Treatment Of Asthma Research Articles

Features of children with critical asthma hospitalized in a pediatric intensive care unit: Results from the ICU-3A study.

Despite improvements in long-term asthma treatment, an increasing number of children are being hospitalized in pediatric intensive care units (PICU) for asthma. The main objective of this study was to describe a recent cohort of children hospitalized in PICU for asthma to identify risk factors associated with a need for respiratory support, and multiple PICU stays. We conducted a retrospective cohort study in three PICUs in Paris (intensive care units 3A Study), using medical files of children hospitalized for asthma between February 2019 and October 2020. Need for respiratory support was defined by the need for high-flow nasal cannula or mechanical ventilation (MV) (either noninvasive [NIV] or invasive [IMV]). During the study period, 252 stays corresponding to 234 patients were analyzed. MV was required in 17.5% of stays, for significantly younger patients (2.37 vs. 4.18 years, p = 0.002). On multivariate analysis, a higher risk of progression to a need for respiratory support was found for children requiring magnesium sulfate or oxygen therapy ≥6 L/mn before PICU admission (RR 4.48; CI95% [1.85-10.89]; p = 0.001, and RR 2.86; CI95% [1.13-7.22]; p = 0.03, respectively), and those with atelectasis detected on chest radiography (RR 3.38; CI95% [1.43-8.00]; p < 0.01). Multiple PICU stays were associated with greater social deprivation (RR for French Deprivation Index 1.25; CI95% [1.03-1.51]; p = 0.03). Children experiencing social deprivation are at greater risk of multiple PICU stays for severe asthma. After transfer to PICU, children with chest radiograph detected atelectasis on admission are at higher risk of needing respiratory support.

Opportunities to rehabilitation of multimorbid patients with asthma and obesity

BACKGROUND: The challenges of rehabilitation and achieving asthma control in patients with multimorbid conditions remain relevant despite advances in asthma treatment. Improving therapeutic approaches requires not only the development of new drugs, but also the creation of comprehensive individualized rehabilitation programs. AIM: To develop complex rehabilitation programs for patients with asthma and multimorbid diseases (obesity, osteoarthritis) and assess their impact on asthma and comorbid conditions. MATERIALS AND METHODS: 70 patients with asthma and obesity were divided into two groups: a rehabilitation group and a control group. The study evaluated external respiration functions, quality of life using Asthma Quality of Life Questionnaire (standardized), asthma control with Asthma Control Questionnaire-5 (ACQ-5), multimorbid pathology with Cumulative Illness Rating Scale (CIRS), Lequesne index, exercise capacity via 6-minute walk test, physical activity using questionnaire ODA23+, and levels of interleukin-6, interleukin-4, tumor necrosis factor alpha, leptin. RESULTS: Both groups were comparable across all assessed parameters, with most participants presenting moderate to severe asthma. Physical activity levels were low to moderate. The CIRS index was 10.0 ± 1.1 in group 1 and 9.2 ± 1.1 in group 2 (p 0.05), while the Lequesne index was 9.70 ± 1.47 and 8.80 ± 1 (p = 0.3900), respectively. After rehabilitation program, the Lequesne index in the group 1 decreased by 2.37 ± 0.60 (р 0,05), which correlated with improved exercise tolerance (6-minute walk test) and increased physical activity by 6.57 ± 2.00 (р 0.05), and increased asthma control (with ACQ-5 decreasing by 0.74 ± 0.20 points; р 0.05) and quality of life with Asthma Quality of Life Questionnaire (standardized) 3.8 ± 0.4 to 4.5 ± 0.3 (р 0.05). In group 2, no significant changes were observed in the Lequesne index, physical activity, asthma control, or quality of life (p 0.05). Proinflammatory cytokines, including interleukin-6, tumor necrosis factor alpha, and leptin, decreased significantly in group 1, while the control group showed no significant changes. CONCLUSIONS: Multicomponent rehabilitation programs tailored to the individual characteristics of patients with multimorbid conditions contribute to better management of both asthma and comorbidities. Rehabilitation improves asthma control, quality of life, and exercise tolerance. It also helps to reduce pain syndrome, increase physical activity, and decrease proinflammatory cytokines and leptin levels.

Exploring the potential mechanisms of Mahuang Fuzi Xixin decoction in treating elderly bronchial asthma through network pharmacology, molecular docking, and molecular dynamics simulations.

Modern medical practice has confirmed the efficacy of Mahuang Fuzi Xixin Decoction (MHFZXXD) in treating elderly bronchial asthma, but its specific mechanisms of action remain to be clarified. Therefore, this study utilizes network pharmacology, molecular docking techniques, and molecular dynamics simulations to explore the key active components, core target genes, and potential mechanisms of MHFZXXD in the treatment of elderly bronchial asthma. Active components and related targets of MHFZXXD were identified through the retrieval and screening of the TCMSP, Swiss Targets Prediction, and Uniprot databases. Relevant targets for elderly bronchial asthma were searched using the GeneCards, OMIM, and Pharm GKB databases, followed by the selection of intersecting targets between the drug's active components and the disease. A PPI network diagram was created using String and Cytoscape software, and the intersecting targets of the disease and the active components of traditional Chinese medicine were imported into the DAVID database for GO and KEGG enrichment analysis to further explore their potential mechanisms of action. Subsequently, molecular docking and molecular dynamics simulations were performed using AutoDock Vina and Gromacs to verify the binding capacity and stability of the core genes with the key active components. The study results indicate that the active components of MHFZXXD, such as quercetin, luteolin, and kaempferol, target multiple genes including AKT1, EGF, MYC, TGFB1, PTEN, and CCND1. They exert effects through signaling pathways such as TNF, PI3K-Akt, and HIF-1. Molecular docking and dynamics simulations show that the core targets bind stably with the key active components. Overall, MHFZXXD may reduce inflammatory responses and improve hypoxic conditions and apoptosis during the progression of elderly bronchial asthma through multiple active components, targets, and signaling pathways, thereby delaying the malignant progression of the disease. This provides relevant evidence and experimental data for clinical treatment and further research.

Effect of continuous inhaled corticosteroids on glycated hemoglobin in asthmatic children: a pilot study

BackgroundAsthma is a prevalent chronic disease with significant impact on patients, families, and communities. Inhaled corticosteroids (ICS) are the mainstay of treatment for persistent and uncontrolled asthma. However, concerns remain about the potential adverse effects of ICS, including HbA1c level. This study aims to evaluate the influence of ICS on Hemoglobin A1c (HbA1c) levels in children with bronchial asthma.MethodsThis prospective cohort study included 48 pediatric asthma patients aged 2 to 15 years who had been using ICS for at least 6 months. Comprehensive clinical assessments and measurements of HbA1c levels were conducted at the start of recruitment and after 6 months of ICS use. The types and doses of ICS used followed the guidelines provided by the Global Initiative for Asthma (GINA).ResultsThe initial HbA1c levels ranged from 4.46 to 6.11, with a mean of 5.32 ± 0.35. Three patients (6.3%) had persistent prediabetes status after 6 months. There was no significant relationship between glycemic status and the characteristics of ICS. The duration of ICS therapy and the doses used did not significantly affect HbA1c levels. A weak positive correlation was observed between initial and subsequent HbA1c levels.ConclusionThe study found no significant difference in HbA1c levels among asthmatic children using ICS after six months of treatment. Additionally, there was no significant difference in HbA1c levels between patients using different types of ICS. Regular monitoring of HbA1c levels is recommended, particularly for children on high doses or prolonged use of inhaled Fluticasone.

Dupilumab induced maculopapular exanthema: A case report

Dupilumab is a fully human anti-interleukin-4-and 13 monoclonal antibody commonly used in the treatment of severe atopic dermatitis and severe asthma. We report a case of maculopapular exanthema that occurred after the first injection of dupilumab in a young patient treated for severe asthma.

Left ventricular systolic function after inhalation of beta-2 agonists in healthy athletes

Inhaled beta-2 adrenoceptor agonists (iβ2A) are routinely used as bronchodilators in the treatment of asthma. However, their cardiac effects in athletes are scarcely examined. Thus, the aim of this study was to evaluate the effects of iβ2A on left ventricular (LV) systolic function (SF) by echocardiography in healthy, non-asthmatic female and male endurance athletes. A randomized, double-blinded, placebo-controlled, balanced, 4-way complete block cross-over study was conducted. Twenty-four healthy athletes (12f/12m: 22.9 ± 2.7/24.4 ± 4.6 years) randomly completed 4 study arms (placebo; salbutamol; formoterol; formoterol + salbutamol). After inhalation of the study medication, the participants performed a 10-min time trial (TT) on a bicycle ergometer. After each TT an echocardiography was performed to determine LVSF. Blood samples were collected pre, post, 3 h and 24 h post TT. In females, total serum concentrations for salbutamol and formoterol were higher. LV ejection fraction (LVEF) and LV global longitudinal strain (LVendoGLS) showed a treatment effect for the whole study group (p < 0.0001) and a sex effect on LVEF (p = 0.0085). In women, there was a significant treatment effect for all medication arms (at least p ≤ 0.01) both on LVEF and LVendoGLS. In men only formoterol and formoterol + salbutamol displayed a treatment effect on LVEF (p = 0.0427, p = 0.0330; respectively), whereas on LVendoGLS only formoterol + salbutamol was significant (p = 0.0473). The iβ2A significantly influenced LVSF after an acute bout of exercise in healthy endurance athletes. These effects were even more pronounced when combining both iβ2A that supports a dose-dependent effect on cardiac function. Moreover, female athletes had higher serum concentrations of β2 agonists and stronger effects on LVSF compared to male athletes. This is mainly explained by differences in body weight and related plasma volume and may indicate a potential risk when increasing dose above the tested concentrations. Trial registration: At the European Union Drug Regulating Authorities Clinical Trials (Eudra CT) with the number 201,500,559,819 (registered prospectively on 09/12/2015) and at the German register for clinical studies (DRKS number 00010574 registered retrospectively on 16/11/2021).

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience

Background Patients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking. Materials and methods In this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test‐22 (SNOT‐22, 0 – 110), Visual Analog Scale symptom scores (VAS, 0–10), and Asthma Control Test (ACT, 5–25) and the proportion of patients meeting the minimal clinically important difference (MCID). Results Disease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0–52 vs 10, IQR:0–30 vs 0, IQR:0–15 vs 0, IQR:0–12, p < 0.001, VAS score: 1, IQR: 0–5 vs 0, IQR:0–3 vs 0, IQR:0-2 vs 0, IQR 0–1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline. Conclusions The study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease. The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the “X International Workshop on Lung Health – Respiratory Disease and Immune Response”, held in Nice on 19–21 January 2023.

Evaluation of Infants Hospitalized in Intensive Care Unit Due to Acute Severe Bronchiolitis in Terms of Recurrent Wheezing or Asthma Development

Objective: Bronchiolitis stands out as the most prevalent lower respiratory tract infection among young children. Severe bronchiolitis, or bronchiolitis requiring admission to the hospital, affects 2-3% of all infants. The aim of this study was to evaluate individuals who were followed up in the pediatric intensive care unit (PICU) due to severe bronchiolitis in terms of asthma development. Material and Methods: Patients who were admitted Ankara Bilkent City Hospital PICU between January 2013 and December 2022, who were diagnosed with severe bronchiolitis and who had no additional systemic disease were included in the study. Demographic and clinical characteristics of patients, intensive care support treatments, duration of hospital stays, atopic conditions, and respiratory viral panel cultures was documented. The current clinical condition of the patients was documented through hospital records and telephone interviews conducted with their caregivers. The existence of asthma symptoms and the utilization of treatments within the last 12 months were evaluated according to the guidelines of the Global Initiative for Asthma (GINA) and the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Results: The mean age of the 60 patients admitted to the intensive care unit who met the study criteria was 13.5±7.2 months. The mean age of the children at the time of the study was 42.5 months. Male gender was more predominant (n=39, 65%). The mean number of days that respiratory support was received in intensive care was 4.9 (±3.5) days and the mean number of days of systemic steroid therapy was 3.8 (±1.7) days. In the viral respiratory tract, Respiratory Syncytial Virus (RSV) was isolated at the highest frequency in 27 patients, accounting for 45%, followed by rhinovirus (n=6, 10%) and Bocavirus (n=5, 8.3%). The number of patients receiving current asthma treatment was (n=33, 55%). Upon assessing the current status, it was found that there had been 25 (41.6%) patients with asthma attacks over the past 12 months. Conclusion: This study revealed that over half of the patients who experienced severe bronchiolitis subsequently developed asthma, with some not being referred to an allergy clinic. Furthermore, it was observed that certain patients, despite presenting with asthma symptoms, were unaware that these symptoms were attributable to asthma. We recommend that patients admitted to the PICU with a diagnosis of severe bronchiolitis be closely monitored for the potential development of asthma and that families be thoroughly informed at the time of discharge.

6813 Des-Ciclesonide: A Novel Selective Glucocorticoid Receptor Modulator With Therapeutic Potential for Bronchopulmonary Dysplasia, a Chronic Lung Disease of Prematurity

Abstract Disclosure: N. El Khoury: None. J. Jaumotte: None. C. Min: None. C. Madigan: None. J. Wang: None. U. Chandran: None. V. Sampath: None. T.J. Cole: None. P. Monaghan-Nichols: None. R. Houtman: None. K.W. Nettles: None. D.B. DeFranco: None. Infants born before 30 weeks gestation are at risk of developing bronchopulmonary dysplasia (BPD), a prevalent chronic lung disease of prematurity. Glucocorticoids (GCs) such as dexamethasone (DEX) have been a mainstay of BPD prevention as they reduce lung inflammation and injury. However, their use is encumbered with several adverse effects including hyperglycemia, impaired somatic and brain growth and cerebral palsy. These major concerns have resulted in the AAP recommending caution in GC use in preterm infants.Ciclesonide (CIC), an inhaled GC prodrug approved for the treatment of asthma and allergic rhinitis in children, is converted to the potent glucocorticoid receptor (GR) agonist des-ciclesonide (DES) by enzymes enriched in the airways. We previously reported that s.c. delivery of CIC in neonatal rats activated GR transcriptional responses in lung but did not trigger the adverse effects on somatic growth, brain weight or cerebral white matter loss caused by DEX leading us to propose CIC as a potential new pharmacotherapy for BPD. To determine whether limited systemic metabolism of CIC in neonatal rats was solely responsible for its enhanced safety profile, we assessed various outcomes in neonatal rats followed s.c. delivery of its active metabolite DES. Consistent with previous studies, five daily s.c. injections of DEX led to a reduction in body and brain weight as well as reduced serum levels of insulin-like growth factor-1 and chronic hyperglycemia. Surprisingly, analogous s.c. injection of neonatal rats with DES, which has a higher binding affinity for GR than DEX, did not trigger any of these adverse effects. However, DES is as effective as DEX in reducing the expression of various proinflammatory cytokine mRNAs in neonatal rat lung induced by an 11-day systemic treatment with bleomycin. Bulk RNAseq analyses revealed transcriptional responses of neonatal lung and liver to DES, although less robust than that observed to DEX (i.e., 25% and 13% in lung and liver, respectively). Nonetheless, a NAPing assay for coregulator peptide binding showed increased binding of all the DES responsive peptide interactions relative to DEX and cortisol. All-atom molecular dynamics simulations revealed site-specific H-bonding changes within the GR ligand binding domain (LBD) caused by the bulky C16/C17substitution within DES, which was translated into broader changes in LBD structure, specifically revealed as differences in RMSF in helix 7/8 and the surfaces interacting with the NCOA2 peptide. Furthermore, network pathway analysis illustrated that DES mobility at helix 7/8 uniquely generated a meaningful allosteric signaling pathway between Q642 and NCOA2 peptide. In conclusion, the pharmacokinetic properties of the GR prodrug CIC coupled with the tissue-selective pharmacodynamic properties of its active metabolite DES make this FDA approved drug a potential new therapeutic agent for BPD. Presentation: 6/3/2024

Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

Early diagnosis and treatment of chronic obstructive pulmonary disease and bronchial asthma

Early diagnosis and treatment of chronic obstructive pulmonary disease and bronchial asthma

Cost-effectiveness of allergen immunotherapy.

Allergic rhinitis is a relevant and global health problem affecting up to 5-50% of the general population and its prevalence is increasing due to climate change and pollution among other factors and counts among the 10 most frequent reasons for medical consultation, generating an important economic impact. Allergen immunotherapy (AIT) is the only allergy-disease-modifying treatment and there is plenty of evidence of its effectiveness with regards subcutaneous and oral routes of AIT.This narrative review article examines published literature in the last 24 months regarding the pharmacoeconomics of AIT versus standard of care treatment (SOC) for the treatment of allergic rhinitis and asthma. Farraia et al. assessed in 2022 subcutaneous immunotherapy (SCIT, _438/$500.28) and sublingual immunotherapy (SLIT) (_1021/$1116.19) plus symptomatic treatment versus SOC treatment in children with HDM-driven allergic asthma, measuring QALYs, decrease of medication, decrease of exacerbations and symptoms. They used the cost-effective threshold: _18 482.80 ($21 110.14), finding that AIT is cost-effective.Also, SCIT and SLIT plus symptomatic treatment was assessed versus SOC treatment in children with grass pollen allergic rhinitis. The authors concluded that SCIT (_933/$1065.67) and SLIT (_1408/ $1608.22) seem cost-effective, particularly SCIT. Allergen immunotherapy is cost-effective in the management of allergic rhinitis and asthma as compared with SOC alone. As most studies consider only during-treatment costs and no long-term benefits or preventive effects are being assessed, the real cost-effectiveness of allergen immunotherapy could be even higher.

Research progress in the clinical application of inhaled anesthetic sevoflurane.

Sevoflurane has been widely used in clinical anesthesia as an inhalation anesthetic. With the development of medicine, there have been several new applications in recent years, such as daytime surgery, labor analgesia, and combined nerve block for some surgeries. Moreover, as research progresses, it has been found that it not only has potential organ protection effects but can also be used to treat severe asthma and relieve the tracheal spasm state. In addition, local administration can effectively treat vascular ulcers. We briefly review the organ protective effect of sevoflurane, its application in dental treatment, asthma treatment, vascular ulcer treatment and some new progress in clinical application.

Quercetin inhibits ferroptosis through the SIRT1/Nrf2/HO-1 signaling pathway and alleviates asthma disease.

Quercetin (QCT) is a bioflavonoid derived from vegetables and fruits that has anti-inflammatory and anti-ferroptosis effects against various diseases. Previous studies have shown that QCT modulates the production of cellular inflammatory factors in asthma models and delays the development of chronic airway inflammation. However, the regulatory mechanism of QCT, a traditional Chinese medicine, in the treatment of asthma has not been elucidated. The aim of the present study is to investigate whether QCT can inhibit ferroptosis via the SIRT1/Nrf2 pathway and play a therapeutic role in asthma. An ovalbumin-induced mouse asthma model was established, and its function was verified by hematoxylin eosin staining, enzyme linked immunosorbent assay, ferric ion assay, malondialdehyde and superoxide dismutase assays, dihydroethidium staining, immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction. Our results indicated that an ovalbumin-induced asthma mouse model had been successfully established and that QCT inhibited inflammation, reduced serum levels of inflammatory factors IL-4, IL-5 and IL-13, increased superoxide dismutase levels in lung tissue homogenates, and reduced malondialdehyde and ferric ion production in asthmatic mice. In addition, we found that QCT was able to reverse the expression of SIRT1, Nrf2 and HO-1 in an in vivo asthma mouse model. The data from this study indicate that QCT can alleviate asthma, and its mechanism is related to the regulation of ferroptosis, oxidative stress, and the expression of SIRT1 protein.

Traditional Chinese medicine to improve immune imbalance of asthma: focus on the adjustment of gut microbiota.

Asthma, being the prevailing respiratory ailment globally, remains enigmatic in terms of its pathogenesis. In recent times, the advancement of traditional Chinese medicine pertaining to the intestinal microbiota has yielded a plethora of investigations, which have substantiated the potential of traditional Chinese medicine in disease prevention and treatment through modulation of the intestinal microbiota. Both animal models and clinical trials have unequivocally demonstrated the indispensable role of the intestinal microbiota in the pathogenesis of asthma. This article presents a summary of the therapeutic effects of traditional Chinese medicine in the context of regulating gut microbiota and its metabolites, thereby achieving immune regulation and inhibiting airway inflammation associated with asthma. It elucidates the mechanism by which traditional Chinese medicine modulates the gut microbiota to enhance asthma management, offering a scientific foundation for the utilization of traditional Chinese medicine in the treatment of asthma.

CLCA1 and BPIFB1 are potential novel biomarkers for asthma: an iTRAQ analysis.

Asthma is a chronic respiratory disease that affects billions of people. Due to its diverse phenotypes and endotypes with distinct pathophysiological mechanisms, significant challenges arise in its clinical diagnosis and treatment. The discovery of potential biomarkers of asthma has significant implications for its clinical classification and precise treatment. The purpose of this study is to identify potential biomarkers for asthma, providing a foundation for its diagnosis and treatment. We constructed an ovalbumin (OVA)-sensitized asthmatic mice model and used isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) technology to identify differentially expressed proteins (DEPs) in lung tissues. We then performed enrichment analyses of the DEPs using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and constructed protein-protein interaction (PPI) networks. We identified 242 DEPs in the asthmatic mice model and showed that heat shock protein family A (Hsp70) member 5 (HSPA5) is a central protein in asthma. Consistent with our bioinformatics analysis, our western blot validation confirmed that the protein levels of arginase 1 (ARG1), chitinase-like protein 3 (CHIL3), chloride channel accessory 1 (CLCA1), and bactericidal/permeability-increasing protein (BPI) fold-containing family B member 1 (BPIFB1) were significantly increased in asthma group compared to the control group. Thus, we found that CLCA1 and BPIFB1 were the most promising potential biomarkers of asthma. Our iTRAQ analysis and western blot verification of asthmatic mice showed that HSPA5 is a central protein in asthma, and CLCA1 and BPIFB1 are novel potential biomarkers that could play significant roles in the diagnosis and treatment of asthma.

A partial loss-of-function variant in STAT6 protects against T2 asthma

BackgroundSignal Transducer and Activator of Transcription 6 (STAT6) is central to Type 2 (T2) inflammation and common non-coding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment. ObjectiveTo test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture. MethodsWe tested association of p.L406P with plasma protein levels, white blood cell counts and the risk of asthma and allergic phenotypes. We tested significant associations in other cohorts using a burden test. The effects of p.L406P on STAT6 protein function were examined in cell lines and by comparing CD4+ T-cell responses from carriers and non-carriers of the variant. Resultsp.L406P associated with reduced plasma levels of STAT6 and IgE as well as with lower eosinophil and basophil counts in blood. It also protected against asthma, mostly driven by severe T2 high asthma. We showed that p.L406P led to lower IL-4-induced activation in luciferase reporter assays and lower levels of STAT6 in CD4+ T cells. We identified multiple genes with expression that was affected by the p.L406P genotype upon IL-4 treatment of CD4+ T cells; the effect was consistent with a weaker IL-4 response in carriers than non-carriers of p.L406P. ConclusionsWe report a partial loss-of-function variant in STAT6, resulting in dampened IL-4 responses and protection from T2 high asthma, implicating STAT6 as an attractive therapeutic target.

Effects of Medication on Asthma and the Development of Caries Cavities in Children Aged 3-15 at Luz Hospital in Lisbon, Portugal.

To examine the impact of medication on asthma treatment and the occurrence of caries cavities in children aged 3 to 15 years old (Luz Hospital in Lisbon, Portugal). The frequency of caries cavities in 3 different groups was examined. In addition, the possible association of caries cavities with different asthmatic medication was also assessed. Asthma and caries cavities affect many children worldwide. Investigating the connection between asthma medication and the development of caries cavities is important for enhancing asthma treatment while reducing oral health risks. Exploring the relationship between asthma medication and caries cavities is compelling due to the limited number of conclusive studies on the subject. A descriptive observational study was conducted on children aged 3 to 15 years old, who attended the immunology-allergology and dentistry services at the Luz Hospital in Lisbon, Portugal. between January 2021 and February 2022. The sample was divided into 3 groups (medicated asthmatics, unmedicated asthmatics, and healthy children without asthma). An intraoral examination was performed to collect the DMFT index (decayed, missing, and filled teeth) to assess the presence of caries cavities. Clinical and dietary data were supplemented with a questionnaire and medical history in all groups. All variables used were qualitative and described using absolute frequencies and percentages. These results showed that anti-asthmatic medications may influence the development of caries cavities. The occurrence of caries cavities is more prominent in medicated asthmatic children when compared to unmedicated asthmatic children.

Effects of PACK training on the management of asthma and chronic obstructive pulmonary disease by primary care clinicians during 2 years of implementation in Florianópolis, Brazil: extended follow-up after a pragmatic cluster randomised controlled trial with a stepped-wedge design

BackgroundTraining primary care doctors and nurses to use Practical Approach to Care Kit (PACK) improved management of asthma and chronic obstructive pulmonary disease (COPD) in a previous randomised trial. The...

Troponin I versus Creatinine Kinase-MB as Predictor Markers of the Severity and Outcomes in Acute Theophylline Toxicity

Abstract Theophylline is a type of diethylxanthine that continues to be widely used in many developing countries for the treatment of acute and chronic bronchial asthma, chronic obstructive pulmonary disease (COPD) and apnea of prematurity. Methylxanthine cardiotoxicity is based on diverse, complex mechanisms. PDE inhibition and blocking adenosine receptors cannot explain all the cardiotoxic effects of methylxanthine. In addition, methylxanthines are cardiac stimulants and result in positive inotropy and chronotropy even with therapeutic dosing; myocardial ischemia and myocardial infarction (MI) are associated with acute theophylline poisoning. The current study aimed to investigate troponin I and creatine kinase-MB as predictors of the severity and outcomes in cases of acute theophylline intoxication. No previous studies have proposed early predictors of cardiovascular toxicities among methylxanthine users, early recognition of the severity of theophylline toxicity can be lifesaving and needs aggressive supportive care to improve clinical outcomes in patients. This study was a prospective cohort study conducted on 34 patients admitted to the Poison Control Center at Ain Shams University Hospitals (PCC-ASUH) for a 6-month duration from January 2022 to June 2022 with a history of acute exposure to theophylline toxicity. with history of acute exposure to theophylline toxicity. Patients were subjected to personal and toxicological history taking, vital signs collection, grading of acute theophylline toxicity and measurement of serum theophylline level. Both troponin I and creatine kinase-MB were measured at 6 and 12 hours post admission. Results revealed that, troponin I level at 6 hours post ingestion and 12 hours post ingestion in addition to creatine kinase-MB level at 12 hours post ingestion were significantly higher in cases with severe acute theophylline intoxication and patients who required intensive care unit admission and hemodialysis. It was concluded that, troponin I could predict the severity and the requirement of ICU admission and hemodialysis in patients with acute theophylline toxicity either with early or delayed presentation. On the other hand, CK-MB could be considered for patients with delayed presentation. Depending on time of admission, proper choosing of the biomarker to be investigated will allow for better evaluation of patients with saving extra cost.