Use of Fractional Exhaled Nitric Oxide to Guide the Treatment of Asthma: An Official American Thoracic Society Clinical Practice Guideline.

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.

Global Quality Standard for Identification and Management of Severe Asthma.

INTRODUCTION: Severe asthma is a debilitating, life-threatening disease associated with substantial global morbidity, mortality, and health care resource utilization. Patients may not receive guideline-directed medical care for severe asthma. Moreover, viable precision-based assessment tools and newer preventive therapies that can reduce the frequency of exacerbations and associated functional impact are underused. As a result, high rates of poorly controlled severe asthma persist, and patient health-related quality of life suffers. METHODS: In 2019, the Improve Access to Better Care Task Force of the PRECISION Steering Committee set out to develop a global template on quality standards for severe asthma care to support improved access to and delivery of quality care. This Quality Standard is grounded in the vast body of published evidence available for severe asthma care, published clinical guidelines (i.e., from the Global Initiative for Asthma in 2019 and the European Respiratory Society/American Thoracic Society in 2014), and the 2018 PRECISION-supported Charter to Improve Patient Care in Severe Asthma. RESULTS: The Quality Standard developed emphasizes four key elements aimed at optimizing clinical care and outcomes in severe asthma: (1) organization of services, (2) timely identification and referral for suspected severe asthma, (3) specialized assessment and management of severe asthma to optimize outcomes, and (4) patient-centric care and shared decision-making that is reflective of the patient's expectations, priorities, and values. Four key Quality Statements are provided, along with quality metrics and strategies for local adaptation to optimize implementation. CONCLUSION: This Global Quality Standard is intended to mobilize policymakers, health care providers, and patient advocacy groups to build consensus on the definition and expectations of quality care in severe asthma, to promote patient-centric care, to identify gaps in care and areas for improvement, and systematically implement improvement measures and outcomes and to reduce the burden of illness for patients with severe asthma.

Although only 10% of patients with asthma have severe disease, these patients use up to half of all health care resources used to treat asthma. For the patient, severe asthma is associated with substantial morbidity, increased risk of death, and poor quality of life. Effective treatments for severe asthma are available, yet access to these treatments varies for many patients around the globe, and they are not always used effectively when available. A task force of leading global asthma experts was recently assembled to develop global standards to support improved access and delivery of quality care for patients with severe asthma. The task force identified four key elements to optimize management and outcomes: (1) coordination of services, (2) timely detection and referral of patients with severe asthma, (3) use of guideline-recommended assessments and therapies, and (4) integration of patient expectations and values when making treatment decisions. This Quality Standard details each of these elements by providing supporting rationale, ways to measure improvements in each area, and strategies to implement these elements at local clinics around the world. Ultimately, this Quality Standard is intended to help policymakers, health care providers, patient advocacy groups, and other key stakeholders build consensus on the requirements for quality care in severe asthma to improve patient care while also reducing the overall global burden of severe asthma.

Improving Asthma Conditions for Children and Adolescents by Expanding the Statewide Learning Collaborative Model Through Health Homes.

BACKGROUND AND OBJECTIVES: Asthma is one of the most common diseases among children in the United States. Increasing provider adherence to national asthma guidelines and connecting patients to Health Homes can increase optimal asthma care. The objectives of this article are to report the results of an asthma learning collaborative and explore the role of Health Homes in contributing to its success. METHODS: Quantitative and qualitative data were collected regarding the experiences of 14 pediatric primary care practices and 6 Health Homes participating in a 9-month learning collaborative. RESULTS: Practices exceeded process aims of 80% compliance with optimal asthma care and the use of an Asthma Action Plan among patients aged 2 to 21 years. Health Home care coordinators also reported improvements in self-management strategies for asthma conditions, including the presence of an Asthma Action Plan, medications, spacers, and proper spacing techniques. Providers and Health Home care coordinators identified role clarity, mitigation of environmental triggers, and management of asthma conditions as benefits of the experience. CONCLUSIONS: The results of this asthma learning collaborative increased provider adherence to national guidelines and significantly improved optimal asthma care for patients. This multipronged, holistic approach to asthma care proved successful for controlling and maintaining asthma conditions among patients.

Does benralizumab effectively treat chronic obstructive pulmonary disease? A protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to investigate the efficacy and safety of benralizumab for the treatment of patients with chronic obstructive pulmonary disease (COPD). METHODS: This study will systematically and comprehensively search relevant literatures in electronic databases (MEDLINE, EMBASE, Cochrane Library, Global health, PsycINFO, Scopus, WANGFANG, and CNKI) from inception to the present without language and publication time restrictions. Two reviewers will independently carry out literature identification, data collection, and study quality assessment. Any disagreement will be settled down by a third reviewer through discussion and a consensus will be reached. RevMan 5.3 software will be used for statistical analysis performance. RESULTS: This study will summarize up-to-date evidence to assess the efficacy and safety of benralizumab for the treatment of COPD. CONCLUSION: The findings of this study will provide helpful evidence to determine whether benralizumab is effective or not for the treatment of COPD. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040039.

Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology.

The Global Initiative for Asthma guidelines use the traditional terminology of "low," "medium," and "high" doses of inhaled corticosteroids (ICS) to define daily maintenance doses of 100 to 250 µg, >250 to 500 µg, and >500 µg, respectively, of fluticasone propionate or equivalent for adults with asthma. This concise clinical review proposes that this terminology is not evidence based and that prescribing practice based on this terminology may lead to the use of inappropriately excessive doses of ICS. Specifically, the ICS dose that achieves 80-90% of the maximum obtainable benefit is currently classified as a low dose, with the description of two higher dose levels of medium and high, which are associated with significant risk of systemic adverse effects. Asthma guidelines and clinician prescribing practice need to be modified in accordance with the currently available evidence of the dose-response relationship of ICS in adult asthma. We propose a reclassification of ICS doses based on a "standard daily dose," which is defined as 200-250 µg of fluticasone propionate or equivalent, representing the dose at which approximately 80-90% of the maximum achievable therapeutic benefit of ICS is obtained in adult asthma across the spectrum of severity. It is recommended that ICS treatment be started at these standard doses, which then represent the doses at which maintenance ICS are prescribed at step 2 and within ICS/long-acting ß-agonist combination therapy at step 3. The opportunity is available to prescribe higher doses within ICS/long-acting ß-agonist maintenance therapy in accordance with the stepwise approach to asthma treatment at step 4.

Economic Burden Associated with Receiving Inhaled Corticosteroids with Leukotriene Receptor Antagonists or Long-Acting Beta Agonists as Combination Therapy in Older Adults.

BACKGROUND: There is a paucity of literature on the health care expenditures associated with different pharmacologic treatments in older adults with asthma that is not well controlled on inhaled corticosteroids (ICS). OBJECTIVE: To compare asthma-related and all-cause health care expenditures associated with leukotriene receptor antagonists (LTRA) versus long-acting beta agonists (LABA) when added to ICS in older adults with asthma. METHODS: A retrospective cohort was constructed using 2009-2010 Medicare fee-for-service medical and pharmacy claims from a 10% random sample of beneficiaries continuously enrolled in Parts A, B, and D in 2009. The sample comprised patients who were aged 65 years and older, diagnosed with asthma, and treated exclusively with ICS + LABA or ICS + LTRA. Outcomes assessed were asthma-related expenditures (medical, pharmacy, and total) and all-cause health care expenditures (medical, pharmacy, and total). Outcomes were measured from the date of the first prescription for the add-on treatment (LABA or LTRA in combination with ICS) after having at least a 4-month "wash-in" period in which patients were receiving no controller, ICS alone, or ICS plus the add-on treatment of the follow-up period. Patients were followed until death, switching to or adding the other add-on treatment, or the end of the study (December 31, 2010). Multivariable regression models with nonparametric bootstrapped standard errors were used to compare all-cause and asthma-related expenditures per patient per month (PPPM) between ICS + LABA and ICS + LTRA users. All models were adjusted for demographics, comorbidities, and county-level health care access variables. RESULTS: The primary analysis included 14,702 patients, of whom 12,940 were treated with ICS + LABA and 1,762 were treated with ICS + LTRA. The mean (SD) follow-up periods were 12.3 (± 5.7) months for the ICS + LABA group and 15.3 (± 5.1) months for the ICS + LTRA group. Adjusted asthma-related expenditures PPPM were $400 for the ICS + LTRA group compared with $286 for the ICS + LABA group (P < 0.001). However, adjusted total all-cause expenditure PPPM was significantly lower for patients treated with ICS + LTRA ($6,087 for ICS + LTRA compared with $6,975 for ICS + LABA, P = 0.029). CONCLUSIONS: Older adults with asthma often experience economic burden from asthma and other chronic illnesses. Compared with ICS + LTRA, ICS + LABA was associated with lower asthma-related expenditures but with higher all-cause expenditures in older adults. DISCLOSURES: Support for this study was provided by the University of Pittsburgh School of Pharmacy and the Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA P30 AGAG024827). C. Thorpe reports grants from the National Institute of Aging during the conduct of this study. The other authors have nothing to disclose.

Identifying Persistent Asthma in Children: A Comparison of Healthcare Effectiveness Data and Information Set Criteria and National Heart, Lung, and Blood Institute Guidelines.

Persistent asthma requires a daily controller medication. National Heart, Lung, and Blood Institute (NHLBI) guidelines and Healthcare Effectiveness Data and Information Set (HEDIS) quality measures are used to identify persistent asthma, the former method used by clinicians, and the latter by managed care organizations (MCOs). This study aims to determine the degree of agreement between these criteria in classifying pediatric persistent asthma. Asthmatic patients aged 5-18 years old in a university pediatric practice who were continuously enrolled with one MCO from January 1, 2012 to December 31, 2013 (Cohort 1: 329 patients) and January 1, 2013 to December 31, 2014 (Cohort 2: 212 patients) were identified. Subjects with at least one asthma visit were included. Independence of NHLBI and HEDIS criteria was determined by the McNemar test. Agreement was determined by confusion matrix analysis and Cohen kappa statistic with continuity correction. Agreement in controller assignment was 82% in Cohort 1 and 88% in Cohort 2. Agreement was fair in Cohort 1 (Cohen kappa = 0.364; 95% confidence interval [CI] = 0.217-0.511) and moderate in Cohort 2 (Cohen kappa = 0.447; 95% CI = 0.247-0.646). The HEDIS misclassified persistent asthma by 16.4% (95% CI: 11.5-21.2%) and 11.8% (95% CI: 6.8-16.7%) in Cohorts 1 and 2, respectively. NHLBI and HEDIS criteria show fair to moderate agreement; however, the HEDIS consistently misclassified persistent asthma, suggesting that it is a poor measure of practice performance.

A Recombinant DNA Plasmid Encoding the sIL-4R-NAP Fusion Protein Suppress Airway Inflammation in an OVA-Induced Mouse Model of Asthma.

Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.

Novel montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats.

To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.

Establishment of a standard reference material (SRM) herbal DNA barcode library of Vitex negundo L. (lagundi) for quality control measures.

The majority of the population in the Philippines relies on herbal products as their primary source for their healthcare needs. After the recognition of Vitex negundo L. (lagundi) as an important and effective alternative medicine for cough, sore throat, asthma and fever by the Philippine Department of Health (DOH), there was an increase in the production of lagundi-based herbal products in the form of teas, capsules and syrups. The efficiency of these products is greatly reliant on the use of authentic plant material, and to this day no standard protocol has been established to authenticate plant materials. DNA barcoding offers a quick and reliable species authentication tool, but its application to plant material has been less successful due to (1) lack of a standard DNA barcoding loci in plants and (2) poor DNA yield from powderised plant products. This study reports the successful application of DNA barcoding in the authentication of five V. negundo herbal products sold in the Philippines. Also, the first standard reference material (SRM) herbal library for the recognition of authentic V. negundo samples was established using 42 gene accessions of ITS, psbA-trnH and matK barcoding loci. Authentication of the herbal products utilised the SRM following the BLASTn and maximum-likelihood (ML) tree construction criterion. Barcode sequences were retrieved for ITS and psbA-trnH of all products tested and the results of the study revealed that only one out of five herbal products satisfied both BLASTn and ML criterion and was considered to contain authentic V. negundo. The results prompt the urgent need to utilise DNA barcoding in authenticating herbal products available in the Philippine market. Authentication of these products will secure consumer health by preventing the negative effects of adulteration, substitution and contamination.

Orally inhaled fixed-dose combination products for the treatment of asthma and chronic obstructive pulmonary disease: not simple math.

Over the past decade, orally inhaled fixed-dose combination products (FDCs) have emerged as an important therapeutic class for the treatment of asthma and chronic obstructive pulmonary disease. However, the conceptual simplicity of inhaled FDCs belies both the complexity of their development, and the profound advantages they offer patients. The benefits of combining agents are not merely additive, and range from increased compliance via simple convenience to complex receptor-level synergies. Similarly, though, the development challenges often exceed the sum of their parts. FDC formulation and analytical method development is generally more complex than for two monotherapy products. Likewise, FDC clinical programs can easily eclipse those of their monotherapy peers and their inherent complexity is often furthered by the diverse regulatory requirements for worldwide approval. As such, the proposition of developing an orally inhaled FDC for global registration often represents a significant increase in both the potential rewards and assumed risks of drug development.

Medication use patterns among urban youth participating in school-based asthma education.

Although pharmaceutical management is an integral part of asthma control, few community-based analyses have focused on this aspect of disease management. The primary goal of this analysis was to assess whether participation in the school-based Kickin' Asthma program improved appropriate asthma medication use among middle school students. A secondary goal was to determine whether improvements in medication use were associated with subsequent improvements in asthma-related symptoms among participating students. Students completed an in-class case-identification questionnaire to determine asthma status. Eligible students were invited to enroll in a school-based asthma curriculum delivered over four sessions by an asthma health educator. Students completed a pre-survey and a 3-month follow-up post-survey that compared symptom frequency and medication use. From 2004 to 2007, 579 participating students completed pre- and post-surveys. Program participation resulted in improvements in appropriate use across all three medication use categories: 20.0% of students initiated appropriate reliever use when "feeling symptoms" (p < 0.001), 41.6% of students reporting inappropriate medication use "before exercise" initiated reliever use (p < 0.001), and 26.5% of students reporting inappropriate medication use when "feeling fine" initiated controller use (p < 0.02). More than half (61.6%) of participants reported fewer symptoms at post-survey. Symptom reduction was not positively associated with improvements in medication use in unadjusted and adjusted analysis, controlling for sex, asthma symptom classification, class attendance, season, and length of follow-up. Participation in a school-based asthma education program significantly improved reliever medication use for symptom relief and prior-to-exercise and controller medication use for maintenance. However, given that symptom reduction was not positively associated with improvement in medication use, pharmaceutical education must be just one part of a comprehensive asthma management agenda that addresses the multifactorial nature of asthma-related morbidity.

Characteristics of asthma attack with long-term management for bronchial asthma.

BACKGROUND: There have been no reports on the evaluation of the usefulness of long-term asthma management based on the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2005 (JPGL 2005). METHODS: The purpose of the present study was to retrospectively investigate the records of 350 patients admitted to Yamaguchi University Hospital who had asthma attacks from January 2006 to June 2008. There were 149 patients who were treated for more than 3 months in accordance with the guideline (long-term management group) and 201 who were not (non-long-term management group). The patients were divided into three age groups: 100 infants, 159 toddlers, and 91 schoolchildren. RESULTS: The onset age of asthma in the long-term management group was earlier than that in the non-long-term management group in toddlers and schoolchildren. The white blood cell counts and C-reactive protein levels were higher in the non-long-term management group in schoolchildren, suggesting the complication of some infections. The severity of asthma in the long-term management group was greater than that in the non-long-term management group among all three age groups. There were no significant differences, however, in the severity of asthma attack at admission between the long-term and non-long-term management groups in the three age groups. CONCLUSION: Patients who had severe asthma tended to be treated with long-term management, which suggests that long-term asthma management according to JPGL 2005 may reduce the severity of asthma attack at that admission, because the severity of asthma in patients undergoing long-term management correlates with the severity of asthma attack.