Masashi Komori

Decrease of Interleukin-10-Producing T Cells in the Peripheral Blood of Severe Unstable Atopic Asthmatics

Background: Although IL-10 is known as an immunoregulatory cytokine produced by various cells including T cells, its basic profile in atopic asthma remains uncertain. Objective: The profiles of IL-10 production in circulating CD4+ T cells of atopic asthmatics were investigated with respect to clinical severity. Methods: Forty atopic asthmatics were divided into three groups: mild, and severe but stable and severe unstable asthmatics. Eosinophils were counted in the peripheral blood and sputum, and exhaled nitric oxide was assessed. PBMCs were stimulated with or without anti-CD3 and anti-CD28 antibodies and then processed for detecting IL-10-producing CD4+ cells using flow cytometry. Results: There was no difference in the eosinophil count in blood or sputum and in nitric oxide level among the three groups. IL-10-producing CD4+ cells were mainly detected in a CD45RO+ memory population. The frequency of IL-10-producing cells after stimulation was significantly lower in the severe unstable group compared to the mild group. In addition, the frequency of IL-10-producing cells in the severe unstable group was significantly lower than that in the severe stable group despite the fact that both groups received similar treatments with high-dose inhaled corticosteroids. The IL-10 production of CD4+CD45RO+ cells in response to dexamethasone did not differ among the three groups. Conclusions: IL-10-producing CD4+CD45RO+ cells in the peripheral blood are decreased in severe unstable asthmatics, which is not explained by the effect of high-dose inhaled corticosteroid medication.

Effect of suplatast tosilate on airway hyperresponsiveness and inflammation in asthma patients

Because eosinophilic airway inflammation is a characteristic of bronchial asthma, the treatment of such inflammation is important in the management of this disease. Suplatast tosilate is a novel anti-asthma drug that suppresses eosinophil proliferation and infiltration through selective inhibition of Th2 cytokine synthesis. We investigated the effect of oral suplatast tosilate therapy in patients with mild and moderate asthma. Twenty-eight asthma patients were randomized into two groups with or without suplatast tosilate treatment (100 mg t.i.d. for 28 days). We examined the blood eosinophil counts, eosinophilic cationic protein level, sputum eosinophil count, exhaled nitric oxide level, and airway responsiveness before and after treatment. In patients treated with suplatast tosilate, the eosinophil count in the blood and sputum was significantly decreased after treatment, while there was no such change in the patients without suplatast treatment. The exhaled nitric oxide level and airway responsiveness (measured using an Astograph) were also decreased after treatment with suplatast tosilate, while there were no significant changes in patients without suplatast tosilate. These results strongly suggest that oral administration of suplatast tosilate suppresses airway hyperresponsiveness in asthma patients by reducing eosinophilic inflammation in the airways.

Effects of Salmeterol in Patients with Persistent Asthma Receiving Inhaled Corticosteroid plus Theophylline

Background: Patients with severe asthma require multiple therapies to improve lung function and reduce symptoms. The use of long-acting inhaled β2-agonists plus theophylline in addition to high doses of inhaled corticosteroids (ICSs) for the treatment of severe asthma has not been extensively studied. Objective: The purpose of this study was to investigate the efficacy and safety of salmeterol combined with high-dose ICSs plus theophylline in severe asthma. Methods: We undertook a randomized, placebo-controlled, crossover study to compare the effect of a single dose of inhaled salmeterol (50 µg) or a placebo in patients with severe asthma whose conditions were not being adequately controlled by therapies with high-dose ICSs plus oral theophylline with or without leukotriene receptor antagonists. Results: Twenty patients took part in the trial. Compared with the placebo, the inhalation of salmeterol significantly increased the FEV1. Even in the 9 patients treated with high-dose ICSs plus theophylline plus a leukotriene receptor antagonist, the FEV1 increased significantly more after salmeterol than after the placebo. Conclusion: Patients with severe asthma receiving high-dose ICSs plus theophylline may benefit from the addition of salmeterol.

Disseminated Cryptococcosis with Marked Eosinophilia in a Postpartum Woman

Disseminated cryptococcosis usually develops in immunosuppressed patients. A 33-year-old postpartum woman developed disseminated cryptococcosis with marked eosinophilia. She presented with a cough and a week-long fever. A computed tomography scan showed multiple pulmonary nodules randomly distributed. Eosinophils were observed to have increased in number in both her peripheral blood and bronchoalveolar lavage fluid. A transbronchial lung biopsy and cerebrospinal fluid specimens revealed findings consistent with cryptococcal infection. Disseminated cryptococcosis can present with marked eosinophilia of the peripheral blood and lung tissues. Additionally, the postpartum immune status may sometimes be involved in the development of opportunistic infections in previously healthy women.

Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma

BACKGROUND Airway hyperresponsiveness is a cardinal feature of asthma. Although the modulation of cholinergic neuroeffector transmission may play a role in airway responsiveness, in vivo evidence remains scarce. It is well known that histamine causes bronchoconstriction partly via vagal reflex, whereas methacholine does not. To investigate the significance of modulating neuroeffector transmission, we compared the effect of low-dose salbutamol-a β2-adrenoceptor agonist-on airway responsiveness to histamine with that to methacholine. METHODS We enrolled 12 subjects with stable asthma. After screening confirmed that inhalation of low-dose salbutamol (1μg) did not change their basic pulmonary function, subjects underwent measurement of airway responsiveness to inhaled histamine and methacholine with or without pretreatment with low-dose salbutamol, in a randomized, crossover fashion. Airway responsiveness was measured by an astograph by which respiratory conductance (Grs) was assessed by the forced oscillation method during continuous inhalation of histamine or methacholine in stepwise incremental concentrations. Airway responsiveness was calculated as the cumulative dose of bronchoconstrictors that induced a decrease of 35% in Grs. RESULTS Inhalation of 1μg of salbutamol significantly attenuated airway responsiveness to histamine but not methacholine. This selective attenuation was observed irrespective of disease severity or phenotype, namely atopy or non-atopy. CONCLUSION Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma. The present study may provide a novel insight into the bronchoprotective mechanism of β2-adorenoceptor agonist in clinical settings.

Different Profiles of IL-10+IFN-γ–IL-4–CD4+ T Cells in the Peripheral Blood in Atopic and Non-Atopic Asthmatics

Background: The impaired production of interleukin (IL) 10 from regulatory T cells has been proposed as a causal mechanism of asthma. Although IL-10-producing (IL-10+) T cells are detectable in the peripheral blood, their significance in the pathophysiology of asthma remains uncertain. Objectives: This study aimed to investigate the profile of circulating IL-10+CD4+ T cells in atopic and non-atopic asthma. Methods: Atopic and non-atopic asthmatics were divided into a mild and severe group. Their peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3 and anti-CD28 antibodies and then processed for triple cytokine flow cytometry directed to IL-10, interferon (IFN) γ and IL-4. Results: IL-10+CD4+ cells were exclusively detected in the IFN-γ–IL-4– population. In atopic asthma, the frequency of IL-10+IFN-γ–IL-4–CD4+ cells in the severe group was significantly lower than that in the mild group. The frequency of IL-10+IFN-γ–IL-4–CD4+ cells in the severe group was not significantly different from that in the mild group of those with non-atopic asthma. The frequency of IL-4+IFN-γ–IL-10–CD4+ cells (Th2) was significantly higher in the group with mild atopic asthma than in that with mild non-atopic asthma. IFN-γ+IL-4–IL-10–CD4+ cells (Th1) did not differ between groups, irrespective whether the subjects suffered from atopic or non-atopic asthma. Conclusions: IL-10+CD4+ cells in PBMCs may be distinct from Th1 or Th2 and likely have the profile of regulatory T cells. The differential association of IL-10+IFN-γ–IL-4–CD4+ cells with clinical severity between atopic and non-atopic asthma implies that its pathophysiological significance may differ among asthma phenotypes.