Therapy Intervention for COPD
4.1 Pharmacotherapy for COPD
Key Points for Step-up Therapy
Pharmacotherapy for patients with COPD is based on a step-up approach:
- Therapy to address symptoms should make use of non-pharmacologic intervention to improve outcomes (i.e., smoking cessation, education, rehabilitation, and pulmonary rehabilitation).
- Pharmacotherapy should balance overall efficacy which includes acceptance and adherence against risks for adverse effects (toxicity).
- Patient symptomatic responses such as dyspnea, as well as a reduction in exacerbations, should be the primary basis for determining response to therapy.
- Continue ongoing evaluation of the patient's response to therapy and progression of disease.
- As COPD progresses, additional pharmacotherapy is usually needed.
- Patient's preference should be considered to improve acceptance and adherence to therapy.
- Patients with severe airflow limitation (FEV1 <50 percent predicted) and minimal symptoms should be considered for a trial of pharmacologic therapy.
- COPD severity based on symptoms and FEV1 should always be documented initially and reassessed periodically based primarily on symptomatic progression of COPD.
- The MMRC scale of dyspnea, in addition to clinical assessment, is indicated to grade symptom severity.
- Treatment is predominantly based on symptoms and a suggested stepped-up approach is recommended (see Table 3 below).
Table 3: Step-Care Pharmacotherapy in COPD (See also Figure 2 in the original guideline document)
Step |
Symptoms1 |
Maintenance Therapy2 |
Rescue Therapy |
Other Interventions |
A |
Asymptomatic |
No medication indicated |
-- |
Smoking cessation; influenza, and other vaccinations |
B |
Symptoms less than daily |
No scheduled medication indicated |
SABA6 |
Smoking cessation; influenza, and other vaccinations |
C |
Symptoms not controlled with rescue therapy or daily symptoms |
Scheduled SAAC
or
Combination SABA + SAAC3
|
SABA6 |
Smoking cessation; influenza, and other vaccinations |
D |
Symptoms not controlled2 |
Combination SAAC + LABA
or
LAAC4
|
SABA6 |
Smoking cessation; influenza, and other vaccinations
Consider Pulmonary Rehabilitation7
|
E |
Symptoms not controlled2 |
Combination LABA + LAAC4 |
SABA6 |
Smoking cessation; influenza, and other vaccinations
Refer to Pulmonary Rehabilitation7
|
F |
Exacerbations of more than one per year and severe disease (FEV1 <50%) |
Consider adding an inhaled glucocorticoid5 |
SABA6 |
Smoking cessation; influenza, and other vaccinations
Refer to Pulmonary Rehabilitation7
|
- Spirometry is essential to confirm the presence of airflow obstruction (low FEV1 and FEV1/VC ratio). Base therapy on symptoms, but consider alternate diagnoses (heart disease, pulmonary emboli, etc.) if out of proportion to spirometry.
- Use the lowest level of therapy that satisfactorily relieves symptoms and maximizes activity level. Assure compliance and proper use of medications before escalating therapy. It is unusual for patients with COPD with FEV1 above 70% to require therapy beyond short-acting bronchodilators; if these patients do not improve they should be considered for alternative diagnoses.
- Consider use of inhaler containing both a short-acting beta 2-agonist and an anticholinergic. Nighttime symptoms are frequently better controlled with a long-acting inhaled beta 2-agonist.
- Consider adding a theophylline trial (slow release theophylline adjusted to the level of 5 to 12 micrograms/ml) with caution due to adverse effects. Nighttime respiratory symptoms are frequently controlled, but theophylline may lead to insomnia. Discontinue if a benefit is not evident within several weeks.
- Consider high dose inhaled glucocorticoids in patients with severe COPD (FEV1 <50 % predicted) and at least one exacerbation in the prior year. A combination of a high dose inhaled glucocorticoid and a long-acting beta 2-agonist may help provide long-term maintenance for symptomatic COPD and improve quality of life (QOL). The use of oral glucocorticoids for maintenance therapy is discouraged.
- Short-acting inhaled beta 2-agonists (less than12 puffs/day) may continue to be used as needed. Inhaled long-acting beta 2-agonists should not be used as rescue therapy.
- Pulmonary rehabilitation should be offered to patients who, despite optimal medical therapy, have reduced exercise tolerance and/or dyspnea limiting exercise.
|
See Table 7 in the original guideline document for effects of commonly used medications on clinical outcomes, along with strength of recommendation ratings.
4.2 Oxygen Therapy
Action Statement
Patients with COPD should be periodically evaluated for the need of supplemental oxygen. Supplemental oxygen for those exhibiting signs of tissue hypoxia may increase survival of patients with severe COPD. Oxygen may also be used for exertional hypoxemia or nocturnal hypoxemia.
Recommendations
- Oximetry should be considered in patients with COPD and should be performed in all patients with severe or very severe COPD (FEV1 <50 percent predicted). [I]
- Evaluation of nocturnal desaturation should be considered in patients with severe or very severe COPD (FEV1 <50 percent predicted) who exhibit unexplained findings indicating nocturnal hypoxemia (e.g., polycythemia, pulmonary hypertension, and nocturnal restlessness). [I]
- Oxygen therapy should be initiated in patients who have hypoxemia (PaO2 <55 mm Hg and/or arterial blood oxygen saturation (SaO2) <88 percent). [A]
- Oxygen therapy should be initiated in patients who have hypoxemia (PaO2 of 56 to 59 mm Hg or SaO2 <89 percent) and signs of tissue hypoxia such as hematocrit above 55, pulmonary hypertension, or cor pulmonale. [A]
- Oxygen therapy should be provided during exercise in stable patients with COPD with exertional hypoxemia (SaO2 <88 percent). [B]
- Oxygen therapy should be considered for nocturnal hypoxemia (SaO2 <88 percent). [I]
- Patients who started to receive oxygen therapy while unstable or on suboptimal medical therapy should be reevaluated within one to 3 months for need of long-term oxygen therapy (LTOT). If repeated evaluation indicates a patient no longer qualifies for oxygen, cessation of oxygen should be considered. [B]
- Patients who continue to receive LTOT should be reevaluated at least annually for continued need of LTOT. [I]
- Patients prescribed oxygen should be cautioned about the potentially extreme fire hazard of smoking or lighting cigarettes in the presence of oxygen. [I]
|
Evidence |
Source |
QE |
Overall Quality |
R |
1 |
Patients who have PaO2 <55mm Hg and/or SaO2 <88 percent will have mortality benefit with LTOT. |
Cranston et al., 2005
"Continuous or nocturnal," 1980
|
I |
Good |
A |
2 |
Oxygen administration slows progression of pulmonary hypertension in hypoxic patients with COPD. |
"Long term domiciliary," 1981
"Continuous or nocturnal," 1980
Weitzenblum et al., 1985
|
I |
Good |
A |
3 |
Patients with mild to moderate hypoxemia without signs of tissue hypoxia did not demonstrate a survival benefit after 3 years of LTOT. |
Gorecka et al., 1997
Cranston et al., 2005
|
I |
Good |
D |
4 |
Oxygen supplementation during exercise improves dyspnea, exercise tolerance, and performance. |
Bradley & O'Neill, 2005
Eaton et al., 2002
Fujimoto et al., 2002
Garrod, Paul, & Wedzicha, 2000
McDonald et al., 1995
Rooyackers et al., 1997
Stein, Bradley & Miller, 1982
|
I |
Good |
A |
5 |
Nocturnal oxygen therapy improves pulmonary hypertension. |
Fletcher et al., 1992 |
I |
Good |
A |
6 |
Nocturnal oxygen therapy does not improve survival. |
Chaouat et al., 1999 |
I |
Good |
A |
QE = Quality of Evidence; R = Strength of Recommendation (See Appendix A in the original guideline document)
4.3 Pulmonary Rehabilitation
Action Statement
Pulmonary rehabilitation should be offered to all patients with COPD, who, despite optimal medical therapy, have reduced exercise tolerance and/or dyspnea limiting exercise. [A]
All patients with COPD with exertional symptoms should be offered a structured program with exercise training to reduce dyspnea and improve exercise tolerance and health-related QOL. [A]
Pulmonary rehabilitation programs with educational components and self-management training reduce healthcare use. [B]
Recommendations
Selection of Patients
- Pulmonary rehabilitation should be considered for patients with COPD who have dyspnea, reduced exercise tolerance, a restriction in activities, or impaired health status. [A]
- Pulmonary rehabilitation should be offered to all patients who consider themselves disabled by COPD (Level 3 and above on the dyspnea scale). [B]
- Pulmonary rehabilitation is recommended for patients with reduced exercise tolerance and restricted activities because of dyspnea. [A]
Exercise Training
- The exercise program should be supervised and should provide cardiovascular reconditioning with endurance and muscle strength training. [A]
- The initial exercise program should be of sufficient length, duration, and frequency (see Appendix B: Structured Exercise Training Program in the original guideline document). [B]
- Endurance training should be performed to improve physical endurance. [A]
- Lower limb strength training should be performed to improve exercise tolerance (walking, cycling); upper extremity training improves arm strength. [B]
- In order to maintain benefits, subsequent exercise training is needed. [B]
- As studies show conflicting results, respiratory muscle training is not recommended to be part of a rehabilitation exercise program. [B]
Education and Self-Management
- Patients with COPD with a prior hospitalization should be referred for pulmonary rehabilitation. [A]
- Educational components and self-management programs should be included in rehabilitation programs, as it can reduce COPD exacerbations, hospital admission, and length of stay. [B]
- Self-management programs should include the following [B]:
- Skills training to optimally control the disease
- Education about medications and devices and how to use them properly
- Instruction on how to deal with exacerbations
- Other aspects of coping with the disease
- The benefit of education, psychosocial support, and nutritional therapy as a single intervention, without exercise, are less well-documented. [I]
|
Evidence |
Source |
QE |
Overall Quality |
Net Effect |
R |
1 |
Significant improvement in dyspnea and COPD QOL (measured by the Chronic Obstructive Pulmonary Disease [CRDQ]). |
Pulmonary rehabilitation: joint American College of Chest Physicians (ACCP) /American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), 1997
Lacasse et al., 2002
|
I |
Good |
Substantial |
A |
2 |
Significant improvement in dyspnea and exercise capacity for patients with an FEV1 above 35 percent for long-and short-term programs. Patients with FEV1 below 35 percent required at least 6 months of program. |
Salman et al., 2003 |
I |
Good |
Substantial |
A |
3 |
Rehabilitation improved dyspnea, QOL, and exercise capacity. |
Kupferberg et al., 2005
Ries et al., 2005
|
II-2 |
Fair |
Substantial |
B |
4 |
Addition of supervised exercise to a dyspnea self-management program that included unsupervised home exercise (walking) led to greater improvement in dyspnea, QOL and exercise capacity |
Carrieri-Kohlman et al., 2005 |
I |
Good |
Substantial |
A |
5 |
Home-based rehabilitation improved exertional dyspnea (Borg), QOL (CRDQ) and exercise capacity. |
Oh, 2003 |
I |
Fair |
Moderate |
B |
Exercise |
6 |
Rehabilitation improves exercise endurance and maximal exercise capacity. |
Pulmonary rehabilitation: joint ACCP/AACVPR, 1997
Lacasse et al., 2002
|
I |
Good |
Substantial |
A |
7 |
Rehabilitation improves peripheral muscle strength. |
Troosters et al., 2005 |
I |
Good |
Moderate |
B |
8 |
Improvements in exercise tolerance are maintained for 6 months to a year. |
Bestall et al., 2003 |
I |
Fair |
Small |
C |
9 |
Respiratory muscle training can improve strength of these muscles, but this does not lead to increased exercise tolerance or better QOL. |
Lotters et al., 2002
Smith et al., 1992
|
I |
Good |
Zero |
D |
Education and Self-Management |
10 |
Pulmonary rehabilitation program with educational components and structured treatment recommendations for COPD exacerbation reduce healthcare use. |
Bourbeau et al., 2003
Gadoury et al., 2005
Gallefoss & Bakke, 2000
Griffiths et al., 2000
Guell et al., 2000
Troosters et al., 2005
|
I |
Fair |
Moderate |
B |
11 |
Self-management programs (that include education about the medications and how to use them, guide behavior change, and provide emotional support) reduce COPD exacerbations, and hospital admissions, and length of stay. |
Bourbeau et al., 2003
Gallefoss & Bakke, 2000
Guell et al., 2000
Monninkhof et al., 2003
Troosters et al., 2005
|
I |
Fair |
Moderate |
B |
QE = Quality of Evidence; R = Strength of Recommendation (See Appendix A in the original guideline document)
4.4 Mucolytics, Antioxidants and Antitussives
Action Statement
The use of mucolytics, antioxidants, or antitussive medications has little evidence of any effect on lung function. [D]
Recommendations
- N-acetylcysteine (NAC) is not recommended for patients with COPD for the purpose of cough suppression. [D]
- N-acetylcysteine (NAC) 600 mg by mouth every day may be considered to decrease the number of exacerbations in selected patients with COPD with primarily chronic bronchitis who are not on inhaled glucocorticoids. [B]
- Antioxidants, such as alpha-tocopherol (contained in vitamin E preparations) or beta-carotene, should not be administered to patients with COPD, as they have no significant effect on phlegm, cough, or dyspnea. [D]
- Antitussives are not indicated in stable COPD. [I]
|
Evidence |
Source |
QE |
Overall Quality |
R |
1 |
There is no effect of NAC on rate of decline in FEV1 or exacerbations in COPD. |
Decramer et al., 2005 |
I |
Good |
D |
2 |
Exacerbations may be decreased with NAC 600 mg by mouth every day or other mucolytics in patients with chronic bronchitis not on inhaled glucocorticoids. |
Decramer et al., 2005
Grandjean et al., 2000
Poole & Black, 2006
Stey et al., 2000
|
I |
Good |
B |
3 |
The antioxidants alpha-tocopherol and beta-carotene are not effective in COPD. |
"The alpha-tocopherol," 1994
Rautalahti et al., 1997
|
I |
Good |
D |
4 |
Antitussives not effective in COPD. |
National Collaborating Centre for Chronic Conditions, 2004 |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (See Appendix A in the original guideline document)
4.5 Alpha-l-Antitrypsin Augmentation Therapy
Action Statement
Patients with COPD due to confirmed or suspected AAT deficiency should be referred to a pulmonary subspecialist. [C]
AAT augmentation therapy should be considered in patients with severe hereditary AAT deficiency and established emphysema. [C]
Recommendations
- Patients with COPD due to AAT deficiency should be provided the usual COPD therapy—smoking cessation, preventive vaccinations, bronchodilators, supplemental oxygen if indicated, and pulmonary rehabilitation. [I]
- Patients with severe AAT deficiency who have stopped smoking and with moderate to severe COPD (FEV1 30 to 60 percent predicted) should be considered for AAT augmentation therapy. Furthermore, benefits are not clear for those with FEV1 either below 30 percent or above 60 percent predicted. [C]
- Augmentation therapy is not indicated for patients without emphysema. [D]
|
Evidence |
Source |
QE |
Overall Quality |
R |
1 |
AAT augmentation therapy may slow the decline in lung function, reduce infection rates, and enhance survival in patients with emphysema and severe AAT deficiency. |
"Survival," 1998
American Thoracic Society/European Respiratory Society (ATS/ERS), 2003
Dirksen et al., 1999
Stoller & Abboussouan, 2005
|
II-2 |
Fair |
C |
2 |
AAT therapy may be most effective in patients with FEV1 30 to 60 percent predicted and is probably ineffective in patients outside that range. |
"Survival," 1998 |
II-2 |
Good |
C |
QE = Quality of Evidence; R = Strength of Recommendation (See Appendix A in the original guideline document)
4.6 Lung Volume Reduction Surgery
Action Statement
Consider lung volume reduction surgery (LVRS) in carefully selected patients with very severe COPD who comply with selection criteria used in studies demonstrating benefit from this intervention. [A]
Recommendations
- Referral for LVRS may be considered for patients with very severe COPD if they meet the following criteria [A]:
- High-resolution CT confirming bilateral emphysema
- Total lung capacity before rehabilitation and after treatment with bronchodilators is greater than 100 percent predicted and residual volume is greater than 150 percent predicted
- Post-bronchodilator FEV1 is less than 45 percent predicted
- PaCO2 less than 60 mm Hg, and PaO2 greater than 45 mm Hg
- Patient has completed a pulmonary rehabilitation program.
- LVRS should not be considered in patients whose FEV1 is less than 20 percent predicted and who either have homogenous emphysema or carbon monoxide diffusing capacity that is less than 20 percent or have non-upper lobe emphysema and high baseline exercise capacity. [D]
- LVRS should only be performed in medical centers with appropriately trained surgeons and availability of necessary equipment. [I]
|
Evidence |
Source |
QE |
Overall Quality |
R |
1 |
LVRS yielded a survival advantage only for patients with upper lobe emphysema and low baseline exercise capacity. |
Fishman et al., 2003 |
I |
Good |
B |
2 |
LVRS demonstrated increased mortality and no functional improvement for patients with non-upper lobe emphysema. |
Berger et al., 2005
Fishman et al., 2003
|
I |
Good |
D |
3 |
LVRS improved exercise capacity and QOL after 2 years among patients with upper lobe emphysema. |
Fishman et al., 2003
Naunheim et al., 2006
Tiong et al., 2006
|
I |
Good |
A |
4 |
LVRS increases mortality compared to optimum medical therapy in patients with COPD with FEV1 <20 percent and homogenous emphysema in chest CT scan or diffusing capacity <20 percent. |
Fishman et al., 2003 |
I |
Good |
D |
QE = Quality of Evidence; R = Strength of Recommendation (See Appendix A in the original guideline document)
4.7 Lung Transplantation Surgery
Action Statement
For patients with severe symptoms, despite maximal medical therapy, lung volume reduction surgery and transplantation may be an option. [C]
Recommendations
- Lung transplantation may be considered in selected patients with advanced COPD. The choice of single lung transplantation (SLT) or bilateral lung transplantation (BLT) for COPD remains controversial. [C]
COPD Disease-Specific Guidelines for Candidate Selection for Lung Transplantation
Guidelines for Referral
- BODE index exceeding 5 (Stands for BMI, Obstructive pulmonary function, dyspnea by MMRC and Exercise by 6-minute walk distance)
Guidelines for Transplantation
- Patients with a BODE index of 7 to 10 or at least 1 of the following:
- History of hospitalization for exacerbation associated with acute hypercapnia (PCO2 exceeding 50 mm Hg).
- Pulmonary hypertension or cor pulmonale, or both, despite oxygen therapy.
- FEV1 of less than 20 percent and either DLCO of less than 20 percent or homogenous distribution of emphysema.
|
Evidence |
Source |
QE |
Overall Quality |
R |
1 |
Lung transplantation results in highly selected patients improved: pulmonary function, exercise capacity. |
Arcasoy & Kotloff, 1999
Bando et al., 1995
Mal et al., 1994
|
III |
Fair |
C |
2 |
Lung transplantation results in highly selected patients improved quality of life |
Orens et al., 2006 |
III |
Good |
C |
3 |
Lung transplantation results in highly selected patients improved survival. |
Hosenpud et al., 1998 |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (See Appendix A in the original guideline document)