Non-atopic Asthma Research Articles

Association of the 5HTR2C gene Ser23 variation with childhood allergic asthma

Abstract Objective: Allergic asthma is the most frequently observed subtype of individuals with asthma. The effects of serotonin plays in the pathophysiology of asthma has not been clearly determined. Thus, this study aimed to investigate the association between the 5HTR2C gene rs 6318 G>C polymorphism and allergic asthma in pediatric patients in Cyprus. Methods: This study included total number of 177 individuals with 118 control and 59 pediatric patients (43 atopic and 16 non-atopic asthma patient). A skin prick test was performed for each patient to confirm asthma diagnosis and to evaluate atopic status. Genotyping for the 5HTR2C was completed by Real Time-PCR analysis. Results: The genotype distribution frequencies were not in agreement with the Hardy-Weinberg Equilibrium in the patients’ group (p<0.00001). The frequency of the risk allele (allele C) was not significantly different between the patient and control groups (p=0.255). The genotypic distribution between atopic asthma and non-atopic asthma within the patientsts groups was not in agreement with the Hardy-Weinberg Equilibrium (p=0.006). However, risk allele presence showed a statistically significant association with atopy-related asthma (p=0.037). Discussion & Conclusion: Overall, despite the finding of no association between the 5HTR2C rs6318 C allele and childhood asthma, the current results indicated that there is a strong association between the 5HTR2C rs6318 C variant and childhood atopic asthma.

Revisiting differences between atopic and non-atopic asthmatics: When age is shaping airway inflammatory profile

BackgroundAtopic asthma is one of the most common asthma phenotypes and is generally opposed to the non-atopic counterpart. There have been very few large-scale studies comparing atopic and non-atopic asthmatics in terms of systemic and airway inflammation across the age spectrum. MethodsHere, we have undertaken a retrospective study investigating 1626 patients (924 atopic and 702 non-atopic asthmatics) recruited from our university asthma clinic who underwent extensive clinical investigations including induced sputum. Atopy was defined by any positive specific IgE to common aeroallergens (>0,35 kU/L). We performed direct comparisons between the groups and sought to appreciate the influence of age on the airway and systemic inflammatory components. The study was approved by the ethics committee of the University Hospital of Liege (Ref. 2016/276). Informed consents were obtained from healthy subjects. ResultsAtopic asthmatics were younger (P < .001), had a higher male/female ratio (P < .001), an earlier disease onset (P < .001) and a greater proportion of treated rhinitis (P < .001) while non-atopic asthmatics had greater smoke exposure (P < .001), lower FEV1/FVC ratio (P = .01) and diffusing capacity (P < .001). There was no difference between the 2 groups regarding FEV1 (% predicted), asthma control, asthma quality of life and exacerbations in the previous 12 months. Regarding inflammation, atopic patients had higher FeNO levels (median = 28 ppb, P < .001), were more eosinophilic both in blood (median = 2.8%, P < .001) and in sputum (median = 2.2%, P < .001) while non-atopic patients displayed greater blood (median = 57%, P = .01) and sputum (median = 58.8%, P = .01) neutrophilic inflammation. However, stratifying patients by age showed that non-atopic asthmatics above 50 years old became equally eosinophilic in the sputum (P = .07), but not in the blood, as compared to atopic patients. Likewise, FeNO rose in non-atopic patients after 50 years old but remained, however, lower than in atopic patients. ConclusionsWe conclude that, while sharing many features, atopic group still differentiates from non-atopic asthmatics by demographics, functional and inflammatory profiles. When atopic asthmatics showed a constant eosinophilic pattern across the age spectrum, non-atopic asthmatics were found to be neutrophilic before the age of 50 but eosinophilic above 50 years old.

Asthma and COVID-19 in the elderly: course, survival, predictors of mortality

Bronchial asthma occurs in 0.9 – 17% of patients hospitalized with COVID-19. However, it is not clear whether asthma is a risk factor for the development and severity of COVID-19. Studies have shown that patients with asthma appear to be more susceptible to COVID-19 infection, but severe disease progression is not related to medication use, including asthma biologics, but rather to older age and comorbidities.Aim.To evaluate the clinical course of SARS-CoV-2 infection in elderly patients with asthma, to examine the effect of asthma and comorbidities on COVID-19related outcomes, and to determine predictors of mortality.Methods.Elderly patients [WHO, 2020] (&gt; 60 years,n= 131, median age 74 (67; 80) years; 59 men, 72 women) with asthma hospitalized for COVID-19 were included in the study. COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a documented diagnosis of asthma (GINA, 2020).Results.Out of 131 patients, 30 (22.9%) died in the hospital, and 15 (14.9%) died after discharge from the hospital (within 90 days). The group of patients with lethal outcome showed the following differences from those who recovered: values of Charlson index, respiration rate, degree of lung damage on CT scan, absolute number of leukocytes, neutrophils and neutrophils-to-lymphocytes ratio, C-reactive protein on the 5th day of hospitalization, and LDH were statistically significantly higher, while absolute number of eosinophils, total protein content, SpO2and SpO2/FiO2levels were lower; steroid intake during the year and non-atopic asthma were more common. Multivariate and ROC analysis revealed the most significant predictors of hospital mortality and their thresholds: Charlson comorbidity index ≥ 6 points, neutrophil/lymphocyte ratio ≥ 4.5, total protein ≤ 60 g/l, eosinophil level ≤ 100 cells/μL.Conclusion.The most significant predictors of hospital mortality in elderly patients with severe COVID-19 against asthma are Charlson comorbidity, neutrophil/lymphocyte ratio; lower eosinophil and total protein levels. Survival time of patients has an inverse correlation with the number of mortality risk factors present.

Effect Of Chemerin Deficiency On Ozone-Induced Lung Injury And Lung Inflammation

Chemerin is a non-chemokine chemoattractant for macrophages, natural killer (NK) cells, and plasmacytoid dendritic cells. Macrophages and NK cells promote lung injury and lung inflammation induced by exposure to ozone (O3), a criteria pollutant, an occupational irritant, and a non-atopic asthma stimulus. We hypothesized that genetic deficiency of chemerin in mice would lessen the severity of O3-induced lung injury and lung inflammation since macrophages and NK cells are unable to respond to a chemotactic signal from chemerin.

Pollutants and climatic conditions related to the childhood asthma and atopic dermatitis

Indoor, outdoor pollutants and climatic conditions in the growing environment can develop childhood asthma and atopic dermatitis. Therefore, it is important to identify the environmental burden of the community on the risk of childhood asthma and atopic dermatitis. To clarify the relationship between regional prevalence rate of childhood asthma and atopic dermatitis among the first grade elementary school students and preschool indoor and outdoor conditions such as smoking rate, photochemical oxidants concentration, ambient temperature and relative humidity, multiple linear regression analysis was performed. Stepwise multiple regression analysis with asthma rate as the objective variable, atopic dermatitis rate, smoking rate, photochemical oxidants, ambient temperature and relative humidity as explanatory variables, revealed that atopic dermatitis rate and smoking rate were significant independent variables. This result suggests that tobacco smoke is a risk factor for non-atopic asthma rather than atopic asthma. Stepwise multiple regression analysis with atopic dermatitis rate among first grade elementary school students as the objective variable, smoking rate, photochemical oxidants, ambient temperature and relative humidity as explanatory variables, revealed that photochemical oxidants and ambient temperature were significant independent variable. Present study suggests that preschool indoor and outdoor conditions such as environmental tobacco smoke, photochemical oxidants, and ambient temperature may be associated with the development of childhood asthma and atopic dermatitis.

Comparison of miRNA expression in patients with seasonal and perennial allergic rhinitis and non-atopic asthma.

MicroRNAs (miRNA) are small non-coding molecules that play a significant regulatory role in several allergic diseases. However, their role in allergic rhinitis is still not clearly understood. The aim of this study was to identify the candidate miRNAs that can discriminate between different forms of allergic rhinitis and also differ in and out of the allergen season. The study included 20 healthy children, 20 patients with seasonal allergic rhinitis (SAR), 20 non-atopic asthmatics (NA-A), and 12 patients with perennial allergic rhinitis (PAR). Patients with SAR were evaluated comparatively in and outside the allergen season. The changes in the expressions of selected miRNAs (miR- 125b, miR-126, miR-133b, miR-181a, and miR-206) that were found related to the allergic diseases according to the literature were determined using quantitative polymerase chain reaction. In the SAR group, expression levels of miR-125b (p=0.040) and miR181a (p=0.014) were lower than in the controls outside of the allergen season. Expression levels of miR-181a were different between patients with SAR and NA-A (p=0.003), also between the SAR and PAR (p=0.001) groups in multiple comparisons. In contrast, the expression of miR-206 was found to be decreased in patients with NA-A and PAR compared with the controls (p=0.005 and p=0.024, respectively). In correlation analysis, expression levels of miR-125b and peak expiratory flow (PEF) values were found to be negatively correlated in the SAR (p=0.013) and PAR (p=0.029) groups. The expression level of miR-206 was positively correlated with total IgE levels in PAR (p=0.007). Receiver operating characteristic analysis revealed that miR-125b and miR-181a predicted the risk of SAR (p=0.040 and p=0.014, respectively), and miR-206 for NA-A and PAR (p=0.005 and p=0.024, respectively). Our study showed that expression levels of miRNAs were different according to the type of allergic diseases and the presence of allergens. miR-181a and miR-125b can be candidate biomarkers for SAR, and miR-206 for NA-A and PAR.

Association Between Clinical Burden and Blood Eosinophil Counts in Asthma: Findings From a Korean Adult Asthma Cohort.

BackgroundSome reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort.MethodsClinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated.ResultsIn total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266–23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083–11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL.ConclusionThe baseline blood eosinophil count may predict the future clinical burden of asthma.

A Novel Nonhuman Primate Model of Nonatopic Asthma.

Nonhuman primate models have an essential role in understanding progressive respiratory disease pathogenesis. Immune and physiologic parameters in the nonhuman primate closely reflect the complexity of human systems and provide an exceptional translational impact for the investigation of the mucosal immune changes in response to environmental exposures. This potential warrants the development of novel models that will clarify the interaction of respiratory disease and the inhalable environment and the potential of novel therapies to alleviate the untoward results of these interactions. Nonhuman primate models of asthma can be spontaneous, induced, or experimentally manipulated by various exposures. Here we describe a model of exacerbation of airway hyperreactivity induced by exposure to an air pollutant, ozone, in a cohort of young adult asthmatic rhesus macaques.

Integrated metabolic and microbial analysis reveals host\u2013microbial interactions in IgE-mediated childhood asthma

A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other (P < 0.01). Highly sensitized asthma associated metabolites were mainly enriched in pyruvate and acetyl-CoA metabolisms. Metabolites associated with highly sensitized atopic asthma were mostly correlated with microbiota in the airways. Acetic acid, a short-chain fatty acid (SCFA), was negatively correlated with the genus Atopobium (P < 0.01), but positively correlated with the genus Fusobacterium (P < 0.05). In conclusion, metabolomics reveals microbes-related metabolic pathways associated with IgE responses to house dust mite allergens in childhood asthma. A strong correlation of metabolites related to highly sensitized atopic asthma with airway microbiota provides linkages between the host–microbial interactions and asthma endotypes.

Pediatric thalassemic patients have higher incidence of asthma: A nationwide population-based retrospective cohort study.

IntroductionPatients with hemoglobinopathies have been reported to have higher rates of pulmonary complications. Few studies have investigated the association between thalassemia and asthma in children.MethodsWe used the data of one million individuals randomly selected from the Registry for Beneficiaries of the National Health Insurance Research Database. One thalassemic child was matched with four control children without thalassemia according to sex, birth year, birth season, prematurity, and previous enteroviral infection.ResultsA total of 800 hundred thalassemic children and 3200 controls were included. Children with thalassemia had higher rates of developing asthma (41.81 vs 25.70 per 1000 person-years, P < 0.001) than the non-thalassemia controls with an adjusted hazard ratio of 1.37 (95% confidence interval [CI] = 1.19–1.58). Boys in the thalassemia cohort had a significantly higher adjusted incidence hazard ratio (IRR) of asthma than those in the non-thalassemia cohort (adjusted IRR = 1.45, 95% CI = 1.02–1.73). The risk of atopic and nonatopic asthma was higher in the thalassemia cohort than in the non-thalassemia cohort (IRR = 1.3, 1.61, respectively).ConclusionsChildren with thalassemia were more likely to develop asthma. More attention should be paid to the early diagnosis of asthma and prevention of asthma attacks.

Asthma Phenotypes and Host Risk Factors Associated With Various Asthma-Related Outcomes in Health Workers.

Background: Work-related asthma phenotypes in health workers (HWs) exposed to cleaning agents have not been investigated extensively as other occupational exposures. This study aimed to describe asthma phenotypes and to identify important host risk factors associated with various asthma-related outcomes.Methods: A cross-sectional study of 699 HWs was conducted in two large tertiary hospitals. A total of 697 HWs completed questionnaire interviews. Sera collected from 682 HWs were analyzed for atopy (Phadiatop) and IgE to occupational allergens (NRL—Hev b5, Hev b6.02; chlorhexidine and ortho-phthalaldehyde—OPA). Methacholine (MCT), bronchodilator challenge (BDR) and fractional exhaled nitric oxide (FeNO) were performed. An asthma symptom score (ASS) used five asthma-related symptoms reported in the past 12 months. Current asthma was based on use of asthma medication or an asthma attack or being woken up by an attack of shortness of breath in the past 12 months. Nonspecific bronchial hyperresponsiveness (NSBH) was defined as having either a positive MCT or a significant bronchodilator response. Two continuous indices of NSBH [continuous index of responsiveness (CIR) and dose-response slope (DRS)] were calculated.Results: The prevalence of current asthma was 10%, atopic asthma (6%) and non-atopic asthma (4%). Overall, 2% of subjects had work-related asthma. There was a weak positive association between NSBH and FeNO [CIR: Beta coefficient (β) = 0.12; CI: 0.03–0.22 and DRS: β = 0.07; CI: 0.03–0.12]. Combining FeNO ≥ 50 ppb with a BDR [mean ratio (MR) = 5.89; CI: 1.02–34.14] or with NSBH (MR = 4.62; CI: 1.16–18.46) correlated better with ASS than FeNO alone (MR = 2.23; CI: 1.30–3.85). HWs with current asthma were twice as likely to be atopic. FeNO was positively associated with atopy (OR = 3.19; CI: 1.59–6.39) but negatively associated with smoking status (GMR = 0.76; CI: 0.62–0.94). Most HWs sensitized to occupational allergens were atopic.Conclusion: Atopic asthma was more prevalent than non-atopic asthma in HWs. Most asthma-related outcomes were positively associated with allergic predictors suggesting a dominant role for IgE mechanisms for work-related symptoms and asthma associated with sensitization to OPA or chlorhexidine.

Prostaglandin D2 metabolites activate asthmatic patient-derived type 2 innate lymphoid cells and eosinophils via the DP2 receptor

BackgroundProstaglandin D2 (PGD2) signaling via prostaglandin D2 receptor 2 (DP2) contributes to atopic and non-atopic asthma. Inhibiting DP2 has shown therapeutic benefit in certain subsets of asthma patients, improving eosinophilic airway inflammation. PGD2 metabolites prolong the inflammatory response in asthmatic patients via DP2 signaling. The role of PGD2 metabolites on eosinophil and ILC2 activity is not fully understood.MethodsEosinophils and ILC2s were isolated from peripheral blood of atopic asthmatic patients. Eosinophil shape change, ILC2 migration and IL-5/IL-13 cytokine secretion were measured after stimulation with seven PGD2 metabolites in presence or absence of the selective DP2 antagonist fevipiprant.ResultsSelected metabolites induced eosinophil shape change with similar nanomolar potencies except for 9α,11β-PGF2. Maximal values in forward scatter of eosinophils were comparable between metabolites. ILC2s migrated dose-dependently in the presence of selected metabolites except for 9α,11β-PGF2 with EC50 values ranging from 17.4 to 91.7 nM. Compared to PGD2, the absolute cell migration was enhanced in the presence of Δ12-PGD2, 15-deoxy-Δ12,14-PGD2, PGJ2, Δ12-PGJ2 and 15-deoxy-Δ12,14-PGJ2. ILC2 cytokine production was dose dependent as well but with an average sixfold reduced potency compared to cell migration (IL-5 range 108.1 to 526.9 nM, IL-13 range: 125.2 to 788.3 nM). Compared to PGD2, the absolute cytokine secretion was reduced in the presence of most metabolites. Fevipiprant dose-dependently inhibited eosinophil shape change, ILC2 migration and ILC2 cytokine secretion with (sub)-nanomolar potencies.ConclusionProstaglandin D2 metabolites initiate ILC2 migration and IL-5 and IL-13 cytokine secretion in a DP2 dependent manner. Our data indicate that metabolites may be important for in vivo eosinophil activation and ILC2 migration and to a lesser extent for ILC2 cytokine secretion.

Different effects of smoking on atopic and non-atopic adult-onset asthma.

BackgroundBoth tobacco smoking and atopy increase the risk of adult‐onset asthma. We studied if there are differences in the effects of smoking on the risks of atopic and non‐atopic adult‐onset asthma, and if gender modifies these effects.MethodsThe Finnish Environment and Asthma Study (FEAS) includes 521 incident cases of adult‐onset asthma and 932 population‐based controls, aged 21 to 63 years, recruited from a geographically defined area of Pirkanmaa, South Finland. Asthma was defined based on symptoms and lung function measurements, atopy by IgE antibodies to common aeroallergens and smoking by the study questionnaire.ResultsAltogether 212 cases were atopic, and 251 cases were non‐atopic. Regular smoking increased the risk of atopic asthma (adjusted OR 1.24, 95% CI 0.83–1.85), this effect was seen in women (aOR 1.77, 1.06–2.95) but not in men (aOR 0.75, 0.39–1.45). Among regular smokers, the amount smoked was lowest among women with atopic asthma. Recent quitting of smoking was related to increased risk of both atopic (aOR 4.91, 2.26–10.65) and non‐atopic (aOR 4.37, 1.87–10.21) asthma. Having quitted smoking over a year ago was related to increased risk of non‐atopic asthma (aOR 1.57, 1.08–2.28), mainly in men (aOR 2.03, 1.06–3.88).ConclusionsIn women, rather small amounts of regular smoking increase the risk of atopic asthma. However, for non‐atopic asthma, the smoking induced risk continues for longer after quitting, especially in men. In conclusion, the effects of smoking on the risks of atopic and non‐atopic asthma differ, and gender modifies these effects.

The predective role of neutrophils to lymphocytes ratio in bronchial asthma

Abstract Background Neutrophil to lymphocyte ratio is an easy and rapid biomarker measured in peripheral blood, and plays a helpful role in assessing prognosis of bronchial asthma and its severity. Aim To assess NLR levels among atopic asthmatics, non-atopic asthmatics and healthy controls. Patient and methods The study included 120 asthmatic patients and 60 healthy control. Results A highly significant difference was observed between asthmatic patients and healthy controls regarding neutrophil\lymphocyte ratio (p &amp;lt; 0.0001). Conclusion Neutrophil to lymphocyte ratio is useful to assess asthma severity.

Asthma and COVID-19: who wins the contested territory of the lower airways?

Among the numerous published studies on COVID-19 in a pandemic year, few listed asthma as a comorbidity, making it therefore difficult to draw any solid conclusions. The respiratory allergy and controlled exposures to allergens are associated with significant reductions in the expression of angiotensin-converting enzyme 2 (ACE2), receptor for SARS-CoV-2 entry into human cells. There is a hypothesis that patients with chronic asthma, due to the type 2 inflammatory profile, may be potentially resistant to developing a severe clinical course of COVID-19. The low IFN-g-mediated response in the respiratory tract of asthmatic patients could limit ACE2 expression in the target cells of SARS-CoV-2 infection. The inflammatory profile of the airways in patients with chronic asthma is mainly related to a Th2 response in type-2 asthma, with production of IL-4, IL-13 and IL-5, presenting antagonistic relationship with pro-inflammatory cytokines such as IFN-g, produced at high levels in severe COVID-19. Published studies, for the most part, are retrospective and may have loss of information or present material with limited possibility for more robust and conclusive analysis. It is important to discuss how patients with atopic or nonatopic asthma seem to protect themselves from new coronavirus infection and how asthma affects COVID-19 and the course of the disease, since there is no increased mortality in asthmatic patients with COVID-19 compared to non-asthmatic patients.

Consumption of differently processed milk products and the risk of asthma in children.

Consumption of unprocessed cow's milk has been associated with a lower risk of childhood asthma and/or atopy. Not much is known about differently processed milk products. We aimed to study the association between the consumption of differently processed milk products and asthma risk in a Finnish birth cohort. We included 3053 children from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Asthma and its subtypes were assessed at the age of 5years, and food consumption by food records, at the age of 3 and 6months and 1, 2, 3, 4, and 5years. We used conventional and processing (heat treatment and homogenization)-based classifications for milk products. The data were analyzed using a joint model for longitudinal and time-to-event data. At the age of 5years, 184 (6.0%) children had asthma, of whom 101 (54.9%) were atopic, 75 (40.8%) were nonatopic, and eight (4.3%) could not be categorized. Consumption of infant formulas [adjusted hazard ratio (95% confidence intervals) 1.15 (1.07, 1.23), p<.001] and strongly heat-treated milk products [1.06 (1.01, 1.10), p=.01] was associated with the risk of all asthma. Consumption of all cow's milk products [1.09 (1.03, 1.15), p=.003], nonfermented milk products [1.08 (1.02, 1.14), p=.008], infant formulas [1.23 (1.13, 1.34), p<.001], and strongly heat-treated milk products [1.08 (1.02, 1.15), p=.006] was associated with nonatopic asthma risk. All these associations remained statistically significant after multiple testing correction. High consumption of infant formula and other strongly heat-treated milk products may be associated with the development of asthma.

Serum microRNAs Catalog Asthma Patients by Phenotype.

Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients. Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

High-Sensitivity Assays for C-Reactive Protein as a Systemic Inflammatory Marker in Assessing Asthma

Asthma is a chronic inflammatory condition, and the main features include airway hyper-responsiveness and inflammation of the airway with the accumulation of inflammatory cells. Increased level of plasma fibrinogen and serum amyloid A suggests the involvement of systemic inflammation in asthma. C-reactive protein (CRP) is an acute-phase protein that produced mainly by hepatocytes and is an inflammatory marker. CRP levels monitoring is useful in the evaluation of early inflammation and efficacy of treatment in acute-phase illnesses. Several studies show that asthma alone can cause an increase in high-sensitivity CRP (hs-CRP) when compared with the healthy controls. Besides that, steroid-naïve patients have a higher mean value of hs-CRP levels compared with those on inhaled corticosteroid. Furthermore, studies have shown that an elevated hs-CRP level has a positive correlation with non-atopic asthma but not atopic asthma. Additionally, an increase in serum hs-CRP levels correlates with the severity of asthma. Therefore, serum hs-CRP is a useful surrogate marker to predict the severity of inflammation of the bronchus in asthma and assess the asthma status.

Predominance of Atopic Asthma in Patients with Severe or Difficult-to-Treat Asthma in the TENOR-II cohort

Atopy, the genetic propensity to produce immunoglobulin E (IgE) against common environmental allergens, is a known risk factor for asthma.1 In 2001, the TENOR I observational study (NCT00091767) was initiated to understand the natural history of disease in patients with severe or difficult-to-treat asthma.2 TENOR II was a multicenter, observational study conducted more than 10 years later using cross-sectional follow-up assessment of patients from TENOR I.2 As the “difficult-to-treat” asthma phenotype remains poorly defined, we sought to determine prevalence of atopy in TENOR II and describe demographic and clinical differences between patients with atopic and nonatopic asthma.

Organization, Clinical and Management Indicators on the First Year of Activity of an Outpatient Clinic Dedicated to the Diagnosis and Treatment of Severe Asthma in Italy.

PurposeA Regional Technical Commission was set in 2017 by Veneto region (Italy) to provide opinions and recommendations on drug prescriptions and to implement treatment-pathway guidelines for severe asthma. In this observational study, we describe the first structured, integrated, multidisciplinary, patient-centered outpatient clinic for the care of severe-asthma patients in Italy, and characterize patients referring to the center for specialist visits.Patients and MethodsTo characterize patients that accessed the outpatient clinic in 2018, data on demographic characteristics, treatments, severity of asthma, phenotypes, and relevant comorbidities by phenotype were collected. Use of biologic agents and indicators of the performance of the outpatient clinic were described.ResultsA structured multidisciplinary outpatient pathway for taking charge of patients and for administration and monitoring of biological agents was developed. A total of 146 patients accessed the outpatient clinic in 2018: 62.3% had uncontrolled asthma upon admission and 27.4% were already being treated with biologic agents. Among patients with uncontrolled asthma, 66% had severe uncontrolled asthma, 22% had moderate–severe uncontrolled asthma, and 12% had mild–moderate uncontrolled asthma. Main asthma phenotypes in uncontrolled-asthma patients were allergic (58% of patients), eosinophilic (22%), allergic plus eosinophilic (10%) and non-atopic asthma (10%). Among patients affected by severe asthma, 47% had allergic asthma, 28% had eosinophilic asthma, 13% had allergic plus eosinophilic asthma, and 12% had non-atopic asthma. Nasal polyps were more frequent in eosinophilic and allergic plus eosinophilic asthma, while gastro-esophageal reflux disease was more frequent in non-atopic asthma.ConclusionThis structure of an outpatient clinic for the treatment of severe asthma, with its dedicated pathway and multidisciplinary approach, may allow a stricter control of asthma and optimization of therapies, as well as minimization of drug misuse.