Characteristics, treatment patterns and burden of illness in US patients with asthma newly initiating multiple-inhaler triple therapy.

INTRODUCTION: For patients with asthma who remain symptomatic on medium-dose inhaled corticosteroid/long-acting ß2-agonist, add-on long-acting muscarinic antagonist is a treatment option, which can be administered as multiple-inhaler triple therapy (MITT). A high proportion of patients (61.5%-88.2%) discontinue MITT use within 1 year postinitiation; however, which patients discontinue and their treatment patterns at initiation are unknown. This study aimed to understand the demographic, clinical and treatment-related characteristics of patients with asthma who newly initiated MITT, by discontinuation status. METHODS: This retrospective cohort study used administrative data from IBM Truven MarketScan Commercial Claims and Encounters Database with Medicare supplement between 1 January 2016 and 31 December 2019. Adult patients with asthma who initiated MITT between 1 January 2017 and 31 March 2019 were included and were classified based on their discontinuation status. 'Continuous users' had continuous use of MITT and 'discontinuers' discontinued treatment within the 6-month period postinitiation. Demographics and clinical characteristics, asthma treatment use prior to MITT initiation (12-month baseline period), mode of MITT initiation and complexity of regimen were described. RESULTS: Of 4132 patients (mean age: 49.0 years, 67.9% female), 78.0% (n=3224) were discontinuers; 22.0% (n=908) were continuous users. Demographic and other clinical and treatment-related characteristics during baseline were broadly similar between cohorts. A significantly higher proportion of continuous users versus discontinuers had ≥6 dispensed claims for short-acting ß2-agonist canisters (16.0% vs 12.5%; p=0.006) during baseline and initiated a once-daily MITT regimen (35.2% vs 26.2%; p<0.001). Fewer continuous MITT users used a mix of once-daily and twice-daily regimens than those who discontinued MITT (64.3% vs 72.3%; p<0.001). CONCLUSIONS: Most patients with asthma discontinued MITT within 6 months. Results indicate that patients with a history of uncontrolled, symptomatic asthma and those using less complex triple therapy regimens at initiation are less likely to discontinue MITT than patients with controlled asthma and those using a complex MITT regimen.

Outcomes of Patients with COPD Treated with ICS/LABA Before and After Initiation of Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI).

INTRODUCTION: Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA). METHODS: This retrospective cohort study included commercial and Medicare Advantage with Part D administrative claims data from September 01, 2016, to March 31, 2020, of patients diagnosed with COPD. The index date was the date of the first FF/UMEC/VI claim (September 2017-March 2019). The 12 months prior to index (baseline) were used to assess patient characteristics and outcomes; the 12 months following index (follow-up) were used to assess study outcomes. All patients had ≥ 30 consecutive days' supply of any ICS/LABA dual therapy during the 12 months prior to FF/UMEC/VI initiation. Subgroup analyses included patients with ≥ 30 consecutive days' supply of budesonide/formoterol (BUD/FORM) during baseline. Analyses of patients with ≥ 1 COPD exacerbation during baseline were reported as well. RESULTS: The overall population included 1449 patients (mean age 70.75 years; 54.18% female), of whom 540 were patients in the BUD/FORM subgroup. Significantly fewer patients experienced any exacerbation during follow-up versus baseline (overall population 53.49% vs 62.59%; p < 0.001; BUD/FORM subgroup 55.00% vs 62.41%; p = 0.004). Effects on exacerbation reduction were more pronounced among patients with ≥ 1 exacerbation during baseline. Lower COPD-related HCRU was observed during the follow-up compared with baseline for both the overall population and the BUD/FORM subgroup. CONCLUSION: Patients with COPD treated with ICS/LABA during baseline, including patients specifically treated with BUD/FORM and those with a history of ≥ 1 exacerbation, had fewer COPD exacerbations and lower COPD-related HCRU after initiating FF/UMEC/VI.

Outcomes Following Initiation of Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol versus Multiple-Inhaler Triple Therapy Among Medicare Advantage with Part D Beneficiaries and Those Commercially Enrolled for Health Care Insurance in the United States.

Purpose: Patients with chronic obstructive pulmonary disease (COPD) have been shown to benefit from triple therapy commonly delivered by multiple-inhaler triple therapy (MITT); however, the complexity of MITT regimens may decrease patient adherence. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a once-daily single-inhaler triple therapy (SITT), became available in the United States (US) in 2017, but real-world data comparing outcomes for SITT versus MITT are currently limited. This study compared outcomes among patients with COPD initiating MITT versus SITT with FF/UMEC/VI who were either Medicare Advantage with Part D (MAPD) beneficiaries or commercial enrollees in the US. Methods: Retrospective study using administrative claims data from the Optum Research Database for patients with COPD who initiated FF/UMEC/VI or MITT between September 1, 2017, and March 31, 2019 (index date: first pharmacy claim for FF/UMEC/VI cohort; earliest day of ≥30 consecutive days-long period of overlap in the day's supply of all triple therapy components for MITT cohort). COPD exacerbations, adherence to triple therapy, and all-cause and COPD-related health care resource utilization (HCRU) and costs were compared between FF/UMEC/VI and MITT initiators. Results: In total, 4659 FF/UMEC/VI initiators and 9845 MITT initiators for the MAPD population, and 821 FF/UMEC/VI initiators and 1893 MITT initiators for the commercial population were included in the study. MAPD beneficiaries initiating FF/UMEC/VI had a significantly lower annual rate of severe exacerbations compared to MITT initiators (0.26 vs 0.29; p=0.014). They also had a significantly higher mean adherence (proportion of days covered) (0.51 vs 0.37; p<0.001) and significantly lower all-cause and COPD-related inpatient stays compared to MITT initiators ([32.02% vs 34.27%; p=0.017], [16.09% vs 17.72%; p=0.037]). Trends were similar among the commercial population, but the results were not statistically significant. Conclusion: FF/UMEC/VI initiators had significantly fewer severe exacerbations, higher triple therapy adherence, and lower HCRU costs compared to MITT initiators for MAPD beneficiaries.

Nebuliser systems for drug delivery in cystic fibrosis.

BACKGROUND: Nebuliser systems are used to deliver medications to the lungs, to control the symptoms and the progression of lung disease in people with cystic fibrosis (CF). There are many different nebulised-medications prescribed for people with CF and there are many different types of nebuliser systems. Some of these nebulised medications are licenced for, and can be taken via only one type of nebuliser system; some are licensed for, and can be taken via more than one type of nebuliser system. This is an update to a previous systematic review. OBJECTIVES: To assess the time efficiency, effectiveness, safety, cost and impact of use (e.g. burden of care, adherence, quality of life (QoL)) of different nebuliser systems, when used with different inhaled medications for people with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books containing conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. We also searched online trial registries. Date of the most recent search: 9 August 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing nebuliser systems, including conventional nebulisers, vibrating mesh technology (VMT) systems, adaptive aerosol delivery (AAD) systems and ultrasonic nebuliser systems. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third review author assessed studies where agreement could not be reached. They assessed the certainty of the evidence using GRADE. MAIN RESULTS: The search identified 216 studies with 33 of these (2270 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic saline and other solutions through the different nebuliser systems in children and adults with CF. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. The certainty of the evidence ranged from low to very low. Some conventional nebuliser systems providing higher flows, higher respirable fractions, and smaller particles decrease treatment time, increase deposition (the amount of drug reaching the lung), and may be preferred by people with CF, as compared to other conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Newer nebuliser systems using AAD, or VMT (or both) reduce treatment time compared to conventional systems. Deposition (as a percentage of priming dose) with AAD is greater than with conventional systems. VMT systems may give greater deposition than conventional systems when measuring sputum levels. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved and that individuals prefer AAD or VMT systems, but also that some nebuliser systems using VMT may be subject to increased system failures. There is limited, unclear evidence on the impact of different nebuliser systems on lung function and a lack of data on the impact of different nebuliser systems on our outcomes of quality of life (QoL), adverse effects, respiratory exacerbations and related implications, adherence, satisfaction, cost and device reliability. AUTHORS' CONCLUSIONS: Newer technologies e.g. AAD and VMT have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, preference and adherence. Data are lacking for all varieties of medications which are used in CF care, including different inhaled antibiotics or hypertonic saline, with all delivery (nebuliser system) possibilities. Long-term RCTs are needed to evaluate different nebuliser systems to determine patient-focused outcomes (such as QoL and burden of care), safe and effective dosing levels of a wide variety of medications, clinical outcomes (such as hospitalisations and need for antibiotics), and an economic evaluation of their use. There are insufficient data to establish whether one nebuliser system is better than another overall. Clinicians should be aware of the variability in the performance of different nebuliser systems, compatibility with specific nebulised medication, and they must work with their patients to choose the best nebuliser system for each individual. This is likely to be an ongoing process as the needs and circumstances of each individual change over time.

Patient and social factors related to nebulizer use in COPD patients at the transition of care: a qualitative study.

BACKGROUND: Transition from hospital to home is a vulnerable period for patients with COPD exacerbations, with a high risk for readmission and mortality. Twenty percent of patients with an initial hospitalization for a COPD exacerbation are readmitted to a hospital within 30 days, costing the health care system over $15 billion annually. While nebulizer therapy directed at some high-risk COPD patients may improve the transition from hospital to home, patient and social factors are likely to contribute to difficulties with their use. Current literature describing the COPD patient's experience with utilizing nebulizer therapy, particularly during care transitions, is limited. Therefore, the objective of this study was to explore underlying COPD patient and social factors contributing to practical difficulties with nebulizer use at the care transition from hospital to home. METHODS: This was a qualitative study conducted between September 2020 and June 2022. Patients were included if they were ≥ 40 years old, had a current diagnosis of COPD, had an inpatient admission at a hospital, and were discharged directly to home with nebulizer therapy. Semi-structured, one-on-one interviews with patients were conducted covering a broad range of patient and social factors and their relationships with nebulizer use and readmission. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using a mixed inductive and deductive approach. RESULTS: Twenty-one interviews were conducted, and subjects had a mean age of 64 ± 8.4 years, 62% were female, and 76% were White. The predominant interview themes were health care system interactions and medication management. The interviews highlighted that discharge counseling methods and depth of counseling from hospitals were inconsistent and were not always patient-friendly. They also suggested that patients could appropriately identify, set up, and utilize their nebulizer treatment without difficulties, but additional patient education is required for nebulizer clean up and maintenance. CONCLUSIONS: Our interviews suggest that there is room for improvement within the health care system for providing consistent, effective discharge counseling. Also, COPD patients discharged from a hospital on nebulizer therapy can access and understand their treatment but require additional education for nebulizer clean up and maintenance.

Cost-Effectiveness of Single-Inhaler Triple Therapy (FF/UMEC/VI) versus Tiotropium Monotherapy in Patients with Symptomatic Moderate-to-Very Severe COPD in the UK.

Purpose: For patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite maintenance treatment, clinical management guidelines recommend a stepwise escalation from monotherapy to dual therapy, and from dual therapy to triple therapy. However, in clinical practice, patients are often escalated directly from monotherapy to triple therapy based on disease severity. This study evaluated the cost-effectiveness of once-daily, single-inhaler fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) triple therapy compared with long-acting muscarinic antagonist monotherapy with once-daily tiotropium (TIO) in patients with symptomatic moderate-to-very severe COPD, from a UK National Health Service perspective. Patients and Methods: The validated GALAXY-COPD disease progression model was populated with patient baseline characteristics and treatment effect data from the 12-week GSK Study 207626 comparing FF/UMEC/VI with TIO in patients with moderate-to-very severe COPD. UK unit costs and drug costs (British Pound, 2021) were applied to healthcare resource utilization and treatments. The base case analysis was conducted over a lifetime horizon, and costs and health outcomes (except for life years [LYs]) were discounted at 3.5% per year. Model outputs included exacerbation rates, healthcare costs, LYs, quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios. Results: Overall, treatment with FF/UMEC/VI resulted in increased clinical benefit (reduction in total exacerbations and increased overall survival and QALYs), coupled with cost savings (derived from lower maintenance and exacerbation healthcare costs) compared with TIO monotherapy. In the base case analysis, FF/UMEC/VI provided an additional 0.393 LYs (95% range: 0.176, 0.655) and 0.443 QALYs (0.246, 0.648), at a cost saving of £880 (£54, £1608) versus TIO. FF/UMEC/VI remained the cost-effective (dominant) treatment option across sensitivity and scenario analyses. Conclusion: FF/UMEC/VI offers greater clinical benefits and is a cost-effective treatment option compared with TIO for the treatment of adult patients with COPD with persistent symptoms and/or who are at risk of exacerbation in the UK.

Plackett-Burman and face-centered composite designs for development and optimization of chromatographic method for the simultaneous determination of glycopyrronium, indacaterol and mometasone in their fixed dose combination inhaler - Green profile assessment.

A novel simple, specific, sensitive, accurate and precise reversed phase high performance liquid chromatographic method (RP-HPLC/UV) was developed and validated for the simultaneous estimation of Glycopyrronium bromide (GLY), Indacaterol acetate (IND) and Mometasone furoate (MOF) in pure form, in laboratory prepared mixtures and in pharmaceutical dosage form. Experimental design methodology was applied by using Plackett-Burman and face-centered composite designs to achieve the best resolution with minimum experimental trials. The designed model was statistically analyzed, graphically presented by surface plots and the relationships between coefficients of the derived polynomial equations were interpreted. Chromatographic separation was achieved on Inertsil ODS C18 column (250 ×4.6 mm, 5 µm) at ambient temperature using a mobile phase composed of methanol: 0.1% glacial acetic acid (pH4) in a gradient elution at a flow rate 1 mL /min. UV detection was carried out at 233 nm. Response was found to be linear in the concentration range of 20-120 µg /mL with regression coefficient (r2 = 0.999) for GLY, 50-300 µg /mL with regression coefficient (r2 = 0.9995) for IND and 50-300 µg /mL with regression coefficient (r2 = 0.9998) for MOF. The method was validated as per ICH guidelines and satisfactory results were achieved. The method was successfully applied for the analysis of the cited drugs in their fixed dose combination (FDC) pharmaceutical formulation. Statistical comparison between the results obtained by the proposed method and the reference methods for GLY, IND and MOF showed no significant difference. The developed method could be implemented in quality control aspects of the cited drugs. Four green metrics were used to evaluate the new RP-HPLC/UV method's greenness and compare it to other published techniques.

Long-Term Cost-Effectiveness of Digital Inhaler Adherence Technologies in Difficult-to-Treat Asthma.

BACKGROUND: Digital inhalers can monitor inhaler usage, support difficult-to-treat asthma management, and inform step-up treatment decisions yet their economic value is unknown, hampering wide-scale implementation. OBJECTIVE: We aimed to assess the long-term cost-effectiveness of digital inhaler-based medication adherence management in difficult-to-treat asthma. METHODS: A model-based cost-utility analysis was performed. The Markov model structure was determined by biological and clinical understanding of asthma and was further informed by guideline-based assessment of model development. Internal and external validation was performed using the Assessment of the Validation Status of Health-Economic (AdViSHE) tool. The INCA (Inhaler Compliance Assessment) Sun randomized clinical trial data were incorporated into the model to evaluate the cost-effectiveness of digital inhalers. Several long-term clinical case scenarios were assessed (reduced number of exacerbations, increased asthma control, introduction of biosimilars [25% price-cut on biologics]). RESULTS: The long-term modelled cost-effectiveness based on a societal perspective indicated 1-year per-patient costs for digital inhalers and usual care (ie, regular inhalers) of €7,546 ($7,946) and €10,752 ($11,322), respectively, reflecting cost savings of €3,207 ($3,377) for digital inhalers. Using a 10-year intervention duration and time horizon resulted in cost savings of €26,309 ($27,703) for digital inhalers. In the first year, add-on biologic therapies accounted for 69% of the total costs in the usual care group and for 49% in the digital inhaler group. Scenario analyses indicated consistent cost savings ranging from €2,287 ($2,408) (introduction biosimilars) to €4,581 ($4,824) (increased control, decreased exacerbations). CONCLUSIONS: In patients with difficult-to-treat asthma, digital inhaler-based interventions can be cost-saving in the long-term by optimizing medication adherence and inhaler technique and reducing add-on biologic prescriptions.

[Assessment of inhalation technique in patients with bronchial asthma and chronic obstructive pulmonary disease].

AIM: Investigate inhalation techniques using different inhalers types and their effect on the course of disease. MATERIALS AND METHODS: This cross-sectional study included 110 patients with asthma, chronic obstructive pulmonary disease using the inhaler at least one month. Inhaler errors performed during demonstration were evaluated for each patient and entered in the check-lists. We also collected information about co-morbidities, education, mMRC dyspnea score, rate of exacerbations, and performed spirometry. RESULTS: 80.9% of patients used metered-dose inhaler, 20.9% - single-dose and 21.8% - multiple-dose dry powder inhaler, 22.7% - soft-mist inhaler. Inhaler errors were made by 80.9% patients. The mean number of mistakes in metered-dose inhaler use was 2±1.6, single-dose powder inhaler -1.5±1.3, multiple-dose dry powder inhaler - 1.25±1.4, soft-mist inhaler - 0.68±0.7 (р=0.003). Age, diagnosis, duration of disease, education level, inhalers usage by relatives have no influence on the inhalation technique. A number of errors was related to female gender (р=0.007) and usage of more than 2 inhalers (r=0.3, p=0.002), previous instruction about inhalation technique (r=0.3, p=0.001). On the other hand, there were correlations between the number of errors and degree of bronchial obstruction, asthma control, severity of dyspnea by mMRC score, exacerbation rate. CONCLUSION: Patients with bronchoobstructive diseases perform many inhaler errors, that substantially influences the severity and course of asthma and chronic obstructive pulmonary disease.

Patient Characteristics to Consider When Selecting an Inhaler for the Treatment of Chronic Obstructive Pulmonary Disease and Available Assessment Methods: A Narrative Review.

Inhaler misuse is common among patients with chronic obstructive pulmonary disease and associated with poor disease control. Many patient characteristics are reported to impact inhaler use, but there are no studies in the literature on the best way to evaluate them. This narrative review aims to identify patient characteristics that influence the correct use of an inhaler and describe the tools available for their assessment. First, we searched four different databases to identify reviews describing patient characteristics reported to impact inhaler use. In a second step, ways to characterize these aspects were searched using the same databases. Fifteen patient characteristics impacting on the use of inhalers were identified. Peak inspiratory flow, dexterity, and cognitive impairment were the most studied characteristics and appeared to have the highest impact on the correct use of inhalers. Notably, peak inspiratory flow can be reliably assessed in clinical practice using the In-Check Dial®. Triggering coordination, breath retention, collaboration/consciousness, and muscle strength in the fingers were important characteristics, but insufficient data exist to recommend the use of a specific tool for their assessment in daily practice. Other identified characteristics have a more uncertain impact. A demonstration of inhalation technique by the patient, combined with the measurement of peak inspiratory flow using the In-Check Dial®, appears to be an effective strategy to assess the characteristics with the highest impact on the correct use of an inhaler. In the future, "smart" inhalers could also play a decisive role in this area.

Children with uncontrolled asthma from economically disadvantaged neighborhoods: Needs assessment and the development of a school-based telehealth and electronic inhaler monitoring system.

BACKGROUND: Children from economically disadvantaged communities often encounter healthcare access barriers, increasing risk for poorly controlled asthma and subsequent healthcare utilization. This highlights the need to identify novel intervention strategies for these families. OBJECTIVE: To better understand the needs and treatment preferences for asthma management in children from economically disadvantaged communities and to develop a novel asthma management intervention based on an initial needs assessment and stakeholder feedback. METHODS: Semistructured interviews and focus groups were conducted with 19 children (10-17 years old) with uncontrolled asthma and their caregivers, 14 school nurses, 8 primary care physicians, and three school resource coordinators from economically disadvantaged communities. Interviews and focus groups were audio-taped and transcribed verbatim and then analyzed thematically to inform intervention development. Using stakeholder input, an intervention was developed for children with uncontrolled asthma and presented to participants for feedback to fully develop a novel intervention. RESULTS: The needs assessment resulted in five themes: (1) barriers to quality asthma care, (2) poor communication across care providers, (3) problems identifying and managing symptoms and triggers among families, (4) difficulties with adherence, and (5) stigma. A proposed video-based telehealth intervention was proposed to stakeholders who provided favorable and informative feedback for the final development of the intervention for children with uncontrolled asthma. CONCLUSIONS: Stakeholder input and feedback provided information critical to the development of a multicomponent (medical and behavioral) intervention in a school setting that uses technology to facilitate care, collaboration, and communication among key stakeholders to improve asthma management for children from economically disadvantaged neighborhoods.

Cognitive impairment according to Montreal Cognitive Assessment independently predicts the ability of chronic obstructive pulmonary disease patients to maintain proper inhaler technique.

BACKGROUND: Maintaining correct inhaler technique is crucial in the management of chronic obstructive pulmonary disease (COPD). We aimed to investigate the inhaler technique in patients with COPD, to compare it immediately after and at 1 month after training, and to identify the predictors of incorrect inhaler use at 1 month after training. METHODS: This prospective study was conducted at the COPD clinic of Siriraj Hospital (Bangkok, Thailand). Patients demonstrating improper inhaler use were trained face-to-face by pharmacists. Inhaler technique was re-assessed immediately after and at 1 month after training. The Montreal Cognitive Assessment (MoCA) score, pulmonary function tests, 6-min walk distance (6 MWD), modified Medical Research Council scale score, and COPD Assessment Test (CAT) score were evaluated. RESULTS: Sixty-six patients with COPD who demonstrated at least one critical error during the use of any controller inhaler were enrolled. The mean age was 73.0 ± 9.0 years, and 75.8% patients had moderate/severe COPD. Immediately after training, all patients used dry powder inhalers correctly and 88.1% used pressurized metered-dose inhalers correctly. At 1 month, the number of patients demonstrating the correct technique decreased across all devices. Multivariable analysis revealed that MoCA score ≤ 16 was independently associated with a critical error at 1 month after training (adjusted odds ratio: 12.7, 95% confidence interval: 1.8-88.2, p = 0.010). At 1 month, CAT score (11.4 ± 8.9 vs. 8.4 ± 5.5, p = 0.018) and 6 MWD (351 ± 93 m vs. 372 ± 92 m, p = 0.009) had significantly improved in patients demonstrating the correct technique, and CAT score met the minimal clinically important difference. CONCLUSIONS: Face-to-face training by pharmacists improved patient performance. However, the number of patients following proper technique had decreased at 1 month after training. Cognitive impairment (MoCA score ≤ 16) independently predicted the ability of COPD patients to maintain proper inhaler technique. Assessment of cognitive function combined with technical re-assessment and repeated training should improve COPD management.

Patenting Strategies on Inhaler Delivery Devices.

BACKGROUND: Patients with asthma and COPD rely on inhalers to control symptoms. Yet, these products remain expensive, in part because brand-name manufacturers have obtained numerous patents on inhalers, including on their delivery devices. Recent antitrust litigation has raised questions about the boundaries of listing device patents with the US Food and Drug Administration (FDA), particularly when patents do not claim any active ingredients. RESEARCH QUESTION: How have manufacturers relied on device patents to preserve market exclusivity on brand-name inhalers? STUDY DESIGN AND METHODS: We identified patents on brand-name inhalers approved for asthma and COPD between 1986 and 2020 using the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). We extracted information about patents from LexisNexis TotalPatent One and Google Patents and searched device patents for mention of active ingredients or other prespecified features linking the patent to the relevant drug. For each inhaler, we determined the duration of protection added by device patents. RESULTS: The FDA approved 53 brand-name inhalers for asthma and COPD from 1986 through 2020, 39 of which had at least one device patent. One hundred thirty-seven distinct device patents were in the final cohort, representing 49% of all patents listed on inhalers. Seventy-seven percent of device patents made no mention of active ingredients or their molecular structures, and 72% made no mention of any relevant prespecified feature connecting the device patent to the drug product. For the 39 brand-name inhalers with one or more device patents listed in the Orange Book, device patents extended the duration of market protection by a median of 5.5 years (interquartile range, 0.0-10.5 years) beyond the last-to-expire nondevice patent. INTERPRETATION: Patent and regulatory reform is needed to promote generic competition and to ensure that patients with asthma and COPD have access to affordable medications.

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.

Manufacturer Revenue on Inhalers After Expiration of Primary Patents, 2000-2021.

This study quantifies the revenue earned on all brand-name inhalers approved by the US Food and Drug Administration from 2000 to 2021 and compared earnings before and after expiration of primary patents on these products.

An aerosol inhalation monitor would improve the accuracy of checklist assessment in drug inhalation techniques.

BACKGROUND: Checklists are usually employed to assess the inhalation techniques in patients, but partial techniques are difficult to evaluate visually. This study aimed to assess the checklist validity and an agreement between checklists and an aerosol inhalation monitor (AIM) assessments. METHODS: This study used a checklist and an AIM to evaluate the participants' inhalation techniques with a pressurized metered-dose inhaler (MDI) and two dry powder inhalers (DPIs). The kappa (κ) coefficient, prevalence-adjusted and bias-adjusted κ (PABAK), sensitivity, specificity, positive predictive value, and negative predictive value were all calculated to determine the agreement between the checklist and AIM in an MDI and DPIs with different inhalation technique steps. RESULTS: The checklist and AIM exhibited poor agreement in the MDI for actuation and inhalation time, and a moderate agreement for inspiratory flow. The fair agreement was observed in DPIs for inspiratory flow between the checklist and AIM. The steps of holding breath in MDI and DPIs were highly correlated between both assessments. The lowest accuracy evaluated with an AIM was found in the step of actuation and inhalation time in the MDI and in the inspiratory flow step in DPIs. CONCLUSION: The checklist tended to overestimate the accuracy of critical techniques including the actuation and inhalation time in MDIs and the inspiratory flow in DPIs. Thus, the AIM device can be used as an objective auxiliary tool to assess and quantify the specific steps of inhalation technique for the users with MDI and DPIs.

Estimated cost-savings from optimizing use of inhaled medications for inpatients with obstructive lung disease.

CONCLUSIONS: Models representing transitions from all-nebulized to nebulizer-plus-MDI respiratory medications resulted in cost savings, largely from the reduction of labor cost of nebulizer administration with nebs-only treatment. Therefore, transitioning from nebs to MDIs can lead to cost savings and could allow greater opportunities for inhaler education.

Guidelines for the selection of hydrogen gas inhalers based on hydrogen explosion accidents.

Despite the fact that we have reported on the dangers of the explosion of hydrogen gas inhalers, hydrogen gas inhalers with explosive hazards are, as a matter of fact, still being sold today. In this study, we investigated past reports of hydrogen gas inhaler explosion accidents to clarify the causes of these explosion incidents. As a result of this investigation, we found that the central cause was the leakage of hydrogen gas inside the hydrogen gas inhaler. Although it is said that the explosive concentration of hydrogen is between 10% and 75%, and that the gas does not explode above 75% due to the lack of oxygen, we confirmed through a series of ignition experiments that explosions can occur even in hydrogen gas inhalers that produce 100% hydrogen gas. Some manufacturers of such highly concentrated hydrogen gas inhalers claim that the high concentration and purity of hydrogen is safe and that there is no risk of explosion. We believe that manufacturing or selling such products that pose a risk of explosion or detonation is a violation of social justice. This paper presents ideas for selecting safe hydrogen gas inhalers based on a survey of past accident cases.