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Gold 2023: Highlights for Primary Care

Author/s: 
Alvar Agustí, Antoni Sisó-Almirall, Miguel Roman, Claus F. Vogelmeier

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has issued its 2023 annual report1. Compared with former versions, it has been significantly updated. Here, we summarize the most relevant changes for a Primary Care audience. The complete document can be downloaded for free from the GOLD web page (www.goldcopd.org), together with a “pocket guide” and a “teaching slide set”.

Keywords 
chronic obstructive pulmonary disease gold primary health care Humans

Why We Should Target Small Airways Disease in Our Management of Chronic Obstructive Pulmonary Disease

Author/s: 
Usmani, O., Dhand, R., Lavorini, F., Price, D.

For more than 50 years, small airways disease has been considered a key feature of chronic obstructive pulmonary disease (COPD) and a major cause of airway obstruction. Both preventable and treatable, small airways disease has important clinical consequences if left unchecked. Small airways disease is associated with poor spirometry results, increased lung hyperinflation, and poor health status, making the small airways an important treatment target in COPD. The early detection of small airways disease remains the key barrier; if detected early, treatments designed to target small airways may help reduce symptoms and allow patients to maintain their activities. Studies are needed to evaluate the possible role of new drugs and novel drug formulations, inhalers, and inhalation devices for treating small airways disease. These developments will help to improve our management of small airways disease in patients with COPD.

Keywords 
Small Airways Disease chronic obstructive pulmonary disease copd

Pharmacologic and Nonpharmacologic Therapies in Adult Patients With Exacerbation of COPD: A Systematic Review

Author/s: 
Dobler, CC, Morrow, AS, Farah, MH, Beuschel, B, Majzoub, AM, Wilson, ME, Hasan, B, Seisa, MO, Daraz, L, Prokop, LJ, Murad, MH, Wang, Z

Objectives. To synthesize existing knowledge about the effectiveness and harms of pharmacologic and nonpharmacologic treatments for exacerbations of chronic obstructive pulmonary disease (ECOPD).

Data sources. Embase®, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE® Daily, MEDLINE, Cochrane Central Registrar of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from database inception to January 2, 2019.

Review methods. We included randomized controlled trials (RCTs) that evaluated pharmacologic intervention or nonpharmacologic interventions for ECOPD. The strength of evidence (SOE) was graded for critical final health outcomes.

Results. We included 98 RCTs (13,401 patients, mean treatment duration 9.9 days, mean followup 3.7 months). Final health outcomes, including mortality, resolution of exacerbation, hospital readmissions, repeat exacerbations, and need for intubation, were infrequently evaluated and often showed no statistically significant differences between groups. Antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate regardless of the severity of ECOPD (moderate SOE). There is insufficient evidence to support a particular antibiotic regimen. Oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate (low SOE). Despite the ubiquitous use of inhaled bronchodilators in ECOPD, we found only a small number of trials that assessed lung function tests, and not final health outcomes. The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor, and statins on final health outcomes. Titrated oxygen reduces mortality compared with high flow oxygen (low SOE). Low SOE suggested benefit from some nonpharmacologic interventions such as chest physiotherapy using vibration/percussion/massage or breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation commenced before hospital discharge during the initial most acute phase of exacerbation rather than the convalescence period (on dyspnea) and whole body vibration training (on quality of life). Vitamin D supplementation may improve quality of life (low SOE).

Conclusions. Although chronic obstructive pulmonary disease is a common condition, the evidence base for most interventions in ECOPD remains limited. Systemic antibiotics and corticosteroids are associated with improved outcomes in mild and moderate to severe ECOPD. Titrated oxygen reduces mortality. Future research is required to assess the effectiveness of several emerging nonpharmacologic and dietary treatments.

Keywords 
copd chronic obstructive pulmonary disease therapy randomized control trial systematic review

Benralizumab for the Prevention of COPD Exacerbations

Author/s: 
Criner GJ, Celli, BR, Brightling CE, Agusti, A, Papi, A, Singh, D, Sin, DD, Vogelmeier, CD, Sciurba, FC, Bafadhel, M, Backer, V, Kato, M, Ramirez-Venegas, A, Wei, YF, Bjermer, L, Shih, VH, Jison, M, O'Quinn, S, Makulova, N, Newbold, P, Goldman, M, Martin, UJ

BACKGROUND:

The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.

METHODS:

In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.

RESULTS:

In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.

CONCLUSIONS:

Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Keywords 
benralizumab chronic obstructive pulmonary disease copd

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Author/s: 
Butler, Christopher C., Gillespie, David, White, Patrick, Bates, Janine, Lowe, Rachel, Thomas-Jones, Emma, Wootton, Mandy, Hood, Kerenza, Phillips, Rhiannon, Melbye, M., Llor, Carl, Cals, Jochen W.L.

BACKGROUND

Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).

METHODS

We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority).

RESULTS

A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.

CONCLUSIONS

CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.)

Keywords 
C-reactive protein primary care chronic obstructive pulmonary disease copd CRP randomized control trial antibiotics

COPD: All You Need to Know in 20 Minutes

Author/s: 
Sciurba, Frank C.

COPD is common enough that it is responsible for 3% of all clinic visits in the United States. Clinicians will undoubtedly deal with this disease in their practice. How to diagnose and manage it is reviewed by Frank C. Sciurba, MD, a professor of medicine from the University of Pittsburgh, Pennsylvania.

Keywords 
chronic obstructive pulmonary disease

Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials

Author/s: 
Jolliffe, David. A, Greenberg, Lauren, Hooper, Richard L., Mathyssen, Carolien, Rafiq, Rachida, de Jongh, Renate T., Camargo, Carlos A., Griffiths, Christopher J., Janssens, Wim, Martineau, Adrian R.

BACKGROUND:

Randomised controlled trials (RCTs) of vitamin D to prevent COPDexacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation.

METHODS:

PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial.

RESULTS:

Four eligible RCTs (total 560 participants) were identified; individual participant datawere obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75).

CONCLUSIONS:

Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels.

TRIAL REGISTRATION NUMBER:

CRD42014013953.

Keywords 
chronic obstructive pulmonary disease vitamin D

Inhaler Technique Education and Exacerbation Risk in Older Adults with Asthma or Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Author/s: 
Maricoto, Tiago, Monteiro, Luís, Gama, Jorge M. R., Correia-de-Sousa, Jamie, Taborda-Barata, Luís

Objectives

To evaluate the effect of inhaler education programs on clinical outcomes and exacerbation rates in older adults with asthma or chronic obstructive pulmonary disease (COPD).

Design

Systematic review and meta‐analysis.

Setting and Participants

Older adults with asthma or COPD, either in primary or secondary health care and pharmacy setting.

Measurements

We searched the Medline, Embase, and Central databases according to the main eligibility criteria for inclusion: systematic reviews, meta‐analysis, clinical trials and quasi‐experimental studies; participants aged 65 and older; education on inhaler technique and reporting of disease control and exacerbation rates. We used the Grading of Recommendations, Assessment, Development and Evaluations scale for quality assessment and used a random‐effect model with Mantel–Haenszel adjustment to perform a meta‐analysis.

Results

We included 8 studies (4 randomized, 4 quasi‐experimental) with a total of 1,812 participants. The most frequent type of intervention was physical demonstration of inhaler technique, training with placebo devices. Five studies showed significant reduction in exacerbation rates (pooled risk ratio=0.71, 95% confidence interval=0.59–0.86; p < .001), although effect on disease control and quality of life showed high discrepancy in the reported results, and all randomized studies revealed uncertainty in their risk of bias assessment.

Conclusion

All interventions seemed to improve inhaler performance and clinically relevant outcomes, but a placebo device could be the most effective. There is evidence that interventions reduce exacerbation risk in older adults, although to an overall moderate degree.

Keywords 
chronic obstructive pulmonary disease patient education inhalers asthma

Different Durations of Corticosteroid therapy for Exacerbations of Chronic Obstructive Pulmonary Disease

Author/s: 
Walters, Julia A.E., Wang, Wendy, Morley, Carla, Soltani, Amir, Wood-Baker, Richard

BACKGROUND:

Current guidelines recommend that patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) should be treated with systemic corticosteroid for seven to 14 days. Intermittent systemic corticosteroid use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could reduce adverse effects.

OBJECTIVES:

To compare the efficacy of short-duration (seven or fewer days) and conventional longer-duration (longer than seven days) systemic corticosteroid treatment of adults with acute exacerbations of COPD.

SEARCH METHODS:

Searches were carried out using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials) and ongoing trials registers up to March 2017.

SELECTION CRITERIA:

Randomised controlled trials comparing different durations of systemic corticosteroid defined as short (i.e. seven or fewer days) or longer (i.e. longer than seven days). Other interventions-bronchodilators and antibiotics-were standardised. Studies with participants requiring assisted ventilation were excluded.

DATA COLLECTION AND ANALYSIS:

We used standard methodological procedures as expected by The Cochrane Collaboration.

MAIN RESULTS:

Eight studies with 582 participants met the inclusion criteria, of which five studies conducted in hospitals with 519 participants (range 28 to 296) contributed to the meta-analysis. Mean ages of study participants were 65 to 73 years, the proportion of male participants varied (58% to 84%) and COPD was classified as severe or very severe. Corticosteroid treatment was given at equivalent daily doses for three to seven days for short-duration treatment and for 10 to 15 days for longer-duration treatment. Five studies administered oral prednisolone (30 mg in four, tapered in one), and two studies provided intravenous corticosteroid treatment. Studies contributing to the meta-analysis were at low risk of selection, performance, detection and attrition bias. In four studies we did not find a difference in risk of treatment failure between short-duration and longer-duration systemic corticosteroid treatment (n = 457; odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46)), which was equivalent to 22 fewer per 1000 for short-duration treatment (95% CI 51 fewer to 34 more). No difference in risk of relapse (a new event) was observed between short-duration and longer-duration systemic corticosteroid treatment (n = 457; OR 1.04, 95% CI 0.70 to 1.56), which was equivalent to nine fewer per 1000 for short-duration treatment (95% CI 68 fewer to 100 more). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non-inferiority and compared five days versus 14 days of systemic corticosteroid treatment (n = 311; hazard ratio 0.95, 95% CI 0.66 to 1.37). In five studies no difference in the likelihood of an adverse event was found between short-duration and longer-duration systemic corticosteroid treatment (n = 503; OR 0.89, 95% CI 0.46 to 1.69, or nine fewer per 1000 (95% CI 44 fewer to 51 more)). Length of hospital stay (n = 421; mean difference (MD) -0.61 days, 95% CI -1.51 to 0.28) and lung function at the end of treatment (n = 185; MD FEV1 -0.04 L; 95% CI -0.19 to 0.10) did not differ between short-duration and longer-duration treatment.

AUTHORS' CONCLUSIONS:

Information from a new large study has increased our confidence that five days of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 days) courses. We graded most available evidence as moderate in quality because of imprecision; further research may have an important impact on our confidence in the estimates of effect or may change the estimates. The studies in this review did not include people with mild or moderate COPD; further studies comparing short-duration systemic corticosteroid versus conventional longer-duration systemic corticosteroid for treatment of adults with acute exacerbations of COPD are required.

Keywords 
corticosteroids copd chronic obstructive pulmonary disease
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