Nebulised Bronchodilators Research Articles

Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits.

High-flow nasal cannula (HFNC) therapy is an oxygen delivery method particularly used in patients affected by hypoxemic respiratory failure. In comparison with the conventional "low flow" oxygen delivery systems, it showed several important clinical benefits. The possibility to nebulize drugs via HFNC represents a desirable medical practice because it allows the administration of inhaled drugs, mostly bronchodilators, without the interruption or modification of the concomitant oxygen therapy. HFNC, by itself has shown to exert a small but significant bronchodilator effect and improves muco-ciliary clearance; thus, the nebulization of bronchodilators through the HFNC circuit may potentially increase their pharmacological activity. Several technical issues have been observed which include the type of the nebulizer that should be used, its position within the HFNC circuit, and the optimal gas flow rates to ensure an efficient drug delivery to the lungs both in "quiet" and "distressed" breathing patterns. The aim of this review has been to summarize the scientific evidence coming from "in vitro" studies and to discuss the results of "in vivo" studies performed in adult subjects, mainly affected by obstructive lung diseases. Most studies seem to indicate the vibrating mesh nebulizer as the most efficient type of nebulizer and suggest to place it preferentially upstream from the humidifier chamber. In a quite breathing patterns, the inhaled dose seems to increase with lower flow rates while in a "distressed" breathing pattern, the aerosol delivery is higher when gas flow was set below the patient's inspiratory flow, with a plateau effect seen when the gas flow reaches approximately 50% of the inspiratory flow. Although several studies have demonstrated that the percentage of the loaded dose nebulized via HFNC reaching the lungs is small, the bronchodilator effect of albuterol seems not to be impaired when compared to the conventional inhaled delivery methods. This is probably attributed to its pharmacological activity. Prospective and well-designed studies in different cohort of patients are needed to standardize and demonstrate the efficacy of the procedure.

Airway Care Interventions for Invasively Ventilated Critically Ill Adults—A Dutch National Survey

Airway care interventions may prevent accumulation of airway secretions and promote their evacuation, but evidence is scarce. Interventions include heated humidification, nebulization of mucolytics and/or bronchodilators, manual hyperinflation and use of mechanical insufflation-exsufflation (MI-E). Our aim is to identify current airway care practices for invasively ventilated patients in intensive care units (ICU) in the Netherlands. A self–administered web-based survey was sent to a single pre–appointed representative of all ICUs in the Netherlands. Response rate was 85% (72 ICUs). We found substantial heterogeneity in the intensity and combinations of airway care interventions used. Most (81%) ICUs reported using heated humidification as a routine prophylactic intervention. All (100%) responding ICUs used nebulized mucolytics and/or bronchodilators; however, only 43% ICUs reported nebulization as a routine prophylactic intervention. Most (81%) ICUs used manual hyperinflation, although only initiated with a clinical indication like difficult oxygenation. Few (22%) ICUs used MI-E for invasively ventilated patients. Use was always based on the indication of insufficient cough strength or as a continuation of home use. In the Netherlands, use of routine prophylactic airway care interventions is common despite evidence of no benefit. There is an urgent need for evidence of the benefit of these interventions to inform evidence-based guidelines.

Distinct lung function and bronchodilator responses between term and preterm young children with recurrent wheezing

Recurrent or unresolved wheezing is a common complaint in certain young children populations, especially those born preterm. Using infant lung function testing, we aimed to distinguish the differences between term and preterm young children with recurrent wheezing. Children under 2 years of corrected age were enrolled if they had 3 or more wheezing episodes during the enrollment period. Healthy term controls of comparable age were also recruited for reference. Measurements of lung function were made, including tidal breathing, passive respiratory mechanics, and forced tidal and raised-volume expiration. For children with recurrent wheezing, raised-volume forced expiration was repeated after an adequate delivery of bronchodilator nebulization was achieved. In total, 68 young children (40 with recurrent wheezing and 28 healthy controls) were recruited. Among children with recurrent wheezing, 23 preterm children (preterm group), and 17 term children (term group) were enrolled. Compared with healthy controls, both the term and preterm groups had lower lung function as measured by absolute values and z scores. The term group performed worse than the preterm group with regard to forced vital capacity, forced expiratory volume at 0.5s (FEV0.5), and peak expiratory flow. Following bronchodilator nebulization, the term group had significantly higher increases in FEV0.5 and forced mid-expiratory flow than the preterm group. Young children with recurrent wheezing, especially term infants, demonstrated lower lung function than healthy controls. Moreover, the term group evidenced greater responsiveness to bronchodilators than the preterm group. The distinct bronchodilator responses may offer further information to guide the diagnosis and treatment of young children with recurrent wheezing.

Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial

BackgroundAccumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients.ResultsIn this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33).ConclusionIn adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube.Trial registration Clinicaltrials.gov Identifier: NCT02159196

Bronchodilator Nebulization – A Rare Presentation of Bilateral Acute Angle Closure Glaucoma

Bronchodilator nebulization is one of the most commonly administered treatment for an acute attack of reactive airway disease. Development of acute angle closure glaucoma following nebulization therapy is a rare occurrence. We report a case of acute angle closure of both eyes in a 54 year old gentleman shortly after receiving therapy with inhaled salbutamol and ipratropium. This patient presented to our tertiary care eye hospital and was immediately treated with medical management and laser iridotomy. This case report highlights this rare but possible side effect of inhaled bronchodilator therapy. Health care providers need to be aware of this uncommon adverse effect and appropriate preventive measures such as identifying at risk individuals, usage of protective eye-wear, etc should be practiced.

Nurse-driven Clinical Pathway Based on an Innovative Asthma Score Reduces Admission Time for Children.

Objective:We recently demonstrated that an innovative asthma score independent of auscultation could accurately predict the requirement for bronchodilator nebulization compared to the physician’s routine clinical judgment to administer bronchodilators. We aimed to standardize inpatient care for children with acute asthma by implementing a clinical pathway based on this innovative asthma score.Methods:We designed a nurse-driven clinical pathway. This pathway included standardized respiratory assessments and a protocol for the nursing staff to administer bronchodilators without a specific order from the physician. We compared the length of stay and the number of readmissions to a historical cohort.Results:Seventy-nine patients with moderate acute asthma completed the pathway. We obtained a total of 858 Childhood asthma scores in these patients, with a median of 11 scores per patient (interquartile range 8–17). Patients treated according to the nurse-driven protocol were 3.3 times more likely to be discharged earlier (hazard ratio, 3.29; 95% confidence interval, 2.33–4.66; P < 0.05), and length of stay was significantly reduced (median 28 versus 53 h) compared to the historical standard practice. On request, the attending physician assessed the patient’s respiratory status 42 times (4.9% of all childhood asthma score assessments). Patient safety was not compromised, and none of the patients were removed from the pathway. In each group, we readmitted two (2.5%) patients within 1 week after discharge.Conclusion:This nurse-driven clinical pathway for children with acute asthma based on an asthma score independent of auscultation findings significantly decreased length of stay without compromising patient safety.

Nasal high-flow bronchodilator nebulization: a randomized cross-over study

BackgroundThere is an absence of controlled clinical data showing bronchodilation effectiveness after nebulization via nasal high-flow therapy circuits.ResultsTwenty-five patients with reversible airflow obstruction received, in a randomized order: (1) 2.5 mg albuterol delivered via a jet nebulizer with a facial mask; (2) 2.5 mg albuterol delivered via a vibrating mesh nebulizer placed downstream of a nasal high-flow humidification chamber (30 L/min and 37 °C); and (3) nasal high-flow therapy without nebulization. All three conditions induced significant individual increases in forced expiratory volume in one second (FEV1) compared to baseline. The median change was similar after facial mask nebulization [+ 350 mL (+ 180; + 550); + 18% (+ 8; + 30)] and nasal high flow with nebulization [+ 330 mL (+ 140; + 390); + 16% (+ 5; + 24)], p = 0.11. However, it was significantly lower after nasal high-flow therapy without nebulization [+ 50 mL (− 10; + 220); + 3% (− 1; + 8)], p = 0.0009. FEV1 increases after facial mask and nasal high-flow nebulization as well as residual volume decreases were well correlated (p < 0.0001 and p = 0.01). Both techniques showed good agreement in terms of airflow obstruction reversibility (kappa 0.60).ConclusionAlbuterol vibrating mesh nebulization within a nasal high-flow circuit induces similar bronchodilation to standard facial mask jet nebulization. Beyond pharmacological bronchodilation, nasal high flow by itself may induce small but significant bronchodilation.

Assessment of the Respiratory Tract Distribution of Fluorescein by Nebulization in Rats (Rattus norvegicus)

Most pet rats have chronic respiratory disease, and end-stage complications are frequently fatal. Drug aerosol delivery in the form of nebulization of antibiotics, expectorants, and bronchodilators is often used as part of their treatment. As rats are obligate nasal breathers, aerosol delivery must be achieved by nasal inhalation, which has the anatomical limitation of a narrower airway lumen. In humans, aerosol delivery of many respiratory drugs is achieved by oral inhalation as it allows administration of very small particles with a concentration loss of only 20% in comparison with 85% by the nasal route. The aim of this pilot study was to determine whether a nebulized fluorescein solution would reach the lungs of rats as no data exists. Ten healthy 13-week-old female Sprague-Dawley rats were nebulized continuously for 15 minutes. The rats were euthanized, and a full postmortem examination was performed. The respiratory tract was sampled, fast-frozen in liquid nitrogen and preserved at −20 °C. Slides were examined with a fluorescence microscope to determine the distribution of fluorescein in the respiratory tract. Fluorescence was observed in the entire respiratory tract of all the nebulized rats, showing that nebulization is an efficient way to deliver medication directly into the alveoli.

Whole-lung lavage complicated with pneumothorax: a case report.

A patient with pulmonary alveolar proteinosis underwent whole lung lavage of the right lung. Lavage of the left lung was not immediately possible because of severe hypoxemia. Three days later, after correction of hypoxemia, we re-attempted the left lung lavage. However, the patient had severe hypoxemia (SpO2 < 80%) within a few minutes of performing right one lung ventilation (OLV). On bronchoscopic examination, proper tube location was confirmed. Bronchodilator nebulization and steroid injection were attempted with no effect. While searching for the cause of the hypoxemia, we found that the breath sound from the right lung had become very weak and distant compared with that from initial auscultation. Right pneumothorax was diagnosed on chest X-ray and a chest tube was inserted. After confirming pneumothorax resolution, we re-tried right OLV and were able to proceed with the left lung lavage without signs of aggravating air leak, loss of tidal volume, or severe hypoxemia.

Nebulized magnesium for moderate and severe pediatric asthma: A randomized trial

SummaryBackgroundIntravenous magnesium sulfate, a rescue therapy added to bronchodilator and systemic steroid therapy for moderate and severe asthma, is uncommonly administered. We hypothesized that nebulized magnesium would confer benefit without undue risk.Design and MethodsPatients aged 2 to 14 y with moderate and severe asthma (PRAM severity score ≥4) admitted to infirmary/observation unit care were randomized double‐blind on admission to receive 800 mg nebulized magnesium or normal saline placebo after all received intensive therapy with combined nebulized albuterol–ipratropium and intravenous methylprednisolone. Time to medical readiness for discharge was the primary outcome; sample size was chosen to detect a 15% absolute improvement. Improvement over time in PRAM severity score and other secondary outcomes were compared for the overall group and severe asthma subset.ResultsOne hundred and ninety‐one magnesium sulfates and 174 placebo patients met criteria for analysis. The groups were similar with mean baseline PRAM scores >7. Blinded active therapy significantly increased blood magnesium level 2 hr post‐treatment completion compared to placebo, 0.85 vs 0.82 mmol/L, P = 0.001. There were no important adverse effects. Accelerated failure time analysis showed a non‐significantly shortened time to medical readiness for discharge of 14% favoring the magnesium sulfate group, OR = 1.14, 95% CI 0.93 to 1.40, P = 0.20. Mean times until readiness for discharge were 14.7 hr [SD 9.7] versuss 15.6 hr [SD 11.3] for the investigational and placebo groups, respectively, P = 0.41.ConclusionsAdding nebulized magnesium to combined nebulized bronchodilator and systemic steroid therapy failed to significantly shorten time to discharge of pediatric patients with moderate or severe asthma. Pediatr Pulmonol. 2015; 50:1191–1199. © 2015 Wiley Periodicals, Inc.

O-203a Inhaled Magnesium For Moderate And Severe Paediatric Asthma

Background Intravenous magnesium sulfate, a rescue therapy added to combined bronchodilator and systemic steroid therapy for moderate and severe asthma, is uncommonly administered. We hypothesised that nebulized magnesium sulfate would confer benefit without undue risk. Methods Patients aged 2 to 14 y with moderate and severe status asthmaticus (PRAM severity score >4) admitted to infirmary care were randomised double-blind to 800 mg nebulized magnesium sulfate or normal saline placebo via Aeroneb Pro and Idehaler, after intensive therapy with combined albuterol-ipratropium and intravenous methylprednisolone. Time to medical readiness for discharge was the primary outcome; sample size was chosen to detect a 10% improvement. Improvement over time in PRAM severity score and other secondary outcomes were compared for the overall group and severe asthma subset. Results 191 magnesium sulfate and 174 placebo patients met criteria for analysis. The groups were similar with mean baseline PRAM scores >7. Blinded active therapy significantly increased blood magnesium level 2 h post-treatment 0.85 (SD 0.07) vs 0.82 (SD 0.06) mmol/L, p = 0.001). There were no important adverse effects. However, accelerated failure time analysis showed a non-significantly shortened time to medical readiness for discharge of 14% favouring the magnesium sulfate group, OR=1.14, 95% CI 0.93 to 1.40, p = 0.20. Mean times until readiness for discharge were 14.6 h [SD 9.7] vs 15.6 h [SD 11.3] for the investigational and placebo groups, respectively, p = 0.9. Conclusions Adding nebulized magnesium sulfate to combined nebulized bronchodilator and systemic steroid therapy fails to provide evident benefit for patients with moderate or severe status asthamticus.

PO-0277 Review Of The Management And Outcome For Patients Treated For Wheeze In A Tertiary Paediatric Emergency Department (ped)

Background and aims To review the management of patients who were treated for wheeze in the PED and compare them to those in the British Thoracic Society (BTS) Guidelines. Methods Reviewed PED flimsy of those patients over 2 who were treated for wheeze in PED in March. Results Number of patients 46. 93% received bronchodilators while 7% were given Prednisolone only. 65% were given maximum nebulised bronchodilator therapy (x3 sets). 89% received steroids and 2% received IV medication. 41% received antibiotics in ED and 50% had a chest x-ray performed. Of those discharged (n = 32), 75% were discharged within 4 h. 31% patients were discharged within 1 h of last bronchodilator and a further 41% within 2 h. Of those treated with maximum nebulised bronchodilators (n = 30), 43% were admitted, 23% discharged within 1 h post last bronchodilator and a further 27% within 2 h. 8% re-attended within 48 h -4% due to elevated temperature, 2% were uncertain with inhaler technique and 2% due to increase in symptoms. No patient had documented evidence of written asthma management plan given or to attend primary care for review within next 48 hrs. Conclusions The low re-attendance rate is supportive that those attending received good clinical care and in a timely manner, with 75% of patients being discharged within the 4 h target. However, education is required to ensure patients stay 3–4 h post last bronchodilator and the need for documented discharge advice. Education is also required on the use of chest x-rays and antibiotics.

Randomised controlled crossover trial of the effect on Ptco2 of oxygen-driven versus air-driven nebulisers in severe chronic obstructive pulmonary disease

BackgroundThe comparative safety of oxygen versus air-driven nebulised bronchodilators in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain. A randomised controlled trial was performed to assess...

Heliox and Forward-Leaning Posture Improve the Efficacy of Nebulized Bronchodilator in Acute Asthma: A Randomized Trial

Heliox and forward-leaning posture (torso inclined forward at 50-60° with the elbows resting on the thighs) are adjuncts in the administration of nebulized bronchodilator to patients with acute asthma. We randomized 59 patients who presented to the emergency department in severe asthma crisis, into 4 treatment groups: nebulized bronchodilator + oxygen; nebulized bronchodilator + oxygen + forward-leaning posture; nebulized bronchodilator + heliox; and nebulized bronchodilator + heliox + forward-leaning posture. Before and after the bronchodilator treatments the subjects were seated with torso erect, breathing room air. Each subject received 2 doses, 20 min apart, of nebulized fenoterol (2.5 mg) plus ipratropium bromide (0.25 mg) in 3 mL of 0.9% saline, delivered with a semi-closed valved aerosol reservoir. The nebulizer was run with oxygen or 80:20 heliox. The post-treatment pulmonary function tests were performed 15 min after the second nebulization. The group's mean age was 35.1 ± 13.6 y, and there were 20 men and 39 women. The oxygen + forward-leaning-posture group had a greater FEV(1) improvement than the oxygen group (59% vs 38%, P = .02). The heliox + forward-leaning-posture group had a greater FEV(1) improvement than the oxygen group (103% vs 38%, P = .001) and the heliox group (103% vs 42%, P = .03). The heliox group had greater reduction in respiratory rate than the oxygen group (P = .03). The heliox + forward-leaning-posture group had significantly greater peak expiratory flow improvement than any of the other groups. Heliox plus forward-leaning posture during bronchodilator nebulization improves bronchodilator efficacy in patients with severe acute asthma. (ClinicalTrials.gov registration NCT00922350).

The Patient with Asthma in the Emergency Department

Asthma is a highly prevalent disease that presents commonly to the emergency department (ED) in acute exacerbation. Recent asthma treatment guidelines have added content dedicated to the management of acute exacerbations. Effective management of an exacerbation requires rapid assessment of severity through physical examination, measurement of peak expiratory flow rate, and response to initial treatment. Most therapies are directed at alleviating bronchospasm and decreasing airway inflammation. While inhaled short-acting beta-agonists, systemic corticosteroids, and supplemental oxygen are the initial and often only therapies required for patients with mild moderate exacerbations, high-dose beta agonists and inhaled anti-cholinergics should also be given to patients with severe exacerbations. Adjunctive therapy with intravenous magnesium and Heliox-driven nebulization of bronchodilators should be considered for patients presenting with severe and very severe exacerbations. Early recognition and appropriate management of respiratory failure are required to mitigate the risk of complications including death. Disposition should be determined based on serial assessments of the response to therapy over the first 4 h in the ED. Patients stable for discharge should receive medications, asthma education including a written asthma action plan, and should have follow-up scheduled for them by ED staff. Rapid implementation of evidence-based, multi-disciplinary care is required to ensure the best possible outcomes for this potentially treatable disease.

Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand. A position statement from the Thoracic Society of Australia and New Zealand and the Australian Lung Foundation

• Consensus recommendations for managing chronic suppurative lung disease (CSLD) and bronchiectasis, based on systematic reviews, were developed for Australian and New Zealand children and adults during a multidisciplinary workshop. • The diagnosis of bronchiectasis requires a high-resolution computed tomography scan ofthe chest. People with symptoms of bronchiectasis, but non-diagnostic scans, have CSLD, which may progress to radiological bronchiectasis. • CSLD/bronchiectasis is suspected when chronic wet cough persists beyond 8 weeks. Initial assessment requires specialist expertise. Specialist referral is also required for children who have either two or more episodes of chronic (> 4 weeks) wet cough per year that respond to antibiotics, or chest radiographic abnormalities persisting for at least 6 weeks after appropriate therapy. • Intensive treatment seeks to improve symptom control, reduce frequency of acute pulmonary exacerbations, preserve lung function, and maintain a good quality of life. • Antibiotic selection for acute infective episodes is based on results of lower airway culture, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients whose condition does not respond promptly or adequately to oral antibiotics are hospitalised for more intensive treatments, including intravenous antibiotics. • Ongoing treatment requires regular and coordinated primary health care and specialist review, including monitoring for complications and comorbidities. • Chest physiotherapy and regular exercise should be encouraged, nutrition optimised, environmental pollutants (including tobacco smoke) avoided, and vaccines administered according to national immunisation schedules. • Individualised long-term use of oral or nebulised antibiotics, corticosteroids, bronchodilators and mucoactive agents may provide a benefit, but are not recommended routinely.

Nebuliser solution bottle cap presenting as a foreign body in the subglottic airway

To the Editor: A 58-yr-old obese male with obstructive sleep apnoea and asthma, for which he used nebulised bronchodilators, presented with a 4-month history of wheeze and stridor on both inspiration and expiration. There was a small amount of fresh haemoptysis if he coughed vigorously. A plain chest radiograph was normal. The patient was treated for an exacerbation of asthma but there was little improvement in his symptoms. A computed tomography scan was performed and a tracheal foreign body shaped like a fish bone was …

Hospital-at-home care for exacerbations of chronic obstructive pulmonary disease: an observational cohort study of patients managed in hospital or by nurse practitioners in the community

The Urgent Care Team (UCT) in Sunderland (pop. 293,000) is a unique nurse practitioner service operating a hospital at home 24/7/365 to deal promptly with patients suffering an exacerbation of their COPD (AECOPD). Treatment is according to patient group directions utilising nebulised bronchodilators, doxycycline and prednisolone. To compare the health status and pathophysiology during and two months after an AECOPD in 60 UCT patients (31 male) and 30 hospital-managed patients (16 male). The St. Georges Respiratory Questionnaire (SGRQ), Mahler Baseline Dyspnoea Index (BDI) and MRC dyspnoea score recorded health status. Spirometry, BMI and grip strength were also measured. All patients were reviewed 2-3 months after the AECOPD. Changes from BDI were measured using the Transitional Dyspnoea Index (TDI). Mean FEV1% predicted was 47%. In the recovery phase the two groups were comparable for all variables. But during their AECOPD hospitalised patients had a significantly lower BDI (P < 0.05) and an oxygen saturation ranging from 84 to 93% compared with 87-96% for UCT patients. Paired t-tests indicated that on recovery SGRQ activity domain and TDI measures improved in both groups. No deaths occurred during these AECOPDs. A hospital-at-home scheme for AECOPDs can deal with patients who have severe COPD safely. The Mahler TDI appears to be a sensitive index of improvement after an AECOPD.

Efficacy and safety of formoterol fumarate delivered by nebulization to COPD patients

Nebulized solutions of long-acting bronchodilators provide an alternative to DPI and MDI delivery, particularly for COPD patients unable to use hand-held devices easily or correctly. The long-acting beta2-agonist, formoterol fumarate, is differentiated by its onset of significant bronchodilation within 5 min of administration. In a randomized, double-blind, double-dummy trial, COPD subjects (n=351, mean forced expiratory volume FEV1=1.3 L, 44% predicted) received nebulized formoterol fumarate (Perforomist inhalation solution; FFIS 20 microg) or DPI (Foradil Aerolizer; FA 12 microg), or placebo twice daily for 12 weeks. Efficacy was assessed with 12-h pulmonary function tests, and quality of life was assessed before and after treatment with the St. George's Respiratory Questionnaire (SGRQ). At the 12-week endpoint, FFIS significantly increased FEV1 AUC0-12h relative to placebo (p<0.0001). No evidence of tachyphylaxis was observed as indicated by maintained FEV1 AUC and reduced rescue albuterol use throughout treatment. FFIS also significantly increased peak FEV1, trough FEV1, and standardized FVC AUC0-12h compared with placebo. SGRQ assessment at Week 12 demonstrated significant and clinically meaningful improvements in total score (FFIS vs placebo, -4.9, p=0.0067), symptom, and impact scores. No significant differences in efficacy were observed between the two active treatments. Drug related AEs in the FFIS arm with a frequency > or = 1% and exceeding placebo were dry mouth, nausea, and insomnia. Nebulized FFIS provided significant improvement in respiratory status and quality of life in subjects with COPD relative to placebo and was well tolerated. The efficacy and safety profile of FFIS was comparable to FA DPI.

Spontaneous pneumomediastinum caused by nebulization of bronchodilators in a young child

Summary We describe a young girl presenting with fever, cough, and respiratory distress. Shortly after resisting nebulization of bronchodilators she developed a spontaneous pneumomediastinum and subcutaneous emphysema.