cosyntropin and Asthma

To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels.. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min.. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%.. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Circadian Rhythm; Cortisone; Cosyntropin; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Saliva

Topical corticosteroids are the recommended first-line treatment for all severities of persistent asthma and moderate to severe allergic rhinitis. Potential adrenal suppression resulting from corticosteroid administration necessitates monitoring of children participating in clinical studies. Measurement of pretreatment cortisol concentrations is necessary to assess effects on adrenal function.. Plasma cortisol concentrations are assay dependent; normal reference range values must be obtained for each assay. Our objective is to provide these values for children as determined by HPLC.. Two multicenter, randomized, double-blind, placebo-controlled studies evaluating basal and cosyntropin-stimulated morning plasma cortisol concentrations for patients aged 5 to younger than 12 months with asthma and patients aged 2 to younger than 6 yr with allergic rhinitis using HPLC were conducted.. Main planned outcomes of these studies are reported elsewhere. This manuscript reports plasma cortisol concentration reference range values.. In general, mean basal plasma cortisol concentrations (n = 177) (mean +/- sd, nmol/liter) were similar among the 5 to younger than 9 months, 9 to younger than 12 months, 2 to younger than 3 yr, 3 to younger than 4 yr, 4 to younger than 5 yr, and 5 to younger than 6 yr age groups (218 +/- 149, 281 +/- 144, 257 +/- 105, 231 +/- 83, 298 +/- 118, and 237 +/- 65, respectively) and increased to comparable levels 60 min after cosyntropin stimulation (n = 178; 622 +/- 176, 638 +/- 176, 697 +/- 99, 655 +/- 103, 662 +/- 113, and 610 +/- 68, respectively). However, patients younger than 12 months had wider ranges of basal and stimulated values.. Basal and cosyntropin-stimulated morning plasma cortisol concentrations of children aged 5 to younger than 12 months and 2 to younger than 6 yr were consistently measurable, with the large majority similar among the age groups examined, and comparable with those reported elsewhere for adults.

Topics: Asthma; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Infant; Male; Rhinitis, Allergic, Perennial; Severity of Illness Index

Inhaled corticosteroids (ICs) are considered first-line therapy for persistent asthma. At medium to high doses, ICs can suppress the hypothalamic-pituitary-adrenal (HPA) axis. Various provocative stimuli have been used to evaluate HPA axis function, but they are labor intensive and time-consuming. Dehydroepiandrosterone sulfate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is suppressible in patients treated with ICs.. To evaluate DHEA-S as a possible marker for HPA axis dysfunction in children treated with ICs.. Children with moderate-to-severe persistent asthma and a history of medium- to high-dose IC exposure for at least 6 months were evaluated using low-dose and standard high-dose cosyntropin stimulation testing to assess adrenal function, and DHEA-S levels were compared with the results.. Thirteen (59%) of 22 patients exhibited an abnormal cortisol response to cosyntropin. Age- and sex-specific mean DHEA-S z scores were significantly lower in cosyntropin abnormal responders (-1.2822) compared with normal responders (0.2964) (P = .008). The receiver operating characteristic curve for DHEA-S z scores had an area of 0.786 (95% confidence interval, 0.584-0.989), reaching 100% sensitivity with a DHEA-S z score of -1.5966 or less and 100% specificity with a DHEA-S z score greater than 0.0225.. Most children develop biochemical evidence of adrenal suppression after treatment with medium to high doses of ICs. The presence of low DHEA-S levels can be used as a screening test to identify the child who needs more formal testing of the HPA axis.

Topics: Administration, Inhalation; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Asthma; Biomarkers; Child; Cosyntropin; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Mass Screening; Pituitary-Adrenal System; ROC Curve

Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events.. To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma.. This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator.. For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate.. These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Patient Compliance; Pituitary-Adrenal System; Pregnenediones

Inhaled corticosteroids (ICSs) reduce local airway inflammation, which is an underlying cause of asthma symptoms. However, potential systemic side effects associated with ICS use are a major concern for asthmatic patients.. Adult patients (n = 60; > or = 18 years of age) with moderate-to-severe asthma were randomized to receive 4 weeks of treatment with ciclesonide (CIC), 320 microg bid (CIC 640), CIC, 640 microg bid (CIC 1280), fluticasone propionate (FP), 440 microg bid (FP 880), FP 880 microg bid (FP 1760), or placebo (PBO) [all doses expressed as ex-actuator; comparable to ex-valve doses of 800 and 1,600 microg/d for CIC and 1,000 and 2,000 microg/d for FP, respectively].. After 29 days of treatment, CIC 640, CIC 1280, and FP 880 had no significant effect on the mean serum cortisol area under the curve for 0 to 24 h (AUC0-24h). FP 1760 produced a statistically significant suppression in mean serum cortisol AUC0-24h compared to PBO (p = 0.0009; 95% confidence interval [CI] -117.5 [corrected] to -32.1). Results obtained with cosyntropin stimulation revealed no statistically significant differences among the groups. The CIC 640 group demonstrated a significant increase compared to the PBO group in 24-h urinary cortisol levels from baseline at week 4 (p = 0.0224; 95% CI, 0.0023 to 0.0283), while the other treatment groups revealed no change in this parameter. The incidence of treatment-emergent adverse events was similar in all groups, and all adverse events were mild or moderate in severity.. Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Pregnenediones

Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma.. Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS.. During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1.. Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages.. Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Asthma; Circadian Rhythm; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Mometasone Furoate; Powders; Pregnadienediols; Respiratory Function Tests; Therapeutic Equivalency

Inhaled corticosteroids are established as maintenance therapy for persistent asthma. A new aerosol formulation of flunisolide delivers a small particle size by using a hydrofluoroalkane (HFA) propellant with a built-in spacer.. To compare efficacy and safety of two different flunisolide formulations, HFA and chlorofluorocarbon (CFC), with placebo treatment over a range of doses.. The multicenter, randomized, double-blind, placebo-controlled trial consisted of a 2-week, active run-in phase with CFC flunisolide 500 microg, twice daily, followed by 12 weeks of double-blind treatment with placebo, HFA flunisolide (85, 170, or 340 microg, twice daily), or CFC flunisolide (250, 500, or 1,000 microg, twice daily). Patients (N = 669) were nonsmokers, at least 12 years of age, with mild to moderate asthma who were being treated with inhaled corticosteroids. Outcome measures were change from baseline in forced expiratory volume in 1 second (FEV1), peak expiratory flow rate, as needed albuterol use, nocturnal awakenings, and asthma symptoms.. After 12 weeks of treatment, patients receiving 170 microg, twice daily, and 340 microg, twice daily, of HFA flunisolide showed a significant (P < 0.01) improvement in percentage increase in FEV1 (12.22% at 170 microg, twice daily, and 14.69% at 340 microg, twice daily) compared with the placebo group (5.35%). At one-third the dose of CFC flunisolide, HFA flunisolide provided similar improvement in pulmonary function versus placebo. Both formulations demonstrated comparable linear dose dependency for the change from baseline in FEV1 without any evidence of cortisol suppression. Outcome values for all seven secondary efficacy measures were numerically superior in patients receiving HFA flunisolide compared with the CFC formulation. Both formulations seemed to be safe and well tolerated.. HFA flunisolide provides comparable efficacy and safety at one-third the dose of CFC flunisolide.

Topics: Administration, Inhalation; Adrenal Glands; Adult; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Cosyntropin; Dose-Response Relationship, Drug; Female; Fluocinolone Acetonide; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Particle Size; Peak Expiratory Flow Rate

To investigate the potential for mometasone furoate (MF) to exert systemic effects following administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI).. Three randomized, evaluator-blind, placebo-controlled, parallel-group, 28-day studies.. Adults with mild-to-moderate persistent asthma.. Study 1 (12 patients per treatment group; MF DPI at 200 microg bid, 400 microg qd, 800 microg qd, or 1,200 microg qd). Study 2 (16 patients per treatment group; MF DPI at 400 microg bid or 800 microg bid, or oral prednisone at 10 mg qd). Study 3 (16 patients per treatment group; MF MDI at 400 microg bid or 800 microg bid, or fluticasone propionate [FP] at 880 microg bid by MDI).. Study 1. Plasma concentrations were near the lower limit of quantitation (50 pg/mL) at the MF DPI 400-microg qd dosage and approximately 250 pg/mL at the 1,200-microg qd dosage. The area under the curve for serum cortisol concentrations over 24 h (AUC(24)) was essentially unaltered at all doses. Study 2. Plasma levels over days 7 to 28 were 100.3 +/- 5.9 pg/mL (mean +/- SEM) for MF DPI 400 microg bid, and 181.0 +/- 10.9 pg/mL for 800 microg bid. Although there were relatively low levels of suppression (19 to 25%) at earlier time points for MF DPI 400 microg bid, serum cortisol AUC(24) levels at day 28 were similar to placebo. MF DPI 800 microg bid and oral prednisone both decreased serum cortisol AUC(24) levels at days 7 to 28 by 28.0 +/- 8.3% and 67.2 +/- 3.6%, respectively. The response to cosyntropin was normal in 15, 14, 11, and 1 of the patients in the placebo, MF DPI 400 microg bid, MF DPI 800 microg bid, and prednisone groups, respectively. Study 3. MF MDI caused even less systemic exposure than by DPI. MF MDI 800 microg bid (24.0 +/- 3.1%) and FP (51.7 +/- 3.8%) caused a significant decrease in serum cortisol AUC(24) on days 14 to 28. MF MDI 400 microg bid was similar to placebo treatment at all time points.. The MF 800-microg bid dosage (1,600 microg/d), which is twice the highest projected clinical dosage, represents the lower limit for consistently detectable systemic effects of MF.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Prednisone; Pregnadienediols

Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis.. The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress.. This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 microg or 220 microg twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400 microg twice daily, prednisone 10 mg once daily, and placebo.. After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P <.05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisone; Time Factors; Triamcinolone Acetonide

Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.

Topics: Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Cosyntropin; Double-Blind Method; Female; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisone; Triamcinolone Acetonide

The efficacy and safety of regular-strength beclomethasone dipropionate MDI prescribed within its recommended dosing range of 2 to 5 puffs three to four times daily has been well established in more than 25 years of worldwide use. A more concentrated formulation delivering 84 microg per puff was developed to provide for a more convenient twice-daily dosing regimen.. This randomized, single-blinded, positive and placebo-controlled, parallel-group, multiple-dose bioactivity study was conducted to assess the potential of a new beclomethasone dipropionate 84 microg double-strength metered-dose inhaler (Vanceril 84 microg Double Strength Inhalation Aerosol/Key) to cause hypothalamic-pituitary-adrenocortical axis suppression.. Beclomethasone dipropionate double-strength 84 microg was compared with beclomethasone dipropionate regular-strength 42 microg, orally administered prednisone, and placebo inhaler after 36 consecutive days of administration in adults with moderate asthma. Beclomethasone dipropionate double-strength was administered as 5 puffs BID and beclomethasone dipropionate regular-strength was administered as 10 puffs BID for the same total daily dose of 840 microg of beclomethasone dipropionate. Oral prednisone was administered by mouth at 10 mg once a day. The potential for hypothalamic-pituitary-adrenocortical axis suppression was evaluated by an adrenocorticotropic hormone (ACTH) stimulation test using cosyntropin 250 microg in 500 mL normal saline infused over six hours on the 36th day of treatment. Sixty-four patients completed this study.. No clinically significant post-study findings were observed from physical examination, electrocardiogram, or clinical laboratory evaluation for any treatment group. No serious or unexpected adverse events were reported. On the 36th day of treatment, there was a significant (P < .01) difference in the plasma cortisol concentration response to cosyntropin stimulation between the prednisone and placebo treatment groups at the sixth hour of infusion. There was no significant difference in the plasma cortisol concentration response to cosyntropin stimulation between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength treatment groups and the placebo group. In addition, comparison of the response between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength groups showed no significant difference.. Beclomethasone dipropionate, administered either via a double-strength (84 microg/puff) or regular-strength (42 microg/puff) inhaler dosed at 840 microg/day showed no evidence of hypothalamic-pituitary-adrenocortical axis suppression in adults with moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adrenocorticotropic Hormone; Adult; Asthma; Beclomethasone; Cosyntropin; Drug Evaluation; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prednisone; Safety; Single-Blind Method

As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects.. This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma.. Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin.. After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 microg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group was the decrease significant (p = 0.03 vs placebo).. In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 microg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.

Topics: Administration, Inhalation; Adolescent; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Cosyntropin; Double-Blind Method; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prednisone

Herein we assess the safety of an inhaled formulation of beclomethasone dipropionate (BDP) which uses the propellant hydrofluoroalkane-134a (HFA) for the treatment of asthma. Acute local tolerability (as assessed by the incidence of cough and mean forced expiratory volume after 1 s inhalation) was similar for both BDP and placebo formulated in either chlorofluorocarbon (CFC) or HFA propellants. A total of 43 patients were treated with HFA-BDP (0, 200, 400 or 800 micrograms day-1) or CFC-BDP (800 micrograms day-1) for 14 days and their 24 h urinary free cortisol (UFC) excretion and response to cosyntropin stimulation were measured. There was no difference in UFC between any of the doses of HFA-BDP and CFC-BDP. Adrenal responsiveness to cosyntropin stimulation was normal in all but one patient. Two large 12 week phase III trials compared HFA-placebo, HFA-BDP 400 micrograms day-1 and CFC-BDP 800 micrograms day-1 (n = 347), and HFA-BDP 800 micrograms day-1 and CFC-BDP 1500 micrograms day-1 (n = 233). For HFA-BDP at either dose, CFC-BDP 800 micrograms day-1 and HFA-placebo, the number of patients with morning plasma cortisol concentrations below normal was less than 4.4% but was 14.6% for CFC-BDP 1500 micrograms day-1. The incidence of adverse events was lower in the HFA-BDP groups than in the CFC-BDP groups (P = 0.012). The data indicate that, at doses of up to 800 micrograms day-1, HFA-BDP is at least as well tolerated as CFC-BDP. Other studies have found that equivalent efficacy is reached at lower doses of HFA-BDP than CFC-BDP. Equivalent efficacy at a lower dose and equivalent safety at the same dose imply that HFA-BDP may have a more favourable risk: benefit ratio than CFC-BDP when used at the recommended lower doses.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Cosyntropin; Cough; Cross-Over Studies; Drug Administration Schedule; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System

A total of 261 patients with symptomatic, mild to moderate asthma were randomized to treatment in this 4-week, double-blind, parallel-group comparison of fluticasone propionate 200 micrograms/d with beclomethasone dipropionate 400 micrograms/d. Improvements from both treatments were seen in diary card data. Morning peak expiratory flow rate (PEFR) improved from 375 to 390 and 371 to 382 l/min with fluticasone propionate and beclomethasone dipropionate, respectively. Symptom scores, percentage of symptom-free days and nights, and use of rescue beta 2-agonist medication also improved, as did clinical lung function. With the exception of percentage of rescue-free days, which was greater for beclomethasone dipropionate, none of the differences between the groups were statistically significant. There was a significant difference between treatments in the number of rescue-free days over days 1-28; however, there was no difference between treatments in the number of rescue-free days over days 1-14, nor was there any difference in the number of inhalations of rescue medication used throughout the study. Very few adverse effects were reported. Although all mean plasma cortisol values were within the normal range, they were significantly different between treatments, rising from 402 to 429 nmol/l with fluticasone propionate, and falling from 435 to 394 nmol/l with beclomethasone dipropionate (P = 0.006). Mean stimulated cortisol levels 30 min after tetracosactin injection were also significantly greater with fluticasone propionate (P = 0.024). In conclusion, fluticasone propionate 200 micrograms/d is as effective as beclomethasone dipropionate 400 micrograms/d with less effect on plasma cortisol levels.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Injections; Male; Middle Aged; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.

Topics: 17-Hydroxycorticosteroids; Administration, Inhalation; Adrenal Glands; Adult; Aged; Asthma; Cosyntropin; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Middle Aged; Time Factors; Triamcinolone Acetonide

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Clinical Trials as Topic; Cosyntropin; Humans; Male; Middle Aged; Placebos

The purpose of this study was to compare the effectiveness of flunisolide aerosol prescribed as .5 mg (two inhalations) twice daily and placebo in terms of oral steroid sparing ability in a population of 32 known steroid-dependent children and adolescents. Patients were stabilized on the lowest tolerated dose of daily AM or alternate AM oral corticosteroid for at least one month before entering the study. They were randomly assigned to either flunisolide or placebo treatment for the 12-week, double-blind trial. Patients were seen every two weeks for symptom assessment, physical examination, and pulmonary function testing. Tests of adrenal function were done initially and at the study's conclusion. The flunisolide group had improved asthma control compared with the placebo group. The daily oral steroid requirement decreased in 100 percent of the flunisolide group compared with 53 percent of the placebo group (P less than .01). Pulmonary function and endocrine function remained stable for both groups. There were no adverse effects. Flunisolide aerosol in doses of .5 mg twice daily appears to be topically active and to have oral steroid potential without apparent adverse effects.

Topics: Adolescent; Aerosols; Aging; Asthma; Child; Child, Preschool; Clinical Trials as Topic; Cosyntropin; Double-Blind Method; Female; Fluocinolone Acetonide; Humans; Hydrocortisone; Male; Placebos; Respiratory Function Tests; Steroids; Time Factors

Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Blood Gas Analysis; Blood Pressure; Cosyntropin; Drug Evaluation; Drug Therapy, Combination; Heart Rate; Humans; Injections, Intravenous; Methylprednisolone; Spirometry; Terbutaline

Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem.

Topics: Adolescent; Adrenal Cortex Function Tests; Aerosols; Asthma; Beclomethasone; Body Height; Body Weight; Child; Clinical Trials as Topic; Cosyntropin; Female; Humans; Male; Methylprednisolone; Placebos; Rhinitis, Allergic, Seasonal

Inhaled beclomethasone dipropionate and inhaled betamethasone valerate have been compared with oral prednisone in the treatment of 75 patients with asthma who were starting long-term corticosteroids for the first time. Both of the inhaled corticosteroids controlled asthma as well as did oral prednisone in those who had responded to therapy in the initial period of the trial. A daily dose of 400 mug of inhaled drug was approximately equivalent to 7-5 mg daily of prednisone. Prednisone suppressed the adrenal response to tetracosactrin, whereas the mean responses in the groups receiving inhaled corticosteroids did not change significantly from pre-trial values. The 30% incidence of other systemic unwanted effects of prednisone contrasted sharply with the low incidence (5%) of symptomatic oropharyngeal candidiasis in the patients receiving inhaled corticosteroids. In a sample of 19 patients no change in exfoliative cytology was detected over the period of the trial nor was there any evidence of fungal colonisation of the bronchial tree. There was no difference between the three treatment groups in the number of antibiotic courses prescribed. The persistent production of sputum made no difference to the response to inhaled corticosteroids. Patients not on sodium cromoglycate did as well in the trial as those receiving sodium cromoglycate. Both inhaled beclomethasone dipropionate and inhaled betamethasone valerate have advantages over oral prednisone in the maintenance treatment of patients with asthma, but in the management of exacerbations systemic corticosteroids will usually be needed as a supplement to inhaled therapy.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adrenal Cortex Function Tests; Adrenal Glands; Aerosols; Asthma; Beclomethasone; Betamethasone; Clinical Trials as Topic; Cosyntropin; Cromolyn Sodium; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Placebos; Prednisone

Two comparable groups of asthmatics each with 10 patients were treated during 2 years at scheduled intervals with either natural or synthetic ACTH up to a total dose of 2000-95-- IU. All patients had previously been given the natural but never the synthetic hormone. Intradermal tests with natural and synthetic ACTH were performed before treatment and after 1, 12 and 24 months. Serum samples were also taken on these occasions and analysed for antibodies against ACTH, vasopressin and porcine gamma-globulin. No sign of clinical allergy to ACTH was noted in any of the patients during the 2-year period. The incidence of intradermal reactions against natural ACTH was high at the onset of treatment but was not increased by treatment with either synthetic or natural ACTH, while the reactivity rate against synthetic ACTH was increased after both types of treatment. The incidence of IgE reactions against synthetic ACTH at the 20 U/ml level was significantly increased after 12 months' treatment with either natural or synthetic hormone. A high incidence of low-titered agglutinating antibodies against natural or synthetic ACTH was demonstrated before treatment in both the groups, but no significant change in incidence or mean titre against natural or synthetic ACTH or porcine gamma-globulin was noted during treatment with the natural or the synthetic preparation. A few patients, however, did display an increased agglutinating titre against ACTH after 12 months' treatment. Rather unexpectedly, most sera reacting with ACTH were found to react also with vasopressin and a significant increase of the incidence of these reactions and of the titres occurred during the treatment with synthetic as well as with natural ACTH. Two cases have been examined in detail, one because of a fulminant shock after synthetic ACTH and the other because of very high antibody titres without clinical symptoms of ACTH allergy.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Antibodies; Antibody Formation; Antigen-Antibody Reactions; Asthma; Cosyntropin; Female; Humans; Immunoglobulin G; Immunoglobulin M; Intradermal Tests; Male; Middle Aged; Vasopressins

In a single-blind trial 29 patients with corticosteroid-dependent asthma reduced their daily dose of oral prednisolone by 1 mg/week while using a placebo inhaler until an unacceptable degree of asthma occurred. Betamethasone-17-vlaerate in a dose of 800 mug/day and if necessary 1600 mug/day was then substituted for the placebo inhaler and the reduction of oral prednisolone continued until the prednisolone was withdrawn completely or an unacceptable degree of asthma recurred. In 22 patients (76%) prednisolone was withdrawn completely, 11 on 800 mug and 11 on 1600 mug betamethasone-17-valerate. The mean reduction of prednisolone was 3-8 mg on placebo, 5-4 mg on 800 mug and a further 1-8 mg in patients requiring 1600 mug of betamethasone-17-valerate. The hypothalamic pituitary adrenal (HPA) axis was assessed by tetracosactrin and insulin stress tests at the start of the study and after withdrawal of oral prednisolone. The results indicate that an HPA axis which is completely suppressed by systemic corticosteroids can regain normal integrity when the systemic steroid is replaced by betamethasone-17-valerate in a dose of either 800 mug/day or 1600 mug/day. Candidiasis was observed, but will be reported later.

Topics: Adrenal Glands; Aerosols; Asthma; Betamethasone; Betamethasone Valerate; Clinical Trials as Topic; Cosyntropin; Female; Humans; Hypothalamus; Insulin; Male; Middle Aged; Pituitary Gland; Pituitary-Adrenal Function Tests; Prednisolone

Topics: Administration, Oral; Adolescent; Adrenocorticotropic Hormone; Adult; Aerosols; Aged; Asthma; Betamethasone; Betamethasone Valerate; Clinical Trials as Topic; Cosyntropin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prednisone; Steroids

Topics: Administration, Oral; Adolescent; Adrenocorticotropic Hormone; Adult; Aerosols; Aged; Asthma; Betamethasone; Betamethasone Valerate; Chronic Disease; Clinical Trials as Topic; Cosyntropin; Female; Humans; Male; Prednisolone

Corticosteroids are known to cause adrenal suppression. The aim of this study was to assess clinical factors affecting responses to a low dose short synacthen test (LDSST) in asthmatic children using corticosteroids.. Patients were recruited from secondary care paediatric asthma populations within the UK.. Asthmatic children (5-18 years), receiving corticosteroids, underwent a LDSST (n = 525).. Demographics and corticosteroid doses were tested for association with baseline and peak (stimulated) cortisol concentrations.. Baseline cortisol was significantly associated with age (log baseline increased 0·04 nm per year of age, P < 0·0001), but not with gender or corticosteroid dose. Peak cortisol was significantly associated with total corticosteroid cumulative dose (decreased 0·73 nm per 200 mcg/day, P < 0·001) but not with age, gender inhaled/intranasal corticosteroid cumulative dose or number of courses of rescue corticosteroids. Biochemically impaired response (peak cortisol ≤500 nm) occurred in 37·0% (161/435) overall, including children using GINA low (200-500 mcg/day beclomethasone-CFC equivalent 32%, n = 60), medium (501-1000 mcg/day (33%, n = 57) and high (>1000 mcg/day 40%, n = 13) doses of inhaled corticosteroid (ICS) similarly, and 36·6% of those using fluticasone ICS ≥500 mcg/day (71/194). Impaired response was more frequent in patients on regular oral corticosteroids (66%, n = 27, P < 0·001).. Children with asthma can develop biochemical adrenal suppression at similar frequencies for all ICS preparations and doses. The clinical consequence of biochemical suppression needs further study.

Topics: Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adrenal Glands; Asthma; Child; Child, Preschool; Cohort Studies; Cosyntropin; Female; Humans; Hydrocortisone; Male; Prevalence; Steroids; United Kingdom

Supported by meta-analyses, the low-dose Synacthen test (LDST) has gained in popularity, with many believing it to be more sensitive than the supraphysiological standard (250 µg) short ST (SSST), particularly when assessing children prescribed high-dose inhaled corticosteroids (HDICS). However, consensus is lacking about its specific clinical application, what is considered 'low dose' and how that dose is made up.. To ascertain current use of the short Synacthen test (SST), a questionnaire was emailed to members of the British Society of Paediatric Endocrinology and Diabetes in the UK and Ireland (N=257), requesting a response from each department (N=92). A reminder was sent a month later to members of departments which had not responded.. The authors received 39 replies, giving a response rate of 42%. All departments use the SST: 82% use an LDST, 87% use the SSST and 69% use both. The 1 µg dose was used by 44% of hospitals, with the other 56% using seven different doses based on age, weight and body surface area. There were 14 different methods of preparing the low dose test. Additionally, variations in the timings of cortisol sampling and the diagnostic cut-offs for adrenal insufficiency were found. Increased requests for SSTs in children with asthma prescribed HDICS were noted by 44% of respondents, with 67% reporting the detection of adrenal suppression in this group.. Standardisation of the SST is required to address the considerable variation in the methodology and application of this test in the UK and Ireland.

Topics: Adrenal Insufficiency; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Hormones; Humans; Ireland; Meta-Analysis as Topic; Sensitivity and Specificity; Surveys and Questionnaires; United Kingdom

To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP).. Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of > or =500 microg and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables.. Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests.. The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Reproducibility of Results

Topics: Adolescent; Adrenal Cortex Function Tests; Anti-Asthmatic Agents; Asthma; Contraindications; Cosyntropin; Down-Regulation; Humans; Hypothalamo-Hypophyseal System; Metyrapone; Pituitary-Adrenal System; Sensitivity and Specificity; Statistics as Topic

Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose.. Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l).. A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day.. Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluticasone; Humans; Hydrocortisone

To determine whether routine outpatient monitoring of growth predicts adrenal suppression in prepubertal children treated with high dose inhaled glucocorticoid.. Observational study of 35 prepubertal children (aged 4-10 years) treated with at least 1000 microg/day of inhaled budesonide or equivalent potency glucocorticoid for at least six months. Main outcome measures were: changes in HtSDS over 6 and 12 month periods preceding adrenal function testing, and increment and peak cortisol after stimulation by low dose tetracosactrin test. Adrenal suppression was defined as a peak cortisol < or =500 nmol/l.. The areas under the receiver operator characteristic curves for a decrease in HtSDS as a predictor of adrenal insufficiency 6 and 12 months prior to adrenal testing were 0.50 (SE 0.10) and 0.59 (SE 0.10). Prediction values of an HtSDS change of -0.5 for adrenal insufficiency at 12 months prior to testing were: sensitivity 13%, specificity 95%, and positive likelihood ratio of 2.4. Peak cortisol reached correlated poorly with change in HtSDS (rho = 0.23, p = 0.19 at 6 months; rho = 0.33, p = 0.06 at 12 months).. Monitoring growth does not enable prediction of which children treated with high dose inhaled glucocorticoids are at risk of potentially serious adrenal suppression. Both growth and adrenal function should be monitored in patients on high dose inhaled glucocorticoids. Further research is required to determine the optimal frequency of monitoring adrenal function.

Topics: Administration, Oral; Adrenal Glands; Androstadienes; Asthma; Body Height; Body Mass Index; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cosyntropin; Female; Fluticasone; Glucocorticoids; Growth; Humans; Hydrocortisone; Male

This cross-sectional study was designed to examine the prevalence of adrenocortical suppression in children with asthma treated with high-dose inhaled fluticasone propionate (FP). Children and adolescents (n=50) with asthma, treated with inhaled FP at a dose of > or = 1,000 mg a day for > or = 6 months, were enrolled. Early morning serum cortisol was performed. Subjects with a serum cortisol of < 400 nmol x L(-1) had a tetracosactrin stimulation test. Fifty subjects of mean age 13.1 yrs were treated with a mean dose of 924.7 microg x m(-2) x day(-1) FP for a mean duration of 2 yrs. Of the 50 subjects, 36 (72%) had serum cortisol levels of < 400 nmol x L(-1) and underwent tetracosactrin stimulation test. Of these, 6 (17%) demonstrated a less than two-fold increase in serum cortisol from baseline and peak cortisol level of < or = 550 nmol x L(-1) at 30 or 60 min poststimulation. There was a significant negative correlation between the dose of FP x m(-2) and stimulated peak cortisol level. Biochemical evidence of adrenocortical insufficiency was demonstrated in 12% of the subjects, indicating that high-dose fluticasone propionate use may be associated with dose-dependent adrenocortical suppression.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cosyntropin; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Hydrocortisone; Male; Statistics, Nonparametric

Anti-inflammatory drugs, particularly inhaled corticosteroids remain the mainstay of treatment of bronchial asthma. However, these drugs have potential side effects. This study was undertaken to evaluate the effects of inhaled beclomethasone dipropionate (400 and 800 micrograms) over a period of six months on the hypothalamo-pituitary-adrenal axis (HPA) suppression.. Assessment of the hypothalamo-pituitary-adrenal axis function was carried out by tetracosactrin test at time zero, (before start of treatment), three months, and six months. The baseline values served as the controls for each patient. Serum cortisol was estimated by radioimmuno assay. The response to short tetracosactrin test was classified as normal if serum cortisol levels rose at least 200 nmol/L to a minimum of 500 nmol/L.. There were seven patients who were inhaling beclomethasone dipropionate in a dose of 400 micrograms/day and another seven patients were taking the same drug in a dose of 800 micrograms/day. There was no side effect of the drug in any patient except in one patient who had dysphonia. The mean basal cortisol levels were normal in all the subjects at 0, 3 and 6 months of therapy. Tetracosactrin stimulation test was also normal in all patients at all the times who were receiving the dose of 400 micrograms/day. However, one patient (14%) receiving 800 micrograms/day had HPA axis suppression at six months. Two patients in this group also had low basal cortisol levels. There was no clinical evidence of such suppression/deficiency.. Beclomethasone dipropionate in a dose of 800 micrograms/day may suppress the hypothalamo-pituitary-adrenal axis if used for long periods (six months). However, this may not have any clinical significance.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Cosyntropin; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System

Adrenal function in stable asthmatics has been extensively studied. The purpose of this study was to determine the effect of asthma exacerbation on adrenal function.. We studied an observational cohort, convenience sample of patients at a university-affiliated county hospital. Adult patients with asthma who were not steroid-dependent and who presented to the emergency department because of their asthma comprised the study group. All patients were examined and pulmonary function tests were performed. Blood samples for determination of initial cortisol levels were obtained, followed by the administration of .25 mg cosyntropin intramuscularly. Standard therapy with aerosolized albuterol was then initiated. Plasma cortisol levels were measured 30 and 60 minutes later. Steroid therapy was withheld until completion of the rapid cosyntropin stimulation test.. A total of 74 patients participated; 64% (47) were women. The range of pretreatment FEV1 was from 10% predicted to 74% predicted. The range of cortisol levels on presentation was from 1.6 micrograms/dL to 35.8 micrograms/dL. Twelve patients had initial cortisol levels greater than 20 micrograms/dL, a level indicative of physiologic stress. Four patients had initial cortisol levels greater than 30 micrograms/dL. Mean plasma cortisol levels at 0, 30, and 60 minutes were 13.7 micrograms/dL (+/- 7.2 micrograms/dL), 28.7 micrograms/dL (+/- 7.4 micrograms/dL), and 33.0 micrograms/dL (+/- 8.2 micrograms/dL). We found an association between evidence of physiologic stress and severe airflow obstruction (P < .03) but no linear correlation (r = -.15).. Few patients with asthma have adrenal suppression on presentation. Asthma exacerbation does not provoke a physiologic stressor response in most asthmatic patients.

Topics: Acute Disease; Adrenal Glands; Adult; Albuterol; Asthma; Bronchodilator Agents; Cosyntropin; Emergency Service, Hospital; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Patient Admission; Sampling Studies; Severity of Illness Index; Stress, Physiological

Little is known about the dose-response relationship of potential, unwanted, effects of inhaled beclomethasone (BDP) on the hypothalamo-pituitary-adrenal (HPA) axis, particularly in nonspecialist clinic settings. The purpose of our study was to investigate the dose-response relationship of inhaled BDP on the HPA axis in a general practice patient population. We also explored the optimal testing strategy in this population and correlated effects of inhaled BDP on the HPA axis with other systemic corticosteroid side effects.. Controlled observational study employing 21 patients on inhaled BDP recruited from general practice, with minimal past and no present exposure to other corticosteroids, and 21 age and gender-matched controls.. Twenty-four-hour urinary free cortisol excretion (UFC), serum cortisol before and 30 minutes after injection of 1 microgram and 250 micrograms of tetracosactrin, serum IGF-I and serum osteocalcin were measured. BDP use was estimated by inhaler weighing and prescription count.. In subjects on inhaled BDP, 24-hour UFC (P < 0.008), serum cortisol 30 minutes after 250 micrograms tetracosactrin (P < 0.05) and the serum cortisol rise after 250 micrograms tetracosactrin (P < 0.04) were significantly lower when compared with controls. Measurements of HPA function correlated inversely with BDP dose estimated by inhaler weighing (all P < 0.03). Serum IGF-I and osteocalcin levels did not differ.. We have demonstrated hypothalamo-pituitary-adrenal axis suppression in nonspecialist-clinic asthma patients on moderate to large doses of inhaled beclomethasone dipropionate. When accurate measurements of inhaled steroid dose are used, there is an exponential relationship between dose and hypothalamo-pituitary-adrenal axis suppression. There appears to be no 'safe' threshold, and around 15% of patients may have clinically significant suppression. However, the significance of hypothalamo-pituitary-adrenal axis suppression as a marker for concomitant corticosteroid effects on other organ systems remains uncertain.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Case-Control Studies; Cosyntropin; Depression, Chemical; Dose-Response Relationship, Drug; Drug Administration Schedule; Family Practice; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Male; Middle Aged; Osteocalcin; Pituitary-Adrenal System

Although the influence of high dose inhaled steroids on hypothalamo-pituitary-adrenal (HPA) function in patients with asthma has been extensively studied worldwide, there has been limited information on Japanese asthmatics, especially in terms of a prospective analysis of HPA function in the course of time. We analyzed the changes in HPA function using 2 serial short tetracosactrin tests (STT) separated by an interval of one year in 11 Japanese asthmatics who were treated with high dose inhaled steroids alone [beclomethasone dipropionate (BDP); mean dose 982 micrograms/day] during the period between 2 STTs. Mean values of plasma cortisol before administration of ACTH, maximum cortisol and the rise in cortisol in response to ACTH in the 2 STTs were 7.8, 20.5 and 12.7 micrograms/dl for the 1st test, and 8.9, 23.6 and 14.7 micrograms/dl for the 2nd test, respectively. Overall, there was no significant change in the course of time in each of these 3 values. Although the results of the 1st STT proved to be abnormal in 3 patients who had been receiving systemic steroids before their 1st STT, they improved uniformly in their 2nd STT. In the remaining 8 patients, who had never received systemic steroids, 4 patients showed improvements while the other 4 showed deterioration in HPA function in their serial STTs over the course of time. The dose of BDP was 800 micrograms/day in the former 4 patients, while it was 1,200 micrograms/day in the latter 4. Furthermore, only one patient, in whom BDP had been increased from 800 micrograms/day to 1,200 micrograms/day between the 2 tests, developed an abnormal response in the 2nd STT. On the other hand, one patient whose BDP dose was increased from 800 micrograms/day to 1,600 micrograms/day showed an improvement in HPA function in the 2nd test. These results indicate that the threshold dose of BDP which may cause HPA suppression in Japanese asthmatics lies between 800-1,200 micrograms/day, although there is a large inter-individual variation in terms of such doses.

Topics: Administration, Inhalation; Adrenal Cortex; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cosyntropin; Female; Follow-Up Studies; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Safety

Ten asthmatic patients receiving long term treatment with high dose of inhaled beclomethasone dipropionate (BDP) (750 to 2,250 micrograms/die, average 1,400 +/- 474 micrograms) underwent evaluation of hypothalamic-pituitary-adrenal (HPA) axis under basal conditions (serum cortisol and ACTH levels at 8.00 AM and 8.00 PM, 24-hours free urinary cortisol) and by means of pharmacological tests (short tetracosactide and Corticotrophin Releasing Factor Tests). Basal ACTH serum levels at 8.00 PM were lower than the normal values in all patients: three patients had reduced 24-hr free urinary cortisol and six subjects showed lower cortisol serum levels at 8.00 PM. A normal response to the short tetracosactide test was observed in all patients, whilst Corticotrophin Releasing Factor (CRF) induced an increase in ACTH and cortisol levels (expressed as delta AUC) that was significantly lower in the BPD treated patients compared with a control group of five healthy subjects (p < 0.05). Thus BPD, in high doses, may cause a partial inhibition of HPA axis. Our results show that determination of basal ACTH level and CRF test are more sensitive than serum cortisol levels and short tetracosactide test to evaluate a suppression of HPA axis in patients receiving long term inhaled high doses of BDP.

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Beclomethasone; Circadian Rhythm; Corticotropin-Releasing Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System

The effect of inhaled steroids on adrenal glands of asthmatic subjects are often difficult to assess because subjects may have received oral steroids before. Moreover, even if the Synacthen test is abnormal, it does not necessarily mean that the adrenals are clinically inefficient. Adrenal insufficiency can certainly occur at high doses of inhaled steroids. Possible long term effects on bone are under study. Ecchymosis has been described. Oropharyngeal candidiasis is frequent but rarely symptomatic and responds well to treatment. Hoarseness is rare but troublesome. In children, inhaled steroids, even taken at low dose, can induce growth impairment. After cessation of inhaled steroids, adrenal insufficiency is only theoretical. Asthmatic flare-ups are more of a threat. Although inhaled steroids are of remarkable efficacy and tolerance, one should not exclude the possibility of long-term negative effects, especially in children.

Topics: Administration, Inhalation; Administration, Topical; Adrenal Glands; Adult; Age Factors; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Cosyntropin; Drug Tolerance; Glucocorticoids; Growth Disorders; Humans; Pregnenediones

High dose inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis. Several tests are available to screen for this suppression but it is not clear which is the most useful. HPA function was assessed in 78 adult asthmatics inhaling long-term, high dose (median 1600 micrograms; range 1200-2650 micrograms) beclomethasone dipropionate (n = 69) or budesonide (n = 9). Screening tests performed in all patients were 9 am serum cortisol, short tetracosactrin test and 24-h urine free cortisol excretion. Eleven patients also underwent insulin stress tests. Subnormal results were: 9 am cortisol less than 190 nmol l-1; urine free cortisol less than 80 nmol 24 h-1; rise in cortisol in response to tetracosactrin or hypoglycaemia less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1. HPA suppression (defined as subnormal results of at least two of the three initial tests and/or subnormal response to hypoglycaemia), was found in 16 patients. In the 11 patients who underwent insulin stress tests, results of all initial tests were normal in three, one test was abnormal in three and two tests were abnormal in four patients. All three tests were abnormal in the remaining patient. The response to hypoglycaemia was normal in the three patients whose screening tests were all normal; HPA suppression was present in seven patients and one patient had a borderline result. Close correlation was observed between the maximum cortisol during hypoglycaemia and both urine free cortisol (rs = 0.84; P = 0.001) and post-tetracosactrin cortisol (r = 0.75; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Cosyntropin; Depression, Chemical; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Bronchitis; Cosyntropin; Female; Humans; Hydrocortisone; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Respiration

The adrenocortical function was investigated in 18 children treated with high-doses of inhaled glucocorticoid aerosol (mean: 1965 micrograms/1.73 m2 body surface a day). Basal serum cortisol was only below the normal range in patients treated with doses exceeding 2500 micrograms/1.73 m2 body surface. 15 of 18 children had normal 24 h urinary free cortisol excretion, compared with 27 normal children matched for age, sex and body surface. Three patients taking more than 2400 micrograms/1.73 m2 body surface showed excretion values below the range for the normal controls. 10 of 12 patients showed a normal response to a short ACTH stimulation test. One patient treated with 3300 micrograms/1.73 m2 body surface showed no response and one patient gave a borderline response to ACTH. We concluded that doses up to 2000 micrograms/1.73 m2 body surface/24 can be administered by pressurized aerosol with little risk of adrenocortical suppression.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex; Asthma; Beclomethasone; Budesonide; Child; Cosyntropin; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Pregnenediones

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Adult; Asthma; Cosyntropin; Delayed-Action Preparations; Humans; Hydrocortisone; Long-Term Care; Middle Aged

Skeletal maturation in severe bronchial asthma was studied in 15 children during and after treatment with depot tetracosactrin and in 6 children during treatment with prednisolone. Attained skeletal maturity before treatment was below the reference mean in the majority of children. Skeletal maturation was enhanced during treatment with depot tetracosactrin, which led to more advanced attained skeletal maturity at withdrawal than at start of treatment. There was a tendency towards larger increases of skeletal maturity than of height. The influence of adrenal androgens, released by ACTH-stimulation and good control of the disease are probably relevant factors for the acceleration of skeletal maturation. After withdrawal of depot tetracosactrin the rate of skeletal maturation normalized. During prednisolone treatment there was a delay of skeletal maturation leading to a progressive relative decrease of attained skeletal maturity, and closely related to a delay in linear growth. Treatment with depot tetracosactrin may thus induce enhancement of skeletal maturation, but with the treatment regimen found to be efficacious in bronchial asthma, the effect is not very pronounced and does not perceptibly affect the ultimate outcome of growth.

Topics: Adolescent; Adrenocorticotropic Hormone; Age Determination by Skeleton; Asthma; Bone and Bones; Child; Child, Preschool; Cosyntropin; Delayed-Action Preparations; Female; Humans; Infant; Longitudinal Studies; Male; Prednisolone; Time Factors

Adrenocortical function was assessed by the intravenous short synacthen test in 22 control subjects and 68 patients admitted to hospital with acute severe asthma. The cortisol increment was subnormal in 19 of the 68 asthmatics. This included 11 of the 14 patients on continuous oral steroids, seven of the 29 patients who had had occasional courses of oral steroids, one of the seven on inhaled steroids only, and none of the 18 who had had no steroids. Adrenal suppression was greatest in those patients taking oral steroids in divided daily doses. Nineteen of 43 patients were on or had taken oral steroids in this fashion. Of those 19 patients with low cortisol increments only one half had received supplementary steroids in the 24 hours preceding admission. Based on the synacthen test, serum DHEA-SO4 values were not a good discriminant of adrenocortical function. Adrenal insufficiency may be an important cause of death in acute severe asthma in New Zealand.

Topics: Acute Disease; Adolescent; Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aged; Asthma; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Male; Middle Aged

Prolonged observation of eight steroid-dependent asthmatics show that the dose of beclomethasone dipropionate aerosol may be increased in some cases up to 2000 micrograms daily without significant impairment in the results of serial tetracosactrin tests of adrenocortical function. These findings contrast sharply with the results of such tests during oral prednisolone therapy.

Topics: Adrenal Glands; Aerosols; Asthma; Beclomethasone; Cosyntropin; Dose-Response Relationship, Drug; Humans; Hydrocortisone

Studies of adrenal function were performed on 54 asthmatic patients who were taking long term high doses of inhaled beclomethasone dipropionate ranging from 500 to 2000 micrograms/day for between six and 60 months. Of the 43 patients taking up to 1500 micrograms/day, 39 (91%) had normal basal plasma cortisol concentrations and normal short tetracosactrin responses and 24 hour urinary free cortisol excretion was within the normal range in eight of nine patients tested. Some evidence of adrenal suppression was found in patients taking 2000 micrograms/day, with basal plasma cortisol below the normal range in four out of 11 patients and 24 hour urinary free cortisol excretion below the normal range in five out of six patients tested. Only one of the 11 patients taking 2000 micrograms/day had a short tetracosactrin response below the normal range: the mean rise in plasma cortisol was, however, significantly lower in this group than in those taking 1000 micrograms/day (328 (SE 30) and 506 (34) nmol/l respectively) (p less than 0.01). Patients taking more than 1500 micrograms/day of inhaled beclomethasone may require systemic corticosteroids during prolonged stress.

Topics: Adolescent; Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adult; Aged; Asthma; Beclomethasone; Circadian Rhythm; Cosyntropin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Male; Middle Aged; Respiratory Therapy

The hypothalamic-pituitary-adrenal axis was investigated in 15 asthmatic children treated with inhaled beclomethasone dipropionate (mean 490 micrograms/day) and 11 asthmatic control subjects receiving no corticosteroid therapy. Measurements of 24-h urinary free cortisol and 17 hydroxy corticosteroids, serum cortisol, response to ACTH, and the oral metyrapone test showed no significant difference between the two groups. All the patients' results were within normal limits, and carbohydrate metabolism, as shown by blood glucose and hemoglobin A1c, was not affected by beclomethasone therapy. Thus, in the above dose, inhaled beclomethasone does not cause suppression of the hypothalamic-pituitary-adrenal axis.

Topics: 17-Hydroxycorticosteroids; Adolescent; Asthma; Beclomethasone; Blood Glucose; Child; Child, Preschool; Cosyntropin; Female; Glycated Hemoglobin; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Pituitary-Adrenal System; Respiratory Therapy

Synthetic 1-24adrenocorticotrophin (tetracosactid, Synacthen) is used in clinical medicine for diagnostic and therapeutic purposes. Side effects may occur due to unphysiological stimulation of endogenous adrenocortical hormone production. Allergic reactions to tetracosactid are rare. Anaphylactic shock leading to death was observed after intravenous injection of tetracosactid in a 14-year-old girl with bronchial asthma. Adrenocorticotrophin antibodies could be demonstrated after death in serum and ascitic fluid using the double antibody method.

Topics: Adolescent; Adrenocorticotropic Hormone; Anaphylaxis; Antibodies; Ascitic Fluid; Asthma; Cosyntropin; Female; Humans

Hypothalamo-pituitary--adrenal (HPA) function was studied using tetracosactrin and insulin hypoglycemia tests in eleven asthmatic patients who were receiving or had taken oral steroids. The patients had been on prednisone, 5--20 mg/day for 2--17 years. As the dose was reduced they used beclomethasone inhalation, up to 800 micrograms/day. Seven insulin hypoglycemia tests were performed when the patients had been off oral steroids for 15--37 months. Plasma cortisol responses were normal in all seven, three had subnormal responses of ACTH. In five patients serial tetracosactrin and insulin hypoglycaemia tests were performed during reduction of steroid dose. Two patterns of recovery of HPA function were observed. In one, both hypothalamo--pituitary and adrenal function seemed to return simultaneously, in the other normal response to tetracosactrin appeared before that to insulin hypoglycaemia. One patient had normal ACTH and cortisol responses to the stress of a vasovagal attack, but failed to respond to subsequent hypoglycaemia. We conclude that a normal response to tetracosactrin does not indicate recovery of the HPA axis after stopping prolonged oral steroid therapy for asthma, and that patients should continue to carry steroid therapy cards for at least 5 years after such treatment has been discontinued.

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal System; Prednisone

Treatment trial over a period of 3 months was conducted with intermittent intramuscular injections of Cortrosyn depot in fourteen children with severe and frequent asthmatic attacks. The basal plasma cortisol levels were generally high, but higher than normal in four (29%) of the patients. At a period of 24 h after the initial Cortrosyn injection was administered, plasma cortisol increases ranging between 4-52 micrograms/100 ml above the basal levels were recorded. At a period of 1 week after the end of daily injections for 1 week, increases of plasma cortisol ranging between 3-71 micrograms/100 ml above the basal levels were observed and presumed to be a reflection of an associated adrenal hypertrophy resulting from repetitive daily Cortrosyn injections. The highest increases at this stage were observed in the youngest patients with the severest asthmatic attacks, but not in their older counterparts. At the end of the trial treatment, clinical improvement was associated with lowered plasma cortisol levels compared with the elevated basal values.

Topics: Adrenocorticotropic Hormone; Asthma; Child; Child, Preschool; Cosyntropin; Humans; Hydrocortisone

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Airway Obstruction; Asthma; Cosyntropin; Drug Hypersensitivity; Female; Humans; Male

The causes for an abnormal five-hour tetracosactrin test in 14 out of 75 patients (18.5% of the entire group), treated continuously with triamcinolone acetonide long-term (mean 3.2 years) for asthma or related syndromes, were investigated. The average daily dosage, duration of treatment and age of the patients were analyzed. Statistical analysis indicated that the risk of adrenocortical suppression was increased by the patient's age and the average patients under the age of 50, receiving less than 1.2 mg triamcinolone acetonide daily, only rarely develop adrenocortical functional impairment.

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adult; Animals; Asthma; Cattle; Cosyntropin; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Long-Term Care; Male; Middle Aged; Triamcinolone Acetonide

Topics: Adult; Aged; Albuterol; Asthma; Cosyntropin; Cyclic AMP; Female; Humans; Hydrocortisone; Middle Aged; Respiratory Function Tests; Theophylline

Among 26,462 carefully monitored medical inpatients, 24, or 0.9 per 1,000, were considered to have died as a result of a drug or group of drugs. Most of the patients were seriously ill prior to the event that caused death. Six of the deaths-five from fluid overload and one from excessive potassium therapy-may have been preventable.

Topics: Adolescent; Adult; Aged; Anaphylaxis; Asthma; Cerebral Hemorrhage; Cosyntropin; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Hemorrhage; Heparin; Hospitalization; Humans; Iatrogenic Disease; Male; Methods; Middle Aged; Pharmaceutical Preparations; Pulmonary Embolism; Streptodornase and Streptokinase; Thrombophlebitis; United States

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Bacterial Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cosyntropin; Drug Tolerance; Female; Humans; Hydrocortisone; Male; Respiratory Tract Infections; Time Factors

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Circadian Rhythm; Cosyntropin; Female; Growth Disorders; Humans; Hydrocortisone; Male; Pituitary-Adrenal System; Time Factors

The difficulties of long term treatment of chronic obstructive lung disease demand knowledge and use of every reasonable therapeutic regimen. In this study effectivity and side effects of Depot-ACTH (Tetracosactid) are presented. The main indications for the use of Depot-ACTH seem to be the uneffectiveness of usual therapy and the attempt of avoiding or reducing corticosteroids. The study confirms the excellent usefulness of Depot-ACTH which did not diminish during long-term application. The side effects are rare and mostly inferior. Only allergic reactions may be serious and must be accounted for.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Asthma; Child; Cosyntropin; Diabetes Complications; Drug Hypersensitivity; Edema; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pregnancy; Pregnancy Complications; Pulmonary Emphysema; Tuberculosis, Pulmonary

Beclomethasone dipropionate aerosol at a dose of 100 mug four times a day was administered to 32 patients suffering from chronic perennial asthma. Twenty-three of these patients had previously received prolonged treatment with corticosteroids, causing various degrees of adrenal suppression in some patients. Almost complete recovery of adrenal function was observed within a period of six months in most patients. Treatment with beclomethasone dipropionate did not affect the hypothalamic-pituitary-adrenal axis in the other nine asthmatic patients who had not received prolonged corticosteroid therapy previously and who served as a control group.

Topics: Administration, Oral; Adrenal Cortex; Adrenal Glands; Adult; Aerosols; Asthma; Beclomethasone; Cosyntropin; Depression, Chemical; Drug Evaluation; Female; Humans; Hydrocortisone; Hydroxycorticosteroids; Hypothalamus; Long-Term Care; Male; Methylprednisolone; Middle Aged; Pituitary Gland; Pituitary Gland, Anterior; Prednisone

An investigation into the use of beclomethasone dipropionate aerosol in the management of 42 severe asthmatic children, ranging in age from two-and-a-half to 16 years with a mean age of seven years is presented.

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Chickenpox; Child; Child, Preschool; Cosyntropin; Humans; Methylprednisolone; Prednisolone

Topics: Adrenocorticotropic Hormone; Adult; Anaphylaxis; Animals; Antibody Formation; Asthma; Cosyntropin; Drug Hypersensitivity; Drug Therapy, Combination; Humans; Injections, Intramuscular; Male; Swine; Zinc

A study of 23 patients admitted to hospital with severe acute asthma is reported in which plasma cortisol level on admission was significantly correlated with the degree of acidaemia and pulse rate. Patients who had not previously received treatment with corticosteroids responded satisfactorily to repeated daily injections of tetracosactrin depot, the rate of improvement being comparable to that observed in other patients treated with intravenous hydrocortisone hemisuccinate. A prompt and sustained rise in plasma cortisol was also seen following tetracosactrin. The total daily dose of hydrocortisone required to achieve plasma cortisol levels above 100 mug/100 ml was less when given by continuous intravenous infusion compared with intermittent injections, and a regime of 3 mg/kg body weight every six hours by infusion appeared satisfactory. Most patients reported subjective improvement by about four hours after starting treatment but objective evidence did not appear until about six hours from the start. Measurements of FEV1 and FVC proved to be the most reliable indices of the beginning of improvement although pulse rate was the first index to show maximum improvement. Previous maintenance treatment with corticosteroids in patients with asthma did not appear materially to affect the plasma half-life of intravenous hydrocortisone (4 mgm/kg body weight) when compared with healthy subjects or other patients with asthma who had not previously been treated with corticosteroids.

Topics: Acute Disease; Adolescent; Adrenocorticotropic Hormone; Adult; Asthma; Child; Child, Preschool; Cosyntropin; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Pulse; Vital Capacity

Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression.

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Asthma; Child; Cosyntropin; Humans; Hydrocortisone; Prednisolone; Prednisone

Lymphocyte transformation to 1-24ACTH, as assessed by the incorporation of tritiated thymidine, has been demonstrated to be associated with severe adverse reactions occurring in patients receiving a Zn-linked 1-24ACTH preparation (Tetra cosactrin depot, 'Synacthen'). Antibodies measured with an isotope-binding assay occurred commonly in all patients receiving therapy and did not correlate with adverse reactions. Lymphocyte transformation with the 1-24ACTH polypeptide, a part of the naturally occurring ACTH molecule, has not been previously recorded. The significance of antibodies and cell-mediated immunity to this polypeptide hormone is discussed.

Topics: Adrenocorticotropic Hormone; Adult; Antibodies; Arthritis, Rheumatoid; Asthma; Child; Cosyntropin; Drug Hypersensitivity; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; Zinc

Topics: Adrenocorticotropic Hormone; Anaphylaxis; Asthma; Cosyntropin; Drug Hypersensitivity; Female; Humans; Male; Middle Aged

Fifty-two steroid-dependent adults with chronic perennial asthma were transferred to beclomethasone dipropionate aerosol. The tests demonstrated a significant improvement with beclomethasone in terms of the diary score, bronchodilator use, and PEF and FEV1.0 measurements, as compared with the previous period of prednisolone treatment. Before the transfer, 26 of the patients displayed one or more diseases or symptoms which were probably due to systemic steroid medication. Morning cortisol levels, along with the response to tetracosactrin had in all cases returned to normal when tests were carried out 41 days after transfer to beclomethasone dipropionate. In a group of 12 patients with the lowest 11-OHCS basal values, the mean of their 11-OHCS values during prednisolone treatment was as low as 0.14 plus or minus 0.06 mumol/l, but tetracosactrin challenge induced an elevation to a normal level, 0.33 plus or minus 0.13 mumol/l. After 41 days of beclomethasone treatment, the corresponding values were 0.56 plus or minus 0.90 plus or minus 0.28 mumol/l. Thirty-seven patients experienced one or more disturbing symptoms after transfer to beclomethasone. In many cases, the symptoms of allergic rhinitis were troublesome and persistent leading to a sixfold increase in the use of antihistaminic tablets. When the patients had learned to exhale through the nose following beclomethasone inhalation, the use of antihistaminic tablets again diminished to some extent. Moreover, two cases of ulcerative colitis were encountered during the beclomethasone treatment. During a follow-up period of one year, 14 patients were again receiving prednisolone; most often, this was due to worsening of the asthma because of respiratory infections. During the beclomethasone treatment, a continuous significant improvement in PEF was noted after isoprenaline inhalation, suggesting that further benefit may be obtained by the employment of bronchodilator aerosols as an essential part of the treatment.

Topics: 11-Hydroxycorticosteroids; Adult; Aerosols; Asthma; Beclomethasone; Chronic Disease; Cosyntropin; Drug Therapy, Combination; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Peak Expiratory Flow Rate; Prednisolone; Respiratory Therapy

Sixteen patients with intrinsic non-atopic asthma with persistent wheezing who had never been treated with corticosteroids showed normal adrenocortical responses to prolonged stimulation with Tetracosactin Depot. In a subgroup of six patients the hypothalamo-pituitary-adrenal (HPA) response to a standard insulin stress test was normal. It is concluded that impaired responsiveness of the HPA axis is unlikely to be a common factor in initiating or maintaining airways obstruction in patients with intrinsic asthma.

Topics: Adrenal Glands; Asthma; Cosyntropin; Humans; Hydrocortisone; Hypothalamus; Insulin; Pituitary Gland

Topics: Adrenocorticotropic Hormone; Aerosols; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Growth Disorders; Humans; Rhinitis; Substance Withdrawal Syndrome

Topics: Adrenal Cortex; Adrenal Glands; Adrenocorticotropic Hormone; Asthma; Cosyntropin; Humans; Hydrocortisone