Risk Factors Associated with Misuse of Soft Mist Inhaler in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD. Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants' handling of the device by using a check list. Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse. Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.

The Effect of Priming new Plastic Spacers with 20 Puffs Salbutamol on Bronchodilator Response in Asthmatic Children.

The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 µg/puff) through either a primed or a new spacer. The change in forced expiratory volume in the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics.

Comparative effectiveness and safety of triple therapy and non-triple therapy interventions for COPD: an overview of systematic reviews.

BACKGROUND: Some systematic reviews (SRs) on triple therapy (consisting of long-acting ß2-agonist, long-acting muscarinic antagonist, and inhaled corticosteroid, LABA/LAMA/ICS) for chronic obstructive pulmonary disease (COPD) have reported conflicting results. As the number of syntheses increases, the task of identifying and interpreting evidence becomes increasingly complex and demanding. OBJECTIVES: To provide a comprehensive overview of the efficacy and safety of triple therapy for COPD. DESIGN: Overview of SRs. METHODS: Two independent reviewers conducted comprehensive searches in PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant SRs that compared triple therapy with any non-triple therapy for COPD, from the inception of these databases until 1 June 2023. The AMSTAR 2 and GRADE tools were utilized to assess the quality of the included studies and the evidence for each outcome. RESULTS: Eighteen SRs encompassing 30 original studies and involving 47,340 participants were analyzed. The overall AMSTAR 2 rating revealed that 3 SRs were of low quality, 13 SRs were of critically low quality, and 2 SRs were of high quality. No high-certainty evidence revealed a significant advantage of triple therapy in improving lung function or reducing acute exacerbations. However, all evidence, including one high certainty, supported the benefits of improving quality of life. Regarding all-cause mortality, no significant difference was found when compared to LAMA or ICS/LABA; however, high-certainty evidence confirmed its effectiveness when compared with LABA/LAMA. Notably, high-certainty evidence indicated that triple therapy was associated with a significant increase in the risk of pneumonia compared to LABA/LAMA. CONCLUSION: Triple therapy demonstrated notable benefits in improving lung function, reducing exacerbations, improving quality of life, and reducing all-cause mortality. However, it is important to note that it may also significantly increase the risk of pneumonia. TRIAL REGISTRATION: This overview protocol was prospectively registered with PROSPERO (No. CRD42023431548).

Comparison of Forced Oscillation Technique, Lung Volumes by Body Plethysmography, and Spirometry in Moderate Persistent Adult Asthma.

BACKGROUND: Spirometry is used extensively, but airway oscillometry is gaining acceptance for evaluating obstructive airway disorders. Moderate persistent asthma requires daily treatment with inhaled corticosteroids (ICS). MATERIALS AND METHODS: We aimed to examine the relationship between airway oscillometry and lung volumes, which are the markers of lung physiology in obstructive airway disease and spirometry in the real-world clinical setting. A total of 72 adults with moderate persistent asthma followed up in our outpatient department from November 2021 to August 2022, and their clinical details and tests of spirometry, forced oscillation technique (FOT), and lung volumes by body plethysmography (BP) performed before and after bronchodilator administration were analyzed. RESULTS: The mean age of the study population was 40 years, and the majority (57%) were females. FOT detected airflow limitation in 12 of the 31 patients with normal spirometry. BP detected abnormalities in more patients than both spirometry and FOT (91.6 vs 73.6%, p < 0.001). Respiratory resistance 5 (R5) had a negative correlation with functional residual capacity (FRC) and total lung capacity (TLC). Reactance 5 (X5) correlated positively with inspiratory capacity (IC) and TLC and negatively with reserve volume (RV)/TLC ratio. A positive correlation was found between IC/TLC% and postbronchodilator X5 and between R5 and 19 and RV/TLC. R5 had a negative and X5 had a positive correlation with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and maximal mid expiratory flow rates (MMEF). ∇X5 had a negative correlation with FEV1, MMEF, and FEV1/FVC. Spirometry detected postbronchodilator responsiveness in more patients than FOT when only the R5 criterion was used and in a comparable number when the X5 criterion was added. ∇X5 and R5-R19/R5 declined significantly after bronchodilators. CONCLUSION: We concluded that there is a moderate correlation between FOT and spirometry and lung volumes by BP. FOT and spirometry should be used together to identify airflow obstruction and postbronchodilator responsiveness in asthma. Lung volumes by BP identify more abnormalities in adults with asthma than both spirometry and FOT. Thresholds to define postbronchodilator responsiveness (PBDR) for ∇X5 and R5-R19 need to be defined.

Prescription patterns and effectiveness of medications for chronic obstructive pulmonary disease: A retrospective study of real-world settings.

This study aimed to define real-world prescription patterns in Korea and compare the effectiveness of chronic obstructive pulmonary disease (COPD) medications. We used national claims data provided by the Health Insurance Review and Assessment Service in Korea and examined patients who were first diagnosed with COPD and started treatment between May 1, 2017, and April 30, 2018, with no change in drug regimen. Among 30,784 patients with COPD, long-acting ß2 agonist (LABA) combined with long-acting muscarinic antagonist (LAMA) (32.7%), inhaled corticosteroid-LABA (ICS-LABA) (25.6%), LAMA (18.3%), ICS (5.8%), or LABA (4.6%) were prescribed as the first-choice inhalers. The use of LABA-LAMA (hazard ratio [HR], 0.248-0.584), LAMA (HR, 0.320-0.641), ICS-LABA (HR, 0.325-0.643), and xanthine (HR, 0.563-0.828) significantly reduced the total and severe exacerbation rates compared with no use of each medication. However, the use of ICS or LABA individually did not yield such effects. The continued use of LABA-LAMA, LAMA, and ICS-LABA showed a significant effect on exacerbation rate, whereas the long-term use of ICS, LABA, and xanthine did not. Moreover, some high doses of ICS-LABA did not show significant effects. This real-world study revealed that LAMA and/or LABA could be the first choice of therapy, as recommended by recent guidelines. However, ICS, xanthine, and high-dose ICS-LABA are still being prescribed frequently as first-line drugs in Korea.

[Quelles indications pour la corticothérapie dans la BPCO ?] / What are the indications for corticosteroid therapy in COPD?

WHAT ARE THE INDICATIONS FOR CORTICOSTEROID THERAPY IN COPD? In stable state chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) should be used in case of frequent exacerbation only, associated with long-term bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). When frequent exacerbations persist despite dual inhaled therapy (LABA + CSI or LABA+LAMA), triple inhaled therapy (LAMA+LABA+CSI) is indicated. In COPD exacerbation, the level of evidence for systemic corticosteroids is very low, justifying not to systematically prescribe systemic corticosteroids and when used to restrict this use to short-term (5 days) and low doses.

QUELLES SONT LES INDICATIONS POUR LA CORTICOTHÉRAPIE DANS LA BPCO ? Dans la bronchopneumopathie chronique obstructive (BPCO) à l'état stable, les corticostéroïdes inhalés (CSI) ne sont à utiliser qu'en cas d'exacerbations fréquentes, en association avec des bronchodilatateurs de longue durée d'action de type bêta-2-agoniste de longue durée d'action (LABA) et anticholinergique de longue durée d'action (LAMA). En cas de persistance d'exacerbations fréquentes malgré une bithérapie inhalée (LABA-CSI ou LAMA-LABA), une triple thérapie (LAMA-LABA CSI) peut être proposée. En cas d'exacerbation de BPCO, le niveau de preuve de la corticothérapie systémique est faible, justifiant ne pas recourir à ce traitement de façon systématique ou de le réaliser en cures courtes (cinq jours) et à faibles doses quand il est prescrit.

Salbutamol Easyhaler provides non-inferior relief of methacholine induced bronchoconstriction in comparison to Ventoline Evohaler with spacer: A randomized trial.

BACKGROUND: Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event. OBJECTIVE: We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed. METHODS: This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV1) were randomized to receive Salbutamol Easyhaler (2 × 200 µg), Ventoline Evohaler with spacer (4 × 100 µg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 µg) as a reliever. The treatment was repeated if FEV1 did not recover to at least -10 % of baseline. RESULTS: 180 participants (69 % females, mean age 46 yrs [range 18-80], FEV1%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV1 difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV1 between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose. CONCLUSION: The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.

In silico investigation of inhalation condition impacts on hygroscopic growth and deposition of salbutamol sulphate in human airways.

The objective of this study is to explore the transport, size growth, and deposition of Salbutamol Sulphate (SS) using Computational Fluid Dynamics (CFD). A CT-based realistic model of human airways from the oral cavity to the 5th generation of the lung was utilized as the computational domain. Four Test Cases (TC) with varying temperature and relative humidity (RH) under two inspiratory waveforms were considered to completely evaluate the impact of inhalation conditions on particle growth. Salbutamol Sulphate (SS) is a ß2-adrenergic agonist and has been extensively used for asthma treatment. A monodispersed distribution of SS particles with an initial diameter of 167 nm was considered at the mouth inlet based on pharmaceutical data. Results indicated that inhalation of saturated/supersaturated air (RH>100%) leads to significant hygroscopic growth of SS particles with a factor of 10. In addition, the deposition efficiency of SS particles under the Quick and Deep (QD) inhalation profile was enhanced as the flow temperature and humidity increased. However, the implementation of Slow and Deep (SD) inspiratory waveform revealed that the same particle size growth is achieved in the respiratory system with lower deposition efficiency in the mouth-throat (less than 3%) and tracheobronchial airway (less than 2.18%). For the escaped particles form the right lung, in the SD waveform under TC 3, the maximum particle size distribution was for 600 nm particles with 25% probability. In the left lung, 30% of the particles were increased up to 950 nm in size. For the QD waveform in TC 3 and TC4, the most frequent particles were 800 nm with 36% probability. This holds practical significance in the context of deep lung delivery for asthmatic patients with enhanced deposition efficiency and large particle size. The findings of the present study can contribute to the development of targeted drug delivery strategies for the treatment of pulmonary diseases using hygroscopic dry powder formulations.

Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study.

BACKGROUND: Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score. This real-world study compared the effectiveness of switching patients with COPD in England from MITT to once-daily SITT with FF/UMEC/VI by evaluating rates of COPD exacerbation, healthcare resource use (HCRU) and associated direct medical costs. METHODS: Retrospective cohort pre-post study using linked primary care electronic health record and secondary care administrative datasets. Patients diagnosed with COPD at age ≥35 years, with smoking history, linkage to secondary care data and continuous GP registration for 12 months pre-switch and 6 months post-switch to FF/UMEC/VI were included. Index date was the first initiation of an FF/UMEC/VI prescription immediately following MITT use from 15 November 2017 to 30 September 2019. Baseline was 12 months prior to index, with outcomes assessed 6/12 months pre-switch and post-switch, and stratified by prior COPD exacerbation status. RESULTS: We included 2533 patients (mean [SD] age: 71.1 [9.9] years; 52.1% male). In the 6 months post-switch, there were significant decreases in the proportion of patients experiencing ≥1 moderate-to-severe (36.2%-28.9%), moderate only (24.4%-19.8%) and severe only (15.4%-11.8%) COPD exacerbation (each, p<0.0001) compared with the 6 months pre-switch. As demonstrated by rate ratios, there were significant reductions in exacerbation rates of each severity overall (p<0.01) and among patients with prior exacerbations (p<0.0001). In the same period, there were significant decreases in the rate of each COPD-related HCRU and total COPD-related costs (-24.9%; p<0.0001). CONCLUSION: Patients with COPD switching from MITT to once-daily SITT with FF/UMEC/VI in a primary care setting had significantly fewer moderate and severe exacerbations, and lower COPD-related HCRU and costs, in the 6 months post-switch compared with the 6 months pre-switch.

Influence of design parameters on sustained drug release properties of 3D-printed theophylline tablets.

The application of three-dimensional printing (3DP) in the pharmaceutical industry brings a broad spectrum of benefits to patients by addressing individual needs and improve treatment success. This study investigates the sustained release properties of 3DP tablets containing Theophylline (TPH), which is commonly used to treat respiratory diseases and recently having a comeback due to its potential in the treatment of conditions like Covid-19. Since TPH is a narrow therapeutic window (NTW) drug with serious side effects in the event of overdose, the release properties must be observed particularly closely. We employed a state-of-the-art single screw extrusion 3D printer, which is fed with granules containing the drug. By employing a Taguchi orthogonal array design of experiments (DOE), tablet design parameters and factor related process stability were sought to be evaluated fundamentally. Following this, examinations regarding tailored TPH dosages were undertaken and a relationship between the real printed dose of selected tablet designs and their sustained drug release was established. The release profiles were analyzed using different mathematical model fits and compared in terms of mean dissolution times (MDT). Finally, in-vivo/in-vitro correlation (IVIVC) and physiologically based pharmacokinetic (PBPK) modeling showed that a paradigm patient group could be covered with the dosage forms produced.

Role of nebulised magnesium sulfate in treating acute asthma in children: a systematic review and meta-analysis.

OBJECTIVES: To review the efficacy of nebulised magnesium sulfate (MgSO4) in acute asthma in children. METHODS: The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO4 as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them. RESULTS: 10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO4/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I2=21%). Children in the MgSO4 group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I2=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups. CONCLUSIONS: There is low-certainty evidence that nebulised MgSO4 as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO4 in paediatric acute asthma management. PROSPERO REGISTRATION NUMBER: CRD42022373692.

Albuterol-budesonide fixed-dose combination rescue inhaler for asthma: a plain language summary of the MANDALA study.

What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.

Bronchodilator response assessment through impulse oscillometry system and spirometry in children and adolescents with cystic fibrosis.

OBJECTIVE: To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis. METHODS: Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation. RESULTS: The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response. CONCLUSIONS: The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.

Budesonide/Glycopyrrolate/Formoterol for the Management of COPD in a UK Primary Care Population: Real-World Use and Early Medication Success.

Purpose: Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data. Patients and Methods: Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori). Results: Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV1: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting ß2-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period. Conclusion: The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.

[Differences in the elastic work of breathing of the pulmonary parenchyma in patients with bronchial asthma and COPD].

AIM: To determine and compare the work of breathing to overcome elastic resistance (Ael) in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) with similar changes in the elastic properties of the parenchyma in the same settings of ventilation disorders (grade 1). MATERIALS AND METHODS: Differences in the manifestations of similar changes in the elastic properties of the lungs in patients with BA and COPD were evaluated. To identify differences, a comparative study was conducted on Аel overcome in BA patients with positive bronchodilator (with salbutamol) and bronchoconstrictor (with methacholine) tests, with reduced and preserved bronchial conductance (groups 1 and 2, respectively), and in COPD patients with negative bronchodilator and bronchoconstrictor tests (group 3). All study patients showed a grade 1 lung ventilation disorder (a decrease in the one-second forced expiratory volume by 15-35%). The results were compared with each other and with the control group (group 4, healthy non-smokers). All study patients were comparable by age and sex. The respiration mechanics was studied using simultaneous registration of spirogram and transpulmonary pressure, and the parameters of bronchial conductance and ventilation were determined using body plethysmopressography using the Jager software and hardware system. RESULTS AND CONCLUSION: In COPD patients, Ael was significantly increased (p>0.05), whereas in both BA groups, it was unchanged. Increased elastic work of breathing in patients with COPD may be associated with the involvement of certain types of contractile elements, which are preserved in patients with BA at the initial stages of the disease.

Improving croup management at a pediatric emergency department.

OBJECTIVES: Over-testing and over-treatment are common in children with croup at pediatric emergency departments (PED). The objective of the study was to improve care for children with croup. METHODS: In this quality improvement (QI) initiative, all pediatric residents starting their rotation in the PED attended an informative presentation about croup and were provided reminders throughout their rotation. The primary outcome of this QI initiative was to reduce nebulized epinephrine (NE) use among children with mild croup by 50% over 7 months. The secondary outcome was to reduce X-rays by 50% over 7 months. Other outcomes included the administration of dexamethasone to all children with croup, reduction of antibiotics, laboratory tests, and revisits, and shortening the duration between physical examination to dexamethasone and NE treatments, and the length of stay (LOS) at the PED. RESULTS: NE administration to patients with mild croup decreased from 80.2% to 36.3% (p < 0.001). The proportion of children with X-rays decreased from 37.4% to 17.1% (p < 0.001). There was a significant increase in dexamethasone administration, and significant decreases in laboratory blood tests, expanded viral PCR panel tests, and antibiotic prescription among all croup cases (p < 0.001). Revisit rates were not significantly different (p > 0.05). Time to dexamethasone and LOS shortened significantly (p < 0.001). CONCLUSION: With this QI intervention, decreases in the rate of administration of NE to mild croup cases, antibiotic prescription, X-ray, laboratory blood and respiratory PCR panel tests in all croup cases were achieved without an increase in revisits. However, unnecessary NE, antibiotic, and X-ray rates are still high.

Suboptimal peak inspiratory flow rate in dry-powder inhaler users for chronic obstructive pulmonary disease in Korea.

BACKGROUND: A suboptimal peak inspiratory flow rate (PIFR) in dry-powder inhaler (DPI) users can lead to insufficient therapeutic effects in the treatment of chronic obstructive pulmonary disease (COPD). However, few data on the prevalence of and factors associated with suboptimal PIFR in Korean patients with COPD are available. METHODS: We conducted a cross-sectional study of patients with COPD who had been using DPIs for more than three months. PIFR was measured using an In-Check DIAL G16 device. Suboptimal PIFR was defined as below the resistance-matched threshold. Multivariable logistic regression analysis was used to determine factors associated with suboptimal PIFR. RESULTS: Of 444 DPI users with COPD, the rate of suboptimal PIFR was 22.0 % (98/444). In a multivariable analysis, significant factors associated with suboptimal PIFR were age (adjusted odds ratio [aOR] = 1.06 by 1-year increase; 95 % confidence interval [CI] = 1.02-1.09), male sex (aOR = 0.28; 95 % CI = 0.11-0.73), body mass index (BMI) (aOR = 0.91 by 1 kg/m2 increase; 95 % CI = 0.85-0.99), post-bronchodilator forced vital capacity (FVC) %pred (aOR = 0.97 by 1%pred increase; 95 % CI = 0.95-0.99), and In-Check DIAL R2-type inhaler [medium-low resistance] use (aOR = 3.70 compared with R1-type inhalers [low resistance]; 95 % CI = 2.03-7.03). CONCLUSIONS: In Korea, more than one-fifth of DPI users with COPD had a suboptimal PIFR. The factors associated with suboptimal PIFR were age, female gender, low BMI, low FVC, and R2-type inhaler use. Therefore, clinicians should carefully evaluate the possibility of suboptimal PIFR when prescribing DPIs.

Pharmacokinetic Models for Inhaled Fluticasone Propionate and Salmeterol Xinafoate to Quantify Batch-to-Batch Variability.

Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development. This work developed the PK models for inhaled FP and SX that could represent potential batch variability. Two batches each of the reference and the test product (R1, R2, T1, T2) of Advair Diskus (100 µg FP/50 µg SX inhalation) were administered to 60 healthy subjects in a 4-period, 4-sequence crossover study. The failure of the bioequivalence (BE) between R1 and R2 confirmed the high between-batch variability of the RLD. Non-linear mixed effect modeling was used to estimate the population mean PK parameters for each batch. For FP, a 2-compartment model with a sequential dual zero-order absorption best described the PK profile. For SX, a 2-compartment model with a first-order absorption model best fit the data. Both models were able to capture the plasma concentration, the maximum concentration, and the total exposure (AUCinf) adequately for each batch, which could be used to simulate the BE study in the future. In vitro properties were also measured for each batch, and the batch with a higher fraction of the fine particle (diameter < 1 µm, < 2 µm) had a higher AUCinf. This positive correlation for both FP and SX could potentially assist the batch selection for the PK BE study.