Bronchodilator Delivery Research Articles

Emergency physicians’ preferences in bronchodilator delivery for asthma exacerbations: a cross-sectional study

Objective Asthma is a chronic respiratory disorder characterized by airway inflammation and narrowing often leading to acute exacerbations that necessitate a visit to the emergency department (ED). While life threatening cases usually require bronchodilator delivery by nebulizers, mild to moderate acute asthma exacerbations can be treated by bronchodilators delivered either by metered dose inhalers (MDI). Numerous studies have attempted to compare between the two modalities and have drawn similar conclusions in that both are comparable in efficacy with minimal differences. What is evident, however, is that physicians remain inclined to favor nebulizers in the majority of acute asthma exacerbations. Methods In this questionnaire-based study, a survey was distributed to physicians who treat asthma exacerbations to examine demographics, knowledge, beliefs, and current practice in regard to bronchodilator therapy. Results The majority (90.8%) of physicians prefer short-acting beta agonists via nebulizer, with 9.2% favoring MDI + spacer. Participants include consultants, residents, and specialists across various emergency disciplines. While 90.1% find MDI + spacer equally effective as nebulizers, advantages cited include cost-effectiveness (49.6%), shorter ED stays (63.4%), quicker administration (67.9%), and ease of use (58.8%). Challenges include availability (66.4%) and ineffectiveness in younger patients (45%). Despite this, 65.6% are willing to switch to MDI for initial asthma management in the ED, while 34.4% are resistant. Conclusion Concerns about availability and effectiveness in younger patients remain barriers. However, a significant number are willing to adopt MDIs with spacers, indicating potential for broader use with better availability and training.

High-flow nasal cannula and in-line aerosolised bronchodilator delivery during severe exacerbation of asthma in adults: a feasibility observational study

BackgroundAsthma is a common chronic respiratory disease affecting 1–29% of the population in different countries. Exacerbations represent a change in symptoms and lung function from the patient's usual condition that requires emergency department (ED) admission. Recently, the use of a High-Flow Nasal Cannula (HFNC) plus an in-line vibrating mesh nebulizer (VMN) for aerosol drug delivery has been advocated in clinical practice. Thus, this pilot observational study aims to investigate the feasibility of HFNC treatment with VMN for in-line bronchodilator delivery in patients with severe asthma. MethodsThis study was conducted from May 2022 to May 2023. Subjects ≥18 years old with a previous diagnosis of asthma who were admitted to the ED during severe exacerbation were included. The primary endpoint was the change in peak expiratory flow ratio (PEFR) after 2-h of treatment with bronchodilator delivered by HFNC with in-line VMN. Additional outcomes were changes in forced expiratory volume in 1 s (FEV1) and clinical variables before treatment. Results30 patients, mean age of 43 (SD ± 16) years, mostly female (67%) were studied. A significant change in PEFR (147 ± 31 L/m vs. 220 ± 38 L/m; p < 0.001) was observed after treatment with HFNC and in-line VMN with significant improvement in clinical variables. And no subjects required invasive mechanical ventilation (IMV) during the study. ConclusionsHFNC treatment with in-line VMN for bronchodilator delivery appears feasible and safe for patients with severe asthma exacerbation. These preliminary promising results should be confirmed with appropriately large-designed studies.

Impact of nebulization versus metered-dose inhaler utilization on viral particle dispersion in patients with COVID-19.

Conflicting guidance exists regarding the characterization of nebulization as an aerosol-generating procedure and subsequent risk of transmission of SARS-CoV-2 to healthcare workers. This study sought to address whether SARS-CoV-2 viral load distribution was impacted by bronchodilator delivery via nebulizer versus metered-dose inhaler (MDI). Adults infected with COVID-19 were enrolled and received a single dose of albuterol sulfate nebulized solution (2.5mg/3mL via breath-actuated nebulizer with filtered mouthpiece) or albuterol sulfate hydrofluoroalkane inhalation aerosol (90µg/actuation; two puffs via MDI with spacer) in a randomized crossover sequence. Air and surfaces were sampled at predefined locations within patients' hospital rooms to assess SARS-CoV-2 dispersion over three periods (baseline, MDI, and nebulizer). Eleven patients received crossover therapy. Six patients had detectable SARS-CoV-2 RNA during one treatment period (n = 3 each for MDI and nebulizer) and one during both treatment periods. No viral RNA was found in the rooms of four (36.4%) patients. Overall, few environmental samples (17/397; 4.3%) contained detectable viral RNA, with no meaningful differences in positivity rate across periods; RNA genome copy numbers were low in positive samples. No correlation between dispersion and patient clinical status or environmental parameters was observed. In this first prospective trial evaluating viral load distribution following use of nebulizer versus MDI in hospitalized patients with COVID-19, low environmental contamination was found regardless of administration method. Findings support the use of either device when needed to treat patients with COVID-19.

Development of a Novel Bronchodilator Vaping Drug Delivery System Based on Thermal Degradation Properties.

This work aims to investigate bronchodilator delivery with the use of different vaping drug delivery systems (VDDS) by determining the dose equivalence delivered in relation to different references: a clinical jet nebulizer, a pMDI (pressurized metered dose inhaler) and a DPI (dry powder inhaler). Three different bronchodilators were used (terbutaline, salbutamol hemisulfate, ipratropium bromide). The e-liquids contained the active pharmaceutical ingredient (API) in powder form. Two different VDDS were tested (JUUL and a GS AIR 2 atomizer paired with a variable lithium-ion battery (i-stick TC 40 W), 1.5 ohm resistance, and 15 W power). Samples were collected using a glass twin impinger (GTI). High-performance liquid chromatography (HPLC) was used to quantify the drugs. A next-generation impactor (NGI) was used to measure the particle size distribution. Terbutaline emerged as the optimal API for bronchodilator delivery in both VDDS devices. It achieved the delivery of a respirable dose of 20.05 ± 4.2 µg/puff for GS AIR 2 and 2.98 ± 0.52 µg/puff for JUUL. With these delivered doses, it is possible to achieve a dose equivalence similar to that of a jet nebulizer and DPI, all while maintaining a reasonable duration, particularly with the GS AIR 2. This study is the first to provide evidence that vaping bronchodilators work only with appropriate formulation, vaping technology, and specific drugs, depending on their thermal degradation properties.

Response to Bronchodilators Administered via Different Nebulizers in Patients With COPD Exacerbation.

The recommended treatment of COPD exacerbations includes administration of short-acting bronchodilators that act to reverse bronchoconstriction, restore lung volumes, and relieve breathlessness. In vitro studies demonstrate vibrating mesh nebulizers (VMNs) provide greater drug delivery to the airway compared to standard small-volume nebulizers (SVNs). We examined whether the physiological and symptom response to nebulized bronchodilators during a COPD exacerbation differed between these 2 modes of bronchodilator delivery. Subjects hospitalized with a COPD exacerbation participated in a comparative clinical effectiveness study of 2 methods of nebulization. Using block randomization, 32 participants in this open-label trial were administered salbutamol 2.5 mg/ipratropium bromide 0.5 mg via vibrating mesh (VMN group, n = 16) or small-volume jet nebulizer (SVN group, n = 16) on one occasion. Spirometry, body plethysmography, and impulse oscillometry were performed and Borg breathlessness scores recorded pre bronchodilator and at 1 h post bronchodilator. Baseline demographics were comparable between groups. Mean FEV1 was 48% predicted. Significant changes in lung volumes and airway impedance were seen in both groups. Inspiratory capacity (IC) increased by 0.27 ± 0.20 L and 0.21 ± 0.20 L in the VMN and SVN group, respectively, between group difference P = .40. FVC increased in the VMN group by 0.41 ± 0.40 L compared to 0.19 ± 0.20 L with SVN, between group difference P = .053; and residual volume (RV) decreased by 0.36 ± 0.80 L and 0.16 ± 0.50 L in the VMN and SVN group, respectively, between group difference P = .41. The VMN group had a significant reduction in Borg breathlessness score, P = .034. Greater improvement in symptoms, and larger absolute change in FVC, was observed in response to equivalent doses of standard bronchodilators administered by VMN, compared to SVN, but no substantial difference in change in IC.

Delivery of Aerosolized Bronchodilators by High-Flow Nasal Cannula During COPD Exacerbation.

Bronchodilator delivery via a high-flow nasal cannula (HFNC) has generated interest in recent years. The efficacy of in-line vibrating mesh nebulizers with an HFNC during COPD exacerbation is limited. The aim of this study was to evaluate the clinical response of subjects with COPD exacerbation who require bronchodilator therapy (anticholinergic and β-agonist) by using a vibrating mesh nebulizer in line with an HFNC. This was a prospective single-center study performed in a respiratory intermediate care unit that enrolled patients with a diagnosis of COPD exacerbation who required noninvasive ventilation on admission. All the subjects underwent noninvasive ventilation breaks with an HFNC. After clinical stability, pulmonary function tests were performed to assess changes in FEV1 and clinical parameters before and after bronchodilation by using a vibrating mesh nebulizer in line with an HFNC. Forty-six patients with COPD exacerbation were admitted. Five patients who did not use noninvasive ventilation and 10 patients who did not receive bronchodilator treatment with a vibrating mesh nebulizer were excluded. Thirty-one were selected, but 1 subject was secondarily excluded due to loss of data. Finally, 30 subjects were included. The primary outcome was spirometric changes in FEV1. The mean ± SD FEV1 before receiving bronchodilator treatment by using a vibrating mesh nebulizer in line with an HFNC was 0.74 ± 0.10 L, and, after receiving treatment, the mean ± SD FEV1 changed to 0.88 ± 0.12 L (P < .001). Similarly, the mean ± SD FVC increased from 1.75 ± 0.54 L to 2.13 ± 0.63 L (P < .001). Considerable differences were observed in breathing frequency and heart rate after receiving bronchodilator treatment. No relevant changes were observed in the Borg scale or Sp O2 after treatment. The mean clinical stability recorded was 4 d. In subjects with COPD exacerbation, bronchodilator treatment by using a vibrating mesh nebulizer in line with an HFNC showed a mild but significant improvement in FEV1 and FVC. In addition, a decrease in breathing frequency was observed, suggesting a reduction in dynamic hyperinflation.

Technical features of vaping drug delivery system for bronchodilator delivery

PurposeSeveral technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS). MethodsTerbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL). ResultsGS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization. ConclusionWe proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

Bronchodilator Delivery via High-Flow Nasal Cannula: A Randomized Controlled Trial to Compare the Effects of Gas Flows.

(1) Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted increasing clinical interest. In vitro studies report that the ratio of HFNC gas flow to patient inspiratory flow (GF:IF) is a key factor in the efficiency of trans-nasal aerosol delivery. (2) Methods: In a randomized controlled trial, patients with a history of COPD or asthma and documented positive responses to inhaled bronchodilators in an outpatient pulmonary function laboratory were recruited. Subjects were randomized to receive inhalation at gas flow ratio settings of: GF:IF = 0.5, GF:IF = 1.0, or GF = 50 L/min. Subjects were assigned to inhale saline (control) followed by salbutamol via HFNC with cumulative doses of 0.5 mg, 1.5 mg, 3.5 mg, and 7.5 mg. Spirometry was performed at baseline and 10–12 min after each inhalation. (3) Results: 75 subjects (49 asthma and 26 COPD) demonstrating bronchodilator response were enrolled. Per the robust ATS/ERS criteria no difference was observed between flows, however using the criteria of post-bronchodilator forced expiratory volume in the first second (FEV1) reaching the screening post-bronchodilator FEV1 with salbutamol, a higher percentage of subjects receiving GF:IF = 0.5 met the criteria at a cumulative dose of 1.5 mg than those receiving GF:IF = 1.0, and GF = 50 L/min (64% vs. 29% vs. 27%, respectively, p = 0.011). Similarly at 3.5 mg (88% vs. 54% vs. 46%, respectively, p = 0.005). The effective dose at GF:IF = 0.5 was 1.5 mg while for GF = 50 L/min it was 3.5 mg. (4) Conclusions: During salbutamol delivery via HFNC, cumulative doses of 1.5 mg to 3.5 mg resulted in effective bronchodilation. Applying the robust ATS/ERS criteria no difference was observed between the flows, however using the more sensitive criteria of subjects reaching post screening FEV1 to salbutamol via HFNC, a higher number of subjects responded to the doses of 0.5 mg and 1.5 mg when HFNC gas flow was set at 50% of patient peak inspiratory flow.

Effect of different accessory devices on the dose delivered from pressurised metred-dose inhalers.

Improved aerosol delivery of bronchodilators to chronic obstructive pulmonary disease (COPD) subjects is a cornerstone in the treatment approach. Drug delivery and response are improved with the use of accessory devices [spacers and valved holding chambers (VHCs)] with metred-dose inhalers (pMDIs). However, different accessory devices are available in the market with different properties that could affect aerosol delivery. Thus, this study aimed to assess the relative lung deposition and systemic bioavailability and compare bronchodilator response of salbutamol delivered using different accessory devices attached to pMDIs. Twelve healthy subjects and twelve COPD subjects inhaled 300 μg salbutamol (3 pMDI puffs) using five different accessory devices with either masks or mouthpieces (Able, Aerochamber plus flow Vu, Dolphin chamber, Tipshaler spacer, and modified Drink bottle spacer). Urine samples were collected thirty minutes post-dosing and cumulatively for the next twenty-four hours, to determine and compare the relative lung deposition [0-0.5 hour excretion of urinary salbutamol (USAL0.5)] and systemic bioavailability [0.5-24hours excretion of urinary salbutamol (USAL24)] of salbutamol from the selected accessory devices. Also, the difference between pre and post-inhalation forced expiratory volume in one second (ΔFEV1 %) of predicted was determined for each accessory device. Urinary excretion of salbutamol (both USAL0.5 and USAL24 samples) in COPD subjects was significantly (P<.05) lower than in healthy subjects for all accessory devices. USAL0.5 and USAL24 in non-antistatic spacers (modified Drink bottle spacer and Dolphin chamber spacers) were significantly lower (P<.05) than that for antistatic spacers (Aerochamber plus flow Vu, Able and Tips-haler). No significant difference in USAL0.5 and USAL24 was observed between facemasks and mouthpieces. There was a significant difference (P<.05) in ΔFEV1 % of predicted values between COPD subjects and healthy subjects. However, within the COPD group and the healthy group there was no significant difference in ΔFEV1 % of predicted values between all accessory devices or between with mouthpiece or with a mask. COPD subjects had lower aerosol delivered compared with healthy subjects. Anti-static accessory devices delivered a higher amount of aerosol compared with non-antistatic accessory devices. Even though the presence of a significant difference in aerosol delivery between non-antistatic and antistatic accessory devices no significant difference was found in the ΔFEV1 % between all accessory devices.

Carrier Gases and Their Effects on Aerosol Drug Delivery.

Carrier gases provide the medium for delivery of inhaled aerosol therapies. The physical properties of these gases substantially affect both fluid and aerosol mechanics in the lung. Gas density affects both the pressure/flow relationship in the airways and the extent of turbulence within the flow. These physical properties also affect the operation of some components of respiratory and aerosol drug delivery equipment. The lower resistance associated with breathing low density gases has prompted many studies of therapeutic applications. This includes the respiration of helium-oxygen gas mixtures to improve oxygenation and carbon dioxide removal, and the use of these gases to improve the delivery of inhaled medications. Results of these studies have been mixed but meta-analyses indicate a benefit of helium-oxygen respiration for croup and bronchiolitis and for bronchodilator delivery in obstructive disease. Some of the variability demonstrated in these studies is likely associated with specific technical aspects of how the gases are delivered. The utility of alternate carrier gases for aerosol delivery would be facilitated by simultaneous assessment of both aerosol deposition and clinical effect during studies. Previous successful applications may offer a basis for improved delivery system designs that fully realize the effects that might be available with these gases.

Рossibilities of clinical application of modern nebulizers

The simplicity of converting medicinal solutions and suspensions into aerosols using mechanical and thermal energy, convenient delivery to the airways allows nebulizers to take a worthy place in the treatment of hospitalized and outpatient patients. Different types of nebulizers are available for use in the home and in medical settings (jet, ultrasound, membrane), and researches show that the performance and characteristics of the aerosol vary between different devices and manufacturers. Jet nebulizers are still the most used devices that do not require coordination of inhale and delivery of aerosol to the respiratory tract. To reduce the consumption of medicinal aerosol and optimize the air flow, virtual valve technology (V.V.T.) is being improved, and breath-actuated nebulizers are being created. The advantage of nebulizer therapy is the ability to apply large doses of medications, use substances that exist only in inhaled form. The choice falls on the nebulizer in cases where the patient can not use other delivery devices, for example, if the patient is unable to coordinate the inhalation and intake of the drug into the respiratory tract, with a severe exacerbation of obstructive disease, in the presence of motor disorders. The optimal delivery device for children of any age, including newborns, is a nebulizer. The most common indication for nebulizer therapy is the delivery of bronchodilators and inhaled corticosteroids for asthma or chronic obstructive pulmonary disease, as well as the treatment of upper respiratory tract diseases, in particular croup in children. An important place is given to nebulizers when it is necessary to prescribe certain mucolytics and antibiotics. In the treatment of emergency conditions, inhalation administration of drugs may be required, including situations when the patient is on mechanical ventilation or has a tracheostomy installed. The significance of nebulizers in the treatment of cystic fibrosis, pulmonary arterial hypertension, and alpha-1-antitrypsin deficiency is being studied. The possibilities of endobronchial delivery of heparin, insulin, and monoclonal antibodies are evaluated.

Application of acetylcysteine in inhalation form in complex treatment of patients with bronchial asthma with neutrophilic type of inflammation

Background. Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. On the base of this heterogeneity, among other factors, a significant role is played by the type of inflammation (eosinophilic, neutrophilic or malogranulocytic). In this regard it is offered to allocate separate endotypes of the disease. BA with a neutrophilic type of inflammation is characterized by more severe course with the presence of obstruction at the level of small bronchi and fixed bronchoobstruction. In the presence of disorders at the level of small bronchi, it is advisable to prescribe anti-inflammatory drugs in delivery devices that can create a high concentration of drugs in the peripheral departments (eg, Respimat, inhaled inhalers, fine aerosols). Mucolytics disrupt the structure of the mucus gel, thereby reducing its viscosity and elasticity and, thus, improving the viscoelastic properties of sputum, which facilitate airway clearance and promote the targeted delivery of bronchodilators and anti-inflammatory drugs to the small bronchi.&#x0D; Objective. To evaluate the effectiveness of the use of ultrafine-particle glucocorticoid tiotropium bromide through Respimat in standard therapeutic doses and inhalation of a10 % solution of acetylcysteine with a nebulizer once a day for 10 days as basic therapy.&#x0D; Materials and methods. The diagnosis of BA with the neutrophilic type of inflammation was established in patients, whose results of the blood analysis by microscopy showed the level of neutrophils ≥4000 in 1 μl. The effectiveness of treatment of patients having BA with neutrophilic type of inflammation was studied in 30 patients. First (control) group consisted of 15 patients (5 men and 10 women, mean age – 53.2±4.9 years, FEV1 after test with a bronchodilator – 50.6±16.3 %, FEV1/FVC – 66.4±17,8), who received as a standard therapy a combined drug – 320 mcg of budesonide and 9 mcg of formoterol – twice a day in complex treatment. Second (main) group consisted of 15 patients (9 men and 6 women, mean age – 53.6±3.8 years, FEV1 – 51.5±4.7 %, FEV1/FVC – 67,2±3,5), who were administered the inhalation of 250 μg of ultrafine-particle beclomethasone dipropionate and 12 μg of formoterol twice a day, 5 mcg tiotropium bromide as inhalations through the delivery device respimat once a day for 3 months. In the complex treatment, the inhalation of acetylcysteine (3 ml of 10 % solution) with a nebulizer once a day in the morning (duration of an inhalation session – 10 min) for 10 days was additionally prescribed.&#x0D; Results and discussion. After 3 months in patients of group 2, the effectiveness of treatment was 93.3 %. There was a statistically significant increase in the total score of the test for asthma control (ACT) from 14.3±1.3 to 20.3±0.8 points (p&lt;0.05), a decrease in the total score evaluation of the questionnaire for the control of asthma symptoms (ACQ) from 2.3±0.2 to 1.1±0.1 points (p&lt;0.05), which indicated an improvement in the control of asthma symptoms and a reduction in exacerbations; clinically significant decrease in the number of symptoms from 71.4±5.6 to 51.3±5.0 points (p&lt;0.05) according to the results of the St. George’s Hospital quality of life questionnaire, which indicated an improvement in the quality of life of patients; an increase in MEF50 from 28.9±4.5 % to 41.6±4.2 %, MEF25 from 19.1±2.9 % to 27.6±2.6 % and FEV1/FVC from 67.2±3.5 % to 76.1±2.3 %, which indicated an improvement in bronchial patency at the level of small bronchi and a decrease in fixed bronchial obstruction; an increase in the number of passed meters 6MWT from 266.3±16.2 to 312.0±14.4 m, a decrease in shortness of breath on the Borg scale from 2.5±0.3 to 1.5±0.1 points before the test and from 4.1±0.3 to 3.1±0.3 points after the test, which testified to the increase of tolerance to physical activity. The complex therapy was well tolerated by patients and was not accompanied by the development of side effects. In patients of the control group, statistically significant dynamics of the studied indicators was not detected.&#x0D; Conclusions. Prescription to patients with BA with the neutrophilic type of inflammation according to the severity of the disease as a basic therapy of ultrafine-particle inhaled glucocorticoid tiotropium bromide through a modern technical device Respimat in a standard therapeutic dose, and formoterol 12 μg twice a day for 10 days led to a positive dynamics of clinical symptoms of asthma, improved respiratory function, increased tolerance to physical activity, and improved the quality of life, thus, resulted in the effectiveness of treatment of patients with BA with the neutrophilic type of inflammation being 93.3 %.

Health-Related Effects of Home Nebulization With Glycopyrronium on Difficult-to-Treat Asthma: Post-Hoc Analyses of an Observational Study.

BackgroundBronchial asthma remains a clinical enigma with poorly controlled symptoms or exacerbations despite regular use of inhaled corticosteroids. Home nebulization offers a simplified solution for the delivery of rescue and maintenance bronchodilators, which is especially true for patients with frequent exacerbations during management of uncontrolled or difficult-to-treat asthma.ObjectiveWe aimed to assess the clinical impact and outcomes associated with home nebulization—delivered long-acting bronchodilators for uncontrolled or difficult-to-treat asthma.MethodsThis observational, concurrent study was conducted with 60 patients at 2 centers during November 2018. Statistical analyses for prebronchodilator forced expiratory volume in one second (FEV1) and Global Initiative for Asthma (GINA) asthma control score in patients on long-acting bronchodilators and corticosteroids were conducted, with two-tailed P values <.05 considered statistically significant.ResultsPer protocol analyses (53/60) for consecutive cases receiving home nebulization with long-acting bronchodilators and corticosteroids were conducted. The baseline demographics included a male-to-female ratio of 30:23 and mean values of the following: age, 60.3 years (SD 11.8 years); weight, 64 kg (SD 16.8 kg); FEV1, 43% (SD 16%); GINA asthma control score, 3.0 points (SD 0.8 points); serum eosinophil level, 4% (SD 3%); fractional exhaled nitric oxide (FeNO), 12.1 ppb (SD 6 ppb). Of the patients, 100% (53/53) had uncontrolled symptoms, 69.8% (37/53) had prior exacerbations, 100% (53/53) used formoterol/budesonide, and 75.5% (40/53) used glycopyrronium. The per protocol group (n=53) had significantly improved mean prebronchodilator FEV1 (23.7%, SD 29.8%; 0.46 L, SD 0.58 L; P<.001) and GINA asthma control score (2.1 points, SD 0.8 points, P<.001). At baseline, patients (n=40) receiving glycopyrronium/formoterol/budesonide (25/20/500 mcg) nebulization admixture had the following mean values: prebronchodilator FEV1, 38% (SD 15%); GINA asthma control score, 3.0 points (SD 0.8 points); reversibility, 12% (SD 6%); peripheral eosinophil level, 4% (SD 3%); FeNO, 12 ppb (SD 5.7 ppb). In the post hoc analyses, these patients had significantly improved mean prebronchodilator FEV1 of 27.7% (SD 26.2%; 0.54 L, SD 0.51 L; P<.001) at 8 weeks compared with baseline. At baseline, patients (n=13) receiving formoterol/budesonide (20/500 mcg) nebulization had the following mean values: FEV1, 55% (SD 12%); GINA asthma control score, 3.0 points (SD 1.2 points); reversibility, 14% (SD 7%); serum eosinophil level, 4% (SD 3%); FeNO, 13.3 ppb (SD 6.8 ppb). In the post hoc analyses, these patients showed a significant improvement in prebronchodilator FEV1 of 11.2% (SD 13.1%; 0.22 L, SD 0.25 L; P<.001) from baseline. Breathlessness of mild to moderate intensity was reported by 10 cases (10/53, 18.9%), with no other treatment-emergent adverse events or serious adverse events.ConclusionsHome nebulization remains a viable option for symptomatic difficult-to-treat asthma cases with frequent use of rescue medications. Glycopyrronium as add-on therapy offers a synergistic response in patients on corticosteroids with difficult-to-treat asthma.Trial RegistrationClinical Trial Registry of India CTRI/2018/11/016319; https://tinyurl.com/y78cctm3

Nebulized Delivery of Albuterol during Exercise is Safe and Effective in Individuals with Cystic Fibrosis, but does not Augment Bronchodilation or Drug Delivery

ObjectiveExercise is a cornerstone of therapeutic intervention for individuals with cystic fibrosis (CF). However, daily breathing treatments (e.g. chest physiotherapy and inhalation of nebulized albuterol) typically last ~90 minutes, providing a time‐barrier to completing daily exercise. Thus, the purpose of our study was to determine the effects of a combination therapy (exercise and nebulized albuterol) on airway function and bronchodilator delivery. We tested the hypotheses that combination therapy (exercise + nebulized albuterol) would 1) augment the bronchodilator effect compared to either intervention alone, and 2) increase the plasma concentration of albuterol compared to nebulized albuterol alone.MethodsParticipants with CF (n=9, 5 female, 25±2yrs, forced expiratory volume in 1 second (FEV1) =82±5%predicted) first completed a screening visit (V̇O2max test, cycle ergometer) and then three study visits in a randomized order. During each study visit, participants completed measures of airway function [FEV1 and forced expiratory flow from 25–75% of forced vital capacity (FEF25–75)], and a blood draw (n=8) to determine plasma albuterol concentration. Participants then completed one of three interventions [albuterol only, (A): 2.5mg nebulized albuterol over 15min; exercise only (E): 30min cycling exercise at 50% of peak watts; albuterol and exercise (A+E): 30min cycling exercise at 50% of peak watts with 2.5mg nebulized albuterol nebulized over the last 15min of cycling). Airway function and plasma albuterol were measured at 0, 15, 30, 45, 60, 90, 120, 180, and 240min after the intervention. Additional plasma albuterol measures were taken 5, and 6hrs post intervention. Data are mean±SD.ResultsDelivery of nebulized albuterol during exercise did not augment or prolong the bronchodilator effect compared to exercise or albuterol alone. The transient improvement in airway function during the interventions—increase in FEV1 (time=0.050, intervention p=0.166, interaction p=0.135) or increase in FEF25–75 (time p=0.001, intervention p=0.207, interaction p=0.990) — was not different between the three interventions. Delivery of nebulized albuterol during exercise did not increase the plasma concentration of albuterol compared to nebulized albuterol alone. The maximum plasma concentration of albuterol (Cmax) and the area under the curve (AUC) of albuterol concentration over time were not different between interventions (Cmax= 2.57±1.60 vs. 2.56±1.13ng·mL−1, p=0.982; AUC0–6hrs= 6.1±3.6 vs. 6.9±3.3hr·ng·mL−1, p=0.188; A vs. A+E interventions, respectively).ConclusionsDelivery of nebulized albuterol during moderate intensity exercise did not significantly alter bronchodilator effects or plasma levels of albuterol compared to albuterol or exercise alone. These data suggest that delivery of nebulized albuterol during exercise is safe and effective, but does not augment bronchodilator effects or drug delivery. This combination intervention (A+E) may be a time efficient method for individuals with cystic fibrosis to gain therapeutic effects of exercise and breathing treatments.Support or Funding InformationF32 HL131151, Cystic Fibrosis Research Inc.

Feasibility of Aerosol Bronchodilators Delivery Through High-Flow Nasal Cannula in Pediatric Subjects With Respiratory Distress.

High-flow nasal cannula (HFNC) is commonly used to provide respiratory support to pediatric patients with respiratory failure. Although the use of bronchodilators via HFNC has been described, the feasibility and safety of aerosolized bronchodilator delivery via HFNC are controversial. In this study, we sought to evaluate whether the HFNC system can be used to deliver nebulized bronchodilators at lower gas flow of 2-4L/min, increase patient comfort, and minimize respiratory therapist (RT) bedside time when compared to traditional interfaces. A retrospective chart review of all pediatric subjects who were admitted to the pediatric ICU in a tertiary care children's hospital and required nebulized bronchodilators between December 2017 and June 2018. A total of 205 nebulizations were administered to 28 children; 31% of nebulized bronchodilators were given using a nebulization system integrated into the HFNC. Nebulized treatments resulted in an average increase in heart rate of 9.98 (95% CI 3.72-16.2) beats/min when HFNC was used and 0.64 (95% CI -1.65 to 2.93) beats/min when traditional interfaces were used, a difference of 9.34 (95% CI 2.30-16.4) beats/min (P < .001). RT bedside time was significantly longer for HFNC nebulized treatments (P = .031). Subjective level of comfort was not statically different when nebulized bronchodilators were delivered via HFNC or via traditional interfaces. Length of pediatric ICU stay was not statistically different between subjects who received some aerosol nebulized bronchodilators via HFNC versus those who received all bronchodilators through traditional interfaces (P = .11). Aerosol bronchodilator delivery using HFNC is feasible at low gas flow (ie, 2-4 L/min). However, the use of HFNC did not improve subjects' comfort, and it increased RT bedside time. Further prospective randomized studies are needed to determine the efficacy and efficiency of aerosol therapy delivered through HFNC and potential patient-oriented outcomes.

Nebulization in the pandemic of coronavirus disease 2019

Inhaled therapy is the cornerstone in the management of obstructive airway diseases (OADs). Nebulization is often used for the delivery of bronchodilators and corticosteroids among the elderly and children. The present pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified, highly contagious, novel coronavirus, called severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is responsible for great morbidity and mortality globally. There is a great concern regarding person-to-person transmissibility of this virus. There is also a great concern of viral transmission of this virus to the health-care personnel and the bystanders through aerosol-generating procedures including frequently used nebulization therapy. Most of the patients with OAD, during the current pandemic, who were undergoing nebulization therapy, on getting infected with SARS-CoV-2 or on its suspicion, have been shifted to other handheld devices out of fear of transmission of infection. Presently, there exist not enough evidences either on the safety or on the risk of transmissibility of SARS-CoV-2 during nebulization in COVID-19 patients. In addition, there are concerns about nebulization in OAD cases even in the absence of COVID-19 and about the use of inhaled or systemic corticosteroids in these cases. We have made some observations based on all the current information available related to these issues, which may help provide some guidance in the use of nebulizer therapy and also discussed the measures to be taken to minimize the risk of infection, if any, during the procedure.

A comparison of the costs of bronchodilator delivery methods in children with asthma exacerbations treated in hospital. The first Polish study in children.

IntroductionRecommended methods of administering bronchodilator drugs in children with asthma exacerbations in a hospital include the pressurized metered-dose inhaler (pMDI) and nebulization (NEB). These methods differ in clinical effectiveness, safety and, as some studies indicate, the cost of their use in a child.AimTo calculate the direct costs of hospital therapy conducted with the use of short-acting β2-agonist (SABA) or its combination with short-acting muscarinic antagonist (SAMA) administered via pMDI with valved holding chamber (VHC) versus the same drugs in NEB in children with asthma exacerbation.Material and methodsA retrospective analysis of the costs of SABA (salbutamol) and SABA + SAMA (fenoterol + ipratropium bromide) inhalation therapy was performed. Based on the data obtained from the financial department, the pharmacy, and the sterilization department of the university hospital, the direct unit cost of the inhalation therapy in the child was calculated.ResultsThe results of the analysis indicate that in a hospital setting the cost of one-time SABA or SABA + SAMA administration via pMDI+VHC is 1.5–2.4 times lower compared to NEB. The payer incurred the lowest costs during anti-obstructive treatment using SABA with pMDI + VHC (PLN 9.39 for one inhalation procedure). The working time of medical staff during the inhalation treatment is the component generating the highest cost for the hospital (up to 40% of direct costs).ConclusionsIn hospital conditions, the supply of SABA or SABA + SAMA with the use of pMDI + VHC in a child with asthma exacerbation is more beneficial financially than the supply of the same drugs in NEB.

Effects of flow rate on transnasal pulmonary aerosol delivery of bronchodilators via high-flow nasal cannula for patients with COPD and asthma: protocol for a randomised controlled trial

IntroductionBoth in vitro and in vivo radiolabelled studies on nebulisation via high-flow nasal cannula showed that inhaled dose decreases as the administered gas flow increases. In our previous in vitro...

PRS23 - PERSISTENCE TO COPD THERAPIES AND IMPACT ON COSTS RELATED TO HEALTHCARE CONSUMPTION: A FRENCH CLAIMS DATA STUDY

Adherence to COPD therapies and impact on healthcare use is poorly documented in France. Our objective was to describe persistence in newly treated COPD patients in France, and to assess a potential impact of non-persistence on costs related to healthcare use. All patients aged 45 and over, having at least one delivery of bronchodilator over 3 consecutive quarters between 2007 and 2014, and without asthma markers, were selected in the Echantillon Généraliste des Bénéficiaires (EGB). It is a 1/97e random sample of the French claims database which collects details of healthcare reimbursed, for each beneficiary. Persistence was measured at 12 months in newly treated patients and assessed by non-interruption of deliveries during at least 90 days. Healthcare-related costs were compared between persistent and non-persistent patients, after matching and adjustment for available confounding factors. In 721 persistent patients to new therapy for COPD and 721 non-persistent patients, numbers of COPD therapies and visits to healthcare professionals were similar. However, medical procedures were less frequent in non-persistent patients than in persistent patients, especially pulmonary function testing, X-rays and chest scan. The total annual health care cost was higher for persistent than for non-persistent patients (€3,677 vs. €3,460), due to higher drug costs (€542 vs. €178). Hospitalisation costs were similar in both groups (€2,138 for persistent patients vs. €2,181 for non-persistent patients). In this population of mild to moderate COPD patients, no difference on health care costs was observed between persistent and non-persistent patients. It can be explained by the similar numbers of exacerbations in both groups and, as is always the case with observational data, residual confounding factors could explain part of the results (e.g. disease severity).

Evaluation of Bronchodilator Use During Chronic Obstructive Pulmonary Disease Exacerbation Inpatient Admissions.

Background: It is unknown whether the timing of initiation of a long-acting bronchodilator (LABD) during a chronic obstructive pulmonary disease (COPD) exacerbation or the method of short-acting bronchodilator (SABD) delivery may aid in improving patient outcomes. Objective: The goal of this study was to determine the impact of bronchodilator management in the hospital setting on clinical outcomes in patients with COPD exacerbation. Methods: This retrospective, single-center study evaluated patients admitted to the non-intensive care unit setting with a COPD exacerbation as defined by the International Classification of Diseases, Ninth Revision codes. The primary outcome was difference in 30-day readmission rates for early LABD therapy (<24 hours from hospital admission) versus late/no LABD therapy (>24 hours from hospital admission or not during hospitalization). Secondary objectives included length of stay (LOS) for this group, and 30-day readmission rates and LOS for the SABD via inhaler versus nebulizer groups. Results: Two hundred twenty patients were included. There was no difference in 30-day readmission rate (15.2% vs 18.2%, P = .6) and LOS (median 4 [interquartile range, IQR 3-6]) days for both groups, P = .34) between early versus late/no LABD therapy initiation, respectively. No difference was observed in 30-day readmission rate (16.7% vs 16.6%) and LOS (median 2.5 [IQR 1.1-3.9] days vs median 4 [IQR 2-6] days) between inhaler and nebulizer SABD therapy groups. Conclusions: No difference was observed in 30-day readmission rates or LOS when utilizing early LABD compared with late/no LABD therapy or comparing inhaler and nebulizer SABD delivery methods during COPD exacerbation.