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)Emphysema 1) Chronic Bronchitis (C.B.): Defined clinically as chronic excessive secretion into bronchial tree occurring most days during a period least 3 months /yr 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 production 3)Worsening of gas exchange 4)Worsening of airway obstruction assoc. w/ an increased risk of resp. failure.

Clinical Presentation & Diagnosis: Clinical assessment of COPD pts. includes: 1) Medical history 2) 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 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. HTN 2)Cor Pulmonale & Rt. CHF ( Blue Bloaters ) 3)Polycythemia 4)Hypoxemia & resp. acidosis 5)Emphysematous (Pink Puffers)

An individualized approach to therapy should be:1) Appropriate 2) Based on the severity classification 3) 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 function 2. Improving exercise tolerance 3. Improving quality of life 4. Reducing frequency of exacerbations

B) Anticholinergics: 1)Short Acting: Ipratropium Br.: (by inhalation) * ≥ bronchodilation than 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 1 st 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 3 rd - 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 Cessation 2)Pulmonary Rehabilitation 3)Nutritional Therapy 4)Keeping Immunization Current 5)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<55mmHg or -pO₂<60mmHg w/ evidence of end- organ effect of COPD, i.e.:*Cor pulmonale *Polycythemia *Cognitive impairment

Greatest benefit shown in those who used O₂ 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 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 exchange 2. 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 mg/kg/d X 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 dyspnea 2. 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 p.935: General Principles for Pharmacotherapy of COPD 2)Table p. 936