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Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause an intractable asthma. The number of patients with asthma has increased, while the number of patients who die from asthma has decreased (1.7 per 100,000 patients in 2009). The aim of asthma treatment is to enable patients with asthma to lead a healthy life without any symptoms. A partnership between physicians and patients is indispensable for appropriate treatment. Long-term management with agents and elimination of causes and risk factors are fundamental to asthma treatment. Four steps in pharmacotherapy differentiate mild to intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid (ICS), varying from low to high doses. Long-acting β(2) agonists (LABA), leukotriene receptor antagonists, and theophylline sustained-release preparation are recommended as concomitant drugs, while anti-IgE antibody therapy is a new choice for the most severe and persistent asthma. Inhaled β(2) agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, etc., are used as needed against acute exacerbations. Allergic rhinitis, chronic obstructive pulmonary disease (COPD), aspirin induced asthma, pregnancy, and cough variant asthma are also important factors that need to be considered.

BackgroundThe effects of airborne particulate matter (PM) are a major human health concern. In this panel study, we evaluated the acute effects of exposure to PM on peak expiratory flow (PEF) and wheezing in children.MethodsDaily PEF and wheezing were examined in 19 asthmatic children who were hospitalized in a suburban city in Japan for approximately 5 months. The concentrations of PM less than 2.5 µm in diameter (PM2.5) were monitored at a monitoring station proximal to the hospital. Moreover, PM2.5 concentrations inside and outside the hospital were measured using the dust monitor with a laser diode (PM2.5(LD)). The changes in PEF and wheezing associated with PM concentration were analyzed.ResultsThe changes in PEF in the morning and evening were significantly associated with increases in the average concentration of indoor PM2.5(LD) 24 h prior to measurement (-2.86 L/min [95%CI: -4.12, -1.61] and -3.59 L/min [95%CI: -4.99, -2.20] respectively, for 10-µg/m3 increases). The change in PEF was also significantly associated with outdoor PM2.5(LD) concentrations, but the changes were smaller than those observed for indoor PM2.5(LD). Changes in PEF and concentration of stationary-site PM2.5 were not associated. The prevalence of wheezing in the morning and evening were also significantly associated with indoor PM2.5(LD) concentrations (odds ratios = 1.014 [95%CI: 1.006, 1.023] and 1.025 [95%CI: 1.013, 1.038] respectively, for 10-µg/m3 increases). Wheezing in the evening was significantly associated with outdoor PM2.5(LD) concentration. The effects of indoor and outdoor PM2.5(LD) remained significant even after adjusting for ambient nitrogen dioxide concentrations.ConclusionIndoor and outdoor PM2.5(LD) concentrations were associated with PEF and wheezing among asthmatic children. Indoor PM2.5(LD) had a more marked effect than outdoor PM2.5(LD) or stationary-site PM2.5.

SUMMARYThe immunological mechanisms by which respiratory syncytial virus (RSV) contributes to the development of asthma are poorly understood. gd T cells are important in mucosal defence, and may contribute to the establishment of primary immune responses by producing cytokines early during respiratory infections. Thus, we used flow cytometry and intracellular cytokine staining to investigate the expression of interferon (IFN)-g and interleukin (IL)-4 by mitogen-stimulated gd T cells from the peripheral blood of 15 hospitalized infants with RSV bronchiolitis, seven rotavirus-infected infants and eight normal controls. gd T cells from RSV-infected infants had a lower proportion of IFN-g -producing cells (median, 4.00%; range, 0.58-6.60%) and a slightly but significantly higher proportion of IL-4-producing cells (median, 0.40%; range, 0.13-2.76%) than rotavirus-infected infants (median, 32.10%; range, 14.43-61.21%; P < 0·01, median, 0.00%; range, 0.00-0.00%; P < 0·05) in the acute phase. By contrast, differences in cytokine production by total CD3 + T cells did not differ significantly between patient groups. Thus, reduced IFN-g -production by gd T cells in the peripheral blood of RSV-infected infants is accompanied by increased Th2 cytokine production during the acute phase of disease. At follow-up, eight children had recurrent episodes of wheezing. The frequencies of IFN-g -producing gd T cells were significantly lower in patients who developed recurrent wheezing (median, 0.65%; range, 0.02-1.75%) than in patients without recurrent wheezing (median, 6.90%; range, 5.25-10.98%; P < 0·005). Cytokine production by gd T cells may therefore be important in the pathogenesis of acute RSV disease, and play a part in the development of recurrent childhood wheezing after bronchilolitis.

BackgroundLittle information is available on the possible association between hourly short-term air pollution and peak expiratory flow (PEF) in asthmatic children.MethodsPEF was measured twice daily, from October through December, 2000, in 17 children aged 8 to 15 years hospitalized with severe asthma. A total of 1198 PEF measurements were made at 7 a.m. and 1175 at 7 p.m. Measurements were conducted immediately prior to medication under the guidance of trained nurses. PEF changes were estimated in 10-μg/m3 increments of particulate matter with a 50% cut-off aerodynamic diameter of ≤2.5 μm (PM2.5), with adjustment for sex, age, height, and temperature. Lagged-hour exposures of up to 24 hours were examined.ResultsIncreased 24-hour mean concentration of PM2.5 was associated with a decrease in both morning and evening PEF (-3.0 l/minute; 95%CI: -4.6, -1.4 and -4.4 l/minute; 95%CI: -7.1, -1.7, respectively). In addition, hourly concentrations of PM2.5 and PEF showed a significant association between some lags of PM2.5 and PEF. Effect size was almost -3 l/minute in both morning and evening PEF for an hourly PM2.5 concentration of 10 μg/m3 in several lags. Even after adjustment for other air pollutants, some of the significant associations with PEF remained.ConclusionAmong hospitalized children with severe asthma, increased hourly concentration of PM2.5 was associated with a decrease in PEF.

Background: In allergic rhinitis, the major symptoms of runny nose, sneezing, and stuffy nose tend to become worse upon waking up in the morning, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether the worsening of allergic rhinitis in the morning is associated with changes in the activity of inflammatory cells. Methods: Nasal reactivity to methacholine was assessed twice in 8 children with allergic rhinitis and 8 healthy control subjects at 6.00 a.m. and 3.00 p.m. The amounts of eosinophil cationic protein (ECP), histamine and tryptase in induced nasal secretions and peripheral blood were also measured. Results: Nasal reactivity to methacholine was higher at 6.00 a.m. not only in patients but also in healthy controls. Serum ECP and plasma histamine levels showed no circadian patterns. On the other hand, significantly higher levels of inflammatory activation products were found in nasal secretions at 6.00 a.m., thus showing a direct association with nasal reactivity. Conclusion: These results suggest that the circadian variation in nasal reactivity is associated with changes in the activity of eosinophils and basophilic cells in the nasal mucosa.

The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2013 (JAGL 2013) describes childhood asthma after the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. JAGL 2013 provides information on diagnosis by age group from infancy to puberty (0-15 years of age), treatment for acute exacerbations, long-term management by anti-inflammatory drugs, daily life guidance, and patient education to allow non-specialist physicians to refer to this guideline for routine medical treatment. JAGL differs from the Global Initiative for Asthma Guideline (GINA) in that JAGL emphasizes early diagnosis and intervention at <2 years and 2-5 years of age. A management method, including step-up or step-down of long-term management drugs based on the status of asthma control levels, as in JAGL, is easy to understand, and thus the Guideline is suitable as a frame of reference for routine medical treatment. JAGL has also introduced treatment and management using a control test on children, recommending that the physician aim at complete control by avoiding exacerbation factors and by appropriate use of anti-inflammatory drugs.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.