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Journal of Aerosol Medicine and... Aug 2023The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for...
The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. An model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns ( = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. The model showed that the inspiratory time to total respiratory cycle time (/; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The model showed that / was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.
Topics: Adult; Humans; Administration, Inhalation; Aerosols; Albuterol; Bronchodilator Agents; Equipment Design; Nebulizers and Vaporizers
PubMed: 37219568
DOI: 10.1089/jamp.2022.0055 -
The Annals of Pharmacotherapy Jul 2023Critically ill patients are often prescribed both inhaled beta-agonists and intravenous vasoactive; however, the interaction of the additive beta-agonist effects of...
BACKGROUND
Critically ill patients are often prescribed both inhaled beta-agonists and intravenous vasoactive; however, the interaction of the additive beta-agonist effects of these 2 agents remains largely uncharacterized.
OBJECTIVE
The purpose of this study was to evaluate how concomitant use of albuterol and vasoactive or inotropes affected ventilator-free days (VFDs) by re-analyzing the data from the Albuterol to Treat Acute Lung Injury (ALTA) trial.
METHODS
In this study, subjects were grouped to albuterol-vasoactive (n = 84) (vs) placebo-vasoactive (n = 62). Ventilator-free days, intensive care unit (ICU)-free days, organ failure-free days, cardiovascular adverse events, and 90-day mortality were compared. The primary outcome was VFDs.
RESULTS
Patients in the albuterol-vasoactive group had significantly fewer VFDs than patients in the placebo-vasoactive group (11 vs 19, = 0.05). Patients in the albuterol-vasoactive group also had significantly fewer ICU-free days (9.5 vs 18.5, = .006). The 90-day mortality was similar between groups (36.9% vs 27.4%, = .20). Similarly, no significant difference in cardiac adverse events between the groups (14.3% vs 11.3%, = 0.59).
CONCLUSION AND RELEVANCE
This study has shown fewer VFDs for patients who received both vasoactive and albuterol. There were also fewer ICU-free days when compared to those on vasoactive only. Given the common use of both agents, a prospective evaluation of the additive adverse effects of beta-agonism is warranted.
Topics: Humans; Acute Lung Injury; Administration, Intravenous; Albuterol; Drug-Related Side Effects and Adverse Reactions; Intensive Care Units
PubMed: 36189647
DOI: 10.1177/10600280221128014 -
JAMA Network Open Aug 2023High-deductible health plans with health savings accounts (HDHP-HSAs) incentivize patients to use less health care, including necessary care. Preventive drug lists...
IMPORTANCE
High-deductible health plans with health savings accounts (HDHP-HSAs) incentivize patients to use less health care, including necessary care. Preventive drug lists (PDLs) exempt high-value medications from the deductible, reducing out-of-pocket cost sharing; the associations of PDLs with health outcomes among patients with asthma is unknown.
OBJECTIVE
To evaluate the associations of a PDL for asthma medications on utilization, adverse outcomes, and patient spending for HDHP-HSA enrollees with asthma.
DESIGN, SETTING, AND PARTICIPANTS
This case-control study used matched groups of patients with asthma before and after an insurance design change using a national commercial health insurance claims data set from 2004-2017. Participants included patients aged 4 to 64 years enrolled for 1 year in an HDHP-HSA without a PDL in which asthma medications were subject to the deductible who then transitioned to an HDHP-HSA with a PDL that included asthma medications; these patients were compared with a matched weighted sample of patients with 2 years of continuous enrollment in an HDHP-HSA without a PDL. Models controlled for patient demographics and asthma severity and were stratified by neighborhood income. Analyses were conducted from October 2020 to June 2023.
EXPOSURES
Employer-mandated addition of a PDL that included asthma medications to an existing HDHP-HSA.
MAIN OUTCOMES AND MEASURES
Outcomes of interest were utilization of asthma medications on the PDL (controllers and albuterol), asthma exacerbations (oral steroid bursts and asthma-related emergency department use), and out-of-pocket spending (all and asthma-specific).
RESULTS
A total of 12 174 participants (mean [SD] age, 36.9 [16.9] years; 6848 [56.25%] female) were included in analyses. Compared with no PDL, PDLs were associated with increased rates of 30-day fills per enrollee for any controller medication (change, 0.10 [95% CI, 0.03 to 0.17] fills per enrollee; 12.9% increase) and for combination inhaled corticosteroid long-acting β2-agonist (ICS-LABA) medications (change, 0.06 [95% CI, 0.01 to 0.10] fills per enrollee; 25.4% increase), and increased proportion of days covered with ICS-LABA (6.0% [0.7% to 11.3%] of days; 15.6% increase). Gaining a PDL was associated with decreased out-of-pocket spending on asthma care (change, -$34 [95% CI, -$47 to -$21] per enrollee; 28.4% difference), but there was no significant change in asthma exacerbations and no difference in results by income.
CONCLUSIONS AND RELEVANCE
In this case-control study, reducing cost-sharing for asthma medications through a PDL was associated with increased adherence to controller medications, notably ICS-LABA medications used by patients with more severe asthma, but was not associated with improved clinical outcomes. These findings suggest that PDLs are a potential strategy to improve access and affordability of asthma care for patients in HDHP-HSAs.
Topics: Humans; Female; Adult; Male; Case-Control Studies; Deductibles and Coinsurance; Asthma; Albuterol
PubMed: 37642963
DOI: 10.1001/jamanetworkopen.2023.31259 -
The Journal of Allergy and Clinical... Feb 2024Digital health tools have been shown to help address challenges in asthma control, including inhaler technique, treatment adherence, and short-acting β-agonist overuse.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Digital health tools have been shown to help address challenges in asthma control, including inhaler technique, treatment adherence, and short-acting β-agonist overuse. The maintenance and reliever Digihaler System (DS) comprises 2 Digihaler inhalers (fluticasone propionate/salmeterol and albuterol) with an associated patient App and web-based Dashboard. Clinicians can review patients' inhaler use and Digihaler inhalation parameter data to support clinical decision-making.
OBJECTIVE
CONNECT2 evaluated asthma control in participants using the DS versus standard-of-care (SoC) maintenance and reliever inhalers.
METHODS
Participants (13 years or older) with uncontrolled asthma (Asthma Control Test [ACT] score <19) were randomized 4:3 (open-label) to the DS (n = 210) or SoC (n = 181) for 24 weeks. The primary endpoint was the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥20 or increase from baseline of ≥3 units at week 24).
RESULTS
There was an 88.7% probability that participants using the DS would have greater odds of achieving improvement in asthma control compared with SoC after 24 weeks. The mean odds ratio (95% credible interval) for DS versus SoC was 1.35 (0.846-2.038), indicating a 35% higher odds of improved asthma control with the DS. The DS group had more clinician-participant interactions versus SoC, mainly addressing a poor inhaler technique. DS participants' maintenance treatment adherence was good (month 1: 79.2%; month 6: 68.6%); reliever use decreased by 38.2% versus baseline. App and Dashboard usability was rated "good."
CONCLUSION
The positive results in asthma control in this study after 24 weeks demonstrate the effectiveness of the DS in asthma management.
Topics: Humans; Budesonide; Formoterol Fumarate; Ethanolamines; Anti-Asthmatic Agents; Drug Combinations; Asthma; Albuterol; Administration, Inhalation; Bronchodilator Agents
PubMed: 38040117
DOI: 10.1016/j.jaip.2023.11.037 -
Pharmaceutics Oct 2023To assess and compare the effects of two pediatric anti-asthmatic medication doses on the microhardness of enamel and microhardness, surface roughness and color of...
OBJECTIVE
To assess and compare the effects of two pediatric anti-asthmatic medication doses on the microhardness of enamel and microhardness, surface roughness and color of restorative materials.
METHODS
Human enamel samples and packable and flowable composite restorations were used. The samples were exposed to Salbutamol (0.6 mL/6 mL saline) and Budesonide (2 mL/2 mL saline) via a custom-made chamber connected to a nebulizer. Medication administration was conducted for 10 days. The samples were brushed with an electronic brush in a continuous and circular mode for 10 s after 10 min of medication administration. Assessments of microhardness, surface roughness and color were carried out at three different time intervals: baseline (T), 5 days (T) and 10 days (T). One-way analysis of variance (ANOVA), a two-sample t-test and a Bonferroni multiple comparison test were used to analyze the data and compare between the groups.
RESULTS
Both medications significantly ( < 0.05) decreased the microhardness of the enamel and composite samples after 10 days. Both medications lowered the surface roughness of both types of composite with a greater effect observed after 10 days of Budesonide administration ( < 0.05). Both medications had comparable detectable color change on both types of composite with a greater effect observed after 10 days of Budesonide administration ( < 0.05).
CONCLUSION
Salbutamol and Budesonide significantly decreased microhardness in the enamel samples. Both medications affected the properties of packable and flowable composites. The packable composite showed more resistance to microhardness changes. Both medications showed a clinically detectable change in the color of packable and flowable composites.
PubMed: 38004507
DOI: 10.3390/pharmaceutics15112527 -
The Journal of Allergy and Clinical... Sep 2023With the expanding treatment landscape for asthma, the process of identifying best-fit, individualized management options is becoming increasingly complicated....
BACKGROUND
With the expanding treatment landscape for asthma, the process of identifying best-fit, individualized management options is becoming increasingly complicated. Understanding patients' preferences can inform shared decision-making between clinicians and patients.
OBJECTIVES
To examine preferences of adults with asthma for therapeutic and management attributes and determine how these preferences vary among patients.
METHODS
We conducted an online discrete choice experiment survey in US adults with asthma. Patient preferences were analyzed using logit models. Factors affecting patients' preferences were identified by least absolute shrinkage and selection operator analysis.
RESULTS
A total of 1,184 patients completed the survey (60% female; mean [SD] age, 49.2 [15.0] years). Patients most valued fewer asthma attacks requiring urgent health care professional visits, fewer exacerbations requiring oral corticosteroids, and a reduced risk for oral thrush. Higher value was placed on reducing the risk of short-term (oral thrush) versus long-term side effects (diabetes). Patients were willing to increase rescue medication use in exchange for decreasing exacerbations requiring oral corticosteroids and attacks requiring urgent health care professional visits. Patients preferred a single inhaler for rescue and maintenance and least valued asthma action plans. Demographic, socioeconomic, and clinical factors affected patient preferences.
CONCLUSIONS
Patients sought convenient management options that focused mainly on decreasing the short-term morbidity associated with asthma exacerbations and therapies. Preferences varied by demographics, clinical factors, and socioeconomics. It is important for shared decision-making discussions to include conversations about morbidity and how available therapeutic options align with individual patient preferences.
Topics: Adult; Humans; Female; Middle Aged; Male; Patient Preference; Asthma; Adrenal Cortex Hormones; Nebulizers and Vaporizers; Disease Management; Anti-Asthmatic Agents
PubMed: 37182565
DOI: 10.1016/j.jaip.2023.04.046 -
Farmacia Hospitalaria : Organo Oficial... May 2024To identify the administration characteristics and connection methods of bronchodilators by pressurized inhalers to the ventilatory circuit of patients under invasive... (Review)
Review
OBJECTIVE
To identify the administration characteristics and connection methods of bronchodilators by pressurized inhalers to the ventilatory circuit of patients under invasive mechanical ventilation.
METHODS
A scope review was conducted following the PRISMA for Scoping Review, using the PubMed, Embase Elsevier, Cochrane Library, and Lilacs databases without language restrictions, up to July 2023. Eligible sources included reviews and consensuses (based on clinical studies), experimental and observational studies involving adult patients admitted to the intensive care unit and undergoing invasive mechanical ventilation, regardless of the underlying condition, who used bronchodilator drugs contained in pressurized inhalers. Information regarding inhalation technique, pressurized inhalers connection mode to the circuit, and patient care were collected by 2 researchers independently, with discrepancies resolved by a third reviewer. Studies involving bronchodilators combined with other pharmacological classes in the same device, as well as reviews containing preclinical studies, were excluded.
RESULTS
In total, 23 publications were included, comprising 19 clinical trials and 4 non-randomized experimental studies. Salbutamol (albuterol) was the bronchodilator of study in the majority of the articles (n=18), and the spacer device was the most commonly used to connect the pressurized inhaler to the circuit (n=15), followed by an in-line adapter (n=3), and a direct-acting device without chamber (n=3). Concerning the pressurized inhaler placement in the circuit, 18 studies positioned it in the inspiratory limb, and 19 studies synchronized the jet actuation with the start of the inspiratory phase. Agitation of the pressurized inhaler before each actuation, waiting time between actuations, airway suction before administration, and semi-recumbent patient positioning were the most commonly described measures across the studies.
CONCLUSIONS
This review provided insights into the aspects related to inhalation technique in mechanically ventilated patients, as well as the most prevalent findings and the existing gaps in knowledge regarding bronchodilator administration in this context. The evidence indicates the need for further research on this subject.
PubMed: 38806364
DOI: 10.1016/j.farma.2024.03.012 -
The Journal of Physiology Oct 2023This study provides an in-depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid-induced respiratory depression (OIRD). We...
This study provides an in-depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid-induced respiratory depression (OIRD). We explored the physiological implications of both drugs on ventilation and airway patency in anaesthetized mice. Our results revealed a similar reduction in respiratory frequency with equivalent scaled dosages of fentanyl and morphine, though the onset of suppression was more rapid with fentanyl. Additionally, fentanyl resulted in transient airflow obstructions during the inspiratory cycle, which were absent following morphine administration. Notably, these fentanyl-specific obstructions were eliminated with tracheostomy, implicating the upper airways as a major factor contributing to fentanyl-induced respiratory depression. We further demonstrate that bronchodilators salbutamol and adrenaline effectively reversed these obstructions, highlighting the bronchi's contribution to fentanyl-induced airflow obstruction. Our study also uncovered a significant reduction in sighs during OIRD, which were eliminated by fentanyl and markedly reduced by morphine. Finally, we found that fentanyl-exposed mice had reduced survival under hypoxic conditions compared to mice given morphine, demonstrating that fentanyl becomes more lethal in the context of hypoxaemia. Our findings shed light on the distinct and profound impacts of these opioids on respiration and airway stability and lay the foundation for improved opioid use guidelines and more effective OIRD prevention strategies. KEY POINTS: Both morphine and fentanyl significantly suppressed respiratory frequency, but the onset of suppression was faster with fentanyl. Also, while both drugs increased tidal volume, this effect was more pronounced with fentanyl. Fentanyl administration resulted in transient obstructions during the inspiratory phase, suggesting its unique impact on airway stability. This obstruction was not observed with morphine. The fentanyl-induced obstructions were reversed by administering bronchodilators such as salbutamol and adrenaline. This suggests a possible therapeutic strategy for mitigating the adverse airway effects of fentanyl. Both drugs reduced the frequency of physiological sighs, a key mechanism to prevent alveolar collapse. However, fentanyl administration led to a complete cessation of sighs, while morphine only reduced their occurrence. Fentanyl-treated mice showed a significantly reduced ability to survive under hypoxic conditions compared to those administered morphine. This indicates that the impacts of hypoxaemia during opioid-induced respiratory depression can vary based on the opioid used.
Topics: Mice; Animals; Morphine; Fentanyl; Analgesics, Opioid; Bronchodilator Agents; Respiration; Respiratory Insufficiency; Hypoxia; Albuterol; Epinephrine
PubMed: 37778015
DOI: 10.1113/JP285163 -
Hospital Pediatrics Jun 2024Viral testing and treatments such as systemic steroids and inhaled corticosteroids are low-value care for routine bronchiolitis. We sought to determine the impact of the...
BACKGROUND
Viral testing and treatments such as systemic steroids and inhaled corticosteroids are low-value care for routine bronchiolitis. We sought to determine the impact of the COVID-19 pandemic on low-value care in young children with bronchiolitis.
METHODS
This was a retrospective, cross-sectional study using the Pediatric Health Information Systems database. We included children <2 years seen in a pediatric emergency department for bronchiolitis. We selected a priori 3 study periods: September 2018 to February 2020 (prepandemic), March 2020 to August 2022 (early pandemic), and September 2022 to January 2023 (late pandemic). Low-value care included respiratory syncytial virus testing, chest radiography, albuterol, or corticosteroids and was compared across the 3 time periods.
RESULTS
At least 1 element of low-value care was provided in 45%, 47%, and 44% of encounters in the prepandemic, early pandemic, and late pandemic periods, respectively. There was little variation in the use of albuterol and chest radiography across time periods and a slight increase in systemic corticosteroid use from prepandemic to early and late pandemic groups. Viral testing increased from 36% prepandemic to 65% early pandemic and 67% late pandemic, which appeared to be driven by SARS-CoV-2 testing and combination viral testing.
CONCLUSIONS
There was no clinically significant change in low-value care for bronchiolitis during the pandemic. Because of SARS-CoV-2 testing, however, overall frequency of viral testing increased dramatically over time. This marked increase in overall viral testing should be taken into consideration for future quality improvement efforts.
PubMed: 38872617
DOI: 10.1542/hpeds.2024-007751 -
BMC Pulmonary Medicine Jan 2024In tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of twice daily inhaled albuterol on cardiopulmonary exercise outcomes, dynamic hyperinflation, and symptoms in secondhand tobacco-exposed persons with preserved spirometry and air trapping: a randomized controlled trial.
BACKGROUND
In tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and exercise capacity. The physiologic nature of air trapping in the absence of spirometric airflow obstruction remains unclear. The aim of this study was to examine the underlying pathophysiology of air trapping in the context of preserved spirometry and to determine the utility of bronchodilators in SHS tobacco-exposed persons with preserved spirometry and air trapping.
METHODS
We performed a double-blinded placebo-controlled crossover randomized clinical trial in nonsmoking individuals at risk for COPD due to exposure to occupational SHS who had preserved spirometry and air trapping defined as either a residual volume-to-total lung capacity ratio (RV/TLC) > 0.35 or presence of expiratory flow limitation (EFL, overlap of tidal breathing on maximum expiratory flow-volume loop) on spirometry at rest or during cardiopulmonary exercise testing (CPET). Those with asthma or obesity were excluded. Participants underwent CPET at baseline and after 4-week trials of twice daily inhalation of 180 mcg of albuterol or placebo separated by a 2-week washout period. The primary outcome was peak oxygen consumption (VO) on CPET. Data was analyzed by both intention-to-treat and per-protocol based on adherence to treatment prescribed.
RESULTS
Overall, 42 participants completed the entire study (66 ± 8 years old, 91% female; forced expiratory volume in 1 s [FEV] = 103 ± 16% predicted; FEV to forced vital capacity [FVC] ratio = 0.75 ± 0.05; RV/TLC = 0.39 ± 0.07; 85.7% with EFL). Adherence was high with 87% and 93% of prescribed doses taken in the treatment and placebo arms of the study, respectively (P = 0.349 for comparison between the two arms). There was no significant improvement in the primary or secondary outcomes by intention-to-treat or per-protocol analysis. In per-protocol subgroup analysis of those with RV/TLC > 0.35 and ≥ 90% adherence (n = 27), albuterol caused an improvement in peak VO (parameter estimate [95% confidence interval] = 0.108 [0.014, 0.202]; P = 0.037), tidal volume, minute ventilation, dynamic hyperinflation, and oxygen-pulse (all P < 0.05), but no change in symptoms or physical activity.
CONCLUSIONS
Albuterol may improve exercise capacity in the subgroup of SHS tobacco-exposed persons with preserved spirometry and substantial air trapping. These findings suggest that air trapping in pre-COPD may be related to small airway disease that is not considered significant by spirometric indices of airflow obstruction.
Topics: Aged; Female; Humans; Male; Middle Aged; Albuterol; Exercise; Forced Expiratory Volume; Lung; Pulmonary Disease, Chronic Obstructive; Spirometry; Vital Capacity
PubMed: 38245665
DOI: 10.1186/s12890-023-02808-7