Background Individual studies have suggested the utility of fractional exhaled nitric oxide (F eno ) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients ...with chronic cough. Objective We sought to obtain summary estimates of diagnostic test accuracy of F eno measurement in predicting CVA, EB, or both in adults with chronic cough. Methods Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of F eno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of F eno measurement. Results A total of 15 studies involving 2187 adults with chronic cough were identified. F eno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 95% CI, 0.81-0.88 and 0.72 95% CI, 0.61-0.81, respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 95% CI, 0.77-0.84), and specificity was inconsistent. Conclusions The present meta-analyses indicated the diagnostic potential of F eno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, F eno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of F eno measurement in clinical practice of patients with chronic cough.
Background
The effect of novel tobacco products, such as electronic cigarettes (EC) and heated tobacco products (HTP), on allergic rhinitis (AR) and asthma is not well known.
Objective
To evaluate ...the health effect of novel tobacco products on asthma and AR.
Methods
This study was conducted using large survey data on Korean middle and high school students. The relationship between current asthma/AR and novel tobacco products user status was evaluated. In order to compare the combined effects of conventional cigarette (CC), EC, and HTP use on current allergic diseases, the participants were classified into 18 groups based on CC (current, former, and never), EC (current, former, and never), and HTP (ever and never) status.
Results
A total of 60,040 participants representing 2,850,118 Korean adolescents were analyzed. Of all participants, 6.7%, 2.7%, and 2.9% were current CC, current EC, and ever HTP users, respectively. Current CC and ever HTP use was significantly associated with current asthma and AR in adjusted models. Current EC showed association with current AR but the association with asthma disappeared in the adjusted model. Among 18 groups, the groups including current CC use showed higher risk of current AR and asthma than never HTP‐never EC‐never CC group. The odds ratio of current asthma especially increased more in those who used EC and/or HTP with CC concurrently than those in the never HTP‐never EC‐current CC user group.
Conclusion
Using EC and/or HTP in adolescents might enhance the adverse effect of CC on AR and asthma.
Among Korean adolescents aged from 12 to 18 years old, 6.7% and 2.7% currently use conventional cigarettes and electronic cigarettes, respectively and 2.9% ever used heated tobacco products. The use of conventional cigarette, electronic cigarette, and heated tobacco product, respectively and in combination increases the risk of allergic rhinitis and asthma in Korean adolescents. The use of heated tobacco product especially enhances the impact of conventional cigarettes on allergic rhinitis and asthma.
Background
Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the ...anti‐asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation.
Methods
Six‐week‐old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH‐S) treated with or without A. lwoffii before IL‐13 stimulation were analysed by quantitative RT‐PCR.
Results
In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+M2a and CD11b+M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down‐regulated the expression of M2 markers related but up‐regulated those related to M2b macrophages.
Conclusions and Clinical Relevance
Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.
Flow cytometry was performed on a murine asthma model to assess the phenotype of macrophages, innate lymphoid cells and T cells. Intranasal administration of Acinetobacter lwoffii alleviated Th2 inflammation through modulation of macrophage polarization: the lung macrophages tended to be M2b and less M2a, M2c. A. lwoffii also modulated innate lymphoid cells and T cells resulting in a lowered type 2 immune response.
Summary Background Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine ...hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans. Methods Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens–Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis. Results Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients ( P = 0.011, Pc = not significant; OR = 18.0(2.3–141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls ( Pc = 0.011, OR = 8.8(2.5–30.7) and Pc = 0.013, OR = 7.3(2.3–22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population. Conclusions HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population.
Recent work has shown that meningeal lymphatic vessels (mLVs), mainly in the dorsal part of the skull, are involved in the clearance of cerebrospinal fluid (CSF), but the precise route of CSF ...drainage is still unknown. Here we reveal the importance of mLVs in the basal part of the skull for this process by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF. Unlike dorsal mLVs, basal mLVs have lymphatic valves and capillaries located adjacent to the subarachnoid space in mice. We also show that basal mLVs are hotspots for the clearance of CSF macromolecules and that both mLV integrity and CSF drainage are impaired with ageing. Our findings should increase the understanding of how mLVs contribute to the neuropathophysiological processes that are associated with ageing.
Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 innate lymphoid cells (ILC2s) in asthma is well studied: however, the ...participation of other types of ILCs in the development of asthma remains unclear.
This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.
Each subset of ILCs and macrophages in induced sputum from 51 steroid-naive patients with asthma and 18 healthy donors was analyzed by using flow cytometry. Alveolar macrophages (AM) were sorted and cocultured with each subset of ILCs to determine whether the polarization of macrophages could be regulated by ILCs.
In addition to ILC2s, numbers of group 1 innate lymphoid cells (ILC1s) and group 3 innate lymphoid cells (ILC3s) were increased in induced sputum from asthmatic patients when compared with those in healthy control subjects. The dominance of macrophages in induced sputum was more prominent in asthmatic patients than in healthy control subjects. A positive correlation between numbers of ILC2s and numbers of M2 macrophages and those of ILC1s/ILC3s and M1 macrophages was observed. Coculture of ILC2s with AMs induced expression of M2 macrophage–related genes, whereas coculture of ILC1s and ILC3s with AMs induced expression of M1 macrophage–related genes through cytokine secretion, as well as cell-cell contact. According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages, and those with noneosinophilic asthma have an M1 macrophage–dominant profile.
A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.
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Background
While the clinical characteristics and outcomes of asthma‐chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the ...prevalence and features of ACO in patients with severe asthma are unclear.
Objectives
Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry.
Methods
At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non‐ACO groups, and the demographic and clinical characteristics of these two groups were compared.
Results
Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex‐ or current smokers (P < .001) compared with those in the non‐ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non‐ACO group. The ACO group used more inhaled long‐acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006).
Conclusion
Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.
We found that about one‐fourth of patients with severe asthma was diagnosed with ACO by specialists. The most common reason for ACO diagnosis was smoking history. ACO patients were predominantly male, older, and had more smoking history compared with non‐ACO patients. ACO patients had higher blood neutrophil count, but lower lung function. ACO patients used more LAMA, methylxanthine, and systemic corticosteroid and had more frequent exacerbations related to ER visits compared with those with severe asthma only. Abbreviations: ACO, asthma‐COPD overlap; ER, emergency room; FEV1, forced expiratory volume in one second.
Background
Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to ...date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma.
Methods
Nasopharyngeal swabs were collected from young adult and elderly asthma patients and non‐asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high‐throughput sequencing.
Results
The composition of microbiota differed between young adult and elderly, and it was different between asthmatics and non‐asthmatics in each age group. Different bacteria were related to FEV1% predicted in each age group. Genes related to lysine degradation, N‐glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction in inflammation and degradation of air pollutants, were higher in non‐asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis—which may all be related to increased inflammation and colonization of pathogenic bacteria—were higher in young adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity.
Conclusions
These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.
The upper airway microbiome was different between young adults and elderly, and their association with asthma was also different.
The microbiome genes reducing airway inflammation and degrading air pollutants were lower in asthmatics, whereas genes enhancing inflammation and mucosal bacterial colonization were higher in asthmatics of young adults.
The composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.
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