Anti-asthmatic Drugs Research Articles

Efficacy and safety of moxibustion as a complementary and alternative therapy for asthma: A systematic review and meta-analysis

ObjectiveThis systematic review of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of moxibustion as a complementary or alternative treatment for asthma. MethodsSeven databases were searched up to June 23, 2024, to identify RCTs assessing moxibustion for bronchial asthma. The outcomes of interest included response to treatment, asthma control, quality of life, lung function, immunological indicators, and incidence of adverse events (AEs). The treatment effects were measured by proportional odds ratios or mean differences with 95% confidence intervals. ResultsThirty-seven RCTs (n = 2,879) were included. Moderate- to very low-quality evidence showed that compared with anti-asthmatic drugs alone, moxibustion plus anti-asthmatic drugs led to a significantly better response and greater increases in lung function, asthma control, and IgE levels. However, the combination therapy had no effect on children’s quality of life. In the active comparisons, moxibustion resulted in a superior response to treatment and a greater improvement in asthma control and had comparable effects on lung function, quality of life, and IgE levels compared with anti-asthmatic drugs. The effects of moxibustion on the proportions of CD4 + and CD8 + T cells and the eosinophil count were inconsistent between the add-on and active comparisons. All reported AEs related to moxibustion were mild. ConclusionsMoxibustion, as an adjunctive treatment or used alone, may improve the response to treatment, lung function, asthma control, and IgE levels in patients with asthma with good safety. Its effects on children’s quality of life and immune cell levels remain uncertain.

Ficus pumila fruit polysaccharide attenuate ovalbumin-induced allergic asthma in mice associated with changes in microbiota involving the lung-intestinal axis

Allergic asthma accounts for more than 50 percent of adult asthma in life. Glucocorticoids and leukotriene receptor antagonists are commonly used to treat asthma, but these drugs not only have high side effects but also cannot cure the disease. In contrast, natural active ingredients are relatively safe to the organism and show great potential for improving the organism. Polysaccharides, as the main active ingredient in aqueous extract, may be equally beneficial for biological activity. The aim of this study is to investigate the alleviating effect and mechanism of action of Ficus pumila fruit polysaccharide (FPP) and aqueous extract of Ficus pumila fruit (FPW) on mice with allergic asthma. The results showed that FPP and FPW could regulate the secretion of the cytokines IL-4, IL-5, IL-13, and IFN-γ. FPP and FPW also reduced the inflammation, mucus secretion, and collagen deposition in mouse lung tissue, and down-regulated the expression of matrix metallopeptidase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and α-smooth muscle actin (α-SMA) proteins. In addition, FPP and FPW modulated the intestinal microbiota by augmenting the alpha diversity and adjusting the taxonomic composition at the phylum and family levels, thereby ensured the sustenance of regular physiological processes in the body. This study demonstrated that FPP and FPW may attenuate asthma by inducing beneficial microbiota in the gut-lung axis and provide an effective basis for the future clinical treatment of allergic asthma with Ficus pumila and the development and utilization of new anti-asthma drugs.

Risks of dairy derived excipients in medications for lactose intolerant and cow milk protein allergic patients

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.

Obesity-associated Airway Hyperresponsiveness: Mechanisms Underlying Inflammatory Markers and Possible Pharmacological Interventions.

Obesity is rapidly becoming a global health problem affecting about 13% of the world's population affecting women and children the most. Recent studies have stated that obese asthmatic subjects suffer from an increased risk of asthma, encounter severe symptoms, respond poorly to anti-asthmatic drugs, and ultimately their quality-of-life decreases. Although, the association between airway hyperresponsiveness (AHR) and obesity is a growing concern among the public due to lifestyle and environmental etiologies, however, the precise mechanism underlying this association is yet to establish. Apart from aiming at the conventional antiasthmatic targets, treatment should be directed towards ameliorating obesity pathogenesis too. Understanding the pathogenesis underlying the association between obesity and AHR is limited, however, a plethora of obesity pathologies have been reported viz., increased pro-inflammatory and decreased anti-inflammatory adipokines, depletion of ROS controller Nrf2/HO-1 axis, NLRP3 associated macrophage polarization, hypertrophy of WAT, and down-regulation of UCP1 in BAT following down-regulated AMPKα and melanocortin pathway that may be correlated with AHR. Increased waist circumference (WC) or central obesity was thought to be related to severe AHR, however, some recent reports suggest body mass index (BMI), not WC tends to exaggerate airway closure in AHR due to some unknown mechanisms. This review aims to co-relate the above-mentioned mechanisms that may explain the copious relation underlying obesity and AHR with the help of published reports. A proper understanding of these mechanisms discussed in this review will ensure an appropriate treatment plan for patients through advanced pharmacological interventions.

Development and Validation of a Systematized Liquid Chromatographic Method for Estimation of Roflumilast in Tablets and in Presence of its Degradation Products

Background: Roflumilast (ROF) is an antiasthmatic drug used frequently for treating chronic obstructive pulmonary disease (COPD). The various reported methods developed with a non-systematised traditional workframe for routine estimation of ROF in formulations indicated the demand for developing a systematised new method. Objective: In the present study, an attempt was made to develop a new validated liquid chromatographic method with federal flexibilities and stability-indicating potential. Method: A time-efficient, rapid, and systematised quality by design (QbD) approach was developed to avail regulatory flexibilities with assured performance. Defining the analytical target profile (ATP) and associated critical analytical attributes (CAAs) helped control the method’s performance. Methanol proportion, flow rate, pH, and detection wavelength were the four identified critical method variables (CMVs) that were further studied for robustness investigation. Moreover, the control strategies for CMVs were defined as per method intent. Chromatography constituted methanol: water (pH 3.5 maintained by orthophosphoric acid) (90:10% v/v) as the mobile phase, flowing at 1.2 ml/min on a ShimPack GWS C18 column. The photodiode array (PDA) detector provided the best results at 250 nm. Results: ROF was eluted at a retention time of 3.1 min with acceptable system suitability values. Validation studies postulated method acceptability and suitability. Results for parameters viz. linearity (0.5–160 µg/ml), accuracy (> 98%), and precision (< 1%) advocated method reliability. ROF was susceptible to applied acidic and alkaline stress, requiring adequate preventive measures during formulation development. Conclusion: Overall, this method worked well for figuring out ROF even when there were product additives and possible degradation products present, showing that it can be used on a regular basis.

Modern asthma management

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

Morbidity profile and pharmaceutical management of adult outpatients between primary and tertiary care levels in Sri Lanka: a dual-centre, comparative study

BackgroundOutpatient care is central to both primary and tertiary levels in a health system. However, evidence is limited on outpatient differences between these levels, especially in South Asia. This study aimed to describe and compare the morbidity profile (presenting morbidities, comorbidities, multimorbidity) and pharmaceutical management (patterns, indicators) of adult outpatients between a primary and tertiary care outpatient department (OPD) in Sri Lanka.MethodsA comparative study was conducted by recruiting 737 adult outpatients visiting a primary care and a tertiary care facility in the Kandy district. A self-administered questionnaire and a data sheet were used to collect outpatient and prescription data. Following standard categorisations, Chi-square tests and Mann‒Whitney U tests were employed for comparisons.ResultsOutpatient cohorts were predominated by females and middle-aged individuals. The median duration of presenting symptoms was higher in tertiary care OPD (10 days, interquartile range: 57) than in primary care (3 days, interquartile range: 12). The most common systemic complaint in primary care OPD was respiratory symptoms (32.4%), whereas it was dermatological symptoms (30.2%) in tertiary care. The self-reported prevalence of noncommunicable diseases (NCDs) was 37.9% (95% CI: 33.2–42.8) in tertiary care OPD and 33.2% (95% CI: 28.5–38.3) in primary care; individual disease differences were significant only for diabetes (19.7% vs. 12.8%). The multimorbidity in tertiary care OPD was 19.0% (95% CI: 15.3–23.1), while it was 15.9% (95% CI: 12.4–20.0) in primary care. Medicines per encounter at primary care OPD (3.86, 95% CI: 3.73–3.99) was higher than that at tertiary care (3.47, 95% CI: 3.31–3.63). Medicines per encounter were highest for constitutional and respiratory symptoms in both settings. Overall prescribing of corticosteroids (62.7%), vitamin supplements (45.8%), anti-allergic (55.3%) and anti-asthmatic (31.3%) drugs was higher in the primary care OPD, and the two former drugs did not match the morbidity profile. The proportion of antibiotics prescribed did not differ significantly between OPDs. Subgroup analyses of drug categories by morbidity largely followed these overall differences.ConclusionsThe morbidities between primary and tertiary care OPDs differed in duration and type but not in terms of multimorbidity or most comorbidities. Pharmaceutical management also varied in terms of medicines per encounter and prescribed categories. This evidence supports planning in healthcare and provides directions for future research in primary care.

Anti-asthmatic activity of Tinospora cordifolia leaves extract against ach and citric acid-induced asthma in rats

Asthma is one of the common clutters experienced in clinical medication in both grown-ups and children are asthma and it is characterized by irritation of the aviation routes which causes aviation route brokenness. Breathed-in bronchodilators and anti-inflammatory drugs are accessible and compelling and they require long term utilize and are related with side impacts. Typically, why elective and complementary medication is being sort after to anticipate these side impacts. A few restorative plants have anti-inflammatory impact and have demonstrated successful within the treatment of asthma. Citric corrosive, Acetylcholine, Histamine is basically utilized for assessing anti-asthmatic movement of specific sedate. Numerous plants gotten from the normal source play a critical part within the wellbeing care framework. Writing overview on home grown drugs has appeared noteworthy anti-asthmatic movement which has not shown any momentous side impact. The pharmacological component that the phytoconstituents creating the hostile to asthmatic action are not clearly caught on till date. A few herbal formulations have been determined from the Ayurveda, conventional framework of Indian medicine and its extra framework of medication, however to be experimentally approved that they have exhibited pharmacological activity against Asthmatic. As it were less number of logical data of conventional medications is accessible for the treatment of Asthmatic. This survey contains list of restorative plant which have been tried for anti-asthmatic action within the Citric corrosive, Acetylcholine actuated asthmatic in Rodent demonstrate. Rats were divided into 4 groups and given each of them individual intervention based on the activity. Tinospora cordifolia leaf extract shows an anti-asthmatic activity in rats. hence, the data given in this inquiry will offer assistance the analysts for the advancement of elective strategies instead of inhalers and verbal anti-asthmatic drugs for the treatment of asthma and COPD which can minimize the complications.

Preclinical Pharmacokinetic Study and Lung Penetration of a Coumarin Extracted from Zanthoxylum tingoassuiba.

The compound 6-methoxyseselin, derived from Zanthoxylum tingoassuiba, demonstrates various therapeutic properties, including vasorelaxation, antinociceptive, anti-inflammatory, and immunomodulatory effects, along with recently discovered antiasthmatic properties. This study aimed to evaluate its preclinical pharmacokinetics and pulmonary delivery in Balb/c mice. The method involved administering the compound via inhalation and intravenous routes, followed by blood sample collection for analysis using high-performance liquid chromatography with diode array detection (HPLC-DAD). The results indicated good linearity, precision, accuracy, and stability of the compound in the biological samples. Pharmacokinetic parameters such as the rate of elimination, half-life, clearance, volume of distribution, area under the curve, and mean residence time were determined for both administration routes, showing similar profiles. The lung concentrations were notably higher than the plasma concentrations, indicating significant lung penetration. These findings suggest 6-methoxyseselin as a promising candidate for new anti-asthmatic drugs, supported by its favorable pharmacokinetic profiles and high lung penetration factors. This study represents the first exploration of the pharmacokinetics and pulmonary delivery of 6-methoxyseselin in mice, highlighting its potential for further drug development.

Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study.

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

Majie Cataplasm Alleviates Asthma by Regulating Th1/Th2/Treg/Th17 Balance

Introduction: T cells play a critical role in inflammatory diseases. The aim of the present study was to investigate the effects of Majie cataplasm (MJC) on asthma and to propose a possible mechanism involved in this process. Methods: Airway inflammation, infiltration of inflammatory cells, levels of interleukin (IL)-4, IL-10, IL-17, and interferon (IFN)-γ, levels of Th2, Treg, Th17, and Th1 cells, and the expressions of IL-4, IL-10, IL-17, IFN-γ, GATA binding protein 3 (GATA-3), Foxp3, RAR-related orphan receptor gamma (RORγt), and T-bet were detected. Result: MJC treatment reduced lung airway resistance and inflammatory infiltration in lung tissues. MJC treatment also reduced the numbers of eosinophils and neutrophils in the blood and bronchoalveolar lavage fluid (BALF). The levels of IL-4 and IL-17 in the blood, BALF, and lungs were suppressed by MJC, and IFN-γ and IL-10 were increased. Furthermore, MJC suppressed the percentage of Th2 and Th17 and increased the percentage of Th1 and Treg in spleen cells. In addition, MJC can inhibit asthma by increasing expressions of IFN-γ, IL-10, T-bet, and Foxp3, as well as decreasing expressions of IL-4, IL-17, GATA-3, and RORγt. Conclusion: MJC may improve airway hyperresponsiveness and inflammation by regulating Th1/Th2/Treg/Th17 balance in ovalbumin-induced rats. And MJC may be a new source of anti-asthma drugs.

Montelukast improves disease outcome in SOD1G93A female mice by counteracting oligodendrocyte dysfunction and aberrant glial reactivity.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro-regenerative local milieu and re-establish proper oligodendrocyte functions may be beneficial. Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein-coupled receptor 17 (GPR17) and of cysteinyl-leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches. Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro-regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex-based difference in the protective activity of MTK. Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti-asthmatic drug, may be a promising sex-specific strategy for personalized ALS treatment.

Evaluation of the Pharmacological Potential of Nyctanthes Arbor-Tristis Flowers Extract against Milk Induced Asthmatic Disorder in Swiss Albino Mice

Evaluation of the Pharmacological Potential of Nyctanthes Arbor-Tristis Flowers Extract against Milk Induced Asthmatic Disorder in Swiss Albino Mice

Repurposing of an antiasthmatic drug may reduce NETosis and myocardial ischaemia/reperfusion injury.

Repurposing of an antiasthmatic drug may reduce NETosis and myocardial ischaemia/reperfusion injury.

Relaxant Activity of 4H-Pyran and 1,6-Dihydropyridine Derivatives on Isolated Rat Trachea

Derivatives of 4H-pyrans and 1,6-dihydropyridines have generated considerable attention due to their interesting biological and therapeutic values. Their pharmacological activities include vasorelaxant, anticarcinogenic, antimicrobial, and antioxidant activities. Thus, the aim of the current work is to determine the relaxant effect of synthesized 4H-pyran and 1,6-dihydropyridine derivatives with potential anti-asthmatic properties on the smooth muscle airway, with a possible Ca2+-channel blockade as a mechanism of action due to their analogy with 1,4-dihidropyridines. 4H-pyrans and 1,6-dihydropyridines were achieved using multicomponent reactions by microwave and conventional heating. Also, test samples were evaluated ex vivo to determine their relaxant effect on isolated rat tracheal rings pre-contracted with carbachol. All compounds evaluated showed a significant relaxant effect on carbachol-induced contraction in tracheal rat rings. Compounds 4b, 4e, 7a, and 8d were the most potent from the entire series and were also more potent than theophylline, used as a positive control. In conclusion, in the current work some relaxant compounds of the airway smooth muscle with potential to be developed as anti-asthmatic drugs were obtained.

The Efficacy & Molecular Mechanisms of a Terpenoid Compound Ganoderic Acid C1 on Corticosteroid-Resistant Neutrophilic Airway Inflammation: In vivo and in vitro Validation.

Neutrophil predominant airway inflammation is associated with severe and steroid-resistant asthma clusters. Previously, we reported efficacy of ASHMI, a three-herb TCM asthma formula in a steroid-resistant neutrophil-dominant murine asthma model and further identified Ganoderic Acid C1 (GAC1) as a key ASHMI active compound in vitro. The objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model. In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α. The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P < 0.01-0.001 vs Sham) and airway neutrophilia (P < 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P < 0.05-0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P < 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was -10.8 kcal/mol. GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma.

Phenome-wide causal associations between osteoarthritis and other complex traits through the latent causal variable analysis

BackgroundIndividuals with osteoarthritis present with comorbidities, and the potential causal associations remain incompletely elucidated. The present study undertook a large-scale investigation about the causality between osteoarthritis and variable traits, using the summary-level data of genome-wide association studies (GWAS).MethodsThe present study included the summary-level GWS data of knee osteoarthritis, hip osteoarthritis, hip or knee osteoarthritis, hand osteoarthritis, and other 1355 traits. Genetic correlation analysis was conducted between osteoarthritis and other traits through cross-trait bivariate linkage disequilibrium score regression. Subsequently, latent causal variable analysis was performed to explore the causal association when there was a significant genetic correlation. Genetic correlation and latent causal variable analysis were conducted on the Complex Traits Genomics Virtual Lab platform (https://vl.genoma.io/).ResultsWe found 133 unique phenotypes showing causal relationships with osteoarthritis. Our results confirmed several well-established risk factors of osteoarthritis, such as obesity, weight, BMI, and meniscus derangement. Additionally, our findings suggested putative causal links between osteoarthritis and multiple factors. Socioeconomic determinants such as occupational exposure to dust and diesel exhaust, extended work hours exceeding 40 per week, and unemployment status were implicated. Furthermore, our analysis revealed causal associations with cardiovascular and metabolic disorders, including heart failure, deep venous thrombosis, type 2 diabetes mellitus, and elevated cholesterol levels. Soft tissue and musculoskeletal disorders, such as hallux valgus, internal derangement of the knee, and spondylitis, were also identified to be causally related to osteoarthritis. The study also identified the putative causal associations of osteoarthritis with digestive and respiratory diseases, such as Barrett’s esophagus, esophagitis, and asthma, as well as psychiatric conditions including panic attacks and manic or hyperactive episodes. Additionally, we observed osteoarthritis causally related to pharmacological treatments, such as the use of antihypertensive medications, anti-asthmatic drugs, and antidepressants.ConclusionOur study uncovered a wide range of traits causally associated with osteoarthritis. Further studies are needed to validate and illustrate the detailed mechanism of those causal associations.

Machine learning-aided search for ligands of P2Y6 and other P2Y receptors.

The P2Y6 receptor, activated by uridine diphosphate (UDP), is a target for antagonists in inflammatory, neurodegenerative, and metabolic disorders, yet few potent and selective antagonists are known to date. This prompted us to use machine learning as a novel approach to aid ligand discovery, with pharmacological evaluation at three P2YR subtypes: initially P2Y6 and subsequently P2Y1 and P2Y14. Relying on extensive published data for P2Y6R agonists, we generated and validated an array of classification machine learning model using the algorithms deep learning (DL), adaboost classifier (ada), Bernoulli NB (bnb), k-nearest neighbors (kNN) classifier, logistic regression (lreg), random forest classifier (rf), support vector classification (SVC), and XGBoost (XGB) classifier models, and the common consensus was applied to molecular selection of 21 diverse structures. Compounds were screened using human P2Y6R-induced functional calcium transients in transfected 1321N1 astrocytoma cells and fluorescent binding inhibition at closely related hP2Y14R expressed in CHO cells. The hit compound ABBV-744, an experimental anticancer drug with a 6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine scaffold, had multifaceted interactions with the P2YR family: hP2Y6R inhibition in a non-surmountable fashion, suggesting that noncompetitive antagonism, and hP2Y1R enhancement, but not hP2Y14R binding inhibition. Other machine learning-selected compounds were either weak (experimental anti-asthmatic drug AZD5423 with a phenyl-1H-indazole scaffold) or inactive in inhibiting the hP2Y6R. Experimental drugs TAK-593 and GSK1070916 (100µM) inhibited P2Y14R fluorescent binding by 50% and 38%, respectively, and all other compounds by < 20%. Thus, machine learning has led the way toward revealing previously unknown modulators of several P2YR subtypes that have varied effects.

Update on asthma 2024 - what the ENT specialist needs to know

The lifetime prevalence of 8.6% of asthma in Germany reflects the high medical and socioeconomic impact of the disease. Asthma treatment goals have changed during the last decades: from symptom control to symptom prevention, with highly effective, disease-modifying anti-asthmatic drugs (DMAADs) aiming at asthma remission. In order to achieve this goal, phenotyping of patients (including an evaluation of allergies and type 2 biomarkers) is crucial for personalized treatment. The identification and effective treatment of concomitant diseases, such as allergic rhinitis or chronic rhinosinusitis with nasal polyps (CRSwNP), plays a major role for successful treatment. This underlines the importance of interdisciplinary collaboration of otolaryngologists and respiratory physicians in the management of patients with asthma. This CME article informs the reader about current guidelines on the diagnosis and treatment of asthma, focusing on clinically relevant recommendations for ENT physicians.

Precision medicine in the diagnosis and treatment of asthma

Due to the availability of disease-modifying anti-asthmatic drugs (DMAADs), especially inhaled steroids (alone or in combination with long-acting bronchodilators), biologics and modern allergen immunotherapy, the treatment of asthma has fundamentally changed. The aims of modern asthma precision medicine are prevention of symptoms and the induction and maintenance of asthma remission (long-term asthma control, freedom from exacerbations and stable lung function without the use of systemic steroids). A treat to target approach is used as for other chronic inflammatory diseases in internal medicine: the aim is to achieve remission by an individually tailored treatment with DMAADs; however, the prerequisite for modern asthma precision medicine is asthma phenotyping, including a detailed medical history, lung function testing, allergological diagnostics and measurement of type 2 markers (blood eosinophils and, if available, exhaled nitric oxide, FeNO).