Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)62116-4.pdf

Chronic obstructive pulmonary disease in non-smokers

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

/pdf/outcomes-for-copd-pharmacological-trials-from-lung-function-4a4k924y7q.pdf

Outcomes for COPD pharmacological trials: From lung function to biomarkers

In a follow–up to the 2011 United Nations (UN) high level political declaration on non-communicable diseases (NCDs) [1], the World Health Assembly, in 2012, endorsed a new health goal (the “25 by 25 goal”), which focuses on reduction of premature deaths from COPD and other NCDs by 25% by the year 2025 [2]. Despite this initiative, experts have reported that COPD remains a growing [3], but neglected global epidemic [4]. The World Health Organization (WHO) estimated that there were about 62 million people with moderate to severe COPD in 2002, with the total number of COPD cases predicted to increase to about 200 million in 2010 [5,6]. According to the 2010 Global Burden of Disease (GBD) study, COPD was responsible for about 5% of global disability–adjusted life years – DALYs (76.7 million) – and 5% of total deaths (2.9 million) [7,8]. COPD is currently rated the fourth most common specific cause of death globally and predicted to be the third by 2030, in the absence of interventions that address the risks – especially tobacco smoking, exposures to combustion products of biomass fuels and environmental pollution [9,10].

The burden of COPD has been reported to be high in some high–income countries (HIC), particularly due to high prevalence of smoking in these settings [11]. For example, between years 2000 and 2010, about 4%–10% of adults were diagnosed with non–reversible and progressive airway obstruction (a basic feature of COPD) in population–based surveys across many European countries, with smoking indicated as a major risk [12]. The WHO has estimated that in many HIC up to 73% of COPD deaths are related to tobacco smoking [6]. The European Union (EU) reported that the direct cost from COPD was over 38.6 billion Euros in 2005, representing about 3% of total health care expenditure [13,14]. In the United States (US), over 2.7 million adults were estimated to have COPD in 2011, with about 135 000 deaths reported [15]. In 2010, the US government spent nearly US$ 49.9 billion on COPD, including 29.5 billion spent on direct health care, 8.0 billion on indirect morbidity and 12.4 billion on indirect mortality costs, respectively [15].

Meanwhile, it has been estimated that despite a high prevalence of COPD in some HIC, 90% of COPD deaths still occur in low– and middle–income countries (LMIC)in the future

[4] and 40% of these deaths are attributable to smoking [6]. The burden in LMIC has been comparatively high owing to relatively low COPD awareness, challenges with COPD diagnosis and increased exposures to additional risk factors, especially combustion products of biomass fuels [16]. Salvi and colleagues reported that about 3 billion people globally are exposed to smoke from biomass fuel, compared to 1 billion people who smoke tobacco globally [17]. In many developing countries COPD is neglected by governments, physicians, experts and the pharmaceutical industry, although it's been identified as an important public health problem [4].

In the last two decades, the Burden of Obstructive Lung Disease (BOLD) initiative has been collecting country–specific data on the prevalence, risk factors and socioeconomic burden of COPD, using standardized and tested methods for conducting COPD surveys in the general population [18]. This is expected to provide governments of many nations with country–specific evidence on which to develop policy on COPD prevention and management [18]. As noted above, this initiative is yet to take a full effect in many LMIC [19]. In addition, spirometry (the gold standard for COPD diagnosis) is not widely available in many LMIC [16]. Even when it is there, professionals in LMIC are often not being trained properly on how to use spirometers or interpret spirometry results. There is concern that COPD burden has been underestimated, owing to over–reliance on doctor’s diagnosis, with many diagnoses not being based on spirometry and international diagnostic guidelines [20]. The lack of routine COPD data collation and effective health information management system in many LMIC also implies that these settings could have been grossly under–represented in global burden of COPD estimates [11].

Some global and regional estimates of COPD burden have been published [1,21–23]. However, despite the fact that COPD is now prevalent in both HIC and LMIC, experts have raised concerns that reliable estimates of COPD prevalence are still few in many parts of the world. Moreover, many of the estimates are based on varying definitions and diagnostic criteria of COPD [9]. Also, some of the current estimates were reported before the BOLD surveys in several countries, thereby failing to account for the additional spirometry–based epidemiological data from the BOLD surveys. There is a need for a revised and updated estimate of COPD prevalence across world regions. We conducted a systematic review of COPD prevalence based on spirometry data across world regions. Our aim was to provide global and regional prevalence rates of COPD that could facilitate adequate policy response in these regions.

/pdf/global-and-regional-estimates-of-copd-prevalence-systematic-hk9qdazoi3.pdf

Global and regional estimates of COPD prevalence: Systematic review and meta-analysis.

Background
Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results.

Objectives
To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay).

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012.

Selection criteria
Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days.

Data collection and analysis
Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence.

Main results
Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I2 = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I2 = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I2 = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence).

Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference -9.60 days; 95% CI -12.84 to -6.36 days). One trial showed no effect of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between the treatment and control group.

Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high-quality evidence).

Authors' conclusions
Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient-reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.

/pdf/antibiotics-for-exacerbations-of-chronic-obstructive-3imoue2ve4.pdf

Antibiotics for exacerbations of chronic obstructive pulmonary disease

Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are not precisely understood. The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AECOPD. Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AECOPD were prospectively assessed. Patients were followed-up for 3 yrs. Factors determining short- and long-term mortality were analysed. In total, 17 patients (8.3%) died in hospital. In-hospital mortality was significantly associated with lower arterial oxygen tension (P(a,O2)), higher carbon dioxide arterial tension, lower arterial oxygen saturation and longer hospital stay. The overall 6-month mortality rate was 24%, with 1-, 2- and 3-yr mortality rates of 33%, 39% and 49%, respectively. Cox regression analysis revealed that long-term mortality was associated with longer disease duration (relative risk (RR) = 1.158), lower albumin (RR = 0.411), lower P(a,O2) (RR = 0.871) and lower body mass index (RR = 0.830). When the model was run for the time elapsed since first hospitalisation, it also appeared as statistically significant (RR = 1.195). These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival. Prediction of survival status may be enhanced by considering arterial oxygen tension, albumin, body mass index, disease duration and time elapsed since the first hospitalisation.

https://erj.ersjournals.com/content/erj/26/2/234.full.pdf

Factors affecting survival of hospitalised patients with COPD

Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease

The aim of the present study was to determine the prevalence of and risk factors for venous thromboembolism (VTE) in exacerbations of chronic obstructive pulmonary disease (COPD). COPD patients hospitalised with an exacerbation were included consecutively. Symptoms, signs and clinical, haematological and epidemiological parameters on admission were noted. All patients underwent computed tomographic angiography and ultrasonographic examination for deep vein thrombosis and pulmonary embolism (PE). Wells and Geneva scores were calculated. Patients were followed-up for 1 yr in order to determine mortality. Deep vein thrombosis and PE were detected in 14 and 18 patients, respectively. The prevalence of VTE was three times higher in patients with an exacerbation of unknown origin than in patients with an exacerbation of known origin (p = 0.016). Of patients with VTE, 20 (95%) had high D-dimer levels. The negative predictive value of D-dimer testing was 0.98. Although the moderate- and high-risk categories of both the Wells and Geneva methods covered all PE patients, the Wells method identified 49% less potential patients for PE investigation. Mortality at 1 yr was higher (61.9% versus 31.8%) in VTE patients (p = 0.013). VTE is a common problem in COPD patients hospitalised with an exacerbation, leading to high long-term mortality. D-dimer levels and the Wells criteria can be used to determine whether or not these patients are assessed for a thromboembolic event.

https://erj.ersjournals.com/content/erj/35/6/1243.full.pdf

Venous thromboemboli and exacerbations of COPD

The present study was designed to evaluate the hypothesis that nebulised budesonide (NB) might be an alternative to systemic corticosteroids (SC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (ECOPD). Patients hospitalised with ECOPD (n = 159) were randomised into three groups. Group 1 received only standard bronchodilator treatment (SBDT), group 2 received SC (40 mg prednisolone) plus SBDT, and group 3 received NB (1,500 microg q.i.d.) plus SBDT. Improvement during 10-day hospitalisation was compared with exacerbation and rehospitalisation rates after discharge. While mean+/-sd age was 64.1+/-8.9 yrs (female/male = 0.1), mean forced expiratory volume in one second (FEV(1)) at admission was found to be 37.2+/-12.2% predicted. Arterial blood gases and spirograms recovered faster in groups 2 and 3. While improvements in arterial oxygen tension (P(a,O(2))) and forced vital capacity (FVC) in group 2, and improvements in P(a,O(2)), FVC and FEV(1) in group 3, became significant at 24-h control, the first significant improvement in group 1 appeared in arterial oxygen saturation at 72-h control. The mean improvement of P(a,O(2)) after 10 days was 1.20 and 1.06 kPa (9 and 8 mmHg) higher in group 2 and 3, respectively, than in group 1. Blood glucose exhibited an upward trend only in group 2. The study demonstrates that nebulised budesonide may be an effective and safe alternative to systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease.

https://erj.ersjournals.com/content/erj/29/4/660.full.pdf

Süleyman Savaş Hacıevliyagil

Papers

Factors affecting survival of hospitalised patients with COPD

Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease

Venous thromboemboli and exacerbations of COPD

The role of nebulised budesonide in the treatment of exacerbations of COPD

Prevalence of COPD: first epidemiological study of a large region in Turkey.