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Beclomethasone dipropionate aerosol in the treatment of chronic bronchial asthma
eclomethasone dipropionat in the treatment of chronic asthma Frank Vogt, M.D., Paul Chervinsky, Michael Grieco, M.D.
M.D., Joseph
Bloomfield, N. J., New Bedford, Xass., Plushixg, New York, N. Y.
onchial Dwek,
M.D., an
N. Y., a,nd
patients with a double-bEind, randomized sttiay, 93 corticosteriod-independent chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 gg per day or its vehicle for 4 ~16 to determine and compare the effectiveness and safety of tke preparations. Evaluations made before, nt weekly interGals during, rind 1 wk after treatment indicated that beclomethasone dipropionate aerosol ZL’CES superior to its vehicle in improving FBC, FEP,, PEF,i%.7s?o, and clin~icnl signs and evduntions by both the investigators and, the patients. symptoms, and in the overall P1asm.a cortisd levels measured at the end of the second and fourth weeks were not substantially diferent from those before treatment in either group. No significnn.t side effects or abnormalities in laboratory results wc~c noted.
In
The clinical use of corticosteroids in the management of severe bronchial asthma is well established. However, the therapeutic benefit of orally administered corticosteroids is often accompanied by undesirable and frequently severe adverse effects.l Beclomethasone dipropionate has been studied extensively as a topical anti-inflammatory agent; its topical activity and low solubility provided good bases for its use as an aerosol. In Great Britain and elsewhere, beelomethasone dipropionate aerosol was effective in the management of asthma in steroid-independent patients,*-4 unaccompanied by systemic effects including hypothalamiepituitary-adrenal axis suppression. For many steroid-dependent asthmatics, beclomethasone dipropionate aerosol was an effective alternative to oral therapy.“-I0 The present report summarizes the results of a double-blind multicentric study comparing beclomethasone dipropionate aerosol with its vehicle aerosol in patients with chronic bronchial asthma. From the Sehering Corporation, Allergy Associates, Inc., Booth Memorial Medical Center and The Roosevelt Hospital, R. A. Cooke Institute of Allergy. Presented at the Thirty-first Annual Meeting of the American Academy of Allergy, San Diego, Calif., 1975. Received for publication Sept. 15, 1975. Accepted for publication Dec. 24, 1975. Reprint requests to: Dr. Frank Vogt, Sehering Corporation, Bloomfield, N. J. 07OOS. Vol. 58, iVo. 2, pp. 316-381
VOLUME 58 NUMBER 2
Beclomethasone 3.00
r
!jf,SE
aerosol
in treatment
of asthma
BECLOMETHASONE DIPROPIONATE
WEEK 1
WEEK2
WEEK 3
FIG. 1. Mean responses
WEEK 4
AFTER TREATMENT
of WC (L].
MATERIALS AND METHODS Selection of patients Ninety-three patients (33 males and 60 females) between 14 and 65 yr of age were enrolled in the study after giving informed consent; 41 patients were over 40 yr of age, and 52 were under 40 yr. All had reversible obstructive airway disease and required the continuous use of bronchodilators; none was steroid-dependent. Two-thirds (62) of the patients had had asthma for up to 15 yr, and 5 had had the condition for over 45 yr. In 86 patients the asthma was severe or moderately severe. The asthma was extrinsic in 34 patients, intrinsic in 9, and of mixed causes in the other 50. Eighty-five patients had cough on admission to the study; only 7 had a sensitivity to aspirin. All patients had a forced expiratory volume in one second (FEV,) of between 20% and 80% of the predicted normal, and reversibility of airways obstruction was established by an improvement in FEV, of 15vo or more after a standard dose of isoproterenol aerosol. None of the patients had received corticosteroids within 4 wk of enrollment. Before treatment, each patient was given a physical examination, with particular reference to clinical manifestations of bronchial asthma, and the following clinical laboratory determinations were performed to detect any potential drug effect : hemoglobin, hematocrit, total leukocyte count and differential, fasting blood glucose, blood carbon dioxide, serum alkaline serum glutamic-oxalacetic transaminase, serum electrolytes, plasma eortisol phosphatase, (measured twice), and urinalysis.
Treatment
regimen
The patients were assigned to one of stratified, randomized master code. Each of beelomethasone dipropionate aerosol 4 47 patients received two inhalations of the were instructed to continue the use of their
linical
two treatment groups according to a double-blind, of 46 patients received two inhalations (100 pg’) times a day for 4 wk, and each of the remaining vehicle aerosol 4 times a day for 4 wk. The patients nonsteriod medication.
evaluations
During the 4-wk treatment period, the patients recorded signs and symptoms daily and were evaluated weekly. At each visit, pulmonary function tests (forced vital capacity [FVC], forced expiratory volumo in 1 second [FEV,], and forced expiratory fiow between 25% and 75ol, [FEF,,B.~e%] ) were performed, findings of physical examinations and side effects were recorded, and the patients’ symptom diaries were reviewed. After 2 and 4 wk of treatment, *Delivery
at the valve;
delivery
at the mouthpiece
is approximately
85 pg.
Vogt et al.
J. ALLERGY CLIN. IMMUNOL. AUGUST 1976
BECLOMETHASONE DIPROPIONATE .-.
VEHICLE
1.40 1.201 BASE LINE FIG.
WEEK 1 2. Mean
WEEK2
WEEK 3
WEEK4
responses
of
(I).
FEV,
AFTER TREATMENT
2.2Or
VEHICLE
I I.001 @;“N”E WEEK I FIG.
3. Mean
I WEEK 2
responses
of
I WEEK 3
I WEEK 4
I AFTER TREATMENT
FEF2s0/o-75B (L/xc).
plasma cortisol levels were determined from blood samples drawn at 8:00 A.M.; the other clinical laboratory determinations were repeated at the end of the treatment regimen. One week later, during which no aerosol was administered, the patients were re-evaluated.
No significant differences were found before treatment between the two groups for signs, symptoms, type of asthma, severity or duration of asthma, bronchodilatory medication, or results of pulmonary function tests. Of the 93 patients enrolled, 86 completed the 4-wk course of treatment. The 7 patients who withdrew from the study were all in the vehicle-treated group; 4 of these discontinued due to treatment failure, another did so because of side effects (dry mouth, fatigue, and headache), and the other two withdrew for reasons unrelated to drug administration. hysicians’
and patients’
evaluation
of signs and symptoms
At each weekly visit, the physicians evaluated the severity of the patients’ wheezing and rhonchi; the decrease in each symptom was more pronounced in the drug-treated group than in the vehicle-treated group. Comparable results were observed in the patients’ evaluations of shortness of breath, wheezing, tightness of the chest, and cough.
Beclomethasone
VOLUME 58 NUMBER 2
TABLE 1. Mean values, standard pulmonary function tests
Initial visit Beclomethasone Vehicle Week 1 Beclomethasone Vehicle Week 2 Beclomethasone Vehicle Week 3 Beclomethasone Vehicle Week 4 Beclomethasone Vehicle One week after treatment Beclomethasone Vehicle
deviations
aerosol
in treatment
(SD), and standard
error
of asthma
of the means
(SE) for
t:
2.30 2.46
0.73 0.87
0.11 0.13
1.47 1.55
0.58 0.69
0.08 0.10
1.13 1.14
0.69 0.70
0.10 0.10
2
2.69 2.57
0.95 0.96
0.14 0.15
1.84 1.69
0.81 0.70
0.12 0.11
1.43 1.23
0.91 0.70
0.14 0.11
if
2.72 2.52
1.05 0.85
0.15 0.13
1.90 1.63
0.86 0.69
0.13 0.11
1.52 1.14
1.00 0.17
0.15 0.12
i:
2.74 2.46
0.88 0.92
0.13 0.14
1.93 1.65
0.73 0.75
0.11 0.12
1.60 1.26*
0.91 0.80
0.13 0.13
t:
2.75 2.55
0.97 1.07
0.14 0.17
1.95 1.66
0.79 0.80
0.12 0.13
1.62 1.20
0.98 0.78
0.14 0.12.
t:
2.60 2.57
1.oo 0.94
0.15 0.15
1.76 1.65
0.79 0.77
0.12 0.12
1.35 1.23
0.84 0.81
0.12 0.13
*One response not specified. TABLE II. Mean
scores for pulmonary
FVC (L) ~e;loothasone P value FEV, (L in 1 set) Beclomethasone Vehicle P value ~~Fzs~b.75~ CL) Beclomethasone Vehicle P value
2.46 2.30 20.327
function
21.0
tests
20.5
23.4 2.9
23.7
;::39
z34
0.002
1.47 1.55 0.478
30.8 14.2 0.091
34.5 :::06
38.7 11.3 0.003
39.5 10.9 0.005
26.8 9.7 0.057
1.13 1.14 >0.800
44.7 15.0 0.075
52.0 t%4
62.5 19.5 0.013
63.9 1.1 0.0007
38.9 12.7 0.047 only those
his
*Mean and lowest probability indicated for responses prior to each weekly visit; patients present at visits were included. ulmonary
16.9 ;::36
function
The mean values for FVC, FEV1, and FEFZjro-7j% in each treatment group are plotted in Figs. 1 to 3, respectively. The mean values with standard deviations and standard errors of the means are given in Table I. Pulmonary function data were analyzed as a percentage of change from the values before treatment (Table II) using Student’s t test. It was found that the differences between the groups for each parameter were statistically significant after week 1 (p < 0.10) and weeks 2, 3, and 4 (p 5 0.05). For the drug-treated patients, the improvement in each parameter was also significant (p < 0.01) when the responses for each
Vogt et al.
3
J. ALLERGY CLIN. IMMUNOL. AUGUST 1974
TABLE HI. Mean scores* for physicians’
and patients’ evaluations
Aerosol (physicians) Beclomethasone 2.4 2.2 Vehicle 3.0 :z :fz P value? 0.001 ;:;02 <0:001
levels
Beclomethasone Vehicle
for
plasma
16.14144 15.96145
cortisol
(fig/100
ml) by numbers
15.90/46 15.75145
11.22/40 15.15/42
of patients
16.89144 15.08/37
15.56146 14.74137
week of treatment were compared with those obtained before treatment : FVC had increased by 20% or more, FEV, by 30% or more, and FEF25W-75W,which reflects the condition of both large and small airways, had increased by more than SOY, after 3 wk of treatment. In contrast, the changes observed in the vehicletreated group were not significant. At 1 wk after the discontinuation of aerosol use, the improvement in pulmonary function attained by the patients using bec.lomethasone dipropionate had decreased. Evaluation
of the aerosol
When the patients and physicians rated the aerosols and the patients evalof relief (Table III), beclomethasone dipropionate aerosol was uated the extent significantly superior to the vehicle aerosol after each of the 4 wk of treatment (p < 0.01) and in the overa,ll evaluation at the end of the study (p 5 0.001). Clinical
laboratory
results
No evidence of a drug effect was observed in the results of clinical laboratory determinations. The mean levels for plasma cortisol indicated that neither preparation affected this parameter (Table IV). dverse
reactions
In the drug-treated group, one patient reported a flushed feeling during the first three days, and another complained of a salty taste during the first week. Four vehicle-treated patients complained of dryness of the mouth.
VOLUME 58 NUMBER 2
Beclomethasone
aerosol
in treatment
of asthma
The results of this double-blind, multicentric study in 93 patients demonstrated that a daily dosage of 400 pg of beclomethasone dipropionate by inhalation for 4 wk was effective in the management of chronic bronchial asthma and clearly superior to its vehicle. Results of pulmonary function tests and clinical signs and symptoms improved significantly in the drug-treated patient,s. The absence of drug effect on the clinical laboratory studies, including plasma cortisof; levels, and the low incidence and mild nature of adverse reactions support the safety of beclomethasone dipropionate aerosol when used over a one-month period. These findings indicate that beclomethasone dipropionate aerosol seems to be an effective alternative to systemically active steroids in the treatment of chronic bronchial asthma. REFERENCES
1 Streeten, 2
3 4 5 6 7
8 9 10
D. H. P.: Corticosteroid therapy. II. Complications and therapeutic indications, J. A. M. A. 232: 1046, 1975. MeAllen, M. K., Kochanowski, S. J., and Shaw, K. M.: Steroid aerosols in asthma: An assessment of betamethasone valerate and a 1%month study of patients on maintenance treatment, Br. Med. J. I.: 171, 1974. (This article includes the use of beelomethasone dipropionate aerosol.) Gaddie, J., Petrie, G. R., Reid, I. W., et al.: Aerosol beclomethasone dipropionate in chronic bronchial asthma, Lancet 1: 691, 1973. Smith, A. P., Booth, M., and Davey, A. J.: A controlled trial of beclomethasone dipropionate for asthma, Br. J. Dis. Chest 67: 208, 1973. Smith, J. M.: A clinical trial of beclomethasone dipropionate aerosol in children and adolescents with asthma, Clin. Allergy 3: 249, 1973. Maberly, D. J., Gibson, G. J., and Butler, A. G.: Recovery of adrenal function after substitution of beclomethasone dipropionate for oral corticosteroids, Br. Med. J. 1: 778, 1973. Chatterjee, S. S., Ross, A. E., Carroll, K., et al.: Respira.tory function on asthmatic patients using beclomethasone dipropionate administered by pressurised aerosol, Curr. Med. Res. Opin. 1: 173, 1972. P.: Asthma-treatment with the aerosol steroid beclomethasone Godfrey, S., and K&rig, dipropionate, Ann. Allergy 33: 150, 1974. dipropionate aerosol in childDickson, W., Hall, C. E., Ellis, M., et al. : Beclomethasone hood asthma, Arch. Dis. Child. 48: 671, 1973. dipropionate aerosol in adult steroidVilsvik, J. S., and Schaanning, J.: Beclomethasone dependent obstructive lung disease, &and. J. Respir. Dis. 55: 169, 1974.
M.D., Joseph
Bloomfield, N. J., New Bedford, Xass., Plushixg, New York, N. Y.
onchial Dwek,
M.D., an
N. Y., a,nd
patients with a double-bEind, randomized sttiay, 93 corticosteriod-independent chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 gg per day or its vehicle for 4 ~16 to determine and compare the effectiveness and safety of tke preparations. Evaluations made before, nt weekly interGals during, rind 1 wk after treatment indicated that beclomethasone dipropionate aerosol ZL’CES superior to its vehicle in improving FBC, FEP,, PEF,i%.7s?o, and clin~icnl signs and evduntions by both the investigators and, the patients. symptoms, and in the overall P1asm.a cortisd levels measured at the end of the second and fourth weeks were not substantially diferent from those before treatment in either group. No significnn.t side effects or abnormalities in laboratory results wc~c noted.
In
The clinical use of corticosteroids in the management of severe bronchial asthma is well established. However, the therapeutic benefit of orally administered corticosteroids is often accompanied by undesirable and frequently severe adverse effects.l Beclomethasone dipropionate has been studied extensively as a topical anti-inflammatory agent; its topical activity and low solubility provided good bases for its use as an aerosol. In Great Britain and elsewhere, beelomethasone dipropionate aerosol was effective in the management of asthma in steroid-independent patients,*-4 unaccompanied by systemic effects including hypothalamiepituitary-adrenal axis suppression. For many steroid-dependent asthmatics, beclomethasone dipropionate aerosol was an effective alternative to oral therapy.“-I0 The present report summarizes the results of a double-blind multicentric study comparing beclomethasone dipropionate aerosol with its vehicle aerosol in patients with chronic bronchial asthma. From the Sehering Corporation, Allergy Associates, Inc., Booth Memorial Medical Center and The Roosevelt Hospital, R. A. Cooke Institute of Allergy. Presented at the Thirty-first Annual Meeting of the American Academy of Allergy, San Diego, Calif., 1975. Received for publication Sept. 15, 1975. Accepted for publication Dec. 24, 1975. Reprint requests to: Dr. Frank Vogt, Sehering Corporation, Bloomfield, N. J. 07OOS. Vol. 58, iVo. 2, pp. 316-381
VOLUME 58 NUMBER 2
Beclomethasone 3.00
r
!jf,SE
aerosol
in treatment
of asthma
BECLOMETHASONE DIPROPIONATE
WEEK 1
WEEK2
WEEK 3
FIG. 1. Mean responses
WEEK 4
AFTER TREATMENT
of WC (L].
MATERIALS AND METHODS Selection of patients Ninety-three patients (33 males and 60 females) between 14 and 65 yr of age were enrolled in the study after giving informed consent; 41 patients were over 40 yr of age, and 52 were under 40 yr. All had reversible obstructive airway disease and required the continuous use of bronchodilators; none was steroid-dependent. Two-thirds (62) of the patients had had asthma for up to 15 yr, and 5 had had the condition for over 45 yr. In 86 patients the asthma was severe or moderately severe. The asthma was extrinsic in 34 patients, intrinsic in 9, and of mixed causes in the other 50. Eighty-five patients had cough on admission to the study; only 7 had a sensitivity to aspirin. All patients had a forced expiratory volume in one second (FEV,) of between 20% and 80% of the predicted normal, and reversibility of airways obstruction was established by an improvement in FEV, of 15vo or more after a standard dose of isoproterenol aerosol. None of the patients had received corticosteroids within 4 wk of enrollment. Before treatment, each patient was given a physical examination, with particular reference to clinical manifestations of bronchial asthma, and the following clinical laboratory determinations were performed to detect any potential drug effect : hemoglobin, hematocrit, total leukocyte count and differential, fasting blood glucose, blood carbon dioxide, serum alkaline serum glutamic-oxalacetic transaminase, serum electrolytes, plasma eortisol phosphatase, (measured twice), and urinalysis.
Treatment
regimen
The patients were assigned to one of stratified, randomized master code. Each of beelomethasone dipropionate aerosol 4 47 patients received two inhalations of the were instructed to continue the use of their
linical
two treatment groups according to a double-blind, of 46 patients received two inhalations (100 pg’) times a day for 4 wk, and each of the remaining vehicle aerosol 4 times a day for 4 wk. The patients nonsteriod medication.
evaluations
During the 4-wk treatment period, the patients recorded signs and symptoms daily and were evaluated weekly. At each visit, pulmonary function tests (forced vital capacity [FVC], forced expiratory volumo in 1 second [FEV,], and forced expiratory fiow between 25% and 75ol, [FEF,,B.~e%] ) were performed, findings of physical examinations and side effects were recorded, and the patients’ symptom diaries were reviewed. After 2 and 4 wk of treatment, *Delivery
at the valve;
delivery
at the mouthpiece
is approximately
85 pg.
Vogt et al.
J. ALLERGY CLIN. IMMUNOL. AUGUST 1976
BECLOMETHASONE DIPROPIONATE .-.
VEHICLE
1.40 1.201 BASE LINE FIG.
WEEK 1 2. Mean
WEEK2
WEEK 3
WEEK4
responses
of
(I).
FEV,
AFTER TREATMENT
2.2Or
VEHICLE
I I.001 @;“N”E WEEK I FIG.
3. Mean
I WEEK 2
responses
of
I WEEK 3
I WEEK 4
I AFTER TREATMENT
FEF2s0/o-75B (L/xc).
plasma cortisol levels were determined from blood samples drawn at 8:00 A.M.; the other clinical laboratory determinations were repeated at the end of the treatment regimen. One week later, during which no aerosol was administered, the patients were re-evaluated.
No significant differences were found before treatment between the two groups for signs, symptoms, type of asthma, severity or duration of asthma, bronchodilatory medication, or results of pulmonary function tests. Of the 93 patients enrolled, 86 completed the 4-wk course of treatment. The 7 patients who withdrew from the study were all in the vehicle-treated group; 4 of these discontinued due to treatment failure, another did so because of side effects (dry mouth, fatigue, and headache), and the other two withdrew for reasons unrelated to drug administration. hysicians’
and patients’
evaluation
of signs and symptoms
At each weekly visit, the physicians evaluated the severity of the patients’ wheezing and rhonchi; the decrease in each symptom was more pronounced in the drug-treated group than in the vehicle-treated group. Comparable results were observed in the patients’ evaluations of shortness of breath, wheezing, tightness of the chest, and cough.
Beclomethasone
VOLUME 58 NUMBER 2
TABLE 1. Mean values, standard pulmonary function tests
Initial visit Beclomethasone Vehicle Week 1 Beclomethasone Vehicle Week 2 Beclomethasone Vehicle Week 3 Beclomethasone Vehicle Week 4 Beclomethasone Vehicle One week after treatment Beclomethasone Vehicle
deviations
aerosol
in treatment
(SD), and standard
error
of asthma
of the means
(SE) for
t:
2.30 2.46
0.73 0.87
0.11 0.13
1.47 1.55
0.58 0.69
0.08 0.10
1.13 1.14
0.69 0.70
0.10 0.10
2
2.69 2.57
0.95 0.96
0.14 0.15
1.84 1.69
0.81 0.70
0.12 0.11
1.43 1.23
0.91 0.70
0.14 0.11
if
2.72 2.52
1.05 0.85
0.15 0.13
1.90 1.63
0.86 0.69
0.13 0.11
1.52 1.14
1.00 0.17
0.15 0.12
i:
2.74 2.46
0.88 0.92
0.13 0.14
1.93 1.65
0.73 0.75
0.11 0.12
1.60 1.26*
0.91 0.80
0.13 0.13
t:
2.75 2.55
0.97 1.07
0.14 0.17
1.95 1.66
0.79 0.80
0.12 0.13
1.62 1.20
0.98 0.78
0.14 0.12.
t:
2.60 2.57
1.oo 0.94
0.15 0.15
1.76 1.65
0.79 0.77
0.12 0.12
1.35 1.23
0.84 0.81
0.12 0.13
*One response not specified. TABLE II. Mean
scores for pulmonary
FVC (L) ~e;loothasone P value FEV, (L in 1 set) Beclomethasone Vehicle P value ~~Fzs~b.75~ CL) Beclomethasone Vehicle P value
2.46 2.30 20.327
function
21.0
tests
20.5
23.4 2.9
23.7
;::39
z34
0.002
1.47 1.55 0.478
30.8 14.2 0.091
34.5 :::06
38.7 11.3 0.003
39.5 10.9 0.005
26.8 9.7 0.057
1.13 1.14 >0.800
44.7 15.0 0.075
52.0 t%4
62.5 19.5 0.013
63.9 1.1 0.0007
38.9 12.7 0.047 only those
his
*Mean and lowest probability indicated for responses prior to each weekly visit; patients present at visits were included. ulmonary
16.9 ;::36
function
The mean values for FVC, FEV1, and FEFZjro-7j% in each treatment group are plotted in Figs. 1 to 3, respectively. The mean values with standard deviations and standard errors of the means are given in Table I. Pulmonary function data were analyzed as a percentage of change from the values before treatment (Table II) using Student’s t test. It was found that the differences between the groups for each parameter were statistically significant after week 1 (p < 0.10) and weeks 2, 3, and 4 (p 5 0.05). For the drug-treated patients, the improvement in each parameter was also significant (p < 0.01) when the responses for each
Vogt et al.
3
J. ALLERGY CLIN. IMMUNOL. AUGUST 1974
TABLE HI. Mean scores* for physicians’
and patients’ evaluations
Aerosol (physicians) Beclomethasone 2.4 2.2 Vehicle 3.0 :z :fz P value? 0.001 ;:;02 <0:001
levels
Beclomethasone Vehicle
for
plasma
16.14144 15.96145
cortisol
(fig/100
ml) by numbers
15.90/46 15.75145
11.22/40 15.15/42
of patients
16.89144 15.08/37
15.56146 14.74137
week of treatment were compared with those obtained before treatment : FVC had increased by 20% or more, FEV, by 30% or more, and FEF25W-75W,which reflects the condition of both large and small airways, had increased by more than SOY, after 3 wk of treatment. In contrast, the changes observed in the vehicletreated group were not significant. At 1 wk after the discontinuation of aerosol use, the improvement in pulmonary function attained by the patients using bec.lomethasone dipropionate had decreased. Evaluation
of the aerosol
When the patients and physicians rated the aerosols and the patients evalof relief (Table III), beclomethasone dipropionate aerosol was uated the extent significantly superior to the vehicle aerosol after each of the 4 wk of treatment (p < 0.01) and in the overa,ll evaluation at the end of the study (p 5 0.001). Clinical
laboratory
results
No evidence of a drug effect was observed in the results of clinical laboratory determinations. The mean levels for plasma cortisol indicated that neither preparation affected this parameter (Table IV). dverse
reactions
In the drug-treated group, one patient reported a flushed feeling during the first three days, and another complained of a salty taste during the first week. Four vehicle-treated patients complained of dryness of the mouth.
VOLUME 58 NUMBER 2
Beclomethasone
aerosol
in treatment
of asthma
The results of this double-blind, multicentric study in 93 patients demonstrated that a daily dosage of 400 pg of beclomethasone dipropionate by inhalation for 4 wk was effective in the management of chronic bronchial asthma and clearly superior to its vehicle. Results of pulmonary function tests and clinical signs and symptoms improved significantly in the drug-treated patient,s. The absence of drug effect on the clinical laboratory studies, including plasma cortisof; levels, and the low incidence and mild nature of adverse reactions support the safety of beclomethasone dipropionate aerosol when used over a one-month period. These findings indicate that beclomethasone dipropionate aerosol seems to be an effective alternative to systemically active steroids in the treatment of chronic bronchial asthma. REFERENCES
1 Streeten, 2
3 4 5 6 7
8 9 10
D. H. P.: Corticosteroid therapy. II. Complications and therapeutic indications, J. A. M. A. 232: 1046, 1975. MeAllen, M. K., Kochanowski, S. J., and Shaw, K. M.: Steroid aerosols in asthma: An assessment of betamethasone valerate and a 1%month study of patients on maintenance treatment, Br. Med. J. I.: 171, 1974. (This article includes the use of beelomethasone dipropionate aerosol.) Gaddie, J., Petrie, G. R., Reid, I. W., et al.: Aerosol beclomethasone dipropionate in chronic bronchial asthma, Lancet 1: 691, 1973. Smith, A. P., Booth, M., and Davey, A. J.: A controlled trial of beclomethasone dipropionate for asthma, Br. J. Dis. Chest 67: 208, 1973. Smith, J. M.: A clinical trial of beclomethasone dipropionate aerosol in children and adolescents with asthma, Clin. Allergy 3: 249, 1973. Maberly, D. J., Gibson, G. J., and Butler, A. G.: Recovery of adrenal function after substitution of beclomethasone dipropionate for oral corticosteroids, Br. Med. J. 1: 778, 1973. Chatterjee, S. S., Ross, A. E., Carroll, K., et al.: Respira.tory function on asthmatic patients using beclomethasone dipropionate administered by pressurised aerosol, Curr. Med. Res. Opin. 1: 173, 1972. P.: Asthma-treatment with the aerosol steroid beclomethasone Godfrey, S., and K&rig, dipropionate, Ann. Allergy 33: 150, 1974. dipropionate aerosol in childDickson, W., Hall, C. E., Ellis, M., et al. : Beclomethasone hood asthma, Arch. Dis. Child. 48: 671, 1973. dipropionate aerosol in adult steroidVilsvik, J. S., and Schaanning, J.: Beclomethasone dependent obstructive lung disease, &and. J. Respir. Dis. 55: 169, 1974.