Lung Sound Analysis Is Useful for Monitoring Therapy in Patients With Bronchial Asthma.

BACKGROUND AND OBJECTIVE: Lung sound analysis (LSA) has been reported to be useful for predicting airway obstruction and inflammation in patients with bronchial asthma. Objectives: We examined whether the exhalation-to-inhalation sound pressure ratio in the middle frequency range (200-400 Hz) (E/I MF) is useful for monitoring therapy in patients with asthma. METHODS: The study population comprised 84 patients with mild to moderate asthma whose LSA data were available before and after 1 year of daily treatment with (budesonide 800 µg). We analyzed whether the E/I MF before and after treatment was associated with the fractional exhaled nitric oxide (FeNO) level, sputum eosinophil percentage, respiratory function, and airway hyperresponsiveness. RESULTS: Prior to treatment with budesonide, the E/I MF was significantly correlated with respiratory function, airway hyperresponsiveness, FeNO, and sputum eosinophil percentage. The cutoff values for the E/I MF to detect the abnormalities of respiratory function, FeNO, and sputum eosinophil percentage were 0.367, 0.358, and 0.363, respectively. With respect to the reference value, the E/I MF improved significantly in patients whose respiratory function and FeNO benefited from therapy with budesonide compared with patients whose respiratory function did not benefit from budesonide (odds ratios of 6.39 and 4.78, respectively). According to the multivariate analysis, patients whose E/I MF did not improve had a longer history of smoking (P=.038), poorer posttreatment respiratory function (P=.028), and higher posttreatment FeNO (P=.0095). CONCLUSIONS: Similar to respiratory function and FeNO, E/I MF based on LSA is a useful indicator for monitoring the efficacy of therapy in asthmatic patients.

Lung sound analysis is useful for monitoring therapy in patients with bronchial asthma

Background: Lung sound analysis (LSA) has been reported to be useful for predicting airway obstruction and inflammation in patients with bronchial asthma. Objectives: We examined whether the exhalation-to-inhalation sound pressure ratio in the middle frequency range (200-400 Hz) (E/I MF) is useful for monitoring therapy in patients with asthma. Methods: The study population comprised 84 patients with mild to moderate asthma whose LSA data were available before and after 1 year of daily treatment with (budesonide 800 μg). We analyzed whether the E/I MF before and after treatment was associated with the fractional exhaled nitric oxide (FeNO) level, sputum eosinophil percentage, respiratory function, and airway hyperresponsiveness. Results: Prior to treatment with budesonide, the E/I MF was significantly correlated with respiratory function, airway hyperresponsiveness, FeNO, and sputum eosinophil percentage. The cutoff values for the E/I MF to detect the abnormalities of respiratory function, FeNO, and sputum eosinophil percentage were 0.367, 0.358, and 0.363, respectively. With respect to the reference value, the E/I MF improved significantly in patients whose respiratory function and FeNO benefited from therapy with budesonide compared with patients whose respiratory function did not benefit from budesonide (odds ratios of 6.39 and 4.78, respectively). According to the multivariate analysis, patients whose E/I MF did not improve had a longer history of smoking (P=.038), poorer posttreatment respiratory function (P=.028), and higher posttreatment FeNO (P=.0095). Conclusion: Similar to respiratory function and FeNO, E/I MF based on LSA is a useful indicator for monitoring the efficacy of therapy in asthmatic patients (AU)

Introducción: El análisis de los sonidos pulmonares ha demostrado ser una prueba de utilidad para objetivar la presencia de obstrucción e inflamación en las vías respiratorias de pacientes con asma bronquial. Objetivos: Hemos evaluado si el cociente sonido inspiración-espiración por presión en el rango de frecuencias medias, de 200 a 400 Hz, (E/I MF) tenía utilidad en la evaluación de la respuesta al tratamiento en pacientes con asma bronquial. Métodos: El estudio incluyó 84 pacientes con asma leve o moderada que tuvieran registros de LSA antes y tras un año de tratamiento con 800 μg de budesonida inhalada. Analizamos si los cambios en E/I MF tras el tratamiento se correlacionaban con los cambios en los niveles de óxido nítrico en aire exhalado (FeNO), el porcentaje de eosinófilos en muestras de esputo inducido, la función pulmonar y la hiperreactividad bronquial. Resultados: Antes de iniciar el tratamiento con budesonida inhalada, el cociente E/I MF se correlacionaba significativamente con la función pulmonar, la hiperreactividad bronquial, los niveles de FeNO y el porcentaje de eosinófilos en las muestras de esputo. Los puntos de corte del cociente E/I MF para detectar valores anómalos en la función pulmonar, los niveles de FeNO, y el porcentaje de eosinófilos en esputo eran 0,367, 0,358 y 0,363 respectivamente. El cociente E/I MF mejoraba significativamente en el grupo de pacientes en los que la budesonida inhalada inducía cambios significativos en la función pulmonar o en los niveles, con respecto a los valores de referencia apropiados comparados con los de los grupos de pacientes que no presentaban mejoría en estos parámetros (odds ratios de 6,39 y 4,78, respectivamente). En un análisis multivariante los pacientes que no presentaban mejoras significativas en el cociente E/I MF presentaban una historia de tabaquismo activo significativamente más larga (p=,038), unos niveles de función pulmonar tras tratamiento significativamente más bajos (p=,028), y paralelamente unos niveles de FeNO, tras tratamiento, más elevados (p=,0095). Conclusiones: Al igual que la función pulmonar y los niveles de FeNO, el cociente E/I MF obtenido mediante el LSA es un indicador útil para evaluar la eficacia del tratamiento en pacientes con asma bronquial (AU)

Association of serum arginase I with L-arginine, 3-nitrotyrosine, and exhaled nitric oxide in healthy Japanese workers.

The associations of serum arginase I with serum L-arginine, serum 3-nitrotyrosine, and fractional exhaled nitric oxide (FENO) were evaluated cross-sectionally in healthy Japanese workers. The serum median (minimum-maximum) levels of arginase I, 3-nitrotyrosine, and FENO in healthy people (n = 130) were 14.6 (0.94-108.1) ng/mL, 81.0 (0.27-298.6) pmol/mg protein, and 14.0 (5.0-110.0) parts per billion, respectively. Significant correlations of arginase I with FENO, L-arginine, 3-nitrotyrosine, and percent predicted forced expiratory volume in 1 s (FEV1 (% predicted)) were observed, and correlations of FENO with immunoglobulin E (IgE), NOx, arginase I, and sex and allergy were also observed. By multiple regression analysis, arginase I showed positive associations with FENO and 3-nitrotyrosine, and a negative association with L-arginine; and FENO showed positive associations with IgE and NO2(-) + NO3(-) (NOx), and a negative association with L-arginine, as well as an association with sex. Moreover, logistic regression analysis showed linear inverse associations of arginase I and 3-nitrotyrosine with L-arginine, and showed linear positive associations of FENO with IgE and NOx. It was concluded that serum arginase I might regulate serum L-arginine and 3-nitrotyrosine via L-arginine, and that IgE or NOx might regulate FENO in a healthy Japanese population.

Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children.

BACKGROUND: The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo. METHODS: We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide. RESULTS: At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms. CONCLUSIONS: Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens.

Clinical evaluation of the QuantiFERON-TB Gold test in patients with non-tuberculous mycobacterial disease.

OBJECTIVE: To evaluate the clinical usefulness of the QuantiFERON TB-2G (QFT-2G) test in patients with non-tuberculous mycobacterial (NTM) disease without a previous history of tuberculosis (TB). METHODS: The study consisted of 214 patients with NTM disease who satisfied the diagnostic guidelines of the American Thoracic Society. RESULTS: The causative microorganism was Mycobacterium avium in 83 patients, M. intracellulare in 80, M. kansasii in 33, M. marinum in 12, M. szulgai in 3, M. abscessus in 2 and M. chelonei in 1. The positive response rate of QFT-2G test result was 2% in 163 patients with M. avium-intracellulare complex (MAIC) disease, 52% in 33 with M. kansasii disease, 58% in 12 with M. marinum disease, 33% in 3 with M. szulgai disease, 0% in two with M. abscessus disease and 0% in one with M. chelonei disease. The positivity of the QFT-2G test was 52% in patients with NTM disease, thought to be because NTM possesses common M. tuberculosis-specific antigens. CONCLUSIONS: Although QFT-2G may be a useful diagnostic method to differentiate TB from MAIC disease, there are several problems to be resolved before it can be used as a diagnostic method for NTM disease (M. kansasii disease), including the determination of the positive cut-off level for QFT-2G test.

Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice.

The present authors assessed risk factors that can promote indeterminate results of QuantiFERON TB-2G (QFT-2G; Cellestis Ltd, Carnegie, Australia) tests. The subjects were 704 patients with suspected tuberculosis (TB) and latent TB infection between January 2005 and December 2007. The QFT-2G test and the tuberculin skin test (TST) were performed for all subjects. If the results of the QFT-2G test were indeterminate, the test was repeated within 1 month. In total, 72 (10.2%) patients showed indeterminate results on the QFT-2G test. Indeterminate results were due to positive control failure in 68 (88.9%) patients and negative control failure in four patients. The results of the TST were negative for 64 patients showing indeterminate results, the remaining eight patients showed a positive response to the TST. Indeterminate results were significantly associated with elderly and immunocompromised patients. Lymphocytopaenia and hypoalbuminaemia were significantly associated with indeterminate laboratory findings. When the QFT-2G test was repeated for all patients showing indeterminate results, 12 (16.7%) patients demonstrated determinate results on the subsequent test. Indeterminate results of the QuantiFERON TB-2G test under routine clinical practice are not infrequent. When scoring QuantiFERON TB-2G test results for elderly and immunocompromised patients, one must be careful because the possibility of obtaining determinate results may be low even if the test is repeated.

Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients.

The usefulness of the tuberculin skin test (TST) and the QuantiFERON TB-2G (QFT-TB) test were compared in immunocompromised patients. The subjects consisted of 252 immunocompromised patients who were clinically suspected of tuberculosis (TB) infection between April 2005 and December 2006. Regarding the underlying diseases, 74 subjects had malignant diseases, 72 were undergoing immunosuppressive treatment, 52 had diabetes mellitus, 50 had chronic renal failure and four had HIV infection. While the positive rate of the QFT-TB test for the diagnosis of TB infection (TB disease or latent TB infection) was 78.1%, that of TST for TB infection was 50.0%. The QFT-TB test was significantly better than TST. However, 32 (13%) patients had an indeterminate QFT-TB result. Indeterminate findings were significantly more frequent in patients receiving immunosuppressive treatment (28%), especially with lymphocytopaenia in the peripheral blood, than in those who had other underlying diseases. While TST-positive and QFT-TB test-negative results were recognised in immunocompromised patients with bacille Calmette-Guérin vaccination or nontuberculous mycobacterial disease, TST-negative and QFT-TB test-positive results were recognised in immunocompromised patients with a past history of TB infection. It was concluded that the QuantiFERON TB-2G test is a more useful diagnostic method for tuberculosis infection than tuberculin skin test for immunocompromised patients suspected of tuberculosis disease. However, because the results of the QuantiFERON TB-2G test show an indeterminate response for patients receiving immunosuppressive treatment, especially for those with lymphocytopaenia due to severe underlying diseases, care must be taken in the interpretation of the QuantiFERON TB-2G test for these patients.

Effects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cells.

BACKGROUND: Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. beta2-agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. OBJECTIVES: To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. METHODS: Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. RESULTS: Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in beta2-agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. CONCLUSIONS: Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting beta2-agonists do not modify DCs-induced allergic airway inflammation.

Effects of primary and secondary low-grade respiratory syncytial virus infections in a murine model of asthma.

BACKGROUND: Respiratory syncytial virus (RSV) infection is known to develop and exacerbate asthma in young children. In adult, RSV causes recurrent but asymptomatic infections. However, the impact of asymptomatic RSV infection on adult asthma is yet to be determined. The present study is designed to determine the effects of primary and secondary low-grade RSV infections on allergic airway inflammation in a murine model of allergic asthma. METHODS: A low-grade RSV (2 x 10(3) plaque-forming units/mouse) was inoculated, and this caused neither pulmonary inflammation nor symptoms but induced significant IFN-gamma production in thoracic lymph nodes. To investigate interaction between low-grade virus and Dermatophagoides farinae (Df), airway hyper-responsiveness, lung inflammation and cytokine production from thoracic lymph nodes were compared after primary and secondary low-grade RSV infections in four groups of mice; control, Df allergen-sensitized, RSV-infected and Df-sensitized RSV-infected mice. A direct comparison between low- and high-grade RSV infections was also performed in primary infection. To investigate the role of IL-5 during secondary RSV infection, anti-IL-5 monoclonal antibody (anti-IL-5 mAb) was injected in mice and similar parameters were compared in four groups of mice. RESULTS: Primary high-grade RSV infection increased allergen-induced airway inflammation, while primary low-grade RSV infection attenuated allergen-induced airway inflammation concomitant with significant IFN-gamma production in lung-draining lymph nodes. In marked contrast, secondary low-grade RSV infection increased both IFN-gamma and IL-5 production, resulting in exacerbation of allergen-induced airway inflammation. Anti-IL-5 mAb treatment in secondary low-grade RSV infection and Df allergen-sensitized mice attenuated virus and allergen-induced airway inflammation. CONCLUSIONS: Low-grade RSV infection per se does not cause pulmonary inflammation, whereas it induces a significant immunological response in the allergen-sensitized host. These results indicate that subclinical and recurrent RSV infection may play an important role in exacerbation and maintenance of asthma in adults, wherein IL-5 is critically involved.

No effect of montelukast on asthma-like symptoms in elite ice hockey players.

BACKGROUND: Controlled clinical trials on the effects of leukotriene antagonists on asthma-like symptoms, bronchial hyperresponsiveness and airway inflammation have not been performed in elite athletes. METHODS: In 2001, we examined 88 of 102 (86%) players from three junior, national league ice hockey teams in Helsinki. Athletes were included in the intervention if they reported at least two exercise-induced bronchial symptoms (wheeze, cough, shortness of breath) weekly during the previous month on a previously validated respiratory-symptom questionnaire. Sixteen male ice hockey players fulfilled the study criteria. A double-blind, randomized, cross-over, placebo-controlled study included 4-week active treatment (10 mg oral montelukast, bedtime), 1-week washout period, and 4-week placebo treatment. Before entering the study, all patients were clinically examined, skin prick tested, filled in a respiratory symptom questionnaire, performed a spirometry and a histamine challenge test, and gave induced sputum samples. Exhaled NO was measured. These measures were repeated after both treatment periods. During the treatment the athletes kept daily diary on lower respiratory tract symptoms on a scale from 0 (no symptoms) to 10 (most severe symptoms), morning peak expiratory flow (PEF), training amount, and use of study medication. Primary end-point was daily lower respiratory tract symptom score. RESULTS: Montelukast had no effect on daily lower respiratory symptom scores, spirometry parameters [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, PEF], bronchial hyperresponsiveness, sputum eosinophil or neutrophil cell counts, exhaled NO measurements, or morning PEF. Nine subjects were atopic in skin prick test, but their results did not differ from the nonatopic subjects. CONCLUSION: A leukotriene antagonist, montelukast, was of no benefit in the treatment of asthma-like symptoms, increased bronchial hyperresponsiveness or a mixed type of eosinophilic and neutrophilic airway inflammation in highly-trained ice hockey players.

Airway inflammation, bronchial hyperresponsiveness and asthma in elite ice hockey players.

There is little information of lower respiratory symptoms, bronchial hyperresponsiveness and airway inflammation in elite ice hockey players. A total of 88 highly trained ice hockey players and 47 control subjects were studied. All the subjects were subjected to skin-prick tests, resting spirometry examinations and histamine-challenge tests. Adequate induced sputum samples were obtained from 68 of the ice hockey players and from 18 symptom-free control subjects on a separate day. Bronchial hyperresponsiveness in a histamine-challenge test was found in 21 (24%) of the athletes and in five (11%) of the controls. Current asthma (current asthmatic symptoms and increased bronchial responsiveness) was observed in 13 (15%) of the athletes and in one (2%) of the control subjects. Total asthma (current asthma or previously physician-diagnosed asthma) occurred in 19 (22%) of the athletes and in two (4%) of the controls. Atopy, according to skin-prick tests, was observed in 51 (58%) of the athletes and 17 (36%) of the control subjects. The differential cell counts of eosinophils (2.6 versus 0.2%) and neutrophils (80.9 versus 29.9%) in the sputum samples of the ice hockey players were significantly higher than in those of the control subjects. Asthma is common in elite ice hockey players and they show signs of a mixed type of neutrophilic and eosinophilic airway inflammation. Inhalation of cold air associated with exposure to indoor pollutants during intensive training is a possible causative factor.

Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics.

BACKGROUND: The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of inflammatory cytokine production is yet to be determined. OBJECTIVE: The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics. METHODS: PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF-alpha and nuclear-translocation of nuclear factor kappa B (NF-kappa B) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined. RESULTS: PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF-alpha production and nuclear translocation of NF-kappa B compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-alpha and nuclear-translocation of NF-kappa B in PBM of atopic asthmatics (P < 0.01). An additive effect of pranlukast on low-dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF-alpha production or NF-kappa B nuclear translocation. CONCLUSION: Our results suggest that pranlukast may inhibit TNF-alpha production via suppression of NF-kappa B activation through pathways distinct from cysLTR1 antagonism.

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma.

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.

Screening for acetaldehyde dehydrogenase 2 genotype in alcohol-induced asthma by using the ethanol patch test.

BACKGROUND: We have previously reported that alcohol-induced asthma in Japanese patients is caused by increased blood acetaldehyde concentration resulting from abnormalities of acetaldehyde dehydrogenase 2 (ALDH2) enzyme activity on the basis of ALDH2 genotype differences. OBJECTIVES: The purpose of the present study was to determine whether the ethanol patch test could predict the ALDH2 genotype in Japanese asthmatic subjects. METHODS: An ethanol patch test on the upper arm and a questionnaire survey addressing the past history of alcohol-induced asthma were administered to 148 adult Japanese asthmatic subjects. The ALDH2 genotypes in these 148 subjects were also determined by means of PCR. RESULTS: The genotype distribution of ALDH2 determined by PCR in 68 subjects with positive ethanol patch test results was 4 (5.9%), 56 (82.4%), and 8 (11.8%) for genotypes NN (normal homozygote), NM (mutant heterozygote), and MM (mutant homozygote). The ALDH2 genotype in 80 subjects with a negative test result was only NN. The distribution of ALDH2 genotype in 78 (52.7%) subjects who had experienced alcohol-induced asthma symptoms on the basis of the questionnaire was 27 (34.6%), 44 (56.4%), and 7 (9.0%) for genotypes NN, NM, and MM, respectively. On the other hand, 70 subjects had never experienced alcohol-induced asthma symptoms. In these subjects the ALDH2 genotype was NN in 51 (72.9%), NM in 18 (25.7%), and MM in 1 (1.4%). CONCLUSIONS: Our results indicate that the results of ethanol patch testing correlate well with ALDH2 genotype, as determined by means of PCR, suggesting that the ethanol patch test is useful for the screening of alcohol-induced asthma.

Airway hyperresponsiveness and pulmonary function in adult asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) is a very important factor in the pathogenesis of bronchial asthma. OBJECTIVES: To examine the relationship between airway obstruction and AHR in adult asthma. METHODS: This study was a retrospective study in 161 adult asthmatic patients. Nonspecific AHR to methacholine was measured. We examined the correlations between AHR and pulmonary function, severity of asthma, type of asthma and age. RESULTS: In the moderate and severe groups, peripheral airway obstruction was more aggravated compared to the mild group, and AHR was significantly more severe. Analysis of AHR by age showed that the degree of airway obstruction increased with aging, but age did not clearly correlate with airway sensitivity. Airway reactivity decreased with aging. Aspirin-induced asthma tended to be severe. In fatal asthma, central airway obstruction was significantly more severe. Although AHR in fatal asthma did not significantly differ from that in the severe group, airway sensitivity and airway reactivity tended to be increased. CONCLUSIONS: AHR is an important factor determining the severity of asthma, and airway obstruction is an important index for the prediction of death from asthma. An evaluation of the degree of AHR and airway obstruction is considered to be the first step in controlling asthma.

Effects of amphotericin B gargles on oral colonization of Candida albicans in asthmatic patients on steroid inhalation therapy.

BACKGROUND: Early use of inhaled steroids is recommended for bronchial asthma. The side effects are rare, but oral discomfort and candidiasis are clinically important complications. Most previous studies reported that the use of spacer and water gargling was necessary to prevent oral complications. However, in some patients, this may fail to prevent such complications. OBJECTIVE: To compare the effects of water gargling with those of amphotericin B, in the prevention of oral complications in asthmatics using inhaled steroids. METHODS: Pharyngeal swab samples were obtained aseptically from the posterior pharyngeal wall of 128 asthmatics who have been using inhaled steroids (beclomethasone dipropionate) for more than 1 year. The amount of Candida albicans in cultured swabs was evaluated based on the following criteria: oral symptoms, method of gargling, dose of inhaled steroids, type of spacer and serum cortisol level. RESULTS: The number of isolated C. albicans was significantly higher in asthmatics with oral symptoms than in those free of symptoms. It was also significantly higher in patients who gargled with water or 1,000 times dilution than in those who gargled with 100 or 50 times dilutions of amphotericin B. Moreover, it was significantly higher in patients with low levels of serum cortisol than in those with normal serum cortisol. CONCLUSION: We demonstrated that at least in a subgroup of asthmatics using steroid inhalers, gargling with water or even weak concentrations of amphotericin B does not prevent colonization of the throat with C. albicans. This group at high risk of developing oral candidiasis should gargle with amphotericin B at concentrations higher than 100 times dilution that can prevent clinically detectable oral candidiasis.

Preoperative steroid therapy inhibits cytokine production in the lung parenchyma in asthmatic patients.

OBJECTIVES: During or after surgery, asthma attacks due to airway hyperresponsiveness (AHR) are likely to occur in patients with bronchial asthma. Preoperative administration of corticosteroid for prevention of perioperative asthma attacks is useful. We examined the mechanism of prevention of perioperative asthma attacks by the preoperative administration of corticosteroid in vitro. DESIGN: Five patients with asthma were treated with 20 mg of prednisolone orally for 2 preoperative days and 80 mg of methylprednisolone IV immediately before and after surgery. In another five patients without asthma, no steroids were administered. A noncarcinomatous part of the resected tissue from each patient with lung cancer was passively sensitized with the serum of an atopic patient. In the patients without asthma, the tissue was treated with or without dexamethasone, and then mite antigen was added. MEASUREMENTS: The culture supernatant and lung tissue were recovered, and the supernatant was assayed for histamine, leukotriene E(4) (LTE(4)), interleukin (IL)-5, and tumor necrosis factor (TNF)-alpha. Degranulation of mast cells was measured by tryptase staining of the lung tissue, and the expression of messenger RNA (mRNA) of IL-5 and TNF-alpha was determined by the reverse transcriptase-polymerase chain reaction method. RESULTS: While preoperative administration of corticosteroid did not suppress the release of histamine and LTE(4) from the lungs of asthmatic patients, it completely suppressed IL-5 and TNF-alpha production at the mRNA level. The same results were obtained in lung tissues of nonasthmatic patients treated in vitro with dexamethasone. CONCLUSIONS: Our results suggest that corticosteroid treatment reduces AHR and prevents perioperative attacks of asthma primarily by suppressing the production of inflammatory cytokines.

Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.

BACKGROUND: Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.

Efficacy and safety of long-term treatment of asthmatic patients with pranlukast, a cysteinyl-leukotriene-receptor antagonist: four-year followup study.

BACKGROUND: There are few studies that have examined the long-term efficacy and safety of pranlukast, a leukotriene receptor antagonist, in asthmatic patients. METHODS: Sixty-three asthmatic patients were entered in this 4-year study [group 1, mild or moderate (N = 22); group 2, severe without using oral prednisolone (N = 22); group 3, severe with using oral prednisolone (N = 19)]. Pranlukast was administered at 225 mg twice daily to 14 subjects in group 1 (group 1p), 14 in group 2 (group 2p), and 11 in group 3 (group 3p), chosen for pranlukast additional therapy at random. Another group of 24 asthmatic patients was assigned to conventional therapy group (groups 1c, 2c, and 3c). Efficacy was determined by improvement in symptom score, peak expiratory flow rate (PEFR) percentage predicted, reduced daily variability of PEFR (percentage), and reduced frequency of use of rescue beta2-agonist (times per week). RESULTS: In groups 1p and 2p, PEFR percentage predicted began to improve from 2 weeks after commencement of treatment. The symptom score, daily variability of PEFR, and use of rescue beta2-agonist diminished significantly. In group 3p, pranlukast was ineffective in improving PEFR percentage predicted. All but two patients continued to receive pranlukast and no adverse effects were noted, at least during the 16-week therapy. Further, 22 patients continued to receive pranlukast for 4 years, and none experienced any adverse effects. CONCLUSIONS: We showed in this study that long-term treatment with pranlukast is effective for asthmatic patients without any adverse effects.

Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients.

BACKGROUND: Aspirin inhibits cyclooxygenase activity and modifies production of the arachidonate cascade in aspirin-induced asthma. The aim of the present study was to examine the effects of leukotriene (LT) receptor antagonist on aspirin challenge on eosinophil activity and chemical mediators released into the airway of asthmatic patients. METHODS: Aspirin oral provocation test was performed in aspirin-intolerant asthmatic patients (AIA; N = 7) and aspirin-tolerant asthmatic patients (ATA; N = 7). In AIA, LT receptor antagonist (pranlukast) was administered orally 2 hours before the test, and its inhibitory effects on sputum LTC4+C4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine (Cr), 11-dehydrothromboxane (11-dhTX) B2/Cr, serum LTC4+D4, ECP, and peripheral blood eosinophil count were compared with the findings in ATA subjects. RESULTS: In AIA, aspirin induced an immediate reaction associated with increased urinary LTE4/Cr and sputum ECP and a fall in urinary 11-dhTXB2/Cr. Pranlukast inhibited the bronchial reaction and an increase in sputum ECP after threshold dosed of ASA, but failed to change aspirin-induced LT production in sputum and urine. In ATA, aspirin challenge was only associated with a fall in urinary 11-dhTXB2. CONCLUSIONS: Our results indicated that aspirin-induced asthma is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade and that leukotriene receptor antagonist are useful for AIA through inhibition of production of LT and eosinophilic inflammation in the airway.