An in vitro investigation into the release of fugitive medical aerosols into the environment during manual ventilation.

BACKGROUND: During manual resuscitation, nebulizer therapy may be used to deliver therapeutics to patients in respiratory distress. However, the devices used to generate and deliver these medical aerosols have the potential to release these therapeutics into the local environment and expose caregivers to unwanted medical aerosols. AIM: To quantify the levels of fugitive medical aerosol released into the environment during aerosol drug delivery using a manual resuscitation bag with and without filtration. METHODS: Time-varying fugitive aerosol concentrations were measured using an aerodynamic particle sizer placed at a position designed to mimic a caregiver. Two nebulizer types were assessed, a vibrating mesh nebulizer and a jet nebulizer. The aerosol dose delivered to the simulated patient lung was also quantified. FINDINGS: Filtration of the exhalation port of the manual resuscitation bag was seen to reduce fugitive medical aerosols to ambient levels for both nebulizer types. The vibrating mesh nebulizer delivered the greatest quantity of aerosol to the simulated adult patient (18.44 ± 1.03% versus 3.64 ± 0.26% with a jet nebulizer). CONCLUSIONS: The results highlight the potential for exposure to fugitive medical aerosols released during the delivery of aerosol therapy with a manual resuscitation bag and also the potential for significant variation in patient lung dose depending on nebulizer type.

Observational study of newborn infant parasympathetic evaluation as a comfort system in awake patients admitted to a pediatric intensive care unit.

To compare the newborn infant parasympathetic evaluation system (NIPE) scores with a validated clinical scale using two different nebulizers in children with bronchiolitis admitted to a PICU. Comfort was evaluated using the COMFORT-behavior scale (CBS) before (T1), during (T2) and after (T3) each nebulization. In order to compare NIPE and CBS values during the whole T1 to T3 period, the variable Dif-CBS was defined as the difference between maximal and minimal CBS scores, and Dif-NIPE as the difference between 75th and 25th percentile NIPE values. Analyses were carried out, firstly for the total of nebulizations and secondly comparing two different nebulization systems: a jet nebulizer (JN) and a nebulizer integrated in high flow nasal cannulas (NHF). 84 nebulizations were recorded on 14 patients with a median [25th-75th percentile] age of 6 months (3.1-9.5). A Dif-CBS of 4 points (2-7), as well as changes in CBS scores between T1 and T2, defined the nebulization as a discomfort stimulus. The NIPE system, represented as the Dif-NIPE, showed a median variation of 9 points (7-10), and was poorly correlated to Dif-CBS [rs 0.162 (P = 0.142)]. Discomfort during nebulization, assessed by CBS was greater with the JN system compared to NHF: 17 (13-22) vs 13 (9-15) (P = 0.001). NIPE monitoring detected no significant differences between both nebulization systems (P = 0.706). NIPE monitoring showed a variation in comfort during nebulization in the patient with bronchiolitis, though correlation with CBS was poor. Further research is required before NIPE can be suggested as a comfort monitoring system for the awake infant.

The Impact of Adding a Training Device to Familiar Counselling on Inhalation Technique and Pulmonary Function of Asthmatics.

INTRODUCTION: We have investigated the effect of adding a pressurized metered dose inhaler (pMDI) training device to verbal counselling on pulmonary function and inhalation technique. METHODS: A total of 304 adult asthmatic subjects (> 18 years old) were enrolled in a 3-month study of assessment and education. They were divided into an investigation group (Trainhaler plus Flo-Tone and verbal counselling, n = 261, mean age 49.2 years) and a control group (verbal counselling only, n = 43, mean age 48.7 years). Pulmonary function and inhalation technique were evaluated, mistakes noted, and the correct technique advised at three consecutive monthly visits. Visits also included verbal pMDI counselling (both groups) and training device coaching (investigation group). RESULTS: By visit 2, the mean number of technique errors decreased significantly (p < 0.05) in both groups (investigation group p < 0.001). The investigation group demonstrated a marked decrease in the frequency of the critical error of maintaining a slow inhalation rate until the lungs are full-a technique difficult to learn via verbal counselling alone. The improvement in pulmonary function was significant from the second clinic visit in the investigation group (p < 0.05) and from the third visit in both groups (p < 0.001). CONCLUSIONS: Use of a training device combined with verbal counselling improved inhalation technique. An earlier, significant improvement was also noted in pulmonary function.

[The Aut-idem Rule and the Importance of Patient-Individual Selection of Inhalers for the Therapy of Airway Diseases in Practices of Pneumologists and General Practitioners - Assessment and Implementation by Pneumologists and General Practitioners]. / Aut-idem-Regelung und Inhalatorauswahl bei inhalativer Therapie in pneumologischen und hausärztlichen Praxen unter Alltagsbedingungen ­ Einschätzung und Umsetzung durch Pneumologen und Hausärzte.

Drug therapy of obstructive airway diseases mainly relies on inhaled medication. The success of this therapy depends primarily on the selection of the appropriate inhaler considering patient's choice and the correct application. The aut-idem-rule, an active exclusion of the optional substitution by the pharmacist, allows prescribing physicians to ensure the delivery of a particular inhaler, which was selected for that patient, who was trained to use specifically that inhaler. This survey shows that pneumologists and, to a greater extent general practitioners, do not consistently make use of this option, although they unanimously agree on the importance of targeted inhaler selection. As a result, patients may receive different inhalers in the pharmacy, where the inhaler is chosen under consideration of market-driven aspects such as rebate contracts or stock. This causes that patients get confused by the exchange of their inhaler. Thus the exchange of the inhaler by the pharmacist leads to uncertainty and application problems in patients. Hence, the success of the comparatively complex inhaled therapy is endangered. This could be prevented, if prescribing physicians were informed and supported consistently regarding the use of aut-idem exclusion to ensure an optimal therapy for each individual patient.

A cross-sectional study to assess inhalation device handling and patient satisfaction in COPD.

Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD). Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ) to assess the handling and satisfaction for Respimat(®) Soft Mist™ Inhaler (SMI) compared with the Breezhaler(®) dry powder inhaler (DPI) among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA(®) (tiotropium) Respimat(®) or with Hirobriz(®)/Onbrez(®)/Oslif(®) (indacaterol) Breezhaler(®) for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ total score in the Respimat(®) and Breezhaler(®) groups was 80.7 and 79.9, respectively (difference of 0.8, 95% confidence interval [CI] -2.9 to 4.5; P=0.67). The mean total performance scores were 82.5 and 78.2 (difference of 4.3, 95% CI -0.3 to 8.9; P=0.06), and the mean total convenience scores were 78.6 and 81.9 (difference of -3.3, 95% CI -7.0 to 0.4; P=0.08) for the Respimat(®) and Breezhaler(®) groups, respectively. Patients gave the Respimat(®) SMI and the Breezhaler(®) DPI overall satisfaction PASAPQ scores of 6.0 and 5.9, respectively, which shows that patients were satisfied with these inhalers.

Schedules of Controlled Substances: Table of Excluded Nonnarcotic Products: Vicks® VapoInhaler®.

This final rule adopts the interim final rule, with a correction to spelling of the manufacturer's name that was published in the Federal Register on October 27, 2015. The Drug Enforcement Administration is amending the table of Excluded Nonnarcotic Products to update the listing for Vicks® VapoInhaler®, containing 50 mg levmetamfetamine in a nasal decongestant inhaler, marketed by The Procter & Gamble Company. This over-the-counter, non-narcotic drug product is excluded from provisions of the Controlled Substances Act.

Schedules of Controlled Substances: Table of Excluded Nonnarcotic Products: Nasal Decongestant Inhaler/Vapor Inhaler. Final rule.

This final rule adopts, without change, the interim final rule that was published in the Federal Register on October 27, 2015. The Drug Enforcement Administration is amending the table of Excluded Nonnarcotic Products to update the company name for the drug product Nasal Decongestant Inhaler/Vapor Inhaler (containing 50 milligrams levmetamfetamine) to Aphena Pharma Solutions--New York, LLC. This over-the-counter, nonnarcotic drug product is excluded from the provisions of the Controlled Substances Act.

[Inhaled treatments: Choice of devices, systemic absorption of inhaled drugs and bitter taste receptors in the respiratory tract]. / Traitements inhalés : critères de choix des dispositifs, absorption systémique des médicaments par voie inhalée et récepteurs pulmonaires à l'amertume.

Inhaled drugs are now routinely prescribed in daily medical practice. Recent topics about these treatments have been developed during the fourth annual meeting of the Groupe de travail aérosolthérapie (GAT) of the French-speaking respiratory society (Société de pneumologie de langue française). This article focuses mainly upon the choice of devices, systemic absorption of inhaled drugs and bitter taste receptors in the respiratory tract, a potential new target for drug development.

Comparison of the provocative concentration of methacholine causing a 20% fall in FEV1 between the AeroEclipse II breath-actuated nebulizer and the wright nebulizer in adult subjects with asthma.

RATIONALE: The American Thoracic Society guidelines for methacholine testing for the diagnosis of asthma recommends the 2-minute tidal breathing protocol with the Wright nebulizer, which produces more aerosol than required, generates a small particle size, and requires cleaning between tests. OBJECTIVES: To evaluate methacholine testing using a disposable, breath-actuated AeroEclipse II, which produces aerosol during inspiration and was developed for single-patient use. METHODS: Forty-six adult subjects with asthma (19 men), aged 27.3 (SD, 9.5) years, with FEV1 98.5 (SD, 18.1) % predicted participated in a randomized, crossover, observational study. Subjects were first screened using the Wright nebulizer, then assigned to 2 minutes of tidal breathing from the Wright or 20 seconds of tidal breathing from the AeroEclipse nebulizer on 2 separate days, in random order. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) values were calculated by linear interpolation of log dose-versus-response curves, log-transformed, and compared using paired Student t test and Pearson correlation. MEASUREMENTS AND MAIN RESULTS: The 38 subjects demonstrating reproducible PC20 measurements of within 1.5 doubling concentrations were included in the comparison. The geometric mean methacholine PC20 measured with the AeroEclipse nebulizer was approximately 1 doubling concentration lower than the geometric mean methacholine PC20 of the Wright nebulizer (P < 0.05). The Pearson correlation coefficient between the two nebulizers was 0.86 (P < 0.05). CONCLUSIONS: The PC20 measurements using the two nebulizers were highly correlated; however, the PC20 determined with the AeroEclipse nebulizer was significantly lower than those determined using the Wright nebulizer. Clinical trial registered with www.clinicaltrials.gov (NCT 01919424).

[The choice of inhalation device: A medical act]. / Le choix du dispositif d'inhalation (hors nébulisation) : un acte médical.

Inhaled treatments are essential for respiratory diseases management, including COPD and asthma. Optimal control of the disease largely depends on patient's compliance and proper use of these treatments. Different types of ready-to-use inhaler devices are available: metered dose inhaler, dry powder inhaler or soft mist inhaler. Each of these devices presents specific characteristics and constraints that have to be evaluated and taken into account before prescription. In order to optimize adherence and treatment efficacy, the choice of inhaler device should depend on the specific needs, abilities and preferences of each patient and a specific education to treatment should be provided. Inhaled treatments, even containing the same drug, have different technical constraints and are thus not easily interchangeable. Their substitution without prior medical consent and without proper training can lead to errors in taking treatment, treatment failures and increased health care consumption. In France, substitution by the pharmacist is not authorized. While patient education must be carried out in collaboration with all health professionals, it is preferable that the choice of inhaler device remains the responsibility of the physician.

The importance of continuity in inhaler device choice for asthma and chronic obstructive pulmonary disease.

Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease. Physicians consider many factors when selecting the most appropriate inhaler device, including device efficacy and the cost to the health care system. This review aims to discuss the factors that are important when considering inhaler devices and the importance of continuity in the choice of inhaler device. A large number of factors can contribute to therapeutic outcomes with inhalation devices. The inhalation technique is critical to treatment success and differs substantially between inhaler devices. Misuse of an inhaler is common, and thorough training of patients and physicians is important to ensure correct utilization. Patient satisfaction is an important consideration because it is significantly correlated with compliance and better outcomes. Financial pressures contribute to decision making: although selecting the less expensive inhaler device might reduce direct treatment costs, it can have a large impact on disease control and the patient's well-being. Switching may be associated with a poor inhalation technique, reduced disease control and quality of life, increased use of other treatments and health care resources, and a greater chance of unsuccessful treatment. Nonconsensual switches can result in patient discontent, reduced confidence in the medication, and uncertainty regarding the degree of disease control. It is recommended that patients with stable disease remain on their current device. If a switch is considered, the patient should be consulted and the physician should take into account the patient's preference, their ability to correctly use the device, and the availability of the preferred drug in the preferred device.

A comparative study of two nebulizers in the emergency department: breath-actuated nebulizer and handheld nebulizer.

INTRODUCTION: The breath-actuated nebulizer (BAN) and the handheld nebulizer (HHN) are 2 nebulizers used in the ED of Cooper University Hospital. The purpose of this study was to compare the nebulizers to identify which device resulted in a resolution of symptoms with fewer treatments. The primary hypothesis was that adult ED patients with a chief complaint of wheezing and dyspnea who were given nebulized treatments via the BAN would require less nebulizer treatments than those patients given nebulized treatments via HHN. In addition, the secondary purposes of the study was to determine if the BAN would have significantly higher peak expiratory flow measurements, lower Modified Borg Score, overall decreased respiratory rate, and lower heart rates compared to subjects receiving nebulized treatments via HHN. METHODS: A single-site, prospective, randomized, comparative design study was conducted in the ED between March 2010 and February 2011. Fifty-four subjects presenting with dyspnea and wheezing and an Emergency Severity Index of 3 or 4 were enrolled and randomly assigned to 1 of 2 groups (BAN or HHN). Subjects were administered 1 to 3 nebulizer treatments (#1 ipratropium bromide and albuterol sulfate, #2 ipratropium bromide and albuterol sulfate, #3 albuterol sulfate), which was consistent with the ED Advanced Nursing Guideline for Wheezing. Nebulizer treatments were discontinued if a patient's dyspnea or wheezing resolved. IRB approval was obtained prior to study commencement. RESULTS: There was no significant difference found between the HHN and BAN in respect to number of treatments, respiratory rate, peak flow measurements, and Modified Borg scores in the 54 subjects. There was a difference of 7 points in pulse rate between the pre- and post-second BAN treatment (n = 51, P = 0.01). Subjects in the BAN group who completed all 3 treatments (n = 18) had a total treatment time that was on average of 10 minutes longer than those in the HHN group. CONCLUSIONS: This study demonstrated no clinical difference between the BAN and HHN in terms of respiratory rate, peak flow, perception of dyspnea, and number of treatments. It is possible that the longer treatment times account for the elevated pulse rate. The data suggests that the higher cost and the longer treatment time do not justify the use of the BAN in this setting. We recommend that these devices be tested with a larger sample size to further test the differences between these 2 devices.

Budesonide/formoterol via Turbuhaler® versus formoterol via Turbuhaler® in patients with moderate to severe chronic obstructive pulmonary disease: phase III multinational study results.

BACKGROUND AND OBJECTIVE: The efficacy and tolerability of budesonide/formoterol versus formoterol in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was evaluated. METHODS: In this randomized, double-blind, parallel-group, phase III study (NCT01069289), patients with moderate to severe COPD for ≥2 years received either budesonide/formoterol 160/4.5 µg two inhalations twice daily via Turbuhaler® or formoterol 4.5 µg two inhalations twice daily via Turbuhaler® for 12 weeks. Salbutamol was available as reliever medication. Primary outcome variable: change from baseline to average during treatment in pre-dose forced expiratory volume in 1 s (FEV1 ). RESULTS: One thousand two hundred ninety-three patients were randomized (budesonide/formoterol n = 636; formoterol n = 657). Both budesonide/formoterol and formoterol increased pre-dose FEV1 versus baseline (improvements of 4.6% and 1.5% over baseline, respectively), with the increase from baseline being significantly greater with budesonide/formoterol versus formoterol (budesonide/formoterol:formoterol ratio 1.032; 95% confidence interval: 1.013-1.052; P = 0.0011). The budesonide/formoterol group had a significantly prolonged time to first exacerbation versus the formoterol group (hazard ratio: 0.679; 95% confidence interval: 0.507-0.909; P = 0.0094) and significantly greater improvements in many secondary outcome measures. Both treatments were well tolerated; the incidence and type of adverse events were similar: most commonly reported (budesonide/formoterol vs formoterol): COPD (8.0% vs 9.4%) and nasopharyngitis (5.5% vs 4.9%). CONCLUSIONS: Budesonide/formoterol 160/4.5 µg two inhalations twice daily was effective and well tolerated in patients with moderate to severe COPD, offering benefits over formoterol alone in terms of improved lung function and reduced risk of exacerbation.

Advances in inhalation therapy in pediatrics.

OBJECTIVES: To review the most relevant articles regarding the technical aspects of inhalation therapy, inhalers currently available, and especially major advances in inhalation therapy in pediatrics. SOURCES: Articles of MEDLINE database from 1983 were reviewed, in addition to book chapters, and the most important studies were selected according to the criteria established for this article. SUMMARY OF THE FINDINGS: Conventional nebulizers have a number of inconveniences, and breath-enhanced and breath-actuated inhalers are more attractive options. Among dry powder inhalers, we highlight those using passive and active powder dispersion mechanisms, which provide higher rates of drug deposition in the lung. Among pressurized metered-dose inhalers, we highlight breath-actuated, breath-coordinated, and velocity-modifying inhalers. These inhalers should be used preferably together with spacers, since the use of spacers produces a twofold increase in pulmonary drug deposition. CONCLUSIONS: For children younger than 8 years, pressurized metered-dose inhalers with spacers are the most appropriate devices, since they provide a practical approach associated with greater lung deposition. In children older than 8 years who can generate high inspiratory flow rates, dry powder devices are best suited.

Avanços na inaloterapia em pediatria / Advances in inhalation therapy in pediatrics

OBJETIVOS: Revisar os artigos mais relevantes a respeito dos aspectos técnicos da terapêutica inalatória, dos inaladores disponíveis e principalmente dos principais avanços obtidos na inaloterapia em pediatria. FONTES DOS DADOS: Foram revisados os artigos contidos na base de dados MEDLINE a partir de 1983, além de capítulos de livros, e selecionados os de maior importância de acordo com os critérios estabelecidos para este artigo. SÍNTESE DOS DADOS: Os nebulizadores convencionais apresentam uma série de inconveniências, sendo que inaladores com desempenho melhorado pela respiração e os ativados pela respiração são opções mais atrativas. Dentre os inaladores de pó seco, destacam-se os que utilizam mecanismos passivos e ativos de dispersão de pó, que propiciam maiores taxas de deposição pulmonar das drogas. Entre os inaladores pressurizados dosimetrados destacam-se os ativados pela respiração, os coordenados pela respiração e os modificadores de velocidade. Devem ser usados preferencialmente em conjunto com espaçadores, pois a utilização deste aumenta em até duas vezes a deposição pulmonar das drogas. CONCLUSÕES: Para menores de 8 anos, os inaladores pressurizados dosimetrados com espaçadores são os mais adequados, dada a sua praticidade associada à elevada deposição pulmonar que proporcionam. Nos maiores de 8 anos capazes de gerar altos fluxos inspiratórios, os dispositivos de pó são os mais indicados.

OBJECTIVES: To review the most relevant articles regarding the technical aspects of inhalation therapy, inhalers currently available, and especially major advances in inhalation therapy in pediatrics. SOURCES: Articles of MEDLINE database from 1983 were reviewed, in addition to book chapters, and the most important studies were selected according to the criteria established for this article. SUMMARY OF THE FINDINGS: Conventional nebulizers have a number of inconveniences, and breath-enhanced and breath-actuated inhalers are more attractive options. Among dry powder inhalers, we highlight those using passive and active powder dispersion mechanisms, which provide higher rates of drug deposition in the lung. Among pressurized metered-dose inhalers, we highlight breath-actuated, breath-coordinated, and velocity-modifying inhalers. These inhalers should be used preferably together with spacers, since the use of spacers produces a twofold increase in pulmonary drug deposition. CONCLUSIONS: For children younger than 8 years, pressurized metered-dose inhalers with spacers are the most appropriate devices, since they provide a practical approach associated with greater lung deposition. In children older than 8 years who can generate high inspiratory flow rates, dry powder devices are best suited.

Use of ozone-depleting substances; removal of essential-use designation (flunisolide, etc.). Final rule.

The Food and Drug Administration (FDA), after consultation with the Environmental Protection Agency (EPA), is amending FDA's regulation on the use of ozone-depleting substances (ODSs) in self-pressurized containers to remove the essential-use designations for flunisolide, triamcinolone, metaproterenol, pirbuterol, albuterol and ipratropium in combination, cromolyn, and nedocromil used in oral pressurized metered-dose inhalers (MDIs). The Clean Air Act requires FDA, in consultation with the EPA, to determine whether an FDA-regulated product that releases an ODS is an essential use of the ODS. FDA has concluded that there are no substantial technical barriers to formulating flunisolide, triamcinolone, metaproterenol, pirbuterol, albuterol and ipratropium in combination, cromolyn, and nedocromil as products that do not release ODSs, and therefore they will no longer be essential uses of ODSs as of the effective dates of this rule. MDIs for these active moieties containing an ODS may not be marketed after the relevant effective date.

Schedules of controlled substances; table of excluded nonnarcotic products: nasal decongestant inhalers manufactured by Classic Pharmaceuticals, LLC. Final rule.

Under this Final Rule, the Drug Enforcement Administration (DEA) is updating the Table of Excluded Nonnarcotic Products found in 21 CFR 1308.22 to include the Nasal Decongestant Inhaler/Vapor Inhaler (containing 50 mg Levmetamfetamine) manufactured by Classic Pharmaceuticals, LLC and marketed under various private labels (to include the "Premier Value" and "Kroger" labels). This nonnarcotic drug product, which may be lawfully sold over the counter without a prescription under the Federal Food, Drug, and Cosmetic Act, is excluded from provisions of the Controlled Substances Act (CSA) pursuant to 21 U.S.C. 811(g)(1).