Moderate Asthma Research Articles

Correlation between changes in serum YKL-40, LXRs, PPM1A, and TGF-β1 levels and airway remodeling and lung function in patients with bronchial asthma

Objective This study investigates the correlation between serum levels of YKL-40, LXRs, PPM1A, and TGF-β1 and airway remodeling and lung function in bronchial asthma patients. Methods The study involved 80 bronchial asthma patients and 92 healthy individuals. Serum cytokines, airway remodeling, and lung function markers were compared across mild, moderate, and severe asthma cases using high-resolution CT, t-tests, ANOVA, and Pearson correlation analysis. Results Asthmatic patients exhibited higher levels of serum YKL-40, LXRα, LXRβ, TGF-β1, airway wall thickness (T)/outer diameter (D), and WA% of total cross-sectional area compared to controls. Conversely, their serum PPM1A, Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1) were lower. Serum YKL-40 and TGF-β1 levels were positively correlated with T/D and WA%, and negatively correlated with PEF and FEV1. PPM1A levels were strongly associated with T/D, WA%, PEF, and FEV1. Conclusion The severity of bronchial asthma is associated with increased serum levels of YKL-40, LXRα, LXRβ, and TGF-β1 and decreased PPM1A. The levels of YKL-40, PPM1A, and TGF-β1 have a significant correlation with airway remodeling and lung function.

Hypertonic saline inhalation therapy among patients with moderate asthma and functional dyspepsia commorbidity

Aim: Dry powder hypertonic saline inhalation use possibilities evaluation in moderate asthma and functional dyspepsia patients. Materials and Methods: 68 moderate asthma and functional dyspepsia patients were examined and treated according to the standard protocols, serum and erythrocytes membrane fatty acid levels were evaluated. The groups of patients with (n=35) and without (n=33) additional dry powder hypertonic saline inhalation use were compared after 1 month. Results: After additional use of dry powder hypertonic saline inhalations vs only standard treatment the rate of well controlled asthma was 3 fold higher with significantly higher FEV1. We also observed positive dynamics of serum arachidonic and docosahexaenoic acids levels indicating resolution of inflammatory reaction with erythrocytes membranes linoleic acid level normalization (source of antiinflammatory cytokines synthesis) among patients with dry powder hypertonic saline inhalation use vs without it. Among patients who used only standard therapy compared to the control group, the erythrocytes membrane linoleic acid level remained decreased with high serum arachidonic and docosahexaenoic acids levels. Follow-up results (after 1 year) showed a significant decrease in exacerbations frequency among patients who underwent dry powder hypertonic saline inhalation vs only the standard treatment. Conclusions: Among moderate asthma patients with functional dyspepsia use of dry powder hypertonic saline inhalation therapy additionally to the standard treatment allows to improve not only clinical and functional parameters but serum and erythrocytes membranes fatty acids spectrum as well leading to the systemic inflammatory reaction reduction and exacerbations prevention in remote period.

Обґрунтування вибору флутиказону пропіонату у доставковому пристрої циклохалер для базисної терапії бронхіальної астми

Abstract. The basis of the treatment of bronchial asthma (BA) is anti-inflammatory therapy with the help of inhaled corticosteroids (ICS). Expectations of high efficacy (small particle size, high receptor affinity, high lipophilicity and lung residence time) and safety (low oral bioavailability, low systemic absorption, high protein binding and rapid systemic clearance) are placed on ICS. According to these characteristics, fluticasone propionate has the optimal therapeutic index. The aim: to study the possibilities of the use of fluticasone propionate in the cyclohaler device for the basic therapy of BA. Materials and methods. The study enrolled 376 patients who received fluticasone propionate 125 μg and 250 μg twice daily in a cyclohaler delivery device compared with the original fluticasone propionate 500 μg in patients with moderate asthma. All patients underwent spirometry, peak flowmetry, laboratory studies, registration of asthma symptoms, need in the rescue therapy, vital signs, adverse events. Results. The clinical and functional efficacy of fluticasone 125 μg twice daily is no inferior than the efficacy of the original fluticasone 500 μg twice daily. There is no clinically significant difference between the effectiveness of the drug in a dose of 125 and 250 μg when taken twice daily with the use of the new generation cyclohaler, which confirms the almost parallel linear dose-effect relationship in the range of medium and high doses of the drug. The incidence of the adverse effects was significantly lower in the group of patients treated with fluticasone 250 μg compared to patients in the other two groups. There were no differences between the groups in laboratory results. There were no differences in cortisol concentrations in blood plasma and 24-hour urine before and after 12 weeks of treatment in the groups using cyclohaler and the reference drug. Conclusion. Fluticasone propionate administered through a new generation cyclohaler at doses of 125 and 250 μg twice daily is an effective therapy for asthma of moderate severity, and the dose of 250 μg with the use of new generation cyclohaler is clinically equivalent to a twofold higher dose of the reference fluticasone propionate. The safety profile of fluticasone when using of the new generation cyclohaler can be compared with the safety profile of the reference substance.

Markers of eosinophilic airway inflammation in patients with asthma and allergic rhinitis.

Background: Measurement of airway inflammation is an important step to determine phenotype of asthma and allergic rhinitis (AR). Objective: To assess the level of nitric oxide in exhaled air (FeNO), nasal fraction of nitric oxide (nasal NO), their relationship with clinical control and blood eosinophils in patients with steroid-naive mild and moderate asthma and AR. Methods: One hundred forty-seven patients (65 men), ages 26-49.5 years (mean age, 32 years) with AR (n = 81) or AR and concomitant asthma (n = 46) and 20 healthy subjects were included in a single-center cohort study. All the patients underwent spirometry with reversibility test. Control of asthma and AR was assessed by using the Asthma Control Questionnaire and the visual analog scale, respectively. Levels of FeNO and nasal NO were measured by chemiluminescent analyzer, peripheral blood eosinophils were counted by automatic analyzer. Results: The FeNO level was significantly elevated in the patients with asthma and concomitant AR compared with the healthy subjects and was associated with control of both asthma and AR. There was no correlation between nasal NO and control of AR. Receiver operating characteristic analysis revealed that the level of eosinophils of 150 cells/μL may be a cutoff for lower airway eosinophilic inflammation. Blood eosinophils count was unable to distinguish eosinophilic and non-eosinophilic upper airway inflammation. Conclusion: We confirm that FeNO but not nasal NO is a marker of eosinophilic airway inflammation in patients with mild-moderate steroid-naive AR and concomitant asthma. A blood eosinophil level of ≥150 cells/µL may be a simple marker of eosinophilic airway inflammation in patients with asthma. However, its low specificity requires repeated measurements and use in combination with other biomarkers.

Assessment of left ventricular function in asthmatic children using speckle tracking and tissue doppler echocardiography

Background Acute bronchial asthma affects many organs including the cardiovascular system. Recurrent hypoxia and the production of inflammatory mediators lead to chronic inflammation, pulmonary vasoconstriction, and pulmonary hypertension, which can affect cardiac function. Aim This study aimed to assess left ventricular function in children with acute bronchial asthma using two-dimensional (2D), three-dimensional (3D) speckle tracking echocardiography (STE), and tissue doppler imaging (TDI). Patients and methods Fourty-five children with moderate persistent asthma aged 5–16 years and 15 matched controls were enrolled in this study. In addition to pulmonary function testing with spirometry, all participants underwent cardiac evaluation using conventional echocardiography, TDI, and 2D and 3D STE. Results The asthmatic children had significantly lower left ventricular systolic and diastolic functions (P = 0.017, P < 0.001, respectively) but significantly higher myocardial performance index (MPI) (P < 0.001) than that of the control group by TDI. By using 3D STE, 3D longitudinal strain, 3D circumferential strain, 3D area strain, and 3D radial strain were significantly lower in asthmatic children than the healthy control. Conclusion Children with asthma are more likely to have left ventricular dysfunction of different severities, which can be identified early using TDI and 3D STE.

The frequency of sleep-disordered breathing in preschool children with asthma and its effects on control of asthma.

The frequency and score of SDB were higher in patients with uncontrolled asthma. Frequency and score of SDB were significantly affected by the severity of asthma. SDB must be evaluated in preschool children with uncontrolled asthma. Sleep-disordered breathing (SDB) is more common in asthmatic patients than in non-asthmatic persons, and SDB affects negatively to control asthma. A limited number of studies are discovered on the effect of SDB in preschool asthmatic children. In this study, we aimed to investigate the prevalence of SDB and its effect on control and severity of asthma in preschool children. A pediatric sleep questionnaire was completed by parents of asthmatic children. Patients who received a score of 0.33 or higher were diagnosed with SDB. Control and severity of asthma was assessed by a pediatric allergy specialist based on the Global Initiative for Asthma (GINA) criteria. The study included 249 patients, with a mean±SD age of 4.37±1.04 (range: 2-5.9) years; 69% were boys; 56.6% children had uncontrolled asthma and 28.7% had SDB. The SDB score was significantly different between controlled and uncontrolled asthma (0.19 vs 0.28; P < 0.001). The frequency of uncontrolled asthma in patients with and without SDB was 74.3% and 49.4%, respectively (P < 0.010). Based on the severity of asthma, the frequency of SDB among patients with mild, moderate, and severe asthma was 23.4%, 35.2%, and 47.4%, respectively (P = 0.010).

Effect of adjuvant yoga therapy for asthma control: A randomized controlled trial

BackgroundAsthma is a chronic respiratory disease with symptoms of attacks of wheezing, shortness of breath, & tightness in the chest. Even with pre-existing treatment exacerbations go uncontrolled. ObjectiveThis study compared asthma control in yoga intervention versus non-yoga intervention group using Asthma Control Test. MethodsIn this randomized controlled trial, participants were allocated into two groups in 1:1 ratio - yoga intervention versus non-yoga intervention. Only outcome assessor was blinded. Sample size of 200 was calculated. Individuals between 18 and 60 years of age, diagnosed with mild to moderate asthma with no exacerbation in past one month were screened and enrolled. Per-protocol analysis was done to assess the outcomes of Asthma Control Test and expenditure.(CTRI/2020/02/023534) ResultsA total of 192 participants enrolled, 165 completed this study who were considered for final analysis. A significant difference (p < 0.001) was found between yoga and non-yoga exercise group at 13 weeks. Expenses were more in non-yoga exercise group. ConclusionOur findings confirm that yoga exercise with routine medical care reduces exacerbations and improves asthma control.

Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma: TRAVERSE Continuation Study

Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years. The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028). Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation. A total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4%) received more than 958 days of treatment. A total of 214 (54.5%) patients reported at least 1 TEAE (event rate: 171.4); 37 (9.4%) experienced at least 1 treatment-related TEAE, none of which were considered severe; 2 patients reported 6 TEAEs of moderate intensity. A total of 22 (5.6%) patients reported serious AEs (event rate: 6.9). AEs of special interest were reported in 24 patients (6.1%; event rate: 6.0). Five (1.3%) deaths occurred (event rate: 1.2) following serious AEs of coronavirus disease 2019 (COVID-19)-related pneumonia (3 patients), pancreatitis (1 patient), and pulmonary embolism (1 patient). None of the TEAEs leading to death were considered treatment-related. Dupilumab treatment was well tolerated for up to an additional 3 years. Safety findings were consistent with the known safety profile of dupilumab. These findings further support the long-term use of dupilumab in patients with moderate to severe asthma.

Mild asthma: Conundrums, complexities and the need to customize care.

Mild and moderate asthma cover a wide range of asthma presentations, phenotypes and symptom burden, and account for the majority of people with asthma worldwide. Mild asthma has been difficult to define because of its heterogeneity and wide spectrum of impact and outcomes, including being associated with severe exacerbations. Assessment of mild-moderate asthma is best made by combining asthma symptom control and exacerbation risk as the principle means by which to determine treatment needs. Incontrovertible evidence and guidelines support treatment initiation with anti-inflammatory medication, completely avoiding reliever-only treatment of mild asthma. Shared decision making with patients and a treatable traits approach will ensure that a holistic approach is taken to maximize patient outcomes. Most importantly, mild asthma should be regarded as a reversible, potentially curable condition, remaining in long-term remission through minimizing triggers and optimizing care.

Impact of a discharge prescription for dexamethasone on outcomes of children treated in the emergency department for acute asthma exacerbations

Objective To evaluate dexamethasone prescribing practices, patient adherence, and outcomes by dosing regimen in children with acute asthma discharged from the emergency department (ED). Study design Prospective study of children 2–18 years treated with dexamethasone for acute asthma prior to discharge from an urban, tertiary care ED between 2018 and 2022. Demographics, clinical characteristics, ED treatment, and discharge prescriptions were collected via chart review. The exposure was discharge prescription (additional dose) versus no discharge prescription for dexamethasone. The primary outcome was treatment failure, defined as return ED visit, unplanned primary care visit, and/or ongoing bronchodilator use. Secondary outcomes included medication adherence, symptom persistence, quality-of-life, and school/work absenteeism. Outcomes were assessed by telephone 7–10 days after discharge. Results 564 subjects were enrolled; 338 caregivers (60%) completed follow-up. Children were a median age 7 years, 30% Black or African American, 49% Hispanic, and 79% had public insurance. A discharge prescription for dexamethasone was written for 482 (86%) children and was significantly associated with exacerbation severity, number of combined albuterol/ipratropium treatments, and longer length of stay. There was no difference in treatment failure between the discharge prescription and no discharge prescription groups (RR 0.87; 0.67, 1.12), including after adjusting for potential confounders; there was no difference between groups in secondary outcomes. Conclusions Prescription for an additional dexamethasone dose was not associated with reduced treatment failure or improved outcomes for children with acute asthma discharged from the ED. Single, ED-dose of dexamethasone prior to discharge may be sufficient for children with mild to moderate asthma exacerbations.

Progressive clinical effects of the combination omalizumab and HDM – allergen immunotherapy in asthma

Objective The combination of allergen immunotherapy (AIT) and omalizumab is used to treat patients at risk of anaphylaxis. There is currently a very little evidence that this combination increases the effectiveness of AIT in patients with inhalant allergies. The study aimed to evaluate the effectiveness of HDM-SCIT therapy (injection immunotherapy for house dust mites) in combination with omalizumab in treating HDM-induced asthma. Methods This study was a placebo-controlled, randomized, multicenter trial including 82 patients with HDM-driven mild to moderate asthma. Omalizumab alone (A), HDM SCIT + omalizumab (B), SCIT alone (C), or placebo (D) for 24 months were applied. All patients received asthma treatment in accordance with GINA recommendations. The treatment efficacy was defined by a reduction in the daily dose of inhaled steroids (ICS) and a reduction in the number of asthma exacerbations (AX). Results After 24 months of therapy, a statistically significant reduction in the daily doses of ICS in groups A and B was observed (p = 0.021 and p = 0.008). Daily ICS reduction was considerably more significant in group B (p = 0.01). During 24 months of observation, the AX was significantly reduced in all study groups, with the greatest significant difference observed between groups A and B and groups C and D (placebo) as follows: 0.42 patient/per year vs. 0.39 vs. 0.84 vs. 0.91 (p = 0.023). Conclusion The combination of HDM SCIT and omalizumab is significantly and progressively reducing ICS use and AX in a 24-month study. The combination is significantly more effective than the single treatments or placebo.

Calcium-sensing receptor protein as a prognostic predictor of asthma formation and exacerbation in young children

Asthma remains the most common non-communicable disease among children, which often has a chronic course and leads to disability. Particular attention should be paid to the diagnosis of asthma in young children. To date, the calcium-sensing receptor (CaSR) is considered to be one of the specific markers in the development of bronchial obstructive diseases. Purpose - to assess the level of CaSR protein and its significance in preschool children with asthma. Materials and methods. The study included 37 patients divided into 3 groups. The Group 1 - children with mild persistent asthma (n=20), the Group 2 - children with moderate persistent asthma (n=17), the Group 3 - almost healthy children (n=20). The study of CaSR protein levels in the blood serum of patients with asthma was performed twice - in the first 2 days of clinical manifestations of the disease and when remission was achieved. The level of CaSR protein in the blood serum was analyzed by enzyme-linked immunosorbent assay (ELISA). All statistical analyses were performed using StatSoft STATISTICA version 8.0 (Tulsa, Oklahoma) and MedCalc version 17.2 statistical software. Results. There was no significant difference in CaSR protein levels between the Group 1 and the Group 2. The level of CaSR protein was significantly lower in the Group 1 and the Group 2 both in the period of acute and remission than in the control group. The level of the marker in the period of disease flare-up in the Group 1 and the Group 2 was significantly lower than in children of the same groups in the period of remission. Conclusions. In all patients with asthma, the level of CaSR protein at the acute stage of the disease is lower than at the remission stage, which is obviously associated with its redistribution from the peripheral blood to the smooth muscle of the lungs. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Influence of drugs of protocol therapy on the production of pro-inflammatory cytokines of t-lymphocytes of children with bronchial asthma

ABSTRACT. At the current stage of solving the problem in the pathogenesis of atopic BA in moderate-severe and severe course of the disease, the leading role is played by pro-inflammatory cytokines of T-lymphocytes and factors of the late phase of allergic inflammation. Goal. To determine the effect of the drugs of the therapy protocol recommended by GINA (2021) and the Ministry of Health of Ukraine No. 2856 on the production of pro-inflammatory cytokines in children with AD. Materials and methods. The study was conducted in 106 patients with BA and 20 healthy children aged 5 to 14 years in the period of disease remission before and after therapy. The impact of the protocol therapy scheme on the production of pro-inflammatory cytokines and their antibody control in children with different degrees of severity of the course of the disease was evaluated. The results. In asthma in children with a mild persistent course, protocol therapy reduces the release of mediators of the early phase of the allergic disease and the partial production of pro-inflammatory cytokines, which leads to clinical remission of the disease. With a moderately severe persistent course of AD, the influence of protocol therapy drugs reduce the level of production of pro-inflammatory cytokines to weakly positive values, which indicates incomplete control of therapy and unstable clinical remission. In severe persistent AD, protocol therapy partially reduces the production of pro-inflammatory cytokines, but does not affect the late phase of allergic inflammation and the autoimmune component of the pathogenesis of the disease. Conclusions. The recommended GINA protocol therapy (2021) eliminates the early phase and does not affect the late phase of allergic inflammation and the autoimmune component. This requires the development of additional therapy for moderate and severe asthma in children.

Association of &lt;i&gt;NR3C1 Bcl1&lt;/i&gt; gene polymorphism with impaired programmed cell death of lymphocytes in patients with atopic bronchial asthma

Atopic asthma is a chronic disease characterized by airway obstruction, bronchial hyperresponsiveness, and inflammation. Patients show increased activation of immune cells in the airways, especially T-lymphocytes, leading to chronic inflammation. The lymphocytes of asthma patients are known to have an impairment of the type 1 and 2 programmed cell death, i.e., apoptosis and autophagy, thus contributing to prolongation and intensification of inflammatory process. As compared to apoptosis, autophagy may also contribute to cell survival under stress conditions. Its disruption and hyperactivation leads to exacerbation of allergic responses. Glucocorticoids are the main drugs for the treatment of atopic bronchial asthma by activating the glucocorticoid receptor, thus triggering anti-inflammatory response and apoptosis of the cells. However, some patients exhibit resistance to therapy due to various factors, including single nucleotide polymorphisms of NR3C1 glucocorticoid receptor gene. The highest association between asthma severity and resistance to therapy was found for the GG variant of the NR3C1 Bcl1 polymorphism. Common molecular pathways for glucocorticoid receptor activation and programmed cell death and mediating molecules suggest a significant role for the polymorphic receptor variant in cell death. The aim of our study was to evaluate the effect of a single nucleotide polymorphism (G allele, i.e., Bcl1 polymorphism of NR3C1 gene) of glucocorticoid receptor on expression levels of genes that regulate apoptosis (BCL2, CASP3) and autophagy (BECN1, LC3) in lymphocytes of patients with moderate and severe atopic bronchial asthma. The study was performed with peripheral blood samples of 24 patients aged 20 to 45 years with an established diagnosis of moderate to severe atopic bronchial asthma. Using PCR technique with restriction fragment length polymorphism (RFLP) assay, the patients were distributed according to the genotypes of the BclI polymorphism of the NR3C1 gene: 12 patients with CC genotype, 8 persons with GC genotype, and 4 cases with GG genotype. The lymphocytes were isolated in Ficoll density gradient and cultivated with dexamethasone under the conditions of nutrient depletion. The level of gene expression was determined by real-time PCR. When studying associations between various genotypes of Bcl1 polymorphism and expression of cell death marker genes, the anti-apoptotic reactions were detected in lymphocytes of patients with GG polymorphism under the influence of dexamethasone thus being a potential mechanism for development of resistance to glucocorticosteroid therapy in asthma. Impaired activation of BECN1 gene expression in patients with the GG genotype may suggest deregulation of the autophagy in this group of patients, as a mode of programmed cell death. Moreover, in patients with GC genotype during long-term cultivation, exposure to dexamethasone increases the expression of the LC3 gene, indicating a more pronounced activation of autophagy. Hence, this work demonstrates differences in response of lymphocytes to synthetic glucocorticoid therapy, and probable effect of G allele (Bcl1 polymorphism) on dysregulation of programmed cell death under the influence of dexamethasone.

Medical resource utilization and the associated costs of asthma in China: a 1-year retrospective study

BackgroundDespite evidence that severe and poorly controlled asthma are associated with more clinical unmet needs and intensive utilization of healthcare resources, limited data is available on severe asthma expenditure in China. The study aimed to assess Medical Resource Utilization (MRU) costs of asthma and explore the cost drivers in order to better understand the economic burden of the Chinese population suffered from asthma.MethodsA retrospective analysis was conducted using Chinese sampled national claim database. Patients aged 6 years and above with primary diagnosis of asthma and asthma-related medical visit/hospitalization during 2015 were included. Medication was used as a proxy per the GINA and China guideline to identify asthma severity (i.e. mild, moderate, and severe). multiple linear regression model was conducted to identify MRU costs drivers.Results7,254 patients diagnosed with asthma were included: 4,529 (62.4%), 2,200 (30.3%), and 525 (7.2%) had mild, moderate, and severe asthma, respectively. On average, each severe patient spent 6,782 Chinese Yuan (CNY) on asthma treatment and had 57.0% hospitalization rate during the year, 3.9- and 4.4-fold of the average of overall population (P < 0.001 for both). The proportion of patients experiencing exacerbation significantly higher in the severe asthma population (66.5%; P < 0.001) compared to mild (30.0%) and moderate (16.8%) groups. In subgroup with 1,660 samples had annual consecutive data, severe patients had annual cost of CNY 8,314 and 52.2% hospitalization rate. 13% of severe patients who had frequent severe exacerbation (≥ 2 events) experienced the highest annual average cost CNY 23,037, P < 0.001) whereas children aged from 6 to 14 with a lower annual cost of CNY 1,094.2, 1,660.2 and 3,020.2 for mild, moderate, and severe patients respectively. The multiple model identified degree of severity, control status, complications, age, and live region as independent drivers of MRU costs.ConclusionsChinese asthma patients bear heavy economic burden. Severe asthma associated with higher MRU (mainly from hospitalization) and costs compared with mild to moderate asthma in China. More efforts should be devoted to the control of the disease severity and complication as the main drivers of asthma cost.

Adherence to National Asthma Guidelines in the Acute Care Setting: A Retrospective Cohort Study.

Peak flow is a crucial but simple test used to categorize the severity of an episode of an acute exacerbation of asthma.It should be regularly done in all the patients who present with asthma acute exacerbation in the emergency department. The British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) guidelines stipulate peak flow use as one of the main tools to categorize acute asthma into moderate, severe, and life-threatening asthma. The BTS and SIGN guidelines also state peak flow is to be utilized in monitoring the disease and to guide in treating patients with acute asthma. This study aims to identify the adherence to BTS/SIGN guidelines around the use of peak expiratory flow rate (PEFR) in assessing the severity of patients presenting with acute exacerbation of asthma in a district general hospital. The retrospective cohort study involved collating data between October 2022 and February 2023 from our hospital electronic system. The data collected about the use of PEFR and whether the patients were being classified by severity in presentation following this was compared to the BTS/SIGN 158 asthma guidelines. Following this, the data analysis was done using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States). Data from 92 patients were collated. PEFR was recorded for 29.3% (n=27) of patients and acute exacerbation of asthma severity was documented in merely 17.4% (n=16) patients. The results indicate a significant proportion of the patient cohort analyzed did not have peak flow readings, there is clear room for improvement, and further intervention is needed in order for the department to adhere to the gold standard guidelines (i.e., BTS/SIGN 158), and thus improve the management and monitoring of acute asthma exacerbations. Future directions can include departmental education, posters as a reminder, and prompts on the electronic system used to alert users to check PEFR when a diagnosis of acute asthma exacerbation is documented.

Successful Use of Therapeutic Plasma Exchange Following Red Blood Cell Exchange for Severe Acute Chest Syndrome: A Single Institution Experience

Introduction: Severe acute chest syndrome (ACS) is a potentially fatal complication of sickle cell disease (SCD) that can progress to multiorgan failure. Treatment includes red blood cell (RBC) exchange to improve oxygenation and reduce vaso-occlusion by decreasing the proportion of hemoglobin (Hb) S. Patients with poor response to RBC exchange are at high risk for mortality. Therapeutic plasma exchange (TPE) may be beneficial in cases of severe organ dysfunction refractory to RBC exchange. TPE is postulated to remove pro-inflammatory cytokines, reduce circulating free hemoglobin, and decrease complement products that contributes to vaso-occlusion and inflammation. The use of TPE for severe ACS and multiorgan failure has been rarely described in adult patients and is even less commonly described for pediatric patients. Aim: To describe use of TPE for the management of severe ACS with multiorgan failure in two pediatric patients and one young-adult patient who did not respond to standard medical management with RBC exchange transfusion. Methods: Case reports Case 1: A six-year-old male with homozygous SCD (HbSS) and moderate persistent asthma was admitted for ACS. His course was complicated by hypoxemia requiring intubation, oliguria, and hypotension. On hospital day 3, he underwent RBC exchange with four units of RBCs. Despite decrease of Hb S to 15%, he remained hypoxic on high ventilatory support and developed acute respiratory distress syndrome. After multidisciplinary discussion, TPE was trialed in hopes of improving oxygenation and reversing multiorgan dysfunction. He underwent 3 TPEs, each with 1.5 total plasma volume (TPV) using 5% albumin (days 4, 5 and 7). After a single session of TPE, his oxygenation saturations improved to the 90s, and his ventilator support was weaned. He was extubated on day 8 and was discharged on day 13 in stable condition. Case 2: A sixteen-year-old male with HbSS, recurrent hyper-hemolytic syndrome, and sickle cell hepatopathy was admitted for medical optimization before scheduled cholecystectomy. His Hb was raised pre-operatively with erythropoietin, in lieu of RBC transfusion, due to history of severe refractory hyper-hemolysis with transfusions. He underwent uncomplicated cholecystectomy on hospital day 2. On day 3, he developed ACS, septic shock, and an exacerbation of known hepatopathy. He was intubated and underwent RBC exchange with 8 units of RBCs. His Hb S decreased to 20% but he had no improvement in clinical status. High-dose steroids and TPE were then trialed. The use of TPE was dual purposed to reduce inflammatory cytokines contributing to systemic dysfunction and to prevent hyper-hemolysis following exchange transfusion. He underwent 3 TPEs each with 1.5 TPV using 5% albumin for three days (days 5, 6, and 7). Throughout his course of TPE, he was extubated (day 6), weaned off pressor support (day 6), and his liver dysfunction began to improve (day 7). He was discharged home on day 16. Case 3: A thirty-five-year-old female with HbSS without chronic complications was transferred from an outside hospital where she presented 3 days prior with ACS and progressive neurologic deterioration with minimal responsiveness. Imaging revealed diffuse pulmonary infiltrates and extensive cerebral micro emboli consistent with fat embolism syndrome. She underwent RBC exchange on the day of arrival to our facility (hospital day 4) with 5 units of RBCs. Her Hb S decreased to 20% but she had no improvement in neurologic function. After multidisciplinary evaluation, TPE was trialed alongside high-dose steroids. She underwent 5 TPEs each with 1.0 TPV using 5% albumin (days 5, 6, 8, 9, and 12). Shortly after initiating TPE, she began recovering neurologically with eye-opening, response to noxious stimuli, and tracking (day 6). After 3 days of TPE, CRP fell from 21 to 5 and ESR from 49 to 23 (day 8). She followed commands on day 10 and was taken off oxygen on day 15. She was discharged to a rehabilitation facility on day 30 with significant improvements in mental status, cognition, and functional abilities. Conclusions: TPE for three to five days should be considered in patients with severe ACS and multiorgan failure with high risk of mortality when standard management fails. The early initiation of TPE likely contributed to the successful recoveries of these three cases. Further studies are needed to delineate the role of TPE in the management of acute complications of SCD.

Psychometric evaluation of an electronic Asthma Symptom Diary for young children

BackgroundPatient-reported outcome measures that facilitate self-report by children are needed to reduce the bias of proxy report. We previously developed an electronic Pediatric Asthma Symptom Diary (ePASD) to assess the severity of daily asthma symptoms and proximal impacts in children aged 6–11 years with mild to severe asthma. The ePASD, administered via a digital application with visuals, sounds, and text, is uniquely designed to minimize the importance of reading skills on children’s ability to self-report accurately. Here, we describe the ePASD’s psychometric properties.MethodsNinety-one children aged 6–11 years with mild to severe asthma and their caregivers participated in 2 study visits, which consisted of training on the provisioned device and completing asthma-specific clinical outcome assessment (COA) questionnaires. The children self-completed the ePASD at home twice daily for 8 consecutive days. The scoring of the ePASD was guided by factor analyses, inter-item correlations, and internal consistencies. Reliability, discriminating ability, construct validity, and responsiveness were evaluated for ePASD items and candidate scores.ResultsAll COAs included in the study—the ePASD, Asthma Control Questionnaire (ACQ), Childhood Asthma Control Test, Pediatric Asthma Quality of Life Questionnaire–Standardized (PAQLQ[S]), and global ratings—demonstrated that the children exhibited few asthma-related symptoms and impacts at all timepoints, and consequently, showed little change over time. Internal consistencies (all Cronbach’s alphas ≥ 0.52) and test-retest reliabilities (all intraclass correlation coefficients ≥ 0.60) were largely satisfactory. Patterns of convergent and divergent correlations supported the construct validity of ePASD scores. The ePASD symptom scores correlated moderately to strongly with PAQLQ(S) Symptom scores (all correlations ≥ − 0.46) and with ACQ scores (all correlations ≥ 0.42), as predicted. Evidence of the discriminating ability of ePASD items and composite scores was demonstrated by known-groups analyses.ConclusionsThe ePASD is a reliable and valid measure of asthma symptoms and proximal impacts in children aged 6–11 years with mild, moderate, or severe asthma. These results lay the psychometric groundwork for use of the ePASD in future clinical trials for the management of pediatric asthma. An ongoing pediatric asthma treatment trial is anticipated to provide evidence of the ePASD’s responsiveness to change.

The RNA binding proteins ZFP36L1 and ZFP36L2 are dysregulated in airway epithelium in human and a murine model of asthma.

Introduction: Asthma is the most common chronic inflammatory disease of the airways. The airway epithelium is a key driver of the disease, and numerous studies have established genome-wide differences in mRNA expression between health and asthma. However, the underlying molecular mechanisms for such differences remain poorly understood. The human TTP family is comprised of ZFP36, ZFP36L1 and ZFP36L2, and has essential roles in immune regulation by determining the stability and translation of myriad mRNAs encoding for inflammatory mediators. We investigated the expression and possible role of the tristetraprolin (TTP) family of RNA binding proteins (RBPs), poorly understood in asthma. Methods: We analysed the levels of ZFP36, ZFP36L1 and ZFP36L2 mRNA in several publicly available asthma datasets, including single cell RNA-sequencing. We also interrogated the expression of known targets of these RBPs in asthma. We assessed the lung mRNA expression and cellular localization of Zfp36l1 and Zfp36l2 in precision cut lung slices in murine asthma models. Finally, we determined the expression in airway epithelium of ZFP36L1 and ZFP36L2 in human bronchial biopsies and performed rescue experiments in primary bronchial epithelium from patients with severe asthma. Results: We found ZFP36L1 and ZFP36L2 mRNA levels significantly downregulated in the airway epithelium of patients with very severe asthma in different cohorts (5 healthy vs. 8 severe asthma; 36 moderate asthma vs. 37 severe asthma on inhaled steroids vs. 26 severe asthma on oral corticoids). Integrating several datasets allowed us to infer that mRNAs potentially targeted by these RBPs are increased in severe asthma. Zfp36l1 was downregulated in the lung of a mouse model of asthma, and immunostaining of ex vivo lung slices with a dual antibody demonstrated that Zfp36l1/l2 nuclear localization was increased in the airway epithelium of an acute asthma mouse model, which was further enhanced in a chronic model. Immunostaining of human bronchial biopsies showed that airway epithelial cell staining of ZFP36L1 was decreased in severe asthma as compared with mild, while ZFP36L2 was upregulated. Restoring the levels of ZFP36L1 and ZFP36L2 in primary bronchial epithelial cells from patients with severe asthma decreased the mRNA expression of IL6, IL8 and CSF2. Discussion: We propose that the dysregulation of ZFP36L1/L2 levels as well as their subcellular mislocalization contributes to changes in mRNA expression and cytoplasmic fate in asthma.

Changes in immunity during the second trimester of pregnancy in women with exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection

Aim. To evaluate changes in immunity in the second trimester of pregnancy in women with exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection (CMVI).Materials and methods. The concentration of secretory immunoglobulin A (sIgA), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and circulating immune complexes (CIC) was studied in 112 women at 21-24 weeks of uncomplicated pregnancy and pregnancy complicated by exacerbation of mild-to-moderate asthma associated with CMVI. The first group included 30 women seronegative for CMV, with an uncomplicated pregnancy. The second group consisted of 30 patients with exacerbation of mild asthma, initiated by the acute phase of CMVI, which induces the development of chronic compensated placental insufficiency. The third group consisted of 27 patients with moderate asthma in the acute stage against the background of the acute phase of CMVI, leading to the formation of chronic compensated placental insufficiency. The fourth group included 25 patients with exacerbation of moderate asthma with CMV etiology, initiating the development of chronic subcompensated placental insufficiency.Results. In women of the second group, the concentration of sIgA was 5.91±0.371 mg/L, IgA – 2.64±0.089 mg/mL, IgG – 15.4±0.791 mg/mL, IgM – 2.32±0.144 mg/mL, CIC – 0.176±0.004 optical density units (in the first group, respectively, 4.31±0.266 mg/L, p&lt;0.001; 2.37±0.06 mg/mL, p&lt;0.05; 13.3±0.293 mg/mL, p&lt;0,05; 1.11±0.06 mg/mL, p&lt;0.001; 0.092±0.005 optical density units, p&lt;0.001). In patients of the third group, in contrast to the second one, no differences in immunity parameters were detected. In the fourth group, in comparison with the third one, lower parameters of sIgA (3.21±0.213 mg/L, p&lt;0.001), IgA (1.43±0.081 mg/mL, p&lt;0.001), as well as higher IgG values were detected (19.8±0.418 mg/mL, p&lt;0.001), IgM (2.94±0.082 mg/mL, p&lt;0.01) and CIC (0.198±0.005 optical density units, p&lt;0.05).Conclusion. In patients with moderate asthma with exacerbation against the background of CMVI reactivation, which initiates the formation of chronic subcompensated placental insufficiency, in contrast to women with moderate asthma in the stage of CMVI exacerbation in the second trimester of pregnancy, leading to chronic compensated placental insufficiency in the third trimester of gestation, a more pronounced imbalance of humoral immunity and autoimmune disorders are found, which are important in the development of chronic placental dysfunction.