Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of ...side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.
The number of pharmacological medications available to treat patients with COPD has increased over the past few decades. Most of the improvement has come from the modification of older compounds that ...are now more potent, of longer duration, and delivered in improved devices. They are now available as single, double, and even triple combinations that, although attempting to simplify administration, have also resulted in a large number of preparations. These medications are clearly effective and should be used as a central component of the multidimensional approach to the patient affected with COPD. The preferred route remains the inhaled direct delivery to the airways, but the favorable results obtained with systemic agents such as macrolides and roflumilast and the preliminary results of some biologicals are opening the door for the development of new drugs or reformulation of medications that have been used for other indications. Perhaps the most pressing need is to study the effect of these agents at early points in the course of the disease, because until now most, if not all, studies have been conducted in patients usually older than age 60 years, when most of the natural course of the disease has already been run. This monograph reviews the available pharmacological therapy based on current evidence and provides practical recommendations to health providers caring for patients with COPD.
Patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remains poorly defined ...and lacking firm evidence. To date, there is no universally accepted definition of ACOS, which has made it difficult to understand its epidemiology or pathophysiology. Despite many uncertainties, there is emerging agreement that some of the key features of ACOS include persistent airflow limitation in symptomatic individuals 40 years of age and older, a well-documented history of asthma in childhood or early adulthood and a significant exposure history to cigarette or biomass smoke. In this perspective, we propose a case definition of ACOS that incorporates these key features in a parsimonious algorithm that may enable clinicians to better diagnose patients with ACOS and most importantly enable researchers to design therapeutic and clinical studies to elucidate its epidemiology and pathophysiology and to ascertain its optimal management strategies.
Summary Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in adults. Although FEV1 remains the most important physiologic indicator of the severity of airflow ...obstruction in COPD, its predictive value for mortality is weak when it is higher than 50% of predicted. Furthermore, other easily obtainable clinical variables predict mortality better than the FEV1 in COPD patients with a wide range of airflow limitation. Chief among these predictors are functional dyspnea, exercise capacity, and the body mass index (BMI), although emerging research suggests a potential role for biomarker profiles in outcome predictions. The validated multidimensional BMI (B), degree of airflow obstruction as expressed by the FEV1 (O), dyspnea with the modified medical research council (D), and exercise (E) measured with the 6 min walk or BODE index encompasses the predictive validity of the best of these variables into a single surrogate measure of disease severity and survival. This article reviews these predictors of mortality in COPD.
Summary Background Chronic obstructive pulmonary disease (COPD) often coexists with cardiovascular disease. Treatments for airflow limitation might improve survival and both respiratory and ...cardiovascular outcomes. The aim of this study was to assess whether inhaled treatment with a combined treatment of the corticosteroid, fluticasone furoate, and the long-acting β agonist, vilanterol could improve survival compared with placebo in patients with moderate COPD and heightened cardiovascular risk. Methods In this double-blind randomised controlled trial (SUMMIT) done in 1368 centres in 43 countries, eligible patients were aged 40–80 years and had a post-bronchodilator forced expiratory volume in 1 s (FEV1 ) between 50% and 70% of the predicted value, a ratio of post-bronchodilator FEV1 to forced vital capacity (FVC) of 0·70 or less, a smoking history of at least 10 pack-years, and a score of 2 or greater on the modified Medical Research Council dyspnoea scale. Patients had to have a history, or be at increased risk, of cardiovascular disease. Enrolled patients were randomly assigned (1:1:1:1) through a centralised randomisation service in permuted blocks to receive once daily inhaled placebo, fluticasone furoate (100 μg), vilanterol (25 μg), or the combination of fluticasone furoate (100 μg) and vilanterol (25 μg). The primary outcome was all-cause mortality, and secondary outcomes were on-treatment rate of decline in forced expiratory volume in 1 s (FEV1 ) and a composite of cardiovascular events. Safety analyses were performed on the safety population (all patients who took at least one dose of study drug) and efficacy analyses were performed on the intention-to-treat population (safety population minus sites excluded with Good Clinical Practice violations). This study is registered with ClinicalTrials.gov , number NCT01313676. Findings Between Jan 24, 2011, and March 12, 2014, 23 835 patients were screened, of whom 16 590 were randomised. 16 485 patients were included in the intention-to-treat efficacy population; 4111 in the placebo group, 4135 in the fluticasone furoate group, 4118 in the vilanterol group, and 4121 in the combination group. Compared with placebo, all-cause mortality was unaffected by combination therapy (hazard ratio HR 0·88 95% CI 0·74–1·04; 12% relative reduction; p=0·137) or the components (fluticasone furoate, HR 0·91 0·77–1·08; p=0·284; vilanterol, 0·96 0·81–1·14; p=0·655), and therefore secondary outcomes should be interpreted with caution. Rate of decline in FEV1 was reduced by combination therapy (38 mL per year SE 2·4 vs 46 mL per year 2·5 for placebo, difference 8 mL per year 95% CI 1–15) with similar findings for fluticasone furoate (difference 8 mL per year 95% CI 1–14), but not vilanterol (difference −2 mL per year 95% CI −8 to 5). Combination therapy had no effect on composite cardiovascular events (HR 0·93 95% CI 0·75–1·14) with similar findings for fluticasone furoate (0·90 0·72–1·11) and vilanterol (0·99 0·80–1·22). All treatments reduced the rate of moderate and severe exacerbation. No reported excess risks of pneumonia (5% in the placebo group, 6% in the combination group, 5% in the fluticasone furoate group, and 4% in the vilanterol group) or adverse cardiac events (17% in the placebo group, 18% in the combination group, and 17% in the fluticasone furoate group, and 17% in the vilanterol group) were noted in the treatment groups. Interpretation In patients with moderate COPD and heightened cardiovascular risk, treatment with fluticasone furoate and vilanterol did not affect mortality or cardiovascular outcomes, reduced exacerbations, and was well tolerated. Fluticasone furoate, alone or in combination with vilanterol, seemed to reduce FEV1 decline. Funding GlaxoSmithKline.
COPD is highly prevalent and will continue to be an increasing cause of morbidity and mortality worldwide. COPD is now viewed
under a new paradigm as preventable and treatable. In addition, it has ...become accepted that COPD is not solely a pulmonary
disease but also one with important measurable systemic consequences. Patients with COPD have to be comprehensively evaluated
to determine the extent of disease so that therapy can be adequately individualized. We now know that smoking cessation, oxygen
for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe
exacerbations have an impact on mortality. The completion of well-planned pharmacologic trials have shown the importance of
decreasing resting and dynamic hyperinflation on patient-centered outcomes and the possible impact on mortality and rate of
decline of lung function. In addition, therapy with pulmonary rehabilitation and lung transplantation improve patient-centered
outcomes such as health-related quality of life, dyspnea, and exercise capacity. Rational use of single or multiple therapeutic
modalities in combination have an impact on exacerbations and hospitalizations. This monograph presents an integrated approach
to patients with COPD and updates their management incorporating the recent advances in the field. The future for patients
with COPD is bright as primary and secondary prevention of smoking becomes more effective and air quality improves. In addition,
current research will unravel the pathogenesis, clinical, and phenotypic manifestations of COPD, thus providing exciting therapeutic
targets. Ultimately, the advent of newer and more effective therapies will lead to a decline in the contribution of this disease
to poor world health.
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The pathology and impact of chronic obstructive pulmonary disease (COPD) results from an abnormal inflammatory process resulting in tissue damage with ineffective repair in response to toxic ...inhalants (especially cigarette smoke). Identification of mechanisms provides the opportunity to develop new therapies and a personalized approach to management. The collection of multiple genetic and detailed biochemical data from small and large patient cohorts has led to an explosion of studies investigating biomarkers to achieve these aims. Despite widespread enthusiasm and many statistically significant associations, the interpretation of COPD biomarker results requires thought and leaves many questions unanswered. The present review assesses the importance of these associations, whether they represent cause or effect, reflect disease severity or activity, the complexity of the pathway to the final pathogenic and hence interventional step, and problems with interpreting cross-sectional studies without knowing individual disease trajectories. The complexity of biomarker specificity without sufficient clinical phenotype and endotype information contributes to problems of interpretation. A strategic change is needed to develop useful COPD biomarkers; this includes focusing on endotype biomarkers within specific clinical phenotypes, biomarkers in early COPD, exacerbation subtype biomarkers, and biomarkers to predict or measure drug effects.
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