Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease associated with a heightened long-standing inflammatory response to noxious stimuli in the airways. Patients often suffer from progressive worsening of their airways in an obstructive pattern, which can be divided into various subtypes, such as emphysema, chronic bronchitis, and chronic obstructive asthma. It is a leading cause of hospitalizations and death in Canada, and is often suboptimally managed.

Pathophysiology
The onset of COPD is characterized by insidious, progressive and persistent inflammation of the lung parenchyma and both the large central (bronchi) and the small airways (bronchioles), causing virtually non-reversible impediments on a patient's expiratory flow. The changes in the lung parenchyma and small airways often leads to air trapping and hyperinflation, secondary to collapse of the bronchioles associated with expiration.

The inflammation hypothesis for COPD postulates that COPD is brought upon via chronic exposure of the lung parenchyma to noxious irritants, leading to influx and accumulation of polymorphonuclear leukocytes and macrophages, which release elastases and other destructive proteins (eg. MMPs) that lead to parenchymal cell apoptosis and tissue necrosis.

Epidemiology
COPD is notoriously underdiagnosed in Canada. Despite this, it is still the fourth leading cause of death among Canadians and is estimated to affect ~700,000 people. From the 2008 Canadian Thoracic Society COPD guidelines, it is noted that around 4.4% of Canadians above the age of 35 meet COPD criteria based off of self reported symptoms. As with most chronic diseases, the prevalence increases with age. Women also have a higher prevalence of the disease than men.

Risk Factors
The largest risk factors for COPD are smoking and age. Smokers or ex-smokers of age 40 years or above should be screened with the following questions (taken from the 2008 CTS COPD guidelines): If the patient answers yes to any of these above screening questions, spirometry should be performed.
 * Do you cough regularly?
 * Do you cough up phlegm regularly?
 * Do even simple chores make you short of breath?
 * Do you wheeze when you exert yourself, or at night?
 * Do you get frequent colds that persist longer than those of other people you know?

A thorough smoking history should be obtained, including quantifying the number of pack years (packs per day X number of years as a smoker), as well as quantifying the amount of current disability. Patients should also be screened for concurrent symptoms of cor pulmonale, such as leg edema, as this can indicate a significant disease burden (given evidence of right heart strain).

Spirometry with post-bronchodilator response, with considerations for full pulmonary function testing, are usually used for diagnosis of COPD. In patients who have been found to have a FEV1 of <40% predicted, arterial blood gasses should be done to assess for hypoxemia and hypercapnia - if the SaO2 is less than 90% on RA, there should be a consideration for home O2.

Management of COPD in primary care settings
The management of COPD revolves around the goals of preventing disease progression, reducing the frequency and severity of acute exacerbations and hospitalizations, improving dyspnea and exercise tolerance, and reduction of mortality.

Smoking cessation
The single most effective intervention for managing COPD is smoking cessation. It is the only intervention that has been found to decrease the rate of lung function decline. See Smoking Cessation.

Patient education
Education is an important component of managing the disease. Aside from smoking cessation, patients should be informed around appropriate self-management techniques, such as proper inhaler technique and use, recognition of the early signs of acute exacerbations, keeping up to date with recommended vaccinations, and end-of-life care plans.

Vaccinations
All patients with diagnosed COPD should receive the annual influenza vaccine. Studies have shown that the annual influenza vaccine reduces morbidity and mortality of disease in elderly populations by as much as 50%, and reduces the incidence of hospitalizations by as much as 39%.

It is also recommended that patients with COPD receive their pneumococcal vaccination every 5-10 years.

Short acting bronchodilators
Short acting bronchodilator agents (eg. salbuterol, ipratropium) improve dyspnea, exercise tolerance and pulmonary function in patients with moderate to severe COPD. Short acting beta-agonists (SABAs) Short acting anti-cholinergics (SAACs)
 * Salbuterol (Ventolin)
 * Terbulatine
 * Ipratropium (Atrovent)

Long acting beta-agonists (LABAs)
LABAs provide sustained bronchodilation and improvements in pulmonary function, dyspnea and health status in patients with moderate to severe COPD. Although there has not been any noted evidence of significant mortality benefit, LABAs have been associated with decreased frequency of acute COPD exacerbations.
 * Salmeterol
 * Formoterol

Long acting anti-cholinergics (LAACs)
As with LABAs, LAACs have been shown to provide sustained improvements in pulmonary function, dyspnea and health status, with the additional benefit of increased exercise tolerance in patients with moderate to severe COPD.
 * Tiotropium

Inhaled corticosteroids (ICS)
ICS monotherapy is not recommended in COPD, as they have not been shown to provide much benefit in reducing the rate of lung function decline. With the advent of combination ICS/LABA therapies, there are little to no indications for use of ICS monotherapy in COPD.

Combined LABA/ICS
Combined LABA/ICS inhaler therapy has been shown to consistently improve respiratory function, exercise capacity, overall health status, and reduce overall mortality from the disease.

Two formulations of combined inhaler medication exist currently in Canada:
 * Salmeterol + fluticasone (Advair) 
 * Formoterol + budesonide (Symbicort)

Management of acute COPD exacerbations
Acute exacerbations of COPD are defined as sudden sustained worsenings of dyspnea, cough or sputum production associated with the underlying disease.

Etiologies of AECOPD include:
 * Infection (pneumonia/bronchitis)
 * CHF (LV failure)
 * Atrial fibrillation
 * Aspiration
 * Pulmonary embolus
 * Mucous plugging
 * Pneumothorax
 * Sedation
 * Non-compliance with medications

Workup
For early signs of exacerbation, empiric treatment with steroids, increased use of inhalers, and antibiotics (if suspected infectious etiology) is appropriate, especially in an outpatient setting. For exacerbations that worsen despite early empiric treatment, it would be reasonable to do further investigations:
 * CBC, electrolytes, Cr, BUN
 * Chest X-Ray (AP+lateral)
 * Look for consolidations, signs of hyperinflation, signs of pulmonary edema
 * VBG
 * ECG

Inhalers

 * Ventolin 2-4 puffs q4h straight OR 5mg nebs q4h straight
 * Atrovent 2-4 puffs q4h straight OR 500mcg nebs q4h straight
 * Ventolin 2-4 puffs q2h prn
 * Atrovent 2-4 puffs q2h prn

Steroids

 * Prednisone 50mg po daily x 5 days (no taper needed)

Antibiotics (if suspected infectious source)
First line Second line Complicated/Severe cases
 * Azithromycin 500mg po x 1 day, then 250mg po daily x 4 days
 * Amoxicillin 500mg po TID x 5 days
 * Doxycycline 100mg po BID x 1 day then 100mg po daily x 4 days
 * Septra DS 1 tab po BID x 5 days
 * Clarithromycin (Biaxin) 500mg po BID x 5 days
 * Cefuroxime 500mg po BID x 5 days
 * Cefprozil 500mg po BID x 5 days
 * Levofloxacin 750mg po daily x 5 days
 * Moxifloxacin 400mg po daily x 5 days
 * Amoxicillin-clavulanate 500mg po TID x 5 days
 * Ciprofloxacin 500mg po BID x 5 days (if concerned for Pseudomonas)

Resources
Please see Google Drive for relevant documents.