Cross-sectional study of bone density in asthmatic children.

The emphasis in treatment of asthma in children has shifted from bronchodilators to inhaled anti-inflammatory medications, including inhaled corticosteroids (ICS). Children with chronic asthma and moderate to severe symptoms have been targeted as particularly deserving of maintenance therapy with ICS. We have previously reported a cross-sectional study of bone density in children treated with ICS. There was no significant difference between the total bone density of asthmatic patients and controls. We sought to extend the information available on bone density in asthmatic children by evaluating 15 asthmatic subjects taking daily ICS (beclomethasone dipropionate) and comparing them with age- and sex-matched controls. We compared total and regional bone density, bone age, and calcium intakes in these subjects. Asthmatic subjects were on ICS for 4-60 months, with doses ranging from 200 to 450 micrograms/day. There was no significant difference between asthmatics and matched controls for height, weight, % RDA Ca2+, or bone age. The asthmatic subjects had bone density (total and regional measurements) equivalent to their controls. These results provide additional support for the safety of low-dose ICS on bone density in asthmatic children.

Longitudinal assessment of bone mineral density in children with chronic asthma.

BACKGROUND: With the emphasis on asthma as a chronic inflammatory process, the management of moderate to severe asthma, even in the pediatric population, has shifted to the regular use of inhaled anti-inflammatory agents, including inhaled corticosteroids. Accompanying the use of these agents has been the precaution that long-term use may have subtle or potential side effects, including growth suppression or decreased bone mineral deposition. OBJECTIVE: We sought to study the effects of inhaled anti-inflammatory agents on bone mineral density accumulation in growing asthmatic children. Included in this report is the longitudinal acquisition of bone mineral density in children with moderate to severe asthma. METHODS: Bone mineral density in normal and asthmatic children was measured longitudinally by dual-energy absorptiometry. Bone densitometry was determined twice over a 7- to 16-month period in 21 asthmatic children and a 13- to 60-month period in 14 normals. These children with two longitudinal visits were compared with a group of 107 normal children who had a single bone mineral density measurement. RESULTS: Nineteen of 21 asthmatic children used regular inhaled corticosteroids during the interval visits. The majority of the asthmatic boys had bone mineral density measurements, at both visits, that were at a higher percentile than normal boys with two visits. Asthmatic girls had bone density measurements at percentiles not significantly different than normal girls with two visits. CONCLUSIONS: The advancement of bone mineral density in asthmatic children provides support for the safety of inhaled anti-inflammatory medications on bone mineral density in children with significant asthma.

The usefulness of questionnaire-derived information to predict the degree of nonspecific bronchial hyperresponsiveness.

Nonspecific bronchial hyperresponsiveness (BHR) is a hallmark of clinical asthma, but can be present in nonasthmatics as well. The diagnosis of asthma is based on clinical grounds, and no laboratory procedure can definitely establish its presence. This poses a problem in studies of asthma. If epidemiological studies are to provide valid information, the tools used must have a relative degree of predictive or diagnostic ability. This report determined whether the American Thoracic Society-Division of Lung Disease (ATS-DLD) respiratory questionnaire has the ability to predict different degrees of non-specific BHR. In the years 1983-1990, when the ATS-DLD questionnaire was used in our Natural History of Asthma study, 192 subjects completed the ATS-DLD questionnaire and underwent a standardized methacholine challenge. A recursive partitioning analysis of the ATS-DLD questionnaire was able to predict which questions would likely be answered if the subject had nonspecific bronchial reactivity to inhaled methacholine of 100 and 200 breath units. Positive responses for questions concerning treatment for asthma, wheezing, or shortness of breath, and emergency treatment for asthma predicted the presence of increased bronchial reactivity.

Evaluation of growth hormone secretion in children with juvenile rheumatoid arthritis and short stature.

Children with juvenile rheumatoid arthritis (JRA) often exhibit delayed skeletal development. Previous evaluations of growth hormone (hGH) levels in these children have used single-value blood determinations. We sought to extend information on possible hGH deficiency in children with short stature and JRA by measuring 24-hour hGH pulsatile secretion. Five children with JRA were identified as having a height less than the 3rd percentile, and one child with a height at the 25th percentile. Three of these had abnormally low 24-hour serum hGH secretion. Two underwent a 24-month trial of human recombinant hGH; both exhibited only marginally accelerated growth. These results suggest that children with JRA and persistent short stature may have low hGH secretion without an adequate physiologic response to exogenous hGH administration.

Longitudinal measurement of airway hyperresponsiveness in selected subjects with persisting pulmonary symptoms.

The relationship between airway hyperresponsiveness and pulmonary symptoms was examined longitudinally in 52 subjects. Subjects were part of a larger study, the Natural History of Asthma, and had repeated measures of airway hyperresponsiveness using methacholine. Atopy was determined using skin tests and serum IgE levels. The subjects completed a standardized respiratory questionnaire. Each subject reported respiratory and pulmonary symptoms at either their initial or follow-up visit. The subjects did not, however, have a physician-confirmed diagnosis of asthma. Subjects were divided into groups according to the current status of their respiratory symptoms. The four groups included subjects who were initially normal but developed respiratory symptoms at follow-up; subjects who had symptoms at all visits; subjects with respiratory symptoms at their initial visit but who had no symptoms at follow-up; and subjects who had respiratory symptoms prior to their initial visit and who did not have a recurrence during follow-up. There was no statistical difference in airway hyperresponsiveness, IgE, or skin test scores at the initial visits. Subjects who had airway responsiveness were significantly more atopic than subjects who did not have airway responsiveness. Subjects were classified as "consistently positive," "variable," or "consistently negative" responders according to the pattern of methacholine-induced airway hyperresponsiveness. Overall, among the four groups, 33% were consistently positive at all visits, 43% were variable, and 22% were consistently negative. Airway hyperresponsiveness was statistically associated with atopy, but not necessarily associated with questionnaire-based respiratory symptomatology. These factors need to be considered in epidemiological studies of asthma utilizing respiratory questionnaires.

Longitudinal changes in bronchial hyperresponsiveness in asthmatic and previously asthmatic children.

To determine if nonspecific bronchial hyperresponsiveness is present to the same degree in previously asthmatic children compared with currently asthmatic children, a longitudinal study was conducted. On the basis of a standardized respiratory questionnaire, 139 children from asthmatic families, between the ages of 6 and 21 years, were identified. Subjects had skin tests, a serum IgE level, and a methacholine challenge test. IgE and skin tests demonstrated atopy in both the previously and currently asthmatic children, which persisted over time. Bronchial hyperresponsiveness within the asthmatic children was not significantly different between visits. Previously asthmatic children did have significantly decreased airway hyperresponsiveness over time. Age did not affect the results of the bronchial hyperresponsiveness in the currently asthmatic children. Currently asthmatic children, however, were significantly more atopic when compared with previously asthmatic children at their initial evaluation. Currently asthmatic children were also more bronchial responsive and remained so over time. Bronchial hyperresponsiveness is persistent in children with current asthma symptoms.

Estimation of bone mineral density in children with juvenile rheumatoid arthritis.

Bone mineral content of different areas of the skeleton was measured by dual photon absorptiometry in 20 children with juvenile rheumatoid arthritis (JRA) and compared to 20 age and sex matched healthy children. Spinal density was similar in both groups in prepubertal children but decreased in the postpubertal girls with JRA. Total bone density was also decreased in the postpubertal girls. Six children with JRA had repeat scans 12 to 24 months later; in 3 children total bone mineral content increased significantly with an intensive management program. Our study suggests that bone mineral density does not show a pubertal increase in children with JRA, as it does in healthy children.

Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents.

Nonspecific bronchial reactivity (BR) is commonly associated with asthma. It can be found, however, in subjects with allergic rhinitis. Studies have not been done looking at changes in nonspecific BR in allergic children over time. Therefore, we report on our longitudinal study of BR in allergic children and adolescents. The reported subjects are part of a larger ongoing study in a selected population of families with asthma and of twins. Initiated in 1972, the subjects reported in this study are subjects who have had at least one follow-up visit through 1989 and did not have asthma, but had allergic histories at either their initial visit or follow-up visits. Subjects completed a questionnaire, had skin tests, determination of a serum IgE level, and a determination of nonspecific BR with a methacholine challenge. Subjects were 6 years of age or older or 21 years of age or younger at initial visit. Subjects from families with asthma (N = 76; mean age, 12.09 years; +/- 4.6 SD) and twins (N = 36; mean age, 11.81 years; +/- 3.81 SD) were followed longitudinally, and their age at follow-up visits was not restricted. In this study we observed that, of 106 subjects, 66% initially demonstrated nonspecific BR. At their first and second follow-up visits, 70.4% and 61.3% demonstrated persistence of their BR. These data demonstrate that allergic children and adolescents have increased nonspecific BR. There was not a significant loss of BR over time in the studied subjects.