Growth deceleration of children on inhaled corticosteroids is compensated for after the first 12 months of treatment

Timing and duration of linear growth suppression in children on long-term inhaled corticosteroids (ICS) are not entirely clear; we undertook a "pragmatic" study to determine growth of asthmatic children on long-term ICS managed by a flexible dosing step-down approach. Standard deviation scores of height (HSDS), height velocity (HVSDS), and body mass index (BMISDS) of pre-pubertal asthmatic children on maintenance therapy with either budesonide (BUD) or fluticasone propionate (FP) were calculated in a prospective open-label non-randomized study. Outcomes were recorded at initiation of ICS, 6, 12, 24, and 36 months, as applicable, and 6 months after ICS treatment discontinuation. Three hundred twenty-two children on BUD and 319 on FP were enrolled after the completion of 6-month treatment. The median (range) daily dose at initiation was 400 mcg (400-1,200) and 200 mcg (200-500), the final maintenance 200 mcg (200-400) and 100 mcg (100-200), respectively. In the first 6-12 months, a decrease in HSDS of approximately 18% below baseline values was noted (P < 0.01) that was restored to almost baseline average levels by 24 months, and slightly increased to above baseline during the third year. HVSDS showed a linear increase in both treatment arms (P < 0.01). No differences were found between the two treatment arms regarding HSDS, HVSDS, and BMISDS at any time point over the course of the study. In conclusion, growth deceleration of asthmatic children on maintenance ICS is compensated for after the first 12 months of treatment. This effect does not differ between BUD and FP treatment, despite some variation in the pattern of linear growth.     

Growth of asthmatic children before long-term treatment with inhaled corticosteroids.

The aim of this study was to examine the growth of asthmatic children before any long-term inhaled corticosteroid treatment. We studied 436 asthmatic children (254 boys and 182 girls), age range 3.9-15.4 years, that had not been treated with long-term inhaled corticosteroids. In each child height and weight were measured, and the height standard deviation score (HSDS) and the weight for height ratio (%WFH) were calculated. We also estimated asthma severity and tested atopic status by skin testing. Children were grouped into three age groups: prepuberty (3.9-7.9 years), peripuberty (8-11.9 years), and puberty (12-15.5 years). HSDS was correlated to asthma severity and duration, atopic status, and other coexisting allergic diseases. Seven hundred ten healthy children (345 boys, 365 girls) ages 4.1-15.5 years were used as controls for height and weight. There was no statistically significant difference in HSDS and %WFH between patients and controls, except for HSDS of pubertal female patients that was significantly less than that of controls, x: 0.06 (0.80) vs. x: 0.40 (0.90), respectively, p < 0.02. There was also no significant correlation between HSDS or %WFH and severity or duration of the disease, allergy status and other coexisting allergic diseases. However, there was significant difference in menarcheal age between asthmatic girls x: 12.49 (0.12) and controls x: 12.00 (0.10), p < 0.001. In conclusion, our data show that the growth of asthmatic children before any long-term treatment with inhaled corticosteroids is not different from the control population, except for the asthmatic girls of pubertal age who are shorter than control girls probably because of delay in pubertal maturation.     

The hypothalamic-pituitary-adrenal axis in asthmatic children.

Reduced responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in patients with various chronic allergic inflammatory disorders and a blunted HPA axis response of poorly controlled asthmatics before long-term treatment with inhaled corticosteroids (ICS) have been reported. It seems that pro- and anti-inflammatory cytokines might be involved in the attenuation of cortisol and adrenocorticotropic hormone (ACTH) responses to stress in these patients. Although long-term ICS treatment might produce mild adrenal suppression in some asthmatic children, improvement of adrenal function has been detected in the majority of cases. We postulate that the anti-inflammatory effects of ICS result both in asthma remission and HPA axis improvement. Adrenal suppression of some asthmatic patients on maintenance ICS seems to be a separate phenomenon, possibly constitutionally or genetically determined.     

Adrenal function and lipid metabolism in asthmatic children treated with budesonide]

OBJECTIVE: To assess the effect of low doses of inhaled budesonide on the adrenal function and lipid metabolism of asthmatic children. MATERIAL AND METHODS: The study included 10 asthmatic children (mean age, 8.8 years) treated with inhaled budesonide (200-300 micrograms/day) for a period longer than 3 months (group A); 15 asthmatic children (mean age, 7.8 years) without steroid treatment (group B) and 10 non-asthmatic children (group C). Basal cortisol levels, as well as postACTH, adrenal androgens, lipids and urinary cortisol were determined. RESULTS: No significant differences were detected between groups A and B in the studied variables. In asthmatic children, urinary cortisol was significantly higher than in non-asthmatic children. Triglycerides, total cholesterol, low density lipoprotein cholesterol and atherogenic index levels were higher in asthmatic children with and without budesonide treatment, compared with non-asthmatic children. CONCLUSIONS: Treatment of asthmatic children with low doses of inhaled budesonide did not modify the adrenal axis function nor lipid metabolism. Asthmatic patients showed an atherogenic lipid profile which could increase the risk of cardiovascular disease.     

Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma

PURPOSE: Inhaled corticosteroids have beneficial effects on pulmonary function and inflammation in patients with asthma, but they also cause systemic adverse effects, such as adrenal suppression. We evaluated the therapeutic index of inhaled corticosteroids in asthmatic patients by comparing their dose-response effects on lung function, surrogate markers of airway inflammation, and tests of adrenal function. SUBJECTS AND METHODS: After a 10-day placebo run-in, we evaluated the effects of 200 microg, 400 microg, and 800 microg of inhaled budesonide, each dose given twice daily sequentially for 3 weeks in 26 patients, aged 35 +/- 12 years (mean +/- SD), with mild-to-moderate asthma. Measurements were made of bronchial reactivity, exhaled nitric oxide (a marker of airway inflammation), spirometry, serum eosinophilic cationic protein concentration, and 10-hour overnight urinary cortisol excretion. Plasma cortisol levels were measured at 8 AM and after stimulation with human corticotropin releasing factor. RESULTS: For measurements of pulmonary function and exhaled nitric oxide, there was a plateau in the mean response to budesonide between 400 microg (low dose) and 800 microg (medium dose) per day, whereas for eosinophilic cationic protein and bronchial challenge, maximal benefits occurred between 800 and 1,600 microg (high dose) per day. Effects on plasma cortisol levels showed maximal suppression at 1,600 microg of budesonide per day. The proportion of patients with an optimal therapeutic index, in terms of a good airway response (fourfold decrease in bronchial hyperreactivity) and minimal systemic response (overnight urinary cortisol greater than 20 nmol), was similar at low-dose (46%) and at high-dose (52%) budesonide. The proportion of patients with a suboptimal therapeutic index, a good airway response with a marked systemic response (overnight urinary cortisol greater than 20 nmol), increased from 4% at low dose to 38% at high dose. CONCLUSIONS: In patients with mild-to-moderate atopic asthma, there were dose-related effects of budesonide on surrogate markers of inflammation (bronchial hyperreactivity and serum eosinophilic cationic protein), although higher doses were associated with adrenal suppression and a decrease in the therapeutic index.     

Highdose inhaled steroid therapy and the cortisol stress response to acute severe asthma

Systemic absorption of inhaled corticosteroids taken in high doses (> or = 1500 micrograms beclomethasone dipropionate or budesonide daily), may cause suppression of the hypothalamo-pituitary-adrenal axis. Patients taking long-term high dose inhaled steroid therapy might therefore be at risk of adrenal crisis at times of stress. Plasma cortisol levels were measured in 24 adults with severe acute asthma who had not received treatment with systemic corticosteroids prior to hospital attendance. Seven were not taking inhaled steroids, four were taking 600-1200 micrograms and 13 were taking 1500-2400 micrograms beclomethasone dipropionate or budesonide daily. Plasma cortisol levels in these 13 (median 594 nmol l-1, interquartile range 399-620 nmol l-1) were similar to levels in those taking lower dose/no inhaled steroids (median 512 nmol l-1, interquartile range 287-1050 nmol l-1): there was no relationship between inhaled steroid dose and cortisol level. Nine of the 24 patients failed to achieve plasma cortisol values > 500 nmol l-1 (the normal response to an insulin stress test). When compared with the remaining 15, they had less severe asthma as indicated by higher arterial oxygen tension (P < 0.01) and peak expiratory flow (P < 0.03). Patients taking long-term high dose inhaled corticosteroids appear to be able to mount an appropriate adrenocortical response to the stress of severe acute asthma.     

Study on serum and urinary cortisol levels of asthmatic patients after treatment with high dose inhaled beclomethasone dipropionate or budesonide

BACKGROUND: The potential for long-term adverse effects from inhaled corticosteroids relates to their systemic absorption. With increasing use of high dose inhaled corticosteroids, there is need to establish whether similar doses of beclomethasone dipropionate (BDP) and budesonide (BUD) produce clinically important differences in untoward side effects specially hypothalamo-pituitary-adrenal (HPA) axis suppression. METHODS: Fifteen asthmatic patients were started on BDP or BUD (2000 microg/day) through spacer for six weeks. Serum cortisol (9 AM and 4 PM), 24-hour urinary steroid and pulmonary function testing parameters were performed. RESULTS: The serum cortisol levels were not found to be suppressed with either BDP or BUD. Similarly no significant changes were found in 24 hours urinary excretion of steroids with either of the drugs. Significant improvement was found in values of forced expiratory volume in the first second (FEV1) with BDP. With BUD the changes in forced vital capacity (FVC) and FEV1 were found to be significant. CONCLUSION: BDP or BUD in high doses of 2000 microg/day given upto six weeks through spacer are equally effective for treatment of bronchial asthma and do not cause any significant change in serum and urinary cortisol levels, and adrenal function/HPA axis.     

Growth of Asthmatic Children Before Long-Term Treatment with Inhaled Corticosteroids

The aim of this study was to examine the growth of asthmatic children before any long-term inhaled corticosteroid treatment. We studied 436 asthmatic children (254 boys and 182 girls), age range 3.9–15.4 years, that had not been treated with long-term inhaled corticosteroids. In each child height and weight were measured, and the height standard deviation score (HSDS) and the weight for height ratio (%WFH) were calculated. We also estimated asthma severity and tested atopic status by skin testing. Children were grouped into three age groups: prepuberty (3.9–7.9 years), peripuberty (8–11.9 years), and puberty (12–15.5 years). HSDS was correlated to asthma severity and duration, atopic status, and other coexisting allergic diseases. Seven hundred ten healthy children (345 boys, 365 girls) ages 4.1–15.5 years were used as controls for height and weight. There was no statistically significant difference in HSDS and %WFH between patients and controls, except for HSDS of pubertal female patients that was significantly less than that of controls, x: 0.06 (0.80) vs. x: 0.40 (0.90), respectively, p<0.02. There was also no significant correlation between HSDS or %WFH and severity or duration of the disease, allergy status and other coexisting allergic diseases. However, there was significant difference in menarcheal age between asthmatic girls x: 12.49 (0.12) and controls x: 12.00 (0.10), p<0.001. In conclusion, our data show that the growth of asthmatic children before any long-term treatment with inhaled corticosteroids is not different from the control population, except for the asthmatic girls of pubertal age who are shorter than control girls probably because of delay in pubertal maturation.     

Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids

The aim of the present study was to evaluate the prevalence of adrenal suppression and growth retardation in children using moderate doses of budesonide or fluticasone propionate. Seventy-five asthmatic children were randomly divided into three treatment groups: 30 to the fluticasone propionate (FP), 30 to the budesonide (BUD), and 15 to the cromone (CROM) group. FP doses were 500 microg/day during the first 2 months and 200 microg/day thereafter. The respective BUD doses were 800 and 400 microg/day. A low dose ACTH (0.5 microg/1.73 m2) test was performed before treatment and 2, 4, and 6 months later. The test was considered abnormal if the stimulated serum cortisol concentration was more than 2 SD lower than the pretreatment mean (<330 nmol/L). The low dose ACTH test was abnormal after both the high and low steroid doses in 23% of the children. At the 4 month measurement there were more abnormal tests in the BUD (n = 9) than in the FP (n = 5) group (P < 0.05). At that time also the stimulated concentration of serum cortisol was lower in the BUD than in the CROM group (P < 0.01), whereas the difference between the FP and CROM groups was not significant. During the study year the mean decrease in height SD score was 0.23 in the children treated with BUD, 0.03 in the children treated with FP, and 0.09 in the children treated with CROM; the difference between the BUD and FP groups was significant (P < 0.05). In conclusion, the low dose ACTH test revealed mild adrenal suppression in a quarter of the children using moderate doses of inhaled steroids. A FP dose of 200 microg/day caused less adrenal and growth suppression than did a BUD dose of 400 microg/day.     

Safety,tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients

The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two inhalations twice daily for 12 weeks.There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group.Urine free cortisol and urine cortisol/ creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler was generally considered more acceptable to the patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.     

Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate.

Four cases of asthma (one adult, three children) developing acute adrenal crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7-9 yrs, had been prescribed inhaled fluticasone, dosage 500-2,000 microg x day(-1) and duration 5 months-5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3-1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000-2,000 microg x day(-1) for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute adrenal crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-adrenal axis suppression were excluded.     

Effects of inhaled corticosteroids on growth in asthmatic children: a comparison of fluticasone propionate with budesonide.

In asthmatic children inhaled corticosteroids are widely used. However, there are some concerns about the systemic adverse effects of these drugs, especially in the growing child. We performed this prospective study in order to compare the effects of 400 microg/day of budesonide (BUD) and 250 microg/day of fluticasone propionate (FP) on growth in prepubertal (aged 4-11.5 years), moderate persisting asthmatic children. One hundred patients (51 boys and 49 girls), who were randomized into two groups, were recruited for the study. The first group was treated with BUD, 2X 200 microg/day, and the second group was treated with FP, 2X 125 microg/day, by using a medium-size volume-spacer metered-dose inhaler. Growth in children with asthma who were treated by inhaled corticosteroids was calculated by growth velocity over a 12-month period. Comparisons between treatment groups were calculated by t-test and chi-square test. There were no significant differences between BUD and FP groups for sex, age, first height, and growth velocity. Moderate persisting, prepubertal asthmatic children treated with 250 microg/day of FP appeared to have no different linear growth than those children who received 400 microg/day of BUD.     

Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.

OBJECTIVE: To appraise the data on systemic adverse effects of inhaled corticosteroids. METHODS: A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. RESULTS: Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. CONCLUSIONS: All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.     

Chronic treatment with inhaled corticosteroids does not modify leptin serum levels.

AIM: To assess the influence of a short-term treatment with low-dose inhaled corticosteroids on leptin serum levels. PATIENTS: 14 prepubertal children, mean age 5.1 +/- 2.4 years, treated with inhaled fluticasone propionate 100 microg b.d. and 16 prepubertal children, mean age 8.3 +/- 1.3 years, treated with inhaled budesonide 200 microg b.d. METHODS: All children underwent a CRH test with evaluation of leptin, cortisol and ACTH levels before and after 3 months of treatment. RESULTS: Fluticasone group: no difference was found between basal cortisol level, delta and area under the curve (AUC) before and after treatment, though cortisol peak was significantly lower following treatment. Basal ACTH level, peak and AUC were significantly lower after treatment. Budesonide group: no statistically significant difference in any of the parameters regarding cortisol and ACTH secretion was observed before and after treatment. No significant changes in basal serum leptin levels and AUC were observed following treatment in both groups. Furthermore no significant variation in leptin level was observed during both CRH tests. DISCUSSION: Leptin secretion does not seem to be affected by low-dose inhaled corticosteroids; moreover leptin does not seem to be involved in the response of the HPA axis to stress.     

Evaluation of adrenocortical function in 3-7 aged asthmatic children treated with moderate doses of fluticasone propionate: reliability of dehydroepiandrosterone sulphate (dhea-s) as a screening test

BackgroundInhaled corticosteroids (ICS) are the first-line therapy in the treatment of persistent asthma. At medium to high doses and prolonged usage, ICS can supresss the hypothalamic-pituitary-adrenal axis. Dehydroepiandrosterone sulphate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is supressible in patients treated with ICS.ObjectivesTo evaluate the adrenal axis in asthmatic children treated with moderate doses of fluticasone propionate and to evaluate the DHEA-S as a possible marker for adrenal axis ?n preadrenarchal children.MethodsTwenty-eight children with persistent asthma with a mean age of 4.4 years (median 4.2; range 2.5-7.1) on long term treatment (mean 6.16; median 6; range 4.5-9 months) with moderate doses (mean 250; median 253; range 158-347 (g/m²/day) of inhaled fluticasone propionate were evaluated with low-dose ACTH stimulation test to assess adrenal function, and DHEA-S levels were compared with the results.ResultsOne out of 28 patients (3.57%) demonstrated an abnormal cortisol response to low-dose ACTH test. There was no correlation between DHEA-S and peak cortisol, morning cortisol and fasting blood glucose levels. However, mean inhaled corticosteroid dosages were inversely correlated with the DHEA-S.Conclus?onsIn most of the children with persistent asthma, mild to moderate fluticazone propionate doses supress the hypothalamic-pituitary-adrenal axis rarely. Chronic moderate doses of ICS may suppress adrenal androgen levels without supression of cortisol production. DHEA-S levels may be used as a practical method to follow adrenal functions and may be an earlier indicator of adrenal dysfunction in children.     

Ciclesonide and beclomethasone dipropionate coadministration: effect on cortisol in perennial allergic rhinitis.

Coexisting asthma and allergic rhinitis (AR) are often treated with both intranasal and inhaled corticosteroids. This study investigated whether intranasal ciclesonide 200 microg once daily has an additional effect on cortisol suppression when coadministered with inhaled hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP). Adult patients (n = 150) with perennial AR received HFA-BDP 320 microg twice daily and placebo once daily during a run-in period. Patients were then randomized to ciclesonide or placebo and HFA-BDP (43 days). A single 2-mg dose of dexamethasone was administered on the last treatment day. Plasma cortisol decreased by 67.8 microg x h/dL (p < 0.001) during the run-in period. When ciclesonide was added, the change in mean plasma cortisol was similar for ciclesonide and placebo (8.5 microg x h/dL and 1.0 microg x h/dL, respectively). Dexamethasone decreased mean plasma cortisol (p < 0.001), demonstrating that further cortisol suppression was possible. This study suggests that intranasal ciclesonide can be used with an inhaled corticosteroid without increased cortisol suppression.     

Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids

The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose (greater than 1000 micrograms daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600 micrograms, range 1200-2650 micrograms daily). All patients except one were using metered dose aerosols; 15 were using large volume spacer devices. Median duration of high dose therapy was 13 months (range 1-54). Sixty-nine patients were taking beclomethasone dipropionate (1500 micrograms, n = 36; 2000 micrograms, n = 26, greater than 2000 micrograms, n = 7) and nine budesonide (1200 micrograms, n = 2; 1600 micrograms, n = 6; 1800 micrograms, n = 1). Four patients, all of whom were taking greater than 2000 micrograms beclomethasone dipropionate, were taking 200-400 micrograms of their total dose intranasally. Twenty-six patients had discontinued long term systemic corticosteroid treatment (at least 5 mg prednisolone daily, or equivalent, for a minimum of 6 months) between 7 months and 22 years prior to assessment. All patients had measurements of 9 am serum cortisol and 24-h urine free cortisol excretion and a short tetracosactrin test. Subnormal results were: 9 am cortisol less than 190 nmol l-1; rise in serum cortisol in response to tetracosactrin less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1; urine free cortisol less than 80 nmol 24 h-1. Hypothalamo-pituitary-adrenal suppression was defined as subnormal results in at least two of the three tests. Tests were performed at least 2 weeks after completion of any short course prednisolone treatments. Suppression was found in 16 (20.5%) patients (1500 micrograms, n = 6; 1600 micrograms, n = 1; 2000 micrograms, n = 7; 2400 micrograms, n = 2). Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, chi 2 = 6.1, P less than 0.02); and (b) increasing duration of high dose inhaled therapy (median 28.5 months in suppressed vs. 12 months in normal, P less than 0.05). No clear relationship was identified between HPA function and dose, even when corrected for body surface area and there was no relationship between suppression and number of short courses of prednisolone in the preceding 12 months. Screening tests of HPA function should be performed in all asthmatics taking greater than or equal to 1500 micrograms inhaled corticosteroid daily. Unless function has been shown to be normal, all patients taking these doses should carry steroid cards.     

Inhaled Corticosteroids and Bone Density of Children with Asthma

In this cross-sectional study we aimed to compare anteroposterior (AP) spine and total body bone mineral density (BMD) measurements of children with asthma treated with long-term inhaled budesonide (n = 52, mean age 6.4 ± 2.2 yr, M/F = 22/30) (Group I) with those of asthmatic children who had never received treatment with inhaled corticosteroids (Group II) (n = 22, mean age 6.8 ± 2.2, M/F = 10/12). Boys and girls were comparable for age, weight, height, cumulative corticosteroid (CS) dosage, duration of disease and inhaled corticosteroid (ICS) treatment within each group. The mean total accumulated dosage of budesonide for children in Group I was 154.0 ± 135.3 mg (mean daily dosage = 419 ± 154 µg) and the mean treatment duration was 13.0 ± 9.8 months. The two groups were comparable with respect to age, gender, weight, height, Tanner's stage and duration of disease. There was no significant difference between subjects in the two groups for total (p = 0.214) and (AP) spine BMD results (p = 0.661), respectively. Our results provide additional support for the safety of ICS therapy on bone density of asthmatic children.     

Inhaled corticosteroids reduce growth. Or do they?

The class label warning in the United States for inhaled corticosteroids (ICS's) states that these drugs may reduce growth velocity in children. In this paper, the evidence for this warning is reviewed from a clinical point of view. Children with asthma tend to grow slower than their healthy peers during the prepubertal years because they go into puberty at a later age. However, asthmatic children do achieve a (near) normal adult height. In randomized controlled clinical trials, the use of inhaled beclomethasone, budesonide and fluticasone is associated with a reduced growth during the first months of therapy, in the order of magnitude of approximately 0.5-1.5 cm x yr(-1). It is, however, unlikely that such an effect continues or persists because accumulating evidence shows that asthmatic children, even when they have been treated with ICS for years, attain normal adult height. Individual rare cases have been reported, however, where ICS use was associated with clinically relevant growth suppression. Inhaled corticosteroids are the most effective therapy available for maintenance treatment of childhood asthma. Fear of reduced growth velocity is based on exceptional cases and not on group data. It should, therefore, not be a reason to withhold or withdraw such highly effective treatment in children with asthma.     

Maximal response plateau to methacholine as a reliable index for reducing inhaled budesonide in moderate asthma.

Although some studies suggest that asthma deteriorates after reducing inhaled steroids, results of long-term studies indicate that this might not be true for all patients. The aim of this study was to determine the utility of the detection of a plateau on the concentration-response curves to inhaled methacholine as a marker for safely reducing the dose of inhaled budesonide in asthmatic patients who are well-controlled with a moderately high dose of this inhaled steroid. A total of 46 patients with moderate asthma, well-controlled for at least 6 months by treatment with 800 microg budesonide daily, were included in the study. Subjects were treated for a 2-week run-in period with their usual dose of budesonide. At the end of the run-in, all subjects were challenged with methacholine (0.095-200 mg x mL(-1)). Plateau responses, median effective concentration values, slopes and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) values were measured. For the subsequent 12 weeks, patients were treated in an open design with budesonide at a reduced dose (200 microg once daily), and were asked to record their peak expiratory flow (PEF) in the morning and in the evening. In addition, asthma symptoms and use of rescue terbutaline were recorded in diaries. Plateaus were present in 24 patients, whereas 22 subjects showed concentration-response curves without evidence of a plateau. Ten patients in the nonplateau group deteriorated after reducing inhaled budesonide, compared to one patient in the plateau group (p = 0.002). In the nonplateau group, FEV1 decreased from a baseline value of 3.28+/-0.19 L to 2.94+/-0.20 L at week 12 (p<0.0001). Likewise, morning PEF decreased from 419+/-19 L x min(-1) at baseline to 394+/-19 L x min(-1) at week 12 (p = 0.02). By contrast, these variables remained unchanged in the plateau group. In conclusion, in asthmatic patients, well-controlled with a moderately high dose of budesonide, the detection of a plateau on the concentration-response curve to inhaled methacholine may be used as a marker for safely reducing the corticosteroid dose.