Accepted Manuscript

Review

Inhaled Corticosteroid-phobia and Childhood Asthma: Current Understanding

and Management Implications

Rex Wan Hin Hui

PII: S1526-0542(19)30035-1
DOI: https://doi.org/10.1016/j.prrv.2019.03.009
Reference: YPRRV 1322

To appear in: Paediatric Respiratory Reviews

Received Date: 4 February 2019

Revised Date: 20 March 2019
Accepted Date: 31 March 2019

Please cite this article as: R.W.H. Hui, Inhaled Corticosteroid-phobia and Childhood Asthma: Current Understanding
and Management Implications, Paediatric Respiratory Reviews (2019), doi: https://doi.org/10.1016/j.prrv.
2019.03.009

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Inhaled Corticosteroid-phobia and Childhood Asthma: Current Understanding and

Management Implications

Rex Wan Hin HUI 1*

1
Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong

*corresponding author

huirex@connect.hku.hk

Declaration of interests: none

Funding sources: none

1
Inhaled Corticosteroid-phobia and Childhood Asthma: Current Understanding and

Management Implications

ABSTRACT

Asthma is the most prevalent chronic disease in children. Inhaled corticosteroids (ICS) is the

first-line controller therapy for children with persistent asthma, however, suboptimal

compliance to ICS therapy remains as a major obstacle in paediatric asthma management.

Steroid-phobia, the fear of side-effects and subsequent aversion of ICS, has been widely

reported in parents of asthmatic children. The reported prevalence of steroid-phobia varies

widely from 19-67% in different populations. The concerns about ICS frequently raised by

parents include growth suppression, weight gain, bone weakness, addiction and psychiatric

disturbances. Outside of growth suppression, which is statistically significant yet mild in

clinical studies, the other concerns are not evidence-based and are misconceptions.

Conflicting results have been reported regarding the impact of steroid-phobia on ICS

compliance. In contrast, steroid-phobia has consistent and negative effects on asthma control

in children. While asthma educational programmes have demonstrable benefits in general

paediatric populations, the generalisability of such programmes to steroid-phobic parents

remain undetermined. There is a paucity of data on specific educational programmes to clear

misconceptions and reduce steroid-phobia. Given the continually raising prevalence of

paediatric asthma, high-quality studies are warranted to investigate the prevalence and impact

of steroid-phobia, with an ultimate goal of developing effective strategies to tackle steroid-

phobia and improve asthma care in children.

KEYWORDS

asthma, inhaled corticosteroids, steroid-phobia, children.

2
INTRODUCTION

Asthma is the most common chronic disease in the paediatric population, and has shown

increasing incidence and prevalence in recent decades [1-4]. Aside from morbidity and

mortality, asthma in children also yields substantial socioeconomic consequences and places

substantial burden on healthcare systems [4].

Inhaled corticosteroids (ICS) is the first-line controller therapy for children with persistent

asthma [1]. Through targeting inflammatory mediators, ICS reduces inflammation and

bronchial hypersensitivity [5]. ICS has been shown to improve symptom control, reduce

exacerbations, improve lung function [6, 7], reduce hospitalisations [8], and reduce asthma

mortality.[9] Despite its proven benefits, suboptimal adherence to ICS remains a key

challenge in asthma management. ICS adherence rate is estimated to be 49-71% in children,

and the low compliance is a major cause of poor disease control [10].

While factors such as knowledge on inhaler use and parental education influence ICS

compliance, steroid-phobia is a specific factor that is frequently incriminated as a determinant

of poor ICS adherence [1, 10]. Steroid phobia, the fear of steroid side effects and subsequent

aversion of steroids, has been documented in the literature since 1979 [11, 12], and is well-

recognised among both paediatric [13] and adult [14] populations. The article will review the

literature on steroid-phobia towards ICS in childhood asthma, and explore its management

implications.

PREVALENCE OF INHALED CORTICOSTEROID-PHOBIA

The prevalence of steroid-phobia among parents of asthmatic children has been described in a

range of studies. A commonly used tool to assess concerns was the Beliefs about Medicines

Questionnaire (BMQ), a validated questionnaire to quantify patient’s perceptions towards a

prescribed medication. The questionnaire is further divided into the BMQ-Necessity and

BMQ-Concerns subscales to assess opinions on the necessity of the drug and concerns

3
regarding the drug respectively [15]. Percentage of parents with strong concerns about ICS

use in their children, as defined by the BMQ, ranged from 19-30% (Table 1) [16-19]. Other

studies have also described parental concerns regarding ICS in asthma, yet the studies utilised

non-validated questionnaires to measure the outcome. The percentage of parents who have

expressed concerns ranged from 19-67% among studies using non-validated questionnaires

(Table 1) [20-27]. Outside of a 1996 study from Singapore [27], the other studies using non-

validated questionnaires generally reported a higher prevalence of strong concerns when

compared with the studies using BMQ. This discrepancy could be attributable to disparities in

the assessment instruments. Also, it should be noted that the four studies using BMQ were

sub-studies embedded in larger clinical studies. The families may have received additional

physician advice and education while they took part in the research, and hence have lower

concerns about ICS. Future studies should aim for a comprehensive assessment of steroid-

phobia among all parents of asthmatic children. Since the BMQ questionnaire can be easily

administered, it may be incorporated into routine care, and regular assessment of parental

concerns can be done during the initial prescription of ICS and follow-ups for all patients.

This will avoid response bias, which is likely present in the current studies, and will provide a

more accurate depiction of the steroid-phobia rates. The valuable data generated may be

beneficial to asthma care in children.

Koster et al. adopted an alternate approach, and directly administered the BMQ on 182

asthmatic adolescents, rather than their parents [28]. In the study, only 10.1% of adolescents

reported strong concerns against ICS usage. Overall, the data on steroid-phobia among

adolescents is scarce. Future studies should aim to assess the prevalence of steroid-phobia in

adolescents, as adolescents are likely responsible for handling their own medications and their

views on ICS may have greater impact than the views of their parents. It would also be

interesting to study adolescents and their parents simultaneously to assess whether there is

any concordance or discrepancy in their views towards ICS.

4
Table 1. Prevalence of inhaled corticosteroid-phobia among parents of asthmatic children

Study Cohort (parents of) BMQ used Strong concerns (%)

Koster et al. 2011 170 patients from the PIAMA cohort Yes 19.4

[16] study, Netherlands

Koster et al. 2011 527 patients from the PACMAN Yes 21.6

[17] cohort study, Netherlands

Conn et al. 2007 622 patients from a trial on physician- Yes 30.0

[18] led asthma education, US

Conn et al. 2005 67 patients from a trial on preventive Yes 34.0

[19] asthma medications, US

Ip et al. 98 outpatients from a regional No 35.7

2017 [20] hospital, Hong Kong

Binsaeed et al. 2014 158 outpatients from a teaching No 56.3

[21] hospital, Saudi Arabia

Zhao et al. 2013 2485 outpatients from tertiary asthma No 67.3

[22] clinics from 29 cities, China

Zedan et al. 2010 100 outpatients from a teaching No 53.0

[23] hospital, Egypt

Gazala et al. 2005 50 outpatients from a teaching No 30.4

[24] hospital, Israel

Yoos et al. 2003 109 outpatients from a teaching No 62.0

[25] hospital, US

Chan et al. 2000 170 outpatients from a teaching No 65.9

[26] hospital, Malaysia

Lim et al. 1996 [27] 210 outpatients from a teaching No 19.0

hospital, Singapore

BMQ: Beliefs about Medicines Questionnaire; PACMAN: Pharmacogenetics of Asthma Medication in

Children: Medication with Anti-inflammatory Effects; PIAMA: Prevention and Incidence of Asthma

and Mite Allergy

5
PARENTAL UNDERSTANDING ABOUT INHALED CORTICOSTEROIDS SIDE

EFFECTS

As with all drugs, ICS have potential side effects. While ICS adverse effects may have

formed the basis for steroid-phobia, studies have revealed that ICS are shrouded in myths and

misconceptions. Common concerns that parents have raised regarding ICS include growth

suppression [20,22-24], weight gain [23, 24], bone weakness [23], addiction and dependence

[21-24, 26, 27, 29], and psychiatric disturbances [22, 24]. This section will review the

common reasons for parents to fear ICS and explore whether the reasons are valid.

Growth suppression

Growth suppression due to ICS is one of the most commonly stated concerns among parents

[20, 22-24]. This concern is supported by the literature, as a meta-analysis involving 8741

asthmatic children demonstrated that regular use of ICS led to a mean reduction of linear

growth velocity by 0.48 cm per year [30]. Another meta-analysis published in 2014 focused

on the effect of different ICS dosages, and patients on medium dosage ICS had a reduced

growth rate of 0.20 cm per year when compared with low dose ICS users [31]. The long-term

growth effect of ICS has also been studied. In the Childhood Asthma Management Program

trial, patients on ICS had reduced growth velocity in the first year when compared with

patients on inhaled nedocromil or placebo. At the end of the six-year study, the ICS group had

a 1.1cm lower mean height increase when compared with the other groups [32]. After 12

years of longitudinal follow-up of the trial patients, the mean adult height in the ICS group

remained 1.2cm lower than that in the controls [33].

Although the effect of ICS on growth suppression is statistically significant, the clinical

significance of the relatively small effect size is debatable [34], and parents should be

reassured that other factors such as nutrition and genetics have a greater influence on height

[35]. While ICS leads to growth suppression, it should also be noted that uncontrolled asthma

can lead to poor growth as well [36, 37]. Aversion of ICS may lead to poorly-controlled

asthma, which also limits a child’s growth potential.

6
Weight gain

Weight gain secondary to ICS has been reported in small-scale studies in adult populations

[38]. However, a meta-analysis in the paediatric population has demonstrated ICS to have no

impact on patients’ body weight or body mass index [31]. Nonetheless, the authors of the

meta-analysis noted that the studies on weight changes in children were of low quality and

were limited by imprecise measurements.

Bone weakness

While oral corticosteroids are known to reduce bone density and increase fracture risk in

children [39], a similar impact of ICS on children’s bone health has yet been documented.

ICS has been shown to reduce serum markers of osteogenesis [40], however ICS use did not

significantly reduce the bone mineral density [32, 41], nor did it increase the risk of fractures

among asthmatic children [42-44].

Addiction and dependence

Inhaler abuse has been previously documented in the literature, yet the studies reported short-

acting beta agonists as the type of inhaler abused, since patients sought the sympathomimetic

effects of the drug [45, 46]. Addiction and abuse of ICS has not been documented in the

literature. Steroid-addiction is a phenomenon that has been documented among eczema

patients on topical corticosteroid ointment [47, 48], yet it should be noted that steroid

ointment exerts visible effects on skin lesions. In contrast, the effects of ICS on the airway

takes a long period to act and the effects are less noticeable, hence patients are unlikely to

misuse ICS based on its effects. Experts hypothesize that the concern about ICS addiction

may originate from socio-cultural perceptions of inhaled drugs such as marijuana and heroin

[26, 27].

Psychiatric disturbance

7
Psychiatric adverse effects have also been raised by parents [22, 24]. In particular, negative

impact on their children’s intelligence has been raised by 24% of parents in a large cross-

sectional study in China [22]. Articles have reported about potential psychiatric effects

secondary to ICS in children, and reported effects include agitation, anxiety, hyperactivity and

mood changes [49, 50]. Nonetheless, the number of reported cases are limited, and the studies

are limited by attribution bias. It is also possible that the behavioural changes were secondary

to improved disease control. Children with uncontrolled asthma may have limited exercise

tolerance, which was subsequently improved upon ICS treatment and manifested as

hyperactivity or agitation to the parents [50]. Conversely, the Childhood Asthma Management

Program study assessed the Children’s Depression Inventory as a secondary outcome and

revealed that the ICS group had significantly lower scores than the controls, suggesting that

ICS treatment may lead to lower incidences of depressive symptoms in children [32]. The

data on psychiatric disturbances in children treated with ICS is limited and inconclusive.

Further research should aim to better delineate the potential psychiatric effects of ICS.

Are the concerns valid?

Among the frequently raised concerns regarding ICS, growth suppression is a side effect that

is well-recognised and supported by the medical literature. The other concerns regarding

weight gain, bone weakness, addiction, and psychiatric disturbances all do not have evidence-

based support and can be considered as misconceptions. Interestingly, while parents

recurrently expressed concerns regarding ICS, none of the interviewed parents in the studies

raised concerns about the most common adverse effect in ICS use – local oropharyngeal

disturbances. Local oropharyngeal disturbances, namely oral candidiasis and dysphonia, occur

in 5-10% of patients using ICS [51]. Despite its high prevalence, these oropharyngeal effects

are mild and rarely disabling [52], and the relatively benign and transient nature may explain

why the parents seldom raise these local adverse effects as their concerns. Another ICS

adverse effect that has not been documented among steroid-phobic parents is adrenal

suppression. ICS has been demonstrated to have a potential dose-dependent suppressive effect

on the hypothalamic-pituitary-adrenal axis in children. Among asthmatic children on ICS,

8
effects of reduced serum cortisol [53, 54], reduced response to the insulin tolerance test [55],

and reduced response to the short Synacthen test [56] have all been documented. Cases of

patients with acute adrenal crisis and presenting with hypoglycaemia, convulsions or coma

have also been reported [57]. Nonetheless, symptomatic cases of ICS-induced adrenal

suppression are very uncommon, and life-threatening cases are even rarer [58], hence it is

predictable that parents have very limited knowledge about this potentially life-threatening

side effect.

Among parents with strong concerns about ICS, it is intriguing that some have explicitly

stated the preference of oral corticosteroids over ICS [23, 25-27]. While the exact reason for

the preference of oral steroids has not been delineated, this is likely attributable to the low

knowledge level regarding asthma treatment and the failure to recognise the more severe

systemic effects from oral steroids. The misperception that oral medications can target the

lungs more directly is another potential explanation [26, 27].

IMPACT OF INHALED CORTICOSTEROID-PHOBIA

In spite of the high prevalence of concerns about ICS, the impact of steroid-phobia on

paediatric asthma patients has not been well-defined [10]. This section will review articles

that have reported on clinical outcomes and impact of steroid-phobia.

Compliance to inhaled corticosteroids

In a 2011 study on 527 parents of asthmatic children, the BMQ-Concern score and the BMQ-

Necessity score on ICS were both associated with drug compliance, as determined by the

Medication Adherence Report Scale (MARS). However, the association between BMQ-

Concern and compliance became non-significant in multivariate analysis, and the only

remaining independent predictor of ICS compliance in that study was the BMQ-Necessity

score [17]. These results have been mirrored in other studies [18, 59], suggesting that in spite

9
of reported concerns about ICS, the impact of parental perception about the necessity of the

drug may have greater influence on ICS compliance.

Other studies have yielded negative results, where both the ICS concerns in parents [20] or in

the patient themselves [28] were not significant determinants of drug adherence. Contrasting

results have been drawn from other studies. Studies have shown that parents with higher

concerns about ICS were significantly more likely to self-taper or omit the ICS use among

their children [24, 26]. A study from the US has also reported that higher ICS concerns were

associated with a lower MARS score, and the inverse correlation remained significant in

multivariate analysis [19].

The inconclusive results regarding ICS adherence may be due to methodological limitations.

Several studies used non-validated questionnaires to assess drug compliance [20, 24], and

hence the comparability of results between studies may be limited. Some of the studies were

also conducted during routine clinical or pharmacy visits by the medical staff caring for the

patient [17, 20]. This may result in overestimation of compliance due to social desirability

bias. Approaches to tackle this problem may include using telephone interviews, or having the

questionnaires administered by medical staff not actively involved in patient management.

Asthma control

Conn et al. reported that steroid-phobia in parents was associated with more asthmatic

symptoms among children. Yet this association became non-significant in multivariate

analysis after controlling for drug adherence [19]. This may simply reflect the high inter-

correlation between drug adherence and asthmatic symptoms. Steroid-phobia is also

associated with a higher number of acute asthmatic exacerbations which required nebulisation

treatment [26]. Using the validated Asthma Control Test, Ip et al. demonstrated that parents

with higher ICS concerns had children with significantly lower mean Asthma Control Test

score [20], signifying the negative impact of steroid-phobia on asthma control. Similar results

have also been reported in a 2011 study from Netherlands, where a high BMQ-Concern score

10
led to a two-fold increased risk of uncontrolled asthma, with the results remaining significant

in multivariate analysis [16].

Given the potential overestimation of compliance and the significant effect of ICS adherence

on asthma control [10], the consistent outcome of poor asthma control may be a more

accurate and objective portrayal of the impact of steroid-phobia on paediatric steroid asthma

than reported drug compliance.

4.3) Other outcomes

Steroid-phobia may result in parents seeking alternative therapy for their children’s asthma. A

2005 study from Israel reported that parents with strong ICS concerns were significantly more

likely to resort to homeopathic treatment for their children’s asthma [24]. Similar results have

been shown in a 2017 study from Hong Kong, where parental steroid-phobia was associated

was traditional Chinese medicine (TCM) use in asthmatic children [20]. An interesting case

series has previously reported five cases of inadvertent steroid use in eczematous children

with steroid-phobic parents. The parents of all five patients opted to use TCM instead of

topical steroids for their children’s eczema and reported noticeable disease improvements.

However it was later discovered that the TCM illegally contained potent corticosteroids when

the children presented with varying degrees of Cushingoid features [60]. Among paediatric

asthma cases, particularly in the Chinese population, it may be beneficial to remind parents to

be vigilant while seeking care from TCM practitioners.

Steroid-phobic parents were also more likely to have discussed their fears about ICS with a

doctor [20], and were more likely to seek information from the lay literature [24]. While this

could be due to a change in health-seeking behaviour secondary to steroid-phobia, reverse

causality should also be considered. Parents may simply have greater concerns about ICS

because they were educated about more side effects from their doctors, or because they

received misinformation from the lay literature.

11
MANAGEMENT OF INHALED CORTICOSTEROID-PHOBIA

Educational programmes in paediatric asthma have demonstrable benefits and can improve

asthma care in children [61-65]. However, these educational programmes have focused on

general paediatric populations. There is a paucity of data on educational programmes in

specific subpopulations that may face more treatment obstacles, such as in parents with

steroid-phobia. The generalisability of patient/parent education interventions to specific

subpopulations is unclear. Indeed, a previous trial has shown that the same set of paediatric

asthma educational intervention may not be applicable and efficacious among different

patient populations [66]. Given the high prevalence of steroid-phobia and its potential

negative effects on asthma control, specific educational programmes targeting steroid-phobia

may be beneficial and should be further studied.

The prescribing physician should clearly explain to the parents about the balance between

risks and benefits in using ICS for asthma [67]. Parents should be reminded of the proven

benefits of ICS in disease control [6-9], and should also be reassured that most ICS side

effects are mild and manageable. Another point that may be raised is that while trials focused

on ICS usage for prolonged periods, ICS regimens are likely to be tapered and adjusted in the

real-world setting, and patients may even be taken off ICS upon satisfactory control. The

patients’ exposure to ICS in the real-world setting is likely to be lower than that in trial

settings, and hence the side effects may also possibly be lower.

CONCLUSION

Steroid-phobia has been reported in parents of asthmatic children and the prevalence varied

considerably. Frequently raised concerns by parents regarding ICS include growth

suppression, weight gain, bone weakness, addiction and psychiatric disturbances. Outside of

12
growth suppression, which is statistically significant yet mild in clinical studies, the other

concerns raised are not evidence-based and are misconceptions. Conflicting results have been

reported regarding the impact of steroid-phobia on the compliance to ICS. In contrast, steroid-

phobia in parents has consistent and negative effects on asthma control in children. As of

now, there is a paucity of data on specific educational programmes to clear misconceptions

and reduce steroid-phobia. Given the continually raising prevalence of paediatric asthma,

high-quality studies are warranted to investigate the prevalence and impact of steroid-phobia,

with an ultimate goal of developing effective strategies to tackle steroid-phobia and improve

asthma care in children.

EDUCTIONAL AIMS

The reader will be able :

 To describe the prevalence and reasons behind steroid-phobia among parents of

paediatric asthma patients

 To describe the impact of steroid-phobia on paediatric asthma management, including

its impact on inhaled corticosteroid compliance and asthma control

FUTURE RESEARCH DIRECTIONS

 Large-scale comprehensive assessment of steroid-phobia among parents of paediatric

asthma patients and adolescents with asthma by using validated scales

 Specific educational programmes targeting steroid-phobia in parents of paediatric

asthma patients should be studied. The programmes and related interventional studies

should focus on patient-centered outcomes, as long-term asthma management in the

paediatric population will require the understanding and input of patients and families

 Mixed methods studies to incorporate both qualitative and quantitative data in order to

enhance understanding of patients’ and parents’ perspectives in steroid-phobia

13
14
REFERENCES
[1] Papi, A., et al., Asthma. Lancet, 2018. 391(10122): p. 783-800.

[2] Wong, G.W., T.F. Leung, and F.W. Ko, Changing prevalence of allergic diseases in the Asia-

pacific region. Allergy Asthma Immunol Res, 2013. 5(5): p. 251-7.

[3] Lau, Y.L. and J. Karlberg, Prevalence and risk factors of childhood asthma, rhinitis and

eczema in Hong Kong. J Paediatr Child Health, 1998. 34(1): p. 47-52.

[4] Nunes, C., A.M. Pereira, and M. Morais-Almeida, Asthma costs and social impact. Asthma

Res Pract, 2017. 3: p. 1.

[5] Szefler, S.J., Glucocorticoid therapy for asthma: clinical pharmacology. J Allergy Clin

Immunol, 1991. 88(2): p. 147-65.

[6] Rachelefsky, G., Inhaled corticosteroids and asthma control in children: assessing

impairment and risk. Pediatrics, 2009. 123(1): p. 353-66.

[7] Castro-Rodriguez, J.A. and G.J. Rodrigo, Efficacy of inhaled corticosteroids in infants and

preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis.

Pediatrics, 2009. 123(3): p. e519-25.

[8] Suissa, S., P. Ernst, and A. Kezouh, Regular use of inhaled corticosteroids and the long term

prevention of hospitalisation for asthma. Thorax, 2002. 57(10): p. 880-4.

[9] Suissa, S., et al., Low-dose inhaled corticosteroids and the prevention of death from asthma.

N Engl J Med, 2000. 343(5): p. 332-6.

[10] Desager, K., F. Vermeulen, and E. Bodart, Adherence to asthma treatment in childhood and

adolescence - a narrative literature review. Acta Clin Belg, 2017: p. 1-8.

[11] Tuft, L., "Steroid-phobia" in asthma management. Ann Allergy, 1979. 42(3): p. 152-9.

[12] Patterson, R., et al., Prednisonephobia. Allergy Proc, 1989. 10(6): p. 423-8.

[13] Patterson, R., P.A. Greenberger, and D.R. Patterson, Potentially fatal asthma: the problem of

noncompliance. Ann Allergy, 1991. 67(2 Pt 1): p. 138-42.

[14] Boulet, L.P., Perception of the role and potential side effects of inhaled corticosteroids among

asthmatic patients. Chest, 1998. 113(3): p. 587-92.

[15] Horne, R., J. Weinman, and M. Hankins, The beliefs about medicines questionnaire: The

development and evaluation of a new method for assessing the cognitive representation of

medication. Psychology & Health, 1999. 14(1): p. 1-24.

15
[16] Koster, E.S., et al., Uncontrolled asthma at age 8: the importance of parental perception

towards medication. Pediatr Allergy Immunol, 2011. 22(5): p. 462-8.

[17] Koster, E.S., et al., Inhaled corticosteroid adherence in paediatric patients: the PACMAN

cohort study. Pharmacoepidemiol Drug Saf, 2011. 20(10): p. 1064-72.

[18] Conn, K.M., et al., The impact of parents' medication beliefs on asthma management.

Pediatrics, 2007. 120(3): p. e521-6.

[19] Conn, K.M., et al., Parental beliefs about medications and medication adherence among

urban children with asthma. Ambul Pediatr, 2005. 5(5): p. 306-10.

[20] Ip, K.I., et al., Steroid phobia, Chinese medicine and asthma control. Clin Respir J, 2017.

[21] BinSaeed, A.A., Caregiver knowledge and its relationship to asthma control among children

in Saudi Arabia. J Asthma, 2014. 51(8): p. 870-5.

[22] Zhao, J., et al., The knowledge, attitudes and practices of parents of children with asthma in

29 cities of China: a multi-center study. BMC Pediatr, 2013. 13: p. 20.

[23] Zedan, M.M., et al., Steroid Phobia among Parents of Asthmatic Children: Myths and Truth.

Iran J Allergy Asthma Immunol, 2010. 9(3): p. 163-8.

[24] Gazala, E., R. Sadka, and N. Bilenko, Parents' Fears and Concerns Toward Inhaled

Corticosteroid Treatment for Their Asthmatic Children. Pediatric Asthma, Allergy &

Immunology, 2005. 18(2): p. 82-87.

[25] Yoos, H.L., H. Kitzman, and A. McMullen, Barriers to anti-inflammatory medication use in

childhood asthma. Ambul Pediatr, 2003. 3(4): p. 181-90.

[26] Chan, P.W. and J.A. DeBruyne, Parental concern towards the use of inhaled therapy in

children with chronic asthma. Pediatr Int, 2000. 42(5): p. 547-51.

[27] Lim, S.H., et al., Parents' perceptions towards their child's use of inhaled medications for

asthma therapy. J Paediatr Child Health, 1996. 32(4): p. 306-9.

[28] Koster, E.S., et al., Adolescents' inhaled corticosteroid adherence: the importance of

treatment perceptions and medication knowledge. J Asthma, 2015. 52(4): p. 431-6.

[29] Roncada, C., et al., Asthma treatment in children and adolescents in an urban area in

southern Brazil: popular myths and features. J Bras Pneumol, 2016. 42(2): p. 136-42.

[30] Zhang, L., S.O. Prietsch, and F.M. Ducharme, Inhaled corticosteroids in children with

persistent asthma: effects on growth. Cochrane Database Syst Rev, 2014(7): p. Cd009471.

[31] Pruteanu, A.I., et al., Inhaled corticosteroids in children with persistent asthma: dose-

response effects on growth. Cochrane Database Syst Rev, 2014(7): p. Cd009878.

16
[32] Szefler, S., et al., Long-term effects of budesonide or nedocromil in children with asthma. N

Engl J Med, 2000. 343(15): p. 1054-63.

[33] Kelly, H.W., et al., Effect of inhaled glucocorticoids in childhood on adult height. N Engl J

Med, 2012. 367(10): p. 904-12.

[34] Loke, Y.K., et al., Impact of Inhaled Corticosteroids on Growth in Children with Asthma:

Systematic Review and Meta-Analysis. PLoS One, 2015. 10(7): p. e0133428.

[35] Perkins, J.M., et al., Adult height, nutrition, and population health. Nutr Rev, 2016. 74(3): p.

149-65.

[36] Doull, I.J., The effect of asthma and its treatment on growth. Arch Dis Child, 2004. 89(1): p.

60-3.

[37] Pedersen, S., Long-term outcomes in paediatric asthma. Allergy, 2002. 57 Suppl 74: p. 58-74.

[38] Rizk, A.K., et al., Sex differences in the effects of inhaled corticosteroids on weight gain

among patients with asthma. ISRN Pulmonology, 2012. 2012.

[39] Kelly, H.W., et al., Effect of long-term corticosteroid use on bone mineral density in children:

a prospective longitudinal assessment in the childhood Asthma Management Program

(CAMP) study. Pediatrics, 2008. 122(1): p. e53-61.

[40] Sorva, R., et al., Effects of inhaled budesonide on serum markers of bone metabolism in

children with asthma. J Allergy Clin Immunol, 1992. 90(5): p. 808-15.

[41] Bahceciler, N.N., et al., Inhaled corticosteroids and bone density of children with asthma. J

Asthma, 2002. 39(2): p. 151-7.

[42] Gray, N., et al., Association Between Inhaled Corticosteroid Use and Bone Fracture in

Children With Asthma. JAMA Pediatr, 2018. 172(1): p. 57-64.

[43] Schlienger, R.G., S.S. Jick, and C.R. Meier, Inhaled corticosteroids and the risk of fractures

in children and adolescents. Pediatrics, 2004. 114(2): p. 469-73.

[44] Loke, Y.K., et al., Bone mineral density and fracture risk with long-term use of inhaled

corticosteroids in patients with asthma: systematic review and meta-analysis. BMJ Open,

2015. 5(11): p. e008554.

[45] Boyd, C.J., C.J. Teter, and S.E. McCabe, Pilot study of abuse of asthma inhalers by middle

and high school students. J Adolesc Health, 2004. 34(6): p. 531-4.

[46] Boyd, C.J., S.E. McCabe, and C.J. Teter, Asthma inhaler misuse and substance abuse: a

random survey of secondary school students. Addict Behav, 2006. 31(2): p. 278-87.

17
[47] Rapaport, M.J. and M. Lebwohl, Corticosteroid addiction and withdrawal in the atopic: the

red burning skin syndrome. Clin Dermatol, 2003. 21(3): p. 201-14.

[48] Hajar, T., et al., A systematic review of topical corticosteroid withdrawal ("steroid addiction")

in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol, 2015. 72(3): p.

541-549.e2.

[49] Hederos, C.-A., Neuropsychologic changes and inhaled corticosteroids. Journal of Allergy

and Clinical Immunology, 2004. 114(2): p. 451-452.

[50] de Vries, T.W., et al., Reported adverse drug reactions during the use of inhaled steroids in

children with asthma in the Netherlands. Eur J Clin Pharmacol, 2006. 62(5): p. 343-6.

[51] Rachelefsky, G.S., Y. Liao, and R. Faruqi, Impact of inhaled corticosteroid-induced

oropharyngeal adverse events: results from a meta-analysis. Ann Allergy Asthma Immunol,

2007. 98(3): p. 225-38.

[52] Galvan, C.A. and J.C. Guarderas, Practical considerations for dysphonia caused by inhaled

corticosteroids. Mayo Clin Proc, 2012. 87(9): p. 901-4.

[53] Phillip, M., et al., Integrated plasma cortisol concentration in children with asthma receiving

long-term inhaled corticosteroids. Pediatr Pulmonol, 1992. 12(2): p. 84-9.

[54] Wyatt, R., et al., Effects of inhaled beclomethasone dipropionate and alternate-day

prednisone on pituitary-adrenal function in children with chronic asthma. N Engl J Med,

1978. 299(25): p. 1387-92.

[55] Mahachoklertwattana, P., et al., Decreased cortisol response to insulin induced

hypoglycaemia in asthmatics treated with inhaled fluticasone propionate. Arch Dis Child,

2004. 89(11): p. 1055-8.

[56] Paton, J., et al., Adrenal responses to low dose synthetic ACTH (Synacthen) in children

receiving high dose inhaled fluticasone. Arch Dis Child, 2006. 91(10): p. 808-13.

[57] Todd, G.R., et al., Survey of adrenal crisis associated with inhaled corticosteroids in the

United Kingdom. Arch Dis Child, 2002. 87(6): p. 457-61.

[58] Smith, R.W., et al., Prevalence of hypothalamic-pituitary-adrenal axis suppression in children

treated for asthma with inhaled corticosteroid. Paediatr Child Health, 2012. 17(5): p. e34-9.

[59] Wijga, A.H., et al., Guideline-recommended use of asthma medication by children is

associated with parental information and knowledge: the PIAMA birth cohort.

Pharmacoepidemiol Drug Saf, 2014. 23(4): p. 406-10.

18
[60] Hon, K.L., et al., Paradoxical use of oral and topical steroids in steroid-phobic patients

resorting to traditional Chinese medicines. World J Pediatr, 2012. 8(3): p. 263-7.

[61] Coffman, J.M., et al., Effects of asthma education on children's use of acute care services: a

meta-analysis. Pediatrics, 2008. 121(3): p. 575-86.

[62] Krishna, S., et al., Internet-enabled interactive multimedia asthma education program: a

randomized trial. Pediatrics, 2003. 111(3): p. 503-10.

[63] Lozano, P., et al., A multisite randomized trial of the effects of physician education and

organizational change in chronic-asthma care: health outcomes of the Pediatric Asthma Care

Patient Outcomes Research Team II Study. Arch Pediatr Adolesc Med, 2004. 158(9): p. 875-

83.

[64] Shah, S., et al., Effect of peer led programme for asthma education in adolescents: cluster

randomised controlled trial. BMJ, 2001. 322(7286): p. 583-5.

[65] Chan, D.S., et al., Internet-based home monitoring and education of children with asthma is

comparable to ideal office-based care: results of a 1-year asthma in-home monitoring trial.

Pediatrics, 2007. 119(3): p. 569-78.

[66] Stevens, C.A., et al., Parental education and guided self-management of asthma and wheezing

in the pre-school child: a randomised controlled trial. Thorax, 2002. 57(1): p. 39-44.

[67] Hossny, E., et al., The use of inhaled corticosteroids in pediatric asthma: update. World

Allergy Organ J, 2016. 9: p. 26.

19