Chronic Obstructive Pulmonary Disease (COPD)

• COPD is characterized by :**Chronic airflow obstruction & accelerated loss of lung function which is progressive & NOT

fully reversible.** COPD is preventable & treatable but NOT curable.**In COPD, airway obstruction is fixed & irreversible

w/ different degrees of reversibility according to patients.

• COPD is assoc. w/ abnormal response to noxious chemicals or gases.

• Most common risk factor for COPD is SMOKING• COPD pts. experience: -productive cough

-dyspnea

**See table2 p.920 for comparative table b/w asthma & COPD

• General Goals of Management of COPD:1) Prevent or slow disease progression.2) Relieve symptoms.3) Improve exercise tolerance.4) Improve overall health status.5) Prevent & treat complications.6) Prevent & treat exacerbations.7) Decrease mortality.

• 2 Major Forms of COPD:1) Chronic Bronchitis (C.B.)2) Emphysema1) Chronic Bronchitis (C.B.):

Defined clinically as chronic excessive secretion into bronchial tree occurring most days during a period of @ least 3 months /yr for @ least 2 consecutive yrs.

2) Emphysema:Defined anatomically as abnormal permanent enlargement of the alveoli distal to terminal bronchioles accompanied by destruction of their walls without fibrosis.

• Both C.B.& emphysema are :1) Indistinguishable. 2) Have different risk factors.3) Have similar management strategies.

** Although Asthma & COPD are both characterized by airflow obstruction, their pathophysiologic features & response to treatment are different.

• Etiology:*Smoking is major risk factor for COPD.• About 80-90% of COPD pts. have a history of current or past

smoking although only 15-20% of smokers develop COPD due to genetic variation.

• Other R.F. include:1. Environmental factors(pollution&occupational)2. Recurrent pulm. infections in childhood.3. α₁ antitrypsin deficiency: Rare & inherited (<1% of

emphysema cases)

• Exacerbations of COPD typically have an infectious etiology, either viral or bacterial.

• During an exacerbation, there is:1) Increased S/S 2) Increased mucus production3) Worsening of gas exchange4) Worsening of airway obstruction assoc. w/ an

increased risk of resp. failure.

• Clinical Presentation & Diagnosis:• Clinical assessment of COPD pts. includes:

1) Medical history2) Physical examination

• Diagnosis of COPD is considered w/complaints of:*Chronic cough

*Dyspnea*Sputum production* + History of risk factors

• Signs & Symptoms:• Pathophysiologic changes progress over yrs. & clinical symptoms occur later.• By time pt. seeks med. help, disease is far advanced.• Sig. overlap b/w clinical presentation of C.B. & Emphysema.* Productive cough is assoc. more w/ C.B.• Dyspnea is more assoc. w/ Emphysema.• Obesity is assoc. w/ C.B. (Blue bloaters)• Wt. loss is assoc. w/ Emphysema (Pink puffers)• Gold standard for COPD diagnosis is spirometry: FEV1/FVC < 70% • When SABA is administered & spirometry is repeated in 15-30 min.:

-COPD is typically characterized by < 12% improvement in FEV1 (or <200ml in pts w/ very low lung volumes).- A large increase in FEV1 is more consistent w/ asthma.

• COPD progression may develop acute & chronic complications, i.e.:

1)Pulm. HTN2)Cor Pulmonale & Rt. CHF ( Blue Bloaters )3)Polycythemia4)Hypoxemia & resp. acidosis 5)Emphysematous (Pink Puffers)

• An individualized approach to therapy should be: 1) Appropriate

2) Based on the severity classification3) Patient’s risk factors

• Important initial intervention: to reduce or eliminate exposure to risk factors.

• Smoking cessation: the only treatment strategy proven to slow the chronic progressive loss of lung function.

• Approaches to Treatment:• Pharmacotherapy:• None of the currently available therapies is shown

to prevent or slow progressive loss of lung function.

• 1⁰ role : symptomatic relief• 1⁰ strategy: using bronchodilators.• Response to meds. : Different among pts. • Assessment of response & S/Es (table35.8 p.926)

• Reversibility of airflow limitation through spirometry (FEV1) : Not shown in many pts.

• Dyspnea : Major debilitating symptoms for advanced dz. pts.

• Inhaled route of adm.(MDI, DPI, Neb.): -Pref. because > effective, faster onset & safer than oral.

-All inhaled mechanisms are equally effective in chronic management.

-MDI & DPI: > convenient-Nebulizer: initial treatment in exacerbation.

*Bronchodilator combination used for additive benefits & reduced S/Es.

1) Bronchodilaters:A. Beta-2 Agonists:

-SABA-LABA

B. Anticholinergics:-SA Ach-LA Ach

C. Methylxanthines

I. Bronchodilators:A) Beta-2 Agonists:Examples of SABA:-Albuterol-Pirbterol-Terbutaline

*Albuterol:- Most commonly used inhaled SABA.- < 5 min OA-Relativ. short DA ( 4hrs.w/chronic use) ̴�

*In COPD, SABA: -Relieves symptoms -Improves exercise tolerance -No sig. lung function improvement

Examples of LABA: ( DA 12hrs) ̴�-Formoterol (OA 5min., pk. 30min.) Difference NOT ̴� ̴�-Salmeterol ( OA 15min., pk. 1-2 hrs.) important ̴� ̴�

clinically*Sig. advantage of LABA over SABA*Considered for those NOT controlled w/ SABA• For more frequent or chronic symptoms, long acting

bronchodilators (LABA, LA Ach.) are more effective in:1. Improving lung function2. Improving exercise tolerance3. Improving quality of life4. Reducing frequency of exacerbations

B) Anticholinergics:1) Short Acting:Ipratropium Br.: (by inhalation)* ≥ bronchodilation than SABA @usual doses.*Little systemic absorption.*OA within 15 min., DA 4-6 hrs.*@ max. doses bronchodilation by beta-2 agonists maybe = to that of ipratropium in COPD but S/Es are more common w/SABA. *Due to slower OA, SABA may be preferred for acute bronchospasm w/ ipratropium used on scheduled basis.*Given as 2 inhalations QID increased to 6 inh. if needed.

2) Long Acting:Tiotropium:*Once daily dosing regimen.*Comparing Tiotropium w/Ipratropium in COPD:1.Tiotrop. used QD, Ipratrop. used QID.2. < Multiple exacerbations w/ Tiotrop.3. Sig. longer time to 1st exacerbation w/Tiotrop.4. For most outcomes, Tiotrop.> effective than

Ipratrop. but > expensive.

• Studies did NOT show significant clinical difference between LABA & Tiotropium in COPD management.

• Short- acting bronchodilators (Albuterol + Ipratropium) combination increase effectiveness & as per treatment guidelines are commonly used in the management of Mild-Mod. COPD.

• Limited data are available on the use of Long-Acting Bronchodilators combination, however,(LABA + Tiotropium) combinations are used for severe COPD patients.

C) Methylxanthines:

• Theophylline is currently considered a 3rd- line agent in the management of COPD due to the availability of safer & more potent therapies & its risk of toxicities.

• Issues to be considered with the use of Theoph.:1) Different dosage forms &salts of theoph. are

available.(SR QD or BID are most appropriate)2) Significant variability in bioavail. between different

products & patients.3) Recommended therapeutic range for COPD 8-12ug/ml.4) Smoking , other drugs, & disease factors interact w/

theoph. Careful monitoring of serum theoph. conc. is important.

5) Sig. S/E profile involves: GI, CNS, CV.

• Summary of Bronchodilator Therapy:1) Bronchodilators are the mainstay of therapy for chronic COPD

management.2) Inhaled form preferred over systemic.3) Short-acting agents are used initially.4) If symptoms continue, LA agents are >effective & convenient:

Different trials showed long-acting bronchodilators (LABA & LA Ach) provided > benefit in improving different outcome measures than Short-Acting agents(SABA & SA Ach).

5) Bronchodilator combinations are commonly used with added benefit & reduced S/Es from higher doses of a single agent.

6) Oral theoph. Is an option reserved for those NOT responding to inhaled regimens or refuse to use inhaled meds.

II. Corticosteroids:• Did NOT result in dramatic response (unlike in

asthma) which may be due to neutrophilic nature of COPD.

• Systemic corticosteroid should be avoided in chronic COPD due to its lack of benefit & serious toxicity.

• ICS has superior safety over systemic.

• Current Guidelines suggest:Trial of ICS therapy warranted in patients: 1) whose FEV1 < 50%.

& 2) who experience frequent exacerbations.

*Newer ICS agents i.e.: -budesonide -fluticasone

-mometasone May have less of a risk of S/Es.

• Combination of LABA & ICS:-For convenience & ease of use.-Showed greatest FEV1 response w/ No difference in the exacerbation rate.

*Mucolytic/Expectorant agents:- Showed NO clinical benefit in COPD.

*Respiratory stimulants:-Not recommended due to short-lived effect + potential risk.

• α₁-Antitrypsin Replacement Therapy:

- Only used for the rare inherited form of emphysema.

- Requires weekly or twice weekly infusions.

- Not indicated for other forms of emphysema.

• Non-pharmacologic Approaches:1) Tobacco Cessation2) Pulmonary Rehabilitation3) Nutritional Therapy4) Keeping Immunization Current5) Supplemental O₂ Therapy

1) Tobacco Cessation:* Difficult to achieve & maintain.• The most important intervention in the

prevention & treatment of COPD.• Slows the rate of loss of lung function• Most important & beneficial intervention• Associated w/ immediate & sustained health

benefit.

2) Pulmonary Rehabilitation:a. Patient Education ( Dz., technique, ̴�

adherence, self management skills).b. Exercise Training.c. Psychological Support & intervention

(for anxiety & depression).d. Nutritional Therapy.

3) Nutritional therapy in COPD was shown to be valuable in: 1. Relieving symptoms

2. Improving exercise tolerance 3. Improving overall health status

• Poor nutrition has sig. impact on COPD.• Pulm. Rehab.: 1. Less beneficial in preventing complications &

exacerbations. 2. No effect in reducing mortality or slowing dz.

progression.

4) Keeping Immunization Current:

a. The inactivated IM Influenza virus vaccine should be used because it has been shown to reduce serious illness & death in COPD pts.

b. Pneumococcal vaccine is recommended to be given SQ or IM because it provides prophylaxis against most common strains of Strep. Pneumiae.

5) Supplemental O₂ Therapy: (Long-Term Therapy)-Improves survival in COPD pts. w/ chronic hypoxemia.-Benefit seen if:

- pO₂<55mmHgor -pO₂<60mmHg w/ evidence of end- organ effect

of COPD, i.e.:*Cor pulmonale *Polycythemia *Cognitive impairment

• Greatest benefit shown in those who used O₂for @ least 15hrs/d.

• Nasal Cannula: The most common & convenient method of O₂ supplementation.

• ABGs & Pulse Oximetry: The 1⁰ methods for determining O₂ saturation.

• Goal of Therapy: Maintain O₂ saturation ≥ 90%.• Most are managed @ flow rates of 1-4L/min.

• Surgical Management:• For those who can NOT be managed medically.1. Bullectomy: -Removing bullea (large air spaces in

lungs)not participating in gas exchange2. Lung Volume Reduction Surgery (LVRS):

-More common-More comprehensive procedure in removing non-functional segments of lung tissue.

3. Lung Transplantation:-Used in advanced COPD

• Managing Exacerbations:• Associated w/ increased morbidity & mortality.• Acute worsening in patient’s baseline, i.e.:

-worsening dyspnea-increased cough-change in volume & appearance of sputum

beyond the day-to-day variations.• Severity: Levels 1-3

-Level 1: Managed as outpatient (E.R.)-Level 2: Requires hospitalization-Level 3: Complicated by respiratory failure

• General Management:1) Supplemental O₂ if warranted.2) Intensification of bronchodilation therapy.3) Systemic corticosteroid therapy.4) Antibiotics in most cases.5) Ventilatory support if respiratory failure is

present.

1) Level 1:• Commonly treated w/ intensification of

bronchodilator therapy: -Increase dose of SA bronchodilators (comb. SABA + Ipratropium) by MDI or Neb.-Less evidence to the role of LA

bronchodilators: Guidelines recommend LA bronchodilators to be

continued or added if pt’s condition warrants.

• Level 1 therapy involves use of Short Course of Systemic Corticosteroid:

-improves lung function. & -reduces relapse rate. **Prednisone 0.5-1 mg/kg/d X 10-14 d* Insufficient data on ICS use in COPD

exacerbation

• Antibiotics are commonly used in COPD exacerbations:

* S.Pneumoniae, M.Catarrhalis, H.Influenzae were found in pts. w/ stable COPD or exacerbation representing either colonization or infection.

*The presence of 2 of 3 of the following is an indicator for antibiotic use:

1. Increased dyspnea2. Increased sputum 3. Increased sputum purulance

**Traditional antibiotics are as effective as newer ones** Duration of antibiotic therapy= 7-10 days

2) Level 2:• Frequently treated as inpatients.• Treatment approach similar to level 1.• Oral antibiotics & corticosteroid if possible

(as effective as parenteral)• Consider extended-spectrum antibiotics

esp. if Ps. Auroginosa is suspected.

3) Level 3:• May require ventilatory support. • Aggressive bronchodilator therapy.• Corticosteroid therapy.• Broad-spectrum antibiotics may be warranted

initially.• Follow-up w/in 1 month of hospitalization.

* Theophylline oral or IV has minimum benefit in acute exacerbations of COPD.

** Prophylactic Antibiotics to reduce exacerbations is NOT proven effective & increases the risk of resistance.

** Very Important Tables:1) Table 35.11 p.935: General Principles for

Pharmacotherapy of COPD

2) Table 35.12 p. 936