Reduced height in Swedish men with asthma at the age of conscription for military service

doi:10.1067/mpd.2000.107384

The Journal of Pediatrics

Volume 137, Issue 1, July 2000, Pages 25-29

https://doi.org/10.1067/mpd.2000.107384 Get rights and content

Abstract

Objective: To investigate the influence of asthma on growth in Swedish children during a period when inhaled corticosteroids (ICS) have been first-line therapy for persistent asthma. Study design: We analyzed the height of conscripts with and without asthma in the year they turned 18 years old, using Swedish military conscription records from 1983, 1986, 1993, and 1996, and assessed exposure to ICS using prescription records over the same period. Result: The mean height for conscripts without asthma was 179.3 cm (SD = 6.6 cm, n = 164,503) and for conscripts with asthma 178.6 cm (SD = 6.6 cm, n = 8,531, P <.001). The severity of asthma had a negative correlation with height in all study populations (P <.001 in each year tested). Since 1985, increasing numbers of children with asthma have been treated with ICS in Sweden. Sales of ICS for males from birth to age 19 years increased from 68,000 daily doses in 1983 to more than 3,000,000 in 1995-1996. During this period, there was no statistically significant change in the height difference between conscripts with and without asthma. Conclusion: The introduction of inhaled steroids in Sweden, where budesonide is the predominant medication, has not changed the mean difference in heights between Swedish conscripts with and without asthma. (J Pediatr 2000;137:25-9)

Section snippets

Swedish conscription data

Sweden has compulsory military service; about 45,000 to 60,000 male Swedish citizens are called for mandatory conscription every year, usually during the year they turn 18 years old. Approximately 1,500 to 2,000 each year do not qualify for conscription for various reasons—for example, they live abroad, or are disabled or institutionalized. A standardized medical examination is performed at the conscription. We examined computerized conscription medical records for the years 1983, 1986, 1993,

Mean heights in conscripts with and without asthma

Of the 61,050 male Swedish citizens who turned 18 in 1983, 87% were conscripted that same year. Corresponding figures for the other years are 75% of 56,033 in 1986, 76% of 51,293 in 1993, and 83% of 46,869 in 1996. The mean height of Swedish conscripts with asthma for the years 1983, 1986, 1993, and 1996 combined was 178.6 cm (SD = 6.6 cm, n = 8,531) and without asthma was 179.3 cm (Std = 6.6 cm, n = 164,503). The minimum recorded height was 138 cm and the maximum was 213 cm. The mean height of

Discussion

In children with asthma, growth represents the sum effect of both asthma treatment and of asthma itself. The present data constitute the largest population-based assessment of asthma and height available. Furthermore, the period in the present study is unique in that it covers a time when inhaled steroids were introduced in asthma treatment.

This study demonstrates a relationship between height and both having the diagnosis of asthma and severity of asthma. It is obvious from the present study

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Cited by (39)

Inhaled corticosteroids in children: Effects on bone mineral density and growth
2014, The Lancet Respiratory Medicine
Citation Excerpt :
Whether this temporary reduction in growth velocity would eventually result in a permanent decrement in adult height was not established by these study findings, as shown by the required standardised labelling of these drugs: “The long-term effects of this reduction in growth velocity associated with [orally inhaled/intranasal] corticosteroids, including the impact on final adult height, are unknown.”5 Investigators of most cross-sectional retrospective cohort studies10–14 in adults reported no differences in target heights between patients with asthma who received inhaled corticosteroids as children and age-matched and sex-matched controls (either patients with asthma who had not received inhaled corticosteroids, or controls without asthma). However, findings from one study10 showed a significantly lower difference for adult height minus target height in adults who received inhaled corticosteroids as children than for those with asthma who had never received the drugs, despite no differences in mean adult height or height standard-deviation scores.
Potent, topically active corticosteroids with minimum systemic activity have fewer adverse effects than do systemic corticosteroids, and can control both asthma and allergic rhinitis when given in recommended doses. However, study findings show that children with asthma receiving budesonide and beclometasone dipropionate have decreased linear growth, and that children who receive long-term inhaled corticosteroid therapy for asthma have height deficits 1–2 years after treatment initiation that persist into adulthood. The effects of inhaled corticosteroids on growth seem to be dependent on both dose and duration; the degree of systemic effects is dependent on pharmacokinetic properties (ie, absorption, distribution, and elimination), whereas the effective dose delivered is dependent on the delivery system and potency of the molecule. The effects of corticosteroids on bone mineral density in children seem to be more amenable to intervention; long-term therapy with inhaled corticosteroid therapy is safer than frequent bursts of oral corticosteroids on bone mineral accretion in this regard. Importantly, adequate nutrition (particularly sufficient intake of calcium and vitamin D) should prevent or blunt the effects of corticosteroids on bone mineral density. The potential adverse effects of inhaled corticosteroids need to be weighed against the large and well established benefit of these drugs to control persistent asthma. To minimise any adverse effects, treatment with inhaled corticosteroids should always aim to reach the lowest effective dose that gives the patient good asthma control.
Normal and Aberrant Growth
2011, Williams Textbook of Endocrinology, Twelfth Edition
Untreated asthma, final height and sitting height/leg length ratio in Chile
2006, Respiratory Medicine
There is uncertainty as to whether asthma has an effect on final height. We investigated using subjective and objective assessments whether untreated asthma is associated with final height, leg length and sitting height to leg length ratio in an area of Chile in which almost no one received asthma treatment.
We collected data on 1232 males and females aged 22–28 years in a semi-rural area of Chile. Information on asthma was collected using the European Community Respiratory Health Survey (ECRHS) questionnaire. We assessed sensitisation to eight allergens and bronchial hyper-responsiveness (BHR) to methacholine as a dichotomous variable and as a log slope. Information on possible confounders in terms of smoking, birth weight, number of siblings and socio-economic factors such as household possessions, car ownership and education was available.
Regardless of the asthma assessment used, there was no association between asthma symptoms, diagnosis of asthma, atopy, BHR as log slope, binary or categorical and height, leg length or the ratio of sitting height to leg length. The latter was used as a potentially more appropriate measure to assess a detriment of growth.
Asthma as assessed in community studies is unrelated to final height or body proportions.
Adult asthma severity in individuals with a history of childhood asthma
2005, Journal of Allergy and Clinical Immunology
Citation Excerpt :
A modest negative correlation between inhaled corticosteroid use and percentile height existed only at the start of the original clinical trial (r = −0.27; P = .02). No other significant correlations between stature and oral and/or inhaled corticosteroid usage in childhood were observed, consistent with previous published studies.17,18 In summary, we conclude that the degree of atopy is a major determinant of the prognosis of childhood allergic asthma in adulthood.
Childhood asthma can have a range of outcomes in adulthood.
To identify clinical features and exposures associated with persistence and severity of childhood asthma in adulthood.
Eighty-five of 121 subjects previously enrolled in a study of immunotherapy for childhood allergic asthma (age 5-12 years) were re-evaluated with allergy skin testing, spirometry, and interviews about asthma symptoms and medications. These young adults (age 17-30 years; 74% male) all had moderate to severe childhood asthma. Adult asthma severity was scored by using a modified version of National Heart, Lung, and Blood Institute severity categories.
Thirteen (15.3%) of 85 adult subjects were in remission despite persistent childhood asthma. Another 19 subjects (22.4%) had only intermittent asthma. The remaining 53 had persistent asthma, of whom 12 (14.1%) had mild asthma, 25 (29.4%) had moderate asthma, and 16 (18.8%) had severe asthma. Subjects in remission, compared with subjects with intermittent or persistent asthma, had lower total serum IgE in childhood (412 ng/mL vs 1136 ng/mL vs 968 ng/mL; P = .02) and fewer positive allergy skin tests (7 vs 9 vs 10 from panel of 18; P = .02). Subjects in remission also had milder childhood asthma, indicated by lower average daily medication usage scores (1.6 vs 3.5 vs 4.4; P = .005) and lower percentage of days on inhaled corticosteroids (13.7% vs 24.7% vs 40.9%; P = .008). No significant association was found between current asthma severity and childhood immunotherapy (P = .46).
The prognosis of childhood allergic asthma in adulthood is largely determined early in life. The degree of atopy appears to be a critical determinant of asthma persistence.
On the good usage of inhaled corticosteroids in asthmatic children
2004, Revue des Maladies Respiratoires
Relationship between systemic corticosteroid exposureand growth velocity: Development and validation of a pharmacokinetic/pharmacodynamic model
2004, Clinical Therapeutics
Use of high-dose oral corticosteroids (CSs) can reduce growth velocity (GV) in children, whereas use of low-dose topical CSs has either no effect or transient effects on short-term growth and no effect on final adult height Despite the large body of literature on this topic, some fundamental questions remain concerning the relationship between CS exposure and growth effects.
The aims of this study were to determine the relationship between CS exposure and GV in children receiving CS therapy for asthma or rhinitis, and to examine whether there is likely to be a link between GV and cortisol suppression.
Data from 32 published studies of the effect on growth of inhaled, intranasal, and oral CSs, includingdelivery by dry powder inhaler, metered-dose inhaler, and aqueous nasal spray, were consolidated by expressing CS exposure in cortisol equivalents using a physiologically based pharmacokinetic/pharmacodynamic approach. The relationship between change in GV and CS exposure in cortisol equivalents was described using a nonlinear sigmoid maximum-effect (E_max) model with the following parameters: E_max = −5.9 cm/y; steady-state unbound AUC for 50% reduction in GV, in cortisol equivalents = 20,000 ng-h/L; Hill constant= 1.2; and change in GV at zero systemic exposure = 0.06 cm/y. Validation was achieved by comparing the model's predictions with data from 5 studies that were not included in the model development The model was also used to predict the potential of various CS regimens to reduce GV
Exploratory data analysis established that change in GV was highly correlated with exposure in cortisol equivalents (P < 0.001). CSs with high systemic bioavailability by the intranasal route were predicted to have short-term growth effects exceeding the clinical equivalence limit for change in GV (±0.8 cm/y), whereas those with lower bioavailability were predicted to produce systemic exposures below the threshold for significant effects on GV The findings were similar for inhaled CSs and for regimens combining delivery by the intranasal and inhaled routes. In descending order, the model predicted the following ranking of the potential of the various intranasal, inhaled, and oral regimens to reduce GV, expressed as fractions or multiples of the pediatric dose (in μg/d): oral prednisolone 5000 μg/d, 0.14; inhaled beclomethasone dipropionate metered-dose inhaler 400 μg/d, 0.54; inhaled budesonide dry powder inhaler 400 μg/d, 0.66; intranasal triamcinolone acetonide aqueous nasal spray 220 μg/d, 0.74; inhaled triamcinolone acetonide metered-dose inhaler 400 μg/d, 0.75; intranasal beclomethasone dipropionate aqueous nasal spray 336 pg/d, 0.89; inhaled mometasone furoate dry powder inhaler 200 μg/d, 2.4; intranasal budesonide aqueous nasal spray 128 μg/d, 2.5; inhaled fluticasone propionate dry powder inhaler 200 μg/d, 2.6; intranasal mometasone furoate aqueous nasal spray 100 μg/d, 120; and intranasal fluticasone propionate aqueous nasal spray 100 pg/d, 150. Values >1 are predictive of no significant effect on GV The model predicted that a 10% to 15% reduction in plasma cortisol concentration should be detectable at the lower equivalence limit for growth reduction (−0.8 cm/y). The validation procedure showed that the model was capable of predicting the results of the 5 comparative growth studies not included in model development with a correlation coefficient of 0.98.
Growth effects appear to be nonlinearly related to CS exposure; therefore, no-effect exposure should be possible for CSs with low systemic exposure. Growth inhibition appears unlikely to occur in the absence of detectable reductions in cortisol concentrations.

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Original ArticlesReduced height in Swedish men with asthma at the age of conscription for military service☆

Abstract

Section snippets

Swedish conscription data

Mean heights in conscripts with and without asthma

Discussion

J Allergy Clin Immunol

Respir Med

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Continued decrease in hospitalization for asthma in school children but not in young children with increased use of inhaled corticosteroids [abstract]

J Allergy Clin Immunol

Inhaled corticosteroids and the prevention of readmission to hospital for asthma

Am J Respir Crit Care Med

First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma

Thorax

One year treatment with salmeterol compared with beclomethasone in children with asthma

Am J Respir Crit Care Med

A comparison of beclomethasone, salmeterol, and placebo in children with asthma

N Engl J Med

Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma

Pediatr Pulmonol

Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone

Eur Respir J

Original Articles
Reduced height in Swedish men with asthma at the age of conscription for military service☆