Table.
GRADE Evaluation of interventions for COPD.
| Important outcomes | COPD exacerbation and worsening of symptoms, Lung function and exercise capacity, Mortality, Quality of life | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of maintenance drug treatment in stable COPD? | |||||||||
| 4 (1651) | Lung function and exercise capacity | Anticholinergics (short-term treatment) versus placebo | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 1 (780) | COPD exacerbation and worsening of symptoms | Anticholinergics (short-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (780) | Quality of life | Anticholinergics (short-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 17 (17,606) | Mortality | Anticholinergics (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 9 (4769) | Lung function and exercise capacity | Anticholinergics (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality points deducted for incomplete reporting of results |
| 9 (4835) | COPD exacerbation and worsening of symptoms | Anticholinergics (long-term treatment) versus placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 4 (2386) | Quality of life | Anticholinergics (long-term treatment) versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 7 (at least 405) | Lung function and exercise capacity | Short-acting beta2 agonists (short-term treatment) versus placebo | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for heterogeneity among RCTs |
| 5 (379) | COPD exacerbation and worsening of symptoms | Short-acting beta2 agonists (short-term treatment) versus placebo | 4 | −1 | −2 | 0 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency points deducted for heterogeneity among RCTs included in review and different results for different measures of the same outcome |
| 13 (8400) | Mortality | Long-acting beta2 agonists (short-term or long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (1797) | Lung function and exercise capacity | Long-acting beta2 agonists (short-term or long-term treatment) versus placebo | 4 | 0 | −1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results for outcomes assessing exercise capacity |
| 20 (8614) | COPD exacerbation and worsening of symptoms | Long-acting beta2 agonists (short-term or long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 12 (8375) | Quality of life | Long-acting beta2 agonists (short-term or long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (2248) | Lung function and exercise capacity | Short-acting anticholinergic plus short-acting inhaled beta2 agonist (short-term treatment) versus short-acting beta2 agonist alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 5 (at least 1529) | COPD exacerbation and worsening of symptoms | Short-acting anticholinergic plus short-acting inhaled beta2 agonist (short-term treatment) versus short-acting beta2 agonist alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (1529) | Quality of life | Short-acting anticholinergic plus short-acting inhaled beta2 agonist (short-term treatment) versus short-acting beta2 agonist alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (1186) | COPD exacerbation and worsening of symptoms | Short-acting anticholinergic plus short-acting inhaled beta2 agonist (short-term treatment) versus short-acting anticholinergic alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (94) | Lung function and exercise capacity | Short-acting anticholinergic plus long-acting inhaled beta2 agonist (short-term treatment) versus beta2 agonist alone | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (172) | Lung function and exercise capacity | Short-acting anticholinergic plus long-acting inhaled beta2 agonist (short-term treatment) versus short-acting anticholinergic plus short-acting inhaled beta2 agonist | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 6 (1917) | Lung function and exercise capacity | Short-acting anticholinergic versus short-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (1529) | COPD exacerbation and worsening of symptoms | Short-acting anticholinergic versus short-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (1529) | Quality of life | Short-acting anticholinergic versus short-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 2 (at least 471) | Lung function and exercise capacity | Short-acting anticholinergic versus long-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 4 (1241) | COPD exacerbation and worsening of symptoms | Short-acting anticholinergic versus long-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (467) | Quality of life | Short-acting anticholinergic versus long-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (1460) | Mortality | Long-acting anticholinergic versus long-acting beta2 agonist | 4 | 0 | 0 | 0 | 0 | High | |
| 2 (1382) | Lung function and exercise capacity | Long-acting anticholinergic versus long-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (1460) | COPD exacerbation and worsening of symptoms | Long-acting anticholinergic versus long-acting beta2 agonist | 4 | 0 | 0 | 0 | 0 | High | |
| 2 (807) | Quality of life | Long-acting anticholinergic versus long-acting beta2 agonist | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 11 (at least 740) | Lung function and exercise capacity | Theophylline (short-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (964) | Lung function and exercise capacity | Theophylline (long-term treatment) versus placebo | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for inclusion of a 3-armed RCT with 1 open-label arm |
| 1 (110) | COPD exacerbation and worsening of symptoms | Theophylline (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 10 (445) | Lung function and exercise capacity | Oral corticosteroids versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (424) | Lung function and exercise capacity | Inhaled corticosteroids (short-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 6 (15,407) | Mortality | Inhaled corticosteroids (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for poor methodology in 1 very large RCT (analysis included people who had discontinued study medication) |
| 6 (at least 3747) | Lung function and exercise capacity | Inhaled corticosteroids (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 13 (9578) | COPD exacerbation and worsening of symptoms | Inhaled corticosteroids (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 6 (3230) | Quality of life | Inhaled corticosteroids (long-term treatment) versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 9 (7342) | Mortality | Corticosteroid plus long-acting beta2 agonist versus placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 10 (4070) | Lung function and exercise capacity | Corticosteroid plus long-acting beta2 agonist versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (5804) | COPD exacerbation and worsening of symptoms | Corticosteroid plus long-acting beta2 agonist versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 8 (5205) | Quality of life | Corticosteroid plus long-acting beta2 agonist versus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (6682) | Mortality | Corticosteroid plus long-acting beta2 agonist versus corticosteroid alone | 4 | 0 | 0 | 0 | 0 | High | |
| 6 (1831) | Lung function and exercise capacity | Corticosteroid plus long-acting beta2 agonist versus corticosteroid alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (4930) | COPD exacerbation and worsening of symptoms | Corticosteroid plus long-acting beta2 agonist versus corticosteroid alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 5 (at least 3697) | Quality of life | Corticosteroid plus long-acting beta2 agonist versus corticosteroid alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 11 (10,013) | Mortality | Corticosteroid plus long-acting beta2 agonist versus beta2 agonist alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for unclear allocation concealment in some RCTs |
| 13 (10,695) | Lung function and exercise capacity | Corticosteroid plus long-acting beta2 agonist versus beta2 agonist alone | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and unclear allocation concealment in some RCTs |
| at least 14 (at least 12,297) | COPD exacerbation and worsening of symptoms | Corticosteroid plus long-acting beta2 agonist versus beta2 agonist alone | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and unclear allocation concealment in some RCTs |
| 10 (9329) | Quality of life | Corticosteroid plus long-acting beta2 agonist versus beta2 agonist alone | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and unclear allocation concealment in some RCTs |
| at least 7 (at least 5764) | COPD exacerbation and worsening of symptoms | Mucolytics (long-term treatment) versus placebo | 4 | −1 | −2 | −1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency points deducted for conflicting results and for heterogeneity among RCTs. Directness point deducted for inclusion of people without COPD |
| 11 (2625) | Quality of life | Mucolytics (long-term treatment) versus placebo | 4 | −1 | −1 | −1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for heterogeneity among RCTs. Directness point deducted for inclusion of people without COPD |
| 1 (709) | Lung function and exercise capacity | Mucolytics (long-term treatment) versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting. Directness point deducted for differences in additional medications between groups at baseline |
| 11 (at least 888) | COPD exacerbation and worsening of symptoms | Prophylactic antibiotics versus placebo | 4 | −1 | 0 | −2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for inclusion of people without COPD and uncertainty about generalisability of results as some included trials were >30 years old |
| 7 (755) | Quality of life | Prophylactic antibiotics versus placebo | 4 | −1 | 0 | −2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for inclusion of people without COPD and uncertainty about generalisability of results as some included trials were >30 years old |
| 1 (109) | Lung function and exercise capacity | Prophylactic antibiotics versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for possible drug–drug interactions |
| 3 (250) | Mortality | Oxygen versus no oxygen (long-term treatment) | 4 | 0 | −1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results in different populations |
| 1 (28) | Lung function and exercise capacity | Oxygen versus no oxygen (long-term treatment) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (28) | COPD exacerbation and worsening of symptoms | Oxygen versus no oxygen (long-term treatment) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (56) | Lung function and exercise capacity | Alpha1 antitrypsin versus placebo (long-term treatment) | 4 | −1 | 0 | −1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for narrowness of population (people with diagnosis of emphysema) |
| What are the effects of smoking cessation interventions in people with stable COPD? | |||||||||
| 1 (3926) | Mortality | Psychosocial interventions versus usual care | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted for combined analysis at long-term analysis (analysis at 14 years, includes smoking cessation with ipratropium) |
| 1 (5887) | Lung function and exercise capacity | Psychosocial interventions versus usual care | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted for combined analysis at long-term analysis (analysis at 11 years includes smoking cessation with ipratropium) |
| 1 (5887) | COPD exacerbation and worsening of symptoms | Psychosocial interventions versus usual care | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted for combined analysis (includes smoking cessation with ipratropium) |
| 1 (3925) | Mortality | Psychosocial plus pharmacological interventions versus usual care | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted for combined analysis for long-term results (analysis at 14 years includes smoking cessation without ipratropium) |
| 1 (5887) | Lung function and exercise capacity | Psychosocial plus pharmacological interventions versus usual care | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted for combined analysis at 11 years (includes smoking cessation without ipratropium) |
| 1 (5887) | COPD exacerbation and worsening of symptoms | Psychosocial plus pharmacological interventions versus usual care | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted for combined analysis at 11 years (includes smoking cessation without ipratropium) |
| 1 (3923) | Mortality | Psychosocial plus pharmacological interventions versus psychosocial intervention alone | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (5887) | Lung function and exercise capacity | Psychosocial plus pharmacological interventions versus psychosocial intervention alone | 4 | 0 | 0 | 0 | 0 | High | |
| What are the effects of non-drug interventions in people with stable COPD? | |||||||||
| at least 25 (at least 1220) | Lung function and exercise capacity | Pulmonary rehabilitation versus usual care | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 14 (at least 802) | COPD exacerbation and worsening of symptoms | Pulmonary rehabilitation versus usual care | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 15 (at least 765) | Quality of life | Pulmonary rehabilitation versus usual care | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 16 (at least 410) | Lung function and exercise capacity | Inspiratory muscle training (IMT) versus control or no IMT | 4 | −1 | −1 | −1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for lack of consistent benefit. Directness point deducted for inclusion of co-intervention (general exercise rehabilitation) |
| 2 (number of people not reported) | COPD exacerbation and worsening of symptoms | Inspiratory muscle training (IMT) versus control or no IMT | 4 | −1 | 0 | −1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of co-intervention (general exercise rehabilitation) |
| at least 6 (number of people not reported) | Lung function and exercise capacity | Inspiratory muscle training (IMT) plus general exercise reconditioning versus general exercise reconditioning alone | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for lack of consistent benefit |
| at least 13 (at least 330) | Lung function and exercise capacity | Inspiratory muscle training (IMT) versus sham IMT | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for lack of consistent benefit |
| 4 (96) | COPD exacerbation and worsening of symptoms | Inspiratory muscle training (IMT) versus sham IMT | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 2 (69) | Quality of life | Inspiratory muscle training (IMT) versus sham IMT | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| at least 7 (at least 261) | Lung function and exercise capacity | Peripheral muscle training versus no treatment or other exercise training | 4 | −1 | 0 | −1 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for lack of consistent benefit |
| 6 (249) | Lung function and exercise capacity | General physical activity enhancement versus control | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for inconsistent effects |
| 2 (61) | COPD exacerbation and worsening of symptoms | General physical activity enhancement versus control | 4 | −2 | −1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| 3 (100) | Quality of life | General physical activity enhancement versus control | 4 | −2 | −1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| at least 6 (at least 156) | Lung function and exercise capacity | Nutritional supplementation versus placebo or usual diet | 4 | −1 | −1 | −2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for heterogeneity among RCTs. Directness points deducted for lack of standardisation of interventions and variations among studies |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.