Office Assessment and Therapeutic Management of Chronic Obstructive Pulmonary Disease

COPD is a chronic, systemic disease largely caused by smoking, which affects the respiratory system by progressive and persistent airflow obstruction. It is a condition that is well known to practicing family physicians.

Although the physical examination is relatively insensitive for diagnosis, signs of hyperinflation, hypoxemia and pulmonary hypertension being late clinical findings, spirometry can be very useful in confirming your suspicions. In fact demonstration of airflow obstruction is mandatory for the diagnosis of COPD.1 Spirometry before and after bronchodilator is the gold standard for the diagnosis and risk stratification of COPD. A post bronchodilator FEV1 <80% of the predicted value associated with an FEV1/FVC <70% indicates airflow obstruction and both are necessary for the diagnosis of COPD to be established.

Target populations for spirometry screening include:
  • All smokers 35 years of age and older
  • Past smokers with a 20-pack/year history of smoking whether or not the patient complains of the symptoms.
  • Patients with recurrent or chronic respiratory symptoms including cough and breathlessness on exertion.
  • Patients with a family history of obstructive pulmonary disease
  • Patients who have significant occupation exposure to respiratory irritants

Additional Investigations might include a chest radiograph, pulse oximetry +/- arterial blood gases if FEV1 ≤ 35% predicted and alpha1 antitrypsin level if patient presents with emphysema < 40 years old.

The goals of therapy are :
  • To decrease or abolish dyspnea
  • To improve exercise capacity
  • To reduce the frequency of exacerbations
  • To improve quality of life
  • To reduce impairment, disability and handicap

To this end there are a number of therapeutic options. Non-pharmacological management includes:

  • Education of patients and their families
  • Smoking cessation advice
  • Encourage physical activity
  • Annual vaccination against influenza early each fall. Pneumococcal vaccine is recommended as a once in a lifetime measure.
  • Review of inhaler technique with repeated instruction and demonstration
  • Involvement of groups including the Lung Association.
  • Rehabilitation programs providing respiratory, physical and occupational therapy, exercise conditioning, nutritional assistance and psychological vocational rehabilitation. Although this is a limited resource, it benefits patients in all stages of the disease (including severe). Early referral of motivated patients suggested.2

There are a few pharmacological principles to note. Initial pharmacological therapy of COPD is based on obtaining optimal bronchodilation with the use of PRN and then regular bronchodilators.3,4,5 Small improvement in airflow in COPD patients with severe obstruction may be of significant clinical benefit. Initial therapy commenced with PRN beta-agonists may be supplemented by regular anticholinergics. Maximum bronchodilation may be obtained by a combination of long acting B2 agonists and anticholinergic products.6,7

The proper use of inhalers is not intuitive and patients need careful instruction along with demonstration before therapy is initiated. Inhaler technique needs to be checked and reinforced at each subsequent visit by all health care providers.

The most commonly used inhaler has been a meter-dosed inhaler MDI. If inhaler technique isn't adequate then a spacer device which will improve deposition of the medication to the lower respiratory tract should be considered. Recently, utilization of dry powder devices which require fewer steps to obtain optimal delivery have become more prevalent. Appropriately used, inhalers provide optimal delivery for the vast majority of individuals and should be encouraged over nebulizers.

MDIs with a CFC-free propellent are now available. There are no concerns regarding the safety of the CFC MDI's patients are currently using. The transition to non-CFC MDI's is for environmental reasons only. Some patients may notice certain differences in the taste and sound of their new HFA MDI or they may perceive that the spray is softer and warmer than that of their CFC containing MDI. The HFA cannister is lighter than the CFC container. These differences are due to the new HFA formulation and do not affect the delivery, safety profile or efficacy of the medication.

We have a number of pharmacologic choices available to us.

Anticholinergic Agents:
The short acting anticholinergic , Ipratropium bromide , has a slower onset of action than beta-agonists, but its duration of action is longer. It is available as a meter dose inhaler (MDI) and as a nebulizer solution. The recommended dose (20 mcg i.e. two inhalations 3 to 4 times per day) produces less than maximal bronchodilation and may be doubled or tripled without notable side effects.

A newer long acting anticholinergic, Tiotropium bromide, is available as a dry powder inhaler. A dose of 18 mcg once a day gives maximal anticholinergic activity over a full 24 hours. 8 The major advantage of the long acting anticholinergic is its potential to improve quality of life and reduce exacerbations compared to regular Ipratropium bromide. 9

Beta2-agonists:
Short acting B2-agonists (SABA) like salbutamol, terbutaline and fenoterol have similar efficacy with respect to side effects, time of onset and duration of bronchodilator effect. Recommended doses of B2-agonists result in less than maximal bronchodilation and the dose may be doubled or tripled, although tremor and potential for inducing hypokalemia must be recognized and monitored for in patients at risk. Oral beta2-agonists offer few advantages and increase side effects.

Long acting beta2-agonists (LABA) such as salmeterol and formoterol may be of additional benefit in COPD. Formoterol has the added advantage of rapid onset of bronchodilation as well as twelve-hour maintenance bronchodilation. This rapid onset of action is not a feature of salmeterol. Recent studies have shown improved quality of life and reduction of exacerbations with use of LABAs compared to short Ğacting bronchodilators.6,7

Inhaled Corticosteroids:
Recent studies suggest that inhaled cortiocosteroids reduce the frequency of exacerbation in advanced symptomatic disease and should be prescribed to patients with recurrent exacerbations or FEV1 <35%.10 However, before considering inhaled corticosteroid therapy the physician should make sure that the patient is on optimal treatment with maximal use of bronchodilators.

Combination Products of Inhaled Corticosteroids and LABAs:
Recently studies have been completed addressing the efficacy of products combining inhaled corticosteroids and LABAs in a single inhaler. The results have been mixed. No significant reduction of exacerbations12 was seen in the Tristan study of the combination of salmeterol/fluticasone (Advair), using high dose Advair 500mcg bid compared to high dose Flovent 500 mcg bid or Serevent 50 mcg bid. The Szafranski study used oxeze/pulmicort (Symbicort), comparing Symbicort 200mcg two inhalations bid ( a more moderate dose of inhaled corticosteroid) against Pulmicort 200 mcg two inhalations bid or Oxeze 6 mcg two inhalations bid. It showed a significant reduction of exacerbations with the combination product Symbicort over the individual components.13 Further studies and the exact role of these products in COPD management are awaited.

Oral Medications

Theophylline:
The use of oral theophylline treatment of COPD is controversial and has significantly fallen out of favor in recent years. Theophylline is a phosphodiesterase inhibitor and increases levels of cyclic AMP. In clinical practice it may have little bronchodilator effect beyond that of optimal dosing of bronchodilator inhaler medications. Theophylline therapy provides other non-bronchodilating effects such as positive inotrophic activity, a direct diuretic effect and respiratory stimulation. Unfortunately all of these additional benefits are weak. It is also the only drug available for COPD with the potential for life threatened acute adverse events. If it is prescribed therapeutic monitoring by assessing serum levels is recommended. The oral dosing regimen should be tailored to obtain levels in the low therapeutic range (55-85 mcg/l) to minimize adverse effects. Physicians should also be aware of the significant drug interactions. Theophyline levels may be doubled by smoking cessation or the addition of such medications such as cimetadine or antibiotics commonly used during COPD exacerbation's ( clarithromycin or ciprofloxacin).

Oral Corticosteroids:
There is no role for oral steroid maintenance therapy for patients with COPD. In the past, oral corticosteroid challenges were performed to identify individuals who might benefit from prescription use of inhaled corticosteroids. (an improvement of 200 cc and 20% FEV1 on spirometry). An acute response to oral steroid challenge does not discriminate a benefit from inhaled corticosteroid and is no longer recommended.

Oxygen Therapy:
Oxygen therapy reduces the risk of death in selected patients. In COPD patients with significant hypoxemia (PaO2 < 55 mmHg or SaO2 < 90%), long term oxygen therapy may increase the lifespan by 6 to 7 years. Improved survival has only been seen when oxygen is administered for at least 12 hours per day, including nocturnally. The greatest survival benefit is with continuously administered oxygen therapy. A patient whose PO2 is between 55 and 59 may also benefit from oxygen therapy if there is indirect evidence of hypoxemia or organ damage. Oxygen therapy is usually prescribed through nasal prongs with a flow rate sufficient to produce resting PaO2 between 65 and 80 mmHg. Flow rates are often increased by 1 or 2 L/min during exercise and sleep.

Here are some therapeutic tips.
  • Spirometry with bronchodilator assessment is the most essential diagnostic tool to perform in patients with significant smoking history or respiratory symptoms.
  • The patient should be encouraged to remain active, despite the fact that exercise may be associated with dyspnea ,to prevent the vicious cycle of decreasing mobility and increasing dyspnea.
  • A step wise approach to treatment is appropriate, with positive reinforcement at all stages to encourage compliance with therapy.

Consider in advanced disease in individual basis:

  1. Combination ICS & LABA e.g., Advair and Symbicort to assist compliance and perhaps reduce exacerbations.
  2. Theophylline with serum monitoring.
  3. Oxygen if meets arterial blood gas criteria.

- Andrew McIvor

Thanks to Dr. Scott Rappard, Consultant Respirologist at St. Martha's Regional Hospital, Antigonish, Nova Scotia for reviewing the draft copy of this article.

References and Suggested reading list:

  1. McIvor RA, Tashkin DP. Underdiagnosis of chronic obstructive pulmonary disease: A rationale for spirometry as a screening tool. Can Resp J 2002;8(3):153-158.
     
  2. Lacasse Y, Wong E, Guyatt GH, King D, Cook DJ, Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. Lancet 1996;348:1115-9.
     
  3. Pauwels RA, Buist AS, Calverley PMA, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO global initiative for chronic obstructive lung disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001;163:1256-76.
     
  4. Snow V, Lascher S, Mottur-Pilson C. Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Ann Intern Med 2001; 134(7):595-599.
    Website - Gold Guidelines are available at www.copd.com
     
  5. Siafakas NM, Vermeire P, Pride NB, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995;8:1398-420.
     
  6. Mahler DA, Donohue JF, Barbee RA, et al. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest 1999;115:957-65.
     
  7. Maesen BL, Westermann CJ, Duurkens VA, van den Bosch JM. Effects of formoterol in apparently poorly reversible chronic obstructive pulmonary disease. Eur Respir J 1999;13:1103-8.
     
  8. Disse B, Speck GA, Rominger KL, Witek TJ Jr, Hammer R. Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease. Life Sci 1999;64:457-64.
     
  9. Casaburi R, Mahler DA, Jones PW, Wanner A, San Pedro G, ZuWallack RL et al., A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive lung disease. Eur Respir J 2002; 19:217-212
     
  10. Burge PS, Calverley PMA, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double-blind, placebo-controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000;320:1297-303.
     
  11. Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 1999;354:456-60.
     
  12. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulisvik A et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease : a randonized controlled trial. Lancet 2003;361:449-56
     
  13. Szafranski W, Cukier A, Ramirez A, Sansores R, Nahabedian S et al Efficacy and safety of budesonide/formotorol in the management of chronic obstructive pulmonary disease Eur Respir J 2003;21:74-81

Physician/Health Care Worker Website: Global Obstructive Lung Disease (GOLD) Guidelines

Patient Website: Patient Information from the Lung Association
BREATHWORKS Toll-Free Helpline: 1-866-717-COPD (2673)
Staffed by COPD Educators (www.lung.ca/breathworks/)

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