Including Inhaled Corticosteroids Research Articles

Delphi Consensus on Clinical Applications of GOLD 2023 Recommendations in COPD Management: How Aligned are Recommendations with Clinical Practice?

The objective of this Delphi study was to understand and assess the level of consensus among respiratory experts on the clinical application of GOLD 2023 recommendations in management of patients with chronic obstructive pulmonary disease (COPD). The study comprised two online surveys and a participant meeting with 34 respiratory experts from 16 countries. Responses of 73 questions were recorded using a Likert scale ranging from 0 (disagreement) to 9 (agreement). The consensus threshold was 75%. Survey 1 and survey 2 had 34 and 32 participants, respectively; and 25 attended the participant meeting. Consensus was reached on survey 1: 28/42; survey 2: 18/30 close-ended questions. A consensus was reached on the clinical relevance of most updates in definitions and diagnosis of COPD. Mixed results for the treatment recommendations by GOLD were noted: 74% agreed with the recommendation to initiate treatment with dual bronchodilators for group E patients; 63% agreed for including inhaled corticosteroids (ICS)/long-acting β2 agonist(LABA)/ Long-acting muscarinic receptor antagonists (LAMA) as a treatment option for GOLD B patients. Also, consensus lacked on removing ICS + LABA as an initial therapeutic option, in countries with challenges in access to other treatment option;. 88% agreed that they use GOLD recommendations in their daily clinical practice. This Delphi study demonstrated a high level of consensus regarding key concepts of GOLD 2023 report, with most participants favoring recent updates in definitions, diagnosis, management, and prevention of COPD. More evidence on the etiotype based management and treatment options for group B and E are required which could further strengthen clinical application of the GOLD report.

COVID-19 in Patients with Asthma: Review and Implications for Care of Adult Patients with an Osteopathic Component

Patients with asthma who have COVID-19 typically present with rhinitis, rhinosinusitis, cough, and shortness of breath and rarely with wheezing. Family physicians should consider a patient’s asthma subtype, pertinent medical history, and medications. Maintenance medications, including inhaled corticosteroids (ICS), should be continued for most patients. Whether to start ICS in patients with asthma who have COVID-19 should be considered, as the risks and benefits are unclear, and systemic corticosteroids should be avoided in patients with asthma who have COVID-19 if alternatives exist. Pregnant patients with both asthma and COVID-19 should be comanaged by an obstetrician, with consideration for early induction of labor. Behavioral health topics and osteopathic principles and manipulative techniques should be considered in patients with COVID-19 and asthma. Generalities are challenging to make, but patients with asthma do not seem to have worse outcomes with COVID-19 than patients without asthma.

Correct treatment regimen and inhalation technique are the components of success in bronchial asthma in the era of COVID-19

The goal of Asthma treatment is to achieve a controlled condition, that is, to minimize the burden of symptoms and the risk of exacerbations. Many factors hinder the achievement of this goal: non-compliance with recommendations for drug therapy, the influence of concomitant diseases, the impact of triggers, low patient adherence to prescribed treatment, violation of inhalation technique. In general, there is no significant difference in the risk of hospitalization or mortality due to COVID-19 in patients with Asthma. At the same time, studies show that non-allergic Asthma, severe Asthma, Asthma in combination with obesity, lack of adequate basic therapy can create the greatest risk of infection and severe clinical outcomes of COVID-19. Asthma can be a predictor of a prolonged intubation period in severe respiratory failure during COVID-19, especially in people younger than 65 years. GINA experts agree that during a pandemic, it is especially important that patients with Asthma continue taking basic therapy, including inhaled corticosteroids (ICS), as prescribed by the recommendations. ICS therapy in combination with long-acting β2-agonists (LABA) is the main pharmacological method of treating moderate and severe Asthma in adolescents and adults. A single inhaler regimen with the use of a combination of ICS/formoterol is associated with a lower risk of severe exacerbations compared with supportive treatment of ICS/LABA in combination with SABA on demand. Studies show that the technique of inhalation maneuver can significantly affect the success of therapy. A wide variety of DPI causes problems with the choice and use by patients.

Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting β2-agonists and corticosteroids.

Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis.Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment.Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects.Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.

The Effects of Inhaled Airway Directed Pharmacotherapy on Decline in Lung Function Parameters Among Indigenous Australian Adults With and Without Underlying Airway Disease.

BackgroundThe trajectory of lung function decline among Indigenous patients with or without underlying chronic airway disease (COPD and concomitant bronchiectasis) and with use of inhaled pharmacotherapy, including inhaled corticosteroids (ICS), has not been reported in the past.MethodsAdult Indigenous Australian patients identified to have undergone at least two or more lung function tests (LFTs) between 2012 and 2020 were assessed for changes in the lung function parameters (LFPs) between the first and last recorded LFTs.ResultsOf the total 1350 patients identified to have undergone LFTs, 965 were assessed to fulfil session quality, 115 (n=58 females) were eligible to be included with two or more LFTs. Among the 115 patients, 49% showed radiological evidence of airway diseases, and 77% were on airway directed inhaled pharmacotherapy. Median time between LFTs was 1.5 years (IQR 0.86,5.85), with no significant differences in LFPs noted between first and last LFT. Overall rate of change (mL/year) showed considerable variation for FVC (median −37.55 mL/year [IQR −159.88,92.67]) and FEV1 (−18.74 mL/year [−102.49,71.44]) with minimal change in FEV1/FVC (0.00 ratio/year [−0.03,0.01]). When stratified by inhaled pharmacotherapy group, however, patients using ICS showed significantly greater rate of FEV1 decline (−48.64 mL/year [−110.18,62.5]) compared to those using pharmacotherapy with no ICS (15.46 mL/year [−73.5,74.62]) and those using no pharmacotherapy (−5.76 mL/year [−63.19,67.34]) (p=0.022). Additionally, a greater proportion of these patients reached the threshold for excessive FEV1 decline (64%) compared to those using pharmacotherapy without ICS (44%) and those using no pharmacotherapy (52%).ConclusionDecline in LFPs occurs commonly among adult Indigenous population, especially, excessive so among those using inhaled pharmacotherapy containing ICS.

ІНГАЛЯЦІЙНІ КОРТИКОСТЕРОЇДИ В ЛІКУВАННІ ПАЦІЄНТІВ З COVID-19

INHALED CORTICOSTEROIDS IN THE TREATMENT OF PATIENTS WITH COVID-19 S. V. Zaikov Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine Abstract. Theoretically, patients with bronchial asthma (BA) should have an increased susceptibility to SARS-CoV-2 infection, its more severe course and a high risk of exacerbation of asthma due to a lack of antiviral protection. However, a number of studies have shown that asthma not only does not cause a severe course of new coronavirus infection, but can also have a certain protective effect. Thus, people with asthma have a lower susceptibility to COVID-19, a less severe course and a lower risk of hospitalization due to COVID-19. But more recent reports from the United States, several European countries, including the United Kingdom, and South Korea report a higher prevalence of asthma in patients with COVID-19, and suggest that asthma is more common in patients with COVID-19 than in other patients. A joint study by OpenSAFELY (UK) noted a significant increase in the risk of severe COVID-19 disease and mortality among patients with asthma, especially those with recent illnesses who required oral corticosteroids. Therefore, further research is needed in this direction to improve our understanding of the relationship between asthma and the severity of COVID19. At present, however, it seems logical to include patients with asthma in the risk groups for COVID-19. Experts from international asthma groups stress that in a COVID-19 pandemic, patients with asthma should continue to receive basic therapy, including inhaled corticosteroids (ICS). There is also evidence that allergic asthma or its eosinophilic phenotype, taking ICS have a positive effect on the course of COVID-19, because in such patients the level of expression of angiotensin-converting enzyme 2 (ACE-2) in the upper and lower respiratory tract, which is the entrance receptors for SARS-CoV-2 virus is lower. ICS, such as budesonide or ciclesonide, are able to inhibit the replication of SARS-CoV-2 genomic RNA through exposure to viral endonuclease NSP15 and TMPRSS-2 (serine 2 transmembrane protease), a protease involved in the virus entry into the cell. Some ICS (including budesonide) reduce or block SARS-CoV-2 replication in vitro. And according to the results of current studies, the appointment of ICS, in particular budesonide, in patients with COVID-19 reduces the risk of hospitalization or the need for emergency care by 91 % and significantly accelerates clinical recovery. Unfortunately, there are currently no specific etiotropic therapies for SARS-CoV-2 infection, but physicians should use all potential measures to reduce the risk of severe disease. One of such measures is the use of ICS, which may be promising drugs for COVID-19. However, this issue needs further study. Key words: inhaled corticosteroids, COVID-19, bronchial asthma. Sergii V. Zaikov Shupyk National Healthcare University of Ukraine Doctor of medicine, Professor of phthisiology and pulmonology department, 10, M. Amosova str., 03038, Kyiv, Ukraine, zaikov1960@gmail.com Аsthma and Allergy, 2021, 3, P. 5–15

The use of short-acting beta-2 adrenergic receptor agonists for asthma increased among Finnish and Swedish children from 2006 to 2017.

Paediatric asthma hospitalisation has decreased in Finland, but has remained stable in Sweden. The reasons for these intercountry differences are unclear. The aim of this study was to explore the trend of dispensed asthma medication, including inhaled corticosteroids (ICS), among paediatric populations in the two countries. We explored trends in dispensed asthma medication among paediatric populations aged 0-19 in Finland and Sweden from 2006 to 2017. The Finnish Statistics on Reimbursements for Prescription Medicines and The Swedish Prescribed Drug Register provided data on all dispensed asthma prescriptions. During the study period, the prevalence of dispensed ICS in paediatric populations was fairly stable in Finland and Sweden. Among children aged 0-4, ICS were 1.5 times more commonly dispensed in Sweden than in Finland. The prevalence of children dispensed short-acting beta-2 adrenergic receptor agonists (SABA) increased in both countries, but rose more in Finland (51%) than in Sweden (27%). Inhaled corticosteroids were more commonly dispensed for children aged 0-4 in Sweden than in Finland during the study period. This study showed an increasing prevalence of children dispensed SABA in Finland and Sweden, particularly in Finland. Differences and trends in asthma medication may effect asthma hospitalisation and asthma deaths.

Positioning of Long-Acting Muscarinic Antagonists in the Management of Asthma.

Despite a range of efficacious therapies for asthma, including inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), a significant proportion of patients have poor asthma control and retain a risk of future worsening of their symptoms. Long-acting muscarinic antagonist (LAMA) bronchodilators offer a well-tolerated, efficacious, and cost-effective add-on to a patient's treatment. Of the LAMAs currently under investigation or available for the treatment of asthma, evidence from a comprehensive clinical trial program in adults and children shows that once-daily treatment with tiotropium provides benefits for patients with uncontrolled asthma despite the use of ICS and LABAs. Tiotropium is included in the Global Initiative for Asthma (GINA) strategy document as an add-on therapy option for patients at Step 4 or 5 with a history of asthma exacerbations. Tiotropium Respimat® has demonstrated safety and efficacy in patients with a range of disease severities, ages, and phenotypes. This review describes the evidence for the use of LAMA as add-on therapy for patients with asthma who remain uncontrolled despite the use of ICS and LABA treatments.

Inhaled steroids / long6acting β2-agonists in treatment of chronic obstructive pulmonary disease: the discussion goes on

Chronic obstructive pulmonary disease (COPD) is an actual healthcare problem. Inflammation is a part of pathogenesis of COPD; therefore, antiinflammatory agents including inhaled corticosteroids (ICS) play an important role in therapy of this disease. Favorable effects of ICS on outcomes of COPD were confirmed, but treatment with ICS in these patients is associated with an increased risk of adverse events, particularly pneumonia. Results of clinical trials demonstrated long"term effects of ICS and long"acting β2"agonists (LABA) in patients with different stages of COPD. Efficacy and safety of novel fluticasone furoate / vilanterol once"daily combination have been discussed in this review. Data on pneumonia as the most troubling adverse effect of ICS / LABA treatment and recent evidence on class specificity of this effect have been reviewed. Blood eosinophilia is considered as a biomarker that potentially could distinguish patients who would have more benefit from ICS prescription.

Use of Leukotriene Receptor Antagonists Are Associated With a Similar Risk of Asthma Exacerbations as Inhaled Corticosteroids

AC Wu, L Li, V Fung. J Allergy Clin Immunol Pract. 2014;2(5):607–613 To assess the risk of asthma exacerbation in children with asthma treated with various controller medications, including inhaled corticosteroids (ICS), leukotriene antagonists (LTRA), and ICS/long-acting β-agonist combinations (ICS-LABA). The study subjects included 26 191 controller-naive asthmatic children aged 4 to 17 years with uncontrolled asthma defined as at least 1 previous asthma exacerbation in the preceding year requiring an ED visit, hospitalization, or a short course of oral corticosteroids. Subjects were recruited from the databases of 6 private health plans (59%) and from the Tennessee Medicaid population (41%). This was a retrospective cohort study of …

Association between inhaler use and risk of haemoptysis in patients with non-cystic fibrosis bronchiectasis.

Inhaled medications have been widely applied to patients with airflow limiting non-cystic fibrosis (non-CF) bronchiectasis. However, the association between the use of inhalers and the development of haemoptysis has rarely been explored. The objective of this study was to assess the association between the risk of haemoptysis and the use of inhalers in patients with non-CF bronchiectasis. A nested case-control study was performed using a national claims database from 1 January 2009 to 31 December 2011. Inhalers including inhaled corticosteroids (ICS), long-acting β2 agonists (LABA), long-acting muscarinic antagonists (LAMA), short-acting β2 agonists (SABA), short-acting muscarinic antagonists (SAMA) and their combinations were tested for the risk of clinically significant haemoptysis events. Among the 62 530 eligible new users of inhalers with non-CF bronchiectasis, 6180 patients with haemoptysis and 27 486 strictly matched controls were selected. In the unadjusted analyses, SAMA, LAMA, SABA and ICS/LABA significantly increased the risk of haemoptysis. After adjustment for other inhaled respiratory medications, comorbidities, health-care utilization and concomitant medications, SAMA, SABA and LAMA consistently increased the risk of haemoptysis (SAMA: odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-1.4; LAMA: OR, 1.2; 95% CI: 1.1-1.2; SABA: OR, 1.2; 95% CI: 1.1-1.2). The association between anticholinergics (SAMA and LAMA) and risk of haemoptysis showed a dose-dependent trend (P for trend, <0.001). The use of SABA and inhaled anticholinergics in patients with non-CF bronchiectasis increased the risk of haemoptysis. The risk-benefit ratio of inhaled bronchodilators should be considered in the haemoptysis-susceptible population.

Chapter 16: Asthma in pregnancy

The course of asthma during pregnancy may be affected by maternal physiological changes and triggers of asthma such as viral infections, exposure to allergens, and nonadherence with therapy. If asthma is uncontrolled, there are recognized harmful effects not only to the mother but also to the fetus. However, with effective asthma control, most women have outcomes, at or near that of the general population. Many medications are considered appropriate for use in pregnancy including inhaled corticosteroids (ICSs) such as budesonide, beclomethasone dipropionate, and fluticasone and the leukotriene receptor antagonists montelukast and zafirlukast. When ICSs or ICS/long-acting beta(2)-adrenergic agonist combinations are not effective during exacerbations of asthma, short courses of oral corticosteroids should be administered earlier rather than later. Spirometry and flow volume loop tracings are useful measures of pulmonary function for gravidas. Results may be compared with nonpregnant reference values. Vocal cord dysfunction may be suspected when the inspiratory loop is truncated. The gravida does not reject the fetus because of lack of vascular continuity, a trophoblast layer causing separation, and suppressive mechanisms at the placental interface. The secretion of IL-10 increases in pregnancy and is lower in women with recurrent spontaneous abortions. Only immunoglobulin G (IgG) subclasses are transported across the placenta, especially IgG1, IgG3, and IgG4. Fetal B cells can produce endogenous IgE by 20 weeks of gestation.

Asthma Mortality and Long-Acting Beta2-Agonists in Five Major European Countries, 1994–2004

Objectives. Over the last few decades, important changes occurred in the pharmacological approach to asthma control. However, the possible link between pharmacologic treatment and asthma death remains controversial. Study Design and Setting. Age-standardized asthma mortality rates were computed over the 1994–2004 period for France, Germany, Spain, the UK, and Italy. Rates for children and young adults 5 to 34 years of age, middle age adults 35 to 64 years of age, and elderly adults ≥ 65 years. Joinpoint regression was performed to identify years where significant changes in mortality trends occurred. Consumption of inhaled long-acting beta-2-agonists (LABA), including inhaled corticosteroids (ICS) when combined with LABAs in a single inhaler, derived from sales estimates. Results. In 1994, the highest asthma mortality rates were in Germany (4.7/100,000), and the lowest ones were in Italy and Spain (0.5/100,000). Steady downward trends were observed in all the countries considered. The largest decline was registered in Germany and the smallest one was in the UK. LABA sales increased steadily since 1994, particularly in France, Spain, and the UK, reaching values around 14 Defined Daily Doses (DDD)/1,000 inhabitants in 2004. Conclusion. While the use of LABAs (with or without ICS) increased over the last decade, asthma mortality declined in major western European countries.

Successful Treatment of Previously Uncontrolled Adult Asthma with Budesonide Inhalation Suspension: Five-Year Case Histories

To determine whether nebulized budesonide inhalation suspension (BIS) is effective in treating adults with asthma that has been uncontrolled by inhaled therapies. Three adults with severe persistent asthma were switched to BIS after poor outcomes with other controller medications, including inhaled corticosteroids (ICSs). BIS dosages were initiated with 1 mg twice daily. Based on physician discretion as symptoms improved, dosages were decreased to 0.5 mg twice daily (2 pts.) or once daily (1 pt.). Patients were instructed to self-manage their asthma, increasing their dosages during periods of asthma worsening. Peak expiratory flow (PEF) was assessed before and after the initiation of BIS. The number of healthcare visits and oral corticosteroid courses recorded in patient medical records during the 3 years before and 5 years after initiation of BIS therapy were compared. In all 3 cases, BIS improved asthma control. BIS consistently increased PEF and reduced the number of urgent care visits and oral corticosteroid courses. All patients reported satisfaction with BIS therapy. Despite proven effectiveness of ICSs for persistent asthma, some patients fail to respond optimally to treatment administered via an inhaler. These 3 case reports suggest that BIS is effective in treating adults with severe persistent asthma who fail to respond optimally to treatment with other ICS preparations. Failure to use inhalers properly, previous poor adherence in 1 case, or patient preference for the nebulizer might explain why nebulized BIS was more effective than other inhaler therapies. Switching adults with uncontrolled asthma to BIS therapy may be a valuable treatment option for those who are unable to achieve optimal asthma control, despite asthma education and training on inhaler technique.

Cost-effectiveness of budesonide Turbuhaler in the treatment of mild-to-moderate asthma in Japan

ABSTRACT Asthma therapy including inhaled corticosteroids (ICS) has been shown to be effective in many parts of the world, but its use is still limited in Japan. A 6-week, randomized, placebo-controlled, clinical trial was therefore undertaken to assess the efficacy of the ICS budesonide Turbuhaler (budesonide administered via the dry-powder inhaler Turbuhaler) in patients in Japan with mild-to-moderate asthma. Prior to, and during, the study, all concomitant medications, except corticosteroid preparations, were allowed (i.e. all pre-study medication was to be maintained throughout the study). In total, 218 patients randomized to receive budesonide Turbuhaler 200μg/day ( n = 53), 400μg/day ( n = 55), 800μg/day ( n = 57) or placebo ( n = 53) were included in the analysis. Due to the increased demand and interest for health economic data in Japan, this retrospective cost-effectiveness analysis reports on the economic impact of budesonide Turbuhaler compared with placebo (i.e. usual care), based on this clinical trial. At each dosage, budesonide Turbuhaler was significantly more effective than the placebo, according to the number of symptom-free and episode-free days. The number of emergency visits, days of lost production and days of hospitalization were all lower in the budesonide Turbuhaler groups, leading to significantly ( P

Cross-sectional study of bone density in asthmatic children.

The emphasis in treatment of asthma in children has shifted from bronchodilators to inhaled anti-inflammatory medications, including inhaled corticosteroids (ICS). Children with chronic asthma and moderate to severe symptoms have been targeted as particularly deserving of maintenance therapy with ICS. We have previously reported a cross-sectional study of bone density in children treated with ICS. There was no significant difference between the total bone density of asthmatic patients and controls. We sought to extend the information available on bone density in asthmatic children by evaluating 15 asthmatic subjects taking daily ICS (beclomethasone dipropionate) and comparing them with age- and sex-matched controls. We compared total and regional bone density, bone age, and calcium intakes in these subjects. Asthmatic subjects were on ICS for 4-60 months, with doses ranging from 200 to 450 micrograms/day. There was no significant difference between asthmatics and matched controls for height, weight, % RDA Ca2+, or bone age. The asthmatic subjects had bone density (total and regional measurements) equivalent to their controls. These results provide additional support for the safety of low-dose ICS on bone density in asthmatic children.