrolysis (Wayne, L. G., Doubke, J. R.& Russell, R. L.: Amer. Rev. Resp. Dis., 90: 588-597, 1964); ethambutol resistance for differentiating pathogenic and non-pathogenic ones of Group II and Group III (Tsukamura, M.: Kekkaku, 45: 237-240, 1970); alpha and beta-esterases (Käppler, W.: Beitr. Kiln. Tuberk., 130: 1-4, 1965); tolerance to nitrite (Tsukamura, M.& Tsukamura, S.: Amer. Rev. Resp. Dis., 98: 505-506, 1968).
Clinical feature of lung disease due to M. intracellulare was observed in 64 patients hospitalized in 11 participant hospitals during the period from April 1971 to September 1972.
Screening for atypical mycobacteria (mycobacteria other than tubercle bacilli) were carried out in thirteen participating hospitals by using the p-nitrobenzoic acid-Ogawa egg medium. The subjects ...were the patients who were under hospitalization in June, September and December, 1975 and March, 1976. The isolation of mycobacteria was carried out using Ogawa egg medium which was inoculated with a sputum specimen after treatment with equal volume of a 4% (2%) NaOH solution for 15 minutes. 1. The ratio of atypical mycobacteria (including Gordona) among all mycobacteria was 7.8% in average and the ratio in senso stricto (excluding Gordona) was 7.5% in average (Table 1). The ratio was high in the hospitals located in South coast of Honshu and Shikoku islands facing Pacific Ocean (Fig. 1). 2. The kinds of species of atypical mycobacteria are shown in Table 2. The results agreed well with the results obtained by previous two studies (National Chest Hospital Group: Kekkaku, 48: 203-211, 1973; 51: 99-107, 1976). 3. The number of patients with lung disease due to atypical mycobacteria who were hospitalized in the period April, 1975 to March, 1976 was 128. Out of these, ca. 94% of the patients belonged to the disease due to M. avium-intracellulare omplex, and only 3% to that due to M. kansasii. Two cases showed the disease due to M fortuitum (Table 3). The frequency of occurrence of disease, so far observed using a ratio, the number of patients with disease due to atypical mycobacteria per the number of patients with lung disease (including tuberculosis) under hospitalization per day, as an index, was high in the hospitals located in the South coast of Honshu and Shikoku islands facing Pacific Ocean (Table 4 and Fig. 2). 4. The kinds of species isolated from sputa of patients with cavitary lung disease (mostly tuberculosis) and/or bronchiectasis were almost the same in three studies (Table 5). However, decrease in the ratio of M. nonchromogenicum was observed (1968 7.5%, 1971 4.4%, 1974 2.3%, t975 0.4%). 5. The kinds of species that caused lung disease were almost similar in our three studies (Table 6). Disease due to M. aviwn-intracellulare complex showed 94 to 96% of all atypical mycobacterioses, and disease due to M. kansasii 2 to 4% (Table 6). So far observed from the index used, the ratio of patients with lung disease due to atypical mycobacteria is increasing (Table 6). This increase has been suggested to be due to accumulation of such patients, as our another study (Kekkaku, 51: 447-451, 1976) showed that the prevalence rate of the disease among newly hospitalized patients was almost the same in recent five years (1971 to 1975).
The isolation rate of atypical mycobacteria (mycobacteria other than tubercle bacilli) and their kinds of species were studied in twelve participating hospitals located in various places of Japan ...during 5 years (1971 to 1975). The subject of the study was patients hospitalized in these hospitals during screening-months, June, September, December and March, of every year. The isolation rate (ratio of the number of atypical mycobacterial strains per the number of all mycobacterial strains) was significantly higher in four hospitals (Tokyo, Tenryuso, Chubu and Kinki) locating in Tokyo, Shizuoka, Aichi and Osaka Prefectures, respectively (refer to Fig.1), than the average (6.2%), and the rates in these hospitals were about 8%. Three hospitals, Kanagawa, Tochigi and Nagasaki, showed the rates of about 5%, three hospitals, Miyagi, Niigata and Fukuoka, showed the rates of 2 to 3%, and two hospitals, Sapporo and Ehime only 0.7 to 0.8% (Table 1). Distribution of the kind of species in various hospitals did not differ significantly from each other, except for a few cases. (1) The ratio of M. kansasii in Tokyo and Kanagawa Hospitals was significantly higher than the others. (2) The ratio of M. fortuitum in Fukuoka Hospital was significantly higher than the average. (3) The ratio of M. gordonae was significantly higher in Kanagawa Hospital than the average in all hospitals. The ratios of species of 950 strains of atypical mycobacteria are shown in Table 2.
Background: Although aberrant proliferation and activation of lung fibroblasts are implicated in the initiation and progression of idiopathic pulmonary fibrosis (IPF), the underlying mechanisms are ...not well characterized. Numerous microRNAs (miRNAs) have been implicated in this process; however, miRNAs derived from exosomes and the relevance of such miRNAs to fibroblast-to-myofibroblast differentiation are not well understood. In this study, we attempted to identify exosome-derived miRNAs relevant to fibrosis development. Methods: Using miRNA array analysis, we profiled exosome-derived miRNA expression in sera of C57BL/6 mice exhibiting bleomycin-induced pulmonary fibrosis. After validating a selected miRNA by quantitative reverse-transcription polymerase chain reaction, its effect on fibroblast-to-myofibroblast differentiation was investigated in human lung fibroblasts. Furthermore, we determined the role of the selected miRNA in an in vivo model of pulmonary fibrosis. Results: MiRNA array analysis revealed that miR-22 expression was increased by up to 2 fold on day 7 after bleomycin treatment compared with that in vehicle-treated mice. In vitro, miR-22 transfection suppressed TGF-β1-induced α-SMA expression. This was mediated via inhibition of the ERK1/2 pathway. Baseline α-SMA expression was increased upon miR-22 inhibitor transfection. Furthermore, miR-22 negatively regulated connective tissue growth factor expression in the presence of TGF-β1. In vivo, administration of a miR-22 mimic on day 10 after bleomycin challenge ameliorated pulmonary fibrosis lesions accompanied by decreased α-SMA expression in the model mice. Conclusions: Exosomal miR-22 modulates fibroblast-to-myofibroblast differentiation. The present findings warrant further study, which could shed light on miR-22 as a novel therapeutic target in IPF.
Objectives Acute exacerbation of idiopathic pulmonary fibrosis (IPF-AE) has been recognized as a fatal pulmonary disorder, but the exact prognostic factors are unknown. The aim of the present study ...was to analyze the clinical characteristics of patients with IPF-AE and identify the prognostic factors. Methods The medical records of 59 cases of IPF-AE were retrospectively reviewed. Clinical data, laboratory data, radiographic findings, treatment, and time from the onset of symptoms to the initiation of corticosteroid pulse therapy, i.e. symptom duration, and outcome were analyzed. Results The IPF Stage, Gender-Age-Physiology (GAP) Index, symptom duration, and the high-resolution computed tomography (HRCT) score were significantly related to the prognosis in the univariate analysis. In the multivariate analysis, the symptom duration remained a significant prognostic factor (hazard ratio of 1-day increase, 1.11; 95% confidence interval, 1.01-1.15; p=0.0427). The area under the receiver operating characteristics curve of symptom duration was statistically significant for survivors versus non-survivors (area under the curve, 0.73; p=0.012). The survival period was significantly shorter in the late-treatment groups (≥5 days; n=30) than in the early-treatment groups (<5 days; n=29; log-rank test; p<0.0001). Conclusion The time interval between the onset of symptoms and the initiation of corticosteroid pulse therapy may be an independent prognostic factor in patients with IPF-AE.
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