Journal of Asthma, 44:1–12, 2007

Copyright C 2007 Informa Healthcare

ISSN: 0277-0903 print / 1532-4303 online

DOI: 10.1080/02770900601118099

REVIEW ARTICLE

Evidence-Based Selection of Inhaled Corticosteroid for Treatment

of Chronic Asthma
ANWAR K. ABDULLAH, M.D., F.R.C.P.C., F.C.C.P.1,†,∗ AND SALMAN KHAN, M.D.2
1
Virginia Center for Behavioral Rehabilitation, Petersburg, Virginia, USA
2
Central State Hospital, Petersburg, Virginia, USA

Published literature relevant to comparison of various inhaled corticosteroids (ICSs) was reviewed. Marked heterogeneity was found in the reported
results. The efficacy and side effects of ICSs depend on their formulation, dosing and device used, and the subjects’ age, severity of asthma, and
inhaler technique. All these factors have not been included uniformly in most study designs. Notwithstanding this limitation, it appears that fluticasone
is generally very effective and safe in low-to-medium doses and may be used for most patients. Budesonide is the only Pregnancy Category B ICSs,
all others being Category C, and it is available as nebulizer suspension suitable for use in children over 6 months of age. Budesonide, also available
as dry powder inhaler, and beclomethasone, available as metered-dose inhaler, are equal in efficacy, and side effects and may be chosen according
to the patient’s ability to handle the device. Flunisolide causes fewer side effects but is also relatively less effective. Triamcinolone is generally less
effective and causes more side effects than most of the other ICSs. Mometasone may be preferred if once-daily dosing is desired. Ciclesonide has
been found highly effective in once-daily dose and without side effects even in high doses. Further studies comparing it with other ICSs over longer
periods of use will determine its place in treatment of chronic asthma.

Keywords asthma, corticosteroids, evidence-based medicine, beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone,
triamcinolone

INTRODUCTION ticles were selected for their relevance to comparison of the

Most asthma treatment guidelines recommend that all pa-
tients with chronic persistent asthma should be treated with
an inhaled corticosteroid (ICS) (1). Corticosteroids control
asthma by suppressing inflammation by binding to gluco-
corticoid receptors in the lungs (2). But they may also bind
to the same receptor types in extrapulmonary tissues and
cause systemic side effects, e.g., adrenal suppression, stunt-
ing of growth, osteoporosis, cataract, glaucoma, skin thin-
ning, and bruising (3). Additionally, orally inhaled corti-
costeroids can cause local complications, e.g., hoarseness,
dysphonia, pharyngitis, and oral candidiasis (4). Six ICS
preparations are currently available in the United States, and
another is likely to become available soon. Many publica-
tions exist highlighting their benefits and risks individually
or comparing one with others. This review presents all pub-
lished information helpful in selecting an ICS with the most
favorable risk-benefit ratio for a given situation.
METHODS
A comprehensive search of published literature (January
1965 to March 2006) was conducted using PubMed with
search terms (inhaled corticosteroids OR beclomethasone
OR budesonide OR ciclesonide OR flunisolide OR flutica-
sone OR mometasone OR triamcinolone) AND asthma. Ar-
†
Formerly Professor of Medicine & Head of Pulmonary Division, College
of Medicine, Riyadh University, Saudi Arabia.
∗
Corresponding author: Anwar K. Abdullah, M.D., 12909, Scrimshaw
Circle, Chester, VA 23836; E-mail: anwar.abdullah@vcbr.dmhmrsas.
virginia.gov
1
above-listed ICSs for efficacy and side effects, and placed
in Tables 1 through 5 according to their conclusions, and
grouped according to Quality of Evidence (QoE) grades A,
B, or C, using American College of Chest Physicians’ crite-
ria (5). Review articles or meta-analyses were starred with an
asterisk, and their constituent primary articles were excluded
from tables. Majority of included articles were of grades A
or B.
PHARMACOKINETICS, EFFICACY, AND SIDE EFFECTS
The ideal ICS would maximize the amount of active
drug presented to receptors in airways to produce maximum
benefit while minimizing its delivery to receptors at non-
pulmonary sites to reduce adverse effects (6). Physical and
pharmacokinetic features of ICSs affect their efficacy and
side effects (6–9) as summarized below:
1. Receptor affinity and lipid solubility of an ICS determine
its potency and half-life, respectively. Adjusting the dose
can compensate both. They confer no benefit/risk advan-
tage since both affect benefit and risk similarly (6).
2. Small (2- to 6-μm) aerosol particles provide more ben-
efit by increasing availability in airways compared to
large (>6-μm) particles, which settle more in orophar-
ynx causing local side effects and are also swallowed
and absorbed into circulation (oral bioavailability) caus-
ing systemic side effects (8). Very small particles (<2
μm) reach deeper into alveolar space (8) and are absorbed
into circulation (pulmonary bioavailability) bypassing the
hepatic clearance mechanism and cause systemic side
effects.
2 A. K. ABDULLAH AND S. KHAN

TABLE 1.—Beclomethasone vs. other inhaled corticosteroids.

Beclomethasone Triamcinolone Flunisolide Budesonide Fluticasone Mometasone Ciclesonide
(BDP) (TA) (FH) (BUD) (FP) (MF) (CIC)
MDI-HFA-solution vs. MDI-CFC-suspension MDI-HFA-solution DPI, nebulizer susp. MDI-HFA-suspension, DPI DPI MDI-HFA-solnution

Efficacy References References References References References References

Symptoms/airways Better [12] {11∗ } [13] {11∗ } [13] {11∗ , 14} [60]
function∗1
Equal [15] [24∗ , 28∗ , 27] {25, [30∗ , 31∗ , 29]
26}
Worse (16) [17] [18] {19} [32∗ , 34∗ ] {11∗ , 33} [20, 21, 22, 23]
(35, 36)
Taste: no report No taste [84] Bitter [84]
Quality of life∗2
Equal [31∗ ]
Worse [41, 39] {40}
Cost-effectiveness Better (37, 38) (37, 38) (37)
Worse (65)
Side effects
Local∗3
Better [32∗ ] {42} {21}
Equal [15] (16) (43) [34∗ ]
Worse {44} (45) (46)
Adrenal Better [47] [3∗ , 47] {48}
suppression∗4
Equal [3∗ ] (16) [65] [3∗ , 28∗ ] {25, 26, 62} [30∗ , 54, 58, 59, 60] No report
(63, 64) {55, 56, 57, 61} comparing
Worse [47] [47] [34∗ , 52, 53] {40, 49, {21} BDP with CIC is
50, 51} available.
Acute adrenal crisis: 2 1 of 33 cases (122) 30 of 33 cases (122)
of 33 cases (122)
Bone metabolism/ Better [68∗ ]
BMD reduction∗5
Equal [28∗ ] {25} (66) {50, 67}
Worse [68] {69} {56, 57}
Growth retardation∗6 Better
Equal [28∗ ] {25}
Worse [70∗ ] [65] [70∗ ] [70∗ , 54, 71] {50, 72} [70∗ ]
Pregnancy category:
Category C {90} Category C {90} Category C {90} Category B {90} Category C {90} Category C {137}
BDP advantages BDP may be more BDP is more effective BDP is about as BDP appears to be BDP is available as
effective than TA, and more cost- effective as BUD equal to or better MDI-HFA Inhaler.
cause less BMD effective than FH. and is available as than FP regarding
reduction and be MDI-HFA inhaler. local side effects.
more cost-effective.
BDP disadvantages BDP may cause more BDP may cause more BDP may cause more BDP may be less BDP is less effective
local side effects, adrenal local & systemic effective and cause & has more
adrenal suppression, suppression than side effects than more systemic side frequent systemic
& growth retardation FH. BUD. Not effects than FP, side effects than
than TA. available as neb. and is not available MF.
susp. and is Preg. as DPI.
Cat. C.
Overall Preference BDP BDP may be preferred BDP may be BUD may be FP may be preferred MF may be preferable
vs. other ICSs over TA because of preferable to FH, preferred over over BDP unless to BDP unless
its cost-effectiveness, but watch for BDP except when local side effects patient is unable to
unless it causes side possible adrenal MDI is the from FP are a use a DPI.
effects. supression. preferred device. problem.

Notes: Quality of evidence [ ] = A, {} = B, ( ) = C; reference marked by a star (∗ ) is a review article or meta-analysis.

∗1
Includes studies reporting effects on one or more of following: cough. wheezing, nocturnal waking, frequency of exacerbations, need for rescue bronchodilators, oral steroid dependence;
PEF, FEV1 , small airways function, bronchodilator reversibility, airway hyperresponsiveness to Methacoline, Histamine, or cAMP; exhaled nitric oxide concentration.
∗2
Studies using an asthma quality of life questionnaire.
∗3
Includes studies reporting occurance of hoarseness/dysphonia, throat irritation/sore throat/pharyngitis, oral candidiasis.
∗4
Includes studies reporting effects on one or more of following: morning plasma cortisol, plasma cortisol area under curve (AUC), 24-hr urinary cortisol; cosyntropin, ACTH, or hCRF
stimulation test.
∗5
Includes studies reporting effects on one or more of following: Indices of bone formation (serum osteocalcin, collagen type-1 C-terminal propeptide (P1CP), Collagen type-3
NH-terminal propeptide (P3NP)); Indices of bone resorption (urinary calcium, collagen type-1 C-terminal telopeptide, and deoxypyridinoline crosslinks); Bone mineral density (BMD)
measurements.
∗6
Includes studies reporting effects on height centiles and/or growth velocity measured by knemometry or stadiometry.

3. ICSs with low protein binding cause more side ef-
fects by leaving more free drug available to bind with
extra-pulmonary receptors (6).
4. Lipid conjugation of ICS occurs exclusively in lungs.
Higher lipid conjugation increases pulmonary half-life by
increasing lung residence time without increasing sys-
temic half-life, thus increasing benefit/risk ratio (6).
5. An ICS in pro-drug form, which is activated only in lungs,
has a more favorable benefit/risk ratio than one that is
active on administration or converts to active form in both
pulmonary and non-pulmonary tissues (6).
COMPARISON OF INHALED CORTICOSTEROIDS
Salient pharmacological properties of each ICS are briefly
described below, followed by results of studies comparing it
with other ICSs regarding efficacy and side effects. No study
comparing different ICSs for their effects on eyes or skin
were found.
Beclomethasone
Introduced in 1972 as a chlorofluorocarbon-propelled
metered-dose inhaler (CFC-MDI), beclomethasone is now
EVIDENCE-BASED SELECTION OF INHALED CORTICOSTEROID
available as hydrofluoroalkane-propelled inhaler (HFA-
MDI), which is more environment friendly and also more
effective due to smaller aerosol particle size (10). High
plasma protein binding (87%), high first pass hepatic clear-
ance (150 L/h), and short systemic half-life (0.5 h) of be-
clomethasone contribute to its low side effects potential
(7). It is inhaled as a prodrug, beclomethasone dipropionate
(BDP), with relative receptor affinity (RRA) of 43–53 (vs.
100 for dexamethasone) and metabolized to the active form
17-beclomethasone monopropionate (BMP) with RRA of
1,345 (7). Since this conversion occurs in extra-pulmonary
tissues also, and even in the pro-drug form its RRA is much
greater than endogenous cortisol, it can cause significant side
effects.
Beclomethasone vs. Other Inhaled Corticosteroids
Efficacy. Comparing the ratios of clinical efficacy rela-
tive to fluticasone (FP) determined by reevaluation of 29
published studies (Table 1), BDP was found better than tri-
amcinolone (TA), flunisolide (FH), and budesonide (BUD),
and worse than fluticasone (FP) (11). Other studies found
BDP better than TA (12), FH (13), and BUD (13, 14); equal
to TA (15); or worse than TA (16), FH (17), BUD (18, 19),
and Mometasone (MF) (20–23). However, most studies, have
found BDP equal to BUD (24–28); and equal (29–31) or in-
ferior to FP (32–36). BDP was more cost-effective than TA
and FH (37, 38), or BUD (37); but less than FP (37). It was
found equal (31) or inferior to FP in quality-of-life (QoL)
measures (39–41).
Local Side Effects. BDP was found better than FP (32,
42), and MF (21), equal to FP (34), TA (15, 16), and BUD
(43), and inferior to TA (44, 45), and BUD (46) in different
studies. Comparison with FH or ciclesonide (CIC) has not
been reported.
Adrenal Suppression. A meta-analysis of 34 studies
found BDP causing less adrenal suppression than FP, and
the difference between BDP and TA or BUD was not signif-
icant (3). On comparing equisystemic doses, BDP required
higher doses than BUD or FP, and lower doses than TA or FH
to produce 10% cortisol suppression (47). One study found
greater increase in morning plasma cortisol after changing
over from other ICS to BDP-extrafine than to FP (48). But
other studies found BDP causing more adrenal suppression
than FP (34, 40, 49–53), and MF (21); or equal to FP (30,
54–61), BUD (25, 26, 28, 62–64), TA (16), and FH (65). No
study comparing BDP with CIC was found.
Effect on Bone and Growth. BDP was found better than
TA (68), but equal to BUD (25, 28, 66), and FP (50, 67) in
some studies and worse than FH (65), BUD (68, 69), and FP
(56, 57), in others on effects on bone; and equal to (25, 28)
or worse than BUD (70) in causing growth retardation; but
all studies found more growth retardation with BDP than TA
(70), FP (50, 54, 70–72), and MF (70). Comparison with FH
or CIC has not been reported.
Triamcinolone
Triamcinolone acetonide, first used as aerosol suspension
in 1974, is still dispensed as CFC-MDI. Its relatively low
3
RRA (233), low plasma protein binding (78%), low clear-
ance rate (37 L/h), high oral bioavailability (23%), and high
systemic half-life (7 h) (73) increase its systemic side ef-
fects potential, and its large aerosol particle size (4.5 μm)
(74) predisposes it to cause oral side effects. As CFC-
containing MDIs are phased out, it will become unavailable
by 2008.
Triamcinolone vs. Other Inhaled Corticosteroids
Efficacy. Most studies found TA less effective than BDP
(11, 12), FH (11), BUD (11, 75), and FP (Table 2) (11, 34,
76, 77). Only one study found TA equal to BDP (15), and
another reported further improvement in symptoms when
BDP was replaced with TA (16). It was found more cost-
effective than FH (37, 38) and BUD (37), but less so than BDP
(37, 38) and FP (37), and inferior to BUD in QoL measures
(78).
Local Side Effects. TA was reported equal to (15, 16) or
better (44, 45) than BDP, and better (76) or worse than FP
(79). No report comparing TA with other ICS was found.
Adrenal Suppression. In the equisystemic effects study
(47), 10% adrenal suppression occurred at higher doses of
TA than BDP, BUD, or FP, but lower than FH. However,
other studies found TA equal to BDP (3, 16), FH (79, 80),
BUD (3, 81, 82), and FP (76, 79), and one reported more
adrenal suppression by TA than by FP (83). No study has
compared TA with MF or CIC.
Effect on Bone and Growth. A meta-analysis of 11 trials
concluded that TA caused more deleterious effect on bone
than BDP or BUD (68). A study using data from 32 previously
published studies found that TA was less likely than BDP or
BUD and more likely than FP or MF to reduce growth velocity
(70).
Flunisolide
Flunisolide hemihydrate, introduced in 1979 as CFC-MDI
suspension, is now available as HFA-MDI solution with all
the advantages over CFC-MDI as described above for be-
clomethasone. A menthol-containing preparation masking its
unpleasant taste is also available (84). Its RRA (180) is low-
est of all ICS (7). Its short systemic half-life (1.6 h) is an
advantage relative to systemic side effects, but its low protein
binding (80%) and low clearance rate (58 L/h) (7) increase
its potential for side effects.
Flunisolide vs. Other Inhaled Corticosteroids
Efficacy. FH was found better than BDP (17), TA, and
BUD (11), or equal to BUD (85), in some studies; but worse
than BDP (11, 13), and FP (11, 34, 79, 86, 87), in other studies
in efficacy. It was found worse than FP in QoL outcomes (87),
and worse than BDP and TA (37, 38), BUD (37), and FP (37,
86) in cost-effectiveness (Table 3).
Local Side Effects. One study found less throat irritation
with FH than with FP (79). No comparison with other ICS
was found.
Adrenal Suppression. In the equisystemic doses study
(47), FH required the largest dose to produce 10% cortisol
4 A. K. ABDULLAH AND S. KHAN

TABLE 2.—Triamcinolone vs. other inhaled corticosteroids.

Triamcinolone Beclomethasone Flunisolide Budesonide Fluticasone Mometasone Ciclesonide
(TA) (BDP) (FH) (BUD) (FP) (MF) (CIC)
MDI-CFC-suspension vs. MDI-HFA-solution MDI-HFA-solution DPI, nebulizer susp. MDI-HFA-suspension, DPI DPI MDI-HFA-solnution
Efficacy References References References References References References
Symptoms/airways Better (16)
function∗1
Equal [15]
Worse [12] {11∗ } {11∗ } [75] {11∗ } [34, 76, 77] {11∗ }
Taste: no taste [84] Bitter [84]
Qality of life∗2 Worse [78]
Cost-effectiveness Better (37, 38) (37)
Worse (37, 38) (37)
Side effects
Local∗3
Better {44} (45) [76]
Equal [15] (16)
Worse [79]
Adrenal suppression∗4 Better [47] [47] [3∗ , 47]
Equal [3∗ ] (16) [79] {80} [3∗ ] {81, 82} [76, 77] No report
comparing
Worse [47] [83] TA with CIC is
available.
Acute adrenal crisis
No report 2 of 33 cases (122) 1 of 33 cases (122) No report 30 of 33 cases (122)
Bone metabolism/ Better
BMD reduction∗5 Equal
Worse [68∗ ] [68∗ ]
Growth retardation∗6 Better [70∗ ] [70∗ ]
Equal
Worse [70∗ ] [70∗ ]
Pregnancy Category C {90} Category C {90} Category B {90} Category C {90} Category C {137}
Category:Category
C {90}
TA advantages TA may cause less TA is tasteless and is TA causes less adrenal TA causes less local TA is in clinical use
local side effects, more cost-effective. suppression and side effects and for longer time
adrenal suppression growth retardation adrenal suppression than MF.
and growth and is more than FP.
retardation than cost-effective.
BDP.
TA disadvantages TA may be less TA may be less TA is less effective and TA is less effective, TA must be given at
effective, less effective and cause causes more BMD less cost-effective, least BID, and it
cost-effective and more adrenal reduction than and causes more has caused more
cause more BMD suppression than BUD. growth retardation growth retardation
reduction than BDP. FH. than FP. than MF.
Overall preference BDP may be preferred FH may be preferable BUD may be preferred FP may be preferred MF may be preferable
TA vs. other ICSs over TA because of to TA unless taste is except if growth over TA because of to TA, although
its cost- unacceptable to retardation is a its effectiveness, clinical experience
effectiveness, unless patient. concern. unless it causes side with MF is still
it causes side effects. limited.
effects.

Notes: See Table 1.

suppression. In one trial FH caused less adrenal suppression
than FP (88) but in another it was equal to FP (79). Two trials
found it equal to TA (79, 80).
Effect on Bone and Growth. One study reported mean
change from baseline height at week 54 of treatment of 6.2 cm
for children given FH and 5.1 cm for BDP (65). No study
comparing FH with other ICSs for effects on bone or growth
was found.
Budesonide
Budesonide has been in use since 1980 as a dry powder
inhaler (DPI), which does not require hand—breath coordi-
nation to operate, therefore preferred by some who are unable
to use an MDI device properly. But it requires strong inspi-
ratory effort to initiate the dry powder’s delivery that may be
difficult for some to generate. It is also available as nebulizer
suspension. Its high RRA (935), protein binding (85%), clear-
ance rate (84 L/h), and low oral (11%) and inhalation (28%)
bioavailability (7) make BUD relatively more effective and
safer. Its high pulmonary residence time allows step-down to
once-daily dosing in mild to moderate asthma, increasing pa-
tient compliance (89). The large DPI particle size (4.0 μm)
(74) increases the chances of oral side effects. BUD is the
only Pregnancy Category B ICS, all others being category C
(90), and is therefore the preferred ICS for use in pregnancy.
However, National Asthma Education and Prevention Pro-
gram (NAEPP) Guidelines (91) recommend that since there
is no data indicating that other ICS are unsafe during preg-
nancy, they may be continued in patients already controlled
on them.
Budesonide vs. Other Inhaled Corticosteroids
Efficacy. Two studies (18, 19) found BUD more effective
than BDP, but another three suggest that BUD is inferior to
BDP in efficacy (11, 13, 14); and a review of published data
(28), a meta-analysis of 24 trials (24), and three additional
studies (25–27) concluded that BUD and BDP are equal (Ta-
ble 4). Thus preponderance of evidence indicates that BUD
is equal to BDP in efficacy. It was found better than TA in
two studies (11, 75), and equal to FH in one (85), but less
effective than FH in another (11). One study reported BUD
more effective than FP given in half the dose of BUD (60)
(which is the recommended practice) (1), but all others have
found BUD equal (92–94) or inferior (11, 30, 32, 95–97) to
FP. It was also found equal to MF (98, 99) and CIC when
EVIDENCE-BASED SELECTION OF INHALED CORTICOSTEROID 5
TABLE 3.—Flunisolide vs. other inhaled corticosteroids
Flunisolide Beclomethasone Triamcinolone Budesonide Fluticasone Mometasone Ciclesonide
(FH) (BDP) (TA) (BUD) (FP) (MF) (CIC)
DI-HFA-solution vs. MDI-HFA-solution MDI-CFC-suspension DPI, Nebulizer susp. MDI-HFA-suspension, DPI DPI MDI-HFA-solnution
Efficacy References References References References References References
Symptoms/airways Better [17] {11∗ } {11∗ }
function∗1 Equal [85]
Worse [13] {11∗ } [34∗ , 79, 86]
{11∗ , 87}
Taste: bitter [84] No taste [84]
Quality of life∗2 Worse {87}
Cost-effectiveness Worse (37, 38) (37, 38) (37) [86] (37)
Side effects
Local∗3 Better [79]
Adrenal Better [47] [47] [47] [47, 88]
suppression∗4 Equal [65] [79] {80} [79]
Acute adrenal crisis
1 of 33 cases (122) 2 of 33 cases (122) 30 of 33 cases (122)
Bone metabolism/ No report No report
BMD reduction∗5 No report No report No report No report comparing comparing
Growth retardation∗6 Better [65] No report No report No report FH with MF is FH with CIC is
available. available.
Pregnancy category
Category C {90} Category C {90} Category C {90} Category B {90} Category C {90} Category C {137}
FH advantages FH causes less FH is more effective FH may be equal to or FH may cause less
adrenal and causes less more effective and adrenal supression
suppression and adrenal cause less adrenal than FP.
growth retardation suppression than suppression than
than BDP. TA, and is BUD
available as
HFA-MDI.
FH disadvantages FH is less effective FH has unpleasant FH has unpleasant FH is less effective
and less taste and is less taste and is less and less
cost-effective than cost-effective than cost-effective than cost-effective. It
BDP and has TA. BUD. It is not has unpleasant
unpleasant taste. available as taste and is not
nebulizer Susp. or available as DPI.
DPI.
Overall preference FH BDP may be FH may be preferable FH may be preferred FP may be preferred
vs. other ICSs preferred over FH, to TA unless taste over BUD except over FH, but watch
but watch for is unacceptable to in pregnancy and for side effects.
possible adrenal patient. when nebulizer or
suppression and DPI must be used,
growth e.g., in infants or
retardation. elderly.

Notes: See Table 1.

given twice daily (100, 101), but inferior to CIC when given
once daily (102). In QoL measures, BUD was reported worse
than TA (78) and FP (40, 41); and in cost-effectiveness it was
better than FH (37) but worse than BDP and TA (37) and FP
(37, 103, 104).
Local Side Effects. BUD caused less local side effects
than BDP in children (46) but equal in adults (43). A system-
atic review of 56 studies concluded that BUD was better than
FP (32). In another study it was found equal to MF (99).
Adrenal Suppression. BUD was found equal to BDP in
two reviews of published studies (3, 28) and several addi-
tional trials (25, 26, 62–64). It was also found equal to TA
(3, 81, 82) and MF (99). In the equisystemic dose study (47),
BUD caused 10% adrenal suppression at smaller doses than
BDP, TA, or FH, but at larger doses than FP. In addition,
comparing BUD with FP, a meta-analysis of seven trials (3)
and three subsequent studies (105–107) also found that BUD
caused less adrenal suppression than FP. But several other
studies have found them equal (60, 93–97), and another meta-
analysis of seven trials (30) and a subsequent randomized trial
(40) found that BUD caused more adrenal suppression than
FP.
Effect on Bone and Growth. BUD was found equal to
(25, 28, 66) or better than BDP (68, 69), better than TA (68)
and equal (93, 96) or inferior to FP (107) in adversely af-
fecting bone. Regarding growth retardation, BUD was re-
ported better than (70) or equal to (25, 28) BDP, equal (108,
109) or inferior (70, 97) to FP, and inferior to TA and MF
(70).
Fluticasone
Fluticasone propionate, developed in 1990, is available as
HFA-MDI suspension alone and as DPI with the long-acting
beta-agonist salmeterol. Its very high RRA of 1,800, high pro-
tein binding (90%), high clearance rate (69 L/h), long inhala-
tion half-life (10–14 h), and low oral (<1%) and pulmonary
(26%) bioavailability (7) makes it very effective with low sys-
temic side effect potential. It has very favorable benefit/risk
ratio in low-to-medium doses, but in higher doses its dose-
response curve flattens and incidence of adrenal suppression
increases (110). A drug interaction causing adrenal suppres-
sion, osteoporosis, crush fracture, or exacerbation of pre-
existing diabetes occurred when fluticasone was given to hu-
man immunodeficiency virus patients on Ritonavir (Norvir,
Abbott Laboratories, North Chicago, IL, USA), a protease
inhibitor that also inhibits cytochrome P450-3A necessary
for hepatic clearance of corticosteroids (111).
6
TABLE 4.—Budesonide vs. other inhaled corticosteroids.
Budesonide Beclomethasone Triamcinolone Flunisolide Fluticasone Mometasone Ciclesonide
(BUD) (BDP) (TA) (FH) (FP) (MF) (CIC)
DPI, Nebulizer susp. vs. MDI-HFA-solution MDI-CFC-suspension MDI-HFA-solution MDI-HFA-suspension, DPI DPI MDI-HFA-solnution
Efficacy References References References References References References
Symptoms/airways Better [18] {19} [75] {11∗ } [60]
Function∗1 Equal [24∗ , 28∗ , 27] {25, 26} [85] [94] {92} (93) [100, 101]
Worse [13] {11∗ , 14} {11∗ } [30∗ , 32∗ , 96, 97] {11∗ , 95} [98, 99] [102]
Taste: No report No taste (84) Bitter (84)
Quality of life∗2 Better [78]
Worse [41] {40}
Cost-effectiveness Better (37)
Worse (37) (37) [103∗ , 104∗ ] (37)
Side effects
Local∗3 Better (46) [32∗ ]
Equal (43) [99]
Worse
∗4 ∗
Adrenal suppression Better [3 , 47] {105, 106, 107}
Equal [3∗ , 28∗ ] {25, 26, 62} (63, 64) [3∗ ] {81, 82} [60, 94, 96, 97] {95} (93) [99]
Worse [47] [47] [47] [30∗ ] {40}
Acute adrenal crisis
No report 2 of 33 cases (122) 1 of 33 cases (122) 30 of 33 cases (122)
Bone metabolism/BMD Better [68∗ ] {69} [68∗ ]
reduction∗5
Equal [28∗ ] {25} (66) [96] (93)
Worse {107}
Growth retardation∗6 Better [70∗ ]
Equal [28∗ ] {25} [109] {108}
Worse [70∗ ] [70∗ , 97] [70∗ ]
Pregnancy category
Category B {90} Category C {90} Category C {90} Category C {90} Category C {90} Category C {137}
BUD advantages BUD is about as effective as BUD is more effective and BUD is more cost-effective, BUD may cause less adrenal BUD is available as BUD is available as neb.
BDP, may cause less side causes less BMD reduction is Pregnancy Category B & supression than FP in nebulizer suspension susp. It is as effective
effects, is Preg. Cat.B, and than TA, is Preg. Cat.B and available as nebulizer susp. many cases, is Preg. Cat.B for children who as CIC if given twice
available as nebulizer available as nebulizer and is available as cannot handle DPI daily.
suspension. suspension. nebulizer suspension. device.
BUD disadvantages BUD is not available as MDI. BUD causes more adrenal BUD may be equal or less BUD causes more growth BUD is less effective BUD is less effective
suppression and growth effecive than FH and cause retardation, and is less than MF and has than CIC when given
retardation than TA. more adrenal suppression. effective and less shown more growth once daily.
cost-effective than FP. retardation.
Overall preference BUD vs. BUD may be preferable to BDP, BUD may be preferable to TA FH may be preferred, except FP may be preferable to MF may be preferred, Not enough information
other ICSs especially in pregnancy and except in growing children. in pregnancy and when a BUD except in pregnancy except in pregnancy, is available to
when patient is unable to nebulizer or DPI must be and when a nebulizer and when a nebulizer determine preference.
handle MDI. used. must be used. must be used.

Notes: See Table 1.

EVIDENCE-BASED SELECTION OF INHALED CORTICOSTEROID
Fluticasone vs. Other Inhaled Corticosteroids
Efficacy. A systematic review of 56 trials concluded that
FP given at half the dose of BDP or BUD caused more im-
provement in airway caliber (32). A retrospective analysis of
15 trials found additional improvement when BDP, TA, or FH
was changed to lower doses of FP (34). The ratio of clinical
efficacy of FP to BDP, TA, FH, and BUD determined by re-
evaluation of data from 29 studies was found highest for FP
(11). Other trials also found FP more effective than BDP (35,
36), TA (76, 77), FH (79, 86, 87), and BUD (30, 32, 95–97).
But a systematic review of seven studies comparing CFC- or
HFA-FP with HFA-BDP found no significant difference (31).
Several other studies also found FP equal in efficacy to BDP
(29, 30), BUD (92–94), MF (112, 113), and CIC (114, 115).
However, one trial in 96 children concluded that although FP
at half the dose of BUD or BDP maintained reasonable con-
trol of symptoms, a mild decrease in lung function persisted,
indicating that FP may not be twice as potent as BUD or BDP
(60). In QoL measures, FP was reported equal to BDP-HFA
(31), and better than BDP-CFC (39–41), FH (87), or BUD
(40, 41) In cost-effectiveness FP was found better than BDP
(37), TA (37), FH (37, 86), and BUD (37, 103, 104).
Local Side-Effects. Several studies found more local side
effects with FP than with BDP (32, 42), TA (76), FH (79),
BUD (32), or CIC (116, 117), but some others found it equal
to BDP (34) and MF (112). Only one study reported more
frequent throat irritation with TA than with FP (79).
Adrenal Suppression. Studies comparing FP with other
ICSs have reached conflicting conclusions, reporting less
adrenal suppression than BDP (34, 40, 49–53), TA (83), and
BUD (30, 40), equal to BDP (30, 54–61), TA (76, 79), FH
(79), BUD (60, 93–97), and MF (118); or more than BDP
(3, 47, 48), TA (3, 47), FH (47, 88), BUD (3, 47, 105–107),
and MF (119). A systematic review of 56 trials comparing FP
with BDP/BUD did not reach a firm conclusion due to lim-
itations in the presentation of primary trial results (32). All
studies so far have found FP inferior to CIC in this respect
(114–116, 120, 121). Acute adrenal crisis has been reported
most frequently with FP, 30 of 33 reported cases in one review
were related to FP, 2 to BDP, and 1 to FH (122).
Effect on Bone and Growth. FP was found better than (56,
57) or equal to (50, 67) BDP and better than (107) or equal
to (93, 96) BUD in affecting bone. It also caused less growth
retardation than BDP (50, 54, 70–72), TA (70), BUD (70,
97), and MF (70), although two studies (108, 109) found it
equal to BUD in this respect. In pre-clinical animal studies FP
was found 22 times more active than CIC in causing femoral
growth plate hypoplasia (120).
Mometasone
Mometasone furoate, first used in asthma in 1999, was
approved in the United States in April 2005 as DPI and is
the only ICS-approved for once daily use. It has less than 1%
systemic bioavailability and no intestinal absorption when
orally inhaled (123). Despite 99% protein binding (vs. 90%
for FP), MF has shown adrenal suppression similar to FP in
medium-to-high doses (118), probably due to formation of
systemically active metabolites with lower protein binding
7
(124). Its relatively long systemic half-life (5 hours) and large
volume of distribution (152 L) make it highly effective in
once-daily dose (125–127). Compared to this, effectiveness
of both BUD and FP lasts only 12 hours (92), and a meta-
analysis of six trials found FP once daily significantly less
effective than twice daily (128).
Mometasone vs. Other Inhaled Corticosteroids
All studies comparing MF with BDP, TA, BUD, and FP are
included in Tables 1, 2, 4, and 5. There is no study comparing
MF with FH or CIC.
Efficacy. MF was found to be better than BDP (20–23) or
BUD (98, 99) and equal to FP (112, 113) in efficacy.
Local Side-Effects. Throat symptoms with MF occurred
slightly more frequently than with BDP (21) and equally
compared to BUD (99) and FP (112).
Adrenal Suppression. MF caused less adrenal suppres-
sion than BDP (21), equal to BUD (99), and less than FP in
one study (119) but equal to it in another (118).
Effect on Bone and Growth. One study reported equal
suppression of serum osteocalcin by MF and FP (118). Us-
ing a pharmacokinetic/pharmacodynamic model, MF was es-
timated to be less likely than BDP, TA, or BUD and more
likely than FP to reduce growth velocity (70).
Ciclesonide
Ciclesonide, dispensed as HFA-MDI solution, is the newest
ICS, approved in Australia and United Kingdom in 2004, and
awaiting approval elsewhere including in the US. Its small
particle size (1.1–2.1 μm) results in high (52%) lung depo-
sition and low (38%) oropharyngeal deposition (117). The
parent compound (CIC) is a prodrug having a very low RRA
of 12, which increases to 1,200 after hydrolysis to active form
desisobutyryl-CIC (des-CIC) primarily in the lungs, while in
oropharynx less than 20% of inhaled CIC is converted to des-
CIC (117). Its very low systemic bioavailability (<1%), rapid
degradation to inactive metabolites, very high clearance rate
(396 L/h), and plasma protein binding (>99%) result in negli-
gible amounts of free des-CIC remaining in circulation (120,
129, 130), therefore no adrenal suppression occurs even in
high doses (121, 131). Reversible lipid conjugates of des-CIC
formed in the lungs prolong its lung residence time, causing
longer duration of action, making possible once-a-day dos-
ing (132, 133). Thus, its pharmacokinetics is close to ideal
(134), and clinical experience so far indicates that it is highly
effective even in small doses (135) and causes minimal side
effects even in high doses (114–116, 120, 121). It has shown
no drug-drug interaction with erythromycin (136), and it re-
mains to be seen whether, unlike FP, it proves safe to give
with Ritonavir or other cytochrome P450-3A inhibitors.
Ciclesonide vs. Other Inhaled Corticosteroids
Only few studies comparing CIC with BUD and FP are
available and are included in Tables 4 and 5. There are no
reports comparing CIC with BDP, TA, FH, or MF.
8 A. K. ABDULLAH AND S. KHAN

TABLE 5.—Fluticasone vs. other inhaled corticosteroids.

Fluticasone Beclomethasone Triamcinolone Flunisolide Budesonide Mometasone Ciclesonide
(FP) (BDP) (TA) (FH) (BUD) (MF) (CIC)
MDI-HFA-susp., DPI vs. MDI-HFA-solution MDI-CFC-suspension MDI-HFA-solution DPI, Nebulizer susp. DPI MDI-HFA-solnution
Efficacy References References References References References References
Symptoms/airways Better [32∗ , 34∗ ] {11∗ , 33} [34∗ , 76, 77] {11∗ } [34∗ , 79, 86] [30∗ , 32∗ , 96, 97]
function∗1 (35, 36) {11∗ , 87} {11∗ , 95}
Equal [30∗ , 31∗ , 29] [94] {92} (93) [112, 113] {114, 115}
Worse [60] [60]
Taste: no report No taste [84] Bitter [84]
Quality of life∗2 Better [39, 41] {40} {87} [41] {40}
∗
Equal [31 ] {114}
Cost-effectiveness Better (37) (37) [86] (37) [103∗ , 104∗ ] (37)
Side effects
Local∗3 Better [79]
Equal [34∗ ] [112]
Worse [32∗ ] {42} [76] [79] [32∗ ] [116] {117}
Adrenal Better [34∗ , 52, 53] {40, [83] [30∗ ] {40}
suppression∗4 49, 50, 51}
Equal [30∗ , 54, 58, 59, 60] [76, 79] [79] [60, 94, 96, 97] {95} {118}
{57, 61, 55, 56} (93)
Worse [3∗ , 47] {48} [3∗ , 47] [47, 88] [3∗ , 47] {105, 106, [119] [116, 121]
107} {114, 115} (120)
Acute adrenal crisis:
30 of 33 cases 2 of 33 cases (122) 1 of 33 cases (122)
(122)
Bone metabolism/ Better {56, 57} {107}
BMD reduction∗5 Equal {50, 67} [96] (93) {118}
Worse
∗6
Growth retardation Better [70∗ , 54, 71] [70∗ ] ∗
[70 , 97] [70∗ ]
{50, 72}
Equal [109] {108}
Worse (120)
Pregnancy category: Category C {90} Category C {90} Category C {90} Category B {90} Category C {137}
Category C {90}
FP advantages FP may to be more FP may be more FP is more effective FP is equal or more FP is equal to MF in FP is in clinical use
effective and effective, and and more effective and effectiveness and for over 10 years
cause less cause less growth cost-effective than cost-effective and causes less growth while CIC is not
systemic side retardation than FH. causes less growth retardation. yet available in US.
effects than BDP. TA. retardation than
BUD.
FP disadvantages FP may cause more FP may cause more FP causes more FP causes more local FP must be given FP must be given
local side effects local side effects adrenal side effects and BID in most cases, BID to be as
than BDP. and adrenal suppression than adrenal while MF may be effective as CIC
suppression than FH. suppression than sufficient once once daily, and it
TA. BUD and is not daily. has more side
available for effects than CIC.
nebulizer.
Overall preference FP FP may be preferred FP may be preferred FP may be preferred FP may be preferable MF may be preferred CIC may be preferred
vs. other ICSs over BDP unless over TA because over FH, but watch to BUD except in for the over FP if it fulfills
local side effects of its greater for adrenal pregnancy and convenience of its early promises
with FP is a effectiveness suppression. when a nebulizer once daily dosing of efficacy and
problem. unless it causes must be used. unless growth safety on further
side effects. retardation is of clinical experience.
concern.

Notes: See Table 1.

Efficacy. CIC given once daily was found equal to BUD
given twice daily (100, 101), but superior to BUD given once
daily (102). Two studies (114, 115) found CIC once or twice
daily and FP twice daily equally effective.
Local Side-Effects. In one study oropharyngeal deposi-
tion of CIC was half that of FP, and 90% less active metabolite
of CIC remained in the throat 60 minutes later as compared to
FP (117). In another study oral candidiasis rate was only 2.5%
for CIC compared to 22% for FP (116). No study comparing
CIC with any other ICS has been reported.
Adrenal Suppression. No adrenal suppression by even
high doses of CIC occurred compared to FP (114–116, 120,
121). Thus, while CIC 800 μg BID (twice daily) caused no
adrenal suppression (114), FP 440 μg BID caused 29% sup-
pression (115). In rats CIC caused 44-fold less adrenal invo-
lution than FP (120).
Effect on Bone and Growth. In one experimental study
in rats CIC was found 22-fold less active than FP in causing
femoral growth plate hypoplasia (120).
DISCUSSION
Studies comparing ICS show marked heterogeneity in re-
sults, perhaps because of lack of uniformity in study designs.
The efficacy and side effects of ICSs depend on several fac-
tors, e.g., their formulation, dosing and device used, and the
subjects’ age, asthma severity, and correct inhaler technique
(6), and a study design taking all these factors into account
has not yet been devised (9). A study comparing all ICS for
all beneficial and harmful effects using the same subjects,
methods, and outcome measures has never been conducted
and is probably not feasible. Notwithstanding this limitation,
from the review of literature presented above, FP appears to
be very effective and safe for most patients over 4 years of
age when administered in low-to-medium doses, but it does
EVIDENCE-BASED SELECTION OF INHALED CORTICOSTEROID
show significant oral side effects and adrenal suppression in
high doses. BUD is the only ICS available in the US as a
nebulizer solution and is also the only Pregnancy Category
B ICS; therefore it is often preferred for young children and
in pregnancy. BDP and BUD are equal in efficacy and both
cause fewer side effects than FP, hence either may be tried if
FP caused side effects. BDP is available as MDI and BUD as
DPI or nebulizer suspension and may be used according to
patient’s preference/ability to handle the device. FH has the
least potential for adrenal suppression but has been found less
effective than BDP and FP and less cost-effective than other
ICSs, and also has a bitter taste. TA is generally less effective
and causes more side effects than most of the other ICSs.
CIC is not yet available in the US. Studies so far have found
it highly effective and free of side effects even in high doses.
Further studies comparing it with other ICSs for efficacy and
safety over longer periods of use will determine its position in
the armamentarium of physicians treating chronic persistent
asthma.
REFERENCES
1. Global Strategy for Asthma Management and Prevention. NIH publica-
tion 02-3659 Issued January 1995 (updated 2002). Management Segment
(Chapter 7) updated 2005 from the 2004 document. The GINA reports are
available on www.ginasthma.org
2. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J
1998; 12:221–234.
3. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy:
a systematic review and meta-analysis. Arch Intern Med 1999; 159:941–
955.
4. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticos-
teroids: current understanding and review of the literature. Chest 2004;
126:213–219.
5. Guyatt G, Gutterman D, Baumann MH, Addrizzo-Harris D, Hylek EM,
Phillips B, Raskob G, Lewis SZ, Schunemann H. Grading strength of
recommendations and quality of evidence in clinical guidelines. Report
from an American College of Chest Physicians Task Force. Chest 2006;
129:174–181.
6. Allen DB, Bielory L, Derendorf H, Dluhy R, Colice GL, Szefler SJ. Inhaled
corticosteroids: past lessons and future issues. J Allergy Clin Immunol
2003; 112(suppl 1):S1–S40.
7. Rohatagi S, Appajosyula S, Derendorf H, et al. Risk-benefit value of in-
haled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective.
J Clin Pharmacol 2004; 44:37–47.
8. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: Physiological
factors affecting therapeutic effectiveness of aerosolized medications. Brit
J Clin Pharmacol 2003; 56:588–599.
9. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corti-
costeroids. New developments. Am J Respir Crit Care Med 1998; 157(Pt
2):S1–S53.
10. Zeidler M, Corren J. Hydrofluoroalkane formulations of inhaled corticos-
teroids for the treatment of asthma. Treat Respir Med 2004; 3:35–44.
11. Rohdewald PJ. Comparison of clinical efficacy of inhaled glucocorticoids.
Arzneimittelforschung 1998; 48:789–796.
12. Bronsky E, Korenblat P, Harris AG, Chen R. Comparative clinical study
of inhaled beclomethasone dipropionate and triamcinolone acetonide in
persistent asthma. Ann Allergy Asthma Immunol 1998; 80:295–302.
13. Ederle K, Multicentre Study Group. Improved control of asthma symp-
toms with a reduced dose of HFA-BDP extrafine aerosol: An open-label,
randomised study. Eur Rev Med Pharmacol Sci 2003; 7:45–55.
14. Pethica BD, Penrose A, MacKenzie D, Hall J, Beasley R, Tilyard
M. Comparison of potency of inhaled beclomethasone and budesonide
in New Zealand: retrospective study of computerised general practice
records. Br Med J 1998; 317(7164):986–990.
9
15. Berkowitz R, Rashelefski G, Harris AG, Chen R. A comparison of triam-
cinolone acetonide MDI with a built-in tube extender and beclomethasone
dipropionate MDI in adult asthmatics. Chest 1998; 114:757–765.
16. Hartley TF, Romero RC. Evaluation of aerosolized triamcinolone ace-
tonide as a replacement for aerosolized beclomethasone dipropionate.
J Asthma. 1986; 23:139–143.
17. Dry J, Sors C, Gervais P, van Straaten L, Perrin-Fayolle M, Paramelle
B. Comparison of flunisolide inhaler and beclomethasone dipropionate
inhaler in bronchial asthma. J Int Med Res 1985; 13:289–293.
18. Miyamoto T, Takahashi T, Nakajima S, Makino S, Yamakido M, Mano K,
Nakashima M, Tollemar U, Selroos O. On behalf of a Japanese Pulmicort
Turbuhaler Study Group. Efficacy of budesonide Turbuhaler compared
with that of beclomethasone dipropionate pMDI in Japanese patients with
moderately persistent asthma. Respirology 2001; 6:27–35.
19. Ohaju-Obodo JO, Chukwu C, Okpapi J, Egbagbe E, Ige MO, Chukwuka
C, Adedapo DA. Comparison of the efficacy and safety of budesonide
turbuhaler administered once daily with twice the dose of beclomethasone
dipropionate using pressurised metered dose inhaler in patients with mild
to moderate asthma. West Afr J Med 2005; 24:190–195.
20. Chervinsky P, Nelson HS, Bernstein DI, Berkowitz RA, Siegel SC. Com-
parison of mometasone furoate administered by metered dose inhaler with
beclomethasone dipropionate. Int J Clin Pract 2002; 56:419–425.
21. Chrousos GP, Ghaly L, Shedden, A, Iezzoni DG, Harris AG. Effects of
mometasone furoate dry powder inhaler and beclomethasone dipropionate
hydrofluoroalkane and chlorofluorocarbon on the hypothalamic-pituitary-
adrenal axis in asthmatic subjects. Chest 2005; 128:70–77.
22. Nathan RA, Nayak AS, Graft DF, Lawrence M, Picone FJ, Ahmed T,
Wolfe J, Vanderwalker ML, Nolop KB, Harrison JE. Mometasone furoate:
efficacy and safety in moderate asthma compared with beclomethasone
dipropionate. Ann Allergy Asthma Immunol 2001; 86:203–210.
23. Bernstein DI, Berkowitz RB, Chervinsky P, Dvorin DJ, Finn AF, Gross
GN, Karetzky M, Kemp JP, Laforce C, Lumry W, Mendelson LM, Nelson
H, Pearlman D, Rachelefsky G, Ratner P, Repsher L, Segal AT, Selner
JC, Settipane GA, Wanderer A, Cuss FM, Nolop KB, Harrison JE. Dose-
ranging study of a new steroid for asthma: mometasone furoate dry powder
inhaler. Respir Med 1999; 93:603–612.
24. Adams N, Bestall JM, Jones PW. Inhaled beclomethasone versus budes-
onide for chronic asthma. The Cochrane Database of Systematic Reviews
2000, Issue 1: CD003530. DOI: 10.1002/14651858.CD003530.
25. Delacourt C, Dutau G, Lefrancois G, Clerson P, Beclospin. Clinical De-
velopment Group. Comparison of the efficacy and safety of nebulized be-
clometasone dipropionate and budesonide in severe persistent childhood
asthma. Respir Med 2003; 97(suppl B):S27–33.
26. Kaur C, Bansal SK, Chhabra SK. Study on serum and urinary cortisol
levels of asthmatic patients after treatment with high dose inhaled be-
clomethasone dipropionate or budesonide. Indian J Chest Dis Allied Sci
2005; 47:89–95.
27. Reichel W, Dahl R, Ringdal N, Zetterstrom O, van den Elshout FJ,
Laitinen LA. Extrafine beclomethasone dipropionate breath-actuated in-
haler (400 micrograms/day) versus budesonide dry powder inhaler (800
micrograms/day) in asthma. Int J Clin Pract 2001; 55:100–106.
28. Davies B. A comparison of beclomethasone dipropionate and budesonide
in the treatment of asthma. Br J Clin Pract 1993; 47:87–93.
29. Terzano C, Ricci A, Burinschi V, Nekam K, Lahovsky J. Comparison of
the efficacy of beclometasone dipropionate and fluticasone propionate sus-
pensions for nebulization in adult patients with persistent asthma. Respir
Med 2003; 97(suppl B):S35–40.
30. Barnes NC, Hallett C, Harris TA. Clinical experience with fluticasone
propionate in asthma: a meta-analysis of efficacy and systemic activity
compared with budesonide and beclomethasone dipropionate at half the
microgram dose or less. Respir Med 1998; 92:95–104.
31. Lasseron T, Cates C, Jones AB, Steele EH, White J. Fluticasone versus
HFA-beclomethasone dipropionate for chronic asthma in adults and chil-
dren. Cochrane Database Syst Rev 2005; (4):CD005309.
32. Adams N, Bestall J, Lasserson T, Jones PW. Inhaled fluticasone versus
inhaled beclomethasone or inhaled budesonide for chronic asthma in adults
and children. Cochrane Database Syst Rev 2005; (2):CD002310.
10
33. Frezza G, Terra-Filho J, Martinez JAB, Vianna EO. Rapid effect of inhaled
steroids on nocturnal worsening of asthma. Thorax 2003; 58:632–633.
34. Stoloff SW, Srebro SH, Edwards LD, Johnson MC, Rickard KA. Improved
asthma control after changing from low-to-medium doses of other inhaled
corticosteroids to low-dose fluticasone propionate. MedGenMed 2001;
3:2. www.medscape.com/viewarticle/408139 Accessed on 16 June 2005.
35. Suzuki T, Hasegawa T, Suzuki E, Sasahara K, Kawada T, Koya T, Akazawa
K, Satoh H, Gejyo F. Efficacy of fluticasone propionate compared with
beclomethasone dipropionate in bronchial asthma: improvement in com-
pliance and symptoms by fluticasone. Allergy Asthma Proc 2003; 24:347–
351.
36. Leru P, Rascu A, Otelea M, Mohora M, Muscurel C, Galca M, Dinu V.
Study of fluticasone propionate efficacy in the treatment of patients with
bronchial asthma not controlled by other inhaled corticosteroids. Rom J
Intern Med 1998; 36:105–111.
37. Stempel DA, McLaughlin T, Griffis DL, Stanford RH. Cost analysis of
the use of inhaled corticosteroids in the treatment of asthma: a 1-year
follow-up. Respir Med 2001; 95:992–998.
38. Holzer SS, Engelhart L, Crown WH, L’Herrou TA, Kennedy ST. Asthma
treatment costs using inhaled corticosteroids. Am J Manag Care 1997;
3:891–897.
39. Kondo T, Tanigaki T, Ono Y, Tazaki G, Urano T, Tajiri S, Eguchi K. Im-
pact of Fluticasone Diskhaler on health-related quality of life in asthmatic
patients. Tokai J Exp Clin Med 2002; 27:79–84.
40. Berend N, Kellett B, Kent N, Sly PD. Collaborative Study Group of the
Australian Lung Foundation. Improved safety with equivalent asthma con-
trol in adults with chronic severe asthma on high-dose fluticasone propi-
onate. Respirology 2001; 6:237–246.
41. Rutherford C, Mills R, Gibson PG, Price MJ. Improvement in health-
related quality of life with fluticasone propionate compared with budes-
onide or beclomethasone dipropionate in adults with severe asthma.
Respirology 2003; 8:371–375.
42. Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T,
Kohno S. Oral candidiasis associated with inhaled corticosteroid use: com-
parison of fluticasone and beclomethasone. Ann Allergy Asthma Immunol
2003; 90:646–651.
43. Williamson IJ, Matusiewicz SP, Brown PH, Greening AP, Crompton GK.
Frequency of voice problems and cough in patients using pressurized
aerosol inhaled steroid preparations. Eur Respir J 1995; 8:590–592.
44. Shim CS, Williams MH Jr. Cough and wheezing from beclomethasone
dipropionate aerosol are absent after triamcinolone acetonide. Ann Intern
Med 1987; 106:700–703.
45. Watkins KL, Ewanowski SJ. Effects of aerosol corticosteroids on the voice:
triamcinolone acetonide and beclomethasone dipropionate. J Speech Hear
Res 1985; 28:301–304.
46. Dubus JC, Marguet C, Deschildre A, Mely L, Le Roux P, Brouard J,
Huiar L. Local side effects of inhaled corticosteroids in asthmatic children:
influence of drug, dose, age, and device. Allergy 2001; 56:944–948.
47. Martin RJ, Szefler SJ, Chinchilli VM, Kraft M, Dolovich M, Boushey HA,
Cherniack RM, Craig TJ, Drazen JM, Fagan JK, Fahy JV, Fish JE, Ford
JG, Israel E, Kunselman SJ, Lazarus SC, Lemanske Jr., RF, Peters SP, and
Sorkness CA for the National Heart, Lung, and Blood Institute’s Asthma
Clinical Research Network. Systemic effect comparisons of six inhaled
corticosteroid preparations. Am J Respir Crit Care Med 2002; 165:1377–
1383.
48. Fairfax A, Hall I, Spelman R. A randomized, double-blind comparison of
beclomethasone dipropionate extrafine aerosol and fluticasone propionate.
Ann Allergy Asthma Immunol 2001; 86:575–582.
49. Niitsuma T, Okita M, Sakurai K, Morita S, Tsuyuguchi M, Matsumura Y,
Hayashi T, Koshishi T, Oka K, Homma M. Adrenal function as assessed by
low-dose adrenocorticotropin hormone test before and after switching from
inhaled beclomethasone dipropionate to inhaled fluticasone propionate.
J Asthma 2003; 40:515–522.
50. Rao R, Gregson RK, Jones AC, Miles EA, Campbell MJ, Warner JO.
Systemic effects of inhaled corticosteroids on growth and bone turnover
in childhood asthma: a comparison of fluticasone with beclomethasone.
Eur Respir J 1999; 13:87–94.
A. K. ABDULLAH AND S. KHAN
51. Yiallouros PK, Milner AD, Conway E, Honour JW. Adrenal function and
high dose inhaled corticosteroids for asthma. Arch Dis Child 1997; 76:405–
410.
52. Lorentzen KA, Van Helmond JL, Bauer K, Langaker KE, Bonifazi F, Harris
TA. Fluticasone propionate 1 mg daily and beclomethasone dipropionate
2 mg daily: a comparison over 1 yr. Respir Med 1996; 90:609–617.
53. Leblanc P, Mink S, Keistinen T, Saarelainen PA, Ringdal N, Payne
SL. Comparison of fluticasone propionate 200 micrograms/day with be-
clomethasone dipropionate 400 micrograms/day in adult asthma. Allergy
1994; 49:380–385.
54. de Benedictis FM, Teper A, Green RJ, Boner AL, Williams L, Medley H.
International Study Group. Effects of 2 inhaled corticosteroids on growth:
results of a randomized controlled trial. Arch Pediatr Adolesc Med 2001;
155:1248–1254.
55. Fitsgerald D, Van Asperen P, Mellis C, Honner M, Smith L, Ambler G.
Fluticasone propionate 750 micrograms/day versus beclomethasone dipro-
pionate 1500 micrograms/day: comparison of efficacy and adrenal function
in paediatric asthma. Thorax 1998; 53:656–661.
56. Pauwels RA, Yernault JC, Demedts MG, Geusens P. Safety and efficacy
of fluticasone and beclomethasone in moderate to severe asthma. Belgian
Multicenter Study Group. Am J Respir Crit Care Med 1998; 157:827–
832.
57. Bootsma GP, Dekhuizen PN, Festen J, Mulder PG, Swinkels LM, van Her-
waarden CL. Fluticasone propionate does not influence bone metabolism
in contrast to beclomethasone dipropionate. Am J Respir Crit Care Med
1996; 153:924–930.
58. Lundback B, Alexander M, Day J, Herbert J, Holzer R, Van Uffelen R,
Kesten S, Jones AL. Evaluation of fluticasone propionate (500 micrograms
day-1) administered either as dry powder via a Diskhaler inhaler or pres-
surized inhaler and compared with beclomethasone dipropionate (1000
micrograms day-1) administered by pressurized inhaler. Respir Med 1993;
87:609–620.
59. Fabbri L, Burge PS, Croonenborgh L, Warlies F, Weeke B, Ciaccia A,
Parker C. Comparison of fluticasone propionate with beclomethasone
dipropionate in moderate to severe asthma treated for one year. Interna-
tional Study Group. Thorax. 1993; 48:817–823.
60. Karakoc F, Karadag B, Kut A, Ersu R, Bakac S, Cebeci D, Dagli E. Com-
parison of the efficacy and safety of a half dose of fluticasone propionate
with beclamethasone dipropionate and budesonide in childhood asthma. J
Asthma 2001; 38:229–237.
61. Currie GP, Fowler SJ, Wilson AM, Sims EJ, Orr LC, Lipworth BJ. Airway
and systemic effects of hydrofluoroalkane fluticasone and beclomethasone
in patients with asthma. Thora 2002; 57:865–868.
62. Svendsen UG, Frolund L, Heinig JH, Madsen F, Nielsen NH, Weeke B.
[High dose inhaled steroids in the treatment of bronchial asthma. A com-
parison of the effects of budesonide and beclomethasone dipropionate on
pulmonary function, symptoms, bronchial reactivity and adrenocortical
function]. [Article in Danish] Ugeskr Laeger 1993; 155:2197–202.
63. Ebden P, Jenkins A, Houston G, Davis BH. Comparison of two high dose
corticosteroid aerosol treatments, beclomethasone dipropionate (1500
micrograms/day) and budesonide (1600 micrograms/day), for chronic
asthma. Thorax 1986; 41:869–874.
64. Prahl P. Adrenocortical suppression following treatment with beclometha-
sone and budesonide. Clin Exp Allergy 1991; 21:145–146.
65. Gillman SA, Anolik R, Schenkel E, Newman K. One-year trial on safety
and normal linear growth with flunisolide HFA in children with asthma.
Clin Pediatr (Phila) 2002; 41:333–340.
66. Packe GE, Robb O, Robins SP, Reid DM, Douglas JG. Bone density in asth-
matic patients taking inhaled corticosteroids: comparison of budesonide
and beclomethasone dipropionate. J R Coll Physicians Lond 1996; 30:128–
132.
67. Gregson RK, Rao R, Murrills AJ, Taylor PA, Warner JO. Effect of inhaled
corticosteroids on bone mineral density in childhood asthma: comparison
of fluticasone propionate with beclomethasone dipropionate. Osteoporos
Int 1998; 8:418–422.
68. Richy F, Bousquuet J, Ehrlich GE, Meunier PJ, Israel E, Morii H, Devoge-
laer JP, Peel N, Haim M, Bruyere O, Reginster JY. Inhaled corticosteroids
EVIDENCE-BASED SELECTION OF INHALED CORTICOSTEROID
effects on bone in asthmatic and COPD patients: a quantitative systematic
review. Osteoporos Int 2003; 14:179–190.
69. Birkebaek NH, Esberg G, Andersen K, Wolthers O, Hassager C. Bone and
collagen turnover during treatment with inhaled dry powder budesonide
and beclomethasone dipropionate. Arch Dis Child 1995; 73:524–527.
70. Daley-Yates PT, Richards DH. Relationship between systemic corticos-
teroid exposure and growth velocity: development and validation of a
pharmacokinetic/pharmaco-dynamic model. Clin Ther 2004; 26:1905–
1919.
71. Sharek PJ, Bergman DA. The effect of inhaled steroids on the linear growth
of children with asthma: a meta-analysis. Pediatrics 2000; 106:E8.
72. Wolthers OD, Pedersen S. Short-term growth during treatment with inhaled
fluticasone propionate and beclomethasone dipropionate. Arch Dis Child
1993; 68:673–676.
73. Derendorf H. Pharmacokinetic and pharmacodynamic properties of in-
haled corticosteroids in relation to efficacy and safety. Respir Med 1997;
91(suppl A):22–28.
74. Martin RJ. Therapeutic significance of distal airway inflammation in
asthma. J Allergy Clin Immunol. 2002; 109(Suppl):S447–S460.
75. Weiss KB, Liljas B, Schoenwetter W, Schatz M, Luce BR. Effectiveness
of budesonide administered via dry-powder inhaler versus triamcinolone
acetonide administered via pressurized metered-dose inhaler for adults
with persistent asthma in managed care settings. Clin Ther 2004; 26:102–
114.
76. Condemi JJ, Chervinsky P, Goldstein MF, Ford LB, Berger WE, Ayars GH,
Rogenes PR, Edwards L, Pepsin PJ. Fluticasone propionate powder admin-
istered through Diskhaler versus triamcinolone acetonide aerosol admin-
istered through metered-dose inhaler in patients with persistent asthma.
J Allergy Clin Immunol 1997; 100:467–474.
77. Baraniuk J, Murray JJ, Nathan RA, Berger WE, Johnson M, Edwards LD,
Srebro S, Rickard KA. Fluticasone alone or in combination with salmeterol
vs. triamcinolone in asthma. Chest 1999; 116:625–632.
78. Weiss KB, Paramore LC, Liljas B, Revicki DA, Luce BR. Patient satisfac-
tion with budesonide turbuhaler versus triamcinolone acetonide admin-
istered via pressurized metered-dose inhaler in a managed care setting.
J Asthma 2005; 42:769–776.
79. Sorkness CA, LaForce C, Storms W, Lincourt WR, Edwards L, Rogenes
PR. Effects of the inhaled corticosteroids fluticasone propionate, triamci-
nolone acetonide, and flunisolide and oral prednisone on the hypothalamic-
pituitary-adrenal axis in adult patients with asthma. Clinical Therapeutics
1999; 21:353–367.
80. Wilson AM, McFarlane LC, Lipworth BJ. Effects of low and high doses
of inhaled flunisolide and triamcinolone acetonide on basal and dynamic
measures of adrenocortical activity in healthy volunteers. J Clin Endocrinol
Metab 1998; 83:922–925.
81. Argenti D, Shah B, Heald D. A study comparing the clinical pharma-
cokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide
HFA-134a metered-dose inhaler and budesonide dry-powder inhaler fol-
lowing inhalation administration. J Clin Pharmacol 2000; 40:516–526.
82. Wilson, AM, Brewster HJ, Lipworth BJ. Dose-response comparison of
systemic bioactivity with inhaled budesonide and triamcinolone acetonide
in asthmatic adults. J Allergy Clin Immunol 1998; 102:751–756.
83. Li JT, Goldstein MF, Gross GN, Noonan MJ, Weisberg S, Edwards L,
Reed KD, Rogenes PR. Effects of fluticasone propionate, triamcinolone
acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal
axis. J Allergy Clin Immunol 1999; 103:622–629.
84. Silvers WS, Cohen R, D’Alonzo G. Comparative taste evaluation of
aerosolized formulations of triamcinolone acetonide, flunisolide, and flu-
nisolide with menthol. Clin Ther 1993; 15:988–993.
85. Newhouse A, Knight A, Wang S, Newman K. Comparison of efficacy
and safety between flunisolide/AeroChamber and budesonide/turbuhaler
in patients with moderate asthma. AER-MD-04 Study Group. Ann Allergy
Asthma Immunol 2000; 84:313–319.
86. Volmer T, Kielhorn A, Weber HH, Wiessmann KJ. Cost effectiveness of
fluticasone propionate and flunisolide in the treatment of corticosteroid-
naive patients with moderate asthma. Pharmacoeconomics 1999; 16:525–
531.
11
87. Sheikh S, Goldsmith LJ, Howell L, Eid N. Comparison of the efficacy
of inhaled fluticasone propionate, 880 microg/day, with flunisolide, 1500
μg/day, in moderate-to-severe persistent asthma. Ann Allergy Asthma
Immunol 1999; 83:300–304.
88. Casale TB, Nelson HS, Stricker WE, Raff H, Newman KB. Suppression
of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide
and fluticasone propionate in adult asthma patients. Ann Allergy Asthma
Immunol 2001; 87:379–385.
89. Masoli M, Weatherall M, Holt S, Beasley R. Budesonide once versus
twice-daily administration: meta-analysis. Respirology 2004; 9:528–534.
90. Gluck JC, Gluck PA. Asthma controller therapy during pregnancy. Am J
Obstet Gynecology 2005; 192:369–380.
91. National Asthma Education and Prevention Program Asthma and Preg-
nancy Working Group. Quick Reference from the Working Group Re-
port on Managing Asthma during Pregnancy: Recommendations for Phar-
macologic Treatment. Update 2004. www.nhlbi.nih.gov/health/prof/lung/
asthma/astpreg.htm
92. Subbarao P, Dorman SC, Rerecich T, Watson RM, Gauvreau GM, O’Byrne
PM. Protection by budesonide and fluticasone on allergen-induced airway
responses after discontinuation of therapy. J Allergy Clin Immunol 2005;
115:745–50.
93. Harmanci E, Colak O, Metintas M, Alatas O, Yurdasiper A. Fluticasone
propionate and budesonide do not influence bone metabolism in the long
term treatment of asthma. Allergol Immunopathol (Madr) 2001; 29:22–27.
94. Agertoft L, Pedersen S. A randomized, double-blind dose reduction study
to compare the minimal effective dose of budesonide Turbuhaler and fluti-
casone propionate Diskhaler. J Allergy Clin Immunol 1997; 99:773–780.
95. Ringdal N, Lundback B, Alton M, Rak S, Eivindson A, Bratten G, Kjaers-
gaard P. Comparable effects of inhaled fluticasone propionate and budes-
onide on the HPA-axis in adult asthmatic patients. Respir Med 2000;
94:482–489.
96. Heinig JH, Boulet LP, Croonenborghs L, Mollers MJ. The effect of high-
dose fluticasone propionate and budesonide on lung function and asthma
exacerbations in patients with severe asthma. Respir Med 1999; 93:613–
620.
97. Ferguson AC, Spier S, Manjra A, Versteegh FG, Mark S, Zhang P. Ef-
ficacy and safety of high-dose inhaled steroids in children with asthma:
a comparison of fluticasone propionate with budesonide. J Pediatr 1999;
134:422–427.
98. Corren J, Berkowitz R, Murray JJ, Prenner B. Comparison of once-daily
mometasone furoate versus once-daily budesonide in patients with mod-
erate persistent asthma. Int J Clin Pract 2003; 57:567–572.
99. Bousquet J, D’Urzo A, Hebert J, Barraza CH, Boulet L-P, Suarez-Chacon
R, Harnest U, Lundba B, Martinez Morales G, Nieminen MM, Nolop KB,
Visser S, Lutsky BN. Comparison of the efficacy and safety of mometasone
furoate dry powder inhaler to budesonide Turbuhaler. Eur Respir J 2000;
16:808–816.
100. Reynolds NA, Scott LJ. Ciclesonide. Drugs 2004; 64:511–519.
101. Niphadkar P, Jagannath K, Joshi JM, Awad N, Boss H, Hellbardt S, Gadgil
DA. Comparison of the efficacy of ciclesonide 160 mug QD and budes-
onide 200 mug BID in adults with persistent asthma: A phase III, random-
ized, double-dummy, open-label study. Clin Ther 2005; 27:1752–1763.
102. Boulet LP, Drollmann A, Magyar P, Timar M, Knight A, Engelstatter R,
Fabbri L. Comparative efficacy of once-daily ciclesonide and budesonide
in the treatment of persistent asthma. Respir Med. 2006; 100:785–794.
Epub 2006 Jan 19.
103. Stempel DA, Stanford RH, Thwaites R, Price MJ. Cost-efficacy compar-
ison of inhaled fluticasone propionate and budesonide in the treatment of
asthma. Clin Ther 2000; 22:1562–1574.
104. Barnes NC, Thwaites RM, Price MJ. The cost-effectiveness of inhaled
fluticasone propionate and budesonide in the treatment of asthma in adults
and children. Respir Med 1999; 93:402–407.
105. Thorsson L, Edsbacker S, Kallen A, Löfdahl C-G. Pharmacokinetics and
systemic activity of fluticasone via Diskus and pMDI, and of budesonide
via Turbuhaler. Br J Clin Pharmacol 2001; 52:529–538.
106. Derom E, Van Schoor J, Verhaeghe W, Vinken W, Pauwels R. Sys-
temic effects of inhaled fluticasone propionate and budesonide in adult
12
patients with asthma. Am J Respir Crit Care Med 1999; 160:157–
161.
107. Harrison TW, Wisniewski A, Honour J, Tattersfield AE. Comparison of
the systemic effects of fluticasone propionate and budesonide given by dry
powder inhaler in healthy and asthmatic subjects. Thorax 2001; 56:186–
191.
108. Agertoft L, Pedersen S. Short-term knemometry and urine cortisol excre-
tion in children treated with fluticasone propionate and budesonide: a dose
response study. Eur Respir J. 1997; 10:1507–1512.
109. Acun C, Tomac N, Ermis B, Onk G. Effects of inhaled corticosteroids on
growth in asthmatic children: a comparison of fluticasone propionate with
budesonide. Allergy Asthma Proc 2005; 26:204–206.
110. Masoli M, Weatherall M, Holt S, Beasley R. Systematic review of the dose-
response relation of inhaled fluticasone propionate. Arch Dis Childhood
2004; 89:902–907.
111. Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA. Iatrogenic
Cushing’s syndrome with osteoporosis and secondary adrenal failure in
human immunodeficiency virus-infected patients receiving inhaled cor-
ticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin
Endocrinol Metab 2005; 90:4394–4398.
112. O’Connor B, Bonnaud G, Haahtela T, Luna JM, Querfurt H, Wegener
T, Lutsky BN. Dose-ranging study of mometasone furoate dry powder
inhaler in the treatment of moderate persistent asthma using fluticasone
propionate as an active comparator. Ann Allergy Asthma Immunol 2001;
86:397–404.
113. Wardlaw A, Larivee P, Eller J, Cockcroft DW, Ghaly L, Harris AG. Effi-
cacy and safety of mometasone furoate dry powder inhaler vs. fluticasone
propionate metered-dose inhaler in asthma subjects previously using flu-
ticasone propionate. Ann Allergy Asthma Immunol 2004; 93:49–55.
114. Lee DK, Fardon TC, Bates CE, Haggart K, McFarlane LC, Lipworth BJ.
Airway and systemic effects of hydrofluoroalkane formulations of high-
dose ciclesonide and fluticasone in moderate persistent asthma. Chest
2005; 127:851–860.
115. Derom E, Van De Velde V, Marissens S, Engelstätter R, Vinken W, Pauwels
R. Effects of inhaled ciclesonide and fluticasone propionate on cortisol
secretion and airway responsiveness to adenosine 5’monophosphate in
asthmatic patients. Pulm Pharmacol Ther 2005; 18:328–336.
116. Lipworth BJ, Kaliner MA, LaForce CF, Baker JW, Kaiser HB, Amin D,
Kundu S, Williams JE, Engelstätter R, Banerji DD. Effect of ciclesonide
and fluticasone on hypothalamic-pituitary-adrenal axis function in adults
with mild-to-moderate persistent asthma. Ann Allergy Asthma Immunol
2005; 94:465–472.
117. Richter K, Kanniess F, Biberger C, Nave R, Magnussen H. Compari-
son of the oropharyngeal deposition of inhaled ciclesonide and flutica-
sone propionate in patients with asthma. J Clin Pharmacol 2005; 45:146–
152.
118. Fardon TC, Lee DK, Haggart K, McFarlane LC, Lipworth BJ. Adrenal
suppression with dry powder formulations of fluticasone propionate and
mometasone furoate. Am J Resp Crit Care Med 2004; 170:960–966.
119. Affrime MB, Kosoglou, T, Thonoor CM, Flannery BE, Herron JM.
Mometasone furoate has minimal effects on the hypothalamic-pituitary-
adrenal axis when delivered at high doses. Chest 2000; 118:1538–1546.
120. Belvisi MG, Bundschuh DS, Stoeck M, Wicks S, Underwood S, Battram
CH, Haddad E, Webber SE, Foster ML. Preclinical profile of ciclesonide:
a novel corticosteroid for the treatment of asthma. J Pharmacol Exp Ther
2005; 314:568–574.
A. K. ABDULLAH AND S. KHAN
121. Szefler S, Rohatagi S, Williams J, Lloyd M, Kundu S, Banerji D.
Ciclesonide: a novel inhaled steroid, does not affect hypothalamic-
pituitary-adrenal axis function in patients with moderate-to-severe per-
sistent asthma. Chest 2005; 128:1104–1114.
122. Todd GR, Acerini CL, Ross-Russell R, Zahra S, Warner TJ, McCance
D. Survey of adrenal crisis associated with inhaled corticosteroids in the
United Kingdom. Arch Dis Child 2002; 87:457–461.
123. Affrime MB, Cuss F, Padhi D, Wirth M, Pai S, Clement RP, Lim J, Kante-
saria B, Alton K, Cayen MN. Bioavailability and metabolism of mometa-
sone furoate following administration by metered-dose and dry-powder
inhalers in healthy human volunteers. J Clinical Pharmacol 2000; 40:1227–
1236.
124. Valotis A, Högger P. Significant receptor affinities of metabolites and a
degradation product of mometasone furoate. Respir Res 2004; 5:7. Open
access online at http://respiratory.research.com/content/5/1/7
125. Sharpe M, Jarvis B. Inhaled mometasone furoate: a review of its use in
adults and adolescents with persistent asthma. Drugs 2001; 61:1325–1350.
126. Karpel JP, Busse WW, Noonan MJ, Monahan ME, Lutsky B, Staudinger
H. Effects of mometasone furoate given once daily in the evening on lung
function and symptom control in persistent asthma. Ann Pharmacother
2005; 39:1977–1983.
127. D’Urzo A, Karpel JP, Busse WW, Boulet LP, Monahan ME, Lutsky B,
Staudinger H. Efficacy and safety of mometasone furoate administered
once-daily in the evening in patients with persistent asthma dependent on
inhaled corticosteroids. Curr Med Res Opin 2005; 21:1281–1289.
128. Masoli M, Weatherall M, Beasley R. Fluticasone given once versus twice
a day: meta-analysis. Respirology 2005; 10:183–188.
129. Rohatagi S, Arya V, Zech K, Nave R, Hochhaus G, Jensen BK, Barrett
JS. Population pharmacokinetics and pharmacodynamics of ciclesonide.
J Clinical Pharmacol 2003; 43:365–378.
130. Christie P. Ciclesonide: a novel inhaled corticosteroid for asthma. Drugs
Today (Barc) 2004; 40:569–576.
131. Rohatagi S, Krishnaswami S, Pfister M, Sahasranaman S. Model-based
covariate pharmacokinetic analysis and lack of cortisol suppression by
the new inhaled corticosteroid Ciclesonide using a novel cortisol release
model. Am J Ther 2005; 12:385–397.
132. Chapman KR, Patel P, D’Urzo AD, Alexander M, Mehra S, Oedekoven
C, Engelstätter R, Boulet LP. Maintenance of asthma control by once-
daily inhaled ciclesonide in adults with persistent asthma. Allergy 2005;
60:330–337.
133. Pearlman DS, Berger WE, Kerwin E, LaForce C, Kundu S, Banerji D.
Once-daily ciclesonide improves lung function and is well tolerated by
patients with mild-to-moderate persistent asthma. J Allergy Clin Immunol
2005; 116:1206–1212.
134. Zitt MJ. Properties of the ideal corticosteroid therapy. Allergy Asthma
Proc 2005; 26:173–182.
135. Gauvreau GM, Boulet LP, Postma DS, Kawayama T, Watson RM, Duong
ML, Deschesnes F, DeMonchy JGR, O’Byrne PM. Effect of low-dose
ciclesonide on allergen-induced responses in subjects with mild allergic
asthma. J Allergy Clin Immunol 2005; 116:285–291.
136. Nave R, Drollmann A, Steinijans VW, Zech K, Bethke TD. Lack of phar-
macokinetic drug-drug interaction between ciclesonide and erythromycin.
Int J Clin Pharmacol Ther 2005; 43:264–270.
137. Product Information Asmanex Twisthaler 220 mcg (mometasone furoate
inhalation powder). Schering Corporation Kenilworth, NJ 07033 USA.
Rev. 5/05 B-26796016.