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PubMed2001

Effect of inspiratory flow rate on beta2-agonist induced bronchodilation in mechanically ventilated COPD patients.

OBJECTIVES: To test the effect of two different inspiratory flow rates on the bronchodilation induced by beta2-agonists administered by metered dose inhaler (MDI). PATIENTS: Ten patients with acute exacerbation of chronic obstructive pulmonary disease and receiving mechanical ventilation with constant inspiratory flow (V'I). DESIGN: Patients received four puffs of salbutamol (100 microg/puff) with either low V'I (0.6 l/s) or high V'I (1.2 l/s) administered with an MDI adapted to inspiratory limb of the ventilator circuit using an aerosol cloud enhance spacer. After a 6-h washout patients were crossed-over to receive the drug by the alternative mode of administration. MEASUREMENTS AND RESULTS: Static and dynamic airway pressures, intrinsic positive end-expiratory pressure, and minimum and maximum inspiratory resistance values showed a significant decrease after salbutamol. These changes were not affected by the inspiratory flow rate and were evident 15, 30, and 60 min after administration. Heart rate, static end-inspiratory respiratory system compliance, and the difference between minimum and maximum inspiratory resistance were unchanged after salbutamol. CONCLUSIONS: Salbutamol delivered by MDI and spacer device induces significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, but the magnitude of the effect is not affected by the inspiratory flow rate. These results do not support flow rate manipulations when bronchodilators are administered during controlled mechanical ventilation.

Adrenergic beta-Agonists↗
PubMed1998

Using low-frequency oscillation to detect bronchodilator responsiveness in infants.

The potential of the low-frequency forced oscillation technique (FOT) to measure the response to inhaled salbutamol was studied in 13 infants with a history of recurrent wheeze and nine healthy infants. The input impedance of the respiratory system (Zrs) between 0.5 and 20 Hz was measured at a transrespiratory pressure of 20 cm H2O during a brief Hering-Breuer reflex-induced pause in breathing. Parameters representing the airway resistance (Raw) and inertance (law), and a constant-phase tissue damping (G) and elastance (H) were estimated from the Zrs spectra. Lung function was measured before and after the administration of 500 microg of salbutamol via a small-volume metal spacer. Six of these infants also received a placebo aerosol. A fall in Raw (13% for the entire group) occurred following treatment with salbutamol (p < 0.008) but not placebo. There was no significant difference in the response to salbutamol between the normal infants (7.65% +/- 5.49%) and those with recurrent wheeze (17.58% +/- 8.67%). On grouped data, the fall in G just failed to reach statistical significance (p = 0.05) after correcting the significance level for multiple tests. No significant change occurred in law or H. We conclude that the low-frequency FOT is a suitable methodology for studying bronchodilator responsiveness in infants.

Administration, Inhalation↗
PubMed1999

Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers.

The aim of this study was to investigate whether budesonide, for 10 d, administered at the first sign of an upper respiratory tract infection, could reduce asthma symptoms in 1-3-y-old children with asthma during infections. The primary efficacy variable was symptom scores. The study had a multicentre, randomized, double-blind, placebo-controlled design with parallel groups. Fifty-five children with a mean age of 26 months received either budesonide or placebo via a spacer with a facemask. Each child was monitored for 1 y. Budesonide was given 400 microg q.i.d. for the first 3 d and b.i.d. for 7 d. Symptoms (cough, wheeze, noisy breathing and breathlessness) were scored (0-3) daily by the parents. Asthma symptom scores were lower in children treated with budesonide than in those given placebo. The effect was most pronounced for cough and noisy breathing, but it did not affect the need for hospital care. In conclusion, treatment with budesonide, started at the first sign of a respiratory infection, reduced asthma symptoms in toddlers with episodic asthma.

Asthma↗
PubMed2002

PET imaging-based evaluation of aerosol drugs and their delivery devices: nasal and pulmonary studies.

Three-dimensional (3-D) positron emission tomography (PET) imaging of inhaled radiolabeled aerosol in the nasal or pulmonary regions provides an in vivo measurement of drug distribution using the drug itself as the tracer. Repeated or dynamic PET scans over the time after inhalation provides us with further information about the fate of the deposited drug. These quantitative measurements are sufficient to describe the performance of a drug or device and they are obtained in a noninvasive fashion, which cannot be achieved by using any other methods. Using this PET-imaging paradigm, we conducted a sequence of drug studies to evaluate the performance of aerosol drugs and delivery devices; to compare the performance of similar drugs from different manufacturers; to assess the similarity between different formulations and propellants for the same drug; to appraise delivery devices such as spacers and nebulizers, etc. This paper reviews only the imaging and data analysis techniques developed for the above-mentioned studies that include multi-modality image registration, region definition and region-based data analysis, and nonregion-based data analysis. We separated the techniques into nasal and pulmonary studies because of the uniqueness of each group. Specific drugs or devices are not identified and no result about drug performance is given because the imaging and data analysis methodology, which is the focus of this paper, applies to all these studies regardless of the drugs or their delivery devices. The quantitative data are used as the scientific basis for evaluation although we also developed visualization techniques to enhance the results drawn from the data.

Administration, Inhalation↗
PubMed2004

Asthma in emergency departments: combined adult and paediatric versus paediatric only centres.

OBJECTIVE: To compare the management of paediatric patients with mild or moderate asthma in paediatric-only emergency departments (POEDs) to treatment in a mixed adult-child emergency departments (mixed EDs). METHODS: Prospective, observational study conducted in 36 Australian emergency departments (EDs) for 2 weeks in 2001. Children aged 1-15 years with acute asthma classified as mild or moderate severity. Details of demography, severity assessment, and type of treatment facility, treatment and disposition were collected. Analysis used descriptive statistics, comparison of proportions by chi2, and multiple logistic regression. RESULTS: Two-hundred and nine children were treated at POEDs and 257 at mixed EDs. The groups had similar severity. Spacers to deliver beta-agonists were used more frequently in POEDs (67.5% vs 24.2%; P < 0.01). Children treated at POEDs with a mild attack were more likely to be admitted (20.6% vs 9.5%; P < 0.02) and given salbutamol (82.8% vs 71.9%; P = 0.03). For children with moderate asthma, oral steroid prescription on hospital discharge was more common for those treated in a mixed ED (81.0% vs 95.7%; P = 0.01). Ipratropium bromide (IB) was widely used at both types of ED but more commonly used in mixed EDs (41.7% vs 54.9%; P < 0.01). There were no differences in length-of-stay, representation rate within one month and oral steroid use for attack. Less than 2/3 of children with mild asthma attacks received steroid treatment in the ED. CONCLUSION: Treatment was similar between the two types of ED. IB was overused in mild asthma and oral steroids were underused in moderate asthma, by both ED types. Spacers were under-utilized in mixed EDs.

Adolescent↗
PubMed1996

Metered-dose inhaler technique of patients in an urban ED: prevalence of incorrect technique and attempt at education.

The metered-dose inhaler (MDI) techniques of 125 asthma patients who presented to a county hospital emergency department (ED) were evaluated. Correct technique was divided into 7 steps. Twenty-one percent of the patients performed all 7 steps correctly. Mean number of steps +/- SD performed correctly was 4.8 +/- 1.7. Verbal individualized instruction was used to improve the technique of patients whose technique was less than perfect. The instruction required a mean +/- SD of 8.3 +/- 5.8 minutes (range, 0 to 30) for all 7 steps to be done correctly at least once. All patients were able to perform all steps correctly after instruction. The amount of time required for teaching was proportional to the number of steps performed incorrectly. The Vitalograph Aerosol Inhalation Monitor was used to verify correct patient technique and as a teaching aid with variable success. Education in proper use of the MDI is important in the overall care of the asthma patient; however, instruction requires a definite time commitment and may not be feasible for all patients in a busy ED. For some patients, alternatives that require less lengthy instruction, such as the use of breath-actuated devices, spacers, and reservoirs, may be required.

Anti-Asthmatic Agents↗
PubMed2003

Extra-fine particles improve lung delivery of inhaled steroids in infants: a study in an upper airway model.

BACKGROUND: The particles of a new hydrofluoroalkane-134a (HFA)-beclomethasone dipropionate (BDP) metered-dose inhaler (Qvar; 3M Pharmaceuticals; St. Paul, MN) are considerably smaller than those of chlorofluorocarbon (CFC)-BDP. This may improve lung deposition in infants who inhale nasally and have irregular breathing patterns and small airways. AIM: To compare the dose delivered to the lungs of HFA-BDP and CFC-BDP at different breathing patterns using an upper airway model of an infant. METHODS: An anatomically correct upper airway model of a 9-month-old child with an open nasal airway was connected to an impactor and breathing simulator. HFA-BDP, 100 microg, and CFC-BDP, 100 micro g, were delivered to the model through a detergent-coated, small-volume spacer. The total dose leaving the model (lung dose), its particle size distribution, and median mass aerodynamic diameter (MMAD) were assessed during simulated tidal breathing with tidal volumes (VTs) of 50 mL, 100 mL, and 200 mL, and 30 breaths/min. Dose was expressed as percentage of nominal dose. RESULTS: Lung doses for HFA-BDP were 25.4%, 26.5%, and 30.7% compared with 6.8%, 4.8%, and 2.1% for CFC-BDP at VTs of 50 mL, 100 mL, and 200 mL, respectively. The dose of particles < 2.1 microm to the lung for HFA-BDP was 23 to 28% compared with 0.6 to 0.8% for CFC-BDP. The lung dose of CFC-BDP mainly consisted of particles between 2.1 microm and 4.7 microm. MMAD for HFA-BDP was 1.2 microm, and 2.6 to 3.3 microm for CFC-BDP depending on VT. The lung dose for CFC-BDP decreased significantly with increasing VT. HFA-BDP lung dose did not alter significantly with VT. CONCLUSIONS: In this infant model study, the use of HFA-BDP with a high dose of particles < 2.1 microm improves the dose delivered to the lungs substantially. Furthermore, the large proportion of extra-fine particles in HFA-BDP results in lung doses less dependent on breathing pattern compared with CFC-BDP.

Administration, Inhalation↗
PubMedDate not supplied

Snapshot of acute asthma: treatment and outcome of patients with acute asthma treated in Australian emergency departments.

AIMS: To characterize presentations due to acute asthma at Australian emergency departments (ED), including their severity, treatment and disposition. METHODS: This prospective, observational study involved 38 departments of emergency medicine throughout -Australia participating in the Snapshot of Asthma Study Group project 2000 and 2001. Data were collected for patients presenting with acute asthma between 21 August 2000 and 3 September 2000, and 20 August 2001 and 2 September 2001 and included demographics, severity classification, treatment and disposition. RESULTS: There were 1340 acute asthma presentations in the study periods. Of these presentations, 67% were for children aged <15 years. Asthma severity (according to the Australian National Asthma Guidelines classification) was 'mild' in 49% of cases; 'moderate' in 45% of cases; and 'severe' in 6% of cases. Treatment administered included: (i) salbutamol to 90%, (ii) ipratropium bromide to 59% and (iii) corticosteroids to 71%. Only six patients received aminophylline. Spacer use for salbutamol was rare (1%) in adults and only moderate (43%) in children. Sixty-five percent of patients were discharged home from the ED. Less than 1% of patients required ventilatory assistance, of which half was provided non-invasively. One percent of patients were admitted to the intensive-care unit or high-dependency unit. CONCLUSION: Overall adherence to treatment guidelines was good. There appears to be underuse of spacers and corticosteroids in some groups and overuse of ipratropium bromide. The majority of patients are treated and discharged from the ED.

Adolescent↗
PubMed1999

Direct detection of Histoplasma capsulatum in soil suspensions by two-stage PCR.

Histoplasmosis is the most common pulmonary mycosis in the United States. The responsible fungal pathogen, Histoplasma capsulatum, grows in soils contaminated with bird or bat droppings. Inhalation of dust from contaminated areas containing H. capsulatum spores is a primary route of infection. The ability to detect H. capsulatum in soil samples has been limited by the lack of fast, reliable and inexpensive methods. A polymerase chain reaction (PCR) method was developed that allows the direct detection of H. capsulatum in soil. A two-stage PCR protocol was followed employing both fungal-specific primers and nested primers specific for the internal transcribed spacer (ITS) region of the 5.8S rRNA gene of H. capsulatum. The estimated limit of detection of this method is 10 spores. In contrast to the more expensive and indirect mouse inoculum assay, which requires 6-8 weeks for sample analysis, PCR analysis of soil contaminated with H. capsulatum can be completed in less than 2 days.

Animals↗
PubMed1998

Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a pilot study.

BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility of using a metered-dose inhaler (MDI) to administer methacholine in bronchial provocation tests, and the ability of such a device to diagnose bronchial hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover pilot study, we compared the provocative dose that induces a 20% fall in FEV1 (PD20 FEV1) obtained with the methacholine MDI with that obtained using a conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects. The MDI delivers 400 doses of 100 microg of methacholine, and was used via a spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000 microg with the conventional test using the nebulizer. The tests were performed in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20 FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and the two tests were highly concordant for the diagnosis of BHR (Pearson chi2, 36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of methacholine during bronchial provocation tests, if these results are confirmed in large samples.

Adult↗
PubMed2005

Comparison of the effects of nebulised and inhaled salbutamol on breathlessness in severe COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often report greater relief of breathlessness with nebulised bronchodilators than with the same medicine administered from a metered dose inhaler (MDI). This suggests that the nebulised medicines may have an effect on breathlessness over and above changes in lung function resulting from bronchodilatation. METHODS: Twenty-four subjects with COPD and breathlessness at rest participated in this randomised, crossover trial. The mean age was 72 years and the mean FEV(1) was 26% of predicted. Subjects were studied on four separate days. On two days they were treated with nebulised salbutamol and on the other 2 days with salbutamol from an MDI and spacer. With each method of delivery, local anaesthetic cream was applied to the face on one day and to the back of the hand on the other. RESULTS: Five minutes after administration of salbutamol the subjects were significantly less breathless with nebulised salbutamol but by 45 min both treatments resulted in equivalent relief. There was no difference between the treatments in the change in FEV(1) or VC and application of local anaesthetic to the face did not influence the response. CONCLUSION: There was a small early benefit with nebulised salbutamol but this was not sustained and was not affected by topical anaesthesia. The benefit of nebulisation does not appear to be large enough to warrant the routine, widespread use of nebulised bronchodilators for the treatment of stable COPD.

Aged↗
PubMed1996

Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in vitro model.

Successful bronchodilator therapy with a metered-dose inhaler (MDI) in intubated, mechanically ventilated patients requires adequate delivery of aerosol to the lower respiratory tract. We determined the effect of ventilator mode, inspiratory flow pattern, humidity, and spontaneous respiratory effort on albuterol delivery in a model of the trachea and bronchi. The model was ventilated through an endotracheal tube during controlled mechanical ventilation (CMV), assist control (AC), pressure support (PS), and continuous positive airway pressure (CPAP), separately with a dry and humidified ventilator circuit. Delivery of albuterol administered by a MDI and spacer on filter placed at the ends of the bronchi was measured by spectrophotometry (246 nm). Under dry conditions and with a frequency of 10 breaths/min, albuterol delivery with CMV (VT, 800 ml; 30.3 +/- 3.4%), AC (VT, 800 ml; 31.9 +/- 1.3%), PS 10 cm H2O (VT, 700 ml; 28.8 +/- 4.5%), or PS 20 cm H2O (VT, 800 ml; 30.9 +/- 1.8%) was lower than that observed with simulated spontaneous breaths with CPAP (VT, 800 ml; 39.2 +/- 1.4%) (p < 0.01 for all modes). Delivery was greater under dry (28.8 to 39%) than under humidified conditions (15.9 to 20.2%) (p < 0.005 in all modes). Albuterol delivery showed a linear correlation with both inspiratory time and duty cycle (r > 0.91). Lower respiratory tract delivery of aerosol from a MDI varied from 4.9 to 39.2%. We conclude that in addition to other known factors such as dose, type of spacer, and its position the technique of administering MDIs in mechanically ventilated patients markedly influences lower respiratory tract aerosol delivery.

Aerosols↗
PubMed1992

Nebuhaler versus wet aerosol for domiciliary bronchodilator therapy. A multi-centre clinical comparison.

OBJECTIVE: To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline. DESIGN: Randomised open crossover study over two sequential four week treatment periods, following a two week run-in. SETTING: Multi-centre including five adult thoracic units and three paediatric centres throughout Australia. PATIENTS: Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of greater than or equal to 15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew. INTERVENTIONS: Terbutaline was administered four times daily via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire. RESULTS: No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function. CONCLUSIONS: MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction.

Adult↗
PubMed2000

Effect of a brief educational intervention on medical students' use of asthma devices.

Several studies have shown that a significant percentage of housestaff and attending physicians are deficient in both skill and knowledge of the metered-dose inhaler (MDI). There are no studies involving medical students, or any including the peak flow meter (PFM). The setting was a large health science center with investigators in private conference rooms with individual medical students. Twenty-two medical students in the last semester before graduation were scored in the use of these devices pre-education and post-education (instruction included both discussion and demonstration). Results revealed a lack of skill initially, followed by dramatic improvement after the intervention. The total number of correct steps for each device (MDI with spacer and PFM) improved significantly (p < 0.0001). This group of medical students was deficient in the use of common asthma devices. A short educational intervention was effective in improving skill.

Anti-Asthmatic Agents↗
PubMed2004

Effect of a facemask leak on aerosol delivery from a pMDI-spacer system.

The objective of this investigation was to study the relation between size and position of a mask leak on spacer output and lung dose. An upper-airway model (SAINT model, Erasmus MC) was connected to a breathing simulator. Facemasks with leaks ranging between 0 and 1.5 cm(2) were examined. Leaks were located close to the nose or close to the chin. During simulated breathing, 200 microg budesonide (Pulmicort, AstraZeneca) was delivered to the model via NebuChamber (AstraZeneca) with facemask. Spacer output and lung dose were measured by placing a filter between spacer and facemask or between model and breathing simulator, respectively. Budesonide trapped on the filter was quantified by means of HPLC, and expressed as percentage of the nominal dose. Mean spacer output doses for the nose position were 50, 38, 28, 12, 10, 6, and 0%, and for the chin position were 50, 40, 31, 11, 9, 4, and 0% for leaks of 0, 0.05, 0.1, 0.16, 0.2, 0.3, and larger than 0.4 cm(2), respectively. Mean lung doses for the nose position were 10, 8, 6, 3, 3, 1, 0, 0, 0, and 0%, and for the chin position were 10, 9, 8, 6, 6, 5, 1, 1, 0, and 0% for leaks of 0, 0.05, 0.1, 0.16, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 cm(2). Efficiency of a pMDI-spacer facemask strongly depends on the size of a facemask leak. Spacer output did not depend on the position of the leak. Lung dose was higher for leaks near the chin than for leaks near the nose.

Aerosols↗
PubMed1999

Modular glovebox connector and associated good practices for control of radioactive and chemically toxic materials.

Design and associated good practices are described for a modular glovebox connector to improve control of radioactive and chemically toxic materials. The connector consists of an anodized aluminum circular port with a mating spacer, gaskets, and retaining rings for joining two parallel ends of commercially available or custom-manufactured glovebox enclosures. Use of the connector allows multiple gloveboxes to be quickly assembled or reconfigured in functional units. Connector dimensions can be scaled to meet operational requirements for access between gloveboxes. Options for construction materials are discussed, along with recommendations for installation of the connector in new or retrofitted systems. Associated good practices include application of surface coatings and caulking, use of disposable glovebags, and proper selection and protection of gasket and glove materials. Use of the connector at an inhalation toxicology research facility has reduced the time and expense required to reconfigure equipment for changing operational requirements, the dispersion of contamination during reconfigurations, and the need for decommissioning and disposal of contaminated enclosures.

Aluminum↗
PubMed1994

Feasibility of drug delivery to the respiratory tract by a mechanical micro spray pump.

A hand actuated, propellant free spray device is being developed which may be suitable for medical inhalation therapy. The purpose was to evaluate the feasibility of the mechanical micro spray pump to produce a fine spray whose droplets were suitable for inhalation. The physical and technical requirements have been achieved using an air blast nozzle which has been improved by changing the geometry and therefore the dynamic properties within the spray nozzle. The generation of particles above 50 mum in diameter was suppressed and the injection time of the spray increased. These features resulted in a finer and more uniform spray. In-vivo experiments were conducted, where 15 mul per stroke of a 99mTc labeled saline solution was delivered to test persons. The activity was measured by gamma-scintigraphy. It was observed that without and with a spacer, a respective thoracic deposition of 8 %vol and 13 %vol was achieved on average.

Aerosols↗
PubMedDate not supplied

[How best to perform aerosol therapy. 2. Drugs].

The individuation of a 5:1 ratio for the posology of beta 2-agonist drugs administered respectively by nebulizer or as a spray plus a spacer, allows the use of these drugs by the latter way also during an acute attack of bronchospasm. Other qualifying aspects of beta 2-agonist are the possibility of increasing the dose up to a continuous administration in case of a severe attack of bronchoconstriction and the demonstrated clinical efficacy of these drugs during the first year of life. The question of the correct dose to administer according to the age of the patient appears to be rather complex: in fact if on the one hand during the first months of life the low tidal volume (VT) can reduce the quantity of drug inhaled, on the other the low pulmonary volumes (FRC) of the first years of life determine a lesser dilution of the inhaled drug and therefore a greater pulmonary concentrations. Among corticosteroids for inhalation, the ones with the fewer side effects should be chosen: these may appear although in a subclinical fashion at relatively low doses of about 400 micrograms/day of beclomethasone. The most frequent indication for an antibiotic treatment by inhalation is represented by chronic pulmonary infection caused by bacteria sensible only to parenteral antibiotics (for ex. Pseudomonas infection in cystic fibrosis). The extremely high cost of these treatments requires the use of devices with a very high efficiency, in other words capable of nebulizing very large percentages of drug into small particles (< 6 microns).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗