Early-onset Asthma Research Articles

Association between preterm birth and asthma and atopic dermatitis in preschool children: a nationwide population-based study

Asthma and atopic dermatitis (AD) are representative chronic diseases in childhood. This study aimed to investigate the impact of preterm birth on the incidence and severity of asthma and AD in children, as well as to identify neonatal risk factors for asthma and AD. We used health claims data recorded between 2007 and 2014 in the Korean National Health Insurance Service database. We recruited 2,224,476 infants born between 2007 and 2014 and divided them into three groups: 3518 of extremely preterm (EP) infants (< 28 weeks of gestational age (GA)), 82,579 of other preterm (OP) infants (28–36 weeks of GA), and 2,138,379 of full-term (FT) infants (> 37 weeks of GA). We defined asthma as > 3 episodes of clinical visits in a year before 6 years of age, early asthma as onset at < 2 years of age, and severe asthma as > 1 event of status asthmaticus or admission to a hospital via an emergency room. AD was defined as ≥ 3 diagnoses in a year before 6 years of age, early AD as onset at < 2 years of age, and severe AD as prescription of high-potency topical steroids or immunosuppressants. An association of preterm birth with asthma and AD was assessed using inverse probability of treatment-weighted multivariable Cox regression analysis. Cardiorespiratory conditions, such as respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, and pulmonary hypertension, significantly increased the risk of asthma. Specifically, bronchopulmonary dysplasia emerged as a significant risk factor for both severe and early-onset asthma (odds ratio (OR) 1.36, 95% CI 1.21–1.37 for severe asthma; OR 1.55, 95% CI 1.30–1.85 for early asthma), while it was associated with a decreased risk of AD (OR 0.86, 95% CI 0.80–0.92). Neonatal sepsis, jaundice, and retinopathy of prematurity were also identified as significant risk factors for later asthma. A stepwise increase in the risk of asthma with an increasing degree of prematurity was observed, with the OP group showing an adjusted hazard ratio (aHR) of 1.24 (95% CI: 1.22–1.26) and the EP group showing an aHR of 1.51 (95% CI: 1.41–1.63). Conversely, preterm birth was inversely associated with the risk of AD, with aHRs of 0.73 (95% CI: 0.67–0.79) for the OP group and 0.88 (95% CI: 0.87–0.89) for the EP group. Conclusion Preterm children have a significantly higher risk of asthma and lower risk of AD, with cardiorespiratory conditions significantly increasing the risk of asthma. Thus, we highlight the need for targeted respiratory management strategies for this high-risk population.What is Known:•Asthma and atopic dermatitis are prevalent chronic diseases in childhood, reducing the quality of life of children.•Preterm birth was associated with an increased risk of asthma, but few large nationwide studies.•Research on the relationship between preterm birth and pediatric atopic dermatitis is controversial, with few large nationwide studies.What is New:• Preterm children, especially born before 28 weeks of gestational age, had a significantly higher risk of asthma and lower risk of atopic dermatitis.• Cardiorespiratory comorbidities such as RDS, BPD, PDA, and pulmonary hypertension in neonatal period are prominent risk factors for asthma.• Preterm children are vulnerable to both early-onset and severe asthma.

Late-Onset Asthma: A Review

Asthma is a chronic respiratory condition with a growing global prevalence, affecting millions of individuals annually. While asthma can develop at any age, late-onset asthma is a specific phenotype that begins in adulthood, as recognized by the Global Initiative for Asthma (GINA) in its 2024 guidelines. This form of asthma is often associated with several predisposing factors, including gender, obesity, occupational exposure, rhinitis, respiratory infections, smoking, stress, and diminished lung function. Unlike early-onset asthma, which frequently involves a history of allergies, late-onset asthma tends to lack allergic triggers, making it a distinct and challenging form of the disease. Managing late-onset asthma is often more complex, as it typically requires higher doses of corticosteroids and demonstrates a reduced responsiveness to standard steroid treatments. The exact mechanisms and pathophysiological processes contributing to the increased severity and poorer clinical outcomes in late-onset asthma remain largely unclear. This uncertainty often leads to underdiagnosis and inadequate management, further complicating patient care. Phenotypic analysis is recommended to improve treatment outcomes. This includes assessing clinical features and utilizing biomarkers, such as inflammatory markers and immunoglobulin E (IgE) levels, to guide targeted therapy when conventional steroid treatments are insufficient. However, there is a significant need for further research to elucidate the underlying mechanisms of late-onset asthma. This literature review is essential to develop more effective, personalized treatment strategies that can address the unique challenges posed by this asthma phenotype, ultimately leading to better management and improved patient outcomes.

Pesticide exposure during pregnancy and risk of early onset asthma and wheeze in the offspring

Pesticide exposure during pregnancy and risk of early onset asthma and wheeze in the offspring

Aspergillus-sensitized asthma in children.

Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations. To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters. A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus-sensitized asthma (Af-SA), and 168 (64.9%) with A. fumigatus-unsensitized asthma (Af-UA). Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af-SA. Absolute eosinophil count was higher, and FEV1 was lower in Af-SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut-off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/μL for absolute eosinophil count. In Af-SA compared to Af-UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher. Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af-SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function.

Childhood infections, asthma and allergy trajectories, and chronic rhinosinusitis in middle age: A prospective cohort study across six decades.

Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited. To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age. Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression. In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS. Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS.

Modern asthma management

Symptom prevention and remission are the goals of asthma treatment. Precise phenotyping of the patients, including history, lung function, allergology and measurement of type 2 biomarkers, is the essential prerequisite for treatment success. Basic measures, treatment with DMAADs ("disease-modifying anti-asthmatic drugs": predominantly inhaled corticosteroids, biologics, and allergen immunotherapy) and treatment of comorbidities are the cornerstones of modern asthma management. The treatment of upper airway diseases such as allergic rhinitis (often associated with early-onset asthma) or chronic rhinosinusitis (often associated with adult-onset asthma, with 2 forms: either with nasal polyps, CRSwNP, or without nasal polyps, CRSsNP) is of major importance in this regard.

Identification of exhaled volatile organic compounds that characterize asthma phenotypes: A J-VOCSA study

BackgroundAsthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma. MethodsThis was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS). ResultsUsing the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1–5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p < 0.05 adjusted by false discovery rate (FDR). Comparison of these phenotypes yielded several VOCs showing different trends (p < 0.05); however, no VOCs showed p < 0.05 adjusted by FDR. ConclusionsExhaled VOC profiles may be useful for distinguishing asthma and asthma phenotypes; however, these findings need to be validated, and their pathological roles should be clarified.

Multivariate Cluster Analyses to Characterize Asthma Heterogeneity and Benralizumab Responsiveness

An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions. Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach. In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to analyze 11 clinical characteristics simultaneously. The annualized asthma exacerbation rate, exacerbation incidence, and lung function were analyzed across clusters. Patients (n= 2,281) met criteria for four of five clusters: cluster 2 (early-onset moderate asthma, n= 393), cluster 4 (early-onset severe asthma, n= 386), cluster 3 (late-onset severe asthma, n= 641), and cluster 5 (late-onset severe, obstructed asthma, n= 861); no patients met cluster 1 criteria. Exacerbation rate reductions were significant in late-onset severe asthma (-48% [95% CI, -61% to -31%]; P < .0001) and late-onset severe, obstructed asthma (-50% [95% CI, -59% to -38%]; P < .0001), with nonsignificant reductions in early-onset clusters. These differences could not be fully explained by blood eosinophil count differences. Values for improvements in FEV1 were significant in late-onset severe asthma (+133 mL [95% CI, 66-200]; P= .0001) and late-onset severe, obstructed asthma (+160 mL [95% CI, 85-235]; P < .0001) while maintaining acute bronchodilator responsiveness. Benralizumab reduced exacerbations and improved lung function, primarily in late-onset asthma clusters. This multivariate approach to identify subphenotypes, potentially reflecting pathobiological mechanisms, can guide therapy beyond univariate approaches.

CLINICAL COURSE OF OBESITY-ASSOCIATED ASTHMA DEPENDING ON THE GLN27GLU POLYMORPHIC VARIANT OF THE β2-ADRENORECEPTOR GENE, TAKING INTO ACCOUNT THE AGE OF ONSET

Introduction. Studies have shown that bronchial asthma (BA) associated with obesity has a more severe course, lower control, more frequent cases of low efficacy of basic treatment, and exacerbations. Two phenotypes have been distinguished in BA-obesity comorbidity based on age of onset: early atopic and late non-atopic. It is known that genetic factors associated with β2-adrenoceptor (AR) genes are important in the development of both asthma and obesity.&#x0D; The purpose of the study aimed to analyze the association of the Gln27Glu polymorphism of the β2-adrenoceptor gene with the severity of the course of bronchial asthma with obesity, taking into account the age of its onset.&#x0D; Research material and methods. 195 asthma patients with obesity consented for the study participation were examined. The control group consisted of 95 practically healthy people. Patients were divided into two clinical groups depending on the age of onset of BA: the first group included 100 patients with an early onset, the second group - 95 patients with a late onset. The diagnosis and treatment of asthma followed the guidelines of the Global Initiative for Asthma (2016) and its updated versions. The study was approved by the Bioethics Commission of the Educational and Scientific Medical Institute of Sumy State University. Determination of the Gln27Glu polymorphism of the β2-AR gene (rs1042714) was performed using the polymerase chain reaction with the subsequent analysis of restriction fragments. Statistical analysis of the obtained results was carried out using the SPSS-17 program. Pearson's chi-squared test was used to compare genotype distributions between experimental groups. To determine the risk of BA and obesity, odds ratios and 95% confidence intervals were calculated for dominant, recessive, superdominant, and additive models of inheritance. Their relevance was assessed using the Akaike information criterion. All tests were two-sided, and values p &lt; 0.05 were considered statistically significant.&#x0D; Research results. The frequency of Gln/Gln, Gln/Glu and Glu/Glu genotypes according to the Gln27Glu polymorphism of the β2-AR gene in patients with early-onset obesity-associated asthma was 70.0; 25.0; 5.0% with a mild course and 55.0; 36.2; 8.8% with severe (χ2 = 1.49; p = 0.473); and with a late debut - 50.0; 43.8; 6.2% with mild and 54.0%; 31.7; 14.3%, respectively, with severe (χ2 = 2.10; p = 0.350). Despite the absence of a probable difference in the distribution of genotypes depending on the severity of the course, it was found that the frequency of homozygotes for the minor allele was 1.8 times higher in patients with a severe course of early BA and 2.3 times higher in late BA compared to that in patients with mild BA course.&#x0D; The risk of early-onset BA with obesity and a severe course showed no association in all models of inheritance, and in patients with late-onset BA, there was a 1.66-fold increase (95% CI (1.03 – 2.72), p = 0.04) in the additive inheritance model (p = 0.04).&#x0D; Conclusions. There are no statistically significant differences in the distribution of genotypes according to the Gln27Glu polymorphism of the β2-AR gene depending on the severity of the course of early and late BA with obesity. The risk of developing a severe course of early BA did not depend on the Gln27Glu polymorphism of the β2-AR gene, and late BA increased by 1.66 times in the additive model of inheritance.

Agreement between self-reported and registered age at asthma diagnosis in Finland

IntroductionIn epidemiological studies, the age at asthma onset is often defined by patients’ self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement.MethodsAs part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated.ResultsAltogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was − 2.0 years (IQR − 9.0 to 0) in Helsinki and − 1.0 (IQR − 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently.ConclusionsAgreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria.

Different Impacts of Traffic-Related Air Pollution on Early-Onset and Late-Onset Asthma.

Early-onset asthma (EOA) and late-onset asthma (LOA) are two distinct phenotypes. Air pollution has been associated with an increase in poorer asthma outcomes. The objective of this study was to examine the effects of traffic-related air pollution (TRAP) on asthma outcomes in EOA and LOA patients. A cross-sectional study was conducted on 675 asthma patients (LOA: 415) recruited from a major medical center in Taiwan. The land-use regression (LUR) model was used to estimate the level of exposure to PM10, PM2.5, NO2, and O3 on an individual level. We investigated the association between TRAP and asthma outcomes in EOA and LOA patients, stratified by allergic sensitization status, using a regression approach. An increase in PM10 was associated with younger age of onset, increased asthma duration, and decreased lung function in EOA patients (p<0.05). An increase in PM10 was associated with older age of onset, and decreased asthma duration, eosinophil count, and Asthma Control Test (ACT) score in LOA patients. An increase in PM2.5 was associated with younger age of onset, increased asthma duration, decreased eosinophil count, and lung function in EOA patients (p<0.05). An increase in PM2.5 was associated with decreased lung function and ACT score in LOA patients. An increase in NO2 was associated with increased eosinophil count and decreased lung function in EOA patients (p<0.05). An increase in O3 was associated with decreased lung function in LOA patients (p<0.05). In addition, associations of TRAP with age of onset and eosinophil counts were mainly observed in both EOA and LOA patients with allergic sensitization, and an association with ACT was mainly observed in LOA patients without allergic sensitization. The impact of TRAP on age of onset, eosinophil count, and lung function in EOA patients, and ACT in LOA patients, was affected by the status of allergic sensitization.

Fetal lung growth predicts the risk for early-life respiratory infections and childhood asthma

BackgroundEarly-life respiratory infections and asthma are major health burdens during childhood. Markers predicting an increased risk for early-life respiratory diseases are sparse. Here, we identified the predictive value of ultrasound-monitored fetal lung growth for the risk of early-life respiratory infections and asthma.MethodsFetal lung size was serially assessed at standardized time points by transabdominal ultrasound in pregnant women participating in a pregnancy cohort. Correlations between fetal lung growth and respiratory infections in infancy or early-onset asthma at five years were examined. Machine-learning models relying on extreme gradient boosting regressor or classifier algorithms were developed to predict respiratory infection or asthma risk based on fetal lung growth. For model development and validation, study participants were randomly divided into a training and a testing group, respectively, by the employed algorithm.ResultsEnhanced fetal lung growth throughout pregnancy predicted a lower early-life respiratory infection risk. Male sex was associated with a higher risk for respiratory infections in infancy. Fetal lung growth could also predict the risk of asthma at five years of age. We designed three machine-learning models to predict the risk and number of infections in infancy as well as the risk of early-onset asthma. The models’ R2 values were 0.92, 0.90 and 0.93, respectively, underscoring a high accuracy and agreement between the actual and predicted values. Influential variables included known risk factors and novel predictors, such as ultrasound-monitored fetal lung growth.ConclusionSonographic monitoring of fetal lung growth allows to predict the risk for early-life respiratory infections and asthma.Graphical abstract

Real-world effectiveness and predictors of super-responders to dupilumab in a Chinese uncontrolled asthma cohort.

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multivariable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6-2.4) to 0.4 (0.2-0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0-1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8-22.5 mg/day) to 2.5 mg/day (0.0-10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm³ [300-815 cells/mm³] versus 560 cells/mm³ [220-938 cells/mm³], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286-43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25-50 ppb (OR 35.038 [95% CI, 3.104-395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697-0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders.

Understanding Differential Response to Biologic Therapies in Severe Asthma: Retrospective study

Severe asthma, characterized by airway inflammation and debilitating symptoms, poses a significant challenge to millions of people worldwide. Traditional treatments for treating severe cases are limited, leading to the emergence of biologic therapies as promising alternatives. This retrospective cohort study from a tertiary hospital in Dubai aimed to explore the differential response to biologics in severe asthma patients and identify predictors of treatment outcomes. The baseline characteristics of 129 severe asthma patients receiving biologic therapy were analyzed, revealing a greater incidence of allergic diseases among responders. Multivariate Cox regression analysis revealed that early-onset asthma, urticaria, and rhinosinusitis (p =0.027, 0.037, and &lt;0.001, respectively) were predictors of a positive treatment response. Compared with non-responders, responders demonstrated improved asthma control, reduced exacerbations, and decreased oral corticosteroid usage. Despite the limitations inherent in retrospective studies, our findings underscore the significant clinical benefits of biologic therapy in severe asthma patients. Tailored treatment strategies based on patient characteristics and biologic class could optimize outcomes in this population, emphasizing the importance of personalized medicine in managing severe asthma. Further research into predictive biomarkers and larger cohort studies are warranted to validate these findings and enhance treatment efficacy in severe asthma management.

Neuropsychological signs of the neurodegenerative process in Alzheimer’s disease at the stage of mild cognitive impairment

Currently, a huge number of works by domestic and foreign authors are devoted to the study of the neuropsychological heterogeneity of Alzheimer’s disease (AD) at the stage of mild cognitive impairment (MCI). The purpose of our study was to study the neuropsychological characteristics of AD at the stage of MCI depending on the timing of manifestation. The study involved 173 patients with asthma at the stage of MCI, of which 65 patients had early onset and 108 patients had late onset. All study participants underwent the Montreal Cognitive Assessment (MoCA), the Free Recall Test with selective cues and immediate recall (FCSRT-IR), the route-following test (drawing paths): part A and B; categorical and phonemic verbal fluency, digit recall (DST). The average age of patients with early onset of asthma was 65.1±0.3 years, with late onset — 78.6±0.5 years. According to the results of the study, it was found that patients with a late form of asthma coped with MoCA worse than a patient with an early form (p=0.043). Patients with late onset AD produced fewer words independently in the FCSRT-IR test compared to patients with early onset (p&lt;0.001). Analysis of DST test performance in forward (p=0.41) and reverse order (p=0.197) did not show significant differences. We found that patients with early AD made more errors (p=0.000) and took longer to complete the route-following test, both parts A and B. There was no significant difference when assessing categorical verbal fluency (p=0.67). At the same time, patients with early onset AD named fewer words when assessing phonemic verbal fluency (p=0.000). The results of our study indicate the need for comprehensive, extensive neuropsychological testing in patients with suspected AD.

Overview of asthma patients followed up in a tertiary clinic.

Background. Asthma is a disease that combines different biological mechanisms, inflammatory pathways, and phenotypic features. Our aim was to investigate the demographic and disease characteristics of patients with asthma and to reveal the distribution with different phenotypes according to endotype groups. Methods. Patients were identified as eosinophilic if the absolute eosinophil count was measured at least once ≥ 300/μL during the oral corticosteroid free period or ≥ 150/μL under oral corticosteroids. Patients sensitive to at least one inhalant allergen with skin prick test and/ or spIgE measurement were defined as allergic. They were categorized into four main endotypes. Results. Data of 405 asthma patients with a median age of 50.9 years were analyzed. The prominent clinical and phenotypic characteristics of the study group were being obese (43.2%) or overweight (32%), severe asthma (49.6%), adult-onset (56.1%) or late-onset asthma (35.3%). The distribution of the four main endotypes according to eosinophilic and/or allergic status, is as follows: 22.7% allergic-eosinophilic (AE), 27.9% nonallergic-eosinophilic (NAE), 22.9% allergic-noneosinophilic (ANE), 26.4% nonallergic-noneosinophilic (NANE). While most severe asthma patients were in the AE and NAE groups, those with early-onset asthma were in AE and ANE, and those with late-onset asthma were in the NAE and NANE groups. The proportion of uncontrolled patients was higher in the NAE group. Among the severe asthma patients, the rate of uncontrolled disease was higher in those with NANE asthma. Conclusions. Different phenotypes were more closely related to some endotypes. This may allow the clinicians to identify patients and predict appropriate treatment modalities and response for individualized care.

Analysis of the association of bronchial asthma clinical course with ER22/23EK and TTH111I polymorphic variants in the glucocorticoid receptor gene

bronchial asthma (BA) is one of the important and urgent medical and social problems ofour time due to the high incidence and prevalence, which keep increasing. This is a typical multifactorialdisease determined by the influence of external factors and genetic predisposition. The combination ofthese numerous factors determines the phenotypic heterogeneity of bronchial asthma. Identification ofasthma phenotypes was based mainly on clinical variables; however, further identification of clinicalphenotypes revealed their genetic heterogeneity. Accordingly, the determination of genetic marker datafor clinical phenotypes of bronchial asthma will improve the diagnostic capabilities of preventive andevidence-based medicine in the future. The objective of the study was to determine the features of thecourse of early-onset and late-onset BA depending on the ER22/23EK and Tth111I polymorphisms inthe glucocorticoid receptor gene and to supplement modern data on the role of genetic factors in BAonset and the severity for various phenotypes. We examined 553 BA patients and 95 apparently healthyindividuals. All of them had previously signed an informed consent form. BA diagnosis, severity, andcontrol level were determined according to the GINA recommendations-2016 and its later versions andthe Decree of the Ministry of Health of Ukraine No. 868 issued on 08 October 2013. Respiratory functionwas studied using Kardioplius diagnostic suite (Ukraine). The patients were divided into two clinicalgroups according to the BA onset: Group I included 282 patients with late-onset asthma, and GroupII included 271 patients with early-onset asthma. The Bioethics Committee of the Medical Institute ofSumy State University approved the study. The ER22/23EK (rs 6189/6190) and Tth111I (rs10052957)polymorphic variants in the glucocorticoid receptor (GR) gene were determined using polymerase chainreaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results wasperformed using SPSS–17 program. A statistically significant difference was observed in the distributionof genotypes for the ER22/23EK and TthIIII polymorphisms in the GR gene depending on BA severity,with a higher frequency of minor alleles in both cases in patients with severe BA (χ2 = 6.09; р = 0.048and χ2 = 15.8; р = 0.001, respectively). The relative risk of severe BA did not depend on the ER22/23EKpolymorphism in the GR gene; however, it was 3.63 times higher in the carriers of the TT genotype forthe Tth111I polymorphism vs. carriers of the major allele homozygotes. The risk of severe disease inearly-onset and late-onset BA depended on the Tth111I polymorphism in the GR gene; in the recessivemodel, it increased by 3.7 times for early-onset asthma and by 3.5 times – for late-onset asthma. Analysis&#x0D; of ER22/23EK (rs 6189/6190) and Tth111I (rs10052957) polymorphic variants in the GR gene demon-strated their possible correlation not only with the increased risk of BA, but also with certain phenotypes&#x0D; and severity of the disease.

High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma.

The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed. The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.

Genetic differences according to onset age and lung function in asthma: A cluster analysis.

The extent of differences between genetic risks associated with various asthma subtypes is still unknown. To better understand the heterogeneity of asthma, we employed an unsupervised method to identify genetic variants specifically associated with asthma subtypes. Our goal was to gain insight into the genetic basis of asthma. In this study, we utilized the UK Biobank dataset to select asthma patients (All asthma, n=50,517) and controls (n=283,410). We excluded 14,431 individuals who had no information on predicted values of forced expiratory volume in one second percent (FEV1%) and onset age, resulting in a final total of 36,086 asthma cases. We conducted k-means clustering based on asthma onset age and predicted FEV1% using these samples (n=36,086). Cluster-specific genome-wide association studies were then performed, and heritability was estimated via linkage disequilibrium score regression. To further investigate the pathophysiology, we conducted eQTL analysis with GTEx and gene-set enrichment analysis with FUMA. Clustering resulted in four distinct clusters: early onset asthmanormalLF (early onset with normal lung function, n=8172), early onset asthmareducedLF (early onset with reduced lung function, n=8925), late-onset asthmanormalLF (late-onset with normal lung function, n=12,481), and late-onset asthmareducedLF (late-onset with reduced lung function, n=6508). Our GWASs in four clusters and in All asthma sample identified 5 novel loci, 14 novel signals, and 51 cluster-specific signals. Among clusters, early onset asthmanormalLF and late-onset asthmareducedLF were the least correlated (rg =0.37). Early onset asthmareducedLF showed the highest heritability explained by common variants (h2 =0.212) and was associated with the largest number of variants (71 single nucleotide polymorphisms). Further, the pathway analysis conducted through eQTL and gene-set enrichment analysis showed that the worsening of symptoms in early onset asthma correlated with lymphocyte activation, pathogen recognition, cytokine receptor activation, and lymphocyte differentiation. Our findings suggest that early onset asthmareducedLF was the most genetically predisposed cluster, and that asthma clusters with reduced lung function were genetically distinct from clusters with normal lung function. Our study revealed the genetic variation between clusters that were segmented based on onset age and lung function, providing an important clue for the genetic mechanism of asthma heterogeneity.

Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants associated with late-onset asthma.

Introduction: Asthma is a chronic disease of the airways that impairs normal breathing. The etiology of asthma is complex and involves multiple factors, including the environment and genetics, especially the distinct genetic architecture associated with ancestry. Compared to early-onset asthma, little is known about genetic predisposition to late-onset asthma. We investigated the race/ethnicity-specific relationship among genetic variants within the major histocompatibility complex (MHC) region and late-onset asthma in a North Carolina-based multiracial cohort of adults. Methods: We stratified all analyses by self-reported race (i.e., White and Black) and adjusted all regression models for age, sex, and ancestry. We conducted association tests within the MHC region and performed fine-mapping analyses conditioned on the race/ethnicity-specific lead variant using whole-genome sequencing (WGS) data. We applied computational methods to infer human leukocyte antigen (HLA) alleles and residues at amino acid positions. We replicated findings in the UK Biobank. Results: The lead signals, rs9265901 on the 5' end of HLA-B, rs55888430 on HLA-DOB, and rs117953947 on HCG17, were significantly associated with late-onset asthma in all, White, and Black participants, respectively (OR = 1.73, 95%CI: 1.31 to 2.14, p = 3.62 × 10-5; OR = 3.05, 95%CI: 1.86 to 4.98, p = 8.85 × 10-6; OR = 19.5, 95%CI: 4.37 to 87.2, p = 9.97 × 10-5, respectively). For the HLA analysis, HLA-B*40:02 and HLA-DRB1*04:05, HLA-B*40:02, HLA-C*04:01, and HLA-DRB1*04:05, and HLA-DRB1*03:01 and HLA-DQB1 were significantly associated with late-onset asthma in all, White, and Black participants. Conclusion: Multiple genetic variants within the MHC region were significantly associated with late-onset asthma, and the associations were significantly different by race/ethnicity group.