Evolution of Asthma Concept and Effect of Current Asthma Management Guidelines

Concept of asthma has changed from symptom-complex or airway hypersensitivity to airway inflammation and airway remodeling. Based on this concept asthma management guidelines (JGL) has been developed in Japan. Death from asthma has decreased drastically since the publication of the guidelines, although it is still high in elderly population. Further works are expected for "zero-death" from asthma and for tighter control of airway inflammation and resultant airway remodeling

Linked Color Imaging and Blue Laser Imaging for Upper Gastrointestinal Screening

White light imaging (WLI) may not reveal early upper gastrointestinal cancers. Linked color imaging (LCI) produces bright images in the distant view and is performed for the same screening indications as WLI. LCI and blue laser imaging (BLI) provide excellent visibility of gastric cancers in high color contrast with respect to the surrounding tissue. The characteristic purple and green color of metaplasias on LCI and BLI, respectively, serve to increase the contrast while visualizing gastric cancers regardless of a history of Helicobacter pylori eradication. LCI facilitates color-based recognition of early gastric cancers of all morphological types, including flat lesions or those in an H. pylori-negative normal background mucosa as well as the diagnosis of inflamed mucosae including erosions. LCI reveals changes in mucosal color before the appearance of morphological changes in various gastric lesions. BLI is superior to LCI in the detection of early esophageal cancers and abnormal findings of microstructure and microvasculature in close-up views of upper gastrointestinal cancers. Excellent images can also be obtained with transnasal endoscopy. Using a combination of these modalities allows one to obtain images useful for establishing a diagnosis. It is important to observe esophageal cancers (brown) using BLI and gastric cancers (orange) surrounded by intestinal metaplasia (purple) and duodenal cancers (orange) by LCI

Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/ Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma

Background: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/ LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment. Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies. Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations. Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study. Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.</p

A comparative study of asthma with airflow limitation and asthma-COPD overlap using the forced oscillation technique

The forced oscillation technique（FOT）, which requires breathing without forced action, is a useful tool that can measure respiratory impedance. We investigated the physiological differences between asthma with smoking-unrelated airflow limitation and asthma-chronic obstructive pulmonary disease（COPD）overlap（ACO）using the FOT. Among 275 patients with asthma who presented at the Showa University Hospital from April 2018 through March 2019, 211 were enrolled and assigned into the asthma（BA）, asthma with airflow limitation（AL）, or ACO groups. Respiratory impedance measured using the FOT were compared among the groups. There were no significant differences in spirometry data between the AL and the ACO group. The AL group had higher respiratory resistance at 5Hz（R5）, 20Hz（R20）, and reactance at 5Hz than the ACO group, but there was no significant difference in subtracting R20 from R5（R5-R20）. R5 and R20 were similar between the ACO and the BA groups, but R5-R20, resonant frequency（Fres）, and low-frequency reactance area were significantly higher in the ACO group than the BA group. Fres yielded the highest area under the curve（AUC）to identify airflow limitation, and R20 yielded the highest AUC to identify the ACO group among patients with airflow limitation. An analysis using the cut off value to identify airflow limitation and ACO detected 33 patients as having ACO, 17 of whom were diagnosed with ACO. R5 and R20 measured by FOT are higher in AL than in ACO despite no difference in spirometry data, and are not significantly different between BA and ACO. Therefore, FOT aids our understanding of the physiological characteristics and provides clues for the treatment in asthmatics with airflow limitation

Improvement in Frailty in a Patient With Severe Chronic Obstructive Pulmonary Disease After Ninjin'yoeito Therapy: A Case Report

Frailty is a poor prognostic factor in patients with chronic obstructive pulmonary disease (COPD). Although various studies have assessed the effects of conventional treatment with bronchodilators, nutritional support, and pulmonary rehabilitation for frailty in patients with COPD, none have addressed the effects of traditional Japanese medicine (Kampo medicine). Herein, we report the successful management of frailty using Ninjin'yoeito therapy in a 76-year-old patient with COPD. Despite being prescribed multiple bronchodilators, nutritional supplement therapy, patient education, and pulmonary rehabilitation, the patient exhibited unintentional weight loss, low energy, and low physical activity. Ninjin'yoeito was prescribed and these subjective symptoms began to improve 1 month after treatment initiation. In 6 months, the patient reported no frailty, had increased muscle mass, and had achieved an almost normal healthy state. Ninjin'yoeito has been associated with both physical effects, such as improvement in overall physical strength and appetite, and reduction in fatigue, and psychological effects, such as greater motivation and reduction of depression and anxiety symptoms. Physicians have usually treated COPD primarily with organ-specific treatments, such as bronchodilators; however, addressing both the physiological and psychological vulnerability has been difficult. This case report illustrates the potential usefulness of Ninjin'yoeito treatment for frailty in patients with COPD

Administration of Kampo medicine through a tube at an advanced critical care center

In emergency and critical care medical centers, tube administration is employed for patients who have difficulty swallowing oral drugs owing to decreased consciousness or mechanical ventilation. However, tube clogging due to drug injection is a concern. We compared the crushing method with the simple suspension method for the passage of amlodipine, an antihypertensive drug, in combination with rikkunshito, which has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux in emergency and critical care medical centers, to ascertain the effect of Kampo products on the passage of other drugs during tube administration. When the crushing method was employed, poorly water-soluble solid products were formed, while a uniformly dispersed suspension was obtained using the simple suspension method. In addition, the passage rate of amlodipine through the tube was 64% and 93% in the crushing and simple suspension methods, respectively, thereby indicating that the simple suspension method provided more favorable than the crushing method. The results of this study suggested that the passage rate of amlodipine for patients who received Kampo products concurrently was higher when the simple suspension method was used, and an appropriate drug amount might well be able to administered to patients using this method

Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Chlorella extract （CE） has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin （OVA）-induced airway hyperresponsiveness （AHR） and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups: a control group （no OVA exposure, not given CE）, a CE group （no OVA exposure, given CE）, an asthma group （sensitized/challenged with OVA, not given CE） and a CE＋asthma group （sensitized/challenged with OVA, given CE）. In the asthma and CE＋asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE＋asthma groups, the mice were given feed containing 2％ CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage fluid （BALF）, serum, lung tissue and spleen cells. Administration of CE was associated with significantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines （IL-4, IL-5 and IL-13） in BALF. In addition, administration of CE significantly decreased the numbers of periodic acid-Schiff （PAS）-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma

Mechanism of Airway Remodeling Induced by Repeated Inhalation of Methacholine in a Mouse Model of Asthma

Background:Increased severity of asthma is contributed by airway tissue remodeling, which may be associated with chronic allergic inflammation. A recent study revealed the potential capacity of repeated bronchoconstriction, e.g. induced by a muscarine agonist, methacholine(Mch)challenge, to involve in airway remodeling, even though allergic inflammation is not implicated. We have evaluated the influence of repeated bronchoconstriction induced by Mch inhalation on airway remodeling in a murine model of asthma and have examined its machanisms. Methods:Mice were immunized with ovalbumin(OVA), and consequently, challenged by either daily OVA inhalation(the OVA group;a model of asthma with allergic inflammation)or daily Mch inhalation(the Mch group;a model of asthma without allergic inflammation). Lung tissues were obtained and were evaluated histologically after 5, 10, and 15 consecutive inhalation challenges of both OVA and Mch.Results:Eosinophilia in the airway observed only on the OVA group. Subepithelial collagen-band thickness increased also in the OVA group(p<0.01)after 15 challenges, but not in the Mch group. Significant increase in thickness of airway smooth muscle layer and the number of goblet cells were revealed in both the OVA and Mch group after 10(p<0.05 and p<0.01, p<0.01 and p<0.05, respectively, for the comparison of the two challenge groups with the control group)and 15 challenges(p<0.05 and p<0.01, both p< 0.01, respectively, for the comparison with control), further, all these measurements were greater in the OVA group than in the Mch group after both 10 and 15 challenges(both p<0.05 and p<0.01, respectively). An increase in mast cell counts within the airway wall was shown in the OVA group after 10 challenges (p<0.01 compared with control), not in the Mch group at all. Epithelia expression of transforming growthfactor b (TGF-b)increased in both challenge groups after 15 challenges(both p<0.05 compared with control), and was higher than in Mch(p<0.05).Conclusion:Repeated Mch inhalation may induce airway remodeling, while comparatively mild, potentially resulting in progressive severity of asthma. The results implicate that the potential risk associated with Mch challenge should be considered

Effect of Oral Procaterol in Combination with Inhaled Corticosteroids in Adult Patients with Bronchial Asthma

Background:Bronchial asthma is considered to be a chronic airway inflammatory disease, and inhaledcorticosteroids play a central role in controlling airway inflammation. In some patients, however, it is difficultto control symptoms despite the use of moderate to high doses of inhaled corticosteroids. Long-actinginhaled b2-agonists have recently become available and reconsidered as a controller.Objectives:To examine whether combination of an inhaled corticosteroid and an oral b2-agonist can improvesymptoms in patients with moderate bronchial asthma whose airway obstructive symptoms cannotbe relieved sufficiently by inhaled corticosteroids alone.Methods:Of outpatients in our hospital with moderate bronchial asthma (step 3) given beclomethasoneat a daily dose of 800 mg, whose peak expiratory flow rate in the early morning was 70 % or less of the predictedvalue, 12 patients were enrolled in the study who showed at least 12.5 % improvement in the forcedexpiratory volume in one second (FEV1.0) after inhalation of 20 mg procaterol (Meptin Air from OtsukaPharma. Co.) for 15 minutes. Procaterol tablets (Meptin tablets, 50 mg from Otsuka Pharma. Co.) were administeredin the morning and before bed for 4 weeks, and change in the peak expiratory flow rate, subjectivesymptoms, respiratory function, and the number of puffs of the b2-agonist were evaluated.Results:The peak expiratory flow rate, FEV1.0, forced vital capacity (% FVC),and airway hyperresponsivenessimproved after coadministration of oral procaterol and beclomethasone.Conclusions:The oral b2-agonist in combination with an inhaled corticosteroid might improve asthmasymptoms better than inhaled corticosteroids alone