chronic obstructive pulmonary disease: guideline …
TRANSCRIPT
6/23/2011
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Chronic Obstructive Pulmonary
Disease: Guideline Based
Treatment
Angela D. Gordon, PharmD, BCPS
Central Arkansas Veterans Healthcare
System
Chronic Obstructive Pulmonary Disease: Guideline Based Treatment
Prevalence/burden
Definition, Classification
Risk Factors
Diagnosis
Pathophysiology
Pharmacological treatment
Non-Pharmacological Treatment
The Pharmacist’s Role
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COPD Statistics
• > 12 million diagnosed
• > 12 million undiagnosed
• >126,000 deaths /year
• 4th leading cause of death in US
• $32 billion annually
- www.nhlbi.nih.gov/health/public/lung/copd/campaign-materials/html/copd-atrisk.htm, accessed 4-24-11
- http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5745a4.htm, accessed 5-7-11
-www.thoracic.org/education/breathiing-in-america/resources/chapter-5-chronic-obstructive-pulmonary-disease.pdf,
accessed 4-24-11
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lobal Initiative for Chronic
bstructive
ung
isease
G
O
L
D
GOLD Website Address
http://www.goldcopd.org
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COPD DEFINITION • COPD is a preventable and treatable disease with some
significant extrapulmonary effects that may contribute to the severity in individual patients.
• It’s pulmonary component is characterized by airflow limitation that is not fully reversible.
• The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.
*Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease:
Executive summary 2010. Global Initiative for Chronic Obstrucdtive Lung Disease (GOLD).
Types of COPD
• Chronic
Bronchitis
• Emphysema
• Asthma
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Risk factors for COPD
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Risk Factors for COPD
Nutrition
Infections
Socio-economic
status
Aging
Genes
Low Birth Weight
Asthma
Alpha-1 antitrypsin deficiency
– Alpha-1 antitrypsin inhibits serine proteases
– Serine proteases break down connective tissue in the lungs
– A deficiency of Alpha-1 antitrypsin causes an increase in serine proteases, thus more tissue damage
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Factors for considering a diagnosis of COPD
• Dyspnea
• Chronic Cough
• Chronic Sputum Production
• History of exposure to risk
factors
Differential Diagnosis
• Asthma
• Heart failure
• Bronchiectasis
• Tuberculosis
• Obliterative bronchiolitis
• Diffuse panbronchiolitis
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COPD Diagnosis
• Spirometry *
• Physical Exam
• Chest X-Ray
• Arterial blood gases
• Alpha-1 Antitrypsin
Barrel Chest
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Positions to Relieve Dyspnea
Pursed lip breathing
Tripod Position
Inhale Exhale
COPD Diagnosis
• Spirometry *
• Physical Exam
• Chest X-Ray
• Arterial blood gases
• Alpha-1 Antitrypsin
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What is Spirometry?
Spirometry is a method of
assessing lung function by
measuring the total volume of air
the patient can expel from the
lungs after a maximal inhalation.
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Standard Spirometric Indices
FEV1 - Forced expiratory volume in one second:
The volume of air expired in the first second of the
blow
FVC - Forced vital capacity:
The total volume of air that can be forcibly
exhaled in one breath
FEV1/FVC ratio:
The fraction of air exhaled in the first second
relative to the total volume exhaled
Criteria for Normal
Post-bronchodilator Spirometry
• FEV1: % predicted > 80%
• FVC: % predicted > 80%
• FEV1/FVC: > 0.7 - 0.8, depending
on age
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Confirmation by spirometry of airflow limitation
that is not fully reversible
FEV1 < 80% predicted
FEV1/FVC < 0.70
FEV1 – Forced expiratory volume in 1 second
FVC – Forced vital capacity
Classification of COPD Severity by Spirometry (GOLD)
Stage I: Mild FEV1/FVC < 0.70
FEV1 > 80% predicted Stage II: Moderate FEV1/FVC < 0.70 FEV1 50 to 79% predicted Stage III: Severe FEV1/FVC < 0.70 FEV1 30 to 49 % predicted Stage IV: Very Severe FEV1/FVC < 0.70 FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure
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LUNG INFLAMMATION Neutrophils, macrophages,
CD8 lymphocytes
Structural Damage, Changes (alveolar tissue damage, small airway fibrosis, etc)
Oxidative
stress Proteinases
Repair
mechanisms
Anti-proteinases Anti-oxidants
Host factors
Amplifying mechanisms
Cigarette smoke Biomass particles
Particulates
Pathogenesis of COPD
Inflammatory
mediators
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Physiologic Abnormalities
• Airflow limitation and trapping
• Gas exchange abnormalities
• Mucus hypersecretion
• Pulmonary hypertension
• Sytemic features
– Cachexia
– Osteoporosis
– Depression
– Chronic anemia
– Cardiovascular disease
Goals of Pharmacologic Therapy
• Prevent and control symptoms
• Reduce the frequency and severity of
exacerbations
• Improve health status
• Improve exercise tolerance
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IV: Very Severe III: Severe II: Moderate I: Mild
Therapy at Each Stage of COPD
FEV1/FVC < 70% FEV1 > 80% predicted
FEV1/FVC < 70%
FEV1 50 to 79 % predicted
FEV1/FVC < 70%
FEV1 30 to 49% predicted
FEV1/FVC < 70% FEV1 < 30%
predicted or FEV1 < 50%
predicted plus chronic respiratory failure
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add long term oxygen if chronic respiratory failure. Consider surgical
treatments
Pharmacotherapy: Short
Acting Bronchodilators
• Beta2-agonists
– Albuterol MDI (Proventil HFA®, ProAir HFA®, Ventolin HFA®)
– Levalbuterol (Xopenex ®)
• Anticholinergic
– Ipratropium MDI (Atrovent HFA®)
• Combination
– Albuterol/Ipratropium(Combivent®)
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IV: Very Severe III: Severe II: Moderate I: Mild
Therapy at Each Stage of COPD
FEV1/FVC < 70% FEV1 > 80% predicted
FEV1/FVC < 70%
FEV1 50 to 79 % predicted
FEV1/FVC < 70%
FEV1 30 to 49% predicted
FEV1/FVC < 70% FEV1 < 30%
predicted or FEV1 < 50%
predicted plus chronic respiratory failure
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add long term oxygen if chronic respiratory failure. Consider surgical
treatments
Pharmacotherapy: Long
Acting Bronchodilators
• Beta2-agonists
– Formoterol (Foradil®)
– Salmeterol (Serevent®)
• Anticholinergics
– Tiotropium (Spiriva®)
• Methylxanthines
– Theophylline
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Patients
• 7376 patients (tiotropium n=3707, salmeterol n=3669)
Outcome
• Tiotropium ↑ time to first exacerbation vs salmeterol
– 187 days vs 145 days (17% risk reduction, p< 0.001)
• Tiotropium ↓ the annual number of moderate exacerbations
by 14% compared to salmeterol (p< 0.001)
• Tiotropium ↓ the annual number of severe exacerbations by
28% compared to salmeterol (p<0.001)
Funding
• Boehringer Ingelheim and Pfizer
Vogelmeir C, Hederer B, Glaab T, et al. Tiotropium versus Salmeterol for the
Prevention of Exacerbations of COPD. N Engl J Med. 2011;364 (12) 1093-1103.
Long acting beta2-agonist or anticholinergic?
Patients
• LA anticholinergic, n= 28,563; LA B-Agonist, n = 17,840
Outcome
• Overall mortality rates:
– 36.5% for long-acting B-agonist group
– 39.9% for long acting anticholinergic group,
• (HR 1.14; 95%CI 1.09-1.19; p< 0.001)
Funding
• Government of Ontario, Canada
Gershon A, Croxford R, To T, et al. Comparison of Inhaled Long-Acting
β-Agonist and Anticholinergic Effectiveness in Older Patients With
Chronic Obstructive Pulmonary Disease: A Cohort Study, Ann Intern
Med May 3, 2011 154:583-592; doi:10.1059/0003-4819-154-9-
201105030-00003.
.
Long acting beta2-agonist or anticholinergic?
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Pharmacotherapy: Long
Acting Bronchodilators
• Beta2- agonists
– Formoterol (Foradil®)
– Salmeterol (Serevent®)
• Anticholinergics
– Tiotropium (Spiriva®)
• Methylxanthines
– Theophylline
IV: Very Severe III: Severe II: Moderate I: Mild
Therapy at Each Stage of COPD
FEV1/FVC < 70% FEV1 > 80% predicted
FEV1/FVC < 70%
FEV1 50 to 79 % predicted
FEV1/FVC < 70%
FEV1 30 to 49% predicted
FEV1/FVC < 70% FEV1 < 30%
predicted or FEV1 < 50%
predicted plus chronic respiratory failure
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add long term oxygen if chronic respiratory failure. Consider surgical
treatments
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Pharmacotherapy: Inhaled
Corticosteroids
• Mometasone (Asmanex ®)
• Beclomethasone (Qvar®)
• Budesonide (Pulmicort®)
• Flunisolide (AeroBid®)
• Fluticasone (Flovent®)
• Ciclesonide (Alvesco®)
Risk of Pneumonia complications with
Inhaled Corticosteroids
• European Respiratory
Journal; March 23, 2011
• N=490; 376 using ICS
• No significant difference
in pneumonia severity, or
complications
• Time to stability, length
of hospital stay, and
30d/6mo mortality all
similar
• Journal of Respiratory and
Critical Care Medicine; April 15,
2011
• N=16,000; 8271 using ICS
• Retrospective
• ICS users:
– lower 90d mortality rate
(17.3%vs 22.8%; p<.001)
– Lower 30d & 90day mortality
risk, less use of mechanical
ventilation
– no increased vasopressor use
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Pharmacologic therapy: Other
• Vaccines*
• Systemic corticosteroids
• Alpha-1 antitrypsin
augmentation therapy*
• Antibiotics
• Mucoactive agents
• Antitussives
• Nedocromil and
Leukotriene modifiers
• Narcotics (morphine)*
• Herbals/Alternative
medicine
*Favorable evidence
COPD: Acute Exacerbations
• Change in dyspnea, cough, and/or
sputum
• Beyond normal day-to-day variations
• Acute onset
• May warrant a change in medication
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COPD: Acute Exacerbations
• Administer controlled oxygen
• Bronchodilator therapy
• Methylxanthines IV (Second line)
• Glucocorticosteroids
• Antibiotics
Bronchodilators for acute
exacerbation
• Preferred: Short-acting inhaled Beta2-
agonists
• Increase dose and/or frequency
• Use Spacer or air-driven nebulizer
• May add anticholinergic if poor response
• IV Methylxanthines second line
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COPD: Acute Exacerbations
• Administer controlled oxygen
• Bronchodilator therapy
• Glucocorticosteroids
• Antibiotics
Corticosteroids for acute
exacerbations
• No advantage of IV over oral
• No exact dosing recommendations
• Reasonable dose: 30 to 40 mg daily x 7 to
10 days
• Longer treatment does not result in
greater efficacy and increases the risk of
side effects
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COPD: Acute Exacerbations
• Administer controlled oxygen
• Bronchodilator therapy
• Glucocorticosteroids
• Antibiotics
Most Common Organisms
• Haemophilus influenzae
• Moraxella catarrhalis
• Streptococcus pneumoniae
• Pseudomonas aeruginosa
• Enterobacteriaceae
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Antibiotics for acute exacerbations
• Requirements:
– 2 of 3 cardinal symptoms
• Sputum purulence PLUS
• Increased dyspnea and/or increased sputum volume
– Exacerbation that requires mechanical ventilation
• Route depends on patient’s ability to eat;
oral route preferred
• Duration 3 to 7 days
Mild Exacerbation
• Only 1 of 3 cardinal symptoms
• NO ANTIBIOTICS INDICATED
Cardinal Symptoms
1. Increased sputum Purulence
2. Increased dyspnea
3. Increased sputum volume
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Mild Exacerbation
• 2 of 3 cardinal
symptoms
• No risk factors Risk factors for poor outcome 1. Presence of comorbid diseases
2. Severe COPD
3. Frequent exacerbations > 3 /year
4. Antimicrobial use in last 3 months •Doxycycline
•Trimethoprim/Sulfamethoxazole
•Augmentin
•Azithromycin, Clarithromycin
•Cefuroxime, cefpodoxime, cefdinir
Cardinal Symptoms 1. Increased sputum Purulence
2. Increased dyspnea
3. Increased sputum volume
Moderate Exacerbation
• 2 of 3 Cardinal Symptoms
• One or more risk factors
Cardinal Symptoms 1. Increased sputum Purulence
2. Increased dyspnea
3. Increased sputum volume
Risk factors for poor outcome 1. Presence of comorbid diseases
2. Severe COPD
3. Frequent exacerbations > 3 /year
4. Antimicrobial use in last 3 months
Oral antibiotics
Augmentin
Levofloxacin 750mg
Moxifloxacin
IV antibiotics
Levofloxacin750mg
Ceftriaxone
Cefotaxime
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Severe Exacerbation
• 2 of 3 cardinal symptoms
• One or more risk factors
Oral antibiotics
Levofloxacin 750 mg
Ciprofloxacin
IV antibiotics
Levofloxacin750mg
Cefepime
Ceftazidime
Piperacillin/tazobactam
Risk factors for Psuedomonas
1. Recent hospitalization
2. ≥ 4 courses of antibiotics in
last
year.
3. Severe underlying COPD
exacerbations
4. Isolation of P. aeruginosa
during
a previous exacerbation
5. Colonization during a stable
period.
Cardinal Symptoms 1. Increased sputum Purulence
2. Increased dyspnea
3. Increased sputum volume
Risk factors for poor outcome 1. Presence of comorbid diseases
2. Severe COPD
3. Frequent exacerbations > 3 /year
4. Antimicrobial use in last 3 months
Supplemental Treatment
•Smoking cessation
Medications
Counseling
•Vaccinations Influenza
Pneumococcal
•Pulmonary rehab Exercise training
Nutrition counseling
Education
•Oxygen therapy Pa02
O2Sat
Comorbidities
•Surgery Bullectomy
LVRS
Lung transplantation
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Future Direction
• PDE-4 inhibitors
roflumilast (Daliresp®)
Approved March 2011
cilomilast (not yet approved)
• Antiproteases
investigational
Role of the Pharmacist
Symptom identification and referral
– Are you older than 35 years?
– Do you cough several times most days?
– Do you bring up phlegm or mucus most
days?
– Do you easily get out of breath?
– Are you a current smoker or an ex-smoker
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Role of the Pharmacist
• Proper inhaler use
• Vaccination
• Calcium supplements
• Smoking cessation
JD is a 56 year old woman who presents to her primary
care provider for increasing shortness of breath on
exertion for over a year and a half. She used to walk 9
holes of golf with a group of friends every Tuesday
morning, but over the last 9 months she has had to use a
cart. She has attributed this change to "getting old".
She was told 3 years earlier that she had "a touch of
asthma" and was given an inhaler to use when she was
symptomatic. In the last 6 months, she has had 3 trips
to the emergency department for "acute bronchitis."
She had smoked for about 15 years but stopped 20 years
ago. Post bronchodilator spirometry showed and FEV1
of 63% of that predicted and an FEV1/FVC of 0.59.
Case 1
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What stage of COPD does JD have?
A. Mild
B. Moderate
C. Severe
D. Very severe
Spirometry :
FEV1 63% of predicted
FEV1/FVC 0.59.
What stage of COPD does JD have?
A. Mild
B. Moderate
C. Severe
D. Very severe
Stage I: Mild FEV1/FVC < 0.70
FEV1 > 80% predicted Stage II: Moderate FEV1/FVC < 0.70 FEV1 50 to 79% predicted Stage III: Severe FEV1/FVC < 0.70 FEV1 30 to 49 % predicted Stage IV: Very Severe FEV1/FVC < 0.70 FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure
Spirometry :
FEV1 63% of predicted
FEV1/FVC 0.59.
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If she already has a short acting bronchodilator for
prn use, what is the next step in treatment for JD?
A. Inhaled corticosteroid
B. Theophylline
C. Inhaled long acting bronchodilator
D. Prophylactic antibiotic
If she already has a short acting bronchodilator for
prn use, what is the next step in treatment for JD?
A. Inhaled corticosteroid
B. Theophylline
C. Inhaled long acting bronchodilator
D. Prophylactic antibiotic
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What other recommendations or assistance as her
pharmacist can you offer to JD?
A. Take guaifenesin LA bid and drink plenty of
water.
B. Offer her an influenza vaccine or encourage
her to get a yearly influenza vaccination.
C. Help her choose some herbal supplements from
your OTC stock that are touted to treat COPD.
D. Teach her the proper use of her inhalers.
E. B and D
What other recommendations or assistance as her
pharmacist can you offer to JD?
A. Take guaifenesin LA bid and drink plenty of
water.
B. Offer her an influenza vaccine or encourage
her to get a yearly influenza vaccination.
C. Help her choose some herbal supplements from
your OTC stock that are touted to treat COPD.
D. Teach her the proper use of her inhalers.
E. B and D
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JS is a 79 year old patient with a known history of COPD.
He presents to the Emergency Department with a 3 day
history of progressively worsening shortness of breath
and cough. He reports increased yellow sputum
production and fever. Chest X-ray shows no effusions or
infiltrates (pneumonia ruled out). After further work-up,
he is admitted to the hospital and given an appropriate
diagnosis of severe COPD exacerbation. He is given IV
methylprednisolone 125 mg x 1, started on
albuterol/ipratropium updrafts q4h scheduled with q2h
albuterol updrafts prn. He is place on 4L oxygen via face
mask. He has no known drug allergies.
Case 2
Of the following antibiotics which is the most
appropriate recommendation for JS?
A. No antibiotics are indicated for this patient at
this time.
B. Bactrim DS po bid
C. Levofloxacin 750 mg IV daily
D. Vancomycin 1 gram q 12 hours
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Of the following antibiotics which is the most
appropriate recommendation for JS?
A. No antibiotics are indicated for this patient at
this time.
B. Bactrim DS po bid
C. Levofloxacin 750 mg IV daily
D. Vancomycin 1 gram q 12 hours
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201105030-00003.
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