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Biomedical subjects

M L Everard

Publications and source records attributed to M L Everard.

53 records · Page 3Linked to original sources
PubMed1995

Tryptase and IgE concentrations in the respiratory tract of infants with acute bronchiolitis.

It has been proposed that a specific IgE response contributes to the immunopathology of acute respiratory syncytial virus (RSV) bronchiolitis but previous work has been difficult to replicate. Indirect evidence that might support this contention was sought by measuring total IgE concentrations in bronchoalveolar lavage (BAL) samples obtained from intubated infants and by attempting to detect mRNA for IgE in cells obtained from both the upper and lower respiratory tract. Evidence of significant mast cell activation was sought by measuring tryptase concentrations in BAL fluid and serum. Detectable concentrations of IgE were found in two of seven BAL samples obtained more than five days after intubation and mRNA for IgE was demonstrated in three of six BAL samples and three of six samples obtained from the upper respiratory tract. Tryptase was detectable in 11 of 12 BAL samples with the two highest values detected on day 1. These values were raised compared with control samples but were not such to suggest that mast cell degranulation is the major contributor to the inflammatory process. These results suggest that IgE may be produced in the airways of infants in response to RSV infection. The relationships between IgE production, RSV infection, and symptoms of acute bronchiolitis remain obscure.

Acute Disease↗
PubMed1995

An alternative aerosol delivery system for amiloride.

BACKGROUND: The advent of novel treatments such as aerosolized amiloride are potentially useful additions to the therapeutic options available for the treatment of cystic fibrosis. Unfortunately, amiloride and other aerosolized drugs such as antibiotics are generally administered via jet nebulisers which are time consuming to use, and thus limit the acceptance and efficacy of these forms of treatment. In vitro experiments were performed in order to determine whether amiloride could be administered in dry powder form using a Turbohaler. METHODS: Amiloride was micronised and loaded into 200 micrograms Turbohalers. The dose delivered per actuation and particle size distribution of the generated aerosol were assessed using a flow of 60 l/min through the Turbohaler. The dose of amiloride delivered was measured by collecting the aerosol on a filter and the quantity of drug was assayed by an ultraviolet spectrophotometric method. The particle size distribution was assessed using a Malvern MasterSizer laser particle sizer and compared with that generated by a commercially available 200 micrograms budesonide Turbohaler. RESULTS: The mean (SD) dose delivered per actuation was 246.3 (40.4) micrograms. The volume median diameter of the amiloride aerosol was 3.80 (0.68) micron compared with 3.07 (1.47) microns for budesonide. CONCLUSIONS: These results suggest that therapeutic doses of micronised amiloride could be delivered effectively and conveniently as a dry powder aerosol using a Turbohaler.

Aerosols↗
PubMed1995

Factors affecting total and "respirable" dose delivered by a salbutamol metered dose inhaler.

BACKGROUND: Many factors contribute to the high variability of doses delivered to the lungs of patients using metered dose inhalers (MDIs). Relatively little attention has been paid to the contribution to this variability of the way in which the MDI is handled before the inhalation manoeuvre. Instruction leaflets often recommend procedures at odds with those used for in vitro testing of the device. The standard protocol for in vitro assessment of salbutamol MDIs involves shaking the MDI vigorously for 30 seconds and wasting the first two actuations. Subsequent actuations are introduced into the testing device at five second intervals. Patient instructions do not include a recommendation to waste the first two actuations and recommend a delay of one minute between actuations. A series of experiments was performed to determine whether such differences might be important. METHODS: The total and "respirable" doses delivered by a salbutamol MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a multistage liquid impinger. The quantity of drug deposited on each stage was measured by an ultraviolet spectrophotometric method. The effect on the delivered dose of not shaking the canister, not wasting the first two doses, waiting 30 seconds between actuations, and using multiple rapid actuations was assessed by comparing the results with those obtained using the standard in vitro testing protocol. RESULTS: Compared with a standard protocol, it was found that not shaking the MDI before use reduced the total and "respirable" dose by 25.5% and 35.7%, respectively. The dose delivered when actuating the MDI at 30 second intervals was no different from that when intervals was no different from that when intervals of five seconds were used. Two actuations separated by one second had no effect on the total dose but reduced the "respirable" dose by 15.8%, while four rapid actuations reduced the total and "respirable" doses by 8.2% and 18.2%, respectively. Storing the MDI stem down reduced the total and "respirable" dose delivered in the first actuation by 25.0% and 23.3% despite shaking the MDI before use. CONCLUSIONS: MDIs containing drug in suspension must be shaken before use to resuspend the drug contained in the MDI, but shaking does not alter the composition of the suspension in the metering chamber and hence the dose in the first actuation remains low. Very rapid actuations can reduce the dose delivered per actuation, but salbutamol MDIs can be actuated immediately after a 10 second breath holding pause without affecting the dose delivered.

Albuterol↗
PubMed1995

Bronchiolitis. Origins and optimal management.

There is currently no prospect of an end to the annual epidemics of acute bronchiolitis, which cause considerable morbidity in previously healthy infants and are a major threat to the well-being of infants with underlying cardiac, respiratory or immunological disease. The respiratory syncytial virus remains the major cause of this condition, and prospects of developing a vaccine remain bleak while our understanding of the viral-host interaction remain incomplete. Treatment of patients with this condition has remained essentially unchanged for more than 30 years. Correction of hypoxia with oxygen, minimal handling to reduce the risk of exhaustion and careful noninvasive monitoring for complications such as apnoea and respiratory failure are the mainstays of management. Mortality in at-risk groups has fallen substantially during the past 10 years. This appears to be due to improved supportive and intensive care. The role of the antiviral agent ribavirin in the improved outcome, if any, is unclear. Other novel therapies have been tried, but none have been shown to significantly alter the natural history of the condition. The only effective preventive intervention currently available is strict adherence to measures designed to prevent nosocomial infection. This condition is likely to remain a continuing challenge to paediatricians for the foreseeable future.

Anti-Bacterial Agents↗
PubMed1994

Is tapping jet nebulisers worthwhile?

An in vitro system was used to study the effect of tapping a jet nebuliser on the dose delivered to patients. Using a 2 ml fill, effective drug delivery had ceased by 3 minutes but a further 38% was delivered to the filter by 5 minutes if the chamber was tapped.

Cromolyn Sodium↗
PubMed1994

Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection.

To study the cellular infiltrate that occurs within the airways of infants with respiratory syncytial virus bronchiolitis, samples of airways secretions were obtained by bronchial lavage from the lower respiratory tract of infants ventilated for this condition and from the upper airway of non-intubated infants with this disorder using nasopharyngeal aspirates. Cytospin samples were prepared so that differential cell counts could be performed on the cells obtained and alkaline phosphatase-antialkaline phosphatase immunocytochemical analysis of lymphocyte subsets was carried out using a panel of monoclonal antibodies, which included anti-CD3, anti-CD4, anti-CD8, anti-CD19, and anti-TcR gamma delta. Results from the lower and upper airways were similar. Large numbers of inflammatory cells were obtained, of which neutrophils accounted for a median of 93% in the upper airway and 76% in the lower airway. The numbers of CD8 positive cells detected were small and consistently less than CD4 positive cells, median CD4:CD8 ratios being 22.5:1 and 15:1 for the lower and upper airways. CD19 positive cells were rarely observed and no gamma delta positive lymphocytes were detected. These results indicate that neutrophils probably play a major part in causing symptoms in these infants. They do not support the concept that excessive lymphocyte mediated cytotoxic activity is principally responsible for the pathology in respiratory syncytial virus bronchiolitis.

Acute Disease↗
PubMed1992

Inhaled budesonide for chronic wheezing under 18 months of age.

The role of budesonide in controlling chest symptoms in infants was assessed. It was administered from a metered dose inhaler into a large volume spacer (Nebuhaler) with attached Laerdal mask. Twenty nine infants were recruited into a double blind crossover trial. Five defaulted. The remaining 24 (mean age 11 months) were assessed for the tolerance of the device, adverse effects, treatment failures, parental opinion, and daily symptom and treatment records. Twenty tolerated the modified Nebuhaler. One developed meningitis on placebo. Two experienced exacerbations on placebo. Eleven of 18 parents whose children completed the maximum treatment preferred budesonide to placebo and one preferred placebo. Mean symptom scores on budesonide were better than on placebo for the 15 children with complete symptom records. Fewer bronchodilator doses were used while taking budesonide. Our findings indicate that budesonide given in this way is an effective treatment for infants who may need prophylaxis for their wheezing.

Administration, Inhalation↗
PubMed1992

Drug delivery from holding chambers with attached facemask.

There is much interest in the use of holding chambers with an attached facemask to deliver aerosols from metered dose inhalers to infants. In order to study the influence of various design factors on the dose inhaled at different tidal volumes, a model was constructed in which a Starling ventilator was used to generate an inspiratory/expiratory cycle across a filter. Sodium cromoglycate was administered via a Nebuhaler and mask, Aerochamber and mask, and a coffee cup using tidal volumes of 25, 50, and 150 ml and the dose deposited upon the filter after six breaths was assayed using an ultraviolet spectrophotometric method. At the lowest tidal volume the high aerosol concentration in the smaller chamber enhanced drug delivery while at the highest tidal volume delivery was greatest from the larger chamber reflecting the larger dose available. Multiple breaths ensured that the dose inhaled per kilogram from each chamber was relatively large and also permitted significant drug delivery despite the introduction of a relatively large dead space between valve and filter. The dose delivered was increased by increasing the dose introduced into the chamber though not proportionately. These devices appear likely to deliver significant quantities of aerosol to infants, though drug delivery may be enhanced by the use of an appropriate valve.

Aerosols↗
PubMed1992

Drug delivery from jet nebulisers.

Maximising the rate of drug delivered in particles small enough to reach the lower respiratory tract from jet nebulisers may allow treatment times to be reduced and thus improve the acceptability of this form of treatment, particularly in very young patients. The role of various technical factors such as driving gas flow (DGF) in determining the rate of drug delivery was studied by constructing a model to simulate the respiratory pattern of individuals with different tidal volumes using a Starling ventilator and filter. Sodium cromoglycate was nebulised under a variety of operating conditions and the dose deposited on the filter was assayed. Tidal volumes of 50 and 400 ml were used at a frequency of 32 breaths per minute. Increasing the DGF from 4 to 8 l/minute produced a 264% increase in the rate of drug output but only a 32% increase in aerosol concentration. The mass of drug contained within droplets less than 5 microns increased from 26.8% to 70.8% of the total. The resultant increase in rate of drug delivery to the filter was 34% for a tidal volume of 50 ml and 79% for a tidal volume of 400 ml though the dose contained within droplets less than 5 microns increased by 4-fold at 50 ml tidal volume and by more than 5-fold at the higher tidal volume. Halving the solution concentration halved the rate of drug delivery. Increasing the tidal volume 8-fold from 50 to 400 ml resulted in an increase in the rate of drug deposition upon the filter of only 2.2 to 3-fold depending upon the DGF so that substantially more drug per ml inhaled was delivered at the lower tidal volume. These results are explained by considering factors that influence the rate of drug delivery. At low tidal volumes the rate of drug delivery at a given respiratory rate is dependent on the tidal volume and aerosol concentration. At high tidal volumes it is dependent upon aerosol concentration and volume of available aerosol and is essentially independent of tidal volume.

Aerosols↗
PubMed1992

New aerosol delivery system for neonatal ventilator circuits.

There is mounting evidence that a variety of drugs delivered as aerosols are likely to be of benefit in neonatal units. To avoid many of the problems associated with the use of jet nebulisers in ventilator circuits, a chamber was designed to be used in conjunction with a metered dose inhaler (MDI). The dimensions (4 cm x 11 cm) were chosen in an attempt to maximise drug delivery. In vitro studies were subsequently performed in order to determine the optimum operating conditions. Sodium cromoglycate delivered via this system was collected on a filter placed between the tip of an endotracheal tube and a model lung. The dose delivered was determined by means of an ultraviolet spectrophotometric assay. Using a Draeger Babylog 8000 ventilator it was found that drug delivery as maximised by actuating the device just before the inspiratory cycle when the chamber was placed adjacent to the endotracheal tube and by using a long (one second) inspiratory time. Under these conditions 1.5-2% of the original dose was deposited upon the filter at tidal volumes of 11-22 ml. When considered in terms of body weight this is many times the equivalent dose delivered to adults from an MDI. Effective drug delivery to the filter was confirmed using a radiolabelled aerosol. Radiolabelled studies delivering aerosol to the lungs of intubated rabbits demonstrated that deposition aerosol was distributed uniformly between lobes when corrected for the weight of each lobe. In conclusion, the device appears likely to deliver significant, reproducible quantities of drug to the lower respiratory tract while being simple to use.

Aerosols↗
PubMed1991

Unexpected side-effects of inhaled steroids: a case report.

An asthmatic child is presented who developed a cushingoid appearance with evidence of adrenal suppression and growth impairment while on low dose inhaled topical steroids. When the inhaled steroids were replaced by inhaled sodium cromoglycate his adrenal function recovered while his appearance and growth returned to normal. This report indicates that there are some children who are at risk of developing side-effects on doses of inhaled topical steroids normally considered to be entirely safe.

Administration, Inhalation↗