CHRONIC OBSTRUCTIVE PULMONARY DISEASE: GUIDELINE …

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

http://www.nhlbi.nih.gov/health/public/lung/copd/campaign-materials/html/copd-atrisk.htm,,accessed








http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5745a4.htm

http://www.thoracic.org/education/breathiing-in-america/resources/chapter-5-chronic-obstructive-pulmonary-disease.pdf















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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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FEV1/FVC < 70%


FEV1/FVC < 70%


FEV1/FVC < 70% FEV1 < 30%








treatments

Pharmacotherapy: Long


• 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


• Beta2- agonists

– Formoterol (Foradil®)

– Salmeterol (Serevent®)

• Anticholinergics

– Tiotropium (Spiriva®)

• Methylxanthines

– Theophylline




FEV1/FVC < 70%


FEV1/FVC < 70%


FEV1/FVC < 70% FEV1 < 30%








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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• 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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• 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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• 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



Moderate Exacerbation

• 2 of 3 Cardinal Symptoms

• One or more risk factors




Risk factors for poor outcome 1. Presence of comorbid diseases

2. Severe COPD


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.




Risk factors for poor outcome 1. Presence of comorbid diseases

2. Severe COPD


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

1. CDC. Deaths from Chronic Obstructive Pulmonary Disease --- United

States, 2000— 2005. MMWR 2008;57(45);1229-32.

2. BioMed Central/Respiratory Research (2009, March 13). Smokers'

COPD Risk Is Genetic. ScienceDaily. Retrieved March 23, 2011,

from http://www.sciencedaily.com

/releases/2009/03/090311223425.htm

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from www.nhlbi.nih.gov/health/public/lung/copd/campaign-

materials/html/copd-atrisk.htm, accessed 4-24-11.

4. Global Strategy for the Diagnosis, Management and Prevention of

COPD, Global Initiative for Chronic Obstructive Lung Disease

(GOLD) 2010. Available from: http://www.goldcopd.org.

5. Rennard, SI. Chronic obstructive pulmonary disease: Definition,

clinical manfiestations, diagnosis, and staging. In: UpToDate, Stoller,

JK (Ed), UpToDate, Waltham, MA, 2011.

References







http://www.goldcopd.org/

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20.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.

21.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.

.

References

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