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Biomedical subjects

C M Mellis

Publications and source records attributed to C M Mellis.

At least 19 recordsLinked to original sources

The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand.

OBJECTIVE: To formulate recommendations for the role of corticosteroid therapy in the management of childhood asthma. DATA SOURCES: The recommendations are based on a review of the available literature and a variety of review articles on the efficacy and safety of corticosteroid therapy supplemented by personal experience in managing children with asthma. DATA SYNTHESIS: 1. Preventive therapy. Sodium cromoglycate should be considered first-line treatment. Inhaled corticosteroids are indicated in children who fail to achieve control on this therapy or those with severe disease. An initial dosage of 400-600 micrograms/day is recommended with subsequent variation in dosage related to clinical response. Large volume spacers can be used to improve aerosol delivery and minimise side effects. Indications for specialist assessment include: use of inhaled corticosteroids in children under 3 years of age; the requirement for high dose therapy (greater than 600 micrograms/day); or the need for regular oral corticosteroids. 2. Acute severe asthma. Systemic corticosteroid therapy is a valuable adjunct in the treatment of acute severe asthma and can be used safely in the short term. The efficacy of high dose inhaled corticosteroids in the management of acute severe asthma requires further evaluation. The need for systemic corticosteroid therapy signals the need for reassessment of that child's usual maintenance therapy. CONCLUSION: These recommendations are presented as a guide to the use of corticosteroid therapy in childhood asthma. In the individual child, the benefits of therapy need to be weighted against the possible risks, with the aim of maintaining good asthma control with the minimum dose of corticosteroid.

Asthma

Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis.

The aim of this study was to assess the prognostic significance of mucoid and non-mucoid isolates of Pseudomonas aeruginosa (muPs and non-muPs) from the sputa of patients with cystic fibrosis (CF). Eighty-one children with CF who coughed up sputum daily were recruited and followed over 12 months with frequent sputum cultures. At the end of this observation period they were classified to one of three age-matched groups. In 50 mPs was isolated on one or more occasions; 19 grew non-muPs but not muPs, and 12 grew no isolates of Ps aeruginosa. These 81 children and adolescents were followed for a further 8 years or until they died. Twenty-one (42%) of the muPs patients died compared with two (11%) of the non-muPs and one (8%) of the no Ps patients (P less than 0.01). Stepwise regression indicated that forced expiratory volume in 1 second (FEV1) had the main predictive effect but that age, Shwachman score and muPs also had a predictive effect. Identification of mucoid forms of Ps aeruginosa is an unfavorable prognostic factor but the isolation of non-mucoid strains does not appear to be any more important than the isolation of other common respiratory pathogens.

Adolescent

A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.

The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.

Child, Preschool

Toward a definition of asthma for epidemiology.

Because there is no "gold standard" for defining asthma for epidemiology, we have defined current asthma as bronchial hyperresponsiveness (BHR) plus recent wheeze (in the 12 months prior to study). To describe the characteristics of groups categorized by these measurements, we studied two samples of children aged 7 to 12 yr: 210 from a population sample and 142 self-identified asthmatics. Bronchial responsiveness to histamine was measured by the rapid method, respiratory symptom history, and asthma medication use by self-administered questionnaire to parents and atopy by skin prick tests to 14 allergens. Children recorded daily Airflometer readings and symptom scores for 2 wk. Children with current asthma had more severe bronchial responsiveness, greater Airflometer variability, more symptoms, more atopy (particularly to house dust mites), and used more asthma medication than children with BHR or recent wheeze alone. Children with BHR, but not with recent wheeze, were intermediate between the current asthma and normal groups in terms of bronchial responsiveness, Airflometer variability, and atopy. Children with recent wheeze and normal responsiveness differed from the normal group only in symptoms and medication use. Our definition of current asthma discriminates a group of children that is clearly different in terms of both clinical features and physiologic measures. As such, it is the most useful definition to date for measuring the prevalence of clinically important asthma in populations.

Asthma

Asthma: diagnosis and management in the very young child.

Most wheezy infants do not have a significant medical problem, and most will outgrow the condition in early childhood. A small proportion, however, have troublesome asthma and suffer significant morbidity (such as severe episodes of breathlessness and persistent distressing cough, and are often admitted to hospital). These infants should be offered appropriate asthma medications by inhalation (Table 4) to which most will respond. Although many currently use home nebulisers, alternative inhalation devices (especially the MDI/spacer/face mask) should be encouraged. A few wheezy infants will have a major underlying congenital malformation. Ruling out this group of conditions is essential before embarking on any asthma drug therapy.

Asthma

The cost of asthma in New South Wales.

OBJECTIVE: To determine the economic cost of asthma to the New South Wales community. DESIGN: Direct costs (both health-care and non-health-care) plus indirect costs (loss of productivity) were estimated from various sources to assess retrospectively the dollar costs of asthma. Intangible costs (such as quality of life) were not included. SETTING: Estimates of costs were made at all levels of medical care of asthma patients, including inpatient and outpatient hospitalisations, emergency department visits, and visits to general practitioners and specialist physicians, plus costs of pharmaceuticals, nebulisers and home peak-flow monitoring devices. The cost of time lost by the patient attending for medical visits and loss of productivity due to absence from employment as a result of asthma were also included. RESULTS: The total cost of asthma in New South Wales was $209 million in 1989. This was made up of $142 million in direct health-care costs, $19 million in direct non-health-care costs and $48 million in indirect costs. CONCLUSION: Although we believe that our estimate is an underestimate of the true dollar cost of this disease to the community, it represents $769 per asthmatic person per year, assuming a current prevalence rate for asthma in New South Wales of 6%. The cost effectiveness of any new treatment of asthma should be estimated to ensure that the economic cost to the community does not rise unnecessarily.

Adult

Cystic fibrosis.

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Australia

Edetate sodium aerosol in Pseudomonas lung infection in cystic fibrosis.

In vitro and animal experimental data suggest the combination of edetate sodium (EDTA) by aerosol plus oral antimicrobials might be effective in the treatment of chronic Pseudomonas infection in patients with cystic fibrosis (CF). For six months we studied the effects of edetate sodium administered by ultrasonic nebulizer to ten children with CF and chronic Pseudomonas aeruginosa infection in a double-blind, placebo-controlled, crossover study. The children had evidence of mild to moderate disease at entry in the study, with a mean (+/- SD) forced expiratory volume in the first second of 85% (+/- 18%) of the predicted value and a mean (+/- SD) Shwachman-Kulczycki score of 83 (+/- 7)/100. Each child was on a three-month regimen of aerosolized edetate sodium plus oral tetracycline twice daily followed by three months of placebo aerosol plus tetracycline or vice versa. Progress was assessed by measurement of pulmonary function, physical examination, and sputum cultures at four weekly intervals, plus chest roentgenograms on entry and after each of the three-month treatment periods. Daily symptoms were assessed using a diary card system. Two patients could not complete the study, one because of severe respiratory relapse, the other because of antibiotic side effects. Of the remaining eight patients, none showed any improvement in pulmonary function, weight gain, or growth acceleration, and none was rendered free of Pseudomonas lung infection. Daily symptom scores and chest roentgenograms were unaltered by edetate sodium. We conclude that the combination of aerosol edetate sodium plus oral tetracycline over a three-month period does not modify the clinical course nor the pulmonary flora in patients with CF with chronic Pseudomonas lung infection.

Administration, Oral

Skin test, RAST and clinical reactions to peanut allergens in children.

One-hundred-and-four children were skin-tested with four peanut-allergen preparations, a commercial extract, extracts of raw and roast peanuts prepared by NH4HCO3 extraction, and a wheatgerm lectin-reactive glycoprotein obtained by affinity chromatography. The presence of symptoms after ingestion of peanut or peanut products was also recorded. The roast allergen extract provided the greatest specificity with eight symptomatic children having a positive skin test and only one positive skin-test reaction in an asymptomatic child in the group of 104 children tested. Despite differences in the incidence of skin-test reactions there was a strong correlation between raw, roast and commercial RAST suggesting common allergens were being identified by circulating IgE. Clinical sensitivity was observed particularly in younger children with 75% of the children being under 4 years of age. A positive roast skin test or a RAST test adds confirmation to the clinical history of allergic reactions to peanuts.

Adolescent

The relationship between atopy and salivary IgA deficiency in infancy.

In a prospective study, infants born to atopic parents had a significantly higher prevalence of salivary IgA deficiency at all ages studied than control infants, and the mean non zero IgA level of the potentially atopic infants was significantly lower at 8 and 12 months than of control infants. Of the infants with atopic parents, the prevalence of IgA deficiency was not significantly greater in those who manifested atopic disease during the study period than in those who did not, but the levels were significantly lower at 4 months.

Aging

Skin test reactivity and clinical allergen sensitivity in infancy.

We examined the development of skin test reactivity and clinical allergen sensitivity in infancy. Seventy-eight infants of atopic parents were skin prick tested every 4 mo from 4 to 16 mo and an additional 57 of these infants were tested at 20 mo. Wheal diameters were recorded for histamine (1 mg/ml) and specific allergen reactions by use of cow's milk, egg albumen, wheat, and Dermatophagoides pteronyssinus. The histamine mean wheal diameter was significantly lower at 4 and 8 mo compared to the older infants. Infants at 20 mo also had significantly smaller wheals than adult controls. Histamine reactivity was greater in atopic infants at 4 mo compared to nonatopic infants. Reactions to ingested allergens occurred early in infancy but were usually transient. There was a good correlation between skin sensitivity and clinical immediate-food hypersensitivity to the food concerned. In contrast, reactions to the inhaled allergen, D. pteronyssinus, occurred later in infancy, were persistent, and increased in size with age. Although we found no relationship between the acquisition of skin reactivity to D. pteronyssinus and development of the respiratory symptoms of atopic disease during the period of the study, it is possible that inhaled allergen reactivity may be related to respiratory symptoms at later ages. Despite the decreased histamine reactivity in early infancy, skin tests proved reliable markers of clinical disease in ingested but not inhalant allergen sensitivity.

Allergens

Relationship of diet in the development of atopy in infancy.

We examined the relationship of diet to the development of atopic manifestations in a group of infants with an immediate family history of atopy, followed prospectively from birth for up to 20 months of age. There was no relationship between the development of atopic dermatitis, rhinitis and wheeze and either 2 or 4 months exclusive breast feeding, or the introduction of cow's milk or solids in the first 4 months of life. In addition there was no relationship between the introduction of milk, egg or wheat into the diet and the development of skin-test positivity to these foods. In fact, five infants developed positive skin tests to the food prior to its introduction into the diet, suggesting exposure via maternal breast milk. Thus we have been unable to show a protective effect of either breast feeding or cow's milk or solid avoidance on the development of atopic disease in infancy.

Age Factors

A prospective study of the clinical manifestations of atopic disease in infancy.

We prospectively followed a group of infants with a family history of atopy, from birth for up to 20 months of age. All infants were seen every 4 months and a history, physical examination and skin tests obtained. Atopic dermatitis and rhinitis occurred in about half the infants at some time during the study, while wheezing occurred in about a quarter. Both atopic dermatitis and rhinitis were more common in the first 12 months whereas wheezing occurred later and increased in prevalence with age. Defining atopy by the presence of atopic dermatitis or positive skin tests, only immediate food reactions were significantly associated with atopic infants. In contrast, rhinitis, a single episode of wheezing, colic, vomiting and delayed food reactions were not associated with atopy and thus are unlikely to be due to IgE-related mechanisms during infancy.

Dermatitis, Atopic