Longitudinal changes in the prevalence of adult asthma: An epidemiological survey among Japanese salaried employees and their dependents using healthcare insurance claim from 1999 to 2019.

BACKGROUND: Information on changes in asthma prevalence and the treatment status for asthma is used as basic information for taking medical and administrative measures against asthma. However, this information among adults is relatively limited. METHODS: To elucidate changes in the prevalence of asthma and treatment status over time among Japanese adults, health insurance claim data from some health insurance societies covering salaried employees and their dependents were studied longitudinally. Claim data from FY1999 to 2007 were obtained from two health insurance societies, and data from FY 2011 to 2019 were obtained from three different health insurance societies, and changes in standardized asthma prevalence among subjects aged 20-59 years, proportion of asthma patients prescribed ICS, leukotriene receptor antagonist (LTRA), and LABA, and the mean number of acute asthma exacerbations per year were analyzed. RESULTS: The prevalence of asthma increased from 1.6% in 1999 to 3.0% in 2007 and 2.9% in 2011 to 4.6% in 2019. Increased trends in asthma prevalence from 2011 to 2019 were more noticeable in subjects in their 50s than those in their 20s for both sexes. The number of emergency visits related to asthma was 1.5 per year in 1999, which decreased to 0.8 per year in 2019. The proportion of people prescribed all anti-asthma medications (ICS, LTRA, and LABA) increased over time. CONCLUSIONS: The prevalence of adult asthma among Japanese salaried employees and their dependents has increased over the last 20 years, suggesting more attention should be paid to the prevention of this disease in adults.

Obesity, but not metabolic syndrome, as a risk factor for late-onset asthma in Japanese women.

BACKGROUND: Several cross-sectional studies have suggested an association between obesity and asthma. However, few studies have investigated this relationship longitudinally, especially in middle-aged subjects. Although metabolic syndrome is a well-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial. METHODS: From 2008, specific health checkups for metabolic syndrome have been conducted throughout Japan. To seek relationships of obesity and metabolic syndrome with late-onset asthma in Japan, we analyzed data collected from health insurance claims and specific health checkups for metabolic syndrome at three large health insurance societies. Among subjects aged 40-64 years (n = 9888), multivariate logistic regression analyses were performed to investigate the relationships of obesity and metabolic syndrome in fiscal year 2012 (from April 2012 to March 2013) with the incidence of late-onset asthma in the following two years (from April 2013 to March 2015). RESULTS: In women, BMI 25-29.9 kg/m2 or ≥30 kg/m2, waist circumference ≥90 cm, and waist-to-height ratio ≥0.5 were shown to be significant risk factors for asthma, with adjusted odds ratios (95% CI) of 1.92 (1.35-2.75), 2.24 (1.23-4.09), 1.89 (1.30-2.75), and 1.53 (1.15-2.03), respectively. Significance was retained even after adjustment for metabolic syndrome, and there were no significant relationships between metabolic syndrome itself and the incidence of asthma in men or women. CONCLUSIONS: Only the obesity measures, not metabolic syndrome, were shown to be significant risk factors for the incidence of late-onset asthma but only in middle-aged Japanese women, and not in men.

Association between body mass index and asthma among Japanese adults: risk within the normal weight range.

BACKGROUND: Increasing amounts of data have shown that some Asian populations are more susceptible to increased weight and development of noncommunicable disease than Western populations. However, little is known about the association between increased weight, particularly within the normal range, and the development of asthma among Asian populations. METHODS: To examine the association between increased body mass index (BMI) and asthma among Japanese adults, data from a nationwide population-based cross-sectional survey of asthma prevalence in Japan were analyzed (n = 22,962; age range 20-79 years). BMIs were classified into 7 categories considering WHO recommendations (cutoff points: 17.00, 18.50, 23.00, 25.00, 27.50 and 30.00), and the association between BMI and the prevalences of asthma as well as asthma symptoms were assessed by multivariate logistic regression. RESULTS: The prevalences of obesity (BMI ≥ 30.00) in this population were relatively low (males 3.0%, females 2.3%). BMI categories of 25.00 or higher in both genders were significantly associated with an increased risk of asthma compared with the reference category (BMI 18.50-22.99). Even in females with a BMI of 23.00-24.99, the prevalence of asthma significantly increased (adjusted odds ratio 1.49, 95% confidence interval 1.16-1.92) compared with that in the reference category. CONCLUSIONS: An increase in the prevalence of asthma among Japanese females starts at a BMI of 23.00, which was relatively lower than those reported from Western countries. This finding suggests that the Japanese population is likely to have asthma with a lesser degree of obesity than Western populations.

[Clinical effects of Lactobacillus acidophilus strain L-55-contained yogurt on symptoms of Japanese cedar pollen allergy].

BACKGROUND: It has been reported that oral administration of Lactobacillus acidophilus strain L-55 (L-55) suppressed nasal symptom and antigen-specific IgE induced by antigen challenge in mice. We investigated clinical effects of L-55-contained yogurt on symptoms and IgE production in the patients with Japanese cedar pollinosis. METHOD: The study was performed as a randomized double blind placebo-controlled trial. L-55-contained yogurt (L-55 yogurt) or placebo yogurt was started to administer to each subject from 4 weeks prior to the onset of Japanese cedar pollen release for total 13 weeks. RESULT: The mean value of symptom score and symptom medication score were lower in L-55 yogurt group compared with placebo yogurt group during 5th week to 9th week from the first week of Japanese cedar pollination. Especially, in medicated subjects, total symptom score and throat symptom score were significantly lower in L-55 yogurt group compared with placebo yogurt group at 5th and 4th week from the first week of Japanese cedar pollination, respectively. Moreover, in medicated subjects, change ratio of serum total IgE was significantly lower in L-55 yogurt group compared with placebo yogurt group at 1st week from the first week of Japanese cedar pollination. CONCLUSION: Intake of L-55 during Japanese cedar pollinating season may be effective in alleviating the allergic symptoms related to Japanese cedar pollinosis. From these finding, it was suggested that L-55 is a possible candidate as a complementary medicine for Japanese cedar pollinosis.

Churg-Strauss syndrome with necrosis of toe tips.

Churg-Strauss syndrome (CSS) is a granulomatous necrotizing vasculitis of unknown etiology associated with bronchial asthma. Despite affecting small to medium-sized vessels, necrosis of the digits due to vasculitis is extremely rare. We report a case of CSS with necrosis of the toe tips. A 37-year-old woman with asthma, who had been diagnosed with CSS 2 years ago, was admitted to our hospital with an exacerbation of CSS. The patient had a high grade fever and complained of abdominal pain and numbness of the lower extremities. Blood examination revealed marked eosinophilia. The fever pattern, abdominal pain and blood eosinophilia showed improvement by combination treatment with prednisolone and cyclophosphamide. However, the color of her right toe tips changed, and necrosis finally resulted despite antithrombotic therapy. Arteriography showed narrowing of the dorsalis pedis artery and of the more peripheral arteries of her right leg. Stump plasty with negative pressure dressing therapy for the toe tips, but not amputation, was done to preserve the leg function. While numbness of the extremities remained, no recurrence of necrosis was seen. Clinicians need to be aware that rare complications of CSS, including necrosis of the digits, can occur.

[The relationships between the peak inspiratory flow and the characteristics factors in the asthmatics with inhaled corticosteroid -a multicenter study in Chugoku Shikoku area].

BACKGROUND: Inhaled corticosteroid (ICS) will be effective if used properly. Inadequate intake may result in insufficiency, such as for elderly asthmatics, in particular, for use of dry powder inhalers. METHODS: 312 asthmatics treated with ICS for at least 6 months in the 6 facilities belonging to the Chugoku Shikoku Adult Asthma Research Forum were subject to investigation of the peak inspiratory flow (PIF) measured using In-check® and related factors. RESULTS: Nine (2.8%) patients were considered to have insufficient intake. By multivariate analysis, PIF (L/min) prediction formula was as follows: 79.0+0.19* peak expiratory flow (PEF: L/min)+22.9* FVC (L)-0.68* onset age (years)+34.7* gender (male, 1; female, 0)+16.1* V50/V25, [r^2=0.677, p<0.0001]. Using cluster analysis with Euclidean distance and Ward's method, the PIF without an adaptor was included in the same category as height and PEF, and the PIF with an adaptor was included in the same category as %FVC and %FEV1.0. CONCLUSION: The cases with insufficient PIF are few but present. Adequate device selection and inhalation guidance may be important. The meaning of PIF differs depending on whether or not an adaptor is present. Further investigation of intake is considered necessary.

Nationwide cross-sectional population-based study on the prevalences of asthma and asthma symptoms among Japanese adults.

BACKGROUND: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects. METHODS: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20-79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire. RESULTS: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20-79 years were 10.1% (95% CI: 9.7-10.5%) and 4.2% (95% CI: 4.0-4.5%), respectively. The prevalences among young adults aged 20-44 years were 9.3% (95% CI: 8.7-9.9%) and 5.3% (95% CI: 4.8-5.8%), respectively. The prevalence of current asthma was highest in females aged 30-39 years in comparison with the other gender and age groups. CONCLUSIONS: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults.

[Survey of asthma control and anti-asthma medication use among Japanese adult patients].

BACKGROUND: The purpose of this study was to clarify disease control and medication use among Japanese adult asthmatic patients. METHOD: We studied the reality of adult outpatients and inpatients with asthma at 26 national hospitals across Japan who visited the clinic between September and October 2006. Anti-asthma medication use and asthma control were assessed. Disease severity was determined according to the 2006 Japanese Guideline. The results of this study were compared with those obtained in 1995 after standardization by age and gender. RESULTS: Of 2524 patients, the prevalence of inhaled corticosteroid use in 2006 was 89%, which was higher than that in 1995 (62%). Although the prevalence of patients who experienced asthma hospitalization once or more in their lifetime in 1995 was 73%, that in 2006 decreased to 49%. The prevalences of hospitalization and unscheduled doctor visit in the last 12 months in 2006 were 8% and 25% respectively. The percentage of patients in 2006 who did not reach an acceptable level of control despite treatment at step 4 of the 2006 Japanese guideline was 15%. CONCLUSIONS: A favorable change in asthma medication use and asthma control was observed from 1995 to 2006; that is, increased prevalence of inhaled corticosteroid use and decreased prevalence of patients who experienced hospitalization for asthma once or more in their lifetime. However, some patients remained symptomatic despite high-dose inhaled corticosteroid treatment.

Inflammatory markers in exhaled breath condensate from patients with asthma.

BACKGROUND AND OBJECTIVE: Evaluation of airway inflammation is important for the diagnosis and treatment of asthma. Exhaled breath condensate (EBC) is a minimally invasive method for assessing inflammation and may be useful for monitoring airway inflammation in asthma. The aims of this study were to establish an EBC collection method, to assess biomarkers reflecting asthmatic airway inflammation, and to determine the relationship of these biomarkers with asthma severity and lung function. METHODS: Fifty-eight non-smoking healthy subjects, seven asymptomatic smokers, nine subjects with common cold and 55 asthmatics with disease severity ranging from mild intermittent to severe persistent were studied. The efficacy of a pipette method was compared with that of a commercial collecting device. pH, CRP, albumin, hydrogen peroxide (H(2)O(2)) and nitrite/nitrate levels were measured in EBC. RESULTS: Except for the quantity of EBC collected and albumin levels, there were no differences between the commercial method and the pipette method in levels of biomarkers measured. Levels of CRP, H(2)O(2) and nitrite/nitrate were significantly higher in the asthma group than that in the control group. In terms of asthma severity, pH and levels of CRP, H(2)O(2) and nitrate were significantly higher in the mild persistent group than that in the other groups. In addition, H(2)O(2) levels in EBC correlated significantly with the level of nitrite/nitrate. FEV(1) and PEF showed significant negative correlations with H(2)O(2) and nitrite/nitrate levels. CONCLUSION: Measurement of EBC biomarkers is a non-invasive and useful way to evaluate airway inflammation in patients with asthma.

Comprehensive pulmonary rehabilitation according to severity of COPD.

A new classification for the severity of COPD was proposed at GOLD 2003: stage I: FEV(1) > or = 80% predicted; stage II: 50% < or = FEV(1)<80%; stage III: 30% < or = FEV(1)<50%; and stage IV: FEV(1) < 30%. To elucidate the acute effects of pulmonary rehabilitation (PR) on patients with different stages of COPD, data on pulmonary function, arterial blood gas analysis, the 6-min walk test, respiratory muscle strength, and activities of daily living were analyzed before and after our comprehensive 4- to 8-week inpatient PR program between 1992 and 2003. A total of 225 patients (201 men and 24 women; 21 with stage II, 79 with stage III, and 125 with stage IV COPD) was assessed. There were significant differences in FEV(1)% predicted and % residual volume in stages III and IV, in % vital capacity in stages II, III and IV, and in % total lung capacity in stage II when comparing the changes between pre- and post-PR. Significant differences of PaO(2) in stages III and IV and PaCO(2) in stage IV were found when comparing the changes between pre- and post-PR. The 6-min walk distance was significantly increased after PR by an average of approximately 50m for all staged patients. Respiratory muscle strength was also significantly increased in stages III and IV. Activities of daily living were significantly improved in all stages. These results showed that patients with COPD had benefited from PR regardless of disease severity. The effects included improvement in pulmonary function, arterial blood gas analysis, 6-min walk distance, respiratory muscle strength, and activities of daily living although there were some differences among the three stages.

Distance and oxygen desaturation in 6-min walk test predict prognosis in COPD patients.

The aim of the present study was to predict the prognosis of Chronic obstructive pulmonary disease (COPD) patients who underwent comprehensive pulmonary rehabilitation (PR). A total of 144 patients who performed PR between 1992 and 1999 was assessed. After PR, 67 patients underwent lung volume reduction surgery (LVRS). Baseline data before PR consisted of body mass index, serum albumin levels, use of supplement oxygen at home, pulmonary function, arterial blood gas analysis, and distance and fall of hemoglobin oxygen saturation (DeltaSpO(2)) in 6-min walk test. In addition to pre-PR factors, treatment with LVRS was taken into the analysis. The prognostic significance of variables influencing survival was determined by univariate analysis with Log rank test or multivariate analysis using Cox's proportional hazard model. By a median follow-up time of 8.4 years, the median survival time was 8.1 years (95% confidence interval: 6.9-9.4 years). Albumin level, PaCO(2), distance and DeltaSpO(2) were significant prognostic factors in univariate analysis. LVRS did not affect the prognosis. The multivariate analysis showed short distance and increase of DeltaSpO(2) as significant independent predictors of the risk of death. 6-min walk test was very useful for predicting the prognosis of the COPD patients.

The combination effect of amrubicin with cisplatin or irinotecan for small-cell lung cancer cells.

The single agent of amrubicin is active in untreated small-cell lung cancer (SCLC). Cytotoxicity of amrubicinol, the active form of amrubicin, was evaluated in a parent SCLC cell line (SBC-3); an active metabolite of irinotecan, 7-ethyl-10-hydroxy-camptothecin (SN-38)-resistant subline (SBC-3/SN-38); and cisplatin-resistant subline (SBC-3/CDDP) using AlamarBlue assay. Interaction of the combined drugs was evaluated by median-effect plot analysis, and the fraction of apoptotic cells was determined using flow cytometry. SBC-3/SN-38 was 34-fold more resistant to SN-38 and SBC-3/CDDP was 7.2-fold more resistant to cisplatin than parental SBC-3. However, these resistant sublines retained sensitivity to amrubicinol (1.8- and 1.7-fold, respectively). Simultaneous exposure of SBC-3/SN-38 cells to amrubicinol and cisplatin showed a synergistic effect. Simultaneous exposure of SBC-3/CDDP cells to amrubicinol and SN-38 displayed synergistic or additive effects. The two-drug combination produced an increase of apoptotic cells compared to each single agent alone in both resistant cells. These findings suggest that amrubicin alone and in combination with cisplatin or irinotecan is effective against SCLC refractory to irinotecan and/or cisplatin.

Preparation of 7-Halo-indoles by Thallation of N-formylindoline and their attempted use for synthesis of the right-hand segment of chloropeptin.

7-Substituted (Cl, Br, I) indoles were synthesized by using thallation of N-formylindoline as a key reaction. Two precursor tripeptides for the right-hand segment of chloropeptin were synthesized by using (R)-7'-iodo and 7'-bromotryptophans derived from each 7-substituted indole (I, Br) obtained by the above procedure.

[In vitro antituberculous activity of ofloxacin and levofloxacin against multidrug-resistant tuberculosis and clinical outcomes].

OBJECTIVE: To investigate in vitro antituberculous activity of ofloxacin (OFLX) and levofloxacin (LVFX) against multidrug-resistant tuberculosis and to study the clinical outcomes. SUBJECTS AND METHODS: In vitro antituberculous activity of OFLX and LVFX against multidrug-resistant strains of Mycobacterium tuberculosis isolated from 46 patients with pulmonary tuberculosis and a retropective clinical analysis of 45 patients were investigated. RESULTS: In susceptibility testing, resistance rates to OFLX or LVFX were higher in intractable cases (7/20: 35%) and in cases with prior chemotherapy using new quinolones (5/12: 42 %). Sputum culture conversion was observed in 34 patients (76%), however 9 among them later reverted to positive culture. In a single variate proportional hazards model, risk factors related to poor outcomes (treatment failure or relapse) were resistance to OFLX or LVFX, advanced disease on chest radiograph, and the number of susceptible drugs four or less. In a multiple variate proportional hazards model, a risk factor was resistance to OFLX or LVFX. Eighteen patients (40%) died, and among them, 10 died of tuberculosis. Survival time of treatment failure patients was significantly shorter than patients with sputum culture conversion. CONCLUSION: Resistance to OFLX or LVFX was considered to be a risk factor related to treatment failure and relapse in multidrug-resistant tuberculosis.

Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults.

OBJECTIVE: A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population. METHODS: We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index ≥ 25kg/m2) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation. RESULTS: In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72-0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09-1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI:1.05-2.38) for obesity. CONCLUSIONS: In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered.

Focal tuberculous lymphadenitis in an HIV-1 infected patient.

A 41-year-old man was admitted to the hospital because of focal swelling of the left supraclavicular lymph nodes. Eighteen months prior to admission, he had been diagnosed with human immunodeficiency virus type 1 (HIV-1) infection and was started on highly active antiretroviral therapy (HAART). He responded well to HAART with an increase in CD4+ cell count and improvement in symptoms. However, one year after the initiation of HAART, he developed progressive enlargement of left supraclavicular lymph nodes. An excisional lymph node biopsy was performed for diagnosis, which revealed tuberculous lymphadenitis. Rifabutin, isoniazid, and ethambutol were initiated for treatment.

[Pulmonary tuberculosis case with consistant findings of endobronchial spread in chest roentogenography for about three years: a case report].

We reported a case of pulmonary infection by Mycobacterium tuberculosis complicated by endobronchial spread. Chest roentogenography and CT for an 85-year-old male complaining of cough showed endobronchial spread in right upper lung field. His sputum culture for eight weeks showed 10-20 colonies of Mycobacterium tuberculosis. Transbronchial lung biopsy revealed granulomas with caseous necrosis. Findings in chest XP and CT after the therapy with INH, RFP and EB for six months showed much improvement.

[Tumor markers in pleural effusion of patients with lung cancer and patients with tuberculous pleurisy].

Carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), NCC-ST-439, carbohydrate antigen 19-9 (CA 19-9), cytokeratin 19 fragment (CYFRA 21-1), sialyl Lewis X-i antigen (SLX), progastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) were evaluated in the pleural effusion of 39 patients with lung cancer (29 adenocarcinomas, seven small-cell carcinomas, three squamous cell carcinomas) and 43 patients with tuberculous pleurisy. The levels of the tumor markers other than SCC and NSE were significantly higher in lung cancer than in tuberculosis. High levels of CYFRA 21-1 and SCC were observed in squamous cell carcinoma and high levels of ProGRP and NSE were observed in small-cell carcinoma. According to the validity score, sensitivity (%) + specificity (%) - 100, the optimal cut-off levels of pleural effusion were 8.1 ng/ml for CEA, 660 U/ml for CA 125, 2.6 U/ml for NCC-ST-439, 10 U/ml for CA 19-9, 65 ng/ml for CYFRA 21-1, 140 U/ml for SLX, 23.2 pg/ml for ProGRP, 0.6 ng/ml for SCC and 5 ng/ml for NSE. By comparison of validity scores for each optimal cut-off level and of receiver operating characteristic (ROC) curves, we suggest that a CEA assay is the most useful for pleural effusion. The combined assay of CEA + ProGRP and CEA + ProGRP + CYFRA 21-1 were considered to be useful.

[Interstitial pneumonia due to gefitinib followed in detail by high-resolution CT in a patient with adenocarcinoma of the lung].

We describe the case of a 69-year-old woman with advanced adenocarcinoma of the lung, in whom interstitial pneumonia was induced by gefitinib. The shadow was not clear on chest radiography, but diffuse ground-glass opacity was detected on high-resolution CT. Two treatments with pulse corticosteroids improved the lung injury temporarily. However, it became worse on reduction of the steroids. The improvement and deterioration of the pneumonia had been followed in detail by 8 examinations by high-resolution CT. The ground-glass opacity seen in the CT did not completely disappear or progress rapidly under steroid therapy. The patient died 46 days after the onset of the pneumonia. Autopsy disclosed marked cancerous invasion of the lung, and diffuse alveolar damage was also recognized in parts. The cause of death was considered to be respiratory failure due mainly to cancer progression and additionally to diffuse alveolar damage induced by gefitinib.