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.

β2-agonists in sports: prevalence and impact on athletic performance

Respiratory disorders caused by exercise are expressed in the development of exercise-induced bronchoconstriction (EIB) and exercise-induced asthma (EIA), which are observed in athletes, especially in cyclic sports, much more often than in the population. Ventilation impairments are exacerbated by inhaled allergens, industrial pollutants and adverse environmental conditions, which increase the risk of EIB and asthma symptoms in athletes. The use of β2-agonists can prevent or eliminate ventilation disorders, however, it requires taking into account current anti-doping rules, which allow the use of certain substances in sports without a request for therapeutic use. The studies of the influence of β2-agonists on functional indicators of athletes and sports performance do not allow to make an unambiguous conclusion about its results. Medications with β2-agonists, approved for use in sports in the form of inhalation, do not have a significant effect on the performance of athletes at major sports competitions. At the same time, the systemic use of these substances and the use of any form of terbutaline caused a positive dynamics in functional indicators, which could lead to an illegal increase in the effectiveness of sports performance. Most of the conclusions about the effect of β2-agonists on outcome are based on a small number of studies, their heterogeneity, and an insignificant number of observations. It is necessary to continue studying the effects of β2-agonists in the course of randomized clinical trials in order to individualize therapy and prevent bronchial obstruction in athletes

A Combination of Formoterol and the Histone Deacetylase Inhibitor AR42 has No Effects on Muscle Mass in Tumor-Bearing Rats

Background: Accelerated muscle and adipose tissue loss are two of the main aspects of cancer cachexia. β2-agonists seem to be successful in the treatment of cachexia in experimental animals. The aim if the present investigation was to study the effects on body weight loss in tumor-bearing animals of a combination of formoterol and AR-42, an inhibitor of histone deacetylase (HDAC). Methods: Rats were divided into two groups, namely controls (C) and tumor-bearing (T). TB group was further divided into four subgroups: untreated (saline as a vehicle), treated with Formoterol (F) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with AR-42 (A) (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). and double-treated treated (TFA) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and AR-42 (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). 7 days after tumor transplantation, muscle weights, grip force and total physical activity were determined in all experimental groups. Results: The presence of the Yoshida AH-130 ascites hepatoma induced severe muscle wasting in rats. Treatment of the tumor-bearing animals with the beta2-agonist formoterol (0,3 mg/kg), resulted in a significant improvement in the cachectic state of the animals. Treatment of the tumor-bearing animals with AR42 did not result in any effects on muscle wasting in the cachectic rats. Furthermore, the combination of formoterol and AR42 showed no additional effects to those observed with just formoterol. Conclusion: The results presented question the previously described effects of AR42 on cancer cachexia, probably due to its effect on tumor growth.

Wheezing Characteristics and Predicting Reactivity to Inhaled β2-Agonist in Children for Home Medical Care

Background: Given that wheezing is treated with inhaled β2-agonists, their effect should be reviewed before the condition becomes severe; however, few methods can currently predict reactivity to inhaled β2-agonists. We investigated whether preinhalation wheezing characteristics identified by lung sound analysis can predict reactivity to inhaled β2-agonists.Methods: In 202 children aged 10–153 months, wheezing was identified by auscultation. Lung sounds were recorded for 30 s in the chest region on the chest wall during tidal breathing. We analyzed the wheezing before and after β2-agonist inhalation. Wheezing was displayed as horizontal bars of intensity defined as a wheeze power band, and the wheezing characteristics (number, frequency, and maximum intensity frequency) were evaluated by lung sound analysis. The participants were divided into two groups: non-disappears (wheezing did not disappear after inhalation) and disappears (wheezing disappeared after inhalation). Wheezing characteristics before β2-agonist inhalation were compared between the two groups.The characteristics of wheezing were not affected by body size. The number of wheeze power bands of the non-responder group was significantly higher than those of the responder group (P < 0.001). The number of wheeze power bands was a predictor of reactivity to inhaled β2-agonists, with a cutoff of 11.1. The 95% confidence intervals of sensitivity, specificity, and positive and negative predictive values were 88.8, 42, 44, and 81.1% (P < 0.001), respectively.Conclusions: The number of preinhalation wheeze power bands shown by lung sound analysis was a useful indicator before treatment. This indicator could be a beneficial index for managing wheezing in young children.

Effects of (a Combination of) the Beta2-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction

Expression of bronchodilatory β2-adrenoceptors and bronchoconstrictive muscarinic M3-receptors alter with airway size. In COPD, (a combination of) β2-agonists and muscarinic M3-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β2-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β2-agonist) and glycopyrrolate (anticholinergic) against methacholine- and EFS-induced constrictions of large and small airways was measured in guinea pig and human lung slices using video-assisted microscopy. In guinea pig lung slices, glycopyrrolate (1, 3 and 10 nM) concentration-dependently protected against methacholine- and EFS-induced constrictions, with no differences between large and small intrapulmonary airways. Indacaterol (0.01, 0.1, 1 and 10 μM) also provided concentration-dependent protection, which was greater in large airways against methacholine and in small airways against EFS. Indacaterol (10 μM) and glycopyrrolate (10 nM) normalized small airway hyperresponsiveness in COPD lung slices. Synergy of low indacaterol (10 nM) and glycopyrrolate (1 nM) concentrations was greater in LPS-challenged guinea pigs (COPD model) compared to saline-challenged controls. In conclusion, glycopyrrolate similarly protects large and small airways, whereas the protective effect of indacaterol in the small, but not the large, airways depends on the contractile stimulus used. Moreover, findings in a guinea pig model indicate that the synergistic bronchoprotective effect of indacaterol and glycopyrrolate is enhanced in COPD.

The prevalence and outcome of short-acting β2-agonists overuse in asthma patients in Taiwan

This study aims to investigate the prevalence of short-acting β2-agonist (SABA) overuse in asthma and the associated risk of acute exacerbation and mortality in Taiwan. We used the Taiwanese pay-for-performance asthma program database, which included patients aged between 12 and 100 years who were enrolled in the program between 2001 and 2015. Among a total of 218,039 patients, 34,641 (15.9%) patients are classified as SABA over-users. Compared with patients who did not receive inhaled corticosteroids (ICS) and collected ≤2 canisters, SABA over-users had a higher risk of severe exacerbations. SABA over-users had a higher risk of all-cause mortality compared with patients who did not receive ICS and collected ≤2 canisters. The overall prevalence of SABA overuse in Taiwan is 15.9%, and this is even higher in concomitant ICS users. In addition, the overuse of SABA is associated with an increased risk of severe exacerbation and death.

Over-prescription of short-acting beta agonists in the treatment of asthma

Background Despite a clear guideline for asthma medication, excessive use of short-acting β2-agonists (SABAs) is common in clinical practice. Previous research has shown that excessive use of SABAs is associated with poor asthma control. Objective This study examines current use of asthma medication in primary care and whether excessive use of SABAs is associated with exacerbations. Methods The study design was a retrospective analysis using information from electronical medical records from patients aged 18 and older of five Julius Health Centers located in Utrecht, the Netherlands, in the period of 1 July 2018 through 1 July 2019. Excessive SABA use was defined as ≥400 inhalations per year. An exacerbation was defined as an acute worsening of asthma symptoms with the need for systemic corticosteroids. Results A total of 1161 patients were included in the study. Of the patients using SABAs (n = 766), 193 (25%) overused SABAs. Among the patients with inappropriate SABA use (n = 193), 19% had an exacerbation compared with 7% of the appropriate SABA users. For patients using asthma medication the odds of having an exacerbation were 2.9 times higher if they used an inappropriate number of SABAs than if SABAs were used appropriately (odds ratio, 2.897; 95% confidence interval, 1.87–4.48). Conclusions This study shows that overuse of SABAs is still common and that it is associated with asthma exacerbations. It highlights that clinicians need to be aware of inappropriate SABA use as it is a sign of and can even contribute to poor asthma control.

Impact of bronchiolitis guidelines publication on primary care prescriptions in the Italian pediatric population

In Italy, two clinical practice guidelines for the diagnosis and treatment of bronchiolitis were published in October 2014 and December 2015. We evaluated prescriptions for bronchiolitis in children aged 0–24 months before (December 2012–December 2014), in between (December 2014–December 2015) and after (December 2015–December 2018) the guidelines publications. Data were retrieved from the Pedianet database; the measured outcomes were prescriptions rates of antibiotics, corticosteroids, β2-agonists, and other respiratory drugs. In 1011 out of 1581 episodes, patients received at least one treatment, with a total of 2003 prescriptions. The rate of treated bronchiolitis decreased from 66% to 57% (p < 0.001) after the publication of the second guideline; the highest reduction was in younger patients (from 57% to 44%, p = 0.013). Overall antibiotic prescriptions rate did not change, with 31.6% of the patients still receiving them. Our results confirm unnecessary non-evidence-based treatments in the primary care setting, with few changes after the guidelines publications.