Future Impact of Various Interventions on the Burden of COPD in Canada: A Dynamic Population Model

Background

Chronic obstructive pulmonary disease (COPD) is a growing economic burden worldwide. Smoking cessation is thought to be the single most effective way of reducing the economic burden of COPD. The impact of other strategies such as interventions that predict risk of disease, reduce progression of disease, or reduce exacerbations has not been systematically studied.

Objectives

We estimated the economic and clinical burden of COPD over the next 25 years in Canada and the impact of three potential interventions (screening test for predisposition to COPD, new drugs to avoid progression into more severe disease stages, and predictive test for exacerbations) on COPD burden.

Methods

Using a dynamic simulation model, we projected the total burden of COPD (cost, morbidity, and mortality) from 2011 to 2035 using the population of Canada as a case study. The model stratified population based on sex, age, smoking status, respiratory symptoms, and their COPD stage. The cost and quality adjusted life years (QALYs) associated with each intervention were estimated.

Results

The model indicates that annual societal cost of COPD is $4.52 billion (B) Canadian dollars in 2011 and will reach $3.61B ($7.33B undiscounted) per year in 2035. Over the next 25 years, COPD will be responsible for approximately $101.4B in societal costs ($147.5B undiscounted) and 12.9 million QALYs lost (19.0 million undiscounted). Our results suggested that the best strategy to reduce the financial burden of COPD is by reducing exacerbations. Smoking cessation, while it is the cornerstone of COPD prevention, has only a modest effect in attenuating the financial burden of COPD over the next 25 years in Western countries such as Canada.

Conclusion

Our data suggest that any intervention that can reduce the number of exacerbations has a substantial impact on morbidity and costs of COPD and should be considered in conjunction with the ongoing efforts to reduce smoking rates.     

Global Economic Burden of Norovirus Gastroenteritis

BackgroundDespite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus.MethodsWe developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total) stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization) and productivity losses.ResultsGlobally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2–5.7 billion) in direct health system costs and $60.3 billion (95% UI: $44.4–83.4 billion) in societal costs per year. Disease amongst children <5 years cost society $39.8 billion, compared to $20.4 billion for all other age groups combined. Costs per norovirus illness varied by both region and age and was highest among adults ≥55 years. Productivity losses represented 84–99% of total costs varying by region. While low and middle income countries and high income countries had similar disease incidence (10,148 vs. 9,935 illness per 100,000 persons), high income countries generated 62% of global health system costs. In sensitivity analysis, the probability of hospitalization had the largest impact on health system cost estimates ($2.8 billion globally, assuming no hospitalization costs), while the probability of missing productive days had the largest impact on societal cost estimates ($35.9 billion globally, with a 25% probability of missing productive days).ConclusionsThe total economic burden is greatest in young children but the highest cost per illness is among older age groups in some regions. These large costs overwhelmingly are from productivity losses resulting from acute illness. Low, middle, and high income countries all have a considerable economic burden, suggesting that norovirus gastroenteritis is a truly global economic problem. Our findings can help identify which age group(s) and/or geographic regions may benefit the most from interventions.     

Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients

Background

Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs. Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated. Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.

Methods

Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.

Results

Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline. No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001). In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02]. The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).

Conclusions

In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D. This association was independent of patients’ characteristics and comorbidities.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users.     

Determinants of elevated healthcare utilization in patients with COPD

Background

Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems. Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.

Methods

Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency. Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database. Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.

Results

Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001). The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs. Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6). Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.

Conclusion

Comorbidity burden determines elevated utilization for COPD patients. Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients.     

Distribution and Outcomes of a Phenotype-Based Approach to Guide COPD Management: Results from the CHAIN Cohort

RationaleThe Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes.ObjectiveWe aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes.MethodsWe followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes.ResultsOverall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV₁ and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year.ConclusionsThere is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use.     

Tackling COPD: a multicomponent disease driven by inflammation

In recent years, research has revealed more about the factors underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). In particular, inflammation in the lungs leads to the structural changes observed in COPD, while extrapulmonary symptoms and comorbidities may be systemic manifestations of these inflammatory processes. A new multicomponent disease model is proposed that takes into account all elements that should be considered in treatment decisions. Current monotherapies act on different aspects of COPD and may not address all components. A combination of a long-acting beta2 agonist and an inhaled corticosteroid has complementary effects, addressing a wider range of components of COPD. This combination appears to have greater clinical benefits than either agent alone in reducing the frequency of exacerbations, reducing the number of hospitalizations, and potentially promoting survival. Minimizing the burden of COPD within--and potentially outside--the lung means treating patients early and addressing as many disease components as possible.     

Incidence and Cost of Pneumonia in Older Adults with COPD in the United States

Objectives

To estimate the incidence of pneumonia by COPD status and the excess cost of inpatient primary pneumonia in elders with COPD.

Study Design

A retrospective, longitudinal study using claims linked to eligibility/demographic data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through 2007.

Methods

Incidence rates of pneumonia were calculated for elders with and without COPD and for elders with COPD and coexistent congestive heart failure (CHF). Propensity-score matching with multivariate generalized linear regression was used to estimate the excess direct medical cost of inpatient primary pneumonia in elders with COPD as compared with elders with COPD but without a pneumonia hospitalization.

Results

Elders with COPD had nearly six-times the incidence of pneumonia compared with elders without COPD (167.6/1000 person-years versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders with COPD and CHF compared with elders without COPD. The incidence of inpatient primary pneumonia among elders with COPD was 54.2/1000 person-years compared with 7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to 11.0 for elders with COPD and CHF compared with elders without COPD. The one-year excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697 ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was accrued during the quarter of the index hospitalization. During months 13 through 24 following the index hospitalization, the excess direct medical cost was $ 5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01).

Conclusions

Pneumonia occurs more frequently in elders with COPD than without COPD. The excess direct medical cost in elders with inpatient pneumonia extends up to 24 months following the index hospitalization and represents $28,638 in 2010 dollars.     

Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore

Background

Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings.

Methods and Findings

We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively.

Conclusions

Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.     

Economic and disease burden of Japanese encephalitis in Zhejiang Province, 2013–2018

BackgroundJapanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013–2018, to increase disease awareness and provide evidence for effective health policy.Methodology/Principle findingsWe merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013–2018 in Zhejiang Province. Direct costs were extracted from hospitals’ billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013–2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73–36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%).Conclusions/SignificanceJE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.     

Excess Costs of Comorbidities in Chronic Obstructive Pulmonary Disease: A Systematic Review

Background

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Comorbidities are often reported in patients with COPD and may influence the cost of care. Yet, the extent by which comorbidities affect costs remains to be determined.

Objectives

To review, quantify and evaluate excess costs of comorbidities in COPD.

Methods

Using a systematic review approach, Pubmed and Embase were searched for studies analyzing excess costs of comorbidities in COPD. Resulting studies were evaluated according to study characteristics, comorbidity measurement and cost indicators. Mark-up factors were calculated for respective excess costs. Furthermore, a checklist of quality criteria was applied.

Results

Twelve studies were included. Nine evaluated comorbidity specific costs; three examined index-based results. Pneumonia, cardiovascular disease and diabetes were associated with the highest excess costs. The mark-up factors for respective excess costs ranged between 1.5 and 2.5 in the majority of cases. On average the factors constituted a doubling of respective costs in the comorbid case. The main cost driver, among all studies, was inpatient cost. Indirect costs were not accounted for by the majority of studies. Study heterogeneity was high.

Conclusions

The reviewed studies clearly show that comorbidities are associated with significant excess costs in COPD. The inclusion of comorbid costs and effects in future health economic evaluations of preventive or therapeutic COPD interventions seems highly advisable.     

Blood and sputum protein biomarkers for chronic obstructive pulmonary disease (COPD)

ABSTRACT

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous set of disorders, characterized by airflow limitation, and reduced lung function. Despite increasing knowledge regarding its pathophysiology, there has been limited advancement in therapeutics and the current treatment strategy is symptom management and prevention of exacerbations.

Areas covered: Biomarkers represent important tools for the implementation of precision medicine. As fundamental molecules of all living processes, proteins could provide crucial information about how genes interact with the environment. Proteomics studies could act as important tools in identifying reliable biomarkers to enable a more precise therapeutic approach. In this review, we will explore the most promising blood and sputum protein biomarkers in COPD that have been consistently reported in the literature.

Expert commentary: Given the complexity of COPD, no single protein biomarker has been able to improve the outcomes of COPD patients. According to preliminary studies, precision medicine in COPD will likely require a combination of different proteins in a biomarker panel for clinical translation. With advancements in current mass spectrometry techniques, an enhancement in the identification of new biomarkers will be observed, and improvements in sequence database search can fill in potential gaps between biomarker discovery and patient care.     

Health Benefit Costs and Absenteeism Among Employed Patients With Acromegaly

ObjectiveAcromegaly is associated with increased morbidity and mortality. Limited data are available on these patients’ utilization and costs of health care. This study assessed the impact of acromegaly on employees’ health benefit (direct and indirect) costs and absenteeism.MethodsA retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a U.S. employee database. Patient claims were tracked for 12 months postdiagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables.ResultsForty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson comorbidity index score and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort’s total costs. Total health benefit costs were $54 821 higher (P < .05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly, with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls, but total sick days were similar for the 2 groups.ConclusionThe presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.     

Cost of Disorders of the Brain in Spain

Background

Brain disorders represent a high burden in Europe and worldwide. The objective of this study was to provide specific estimates of the economic costs of brain disorders in Spain, based on published epidemiological and economic evidence.

Methods

A cost-of-illness study with a societal perspective of 19 brain disorders was carried out. Cost data published between 2004 and 2012 was obtained from a systematic literature review. Direct healthcare, direct non-medical and indirect costs were considered, prioritizing bottom-up information. All costs were converted to Euro and to year 2010. The missing values were imputed with European estimates. Sensitivity analyses based on qualitative assessment of the literature and on a Monte Carlo simulation were performed.

Results

The review identified 33 articles with information on costs for 11 disorders (8 neurological, 3 mental). The average per–patient cost ranged from 36,946 € for multiple sclerosis to 402 € for headache. The societal cost of the 19 brain disorders in Spain in 2010 was estimated in 84 € billion. Societal costs ranged from 15 € billion for dementia to 65 € million for eating disorders. Mental disorders societal cost were 46 € billions (55% of the total), while neurological disorder added up to 38 € billion. Healthcare costs represented 37% of the societal costs of brain disorders, whereas direct non-medical constituted 29% and indirect costs 33%.

Conclusion

Brain disorders have a substantial economic impact in Spain (equivalent to almost 8% of the country''s GDP). Economic data on several important brain disorders, specially mental disorders, is still sparse.     

Impact of a COPD Discharge Care Bundle on Readmissions following Admission with Acute Exacerbation: Interrupted Time Series Analysis

ObjectivesWe evaluated the impact of a COPD discharge care bundle on readmission rates following hospitalisation with an acute exacerbation.DesignInterrupted time series analysis, comparing readmission rates for COPD exacerbations at nine trusts that introduced the bundle, to two comparison groups; (1) other NHS trusts in London and (2) all other NHS trusts in England. Care bundles were implemented at different times for different NHS trusts, ranging from October 2009 to April 2011.SettingNine NHS acute trusts in the London, England.ParticipantsPatients aged 45 years and older admitted to an NHS acute hospital in England for acute exacerbation of COPD. Data come from Hospital Episode Statistics, April 2002 to March 2012.ResultsIn hospitals introducing the bundle readmission rates were rising before implementation and falling afterwards (e.g. readmissions within 28 days +2.13% per annum (pa) pre and -5.32% pa post (p for difference in trends = 0.012)). Following implementation, readmission rates within 7 and 28 day were falling faster than among other trusts in London, although this was not statistically significant (e.g. readmissions within 28 days -4.6% pa vs. -3.2% pa, p = 0.44). Comparisons with a national control group were similar.ConclusionsThe COPD discharge care bundle appeared to be associated with a reduction in readmission rate among hospitals using it. The significance of this is unclear because of changes to background trends in London and nationally.     

A Simplified Score to Quantify Comorbidity in COPD

Importance

Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.

Materials and Methods

Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George''s Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS.

Results

Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV₁ (p<0.001 for all comparisons). Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624–0·7676), MMRC (0·7590–0·7644), 6MWD (0·7531–0·7560) and exacerbation risk (0·6831–0·6919). Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341).

Conclusions

Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD.     

Relevance of human metapneumovirus in exacerbations of COPD

Background and methods

Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.

Results

We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10⁵ viral copies/ml in nasal lavage and 1.88 × 10⁵ viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.

Conclusion

HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.     

COPD exacerbation: Lost in translation

The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events. The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease. This definition is pragmatic and compromises the different approaches for exacerbation. However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication") in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiologal process which characterizes exacerbations. It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition. In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism) that can masquerade as exacerbations but they should not be considered as causes of them. The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition. Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung fuction. These fundamental aspects should be accounted in diagnosis/definition of exacerbations. This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events. The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations. However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward in the management of COPD.