The Use of Ipratropium Bromide for the Treatment of Pediatric Sialorrhea: A Retrospective Clinical Case Series.

OBJECTIVE: This retrospective review documents the experience of ipratropium bromide use among pediatric patients with sialorrhea at our multidisciplinary sialorrhea clinic at Children's Hospital at London Health Sciences Centre (LHSC). METHODS: A retrospective chart review of patients diagnosed with sialorrhea at our multidisciplinary clinic between January 2015 and June 2021 was completed. Data on patient demographics, comorbidities, clinical presentation, previous interventions, quality of life, and medication adverse side effects was collected. Drooling Frequency and Severity Scale (DFSS) scores were reviewed to compare sialorrhea management pre- and post-treatment with topical 0.03% ipratropium bromide nasal solution. A descriptive analysis and Wilcoxon signed rank tests were conducted to compare pre- versus post-treatment DFSS scores. RESULTS: A total of 12 patients presented for follow-up and were included in the final analysis. At the pre-treatment visit, the median DFSS score was 4 for frequency and 5 for severity. Post-treatment, median DFSS score was 3 for frequency and 4.5 for severity, (P = .020 and .129, respectively). Minimal adverse effects were encountered. CONCLUSIONS: Ipratropium bromide provided a statistically significant benefit for drooling frequency in the patients studied and may present an additional topical medical option for pediatric sialorrhea with limited adverse effects.

Residual reversibility in COPD patients already on long-acting bronchodilator: The OscilloRevers Study.

BACKGROUND: Dyspnea is a complex symptom of chronic obstructive pulmonary disease (COPD) which is not strongly correlated with lung function measures. Long-acting bronchodilators (LAB) may reduce this dyspnea, but some patients report persistent chronic dyspnea despite this treatment. This study aims to assess residual reversibility and clinical response after short-acting bronchodilator (SAB) in COPD patients already treated by LAB and reporting persistent dyspnea. METHODS: COPD patients with a persistent dyspnea (modified Medical Research Council scale (mMRC) ≥1) despite current stable treatment with at least one LAB were included. Spirometry, plethysmography and impulse oscillometry (IOS) were performed at peak effect of their LAB and repeat 45 min after the intake of two SAB (400 µg of salbutamol and 80 µg of ipratropium). Dyspnea improvement was assessed at 45 min after SAB through a comparative two-sided VAS (-100 mm for maximal improvement; +100 mm for maximal degradation). RESULTS: Twenty-two COPD patients were analyzed, mainly men (59.1 %) with a mean age of 60.6 years and a median FEV1 of 54 % of predicted values. Fifty percent of patients reported a severe basal dyspnea (mMRC ≥2). After SAB, spirometric and plethysmographic measurements were statistically improved. For IOS measurement, reactance at 5 Hz (X5) and area of reactance (AX) were also improved. Fifty percent of patients reported a clinically relevant improvement of their resting dyspnea. However, no correlation was found between dyspnea improvement and functional measures. CONCLUSIONS: Fifty percent of COPD patients regularly treated with one or two LAB still report a relevant improvement of resting dyspnea after the adjunctive intake of double short-acting bronchodilators. Physiological mechanisms associated with this improvement remain to be determined. CLINICAL TRIAL REGISTRATION: NCT02928744.

Nebulized Ipratropium Bromide-induced Anisocoria: Why Is Anisocoria Observed?

Pharmacological anisocoria is a rare but benign condition. This paper presents an eleven-year-old patient with asthma who developed ipratropium bromide-associated anisocoria during nebulizer treatment. Hypotheses regarding the possible causes of anisocoria are discussed and precautions to be taken during treatment are presented. To prevent the development of anisocoria, it was found that it is important to use the appropriate mask during nebulizer treatment, to place the mask on the face properly, and, if possible, to administer drugs by closing the eyes. Further, it is recommended that patients undergo an ophthalmological examination before discharge and that they and their families be informed that the condition is temporary.

Unilateral mydriasis in a child with a ventriculoperitoneal shunt for obstructive hydrocephalus: a diagnostic dilemma.

There are several causes for sudden onset unilateral mydriasis, however impending transtentorial uncal herniation needs to be ruled out. This unique case highlights an uncommon adverse response to a common mode of treatment that leads to a diagnostic dilemma. A 3-year-old boy with a ventriculoperitoneal (VP) shunt for an obstructive hydrocephalus presented with an acute respiratory distress. He developed unilateral mydriasis with absent light reflex during treatment with nebulisers. An urgent CT scan of the brain did not show any new intracranial abnormality. A case of pharmacological anisocoria was diagnosed that resolved completely within 24 hours of discontinuation of ipratropium bromide. Although ipratropium-induced anisocoria has been reported in children, but to our knowledge none in a child with VP shunt for hydrocephalus. This emphasises the urgency in evaluating unilateral mydriasis to rule out life-threatening conditions. Clinicians should remember that ipratropium administered through ill-fitting face masks could cause this completely reversible adverse effect.

Long-acting dual bronchodilator therapy (indacaterol/glycopyrronium) versus nebulized short-acting dual bronchodilator (salbutamol/ipratropium) in chronic obstructive pulmonary disease: A double-blind, randomized, placebo-controlled trial.

INTRODUCTION: Most guidelines recommend long-acting bronchodilators over short-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD). The available evidence for the guidelines was based on dry powder or pressurized metered dose inhalers, but not nebulizations. Nevertheless, there is considerable, poorly evidenced based, use of short acting nebulized bronchodilators. METHODS: This was an investigator initiated, randomized, active controlled, cross-over, double-blind and double-dummy single centre study in patients with stable COPD. The active comparators were indacaterol/glycopyrronium 110/50 µg as Ultibro® via Breezhaler® (IND/GLY) and salbutamol/ipratropium 2,5/0,5 mg via air driven nebulization (SAL/IPR), both given as a single dose on separate days. The primary end point was the area under the FEV1 curve from baseline till 6 h. Secondary end points included change in Borg dyspnoea score, adverse events and change in hyperinflation measured by the inspiratory capacity. RESULTS: A total of 33 COPD patients completed the trial and were evaluable, most of them were ex-smokers. The difference between the tested regimens for the primary endpoint, FEV1 AUC 0-6 h, 2965 ± 1544 mL (mean ± SD) for IND/GLY versus 3513 ± 1762 mL for SAL/IPR, was not significant (P = 0.08). The peak in FEV1 was higher and was reached faster with SAL/IPR compared to IND/GLY. No other significant differences were detected for the secondary endpoints including the Borg score, or adverse events. CONCLUSION: Among patients with stable COPD, dry powder long-acting single inhalation of a LABA and a LAMA (IND/GLY) was not superior compared to nebulized short-acting salbutamol plus ipratropium (SAL/IPR) in its bronchodilating effects over 6 h.The effects of the nebulization kicked in faster and peaked higher. The observed differences may be caused by the difference in dosing between the two regimens. The improvement in Borg dyspnoea score did not favour the nebulization. Long-term outcomes were not assessed in this study.

Metered-dose inhaler ipratropium bromide for children with acute asthma exacerbation: A prospective, non-randomized, observational study.

BACKGROUND: Ipratropium bromide (IB), when administered with ß2-agonists, is effective in reducing hospital admissions of children presenting to the emergency department (ED) with severe asthma. While IB is commonly delivered in its nebulized form, using a metered-dose inhaler (MDI), can, reportedly, shorten patients' length of stay in the ED. However, the effectiveness and safety of IB administration using an MDI with a spacer have not been established. This study aimed to investigate the effectiveness and safety of MDI-delivered IB in pediatric patients with acute asthma exacerbation. METHODS: This prospective, non-randomized, observational study included patients aged ≥4 years with a history of severe asthma exacerbation. Patients received IB via MDI with a spacer three times at 20-min intervals. IB use was determined by the physicians' treatment policy. Propensity score matching was used to adjust the confounding factors related to IB administration. RESULTS: Of the 158 patients, 88 were treated with IB and 70 were treated without IB. A propensity score-matching analysis extracted 54 patients from each group. We found no statistical difference in the admission rate of the two groups (IB group: 25.9% vs non-IB group: 31.5%; P = 0.67). The post-treatment modified pulmonary index scores (mean ± SD) were also similar (IB: 6.6 ± 2.0 vs non-IB: 6.3 ± 2.5; P = 0.53). Only one patient (1.0%) treated with IB experienced vomiting, which resolved spontaneously. CONCLUSION: The metered-dose inhaler IB was ineffective in reducing the admission rate possibly because it was less effective than a nebulizer for IB inhalation.

Midriasis unilateral de origen farmacológico / Unilateral mydriasis of pharmacological origin

No disponible

Nebulized Ipratropium bromide protects against tracheal and bronchial secretion during bronchoscopy: A randomized controlled trial.

BACKGROUND: Anticholinergic administration prior to flexible bronchoscopy has been investigated, but studies have not yielded consistent results. METHODS: Patients were randomized 1:1 to receive nebulized 4 ml ipratropium bromide (1 mg, n = 125) or placebo (n = 125) for 15 minutes as premedication, 20 to 40 minutes before bronchoscopy. Airway secretions, bleeding, patient discomfort, procedure time, and procedure-related adverse events were compared between the groups. RESULTS: Nebulized ipratropium bromide prior to bronchoscopy could reduce airway secretions and patient discomfort (P = .02; P < .001, respectively), but not tracheobronchial bleeding or procedure time (P = .51, P = .36, respectively). Chest nodule or mass was the most common indication for performing bronchoscopy. The adverse events were higher in ipratropium bromide group, and hypertension was the most common complication. CONCLUSION: Nebulized ipratropium bromide prior to bronchoscopy is a more effective regimen that shows a practical benefit on the airway secretions and patient comfort, though these effects may not translate into any marked reduction in bleeding or of procedure time under general anesthesia. We suggest that routine nebulized ipratropium bromide premedication for bronchoscopy could be useful and beneficial. TRIAL REGISTRATION: chictr.org.cn: ChiCTR1800016881.

Reduced Environmental Impact of the Reusable Respimat® Soft Mist™ Inhaler Compared with Pressurised Metered-Dose Inhalers.

INTRODUCTION: Pressurised metered-dose inhalers (pMDIs) are associated with global warming potential values as they contain a hydrofluoroalkane (HFA) propellant, whereas the Respimat® Soft Mist™ inhaler is propellant-free. The original disposable Respimat has recently been updated to provide a reusable device that is similar in performance and use but is more convenient to patients and reduces environmental impact. This study compared the product carbon footprint (PCF) of Respimat (both disposable and reusable) and pMDIs to understand life cycle hotspots, and also to determine the potential quantitative environmental benefits of a reusable Respimat product. METHODS: PCFs of four inhalation products-tiotropium bromide (Spiriva®) Respimat, ipratropium bromide/fenoterol hydrobromide (Berodual®) Respimat, Berodual HFA pMDI and ipratropium bromide (Atrovent®) HFA pMDI-were assessed across their whole life cycle. RESULTS: Data show that Respimat inhalers have a lower PCF (carbon dioxide equivalent per kilogram) than HFA pMDIs: pMDI Atrovent 14.59; pMDI Berodual 16.48; disposable Spiriva Respimat 0.78; disposable Berodual Respimat 0.78. Approximately 98% of the pMDI life cycle total is due to HFA propellant emissions during use and end-of-life phases. The impact of the material used for the Respimat product outweighs the impact of the material used to make the empty cartridge. Furthermore, compared with the single-use device over 1 month, the PCF of Spiriva Respimat was further reduced by 57% and 71% using the device with refill cartridges over 3 and 6 months, respectively. CONCLUSION: Together, these data suggest that Respimat inhalers, and in particular the new reusable inhaler, can reduce the environmental impact associated with inhaler use. FUNDING: Boehringer Ingelheim.

A mesh nebulizer is more effective than jet nebulizer to nebulize bronchodilators during non-invasive ventilation of subjects with COPD: A randomized controlled trial with radiolabeled aerosols.

BACKGROUND: Beneficial effects from non-invasive ventilation (NIV) in acute COPD are well-established, but the impact of nebulization during NIV has not been well described. AIM: To compare pulmonary deposition and distribution across regions of interest with administration of radiolabeled aerosols generated by vibrating mesh nebulizers (VMN) and jet nebulizer (JN) during NIV. METHODS: A crossover single dose study involving 9 stable subjects with moderate to severe COPD randomly allocated to receive aerosol administration by the VMN Aerogen and the MistyNeb jet nebulizer operating with oxygen at 8 lpm during NIV. Radiolabeled bronchodilators (fill volume of 3 mL: 0.5 mL salbutamol 2.5 mg + 0.125 mL ipratropium 0.25 mg and physiologic saline up to 3 mL) were delivered until sputtering during NIV (pressures of 12 cmH2O and 5 cmH2O - inspiratory and expiratory, respectively) using an oro-nasal facemask. Radioactivity counts were performed using a gamma camera and regions of interest (ROIs) were delimited. Aerosol mass balance based on counts from the lungs, upper airways, stomach, nebulizer, circuit, inspiratory and expiratory filters, and mask were determined and expressed as a percentage of the total. RESULTS: Both inhaled and lung doses were greater with VMN (22.78 ±â€¯3.38% and 12.05 ±â€¯2.96%, respectively) than JN (12.51 ±â€¯6.31% and 3.14 ±â€¯1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ±â€¯1.3% versus 46.44 ±â€¯5.83%, p = 0.001). Peripheral deposition of radioaerosol was significantly lower with JN than VMN. CONCLUSIONS: VMN deposited > 3 fold more radioaerosol into the lungs of moderate to severe COPD patients than JN during NIV.

The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China.

BACKGROUND: Patients diagnosed with chronic obstructive pulmonary disease (COPD) in China are commonly prescribed ipratropium plus theophylline (I+T) therapy. Studies have shown that an inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) combination is also efficacious in reducing symptoms and exacerbations. This study evaluated the efficacy and tolerability of adding budesonide/formoterol (BUD/FORM) to I+T in Chinese patients with severe COPD. METHODS: A randomized, parallel-group, open-label, multicenter phase IV study (Clinical Trials.gov identifier: NCT01415518) was conducted in China. Patients received either BUD/FORM (160/4.5 µg; two inhalations twice daily [bid] via Turbuhaler®) + I (20 µg per inhalation, two inhalations four times daily) + T (100 mg bid) or I+T alone for 12 weeks. The primary efficacy variable was change from baseline in predose forced expiratory volume in 1 s (FEV1). RESULTS: A total of 584 patients were randomized equally between treatment groups. At the end of the study, the BUD/FORM plus I+T group displayed significant improvements in predose FEV1 versus the I+T group (between-group difference 6.9%; 95% confidence interval [CI]: 4.3, 9.6; p < 0.0001). Forced vital capacity, inspiratory capacity, peak expiratory flow and health-related quality of life (HRQoL) scores were significantly improved (all p < 0.0001) and exacerbation frequency was reduced (43.5% reduction; rate ratio 0.565, 95% CI 0.325, 0.981; p = 0.0425) with BUD/FORM plus I+T versus I+T alone. CONCLUSION: Patients with severe COPD in China treated with BUD/FORM plus I+T showed significant improvements in lung function and HRQoL and a reduction in exacerbations compared with I+T alone. Both treatments were well tolerated and no safety concerns were noted. The reviews of this paper are available via the supplemental material section.

Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial.

INTRODUCTION: In moderate-severe asthma exacerbation, salbutamol by inhaler (MDI) is superior to salbutamol delivered by nebulizer (NEB); however, to our knowledge, no studies in children with exclusively severe exacerbations were performed. OBJECTIVE: To compare the efficacy of salbutamol and ipratropium bromide by MDI versus by NEB in severe asthma exacerbations. METHODS: We performed a clinical trial enrolling 103 children (2-14 years of age) with severe asthma exacerbations (defined by the Pulmonary Score ≥ 7) seen at the emergency room in Asuncion, Paraguay. One group received salbutamol and ipratropium (two puff every 10 min for 2 h and then every 30 min for 2 h more) by MDI with a valved-holding chamber and mask along with oxygen by a cannula separately (MDI-SIB); and the other received nebulization with oxygen (NEB-SIB) of salbutamol and ipratropium (1 every 20 min for 2 h and then every 30 min for 2 h more). Primary outcome was the rate of hospitalization (Pulmonary Score ≥ 7) after 4 h and secondary outcome was oxygen saturation. RESULTS: Fifty two children received MDI-SIB and 51 NEB-SIB. After the 4th hour, children on MDI-SIB had significantly (P = 0.003) lower rate of hospital admission than on NEB-SIB (5.8% vs 27.5%, RR: 0.21 [0.06-0.69], respectively). Similarly, a significant improved clinical score after 60 min and increase in oxygen saturation after 90 min of treatment was observed in MDI-SIB versus NEB-SIB group (4.46 ± 0.7 vs 5.76 ± 0.65, P < 0.00001; and 90.5 ± 1.7 vs 88.43 1 ± 1, P < 0.00001, respectively). CONCLUSION: Even in severe asthma exacerbations administration of salbutamol and ipratropium by MDI with valved-holding chamber and mask along with oxygen by a cannula separately was more effective than by a nebulizer.

Nebulized Terbutaline and Ipratropium Bromide Versus Terbutaline Alone in Acute Exacerbation of Chronic Obstructive Pulmonary Disease Requiring Noninvasive Ventilation: A Randomized Double-blind Controlled Trial.

BACKGROUND: Short-acting ß2 -agonists are the mainstay of treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the emergency department (ED). It is still unclear whether the addition of short-acting anticholinergics is clinically more effective care compared to treatment with ß2 -agonists alone in patients with hypercapnic AECOPD. OBJECTIVE: The objective was to evaluate whether combining ipratropium bromide (IB) to terbutaline reduces hospital and intensive care unit (ICU) admission rates compared to terbutaline alone in AECOPD hypercapnic patients. METHODS: In this double-blind controlled trial, patients who were admitted to the ED for AECOPD requiring noninvasive ventilation (NIV) were randomized to receive either 5 mg of nebulized terbutaline combined to 0.5 mg of IB (terbutaline/IB group, n = 115) or 5 mg of terbutaline sulfate (terbutaline group, n = 117). Nebulization was repeated every 20 minutes for the first hour and every 4 hours within the first day. Primary outcomes were the rate of hospital admission and need for endotracheal intubation within the first 24 hours of the start of the experimental treatment. Secondary outcomes included changes from baseline of dyspnea, physiologic variables, length of hospital stay, ICU admission rate, and 7-day mortality. RESULTS: The two groups were similar regarding baseline demographic and clinical characteristics. Hospital admission was observed in 70 patients (59.8%) in the terbutaline/IB group and in 75 patients (65.2%) in the terbutaline group (respiratory rate [RR] = 1.09, 95% confidence interval [CI] = 0.93 to 1.27, p = 0.39). ICU admission was required in 37 (32.2%) patients in the terbutaline/IB group and 30 patients (25.6%) in terbutaline group (RR = 1.25, 95% CI = 1.02 to 1.54, p = 0.27). There were no significant differences in dyspnea score, blood gas parameters changes, vital signs improvement, and 7-day death rate between both groups. CONCLUSION: In patients admitted to the ED for AECOPD requiring NIV, combination of nebulized IB and terbutaline did not reduce hospital admission and need to ICU care.

Optimización de la farmacoterapia en paciente con asma severa no controlada / Optimization of the pharmacotherapy in a patient with non-controlled severe asthma and therapeutic non-compliance

Como parte del curso de Atención Farmacéutica II de la Licenciatura en Farmacia de la Universidad de Costa Rica los estudiantes, bajo la supervisión de profesores de la cátedra, ofertan el servicio de Seguimiento Farmacoterapéutico (SFT) a pacientes crónicos polimedicados que lo requieran. Se presenta un caso de una paciente femenina de 50 años con asma bronquial severa no controlada con polimedicación. Se le brinda el servicio de SFT, se identifican resultados negativos asociados a la medicación (RNM) manifestados y potenciales, se realizan intervenciones farmacéuticas que permiten un control del asma evaluado con Asthma Control Test (ACT) de 23 y un valor de pico flujo de 420L/ min luego de la intervención

The students of the Degree in Pharmacy from the University of Costa Rica took part in a course called Pharmaceutical Care II part. As a section of this course and under the supervision of their professors, the students offered a service of pharmacotherapeutic follow-up to polymedicated chronic patients who require it. A case of a 50 years old female patient was presented. She suffered uncontrolled severe bronchial asthma with polymedication. The pharmacotherapeutic follow-up service was given to the patient. Negative results associated to the medication were identified as manifested or potential. Thus, pharmaceutical interventions were performed and allowed to control a health problem as it was shown by an ACT punctuation of 23 and a peak flow value of 420 L/min after the intervention

Short-acting bronchodilators for the management of acute exacerbations of chronic obstructive pulmonary disease in the hospital setting: systematic review.

BACKGROUND: Currently, there is a lack of guidelines for the use of short-acting bronchodilators (SABD) in people admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), despite routine use in practice and risk of cardiac adverse events. AIM: To review the evidence that underpins use and optimal dose, in terms of risk versus benefit, of SABD for inpatient management of AECOPD and collate the results for future guidelines. METHODS: Medline, Embase, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov and International Clinical Trials Registry Platform were searched (inception to November 2017) for published and ongoing studies. Included studies were randomised controlled trials or controlled clinical trials investigating the effect of SABD (ß2-agonist and/or ipratropium) on inpatients with a diagnosis of AECOPD. This review was undertaken in accordance with PRISMA guidelines and a pre-defined protocol. Due to heterogeneous methodologies, meta-analysis was not possible so the results were synthesised qualitatively. RESULTS: Of 1378 studies identified, 10 met inclusion criteria. Narrative synthesis of 10 studies revealed no significant differences in most outcomes of interest relative to dose, delivery via inhaler or nebuliser, and type of ß2-agonist used. However, some evidence demonstrated significantly increased cardiac side effects with increased dosage of ß2-agonist (45% versus 24%), P<0.05). CONCLUSION: This review identified a paucity of methodologically rigorous evidence evaluating use of SABD among AECOPD. The available evidence did not identify any additional benefits for participants receiving higher doses of short-acting ß2-agonists compared to lower doses, or based on type of delivery method or ß2-agonists used. However, there was a small increase in some adverse events for participants using higher doses of ß2-agonists.

Paradoxical Vocal Cord Motion in a Pair of Twin Preterm Infants.

BACKGROUND: Intractable obstructive apneas requiring multiple intubations are rare in newborns. CASE CHARACTERISTICS: We report a pair of twins born at 29 weeks gestation who had severe obstructive apneas due to Paradoxical Vocal Cord Motion (PVCM). OUTCOME: The symptoms resolved promptly with ipratropium nebulization. Follow-up at 12 months of age revealed normal development. MESSAGE: PVCM should be considered in the differential diagnosis of intractable obstructive apneas in very low birth weight preterm infants.

Development of a novel digital breath-activated inhaler: Initial particle size characterization and clinical testing.

BACKGROUND: Delivery of inhaled respiratory medications have been associated with variable delivery of drug due to errors in device operations and have not been designed to monitor true delivery of medication. A fully digital breath-activated inhaled (DBAI) delivery platform has been developed with integrated firmware and software to address these limitations. METHODS: the device was designed to produce similar aerosol particle output to a marketed albuterol MDI and to the albuterol/ipratropium combination in a soft mist inhaler (SMI). Cascade impactor studies were conducted to demonstrate comparable aerodynamic particle size distribution (APSD) metrics. Efficacy was evaluated by pharmacodynamic studies involving spirometry in two separate protocols with adult subjects having COPD (albuterol DBAI vs. albuterol MDI - Study A, albuterol/ipratropium DBAI single arm - Study B). RESULTS: The total emitted doses (TED) were 81.9 ±â€¯10.3, 109.3 ±â€¯15.0 and 121.9 ±â€¯7.0 µg/actuation for the DBAI, SMI and MDI respectively, and the fine (respirable) particle doses (FPD) were 56.2 ±â€¯6.0, 61.7 ±â€¯5.5 and 79.4 ±â€¯2.7 µg/actuation. MMADs for albuterol sulfate were 1.93 ±â€¯0.11, 1.75 ±â€¯0.19, and 2.65 ±â€¯0.05 µm for the DBAI, Respimat soft mist inhaler (SMI) and MDI respectively. The corresponding GSDs were 1.96 ±â€¯0.16, 2.79 ±â€¯0.25, and 1.48 ±â€¯0.02 µm. The corresponding respirable fractions were 68.7 ±â€¯3.2%, 57.3 ±â€¯10.5%, and 65.2 ±â€¯2.4%. Spirometric study A enrolled 23 subjects (age 64 ±â€¯7.3 years, 39% male, FEV1 45 ±â€¯14% predicted). Study B enrolled 23 subjects (age 65 ±â€¯8.6 years, 43% male, FEV1 47 ±â€¯10% predicted). For Study A, FEV1 at 20 min post-dose improved by 120 (167) mL (p = 0.002) for the DBAI device and 109 (183) mL (p = 0.008) for the MDI device (p = 0.86 for between group differences). For Study B, FEV1 (20 min post-dose) improved by 216 (126) mL (p < 0.001). CONCLUSION: The DBAI generated highly respirable aerosols containing albuterol sulfate that were similar to the MDI and SMI in respirable fraction but lower in dose. Subsequent pharmacodynamic studies delivering albuterol sulfate alone and in combination with ipratropium bromide confirmed similar responses for the DBAI compared with the other inhalers, which could possibly be related to a response ceiling. The DBAI breath-activated capability combined with the ability to monitor actual delivery of medication may improve effectiveness by overcoming patient miscoordination.

The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD.

We investigated the short-term bronchodilator effects of RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined with other bronchodilators in chronic obstructive pulmonary disease patients with reversibility (>150 mL to short-acting bronchodilators).Study 1 was a six-way, placebo-controlled crossover study (n=36) with single doses of RPL554 (6 mg), salbutamol (200 µg), ipratropium (40 µg), RPL554 (6 mg)+salbutamol (200 µg), RPL554 (6 mg)+ipratropium (40 µg) or placebo. Study 2 was a three-way crossover study (n=30) of tiotropium (18 µg) combined with RPL554 (1.5 or 6 mg) or placebo for 3 days. Forced expiratory volume in 1 s (FEV1), lung volumes and specific airway conductance (sG aw) were measured.In study 1, peak FEV1 change compared with placebo was similar with RPL554, ipratropium and salbutamol (mean 223, 199 and 187 mL, respectively). The peak FEV1 was higher for RPL554+ipratropium versus ipratropium (mean difference 94 mL; p<0.0001) and RPL554+salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). In study 2 (day 3), both RPL554 doses caused greater peak FEV1 effects than placebo. The average FEV1 (0-12 h) increase was greater with RPL554 6 mg only versus placebo (mean difference 65 mL; p=0.0009). In both studies, lung volumes and sG aw showed greater RPL554 combination treatment effects versus monotherapy.RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.

Experimental Substantiation of Inhalation Administration of Pathogenic Therapy of Toxic Convulsive Disorder for Correction of External Respiration Disorders.

We studied the dynamics of respiratory function in rats during intratracheal poisoning with diisopropyl fluorophosphate and pentylenetetrazole in doses corresponding to the LD50 in humans. The maximum of external respiration impairment was recorded in 30 min after poisoning. Administration of diazepam and atropine both separately and in combination during the development of the first signs of poisoning did not significantly affect the respiration parameters, but reduced the incidence of seizures and contributed to a decrease in the rate of animal death. Intratracheal administration of cholinolytic, ß2-adrenomimetic, or glutamate receptors antagonist promoted correction of the respiratory function. It was found that the maximum therapeutic effect in case of diisopropyl fluorophosphates poisoning was achieved after intratracheal administration of ipratropium bromide (0.086 mg/kg), salbutamol (0.086 mg/kg), and MK-801 (0.1 mg/kg), while in case of pentylenetetrazole poisoning, intratracheal administration of ipratropium bromide (0.086 mg/kg) was most effective.