1. Uncontrolled Asthma: Burden, Patient Perceptions and Clinical Implications
Paolo Tassinari MD
Instituto de Inmunología
Hospital de Clínicas Caracas
Venezuela

2. Outline Asthma control Guidelines: current control and future risk
Predictors of poor asthma control
Burden of uncontrolled asthma
Novel Approaches to Achieve Asthma Control
Summary

3. Ideal Asthma Control Absent/minimal symptoms
Minimal/no requirement for rescue bronchodilators
No night-time or early morning symptoms
Normal lyfestyle
Minimal airway obstruction
No mortality
National Hesart, Lung, and Blood Institute. National Heart, Lung, and Blood Institute. International consensus report on diagnosis and treatment of asthma Eur Respir J 1992; 5: 601–641
Existen muchas guías internacionales para establecer el control del asma

4. Real World
Over 50% of all patients with severe asthma and more than 30% of patients with less severe asthma remain only partially controlled or uncontrolled 
Substantial effect on patient’s quality of life (physical, emotional, social, professional, economic)
Significant burden on the Health Care System
Kardos P. Current Medical Research & Opinion Vol. 27, No. 9, 2011, 1835–1847
Chen h. J Allergy Clin Immunol 2007; 120:
Weiss K. J Allergy Clin Immunol 2001; 107:3-8
Sin embargo, en la vida real, no tenemos control de nada
Aclarar al final que los costos de asma están directamente relacionado de control de asma, así paciengtes bien controlados cuestan menos que los mal controlados.
Ref: Haslkorn J Allergy Clin Immunol 2009; 124:

5. International Guidelines Goals of Asthma Treatment
Control of patient’s current symptoms
Prevention of future adverse outcomes
Greater emphasis on the assessment of asthma control vs. asthma severity
Use of combination measures vs. any single measure for more consistent evaluation of asthma control
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma 2007
Hoy en día, las guías establecen que el control debe cubrir o abordar los síntomas actuales del paciente y prevenir los síntomas adversos a futuro

6. Asthma Control
Asthma control: Extent to which the manifestations of asthma have been reduced or removed by treatment
Current clinical control: symptoms, reliever use, lung function
Future risk: exacerbations, lung function decline
American Thoracic Society/European Respiratory Society Task Force
Taylor DR. Eur Respir J 2008; 32:

7. ATS/ERS Statement: Clinical Recognition of Asthma Exacerbations
Exacerbations are episodes of asthma that:
Are troublesome to patients AND
Prompt a treatment change
Exacerbations can vary considerably in:
Speed of onset (minutes/hours/weeks)
Time to resolution
Absolute severity between and within individuals
Exacerbations can be clinically identified by changes in lung function, rescue use, and/or symptoms outside the patient’s usual range of day-to-day variation
ATS/ERS Statement: Clinical Recognition of Asthma Exacerbations
The ATS/ERS statement recognizes that there was no clear definition of asthma control, and the criteria used in its assessment varied widely in the medical literature.
The primary aim of the ATS/ERS statement was to provide consensus recommendations on standardized definitions and data collection methods for assessing asthma control, asthma severity, and asthma exacerbations in future clinical trials.
The secondary aims were:
To provide consensus recommendations on standardized measures of asthma control and exacerbations that can be obtained retrospectively from existing clinical trial data, to maximize the potential for pooling of data and for making comparisons between clinical trials.
To provide consensus recommendations on the assessment of asthma control, asthma severity, and asthma exacerbations in clinical practice.
Exacerbations are recognized as a common clinical manifestation in patients with severe asthma, and are known to increase the risk of asthma mortality. However, even in patients thought to have mild asthma, the rates of severe asthma exacerbations were much higher than expected.
In clinical practice, exacerbations are recognized as episodes that are troublesome to patients, and that prompt a need for a change in treatment. These episodes vary considerably in speed of onset (from minutes or hours to 2 weeks) and in time to resolution (5 to 14 days); they also vary in their absolute severity, both between and within individual patients. Clinical characteristics that cause acute distress and impairment in one patient may represent another patient’s usual status. These events are therefore clinically identified by being outside the patient’s own usual range of day-to-day variation.
Reference
Reddel HK, Taylor DR, Bateman ED, et al; American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180:59–99.
ATS = American Thoracic Society. ERS = European Respiratory Society
Reddel HK, et al. Am J Respir Crit Care Med. 2009;180:59–99 7

8. Goals of Asthma Management
Overall asthma control
achieving
reducing
CURRENT CONTROL
FUTURE RISK
Defined by
Defined by
Symptoms
Reliever use
Instability/
worsening
Exacerbations
Activity
Lung function
Lung function
loss
Medication
Adverse effects

9. Asthma Control GINA 2006 and classification of asthma control:
Controlled Symptoms frequency
Partly controlled Reliever use
Uncontrolled Night waking
Activity limitation
Airway obstruction
Exacerbations
Global Initiative for Asthma. Global strategy for asthma management and prevention 2006

10. GINA Guidelines Recommend Evaluating Short- and Long-term Patient History to Assess Asthma Control
To achieve and maintain long-term asthma control, GINA guidelines recommend managing both current symptoms and potential future risk
Current Symptoms
Future Risk
Clinical goals for current impairment should be evaluated over the past weeks
Symptoms/exacerbations associated with future risk should be evaluated over the past year
Daytime symptoms occurring twice per week or less
No nocturnal symptoms or awakenings
Need for reliever/rescue treatment twice per week or less
No limitations of activities
Normal lung function
Poor clinical control
Frequent exacerbations
Admission to critical care for asthma
Low FEV1
GINA Guidelines Recommend Evaluating Short- and Long-term Patient History to
Assess Asthma Control
The assessment of asthma control should include not only control of current clinical manifestations (symptoms, night waking, reliever use, activity limitation, and lung function), but also control of the expected future risk to the patient such as exacerbations, accelerated decline in lung function, and side effects of treatment. In general, the achievement of good clinical control of asthma leads to reduced risk of exacerbations.
Reference
GINA Strategy for Asthma Management and Prevention Available at:
FEV1 = forced expiratory volume in 1 second
GINA Strategy for Asthma Management and Prevention Available at: 10

11. GINA Guidelines: Asthma Control Classification and Treatment Approach
Symptoms
Controlled
(all of the following)
Partially Controlled
(any measure present in any week)
Uncontrolled
Daytime Symptoms
≤2 times per week
≥3 times per week
≥3 features of partly controlled asthma present in any weeka
Limitations of Activities
None
Any
Nocturnal Symptoms/Awakening
Need for Reliever Treatment
Lung Function (PEF or FEV1)
Normal
<80% of previous lung function test
Find and maintain lowest controlling step
Controlled
Consider stepping up to gain control
Partly controlled
Step up until controlled
Uncontrolled
GINA Guidelines: Asthma Control Classification and Treatment Approach
The table describes the clinical characteristics of Controlled, Partly Controlled, and Uncontrolled asthma. This is a working scheme based on current opinion and has not been formally validated. However, this classification has been shown to correlate well with the Asthma Control Test and with assessment of asthma control according to the US National Expert Panel Report 3 guidelines.
In clinical practice, this classification should be used in conjunction with an assessment of the patient’s clinical condition and the potential risks and benefits of changing treatment.
The patient’s current level of asthma control and current treatment determine the selection of pharmacologic treatment. For example, if asthma is not controlled on the current treatment regimen, treatment should be stepped up until control is achieved. If control has been maintained for at least 3 months, treatment can be stepped down with the aim of establishing the lowest step and dose of treatment that maintains control. If asthma is partly controlled, an increase in treatment should be considered, subject to whether more effective options are available (eg., increased dose or an additional treatment), safety and cost of possible treatment options, and the patient’s satisfaction with the level of control achieved. The scheme presented is based upon these principles, but the range and sequence of medications used in each clinical setting will vary depending on local availability (for cost or other reasons), acceptability, and preference.
Assessment of future risk (risk of exacerbations, instability, rapid decline in lung function, side-effects)
Features that are associated with increased risk of adverse events in the future include: Poor clinical control, frequent exacerbations in past year, ever admission to critical care for asthma, low FEV1, exposure to cigarette smoke, high-dose medications.
Reference
GINA Strategy for Asthma Management and Prevention Available at:
Treatment Action
Assessment of Future Risk
Risk of exacerbations, instability, rapid decline in lung function, side effects
aAny exacerbation should prompt review of maintenance treatment to ensure that it is adequate
GINA = Global Initiative for Asthma; PEF = peak expiratory flow; FEV1 = forced expiratory volume in 1 second
Adapted from GINA Strategy for Asthma Management and Prevention Available at:

12. Odds Ratio and 95% Confidence Intervals
Consistently Very Poorly Controlled (VPC) Asthma Increased the Risk of Future Asthma Exacerbations
TENOR
(The Epidemiology and Natural history of asthma: Outcomes and treatment Regimens)
Risk of Asthma Exacerbations Associated With Consistently VPC Asthma in TENOR
Adolescents/Adults
(≥12 years)
Hospitalization
Hospitalization/ED Visit/
Corticosteroid Burst
Composite
Hospitalization/
ED Visit Composite
ED Visit
Objective
OR P Value
(95% CI)
(0.64, 37.2)
<0.001
(1.91, 5.33)
<0.001
(1.71, 4.75)
(0.81, 5.97)
(0.72, 5.43)
To evaluate whether current level of control predicts risk for future hospitalizations, emergency department (ED) visits, or corticosteroid bursts
Conclusion
Consistently Very Poorly Controlled (VPC) Asthma Increased the Risk of Future Asthma Exacerbations
The TENOR (The Epidemiology and Natural history of asthma: Outcomes and treatment Regimens) study evaluated whether current level of control, as defined by the impairment domain of the 2007 NAEPP guidelines, predicts risk for future asthma exacerbations, defined as hospitalizations, emergency department (ED) visits, or corticosteroid bursts.
The study included 725 asthma patients aged 12 years and older.
Patients were organized into 2 cohorts:
Consistently VPC asthma from baseline through 2 years of follow-up
Improved from VPC asthma at baseline, with improvement maintained through 2 years of follow-up
Patients with consistently VPC asthma were more likely to have a corticosteroid burst or have a hospitalization, ED visit, or corticosteroid burst (composite).
Reference
Haselkorn T, Fish JE, Zeiger RS, et al; TENOR Study Group. Consistently very poorly controlled asthma, as defined by the impairment domain of the Expert Panel Report 3 guidelines, increases risk for future severe asthma exacerbations in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. J Allergy Clin Immunol. 2009;124:895–902.e4.
Patients with consistently VPC asthma were more likely to have a corticosteroid burst or hospitalization, ED visit, or corticosteroid burst (composite)
Increased Risk →
Odds Ratio and 95% Confidence Intervals
Level of asthma control based on the impairment domain of the NHLBI EPR-3 guidelines
Haselkorn T, et al. J Allergy Clin Immunol. 2009;124:895–902.e4 12

13. Asthma Severity
Asthma severity: Intensity of treatment required to achieve good asthma control
Underlying disease activity
Patient’s phenotype
American Thoracic Society/European Respiratory Society Task Force
Taylor DR. Eur Respir J 2008; 32:

14. Asthma Severity Mild asthma Severe asthma
Good control with very low-intensity treatment
Severe asthma
Need for high-intensity treatment
American Thoracic Society/European Respiratory Society Task Force
Taylor DR. Eur Respir J 2008; 32:

15. Current clinical control Future risk
Asthma control
Current clinical control Future risk
Asthma severity
(based on intensity of
treatment required)
Genetic and
environmental
factors
Treatment
Disease Activity
Asthma phenotypes
Eur Respir J 2008; 32:545

16. Poor Asthma Control Predictors
Underlying severe disease or resistance to therapy
Poor compliance
Poor inhaler technique
Under-prescribing
Environmental factors (allergen exposure, smoking)
Incorrect diagnosis/significant comorbidities
American Thoracic Society. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med 2000; 162:2341–2351

17. Poor Asthma Control Predictors
Armour C, et al. Using the community pharmacy to identify patients at risk of poor asthma control and factors which contribute to this poor control. J Asthma 2011; 48:914-22
96 pharmacies in Australia
570 patients >18 years with doctor-diagnosed asthma and at risk of poor asthma control
Comprehensive asthma assessment: asthma control was classified using a symptom and activity tool based on self-reported frequency of symptoms during the previous month

18. Poor Asthma Control Predictors
Armour C, et al. Using the community pharmacy to identify patients at risk of poor asthma control and factors which contribute to this poor control. J Asthma 2011; 48:914-22
Results:
77% patients had poor asthma control
21% smoked
19% had asthma action plan
69% used combination of ICS/LABA
17-28% used their inhaler device correctly
Adherence:
90% had their ICS or ICS/LABA dispensed <6 times in the previous 6 months

19. Poor Asthma Control Predictors
Armour C, et al. J Asthma 2011; 48:914-22

20. Poor Asthma Control Impact
Wertz D. Impact of asthma control on sleep, attendance at work, normal activities and disease burden. Ann Allergy Asthma Immunol 2010; 105:118-23
In the real world, asthmatic patients have substantially lower levels of asthma control despite the availability of effective treatments
Lower levels of asthma control are positively correlated with measures of morbidity, productivity and medical resources

21. Poor Asthma Control Impact
Wertz D. Impact of asthma control on sleep, attendance at work, normal activities and disease burden. Ann Allergy Asthma Immunol 2010; 105:118-23
Patients aged years enrolled in commercially insured health plans, with at least one medical claim for asthma and one pharmacy claim of asthma controller medication in the last year (Aug 2006)
Survey of 56 items:
21 → for control status (Asthma Therapy Assessment Questionnaire (ATAQ),
9 → extent of disease impact on work and regular activities (Work Productivity and Activity Impairment-Asthma Questionnaire),
15 → Quality of life (Mini Asthma Quality of life Questionnaire)

22. Poor Asthma Control Impact
Baseline Characteristics of the 1,199 Survey Patients
Well-controlled patients
(ATAQ=0) (12%)
Not well-controlled patients
(ATAQ=1-2) (77%)
Very poorly controlled patients
(ATAQ=3-4) (11%)
Comorbid conditions (%)
Insomnia
10.3
8.0
16.2
Depression
17.1
16.7
28.5
Coronary heart disease
2.1
3.1
6.2
Allergies
82.9
86.9
83.8
ATAQ: Asthma Therapy Assessment Questionnaire
Wertz D. Ann Allergy Asthma Immunol 2010;105:118-23

23. Poor Asthma Control Impact
Patient-Reported Asthma Severity
Well-controlled patients
(ATAQ=0) (12%)
Not well-controlled patients
(ATAQ=1-2) (77%)
Very poorly controlled patients
(ATAQ=3-4) (11%)
Asthma severity (%)
Mild
77.4
63.3
23.1
Moderate
20.5
33.2
60.8
Severe
2.1
3.6
16.2
ATAQ: Asthma Therapy Assessment Questionnaire
Wertz D. Ann Allergy Asthma Immunol 2010;105:118-23

24. Poor Asthma Control Impact
Work Productivity and Activity Impairment-Asthma (WPAI-Asthma) Questionnaire
Well-controlled patients
(ATAQ=0) (12%)
Not well-controlled patients
(ATAQ=1-2) (77%)
Very poorly controlled patients
(ATAQ=3-4) (11%)
WPAI-Asthma metric: professional (%)
Work time missed
0.70
3.07
11.92
Impairment while working
10.65
13.62
26.48
Overall work impairment
10.74
14.11
27.55
ATAQ: Asthma Therapy Assessment Questionnaire
Wertz D. Ann Allergy Asthma Immunol 2010;105:118-23

25. Poor Asthma Control Impact
Neffen H. Asthma control in Latin America: The Asthma Insights and Reality in Latrin America (AIRLA) survey. Rev Panam Salud Publica/Pan Am J Health 17;191-7
2.184 adults or parents of children with asthma in 11 Latin American countries in 2003
Daytime asthma symptoms were reported by 56% of respondents
Night wakening by 51% of respondents
>50% had been hospitalized, attended hospital emergency service or made unscheduled emergency visit to healthcare facilities during the previous year

26. Poor Asthma Control Impact
Neffen H. Asthma control in Latin America: The Asthma Insights and Reality in Latrin America (AIRLA) survey. Rev Panam Salud Publica/Pan Am J Health 17;191-7
Patients with severe persistent asthma regarded their disease as being well or completely controlled (44.7%)
Only 2.4% of patients met all criteria for asthma control
Most adults (79%) and children (68%) reported that asthma symptoms limited their activities
Absence from school and work was reported by 58% of the children and 31% of adults respectively

27. Novel Approaches to Achieve Asthma Control
Patient-oriented vs. Disease-oriented management strategies
Combination of pharmacological and nonpharmacological treatment modalities
Sarver N. J Am Academy of Nurse Practitioners 2008; 21:54-65

28. Novel Approaches to Achieve Asthma Control
Solid partnerships between healthcare providers and patients
Comprehensive patient and caregiver education
Personalized written asthma action plans
Patient reported evaluation of symptoms control
Appropriate drug therapy
Strategies for improving compliance with asthma medication regimens
Treatment algorithm that outlines the facets of asthma management
Sarver N. J Am Academy of Nurse Practitioners 2008; 21:54-65

29. Novel Approaches to Achieve Asthma Control
Solid partnerships between healthcare providers and patients:
Establishing open communications
Identifying patient and family concerns regarding asthma control and treatment
Identifying patient and family treatment preferences regarding options and barriers to its implementation
Developing treatment goals together with patients and family
Encouraging active self-assessment and self-management of asthma
National Heart Lung and Blood Institute & National Asthma Education and
Prevention Program 2007

30. Summary
Although the goal of asthma management is to achieve and maintain overall disease control while minimizing adverse events, many patients’ symptoms are not well controlled despite the availability of effective, well-tolerated therapies and evidence-based guidelines containing treatment recommendations
More effective oversight and modification of asthma treatment needs to be targeted to asthmatic patients to improve asthma control and decrease impairment of patients’ quality of life and functional capacity