The Relationship between Symptom Flare of Atopic Dermatitis and Airborne Japanese Cedar and Cypress Pollen Counts: A Self-Scoring Diary Study

Background. With an increase in Japanese cedar and cypress (JC) pollinosis, the relationship between JC pollen and atopic dermatitis (AD) has been studied. Some reports suggest that JC pollen can be one exacerbating factor for AD, but there has been no report that discusses JC pollen counts relating to AD symptom flare although actual airborne JC pollen counts can widely fluctuate throughout the pollen season. Objective. The relationship between symptom flare of AD and airborne JC pollen counts was examined. Methods. We monitored JC pollen counts in real time and divided the counts into low and high level. We then analyzed self-scored “itch intensity” recorded by 14 AD patients through a self-scoring diary. Results. Among the 14 patients, 7 had significantly higher itch intensity while the pollen counts were high. Conclusion. Even during the pollen season, actual airborne pollen counts can widely fluctuate. Our study suggested that symptom flare of AD could be influenced by the actual pollen counts

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

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

Association of Asian Dust with daily medical consultations for pollinosis in Fukuoka City, Japan

Abstract Background The objective is to examine the association between AD and the daily number of medical consultations for pollinosis in Fukuoka City. Methods We analyzed 65,488 daily medical consultations for pollinosis from 4 clinics in Fukuoka City from February to April, 1989–2012. Time-series analyses were performed to estimate the clinic-specific relative risk (RR) of clinical pollinosis associated with AD, adjusting for airborne pollen, suspended particulate matter (SPM), meteorological and temporal factors. Delayed effects were considered. The association with SPM was also examined given its relationship with AD. The clinic-specific RRs were combined using meta-analytic technique. Results AD on the same day (lag 0) and the previous 3 to 5 days (lags 3, 4, and 5) was positively associated with the risk of medical consultations for pollinosis. Clinic visits were 21.5% (95% confidence interval 3.1% – 43.1%) higher when there was an AD event (across lags 0–5). The association with SPM showed comparable lag structure, but with smaller effect estimates. When stratified by the occurrence of AD, the estimated risk increases associated with SPM did not differ between the AD-affected and AD-free days. Conclusion AD is associated with an increased risk of medical consultations for pollinosis in spring. More research is needed to elucidate the roles of air particles with different sizes

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

A Study of the Usefulness of Anti-inflammatory Treatment for Mild Intermittent Asthma (Step 1): Budesonide vs. Montelukast

Background: Early intervention in adult asthma has been evaluated mostly with regard to symptoms, respiratory function and airway hyperresponsiveness, and has rarely been evaluated with regard to airway inflammation. Further, no clinical data concerning prevention of remodeling by anti-inflammatory therapy have been reported. The anti-inflammatory activities of an inhaled steroid and a leukotriene receptor antagonist were compared using sputum induced by inhaled hyperosmotic NaCl solution, and the usefulness of anti-inflammatory treatment for mild intermittent asthma (step 1) was investigated. Methods: The subjects of the study were patients with mild intermittent asthma (step 1) who had not received steroid treatment and had only been treated with inhaled β2-stimulants as needed. The subjects were divided into two groups : one group received 400 μg/day of budesonide (BUD group ; n = 15) and the other group received 10 mg/day of montelukast (MK group ; n = 12). The anti-inflammatory activities of BUD and MK were compared by examining respiratory function, exhaled nitric oxide (ENO) concentrations, airway hyperresponsiveness (acetylcholine provocation test) and the sputum induced by inhalation of hyperosmotic NaCl solution at three time points, i.e., before, 1 month after, and 6 months after the start of treatment. Results: It was shown that even in mild intermittent asthma (step 1) the levels of ENO and sputum eosinophil ratio were elevated, indicating that airway inflammation was clearly present and that airway hyperresponsiveness was elevated. The effects of BUD and MK in improving ENO and sputum eosinophil ratio were almost the same. However, airway hyperresponsiveness in both groups were not significantly improved after 1 and 6 months of treatment. Conclusions: Anti-inflammatory treatment is necessary even for mild intermittent asthma (step 1). We believe that early intervention with anti-inflammatory drugs is important for the prevention of airway remodeling, exacerbation of disease and progression to intractable asthma. Either of the two types of drugs, low-dose inhaled steroids or leukotriene receptor antagonists, can be selected as anti-inflammatory drugs for mild intermittent asthma

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

Association of Matrix Metalloproteinase 8 Genetic Polymorphisms with Bronchial Asthma in a Japanese Population

Asthma has a strong genetic component. The final disease phenotype results from complex interactions between environment and multiple genes of small-to-modest effects. We investigated whether the polymorphism in genes encoding inflammatory mediators and cytokines is important for solving the onset and progression of asthma. We investigated whether 31 single nucleotide polymorphisms (SNPs) in genes encoding cytokines or monokines (interleukin [IL]-5R, matrix metalloproteinase [MMP] 8, beta2 adrenergic receptor, cytotoxic T-lymphocyte-associated antigen 4, IL-3, C-reactive protein, cytochrome P450 (CYP) 2C9, CYP3A4, a disintegrin and metalloproteinase [ADAM] 33, cysteinyl leukotriene receptor [CysLTR] 1, CysLTR2, eosinophilic cationic protein, glucocorticoid receptor, and leukotriene A 4 hydrolase) are related to asthma development in 206 Japanese bronchial asthma patients and 127 healthy controls. Using multifactor dimensionality reduction (MDR), we identified rs17099451 in MMP8, using a single locus model, with a mean cross-validation of 87.0%. Using a two-locus model, combinations of MMP8 and rs44707 in ADAM33, and MMP8 and rs40401 in IL-3, were identified, with mean cross-validation consistencies reaching 45.0%. Of the SNPs selected by the MDR method, rs17099451 in MMP8 and rs40401 in IL-3 were regarded as the most significant results in a 2 × 2 dominant model analysis. The finding that an MMP8 allele was most strongly related to asthma development indicates that metalloproteinase function is crucial to the airflow limitation process involved in this disease