The Use of FKBP51 in the Identification of Non-adherence to Inhaled Corticosteroids in Difficult Asthma
The Use of FKBP51 in the Identification of Non-adherence to Inhaled Corticosteroids in Difficult Asthma
Approximately 5-10% of people with asthma do not respond to to standard therapy and are
 referred to as having difficult asthma. Evidence shows that this poor response is not always
 related to asthma severity and non-adherence to treatment is recognized as a common
 underlying problem, in 35% of these patients. Recognising non-adherence in the clinic is
 problematic as there is no straightforward objective test to identify it.

 Previous studies have demonstrated up-regulation of FKBP51 gene expression following
 treatment with steroids, making it a potential biomarker of steroid exposure. It is therefore
 also a potential biomarker of non-adherence to inhaled corticosteroid therapy. The
 investigators plan to assess the feasibility of distinguishing non-adherent subjects who are
 by omission steroid naïve from adherent subjects, steroid exposed subjects using FKBP51 gene
 expression in sputum and throat swabs.

 To do this the investigators will obtain throat swab and sputum samples from healthy
 volunteers, steroid naïve asthmatics and adherent asthmatics on high dose ICS to assess if
 FKBP51 gene expression is comparable in each group.

 The investigators will then compare the FKBP51 gene expression response to directly observed
 inhaled steroid therapy in steroid naïve, non-adherent and adherent asthmatics. This will
 identify if the response in gene expression distinguishes steroid exposed (adherent) from
 steroid naïve (non-adherent) patients.

 Identifying non-adherence will benefit patients by enabling appropriate tailored management
 for non-adherence to enhance treatment effectiveness. It will also identify patients with
 therapy resistant asthma who have an unmet need and may benefit from expensive novel
 therapies such as Omalizumab.
Inclusion Criteria:

 This pilot study will investigate the following groups (n=10 per group):

 1. Healthy volunteers.

 2. Steroid naïve asthmatics.

 3. Refractory asthmatics adherent to high dose inhaled steroids.

 4. Non-adherent asthmatics.

 Inclusion Criteria

 For inclusion into this study all participants must:

 -  be 16 years old or older

 -  give written informed consent

 Healthy volunteers must:

 -  be in good general health as determined by past medical history and physical.

 -  have no other significant medical history and specifically no prior history of asthma
 or persistent respiratory symptoms.

 -  normal spirometry.

 Steroid naïve subjects

 -  have a diagnosis of asthma

 -  receiving treatment at Step 1 BTS/SIGN Guidelines i.e. no inhaled steroid

 Non-adherent subjects must

 -  have a diagnosis of asthma

 -  be non-adherent to ICS as determined by ICS prescription filling of </=50% in the
 previous 6 months

 Refractory asthmatic adherent subjects must:

 -  have a diagnosis of asthma receiving high dose ICS treatment (beclomethasone
 equivalent dose > 1000 µg per day)

 -  be adherent to ICS as determined by ICS prescription filling >75% in the previous 6
 months

 Exclusion Criteria:

 Participants who fulfill the following criteria will be excluded from study entry:

 -  Current smoker,

 -  Pregnant or lactating,

 -  Other significant respiratory disease

 -  Previous allergic reaction or known hypersensitivity to budesonide or any
 corticosteroid

 Healthy volunteers will be excluded if they have / are :

 -  any significant medical history which the principal investigator (PI) deems
 appropriate to be excluded from the healthy control group

 -  obstructive lung function

 -  taking any medication

 -  a current or history of drug or alcohol abuse

 -  any significant illness during the screening period preceding entry into the study

 Steroid naïve / Non-adherent asthmatics will be excluded if they have:

 -  commenced or increase of oral corticosteroids in the previous 28 days

 -  a concurrent asthma exacerbation

 Refractory / Adherent asthmatics will be excluded if they have:

 -  commenced or increased of oral corticosteroids in the previous 28 days

 -  a concurrent asthma exacerbation