Obesity-associated severe asthma in an adult Japanese population

Background

Severe asthma is increasingly being recognized as an important public health issue. Obesity has been identified as a risk factor for poor asthma control and for worsening of asthma severity. However, most studies investigating obese patients with asthma have been performed in Western countries. Reports on the characteristics of obese Japanese individuals with severe asthma are lacking. Herein, we investigated the clinical characteristics of patients with obesity-associated severe asthma in a Japanese population and the association between obesity and poor asthma control.

Efficacy and safety of mepolizumab in Japanese patients with severe eosinophilic asthma

Background

The MENSA trial assessed the efficacy and safety of mepolizumab in patients with severe eosinophilic asthma. This report describes the efficacy and safety of mepolizumab in Japanese patients from MENSA.

Examination of the cut-off values for a questionnaire used to evaluate asthma control in Japanese asthma patients

Background

The Japan Asthma Control Survey (JACS) questionnaire, developed as a tool for measuring asthma control levels in Japanese asthma patients, was previously tested for its reliability and validity. However, many of the patients enrolled in the original validation study had mild asthma; thus a re-evaluation including severe cases was required to calculate more reliable cut-off values.

Development of a questionnaire to evaluate asthma control in Japanese asthma patients

Background

The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients.

A breath sound analysis in children with cough variant asthma

Background

Cough variant asthma (CVA) is characterized by a chronic cough and bronchial hyperresponsiveness without confirmation of wheezing. Using a breath sound analyzer, we evaluate the characteristics of breath sound in children with CVA.

Three-dimensional imaging forced oscillation technique to assess position-dependent airway obstruction in relapsing polychondritis: A case report

Relapsing polychondritis (RP) is characterized by recurrent systemic inflammation of the cartilages and is accompanied by central airway collapse. We report a case wherein three-dimensional imaging of respiratory system resistance (Rrs) and respiratory system reactance (Xrs) by using MostGraph (CHEST M.I., Tokyo, Japan), a forced oscillation system, revealed that Rrs and Xrs in the inspiratory and expiratory phases correlated with proximal airway collapse. The degree of difference in Rrs and Xrs between the supine and sitting positions reflected airway collapse more closely than did the pulmonary function test. MostGraph could be a useful tool for assessing airway collapse in RP.     

Changes in the breath sound spectrum with bronchodilation in children with asthma

Background

Breath sound parameters have been suggested to be new biomarkers of airway function in patients with asthma.

Phenotype classification using the combination of lung sound analysis and fractional exhaled nitric oxide for evaluating asthma treatment

Background

We report the utility of combining lung sound analysis and fractional exhaled nitric oxide (FeNO) for phenotype classification of airway inflammation in patients with bronchial asthma.We investigated the usefulness of the combination of the expiration-to-inspiration sound power ratio in the mid-frequency range (E/I MF) of 200–400 Hz and FeNO for comprehensively classifying disease type and evaluating asthma treatment.

A questionnaire validated using local treatment guidelines may better predict future asthma risk: MARGIN study

BackgroundAsthma patients often feel satisfied with their current treatment, even when they have been diagnosed as uncontrolled by physicians. The present study investigated the differences in the evaluation of asthma control levels between patients and physicians, and the prediction of future risks.MethodsAsthma patients receiving inhaled corticosteroid/long-acting beta-2 agonists for 4 weeks or more were enrolled and followed-up for 24 weeks. Asthma control levels were evaluated using the following guidelines: Asthma Prevention and Management Guideline, Japan (JGL) and Global Initiative for Asthma (GINA) by physicians, and the Japan Asthma Control Survey (JACS) and a 6-item Asthma Control Questionnaire (ACQ6) by patients, at weeks 0 and 24. Analysis for predictive factors influencing exacerbation was performed using JGL, GINA, JACS, and ACQ6 at week 0.ResultsA total of 420 patients were enrolled. Comparison of the distribution of asthma control levels assessed by physicians and patients showed no statistically significant difference between JGL and JACS (P = 0.19), suggesting a symmetric distribution, while ACQ6 demonstrated a significant difference versus JGL and GINA (both P < 0.001). The predictive factors for exacerbation were unscheduled visits based on GINA (rate ratio; 0.25, 95% CI; 0.14, 0.44), and the use of oral steroids on 3 consecutive days based on JGL (rate ratio; 0.42, 95% CI 0.22, 0.82) and JACS (rate ratio; 0.22, 95% CI; 0.13, 0,40).ConclusionsOur study suggests that evaluation based on treatment guidelines and the questionnaire validated according to the local treatment guidelines is important for improved assessment of asthma control levels and the reduction of future risk.Clinical trial registration numberUMIN000030419.     

A randomized controlled trial on the effect of inhaled corticosteroids on airways inflammation in adult cigarette smokers.

STUDY OBJECTIVE: To determine whether inhaled corticosteroid treatment can reduce airways inflammation in adult cigarette smokers. DESIGN: This was a randomized, placebo-controlled, double-blinded clinical trial. SETTING: The subjects were recruited from the community by advertising. PARTICIPANTS: Seventy-one adults with a > or = 5 pack-year history who were current smokers, had a normal FEV1, and produced sputum daily. INTERVENTION: Sixty subjects were randomized to receive four puffs of placebo or beclomethasone dipropionate ([BDP]; total dosage, 1,000 microg/d) using a metered-dose aerosol inhaler with a valved holding chamber (AeroChamber; Trudell Medical; London, Ontario, Canada) for 28 days. MEASUREMENTS AND RESULTS: Eleven subjects were not randomized because of poor compliance. The primary outcome was fractional airway neutrophilia, as assessed by a differential cell count of sputum. Additional outcome measures were spirometry, measurement of airway responsiveness by methacholine challenge, and lung epithelial permeability measured by the clearance of radiolabeled diethylenetriamine pentaacetic acid. There were no significant differences between the two groups in any outcome measurement after 4 weeks of treatment. CONCLUSIONS: With normal spirometry, we found no benefit of treatment with inhaled BDP, 1,000 microg/d, on noninvasive measures of airways inflammation in adult smokers. This indicates that cigarette smoke-induced inflammation in its early stages (before a demonstrable airflow obstruction) is not steroid sensitive. This may occur because the site of involvement is not accessible to inhaled medications or because the inflammatory process is resistant to moderate doses of inhaled corticosteroids.     

Switching from salmeterol/fluticasone to formoterol/budesonide combinations improves peripheral airway/alveolar inflammation in asthma

BackgroundCombination therapy with an inhaled corticosteroid (ICS) and a long-acting β₂-agonist (LABA) in a single inhaler is the mainstay of asthma management. We previously showed that switching from salmeterol/fluticasone combination (SFC) 50/250 μg bid to a fixed-dose formoterol/budesonide combination (FBC) 9/320 μg bid improved asthma control and pulmonary functions, but not fractional exhaled nitric oxide (FeNO), in patients with asthma not adequately controlled under the former treatment regimen.ObjectiveTo assess whether switching from SFC to FBC improves peripheral airway/alveolar inflammation in asthma (UMIN000009619).MethodsSubjects included 66 patients with mild to moderate asthma receiving SFC 50/250 μg bid for more than 8 weeks. Patients were randomized into FBC 9/320 μg bid or continued the same dose of SFC for 12 weeks. Asthma Control Questionnaire, 5-item version (ACQ5) score, peak expiratory flow, spirometry, FeNO, alveolar NO concentration (CANO), and maximal NO flux in the conductive airways (J’awNO) were measured.ResultsSixty-one patients completed the study. The proportion of patients with an improvement in ACQ5 was significantly higher in the FBC group than in the SFC group (51.6% vs 16.7%, respectively, p = 0.003). A significant decrease in CANO was observed in the FBC group (from 8.8 ± 9.2 ppb to 4.0 ± 2.6 ppb; p = 0.007) compared to the SFC group (from 7.4 ± 7.8 ppb to 6.4 ± 5.0 ppb; p = 0.266) although there was no significant difference in the changes in pulmonary functions between the 2 groups. Similar significant differences were found in the CANO corrected for the axial back diffusion of NO (FBC, from 6.5 ± 8.2 ppb to 2.3 ± 2.5 ppb; and SFC, from 4.3 ± 5.3 ppb to 3.9 ± 4.3 ppb). There was no difference in the changes in FeNO or J’awNO between the 2 groups.ConclusionsSwitching therapy from SFC to FBC improves asthma control and peripheral airway/alveolar inflammation even though there is no improvement in pulmonary functions, and FeNO in asthmatic patients.     

Differential role of mucus plugs in asthma: Effects of smoking and association with airway inflammation

BackgroundThe physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical–physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma.MethodsA total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT.ResultsMore mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics.ConclusionsThe association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma.     

Circulating activated innate lymphoid cells and mucosal-associated invariant T cells are associated with airflow limitation in patients with asthma

BackgroundA variety of innate subsets of lymphoid cells such as natural killer (NK) cells, several populations of innate lymphoid cells (ILCs), and mucosal-associated invariant T (MAIT) cells as innate-like T lymphocytes are involved in asthma and may have important effector functions in asthmatic immune responses. In the present study, we investigated whether NK cells, ILCs, and MAIT cells in the peripheral blood of patients with asthma would be associated with clinical asthma parameters.MethodsWe recruited 75 adult patients with mild to severe asthma. The peripheral blood mononuclear cells in peripheral venous blood samples from the patients were purified and stained with different combinations of appropriate antibodies. The cells were analyzed by flow cytometry.ResultsThe percentage of activated (i.e., CD69⁺) NK cells in the total NK cell population was negatively correlated with FEV₁% which is calculated by the forced expiratory volume in 1 s (FEV₁)/the forced vital capacity (FVC). The percentages of CD69⁺ ILC1s and ILC2s were negatively correlated with FEV₁% and %FEV₁. The percentage of CD69⁺ ILC3s was positively correlated with BMI, and the percentage of CD69⁺ MAIT cells was negatively correlated with FEV₁%. Moreover, the percentage of CD69⁺ NK cells, ILC1s, ILC2s, ILC3s, and MAIT cells were positively correlated with each other.ConclusionsFor the first time, our data showed that activated NK cells, ILC1s, ILC2s, ILC3s, and MAIT cells were positively correlated with each other and may be associated with airflow limitation in patients with asthma.