Association of genetic variants of oxidative stress responsive kinase 1 (OXSR1) with asthma exacerbations in non-smoking asthmatics

Background Asthma exacerbation threatens patient's life. Several genetic studies have been conducted to determine the risk factors for asthma exacerbation, but this information is still lacking. We aimed to determine whether genetic variants of Oxidative Stress Responsive Kinase 1 (OXSR1), a gene with functions of salt transport, immune response, and oxidative stress, are associated with exacerbation of asthma. Methods Clinical data were obtained from 1454 asthmatics and single nucleotide polymorphisms (SNPs) of OXSR1 were genotyped. Genetic associations with annual exacerbation rate were analyzed depending on smoking status. Results Eleven SNPs were selected using Asian data in the International HapMap database. The common allele of rs1384006 C > T of OXSR1 showed a significantly higher annual exacerbation rate than the rare allele in non-smoking asthmatics (CC vs. CT vs. TT: 0.43 ± 0.04 vs. 0.28 ± 0.03 vs. 0.31 ± 0.09, P = 0.004, Pcorr = 0.039). The frequent exacerbators had a significantly higher frequency of the common allele of rs1384006 C > T than did the infrequent exacerbators (74.4% vs. 55.2%, P = 0.004, Pcorr = 0.038). Conclusion The common allele of rs1384006 C > T of OXSR1 was associated with the asthma exacerbation rate and a higher risk of being a frequent exacerbator, indicating that non-smoking asthmatics who carry common alleles may be vulnerable to asthma exacerbations.

Ketamine for Adults with Severe Asthma Exacerbation: A Systematic Review and Meta-analysis

BACKGROUND: Severe asthma mandates careful attention and timely management, and the benefit of ketamine in severe asthma exacerbations in adult patients require further exploration. METHODS: We conducted a systematic review and meta-analysis of the use of ketamine in cases of acute asthma exacerbation in adults. We searched PubMed, Google Scholar, Cochrane databases, and gray literature (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform); we also searched the reference lists of included articles and any systematic reviews and meta-analyses identified therein. Our search covered the period from 1963 to August 20, 2021. Search terms were “ketamine” AND “asthma”. RESULTS: Of 25 540 articles, two studies were included in the analysis. The total number of patients included in the studies was 136 (68 in the ketamine groups and 68 in the placebo group). The pooled effect size was 0.30 (95% CI: -0.04, 0.63) favouring ketamine over placebo, p=0.08, (I2=0%, p=0.39). A paired t-test revealed that ketamine improved the mean peak expiratory flow rate (PEFR) from 242.4 (SD=146.23) to 286.95 (SD=182.22), p=0.33, representing an 18.38% improvement. CONCLUSION: Ketamine can induce a 30% improvement in PEFR, representing a small positive effect in the treatment of acute severe asthma exacerbation in the emergency department (ED). The improvement was not statistically significant; nonetheless, since the improvement could be as great as 63% versus only a 4% possibility of no benefit/harm, the benefit appears to considerably outweigh any harm.

Effect of combined glucocorticoid therapy on bronchial asthma dynamics

This work is aimed to compare the effectiveness of parenteral and inhalation bronchial asthma treatment in combination with glucocorticosteroids and bronchodilators. The study was conducted in 2020 in Botkin City Clinical Hospital (Moscow, the Russian Federation). Case histories of 106 patients diagnosed with bronchial asthma exacerbation of moderate severity were analyzed. Patients were divided into two equal groups based on the therapy method: (1) Group 1 received systemic glucocorticosteroids parenterally in combination with inhalation glucocorticosteroids; (2) Group 2 received systemic glucocorticosteroids parenterally, but inhalation therapy was performed with a nebulizer. Clinical manifestations of bronchial asthma have been recorded. During hospital admission, the breath rate was 22.0 for Group 1 and 21.5 for Group 2, P ≥ 0.05, and heart rates were 93.0 and 92.5, respectively (P ≥ 0.05). All indices (blood saturation, breath rate, peak output rate) in Group 1 remained unchanged 4 h after the start of the therapy, while in Group 2, peak flow rate changed to 53.5% with a median increase of 72.0 ml over 4 h, P ≤ 0.05. On Day 3, patients of Group 1 demonstrated a peak flow rate of 59.5%, P ≤ 0.05, and on Day 10, patients of Group 2 had a peak output rate of 53.0 and 59.5%, respectively (P ≤ 0.05). Systemic glucocorticoids were eliminated in 47 patients of Group 1 and in all patients of Group 2. The treatment tactics applied in Group 2 resulted in faster and more significant improvement in patients diagnosed with bronchial asthma exacerbation. Both treatment regimens showed high results.

SOME ASPECTS OF PREDICTING THE SEVERITY OF VIRUS-INDUCED BRONCHIAL ASTHMA EXACERBATION IN CHILDREN DUE TO COVID-19 PANDEMIC

bronchial asthma is an important medical and social issue directly affects the health of patients, their quality of life, and the direct and indirect economic costs associated with the disease are quite significant. Due to the pandemic caused by a new strain of coronavirus SARS-CoV-2, international and domestic regulations documents have updated the management of patients with asthma. In particular, there have been recommendations for remote visits to assess the patients’ complaints however physical analysis and objective examination are not available during such consultations. It can lead to errors in diagnostic of asthma exacerbation severity and treatment tactic for prescription the reliever therapy. So it is actuality to find out additional indicators to improve the diagnostic and prediction of the severity of the disease exacerbations. Given the urgency of the problem, the aim of the study is to evaluate the clinical and paraclinical parameters in children with virus-induced bronchial asthma exacerbation to predict the severity of the asthma attack and personify the management of patients. Have been examined 47 patients who were hospitalized for disease exacerbation. The severity of a asthma attack was considered a group-forming feature. Statistical analysis was performed using parametric and nonparametric calculation methods, methods of clinical epidemiology and biostatistics. The results of the study give grounds to predict a more severe asthma attack among urban residents who have a phenotype of late-onset asthma. An additional, anamnestic risk of more severe exacerbation of the disease is body weight at birth, which exceeds 3500 g. Among spirometric indicators the highest prognostic criterion for severe bronchial asthma exacerbation was the general index of bronchodilation, which was 15% and above, as well as the index of bronchodilation at the level of the distal airways with a cut-off point of 30% and above. In the presence of the above risk factors for severe asthma attack on the background of confirmed infection with the coronavirus strain SARS-CoV-2 the patient needs hospitalization, antiviral treatment, increasing the dose of inhaled steroids and additional β2-agonists. When predicting a mild or moderate asthma attack provoked by the coronavirus SARS-CoV-2, it is advisable to continue remote monitoring by an allergist and the management of exacerbation includes a temporary increase daily dose of inhaled glucocorticosteroids and additional using of β2-agonists. It is recommended to avoid taking nebulizers and use individual metered powder or aerosol inhalers in cases of inpatient treatment.

Asthma exacerbation due to climate change-induced wildfire smoke in the Western US

Climate change and human activities have drastically altered the natural wildfire balance in the Western US and increased population health risks due to exposure to pollutants from fire smoke. Using dynamically downscaled climate model projections, we estimated additional asthma emergency room visits and hospitalizations due to exposure to smoke fine particulate matter (PM2.5) in the Western US in the 2050s. Isolating the amount of PM2.5 from wildfire smoke is both difficult to estimate and, thus, utilized by relatively few studies. In this study, we use a sophisticated modeling approach to estimate future increase in wildfire smoke exposure over the reference period (2003-2010) and subsequent health care burden due to asthma exacerbation. Average increases in smoke PM2.5 during future fire season ranged from 0.05-9.5 µg/m3 with the highest increases seen in Idaho, Montana, and Oregon. Using the Integrated Climate and Land-Use Scenarios (ICLUS) A2 scenario, we estimated the smoke-related asthma events could increase at a rate of 15.1 visits per 10,000 persons in the Western US, with the highest rates of increased asthma (25.7-41.9 per 10,000) in Idaho, Montana, Oregon, and Washington. Finally, we estimated healthcare costs of smoke-induced asthma exacerbation to be over $1.5 billion during a single future fire season. Here we show the potential future health impact of climate-induced wildfire activity, which may serve as a key tool in future climate change mitigation and adaptation planning.

Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study

IntroductionUncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta2-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations.Methods and analysisThe Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4–11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.Ethics and disseminationThe study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.Trial registrationNCT03769090.