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Small airway disease is recognized as a cardinal pathological process of chronic obstructive pulmonary disease (COPD), and recently small airways have been recognized as a major site of airflow obstruction also in asthmatic patients. The transversal involvement of small airways in COPD and asthma has warranted research efforts to identify therapeutic strategies able to unlock the small airway compartment. The mainstay of COPD treatment is represented by long-acting β2-adrenoceptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs). In asthma, the efficacy of LAMAs administered add-on to inhaled corticosteroids (ICSs) or ICS/LABA combinations has been investigated only in recent years. The aim of this systematic review was to examine the current literature concerning the impact of LAMAs on small airways and their lung deposition in both COPD and asthma. LAMAs administered either alone or in combination induced an effective bronchorelaxant effect of small airways, however the effectiveness of respiratory medications not only relies on the selected drug, but also on the employed inhalation device and patient's adherence. Tiotropium delivered via Respimat® SMI achieved a superior drug deposition in the peripheral lung compared to HandiHaler® dry powder inhaler and metered-dose inhalers (MDIs). The use of co-suspension™ delivery technology for MDIs and the introduction of the eFlow® nebulizer to deliver glycopyrronium improved aerosol drug delivery to the peripheral lung, by achieving uniform distribution of drug particles. This systematic review provides a synthesis of current literature concerning the impact of LAMAs on small airways and an insight on LAMAs distribution within the lung.

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 ± 3.38% and 12.05 ± 2.96%, respectively) than JN (12.51 ± 6.31% and 3.14 ± 1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ± 1.3% versus 46.44 ± 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.

Awareness of the risk of airborne transmission of SARS-CoV-2 makes patients hesitant about using inhaled medications that are considered as a potential source of viral transmission and immunosuppression. However, patients with asthma or COPD should continue all prescribed inhaled medications. Apparently, inhalers, including pMDIs, DPIs, or SMIs, have a low risk of contamination although characteristics of drug formulation can precipitate cough, whereas some researchers do not rule out the probability that nebulizer treatments may increase the risk of infection transmission via droplet nuclei and aerosols. Considering that aerosol therapy generates fugitive emissions that are not inhaled by the patient and are released from the device during expiration, several international professional bodies have provided recommendations for drug delivery via inhalers and in particular, nebulizers. Unfortunately, these recommendations are often in conflict with each other and do not clarify whether it is appropriate to use nebulizers during this COVID-19 pandemic. Considering what is available in literature, there are no known infection-related hazards to an uninfected patient and also a patient with COVID-19 that preclude the use of a nebulizer at home, but it fundamental that all patients, regardless of whether or not suffering from COVID-19, always follow some practical advices., Highlights • Droplets or aerosols predominate in the transmission of SARS-CoV-2. • Established treatments for both asthma and COPD are generally administered by inhalation. • There are no known infection-related hazards that preclude the use of a nebulizer at home. • All patients must always follow some practical advices.

Item does not contain fulltext BACKGROUND: In chronic obstructive pulmonary disease (COPD) the clinical efficacy of bronchodilator therapy delivered via a nebulizer versus an aerochamber on FEV1 is controversial. No studies comparing changes in inspiratory pulmonary function parameters (ILPs) using these inhaler devices are currently available. This information might be of interest because due to dynamic bronchial compression, the relationship between the ILPs and dyspnea is more reliable than that between FEV1 and dyspnea. Therefore, our study aimed to investigate whether changes in ILPs after use of these inhaler devices were similar to the changes in FEV1 and correlate with VAS (Visual Analogue Scale). METHODS: Forty-one stable COPD patients participated in a crossover trial. Spirometry was performed before and after two puffs Combivent (200 mcg salbutamol and 20 mcg ipratropium per puff) using an aerochamber or 2 mL of Combivent (2.5 mg salbutamol and 250 mcg ipratropium per mL) using a nebulizer. Differences in lung function parameters and changes in VAS were measured. RESULTS: ILP values improved significantly from baseline after Combivent administration using both devices (p

Summary Background The methacholine challenge test performed with the tidal breathing method induces a greater fall in FEV 1 than the dosimeter method; however, the effect of the challenge method on methacholine-induced fall in FVC has not been investigated. Objective To determine the influence of the challenge method on methacholine-induced changes in FEV 1 and FVC. Methods Airway responsiveness to methacholine was determined by dosimeter method and tidal breathing method in 37 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method and the same nebulizer model was used for the two challenges. The response was expressed by the provocative concentration of methacholine causing a 20% fall in FEV 1 (PC 20 ) and by the percent fall in FVC at the PC 20 value relative to FVC after saline inhalation. Results The PC 20 values obtained with the tidal breathing method and the dosimeter method were similar, with geometric mean values of 3.15 (95%CI, 1.85–5.34 mg/mL) and 2.51 (1.37–4.61 mg/mL, P = 0.092), respectively. The percent fall in FVC at the PC 20 value obtained with the dosimeter was significantly greater than that obtained with the tidal breathing method, with mean values of 11.8 (95%CI, 10.0–13.5%) and 9.4 (95%CI, 8.1–10.8, P = 0.002), respectively. Conclusions Differences in methacholine PC 20 values obtained with the two challenge methods recommended in guidelines may be overcome by introducing some technical modifications in the dosimeter method. However, the technical factors that affect methacholine sensitivity and air trapping are at least partially different.

Summary COPD is a common disease which is increasing in prevalence. The proportion of patients who vary their inhaler use from what is prescribed and the reasons for variance are largely unknown. The objective of this study was to determine the extent of and reported reasons for patient-reported variance in the use of inhalers prescribed for COPD. A 17-item survey was mailed to 600 ambulatory patients with spirometry-defined COPD. The survey included questions about inhaler use and reasons for using inhalers differently than prescribed. Survey responses were compared between patients reporting no variance vs. variance from prescribed instructions. Logistic regression was used to determine predictors for variance. The response rate was 45.8% (48.7% male; mean age: 73 ± 8 years). Forty percent of respondents were not using inhalers as prescribed. The most common reasons were: feeling the inhalers did not help breathing (20%), forgetting to use inhalers (19%) and cost (15%). Higher education level, home oxygen use and prescriptions for ipratropium were predictors for inhaler variance. The impact of inhaler variance on morbidity of COPD should be evaluated.

Summary Methacholine testing is an important diagnostic tool for asthma. Newly available dosimeter and software technology allows for simplification of the test. This study aimed to evaluate a single-concentration dosimeter protocol for methacholine testing by comparison with a multi-concentration dosimeter protocol similar to that recommended by the American Thoracic Society (ATS) (standard protocol). Fifty young subjects with high pretest probability for bronchial hyperresponsiveness underwent two challenges in randomized order within one week. The novel protocol used a Medic-Aid Sidestream nebulizer and a fixed methacholine concentration of 16mg/mL. Number and duration of nebulizations were matched to the last four doses of the standard protocol, and results were expressed cumulatively. The rank correlation between log slopes ( n =50) was 0.86; that between log provocative doses ( n =18), which differed at low values, was 0.58. When requiring a 20% fall in FEV 1 at any methacholine dose, 18 subjects were hyperresponsive and 28 normoresponsive in both tests (46/50 concordant). One subject was positive only with the standard, and 3 only with the novel protocol (Cohen's kappa 83%). The novel protocol for methacholine testing yielded qualitative results similar to those of the ATS multi-concentration protocol, although there were quantitative differences at low doses. However, its design and handling may offer advantages for clinical practice.

Summary Background Salbutamol, the most widely used short-acting β 2 -agonist, consists of a racemic mixture of equal amounts of two enantiomers, (R)-salbutamol and (S)-salbutamol. The bronchodilator effects of salbutamol are attributed entirely to (R)-salbutamol (levosalbutamol), while (S)-salbutamol has been shown to possess bronchospastic and pro-inflammatory effects both in vitro and in vivo studies. Levosalbutamol, the (R)-enantiomer of salbutamol is currently available only in a liquid formulation for use via a nebulizer. Recently, levosalbutamol to be administered via a pressurized metered dose inhaler (pMDI) has been developed. Aims To compare the time-dependent bronchodilator responses of single doses of 100mcg levosalbutamol and 200mcg racemic salbutamol administered via a pMDI in subjects with stable mild-to-moderate bronchial asthma over a period of 6h. Methods Single doses of 100mcg levosalbutamol, 200mcg salbutamol and placebo were administered with a pMDI in 30 stable asthmatic subjects in a randomized, double-blind, placebo-controlled, three-way cross over study. Forced expiratory volume in 1s (FEV 1 ) and forced vital capacity (FVC) were measured at baseline, and over 6h post-study drug administration. Results Levosalbutamol and salbutamol produced significantly better bronchodilator responses than placebo. Both the drugs showed equivalent time-dependent bronchodilator responses as measured by area under curve for percent change in FEV 1 and FVC over 6h. The time to onset of action, mean maximum bronchodilator response and duration of bronchodilator response were similar between levosalbutamol and salbutamol. Conclusion A single dose of 100mcg levosalbutamol administered by a pMDI produced a similar bronchodilator response as salbutamol when measured over 6h in subjects with stable, mild-tomoderate bronchial asthma.

Summary Nebulization associated with noninvasive ventilation is used in emergency services and intensive care units. Purposes To compare pulmonary radioaerosol deposition during jet nebulization associated to noninvasive ventilation versus spontaneous breathing nebulization; to measure the rate of lung depuration and the correlation between lung deposition, inspiratory flow and tidal volume (Vt) using scintigraphy. Subjects Thirteen healthy volunteers (with normal spirometry), mean age (23.3±1.49) years, body mass index 21.2±2.3 kg/m2. Methods Nebulization was performed in spontaneous breathing and associated with bi-level noninvasive ventilation (inspiratory pressure=12 cm H2O, expiratory pressure=5 cm H2O). The radioaerosol used in the nebulization was technetium (Tc99m) with diethylene triamine penta acetic acid, generated over a period of 9 min in a jet nebulizer. Analysis was performed through scintigraphy. Statistical analysis was performed by analysis of variance (for repeated measures), Bonferroni method, Student's t-test and Person's correlation. Results There was a decrease in radioaerosol lung deposition with nebulization associated to noninvasive ventilation (mean counts in spontaneous breathing 200,510+11,012 and mean counts in noninvasive ventilation 106,093+2811 ( P 0.001 ). During spontaneous breathing nebulization there was a significant correlation between Vt and radioaerosol deposition ( r = 0.565 , P 0.05 ), also between inspiratory flow and radioaerosol deposition in the lungs ( r = 0.141 , P 0.05 ). However, there was no correlation between Vt and pulmonary deposition of radioaerosol in bi-level noninvasive ventilation nebulization ( r = 0.082 ). Conclusion During nebulization with noninvasive ventilation in healthy volunteers, there was an increase in Vt associated to a higher inspiratory flow rate, without resulting in a significant increase in pulmonary radioaerosol deposition.

Pharmacokinetic properties of a drug, and selection and correct usage of an appropriate delivery device, are factors that can affect the outcome of inhaled therapyThe use of nebulization can overcome problems that are associated with other delivery systems used for inhalation therapyThe objective of this open, randomized, single-dose study was to compare the systemic exposure and safety of beclometasone dipropionate (BDP) suspension for nebulization with BDP via metered-dose inhaler (MDI) in healthy subjects. Following a run-in period to assess basal 24-h serum cortisol levels and cortisol urinary excretion, 12 healthy males were administered BDP 1,600 microg given via MDI and were then randomized to receive a single dose of either 1,600 microg (n = 6) or 3,200 microg BDP (n = 6) suspension for nebulization given via a nebulizer Results with respect to systemic exposure to beclometasone-17-monopropionate (B17MP) (the active metabolite of BDP) and systemic effects on the hypothalamic-pituitary-adrenal (HPA) axis were determined by evaluation of a number of pharmacokinetic parameters for plasma B17MP and serum and urinary cortisol, respectively. A statistically significantly greater peak plasma concentration (Cmax) of B17MP was reported with BDP via MDI (1,587 pg ml(-1)) compared with BDP 1,600 microg (455 pg ml(-1)) and BDP 3,200 microg suspensions for nebulization (758 pg ml(-1)), and was achieved more rapidly (Tmax) (1.3 h, 3 h, and 2.5 h, respectively). In addition, elimination half-life (t 1/2(el)) was statistically significantly shorter with BDP via MDI (4.6 h) than with both dosages of BDP suspensions for nebulization (7.4 h and 6.3 h with 1600 microg and 3,200 microg, respectively), as was mean residence time (MRT) (5.4 h, 11.1 h, and 10.0 h, respectively). Total systemic exposure to B17MP (as determined by the area under the concentration-time curve: AUCinfinity) was comparable for BDP via MDI (6,883 pg ml(-1) h(-1)) and BDP 3,200 microg suspension for nebulization (8,201 pg ml(-1) h(-1)), but significantly greater than with BDP 1,600 microg suspension for nebulization (4,870 pg ml(-1); P < 0.05 vs BDP via MDI). All treatments were well tolerated, and no significant differences were found between them with respect to the serum or urinary cortisol pharmacokinetic parameters assessed. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3,200 microg given via a nebulizer and BDP 1,600 microg given via an MDI are equivalent in terms of systemic exposure to B17MP and systemic effects on the HPA axis, with BDP suspension for nebulization having a potentially more prolonged activity. It confirms that use of a double dose of BDP suspension for nebulization administered by nebulizer compared with BDP given via metered-dose inhalation is justified and poses no risk with regard to safety.

Nebulization simplifies the administration of effective inhaled medications to young asthmatics who experience hand-to-lung co-ordination problems and inspiratory difficulties associated with metered-dose and dry-powder inhalers, respectively. The objective of this double-blind, double-dummy multicentre, randomized, parallel-group study was to compare the efficacy and safety of corticosteroids given by nebulization or metered-dose inhalation in paediatric patients with exacerbation of asthma. Following a 24-h run-in period, 151 patients, aged 6-16years, with moderate to severe exacerbation of asthma were randomized to one of two treatment groups for 4 weeks: beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. given via a nebulizer (n = 75), or BDP spray 800 microg day(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 76). Superimposable and statistically significant improvements over baseline were noted at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, asthma symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was the morning pulmonary expiratory flow rate (PEFR). In the BDP nebulization group, mean morning PEFR increased statistically significantly from 233.2 +/- 86.31 min(-1) to 322.0 +/- 101.81 min(-1), while in the BDP MDI group the increase was from 222.9 +/- 87.31 min(-1) to 314.9 +/- 96.61 min(-1). Moreover, an additional 4-week treatment period at half doses, completed by 26 patients, demonstrated that improvements were maintained or further enhanced. The two treatments were equally well tolerated. A total of 25 and 26 patients in the BDP nebulization and BDP MDI groups, respectively reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 1,600 microg day(-1) given via a nebulizer and BDP spray 800 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in paediatric patients with moderate to severe asthma exacerbation.

The difficulty of assessing nebulizer responses in chronic obstructive pulmonary disease (COPD) has been demonstrated before. This study aims to re-examine both the role of domiciliary nebulizers in COPD and also bronchodilator (BD) assessment in individuals. In a double-blind, randomized, cross-over trial, 19 stable patients with severe COPD were given the following medication 6-hourly for 2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer (but no placebo nebulized drugs). Both nebulized and MDI drugs produced highly significant improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual volume. There were no significant differences between BD responses obtained after active nebulized and active MDI BDs. From the diary cards, 2 weeks of active nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less extra inhaler use (0.8 and 1.1 puffs, respectively, P

β2-agonists have questionable symptomatic effect in infants with acute bronchiolitis, whereas inhaled, nebulized racemic adrenaline, commonly used in Norway, appears (clinically) to be effective. Limited lung function observations during acute bronchiolitis exists, and less for assessing possible effects inhaled adrenaline.In this preliminary study, tidal flow-volume loops were measured in 16 infants with acute bronchiolitis and seven healthy controls (mean age 7·9 and 4·4 months, respectively), with repeated measurements 15 min after inhaled nebulized racemic adrenaline (4 mg diluted in 2 ml saline) in nine bronchiolitis patients.The ratio of time to reach peak tidal expiratory flow to total expiratory time (tPTEF/tE) was significantly reduced in children with acute bronchiolitis (mean, 95% CI) (0·08, 0·05–0·10) compared to controls (0·31, 0·18–0·43), with significant improvement after inhaled racemic adrenaline 0·19 (0·13–0·25), parallel with significant clinical improvement.Lung function (tPTEF/tE) was reduced in infants with acute bronchiolitis and improved significantly after inhaled racemic adrenaline. Inhaled racemic adrenaline is potentially an important alternative for treating infants with acute bronchiolitis.

The output of a nebulizer is generally defined as its weight loss during 1 min of nebulization. This mass output includes the weight loss due to evaporation of the solution required to moisten the dry air that is fed through the nebulizer. In order to compare results obtained from studies using different nebulizers we introduce the salt output as the amount of the solution that actually leaves the liquid phase as droplets and not by evaporation. The performance characteristics of a standard jet nebulizer (MA2) and a Sidestream jet neublizer were compared. Mass output was determined at different methacholine concentrations. Salt output was assessed by analysing the remaining salt in the nebulizers after 1 min of nebulization. Overall system performance in terms of forced expiratory volume in 1 sec (FEV 1 ) reduction after 1 min of exposure to individually selected concentrations of methacholine were studied in 15 healthy, non-smoking subjects. Both nebulizer types showed a moderate linear increase of mass output with methacholine concentration. The efficiency coefficient, the quotient between salt output and mass output, was found to be 0·93 and 0·75 for the MA2 and Sidestream nebulizer respectively. These findings were explained by differences in airflow through, and temperature inside, the nebulizers. The salt output of the nebulizers proved to be better correlated to the FEV 1 -reduction following methacholine inhalation than did the mass output. The relative amount of the salt output that adhered to the acrylic walls of the Sidestream nebulizer drying tower was found to be 9%. We conclude that it is more appropriate to use salt output than mass output as a nebulizer performance descriptor. The study also shows the importance of determining nebulizer system performance under conditions as similar to true provocations as possible.

Nebulization therapy is an approach for the treatment of respiratory diseases such as asthma which was not anticipated in the international recommendations for the treatment of asthma and which merits study. Even if the place of nebulizers in the treatment of asthma exacerbations has been validated, this is not the case for adult asthmatic subjects with chronic asthma. While asthma control for most patients can be achieved using metered-dose inhaler and dry powder inhaler therapy, some patients may require regular home nebulized therapy.Before determining the objectives and therapeutic characteristics of nebulization in the treatment of chronic asthma in the adult patient, we shall first describe the pathophysiological elements involved in the treatment of asthma and of the couple ‘nebulized substance-nebulizer’ leading to an optimal nebulization.

The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients. A consistent trend showed the nebulizer treatment to be at least as efficient as the pMDI plus spacer treatment. In actual fact, the apparent order of effect was: 4 mg nebulized suspension treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with spacer treatment. Plasma budesonide and plasma cortisol also exhibited dose-related levels independent of device. The adverse effects reported appeared to be related to the dose rather than delivery device. Accordingly, the effect was related to total mass output, rather than to the small particle fraction of the budesonide aerosol. These results attest to the efficiency of jet-nebulized budesonide suspension, and indicate nebulized budesonide to be equipotent to standard budesonide therapy delivered by pMDI with Nebuhaler, provided nebulization is synchronized with inspiration and no loss of aerosol occurs during expiration.

SummaryBackgroundIn asthma management, poor handling of inhalation devices and wrong inhalation technique are associated with decreased medication delivery and poor disease control. The key to overcome the drawbacks in inhalation technique is to make patients familiar with issues related to correct use and performance of these medical devices. The objective of this study was to evaluate and analyse technique of use of the inhalation device used by patients of COPD and Bronchial Asthma.MethodsA total of 300 cases of BA or COPD patients using different types of inhalation devices were included in this observational study. Data were captured using a proforma and were analysed using SPSS version 15.0.ResultOut of total 300 enrolled patients, 247 (82.3%) made at least one error. Maximum errors observed in subjects using MDI (94.3%), followed by DPI (82.3%), MDI with Spacer (78%) while Nebulizer users (70%) made least number of errors (p = 0.005). Illiterate patients showed 95.2% error while post-graduate and professionals showed 33.3%. This difference was statistically significant (p

This paper describes the results of a questionnaire survey on some aspects of nebulizer use, nebulizer instruction, and features relating to the recognition and management of deteriorating asthma. The study population consisted of 90 children with home nebulizers attending a paediatric asthma clinic, and 200 asthmatic children and 200 asthmatic adults whose nebulizers had been purchased directly from a manufacturer in the U.K. The results suggest that follow-up supervision of the patients who bought their own nebulizers occurred in only approximately 25% of cases. Written information focusing on the management of symptoms was also lacking. Peak flow meters were being under-used. Although the majority (77–100%) of patients were aware of the ‘4 h rule’ for repeat use of bronchodilator therapy at home, there was still some confusion about the acceptable time interval and action to be taken should the dose be required more frequently. Very few (32%) in the nationwide adult group had a crisis action plan should the nebulizer fail to produce relief. This paper recommends that a simple treatment and crisis plan should be included with the purchased nebulizer, highlighting the key areas to be discussed by the patients with the doctor or other medical professionals. Such a package may prevent the occasional disaster that can occur with unsupervised nebulized bronchodilator usage.

A survey was undertaken to determine the current practice in the Yorkshire Health Region for the assessment and provision of home nebulizers for adults with chronic obstructive pulmonary disease (COPD). A detailed postal questionnaire on assessment methods was sent to each of the 22 consultant physicians in respiratory medicine. The 17 consultants who also organized the adult home nebulizer service for their health district were asked about the services offered and funding for the service. Replies were received from all consultants.All physicians use objective measurement for assessing patients for home nebulizer therapy, but there is a variable emphasis on laboratory studies, walking distance and home trials with peak flow measurements. The majority (86%) incorporate a home trial into their assessment. Many physicians also take into account subjective response to nebulized bronchodilators.There is considerable variation in the provision and funding of home nebulizer services. Those districts with a coordinated service appear to offer a more comprehensive service.A consensus on nebulizer provision, with recommendations for minimum levels of provision in each health district, should result in a more uniform delivery of service.

The aim of this study was to assess if administration of bronchodilator via a metered dose inhaler (MDI), rather than by a nebulizer, avoided the early paradoxical deterioration in lung function but, resulted in equally effective late bronchodilation. Fifteen children were studied at a median postnatal age of 9 months (range 9-18), all had been born prematurely at a median gestational age of 27 weeks (range 23-31). Lung function was measured by plethysmography before and 10 min after normal saline and 5 and 15 min after salbutamol given via an MDI and a nebulizer in random order. At 5 min, compared to baseline values, airways resistance (RAW) deteriorated by 16% after nebulized salbutamol but improved by 3% following salbutamol by the MDI (P0.03). At 15 min RAW improved by 14% following nebulized salbutamol and 15% after salbutamol via the MDI, there was no significant difference in the magnitude of bronchodilation between the two methods of administration. Our results therefore suggest, that as the early paradoxical deterioration in lung function is usually avoided by administering salbutamol via an MDI, this should be the preferred method of administration.

One-hundred nebulizer trials were performed in 98 adult patients with chronic airflow limitation who had remained symptomatic despite regular use of bronchodilators by metered dose or dry powder inhalation. Mean baseline FEV1 was 0.9 (SD = 0.41) 1, FVC -2.0 (0.74) 1 and PEFR 169 (77) 1 min-1. After laboratory measurements of reversibility to inhaled salbutamol (5 mg) and ipratropium bromide (0.5 mg), patients were supplied with a compressor and a peak flow meter to make twice daily measurements at home for 3 weeks. They nebulized normal saline, salbutamol (5 mg) and salbutamol (5 mg) ipratropium (0.5 mg) mixture 6-hourly, each for 1 week. A positive nebulizer trial was defined as a 15% increase in mean PEFR over a week on an active treatment compared to the week on saline. Twenty-eight patients had positive trials based on these criteria. Of these nine responded to both active treatments and 16 to the salbutamol/ipratropium mixture. Although no laboratory measurements predicted a positive domiciliary trial, the patients' subjective assessment of benefit had a 93% sensitivity and 87% negative predictive value. We conclude that an appropriate protocol for assessing the value of long-term nebulized bronchodilators is for patients to measure their PEFR during a week of nebulized saline and a week of nebulized beta-agonist/ipratropium mixture. Those with an increase of 15% in mean PEFR in the week on active treatment and who experienced subjective benefit should be supplied with a compressor. Had we conducted our 100 trials in this way we would have started 25 of our 98 patients on long-term home nebulized bronchodilators.

Twenty patients (six severe asthma, 14 chronic obstructive pulmonary disease, COPD) were referred for consideration of domiciliary nebulized treatment. A double blind laboratory assessment demonstrated similar subjective and objective responses to nebulized salbutamol (5 mg), ipratropium bromide (IB) (0.5 mg) or a mixture of these medications in both groups of patients. The patients subsequently self-administered each treatment four times daily for one month. Fourteen patients requested long-term home nebulizer treatment (three salbutamol, four ipratropium bromide, seven mixture), and nine of these had their highest domiciliary peak flow recordings during home nebulizer treatment. However, subjective and objective laboratory assessments did not clearly predict the patients long-term choice of therapy in any case. There was little overall correlation between the laboratory response and the domiciliary response to treatment (Spearman correlation coefficient; subjective score, laboratory vs. home, r = 0.27, P = 0.03; peak flow response 30 min after treatment, laboratory vs. home, r = 0.31, P less than 0.02). The hospital study was also unreliable in predicting side effects during domiciliary nebulizer use. We conclude that prospective laboratory studies are of little value in the assessment of patients for home nebulizer therapy; these assessments must be made by carefully supervised domiciliary trials of nebulized treatment.

Summary Background Nebulised therapy is commonly used in the management of patients with asthma and chronic obstructive pulmonary disease (COPD). There are guidelines setting out standards for maintenance of the compressor and replacement and care of consumables. This study surveys patients using nebulisers to ascertain the reported use and maintenance of the nebulisers and any side effects related to therapy. Methods An anonymous postal questionnaire, requesting information on nebuliser use and maintenance, and side effects was sent to 200 patients who had been maintained on nebuliser therapy and had been in contact with the nebuliser service at Glasgow Royal Infirmary within the last year. Results One hundred and seventeen (58.5%) questionnaires were returned completed or partially completed for analysis. The majority of patients who replied were female (median age of 69 years). The most commonly reported diagnosis was COPD (87/117); 92/117 (79%) were smokers or ex-smokers. The most commonly reported side effects associated with treatment are dry mouth, tremor and chest tightness. The responses to questions on servicing, maintenance and replacement of consumables indicate that patients comply poorly with these activities. Additionally compliance with the prescribed drug regimen occurs in less than 50% of the patient cohort. Conclusions The results of this study indicate that compliance with instructions given on the care and maintenance of home nebulisers may be suboptimal. Additionally patients reported poorer compliance than was predicted. These areas may be improved with the introduction of a new patient information leaflet.

Nebulization for the administration of high doses of inhaled corticosteroids can benefit steroid-dependent asthmatics. The objective of this double-blind, double-dummy, multicentre, randomized, parallel-group study was to compare the efficacy and safety of high-dose corticosteroids given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 2-week run-in period, 124 patients, aged 18-70 years, with moderate to severe asthma treated with high-dose inhaled steroids were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 3,000-4,000 microgday(-1) b.i.d. given via a nebulizer (n = 63), or BDP spray 1,500-2000 microgday(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 61). Comparable improvements over baseline, which were statistically significant in most cases, were reported at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, clinical symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was morning pulmonary expiratory flow rate (PEFR). For the intent-to-treat population, in the BDP nebulization group mean morning PEFR increased statistically significantly from 308.7 +/- 107.81 min(-1) to 3 19.2 +/- 104.01 min(-1) while in the BDP MDI group the increase was from 301.5 +/- 94.71 min(-1) to 309.3 +/- 86.71 min(-1). The two treatments were equally well tolerated.A total of 19 patients in each group reported adverse events during the treatment period, and these were generally mild-moderate in severity. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3,000-4,000 microg day(-1) given via a nebulizer and BDP spray 1,500-2,000 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in steroid-dependent adult patients with moderate to severe asthma.

Reversible airway obstruction is a characteristic feature of asthma (1). On a pathophysiological basis this is produced by bronchoconstriction, mucosal oedema and inspissated secretions (2). Modern drug therapy for asthma is directed towards controlling mucosal inflammation and hence reversing bronchoconstriction and mucosal oedema (3). However, during acute exacerbations, sputum plugging may contribute significantly to the pathophysiology of asthma and this may be more difficult to treat. The possible role of intensive humidification to liquefy inspissated secretions, in conjunction with physiotherapy to mobilize these secretions, has received little recent attention in the management of asthma. We report four cases of acute asthma which failed to reverse fully until intensive humidification of their respiratory tract was achieved. We used an ultra-Neb 99 ultrasonic nebulizer (De Vilbiss Health Care U.K. Ltd, Heston, Middx, U.K.) adjusted to produce an aerosol output of 3 ml min-‘, particle size being 0.5-5pm. Sterile 0.9% sodium chloride warmed to room temperature was used in all instances. In all cases humidification was combined with regular physiotherapy to clear the increased volume of secretions. All patients had been receiving regular physiotherapy as part of standard treatment prior to the introduction of intensive humidification.

The bronchodilatory effect of four doses of salbutamol powder (1·6 mg) from a multi-dose dry powder inhaler, the Diskhaler, was compared to the effect of 2·5 ml salbutamol nebulizer solution (1 mg ml −1 ) from a jet nebulizer, Pari Inhalierboy, in a randomized, double-blind, double-dummy, cross-over study performed on 2 consecutive days. Thirty-two patients with severe chronic obstructive pulmonary disease (COPD), a mean FEV 1 =29% of predicted value, and at least a 15% increase in FEV 1 after inhaling 5 mg nebulized terbutaline were included. Twenty-eight patients were evaluated: 17 women and 11 men with a mean age of 67 years (range 53–82 years). The mean increases in FEV 1 were greater after inhalation via the Diskhaler, although there was no difference in the patients' subjective assessment of the treatments. The powder inhaler was also effective in patients with the lowest baseline FEV 1 and the lowest inspiratory peak flow through the inhaler. The study demonstrates that dry powder inhalation of salbutamol via a Diskhaler is at least as effective as inhalation of salbutamol via a jet nebulizer in providing bronchodilation in patients with severe COPD.

A retrospective audit was performed of a home nebulizer service managed entirely by a Respiratory Nurse Specialist (RNS). We examined (i) the role and workload of the RNS, (ii) the outcome of referrals to the service and (iii) the subsequent compliance with treatment of patients prescribed home nebulized bronchodilators. The case notes and RNS records of all patients referred for consideration of home nebulized bronchodilators over a 9-month period were reviewed. The nebulizer service encompassed patient assessment, trials of nebulized therapy, nebulizer issue and patient registration and an exchange and servicing system. The non clerical aspects of the service took 9h per week, 24% of total RNS time. A further 15 h weekly of clerical time was also required. Of 76 referrals, 57 (75%) patients had chronic airflow obstruction (CAO). In CAO patients, 41 had a trial of nebulized therapy and in 27 (66%) such therapy was considered beneficial. In the other 16 CAO patients the RNS deemed a trial inappropriate or impractical and 12 such patients were prescribed nebulized therapy. Overall, therefore 39/57 (68%) of CAO referrals were prescribed home nebulized therapy. At 3–6 months, seven (18%) patients were using their nebulizer infrequently or not at all, 25 (64%) one to four times daily, and seven (18%) four times daily. We conclude that a RNS can manage a complete nebulizer service, but at a considerable cost in professional time. Clerical assistance is essential if appropriate use is to be made of the skills of an RNS. The RNS identified up to one-third of the CAO patients for whom nebulized therapy was not appropriate or of no benefit. Compliance with therapy was reasonable but RNS contact with patients at 6 months was valuable, in part to retrieve nebulizers that were not being used.

Patients with chronic obstructive pulmonary disease (COPD) are often treated with high dose inhalations of β2-agonists. We compared domiciliary therapy with terbutaline administered by the Turbuhaler® and by a jet nebulizer. Forty nebulizer users with severe COPD were included in the randomized, double-blind, cross-over study. Terbutaline was inhaled t.i.d. for 2 weeks as dry powder (5 doses=2·5 mg) by Turbuhaler® or as solution (2 ml=5 mg) by jet nebulizer (Pari Inhalierboy®). The mean age of the 25 completing patients was 66 years (range: 54–81), the mean FEV1 was 0·73 l or 29% of predicted (range: 11–55%). The period where the Turbuhaler® delivered the active drug was preferred by 16 patients, the nebulizer period by seven (P=0.09). The median score concerning feeling of control over the disease — according to the Chronic Respiratory Disease Questionnaire — was better after the Turbuhaler® period (P=0·01). Other scores concerning disease related quality of life, the daily peak expiratory flow rates, the additional use of a metered dose inhaler were not significantly different for the two types of treatment. It is concluded that high dose domiciliary terbutaline treatment by Turbuhaler® can replace nebulizer treatment in most patients with severe COPD.

The total and regional deposition of aerosol has been compared using four nebulizers; the Pari Boy 37.80, Pari IS-2, RespirGard II and Penta-Sonic. The aerosol was radiolabelled with [99Tcm]DTPA, administered to ten healthy subjects and the distributions monitored by gamma scintigraphy. Median lung aerosol depositions expressed as percentages of the doses initially loaded into the nebulizers were: Pari IS-2 19%, Pari Boy 37.80 13%, RespirGard II 9% and Penta-Sonic 2%. The ratios of the peripheral to central lung deposition, however, were greater with the RespirGard II and Penta-Sonic nebulizers. The choice of the most appropriate nebulizer depends on the pharmaceutical being administered, since aerosol must be delivered to the required site in sufficient quantity, whilst minimizing the incidence of local or systemic side-effects.

Nebulized bronchodilators are commonly used in the management of patients with airflow obstruction, although there is little information available on the bronchodilator output from the nebulizer unit. We have examined the fluid and salbutamol outputs of a single jet nebulizer from two commercial manufacturers at 1 min intervals up to 12 min. The drug and fluid output continued throughout the study period, with a greater fluid output leading to an increase in the concentration of salbutamol remaining within the nebulizer unit. This suggests that weight change is not a good indicator of drug output. Furthermore, there was a marked difference in peak salbutamol output between the two nebulizer units, being 2·9 mg (55%) with the Micro-Neb unit and 1·98 mg (38·7%) with the System 22 unit.

Nedocromi[ sodium is a new pyranoquinoline dicarboxylic acid derivative which is being studied extensively in adults with asthma. However, there are few publications which detail the use of nedocromil sodium in childhood asthma. One such study showed that nedocromil sodium administered by metered dose inhaler is able to protect against exercise-induced bronchoconstriction (1). We report here on the findings of a study to determine whether nedocromil sodium nebulizer solutions block foginduced bronchoconstriction in asthmatic children.

Forty-nine patients (15 asthma, mean FEV1/FVC 1.3/2.1; 34 COPD, mean FEV1/FVC 0.7/1.8) were referred for consideration of home nebulizer treatment. All were monitored for 2 weeks while using their usual inhaled treatment followed by 2 weeks using a 'Nebuhaler' spacer to deliver 1 mg of terbutaline and 80 micrograms of ipratoropium bromide (IB) four times daily. They then borrowed a System 22 nebulizer to self-administer salbutamol nebulizer solution (5 mg), IB unit dose vials (0.5 mg) or a mixture of these drugs four times daily for 1 month each. Both asthmatic and bronchitic patients had a significant rise in their mean daily peak flow rate (PFR) during home nebulizer treatment (P < 0.03) and the COPD patients also had a significant PFR rise during Nebuhaler treatment (P = 0.0004). The mean daily peak flow rates (PFR 1 min-1 were: baseline 179, Nebuhaler 195, salbutamol nebulizer 200, IB nebulizer 198, mixed nebulizer 216). Four patients failed to respond subjectively or objectively to either Nebuhaler or nebulizer treatment. Five patients responded well to Nebuhaler treatment and did not proceed to a home nebulizer trial. Eight further patients preferred Nebuhaler to nebulizer treatment or could not tolerate nebulizer treatment (two cases). Thirty-two patients requested home nebulizer treatment for long-term use (nine salbutamol, five IB, 18 mixture). Twenty-seven of these patients had an increased mean daily PFR (compared to their usual therapy) while using their chosen nebulized treatment. The mean increase in PFR for all 32 patients was 191 min-1 (11%).(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to determine the maximum effective dose of nebulized ipratropium bromide, 0·5 or 1·0 mg, in the treatment of acute severe attacks of asthma. Thirty-two patients (ten males, 19–53 years) who were admitted with acute severe asthma were, in a double-blind trial, randomized to receive either 0·5 or 1·0 mg of isotonic, preservative-free ipratropium bromide nebulized in saline. Ear oxygen saturation, peak flow and heart rate were measured on admission and regularly following nebulization. Two hours after nebulization of the ipratropium, terbutaline (5 mg) was administered by nebulizer and further measurements taken 30 min later. Twenty-six patients completed the study, 13 in each group. Peak expiratory flow (PEF) increased by 51% [121 1 min −1 increasing to 1831 min -1 (mean)] in the 0·5-mg ipratropium group, and by 37% (1551 min −1 to 2071 min -1 ) in the 1·0-mg group. There were no significant differences in heart rate or ear oxygen saturation changes between the groups. Nebulized terbutaline led to a small further rise in peak flow in both groups (341 min −1 in the 0·5-mg group; 411 min −1 in the 1·0-mg group). No side-effects were noticed in either group. We conclude that 0·5 mg of nebulized ipratropium is as effective as 1·0 mg in the treatment of acute severe asthma.

Whilst there is no doubt that nebulized bronchodilators are indicated in acute, severe and brittle asthma, whether treated in hospital or in the community, there is continued concern over the increasing use of nebulizers for regular home therapy in chronic persistent asthma (I). Controversy applies only to use for bronchodilator therapy (chiefly fl2-stimulants) rather than for preventative anti-inflammatory drugs. In fact, disodium cromoglycate and steroids are very rarely delivered by nebulizer to adults (as opposed to children) though this would be indicated if use of other devices proved impossible.

Patients with severe chronic airways obstruction often respond poorly to inhaled salbutamol in conventional dosage from a pressurized aerosol. We have investigated the response to high dose salbutamol in 18 patients with chronic airways obstruction (mean age 64.4 years, mean FEV1 40.2% predicted, less than 15% response to 400 micrograms salbutamol). Patients were given 1 mg, 2 mg and 5 mg of salbutamol by either Rotacaps or nebulizer in random order on separate days. Response was measured over 8 h as a change in airway calibre (FEV1, FVC and PEF). The frequency of tremor, palpitations and arrhythmias was noted. Area under the curve for change from baseline values for FEV1, FVC and PEF showed that larger doses of salbutamol (nebulized or Rotacaps) result in larger areas from all three variables. Analysis of peak response, for FEV1, FVC and PEF showed no significant difference for the six treatments used except that the peak response for 2 mg Rotacaps for FEV1 was significantly larger than that for 1 mg Rotacaps (P less than 0.05). The results of this study show that in severe chronic airflow obstruction 1, 2 and 5 mg of salbutamol inhaled via a rotahaler device are just as effective as 1, 2 and 5 mg salbutamol inhaled from a nebulizer in producing bronchodilation. High dose salbutamol is well tolerated and side effects are minimal. Rotacaps have the advantage of being more portable than a wet nebulizer.

Domiciliary nebulizer use is evaluated in a well-defined population on the Isle of Wight covering all ages. A questionnaire was administered to 167 known users and all were completed. The indication for nebulizer therapy was asthma (137), bronchitis (32) and emphysema (30). Twenty-three had never had a simple inhaler device prescribed and, of the others, 13 had never had instruction in its use. One hundred and fifty-three had used the nebulizer within the previous year and, of these, instruction was provided by physiotherapist (87), general practitioner (30), nurse (19) and hospital doctor (6). Nine received no advice. The drugs used comprised mostly salbutamol (140) and sodium cromoglycate (51). Twenty-six mixed medicines for use in the nebulizer and 24 admitted to exceeding the recommended dose. Twenty-three patients had a peak flow meter available at home. With treatment failure, 108 would call a doctor or report to hospital, while 25 would persist with nebulizer therapy. Thirty-two patients had no help at home in the event of an emergency. Most patients thought that they benefited greatly from nebulizer treatment at home, but better selection of patients and monitoring of treatment is needed. Comparison with previous studies suggests that there has been little improvement in the domiciliary use of nebulizers.

Continuous positive airway pressure (CPAP) is frequently used in patients attending emergency units. Its combination with nebulization is sometimes necessary in those patients presenting with a CPAP dependency. STUDY OBJECTIVE: To compare lung deposition of amikacin delivered by a classical jet nebulizer (SideStream; Medic-Aid; West Sussex, UK) used alone (SST) or coupled to a CPAP device (Boussignac; Vygon; Belgium). METHOD: Amikacin (1g) was nebulized with both devices in six healthy subjects during 5 min on spontaneous breathing. A 1-week wash-out period between each nebulization was applied. Lung deposition was indirectly assessed by urinary monitoring of excreted amount of amikacin. RESULTS: Total daily amount of amikacin excreted in the urine was significantly lower with CPAP than with SST (1.97% initial dose versus 4.88% initial dose, p

Summary Background Systematic reviews and national guidelines conclude that the nebulised route of administration of bronchodilators has no advantage over the use of a spacer in moderately severe exacerbations of asthma. Whether this recommendation is implemented and whether it might affect use of staff time is unknown. Objectives To determine the current method of administration of bronchodilators to those with non-life-threatening asthma attending emergency departments (ED) in London, UK and to monitor the implementation of a new policy to administer bronchodilators by spacers in one ED with a special reference to the time taken by nurses to administer the therapy by two different routes. Methods Thirty-five EDs in Greater London were surveyed regarding their current practice. A time and motion study was then undertaken in one department observing nurses administering bronchodilators in the 3 weeks before and 3 weeks after a departmental policy change to favour the use of spacer devices rather than nebulisers. Results The majority of EDs (94.3%) in Greater London were using the nebulised route of administering bronchodilators to the majority of their adult patients. Spacers were more commonly used for the treatment of children (60.3% of departments using spacers and nebulisers or spacers alone). Over half of the hospitals surveyed (51.4%) were unaware that the British Guidelines on Asthma Management suggested that outcomes were the same and that there were potential advantages in the use of a spacer for both adults and children. Time and motion studies showed that the use of a spacer took no more nursing time than administration of the bronchodilator via a nebuliser; in fact treatment and set-up time were considerably lower for spacers. Conclusion Spacer administration of bronchodilators to those with asthma attending EDs utilises less treatment time than use of a nebuliser. A survey of EDs in Greater London has shown that despite guideline conclusions there appears to be little evidence of reduction in use of nebulisers; a fear that use of alternatives might take nurses longer is not supported by this study.