Asthma Medicines Research Articles

Immunologic Basis of Type 2 Biologics for Severe Asthma.

Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

Anesthesia management of bronchial asthma in Cesarean Section: A literature review

Asthma is a chronic condition that is becoming more common around the world. Asthma has been demonstrated to affect pregnancy in several studies. Because the severity of asthma might fluctuate throughout pregnancy, it is important to know what kind of asthma medicine to take and how much to take. Increased perinatal mortality, stunted fetal growth, early birth, increased cesarean section, low birth weight, and postpartum hemorrhage are all concerns that uncontrolled asthma can cause in infants. The overall course of asthma has been observed to improve, deteriorate, or remain the same throughout pregnancy. Although previous research suggests that patients with more severe asthma are more likely to worsen their condition during pregnancy, other studies have found that asthma severity during pregnancy is comparable to asthma severity a year before pregnancy, as long as the patient takes their prescribed medications. Anxiety is a known asthma trigger; if necessary, it should be handled perioperatively. Spirometry and deep breathing should be encouraged to avoid atelectasis. Theophylline is generally contraindicated in asthmatic patients undergoing surgery, and it should be halted perioperatively if possible. Because the degree of anesthetic is reduced, tracheal extubation, while the patient is awake, reduces the risk of aspiration, but the tracheal tube can stimulate reflexes and cause bronchospasm. Bronchodilators may be used if bronchospasm occurs at the onset. Continued mechanical ventilation in the intensive care unit may be required for refractory bronchospasm.

Pemanfaatan Satwa Liar sebagai Obat Tradisional di Desa Terak dan Teru, Kabupaten Bangka Tengah

Terak and Teru Villages are two of the eleven villages surrounding Gunung Mangkol Grand Forest. Since a long time ago, the people in these villages have fulfilled their daily needs by utilizing the natural resources around Gunung Mangkol Grand Forest. One of the natural resources in the grand forest is wild animals commonly used as traditional medicine. This research was undertaken to find out what wild animals are used as traditional medicine by the people of Terak and Teru Villages; and to find out what parts are used, types of utilization, and processing methods of the wild animals. The research was conducted from November 1, 2021 to November 29, 2021. The research methods used were collecting data by surveys and selecting respondents using the snowball sampling technique. Selected respondents were then interviewed according to the questionnaire. Based on the research results, nine species of wild animals were used as traditional medicine by the people of Terak and Teru Villages. The parts of wild animals used were bile, liver, meat, and whole bodies. The types of use of wild animals were male stamina enhancer, asthma medicine, skin pain medicine, surgical wound medicine, malaria medicine, typhus medicine, cough medicine, toothache medicine, burn treatment, and headache medicine. The methods of processing wild animals were unprocessed, dried in the sun for the oil, roasted / burnt, and fried.

Microbiome Research and Multi-Omics Integration for Personalized Medicine in Asthma.

Asthma is a multifactorial inflammatory disorder of the respiratory system characterized by high diversity in clinical manifestations, underlying pathological mechanisms and response to treatment. It is generally established that human microbiota plays an essential role in shaping a healthy immune response, while its perturbation can cause chronic inflammation related to a wide range of diseases, including asthma. Systems biology approaches encompassing microbiome analysis can offer valuable platforms towards a global understanding of asthma complexity and improving patients’ classification, status monitoring and therapeutic choices. In the present review, we summarize recent studies exploring the contribution of microbiota dysbiosis to asthma pathogenesis and heterogeneity in the context of asthma phenotypes–endotypes and administered medication. We subsequently focus on emerging efforts to gain deeper insights into microbiota–host interactions driving asthma complexity by integrating microbiome and host multi-omics data. One of the most prominent achievements of these research efforts is the association of refractory neutrophilic asthma with certain microbial signatures, including predominant pathogenic bacterial taxa (such as Proteobacteria phyla, Gammaproteobacteria class, especially species from Haemophilus and Moraxella genera). Overall, despite existing challenges, large-scale multi-omics endeavors may provide promising biomarkers and therapeutic targets for future development of novel microbe-based personalized strategies for diagnosis, prevention and/or treatment of uncontrollable asthma.

Efecto y seguridad de un tratamiento ambulatorio de medicina tradicional para el asma en 26 pacientes de Cota, Colombia: una serie de casos

The prevalence, morbidity and costs of asthma care have increased worldwide. This study describes the effect and safety of an outpatient medical treatment with traditional medicine for asthma, through a retrospective case series with patients admitted to outpatient consultation from 1995 to 2015 in Cota, Colombia. Analyzing 26 cases with a clinical diagnosis of asthma, during the treatment 34.6% (9/26) did not present episodes of uncontrolled asthma and 61.5% (16/26) were classified as controlled asthma in their last consultation of control. 88.4% (23/26) of the patients reported no adverse reactions and the three reported were mild. The results allow to generate hypotheses about the effectiveness and safety of an outpatient treatment based on the incorporation of resources from traditional medicine. These observations could be explored with experimental studies to determine their long-term effectiveness, safety and low cost.

Standardization of Diploid Codonopsis laceolata Root Extract as an Anti-Hyperuricemic Source

Codonopsis lanceolate exerts various medicinal effects and has been used as a traditional medicine for inflammation, asthma, gastritis, and liver disease. Recently, we reported the xanthine oxidase inhibitory activity of C. lanceolata extract and that lobetyolin, one of the key components, was a xanthine oxidase inhibitor. Lobetyolin showed anti-hyperuricemic activity in vitro and in vivo. In this study, we prepared various types of C. lanceolata extracts for the development of functional materials and natural drugs. We present the optimal analytical approach for the quality control and extraction optimization of C. lanceolata preparations. We established and validated a HPLC analysis for easy separation and quantification of the lobetyolin biomarker. Solvent extracts of C. lanceolata root were prepared and the profiles of the active marker and the optimal extraction methods were evaluated. The 100% ethanolic extract demonstrated the highest lobetyolin content. The validated HPLC method confirmed that lobetyolin was present in C. lanceolata root extracts. We suggest that the anti-hyperuricemic activities of C. lanceolata extract could be attributed to this marker compound. The results proposed that the 100% ethanolic extract could be used for the prevention of hyperurecemia, and that this analytical method and biomarker could be useful for the quality control of C. lanceolata preparations.

Systemic antibiotics and asthma medicines dispensed to 0-12 year olds significantly decreased during the COVID-19 pandemic in 2020.

AimNationwide lockdowns and social restrictions during the COVID‐19 pandemic have reduced childhood infections. We assessed how many items of systemic antibiotics and asthma medicines were dispensed to children aged 0−12 years in Finland before and during the pandemic and analysed the reimbursement costs.MethodsThe data came from the national Finnish register of reimbursable prescriptions, which is maintained by the country's Social Insurance Institution. It included all prescriptions for antibiotics and asthma medicines dispensed to children aged 0−12 years in 2019 and 2020. Prescription rates per 1000 children were calculated for each quarter and compared using rate ratios and 95% confidence intervals (95% CI).ResultsOverall dispensing for antibiotics decreased by 55.3% and was most prominent for macrolides for children aged 0−5 years (59.6%, 95% CI 60.9%−58.2%). Asthma medicines decreased by 19.8%, and the most prominent reduction was in short‐acting beta‐agonists for children aged 0−5 years (35.2%, 95% CI 36.1%−34.2%). These reduced reimbursement costs by 3.4 million Euros from 2019 to 2020.ConclusionThis nationwide study showed that the number of antibiotics and asthma medicines decreased by 59.6% and 19.8% respectively from 2019 to 2020, generating a cost saving of 3.4 million Euros.

Herbal treatments for asthma, according to Avicenna

Abstract Background and objectives: Conventional therapies using herbal medicine to treat asthma are employed by practitioners in Iran. The use of herbal medicine for asthma is rooted in traditional knowledge. Scientific evaluation of these historical documents could be valuable to find new potential applications in conventional medicine. Traditional Persian Medicine (TPM), which is widely known with the manuscripts of Avicenna and Rhazes, is one of the most ancient medical set of beliefs. Methods: In this study, firstly we introduce a series of medicinal plants that would be enormously valuable for treating asthma on the basis of Avicenna (The Canon of Medicine by Avicenna). After that, we review medicinal plants properties found in the pharmacological studies from electronic databases and then discuss their mechanism of action in asthma. For a detailed review, relevant abstracts and articles related to the above-mentioned areas were selected, including review articles on the subjects, along with clinical trial studies in animals and humans. Results: The physicians of ancient Iran such as Avicenna treated asthma patients with a variety of medicinal herbs. Some of these herbs are currently used, while others have the potential to be used in the future of asthma management. Conclusions: This study demonstrates that the investigated plants are consistent with new studies; therefore, different components of these herbs can be utilized in manufacturing new drugs. Future clinical studies on healthy volunteers and also patients suffering from asthma and reactive airway disease are compulsory to confirm the effectuality of these plants as complementary interventions in asthma.

Asthma and COPD medicines prescription-claims: A time-series analysis of England’s national prescriptions during the COVID-19 pandemic (Jan 2019 to Oct 2020)

ABSTRACT Background During the pandemic, there have been disruptions to how patients seek care. Research design and methods To investigate monthly prescription claims for asthma and chronic obstructive pulmonary disease (COPD) medicines during the first UK wave, interrupted time series (ITS) analysis was used. A national cohort of community patients’ data were examined. Results Descriptive statistics show salbutamol, aminophylline, ipratropium, and theophylline remain below pre-pandemic levels. Montelukast showed pre-pandemic monthly increase (Est. 67,151 doses, P = 0.05, 95% CI: 1011, 133,291), followed by a jump of 1.6 million doses at March , followed by monthly declines (Est. −112,098 doses, P = 0.216, 95% CI: -293,499, 69,303). Before the pandemic, tiotropium, salbutamol, aminophylline, and ipratropium (P = 0.003) show monthly declines but theophylline and beclometasone showed increases. In March , salbutamol (P = 0.033) and ipratropium (P = 0.001) show a significant jump. After March , ipratropium continues with a downward trajectory (P = 0.001), with a generalized negative trend for all other agents. Salbutamol confidence bounds become negative after March 2020. Some brands were unavailable. Conclusions An ‘unmet’ medical gap is identified. While it is essential to understand the underlying reasons, urgent action needs to be taken to reassess patients and ensure continuity of care. PLAIN LANGUAGE SUMMARIES (PLS) Asthma and chronic obstructive pulmonary disease (COPD) are long-term lung conditions, affecting 6 million & 1.2 million people respectively and causing breathing difficulties. Sufferers are at a higher risk of chest infections including the coronavirus. Regular use of prescribed medication stabilizes these conditions and prevents them from getting worse. It is common to be prescribed a combination of five to eight oral and inhaled medications. We investigated the impact of the pandemic on the dispensing of these specific medicines across England during the first wave. The English Prescribing Dataset was checked from January 2019 to February 2020 (14 months before the pandemic) and March to October 2020 (8 months after its onset). We find that since March 2020, salbutamol, aminophylline, ipratropium, and theophylline have not returned to their pre-pandemic levels. However, for all agents, there is great variability. Further analysis suggests these trends are not reversing, suggesting that people have not been using their medication as anticipated for 8 months, which is concerning. As a consequence of this work, we recommend that doctors specifically call these patients and discuss their health as a matter of urgency, we encourage patients to continue to take their medication. We advise policy changes to waive the NHS prescription levy for asthma and COPD medication and we seek more granular data for further harm quantification. There are several strengths and weaknesses to our analysis, and we need to conduct more studies to ask patients about their experiences.

Clinical Evaluation for Sublingual Immunotherapy With Dermatophagoides farinae in Polysensitized Allergic Asthma Patients.

Background: Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS).Method: Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, n = 37) and the SLIT group (further treated with Dermatophagoides farinae drops, n = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, n = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, n = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, n = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT.Results: TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all p < 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all p < 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy (p < 0.05).Conclusion: Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.

Are there differences in the treatment information received to support guided self-management between asthma and allergy patients?: A community pharmacy survey in Finland

BackgroundGuided self-management of asthma supported by health care professionals is a well-established approach. For allergy patients, there is less guidelines and evidence for guided self-management than for asthma patients. ObjectiveThe objective of this study was to find out how commonly asthma and allergy patients receive written action plans, how much and from which sources they receive treatment information to support their self-management, and to identify associated factors that may influence the support of guided self-management, and if there are any differences between these patients. MethodsA nationwide survey was conducted in Finnish community pharmacies (n = 785) in September 2016 targeting patients buying prescription medicines for asthma or allergies. ResultsResponses were received from 46% of targeted pharmacies. Around 73% of the asthma patients, 61% of patients at risk of anaphylaxis, and less than 50% of the other allergy patients had received a written action plan. The most common source of treatment information for both patient groups was pharmacists. Allergy patients sought information more from written sources than asthma patients. Older males and patients with lower education received less treatment information. About 10% of both asthma and allergy patients did not report receiving any treatment information. ConclusionThe majority of asthma patients and allergy patients at risk of anaphylaxis had received a written action plan, while fewer than half of other allergy patients had received a written action plan. For both asthma and allergy patients, community pharmacists are the most common source of treatment information. Allergy patients seek more information from written sources than asthma patients. Pharmacists have a crucial role in the support of self-management for these patients.

Total IgE Variability Is Associated with Future Asthma Exacerbations: A 1-Year Prospective Cohort Study

Few prospective studies have investigated the relationship between IgE variability and risk for asthma exacerbations (AEs). To explore the relationship between IgE variability and AEs. Recruited patients with stable asthma underwent two serum total IgE tests within a month (at screening [baseline IgE] and at 1 month) to obtain the coefficient of variation (CV) of base 10 log-transformed IgE. Patients with IgE CV were divided into IgE CV-high and IgE CV-low cohorts based on the CV median and were observed within 12 months, during which the association between IgE variability and AEs was explored using a negative binomial regression model. The IgE CV levels obtained from 340 patients classified patients into two groups (n= 170 for the IgE CV-high and IgE CV-low groups, respectively) based on the serum total IgE CV median of 2.12% (quartiles 1 and 3: 0.98% and 3.91%, respectively). The IgE CV-high patients exhibited worse asthma control and lung function and more marked airway inflammation, and received more intensive medication use compared with IgE CV-low patients. The IgE CV-high patients exhibited increased rates of moderate-to-severe (adjusted rate ratio= 2.88; 95% confidence interval, 1.65-5.03; P < .001) and severe (adjusted rate ratio= 2.16; 95% confidence interval, 1.08-4.32; P= .029) AEs during the follow-up year compared with IgE CV-low patients. Furthermore, sputum IL-6 partially mediated the associations between IgE CV with moderate-to-severe and severe AEs. Variability in total serum IgE levels is an easily obtained and practical measure for predicting AEs. Future studies are needed to investigate whether IgE variability can be used to guide precision medicine in asthma.

Coping with access barriers to non\u2010communicable disease medicines: qualitative patient interviews in eight counties in Kenya

BackgroundThere is rich literature on barriers to medicines access for the treatment of non-communicable diseases (NCDs) in high-income countries. Less is known about low- and middle-income countries, in particular the differences in coping with medicines access barrier by household wealth and disease. The aim of this study was to compare the coping mechanisms of patients with the lack of availability and affordability of cardio-vascular diseases, diabetes and asthma medicines in Kenya.MethodsThis qualitative study was part of a larger mixed methods evaluation study conducted in eight counties of Kenya from 2016 to 2019. Forty-nine patient interviews at study end line explored their NCD journey, perceptions of availability, stockouts and affordability of NCD medicines, their enrollment in health insurance, and their relationship with the private chemists. Transcribed interviews were coded using Nvivo software. A two-step thematic approach was used, first conducting a priority coding which was followed by coding emerging and divergent themes. ResultsOverall, we found that patients across all disease types and wealth level faced frequent medicine stock-outs at health facilities. In the absence of NCD medicines at health facilities, patients coped by purchasing medicines from local chemists, switching health facilities, requesting a different prescription, admitting oneself to an inpatient facility, establishing connections with local staff to receive notifications of medicine stock, stocking up on medicines, utilizing social capital to retrieve medicines from larger cities and obtaining funds from a network of friends and family. Categorizing by disease revealed patterns in coping choices that were based on the course of the disease, severity of the symptoms and the direct and indirect costs incurred as a result of stockouts of NCD medicines. Categorizing by wealth highlight differences in households’ capacity to cope with the unavailability and unaffordability of NCD medicines.ConclusionsThe type of coping strategies to access barriers differ by NCD and wealth group. Although Kenya has made important strides to address NCD medicines access challenges, prioritizing enrollment of low wealth households in county health insurance programs and ensuring continuous availability of essential NCD medicines at public health facilities close to the patient homes could improve access.

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction.

Asthma is a heterogeneous disease, characterised by different phenotypes and endotypes. Precision medicine in asthma refers to the implementation of a targeted therapy for each individual child, based on the identification of treatable traits, including environmental, immunological and genetic factors. Severe asthma in children is associated with increased hospitalisation rates, a lower quality of life, increased healthcare costs and an increased mortality. In the era of new molecular biologics treatments, it is essential to improve deep phenotyping of children with severe asthma in order to deliver the most effective treatment to each individual child. In this review, we discuss the personalised approach to the assessment and management of severe asthma. We explore the indications and use of the currently licensed biologics, as well as the potential of other emerging treatments.

Compound Unani formulations used in Zeeq-un-Nafas (Bronchial Asthma) with their therapeutic importance: An overview

Asthma is one of the most common chronic diseases in modern society and there is increasing evidence to suggest that its incidence and severity are increasing. There is a high prevalence of usage of complementary medicine for asthma. Current estimates suggest that 300 million people worldwide suffer from Bronchial asthma. This disease is very well recognized since ancient times in Unani system of medicine. Various ancient Unani Scholars and Physicians have use different Arabic terms like Rabu (short inspiration and prolonged expiration), Buhar, Dama, Intesab-un-Nafas and Zeequn Nafas under the caption of bronchial asthma. They also described the etiopathological factors, clinical features, types, and various complications of bronchial asthma that are presented in detail in their concerning treatises. Unani physicians have been treating this disease for thousands of years and they have mentioned various single as well as compound drugs viz; Kakra Seenghi (Pistacia integerrima) Arusa (Adhatoda vasica), Ajmod (Apium graveolens), Aslussoos (Glycyrrhiza glabra), Bazrul banj (Hyoscyamus niger), Biskhapra (Trianthema portulaca), Doodhi (Euphorbia hirta), Nil(Indigofera: tinctoria), Qinnab (Cannabis sativam) etc. and the compound formulations in the forms of - Kushta, Majoon , Hubb, Sharbat, Arqiyat, Joshanda, Khenshanda, Laooq ,Tiryaq, Sikanjabeen, Rub, Roghaniyat for its treatment. The relevance formulations have been described in this review paper with their ingredients and usage also to provide the benefit to the students and researchers for their further researches

Real-world efficacy and safety of dupilumab use in the treatment of asthma

Asthma affects people of all races and ethnic groups worldwide. 1 Fuseini H Newcomb DC Mechanisms driving gender differences in asthma. Curr Allergy Asthma Rep. 2017; 17: 19 Crossref PubMed Scopus (188) Google Scholar Uncontrolled asthma has a major impact on daily life with unscheduled clinic or emergency department visits, hospitalizations, and impact on daily activity. 2 Zeiger RS Schatz M Dalal AA et al. Utilization and costs of severe uncontrolled asthma in a managed-care setting. J Allergy Clin Immunol Pract. 2016; 4 (e3): 120-129 Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar Symptoms of asthma including cough, shortness of breath, chest tightness, and wheezing have a substantial impact on the quality of life. Frequent exacerbations can lead to airway remodeling, worsening obstruction, and reduced lung function. Inhaled corticosteroids and β-agonists have been the treatment of choice for years. Although many patients are well-controlled with inhaled treatment options, many have uncontrolled symptoms and ongoing exacerbations. Those with frequent exacerbations are subjected to systemic corticosteroids, which carry a risk of both short- and long-term adverse effects. The recent development of biologic therapies has broadened treatment options, offering hope to those with difficult to control asthma. One of the newest biologic agents, dupilumab, is a human monoclonal antibody that inhibits the signaling of interleukin 4 and interleukin 13. These TH2 cytokines drive inflammation in allergic diseases such as atopic dermatitis, asthma, and nasal polyposis. 3 Simpson EL Akinlade B Ardeleanu M Two phase 3 trials of Dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2017; 376: 1090-1091 Crossref PubMed Scopus (93) Google Scholar Dupilumab is approved for use as an add-on maintenance treatment for people aged 12 years and older who have moderate-to-severe eosinophilic or oral steroid–dependent asthma that is not controlled with their current asthma medicines. 4 Castro M Corren J Pavord ID et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018; 378: 2486-2496 Crossref PubMed Scopus (863) Google Scholar ,5 Rabe KF Nair P Brusselle G et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018; 378: 2475-2485 Crossref PubMed Scopus (570) Google Scholar Studies on real-world safety and efficacy of dupilumab on asthma treatment are lacking. Our aims were to determine the effectiveness and adverse effects of dupilumab in people with asthma.

Evaluation of serum levels of interleukin-10 and transforming growth factor-β1 among Egyptian children with wheezy asthma phenotype

Background Asthma is known to be a heterogeneous disease that forms a problem in asthma management. Symptom-based asthma phenotyping with endotyping of the proposed phenotype is a trial to solve this problem. Asthma phenotypes and endotypes facilitate research, establish genetic associations, identify biomarkers, and test for new lines of treatment. Aim To clarify the cytokine profile of wheezy asthma phenotype which could pave the way to personalize asthma medicines according to symptom-based asthma phenotypes. Patients and methods A case–control study was conducted in 50 asthmatic patients presented solely with wheezes with a mean±SD of age of 9.54±2.81 years and 50 healthy controls, with a mean±SD of age of 8.98±2.79 years. The studied cases and controls underwent assessment of serum levels of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), total serum immunoglobulin E (IgE), peripheral eosinophilic percent, and pulmonary function tests. Results Wheezy asthma phenotype showed significant increase in parental smoking, positive family history, total serum IgE, peripheral eosinophilic percent, and TGF-β1 compared with controls. However, serum IL-10 showed significant decrease in cases versus controls. Asthmatics with allergic rhinitis showed significant increase in total serum IgE and peripheral eosinophilic percent compared with non-allergic rhinitis asthmatics. Conclusion Wheezy asthma phenotype showed significant increase of serum TGF-β1 as a promoting effect of airway remodeling, significant decrease in serum IL-10, and significant increase of both total serum IgE and eosinophilic percent. This throws a light on the importance of asthma phenotyping according to symptomatology, as a trial toward tailoring asthma medications.

Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats.

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (p < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

Planning a Clinical Development Programme for Medicines for Bronchial Asthma

The need for development of a clinical trial guidance for medicines for bronchial asthma is brought about by the improvement of requirements for research programmmes for new medicines. The aim of the study was to develop a methodological approach to conducting clinical trials of bronchial asthma medicines in Russia in line with the existing international requirements. The authors analysed regulatory documentation on the development of medicines for treatment of bronchial asthma in adults taking into account the current clinical guidelines, and specific aspects of developing medicines for treatment of bronchial asthma in children. The paper also analyses some clinical research aspects related to the development of immunotherapy. The analysis of up-to-date Russian and international clinical guidelines for bronchial asthma treatment, which are focused on bronchial asthma management using basic therapy, revealed the need to use revised disease concepts and new criteria to assess the efficacy of asthma medicines. The authors formulated consistent approaches to planning a clinical development programme for medicines for bronchial asthma, and suggested methodology for conducting clinical research based on recommendations of the European Medicines Agency.

PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment

Severe asthma accounts for almost half the cost associated with asthma. Severe asthma is driven by heterogeneous molecular mechanisms. Conventional clinical trial design often lacks the power and efficiency to target subgroups with specific pathobiological mechanisms. Furthermore, the validation and approval of new asthma therapies is a lengthy process. Alarge proportion of that time is taken by clinical trials to validate asthma interventions. The National Institutes of Health Precision Medicine in Severe and/or Exacerbation Prone Asthma (PrecISE) program was established with the goal of designing and executing a trial that uses adaptive design techniques to rapidly evaluate novel interventions in biomarker-defined subgroups of severe asthma, while seeking to refine these biomarker subgroups, and to identify early markers of response to therapy. The novel trial design is an adaptive platform trial conducted under a single master protocol that incorporates precision medicine components. Furthermore, it includes innovative applications of futility analysis, cross-over design with use of shared placebo groups, and early futility analysis to permit more rapid identification of effective interventions. The development and rationale behind the study design are described. The interventions chosen for the initial investigation and the criteria used to identify these interventions are enumerated. The biomarker-based adaptive design and analytic scheme are detailed as well as special considerations involved in the final trial design.