C. M. Mellis

Clinical outcomes of newborn screening for cystic fibrosis.

AIM To determine how early diagnosis of cystic fibrosis, using neonatal screening, affects long term clinical outcome. METHODS Fifty seven children with cystic fibrosis born before neonatal screening was introduced (1978 to mid 1981) and a further 60 children born during the first three years of the programme (mid 1981 to 1984), were followed up to the age of 10. The cohorts were compared on measures of clinical outcome, including height, weight, lung function tests, chest x-ray picture and Shwachman score. RESULTS Age and sex adjusted standard deviation scores (SDS) for height and weight were consistently higher in children screened for cystic fibrosis than in those born before screening. At 10 years of age, average differences in SDS between groups were 0.4 (95% CI −0.1, 0.8) for weight and 0.3 (95% CI −0.1, 0.7) for height. This translates to an average difference of about 2.7 cm in height and 1.7 kg in weight. Mean FEV1 and FVC (as percentage predicted) were significantly higher in the screened cohort at 5 and 10 years of age, with an average difference of 9.4% FEV1(95% CI 0.8, 17.9) and 8.4% FVC (95% CI 1.8, 15.0) at 10 years. Chest x-ray scores were not different between the groups at any age, but by 10 years screened patients scored an average 5.3 (95% CI 1.2, 9.4) points higher on the Shwachman score. CONCLUSION Although not a randomised trial, this long term observational study indicates that early treatment made possible by neonatal screening may be important in determining subsequent clinical outcomes for children with cystic fibrosis. For countries contemplating the introduction of neonatal screening for cystic fibrosis, its introduction to some areas in a cluster randomised design will permit validation of studies performed to date.

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 cows 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.

Immediate food hypersensitivity reactions on the first known exposure to the food.

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.

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 cows 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 cows milk or solid avoidance on the development of atopic disease in infancy.

Fluticasone propionate 750 μg/day versus beclomethasone dipropionate 1500 μg/day: comparison of efficacy and adrenal function in paediatric asthma

BACKGROUND Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function. METHODS The efficacy and safety of FP 750 μg/day and BDP 1500 μg/day were compared in 30 children with persistent asthma (requiring 1000–2000 μg/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences. RESULTS There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI –6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: –0.06 (95% CI –0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods. CONCLUSIONS FP 750 μg/day is as effective as BDP 1500 μg/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.

A Prospective Study of the Clinical Manifestations of Atopic Disease in Infancy

ABSTRACT. 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.

A review of open biopsy for mediastinal masses

Objective: To review the recent experience with biopsied mediastinal lesions in children and to assess the impact of recent advances in imaging and surgical techniques on diagnosis.

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.

Mucoid Pseudomonas aeruginosa in cystic fibrosis

ABSTRACT. The relative importance of mucoid Ps. aeruginosa, non‐mucoid Ps. aeruginosa and absence of Ps. aeruginosa as indicators of the severity of lung disease was assessed in 82 age matched children and adolescents with cystic fibrosis. Both Shwachman score and forced expiratory volume in one second (FEV1) were significantly lower in subjects whose sputa yielded mucoid strains than in those whose sputa had no Ps. aeruginosa or those with non‐mucoid forms. Furthermore 29 of 32 patients (91%) with a Shwachman score below 80 and 31 of 37 (84%) with a FEV1 of less than 75% predicted had one or more positive cultures for mucoid Ps. aeruginosa. While identification of mucoid forms of Ps. aeruginosa in the respiratory tract of children and adolescents with cystic fibrosis is an unfavourable factor, non‐mucoid forms appear to be of no major significance.

Evaluation and Treatment of Chronic Cough in Children

The characteristic features of the five main causes of chronic or recurrent cough are elucidated, diagnostic considerations are presented, and treatment is outlined.