Transcript case study: a 63-year-old man with moderate/ severe

Dr. Prayudi Santoso, SpPD-KP, M.Kes,FCCP, FINASIM
E-mail: [email protected]
Education :
MD
Internal Med
Pulmonology Consultant
MSc
Medical School, Padjadjaran University, Bandung, Indonesia
Medical School, Padjadjaran University, Bandung, Indonesia
Collegiums of Internal Medicine, Indonesia
Medical School, Padjadjaran University, Bandung Indonesia
Occupation :
Staf of Respirology Division & Critical Care Internal Medicine, Faculty of Medicine Padjadjaran
university/Hasan Sadikin General Hospital, Indonesia
Coordinator of MDR-TB Team Hasan Sadikin General Hospital Bandung, Indonesia
Organization :
Society of Internal Medicine West Java, - Indonesia
Society of Respirologi Indonesia (PERPARI)
Fellow American College of Chest Physcian (ACCP)
Member European Respiratory Society (ERS)
The Role of Salmeterol Fluticasone
Propionate Combination in the
Prevention of Future COPD Exacerbation
Prayudi Santoso
Internal Medicine Department, Division of Pulmonary and
Critical Care, Hasan Sadikin Hospital,
University of Padjadjaran Medical School
Bandung Indonesia
2016
[email protected]
CASE STUDY : A 63-YEAR-OLD MAN WITH MODERATE/
SEVERE COPD AND A CHEST INFECTION
• A 63-year-old self-employed plumber makes a same-day
appointment for another ‘chest infection’. He caught an upper
respiratory tract infection from his grandchildren 10 days ago,
and he now has a productive cough with green sputum, and his
breathlessness and fatigue has forced him to take time off work.
• He has visited his general practitioner with similar symptoms two
or three times every year in the last decade.
• A diagnosis of COPD was confirmed 6 years ago, and he was
started on a short acting β2-agonist. This helped with his day-today symptoms, although recently the symptoms of
breathlessness have been interfering with his work and he has to
pace himself to get through the day.
Tsiligianni, NPJPCRM 2015; 25, 15023
CASE STUDY : A 63-YEAR-OLD MAN WITH MODERATE/
SEVERE COPD AND A CHEST INFECTION
• Recovering from exacerbations takes longer than it used to—
it is often 2 weeks before he is able to get back to work—and
he feels bad about letting down customers.
• He cannot afford to retire, but is thinking about reducing his
workload.
• He last attended a COPD review 6 months ago when his FEV1
was 52% predicted. He was advised to stop smoking and did
not return for the follow-up appointment.
• He attends each year for his ‘flu vaccination’.
• His only other medication is an ACE inhibitor for hypertension.
Tsiligianni, NPJPCRM 2015; 25, 15023
COPD therapeutic goals
• COPD encompasses a complex group of disorders
• There is a need for treatment individualisation
• Key therapeutic goals are to:
Reduce symptoms
•
•
•
Relieve symptoms
Improve exercise tolerance
Improve health status
Reduce risk
•
•
•
Prevent disease progression
Prevent exacerbations
Reduce mortality
1. Adapted from: Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease
(GOLD) 2014. Available from: http://www.goldcopd.org/.2; 3. Marsh SE et al. Thorax 2008;63:761-767
Managing the presenting problem. Is it really
COPD exacerbation?
• A COPD exacerbation is defined as ‘an acute event
characterised by a worsening of the patient’s respiratory
symptoms that is beyond normal day-to-day variation and
leads to change in medications.
• The worsening symptoms are usually increased dyspnoea,
increased sputum volume and increased sputum purulence.
1. Tsiligianni, NPJPCRM 2015; 25, 15023; 2. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for
Chronic Obstructive Lung Disease (GOLD) 2014. Available from: http://www.goldcopd.org/.2.
Acute Exacerbation Management
• Short-term use of systemic corticosteroids and a course of
antibiotics can shorten recovery time, improve lung function
(FEV1) and arterial hypoxaemia and reduce the risk of early
relapse, treatment failure and length of hospital stay.
• SABA with or without SAMA are usually the preferred
bronchodilators for the treatment of an acute exacerbation.
Tsiligianni, NPJPCRM 2015; 25, 15023
Systemic Corticosteroid in the
management of exacerbation
Systemic corticosteroids:
• Shorten recovery time, improve lung function and arterial
hypoxemia
• Reduce risk of early relapse, treatment failure and length of
hospital stay
– A dose of 40mg/day prednisone for 5 days is recommended (Evidence B)
– However, data are insufficient to confirm optimal duration of therapy of acute
exacerbations
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2014. Available from: http://www.goldcopd.org/.2.
Antibiotics should be given to patients with a
COPD exacerbation
Antibiotics should be given to patients with a COPD exacerbation
with:1
– 3 cardinal symptoms (increased dyspnoea, sputum volume and sputum
purulence)
– 2 cardinal symptoms
• if increased purulence is one of the two symptoms OR
• Mechanical ventilation (invasive or non-invasive) is required
• The recommended duration of therapy is 5–10 days
• Choice of antibiotic should be based on local bacterial
resistance
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2014. Available from: http://www.goldcopd.org/.2.
Reviewing the Routine Treatment
• One of the concerns about this patient is that his COPD is
inadequately treated.
• The Global Initiative for Chronic Obstructive Lung Disease
(GOLD) suggests that COPD management be based on a
combined assessment of symptoms, GOLD classification of
airflow limitation, and exacerbation rate.
• The COPD Assessment Tool (CAT) could be used to evaluate
the symptoms/health status.
Tsiligianni, NPJPCRM 2015; 25, 15023
Global Strategy for Diagnosis, Management and Prevention of COPD
4
(C)
or
> 1 leading
to hospital
admission
(D)
3
1 (not leading
to hospital
admission)
2
(A)
(B)
1
0
CAT < 10
CAT > 10
SymptomsmMRC > 2
mMRC 0–1
Breathlessness
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2014. Available from: http://www.goldcopd.org/.2. © 2015 Global Initiative for Chronic Obstructive Lung Disease
(Exacerbation history)
≥2
Risk
(GOLD Classification of Airflow Limitation))
Risk
Combined Assessment of COPD
Prevent future exacerbation
• The fact that he had two to three exacerbations per year puts
the patient into GOLD category C–D despite the moderate
airflow limitation (FEV1 52% predicted).
• This patient is only being treated with short-acting
bronchodilators; however, this is only appropriate for patients
who belong to category A.
• This patient are ‘frequent exacerbator’ type of patient so we
need to choose the right treatment to prevent future
exacerbation.
Tsiligianni, NPJPCRM 2015; 25, 15023
NON-PHARMACOLOGICAL
APPROACH
Non-medication options1
•
•
•
•
Smoking cessation1
Pulmonary rehabilitation1
Influenza and pneumococcal vaccination1
Reduction in biomass fuel exposure1
Patient group
(GOLD)
Essential
Recommended
Depends on local
guidelines
A
Smoking cessation
Physical activity
Flu vaccination
Pneumococcal
vaccination
B–D
Smoking cessation
Pulmonary rehabilitation
Physical activity
Flu vaccination
Pneumococcal
vaccination
1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2014. Available from: http://www.goldcopd.org/.2.
Smoking cessation significantly reduces
mortality at 14.5 years
Sustained Quitter
Intermittent Quitter
Continuing Smokers
Rate of Death per 1000
Person-Years
4
3
2
1
0
CHD
CVD
Lung
Cancer
Other
Cancer
Respiratory
Disease
Causes of Death
CHD: coronary heart disease; CVD: cardiovascular disease
Athonisen et al. Ann Intern Med 2005;142(4):233-239
Other
Unknown
Lung Health Study
• A 5-year, randomised clinical study with 5,887 male and
female smokers, aged 35 to 60 years, with spirometric
signs of early chronic obstructive pulmonary disease,
showed:
– Aggressive smoking intervention programme significantly
reduces the age-related decline in FEV1
– Use of an inhaled anticholinergic bronchodilator results in a
relatively small improvement in FEV1 that appears to be
reversed after the drug is discontinued
– Use of the bronchodilator did not influence the long-term decline
of FEV1
Anthonisen NN et al. JAMA 1994;272(19):1497-505
Quitting smoking is associated with better
survival rates than continuous smoking in COPD:
Lung health study
FEV1 51–70%
FEV1 26–50%
FEV1 <25%
Adapted from Pelkonen M et al. Chest. 2006;130(4):1129-37
Thirty-year cumulative
incidence of chronic
bronchitis and COPD in 582
Finnish men7
PHARMACOLOGICAL APPROACH
Treatment choice based on GOLD
Lung Function
GOLD 4
D
ICS + LABA
or
LAMA
GOLD 3
A
B
GOLD 2
GOLD 1
2 or more
or
> 1 leading
to hospitalization
ICS + LABA
and/or
LAMA
SAMA prn
or
SABA prn
LABA
or
LAMA
1 (not leading to
hospitalization)
0
CAT < 10
CAT > 10
mMRC 0-1
mMRC > 2
© 2015 Global Initiative
for Chronic Obstructive Lung Disease
Symptoms
Exacerbations per year
C
ICS in the COPD treatment
• The recommendation for patient in C and D category is
the addition of ICS to the treatment of COPD
• LABA with ICS can reduce the number of exacerbation
and hospitalization risk
• Long term treatment with ICS is recommended to
moderate/severe COPD patient with high risk of
exacerbation which are no longer adequately managable
with LAMA or LABA
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2014. Available from: http://www.goldcopd.org/.2.
Airflow restriction after bronchodilator remained
significantly higher throughout the study with
Fluticasone compared with placebo: ISOLDE
Adapted from Burge PS et al. BMJ 2000;13;320(7245):1297-303
Annual exacerbation rate was 25% lower in
patients receiving Fluticasone vs. placebo: ISOLDE
1.4
Exacerbation rate/year
1.2
1.32
25% reduction
p=0.026
1
0.99
0.8
0.6
0.4
0.2
0
Placebo
Burge PS et al. BMJ 2000;13;320(7245):1297-303
ICS
TORCH Study: Salmeterol - Fluticasone
combination (SFC) reduce exacerbation rate within
3 years of treatment
17%
25%
Exacerbation that
lead to hospitalization
Moderate to severe
exacerbation
Oral corticosteroid
treated exacerbation
(vs placebo p < 0.01)
(vs placebo p < 0.01)
(vs placebo p < 0.03)
Calverley P et al. N Engl J Med 2007;356:775–789
43%
Secondary analyses suggest that SFC may reduce
the risk of mortality: TORCH
TORCH did not meet its primary endpoint (p=0.052 vs. placebo for all cause mortality)
Risk of death in the combinationtherapy group did not differ
significantly from that in the
salmeterol group, but patients
receiving the combination regimen
were less likely to die than those
receiving ICS alone (hazard ratio for
death, 0.774 [95% CI, 0.641–0.934];
p=0.007)11
Adapted from Calverley P et al. N Engl J Med 2007;356(8):775–78
SFC and Tiotropium (Tio) may reduce the risk of
exacerbations: INSPIRE
ICS-LABA (n=658)
Exacerbations (mean no./yr)
1.4
1.2
LAMA (n=665)
p=0.656 (NS)
1.28
1.32
1
p=0.039
0.8
0.85
0.97
P=0.028
0.82
0.69
0.6
0.4
0.2
0
HCU
Requiring corticosteroid
Requiring antibiotics
HCU: Healthcare utilisation. defined as those that required treatment with oral corticosteroids and/or antibiotics or
required hospitalisation (Primary outcome measure); NS: Not significant
Wedzicha JA et al. Am J Respir Crit Care Med 2008;177:19–26
Secondary analyses suggest that SFC may be
associated with a lower risk of death vs. Tio
treatment in COPD
Time to death on treatment in the ICS-LABA combination
(salmeterol fluticasone Propionate, SFC) and the LAMA (tiotropium)
treatment groups
Adapted from Wedzicha JA et al. Am J Respir Crit Care Med 2008;177:19–26
SFC was associated a longer time to withdrawal
vs. Tio treatment in COPD
Time to withdrawal on treatment in the ICS-LABA combination
(salmeterol fluticasone Propionate, SFC) and the LAMA
(tiotropium) treatment groups
Adapted from Wedzicha JA et al. Am J Respir Crit Care Med 2008;177:19–26
There is an increased risk of pneumonia in COPD
patients using inhaled corticosteroids (ICS)
• In separate analyses, the risk of pneumonia was shown to increase in
patients using ICS when compared with non-ICS patients in clinical trials1618
– Appears to be a class effect
– No higher risk of morbidity or mortality
• However, ICS consistently reduces the risk of exacerbations
– In a 3-year study the hazard ratio for death in ICS-treated group was 0.825
(95%CI, 0.681 to 1.002; p=0.052, adjusted for interim analysis) vs. placebo
group (2.6% reduction in risk of death)11
– This suggests a potential benefit of ICS therapy in selected subjects1
– The addition of an ICS OR the combination of an ICS with a LABA is currently
indicated in COPD patients with a history of exacerbations1
GOLD 2014; Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. GOLD: 2013
Downloaded from: www.goldcopd.com; Calverley PM et al N. Engl. J. Med. 2007; 356(8),775; Nannini LJ et al. Cochrane Database Syst Rev
2012;9:CD006829; 1Nannini LJ et al. Cochrane Database Syst Rev 2013;11:CD003794; Kew KM, Seniukovich A. Cochrane Database Syst
Rev. 2014;10:3:CD010115
Summary
• COPD encompasses a complex group of disorders
• The COPD treatment goal is to reduce symptom and
reduce risk
• COPD treatment should be personalized based on the
GOLD combined assessment, different patient has
different approach
• ICS-LABA combination is recommended to
moderate/severe COPD patient with high risk of
exacerbation
• Salmeterol – Fluticasone combination reduce 25% of
exacerbation rate within 3 years of treatment, improve
lung function and quality of life
HASAN SADIKIN GENERAL HOSPITAL