Transcript Chad Witt, MD - Missouri ACP

Update on the Management of
Chronic Obstructive Pulmonary
Disease
Chad Witt, MD
Assistant Professor of Medicine
September 20, 2015
Department of Medicine
Division of Pulmonary and Critical Care Medicine
Disclosures
• I have no financial conflicts of interest to disclose
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Objectives
• Review the epidemiology of COPD
• Review the definition and clinical manifestations of COPD
• Discuss nonmedical interventions and medical
management of COPD
• Discuss the surgical management of advanced COPD (lung
volume reduction surgery and lung transplantation)
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Objectives
• Review the epidemiology of COPD
• Review the definition and clinical manifestations of COPD
• Discuss nonmedical interventions and medical
management of COPD
• Discuss the surgical management of advanced COPD (lung
volume reduction surgery and lung transplantation)
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Epidemiology
• COPD is the 3rd leading cause of death in the world behind
ischemic heart disease and stroke (lung cancer is 5th)
• Worldwide prevalence ranges from 5.7% (Pune, India) to
23.0% (Cape Town, South Africa) in men and 4.2%
(Nampicuan, Phillipines) to 20.7% (Uppsala, Sweden) in
women
• Associations have been demonstrated between poverty,
rates of smoking, and rates of COPD
Lozano et al. Lancet. 2012
Burney et al. Thorax. 2013
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Prevalence of COPD in the United States
Rosenberg et al. Semin Resp Crit Care Med. 2015
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Objectives
• Review the epidemiology of COPD
• Review the definition and clinical manifestations of COPD
• Discuss nonmedical interventions and medical
management of COPD
• Discuss the surgical management of advanced COPD (lung
volume reduction surgery and lung transplantation)
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Definitions
•
Chronic obstructive lung diseases include emphysema, chronic
bronchitis, chronic airflow obstruction from long standing asthma,
bronchiectasis, obliterative (constrictive) bronchiolitis, etc.
•
Chronic obstructive pulmonary disease (COPD) generally refers to
emphysema and chronic bronchitis resulting from environmental
exposure (most commonly tobacco smoking)
•
GOLD Definition of COPD: “…common preventable and treatable
disease, is characterized by persistent airflow limitation that is
usually progressive and associated with an enhanced chronic
inflammatory response in the airways and the lung to noxious
particles or gases. Exacerbations and comorbidities contribute to
the overall severity in individual patients.”
www.goldcopd.org
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Specific conditions
•
Emphysema: permanent enlargement of distal airspaces with
destruction of airspace walls
•
Chronic bronchitis: chronic productive cough for at least 3
months for 2 consecutive years
•
Alpha-1-antitrypsin deficiency
•
•
•
•
•
•
Normal allele is M
Z allele produces very little alpha-1-antitrypsin
S allele produces a low level of alpha-1-antitrypin
ZZ homozygotes have the disease
MZ and MS heterozygotes are at increased risk of emphysema
Replacement therapy with pooled alpha-1-antitrypsin is available and very
expensive ($60,000-$250,000/quality-adjusted life-year)
Rennard et al. Chest. 1999
Sclar et al. Clin Drug Investig. 2012
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Clinical Manifestations
• Early in the course of disease, exertional dyspnea is
commonly present, although not always severe enough to
bring to attention
• Some patients deny long-standing symptoms, although
this can be detected by asking how active they actually are
and have been for the last several years
• Cough with sputum production, especially in the morning is
another common presenting complaint
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Physical Exam and Diagnostic Testing
• On lung exam, can have normal breath sounds, diminished
breath sounds, or expiratory wheezes
• Patients with advanced COPD may become very cachectic
• Pulmonary function testing:
•
•
Obstruction on spirometry: FEV1/FVC < 0.7
Air trapping on lung volumes: increased TLC and RV
• Patients with suspected COPD should have a chest
radiograph to rule-out other disease processes
• CT for lung cancer screening is beyond the scope of this
talk
• Patients with a new diagnosis of COPD should be evaluated
for alpha-1-antitrypsin deficiency
ATS/ERS. Am J Respir Crit Care Med. 2003
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
GOLD Classification of Severity of Airflow Limitation
in COPD (Based on Post-Bronchodilator FEV1)
GOLD Class
Severity
FEV1
GOLD 1
Mild
FEV1≥80% predicted
GOLD 2
Moderate
50%≤FEV1<80% predicted
GOLD 3
Severe
30%≤FEV1<50% predicted
GOLD 4
Very severe
FEV1<30% predicted
www.goldcopd.org
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Objectives
• Review the epidemiology of COPD
• Review the definition and clinical manifestations of COPD
• Discuss nonmedical interventions and medical
management of COPD
• Discuss the surgical management of advanced COPD (lung
volume reduction surgery and lung transplantation)
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Nonmedical Interventions/Treatments for
COPD
• Smoking Cessation
• Pulmonary Rehabilitation
• Supplemental Oxygen Therapy
• Noninvasive positive pressure ventilation
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Smoking Cessation
• Most important intervention for patients who continue to
actively smoke
• Most cost-effective intervention for COPD
• Also decreases risk of coronary heart disease, cerebral
vascular disease, several types of cancer, and is associated
with an increased life expectancy
• One Candadian study concluded that complete smoking
cessation today would only modestly impact the financial
burden of COPD in developed countries for 25 years
Taylor et al. Am J Public Health. 2002
Najafzadeh et al. PLoS ONE. 2012
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Smoking and Lung Age
Tashkin. Semin Resp Crit Care Med. 2015
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Smoking Cessation Strategies
• Nonmedical: Advice, counseling, and behavioral
interventions
• Nicotine replacement: gum, lozenges, patches, nasal
spray, oral inhaler
• Medication: buproprion and varenicline
• Nicotine vaccines
• E-cigarettes: data is mixed
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Pulmonary Rehabilitation
•
Comprehensive pulmonary rehabilitation is a protocol guided,
supervised exercise program
•
Also includes patient education, upper and lower extremity strength
training, breathing retraining, and psychological support
•
Focuses on aerobic exercise, goal is to walk on a treadmill for 30
minutes consecutively without resting
•
Generally starts with 8-12 week program, ideally followed by a
continued maintenance exercise regimen
•
No adverse effects
•
Some insurance policies do not cover or have a lifetime limit on
the number of pulmonary rehabilitation sessions
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Pulmonary Rehabilitation
• Does not improve lung function
• Has been associated with improvement in dyspnea, quality
of life, exercise tolerance, reduced subsequent
hospitalizations for COPD exacerbations, and may help
with anxiety and depression
• Can have a dramatic effect on patients day-to-day lives
and degree of debilitation
• Crucial part of patient management prior to and immediate
after lung transplantation
Nici et al. Am J Respir Crit Care Med. 2006
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Supplemental Oxygen
• Has been shown to decrease long term mortality in
patients with severe resting hypoxemia (PaO2 < 60 mmHg)
• Results have been mixed with moderate hypoxemia (PaO2
60-70 mmHg)
• Indicated for desaturation to 88% or less either at rest,
with exertion, or while sleeping
Juratsch et al. Chest. 1980
Report of MRC Working Party. Lancet. 1981
Barjaktareic and Cooper. Semin Resp Crit Care Med. 2015
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Noninvasive Positive Pressure Ventilation
(NIPPV)
• NIPPV is an accepted treatment modality for acute
hypercapneic respiratory failure from COPD excerbation
• In stable patients with COPD, nocturnal NIPPV use is
increasing for those with advanced stage disease and
chronic hypercapneic respiratory failure
• Uncontrolled case series have reported improvement in
dyspnea, daytime somnolence, and daytime PaCO2
• Cochrane review in 2013 found no benefit, although
cautioned that small samples precluded a definite
conclusion
Struik et al. Cochrane Database Syst Rev. 2013
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
In practice
• NIPPV is used in patients with advanced COPD and
hypoventilation defined by elevated PaCO2 and symptoms
of hypercapnea, including morning headaches and daytime
somnolence
• PaCO2 generally > 55 mm Hg (frequently much higher)
• To qualify (for Medicare patients)
•
•
PaCO2 > 55 mm Hg AND
Desaturate at night on the patient’s resting daytime oxygen
requirement
• Multiple modalities available, including BiPAP, AVAPs,
IVAPs, etc.
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Medical Management of COPD
•
Treatment should be stepwise and based on patient symptoms,
frequency of exacerbations, and objective findings such as lung
function
•
All patients with COPD should be prescribed short-acting
bronchodilator (anticholinergic and/or beta2-agonist) as need for
shortness of breath
•
The addition of a long-acting anticholinergic (long-acting muscarinic
antagonist, LAMA), long-acting beta2-agonist (LABA), inhaled
corticosteroid (ICS), or a combination of the three follows based on
lung function and symptoms
•
Evidence for phosphodiesterase-4 (PDE4) inhibitor and chronic
azithromycin therapy to reduce exacerbations will be reviewed as
well
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
GOLD Model of Symptoms/Risk
(simplified)
Patient
Category
Characteristics
GOLD
Class
Exacerbations per
year
A
Low risk, less
symptoms
1-2
≤1
B
Low risk, more
symptoms
1-2
≤1
C
High risk, less
sypmtoms
3-4
≥2
D
High risk, more
symptoms
3-4
≥2
www.goldcopd.org
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Treatment Based on Group
• Group A: few symptoms, low risk of exacerbation
•
•
Short-acting anticholinergic, short-acting beta2-agonist, or
combination of the two
Addition of long-acting bronchodilator can be considered, but studies
assessing these agents have generally excluded this patient
population
• Group B: more symptoms, low risk of exacerbation
•
•
•
Long-acting bronchodilators are superior to short-acting and thus
recommended
No evidence for LAMA versus LABA, ease of use (daily versus twice
daily) and cost can be taken into consideration
Can add second long-acting bronchodilator for combination if
symptoms are not controlled
Barr et al. Cochrane Database Syst Rev. 2005
Appleton et al. Cochrane Database Syst Rev. 2006
www.goldcopd.org
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Treatment Based on Group
• Group C: few symptoms, high risk of exacerbation
• First choice:
• ICS/LABA combination or LAMA
• Alternative choices:
• LAMA + LABA
• LAMA + PDE-4 inhibitor
• LABA + PDE-4 inhibitor
* PDE4 inhibitor therapy consideration is recommended in patients with
chronic bronchitis
www.goldcopd.org
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Treatment Based on Group
• Group D: many symptoms, high risk of exacerbation
• First choice:
• ICS + LABA or ICS + LAMA
• Alternative choices:
• ICS + LABA + LAMA
• ICS + LABA + PDE-4 inhibitor
• LAMA + LABA
• LAMA + PDE-4 inhibitor
www.goldcopd.org
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Triple Therapy
• In patients with severe COPD, “triple inhaler” therapy
(LAMA+LABA+ICS) has demonstrated efficacy:
•
UPLIFT Trial: addition of LAMA to LABA+ICS improved airflows,
reduced exacerbations, and improved QOL
•
Retrospective study of VA patients of LAMA+LABA+ICS compared to
matched historical cohort LABA+ICS associated with decreased
mortality, exacerbations, hospitalizations
•
Retrospective cohort study of LAMA+LABA+ICS versus LABA+ICS
associated with lower mortality, fewer hospitalizations, fewer courses
of oral corticosteroids
Tashkin et al. N Engl J Med. 2008
Lee et al. Arch Intern Med. 2009
Short et al. Chest. 2012
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
PDE-4 Inhibitor Therapy
•
Roflumilast is oral PDE-4 inhibitor approved to reduce
exacerbations in patients with 2 or more exacerbations per
year, or 1 requiring hosptilization
•
Reserved for patients with severe and very severe (GOLD 3-4)
COPD with frequent exacerbations not adequately controlled
with inhaled therapies
•
Systematic review concluded that PDE-4 inhibitors modestly
improve lung function and reduce exacerbations, but have
little impact on QOL or symptoms
•
Roflumilast has not been directly compared to azithromycin
Chong et al. Cochrane Database Syst Rev. 2011
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Chronic azithromycin therapy
• Randomized controlled trial comparing azithromycin 250
mg by mouth daily to placebo in addition to usual care
• At one year, azithromycin group decreased frequency of
exacerbations and improved quality of life
•
Hearing decrements higher in treatment group (25% vs 20%)
• Azithromycin has been associated with increased risk of
cardiovascular death
• Generally reserved for patients having recurrent
exacerbations despite maximized medical therapy
Albert et al. N Engl J Med. 2011
Ray et al. N Engl J Med. 2012
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
ICS and Pneumonia
•
Post hoc analysis of Towards a Revolution in COPD Health (TORCH)
study demonstrated an increase in pneumonia in the ICS/LABA
(fluticasone/salmeterol) arm compared to salmeterol alone
•
Investigating New Standards for Prophylaxis in Reduction of
Exacerbations (INSPIRE) study showed increased pneumonia in
patients with fluticasone/salmeterol and exacerbations
•
It is not clear if the pneumonia risk is a class effect or specific to
fluticasone
•
Decrease in exacerbations outweighs risk of pneumonia in most
patients, but recurrent pneumonias should prompt consideration of
stopping the ICS
Crim et al. Eur Respir J. 2009
Calverley et al. Chest. 2011
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Inhalational delivery devices
• There has been a rapid expansion in the availability of
different devices to administer inhaled medications
• Several have theoretical advantages, based on delivery,
particle size, etc.
• No randomized controlled trials have demonstrated
superiority of any one system
• With all inhaled medications, patient education on how to
properly use them is important
• For conventional MDIs, the use of a spacer can increase
efficacy dramatically
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Singh et al. Semin Respir Crit Care Med. 2015
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Bronchodilators available
• Short-acting anticholingeric: ipratropium
• Short-acting beta agonists: albuterol, levalbuterol
• LAMA: tiotropium, aclidinium, umeclidinium,
glycopyrronium
• LABA: salmeterol, formoterol, arformoterol, indacaterol,
vilanterol, and olodaterol
• ICS: fluticasone, budesonide, mometasone
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Estimated monthly cost of medications from
Lexicomp:
Drug Class
Drug
Cost
SABA
albuterol
Proair HFA: $60
Ventolin HFA: $21
albuterol neb: $1-2/neb
levalbuterol
Xopenex HFA: $74
Xopenex neb: $6-10/neb
SAMA
ipratropium
Atrovent HFA: $311
ipratropium neb: $1-2/neb
SABA/SAMA
albuterol/ipratroprium
Combivent respimat: $354
Nebs: $2/neb
LABA
salmeterol
Serevent Diskus: $199
formoterol
Foradil Capsules: $350
Nebs: $14/neb ($840/month)
tiotropium
Spiriva respimat or handihaler: $379
aclidinium
Tudorza Pressair: $169
LAMA
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Estimated monthly cost of medications from
Lexicomp:
Drug Class
Drug
Cost
ICS
fluticasone
Flovent HFA: $360
Flovent Diskus: $270
Arnuity Ellipta: $400
budesonide
Pulmicort Flexhaler: $220
Pulmicort neb: $10-25/neb
fluticasone/salmeterol
Advair diskus: $143
Advair HFA: $200
budesonide/formoterol
Symbicort HFA: $200
fluticasone/vilanterol
Breo ellipta: $130
LAMA/LABA
umeclidinium/vilanterol
Anora ellipta: $200
PDE4 Inh
roflumilast
Dalisresp: $310
Macrolide
azithromycin
Zithromax: $250
azithromycin: $93
ICS/LABA
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Potential monthly cost:
• Spiriva + Symbicort + Daliresp + 2 Proair inhalers
$379
+ $200
+
$310
+ $120 = $1009
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Objectives
• Review the epidemiology of COPD
• Review the definition and clinical manifestations of COPD
• Discuss nonmedical intervention and medical management
of COPD
• Discuss the surgical management of advanced COPD (lung
volume reduction surgery and lung transplantation)
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Lung volume reduction surgery (LVRS)
• Patients with heterogeneous emphysema
• Severe bullous disease in apices with relatively normal lung
in the bases
• NETT Study:
•
•
Increase in short-term (30 and 90 day) mortality
Improvement in QOL, dyspnea, lung function, and in some survival
• FEV1 ≤45% predicted
• PCO2 ≤ 60 mm Hg
• Good candidates for LVRS are rare
NETT Research Group. N Engl J Med. 2003
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Timing of referral and listing for lung
transplant in COPD
• Referral:
•
•
•
•
•
Progressive symptoms despite aggressive therapy
Referral should include assessment for LVRS
BODE index 5-6
PaCO2 > 50 mm Hg, resting PaO2 < 60 mm Hg
FEV1 < 25% predicted
• Listing:
•
•
•
•
BODE index ≥ 7
FEV1 < 20% predicted
≥ 3 exacerbations in the last year or one episode of acute
hypercapneic respiratory failure
Moderate to severe pulmonary hypertension
• Special considerations:
•
•
No life expectancy benefit, only quality of life
Generally are low on the waiting list due to low 1-year mortality
Weill et al. J Heart Lung Transplantation. 2015
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Adult Lung Transplants
Kaplan-Meier Survival by Procedure Type and Era
(Transplants: January 1990 – June 2012)
Diagnosis: COPD/Emphysema, Bilateral/Double Lung
1990-1997 vs. 1998-2004: p = 0.0131
1990-1997 vs. 2005-6/2012: p = 0.0031
1998-2004 vs. 2005-6/2012: p = 0.7588
2014
JHLT. 2014 Oct; 33(10): 1009-1024
Conclusions
• COPD is common and results in significant morbidity and
mortality
• The most important intervention for COPD is smoking
cessation
• Pulmonary rehabilitation is beneficial and likely underutilized
• Treatment of COPD is stepwise and based on severity of
disease and symptoms
• There is an ever-growing list of medications in each class
• Treatment can get expensive
• Surgical options including LVRS and lung transplant are
available for appropriate patients with advanced COPD
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
Chad Witt, MD
660 S Euclid Ave
Campus Box 8052
St. Louis, MO 63110
[email protected]
Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine