Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control.

INTRODUCTION: Severe persistent asthma represents a major and costly public health issue. There is evidence that long-term treatment with omalizumab might have disease-modifying activity but data on the consequences of discontinuing treatment after a positive response are limited. The purpose of this study was to investigate-in real-life prescribing conditions-what happens when omalizumab is discontinued in patients with severe, persistent allergic asthma who have responded well to omalizumab treatment. METHODS: An observational, descriptive, cross-sectional, retrospective study to establish the time to loss of asthma control after the discontinuation of courses of omalizumab treatment of varying duration. RESULTS: 24 lung specialists reviewed data from 61 responder patients who had discontinued omalizumab after a mean duration of 22.7 ± 13.1 [range: 2.5; 59.5] months of treatment. Loss of asthma control was documented in 34 patients (55.7%) with a median interval between discontinuation and loss of control of 13.0 months (mean 20.4 ± 2.6 [95% CI: 8.3-28.1]). No correlation was detected between time to loss of control and duration of treatment, although control tended to be sustained for longer in patients whose response had been classified as "excellent" as opposed to "good" (median: 17.0 vs. 12.8 months; NS). DISCUSSION: The discontinuation of omalizumab was not associated with any rebound effect or exacerbation of the disease, and control was sustained throughout the follow-up period of at least 6 months in nearly half of all patients, including all of those who had been treated for 3.5 years or more. After the reintroduction of omalizumab, 4 out of 20 patients did not respond again.

Omalizumab reduces oral corticosteroid use in patients with severe allergic asthma: real-life data.

BACKGROUND: Long-term oral corticosteroid (OCS) therapy is associated with significant burden on patients and healthcare resources; treatments that may help reduce their use are important to improve asthma management. METHODS: French and German clinicians prescribing omalizumab for >16 weeks to patients with severe persistent allergic asthma collected OCS use data. OCS use was recorded at baseline and at a non-specific time point beyond 16 weeks from initiation of omalizumab. The number of asthma exacerbations (FEV(1) < 60% of personal best, requiring OCS burst and unscheduled doctor/emergency visit or hospitalization) and asthma-related hospitalizations during the 12-months prior to omalizumab treatment and during the observation period were also recorded. RESULTS: Overall, 346 patients were treated with omalizumab for >16 weeks. Of these, 166 (48.0%) were receiving maintenance OCS (France, n = 64; Germany, n = 102). Following omalizumab therapy, 84 (50.6%) patients on OCS at baseline reduced/stopped OCS dose at the time of data collection; 34 (20.5%) stopped and 50 (30.1%) reduced OCS. In all patients receiving maintenance OCS at baseline, mean reduction from baseline in daily OCS dose was 29.6% (7.1 mg prednisolone). In patients who reduced/stopped maintenance OCS, mean reduction from baseline in daily OCS dose was 74.3% (15.4 mg prednisolone). Reductions in exacerbations and hospitalizations were observed from the 12-months prior to baseline in patients at the time of data collection, irrespective of change in OCS dose. CONCLUSION: European real-life experience demonstrates the OCS-sparing potential of omalizumab in some patients with severe allergic (IgE-mediated) asthma.

Omalizumab decreases nonspecific airway hyperresponsiveness in vitro.

BACKGROUND: In asthmatic patients, both symptoms and hyperresponsiveness are related to immunoglobulin E (IgE) concentration in serum. The anti-IgE monoclonal antibody omalizumab improved the control of asthma, but its effect on airway hyperresponsiveness is controversial. Passive sensitization reproduced in vitro a bronchial hyperresponsiveness, an increase in IgE bearing cells, and a mast cell degranulation. This study was designed to examine the effect of omalizumab on passive sensitization-induced hyperresponsiveness, alterations in IgE positive inflammatory cells and mast cell degranulation within the bronchial wall. METHODS: Proximal (3-5 mm diameter) and distal (0.5-1.5 mm diameter) human bronchi dissected out from 10 lung specimens were incubated in normal or asthmatic serum containing various concentrations of omalizumab. Contractile responses to histamine or Dermatophagoides pteronyssinus (D. pter) were recorded using an organ bath system and expressed as percentage of maximal contractile response to acetylcholine (ACh). Immunohistochemistry was performed using monoclonal antibodies directed against IgE or tryptase. Mast cells were classified as fully granulated (type I), partly (type II) or largely degranulated (type III). RESULTS: The specific bronchial hyperresponsiveness to D. pter and the nonspecific bronchial hyperresponsiveness to histamine following passive sensitization were significantly inhibited by omalizumab in both distal and proximal airways. Passive sensitization-induced increase in IgE positive cells was also abolished by omalizumab in a concentration dependent manner. Mast cell degranulation which was inhibited by omalizumab was positively correlated with the contractile response to D. pter. CONCLUSIONS: Omalizumab blocks specific and nonspecific bronchial hyperresponsiveness. Anti-IgE also decreases IgE bearing cell number and mast cell degranulation.

FEV1 reversibility does not adequately predict effect of formoterol via Aerolizer in chronic obstructive pulmonary disease.

Evaluation of patients with chronic obstructive pulmonary disease (COPD) often includes the use of post-bronchodilator reversibility testing to guide treatment decisions. Recommendations for reversibility testing differ and there is no universally accepted method or outcome criterion. A survey of recent clinical trials with beta2-agonists in COPD illustrates the diversity of methods used to assess reversibility and highlights the difficulty of comparing data from such trials. Two recent studies demonstrated the benefits of treatment with the long-acting beta2-agonist bronchodilator formoterol (Foradil Aerolizer) in patients with COPD. When patients were classified according to their degree of reversibility as partially or poorly reversible, improvements were observed in both groups irrespective of the definition applied. These results suggest that bronchodilator reversibility testing should not be used as a rigid basis for treatment decisions with beta2-agonists in COPD patients. There is a pressing need for the role of reversibility testing to be clearly defined.

Clinical efficacy with formoterol in the absence of a response to salmeterol: a review.

Salmeterol and formoterol are both beta 2-agonist bronchodilators with a long duration of action and are often classified together, yet they are distinctly different in their pharmacology. Recent evidence suggests there is a subpopulation of asthmatic patients who do not respond to salmeterol, yet can attain clinical benefit with formoterol. Following a literature search, three published case reports are reviewed as well as results from two published clinical trials designed specifically to document response to formoterol in 'non-responders to salmeterol' asthmatics. Possible mechanisms underlying this observation are discussed, including pharmacological differences of the two drugs relating to agonism at the beta 2-receptor and to effect on nuclear transcription factors.

Rapid onset of bronchodilation in COPD: a placebo-controlled study comparing formoterol (Foradil Aerolizer) with salbutamol (Ventodisk).

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in patients with COPD.

Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma.

Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long-acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma.

Use of formoterol dry powder administered for three months via a single-dose inhaler in 1,380 asthmatic patients.

Formoterol is a long-acting beta 2-adrenoceptor agonist available in a single-dose breath-actuated device (Foradil) for asthma treatment. Since efficacy and ease of use are key factors for compliance to therapy, the aim of this study was to assess correct use, efficacy and safety of Foradil in a 3-month, open, uncontrolled, multicenter trial. This study was performed on 1,380 patients with moderate or severe persistent asthma treated with inhaled corticosteroid (age: 48.4 +/- 16.2 years; FEV1: 65.4 +/- 19.4% of normal). During the study, compliance was over 90%. More than 90% of the patients used the inhaler correctly and found it easy or very easy to use. The mean increase in peak expiratory flow rate (PEFR), 30 to 60 min after inhalation, was 52.3 and 36.7 l/min for the morning and the evening respectively (p = 0.0001). This increase was already significant 5 min after inhalation, confirming the fast onset of action of formoterol. Mean predose PEFR and daytime/nocturnal symptom scores improved during the length of the study. Rescue short-acting beta 2-agonist consumption was more than three times reduced. At study completion, formoterol dosage was 12 micrograms and 24 micrograms twice daily for 71.5% and 28.5% of the patients respectively. Physicians judged the overall efficacy as good or very good in 87.1% of the patients, and they estimated the tolerability as very good or good in 92.6%. Drug-related adverse events were similar to those of other beta 2-agonists. In conclusion, this study demonstrated the ease of use of this formoterol single-dose dry powder inhaler, and confirmed the good efficacy and safety profile of this long-acting bronchodilator in asthma.

Long- and short-acting beta2 adrenoceptor agonists: interactions in human contracted bronchi.

The aim of this study was to systematically compare the interaction of the long-acting beta2-adrenoceptor agonists formoterol and salmeterol with short-acting beta2-adrenoceptor agonists in contracted human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Formoterol or salmeterol at concentrations inducing up to 92 and 94% of their maximal relaxant effect, respectively, were added to bronchial rings contracted with carbachol (10(-6) M). After a time period of 30 min, concentration-response curves for the short-acting beta2-adrenoceptor agonists, salbutamol, terbutaline, isoprenaline and fenoterol were recorded. Administration of equieffective concentrations of salmeterol and formoterol, resulted in only salmeterol inducing a shift to the right of isoprenaline, terbutaline, fenoterol and salbutamol concentration-response curves. The rank order of shift was salbutamol > fenoterol > terbutaline > isoprenaline. Formoterol, up to concentrations of 3x10(-9) M induced submaximal relaxation resulting in no shift in short-acting beta2-adrenoceptor agonist concentration-response curves. Salmeterol but not formoterol appears to antagonize the relaxation of human contracted bronchi induced by short-acting beta2-agonists. These results obtained in vitro cannot be translated in clinical terms. This study, however, highlights the need for clinical studies on the interaction of long-acting and short-acting beta2-adrenoceptor agonists in acute severe asthma.

Therapeutic equivalence of diclofenac sustained-released 75 mg tablets and diclofenac enteric-coated 50 mg tablets in the treatment of painful osteoarthritis.

Efficacy and tolerability of diclofenac sustained-released (SR) 75 mg tablets taken b.i.d. were compared with that of enteric-coated diclofenac sodium 50 mg tablets given t.i.d. in a seven-day, randomised, double-blind, double-dummy, parallel groups study in 294 outpatients suffering from painful femorotibial or hip osteoarthritis. Primary efficacy criteria were spontaneous joint pain assessed on serial visual analogue scales during the first 36 hours and after 48 hours of treatment. The two treatments had equivalent efficacy since all the 90% confidence intervals of differences between means for pain intensity between the two groups were included within the interval (-10 mm; +10 mm). Rates of overall efficacy judged good to excellent ranged from 74.3-78.5% in both groups. One or more drug-related adverse events, mainly gastrointestinal, was reported by 24.5% and 27.2% of patients in diclofenac SR 75 mg and diclofenac 50 mg groups, respectively. Percentage of good compliance (i.e. > 90%) was higher with diclofenac SR 75 mg (p < 0.001).

A population pharmacokinetic study of alminoprofen penetration into synovial fluid.

The pharmacokinetics of alminoprofen in plasma and synovial fluid (SF) at steady state (300 mg t.i.d.) was studied in 45 patients with knee effusion. Plasma and SF samples, one each per patient, were obtained. Six groups were made according to the time of sampling after ingestion of the 13th dose: 1 h (n = 7), 2 h (n = 7), 4 h (n = 7), 6 h (n = 10), 8 h (n = 6), 12 h (n = 8). A three-compartment model was used to describe alminoprofen kinetics in plasma and SF, with two parameterizations, a 'classical' and a 'physiological' one. The non-linear mixed effect model approach was used to estimate the mean and variance of the pharmacokinetic parameters. The mean +/- SE of the estimates (coefficient of variation of interindividual variability as a percentage) were volume of distribution, 11.0 +/- 1.711 (12%); elimination rate constant, 0.236 +/- 0.025 h-1 (18%); absorption rate constant 2.80 +/- 0.31 h-1 (464%), clearance of influx into SF, 0.29 +/- 0.14 mL min-1; clearance of efflux into plasma, 0.56 +/- 0.25 mL min-1. These two clearances were not significantly different, which indicates that passive diffusion occurs in both directions. The mean +/- SD alminoprofen concentration versus time curve in plasma and SF at steady state was simulated and showed that the mean +/- SD maximal concentration in SF was 8.1 +/- 6.3 mg L-1 and was obtained 4 h after dose administration.

Pharmacokinetics of amoxicillin coadministered with a saline-polyethylene glycol solution in healthy volunteers.

The pharmacokinetics of orally administered amoxicillin were investigated in 12 healthy volunteers in a crossover design. They received either a placebo or a saline-polyethylene glycol solution (SPG) for 4 d, the last dose being given simultaneously with 1 g amoxicillin; blood samples were drawn for the next 12 h. Amoxicillin kinetics were similar in the two treatments but small differences in some pharmacokinetic parameters reached significance. The mean +/- SD area under the curve was lower with SPG (43.8 +/- 6.8 against 47.8 +/- 8.2 mg h L-1, p < 0.05) but the treatments were equivalent according to Westlake's test (95% confidence interval = 14.95%). Analysis of SPG against placebo amoxicillin absorption kinetics after fitting the data to a Weibull model revealed a longer duration of the absorption, a slower rate of absorption, and a different shape of the curve. No clinical consequences are expected from these minor variations but possible mechanisms could be relevant to other drugs.

Influence of local radiotherapy on penetration of fluconazole into human saliva.

The pharmacokinetics of fluconazole (50 mg, single oral dose) in saliva and plasma were determined for five healthy subjects and five patients who underwent radiotherapy (dose, > 45 Gy over a 6-week period) in the salivary gland area and suffered from oropharyngeal candidiasis. Saliva was collected after electrical stimulation. Fluconazole was measured by liquid chromatography. From healthy volunteers and patients, saliva and plasma were sampled from 0 to 24 h. Although fluconazole penetration kinetics were significantly slowed down in irradiated patients, saliva concentrations of fluconazole were higher than those in the plasma, except at 1 h. In the postdistribution phase, the saliva/plasma concentration ratio was in the range of 1.2 to 1.4, and there was no significant difference between healthy subjects and patients. The saliva concentration of fluconazole was over 1 mg/liter throughout the entire interval 2 to 24 h after drug intake. From these results, the clinical efficacy of fluconazole for oropharyngeal candidiasis is not expected to be less than that in subjects with normal salivary glands, provided that salivary secretion remains.

Pharmacokinetics and bactericidal activities of one 800-milligram dose versus two 400-milligram doses of intravenously administered pefloxacin in healthy volunteers.

Pefloxacin pharmacokinetics and serum bactericidal activities (SBA) against Escherichia coli and Staphylococcus aureus were compared after intravenous infusion of either a single 800-mg dose or twice-daily 400-mg doses into 16 healthy volunteers. Plasma pefloxacin concentrations were measured for up to 60 h, and SBAs were determined 1, 12, and 24 h after the start of the infusion. The mean areas under the concentration-versus-time curve for plasma were not different (138 versus 136 h.mg/liter). The mean clearances, volumes of distribution, and half-lives were also comparable. The mean (+/- standard deviation) maximal concentration after the 800-mg infusion was 12.11 +/- 1.35 versus 6.51 +/- 0.73 mg/liter after the first 400-mg infusion and 7.42 +/- 0.76 mg/liter after the second 400-mg infusion. Mean trough concentrations at 24 h were significantly different: 2.77 +/- 0.63 (800 mg) versus 1.93 +/- 0.49 (400 mg twice) mg/liter (P = 0.0007). Mean SBAs against E. coli after 800 mg of pefloxacin were higher than 1/128 (1 h), 1/32 (12 h), and 1/16 (24 h). Mean SBAs against S. aureus under the same conditions were higher than 1/64 (1 h), 1/16 (12 h), and 1/8 (24 h). Mean SBAs at 1 and 12 h were significantly higher after the 800-mg infusion than after the 400-mg infusion but were similar at 24 h for both regimens. Comparison of SBAs according to National Committee for Clinical Laboratory Standards criteria showed a similar adequacy at 24 h for both regimens against both strains. Administration of 800 mg of pefloxacin once a day is bioequivalent to 400 mg twice a day, and bactericidal activity of the 800-mg infusion is not less than that of two 400-mg infusions.

Cefotiam concentrations in the sinus fluid of patients with chronic sinusitis after administration of cefotiam hexetil.

Cefotiam hexetil is a prodrug of cefotiam. The concentrations of cefotiam in plasma and sinus secretions were determined in 18 patients (10 males, 8 females, aged 39.3 +/- 13.0 years) with chronic sinusitis. All patients received two 200 mg oral doses of cefotiam hexetil 12 h apart and were divided into four groups according to the time which elapsed between the last dose and collection of secretion samples. The last dose was given 2 h (group I), 3 h (group II), 4 h (group III) or 6 h (group IV) before sinus puncture. Cefotiam concentrations were measured by high-pressure liquid chromatography and microbiological assay, results being very similar with both methods. Mean concentrations of cefotiam with the standard deviation in sinus exudates were 1.04 +/- 0.60 mg/l at 2 h (n = 6), 1.04 +/- 0.33 mg/l at 3 h (n = 4), 0.75 +/- 0.74 mg/l at 4 h (n = 4) and < 0.10 mg/l at 6 h (n = 4). Mean sinus fluid concentrations were higher than mean plasma concentrations in all groups. These results suggest that cefotiam concentrations higher than the MICs for common pathogens are found in sinus secretions up to 4 h after oral administration of cefotiam hexetil.

[Pulmonary and bronchial kinetics of cefuroxime after a single 500 mg intramuscular injection]. / Cinétique pulmonaire et bronchique de la céfuroxime après dose unique de 500 mg par voie intramusculaire.

Thirty-two patients (28 males; mean age 56 +/- 10 years) who were undergoing bronchopulmonary exeresis surgery were included in this study of the pulmonary (pulm), bronchial (br), and plasma (pl) kinetics of cefuroxime after a single 500 mg intramuscular injection. Twenty-nine bronchial specimens and 38 pulmonary and plasma specimens were taken on average at the following times after the cefuroxime injection: 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h. Cefuroxime was assayed using HPLC on ground tissues, with a correction for contamination by blood. Peak concentrations (C) were found after one hour (Cpl = 11.6 +/- 0.8 micrograms/ml; Cpulm = 7.3 +/- 3.3 micrograms/g; Cbr = 3.7 +/- 1.5 micrograms/g) with the following residual values after 8 hours: Cpl = 0.94 +/- 1.04 micrograms/ml, Cpulm = 0.49 +/- 0.45 micrograms/g, Cbr = 0.15 +/- 0.07 micrograms/g (means +/- 1 SD). Elimination kinetics were monoexponential and similar in plasma, lung tissue and bronchial tissue (elimination half-lives: 1.74 h, 1.66 h, and 1.56 h, respectively), suggesting that all three elements belong to the same pharmacokinetic compartment. Mean intrapolated area-under-the-curve values (AUC) were 33.58 micrograms.ml-1.h (plasma), 20.08 micrograms.g-1.h (lung), and 10.22 micrograms/g-1.h (bronchus). The AUCpulm/AUCpl and AUCbr/AUCpl ratios were 0.60 and 0.30, respectively, in agreement with mean values of tissue level/simultaneous plasma level ratios (lung: 0.59; bronchus: 0.33).

[Nocturnal continuous measurement of blood pressure in sleep apnea syndromes. Comparison between normotensive and hypertensive patients]. / Mesure continue nocturne de la pression artérielle au cours du syndrome d'apnées du sommeil. Comparaison entre sujets normotendus et sujets hypertendus.

Sleep apnea syndrome and systemic hypertension are frequently associated but their causal relationship is unclear. We compared the oscillations of systemic blood pressure and heart rate during polysomnography in 8 normotensive subjects (2 females) and 5 hypertensive (supine awake blood pressure: 165 +/- 7/96 +/- 5 mmHg) without treatment. Their ages (normotensive: 52.1 +/- 11.0 yrs, hypertensive: 51.2 +/- 6.4 yrs) and body mass indices (32.6 +/- 9.6 kg/m2 vs 33.2 +/- 5.2 kg/m2 respectively) were not statistically different. Systemic blood pressure was continuously monitored by a non invasive digital plethysmography (Finapres). Both groups had similar respiratory events indices (normotensive: 45.2 +/- 18.1/hr, hypertensive: 48.4 +/- 20.5/hr) and minimal oxygen saturations (79.4 +/- 9.1% vs 82.4 +/- 7.0% respectively). During apneas in slow-wave sleep were observed the minimal values for systolic and diastolic pressures which were significantly higher in hypertensive than in normotensive (138.2 +/- 9.6/83.2 +/- 16.1 mmHg vs 105.9 +/- 11.1/60.5 +/- 10.9 mmHg respectively). During resumption of ventilation maximal blood values were recorded which were also higher in hypertensive than in normotensive (185.0 +/- 13.8/113.2 +/- 21.5 mmHg vs 155.9 +/- 19.8/88.7 +/- 17.1 mmHg respectively) (p less than 0.05). Although absolute variations of blood pressure were similar, relative changes in systolic pressure were significantly higher in normotensive (p less than 0.05). Maximal heart rate was 76.8 +/- 6.2 bpm in normotensive and 76.6 +/- 3.9 bpm in hypertensive during resumption of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Continuous high-dose corticosteroid pressured aerosol therapy in steroid-dependent asthma]. / Corticothérapie continue en aérosols pressurisés à forte dose dans les asthmes corticodépendants.

Two therapeutic trials aimed at determining whether a high-dose inhaled corticosteroid, beclomethasone dipropionate (BDP), could reduce or suppress a long term and continuous treatment with a systemic corticosteroid, triamcinolone acetonide (TA), were carried out in a homogeneous population of severe, steroid-dependent asthmatics. The first one was a controlled, double-blind versus placebo trial involving 25 patients followed up for 5 months. The second one was an open trial involving 105 patients followed up for 12 months. In both trials the mean doses of TA were reduced by 60 to 65 per cent, and TA could be totally or nearly totally suppressed in almost 60 per cent of the cases with clinical and functional results that were equal or superior to those previously obtained with systemic corticosteroid therapy. It is concluded that: (a) continuous systemic corticosteroid therapy in mean doses of more than 5 mg/day of prednisone equivalent is now rarely indicated in patients with steroid-dependent asthma, and (b) inhaled corticosteroid therapy with BDP could be extended to cases of non steroid-dependent asthma inadequately controlled by bronchodilators.