Impact of pharmaceutical care for asthma patients on health-related outcomes: An umbrella review.

Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health-related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health-related outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health-related outcomes in asthma patients.

Expert Consensus on SABA Use for Asthma Clinical Decision-Making: A Delphi Approach.

PURPOSE OF REVIEW: A modified Delphi process was undertaken to provide a US expert-led consensus to guide clinical action on short-acting beta2-agonist (SABA) use. This comprised an online survey (Phase 1), forum discussion and statement development (Phase 2), and statement adjudication (Phase 3). RECENT FINDINGS: In Phase 1 (n = 100 clinicians), 12% routinely provided patients with ≥4 SABA prescriptions/year, 73% solicited SABA use frequency at every patient visit, and 21% did not consult asthma guidelines/expert reports. Phase 3 experts (n = 8) reached consensus (median Likert score, interquartile range) that use of ≥3 SABA canisters/year is associated with increased risk of exacerbation and asthma-related death (5, 4.75-5); SABA use history should be solicited at every patient visit (5, 4.75-5); usage patterns over time, not absolute thresholds, should guide response to SABA overuse (5, 4.5-5). Future asthma guidelines should include clear recommendations regarding SABA usage, using expert-led thresholds for action.

As-needed inhaled corticosteroids as add-on therapy versus SMART therapy: an evolving understanding of the two approaches in the management of moderate-to-severe asthma.

PURPOSE OF REVIEW: Asthma is the most common chronic respiratory disorder, characterized by recurring, reversible airflow obstruction due to inflammation and airway hyperresponsiveness. Although biologics have provided significant advances in the treatment of asthma, they are expensive, and their use remains restricted to more severe asthma. Additional approaches in the management of moderate-to-severe asthma are necessary. RECENT FINDINGS: ICS-formoterol as maintenance and reliever therapy in asthma and its effect on improved asthma control has been demonstrated in multiple cohorts of asthma. Although ICS-formoterol as maintenance and reliever therapy has been widely validated, there are significant design considerations including the requirement for exacerbation and bronchodilator response and the lack of evidence for effectiveness in patients who use nebulized reliever therapies, which may limit the use of this therapy in selected populations. More recent trials of as-needed ICS have demonstrated effectiveness in reducing asthma exacerbations and improvements in asthma control and may provide an additional therapeutic strategy for individuals with moderate-to-severe asthma. SUMMARY: Both ICS-formoterol as a maintenance and a reliever as well as as-needed ICS have demonstrated significant improvements in the control of moderate-to-severe asthma. Future investigational work will be necessary to elucidate whether a strategy of ICS-formoterol as maintenance and reliever therapy or an as-needed ICS strategy demonstrates superiority in asthma control in the context of the cost to individual patients and health systems.

Assessment and management of asthma exacerbations in an emergency department unit

Background: The Pediatric Respiratory Assessment Measure (PRAM) score is a useful tool for the assessment of asthma exacerbations in children. This study aimed to estimate the risk of hospitalization in children, assessed with the PRAM score and having mild–moderate asthma exacerbation, who were treated with salbutamol delivered via a metered-dose inhaler and spacer (MDI/S). Methods: The study population consisted of children aged 3–16 years with mild–moderate asthma exacerbations. All children received 1mg/kg prednisolone p.o. (max 40 mg) and 4–6 puffs of salbutamol via MDI/S. Results: Fifty patients participated in the study. Admission was associated positively with the initial PRAM score (OR: 18.91, CI: 2.42–123.12, P = 0.005) and negatively with the improvement in PRAM score (OR: 0.52, CI: 0.01–0.78, P = 0.032). Conclusion: PRAM is a reliable tool that can be used effectively to estimate the asthma exacerbation severity (AU)

Effect of budesonide formoterol combined with tiotropium bromide on pulmonary function and inflammatory factors in patients with asthma–COPD overlap syndrome

Objective: To investigate the clinical efficacy of combining budesonide formoterol with tiotropium bromide for treating asthma–chronic obstructive pulmonary disease overlap syndrome (AOCS). Methods: The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone). Patients’ clinical efficacy, pulmonary function, fractioned exhaled nitric oxide (FeNO), immune function, endothelial function, serum lipid peroxidation injury indexes, adverse reactions, and quality of life scores were compared. Results: Prior to treatment, no significant differences were observed in various pulmonary function indicators, FeNO, immune function, endothelial function, and lipid peroxidation injury indexes between the two groups (P > 0.05). However, after treatment, all observation indexes in both groups improved to different levels, with the experimental group -demonstrating -significantly superior improvement, compared to the conventional group (P < 0.05). We also observed that adverse reactions in the experimental group were significantly lower than in the conventional group (P < 0.05). Conclusion: The combination of budesonide formoterol to tiotropium bromide in treating asthma–COPD overlap syndrome may significantly improve pulmonary function, endothelial function, and immune status of patients and encourage the recovery of serum lipid peroxidation injury; therefore, this may deserve widespread adoption and application (AU)

Effect of budesonide combined with montelukast sodium on pulmonary function parameters and immunoglobulin levels in children with bronchial asthma

Background and aim: Bronchial asthma is a prevalent type of respiratory disease that affects a large proportion of pediatric patients. The purpose of this study is to further investigate the clinical effects of budesonide combined with montelukast sodium in treating bronchial asthma. Methods: Eighty-six children with bronchial asthma were equally divided into study and control groups via randomized double-blind controlled trial. The control group was treated with aerosol inhalation of budesonide combined with placebo, while the study group was treated with budesonide combined with montelukast sodium. Pulmonary function parameters, immunoglobulin, and recovery of related symptoms, along with the adverse reaction rate, were observed and compared between both groups. Results: Before treatment, there was no marked difference in pulmonary function parameters and immunoglobulin indexes between both groups (P > 0.05). All pulmonary function indicators and immunoglobulin indexes in both groups improved following therapy, with the study group outperforming the control group (P < 0.05). The recovery time of related symptoms in the study group was shorter than that in the control group (P < 0.05). The incidence of adverse reactions in both groups was compared, with notable differences (P < 0.05). Conclusion: Budesonide combined with montelukast sodium in the treatment of bronchial asthma has the value of clinical application and promotion (AU)

Effects of omalizumab combined with budesonide formoterol on clinical efficacy, pulmonary function, immune function, and adverse reactions in children with moderate and severe allergic asthma

Objective: To evaluate the clinical efficacy and safety of combining omalizumab with budesonide formoterol to treat children with moderate and severe allergic asthma, and investigate the effect of this combination therapy on pulmonary and immune functions. Methods: The data of 88 children with moderate and severe allergic asthma, who were admitted to our hospital between July 2021 and July 2022, were included in the study. The patients were randomly assigned either to control group (n = 44; received budesonide formoterol inhalation therapy) or experimental group (n = 44; received omalizumab subcutaneous injection + budesonide formoterol inhalation therapy) using computer-generated randomization. The clinical efficacy, asthma control (measured using childhood Asthma-Control Test [C-ACT] score), pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), immune function (cluster of differentiation 3 cells [CD3+ cells], cluster of differentiation 4 cells [CD4+ cells], immunoglobulin G, immunoglobulin A, and immunoglobulin E), and adverse reactions were observed and compared between both groups. Results: After treatment, the experimental group had improved levels of pulmonary function and immune function indexes, higher C-ACT scores, and a higher overall response rate than the control group (P < 0.05). In addition, the incidence of adverse reactions was not significantly different between both groups (P > 0.05). Conclusion: The combination of omalizumab with budesonide formoterol for treating moderate and severe allergic asthma in children demonstrated promising clinical efficacy and improved their pulmonary and immune functions, leading to more rational asthma control. The combined regimen demonstrated satisfactory clinical safety and deserved clinical promotion (AU)

Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma.

CONTEXT: Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). OBJECTIVE: To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. MATERIALS AND METHODS: We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. RESULTS: SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (-72%), PIK3R1 (-40%), and COL3A1 (-65%) compared with OVA + LPS. CONCLUSIONS: Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA.

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Performance Evaluation of Montelukast Pediatric Formulations: Part II - a PBPK Modelling Approach.

This study aimed to build a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriate in vitro dissolution data to describe drug performance in adults and pediatric patients. Montelukast sodium was chosen as a model drug. Two case studies were investigated: case study 1 focused on the description of formulation performance from adults to children; case study 2 focused on the description of the impact of medicine co-administration with vehicles on drug exposure in infants. The PBPK model for adults and pediatric patients was developed in Simcyp® v18.2 informed by age-appropriate in vitro dissolution results obtained in a previous study. Oral administration of montelukast was simulated with the ADAM™ model. For case study 1, the developed PBPK model accurately described montelukast exposure in adults and children populations after the administration of montelukast chewable tablets. Two-stage dissolution testing in simulated fasted gastric to intestinal conditions resulted in the best description of in vivo drug performance in adults and children. For case study 2, a good description of in vivo drug performance in infants after medicine co-administration with vehicles was achieved by incorporating in vitro drug dissolution (under simulated fasted gastric to fed intestinal conditions) into a fed state PBPK model with consideration of the in vivo dosing conditions (mixing of formulation with applesauce or formula). The case studies presented demonstrate how a PBPK absorption modelling strategy can facilitate the description of drug performance in the pediatric population to support decision-making and biopharmaceutics understanding during pediatric drug development.

Performance Evaluation of Montelukast Pediatric Formulations: Part I-Age-Related In Vitro Conditions.

This study aimed to explore the potential of biopharmaceutics in vitro tools to predict drug product performance in the pediatric population. Biorelevant dissolution set-ups were used to predict how age and medicine administration practices affect the in vitro dissolution of oral formulations of a poorly water-soluble compound, montelukast. Biorelevant age-appropriate dissolution studies of Singulair® (granules and chewable tablets) were conducted with the µDISS profiler™, USP 4 apparatus, USP 2 apparatus, and mini-paddle apparatus. Biorelevant simulating fluids representative of adult and pediatric conditions were used in the dissolution studies. The biorelevant dissolution conditions were appropriately selected (i.e. volumes, transit times, etc.) to mimic the gastrointestinal conditions of each of the subpopulations tested. Partial least squares regression (PLS-R) was performed to understand the impact of in vitro variables on the dissolution of montelukast. Montelukast dissolution was significantly affected by the in vitro hydrodynamics used to perform the dissolution tests (µDISS profiler™: positive effect); choice of simulation of gastric (negative effect) and/or intestinal conditions (positive effect) of the gastrointestinal tract; and simulation of prandial state (fasted state: negative effect, fed state: positive effect). Age-related biorelevant dissolution of Singulair® granules predicted the in vivo effect of the co-administration of the formulation with applesauce and formula in infants. This study demonstrates that age-appropriate biorelevant dissolution testing can be a valuable tool for the assessment of drug performance in the pediatric population.

Anti-asthmatic effects of Phlomis umbrosa Turczaninow using ovalbumin induced asthma murine model and network pharmacology analysis.

BACKGROUND: Phlomis umbrosa Turczaninow has been used as a tradition herbal medicine for treating various inflammatory diseases. PURPOSE: In present study, we explored the effects of P. umbrosa on asthma induced by ovalbumin (OVA) and elucidated the mechanism via in vivo verification and network pharmacology prediction. METHODS: The animals were intraperitoneally injected OVA on day 1 and 14, followed by OVA inhalation on days 21, 22, and 23. The animals were daily treated P. umbrosa extract (PUE, 20 and 40 mg/kg) by oral gavage from day 18 to day 23. RESULTS: PUE significantly decreased airway hyperresponsiveness, eosinophilia, and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with a reduction in airway inflammation and mucus secretion in lung tissue. In network analysis, antiasthmatic effects of PUE were closely related with suppression of mitogen-activated protein kinases and matrix metalloproteinases (MMPs). Consistent with the results from network analysis, PUE suppressed the phosphorylation of ERK and p65, which was accompanied by a decline in MMP-9 expression. CONCLUSION: Administration of PUE effectively reduced allergic responses in asthmatic mice, which was associated with the suppressed phosphorylation of ERK and p65, and expression of MMP-9. These results indicate that PUE has therapeutic potential to treat allergic asthma.

Changes in oral corticosteroid use in asthma treatment-A 20-year Danish nationwide drug utilisation study.

Oral corticosteroids (OCS) are used in asthma management but can cause serious adverse effects. We aimed to investigate the usage trends in a nationwide asthma cohort in Denmark from 1999 to 2018. Using national registers, we identified young adults (18-45 years) with two or more asthma drug collections within 12 months since the age of 15 years as indicative of active asthma. OCS exposure level was stratified as high use (≥5 mg prednisolone/day/year) and low use (<5 mg/day/year). Lorenz curves were computed to illustrate potential skewness of consumption among the OCS users. We identified 318 950 individuals with a median age of 29 years (IQR 20-38 years) whereof 57% were women. The 1-year prevalence of OCS users was stable at 4.8% (median, IQR 4.7%-4.8%), but with nearly 40% decrease in high-users from 0.54% in 1999 to 0.33% in 2018. The median annual exposure decreased from 500 mg/year (1999) to 250 mg/year (2018). We found a substantial skewness in the distribution of OCS usage with 10% of users accounting for almost 50% of all OCS use. The prevalence of OCS users among young adults with active asthma has been relatively stable from 1999 to 2018, but with a decreasing prevalence of high-users and annual consumption.

Severe asthma and COVID-19: lessons from the first wave.

OBJECTIVE: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. METHODS: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. RESULTS: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. CONCLUSIONS: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.

A snapshot of exhaled nitric oxide and asthma characteristics: experience from high to low income countries.

Nitric oxide is a gas produced in the airways of asthmatic subjects and related to T2 inflammation. It can be measured as fractional nitric oxide (FeNO) in the exhaled air and used as a non-invasive, easy to evaluate, rapid marker. It is now widely used in many settings to determine airway inflammation. The aim of this narrative review is to report relationship between FeNO and the physiopathologic characteristics of asthmatic patients. Factors affecting FeNO levels have also been analysed as well as the impact of corticosteroid, target therapies and rehabilitation programs. Considering the availability of the test, spreading this methodology to low income countries has also been considered as a possibility for evaluating airway inflammation and monitoring adherence to inhaled corticosteroid therapy. PubMed data search has been performed restricted to English language papers. Research was limited to studies in adults unless studies in children were the only ones reported for a particular issue. This revision could be useful to summarize the role of FeNO in relation to asthma characteristics and help in the use of FeNO in different clinical settings particularly in low income countries.

Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma.

BACKGROUND: Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standard-of-care therapy. The monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory diseases. METHODS: In this 52-week phase 3, randomized, double-blind, placebo-controlled trial, we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks. All the children continued to receive a stable dose of standard background therapy. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second (ppFEV1) at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) at week 24. End points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype (≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of ≥20 ppb at baseline) or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline. RESULTS: In patients with the type 2 inflammatory phenotype, the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with dupilumab and 0.75 (95% CI, 0.54 to 1.03) with placebo (relative risk reduction in the dupilumab group, 59.3%; 95% CI, 39.5 to 72.6; P<0.001). The mean (±SE) change from baseline in the ppFEV1 was 10.5±1.0 percentage points with dupilumab and 5.3±1.4 percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.1 to 8.3; P<0.001). Dupilumab also resulted in significantly better asthma control than placebo (P<0.001). Similar results were observed in the patients with an eosinophil count of at least 300 cells per cubic millimeter at baseline. The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: Among children with uncontrolled moderate-to-severe asthma, those who received add-on dupilumab had fewer asthma exacerbations and better lung function and asthma control than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; Liberty Asthma VOYAGE ClinicalTrials.gov number, NCT02948959.).