Steroid-dependent Asthmatic Patients Research Articles

Luminol-dependent chemiluminescence of peripheral neutrophils in asthmatic patients

To evaluate the role of the neutrophil in the pathophysiology of bronchial asthma, we examined the luminol-dependent chemiluminescence of peripheral neutrophils (CL) in steroid-dependent asthmatic patients during an acute attack (n = 18), during stable period (n = 10), and in normal controls (n = 21). When stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP 0.1 microM), the CL of patients in acute attack was lower than that of normal controls. (5.29 +/- 1.25 vs. 9.29 +/- 0.84 relative light units p less than 0.01) Among 18 patients, we could examine 10 patients during the stable period after receiving steroids. The CL of those 10 patients during the stable period was significantly higher than their CL during acute attacks, when evaluated by the paired t-test (p less than 0.05), and was not very different than in normal controls. When stimulated with opsonized zymosan (5 mg/ml), CL was similar in the three groups. We also examined the CL of peripheral neutrophils of normal persons after the preincubation with serum of patients during acute attack and stable period. When stimulated with fMLP, CL after preincubation with serum of patients during acute attack was lower than CL after preincubation with the serum of patients during the stable period. It was suggested that the respiratory-burst activity of peripheral neutrophils in acute asthmatic attack was reduced to the chemotactic stimulus of fMLP.

Anatomy, pathology, and physiology of the tracheobronchial tree: Emphasis on the distal airways

This article covers the airway tree with respect to anatomy, pathology, and physiology. The anatomic portion discusses various primate groups so as to help investigators understand similarities and differences between animal models. An emphasis is on distal airway findings. The pathology section focuses on the inflammatory responses that occur in proximal and distal airways. The physiologic review brings together the anatomic and pathologic components to the functional state and proposes ways to evaluate the small airways in patients with asthma.

Variable p‐CREB expression depicts different asthma phenotypes

Chromatin modification may play a role in inflammatory gene regulation in asthma. Cyclic adenosine mono-phosphate response element-binding protein (CREB), with the specific co-activator, the CREB-binding protein (CBP), contributes to the acetylation of chromatin and to the transcription of pro-inflammatory genes. To evaluate the expression of CBP and of phospho-CREB (p-CREB) in bronchial biopsies and in peripheral blood mononuclear cells (PBMC) of controls (C), untreated (UA), inhaled steroid treated (ICS) and steroid-dependent asthmatic (SDA) patients. We used immunohistochemistry in bronchial biopsies and western blot analysis and immunocytochemistry in PBMC. Cyclic adenosine mono-phosphate response element-binding protein expression, in the epithelium was similar in all groups, while p-CREB expression was increased in UA and in SDA in comparison with ICS and C subjects (C vs UA P = 0.002, C vs SDA P = 0.007), (ICS vs SDA P = 0.005), (ICS vs UA P = 0.001). Interestingly, also in the submucosa, p-CREB was increased in UA and SDA in comparison with ICS and C subjects (C vs UA P = 0.0004) (C vs SDA P < 0.0001) (ICS vs UA P = 0.002) (ICS vs SDA P < 0.0001) and positively correlated with leukocyte infiltration within the bronchi (CD45RB+ cells). Similar results were obtained with PBMC isolated from the same patient groups. Incubation of PBMC in vitro, with fluticasone propionate, decreased the p-CREB expression induced by cytokine activation (interferon-gamma, tumor necrosis factor-alpha). This study demonstrates that the expression of p-CREB is related, in asthma, to the persistent inflammation according to the disease severity. p-CREB expression can be modulated by glucocorticoids in responsive patients.

Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study

Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study

Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study

Though several drugs have been tested, the choice of the ideal steroid-sparing agent in steroid-dependent asthmatic patients remains unclear. Our objective was to evaluate the efficacy and tolerance of methotrexate in low weekly doses in order to decrease chronic oral steroid requirements in asthmatic patients. double blind randomized placebo-controlled study. The study was performed in a 760-bed teaching hospital. 46 steroid-dependent asthmatic patients were randomized. PATIENTS received 10mg of methotrexate or placebo once weekly for a year. The 6-methylprednisolone was progressively tapered (2mg/day every two weeks) until FEV1 diminished by 5% or more; 6-methylprednisolone was then increased until the previous FEV1 was reached, and the procedure was repeated throughout follow-up. Blood and urine analyses and bone densitometry were performed at entry and at the end of the study. Pulmonary function was tested monthly during the first three months and then every three months until the end. Thirty-nine patients were evaluated at interim analysis. A 54.8% decrease (9.5+/-4.9 mg/day) in 6-methylprednisolone dose was observed in the methotrexate group and a 4.4% decrease (0.5+/-7.2 mg/day) in the placebo group (P<0.001). There was no significant decrease of FEV1 in either group. No changes in bone metabolism were observed except for a non-statistically significant increase in osteocalcin levels in the treated group compared to a decrease in the placebo group. Toxicity was mild. (1) Methotrexate is an effective steroid-sparing agent. (2) A dosage lower than the one recommended in the literature is effective. (3) Tolerance is good. (4) No benefit or detrimental effects in bone metabolism were observed after one year.

Colchicine as an oral corticosteroid sparing agent for asthma.

Oral corticosteroids are used as a treatment for asthma, but they are often associated with serious side effects. Colchicine is an anti-inflammatory, immuno modulating agent, which could potentially have a beneficial effect in the treatment of asthma as well as act as a steroid-sparing agent. To determine the effectiveness of colchicine as an oral corticosteroid sparing agent for in the treatment of chronic asthma. We searched the Cochrane Airways Group trials register (November 2002), SIGLE (1980 to 2001) and reference lists of potential articles. We also contacted researchers in the field. Randomised controlled trials investigating the addition of colchicine compared to placebo in stable steroid dependent asthmatics. No trials were found that met the inclusion criteria. We were unable to perform any meta-analyses. Two small studies have assessed the efficacy of colchicine subsequent to inhaled steroid withdrawal and as a tapering agent in inhaled steroids. Both studies failed to detect a significant difference between colchicine and placebo. No relevant trials have been published, so there is no evidence to indicate that colchicine is beneficial or otherwise in the management of steroid-dependent asthmatic patients. There is a need for well designed randomised controlled trials to be performed.

ALTERNATIVE ANTI-INFLAMMATORY AND IMMUNOMODULATOR MEDICATIONS FOR ASTHMA

The National Institutes of Health (NIH) 1997 Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma 12 (EPR2) proposes a standard of care for patients with this chronic, predominantly eosinophilic, inflammatory disease: that patients with mild persistent asthma be treated with daily low-dose inhaled corticosteroids, that patients with moderate persistent asthma receive higher doses of inhaled corticosteroids, and that patients with severe persistent asthma be treated with the highest doses of inhaled corticosteroids, long-acting bronchodilators, and the lowest doses of oral corticosteroids that can achieve the therapeutic goal. The EPR2 suggests other medications as add-on therapy or as alternatives. This article reviews randomized clinical trials that address alternative medications for the management of persistent asthma in patients who require daily treatment. When available, head-to-head comparisons are discussed. Traditionally, alternative anti-inflammatory treatments for asthma are given to patients with severe disease that requires higher doses of oral corticosteroids for control of symptoms. The experience of rheumatologists treating patients with arthritis has led to the suggestion that methotrexate, gold salts, hydroxychloroquine, dapsone, and cyclosporin may be of benefit for severe steroid-dependent asthmatic patients. In contrast, for patients with mild to moderate persistent asthma, alternative medications with potential anti-inflammatory effect include cromolyn sodium, nedocromil, theophylline, and the leukotriene modifiers. Several of these agents, as well as long acting oral and inhaled bronchodilators, have also been proposed as effective means to reduce the daily dose of the inhaled corticosteroid while maintaining or improving control of asthma. Outcome parameters vary among studies. The most common objective measures include forced expiratory volume in 1 second (FEV 1 ), peak expiratory flow rate (PEFR), and measures of bronchial hyperreactivity. Dosage levels of oral corticosteroids taken for asthma, albuterol use, and level of symptom control are also reported indicators of efficacy. The adverse drug profile of each therapy needs to be considered. Most clinical studies unfortunately are short-term, and many of the potential safety concerns may appear only after several years of treatment. Study populations, even when controlled for disease severity, differ among clinical investigations and make comparative analysis difficult. Randomized clinical trials of two or more therapies provide the best comparisons. In analyzing the outcomes of alternative medications, one needs to consider the placebo effect on clinical changes. Many clinical trials have demonstrated that enrollment alone can improve lung function and symptom control. In placebo-controlled trials, a clinically significant difference, not just a statistical difference, needs to be demonstrated.

Inhaled and Systemic Corticosteroid Therapies: Do They Contribute to Inspiratory Muscle Weakness in Asthma?

Background: Patients with asthma incur the risk of steroid-induced myopathy, which is a well-known side effect of treatment with corticosteroids. However, the adverse effect of long-term steroid treatment on respiratory muscle function remains controversial. Objective: We aimed to evaluate the effects of long-term moderate dose of systemic corticosteroids and high-dose inhaled beclomethasone on maximal inspiratory and expiratory pressures (PImax and PEmax, respectively) in two groups of asthmatic patients exhibiting comparable levels of hyperinflation. Methods: Twelve steroid-dependent asthmatic patients requiring 10–20 mg/day of prednisone-equivalent corticosteroids for an average of 9.83 ± (SD) 9.86 years; 14 subjects with moderate to severe asthma who have used inhaled beclomethasone for at least 1 year at a daily dose higher than 1,000 μg and 15 healthy controls were included to the study. Results: No significant difference in pulmonary function tests and arterial blood gases appeared between two asthmatic groups with different treatment modalities. PImax as an absolute value was significantly lower in steroid-dependent asthmatics than in patients treated with inhaled beclomethasone and controls (p < 0.01). %PImax was also lower in steroid-dependent asthmatics than in control groups (p < 0.01). A significant correlation was found between %PImax and hyperinflation assessed by %RV, %FRC, %FRC/TLC (p < 0.05) in all asthmatic patients. Conclusions: We believe that hyperinflation plays a major role in inspiratory muscle dysfunction in asthma, but the finding of significantly decreased PImax values in steroid-dependent asthmatics when compared with patients on high-dose inhaled beclomethasone with a comparable level of hyperinflation points to a deleterious effect of long-term, moderate-dose systemic corticosteroid but not high-dose beclomethasone on inspiratory muscle function in asthmatics.

Glucocorticoid receptors in bronchial epithelial cells in asthma.

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

Generation of eicosanoids from 15(S)-hydroxyeicosatetraenoic acid in blood monocytes from steroid-dependent asthmatic patients

The aim of this study was to investigate eicosanoid metabolism by human peripheral blood monocytes (PBM) from steroid-dependent asthmatic patients as compared to control subjects and untreated asthmatic patients. Eicosanoid biosynthesis by PBM isolated from venous blood using Percoll gradient centrifugation was evaluated following stimulation of 5 × 10 6 cells with calcium ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), and analyzed by reverse phase high performance liquid chromatography (RP-HPLC). Without 15(S)-HETE, PBM synthesized leukotriene B 4 (LTB 4) only (40 ± 12 ng and 59 ± 11 ng for untreated and steroid-dependent asthmatics, respectively). In the presence of 15(S)-HETE, PBM produced six-fold smaller amounts of leukotriene B 4 ( P < 0.0001). They also released 5(S),15(S)-dihydroxyeicosatetraenoic acid (5(S),15(S)-diHETE) in similar amounts for all the populations, whereas low amounts of lipoxins (LXs) were produced by PBM from asthmatics only (2.7 ± 0.7 ng and 4.6 ± 2.8 ng for untreated and steroid-dependent asthmatics, respectively). Moreover, PBM were also able to release an unknown compound containing conjugated triene chromophore. Cells from steroid-dependent asthmatic patients synthesized this unknown metabolite in higher amounts than controls and untreated asthmatics (133 ± 18 ng vs 52 ± 19 ng and 68 ± 15 ng, respectively, P < 0.02).This work shows for the first time that human PBM are able to metabolize 15(S)-HETE and lead to lipoxins and to an unknown metabolite, with the amounts of the latter being enhanced by long-term corticosteroid treatment.

Platelet activating factor revisited.

8A2 and acetyltransferase on membrane alkylacyl phospholipids. PAF was found to possess many properties that made it well suited as a proinflammatory mediator of inflammation in many inflammatory diseases. 1...

Methotrexate for steroid-dependent asthmatic children and adolescents

The administration of methotrexate as an antiinflammatory drug in asthma has been discussed and most of the studies were developed in adults. Its indication is restricted to steroid-dependent or steroid-resistant asthmatic patients. This study evaluates the clinical and espirometric parameters of steroid-dependent asthmatic children, receiving methotrexate therapy. Perennial steroid-dependent asthmatic patients (prednisone 30 or 40 mg/dia), without associated disease, were evaluated by means of clinical and spirometric parameters. A maintenance dose of 10 to 17.5 mg/ week of methotrexate was administered. Six patients (3M;3F), aged 7 to 13 years old were included. There was improvement of clinical symptoms during the administration of methotrexate, in all patients, without significant change in the pulmonary function. During the use of methotrexate therapy three patients presented adverse reactions: leukopenia (1/3), vomiting (1/3) or Herpes zoster (1/3). The dose of prednisone was reduced in all patients, with total exclusion of prednisone in 3. Afterwards, there was a worsening of asthmatic symptoms in all patients, with reintroduction of corticosteroids. Methotrexate represents an alternative therapy for steroid-dependent asthmatics, and it may help to control symptoms of asthma and steroids use. Nevertheless, double-blind studies should be developed in children. Adverse effects must be considered before its indication, restricting its use to specialized centers.

Low-Dose Methotrexate Spares Steroid Usage in Steroid-Dependent Asthmatic Patients: A Meta-analysis

To determine if treatment with low-dose methotrexate spares oral steroids in adult, steroid-dependent, asthmatic patients. Articles identified by computer search were excluded if they (1) did not contain original data relating to the primary question, (2) had no controls, or (3) described subjects younger than 18 years of age. From each article, the following was abstracted: reference citation; type of control; whether study incorporated a run-in period in which the baseline level of prednisone was reduced to the lowest possible dose; dosage and length of methotrexate therapy; baseline dosage; and type of steroid. Also, the following was determined during both placebo and methotrexate arms of each study: steroid dosage, FEV1, serious side effects, and alteration in level of serum aspartate aminotransferase. Eleven eligible studies were identified. Methotrexate treatment resulted in a decrease in prednisone or prednisolone usage by an average of 4.37 mg/d or 23.7% of the initial dosage. The summary effect size in standard deviations (SDs) was -0.53 (95% confidence interval=-0.29 to -0.77). Subgroup analysis showed that patients treated with prolonged (6-month) therapy with methotrexate, those with low long-term usage of steroids (< or = 20 mg/d), and those whose study design incorporated a run-in period, tended to have the greatest steroid-sparing effects with methotrexate. Low-dose methotrexate has a significant steroid-sparing effect in steroid-dependent asthmatic patients. The greatest effect was evident in patients in whom an effort was made to reduce baseline steroid dosage and in whom methotrexate was used for 24 weeks.

Rush Immunotherapy: Experience with a One-Day Schedule

Rush immunotherapy is a method for rapidly desensitizing patients to inhalant allergens. The frequency of systemic reactions during rush immunotherapy is similar to conventional immunotherapy when premedication is used. The most rapid protocol for rush immunotherapy reported to date requires one and one-half days which is inconvenient to patients and clinic schedules. To improve this situation and decrease the cost of giving rush immunotherapy, we have developed a 1-day protocol. for this ongoing study, 22 allergic patients received rush immunotherapy consisting of eight injections over six hours followed by two hours of observation in an outpatient clinic. Five had rhinitis and the rest has asthma, seven of whom were steroid-dependent. All were premedicated with astemizole, ranitidine, and prednisone for three days including the day of rush immunotherapy, and peak expiratory low rates were monitored. Systemic reactions were seen in five of 22 (23%). They occurred following the sixth injection (1), seventh injection (2), or the final one (2) and consisted primarily of rhinitis or pulmonary symptoms with one episode of mild anaphylaxis. A systemic reaction was seen in only one steroid-dependent asthmatic patient. A local reaction preceded a systemic reaction in only one patient. All but three reached a maintenance dose in one day. All systemic reactions responded to epinephrine and all patients could go home after rush immunotherapy. Only one patient had a systemic reaction during the three months after rush immunotherapy. One day rush immunotherapy is tolerated by most patients with a systemic reaction rate comparable to conventional immunotherapy. All patients were able to reach a maintenance dose months sooner than weekly schedules. With refinement of this procedure, rush immunotherapy may become a widely used method for desensitizing patients with inhalant allergens, and could make immunotherapy less expensive and more convenient.

Fatal varicella zoster infection in a severe steroid dependent asthmatic patient receiving methotrexate.

A case is described of fatal haemorrhagic varicella zoster in a steroid dependent asthmatic patient concurrently receiving methotrexate. The future management of patients on immunosuppressive steroid sparing drugs is discussed.

Methotrexate in steroid‐dependent asthma: long‐term results

Treatment of 21 steroid-dependent asthmatic patients with methotrexate (MTX) 15 mg/week was prospectively evaluated for a mean of 14.7 (SD 3.7) months. Before MTX, therapy consisted of a mean prednisone dose of 16.6 (SD 9.2) mg, in addition to inhaled beclomethasone/budesonide (mean daily dose 1157 (SD 330) micrograms) and bronchodilators. Thirteen patients were weaned from all regular systemic steroid therapy, a 50% or more reduction was achieved in four patients, and a less than 50% reduction in four patients. Abnormal liver function tests were noted in six of the 21 patients; this resolved despite continuation of MTX in five. In one patient, MTX was stopped because of symptoms as well as a fivefold rise in serum transaminases, and a speedy resolution was noted. Gastrointestinal side-effects were reported in six patients but were resolved in five with intramuscular MTX. There were no hematologic or pulmonary complications. We conclude that MTX appears to be both safe and efficacious as a steroid-sparing agent in most steroid-dependent asthmatic patients when taken over a long period.

Effect of saiboku-to (TJ-96) on bronchial asthma. Induction of glucocorticoid receptor, beta-adrenaline receptor, IgE-Fc epsilon receptor expression and its effect on experimental immediate and late asthmatic reaction.

A remarkable "steroid sparing" effect of Saiboku-to was noted within 6 to 12 months of treatment in steroid-dependent asthmatic patients. Saiboku-to spared the downregulation of glucocorticoid receptor of human lymphocytes, plasma ACTH, and cortisol levels. It also spared downregulation of beta 2 receptor by beta 2 agonists and suppressed mACh receptor at the same time. Saiboku-to increased tyrosine aminotransferase (TAT) production, which was inhibited by actinomycin-D, thus having steroid-like activity. In mite-allergic asthma, Saiboku-to inhibited the induction of expression of IgE-Fc epsilon R/CD23 in the lymphocytes by mite allergen. It also inhibited IgE production by mite allergens. In experimental asthma in guinea pigs the use of Saiboku-to resulted in a decrease in the number of eosinophils in the bronchoalveolar lavage fluid during late asthmatic response. These findings suggest that Saiboku-to may be effective in inhibiting both the expression of IgE-Fc epsilon R2 and the induction of expression of IgE-Fc epsilon R1. Saiboku-to also has a steroid-like action and polyhedral anti-asthmatic activities.

In VivoDetection of a Novel Macrophage-derived Protein Involved in the Regulation of Mucus-like Glycoconjugate Secretion

We previously described a novel 68,000 D macrophage-derived protein (MMS-68) that can stimulate mucus-like glycoconjugate (MLGC) secretion from cultured human airways, respiratory epithelial cells, and the ishikawa adenocarcinoma cell line. To better characterize this mucus secretagogue, we generated monoclonal antibodies against MMS-68 by injecting crushed SDS-PAGE gel slices containing this protein into Balb-C mice followed by fusion with SP2/0, a nonsecreting mouse myeloma cell line. A panel of monoclonal antibodies was produced that identified the 68,000 D MMS by immunoblot analysis and immunoprecipitation. The monoclonal antibodies detected MMS-68 in normal peripheral blood monocytes and pulmonary macrophages by cytofluorographic analysis and in human airways as determined by immunohistochemistry. Utilizing the monoclonal antibodies, an antigen-capture ELISA assay was developed. Statistically significant elevations in levels of MMS-68 were detected in bronchoalveolar lavage fluid (BALF) of chronic bronchitic subjects and cigarette smokers and in monocyte culture supernatants from steroid-dependent asthmatic patients compared to normal control subjects. The 68,000 D MMS is a potent secretagogue and may play an important role in the regulation of mucus secretion, especially in chronic bronchitis and steroid-dependent asthma.

3 CASES OF ASPIRIN-INDUCED ASTHMA

Generally the incidence of aspirin-induced asthma (AIA) in adult asthmatics has been reported about 10%. But in children AIA is relatively rare in Japan. Sixty two asthmatic children were admitted to our hospital. Three of them were diagnosed as AIA. Case I was a 16-year-old girl, and diagnosed as AIA by her anamnesis. After avoidance of aspirin and nonsteroidal antiinflammatory drugs and tartrazine, her asthma attacks have remarkablly decreased. Case 2 was a 16-year-old girl, and diagnosed by her anamnesis and positive reaction to inhalation test with Sulpyrin and Venopirin. Case 3 was 12-year-old girl, and severe, intractable and steroid-dependent asthmatic patient. It was suspected that she had suffered from AIA. She was diagnosed by positive reaction to inhalation test.AIA was characterized by 1) severe and intractable, steroid-dependent, 2) low serum IgE levels with negative allergy skin tests except fungi. Thus in severe and intractable asthmatic children we should consider AIA and conduct examination, then the number of incidences of AIA may increase.

Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study.

Reduced bone mass predisposes patients to the development of vertebral fractures. Measurement of bone mass by non-invasive methods is used to detect patients with involutional osteoporosis at risk from fractures. These methods have not been assessed in patients with steroid dependent osteoporosis. The objective of this study was to assess the value of a predictive fracture threshold value of bone density in patients with steroid dependent asthma. Three groups of patients were studied. Group 1 (67 patients) had steroid dependent asthma (mean daily dose of prednisone 11.7 mg) and no vertebral fractures, group 2 (32 patients) had steroid dependent asthma (mean daily dose of prednisone 12 mg) and vertebral fractures, and group 3 (55 patients) were not taking steroids but had involutional osteoporosis and a recent non-traumatic vertebral fracture. Bone mineral density was measured by dual photon absorptiometry and vertebral fractures by radiography of the lumbar spine. A fracture threshold was determined in the two groups with fractures as the 90th percentile of the mean bone mineral density measured in the lumbar spine. Bone mineral density was significantly higher in the steroid dependent group with fractures (group 2) than in group 3 patients, who had involutional osteoporosis and fractures (0.946 (0.18) g/cm2 v 0.830 (0.16) g/cm2). The fracture threshold value was therefore higher for patients with steroid related vertebral fractures (group 2, 1.173 g/cm2) than for those with involutional osteoporosis (group 3, 0.979 g/cm2). Vertebral fractures were more likely to occur in steroid dependent asthmatic patients with bone density above the fracture threshold value (obtained from subjects with involutional osteoporosis) than in subjects in group 3 (34% v 9%). Vertebral fractures occur in patients treated with steroids in the presence of higher bone mineral density than is the case with patients with involutional osteoporosis. The findings suggests that the assessment of the efficacy of preventive treatment requires measurement of bone mineral density and radiology.