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.

Probability of asthma based on methacholine challenge.

Methacholine inhalation challenge has become an accepted test to determine the presence of airway hyperresponsiveness, a hallmark of asthma. To help physicians interpret the results of a methacholine challenge test in a clinical setting, we analyzed the test data of 1,105 subjects, asthmatics and nonasthmatics. Applying Bayes' theorem, a nomogram was constructed incorporating the prechallenge clinical diagnosis with the response to methacholine to give a posttest probability of the diagnosis of asthma. The resulting curves represent different levels of cumulative breath units at which a methacholine challenge can be considered positive. The results of a methacholine challenge test, in association with a physician's clinical assessment, can be a valuable tool in the diagnosis of asthma in those patients with an atypical history and/or physical examination.

Bone mineral density in normal and asthmatic children.

BACKGROUND: The largest increase in bone mass occurs during childhood and adolescence. A subnormal bone mass is associated with increased risk of fracture. Bone mass is influenced by height, age, race, exercise, and stage of puberty. It is adversely affected by chronic disease states and corticosteroid use. We performed a cross-sectional study of bone density in children with moderate to severe asthma who were treated with inhaled corticosteroids, inhaled cromolyn, oral corticosteroids, or a combination of these, and we compared them with normal children. METHODS: A cross-sectional study of bone density, measured either by dual-photon or dual-energy absorptiometry, was performed on 97 normal white and 30 asthmatic white children, aged 5 to 18. Average daily calcium intake, height, weight, and Tanner stage were determined. The total daily and lifetime doses of inhaled corticosteroids in children with asthma were calculated. T tests, multiple regression, chi square analysis, and analysis of covariance were performed. RESULTS: No significant difference in bone density was demonstrated between children with asthma and normal control subjects. No measure (including calcium intake, Tanner stage, daily or lifetime inhaled corticosteroid dose, or duration of illness), except for height and age, provided a significant contribution to the explanation of bone density in children with asthma. CONCLUSION: Children and adolescents with moderate to severe asthma, including those treated with inhaled corticosteroids, do not appear to have adversely affected bone mass. There was, however, the possibility of a type II error in this study because of the sample size.

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 presence of airway reactivity before the development of asthma.

Exaggerated airway reactivity is an essential component of the current asthmatic. It is not clear, however, if airway reactivity is genetically determined or acquired. To examine the possibility that increased bronchial reactivity exists prior to the development of asthma, we report on 20 subjects who were studied before and after the onset of clinical asthma. Subjects were part of a larger on-going study of the Natural History of Asthma. Thirteen subjects indicated by their answers to the National Heart, Lung, and Blood Institute respiratory questionnaire that they were not asthmatic at their initial visit. Seven subjects had pulmonary symptoms on their initial visit, but had not been diagnosed as asthmatic. Bronchial reactivity was assessed using a standardized methacholine challenge. For the 20 subjects, there was a mean interval of 3.5 yr between the initial visit and the diagnosis of asthma. Ten of 13 nonasthmatic subjects had moderate or strongly positive responses (208 breath units or less) to methacholine prior to onset of asthma. These 13 subjects were compared to age- and sex-matched controls, from both asthmatic and nonasthmatic families, who had not become asthmatic. There was a difference in bronchial responses at the initial visit between the 13 study subjects and their control subjects from nonasthmatic families, but not between the subjects and their controls from asthmatic families. Five of 7 subjects with pulmonary symptoms had responses of 100 breath units or less. Overall, 19 of 20 subjects had strongly positive responses to methacholine after the diagnosis of asthma was established. The results show that enhanced airway reactivity usually precedes the development of asthma, which could support a genetic basis for it.

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.

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.