PHYSIOLOGIC AIRWAY RESPONSES TO INHALED HISTAMINE AND ACETYLCHOLINE IN PATIENTS WITH MILD ASTHMA AS ANALYZED BY FORCED OSCILLATION.

BACKGROUND AND AIMS: Asthma is a chronic disease characterized by airway inflammation; it is sometimes difficult to diagnose. For clinical diagnosis, forced oscillation technique (FOT) measures airway reactance and resistance. By FOT, we investigated respiratory resistance and ventilation perfusion ratio inequality in adults with mild asthma. METHODS: We examined 58 adult patients with mild asthma having no inhaled corticosteroid treatment, and 10 adult patients with post-infectious prolonged cough. Using a MostGraph-01 FOT instrument, we evaluated these patients before and after bronchial hyperresponsiveness to acetylcholine (ACh) or histamine (Hist). We measured the following conditions: change of resistance at 5Hz (R5) and 20Hz (R20), R5-R20, reactance at 5Hz, frequency of resonance (Fres), low-frequency reactance area (ALX), and forced expiratory volume in 1 second (FEV1). RESULTS: There were significant changes of R5, R20, R5-R20, X5, Fres, ALX after provocations for ACh or Hist in all patients with asthma, but not in patients with post-infectious prolonged cough. We calculated the percent decrease in FEV1 after provocation with ACh or Hist. For Ach, this decrease in FEV1 correlated with changes in R20 and Fres for all patients. For Hist, the percent decrease in FEV1 correlated with changes in R5, R20, Fres, and ALX for all patients. Furthermore, we investigated these correlations in patients with normalized bronchial hyperresponsiveness to ACh or Hist. For Ach, the percent decrease in FEV1 correlated with changes in Fres or R5-R20. For Hist, this decrease in FEV1 correlated with changes in R5, R20, and Fres. ROC analysis was used to evaluate the diagnostic value of the ratio of change of Fres in BHR to Hist. The area under the curve was 0.7808 (95% CI=0.657-0.904). A reasonably high specificity (100.0%) and a high sensitivity (53.8%) with a cut-off point of 1.5 in the ratio before and after of Fres were obtained. CONCLUSION: The changes in FOT parameters (before and after bronchial airway responses) may detect airway resistance and ventilation perfusion ratio inequality even in adult patients with asthma having normalized bronchial hyperresponsiveness to ACh or Hist. That results may be useful for an early diagnosis of asthma.

Markers for step-down of inhaled corticosteroid therapy in adult asthmatics.

BACKGROUND: Treatment guidelines recommend the use of inhaled corticosteroids (ICS) as first-line therapy for all stages of persistent asthma. However, it is unknown whether ICS dose reduction in adult asthmatics is compatible with maintaining asthma control. Moreover, there are no predictors of efficacy in maintaining asthma control upon ICS reduction. METHODS: We recruited 90 adult patients with moderate or severe asthma but no clinical symptoms of asthma for at least 6 months. All patients reduced their ICS doses by half but continued taking other asthma-related medications. As a primary outcome, we measured asthma exacerbations during the 12 months following ICS reduction. We also further monitored patients from the above study who had maintained total asthma control for 12 months after ICS reduction and who had continued on their reduced doses of ICS or had further reduced, or stopped, their ICS. RESULTS: Forty of ninety patients (44.4%) experienced exacerbations after ICS reduction (time to first exacerbation: 6.4 ± 3.6 months). Multivariate logistic regression modeling revealed a rank order of predictors of success in ICS reduction while retaining asthma control: acetylcholine (ACh) PC(20) (p < 0.01); length of time with no clinical symptoms before ICS reduction (p < 0.01); FeNO (p = 0.028); and forced expiratory volume in 1 s (FEV(1); % predicted) (p = 0.03). Finally thirty-nine of 50 patients maintained total asthma control for at least 2 years after the initial ICS reduction. CONCLUSIONS: In asthma patients with normalized AChPC(20) of 20mg/mL or 10mg/mL and no clinical symptoms for at least 12 or 24 months it may be possible to successfully reduce ICS without increasing exacerbations for long time.

[Use of forced oscillation technique to detect airflow limitations in adult Japanese asthmatics].

BACKGROUND: The forced oscillation technique (FOT) is a noninvasive method that is used to measure respiratory mechanics, including respiratory resistance and reactance at multiple frequencies. The advantage of FOT over spirometry is that FOT does not require forced expiratory maneuvers. Moreover, a new FOT machine called MostGraph (Chest Co. Ltd., Tokyo, Japan), has been developed in Japan, and can be used clinically to diagnose and monitor asthma. The purpose of this study is to show the standard of FOT measured with MostGraph in adult Japanese asthmatics. METHODS: From our outpatient clinic, we recruited 151 stable asthmatics who were being treated with inhaled corticosteroids at the time of the study. For each subject, we measured the fraction of exhaled nitric oxide (FeNO) by using a chemiluminescent nitric oxide analyzer (Sievers280, GE, Boulder, Co); we determined the levels of forced expiratory volume in 1s (%FEV1) and maximum mid-expiratory flow rate (%MMF) by using spirometory; and we measured resistance at 5 Hz(R5), resistance at 20 Hz(R20), R5-R20, reactance at 5 Hz(X5), frequency of resonance (Fres), and low-frequency reactance area (ALX), by using a MostGraph FOT machine. RESULTS: Each of the FOT parameters measured by using the MostGraph machine was significantly correlated with %FEV1 and %MMF (p<0.001), with Fres showing the strongest association. Three of the FOT parameters, X5, Fres, and ALX, were significantly associated with the subject's age (p=0.01, p<0.001, p<0.001, respectively), and all FOT parameters were significantly associated with the subject's body mass index (BMI) (p<0.001 to p=0.018). The results of multiple regression analyses between FOT parameters and FEV1, age, BMI, and FeNO, showed that Fres was significantly associated with FEV1(p<0.001) and BMI (p<0.001). From the results of the simple linear regression between Fres and FEV1, we estimated that Fres values of 17.5 Hz corresponded to %FEV1 values of 60%; Fres values of 11.3 Hz corresponded to %FEV1 values of 80%; and Fres values of 4.94 Hz corresponded to %FEV1 values of 100%. CONCLUSION: FOT parameters measured by using a MostGraph machine can be used successfully to assess the level of airflow limitation in adult stable asthmatics.

CD203c expression on human basophils is associated with asthma exacerbation.

BACKGROUND: CD203c is a basophil cell surface marker used to diagnose and monitor various allergic diseases, but its relationship to asthma is not clear. OBJECTIVE: We determined whether CD203c expression levels are associated with stable and exacerbated asthma. METHODS: We used flow cytometry to compare spontaneous expression levels of surface markers on basophils from patients with stable or exacerbated asthma and from healthy subjects. Longitudinal changes in these expression levels were measured after basophil stimulation by IgE-dependent or IgE-independent mechanisms and compared with patients' asthma status. RESULTS: Spontaneous expression levels of CD203c were significantly higher on basophils from patients with asthma exacerbation than patients with stable asthma or healthy subjects. In contrast, no differences in spontaneous expression levels of CD63 or CD69 were observed among the 3 groups. Anti-IgE-induced expression of CD203c significantly increased in basophils during asthma exacerbation (P = .005). Low concentrations of Dermatophagoides pteronyssinus or IL-3 induced higher expression levels of CD203c during asthma exacerbation than during clinical improvement; induction of CD203c expression by these antigens therefore correlates with asthma control. In the patients with clinical improvement, there was a correlation between spontaneous CD203c expression levels and the percent predicted values of FEV(1) (r = -0.761; P = .022). CONCLUSION: Asthma exacerbation was accompanied by increased expression of CD203c on basophils that decreased significantly during remission. Basophil expression levels of CD203c might therefore be used to monitor asthma in patients.

Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

BACKGROUND: Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. METHODS: We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). RESULTS: 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. CONCLUSIONS: In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

[Differences in fraction of exhaled nitric oxide values measured by two offline methods or NIOXmino in adult Japanese asthmatics].

BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of asthma control. The FeNO measurement with two offline methods and NIOXmino may be more affordable, no studies have examined the differences in FeNO values measured with various methods in adult asthmatics. METHODS: The study population comprised 39 stable asthmatics treated with inhaled steroids at our outpatient clinic. FeNO values were measured by two offline methods (Sievers and CEIS), NIOXmino. RESULTS: FeNO(NIOXmino) values were significantly correlated with those of FeNO(Sievers) (r=0.935, P< 0.001) and FeNOCEIS (r=0.908, P< 0.001). However, FeNO(NIOXmino) values were low compared with FeNO(Sievers) (FeNO(NIOXmino)=0.848 x FeNO(Sievers)) and FeNO(CEIS) (FeNO(NIOXmino)=0.672 x FeNO(CEIS)). CONCLUSION: Differences exist in the values of FeNO measured by various methods: conversion equations are needed to compare the FeNO values among these three methods.

Changes in exhaled nitric oxide measured by two offline methods predict improvements in bronchial hyperresponsiveness after inhaled steroid therapy in Japanese adults with asthma.

BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. No studies have examined the relationship between the change in FeNO levels measured offline and changes in bronchial hyperresponsiveness (BHR) in asthmatic patients treated with inhaled corticosteroids (ICS). The objective of this study was to investigate the relationship between the change in FeNO levels measured offline and the change in BHR to acetylcholine in asthmatic patients taking ICS. METHODS: The study population comprised 41 ICS-treated asthmatics from our outpatient clinic. We measured FeNO levels by two methods -with a Sievers kit ("FeNOs") and with a kit from the Center for Environmental Information Science, Japan ("FeNOc") at baseline and after 1 year of regular treatment. We also used spirometry to test BHR to acetylcholine (PC(20Ach)). RESULTS: The mean of duration of observation was 406 days. There were significant relationships between DeltalogPC(20Ach) and logPC(20Ach) (r = -0.877, P < 0.001), FeNOs (r = 0.465, P = 0.002), and FeNOc (r = 0.524, P = 0.004) at baseline, but not with age, the dose of ICS, FEV(1), or %FEV(1). Moreover, there was a significant relationship between DeltalogPC(20Ach) and DeltaFeNOs (r = -0.386, P = 0.013) and DeltaFeNOc (r = -0.473, P = 0.004), but not with DeltaFEV(1). CONCLUSIONS: Changes in FeNOs and FeNOc correlated with improvements in BHR to acetylcholine in adult asthmatics after ICS therapy. Our findings suggest that offline monitoring of FeNO will facilitate the management of bronchial asthma in patients treated with ICS.

[Relationship between cysteinyl leukotriene in exhaled breath condensate and the severity of asthma in adult asthmatics in Japan].

BACKGROUND: The measurement of several mediators in exhaled breath condensate (EBC) can be useful as the biomarker for asthma. But there are a few reports about EBC of asthmatics in Japan. AIM: We examined the safety of the collection of EBC and the utility of cysteinyl leukotriene (cysLTs) in EBC as the biomarker of asthma. METHODS: Fifty-three asthmatics and eleven subjects without asthma were recruited. After the measuring of exhaled nitric oxide (eNO) and spirometory, EBC were collected. The levels of cysLTs in EBC were measurement by ELISA within 2 months. RESULTS: The collection of EBC did not induce any other symptoms in all subjects. In 48 subjects, the collection significantly increased their FEV1 and MMF level (DeltaFEV1: 2.27+/-0.77%, DeltaMMF 14.6+/-3.92% (mean+/-SEM). The level of cysLTs in EBC on asthmatics treated with high-dose ICS was significantly high compared with control group (p=0.0034), steroid-naïve asthmatics or asthmatics treated with low-dose ICS (steroid naive vs. high dose ICS, p=0.041, low dose ICS vs. high dose ICS, p=0.021). The relationship between cysLTs in EBC and the levels of LTE4 in urine was significantly correlated (n=34, r=0.32, p=0.0435). The relationship between cysLTs in EBC and the levels of eNO was significantly correlated only in steroid-naïve asthmatics (r=-0.57, p=0.0369). There was no relationship between cysLTs in EBC and FEV1, or log PC20Ach. CONCLUSION: The collection of EBC was perfectly non-invasive. The level of cysLTs can be useful as a biomarker of asthma.

[Cutoff point of the fraction of exhaled nitric oxide (FeNO) with the off-line method for diagnosing asthma and the effect of smoking on FeNO].

Evidences have shown that the fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. There is no study to show the FeNO cutoff point for detecting asthma and the influence of smoking, measured by the Sievers Bag collection kit. The study population comprised 60 steroid-naive asthmatic patients (BA) (32 non-smokers, 28 smokers) and 59 patients with chronic cough (CC) without asthma (42 non-smokers, 17 smokers) in our outpatient clinic. We measured FeNO levels, spirometory, bronchial hyperresponsiveness against acetylcholine, and other parameters. The levels of FeNO were significantly increased in asthmatics compared with subjects with chronic cough. According to the ROC curve, the cutoff point of FeNO was 30 ppb (AUC = 0.83, sensitivity 78.1%, specificity 73.5%, p < 0.001) in non-smokers. The levels of FeNO in smokers were not significantly different from those in non-smokers, both bronchial asthma and chronic cough subjects. But the cutoff point of FeNO was 40 ppb (AUC = 0.65, sensitivity 67.8%, specificity 70.6%, p = 0.012). In conclusion, the cutoff point of FeNO was 30 ppb in non-smokers and 40 ppb in smokers. In smokers, FeNO measurement was less useful.

[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.

[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.

[Clinical features of oral allergy syndrome to plant foods allergens in Kanto regions].

BACKGROUND: Recently, it is recognized that the patients of oral allergy syndrome (OAS) to fruits are increasing. However, there are little knowledges of the background, character, and seriousness about these patients in Kanto regions. OBJECTIVE: We aimed to investigate the clinical features of OAS patients to plant origin foods in Kanto regions. METHODS: The patient, who visited Sagamihara National Hospital from 2000 to 2005 and developed some allergic symptoms to plant origin foods, were studied by a questionary survey. RESULTS: As for the 42 subjects, average age are 36 years old, male:female=8:34, merger of other allergic disease is 35 allergic rhinitis of 42 subjects (83%), 34 of asthma (81%), 14 of atopic dermatitis (33%). The causes of OAS symptoms are 32 rose-family fruits, 34 non-rose family fruits, 14 vegetables, 11 nuts, 2 grains subjects. As for the symptom, only in the oral and pharynx symptoms are found in 12, the systemic symptoms is 29, anaphylaxis is 11 subjects. Allergic rhinitis preceded on the 90% subjects with pollinosis, very high rate. On the other hand, the 20% of all subjects have no symptoms of allergic rhinitis. CONCLUSION: A nasal catarrh symptoms went ahead in most of the OAS subjects in Kanto regions. In addition, considering from some patients have no black alder pollinosis and/or are allergic to many non-rose-family fruits at high frequency, there might be a broad cross-reactivity between many pollens other than alder and plant origin foods.

[Summer-type hypersensitivity pneumonitis-immunological examinations in onset and non-onset members].

We examined immunological differences by non-specific and specific stimuli, using Trichosporon asahii (Ta), in 5 subjects in one family. The mother and her eldest daughter, among the 5 subjects in the family, were given diagnoses of summer-type hypersensitivity pneumonitis (HP) as a result of imaging, serological and histological examinations. The symptoms in both cases improved immediately after systemic corticosteroid therapy. Their home environment was cleaned up, and there has been no recurrence. All family subjects showed a positive reaction for the precipitin of Ta crude antigen, in addition four subjects, but not the father, revealed positive reactions for Type II Ta antigen in agglutination tests. In patients with HP, the concentrations of IFN-gamma by anti-CD3 + and anti-CD28 antibody stimulation were lower than those of healthy subjects. The concentrations of IFN-gamma and TNF-alpha for Ta antigen stimulation revealed no differences between the patients and healthy subjects in the family. In conclusion, we could not find any differences between the patients and non-patients in the family from the results of the serological and cytokine production measurement.

[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.

Influence of inhaled corticosteroids on community-acquired pneumonia in patients with bronchial asthma.

OBJECTIVE: The aim of the present study was to evaluate the influence of inhaled corticosteroids (ICS) on community-acquired pneumonia (CAP) in patients with asthma. PATIENTS AND METHODS: All asthmatic patients who required hospitalization for CAP from the beginning of 1989 through December 2001 were enrolled in this retrospective study. Patients who used oral corticosteroids daily were excluded. Patients were divided into two groups based on whether or not they used ICS, and we analyzed clinical characteristics of the pneumonia. Sixty-two patients (28 males, 34 females; mean age, 54.5 years) were enrolled in this study. Thirty-seven of 62 patients used ICS, with the mean dosage being 777.9 microg/day. RESULTS: We found no significant differences between the two groups with regard to mean age, serum albumin level, duration of asthma, pulmonary function and frequency of intravenous infusion of corticosteroids in the outpatient department. There were no significant differences in body temperature, white blood cell count, and CRP value upon admission between the two groups. Differences were not significant in the period of resolution of the pneumonia or in the frequency of pathogens identified between the two groups. CONCLUSION: ICS therapy appears to have no influence on CAP in patients with asthma. We recommend that ICS should be continued to control asthma with adequate antibiotic therapy when asthmatic patients have CAP.

[Management of patients with bronchial asthma received general anesthesia and surgical intervention].

Stimulation to bronchial mucosa is one of the major risk factor of asthma attack. When patients receive surgical intervention and general anesthesia, they are always exposed to stimulation to bronchial mucosa. Prevention method of bronchial asthma attack during surgical intervention is not established yet. We investigated that clinical course of patients with bronchial asthma who received general anesthesia and surgical intervention. Seventy-six patients with bronchial asthma were received general anesthesia and surgical intervention from 1993 to 1998. Twenty-four patients were mild asthmatic patients, 39 were moderate asthmatic patients and 13 were severe asthmatic patients. Preoperative treatment for preventing asthma attack was as follows; Eight patients were given intravenous infusion of aminophylline before operation. Fifty-two patients were given intravenous infusion of aminophylline and hydrocortisone before operation. Three patients were given intravenous infusion of hydrocortisone for consecutive 3 days before operation. Thirteen patients were given no treatment for preventing asthma attack. One patient was suffered from asthma attack during operation. She was given no preventing treatment for asthma attack before operation. Three patients were suffered from asthma attack after operation. No wound dehiscence was observed in all patients. To prevent asthma attack during operation, intravenous infusion of steroid before operation is recommended, when patients with asthma receive general anesthesia and surgical intervention.

[Clinical properties of community-acquired pneumonia in patients with asthma].

PURPOSE: Many reports were found on the clinical properties of community-acquired pneumonia. The clinical properties of community-acquired pneumonia in patients with asthma have not been elucidated, and we therefore investigated such properties. MATERIALS AND METHODS: Asthmatic patients who required hospitalization for community-acquired pneumonia from the beginning of 1989 through the end of 2001 were enrolled in this study. We performed the study in a retrospective manner. Patients were divided into two groups based on severity of their asthma (mild to moderate asthma vs severe asthma), and we studied the clinical properties of the pneumonia. RESULT: No significant difference was seen in body temperature, white blood cell counts, or CRP value on admission between the two groups. No significant difference was seen in the resolving period of the pneumonia. The frequency of common pathogens (Streptococcus pneumoniae + Haemophilus influenzae) was lower in patients with severe asthma. Asthmatic patients not taking daily oral corticosteroids were divided into two groups based on whether or not they were using a inhaled corticosteroid, and we examined the frequency of pathogendetection. The percentage of common pathogens was almost the same in the two groups. CONCLUSION: The frequency of common pathogens was lower in patients with severe asthma than in those with mild to moderate asthma. This fact is worth considering when empiric therapy for pneumonia is performed in patients with asthma. Inhaled corticosteroid therapy seems to have no influence on the pathogens of pneumonia in patients with asthma.

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.