Accuracy of asthma treatment in schoolchildren in NSW, Australia

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.     

Airway subsensitivity with long-acting beta 2-agonists. Is there cause for concern?

Regular treatment with both long- and short-acting beta 2-agonists results in tolerance to their bronchoprotective effects, although the relevance of this phenomenon in terms of long term asthma control remains unclear. However, there appears to be no appreciable difference between the 2 long-active beta 2-agonists, salmeterol and formoterol, in their propensity to induce beta 2-adrenoceptor down-regulation and subsensitivity. The degree of subsensitivity appears to be somewhat greater with indirect stimuli such as exercise and allergen challenge, compared with direct stimuli such as histamine and methacholine. This loss of functional antagonism with long-acting beta 2-agonist therapy is partial and is not prevented by concomitant inhaled corticosteroid therapy. However, the protective effects of inhaled corticosteroids on their own appear to be additive to those of long-acting beta 2-agonists when both drugs are concomitantly administered in the long term. The subsensitivity to bronchoprotection may be of clinical relevance in terms of patients who are inadvertently exposed to indirect bronchoconstrictor stimuli such as allergens or exercise, suggesting that long-acting beta 2-agonists should not be taken on a regular basis for this particular indication. There is a greater tendency for bronchodilator subsensitivity to develop with longer-acting, than with shorter-acting beta 2-agonists, and this may reflect the longer duration of beta 2-adrenoceptor occupancy and consequent downregulation. As with the bronchoprotective effects of long-acting beta 2-agonists, the development of bronchodilator subsensitivity is only partial and occurs regardless of whether patients are taking concomitant inhaled corticosteroid therapy. The long-term bronchodilator action of the long-acting beta 2-agonist itself is maintained within the twice daily administration interval. However, subsensitivity occurs in relation to a blunted response to repeated doses of short-acting beta 2-agonists, as in the setting of an acute asthma attack. There is considerable inter-individual variability in the propensity for downregulation and subsensitivity, which is determined by genetic polymorphism of the beta 2-adrenoceptor. Current international asthma management guidelines suggest that long-acting beta 2-agonists should be used on a regular basis in patients who ware inadequately controlled on inhaled corticosteroid therapy, so the addition of long-acting beta 2-agonist therapy is an alternative to using higher doses of inhaled corticosteroids. There are, however, concerns that regular long-acting beta 2-agonists might result in masking of inadequately treated inflammation in patients receiving suboptimal inhaled corticosteroid therapy. Physicians should be aware of the airway subsensitivity that develops with long-acting beta 2-agonist therapy, and patients should be warned that they may have to use higher than conventional dosages of short-acting beta 2-agonists to relieve acute bronchoconstriction in order to overcome this effect. In patients receiving an optimised maintenance dose of inhaled corticosteroid, if long-acting beta 2-agonists are to be used on an as required basis, it would seem rational to use formoterol for this purpose, due to its faster onset of action than salmeterol.     

Exudative pleural effusion and pleural leukocytoclastic vasculitis in limited scleroderma

Chlorofluorocarbons (CFCs) damage stratospheric ozone permitting enhanced levels of ultraviolet B radiation to reach the Earth's surface. As a result, production of CFCs is now banned under the Montreal Protocol with the exception of their temporary continued use in pressurized metered dose inhalers used to treat those with airway disorders. Replacement propellants have now been identified and shown to be safe and a major exercise is under way to reformulate the commonly used aerosolized medicines with the new propellants. The new products are now undergoing clinical trials and the first reformulated beta-agonist and corticosteroid inhalers have reached the marketplace. The majority of the current products will have been changed over to the new types over the next 3 yrs, and each country will adapt a transition strategy to oversee this process. The politicians, the environmentalists, the pharmaceutical industry and the regulatory authorities have fulfilled their part in this changeover, and respiratory interested health professionals now need to address what this means for them and their patients so that there may be a seamless transition for the millions of people who use inhaled medicines worldwide.     

Acute corticosteroid myopathy in intensive care patients

Several recent studies have attributed the occurrence of acute myopathy in intensive care unit patients to the combination of corticosteroids and neuromuscular junction blocking agents (NMBAs) used for mechanical ventilation. We present 4 patients who developed acute myopathy after administration of high doses of glucocorticoids during sedation with propofol without any NMBAs. All patients had elevated creatine kinase levels. Electrophysiological studies indicated normal motor and sensory nerve conduction velocities but reduced motor nerve response amplitudes. Needle electromyography identified abnormal spontaneous activity; motor unit potentials were polyphasic of low amplitude and short duration, characteristic of a myopathic process. Muscle biopsy demonstrated a prominent acute necrotizing myopathy in all 4 patients with a loss of thick filaments. Our observations support glucocorticoids rather than NMBAs as the main offending drug in acute corticosteroid myopathy. The predisposing factor should be the hypersensitivity of paralyzed muscles to corticosteroids regardless of the drug inducing paralysis: NMBAs or propofol.     

Comparison of inhaled corticosteroids

OBJECTIVE: To review the comparative studies evaluating both efficacy and safety of inhaled corticosteroids in the management of asthma. Specifically, comparative clinical trials are evaluated that allow clinicians to determine relative potencies of the various inhaled corticosteroids. METHODS: A critical review was performed of the published clinical trials, either as articles or abstracts, comparing the clinical efficacy or systemic activity of inhaled corticosteroids. No a priori criteria were applied, as this was not a meta-analysis. FINDINGS: In vitro measures of antiinflammatory activity of corticosteroids consistently demonstrate potency differences among the various corticosteroids. Traditionally, these in vitro measures have been used to develop new corticosteroids with greater topical activity. While no accepted direct measure of antiasthmatic antiinflammatory activity exists, clinical trials using surrogate measures (e.g., forced expiratory volume in 1 second, peak expiratory flow, bronchial hyperresponsiveness, symptom control) indicate that in vitro measures provide a relatively accurate assessment of antiasthmatic potency. The relative antiinflammatory potency of the inhaled corticosteroids is in the following rank order. flunisolide = triamcinolone acetonide < beclomethasone dipropionate = budesonide < fluticasone. Studies of systemic activity appear to confirm this relative order of potency. Currently, no evidence exists for greater efficacy for any of the inhaled corticosteroids when administered in their relative equipotent dosages. The preponderance of current data suggests that when administered in equipotent antiinflammatory doses as a metered-dose inhaler plus spacer or as their respective dry-powder inhaler, the existing inhaled corticosteroids have similar risks of producing systemic effects. CONCLUSIONS: Delivery systems can significantly affect both topical and systemic activity of inhaled corticosteroids. More direct comparative studies between agents are required to firmly establish comparative topical to systemic activity ratios. The preponderance of evidence suggests that the agents are not equipotent on a microgram basis.     

Endoscopic pancreaticobiliary procedures in patients with a Billroth II resection: a 10-year follow-up study

PURPOSE: To report uveitis associated with human immunodeficiency virus (HIV) infection and to suggest guidelines for treatment. METHODS: Six HIV-seropositive patients (10 eyes) with anterior or posterior uveitis or both were evaluated. After ineffective prolonged treatment with systemic and topical corticosteroids, specific systemic antiretroviral therapy with zidovudine was initiated in all patients. Aqueous humor was cultured in three eyes of three patients, and vitreous humor was cultured in one eye of one patient. RESULTS: In all 10 eyes of six patients, there was resolution of inflammation in 10 to 42 days after commencement of treatment with zidovudine (600 to 800 mg/day), despite no or minimal response to corticosteroids. Cultures of aqueous humor from three eyes of three patients and culture of vitreous humor from one eye of one patient were positive for HIV; no other organism was isolated. Systemic evaluation disclosed no other identifiable cause for the uveitis in any patient. CONCLUSIONS: Infection with HIV appears to be a cause of uveitis. A trial of zidovudine may be warranted in HIV-seropositive patients with uveitis that is poorly responsive to corticosteroid treatment when no other cause is identified. The efficacy of other retroviral agents was not determined.     

Esophageal cancer resection in the elderly

The utilization of corticosteroids in the management of acute and chronic inflammatory processes, such as asthma or inflammatory arthritis, has been implicated in the adverse effects of multiple organ systems. One potential area of these negative consequences in the use of corticosteroids is the development of osteonecrosis of the femoral head. A direct time/dosage relationship for treatment with corticosteroids of patients with an established diagnosis of asthma or inflammatory arthritis and femoral osteonecrosis is unknown. A prospective study was undertaken to evaluate the use of corticosteroids and the incidence of osteonecrosis of the femoral head and potentially establish a time/dosage relationship in this patient population. No direct relationship between corticosteroid dosage and the development of femoral head osteonecrosis in 1420 hip-years was demonstrated at 10-year follow up.     

Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction

Adherence with inhaled beta-agonists and corticosteroids in 24 asthmatic children was tracked over 3 months utilizing the metered-dose inhaler chronolog (MDIC). Patients seldom took all of their medications as prescribed, and failed to take any inhaled corticosteroid doses on a median of 41.8% of days or inhaled beta-agonists on 28.1% of days despite prescribed daily use. Medication nonadherence was correlated with lower levels of asthma knowledge (Asthma Knowledge Questionnaire) and family dysfunction (Family Assessment Device), but not child behavior disorder (Child Behavior Checklist). Patients tended to dramatically over-report medication use. Improved identification of the markers of nonadherence can directly facilitate more efficient targeting of behavioral interventions, resulting in improved adherence, better illness control, and less requirement of urgent medication intervention.     

Common measures of asthma severity lack association for describing its clinical course

BACKGROUND AND OBJECTIVE: To address the problems of increasing asthma morbidity and mortality rates, reliable severity measures must be identified. Accordingly, we compared three measures and their relationship to beclomethasone compliance. METHODS: Three clinical measures (symptom scores, morning peak expiratory flow rates, and number of as needed albuterol inhalations with Nebulizer Chronologs [Forefront Technologies, Inc., Lakewood, Colo.]) were assessed daily in 13 adults with asthma for 8.9 +/- 2.1 weeks. The relationships among these three variables were analyzed in terms of Pearson correlation coefficients. These were evaluated for each of the three possible pairs of the three clinical measures for each of the 13 patients. The relationship between inhaled beclomethasone compliance and the pairwise correlations was studied with the use of nonparametric statistical procedures. RESULTS: In four of the 13 patients, no pairwise correlations between any of the three severity measures were observed. The peak expiratory flow rate-symptom score relationship was observed in eight patients, whereas peak expiratory flow rate-albuterol use and albuterol use-symptom score correlations were each seen in four patients. Mean beclomethasone compliance was 64% and was greatest in those patients whose albuterol use increased concurrently with symptom scores (94% vs 50%, p = 0.02). CONCLUSIONS: The commonly used measures of asthma severity, symptom scores, peak flow rate, and beta-agonist use may not be interchangeable in describing the clinical course. Patients whose beta-agonist use is driven by symptoms tend to be more compliant with use of inhaled corticosteroids.     

Immunotherapy vs inhaled budesonide in bronchial asthma: an open, parallel, comparative trial

BACKGROUND: Budesonide, an inhaled corticosteroid and specific immunotherapy, are both routinely used in the treatment of bronchial asthma. However, there are as yet, no studies comparing the effects of budesonide vs immunotherapy. OBJECTIVE: The aim of this study is to compare the effects of budesonide with immunotherapy in patients having perennial asthma. METHODS: This study is an open, parallel, comparative trial, in which 51 young patients were administered either immunotherapy or budesonide for 1 year and their global symptom scores and FEV1 values assessed. Both treatments were abruptly discontinued after 12 months and the effects of cessation analysed. RESULTS: The use of budesonide resulted in a faster and more striking improvement during the first few months as compared to immunotherapy, with an even more rapid decline in benefits on cessation of budesonide. Immunotherapy on the other hand, resulted in slow but steady improvement which did not decline as rapidly as budesonide on cessation. CONCLUSION: Although this was an open trial, it could be concluded that relief with inhaled corticosteroids in bronchial asthma is more rapid than immunotherapy; however the decline in benefit on cessation of inhaled corticosteroid is even more rapid, a phenomenon not seen with immunotherapy.     

Enteral nutrition in acute Crohn disease

High-dose corticosteroids remain the gold standard of therapy in acute Crohn's disease, but is associated with a variety of side effects. Nutritional therapy could be an interesting alternative, but corticosteroids are meant to be significantly superior according to efficacy. Published studies, identified by references, MEDLINE and meta-analysis, were evaluated for efficacy of nutritional therapy in acute Crohn's disease. In 18 evaluable of 38 identified publications, 571 patients were treated with nutritional therapy: 295 received elemental diet, 214 oligopeptide diet and 62 polymeric diet. Remission rates were 60%, 55% and 66% respectively. However, only intention-to-treat-analysis was performed in all the studies. When correcting for patients who really were treated with nutritional therapy, remission rates were substantially better: 73%, 70% and 67% respectively, thus comparable with that of corticosteroids. Positive predictors for successful treatment were stenosing disease and low ESR. Remission seems to last as long as after corticosteroid treatment, when a reinduction diet is performed. Negative aspects of nutritional therapy are poor tolerance and higher costs. Perspectives for the future aim on broadening of indications, improving acceptance (by adjuvant instead of exclusive nutrition, or new flavors) and efficacy by modification of compounds (such as glutamine, omega-3 fatty acids or trace elements) or combination with other therapeutic agents (e.g., mesalamine).     

Local side-effects during 4-year treatment with inhaled corticosteroids--a comparison between pressurized metered-dose inhalers and Turbuhaler

Local side-effects, such as hoarseness and oropharyngeal candidiasis, are often seen during treatment of patients with inhaled corticosteroids (ICS). We investigated whether changing from pressurized metered-dose inhalers (pMDI) to Turbuhaler influenced the type and frequency of local side-effects. Local side-effects were recorded for a 2-year period in which 154 patients used ICS pMDI with a spacer device. They were followed for an equally long period of time (26.2 +/- 5.7 months) while using Turbuhaler, as were 90 patients who received Turbuhaler as their first ICS preparation. After inhalation, all patients rinsed out their mouths with water. In experienced pMDI-users, the frequency of local side-effects decreased from 21% to 6%. The reduction was due to a lower incidence of hoarseness. Candidiasis or hoarseness was not seen in patients given Turbuhaler as their first ICS device. Our fear of an increased incidence of local side-effects when giving ICS in Turbuhaler was unwarranted.     

The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction

AIMS: The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid. METHODS: The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and "rescue" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded. RESULTS: There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the "trial of steroid" was 0% and 81.3% for positive and negative outcomes respectively. CONCLUSIONS: Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a "trial of steroid" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy.     

Contact allergy to topical corticosteroids and systemic contact dermatitis from prednisolone with tolerance of triamcinolone

We report the case of a 27-year-old female who had an allergic contact dermatitis to topical corticosteroids belonging to the corticosteroid groups A and D. Upon oral treatment with prednisolone a disseminated exanthema began within 24 h. Patch tests revealed sensitization to corticosteroids of group A, C and D, including prednisolone-21-acetate and betamethasone valerate, but not of group B corticosteroids such as triamcinolone. After intradermal testing of corticosteroids the exanthema flared again and the patient was treated with oral triamcinolone, with rapid improvement of her symptoms. A literature review revealed that exanthematous reactions after systemic treatment with corticosteroids have been rarely reported. Since corticosteroids are essential emergency drugs, a safe corticosteroid should be identified for such patients. Patch and intradermal tests may be used for that purpose.     

Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11

BACKGROUND: Varicella pneumonia that results in respiratory failure or progresses to the institution of mechanical ventilation carries a significant morbidity and mortality despite intensive respiratory support and antiviral therapy. There has been no reported study of the role of corticosteroids in life-threatening varicella pneumonia. DESIGN AND METHODS: This was an uncontrolled retrospective and prospective study of all adult patients with a diagnosis of varicella pneumonia who were admitted to the ICUs of the Johannesburg group of academic hospitals in South Africa between 1980 and 1996. Patient demographics, clinical and laboratory features, necessity for mechanical ventilation, and complications were reviewed. The outcome and therapy of varicella pneumonia was evaluated with particular reference to the use of corticosteroids. Patients with comorbid disease and those already taking immunosuppressive agents were excluded. Key endpoints included length of ICU and hospital stay and mortality. MEASUREMENTS AND RESULTS: Fifteen adult patients were evaluated, six of whom received corticosteroids in addition to antiviral and supportive therapy. These six patients demonstrated a clinically significant therapeutic response. They had significantly shorter hospital (median difference, 10 days; p<0.006) and ICU (median difference, 8 days; p=0.008) stays and there was no mortality, despite the fact that they were admitted to the ICU with significantly lower median ratios between PaO2 and fraction of inspired oxygen than those patients (n=9) who did not receive corticosteroid therapy (86.5 vs 129.5; p=0.045). CONCLUSION: When used in addition to appropriate supportive care and early institution of antiviral therapy, corticosteroids appear to be of value in the treatment of previously well patients with life-threatening varicella pneumonia. The observations presented in this study are important and should form the basis for a randomized controlled trial, as no other relevant studies or guidelines are available.     

Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group

BACKGROUND: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. METHODS: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that has occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. RESULTS: Overall survival at the end of the follow-up period was significantly higher for the high-dose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P > 0.4, all comparisons). CONCLUSIONS: In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment.     

Evaluation of intraocular pressure and cataract formation following the long-term use of nasal corticosteroids

It is possible that corticosteroids administered via nasal spray might reach ocular structures in levels sufficient to provoke an ocular hypertensive response and cause posterior subcapsular cataracts (PSCs) in susceptible individuals. In the present study, 26 patients who had undergone endoscopic sinus surgery were evaluated prospectively with respect to intraocular pressure and PSC formation following the use of nasal steroids for at least three months. Eighteen patients (69%) self-administered 200 micrograms/day of budesonide nasal spray twice daily, and eight patients (31%) self-administered 200 micrograms/day of beclomethasone dipropionate nasal spray twice daily, for a period of three to 19 months (mean 8.8 +/- 3.6 months). Ophthalmologic examination, tonometry, visual field testing and biomicroscopic studies revealed no evidence of ocular hypertension or PSCs during postoperative follow-up. We conclude that intranasal corticosteroids can be used safely for prolonged periods without increasing the risk of ocular hypertension or PSCs.     

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 1. General principles

The safety of long-term inhaled corticosteroid therapy at commonly prescribed doses is an issue of growing concern to physicians and international regulatory bodies. This is so because long-term use of these drugs has become the mainstay of chronic asthma management and their introduction now is widely recommended in official treatment guidelines at the 'mild persistent' stage of asthma, where regular daily therapy is first begun. In addition to more frequent use of inhaled corticosteroids, there is a further trend to use higher doses of existing inhaler therapies and to use the newer and more potent compounds that have recently become available. At the same time as these developments have been taking place, there has not been a concurrent move to a more rigorous examination of the safety profile of these inhaled corticosteroid treatments - especially to assess their effects on the hypothalamic-pituitary-adrenal (HPA) axis. Most safety data with respect to HPA axis effects have been derived from testing methods that are limited in their ability to detect HPA system impairment and, more seriously, that can give the impression of functional integrity in the HPA axis when there may be moderate (or even greater) impairment. In this first part of a two-part review of the HPA axis effects of inhaled corticosteroids and of how these effects should be assessed, we examine the currently used and the currently available testing methodologies and also review the present state of knowledge concerning the structure and function of the HPA axis and the effects of its suppression. It is clear that there are state-of-the-art tests to assess in a discriminating manner the safety profile of inhaled corticosteroids. These tests have been insufficiently employed, including during the drug development process, yet they are readily available, relatively inexpensive and can detect adrenal suppression before the appearance of clinical effects. In part 2 of this review we examine what can be learned about the effects of inhaled corticosteroid therapy on the HPA axis from the limited amount of reliable published information from clinical and pharmacological studies describing their use and safety.