Louis I. Landau

The natural history of childhood asthma to adult life.

A randomly selected group of 331 children who had started to wheeze in childhood and a control group of 77 children were prospectively studied clinically and physiologically from 7 to 21 years of age. Most subjects improved during adolescence and about 55% of those whose wheezing had started before 7 years and stopped before adolescence remained wheeze free. Forty-five per cent of subjects who had apparently ceased to wheeze at 14 years had minor recurrences of wheezing between 14 and 21 years of age. Fewer than 20% of those with persistent symptoms in childhood had become totally wheeze free during adolescence, although there was amelioration in symptoms. Girls did less well during adolescence than boys, so that there was no longer an increased preponderance of boys with increasing severity of asthma. Normal growth was achieved in all grades despite the persistence of symptoms in many cases. At 21 years of age features of airways obstruction were often found during an interval phase, especially in those who had more persistent symptoms.

Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood

Given the widely acknowledged inverse relationship between birth weight and blood pressure, a raised blood pressure in the offspring of smoking mothers as compared to those whose mothers did not smoke, would be anticipated by virtue of the reduction in birth weight associated with smoking during pregnancy. The objective of the present study was to test the hypothesis that maternal cigarette smoking during pregnancy has an effect on blood pressure in childhood independent of its effect on birth weight. Data was obtained from a prospective cohort study of 1708 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia, commenced at 16 weeks gestation with serial blood pressure measurements through early childhood. Statistically significant associations were found between maternal smoking during pregnancy and systolic blood pressure at age six, between birth weight and systolic blood pressure at ages three and six, and between maternal smoking during pregnancy and birth weight. The relationship between birth weight and blood pressure in early childhood differed significantly on the basis of maternal cigarette smoking or not during pregnancy. This differential relationship persisted after adjustment for the childs current weight and socio-economic status. We concluded that intra-uterine exposure to maternal cigarette smoking increased childrens blood pressure at age one through to age six. This was not wholly attributable to an effect on birth weight or confounding of the association between birth weight and subsequent blood pressure by the childs current weight or socio-economic factors. Furthermore, maternal smoking during pregnancy does not account for the acknowledged elevation in blood pressure associated with low birth weight. The present study is an exploration of a possible causal pathway underlying the birth weight/blood pressure association rather than simply a confirmation of such an association which has been detailed in many other papers.

Lung function, airway responsiveness, and respiratory symptoms before and after bronchiolitis.

Acute viral respiratory illness during infancy has been implicated as a precursor for subsequent lower respiratory morbidity in childhood. A prospective, longitudinal study of respiratory function, airway responsiveness, and lower respiratory illness during early childhood was performed in a cohort of 253 healthy infants to characterise those who experienced bronchiolitis. Seventeen infants (7% of the cohort), were given a diagnosis of bronchiolitis during the first two years of life with two (1%) requiring hospital admission. Seventy one per cent of those infants with bronchiolitis had a family history of atopy, 53% of asthma, and 29% had a mother who smoked cigarettes. These family history characteristics in this group with bronchiolitis were not different from the rest of the cohort. There were also no differences in the number of older siblings, the number breast fed, the duration of breast feeding, or socioeconomic status of the families between those that did and did not get bronchiolitis. Respiratory function was assessed at 1, 6, and 12 months of age. Maximum flow at functional residual capacity (VmaxFRC) was measured using the rapid thoracic compression technique. Resistance (Rrs) and size corrected compliance (Crs/kg) were obtained from a single brief occlusion at end inspiration. Airway responsiveness was assessed by histamine inhalation challenge and the provocation concentration of histamine resulting in a 40% fall on VmaxFRC from baseline (PC40) was determined. Respiratory measurements were ranked into terciles to assess the distribution of infants who developed bronchiolitis through the cohort. Cough and wheeze were noted to be frequent before the episode of bronchiolitis. This study has demonstrated that infants who develop bronchiolitis have evidence of pre-existing reduced respiratory function and lower respiratory symptoms. It is proposed that bronchiolitis, although potentially contributory, is not usually causative of subsequent lower respiratory morbidity.

Parental factors affecting respiratory function during the first year of life

In a prospective, longitudinal, population‐based cohort study of familial and environmental influences on the development of wheezing respiratory illness in early childhood, we identified infant length, weight, gender, and exposure to maternal cigarette smoking as significant determinants of lung function during the first year of life. A cohort of 237 infants (106 females: 131 males) was evaluated, and 496 lung function measurements were made between the ages of 1–12 months. Respiratory function was assessed using the rapid thoracic compression technique to obtain maximum expiratory flow at functional residual capacity (V′maxFRC). Parental history of asthma and smoking habits during pregnancy were obtained by questionnaire. Data were analyzed using a longitudinal random effects model. Infants with a parental history of asthma and/or in utero passive smoke exposure were compared to a reference group of infants who had no parental history of asthma and in whom neither parent smoked pre‐ or postnatally.

The Long-Term Effects of Breastfeeding on Child and Adolescent Mental Health: A Pregnancy Cohort Study Followed for 14 Years

OBJECTIVES To determine whether there was an independent effect of breastfeeding on child and adolescent mental health. STUDY DESIGN The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women and followed the live births for 14 years. Mental health status was assessed by the Child Behaviour Checklist (CBCL) at 2, 6, 8, 10, and 14 years. Maternal pregnancy, postnatal, and infant factors were tested in multivariable random effects models and generalized estimating equations to examine the effects of breastfeeding duration on mental health morbidity. RESULTS Breastfeeding for less than 6 months compared with 6 months or longer was an independent predictor of mental health problems through childhood and into adolescence. This relationship was supported by the random effects models (increase in total CBCL score: 1.45; 95% confidence interval 0.59, 2.30) and generalized estimating equation models (odds ratio for CBCL morbidity: 1.33; 95% confidence interval 1.09, 1.62) showing increased behavioral problems with shorter breastfeeding duration. CONCLUSION A shorter duration of breastfeeding may be a predictor of adverse mental health outcomes throughout the developmental trajectory of childhood and early adolescence.

Asthma from childhood at age 21: the patient and his disease.

Information was obtained from 336 21-year-olds who had begun wheezing before the age of 7 about their knowledge of asthma and its effect on their current life style. Two-thirds of the subjects were still symptomatic. A control group of 62 subjects was available for comparison. Knowledge about asthma was poor, particularly among those with less troublesome symptoms. Half of those with frequent episodic asthma and one-third with persistent asthma did not regard excess use of bronchodilator aerosols as potentially dangerous. Over three-quarters of those with persistent asthma were not receiving adequate treatment. One-third of third of those with persistent asthma were missing substantial time from work because of respiratory illness, and a similar proportion were restricting sporting activities. The incidence of smoking was disturbingly high in all asthma groups. The higher the number of cigarettes ever smoked and the higher the current tobacco consumption the less satisfactory was the progress of asthma. Both cigarette smoking and severity of asthma contributed to chronic production of sputum. Children and teenagers with asthma should be educated to seek more appropriate medical help and thereby reduce morbidity.

THE EFFECT ON GROWTH OF CHILDHOOD ASTHMA

ABSTRACT. Martin, A. J., Landau, L. I. and Phelan, P. D. (Department of Thoracic Medicine, Royal Childrens Hospital, Melbourne, Australia). The effect on growth of childhood asthma. Acta Paediatr Scand, 70:683,.–The effect on growth of asthma has been documented in a prospective study from age 7 to 21 years in a randomly selected group of 342 subjects. These subjects covered the whole spectrum of childhood wheezing. Growth suppression was first noted at 10 years of age in the more severely affected groups and was most marked at 14 years of age. By 21 years of age, all groups had achieved a height and weight not significantly different from control subjects. Growth delay occurred in children with more persistent asthma even if they had never received oral corticosteroid therapy but growth was more delayed in those receiving oral steroids. The effect of steroids was most significant in those with frequent episodic asthma whose asthma alone was probably not sufficiently severe to retard growth.

Nebulized gentamicin in children and adolescents with cystic fibrosis

A study of 29 children and adolescents with cystic fibrosis over 2 years showed some evidence of benefit from the twice daily inhalation of 20 mg nebulized gentamicin when compared to the inhalation of a nebulized saline mixture. Clinical symptoms, deterioration in pulmonary function, antibiotic usage, days in hospital and development of Pseudomonas aeruginosa in the sputum were recorded. There was no significant difference in antibiotic usage, days in hospital or clinical symptoms between the two regimes. Those subjects with P. aeruginosa in sputum showed significantly less deterioration in lung function over 2 years while using gentamicin aerosol. There was no difference in progress between the two treatment regimes for those subjects with P.aeruginosa in sputum at the beginning of the study, nor was there any difference in the number developing P. aeruginosa in sputum.

Atopy, eczema and breast milk fatty acids in a high-risk cohort of children followed from birth to 5 yr

Background: The incidence of atopic diseases such as eczema is increasing in westernized societies. The suggestion that there is a ‘protective’ association between the unique fatty acid composition of breast milk, particularly the omega‐3 (n‐3) and omega‐6 (n‐6) essential polyunsaturated fatty acid content, and the development of atopic disease in children was investigated in a cohort study of 263 infants born into families with a history of allergy (one or both parents had asthma, hayfever, eczema). The objectives of this study were to determine the lipid profile [specifically in relation to long‐chain polyunsaturated fatty acid (LC‐PUFA) composition] in maternal breast milk samples collected at 6 wk and at 6 months following birth, and to investigate the potential role of these fatty acids in modulating the phenotype of children at high genetic risk of developing atopic disease. Method: Breast milk samples were available from 91 atopic mothers at their childs ages of 6 wk and 6 months. These samples were analysed for the fatty acid spectrum. Analysis of variance was used to detect differences between groups of outcomes (no atopy or eczema, non‐atopic eczema, atopy, atopic eczema) at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to isolate the parameters producing the different results (F‐test, LSD test). For the exposure variables, n‐3 and n‐6 fatty acids are expressed as weight percentage and as a ratio (at both time‐points). Results: The fatty acid profiles of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of n‐6: n‐3 fatty acids in both 6 wk and 6 month milk samples was associated with non‐atopic eczema (p < 0.005) but not atopy alone or atopic eczema. Conclusion: We found milk fatty acids were a significant modulator of non‐atopic eczema but not atopy or atopic eczema in infants at 6 months. In mothers with a history of asthma, hayfever or eczema, their 6‐month‐old infants were more likely to develop non‐atopic eczema if their milk had a higher ratio of n‐6: n‐3 LC‐PUFA.

Generalized Bronchiectasis Due to Extensive Deficiency of Bronchial Cartilage

The clinical, radiological, and physiological findings in 16 patients with extensive bronchiectasis due to deficiency in bronchial cartilage are discussed. These features do not occur in other types of bronchiectasis and comprise a distinctive syndrome. The main clinical features are persistent cough and wheezy breathing. The symptoms are first noticed in infancy often after mild respiratory infection, but at times after measles or pneumonia. Most of the children develop chest deformity and clubbed fingers, and are small in stature. The radiological findings are pulmonary hyperinflation, air-filled dilated bronchi, and, bronchographically, the bronchi balloon during inspiration and collapse with expiration. Physiologically the outstanding features are gross increase in residual lung volume, severe impairment of maximum expiratory flow rates, especially at low lung volumes, a marked decrease in conductance in the upstream segment, poor static elastic recoil, and dynamic compliance which is frequency dependent. It is postulated that this syndrome is due primarily to extensive developmental deficiency of bronchial cartilage, with secondary recurrent respiratory infection.