Allergy, Asthma & Immunology Research最新文献

Purpose: Recently, interest is increasing in using prebiotics, which are nutrient ingredients of live microorganism that improve the intestinal environments by promoting the growth of beneficial gut microflora. Although numerous studies have demonstrated the beneficial effects of probiotics on atopic dermatitis (AD) development, few have examined preventive and therapeutic effects of prebiotics on the onset and progression of AD.

Methods: In this study, we investigated therapeutic and preventive effect of prebiotics, including β-glucan and inulin, using an oxazolone (OX)-induced AD-like mouse model. Prebiotics were orally administered 2 weeks after the end of sensitization period (therapeutic study) and 3 weeks before the initial sensitization (prevention study). The physiological and histological alterations in the skin and gut of the mice were investigated.

Results: In the therapeutic study, the severity of skin lesions and inflammatory responses were effectively reduced after administering β-glucan and inulin, respectively. The expression level of calprotectin was significantly decreased by approximately 2-fold (P < 0.05) in the skin and gut of prebiotics-treated mice compared to the control. In addition, epidermal thickness and the number of infiltrated immune cells were markedly reduced in the dermis of prebiotics-treated mice compared with to those in the OX-induced mice (P < 0.05). These findings were same as in the prevention study. Importantly, pre-administration of β-glucan and inulin prevented the progression of AD by promoting the growth of good bacteria in the gut of OX-induced AD mice. However, the co-administration of β-glucan and inulin did not show enhanced preventive effects on these alterations.

Conclusions: Prebiotics has a therapeutic effect on AD in OX-induced AD mouse model. Moreover, our study suggests that prebiotics prevents the development of AD and this effect is associated with a change in gut microbiome.

Cough is one of the most common symptoms of acute coronavirus disease 2019, but cough may persist for weeks or months. This study aimed to examine the clinical characteristics of patients with post-coronavirus disease (COVID) persistent cough in the Omicron era. We conducted a pooled analysis comparing 3 different groups: 1) a prospective cohort of post-COVID cough (> 3 weeks; n = 55), 2) a retrospective cohort of post-COVID cough (> 3 weeks; n = 66), and 3) a prospective cohort of non-COVID chronic cough (CC) (> 8 weeks; n = 100). Cough and health status was assessed using patient-reported outcomes (PROs). Outcomes, including PROs and systemic symptoms, were longitudinally evaluated in the prospective post-COVID cough registry participants receiving usual care. A total of 121 patients with post-COVID cough and 100 with non-COVID CC were studied. Baseline cough-specific PRO scores did not significantly differ between post-COVID cough and non-COVID CC groups. There were no significant differences in chest imaging abnormality or lung function between groups. However, the proportions of patients with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb were 44.7% in those with post-COVID cough and 22.7% in those with non-COVID CC, which were significantly different. In longitudinal assessment of the post-COVID registry (n = 43), cough-specific PROs, such as cough severity or Leicester Cough Questionnaire (LCQ) scores, significantly improved between visits 1 and 2 (visit interval: median 35 [interquartile range, IQR: 23-58] days). In the LCQ score, 83.3% of the patients showed improvement (change ≥ +1.3), but 7.1% had worsened (≤ -1.3). The number of systemic symptoms was median 4 (IQR: 2-7) at visit 1 but decreased to median 2 (IQR: 0-4) at visit 2. In summary, post-COVID persistent cough was similar in overall clinical characteristics to CC. Current cough guideline-based approaches may be effective in most patients with post-COVID cough. Measurement of FeNO levels may also be useful for cough management.

Purpose: Epithelial cystatin SN (CST1), a type 2 cysteine protease inhibitor, was significantly upregulated in asthma. In this study, we aimed to investigate the potential role and mechanism of CST1 in eosinophilic inflammation in asthma.

Methods: Bioinformatics analysis on Gene Expression Omnibus datasets were used to explore the expression of CST1 in asthma. Sputum samples were collected from 76 asthmatics and 22 control subjects. CST1 mRNA and protein expression in the induced sputum were measured by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The possible function of CST1 was explored in ovalbumin (OVA)-induced eosinophilic asthma. Transcriptome sequencing (RNA-seq) was used to predict the possible regulated mechanism of CST1 in bronchial epithelial cells. Overexpression or knockdown of CST1 was further used to verify potential mechanisms in bronchial epithelial cells.

Results: CST1 expression was significantly increased in the epithelial cells and induced sputum of asthma. Increased CST1 was significantly associated with eosinophilic indicators and T helper cytokines. CST1 aggravated airway eosinophilic inflammation in the OVA-induced asthma model. In addition, overexpression of CST1 significantly enhanced the phosphorylation of AKT and the expression of serpin peptidase inhibitor, clade B, member 2 (SERPINB2), while knockdown using anti-CST1 siRNA reversed the trend. Furthermore, AKT had a positive effect on SERPINB2 expression.

Conclusions: Increased sputum CST1 may play a key role in the pathogenesis of asthma through involvement in eosinophilic and type 2 inflammation through activation of the AKT signaling pathway, further promoting SERPINB2 expression. Therefore, targeting CST1 might be of therapeutic value in treating asthma with severe and eosinophilic phenotypes.

The lungs have their own microbiota which seems to be altered in disease processes such as asthma. Viral infection accounts for many asthma exacerbations. Little is known about the lung virome, and the role that viruses play in non-exacerbating asthmatics. We aimed to assess if detection of virus in bronchoscopy samples of asthmatic patients in a non-exacerbating state influences their asthma control and modulates airway cytokine composition. Patients were recruited from a specialist asthma clinic and underwent bronchoscopy with standardised bronchoalveolar lavage (BAL). Viral analysis was performed; cell differential and cytokine levels were measured. Forty-six samples were obtained of which 10.8% demonstrated evidence of airway virus, and 91.3% of patients in the cohort were classed as severe asthmatics. Oral steroid use was significantly higher in severe asthmatic patients with virus detected, and the forced expiratory volume in one second tended to be lower in the virus-detected group. It was also found that BAL interleukin-13 and tumor necrosis factor-α levels were significantly higher in severe asthmatic patients with virus detected. Our results suggest that in severe asthmatics in a non-exacerbating state, the presence of virus resulted in overall poorer asthma control. The pattern of cytokine elevation seen in asthmatic patients with virus detected may provide insight to the pathophysiology involved.

Purpose: Obstructive sleep apnea (OSA), a highly prevalent and potentially serious sleep disorder, requires effective screening tools. Saliva is a useful biological fluid with various metabolites that might also influence upper airway patency by affecting surface tension in the upper airway. However, little is known about the composition and role of salivary metabolites in OSA. Therefore, we investigated the metabolomics signature in saliva from the OSA patients and evaluated the associations between identified metabolites and salivary surface tension.

Methods: We studied 68 subjects who visited sleep clinic due to the symptoms of OSA. All underwent full-night in-lab polysomnography. Patients with apnea-hypopnea index (AHI) < 10 were classified to the control, and those with AHI ≥ 10 were the OSA groups. Saliva samples were collected before and after sleep. The centrifuged saliva samples were analyzed by liquid chromatography with high-resolution mass spectrometry (ultra-performance liquid chromatography-tandem mass spectrometry; UPLC-MS/MS). Differentially expressed salivary metabolites were identified using open source software (XCMS) and Compound Discoverer 2.1. Metabolite set enrichment analysis (MSEA) was performed using MetaboAnalyst 5.0. The surface tension of the saliva samples was determined by the pendant drop method.

Results: Three human-derived metabolites (1-palmitoyl-2-[5-hydroxyl-8-oxo-6-octenoyl]-sn-glycerol-3-phosphatidylcholine [PHOOA-PC], 1-palmitoyl-2-[5-keto-8-oxo-6-octenoyl]-sn-glycerol-3-phosphatidylcholine [KPOO-PC], and 9-nitrooleate) were significantly upregulated in the after-sleep salivary samples from the OSA patients compared to the control group samples. Among the candidate metabolites, only PHOOA-PC was correlated with the AHI. In OSA samples, salivary surface tension decreased after sleep. The differences in surface tension were negatively correlated with PHOOA-PC and 9-nitrooleate concentrations. Furthermore, MSEA revealed that arachidonic acid-related metabolism pathways were upregulated in the after-sleep samples from the OSA group.

Conclusions: This study revealed that salivary PHOOA-PC was correlated positively with the AHI and negatively with salivary surface tension in the OSA group. Salivary metabolomic analysis may improve our understanding of upper airway dynamics and provide new insights into novel biomarkers and therapeutic targets in OSA.

Purpose: Staphylococcus aureus enterotoxin-specific immunoglobulin E (SE-sIgE) sensitization tends to increase with age and is known to be associated with asthma and severity in older adults. However, the long-term impact of SE-sIgE in the elderly remains unknown. This study aimed to examine the relationships between SE-sIgE and fixed airflow obstruction (FAO) in a cohort of elderly asthmatics.

Methods: A total of 223 elderly asthmatics and 89 controls were analyzed. Patients were assessed for demographics, history of chronic rhinosinusitis (CRS), asthma duration, acute exacerbation frequency, and lung function at baseline and then were prospectively followed up for 2 years. Serum total IgE and SE-sIgE levels were measured at baseline. Airflow obstruction was defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7 at baseline and FAO was defined as FEV1/FVC ratio < 0.7 over the 2-year follow-up.

Results: At baseline, the prevalence of airflow obstruction was 29.1%. Patients with airflow obstruction were significantly more likely to be male, and have a positive smoking history, comorbid CRS, and higher levels of SE-sIgE than those without airflow obstruction. Multivariate logistic regression analysis showed that airflow obstruction was significantly associated with current smoking and SE-sIgE sensitization at baseline. After the 2-year follow-up, baseline SE-sIgE sensitization was consistently related to FAO. Meanwhile, the number of exacerbations per year was significantly correlated with SE-sIgE levels.

Conclusions: Baseline SE-sIgE sensitization was significantly associated with the number of asthma exacerbations and FAO after the 2-year follow-up in elderly asthmatics. These findings warrant further investigation of the direct and mediating roles of SE-sIgE sensitization on airway remodeling.

Purpose: We aimed to investigate epidermal lipid profiles and their association with skin microbiome compositions in children with atopic dermatitis (AD).

Methods: Specimens were obtained by skin tape stripping from 27 children with AD and 18 healthy subjects matched for age and sex. Proteins and lipids of stratum corneum samples from nonlesional and lesional skin of AD patients and normal subjects were quantified by liquid chromatography tandem mass spectrometry. Skin microbiome profiles were analyzed using bacterial 16S rRNA sequencing.

Results: Ceramides with nonhydroxy fatty acids (FAs) and C18 sphingosine as their sphingoid base (C18-NS-CERs) N-acylated with C16, C18 and C22 FAs, sphingomyelin (SM) N-acylated with C18 FAs, and lysophosphatidylcholine (LPC) with C16 FAs were increased in AD lesional skin compared to those in AD nonlesional skin and that of control subjects (all P < 0.01). SMs N-acylated with C16 FAs were increased in AD lesional skin compared to control subjects (P < 0.05). The ratio of NS-CERs with long-chain fatty acids (LCFAs) to short-chain fatty acids (SCFAs) (C24-32:C14-22), the ratio of LPC with LCFAs to SCFAs (C24-30:C16-22) as well as the ratio of total esterified omega-hydroxy ceramides to total NS-CERs were negatively correlated with transepidermal water loss (rho coefficients = -0.738, -0.528, and -0.489, respectively; all P < 0.001). The proportions of Firmicutes and Staphylococcus were positively correlated to SCFAs including NS ceramides (C14-22), SMs (C17-18), and LPCs (C16), while the proportions of Actinobacteria, Proteobacteria, Bacteroidetes, Corynebacterium, Enhydrobacteria, and Micrococcus were negatively correlated to these SCFAs.

Conclusions: Our results suggest that pediatric AD skin shows aberrant lipid profiles, and these alterations are associated with skin microbial dysbiosis and cutaneous barrier dysfunction.

Purpose: A subset of asthmatics suffers from persistent airflow limitation, known as remodeled asthma, despite optimal treatment. Typical quantitative scoring methods to evaluate structural changes of airway remodeling on high-resolution computed tomography (HRCT) are time-consuming and laborious. Thus, easier and simpler methods are required in clinical practice. We evaluated the clinical usefulness of a simple, semi-quantitative method based on 8 HRCT parameters by comparing asthmatics with a persistent decline of post-bronchodilator (BD)-FEV1 to those with a BD-FEV1 that normalized over time and evaluated the relationships of the parameters with BD-FEV1.

Methods: Asthmatics (n = 59) were grouped into 5 trajectories (Trs) according to the changes of BD-FEV1 over 1 year. After 9-12 months of guideline-based treatment, HRCT parameters including emphysema, bronchiectasis, anthracofibrosis, bronchial wall thickening (BWT), fibrotic bands, mosaic attenuation on inspiration, air-trapping on expiration, and centrilobular nodules were classified as present (1) or absent (0) in 6 zones.

Results: The Tr5 group (n = 11) was older and exhibited a persistent decline in BD-FEV1. The Tr5 and Tr4 groups (n = 12), who had a lower baseline BD-FEV1 that normalized over time, had longer durations of asthma, frequent exacerbations, and higher doses of steroid use compared to the Tr1-3 groups (n = 36), who had a normal baseline BD-FEV1. The Tr5 group had higher emphysema and BWT scores than the Tr4 (P = 8.25E-04 and P = 0.044, respectively). Scores for the other 6 parameters were not significantly different among the Tr groups. BD-FEV1 was inversely correlated with the emphysema and BWT scores in multivariate analysis (P = 1.70E-04, P = 0.006, respectively).

Conclusions: Emphysema and BWT are associated with airway remodeling in asthmatics. Our simple, semi-quantitative scoring system based on HRCT may be an easy-to-use method for estimating airflow limitation.