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Biomedical subjects

M L Everard

Publications and source records attributed to M L Everard.

At least 19 recordsLinked to original sources
PubMed2001

The effect of ribavirin to treat previously healthy infants admitted with acute bronchiolitis on acute and chronic respiratory morbidity.

The role of ribavirin in the treatment of acute bronchiolitis is controversial. It has been suggested that the use of ribavirin may be of benefit during the acute illness and may reduce subsequent recurrent respiratory morbidity. This randomized, double-blind, placebo-controlled study was designed to determine whether ribavirin administered during the acute illness would have an influence on respiratory morbidity during both the acute illness and during the following year. Bronchial reactivity 6 months after the acute illness was also assessed. Forty previously well infants with moderately severe acute bronchiolitis were recruited during three winter epidemics. Subjects received study medication for 18 h a day. Management was otherwise unaltered. Subjects were evaluated daily by the investigator and subsequently assessed at 6 weeks, 6 months and 1 year following the acute illness. Assessment of bronchial hyper-responsiveness was assessed at 6 months of age using total body plethysmography and an established ultra-sonically nebulized distilled water challenge. A total of 40 patients (21 ribavirin, 19 placebo) were entered into the study. The two groups did not differ with respect to age, gender or clinical severity on entry to the trial. No significant differences were identified in the rate of clinical improvement over the first 24 h, the time to discharge, bronchial responsiveness at 6 months of age, frequency of significant respiratory symptoms over the first year of life and the frequency of prescribed bronchodilators and inhaled steroids during the year of follow-up. This study was unable to demonstrate any clinical benefit from the use of ribavirin in the acute illness or during subsequent follow-up for 1 year.

Antiviral Agents↗
PubMed2001

Survey of respiratory sounds in infants.

BACKGROUND: Over the last decade there has been an apparent increase in childhood wheeze. We speculated that much of the reported increase may be attributed to the term wheeze being adopted by parents to describe a variety of other forms of noisy breathing. AIMS: To investigate terminology used by parents to describe their children's breath sounds. METHODS: An interview was carried out with the parents of 92 infants with noisy breathing, beginning with an open question and then directed towards a more detailed description. Finally, the parents were asked to choose from a wheeze, ruttle, and stridor on imitation by the investigator and video clips of children. RESULTS: Wheeze was the most commonly chosen word on initial questioning (59%). Only 36% were still using this term at the end of the interview, representing a decrease of one third, whereas the use of the word ruttles doubled. CONCLUSIONS: Our results reflect the degree of inaccuracy involved in the use of the term wheeze in clinical practice, which may be leading to over diagnosis. Imprecise use of this term has potentially important implications for therapy and clinical trials.

Communication↗
PubMed2001

Exhaled nitric oxide is reduced in infants with cystic fibrosis.

BACKGROUND: Exhaled nitric oxide levels are low in patients with cystic fibrosis (CF), despite the chronic inflammation present in the airways. This study aimed to determine whether levels of exhaled nitric oxide were reduced prior to the onset of respiratory symptoms in infants with CF. METHODS: The levels of exhaled nitric oxide were measured using a chemiluminescence analyser in five infants with CF and 11 healthy control subjects, both groups having a mean age of 48.6 days. RESULTS: Mean levels of exhaled nitric oxide were significantly lower in infants with CF than in the control group (4.9 ppb v 12.1 ppb; p=0.01). CONCLUSIONS: This finding may be the key to understanding the inflammatory processes in early cystic fibrosis and may lead to novel treatment approaches.

Breath Tests↗
PubMed2000

Anti-cholinergic drugs for wheeze in children under the age of two years.

BACKGROUND: Wheeze in infancy and early childhood is common and appears to be increasing though the magnitude of any increase is unclear. Most wheezing episodes in infancy are precipitated by respiratory viral infections. Treatment of very young children with wheeze remains controversial. Anti-cholinergics are often prescribed but practice varies widely and the efficacy of this form of therapy remains the subject for debate. OBJECTIVES: Wheeze in infancy and early childhood is common and appears to be increasing. Most wheezing episodes in infancy are a result of viral infection. Bronchodilator medications such as beta2-agonists and anti-cholinergic agents are often used to relieve symptoms, but patterns of use vary. The objective of this review was to assess the effects of anti-cholinergic therapy in the treatment of wheezing infants. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and the reference lists of articles. We contacted researchers in the field and industry sources. SELECTION CRITERIA: Randomised trials that compared anti-cholinergic therapy with placebo or beta2-agonists in wheezing children under two years of age. Children with acute bronchiolitis and chronic lung disease were excluded. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion and quality of trials were assessed independently by two reviewers. MAIN RESULTS: Six trials involving 321 infants in three different settings were included. Compared with beta2-agonist alone, the combination of ipratropium bromide and beta2-agonist was associated with a reduced need for additional treatment, but no difference was seen in treatment response, respiratory rate or oxygen saturation improvement in the emergency department. There was no significant difference in length of hospital stay between ipratropium bromide and placebo; or between ipratropium bromide and beta2-agonist combined compared with beta2-agonist alone. However, combined ipratropium bromide and beta2-agonist compared to placebo showed significantly improved clinical scores at 24 hours. Parents preferred ipratropium bromide over nebulised water or placebo for relief of their children's symptoms at home. REVIEWER'S CONCLUSIONS: There is not enough evidence to support the uncritical use of anti-cholinergic therapy for wheezing infants, although parents using it at home were able to identify benefits.

Asthma↗
PubMed2000

When a "wheeze" is not a wheeze: acoustic analysis of breath sounds in infants.

Epidemiological studies indicate that the prevalence of "wheeze" is very high in early childhood. However, it is clear that parents and clinicians frequently use the term "wheeze" for a range of audible respiratory noises. The commonest audible sounds originating from the lower airways in infancy are ruttles, which differ from classical wheeze in that the sound is much lower in pitch, with a continuous rattling quality and lacking any musical features. The aim of this study was to clearly differentiate wheeze and ruttles objectively using acoustic analysis. Lung sounds were recorded in 15 infants, seven with wheeze and eight with ruttles, using a small sensitive piezoelectric accelerometer, and information relating to the respiratory cycle was obtained using inductive plethysmography. The acoustic signals were analysed using a fast fourier transformation technique (Respiratory Acoustics Laboratory Environment programme). The acoustic properties of the two noises were shown to be quite distinct, the classical wheeze being characterized by a sinusoidal waveform with one or more distinct peaks in the power spectrum display; the ruttle is represented by an irregular nonsinusoidal waveform with diffuse peaks in the power spectrum and with increased sound intensity at a frequency of <600 Hz. It is important for clinicians and epidemiologists to recognize that there are distinct types of audible respiratory noise in early life with characteristic acoustic properties.

Fourier Analysis↗
PubMed1999

IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis.

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.

Acute Disease↗
PubMed1999

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing.

BACKGROUND: Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS: Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS: Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION: Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.

Acute Disease↗
PubMed1998

Treatment of childhood asthma. Options and rationale for inhaled therapy.

Epidemiological studies suggest the prevalence of asthma is increasing, though some remain sceptical as to the magnitude or indeed the presence of an increase. However, despite improved diagnosis and the availability of the potent drugs now available there remains considerable respiratory morbidity associated with asthma. It is clear from a number of studies that failure to deliver drugs to the lungs when using inhaler devices is a factor contributing to this high level of morbidity. Failure of drug delivery may result from the prescribing of inappropriate devices, failure to use devices appropriately or failure to comply with a treatment regimen. For most of the currently available forms of asthma therapy there are significant advantages to be gained from administering them in aerosol form. The benefits to be derived from administering these drugs as an aerosol include a rapid onset of action for drugs such as beta-agonists and a low incidence of systemic effects from drugs such as beta-agonists and corticosteroids. Over the past 25 years our understanding of the nature of asthma has changed. Though this has been reflected in the emphasis on inhaled corticosteroid therapy in recent guidelines, it has not been reflected in the range of inhaler devices available. Manufacturers continue to place drugs such as corticosteroids in the same devices as short acting beta-agonists even though the requirements for these different drug classes are very different. It is likely that this contributes to suboptimal therapeutic responses with inhaled corticosteroids. However, the variability associated with current delivery systems is relatively small compared with the variability introduced by poor compliance. There is no work currently available to indicate how the use of cheap disposable devises which do not incorporate any form of positive feedback influence compliance with inhaled steroids. Optimising aerosolised drug delivery in childhood involves consideration of the class of drugs, the particular drug within a class but more importantly, the age and abilities of the child. Devices must be selected to suit a particular child's needs and abilities. Devices utilising tidal breathing are generally used such as spacing chambers or, less commonly these days, nebulisers. A screaming or struggling child, or failure to use a closely fitting mask, reduces drug delivery to the lungs enormously. Failure to respond to inhaled therapy in early childhood may be attributable to failure of drug delivery. Drug delivery in early childhood using current devices remains more an art than a science.

Administration, Inhalation↗
PubMed1997

Flow early in the inspiratory manoeuvre affects the aerosol particle size distribution from a Turbuhaler.

Several in vitro and in vivo studies have emphasized the importance of generating a high inspiratory flow when using a dry powder inhaler. Little attention has been paid to the influence of the inspiratory flow profile on the particle size distribution contained in aerosols generated by these devices. The internal volume of a device such as the Turbuhaler is small compared with a vital capacity breath and it is possible that all the powder has been drawn from the device before peak inspiratory flow has been achieved, particularly if the time to peak inspiratory flow is prolonged. A series of experiments were performed to assess the effect of different flow profiles through the Turbuhaler, each with a peak flow of 60 1 min-1. A 400 microgram budesonide Turbuhaler was enclosed in a chamber allowing air to pass unimpeded through the dosing channels and entrainment ports. A large three-way tap was used to blow powder from the device across a Malvern Mastersizer laser particle sizer which produced a profile of the particle size distribution within the aerosol. The rate of increase in flow through the Turbuhaler was determined by the rate at which the three-way tap was turned, and recorded by means of a pneumotachograph. The rate of increase in flow was found to significantly affect the particle size-distribution within the aerosol. Failure to attain a flow of 30 1 min-1 before 150 ml of air had passed through the device resulted in the aerosol volume median diameter increasing from less than 6.6 microns to greater than 45.3 microns. These results indicate that flow during the initial part of the inspiratory effort may be important in determining the characteristics of the aerosol generated by a dry powder inhaler. With more sophisticated equipment, it might be possible to explore the relationship between flow profile and particle size distribution generated by dry powder devices in more detail.

Adult↗
PubMed1997

Lung deposition from the Turbuhaler in children with cystic fibrosis.

Drug delivery to patients using dry powder inhalers, such as the Turbuhaler, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m (99mTc)-labelled budesonide was performed in order to determine the effect of age on delivery. Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99mTc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler. Immediately afterwards they inhaled from a noncommercial Turbuhaler containing budesonide labelled with 99mTc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach. As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged > 6 yrs use the Turbuhaler, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics.

Adolescent↗
PubMed1997

Comparison of drug delivery from conventional versus "Venturi" nebulizers.

Attempts to improve drug delivery from conventional jet nebulizers have included the use of storage systems to reduce drug wastage during exhalation. Venturi nebulizers enhance drug delivery during inhalation, reducing treatment times and drug wastage. This study investigated the effect of age on inhaled dose from a conventional jet nebulizer (Acorn) used both with and without a storage chamber (Mizer), compared to two Venturi nebulizers (Ventstream and Pari LC). Filters were attached to the four nebulizer systems, containing salbutamol, and 18 children with cystic fibrosis (3-16 yrs) inhaled through these devices. The quantity of drug collected on the filter was assessed using ultraviolet spectrophotometry. The particle size distribution of the aerosol from each nebulizer system was measured using laser diffraction. Inspiratory filter deposition using the Acorn was lower than the Acorn with Mizer, and both Venturi nebulizers. Filter deposition using the Acorn with Mizer was lower than the Pari LC. No trend with age, height or weight was noted using any nebulizer. Aerosol particle size using the Ventstream was lower than the other nebulizer systems. Drug output from both Venturi nebulizers was more efficient than from the jet nebulizer, used with and without the storage chamber, during inhalation by children with cystic fibrosis. The inhaled dose did not change with the patient's age or size using both types of nebulizer.

Administration, Inhalation↗