Classes Of Asthma Medications Research Articles

Asthma medication use in obese and healthy weight asthma: systematic review/meta-analysis.

Obesity is a common comorbidity in asthma and associated with poorer asthma control, more frequent/severe exacerbations, and reduced response to asthma pharmacotherapy. This review aims to compare use of all classes of asthma medications in obese (body mass index (BMI) ≤30 kg·m-2) versus healthy-weight (BMI <25 kg·m-2) subjects with asthma. Databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, Embase and MEDLINE were searched up to July 2019 for English-language studies that recorded medication use or dose in obese and healthy-weight adults with asthma. A critical appraisal checklist was utilised for scrutinising methodological quality of eligible studies. Meta-analysis was performed and heterogeneity was examined with the use of the Chi-squared test. This review was conducted based on a published protocol (www.crd.york.ac.uk/PROSPERO CRD42020148671). Meta-analysis showed that obese subjects are more likely to use asthma medications, including short-acting β2-agonists (OR 1.75, 95% CI 1.17-2.60; p=0.006, I2=41%) and maintenance oral corticosteroids (OR 1.86, 95% CI 1.49-2.31; p<0.001, I2=0%) compared to healthy-weight subjects. Inhaled corticosteroid (ICS) dose (µg·day-1) was significantly higher in obese subjects (mean difference 208.14, 95% CI 107.01-309.27; p<0.001, I2=74%). Forced expiratory volume in 1 s (FEV1) % predicted was significantly lower in obese subjects (mean difference -5.32%, 95% CI -6.75--3.89; p<0.001, I2=42%); however, no significant differences were observed in FEV1/forced vital capacity (FVC) ratio between groups. We found that obese subjects with asthma have higher use of all included asthma medication classes and higher ICS doses than healthy-weight asthma subjects, despite lower FEV1 and a similar FEV1/FVC %. A better understanding of the factors driving increased medication use is required to improve outcomes in this subgroup of asthmatics.

Treating Pediatric Asthma According Guidelines.

Asthma is a common chronic inflammatory disorder of the lower respiratory airways in childhood. The management of asthma exacerbations and the disease control are major concerns for clinical practice. The Global Strategy for Asthma Management and Prevention, published by GINA, updated in 2017, the British Thoracic Society/Scottish Intercollegiate Guideline Network, revised in 2016, the National Institute for Health and Care Excellence asthma guideline consultation, available in 2017, are widely accepted documents, frequently implemented, with conflicting advices, and different conclusion on asthma definition and treatment. An International Consensus on Pediatric Asthma was carried out in 2012 by a Committee with expertise in the field, to critically review differences on current guidelines. In addition, the specific issue of treating severe and difficult asthma has been recently highlighted throughout the International European Respiratory Society/American Thoracic Society guidelines on severe asthma. The aim of this paper is to describe conventional treatments and some new therapeutic approaches to pediatric asthma according to guidelines, highlighting key aspects, and differences on proposed clinical recommendations for asthma management. Age specific therapy are proposed in steps, according to clinical severity and the level of disease control. If control is not achieved within 3 months, stepping-up should be considered; otherwise, if control is achieved after 3 months, stepping down may be considered. The most used drug classes of asthma medications are beta-2 adrenergic agonists, corticosteroids, and leukotriene modifiers. Intramuscolar triamcinolone has been used for severe asthma treatment. Chromones and xanthines have been extensively used in the past, but they have shown limits related to their efficacy and safety profile. Omalizumab, a monoclonal antibody against IgE, is an immunomodulatory biological agent, used as new drug in patients with confirmed IgE-mediated allergic asthma, only for patient's specific range of total IgE level. There are low evidences in the efficacy of metotrexate, as well as macrolide antibiotics in children with asthma. Antifungal agents are also not recommended in asthmatic patients. Non-pharmacological measures that may improve patient's quality of life should also be attempted. We conclude that treatment decisions on childhood asthma management should be critically made, pondering the differences suggested by agreed international consensus documents.

The effect of glycopyrronium and indacaterol, as monotherapy and in combination, on the methacholine dose-response curve of mild asthmatics: a randomized three-way crossover study

BackgroundMethacholine dose-response curves illustrate pharmacologic bronchoprotection against methacholine-induced airway hyperresponsiveness and can be used to quantitate changes in airway sensitivity (position), reactivity (slope), and maximal responsiveness following drug administration. Our objective was to determine the influence of single-dose glycopyrronium (long-acting muscarinic antagonist) and indacaterol (ultra-long acting β2 agonist), as monotherapy and in combination, on the methacholine dose-response curve of mild asthmatics and to compare these findings with a non-asthmatic control curve.MethodsThis was a randomized, double blind, double dummy, three-way crossover study. For asthmatic participants (n = 14), each treatment arm included a baseline methacholine challenge, drug administration, and repeat methacholine challenges at 1, 24, and 48 h. Non-asthmatic control participants (n = 15) underwent a single methacholine challenge and did not receive any study treatment. Methacholine dose-response curves were graphed as the percent fall in forced expiratory volume in 1 s (FEV1) for each methacholine concentration administered. Best-fit curves were then generated. Differences in airway reactivity were calculated through linear regression. Changes in airway sensitivity were assessed as the shift in the provocative concentration of methacholine causing a 20% fall in FEV1.ResultsCompared to baseline, all treatments significantly reduced airway sensitivity to methacholine at 1 h post-dose (indacaterol ~1.5 doubling concentrations; glycopyrronium ~5 doubling concentrations; combination ~5 doubling concentrations). Bronchoprotection at 24 and 48 h remained significant with glycopyrronium and combination therapy only. Airway reactivity was not influenced by indacaterol whereas glycopyrronium significantly reduced airway reactivity at all time-points (p = 0.003-0.027). The combination significantly decreased slope at 1 (p = 0.021) and 24 (p = 0.039) hours only. The non-asthmatic control and 1-h glycopyrronium curves are nearly identical. Only the non-asthmatic control and 1-h post-combination therapy curves appeared to generate a true response plateau (three data points within 5%), which occurred at a 14% fall in FEV1.ConclusionsMethacholine dose-response curves differentiate the bronchoprotective mechanisms triggered by different classes of asthma medications. Assessment of bronchoprotection using methacholine dose-response curves may be useful during clinical development of respiratory medications when performing superiority, equivalence, or non-inferiority trials.Trial registrationclinicaltrials.gov (NCT02953041). Retrospectively registered on October 24th 2016.

Review on Pharmacogenetics and Pharmacogenomics Applied to the Study of Asthma.

Nearly one-half of asthmatic patients do not respond to the most common therapies. Evidence suggests that genetic factors may be involved in the heterogeneity in therapeutic response and adverse events to asthma therapies. We focus on the three major classes of asthma medication: β-adrenergic receptor agonist, inhaled corticosteroids, and leukotriene modifiers. Pharmacogenetics and pharmacogenomics studies have identified several candidate genes associated with drug response.In this chapter, the main pharmacogenetic and pharmacogenomic studies in addition to the future perspectives in personalized medicine will be reviewed. The ideal treatment of asthma would be a tailored approach to health care in which adverse effects are minimized and the therapeutic benefit for an individual asthmatic is maximized leading to a more cost-effective care.

Changing patterns of asthma medication use related to US Food and Drug Administration long-acting β2-agonist regulation from 2005-2011

Safety concerns associated with long-acting β2-agonists (LABAs) have led to many US Food and Drug Administration (FDA) regulatory activities for this class of drugs. Little is known about the effect of these regulatory activities on use of LABA-containing agents or other asthma medications. We created rolling cohorts of pediatric and adult asthmatic patients in the Mini-Sentinel Distributed Database between January 2005 and June 2011. The proportions of asthmatic patients using LABA-containing products, inhaled corticosteroids (ICSs), leukotriene modifiers, short-acting β2-agonists, oral corticosteroids, other bronchodilators, and no medications were measured on a monthly basis, and the changes were evaluated by using interrupted time series with segmented regression analysis. When the 2005 regulatory activity was announced, there were statistically significant decreases in the use of fixed-dose ICS-LABA agents in children (-0.98 percentage points) and adults (-1.24 percentage points). Increased use of ICSs and leukotriene modifiers was observed just after the regulatory activities were announced in both children and adults. Although of smaller magnitude, continued favorable changes in the use of LABA agents were observed after the 2010 FDA regulatory activity. The 2005 and 2010 FDA regulatory activities might have contributed to reduced use of LABA agents, as intended; however, their effect, independent of other factors, cannot be determined. Use of other classes of asthma medications was similarly affected.

Pharmacogenomics in asthma therapy: where are we and where do we go?

The response to drug treatment in asthma is a complex trait and is markedly variable even in patients with apparently similar clinical features. Pharmaco-genomics, which is the study of variations of human genome characteristics as related to drug response, can play a role in asthma therapy. Both a traditional candidate-gene approach to conducting genetic association studies and genome-wide association studies have provided an increasing list of genes and variants associated with the three major classes of asthma medications: β2-agonists, inhaled corticosteroids, and leukotriene modifiers. Moreover, a recent integrative, systems-level approach has offered a promising opportunity to identify important pharmacogenomics loci in asthma treatment. However, we are still a long way away from making this discipline directly relevant to patients. The combination of network modeling, functional validation, and integrative omics technologies will likely be needed to move asthma pharmacogenomics closer to clinical relevance.

The pharmacological modulation of allergen-induced asthma

Aeroallergens are the most common triggers for the development of asthma. Recent birth cohort studies have identified viral infections occurring against a background of aeroallergen sensitization as a potent risk factor for initiation of asthma. Viral infection enhances immunopathogenic potential of pre-existing inhalant allergy via modulating airway mucosal dendritic cells. By using an allergen inhalation challenge clinical model, studies have shown that the late asthma response (LAR) is associated with more pronounced allergen-induced airway inflammation and airway hyperresponsiveness. The degree of airway eosinophilia, regulated by bone marrow progenitor cells and interleukin-5 level, correlates with the magnitude of the LAR and the increase in hyperresponsiveness. Both myeloid and plasmacytoid dendritic cell subsets have been involved in the pathogenesis of allergen-induced LAR. Myeloid dendritic cells are responsible for the allergen presentation and induction of inflammation and plasmacytoid dendritic cells play a role in the resolution of allergen-induced inflammation. A variety of potential new classes of asthma medication has also been evaluated with the allergen inhalation challenge in mild asthmatic subjects. Examples are TPI ASM8, an inhaled anti-sense oligonucleotide drug product, which attenuated both early and LARs via inhibition of the target gene mRNA of chemokine receptor 3, and the common β chain of interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor receptor. Anti-human antibody interleukin-13 (IM-638) significantly attenuated both early and late allergen-induced asthma response. Pitrakinra, which targets both interleukin-4 and interleukin-13, substantially diminishes allergen-induced airway responses. Allergen-induced airway responses are a valuable way to evaluate the activity of possible new therapies in asthmatic airways.

Concomitant Asthma Medication Use by Patients Receiving Omalizumab 2003–2008

Objective. To examine patterns of omalizumab use in the first 5 years of its availability. Methods. Our study comprised a series of descriptive retrospective cohort analyses using healthcare claims data. The study population comprised patients of any age who had omalizumab claims in the 5 years after 1 July 2003, and we created five 1-year cohorts from this population. Each cohort included patients continuously enrolled for at least 12 months with ≥2 omalizumab claims during the year. Cohorts contained between 302 and 1382 unique omalizumab users, and over 99% of patients with an omalizumab claim had at least one asthma diagnosis. Results. In all years, the specialty most commonly seen in conjunction with the initial omalizumab prescription was allergy/immunology. In all years, omalizumab was used in conjunction with three or more additional classes of asthma medications at least 70% of the time and with five or more classes at least 33% of the time; the proportion of patients filling omalizumab prescriptions who had no other concomitant classes of asthma medications varied from 4% to 8%. The most common pattern of asthma medication treatment in all years was omalizumab with combination steroids/long-acting beta-agonist inhaler, a leukotriene receptor antagonist, a short-acting beta-agonist inhaler, and at least one course of oral corticosteroids. Conclusions. In this study of a large sample of commercial health insurance claims covering the first 5 years after approval of omalizumab, we found that omalizumab was infrequently used as a single agent or without concomitant inhaled corticosteroids, and most omalizumab prescriptions came from specialist physicians.

The pharmacogenetics and pharmacogenomics of asthma therapy

Despite the availability of several classes of asthma medications and their overall effectiveness, a significant portion of patients fail to respond to these therapeutic agents. Evidence suggests that genetic factors may partly mediate the heterogeneity in asthma treatment response. This review discusses important findings in asthma pharmacogenetic and pharmacogenomic studies conducted to date, examines limitations of these studies and, finally, proposes future research directions in this field. The focus will be on the three major classes of asthma medications: β-adrenergic receptor agonists, inhaled corticosteroids and leukotriene modifiers. Although many studies are limited by small sample sizes and replication of the findings is needed, several candidate genes have been identified. High-throughput technologies are also allowing for large-scale genetic investigations. Thus, the future is promising for a personalized treatment of asthma, which will improve therapeutic outcomes, minimize side effects and lead to a more cost-effective care.

Heterogeneity of response to asthma controller therapy: clinical implications

Patients with asthma exhibit heterogeneous responses to all classes of asthma medication. This review examines clinical characteristics, biomarkers of inflammation, and genetic polymorphisms associated with treatment responsiveness in studies of adults and children with asthma, with an emphasis on inhaled corticosteroids and leukotriene modifiers. Recent clinical studies extended previous observations of associations between biomarkers of allergic inflammation and responsiveness to inhaled corticosteroids, and between cigarette smoke exposure and responsiveness to montelukast. Pharmacogenetic studies revealed associations between treatment response and genetic variations in CRHR1, as well as a number of genes encoding proteins involved in the absorption, production, and action of the cysteinyl leukotrienes. Very few studies have attempted to test the ability of these phenotypic and genotypic associations to predict treatment responsiveness. Additional prospective studies of sufficient size, quality, and ethnic diversity are needed to determine how best to incorporate information about genetic variations, clinical characteristics, and biomarkers into decisions about asthma therapy for individual patients.

Pharmacogenetics of Asthma Therapy

Asthma is a chronic disorder causing inflammation and reversible airway obstruction that affects approximately 300 million individuals worldwide. The incidence of asthma has nearly doubled in the past three decades resulting in higher rates of morbidity, mortality and health care costs. Despite the availability of several classes of asthma medications such as beta-agonists, leukotriene modifiers and corticosteroids, up to 50% of asthmatics do not benefit from one or more of these drugs. Studies have shown that asthma and drug response phenotypes such as forced expiratory volume in one second (FEV(1)) are heritable traits, indicating a genetic component of variable response to asthma drugs. This review summarizes the findings of pharmacogenetic investigations on the three main classes of asthma medications. In addition, the limitations of these genetic studies are discussed and future research avenues are proposed to identify novel genetic factors. Although numerous genes have been associated with variable response to common asthma drugs, results are often contradictory across different studies, and remain to be confirmed in larger replication cohorts. Nevertheless, literature in asthma pharmacogenetics demonstrates that genetic variants influence response to asthma treatments and may be used for predictive testing prior to drug administration to avoid adverse reactions and increase drug efficacy.

Asthma Genetics: Personalizing Medicine

Asthma is a chronic inflammatory lung disease that leads to significant morbidity, mortality, and economic burden. The clinical symptoms, which are a result of airway inflammation and reversible airway obstruction, have led to the mainstay of therapies for asthma: anti-inflammatory medications and bronchodilators. However, the efficacies of the various classes of medications are not equal among all patients and may be affected by asthma phenotypes, environmental exposures, and genetic differences. Similarly, the risk for developing asthma and the natural history of the disease show great inter-individual variability due to these same factors. Over the past few decades, much effort has been focused on the genetics of asthma, and investigators have identified more than one hundred potential asthma susceptibility genes, of which at least ten have been replicated in numerous independent studies. In parallel, researchers have also identified genetic factors that impact the pharmacotherapeutic responses to the major classes of asthma medications. While the results of previous studies have been promising, future investigations need to combine genetics, pharmacogenetics, accurate disease phenotyping, and environmental exposures to build the foundation for personalized and predictive medicine for the 21st century. The ultimate goal is to enable physicians to identify those at risk for asthma, intervene to prevent or attenuate the disease, and select the optimal medical regimen for each individual patient. If successful, the resulting paradigm shift in medical practice will lead to improved clinical outcomes and decreased health care expenditures.

Traditional and patient-centred outcomes with three classes of asthma medication

Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.

Acute severe asthma in adults

Despite major improvements in the recognition of patients with asthma and their treatment, both chronically and for acute episodes, acute severe asthma remains a life-threatening condition. Most patients who die from asthma have a history of chronic, often severe disease, but fatal or near-fatal events can occur in patients who have previously exhibited only mild or moderate symptoms. A background of poor behavioural and psychosocial features is well recognized in these patients (Figure 1). Medical factors in at-risk patients include: • prior severe episodes • admission to or attendance at an A&E department with asthma during the last year • ‘heavy’ use of β 2-agonists • those taking three or more classes of asthma medication. • those with 'brittle' asthma. Peaks of asthma deaths occur in the summer in younger patients and the winter in older patients, possibly reflecting triggers of the event. Most asthma deaths occur in the community, and in most patients symptoms develop over hours or days rather than minutes. The importance of patient education about asthma in general, how to recognize the severity of symptoms and the institution of preventive therapy cannot be over-emphasized.

US Physician Adherence to Standards in Asthma Pharmacotherapy Varies by Patient and Physician Characteristics

US Physician Adherence to Standards in Asthma Pharmacotherapy Varies by Patient and Physician Characteristics