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Biomedical subjects

J H Toogood

Publications and source records attributed to J H Toogood.

At least 19 recordsLinked to original sources
PubMed1999

Serum osteocalcin and procollagen as markers for the risk of osteoporotic fracture in corticosteroid-treated asthmatic adults.

BACKGROUND: Dual energy x-ray absorptiometry provides the definitive measure of osteoporotic fracture risk. OBJECTIVE: We sought to determine whether metabolic measures of bone formation and/or common features of clinical hypercortisonism provide a useful guide in selecting corticosteroid-treated asthmatic patients for referral for bone densitometry. METHODS: We measured bone density and 8 AM serum osteocalcin, procollagen, and cortisol levels in 52 asthmatic adults aged 60.7 +/- 12.6 years (mean +/- SD). Years of steroid exposure for these patients was 11.8 +/- 10.7 (prednisone) and 11.78 +/- 4.98 (inhaled steroid). Using stepwise logistic regression, we assessed the capacity of the osteocalcin and procollagen levels, with or without the cortisol level, age, clinical features of hypercortisonism, and different lifetime exposures to inhaled and oral steroids for distinguishing between patients with greater or lesser risk of fracture. RESULTS: Osteoporosis, defined as a bone density T score below -2.5, affected 26% of the group at the spine and 63% at the hip. At the spine, greater risk was associated only with lower cortisol levels (P =.003). Diagnostic accuracy was 71%, the false-positive rate was 26%, and the false-negative rate was 31%. At the hip, greater risk was associated with lower cortisol levels (P =.002), longer prednisone exposure, (P =.003), lower current doses of prednisone (P =.01) and inhaled steroid (P =.02), and older age (P =.01). Diagnostic accuracy was 83%, the false-positive rate was 13%, and the false-negative rate was 21%. CONCLUSIONS: Neither osteocalcin nor procollagen nor any of the clinical criteria analyzed proved sufficiently accurate to be reliable as indicators of the risk of fracture in these elderly, corticosteroid-treated asthmatic adults. They are therefore not useful for selecting such patients for diagnostic densitometry.

Adrenal Cortex Hormones↗
PubMed1998

Side effects of inhaled corticosteroids.

Inhaled corticosteroid (ICS) therapy carries less risk of complicating drug- or disease-related morbidity and mortality than that associated with other antiasthmatic drugs such as prednisone, theophylline, or beta2-agonist bronchodilators. Serious side effects are uncommon, but the risk increases with the daily dose. The degree of risk is most effectively minimized by ensuring each patient uses the smallest daily dose sufficient to maintain optimum control of their disease. Any patient in whom ocular symptoms develop while receiving ICS therapy should promptly be evaluated by an eye specialist. Growth velocity is commonly reduced during ICS therapy and should be monitored routinely. Bone metabolism may be affected by low or medium doses of ICS, but there is no evidence such doses cause osteoporosis or fracture. High-dose therapy may reduce bone density and increase the risk of fracture, particularly if other risk factors for osteoporosis are present. Research is needed to better define the impact of ICS therapy in children on height and peak bone density attained at maturity. Also, there is a need for practice guidelines specifically applicable to the prevention of bone loss during ICS treatment.

Administration, Inhalation↗
PubMed1997

Comparison of the antiasthmatic, oropharyngeal, and systemic glucocorticoid effects of budesonide administered through a pressurized aerosol plus spacer or the Turbuhaler dry powder inhaler.

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler (n = 30) or pMDI + Nebuhaler (n = 28). Dose-dependent effects were demonstrated on asthma symptoms (p = 0.0001), daily peak expiratory flow (p = 0.02), blood eosinophils (p = 0.0001), urinary cortisol output per day (p = 0.0001), serum cortisol (p = 0.006), serum osteocalcin (p = 0.0001), and the oropharyngeal Candida colony count (p = 0.0007. analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (p > or = 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler.

Administration, Inhalation↗
PubMed1997

Differential effects of inhaled budesonide and oral prednisolone on serum immunoglobulin G and its subclasses in healthy adult volunteers.

BACKGROUND: Glucocorticosteroid (GCS) treatment lowers serum IgG and IgG subclass (IgG-SC) levels, but the minimal dose and duration of administration at which this occurs is not known. OBJECTIVE: The aim of this study was to define the daily dose of a 2-week course of GCS at which IgG(-SC) suppression occurs. METHODS: The effects of three GCS treatment schemes on serum IgG(-SC) levels in healthy adults were studied in a double-blind, randomized trial. Group 1 (n = 10) was treated with 40 mg oral prednisolone/day, group 2 (n = 10) with 10 mg oral prednisolone/day and group 3 (n = 10) with 3.2 mg inhaled budesonide/day. Blood sampling was performed at baseline and at the end of the 2-week treatment period. RESULTS: In group 1, IgG1, IgG2 and IgG3 levels were significantly decreased after treatment, while in group 2 this was only so for IgG3. In both groups, the decrease of total IgG tended towards or just reached significance. In group 3, no statistically significant changes were observed. CONCLUSION: A course of 40 mg oral prednisolone/day for 2 weeks induces significant suppression of serum IgG-SC levels; lower doses cause more subtle changes, indicating that GCS-induced IgG-SC suppression is a dose-dependent phenomenon. Short courses of very high doses of inhaled budesonide appear to be devoid of this side-effect.

Administration, Inhalation↗
PubMed1996

A methodological assessment of diurnal variability of peak flow as a basis for comparing different inhaled steroid formulations.

BACKGROUND: A "survival" model offers certain ethical and practical advantages over alternative experimental designs if used to compare antiasthmatic inhaled steroid formulations. The model requires an objective daily measure of therapeutic effect (e.g., peak expiratory flow rate, which may be expressed as the lower of two daily measurements (LPF) or as diurnal variability (DVPF). The relative efficiency of these two measures is unknown. OBJECTIVE: This study was conducted to determine the relative efficiency of LPF and DVPF. METHODS: We analyzed data from a placebo-controlled comparison of an active inhaled formulation of budesonide versus an inactive oral formulation. The primary outcome measure in this design is the number of days from the time the test treatments start until a statistically significant deterioration occurs from an optimal asthma control value established at baseline. RESULTS: DVPF proved less sensitive than LPF; that is, fewer patients relapsed during the 8-week trial period: 32 versus 41, respectively. Also, the median interval until relapse was longer: 24 versus 9 days. With LPF, inhaled budesonide proved more effective than placebo or oral budesonide (p = 0.03), whereas DVPF failed to discriminate among the test treatments (p = 0.38). LPF correlated with all three symptom indices (p > or = 0.003) and two of three spirometric indices measured concomitantly (p < or = 0.04). DVPF did not correlate with any index (p > or = 0.10). CONCLUSION: In this experimental model, LPF proved more sensitive and valid than DVPF as an indicator of differences in antiasthmatic potency between two inhaled steroid formulations.

Administration, Inhalation↗
PubMed1996

Short courses of high-dose inhaled budesonide and serum IgG subclass levels in healthy volunteers.

BACKGROUND: The incidence of systemic side effects of inhaled budesonide increases at doses exceeding 2000 micrograms/day. OBJECTIVE: This study was carried out to investigate whether high-dose inhaled budesonide affects serum IgG subclass concentrations in healthy adult volunteers. METHODS: Two groups of 10 subjects each inhaled 2.4 mg of budesonide per day in a double-blind, crossover study of morning (8:00 AM and noon, group A) and diurnal (8:00 AM and 8:00 PM, group B) dosing schedules for 4 weeks each, separated by a 2-week washout period. The budesonide was inhaled through a pressurized metered-dose inhaler, mounted on a 750 ml Nebuhaler (ASTRA Pharmaceuticals, Lund, Sweden). The IgG subclass levels were determined at baseline and every 2 weeks until the end of the study period (10 weeks). RESULTS: There were no statistically significant changes in the serum IgG subclass concentrations over the 10-week study period in group A, group B, or groups A and B combined. CONCLUSION: Inhalation of budesonide, 2.4 mg/day, through a large-volume spacer for repeated 1-month periods does not influence serum IgG subclass concentrations in healthy adults, suggesting that budesonide does not cause systemic humoral immunosuppression when given at therapeutic doses.

Administration, Inhalation↗
PubMed1996

Respiratory infections and the autumn increase in asthma morbidity.

Unexplained autumn increases in hospital admissions for asthma have been reported in many countries, including the United States, Canada, England and Wales. To investigate the role of infection, the association was tested between hospital admissions for asthma and respiratory infections among preschool children in Metropolitan Toronto, Canada during the period 1981 to 1989. The seasonal pattern in overall hospital utilization was assessed by admissions for nonrespiratory diseases. Time series analysis was used to remove potentially confounding temporal trends and the influence of correlated errors. A fourfold increase in asthma admissions occurred between July and October unaccompanied by similar increases in nonrespiratory admissions. Admissions began increasing during the third week of August, peaked during the third week in September, and slowly decreased during November and December. After adjusting for serial correlation, trends, climate, ambient air pollution and aeroallergens, the seasonal pattern of respiratory infection explained 14% of the variance in asthma admissions. Based on seasonal patterns, respiratory infection is the major identifiable risk factor for the large autumnal increase in asthma admissions.

Air Pollutants↗
PubMed1995

Bone mineral density and the risk of fracture in patients receiving long-term inhaled steroid therapy for asthma.

To determine whether high-dose or prolonged inhaled steroid therapy for asthma increases a patient's risk of osteoporosis and fracture, we measured bone density in 26 men and 43 women (41 postmenopausal, all of whom had received supplemental estrogen therapy) after treatment with an inhaled steroid for 10.1 +/- 5.5 years and oral prednisone for 10.7 +/- 9.7 years (mean +/- SD). Most had stopped receiving prednisone since commencing the inhaled steroid therapy. We found that bone densities (adjusted for age and sex to yield a z score) were lower in association with higher daily doses of inhaled steroid (p = 0.013 ANCOVA) and with the duration of past prednisone therapy (p = 0.032). Larger cumulative inhaled steroid doses were associated with higher bone densities (p = 0.002) and a reduction in the numbers of patients at risk of fracture. Bone density also increased with the amount of supplemental estrogen therapy (p = 0.058) and, at equivalent levels of inhaled and oral steroid use, women showed higher bone density z scores than did men. Women with a lifetime dose of inhaled steroid greater than 3 gm had normal bone density regardless of the amount of past or current prednisone use or the current dose of inhaled steroid. These data indicate that the daily dose, but not the duration, of inhaled steroid therapy may adversely affect bone density, and that estrogen therapy may offset this bone-depleting effect in postmenopausal women.

Administration, Inhalation↗
PubMed1993

Association of ocular cataracts with inhaled and oral steroid therapy during long-term treatment of asthma.

BACKGROUND: Posterior subcapsular cataracts (PSCs) have been reported to occur in some asthmatic patients treated with inhaled steroids. METHODS: We studied the associations between the occurrence of PSCs and inhaled and oral steroid therapy in 48 adults in a cross-sectional survey by slit lamp. Accurate records of the patients' long-term usage of these drugs were available: 9.2 +/- 5.2 years for inhaled steroid and 9.1 +/- 9.3 years for prednisone (mean +/- SD). Their current inhaled steroid dosage averaged 1.46 +/- 0.85 mg/day (range, 0 to 3.2 mg/day). RESULTS: Twenty-seven percent of the group had PSCs. The occurrence of PSCs correlated with the current daily dose and duration of prednisone use (p = 0.002 and p = 0.01, respectively), but not with the dose or duration of inhaled steroid treatment. As judged by multiple logistic regression analysis, neither the particular inhaled steroid drug used, nor its daily dose or cumulative dose, nor the additional nonsteroidal risk factors for PSCs also present in some of these patients contributed significantly to their risk of developing PSCs. CONCLUSIONS: The findings do not exclude the possibility that inhaled steroid therapy might lead to PSCs if a person has an exceptionally high inherent susceptibility. However, in the asthmatic population at large, the risk appears negligible, even if high doses of inhaled steroid are administered.

Administration, Inhalation↗
PubMed1993

Allergic bronchopulmonary mycosis caused by Pseudallescheria boydii.

Two cases of allergic bronchopulmonary pseudallescheriosis (ABPP) are described. These are the first cases of this allergic bronchopulmonary mycosis (ABPM) reported in which the clinical and serologic criteria are described. The first case was in a patient with mild asthma, and it resolved spontaneously after expectoration of a mucous plug. The second was in a patient with recurrent allergic bronchopulmonary aspergillosis with an exacerbation of ABPM caused by Pseudallescheria boydii. The total serum IgE, IgG, and IgE antibodies against P. boydii and the clinical picture well define ABPP. This diagnosis may be important to recognize in order to prevent a progression of the patient's lung disease.

Adult↗
PubMed1991

Effects of dose and dosing schedule of inhaled budesonide on bone turnover.

To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule, we investigated the effects of budesonide (BUD) on serum osteocalcin and the urinary output of hydroxyproline and calcium. Healthy adults were administered 1.2 or 2.4 mg of BUD per day (N = 40) or placebo (N = 8) in a crossover, double-blind comparison of morning versus diurnal dosing schedules for 1 month each. Both BUD doses reduced the 24-hour urinary free-cortisol output (p less than 0.001) and serum osteocalcin (p less than 0.001). The larger dose reduced the morning serum cortisol levels (p = 0.002). Neither dose increased the 8 AM urinary calcium or hydroxyproline output. Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing (p = 0.01). The 24-hour urinary free-cortisol output was the same with either schedule (p = 0.96). Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation, as evidenced by the reduction in osteocalcin levels. Of concern is the possibility of serious bone complications resulting from the long-term use of inhaled steroid, particularly in growing children or patients in whom other risk factors for osteoporosis are present. The clinical advantage, if any, of morning dosing remains questionable.

Administration, Inhalation↗
PubMed1991

Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin.

Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.

Administration, Inhalation↗
PubMed1990

A study of the mechanism of the antiasthmatic action of inhaled budesonide.

Inhaled antiasthmatic steroids have been assumed and yet never proved to exert their antiasthmatic effect by topical action in the airways. We tested the hypothesis that the efficacy of inhaled budesonide (BUD) might be due instead to its systemic activity after absorption. We compared inhaled and oral BUD with doses selected to ensure higher peak plasma levels and a greater area under the plasma concentration curve with the oral treatment. After pretreatment with beclomethasone to maximize asthma control, 47 adults with asthma were randomized to receive 0.4 mg of inhaled BUD per day (n = 16) or 1.4 mg of oral BUD per day (n = 15), or placebo (n = 16) in double-blind fashion and then followed weekly until asthma relapsed or for 8 weeks if no relapse occurred. "Relapse" was defined as a drop in the mean peak expiratory flow rate greater than 2 SEM below the mean during the baseline week before switching to the test drugs. The time to relapse was the primary outcome variable. Time to relapse was longer with inhaled than with oral BUD (medians, 22 versus 7.9 days; p = 0.003) or placebo (medians, 22 versus 9 days; p = 0.004). Oral BUD and placebo did not differ (p = 0.41). The morning serum cortisol levels remained normal during all three treatments. Thus, at conventional dosage the antiasthmatic effect of inhaled BUD may be fully explained by a local intrapulmonary action.

Administration, Inhalation↗
PubMed1990

Complications of topical steroid therapy for asthma.

The oropharyngeal complications of IS therapy are seldom a serious problem. They may be avoided or ameliorated by inhaling the drug via a spacer and/or reducing the dosing frequency. Severe esophageal candidiasis or atrophic glossitis are rare and generally require discontinuation of IS therapy. Reflex cough or bronchospasm triggered by the inhaled drug occur fairly commonly, but are easily corrected by appropriate treatment. The systemic complications of IS therapy are inconsequential in most patients treated with conventional low doses. Higher doses are more effective but also more active systemically. Despite this, the ratio of systemic-to-antiasthmatic activities may be more favorable with high dose IS than with oral prednisone when the two treatments are compared at equivalent levels of asthma response. The potential risk of adverse systemic effects accruing from the long-term use of intermediate or high doses of IS needs to be rigorously studied.

Administration, Inhalation↗
PubMed1989

High-dose inhaled steroid therapy for asthma.

Only a small minority of patients with asthma have symptoms severe enough to require high-dose inhaled steroid therapy. Because they need more aggressive treatment, this group is disproportionately represented in tertiary care referral centers. Therapeutic effects are dose dependent, and the daily dose of steroid required to normalize pulmonary function far exceeds that for symptom relief. Studies show that, if titrated to minimum dose levels of each the combination of inhaled and oral steroids provides a better balance between antiasthmatic and systemic glucocorticoid activity compared with oral steroid alone. Also, rapidly metabolized inhaled steroids such as budesonide may be associated with a lower risk for the osteoporotic complications seen with long-term oral steroid use. However, high dose of inhaled steroids may lead to adrenocortical suppression and hence estrogen deficiency in postmenopausal women. Morning dosing may mitigate this effect. Oropharyngeal thrush may be prevented by lowering the dose frequency or using a spacer. During prolonged inhaled steroid therapy, patient compliance has proved an important determinant of outcome.

Administration, Inhalation↗