Achieving asthma control in
practice: understanding the
reasons for poor control
September 2008
© IPCRG 2007
International panel discussion, Aberdeen, Sept 2007
How to develop tools for use in primary care:
o To identify causes of poor asthma control
o To manage causes of poor asthma control
We're not treating asthma; we're treating patients. Many of
our patients would not be eligible for inclusion in randomised
controlled trials because of comorbidities and other factors.
Thus, the asthma guidelines, which are based on results of
these trials, often do not provide the answers we need for
patient care, particularly in the primary care setting.
-Dr. John Haughney
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Haughney J et al. Achieving asthma control in practice: understanding the reasons for poor control. Respir Med. 2008;102:1681–93.
What is asthma control?
As defined by the Global Initiative for Asthma (GINA), 2007
Minimal to no daytime asthma symptoms
Normal lung function (FEV1 or PEF)
No limitations on activities
No nocturnal symptoms or awakenings
Minimal to no need for reliever or rescue
No exacerbations
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Reasons for poor asthma control
Wrong diagnosis or confounding illness
Incorrect choice of inhaler or poor technique
Concurrent smoking
Concomitant rhinitis
Unintentional or intentional nonadherence
Individual variation in treatment response
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Haughney J et al. Respir Med. 2008;102:1681–93.
Addressing poor asthma control
Step 1: Confirm the diagnosis of asthma
If the patient is not responding as expected to
asthma therapy:
o Confirm the asthma diagnosis and rule out (or in)
confounding illness before changing or
increasing medications
Tools for diagnosing asthma must be stratified
by age
Objective measures of reversible airflow
obstruction (spirometry, PEF) are important if
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IPCRG Guidelines: diagnosis of respiratory diseases in primary care. Prim Care Respir J. 2006;15:20–34.
Diagnosing asthma in primary care
IPCRG guidelines. Prim Care Respir J. 2006;15:20–34.
Compatible clinical history
Episodic or persistent dyspnoea, wheeze, tightness, cough
Triggers (allergic, irritant)
Risk factors for asthma development
Consider occupational asthma for adults with recent onset
Objective evidence
o Spirometry or peak expiratory flow
o Bronchoprovocation test (methacholine challenge)
Ancillary tests
Chest x-ray
Eosinophils, IgE level
Allergy testing
Exhaled nitric oxide
Induced sputum
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Diagnosing asthma in children
Remember that young children commonly wheeze with
Differentials for wheezing include respiratory (upper and
lower) and non-respiratory causes:
o Upper airway: allergic diseases
o Obstruction of large airway: foreign body, vocal cord dysfunction,
vascular rings, laryngeal webs, tracheomalacia, or stenosis
o Obstruction of small airways: viral bronchiolitis, cystic fibrosis,
bronchopulmonary dysplasia, heart disease
o Other: aspiration (gastro-oesophageal reflux disease)
Spirometry is usually impractical for patients < 5 years old
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Bush A. Diagnosis of asthma in children under five. Prim Care Respir J. 2007;16:7–15.
Modified Asthma Prediction Index (mAPI)
A clinical index defining asthma risk in 2–3 year olds
For a child ≥2 years old with a history of ≥4 wheezing
episodes (≥1 confirmed by a physician), the likelihood of
active asthma at age 6-13 yrs increases if the child has:
One of three major risk factors:
1. Parental history of asthma
2. Physician-diagnosed atopic dermatitis
3. Allergic sensitization to ≥1 aeroallergen
OR two of three minor risk factors:
1. Allergic sensitization to milk, egg, or peanuts
2. Wheezing unrelated to colds
3. Blood eosinophils ≥4%
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Guilbert TW et al. J Allergy Clin Immunol. 2004;114:1282–7.
Diagnosing asthma in adults
Differentiate between asthma and chronic
obstructive pulmonary disease (COPD)
Identify triggers such as smoking, pet exposure,
occupational exposure
Common differential diagnoses:
o COPD, cardiac disease, laryngeal, tracheal, or lung
tumour, bronchiectasis, foreign body, interstitial lung
disease, pulmonary emboli, aspiration, vocal cord
dysfunction, hyperventilation
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IPCRG Guidelines: diagnosis of respiratory diseases in primary care. Prim Care Respir J. 2006;15:20–34.
Diagnosing asthma in adults
Comorbidities can worsen asthma
symptoms— identify and treat them:
allergic rhinitis
gastro-oesophageal reflux disease (GERD)
respiratory infection
cardiac disorders
vocal cord dysfunction
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Addressing poor asthma control
Incorrect inhaler choice or poor
There is no clinical difference between inhaler devices
when used correctly, but each type requires a different
pattern of inhalation for optimal drug delivery to the lungs
Problems with inhaler technique are common in clinical
practice & can lead to poor asthma control
Asthma control worsens as the number of mistakes in
inhaler technique increases
All patients should be trained in technique, and trainers
should be competent with the inhalation technique
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Inhaler choice and technique
Key recommendations:
Take patient preference into account when choosing the
inhaler device
Simplify the regimen and do not mix inhaler device types
The choice of steroid inhaler is most important because of the
narrower therapeutic window
Invest the time to train each patient in proper inhaler
• Observe technique & let patient observe self (using video demonstrations)
• Devices to check technique & maintain trained technique are available (eg,
2Tone Trainer & Aerochamber Plus spacer for metered dose inhalers; InCheck Dial, Turbuhaler whistle, Novolizer for dry powder inhalers)
Recheck inhaler technique on each revisit
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Haughney J et al. Respir Med. 2008;102:1681–93.
Resources on inhaler use
Inhaler & spacer diagrams on GINA website:
American College of Chest Physicians/American College
of Asthma, Allergy, and Immunology guidelines:
o Dolovich et al. Chest. 2005;127:335-371.
Educational CD-Roms by Ontario Thoracic Society
Provider Education Program:
Schematic cartoons on the Asthma UK website:
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Resources on inhaler use (cont.)
Correct Inhaler Techniques and Common Mistakes
o June 2008 newsletter, National Asthma Council, Australia:
o Woolcock Institute of Medical Research:
Asthma Management Handbook 2006, National Asthma
Council, Australia:
o Use & care of spacers:
o Delivery devices:
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Addressing poor asthma control
Concurrent smoking
Smoking adversely impacts asthma control
o Current smokers are almost 3 times more likely
than non-smokers to be hospitalised for their
asthma over a 12-month period
Why does smoking adversely impact asthma?
o Asthma misdiagnosed as COPD or concomitant
o Relative steroid resistance
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Price D et al. Clin Exp Allergy. 2005;35:282–7.
Inhaled steroids are less effective in
smokers than nonsmokers with asthma
The pattern of airway inflammation differs
Smokers have a higher percentage of neutrophils in induced sputum, and
steroids are not very effective in reducing neutrophils.
Smoking produces oxidative stress
The oxidative stress produced by smoking impairs the activity of histone
deacetylase-2 (HDAC2), resulting in reduced anti-inflammatory activity of
Smoking triggers leukotriene production
Leukotrienes are not reduced by steroid therapy.
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Boulet LP et al. Chest. 2006;129:661–8. Barnes PJ et al. Lancet. 2004;363:731–3. Fauler J et al. Eur J Clin Invest. 1997;27:43–7.
Steroid resistance in smokers with asthma
Non-Smoking Asthma
Inflammatory stimuli
Smoking Asthma
Cigarette smoke
Oxidative stress
 IL-8
 eotaxin
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 Histone acetylation
GR = glucocorticoid receptors; HDAC2 = histone deacetylase-2; NF- B = nuclear factor- B
Clinical approach to smoking
o Take a smoking history
o Investigate the possibility of COPD
• IPCRG guidance includes tool to differentiate asthma from COPD*
o Encourage smokers to quit!
• IPCRG guidance on smoking cessation:
o Try alternative therapy:
• Leukotriene receptor antagonist
• Possibly theophylline
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*IPCRG Guidelines: diagnosis of respiratory diseases in primary care. Prim Care Respir J. 2006;15:20–34.
Addressing poor asthma control
Concomitant rhinitis
Patients with asthma & concomitant rhinitis use more health
care resources than those without rhinitis
In epidemiologic studies in the UK:
o Adults with asthma & concomitant rhinitis were 50% more likely to
be hospitalised for their asthma & significantly more likely to visit
their primary care physician than those without rhinitis
o Children with asthma & concomitant rhinitis had double the
likelihood of being hospitalised and significantly increased
likelihood of a physician visit for asthma than those without rhinitis
>50% of patients with asthma have rhinitis
o Both allergic & nonallergic rhinitis are linked to asthma
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Price D et al Clin Exp Allergy. 2005;35:282–7.
Thomas M et al. Pediatrics. 2005;115:129–34.
Evidence linking asthma & rhinitis
>50% of patients with asthma have rhinitis
Similar epidemiology
Common triggers
Similar pattern of inflammation:
o T helper type 2 cells, mast cells, eosinophils
Nasal challenge results in asthmatic inflammation
& vice versa
Rhinitis predicts development of asthma
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Thomas M. BMC Pulm Med. 2006;6:S4.
Does treatment of rhinitis
improve asthma control?
Preliminary evidence suggests that it
does improve asthma control
In the COMPACT trial, patients with comorbid
rhinitis who received budesonide plus montelukast,
a leukotriene receptor antagonist effective in
treating rhinitis symptoms in patients with asthma,
showed significantly greater improvement in
morning PEF than the group receiving
monotherapy with doubled dose of budesonide.
This treatment difference was not seen among
patients without comorbid rhinitis, suggesting that
the effects of montelukast on rhinitis improved lung
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Price DB et al. Allergy. 2006;61:737–42.
Clinical approach to rhinitis
Diagnosing rhinitis
o Use the International Study of Asthma and Allergies in
Childhood (ISAAC) question:
• "Do you have an itchy, sneezy, runny, or blocked nose when
you don't have a cold?“
o Take a good history & examine the nose
o Assess severity – as relates to asthma control
Treat the inflammation of both asthma & rhinitis
o Target upper & lower airways concomitantly or
o Combine upper plus lower airway therapies
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IPCRG Guidelines: management of allergic rhinitis. Prim Care Respir J. 2006;15:58–70.
Treatment of comorbid rhinitis & asthma
Upper airway treatment options
Lower airway treatment options
Nasal steroids
Inhaled steroids
Upper and lower airway treatment options
Leukotriene receptor antagonists
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Addressing poor asthma control
Unintentional & intentional nonadherence
• Nonadherence to asthma therapy, particularly to inhaled
steroids, is a common problem contributing to poor asthma
Nonadherence is often a hidden problem as assessment of
adherence is often not included in routine asthma review
Barriers to assessing adherence:
o Patient and physician may prefer to avoid the subject
o Lack of clear, easy methods for addressing barriers to adherence
o Perception that little can be done?
Appreciating the factors involved is the first step toward
improving adherence
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Horne R. Chest. 2006;130:65S–72S.
Unintentional versus intentional nonadherence
Perceptual–Practical Model of Adherence
(can’t take, won’t take)
Capacity & resources
Practical barriers
Perceptual barriers
Intentional nonadherence derives from the balance between the patient’s beliefs about the
personal necessity of taking a given medication relative to any concerns about taking it
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Horne R et al. 2005. National Co-ordinating Centre for NHS Service Delivery and Organisation R&D, London.
Nonadherence: identifying the causes
• Tools for identifying & assessing nonadherence:
o Beliefs about Medicines Questionnaire (BMQ) — developed to measure necessity
beliefs and concerns
o Medication Adherence Report Scale (MARS) — developed to assess patient
o Minimal Asthma Assessment Tool (MAAT) — undergoing pilot testing as a simple, selfadministered patient questionnaire for use before a clinical consultation to evaluate
asthma control, adherence to medication, and comorbidities such as allergic rhinitis
and smoking
Interventions to facilitate optimal adherence are likely to be
more effective if they:
o Facilitate honest discussion of adherence behaviour
o Identify the mix of perceptual & practical barriers for the individual patient
o Help clinicians to elicit and respond to patient beliefs and concerns
We need to tailor the intervention & support according to
specific barriers & patient preferences
Page 26 - © IPCRG 2007
Haughney J et al. Respir Med. 2008;102:1681–93.
Addressing poor asthma control
Individual variation in treatment response
Randomised controlled trials (RCTs) are the basis of
recommendations made by clinical guidelines. However, several
factors limit our ability to generalise RCT results to our patients.
Fewer than 10% of people with asthma in a general practice population
are eligible for the typical RCT
Patient adherence to therapy may be better in an RCT than in the real
The definition of “response” to therapy in an RCT (eg, FEV1
improvement) may not correspond to results relevant for our patients
(eg, improved asthma control, improved quality of life)
The inclusion/exclusion criteria can influence RCT results (eg,
requirement for bronchodilator reversibility may favour β agonist)
Group mean data from RCTs may not predict individual patient
Page 27 - © IPCRG 2007
Haughney J et al. Respir Med. 2008;102:1681–93.
Individual variation in treatment response
Distribution of FEV1 responses among adults with chronic asthma after 12 weeks of therapy
with inhaled beclometasone (white bars) or oral montelukast (striped bars). The mean FEV1
improvement from baseline was 13.1% for beclometasone & 7.4% for montelukast.
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Malmstrom K et al. Ann Intern Med. 1999;130:487–95 .
Individual variation in treatment response
Individual patient versus
average patient
Intraindividual response profile to therapy
among children and adolescents with
persistent asthma. Individual patient
responses (change from baseline in
asthma control days) suggest that, while
some patients responded to both inhaled
steroid and montelukast, others showed a
better response to one or the other.
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Zeiger RS et al. J Allergy Clin Immunol. 2006;117:45–52.
Difficulty in capturing & demonstrating
subjective benefit in clinical trials
Factors driving clinical trials:
• Regulatory requirements
• The needs of industry
• History
o what's been done in the past & is therefore still expected
Ease of measuring certain endpoints
Available technology to measure these endpoints
The need to focus on short-term events of asthma
The limited number of agents available for treating asthma
The need to remove all possible confounding factors to
allow assessment of the intervention studied
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Haughney J et al. Respir Med. 2008;102:1681–93.
Real world measures are needed for clinical trials
Need people with
asthma In real life
Need measures of what
is important to ‘real’
What are real
people looking for?
What is of value
to them?
Do not need repeated
studies for what
you already know
Need to know:
-What is effective?
-In what patient?
-In what circumstances?
-How identify?
-How deliver?
Page 31 - © IPCRG 2007
Haughney J et al. Respir Med. 2008;102:1681–93.
Addressing poor asthma control
Next steps—IPCRG GOALS
Develop tools to aid asthma diagnosis and management
in primary care
Translate tools into local languages and adapt them to
address cultural differences in perceptions about asthma
Test all tools to address issue of low levels of health
literacy in many countries
Coordinate efforts between the IPCRG, member
countries, and patients’ organisations to adapt tools for
individual countries
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