8. Children’s Healthcare of Atlanta
• Smoking cessation is the single most effective
and cost-effective intervention to reduce the
risk of developing COPD and stop its
progression (Evidence A) .
9. Children’s Healthcare of Atlanta
COPD progression
Age (year)
FEV1%ofvalueatage25yr
100
75
50
25
5025 75
Death
Disability
Adapted from:Fletcher C,et al.Br Med J.1977;1:1645-1648
Nonsmokers
20-30 ml/year
COPD
60 mL/year
Symptoms
16. Children’s Healthcare of Atlanta
V
BD
Air flowDeflation
Improvement in flow – FEV1
Improvement in volumes – FVC and IC
Bronchodilator therapy deflates the lung
BD = bronchodilator; V = ventilation; FEV1= forced expiratory volume in 1 second;
FVC= forced vital capacity; IC = inspiratory capacity
17. 17
Expiratory flow-limitation and lung hyperinflation that are only partially reversible to
bronchodilator therapy are pathophysiological hallmarks of COPD
18. • Bronchodilators have been shown to have beneficial
effects in COPD patients on:
Bronchodilators
Symptoms
Quality of life
Exacerbations
(sudden worsening)
COPD, chronic obstructive pulmonary disease
Ferro TJ. Clinical Pulmonary Medicine 2005;12(4 Suppl):S13-S15;
Decramer M. Eur Respir Rev 2006;15(99):51-57.
45. Children’s Healthcare of Atlanta
Proskocil BJ et al. Proc Am Thorac Soc. 2005;2(4):305-310.
SMC relaxationSMC contraction
M3- muscarinic
receptors
Beta Agonists
(LABA)Antocholinergics
(LAMA)
β2-adrenergic
receptors
Mechanisms of action of bronchodilators
on airway smooth muscle
77. Children’s Healthcare of Atlanta
GOLD report 2017:
Current pathways to the diagnosis of COPD
Symptoms to
consider
COPD
•Dyspnoea
•Chronic cough
or
•Sputum
production
Symptoms to
consider
COPD
•Dyspnoea
•Chronic cough
or
•Sputum
production
Spirometry (post-bronchodilator)
FEV1/FVC <0.7 confirms the presence of airway limitation
and/or
history of
exposure to
risk factors
and/or
history of
exposure to
risk factors
Spirometry: Required to establish diagnosis
Symptoms
•Shortness of
breath
•Chronic cough
•Sputum
Risk factors
•Host factors
•Tobacco
•Occupation
•Indoor/outdoor
pollution
78. Children’s Healthcare of Atlanta
(Diagnosis and initial assessment)
Refined A, B, C, D assessment tool: overview
(C) (D)
(A) (B)
FEV1 (%
predicted)
GOLD 1 ≥ 80%
GOLD 2 50-79
GOLD 3 30-49
GOLD 4 < 30
Post-
bronchodilator
FEV1/FVC < 0.7
Post-
bronchodilator
FEV1/FVC < 0.7
≥ 2 or ≥ 1
leading to
hospital
admission
≥ 2 or ≥ 1
leading to
hospital
admission
0 or 1
(not leading
to hospital
admission)
0 or 1
(not leading
to hospital
admission)
Spirometrically
confirmed
diagnosis
Spirometrically
confirmed
diagnosis
Assessment of
airflow
limitation
Assessment of
airflow
limitation
Assessment of
symptoms/risk
of exacerbations
Assessment of
symptoms/risk
of exacerbations
Exacerbation
history
Symptoms
CAT < 10 CAT > 10
mMRC 0–1 mMRC > 2
79. Children’s Healthcare of Atlanta
ABCD assessment 2017 has been refined: Spirometry
Spirometry is still relevant
for:
•Diagnosis
•Prognostication
•Treatment with non-
pharmacological therapies
Classification unchanged!
FEV1 (%
predicted)
GOLD 1 ≥ 80%
GOLD 2 50-79
GOLD 3 30-49
GOLD 4 < 30
Post-
bronchodilator
FEV1/FVC < 0.7
Post-
bronchodilator
FEV1/FVC < 0.7
Spirometrically
confirmed
diagnosis
Spirometrically
confirmed
diagnosis
Assessment of
airflow
limitation
Assessment of
airflow
limitation
80. Children’s Healthcare of Atlanta
ABCD assessment 2017 has been refined:
(C) (D)
(A) (B)
0 or 1
(not leading
to hospital
admission)
0 or 1
(not leading
to hospital
admission)
Assessment of
symptoms/risk
of exacerbations
Assessment of
symptoms/risk
of exacerbations
Exacerbation
history
Symptoms
CAT < 10 CAT > 10
mMRC 0–1 mMRC > 2
Assessment of A, B, C, D and
therapy recommendations
are based exclusively on:
Respiratory symptoms
Exacerbation history
≥ 2 or ≥ 1
leading to
hospital
admission
≥ 2 or ≥ 1
leading to
hospital
admission
85. 85
Bronchodilators
Continue , stop or
try alternative
class of
bronchodilators
Evaluate effect
Group A Group B
A long – acting bronchodilators
( LABA or LAMA )
LAMA + LABA
Persistent
Symptoms
Group C
LAMA
LAMA + LABA LABA + ICS
Further
exacerbation(s)
Group D
LAMA LAMA + LABA LABA + ICS
LAMA
+ LABA
+ ICS
Consider Roflumilast
if FEV1 50% pred.˂
And patient has
chronic bronchitis
Consider
macrolides in
former smokers
Further exacerbation(s)
Further
exacerbation(s)
Persistent
Symptoms / further
exacerbation(s)
86. Children’s Healthcare of Atlanta
Pharmacologic treatment in detail:
GOLD Group A patients
(A)
Continue, stop or try
alternative class of
bronchodilator
Continue, stop or try
alternative class of
bronchodilator
A bronchodilatorA bronchodilator
Evaluate effect
GOLDGroup A
As a preferred choice all group
A patients should be offered a
short- or a long-acting
bronchodilator (dependent on its
effect on breathlessness).
Continuation with treatment if
symptomatic benefit is
documented
If necessary, an alternative class
of bronchodilator can be used if
benefit is not achieved with the
first.
GOLDGroup A
As a preferred choice all group
A patients should be offered a
short- or a long-acting
bronchodilator (dependent on its
effect on breathlessness).
Continuation with treatment if
symptomatic benefit is
documented
If necessary, an alternative class
of bronchodilator can be used if
benefit is not achieved with the
first. In patients with a majordiscrepancy between the perceived level of
symptoms
and severity of airflow limitation, furtherevaluation is warranted
87. Children’s Healthcare of Atlanta
Preferred
treatment
Pharmacologic treatment in detail:
GOLD Group B patients
(B)
A long-acting
bronchodilator
(LABA or LAMA)
A long-acting
bronchodilator
(LABA or LAMA)
Persistent
symptoms
LAMA + LABALAMA + LABA
GOLD Group B
Although a long-acting
bronchodilator is yet
recommended as initial
therapy, LAMA/LABA are
recommended
- if symptoms persist
or
- from the start in patients with
severe breathlessness
GOLD Group B
Although a long-acting
bronchodilator is yet
recommended as initial
therapy, LAMA/LABA are
recommended
- if symptoms persist
or
- from the start in patients with
severe breathlessness
In patients with a majordiscrepancy between the perceived level of
symptoms
and severity of airflow limitation, furtherevaluation is warranted
88. 88
For Group B patients, therapy should begin with a long-
acting bronchodilator LABA or LAMA , (no evidence to
recommend one over another), and should be escalated
to two bronchodilators if breathlessness continues with
monotherapy.
If breathlessness is severe, starting the patient on dual
long-acting bronchodilators can be considered, however
if the second therapy does not improve symptoms, the
guidelines suggest stepping down to one bronchodilator.
89. Children’s Healthcare of Atlanta
(C)
LAMA + LABALAMA + LABA LABA + ICSLABA + ICS
LAMALAMA
Further
exacerbation(s)
Pharmacologic treatment in detail:
GOLD Group C patients
Preferred
treatment
GOLD Group C
Starting therapy with a LAMA
In case of persistent
exacerbations addition of a
LABA LAMA/LABA as
first choice
(LABA/ICS could be an
alternative but patients are on
higher risk for developing
pneumonia)
GOLD Group C
Starting therapy with a LAMA
In case of persistent
exacerbations addition of a
LABA LAMA/LABA as
first choice
(LABA/ICS could be an
alternative but patients are on
higher risk for developing
pneumonia)
In patients with a majordiscrepancy between the perceived level of
symptoms
and severity of airflow limitation, furtherevaluation is warranted
90. 90
For Group C patients, it is recommended that treatment be
started with a single long-acting bronchodilator,
preferably a LAMA (LAMA was superior to the LABA
regarding exacerbation prevention).
A second long-acting bronchodilator or the combination of
LABA/ICS may be used for persistent exacerbations;
The guidelines recommend LABA/LAMA as the addition of
ICS has been shown to increase pneumonia risk in some
patients.
91. Children’s Healthcare of Atlanta
The use of ICS-containing therapies in COPD
• Compared to non-ICS-containing therapies in COPD,
therapies containing ICS, eg, LABA/ICS FDC are
associated with greater risk of:
– Pneumonia1-6
– Bone density decline and fractures7-10
– Candidiasis and skin lesions6,11,12
– Cataracts13
• Evidence linking ICS-containing therapies with
increased risk of diabetes mellitus14,15
1. Calverley PM, et al. N Engl J Med. 2007;356:775-789. 2. Crim C, et al. Eur Respir J. 2009;34:641-647;
3. Drummond MB, et al. JAMA. 2008;300:2407-2416;
4. Rodrigo GJ, et al. Chest. 2009;136:1029-1038. 5. Singh S, Loke YK. Curr Opin Pulm Med. 2010;16:118-122;
6. Yang IA, et al. Cochrane Database Syst Rev. 2012;7:CD002991. 7. Lung Health Study Research Group. N Engl J Med. 2000;343:1902-1909;
8. Scanlon PD, et al. Am J Respir Crit Care Med. 2004;170:1302-1309. 9. Hubbard R, et al. Chest. 2006;130:1082-1088;
10. Loke YK, et al. Thorax. 2011;66:699-708. 11. Alsaeedi A, et al. Am J Med. 2002;113:59-65;
12. Mahler DA, et al. Am J Respir Crit Care Med. 2002;166:1084-1091;
13. Weatherall M, et al. Respirology. 2009;14:983-990;
14. O’Byrne PM, et al. Respir Med. 2012;106:1487-1493;
15. Suissa S, et al. Am J Med. 2010;123:1001-1006.
COPD, chronic obstructive pulmonary disease; FDC, fixed-dose combination;
ICS, inhaled corticosteroid; LABA, long-acting β2-agonist
92. Children’s Healthcare of Atlanta
Pharmacologic treatment in detail:
GOLD Group D patients
(D)
LAMA + LABALAMA + LABALAMALAMA
LAMA +
LABA + ICS
LAMA +
LABA + ICS
Further
exacerbation(s)
Further
exacerbation(s)
Consider roflumilast
if FEV1 <50% pred.
and patient has
chronic bronchitis
Consider roflumilast
if FEV1 <50% pred.
and patient has
chronic bronchitis
Consider
macrolide
(in former
smokers)
Consider
macrolide
(in former
smokers)
Persistent
symptoms/further
exacerbation(s)
De-escalation from ICS containing to
LAMA/LABA treatments if ICS
shows lack of efficacy!
GOLD Group D
•LAMA/LABA is recommended from the
start
-Since a LAMA/LABA combination was superior to a
LABA/ICS combination in preventing exacerbations and
other patient reported outcomes in group D patients
-as the default treatment for patients who are de-
escalated from ICS-containing treatments
•For patients with a history and/or findings of
concurrent asthma, LABA/ICS may be the first
choice
•For patients who develop further exacerbations
on LAMA/LABA two alternatives are suggested
-Escalation to triple therapy
-Switch to LABA/ICS (but no evidence that switching from
LAMA/LABA results in better exacerbation prevention)
GOLD Group D
•LAMA/LABA is recommended from the
start
-Since a LAMA/LABA combination was superior to a
LABA/ICS combination in preventing exacerbations and
other patient reported outcomes in group D patients
-as the default treatment for patients who are de-
escalated from ICS-containing treatments
•For patients with a history and/or findings of
concurrent asthma, LABA/ICS may be the first
choice
•For patients who develop further exacerbations
on LAMA/LABA two alternatives are suggested
-Escalation to triple therapy
-Switch to LABA/ICS (but no evidence that switching from
LAMA/LABA results in better exacerbation prevention)
In patients with a majordiscrepancy between the perceived level of
symptoms
and severity of airflow limitation, further evaluation is warranted
LABA + ICSLABA + ICS
93. 93
For Group D patients, a LABA/LAMA combination is
preferred as initial therapy over LABA/ICS as these patients
may be at higher risk of developing pneumonia with ICS
use.
For patients with high blood eosinophil counts or those
with asthma-COPD overlap, LABA/ICS could be considered
first-line therapy.
94. 94
In patients who develop further exacerbations on
LABA/LAMA therapy we suggest two alternative
pathways:
1.Escalation to LABA/LAMA/ICS (Triple therapy).
2.Switch to LABA/ ICS
If LABA/ICS therapy does not positively impact
exacerbations/symptoms a LAMA can be added.
95. 95
• For patients who still have exacerbations with
LABA/LAMA/ICS, the following three options can be
considered:
• 1) adding roflumilast (for patients with FEV1<50% predicted
and chronic bronchitis)
• 2) adding a macrolide (azithromycin preferred, however,
antibiotic resistance should be factored in decision-
making)
• 3) discontinuing ICS.
99. Children’s Healthcare of Atlanta
The use of ICS-containing therapies in COPD
• Bronchodilators are central to symptom management in
COPD
– GOLD 2017 guidelines recommend bronchodilators in all
patients with COPD
• ICS-containing therapies currently over-used in management of COPD
– More than 70% of patients with COPD are currently receiving an
ICS-containing therapybut, based on GOLD guidelines, this should be
less than 20%
– ICS should be reserved for those patients in whom additional
bronchodilation is failing to control their exacerbations
• ICS in combination with LABA have limited role in COPD
1. Barnes PJ. Chest. 2000;117(2 Suppl):10S-14S;
2. Global Strategy for the
103. 103
6-7 0
S
C
R
E
E
N
I
N
G
Treatment
52Week -6
ICS
(remained on triple therapy from run-in)
Stepwise ICS withdrawal
(remained on dual bronchodilator)
Run-in
Triple
therapy
12
R
A
N
D
O
M
I
S
A
T
I
O
N
ICS stepwise withdrawal Stable
treatment
Reduced to 250 µg BID
Reduced to 100 µg BID
Reduced to 0 µg (placebo)
Fluticasone propionate 12-week
withdrawal schedule
500 µg BID
18
• Tiotropium 18 µg QD
• Salmeterol 50 µg BID
• Fluticasone propionate 500 µg BID
Triple therapy
regimen
WISDOM: Study design
104. 104
With a controlled, stepwise withdrawal of ICS , the risk
of exacerbation would be similar to that with continued
use of ICS in patients with severe or very severe COPD
who were receiving a combination of a LAMA
(tiotropium) and a LABA (salmeterol).
WISDOM Study Results
107. 107
ICS are not recommended as monotherapy in COPD .
ICS-containing pharmaceutical regimens no longer
recommended as first-choice treatments for COPD of any
severity .
In addition, the new GOLD Strategy suggests that ICS therapy
may be withdrawn safely (de-escalation path ) in people with
COPD who are in GOLD group D and stable, by using a
LAMA/LABA regimen.
108. 108
The updated 2017 GOLD Strategy now positions a combination
of a LAMA (long-acting muscarinic receptor antagonists ) and
a LABA (long-acting beta2-agonist), as a mainstay treatment
for people with COPD in GOLD groups B-D.
This represents a significant change versus previous GOLD
guidelines.
109. 109
LAMA/LABA combination plays a central role in COPD management in GOLD
2017 updates and with more restriction on ICS use
LAMA/LAB
A plays a
critical,
central role
for GOLD
groups B-D
Limited role
of ICS in
Group C and
D
Group A
and B
completely
ICS-free
A diagnosis of COPD should be considered in any patient who has cough, sputum production, or dyspnea and/or a history of exposure to risk factors. The diagnosis is confirmed by spirometry.
To help identify individuals earlier in the course of disease, spirometry should be performed for patients who have chronic cough and sputum production even if they do not have dyspnea.
Spirometry is the best way to diagnose COPD and to monitor its progression and health care workers to care for COPD patients should have assess to spirometry.
Key indicators to consider the presence of COPD in an individual patient over the age of 40 are
symptoms with persistent and progressive dyspnoea as the leading symptom of the disease and furthermore cough with or without sputum production
Exposure to risk factors: genetic factors, congenital/developmental disabilities, tobacco smoke/smoke from home cooking/heting fuels, occupational dusts, fumes gases etc.
Spirometry: in the refined assessment process, patients should undergo spirometry to confirm the diagnosis of COPD and to assess the extent and reversibility of airflow limitation. Spirometry is not longer recommended for pharmacological treatment decisions
Furthermore spirometry is a usefool tool for prognosis and non-pharmacological therapies
Spirometry:
Classification as such hasn´t been changed
in the refined assessment process, patients should undergo spirometry to confirm the diagnosis of COPD and to assess the extent and reversibility of airflow limitation The current classification hasn´t changed and is in accordance with the previous classification.
is not longer recommended for pharmacological treatment decisions
Furthermore spirometry is a usefool tool for prognosis and non-pharmacological therapies
is not recommended as a screening tool in asymptomatic individuals whereas in those with specific symptoms or risk factors the diagnostic yield is relatively high and spirometry should be considered as a method for early case finding
Patients at a higher risk of developing pneumonia
current smokers
≥ 55 years of age
history of prior exacerbations or pneumonia
body mass index (BMI) &lt; 25 kg/m2
poor MRC dyspnoe grade
and/or severe airflow limitation
Reference:
Crim C et al Ann ATS 2015; 12:27-34
References
1. Barnes PJ. Chest 2000; 117(2 Suppl): 10S-4S.
2. Suissa S, Barnes PJ. Eur Respir J 2009; 34: 13–16.
3. Barnes P.J. Respiration 2010; 80: 89–95.
4. Calverley PM et al. N Engl J Med. 2007; 356(8): 775-89.
5. Crim C et al. Eur Respir J. 2009; 34(3): 641-7.
6. Ernst P et al. Eur Respir J. 2006; 27(6): 1168-74.
7. Drummond MB et al. JAMA. 2008; 300(20): 2407-16.
8. Rodrigo GJ et al. Chest. 2009; 136(4): 1029-38.
9. Singh S, Loke YK. Curr Opin Pulm Med. 2010; 16(2): 118-22.
10. Yang IA et al. Cochrane Database Syst Rev. 2012; 7: CD002991.
11. Lung Health Study Research Group. N Engl J Med. 2000; 343(26): 1902-9.
12. Scanlon PD et al. Am J Respir Crit Care Med. 2004; 170(12):1302-9.
13. Hubbard R et al. Chest. 2006; 130(4):1082-8.
14. Loke YK et al. Thorax. 2011; 66(8):699-708.
15. Alsaeedi A et al. Am J Med. 2002; 113(1): 59-65.
16. Mahler DA et al. Am J Respir Crit Care Med. 2002; 166(8): 1084-91.
17. Weatherall M et al. Respirology. 2009; 14(7): 983-90.
18. O&apos;Byrne PM, et al. Respir Med. 2012; 106(11):1487-93
19. Suissa S, et al. Am J Med 2010; 123 (11): 1001-06
LAMA/LABA is recommended from the start in Group D patients
since a LAMA/LABA combination was superior to a LABA/ICS combination in preventing exacerbations and other patient reported outcomes in group D patients
as the default treatment for patients who are de-escalated from ICS-containing treatments
Group D patients are on higher risk of developing pneumonia when receiving ICS containing treatment
In some patients initial therapy with LAMA/LABA may be the first choice. These patients may have a history and/or findings of a concurrent asthma.
Potentially high blood eosinophils may also be taken into consideration to support the use of ICS containing treatment – however this is still under debate
In patients suffering from further exacerbations despite LAMA/LABA therapy 2 alternative options are suggested:
Escalation to LAMA/LABA/ICS (triple) therapy
Switch to LABA/ICS although there is no evidence that this will result in a better exacerbation prevention. If there is no positive effect on exacerbations a LAMA can be administered in addition
If patients treated with triple therapy still have exacerbations the following options may be considered:
Add roflumilast (in patients with FEV1&lt; 50% predicted and chronic bronchitis)
Long-term treatment with a macrolide (best available evidence for azithromycin but there is a risk of development of hearing loss).
Withdrawal of ICS if there is no reported benefit. Lack of efficacy, increased risk of adverse effects (pneumonia!) and existing evidence that ICS withdrawal doesn´t harm
References
1. Barnes PJ. Chest 2000; 117(2 Suppl): 10S-4S.
2. Suissa S, Barnes PJ. Eur Respir J 2009; 34: 13–16.
3. Barnes P.J. Respiration 2010; 80: 89–95.
4. Calverley PM et al. N Engl J Med. 2007; 356(8): 775-89.
5. Crim C et al. Eur Respir J. 2009; 34(3): 641-7.
6. Ernst P et al. Eur Respir J. 2006; 27(6): 1168-74.
7. Drummond MB et al. JAMA. 2008; 300(20): 2407-16.
8. Rodrigo GJ et al. Chest. 2009; 136(4): 1029-38.
9. Singh S, Loke YK. Curr Opin Pulm Med. 2010; 16(2): 118-22.
10. Yang IA et al. Cochrane Database Syst Rev. 2012; 7: CD002991.
11. Lung Health Study Research Group. N Engl J Med. 2000; 343(26): 1902-9.
12. Scanlon PD et al. Am J Respir Crit Care Med. 2004; 170(12):1302-9.
13. Hubbard R et al. Chest. 2006; 130(4):1082-8.
14. Loke YK et al. Thorax. 2011; 66(8):699-708.
15. Alsaeedi A et al. Am J Med. 2002; 113(1): 59-65.
16. Mahler DA et al. Am J Respir Crit Care Med. 2002; 166(8): 1084-91.
17. Weatherall M et al. Respirology. 2009; 14(7): 983-90.
18. O&apos;Byrne PM, et al. Respir Med. 2012; 106(11):1487-93
19. Suissa S, et al. Am J Med 2010; 123 (11): 1001-06
