Beta-agonist Research Articles

Overuse of Short-Acting Beta-2 Agonists (SABAs) in Elite Athletes: Hypotheses to Explain It.

The use of short-acting beta-2 agonists (SABAs) is more common in elite athletes than in the general population, especially in endurance sports. The World Anti-Doping Code places some restrictions on prescribing inhaled β2-agonists. These drugs are used in respiratory diseases (such as asthma) that might reduce athletes’ performances. Recently, studies based on the results of the Olympic Games revealed that athletes with confirmed asthma/airway hyperresponsiveness (AHR) or exercise-induced bronchoconstriction (EIB) outperformed their non-asthmatic rivals. This overuse of SABA by high-level athletes, therefore, raises some questions, and many explanatory hypotheses are proposed. Asthma and EIB have a high prevalence in elite athletes, especially within endurance sports. It appears that many years of intensive endurance training can provoke airway injury, EIB, and asthma in athletes without any past history of respiratory diseases. Some sports lead to a higher risk of asthma than others due to the hyperventilation required over long periods of time and/or the high environmental exposure while performing the sport (for example swimming and the associated chlorine exposure). Inhaled corticosteroids (ICS) have a low efficacy in the treatment of asthma and EIB in elite athletes, leading to a much greater use of SABAs. A significant proportion of these high-level athletes suffer from non-allergic asthma, involving the th1-th17 pathway.

Biomarkers, imaging and safety in resmetirom 52 week non-cirrhotic NASH phase 3 clinical trial, completed open-label arm of maestro-NAFLD-1

Background: MAESTRO-NASH (NCT03900429) and MAESTRO-NAFLD-1 (NCT04197479) are 52-week Phase 3 registrational double-blind placebo controlled clinical trials to study the effect of resmetirom, a selective thyroid receptor beta (THR-β) agonist in NASH patients. A goal of MAESTRO-NAFLD-1, a 1200 patient “real life” NASH study is to identify non-invasive markers that correlate with patient response to resmetirom treatment. The 171 patient 100 mg open label arm completed the 52-week study in July 2021.

Effects of increasing supplemental zinc in beef feedlot steers administered a steroidal implant and beta agonist.

Ninety-two Angus-crossbred steers (424 ± 28.3 kg initial body weight) were used in a 98-d study to assess the effects of increasing Zn supplementation on cattle performance, liver and plasma trace mineral concentrations, blood metabolites, and carcass characteristics. All steers were implanted with a Component TE-200 (200 mg trenbolone acetate + 20 mg estradiol; Elanco Animal Health, Greenfield, IN) on d 0 and fed 300 mg‧steer−1‧d−1 of ractopamine hydrochloride (Zoetis, Parsippany, NJ) from d 70 to 98. Cattle were fed via GrowSafe bunks (GrowSafe Systems Ltd., Airdrie, AB, Canada), and steer served as the experimental unit (n = 22 or 23 steers/treatment). Supplemental Zn was administered through the diet at 0, 100, 150, or 180 mg Zn/kg on a dry matter basis from ZnSO4 (Zn0, Zn100, Zn150, or Zn180, respectively). Cattle were weighed on d −1, 0, 9/10, 20, 41, 59, 69, 70, 78/79, 97, and 98. Blood was collected on d 0, 9/10, 69, 78/79, and 97, and liver biopsies on d 9/10 and 78/79 (n = 12 steers/treatment). Data were analyzed as a complete randomized design. Contrast statements were formed to test the linear, quadratic, and cubic effects of Zn supplementation and test Zn0 vs. Zn supplementation. Day 10 and 70 body weight (BW) and d 0 to 10 and 0 to 70 average daily gain were linearly increased with Zn supplementation (P ≤ 0.05), and greater for Zn supplemented steers (P ≤ 0.03). No effects of Zn supplementation were observed on final BW, dressing percentage, ribeye area, 12th rib fat, or marbling (P ≥ 0.11). Hot carcass weight tended to be 7 kg greater for Zn supplemented steers than Zn0 (P = 0.07), and yield grade linearly increased with increasing Zn supplementation (P = 0.02). Day 10 liver Mn concentrations tended to quadratically decrease (P = 0.08) with increasing Zn supplementation, though d 79 liver Mn concentrations and arginase activity were not influenced by Zn (P ≥ 0.28). Day 10 liver arginase activity tended to be (r = 0.27; P = 0.07) and d 10 serum urea nitrogen was correlated with d 10 liver Mn (r = 0.55; P < 0.0001). Zinc supplementation linearly increased d 10 liver Zn and d 10, 69, 79, and 97 plasma Zn concentrations (P ≤ 0.05). A cubic effect of Zn was observed on d 79 liver Zn (P = 0.01) with lesser liver Zn in Zn0 and Zn150 steers. These data suggest increasing dietary Zn improves growth directly following the administration of a steroidal implant and that steroidal implants and beta agonists differ in their effects on protein metabolism.

Epidemic thunderstorm asthma

Epidemic thunderstorm asthma

Pharmacogenomics and Pediatric Asthmatic Medications

Asthma is a respiratory condition often stemming from childhood, characterized by difficulty breathing and/or chest tightness. Current treatment options for both adults and children include beta-2 agonists, inhaled corticosteroids (ICS), and leukotriene modifiers (LTM). Despite recommendations by the Global Initiative for Asthma, a substantial number of patients are unresponsive to treatment and unable to control symptoms. Pharmacogenomics have increasingly become the front line of precision medicine, especially with the recent use of candidate gene and genome- wide association studies (GWAS). Screening patients preemptively could likely decrease adverse events and therapeutic failure. However, research in asthma, specifically in pediatrics, has been low. Although numerous adult trials have evaluated the impact of pharmacogenomics and treatment response, the lack of evidence in children has hindered progress towards clinical application. This review aims to discuss the impact of genetic variability and response to asthmatic medications in the pediatric population.

What are the effects of as-required fixed-dose combination beta agonist plus steroid inhaler for adults with mild asthma?

What are the effects of as-required fixed-dose combination beta agonist plus steroid inhaler for adults with mild asthma?

A prospective study of switching asthma patients from a Fixed-Dose Combination (FDC) Inhaled Corticosteroid [ICS]/Long-Acting Beta Agonist [LABA] therapy delivered by Dry Powder Inhaler (DPI) to ICS/LABA delivered by pressurised Metered Dose Inhaler (pMDI)

BackgroundPrevious real-world studies have suggested that in comparison to a dry powder inhaler (DPI), the rate of critical errors is lower with a pressurised metered dose inhaler (pMDI), and inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) delivered by pMDI is more likely to achieve asthma control. ObjectivesTo evaluate the acceptability, efficacy, safety and cost-effectiveness of switching asthma patients from an ICS/LABA DPI to an ICS/LABA pMDI in a real-world population in Kuwait. MethodsThis was a 12-month, observational, nonblinded, prospective, real world study. Patients with asthma for ≥1 year with 2 or more asthma exacerbations in the last year were assigned to either switch to ICS/LABA pMDI, or to continue with ICS/LABA DPI. ResultsA total of 239 patients were treated with either ICS/LABA pMDI (Switch cohort; n = 119) or ICS/LABA DPI (Maintenance cohort; n = 120). The majority of patients (99/119; 83.2%) in the Switch cohort remained on ICS/LABA pMDI over 12 months of follow-up. Both cohorts experienced an improvement in their FEV1 levels, with mean values in the Switch group reaching normal levels (>80% predicted). On average, at 3 and 12 months, the Switch cohort had significantly better FEV1 values than patients in the Maintenance cohort (p = 0.001). At 12 months, the proportion of patients with controlled asthma increased in the Switch group, but did not change significantly in the Maintenance group. ConclusionsIn patients with asthma symptoms that are not well controlled with an ICS/LABA DPI, switching to an ICS/LABA pMDI provides an alternative choice that may improve asthma control.

Towards codesign in respiratory care: development of an implementation-ready intervention to improve guideline-adherent adult asthma care across primary and secondary care settings (The SENTINEL Project)

Short-acting beta agonist (SABA) overuse (≥3 canisters annually) is associated with worse asthma outcomes and accounts for the majority of greenhouse gas emissions from asthma inhalers in England. Reducing SABA...

PRIMUS - Prompt Initiation of Maintenance Therapy in the US: A Real-World Analysis of Clinical and Economic Outcomes Among Patients Initiating Triple Therapy Following a COPD Exacerbation.

PurposePatients with chronic obstructive pulmonary disease (COPD) may experience moderate (requiring outpatient care) or severe (requiring hospitalization) disease exacerbations. Guidelines recommend escalation from dual to triple therapy (inhaled corticosteroid + long-acting beta agonist + long-acting muscarinic antagonist) after two moderate or one severe exacerbation in a year. This study examined whether prompt initiation of triple therapy lowers risk of future exacerbations and reduces healthcare costs, compared to delayed/very delayed triple therapy after an exacerbation.Patients and MethodsThis retrospective observational study of US healthcare claims included patients ≥40 years old with COPD who initiated triple therapy (1/1/2011–3/31/2020) after ≥2 moderate or ≥1 severe exacerbation in the prior year. The earliest of the second moderate or first severe exacerbation was the index date. Patients were stratified by triple therapy timing: prompt (≤30 days post-index), delayed (31–180 days), very delayed (181–365 days). COPD exacerbations, all-cause and COPD-related healthcare utilization and costs were assessed during 12 months post-index (follow-up). Multivariable regression estimated the effect of each 30-day delay in triple therapy on the odds of exacerbations, number of exacerbations, and costs during follow-up, controlling for patient characteristics.ResultsA total of 24,770 patients were included: 7577 prompt, 9676 delayed, 7517 very delayed. Each 30-day delay of triple therapy was associated with 11% and 7% increases in the odds of any exacerbation and a severe exacerbation, respectively (odds ratio [95% CI]: 1.11 [1.10–1.13] and 1.07 [1.05–1.08]), a 4.3% (95% CI: 3.9–4.6%) increase in the number of exacerbations, a 1.8% (95% CI: 1.3–2.3%) increase in all-cause costs, and a 2.1% (95% CI: 1.6–2.6%) increase in COPD-related costs during follow-up.ConclusionPromptly initiating triple therapy after two moderate or one severe exacerbation is associated with decreased morbidity and economic burden in COPD. Proactive disease management may be warranted to prevent future exacerbations and lower costs among patients with COPD.

Chronic Lung and Gastrointestinal Diseases: Take a Broader Perspective

Chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are often found with gastrointestinal symptoms or even gastrointestinal diseases as one of its comorbid. Vice versa, many cases of gastrointestinal diseases such as gastroesophageal reflux disease (GERD) have developed respiratory dysfunction later. The connection between these two systems has become interesting lately and has led to several studies to prove the association. Several theories have emerged to explain this association. This includes changes in microbiota, the mucosa-related immune system of both systems, side effects of the therapeutic given, and pathomechanism related to gastrointestinal diseases such as GERD. Many studies try to prove the connection between the microbiota in the respiratory and gastrointestinal system, and changing the abundance in one of the systems can affect another. Both of the systems also have a similar mucosal membrane in their lining. Those membranes have an immune defence called Mucosal-Associated Lymphoid Tissue (MALT). Lymphatic and circulatory systems facilitate the migration between two mucosal, and these interconnections influence each other. Although the side effect of the therapeutic agent in respiratory diseases (such as inhaled corticosteroid, beta-2 agonist, or anti-cholinergic) is thought to be one of the causative mechanisms, discontinuation of therapy is the second option. Probiotic supplementation to improve microbiota is still not a strong recommendation for management.

COMPARATIVE ANALYSIS ON NON-VENTILATORY MANAGEMENTS IN ACUTE ASTHMA

Introduction: Acute asthma attacks or acute asthma can be defined as episodes of progressive increase in shortness of breath, cough, wheezing, chest tightness, or some combination of these symptoms. It includes the aggravation, inflammation, and obstruction of the bronchial tubes, which permit air all through the lungs. Most exacerbations are overseen in the outpatient setting. In the United States in 2004 there were 14.7 million visits to doctor workplaces and clinic outpatient divisions for acute asthma. In pediatric patients, a scoring rubric called the Pediatric Respiratory Assessment Measure (PRAM) has been created to evaluate a patient's acute asthma seriousness utilizing a mix of scalene muscle compression, suprasternal withdrawals, wheezing, air entry, and oxygen saturation. noninvasive ventilation has a few possible upper hands over intubation and intrusive mechanical ventilation: there are fewer requirements for sedation, the patient is allowed to talk, ventilation can be briefly suspended to permit the patient to take tastes of liquid or to cough and expectorate, and there is a lower hazard of ventilator-related pneumonia&#x0D; Aims and Objectives: The study intended to compared the efficiency of using oxygen inhalation and rapid-acting bronchodilator as first line management of acute exacerbant asthma.&#x0D; Materials and Methods: The study design is retrospective cross-sectional which was conducted during the period of 7 Months The study has considered 100 patients, among which 45 patients are male and 55 patients are female. The patients who visited the Emergency Department were considered. The patients on arrival to the emergency department was assessed for PRAM score (Initial PRAM score) and was interpreted. Then either oxygen or Short-Acting Beta Agonist (Salbutamol) inhalation was given. Then again, after a fixed interval, the patient’s PRAM score was assessed (Post-Interventional PRAM score). PRAM score was assessed and interpreted.&#x0D; Result: The study found that, after intervention, Group 1 achieved PRAM score of 4.48±1.41 in Group 1 (Oxygen group) while Group 2 (Short-Acting Beta Agonist inhalation) achieved 6.12±1.47. It was found that in patients of Group 1, the mean of changes in all the patients was 6 while in the patients of Group 2 was 4.18.&#x0D; Conclusion: The study concludes that the acute asthmatic episode in emergency department can be managed by oxygen inhalation better than Short-Acting Beta Agonist inhalation. Oxygen inhalation is easier to give as compared to intubation and is also efficient in lowering PRAM score and hence, evidently showed the efficacy for proper management of severe acute asthma in emergency setting.&#x0D; Keywords: pram, acute asthma, oxygen, salbutamol, non-ventilatory

The Natural Estrogen Receptor Beta Agonist Silibinin as a Promising Therapeutic Tool in Diffuse Large B-cell Lymphoma.

About 40% of patients with diffuse large cell lymphoma (DLBCL) still have a poor prognosis. Additionally, DLBCL patients treated with doxorubicin are at risk of cardiac failure. Growing evidence suggests an antitumor and cardioprotective activity exerted by estrogen via its binding to estrogen receptor (ER) β. The aim of this study was to evaluate the anticancer activity of the phytoestrogen silibinin, an ERβ selective agonist, on DLBCL growth, and its potential cardioprotective effect. DLBCL cell lines SUDHL-8, SUDHL-6, and RIVA were used. The anti-tumor activity of silibinin was also evaluated in vivo in NOD/SCID/IL2Rg-/- (NSG) xenografted mice. AC16 human ventricular cardiomyocytes were used to investigate the cardioprotective effects of silibinin. In vitro silibinin induced apoptosis and autophagy, and blocked tumor cell proliferation, also protecting AC16 cardiomyocytes from doxorubicin-induced toxicity. In vivo silibinin induced cell death and autophagy, and reduced tumor volume. Silibinin represents a promising therapeutic tool.

Recent Advances in Long-Term Management of Asthma.

Asthma is one of the most common chronic diseases of childhood with significant morbidity. Management of asthma has evolved from inhaled corticosteroids to personalized therapy in recent years. This article summarizes the recent advances in the management of asthma. The severity of asthma is assessed retrospectively by the level of treatment required to control asthma symptoms.Recently, there has been an emphasis on not to use short-acting beta-2 agonist (SABA) alone, even for intermittent or mild asthma. Single maintenance and reliever therapy (MART) is increasingly being recommended. Asthma therapy should be personalized based on phenotype (clinical presentations) and endotypes (distinct mechanistic pathways) of asthma and by a continuous cycle of assessment of asthma control and risk assessment, treatment, and reviewing the response in children on treatment. Various add-on therapy like tiotropium and biological monoclonal antibodies have been approved for use in a subset of children with severe asthma. Before considering biologicals, it is vital to have a proper diagnosis, good compliance and inhaler technique, and treatment of comorbidities.

The estrogen receptor beta agonist liquiritigenin enhances the inhibitory effects of the cholesterol biosynthesis inhibitor RO 48-8071 on hormone-dependent breast-cancer growth.

Most hormone-dependent human breast cancers develop resistance to anti-hormone therapy over time. Our goal was to identify novel treatment strategies to avoid this drug resistance and thereby control hormone-dependent breast cancer. Sulforhodamine B assays were used to measure viability of cultured human breast-cancer cells. BT-474 cell tumor xenografts in nude mice were used to evaluate tumor growth. Immunohistochemistry was used to assess estrogen-receptor and angiogenesis-marker expression, as well as apoptosis, in tumor-xenograft tissues. MCF-7 and BT-474 breast-cancer cells treated with either RO 48-8071 <[4'-[6-(Allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate] [RO]; a small-molecule inhibitor of oxidosqualene cyclase, a key enzyme in cholesterol biosynthesis> or liquiritigenin [LQ; an estrogen receptor (ER) β agonist] exhibited significantly reduced viability in vitro. RO + LQ treatment further significantly reduced cell viability. Administration of RO, LQ, or RO + LQ significantly inhibited growth of BT-474 tumor xenografts in vivo. RO, LQ, or RO + LQ reduced ERα but induced ER β expression in tumor xenografts. Both compounds significantly reduced angiogenesis-marker expression and increased apoptosis in tumor xenografts; use of RO + LQ significantly enhanced the effects observed with a single agent. The ERβ ligand LQ significantly enhanced the inhibition of breast-cancer cell viability and tumor-xenograft growth by RO. The anti-tumor properties of RO may in part be due to an off-target effect that reduces ERα and increases ERβ, the latter of which can then interact with LQ to promote anti-proliferative effects. The RO + LQ combination may have value when considering novel treatment strategies for hormone-dependent breast cancer.

ЕВОЛЮЦІЯ РЕКОМЕНДАЦІЙ GINA. ПРАКТИЧНІ АСПЕКТИ ЛІКУВАННЯ ПАЦІЄНТІВ З АСТМОЮ ЧЕРЕЗ ПРИЗМУ КЛІНІЧНИХ ДОСЛІДЖЕНЬ

EVOLUTION OF GINA GUIDELINES. PRACTICAL ASPECTS OF ASTHMA MANAGEMENT THROUGH THE PRISM OF CLINICAL TRIALS S. V. Zaikov, F. T. Bogomolov, G. L. Gumeniuk Abstract Through the 28 years lifetime of GINA (Global Initiative for Asthma) recommendations, there’s been a shift in the paradigm of asthma management. GINA is a Global Strategy of treatment and prophylaxis of asthma, established by National Heart, Lung and Blood Institute in collaboration with National Institute of Health and World Health Organization in 1993. First published in 1995 GINA report has become a widespread consensus, which made a basis for clinical recommendations on asthma worldwide. One can define three major periods in evolution of GINA. The first period covered 1994–2004 years since GINA originated and first edition published until experts have recognized the advantage of inhaled rout of asthma drugs administration. It was proved that in many patients the main goal was establishing asthma control, while combination of inhaled corticosteroid with long-acting beta agonist (ICS/LABA) was a preferred option in moderate persistent asthma. In this period it was recommended to chose an approach to managent of asthma, based on scientific evidence, rather then expert’s opinion. In this regard, a second period (2005–2014 years) should be considered outstanding, due to the change in perception of major goals of asthma management, considering exclusively data from numerous studies. Such concepts as patient-medical personnel partnership, patient’s education, guided self-control and goals of treatment have been introduced. GINA recommends to use asthma control as a major approach to treatment instead of severity of disease. Personalized treatment should be aimed on exacerbation risk reduction. Steps 3-5 of treatment algorithm were modified to include ISC-formoterol for maintenance therapy and relief of symptoms (MART-therapy). Third period of GINA started after SYGMA 1 and 2 studies results became available. It was demonstrated that on-demand symptom-relief use of anti-inflammatory therapy with ICS/formoterol combination was highly effective in mild asthma patients. Use of this combination as rescue medication decreased the risk of exacerbation in comparison with short-acting beta agonist (SABA) and may be used in any variant of asthma. Since GINA 2019 edition SABA became not the only one available option even for the mildest forms of asthma. Eventually, in 2021 the culmination of GINA evolution occurred: major algorithm of asthma management has been divided in two tracks: preferred (Track 1) therapy with ICS/formoterol and alternative (track 2) therapy with SABA as rescue medication. The authors of this article review in details the periods of GINA evolution, resulted in dividing asthma management into two tracks, which provide personalized treatment strategy considering all patient’s needs and characteristics such as fast relief of symptoms, decreased risk of exacerbation and establishing asthma control. Key words: asthma, GINA, evolution of treatment approaches. Ukr. Pulmonol. J. 2022;30(1):6–14

An audit of patients admitted to hospital in Nepal for COPD exacerbation.

Objectives:Chronic obstructive pulmonary disease is a large and increasing problem in low- and middle-income countries; Nepal is no exception. We aimed to obtain information on patient characteristics and the level of care provided to patients admitted for acute exacerbation of chronic obstructive pulmonary disease in two Nepalese hospitals and to compare the given care with the Global Initiative for Chronic Obstructive Lung Disease guidelines.Methods:This was a cross-sectional, observational, descriptive study. All patients admitted to two Nepalese hospitals due to acute exacerbation of chronic obstructive pulmonary disease between 18 February and 5 April 2019 were asked to participate.Results:In total, 108 patients with a median age of 70 years participated. Fifty-three (42.7%) were male, 80 (74.8%) were former smokers, and 46 (45.1%) were farmers. Using the Global Initiative for Chronic Obstructive Lung Disease A-D classification, 97 (90.6%) of the patients were classified in group D. All the patients received supplementary oxygen treatment and 103 (95.4%) were treated with short-acting beta2 agonists. A total of 105 (97.2%) patients received antibiotics, and 80 (74.5%) received systemic corticosteroids. The majority was discharged with triple therapy including long-acting muscarinic antagonist, long-acting beta2 agonist, and inhaled corticosteroids, and 72 (75.8%) were discharged with long-term oxygen treatment.Conclusion:All elements of the Global Initiative for Chronic Obstructive Lung Disease guidelines were applied. However, due to a lack of information, it cannot be concluded whether the treatment was provided on the correct indications. The average patient received almost all the treatment alternatives available. This might indicate a very sick population or over-treatment.

Пациент с тяжелой бронхиальной астмой: биологическая терапия vs системные кортикостероиды

Severe bronchial asthma (SBA) is associated with a significantly lower quality of life and increased mortality. The prevalence of SBA is 3–10% of all patients with asthma. The diagnosis of SBA means that patients require high doses of inhaled corticosteroids/long-acting beta agonists (ICS/LABA) or a fixed dose combination of ICS/LABA and long-acting anticholinergics (ICS/LABA/LAAC). If the above therapy is not effective, systemic glucocorticoids (GCs) are commonly prescribed to treat patients with SBA. However, their use increases the risk of such adverse events as fractures, disorders of carbohydrate metabolism, gastrointestinal bleeding, infections, and visual disturbances. In most cases the SBA development is linked to T2-high inflammation which is manifested by elevated eosinophil level in the peripheral blood. In turn, eosinophilia is associated with an increased rate of asthma exacerbations and resistance to the standard anti-inflammatory therapy. Suppression of eosinophil activity is a promising approach to pathogenetic therapy of SBA. The up-to-date biological therapy with monoclonal antibodies helps to improve asthma control, reduce the number of exacerbations and to reduce systemic GCs or even to avoid them. Currently, targeted therapy for SBA includes medicines to circulating IL-5 (mepolizumab, reslizumab), its receptor alpha-subunit, IL-5RA (benralizumab), or IL-4 receptor alpha-subunit (dupilumab). Benralizumab induces potent eosinophil apoptosis, resulting in rapid and nearly complete depletion of eosinophils in the blood and target tissues. KEYWORDS: severe bronchial asthma, biological therapy, benralizumab, interleukin-5, eosinophilic inflammation, systemic corticosteroids. FOR CITATION: Titova O.N., Kuzubova N.A., Sklyarova D.B. A patient with severe bronchial asthma: biological therapy vs systemic corticosteroids. Russian Medical Inquiry. 2022;6(7):393–398 (in Russ.). DOI: 10.32364/2587-6821-2022-6-7-393-398.

Drug-repositioning indicates a way to conquest corticosteroid-insensitivity

Recent advance of medications and devices brings more effective treatment intervention to the patients with asthma. As far as obeying guidelines, approximately 90% of patients with asthma acquire good control. However, there are still small number of patients with asthma who resist conventional treatment. Most of them are corticosteroid-insensitive. It would be thought that there are two ways to deal with this problem. The first one is biologics. However, these are very expensive. The second way is a treatment intervention focusing on cancellation of corticosteroid-resistance. In early 2010s, a new-intracellular signaling pathway (phosphatydilinositol-3-kinese: PI3K pathway) is proven to be closely associated with corticosteroid-resistance. PI3K-inhibitor should be one of the promising candidates to attenuate corticosteroid-resistance. But PI3K-inhibitor also has a toxicity when given systemically. Drug-repositioning (DR) is a good option to deal with it. To find out PI3K-inhibitor from numerous medicines gives an answer how to inhibit PI3K pathway. The presenter has found both low-dose theophylline and long-acting beta-2 agonist have a potential to antagonize PI3K. These medicines have been prescribed for decades and their safety has already been proved. It is possible for clinicians to inhibit PI3K activation in patients with asthma associated with corticosteroid-resistance using these medicines without waiting for development of bran-new PI3K inhibitors. DR revealed that nortriptyline acts as a steroid-enhancer via its anti-PI3K activity. Calcium-channel blocker saves lung function in patients with asthma in long-term observation. DR promises us to find cheap and safe options to treat difficult asthma by inhibiting specific intracellular signaling pathways.

Role of Ipratropium bromide in management of Thunderstorm asthma

Epidemic thunderstorm asthma has been reported to have occurred around twenty times over the past three decades in locations around the world. Thunderstorm asthma events are characterized by a significant increase in asthma presentations, which on occasion can overwhelm local medical services and result in fatalities. Thunderstorm asthma (TA) typically presents during an aeroallergen season in individuals, sensitized to perennial rye grass pollen (RGP) in Australia, in combination with meteorological factors such as thunderstorms and lightning activity. Short acting beta agonist (SABA) only treatment is sub-optimal therapy for prevention of asthma exacerbations. The combined treatment includes inhaled corticosteroids (ICS) and SABA but is found to be contentious. So the present review focuses on suitable alternative, short acting muscarinic antagonist (SAMA), Ipratropium bromide and its efficacy on the management of allergic asthma. Salbutamol induces bronchodilation rapidly but it elicits profound cardiovascular event as the side effects. Meanwhile, ipratropium also has equivalent effect of salbutamol with low side effect profile. Ipratropium also minifies the asthmatic response to grass pollen, allergen induced bronchoconstriction. Further, it also reduces allergen induced early and late asthmatic response and also inhibits the response towards histamine inhalation. In this regard, ipratropium may be considered as a suitable agent in the management of thunderstorm asthma and future trials are highly warranted. Keywords: Thunderstorm asthma, grass pollen, rye grass, short acting beta agonist, Ipratropium bromide

Major change in asthma management

According to the latest recommendations, there is no longer place for the use of short-acting beta-2 agonist alone in chronic asthma treatment, due to an increased risk of severe exacerbations and exacerbation-related mortality. Current management of asthma is based on the use of inhaled corticosteroids in combination with formoterol as maintenance and as rescue treatment, thanks to the rapid and prolonged action of formoterol. General practitioners must evaluate, with the patient's collaboration, the treatable factors linked to poor asthma control. They should provide patients with a written treatment plan in order to help patients recognize and manage asthma exacerbation. The place of the pulmonary specialist is currently reserved for the advanced stages of the disease and in case of diagnostic doubt.