[The methodological aspects of nasal and exhaled nitric oxide levels in adult Japanese asthmatics].

BACKGROUND: Because both allergic rhinitis and asthma are caused by eosinophilic airway inflammation, using the same method to measure the eosinophilic inflammation of both the upper and lower airway would be advantageous. The levels of nitric oxide in exhaled air (FeNO) and nasal air (nNO) are useful as noninvasive markers of eosinophilic airway inflammation. Although the off-line method of measuring these parameters is easier and more useful than the on-line method, studies using the off-line method are rare in Japan. METHODS: In Study 1, we measured the levels of nNO and FeNO in 9 healthy controls and 9 subjects with allergic rhinitis, to validate the methodology for using the off-line method to measure nNO. In Study 2, we measured the nNO and FeNO levels of and performed spirometry on 69 stable asthmatics treated with inhaled corticosteroid. RESULTS: In Study 1, nNO levels were significantly increased in patients with allergic rhinitis compared with healthy subjects (31.0 [20.8 to 41.2] versus 7.4 [0.0 to 14.8] ppb {median [95% confidence interval]}, p=0.018). The 69 patients with asthma that comprised the study population in Study 2 were classified as asthmatics with rhinitis (treatment-naïve, n=14; treated with antiallergic drugs, n=11; treated with intranasal corticosteroid, n=19) and asthmatics without rhinitis (n=15). Although FeNO did not differ among groups, nNO was significantly increased in treatment-naïve asthmatics with rhinitis compared with patients with asthma only (26.5 [17.1 to 35.9] versus 8.0 [-1.1 to 17.1] ppb, p=0.033). CONCLUSION: nNO levels measured by the off-line method are useful markers of allergic rhinitis.

Relationship between exhaled nitric oxide measured by two offline methods and bronchial hyperresponsiveness in Japanese adults with asthma.

BACKGROUND: Exhaled nitric oxide (eNO) is a useful marker of eosinophilic airway inflammation in asthmatics. There have been no studies to show the relationship between eNO measured by offline methods and the degree of bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids. METHODS: The study population comprised asthmatics at our outpatient clinic. We measured eNO levels by two methods ("eNOs" was measured with a Sievers kit; and "eNOc" was measured with a kit from the Center for Environmental Information Science, Japan). We also used spirometry to test bronchial hyperresponsiveness to acetylcholine (PC(20Ach)). RESULTS: We recruited 192 stable asthmatics. There was a significant relationship between eNOs and eNOc (r = 0.919, p < 0.001). LogPC(20Ach) levels were negatively correlated with eNOs or eNOc levels (eNOs, r = -0.31, p < 0.001; eNOc, r = -0.23, p = 0.0013). We classified the subjects into two groups based on eNOs levels ((A) the subjects with high eNOs levels (n = 92) and (B) the subjects with normal eNOs levels (n = 100)) ; logPC(20Ach) was significantly correlated with eNOs (r = -0.34, p = 0.001) or eNOc (r = -0.28, p = 0.0075) but not correlated with %FEV(1) in (A), whereas logPC(20Ach) was not significantly correlated with eNO but significantly correlated with %FEV(1) (r = 0.33, p = 0.002) in (B). CONCLUSIONS: Levels of eNOs and eNOc were correlated with the degree of bronchial hyperresponsiveness to acetylcholine in adult asthmatics treated with inhaled corticosteroids. Our findings suggest that offline monitoring of eNO will facilitate the management of bronchial asthma in patients treated with these drugs.

[The effect of inhaled corticosteroid on the fraction of exhaled nitric oxide (FeNO) with off-line method in adult Japanese asthmatics].

BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of asthma control. The FeNO measurement with our offline method using SIEVERS bag collection kit may be more affordable, but there have been no studies to show the effect of anti-asthmatic therapy on FeNO with our offline method. METHODS: The study population comprised 36 steroid-naïve asthmatics at our outpatient clinic. We treated them according to asthma prevention and management guideline 2006, Japan. We also measured eNO levels by our offline method and spirometory on baseline, 4weeks, and 12 weeks of treatment. RESULTS: All asthmatics were symptom-free on 12 weeks of treatment. The levels of FeNO FEV1/FVC were significantly decreased on 4 weeks and 12 weeks of treatment, compared with that on first visit. We classified the subjects into two groups; (A) FEV1/FVC <70% (n=11) or (B) FEV1/FVC > or =70% (n=25) on baseline. In (A) group, the level of FeNO and FEV1/FVC were significantly improved on 4 and 12 weeks of treatment. In (B) group, on 4 weeks of treatment, the level of FEV1/FVC was significantly increased but the level of FeNO was not significantly changed. On 12 weeks of treatment, the levels of FeNO was significantly decreased, but the level of FEV1/FVC was not significantly changed. CONCLUSION: The levels of FeNO were decreased by antiasthmatic therapy, so that offline monitoring of eNO will facilitate the management of bronchial asthma in patients treated with these drugs.

A retrospective study of bronchial hyperresponsiveness in patients with asthma before the onset of Churg-Strauss syndrome.

Asthma is one of the most common clinical symptoms in Churg-Strauss syndrome (CSS). However, it is not known how lung function and bronchial hyperresponsiveness (BHR) prior to the development of CSS differs from asthmatics do not develop CSS. This retrospective cohort study was conducted to predict the onset of CSS and facilitate diagnosis in the early phase of the disease. We examined 24 pre-CSS asthmatic patients and 294 non-CSS asthmatic patients for clinical features, percent forced expiratory volume at 1 second (%FEV1), BHR to acetylcholine, and evaluated eosinophils (%) in the peripheral blood at their first hospital visit for asthma treatment. All of the 24 pre-CSS patients had adult-onset asthma. The asthma of 87.5% of pre-CSS patients at the first hospital visit before the onset of CSS was severe and was complicated by sinusitis. The eosinophils (%) in the peripheral blood was significantly higher than in non-CSS asthmatic patients. The %FEV1 in both the patients with severe asthma and the patients who developed CSS was lower than in patients with mild or moderate asthma. However, BHR in pre-CSS patients was significantly better than in non-CSS patients with severe asthma and was as mild as in patients with mild asthma. Patients who developed CSS had clinically severe asthma before the onset of CSS. The severity of their asthma was related to airflow limitation and eosinophilic inflammation in the peripheral blood, but not to BHR. These findings should prove useful in future early diagnosis and treatment of CSS.

[The change of exhaled nitric oxide levels in early response after inhaled antigen in antigen-specific provocation test].

BACKGROUND: Inhaled antigen increases exhaled nitric oxide (eNO) in atopic asthmatics. Recent study showed that the increase of eNO levels was observed in late response (8-10 hours after inhaled antigen) but not in early response (1.5 hour after inhaled antigen). But we recognized that in some asthmatics eNO levels were increased during early response induced by antigen. METHODS: Atopic stable subjects with asthma induced by specific antigen (mite 11, housedust 3) were recruited in this study. Through bronchial provocation test with Mite or Housedust antigen, eNO levels were examined. As the control group, 7 atopic asthmatics who were not induced by specific antigen were recruited. RESULTS: In 7 subjects, the levels of eNO were increased during early response after inhaled antigen, and in other 7 subjects the levels of eNO were decreased. There were significant difference in the falling of FEV1 at threshold between the two groups (eNO increased group vs eNO decreased group, 22.1+/-0.87 (%) vs. 44.2+/-6.57 (%), p=0.016). In 6 subjects in control group, the levels of eNO were decreased. CONCLUSION: Inhaled antigen increased the levels of eNO in some asthmatics during early response in bronchial provocation test. The level of eNO has possibility of predicting the sudden decrease of FEV1 in bronchial provocation test.

[The methodological aspects of off-line sampling of exhaled air for nitric oxide measurement in Japanese].

The measurement of exhaled nitric oxide (eNO) is a non-invasive biomarker of bronchial inflammation. Despite the usefulness of eNO measurement, NO analyzers are too expensive for widespread use by general practitioners. In comparison, the off-line (bag collection) method of eNO measurement may be more useful. In Japan, however, there have been few studies about eNO in asthmatics using the off-line method. This study shows methodological aspects of the off-line method. Briefly, with a SIEVERS bag collection kit, we recommend that the flow rate and pressure level of exhaled air should be 70 ml/sec and 10 cm H2O, respectively and that the sampled air should be measured within 12 hours.

Familial Churg-Strauss syndrome in two sisters.

Churg-Strauss syndrome (CSS) is an uncommon systemic vasculitis with an increase in the number of eosinophils in the peripheral blood and tissues. Its pathogenesis is unknown, and there is no evidence that genetic factors influence susceptibility to this disease. We present a case of familial CSS in two sisters with atopic-type bronchial asthma and negative perinuclear anti-neutrophil cytoplasmic antibody results. We investigated the human leukocyte antigen typing of the sisters and their six living siblings but found no evidence for heritability of CSS. To our knowledge, this is the first report of familial CSS.

The relationship between exhaled nitric oxide measured with an off-line method and airway reversible obstruction in Japanese adults with asthma.

BACKGROUND: Exhaled nitric oxide (eNO) is a useful marker of eosinophilic airway inflammation in asthma patients. There is no study to show the relationship between the eNO measured by using an off-line method and the degree of reversibility of airflow limitation in Japanese asthma patients. We sought to investigate the relationship between the eNO level measured by using an off-line method and the degree of reversibility of bronchial constriction in Japanese asthma patients. METHODS: The study population comprised 97 asthma patients in our outpatient clinic with some patients in both groups who received inhaled corticosteroid treatment. We measured eNO levels, forced expiratory volume in one second (FEV1) before and after treatment, reversible airway obstruction (DeltaFEV1) after inhalation of bronchodilator, and other parameters. RESULTS: eNO was significantly correlated with peripheral blood eosinophil counts in asthma patients (in steroid-naïve asthma patients, r=0.544, p<0.0001; in asthma patients treated with inhaled corticosteroid, r=0.463, p=0.026), and subjects with severe eosinophilia in sputum showed high levels of eNO (mild eosinophilia versus severe, p=0.0152). Among patients with obstructive impairment, eNO levels were correlated with DeltaFEV1 regardless of whether patients received (r=0.527, p=0.0435) or did not receive (r=0.64, p = 0.0056) inhaled corticosteroid. In subjects with normal pulmonary function, there was no significant relationship between eNO and DeltaFEV1 with or without inhaled corticosteroid. CONCLUSIONS: In patients with obstructive impairment, eNO reflects the degree of reversible airflow limitation. In subjects with normal pulmonary function, eNO may facilitate the diagnosis and management of asthma, rather than indicate reversible bronchial obstruction. eNO measurement by off-line methods is applicable as a potential tool for the diagnosis of asthma and management of asthma patients.

[Prognosis of bronchial asthma in adults].

BACKGROUND: The prognosis of adult asthma, whether a long-term remission is available, is still unknown. In this paper we investigated the prognosis of adult asthma patients. METHODS We sent a questionnaire by mail to 1168 patients who had been taken care in our clinic until 1990-1992, but disappeared afterward. Those patients were asked their present status of clinical condition of asthma including symptoms, medication, etc. RESULTS: Delivery of mail was failed in 370 patients because of changed address. 430 of 798 patients replied the mail and 86 patients out of 430 patients were in remission state with no symptom without any medications. The characterictis of these patients in remission are early hospital visit after developing asthma, mild in severity, mild in obstructive lung function and mild in bronchial hypersensitivity to acetylcholine at the first visit hospital. CONCLUSION: We concluded that some of adult asthmatic patients might become in clinical remission.

[Antigenic analysis of patients with asthma contracting by exposure to different species of pet hamsters].

BACKGROUND: Hamster-specific IgE antibodies as measured by currently available CAP-RAST tests are used to diagnose allergies associated with exposure to pet hamsters. Among patients with asthma attributed to hamsters, only about 60% are positive for hamster-specific IgE antibodies. We examined whether the results of CAP-RAST tests are related to differences in species-related antigens. METHODS: Currently available mixed specific IgE antibodies against European hamster and Golden hamster antigens (e84) were combined with Djungarian hamster epidermis to produce 3-species mixed specific antibodies. Correlations between results obtained with these mixed antibodies, those obtained with e84 and Djungarian hamster specific IgE antibody were examined in 20 patients with asthma who kept hamsters as pets. In addition, immunoblotting was used to analyze antigens in 9 patients. RESULTS: There was no correlation between results obtained with e84 and those obtained with Djungarian hamster antibody. Results obtained with 3-species mixed specific IgE antibodies positively correlated with those obtained with Djungarian hamster antibody. A specific binding protein for 67-kDa protein were found in patients who tested positive for e84 and Djungarian hamster antibody. A specific binding protein for 20-kDa protein were found in patients positive for only Djungarian hamster antibody. CONCLUSION: The main allergens differ among Golden hamsters, European hamsters, and dwarf Djungarian hamsters.

Adrenal function as assessed by low-dose adrenocorticotropin hormone test before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate.

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 microg/L 73 m2) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33-77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200-900 microg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200-600 microg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6-7.9 microg/dL, p < 0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p < 0.01; evening: 67.3 to 72.1%, both p < 0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p < 0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.