Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a systematic review that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and there is no difference in effectiveness between the intervention and comparison for key outcomes.
Population: Adults with COPD
Intervention: Oral vitamin D supplementation
Comparison: Oral placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Moderate or severe exacerbations: overall | No statistically significant difference | High |
Moderate or severe exacerbations: baseline 25(OH)D <25 nmol/L | Favors intervention | Moderate |
Moderate or severe exacerbations: baseline 25(OH)D ≥25 nmol/L | No statistically significant difference | High |
Proportion with ≥1 severe exacerbation | No statistically significant difference | High |
Proportion with ≥1 serious adverse event | No statistically significant difference | High |
Note This systematic review reported that in the study population as a whole, vitamin D did not influence the rate of moderate or severe COPD exacerbations when compared with placebo. However, subgroup analyses showed that vitamin D supplementation decreased moderate or severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/l but not in those with baseline levels ≥25 nmol/.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes. However, this is uncertain and new evidence could change this in the future.
Population: Adults with acute exacerbations of COPD
Intervention: Systemic corticosteroids
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Clinical failure rate ᵃ | Favors intervention | Low |
Adverse events | No statistically significant difference | GRADE not reported for this outcome |
Recommendations as stated in the source guideline The AAFP recommends that clinicians prescribe corticosteroids for adults with acute exacerbation of COPD to reduce clinical failure (weak recommendation; low quality of evidence). There is insufficient evidence to guide the dose, route of administration, or duration of treatment.
Note The guideline group noted that there were no statistically significant differences in other outcomes of interest, including mortality and rehospitalization. It is unclear which other outcomes of interest were reported in the included studies. The evidence to inform the route of administration (oral; inhaled; intravenous) of corticosteroids in adults with acute exacerbation of COPD was insufficient. No significant difference in outcomes was observed in three studies which evaluated different durations of systemic corticosteroids (3 days vs. 10 days; 5 days vs. 14 days; and 2 weeks vs. 8 weeks) in the inpatient setting. The guideline group also noted that a large observational study published subsequent to the guideline search also found that shorter courses of corticosteroid were noninferior to longer courses, and longer courses were associated with a small increase in pneumonia-associated hospitalization and mortality. ᵃ Clinical failure, the main outcome of interest, was defined as “the lack of a significant improvement of clinical signs and symptoms and/or the requirement for additional or alternate treatment for an acute exacerbation event”.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: People with acute hypercapnic respiratory failure due to chronic obstructive pulmonary disease exacerbation
Intervention: NIV plus usual care
Comparison: Usual care alone (combinations of pharmacologic therapies)
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality (where reported, duration of follow‐up to intensive care unit [ICU] or hospital discharge) | Favors intervention | Moderate |
Need for endotracheal intubation (where reported, duration of follow‐up 3 days to 30 days, ICU discharge, or hospital discharge) | Favors intervention | Moderate |
Symptom scores (1 hour to 3 days) | No statistically significant difference | GRADE assessment not performed for this outcome |
Duration of ICU stay | No statistically significant difference | GRADE assessment not performed for this outcome |
Duration of hospital stay | Favors intervention | Moderate |
Treatment intolerance | Favors comparison | GRADE assessment not performed for this outcome |
Partial pressure of carbon dioxide (PaCO2; 1 hour postintervention) | No statistically significant difference | GRADE assessment not performed for this outcome |
Partial pressure of oxygen (PaO2; 1 hour postintervention) | Favors intervention | GRADE assessment not performed for this outcome |
Complications of treatment: NIV-related | See note ᵃ | GRADE assessment not performed for this outcome |
Complications of treatment: NonNIV-related | Occurs more commonly with usual care alone compared with NIV plus usual care (favors intervention) | GRADE assessment not performed for this outcome |
Note ᵃ 30% of people in the NIV plus usual care group had complications specifically related to NIV (not experienced in the usual care alone groups). See Cochrane Clinical Answer (CCA) for more details.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: Selected adults presenting at emergency rooms with acute exacerbation of COPD ᵃ
Intervention: Hospital-at-home (regular home visits by trained respiratory nurse supported by hospital team)
Comparison: Standard inpatient care
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Hospital re-admission (follow up: 1–6 months) | Favors intervention | Moderate |
Mortality (follow up: 2–6 months) | No statistically significant difference | Moderate |
FEV1 | No statistically significant difference | Low |
FVC | No statistically significant difference | GRADE assessment not performed for this outcome |
Quality of life (follow up: at discharge) | See note ᵇ | Very Low |
Satisfaction with care (follow up: 0–2 weeks after discharge; subgroup: patient satisfaction | No statistically significant difference | Low |
Satisfaction with care (follow up: 0–2 weeks after discharge; subgroup: carer satisfaction) | No statistically significant difference | Very Low |
Speed of exacerbation recovery, recurrent exacerbations | - | None of the studies identified by the review assessed these outcomes |
Note The Cochrane Clinical Answer (CCA) noted that patient characteristics varied across reviewed studies in terms of lung function and reasons for trial exclusion, affecting the generalizability of results. It also noted that the co-interventions given to participants varied across studies. The Cochrane review which underpins this CCA noted that while the review showed that treatment with a hospital-at-home scheme is safe, acceptable, and as effective as inpatient care, the majority of patients will still continue to require hospital care for their exacerbation. They also highlighted that more studies are required to evaluate the cost-effectiveness of hospital-at-home schemes. ᵃ The CCA noted that trials reported variable respiratory exclusion criteria (e.g., respiratory failure, pneumonia, pneumothorax, lung cancer, chest X‐ray changes, pulmonary embolism, hypoxia) and also that patients with acute/unstable co‐morbidities, reduced level of consciousness, and/or confusion were excluded by some trials. ᵇ Results reported narratively. Three RCTs (332 participants) reported quality of life using the St George’s Respiratory Questionnaire. Results could not be combined since one study reported percentage improvement while the other two reported standard deviations. The latter showed no statistically significant difference between treatment groups.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: Adults with acute exacerbations of COPD
Intervention: Antibiotics
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Clinical cure at end of intervention ᵃ | Favors intervention | Moderate |
Clinical failure rate ᵇ | Favors intervention | Moderate |
Adverse events | No statistically significant difference | GRADE not reported for this outcome |
Recommendations as stated in the source guideline The AAFP recommends that clinicians prescribe systemic antibiotics for adults with acute exacerbation of COPD to improve clinical cure and reduce clinical failure (weak recommendation; moderate quality of evidence). Choice of antibiotic should be based on local resistance patterns, affordability, and patient history and preferences because there is insufficient evidence to support a preferential recommendation.
Note The guideline group noted that there were no statistically significant differences in other outcomes of interest, including mortality and quality of life. Outcomes of interest were defined as patient-oriented clinical outcomes. However, it is unclear which other outcomes of interest were reported in the included studies. The guideline group also noted that, although they found studies of one antibiotic versus another and different dosages of antibiotics, there was “insufficient evidence to estimate an effect on most of the outcomes of interest”. No studies were identified for routes of administration of antibiotics in this population. ᵃ Clinical cure was defined as the complete improvement of clinical signs and symptoms following treatment. Three RCTs (633 participants) were included in the clinical cure analysis. One study randomized 223 patients to doxycycline or placebo for seven days in addition to corticosteroids. A second study randomized 100 patients to receive a fluoroquinolone or amoxicillin compared with placebo for 10 days. The third study randomized 310 patients to receive amoxicillin or placebo. ᵇ Clinical failure, the main outcome of interest, was defined as “the lack of a significant improvement of clinical signs and symptoms and/or the requirement for additional or alternate treatment for an acute exacerbation event”.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: People admitted to hospital or to the ICU with exacerbations of COPD
Intervention: Oral or intravenous antibiotics for minimum of 2 days ᵃ
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Treatment failure up to 4 weeks: inpatients ᵇ | Favors intervention | GRADE assessment not performed for this outcome |
Treatment failure up to 4 weeks: ICU patients ᶜ | Favors intervention | Moderate |
All‐cause mortality: inpatients | No statistically significant difference | Moderate |
All‐cause mortality: ICU patients ᶜ | Favors intervention | Moderate |
Duration of hospital stay (days): inpatients | No statistically significant difference | High |
Duration of hospital stay (days): ICU ᶜ | Favors intervention | Moderate |
Improvement in dyspnea measured at the end of the study period: inpatients | No statistically significant difference | GRADE assessment not performed for this outcome |
Health‐related quality of life or functional status measures: inpatients | No statistically significant difference | GRADE assessment not performed for this outcome |
Days off work: inpatients | Favors intervention | GRADE assessment not performed for this outcome |
Overall adverse events | No statistically significant difference | Moderate |
Note The Cochrane review which the CCA is based upon also noted continued uncertainty around the treatment effectiveness of antibiotics for treatment failure, mortality, re-exacerbations, or health-related quality of life in those people with acute exacerbation of COPD, since results are heterogenous and associated with some risk of bias. It also stated that factors such as patient preferences, resistance of bacteria to antibiotics, and cost are important when making recommendations or treatment decisions. There is also a need for research into clinical signs and biomarkers which can help identify patients who would benefit the most from antibiotic treatment. ᵃ Included studies ranging from 5 to 14 days duration of antibiotic/placebo treatment. ᵇ The CCA noted that when reviewers focused on currently prescribed drugs in their analysis, there was no statistical significance between treatment groups for inpatients with severe exacerbations who were not admitted to ICU. ᶜ Evidence for ICU patients was limited to one trial of 93 patients.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: People with a clinical diagnosis of COPD (FEV1/FVC <70%) with a history of smoking
Intervention: Action plan (written guidance detailing self‐initiated interventions such as changing medication regime or visiting a GP or hospital) in response to changes that may suggest the start of an acute exacerbation of COPD ᵃ
Comparison: Usual care (no access to the action plan)
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Hospitalizations for COPD/100 patient years (follow‐up: 12 months) | No statistically significant difference | Moderate |
At least 1 hospital admission (follow‐up: 12 months) | Favors intervention | Moderate |
Hospitalizations & emergency visits for COPD/100 patient years | Favors intervention | High |
Courses of oral corticosteroids: 12 months | Favors intervention | Moderate |
Courses of antibiotics: 12 months | Favors intervention | Moderate |
FEV1 % predicted: 6 months | No statistically significant difference | GRADE assessment not performed for this outcome |
FEV1 % predicted: 12 months | No statistically significant difference | GRADE assessment not performed for this outcome |
Quality of life measured by St George's Respiratory Questionnaire (SGRQ) overall score: 6–12 months | Favors intervention | Moderate |
Mortality (all cause): 12 months | No statistically significant difference | Moderate |
Note ᵃ Accompanied by a single short educational component along with ongoing support directed at use of the action plan, but without a comprehensive self‐management program.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: Adults with severe or very severe COPD experiencing exacerbations
Intervention: Systemic corticosteroids for seven days or fewer
Comparison: Systemic corticosteroids for longer than seven days
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Treatment failure (10–14 days) | No statistically significant difference | Moderate |
Relapse (14–180 days) | No statistically significant difference | Moderate |
Time to re‐exacerbation | No statistically significant difference | GRADE assessment not performed for this outcome |
FEV1 % predicted: 6 days | No statistically significant difference | GRADE assessment not performed for this outcome |
FEV1 % predicted: 30 days | No statistically significant difference | GRADE assessment not performed for this outcome |
Dyspnea | No statistically significant difference | GRADE assessment not performed for this outcome |
Quality of life: 6 days | No statistically significant difference | GRADE assessment not performed for this outcome |
Quality of life: 30 days | No statistically significant difference | Moderate |
Duration of hospital stay | No statistically significant difference | Moderate |
Adverse effects: hyperglycemia | No statistically significant difference | Moderate |
Adverse effects: hypertension | No statistically significant difference | GRADE assessment not performed for this outcome |
Adverse effects: other ᵃ | No statistically significant difference | Low |
Note The Cochrane Clinical Answer (CCA) noted that the number of participants included in the meta-analyses for the primary outcomes of treatment failure and relapse may be too small (450 and 478 participants) to detect differences between treatment groups. The Cochrane review which underpins the CCA noted that one large study carried most of the weight in the meta-analysis, and was therefore responsible for the confidence in the conclusion that shorter courses of oral corticosteroids (for five days) can be used as treatment for COPD exacerbation as they seem to be equally effective as longer courses. The Cochrane review which underpins this CCA noted that the reviewed studies did not include people with mild or moderate COPD and future studies are required in this patient group. The Cochrane review also reported two outcomes not included in the CCA (mortality: no statistically significant difference between treatment groups, moderate GRADE rating; lung function (end of treatment; FEV1; 10–14 days]: no statistically significant difference between treatment groups, very low GRADE rating). ᵃ Other adverse effects included gastrointestinal tract bleeding, symptomatic gastrointestinal reflux, symptoms of congestive heart failure or ischemic heart disease, sleep disturbance, fractures, and depression.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
- How does longer corticosteroid treatment (>7 days) compare with shorter (≤7 days) in people with exacerbations of chronic obstructive pulmonary disease?
- What is the impact of airway clearance techniques when treating acute exacerbations of COPD?
- How do antibiotics compare with placebo in people admitted to hospital or to the intensive care unit with exacerbations of chronic obstructive pulmonary disease?
- How does non-invasive ventilation compare with usual care in people with acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease?
- What are the effects of hospital-at-home in adults with acute exacerbations of chronic obstructive pulmonary disease?
- What are the effects of action plans with limited patient education only in reducing exacerbations of chronic obstructive pulmonary disease?
Use of this content is subject to our disclaimer