Treatment Of Asthma Research Articles

Development of a green synchronous spectrofluorimetric technique for simultaneous determination of Montelukast sodium and Bilastine in pharmaceutical formulations

For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous fluorescence, the current work developed a green, highly accurate, sensitive, and selective spectroscopic approach for estimating Montelukast sodium and Bilastine in pharmaceutical dosage form without previous separation. The selected technique focuses on measuring the synchronized fluorescence of the studied medications at a fixed wavelength range (Δλ) = 110 nm, and using the amplitude of the first derivative's peak at 381 and 324 nm, for quantitative estimation of Montelukast sodium and Bilastine, respectively. The impacts of different factors on the referred drugs' synchronized fluorescence intensity were investigated and adjusted. The calibration plots for were found to be linear over concentration ranges of 50–2000 ng mL−1 for Montelukast sodium and 50–1000 ng mL−1 for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL−1, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL−1, for both drugs, respectively. The developed method was successfully employed to quantify the two drugs in synthetic tablets mixture and in laboratory prepared mixtures containing varied Montelukast and Bilastine ratios. To compare the results with the published analytical approach, a variance ratio F-test and a student t-test were used, which revealed no significant differences.

Medicaciones inhaladas y cámaras de inhalación para el asma infantil. Red española de grupos de trabajo sobre asma en pediatría (REGAP)

Asthma, the most prevalent chronic disease in pediatric age, continues to pose challenges in its management and treatment. National and international guidelines emphasize the importance of therapeutic education (TE) to achieve disease control. TE involves imparting knowledge and skills to the patient and their family, enhancing medication adherence, rectifying errors in inhalation technique, and tailoring treatment based on individual patient characteristics.It is essential for TE to be progressive, gradual, and personalized, spanning all levels of care. Training healthcare professionals in TE is crucial, particularly for pediatricians, who must also be aware of the extensive variability of available meds and inhalers and their respective age-specific indications.Addressing this need, the REGAP Group extensively reviewed inhalers currently available in Spain for pediatric asthma treatment. The review encompassed different inhalation systems and inhaled drugs used for pediatric asthma treatment. This review will be updated annually, providing information on medications, devices, inhalation chambers, indications, and financiation. The REGAP Group hopes that these tables will be a valuable help for pediatricians in their daily clinical practice and serve as an effective TE tool.

Steroid-Insensitive Gene Expression of Extracellular Matrix Components and Pro-fibrotic Factors in the Lung Associated with Airway Hyperresponsiveness in Murine Asthma.

Between 5 and 10% of asthma patients do not respond to glucocorticoid therapy. Experimental animal models are indispensable for investigating the pathogenesis of steroid-resistant asthma; however, the majority of murine asthma models respond well to glucocorticoids. We previously reported that multiple intratracheal administration of ovalbumin (OVA) at a high dose (500 µg/animal) induced steroid-insensitive airway eosinophilia and remodeling with lung fibrosis, whereas a low dose (5 µg/animal) caused steroid-sensitive responses. The aims of the present study were as follows: 1) to clarify whether airway hyperresponsiveness (AHR) in the two models is also insensitive and sensitive to a glucocorticoid, respectively, and 2) to identify steroid-insensitive genes encoding extracellular matrix (ECM) components and pro-fibrotic factors in the lung. In comparisons with non-challenged group, the 5- and 500-µg OVA groups both exhibited AHR to methacholine. Daily intraperitoneal treatment with dexamethasone (1 mg/kg) significantly suppressed the development of AHR in the 5-µg OVA group, but not in the 500-µg OVA group. Among genes encoding ECM components and pro-fibrotic factors, increased gene expressions of fibronectin and collagen types I, III, and IV as ECM components as well as 7 matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, transforming growth factor-β1, and activin A/B as pro-fibrotic factors were insensitive to dexamethasone in the 500-µg OVA group, but were sensitive in the 5-µg OVA group. In conclusion, steroid-insensitive AHR developed in the 500-µg OVA group and steroid-insensitive genes encoding ECM components and pro-fibrotic factors were identified. Drugs targeting these molecules have potential in the treatment of steroid-resistant asthma.

Chalcone-derivative L6H21 attenuates the OVA-induced asthma by targeting MD2

Asthma represents a significant global challenge that affects individuals across all age groups and imposes substantial social and economic burden. Due to heterogeneity of the disease, not all patients obtain benefit with current treatments. The objective of this study was to explore the impact of MD2 on the progression of asthma using L6H21, a novel MD2 inhibitor, to identify potential targets and drug candidates for asthma treatment. To establish an asthma-related murine model and evaluate the effects of L6H21, ovalbumin (OVA) was used to sensitize and challenge mice. Pathological changes were examined with various staining techniques, such as H&E staining, glycogen staining, and Masson staining. Inflammatory cell infiltration and excessive cytokine secretion were evaluated by analyzing BALF cell count, RT-PCR, and ELISA. The TLR4/MD2 complex formation, as well as the activation of the MAPK and NF-кB pathways, was examined using western blot and co-IP. Treatment with L6H21 demonstrated alleviation of increased airway resistance, lung tissue injury, inflammatory cell infiltration and excessive cytokine secretion triggered by OVA. In addition, it also ameliorated mucus production and collagen deposition. In the L6H21 treatment group, inhibition of MAPK and NF-кB activation was observed, along with the disruption of TLR4/MD2 complex formation, in contrast to the model group. Thus, L6H21 effectively reduced the formation of the MD2 and TLR4 complex induced by OVA in a dose-dependent manner. This reduction resulted in the attenuation of MAPKs/NF-κB activation, enhanced suppression of inflammatory factor secretion, reduced excessive recruitment of inflammatory cells, and ultimately mitigated airway damage. MD2 emerges as a crucial target for asthma treatment, and L6H21, as an MD2 inhibitor, shows promise as a potential drug candidate for the treatment of asthma.

The problem of choosing a genetically engineered biological drug in a patient with severe bronchial asthma

Severe bronchial asthma (SA) is asthma whose symptoms are not controlled by high doses of inhaled glucocorticosteroids, the main drug in the treatment of asthma. SA is associated with a high economic burden and remains a serious public health problem. Modern advances in understanding the molecular mechanisms underlying respiratory tract inflammation have led to the development of monoclonal antibody therapy. In recent years, the approach to the treatment of patients with SA has undergone significant changes: six biological drugs have shown their effectiveness in phase 3 studies, especially in reducing exacerbations, improving asthma control, quality of life, lung function and the abolition of systemic corticosteroids or at least reducing their daily dose, with some differences between them. Choosing a targeted drug is always a difficult task, involving a thorough assessment of clinical, anamnestic and laboratory parameters. Biologics have different targets of exposure and, therefore, different therapeutic indications should be expected; however, some patients may be shown more than one drug, which makes it difficult to choose. The analysis of markers of eosinophilic inflammation makes it possible to determine the mechanisms of pathogenesis, predict the response to treatment, monitor its effectiveness or disease progression. Other factors that need to be analyzed are the frequency of symptoms, asthma triggers, baseline spirometry, oral corticosteroid intake status, frequency of exacerbations and concomitant diseases. The appointment of targeted therapy without a thorough assessment of clinical, functional and laboratory parameters, as well as the lack of control of these indicators during therapy can lead to insufficient effectiveness of treatment.

A Parametric 3D Model of Human Airways for Particle Drug Delivery and Deposition

The treatment for asthma and chronic obstructive pulmonary disease relies on forced inhalation of drug particles. Their distribution is essential for maximizing the outcomes. Patient-specific computational fluid dynamics (CFD) simulations can be used to optimize these therapies. In this regard, this study focuses on creating a parametric model of the human respiratory tract from which synthetic anatomies for particle deposition analysis through CFD simulation could be derived. A baseline geometry up to the fourth generation of bronchioles was extracted from a CT dataset. Radial basis function (RBF) mesh morphing acting on a dedicated tree structure was used to modify this baseline mesh, extracting 1000 synthetic anatomies. A total of 26 geometrical parameters affecting branch lengths, angles, and diameters were controlled. Morphed models underwent CFD simulations to analyze airflow and particle dynamics. Mesh morphing was crucial in generating high-quality computational grids, with 96% of the synthetic database being immediately suitable for accurate CFD simulations. Variations in wall shear stress, particle accretion rate, and turbulent kinetic energy across different anatomies highlighted the impact of the anatomical shape on drug delivery and deposition. The study successfully demonstrates the potential of tree-structure-based RBF mesh morphing in generating parametric airways for drug delivery studies.

Transdermally delivered tolerogenic nanoparticles induced effective immune tolerance for asthma treatment

Induction of antigen-specific immune tolerance for the treatment of allergic or autoimmune diseases is an attractive strategy. Herein, we investigated the protective effect of a transdermal microneedle patch against allergic asthma by stimulating allergen-specific immune tolerance. We fabricated biodegradable tolerogenic nanoparticles (tNPs) that are loaded with a model allergen ovalbumin (OVA) and an immunomodulator rapamycin, and filled the tNPs into microneedle tips by centrifugation to form sustained-release microneedles. After intradermal immunization, the microneedles successfully delivered the cargos into the skin and sustainedly released them for over 96 h. Importantly, the microneedles induced allergen-specific regulatory T cells (Treg), decreased the levels of pro-inflammatory cytokines and antibodies while increased anti-inflammation cytokines, finally leading to restored immune homeostasis. The lung tissue analysis illustrated that the sustained-release microneedles significantly reduced the infiltration of eosinophils, decreased the accumulation of mucus and collagen, and significantly relived asthma symptoms. Our results suggested that the sustained-release microneedle-based transdermal delivery system can induce antigen-specific immune tolerance with improved compliance and efficacy, providing a new therapeutic strategy for the treatment of allergic and autoimmune diseases.

Investigation of the treatment and follow-up approaches of pregnant with asthma

Aims: Uncontrolled asthma during pregnancy can lead to complications for both the mother and the fetus. In this study; It was aimed to evaluate the follow-up and treatment of pregnant women with asthma, their knowledge about asthma triggers, their use of inhaler therapy, and their compliance with pulmonologist controls for asthma. Methods: In this study; 64 pregnant patients with asthma who applied to our clinic between 01.01.2022 and 31.07.2022 were reviewed. Demographic patients (mean age, age groups, smoking history, comorbidities), recommended treatment information, and birth information, whether they used asthma treatment or not, were recorded and evaluated according to patient groups. Results: There was a statistically significant difference between drug use during pregnancy according to the age groups of pregnant women with asthma (Chi-square test; χ²=6.684; p=0.035). As the age of the pregnant women increased, the rate of drug use during the pregnancy increased, and there was a correlation between drug use during pregnancy and whether the patients were regularly checked by a pulmonologist (Chi-square test; χ²=12.835; p=0.0001). While 68% of those who were not under the control of a pulmonologist did not use medication, 60.8% of those under the control of a pulmonologist used medication during their pregnancy. Conclusion: Pregnant women with asthma must be followed by a gynecologist and a pulmonologist. Using inhaler therapy in asthma treatment in pregnant women can keep asthma under control and reduce the number and severity of exacerbations.

SMART INHALERS: HARNESSING IOT FOR PRECISE ASTHMA MANAGEMENT

Effective management techniques are required for the widespread chronic respiratory disease known as asthma in order to reduce its negative effects on public health. Smart inhalers are a prime example of how the introduction of Internet of Things (IoT) technology has sparked creative solutions. In this essay, the seamless integration of IoT technology is used to elaborate on the transformational potential of smart inhalers in improving asthma management. The traditional approach to managing asthma relies on individualised prescription regimens that must be consistently followed. But obstacles including patient forgetfulness and insufficient real-time monitoring frequently prevent effective adherence, aggravating symptoms and lowering quality of life. Smart inhalers are the result of the confluence of IoT technology with asthma therapy, signalling a paradigm change. Smart inhalers, driven by IoT, offer a wide range of characteristics and signal a paradigm change in the treatment of asthma. (1) These gadgets can monitor medicine use, inhaler technique, and environmental triggers in real time since they include sensors and connection. Personalised therapy modifications are made possible by the real-time data creation that gives healthcare professionals insights into patient behaviour, adherence trends, and symptom development. The ability of smart inhalers to revolutionise medication adherence is one of their main benefits. (2)Patients are better able to maintain their regimens when they receive prompt guidance on how to use an inhaler and reminders to take prescription drugs as directed. The resultant decline in emergency room visits, hospital admissions, and asthma attacks is evidence of these devices' effectiveness. Healthcare professionals are empowered to quickly react and prevent the progression of symptoms thanks to the real-time data stream from smart inhalers. (3)Asthma care has advanced dramatically with the introduction of IoT-enabled smart inhalers, which are expected to improve asthma sufferers' medication compliance, symptom management, and overall quality of life. Predicted developments in smart inhaler technology, including artificial intelligence and predictive analytics, portend improved personalisation and therapeutic efficacy as the IoT environment changes. The promise of smart inhalers to reshape asthma care resonates deeply with the principles of patient education, engagement, and interdisciplinary collaboration among healthcare professionals, researchers, and technology developers, setting a promising trajectory for respiratory healthcare. (4)

Les plans d’action écrits pour l’asthme : quel usage en font les pneumologues en France ?

Despite evidence of the benefits of the written asthma action plans (WAP) in asthma control, they remain poorly applied. The aim of our study was to assess the practices of French-speaking pulmonologists and paediatricians in their use of WAP for asthma control and to analyse the contents of several WAPs routinely consulted in treatment of asthma patients. Members of three French medical societies (SPLF, G2A, SP2A) were requested to share their WAPs for asthma patients and to participate in an online survey about the possible influence of these documents on their practices. Most (95%) of the 41 WAPs taken into consideration were symptom-based and 34% included peak expiratory flow measurement. All of these action plans were in full compliance with current guidelines. Among the 110 survey respondents, while 65% systematically provided a WAP to their asthma patients, only 30% often or always supplemented the written document with therapeutic education sessions. In almost every case, it was the doctor who presented the WAP to the patient, generally devoting to less than 10minutes to explanation of what they were handing out. In France, WAPs are generally presented to the patient by the physician, which probably limits the time devoted to explanation of their contents. Furthermore, WAPs are rarely reinforced with therapeutic education. The current study suggests ways of improving the utilization of WAPs in asthma care and treatment.

Analysis of risk factors for acute attacks complicated by respiratory failure in children with asthma.

To describe the proportion and clinical characteristics of hospitalized children with acute asthma attacks complicated by respiratory failure and to analyze the risk factors. This retrospective study analyzed hospital admissions of children and adolescents with acute asthma attacks between January 2016 and December 2021. Inclusion criteria were used to identify eligible cases, and demographic information and disease characteristics were collected. Patients were categorized into respiratory failure group and the other group based on the result of artery blood gas analysis. Multivariate logistic regression was utilized to investigate the risk factors associated with respiratory failure resulting from acute asthma attacks. The data were analyzed using SPSS 22.0, and significance was considered at P < 0.05. Our research involved 225 participants, with 18.7% diagnosed with respiratory failure. The respiratory failure group was found to be younger and have higher percentage of male, while birth weight, nationality, and type of residence did not differ between the two groups. In the respiratory failure group, a significant difference was observed in emergency hospitalization, ICU treatment, severe to critical attack, dyspnea and allergy history. The two groups did not differ in admission season, first asthma diagnosis, respiratory infection and comorbidity. The respiratory failure group exhibited a higher proportion of atopy-only asthma and a lower proportion of T2-high asthma. The eosinophil count, and eosinophil percentage were lower in the respiratory failure group, while neutrophil count was higher. Having a history of allergies (OR = 2.46, 95% CI: 1.08-5.59) and neutrophil count (OR = 1.10, 95% CI: 1.00-1.21) were the risk factors for respiratory failure in children with asthma. There also existed that the risk of respiratory failure increases with decreasing age of the children (OR = 0.85, 95% CI: 0.73-0.99). Notably, risk factors for respiratory failure in hospitalized asthma children include age, having a history of allergies, and neutrophil count. The identification of the above factors and the implementation of timely intervention can optimize the treatment of asthma in children.

Can Therapeutic Targeting of the Human Microbiome Influence Asthma Management? A Pro/Con Debate

Asthma is a clinically heterogenous disease and despite substantial improvements in therapies, there remains an unmet need for well-tolerated, effective treatments. Observational studies have demonstrated that alterations in the respiratory and gut microbiome are associated with the development of asthma as well as its severity. These findings are supported by preclinical models demonstrating that respiratory and gut microbes can alter airway inflammation. Therapeutic approaches to target the human microbiome have been increasingly applied to a wide range of acute and chronic diseases, but there are currently no microbiome-based therapeutics approved for the treatment of asthma. This clinical commentary addresses the future role of microbiome-based therapeutics in asthma management from both a pro and con perspective. We examine (1) the prospects for clinical studies demonstrating a causal relationship between the human microbiome and the severity of asthma, (2) the challenges and potential solutions for designing, testing, and implementing a microbiome-based therapeutic, and (3) the possibility of microbiome-based therapeutics for conditions co-morbid to asthma. We conclude by identifying research priorities that will help determine the future of microbiome-based therapeutics for the management of asthma.

Epidemiology of asthma based on the standard questionnaire

Asthma is a common chronic airway disease in the world. Although the guidelines recommend the diagnostic criteria for asthma, which have been widely used in clinical practice, the standardized asthma questionnaire is often recommended for prevalence surveys in large-scale epidemiological surveys of the population, because the standardized asthma questionnaire has the characteristics of good cost-effectiveness and high response rate, and the results are also feasible for comparison between different populations or regions. There are currently four asthma epidemiological surveys in the world, including the European Community Respiratory Health Survey (ECRHS), the International Study of Asthma and Allergies in Childhood (ISAAC), the International Study of Wheezing in Infants (EISL) and World Health Survey (WHS). The above research results were also important data source for estimating the global prevalence of asthma in the Global Burden of Disease Study (GBD). In China, several national surveys were conducted on the prevalence of asthma in children and adults, but the reported prevalence of asthma was not comparable with other countries because clinical diagnostic criteria for asthma were frequently used to define asthma in these previous studies. The China Pulmonary Health (CPH) study was a national cross-sectional study that enrolled a nationally representative sample of Chinese adults aged 20 years or older, using the asthma questionnaire derived from ECRHS, we reported that the prevalence of asthma with wheezing in Chinese adults was 4.2%, representing 45.7 million adult asthmatics. However, it should be realized that these data did not include people under the age of 20 years or those with atypical asthmatic symptoms. In addition, the study shows that asthma is largely under-diagnosed and undertreated in China, and these findings call for national efforts to improve the prevention, detection and treatment of asthma in China.

Inhaled JAK Inhibitor GDC-0214 Nanoaggregate Powder Exhibits Improved Pharmacokinetic Profile in Rats Compared to the Micronized Form: Benefits of Thin Film Freezing.

Asthma is a common chronic disease affecting the airways in the lungs. The receptors of allergic cytokines, including interleukin (IL)-4, IL-5, and IL-13, trigger the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, which involves the pathogenesis of asthma. GDC-0214 is a JAK inhibitor that was developed as a potent and selective target for the treatment of asthma, specifically targeting the lungs. While inhaled GDC-0214 is a promising novel treatment option against asthma, improvement is still needed to achieve increased potency of the powder formulation and a reduced number of capsules containing powder to be inhaled. In this study, high-potency amorphous powder formulations containing GDC-0214 nanoaggregates for dry powder inhalation were developed using particle engineering technology, thin film freezing (TFF). A high dose per capsule was successfully achieved by enhancing the solubility of GDC-0214 and powder conditioning. Lactose and/or leucine as excipients exhibited optimum stability and aerosolization of GDC-0214 nanoaggregates, and aerosolization of the dose was independent of air flow through the device between 2 and 6 kPa pressure drops. In the rat PK study, formulation F20, which contains 80% GDC-0214 and 20% lactose, resulted in the highest AUC0-24h in the lungs with the lowest AUC0-24h in the plasma that corresponds to a 4.8-fold higher ratio of the lung-to-plasma exposures compared to micronized crystalline GDC-0214 powder administered by dry powder inhalation. Therefore, GDC-0214 nanoaggregates produced by TFF provided an improved dry powder for inhalation that can lead to enhanced therapeutic efficacy with a lower risk of systemic toxicity.

"Photo-Adrenalines": Photoswitchable β2 -Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling.

β2 -adrenergic receptor (β2 -AR) agonists are used for the treatment of asthma and chronic obstructive pulmonary disease, but also play a role in other complex disorders including cancer, diabetes and heart diseases. As the cellular and molecular mechanisms in various cells and tissues of the β2 -AR remain vastly elusive, we developed tools for this investigation with high temporal and spatial resolution. Several photoswitchable β2 -AR agonists with nanomolar activity were synthesized. The most potent agonist for β2 -AR with reasonable switching is a one-digit nanomolar active, trans-on arylazopyrazole-based adrenaline derivative and comprises valuable photopharmacological properties for further biological studies with high structural accordance to the native ligand adrenaline.

Characterization of the Function of Carbonic Anhydrase 8

Background/Objective: Severe asthma is a complex pulmonary disease characterized by airway inflammation, bronchoconstriction, and acid-base dysregulation. In the Severe Asthma Research Program bronchoscopies, transcriptomics showed CA8 as a gene that is strongly associated with asthma severity. CA8, however, lacks classical CA enzyme function: it does not catalyze hydration and dehydration of CO2. The function of CA8 in the airway epithelium remains unknown. We hypothesize that CA8 serves a protective role in the airway due to its down regulation in patients with severe asthma. We aim to characterize the function of CA8 bystudying its potential as an enzymatic protein. Methods: We used colorimetric assays to detect and quantify nitrogen oxides. We tested for Snitrosothiolsynthase, denitrosylase, nitrate and nitrite synthase, and nitrite reductase activitiesusing the Griess reagent in conjunction with Saville denitrosylation reagents and with reduction using vanadium chloride. Samples were incubated for 60 minutes. We then went on to design ametabolomic experiment in which products will be identified by NMR: for these, we transfected Chinese hamster ovary (CHO) cells using lentivirus containing GFP-labeled CA8 or emptyvector (negative control). Results: CA8 protein does not have these following enzymatic functions: SNO synthase,denitrosylase, nitrite and nitrate synthase, and nitrite reductase. We successfully transfected with GFP-labeled CA8 and are awaiting results of the metabolomic studies. Conclusion and Potential Impact: Isolated CA8 does not appear to have any nitrogen oxideredox activities relevant to asthma. The next steps include confirmatory western and SNOwestern blots to determine protein s-nitrosylation using transfected CHO whole cell lysate. Extracellular medium pH will also be measured. We will then move on to NMR-basedmetabolomics. This will help us better understand the biochemical mechanisms of CA8.Ultimately, this can provide researchers with a novel approach to asthma treatments.

DEK deficiency suppresses mitophagy to protect against house dust mite-induced asthma.

DEK protein is highly expressed in asthma. However, the mechanism of DEK on mitophagy in asthma has not been fully understood. This study aims to investigate the role and mechanism of DEK in asthmatic airway inflammation and in regulating PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. PINK1-Parkin mitophagy, NLRP3 inflammasome, and apoptosis were examined after gene silencing or treatment with specific inhibitors (MitoTEMPO, MCC950, and Ac-DEVD-CHO) in house dust mite (HDM) or recombinant DEK (rmDEK)-induced WT and DEK-/- asthmatic mice and BEAS-2B cells. The regulatory role of DEK on ATAD3A was detected using ChIP-sequence and co-immunoprecipitation. rmDEK promoted eosinophil recruitment, and co-localization of TOM20 and LC3B, MFN1 and mitochondria, LC3B and VDAC, and ROS generation, reduced protein level of MnSOD in HDM induced-asthmatic mice. Moreover, rmDEK also increased DRP1 expression, PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. These effects were partially reversed in DEK-/- mice. In BEAS-2B cells, siDEK diminished the Parkin, LC3B, and DRP1 translocation to mitochondria, mtROS, TOM20, and mtDNA. ChIP-sequence analysis showed that DEK was enriched on the ATAD3A promoter and could positively regulate ATAD3A expression. Additionally, ATAD3A was highly expressed in HDM-induced asthma models and interacted with DRP1, and siATAD3A could down-regulate DRP1 and mtDNA-mediated mitochondrial oxidative damage. Conclusively, DEK deficiency alleviates airway inflammation in asthma by down-regulating PINK1-Parkin mitophagy, NLRP3 inflammasome activation, and apoptosis. The mechanism may be through the DEK/ATAD3A/DRP1 signaling axis. Our findings may provide new potential therapeutic targets for asthma treatment.

Depressive symptoms are related to asthma control but not self-management among rural adolescents.

Depression, a relevant comorbidity with asthma, has been reported to be associated with asthma morbidity. Asthma self-management is essential to asthma control and may be negatively impacted by depression. We examined these associations in rural adolescents, a group with relatively high asthma morbidity and depressive symptoms, a population often ignored in asthma research. We used baseline data from a randomized trial of an asthma intervention for adolescents in rural South Carolina (n = 197). Adolescents completed the Center for Epidemiological Studies-Depression (CES-D), three indices of asthma self-management (the Asthma Prevention Index, the Asthma Management Index and the Asthma Self-Efficacy Index), and the Asthma Control Test (ACT). Poisson and linear regression tested associations between depression, self-management, and asthma control. The models controlled for demographic variables and included school as a fixed effect. Most participants (mean age = 16.3 ± 1.2 years) self-identified as female (68.5%) and Black (62.43%). The mean CES-D score was 19.7 ± 10.3, with 61.4% of participants at risk for depression. The depressive symptoms were significantly related to asthma control [β = -0.085, 95% confidence interval (CI) = -0.14 to -0.03] but not to prevention [relative risk (RR) = 1.00, 95% CI = 0.99-1.01], management (RR = 1.00, 95% CI = 0.99-1.01), or self-efficacy (β = -0.002, 95% CI = -0.01 to 0.01). In this sample of rural adolescents, as depressive symptoms increased, asthma control declined. Depressive symptoms were not associated with asthma self-management, suggesting that the aspects of self-management we assessed are not an avenue by which depression impacts asthma control. Additional research is needed to further understand the relationship between depressive symptoms, asthma self-management, and control.

The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.

Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from a cross-sectional cohort of 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in adults and children 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways, which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. Several differentially abundant ARGs in the asthma cohort encode resistance to macrolide antibiotics, which are often prescribed to patients with asthma. Lastly, we found that ARG and virulence factor (VF) richness in the microbiome were correlated in both cohorts. ARG and VF pairs co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are coselected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.

APPLICATION OF REFLEXOTHERAPY ACCORDING TO THE “HEXAGRAM BALANCING” METHOD IN THE COMBINED REHABILITATION OF DISEASES OF THE RESPIRATORY SYSTEM WITH PSYCHOEMOTIONAL DISORDERS

Abstract. The article is devoted to one of the most urgent problems of medicine – complex treatment of bronchial asthma. Often, various diseases, especially those that occur with aggravated under the influence of psycho-emotional stress, depression, asthenia and other adverse psychosocial factors, are accompanied by long-term symptoms. Medicinal methods of treatment are not fully effective, so non-medicinal technologies should be resorted to. Combined treatment of bronchial asthma using іn rehabilitation reflexotherapy methods has been used for a long time, it is especially effective when there are also psychosomatic problems. The article as well presents the main theoretical principles of the “balancing of hexagrams” method and its practical implementation. A clinical case is also presented: bronchial asthma in the patient with psychoemotional disorders. The methods of acupuncture diagnosis are presented, the acupuncture diagnosis is characterized in detail, the description of acupuncture correction is given, the methods of medical correction used in treatment, the features of the “favorable” hexagram are considered. Thus, patients with bronchial asthma with psychoemotional disorders are found in the practice of a reflexologist. In the complex of therapeutic measures for bronchial asthma with psychoemotional disorders, the use of the acupuncture method “balancing hexagrams” can be effective. Purpose. To consider the peculiarities of the use of reflexotherapy by the method of “balancing hexagrams” in the complex rehabilitation of patients with diseases of the respiratory system with psycho-emotional disorders. Scientific novelty. For the first time in our country, the technique of making acupuncture prescriptions and acupuncture using the method of “balancing hexagrams” was used in the complex rehabilitation of patients with diseases of the respiratory system with psycho-emotional disorders. Methods. We consider one clinical case of the use of reflexotherapy using the method of “balancing hexagrams” in the complex rehabilitation of diseases of the respiratory organs with psycho-emotional disorders. Results. As a result of treatment using the “balancing hexagrams” method, the patient's condition improved: his psychoemotional state normalized, he was able to completely give up alcohol, went on a diet; his respiratory conditions improved. Conclusions. 1. Bronchial asthma occurs in the practice of a reflexologist, and with this disease, reflexotherapy methods are effective primarily for psycho-emotional disorders. 2. The use of the acupuncture method “balancing hexagrams” can be effective in the complex of treatment measures for bronchial asthma.