Transcript Co-morbidities - Progetto LIBRA

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Is a uniform definition of
severity, control and risk
possible in chronic diseases ?
1- A novel concept of chronic
diseases
2- The example of asthma
3- Tentative uniform definition
4- Needs for a uniform definition
Is a uniform definition of
severity, control and risk
possible in chronic diseases ?
1- A novel concept of chronic
diseases
2- The example of asthma
3- Tentative uniform definition
4- Needs for a uniform definition
Socio-economic
determinants
Life style - environment
Risk and protective factors
Tobacco smoking, Pollutants
Allergens, Nutrition, Infections
Physical exercise, Others
Socio-economic
determinants
Life style - environment
Risk and protective factors
Tobacco smoking, Pollutants
Allergens, Nutrition, Infections
Physical exercise, Others
Genes
Socio-economic
determinants
Life style - environment
Risk and protective factors
Tobacco smoking, Pollutants
Allergens, Nutrition, Infections
Physical exercise, Others
Genes
Biological expression of chronic diseases
Transcripts, proteins, metabolites
Target organ local inflammation
Systemic inflammation
Cell and tissue remodelling
Clinical expression of chronic diseases
Co-morbidities
Severity of co-morbidities
Persistence, remission
Long-term morbidity
Responsiveness - side effects to treatment
Socio-economic
determinants
Life style - environment
Risk and protective factors
Tobacco smoking, Pollutants
Allergens, Nutrition, Infections
Physical exercise, Others
Genes
Biological expression of chronic diseases
Transcripts, proteins, metabolites
Target organ local inflammation
Systemic inflammation
Cell and tissue remodelling
Ageing
Clinical expression of chronic diseases
Co-morbidities
Severity of co-morbidities
Persistence, remission
Long-term morbidity
Responsiveness - side effects to treatment
Socio-economic
determinants
Life style - environment
Risk and protective factors
Tobacco smoking, Pollutants
Allergens, Nutrition, Infections
Physical exercise, Others
Genes
Biological expression of chronic diseases
Transcripts, proteins, metabolites
Target organ local inflammation
Systemic inflammation
Cell and tissue remodelling
Ageing
Clinical expression of chronic diseases
Co-morbidities
Severity of co-morbidities
Persistence, remission
Long-term morbidity
Responsiveness - side effects to treatment
Systems biology on
precise phenotypes
Socio-economic
determinants
Life style - environment
Risk and protective factors
Tobacco smoking, Pollutants
Allergens, Nutrition, Infections
Physical exercise, Others
Genes
Health promotion
Primary prevention
Systems biology on
precise phenotypes
Biological expression of chronic diseases
Transcripts, proteins, metabolites
Target organ local inflammation
Systemic inflammation
Cell and tissue remodelling
Ageing
Clinical expression of chronic diseases
Co-morbidities
Severity of co-morbidities
Persistence, remission
Long-term morbidity
Responsiveness - side effects to treatment
Personalized medicine
- Primary prevention
- Secondary prevention
- Tertiary prevention
- Treatment
Classical phenotypes
Novel phenotypes
Hypothesis-driven
Discovery driven
Patient with chronic disease
CVD
COPD
Diabetes
Co-morbidities
(standardized assessment)
Assessment of co-morbities
and severity
Severity of co-morbidities
(standardized assessment)
Classical phenotypes in
patients with severe defined diseases
and co-morbidities
Novel phenotypes in individual
patients with severe co-morbidities
of chronic diseases
Responsiveness to treatment
Follow up
Responsiveness to treatment
Follow up
Classical phenotypes
Novel phenotypes
Hypothesis-driven
Discovery driven
Patient with chronic disease
CVD
COPD
Diabetes
Co-morbidities
(standardized assessment)
Assessment of co-morbities
and severity
Severity of co-morbidities
(standardized assessment)
Classical phenotypes in
patients with severe defined diseases
and co-morbidities
Novel phenotypes in individual
patients with severe co-morbidities
of chronic diseases
Responsiveness to treatment
Follow up
Responsiveness to treatment
Follow up
Classical phenotypes
Novel phenotypes
Hypothesis-driven
Discovery driven
Patient with chronic disease
CVD
COPD
Diabetes
Co-morbidities
(standardized assessment)
Assessment of co-morbities
and severity
Severity of co-morbidities
(standardized assessment)
Classical phenotypes in
patients with severe defined diseases
and co-morbidities
Novel phenotypes in individual
patients with severe co-morbidities
of chronic diseases
Responsiveness to treatment
Follow up
Responsiveness to treatment
Follow up
Is a uniform definition of
severity, control and risk
possible in chronic diseases ?
1- A novel concept of chronic
diseases
2- The example of asthma
Asthma severity - GINA 2002
Asthma severity
Control
• Symptoms
• Functional limitation
over 2-4 weeks
• Exacerbations over 6-12 mo
Classification of asthma:
GINA 1998
Current treatment step
Step 1
Step 2
Step 3
Step 4
No controller
<500 BDP
200–1000 BDP
+ LABA
>1000 BDP +
LABA + other
Step 1
Symptoms <1 x week
Nocturnal symptoms ≤2x month
Lung function normal between episodes
Intermittent
Mild
persistent
Moderate
persistent
Severe
persistent
Step 2
Symptoms >1 x week
Nocturnal symptoms <1 x week
Lung function normal between episodes
Mild
persistent
Moderate
persistent
Severe
persistent
Severe
persistent
Step 3
Symptoms daily
Nocturnal symptoms ≥1 x week
FEV1 60–80% predicted
Moderate
persistent
Severe
persistent
Severe
persistent
Severe
persistent
Step 4
Symptoms daily
Frequent nocturnal symptoms
FEV1 <60% predicted
Severe
persistent
Severe
persistent
Severe
persistent
Severe
persistent
Clinical features
Asthma control - GINA 2006
Asthma control
Control
• Symptoms
• Functional limitation
over 2-4 weeks
• Exacerbations over 6-12 mo
GINA 2002 (severity)- 2006 (control)
Control of asthma: GINA 2006
characteristics
controlled
Partially
controlled
uncontrolled
Day time
symptoms
none
> 2 / week
3 or more
features
Limitations of
activities
none
any
of uncontrollled
asthma
Nocturnal
symptoms
none
any
present in any
week
Need for reliever
rescue medication
none
> 2 / week
Lung function
(FEV1 or PEFR)
Normal or
near normal
>80% predicted
or personal best
Exacerbations
none
≥ 1 / yr
One in any week
Asthma severity- NAEPP3 (NHLBI)
Asthma severity
Control
• Symptoms
• Functional limitation
over 2-4 weeks
• Exacerbations over 6-12 mo
Responsiveness to treatment
Future risks
• Asthma exacerbations
• Lung function loss
• Lung growth in children
• Adverse reactions from medications)
GINA 2002 - 2010
Definition of severe asthma
(Geneva, 6-7 April 2009)
Asthma severity
WHO definition
Bousquet J et al, J Allergy Clin Immunol 2010
Asthma severity
Control
• Symptoms
• Functional limitation
over 2-4 weeks
• Exacerbations over 6-12 mo
• Level of treatment
• Inhalation technique
• Compliance
Responsiveness to treatment
Future risks
• Asthma exacerbations
• Lung function loss
• Lung growth in children
• Adverse reactions from medications)
Is a uniform definition of
severity, control and risk
possible in chronic diseases ?
1- A novel concept of chronic
diseases
2- The example of asthma
3- Tentative definition
WP 6 Epigenetics and targeted
proteomics
Uniform severity of chronic diseases
Assess and regularly review CONTROL
Diagnosis of chronic disease
Underdiagnosis
Short-term
(eg exacerbation)
Long-term
(eg remodelling)
RISK
Risks due to
co-morbidities
Side effects from
treatment
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Uniform severity of chronic diseases
Diagnosis of chronic disease
Underdiagnosis
Assess and regularly review CONTROL
Patient with uncontrolled chronic disease
Is treatment/prevention effective ?
NO
Short-term
(eg exacerbation)
Long-term
(eg remodelling)
RISK
Risks due to
co-morbidities
Side effects from
treatment
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Uniform severity of chronic diseases
Diagnosis of chronic disease
Underdiagnosis
Assess and regularly review CONTROL
Patient with uncontrolled chronic disease
Is treatment/prevention effective ?
Is treatment available and affordable ?
NO
Short-term
(eg exacerbation)
Untreated
severe disease
Long-term
(eg remodelling)
RISK
Risks due to
co-morbidities
Side effects from
treatment
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Uniform severity of chronic diseases
Diagnosis of chronic disease
Underdiagnosis
Assess and regularly review CONTROL
Patient with uncontrolled chronic disease
Is treatment/prevention effective ?
Is treatment available and affordable ?
NO
Short-term
(eg exacerbation)
Untreated
severe disease
Long-term
(eg remodelling)
Treat according to guidelines
Check if diagnosis is correct
OR if there are other associated diseases
Possible risk
due to other
disease
RISK
Risks due to
co-morbidities
Side effects from
treatment
No asthma
Re-check
asthma
diagnosis
Diagnosis
Severe asthma
due to occupational expoure
to isocyanates
OR
NO
Asthma PLUS another condition
causing current symptoms
No asthma
Re-check
asthma
diagnosis
OR
NO
Asthma PLUS another condition
causing current symptoms
Visit for coarse voice due to high dose ICS (and dyspnea) in a severe asthmatic
FEV1: 1.78 l (72%), post-ß2: 1.92 (+5%), FEV1/FVC: 66%
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Uniform severity of chronic diseases
Diagnosis of chronic disease
Underdiagnosis
Assess and regularly review CONTROL
Patient with uncontrolled chronic disease
Is treatment/prevention effective ?
Is treatment available and affordable ?
NO
Short-term
(eg exacerbation)
Untreated
severe disease
Long-term
(eg remodelling)
Treat according to guidelines
Check if diagnosis is correct
OR if there are other associated diseases
Possible risk
due to other
disease
Check co-morbidies, risk factors
compliance and/or treatment administration
Difficult-to-treat
disease
RISK
Risks due to
co-morbidities
Side effects from
treatment
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Uniform severity of chronic diseases
Diagnosis of chronic disease
Underdiagnosis
Assess and regularly review CONTROL
Patient with uncontrolled chronic disease
NO
Is treatment/prevention effective ?
Short-term
(eg exacerbation)
Untreated
severe disease
Is treatment available and affordable ?
Long-term
(eg remodelling)
Treat according to guidelines
Check if diagnosis is correct
OR if there are other associated diseases
Possible risk
due to other
disease
Check co-morbidies, risk factors
compliance and/or treatment administration
Difficult-to-treat
disease
Treat to the highest recommended dose
Severe disease controlled
with optimal treatment
RISK
Risks due to
co-morbidities
Side effects from
treatment
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Uniform severity of chronic diseases
Diagnosis of chronic disease
Underdiagnosis
Assess and regularly review CONTROL
Patient with uncontrolled chronic disease
NO
Is treatment/prevention effective ?
Short-term
(eg exacerbation)
Untreated
severe disease
Is treatment available and affordable ?
Long-term
(eg remodelling)
Treat according to guidelines
Check if diagnosis is correct
OR if there are other associated diseases
Possible risk
due to other
disease
Check co-morbidies, risk factors
compliance and/or treatment administration
Difficult-to-treat
disease
Treat to the highest recommended dose
Severe disease uncontrolled
despite optimal treatment
Severe disease controlled
with optimal treatment
RISK
Risks due to
co-morbidities
Side effects from
treatment
Uniform severity of chronic diseases
Asthma
Diabetes
Underdiagnosis
Risk of acute exacerbation
Risk of coma and death
Effective treatment
ICS -ß2 agonists
Insulin, oral drugs
No treatment
available/affordable
Risk of acute exacerbation
Risk of coma and death
Incorrect diagnosis
(example)
COPD (adults)
CF (children)
Other coma
Difficult-to-treat disease
Compliance
Inhaler misuse
Risk factors (tobacco,
allergen)
Compliance
Complications
Risk factors (diet, tobacco)
Controlled treatment
dependent disease
Risk of exacerbation when
treatment stopped
Risk of death when
treatment stopped
Uncontrolled treatment
resistant disease
Risk of severe exacerbation
Insulin-resistant diabetes
Is a uniform definition of
severity, control and risk
possible in chronic diseases ?
1- A novel concept of chronic
diseases
2- The example of asthma
3- Tentative uniform definition
4- Needs for a uniform definition
Applicability of the definition
• Public health: to improve the quality of allergy care,
but also to optimize health care planning and policies.
• Clinical practice: simplicity for physicians
• Clinical trials
• Research: Well characterized approved phenotypes
• Epidemiologic studies: Well characterized approved phenotypes
• Drug development
• Applicable to developed and developing countries
• Registries
One step in the phenotype complexity
By courtesy from J Kiley
One step in the phenotype complexity
By courtesy from J Kiley