Contribution of Lung Fibroblast Migration in the Fibrotic Process of Airway Remodeling in Asthma

ABSTRACTBackgroundThe fibrotic process in airway remodeling of asthma may be characterized by an exaggerated deposition of extracellular matrix (ECM) components such as fibronectin and type I, III and IV collagen. In the present study, we established airway remodeling model mice and examined the mechanism of fibrotic change by measuring chemotactic activity of lung fibroblasts and quantifying collagen content in lung tissues.MethodsAirway remodeling model mice were made by ovalbumin (OA) sensitization and inhalation. Bronchoalveolar lavage (BAL) and bronchial biopsy were performed. Cell migration was assessed by the Boyden's chamber technique. The collagen content of lung tissue was measured using ELISA.ResultsThe chemotactic activity in lung fibroblasts toward the mouse BAL fluid (BALF) was significantly increased in OA-inhaled mice. Total soluble collagen content was significantly increased in OA-inhaled mice. We observed markedly increased collagen deposition around the airway wall in OA-inhaled mice, which was not shown in saline-inhaled mice. Furthermore, fibronectin in the BALF of OA-inhaled mice was significantly higher than that in the control mice.ConclusionsThe total soluble collagen content increased during the fibrotic change of airway remodeling in asthma. Furthermore, migration of fibroblasts may play a key role in this remodeling process, and fibronectin and type I and IV collagen seem to be chemotactic factors for the fibroblasts

Three Cases of Tsutsugamushi Disease successfully treated with Clarithromycin.

Three cases of tsutsugamushi disease were successfully treated with clarithromycin, a new macrolide antibiotic. This is the first report describing tsutsugamushi disease in Hirado area and the clinical application of clarithromycin to this rickettsial disease

Fatal Asthma with Rhabdomyolysis Induced by Hair Dye

Hair dyes have been reported to cause exacerbation of asthma in hairdressers through occupational exposure. We report a 54-year-old housewife who developed a fatal asthma attack following the use of a hair dye at home. She was admitted semiconscious with multiple organ failure. Laboratory findings were indicative of rhabdomyolysis. Skin prick and interdermal tests with hair dyes were performed. Hair dyes can be nonspecific stimuli that cause an asthma attack. But in our case, we cannot deny the possibility that the attack resulted from antigen-antibody reaction by the hair dye. We should warn that hair dyes can cause an asthma attack not only through occupational exposure but also through occasional domestic use

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. Methods: A total of 233 patients with bronchial asthma were included. The cutoff values of FeNO and E/I MF were set to 38 ppb and 0.36, respectively, according to a previous study. The patients were divided into 4 subgroups based on the FeNO and E/I MF cutoff values. Respiratory function, the percentages of sputum eosinophils and neutrophils, and patient background characteristics were compared among groups. Results: Respiratory function was well controlled in the FeNO low/E/I MF low group (good control). Sputum neutrophil was higher and FEV1,%pred was lower in the FeNO low/E/I MF high group (poor control). History of childhood asthma and atopic asthma were associated with the FeNO high/E/I MF low group (insufficient control). The FeNO high/E/I MF high group corresponded to a longer disease duration, increased blood or sputum eosinophils, and lower FEV1/FVC (poor control). Conclusions: The combination of FeNO and E/I MF assessed by lung sound analysis allows the condition of airway narrowing and the degree of airway inflammation to be assessed in patients with asthma and is useful for evaluating bronchial asthma treatments. Keywords: Bronchial asthma, E/I MF, FeNO, Lung sound analysis, Phenotyp

Capsaicin Provocation Test as a Diagnostic Method for Determining Multiple Chemical Sensitivity

Background: Multiple chemical sensitivity (MCS) is characterized by chemically induced symptoms from multiple organs. These symptoms occur in response to demonstrable exposure to chemically unrelated compounds at doses far below those known to cause harmful effects in the general population. Although the mechanism of this action remains unclear and no acceptable and well-documented treatment for MCS has yet been established, regarding neurogenic inflammation, it has been hypothesized that an increased density of C-fiber neurons is found in symptomatic tissues. Methods: Using capsaicin, we examined the sensitivity of the cough reflex in patients with MCS and chronic cough (CC) and compared the findings with those in control subjects. Fifteen patients (four males, 11 females; mean (± SD) age 38.3±16.3 years) suffering from MCS and 29 patients (10 males, 19 females; mean age 46.4±15.9 years) who had cough symptoms lasting 4 weeks or longer and normal chest radiograph findings (CC) were enrolled in the present study. Twenty-nine healthy subjects (14 males, 15 females; mean age 37.9±9.5 years) who had no history of coughing during the previous 6 months and no chronic respiratory diseases were enrolled as controls. Subjects inhaled stepwise incremental concentrations of capsaicin (0.122-62.5 |imol/L) for 15 s. Inhalation was performed at 45 s intervals and the number of coughs per minute was counted. The provocation was terminated when the subject coughed five or more times. Ventilatory functions (forced vital capacity (FVC), forced expiratory volume in 1 s and the expiratory flow rate at 50 and 75% FVC (V50 and V25, respectively)) were also measured. Results: No significant differences were observed in ventilatory function test findings between the three groups. The log concentration of capsaicin causing five or more coughs (C5) was 0.150±0.630, 0.611±0.691 and 1.120±0.612 | mol/L in MCS, CC and control subjects, respectively. The log C5 in MCS subjects was significantly lower than that in CC and control subjects. Conclusions: Capsaicin is a cough-inducing agent in humans that possibly acts on non-myelinated C-fiber endings. The findings of the present study indicate that the mechanisms underlying MCS may originate in the sensory nervous system

Lung sound analysis can be an index of the control of bronchial asthma

Background: We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). Methods: 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. Results: E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV1/FVC ratio during the ICS treatment (r = −0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV1/FVC and V50,%pred (p < 0.001), and significantly higher FeNO and sputum eosinophil percentages (p = 0.008 and p < 0.001, respectively). Conclusions: The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients

Peripheral bronchial obstruction evaluation in patients with asthma by lung sound analysis and impulse oscillometry

Background: Computer-aided lung sound analysis (LSA) has been reported to be useful for evaluating airway inflammation and obstruction in asthma patients. We investigated the relation between LSA and impulse oscillometry with the evaluation of peripheral airway obstruction. Methods: A total of 49 inhaled corticosteroid-naive bronchial asthma patients underwent LSA, spirometry, impulse oscillometry, and airway hyperresponsiveness testing. The data were analyzed to assess correlations between the expiration: inspiration lung sound power ratio (dB) at low frequencies between 100 and 195 Hz (E/I LF) and various parameters. Results: E/I LF and X5 were identified as independent factors that affect V˙50,%predicted. E/I LF showed a positive correlation with R5 (r = 0.34, p = 0.017), R20 (r = 0.34, p = 0.018), reactance area (AX, r = 0.40, p = 0.005), and resonant frequency of reactance (Fres, r = 0.32, p = 0.024). A negative correlation was found between E/I LF and X5 (r = −0.47, p = 0.0006). E/I LF showed a negative correlation with FEV1/FVC(%), FEV1,%predicted, V˙50,%predicted, and V˙25,%predicted (r = −0.41, p = 0.003; r = −0.44, p = 0.002; r = −0.49, p = 0.0004; and r = −0.30, p = 0.024, respectively). E/I LF was negatively correlated with log PC20 (r = −0.30, p = 0.024). Log PC20, X5, and past smoking were identified as independent factors that affected E/I LF level. Conclusions: E/I LF as with X5 can be an indicator of central and peripheral airway obstruction in bronchial asthma patients

Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide

Background: We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. Methods: Steroid-naive bronchial asthma patients were classified into four phenotypes, including “Low inflammation” (35 patients), “Eosinophilic type” (58 patients), “Neutrophilic type” (15 patients), and “Mixed type” (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. Results: The median E/I LF value was highest in the “Mixed type” and lowest in the “Low inflammation” group. FeNO differentiated between the “Low inflammation” and “Eosinophilic type” groups, “Low inflammation” and “Neutrophilic type” groups, and “Neutrophilic type” and “Mixed type” (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the “Low inflammation” and “Eosinophilic type” groups (p = 0.006). E/I LF could distinguish the “Mixed type” group from the “Low inflammation” and “Eosinophilic type” groups (p = 0.002). Conclusions: A combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma