Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

Paucigranulocytic asthma most likely represents a "benign" asthma phenotype, related to a good response to treatment, rather than a "true" phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.

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Background Osteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this study was to investigate the levels of OPN in sputum supernatants of patients with SRA, to compare them with milder forms of the disease and to investigate their possible association with mediators and cells involved in the inflammatory and remodelling process. Methods 33 patients with SRA, 29 with moderate asthma, 21 with steroid-naïve asthma and 20 healthy subjects were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of OPN, vascular endothelial growth factor, transforming growth factor b1 (TGF-b1), cysteinyl leukotrienes, interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum supernatants. Results Median (IQR) OPN levels (pg/ml) were significantly higher in patients with SRA than in those with moderate asthma, steroid-naive asthma and healthy control subjects (1840 (1125e11000) vs 130 (100e210) vs 100 (67e130) vs 50 (42e70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-b1 and ECP. TGF-b1 represented the strongest association with OPN. The above associations were not observed in milder forms of the disease or in healthy subjects. Conclusions The results indicate that OPN levels are higher in SRA than in less severe forms of the disease. Moreover, OPN is associated with mediators involved in both the inflammatory and remodelling process such as TGF-b1, IL-13 and cysteinyl leukotrienes only in SRA.

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OPN levels are higher in patients with COPD compared with healthy subjects. OPN may play a role in the neutrophilic inflammation and in the pathogenesis of emphysema.

ObjectiveCOPD is associated with significant economic burden. The objective of this study was to explore the direct and indirect costs associated with COPD and identify the key cost drivers of disease management in Greece.MethodsA Delphi panel of Greek pulmonologists was conducted, which aimed at eliciting local COPD treatment patterns and resource use. Resource use was translated into costs using official health insurance tariffs and Diagnosis-Related Groups (DRGs). In addition, absenteeism and caregiver’s costs were recorded in order to quantify indirect COPD costs.ResultsThe total costs of managing COPD per patient per year were estimated at €4,730, with direct (medical and nonmedical) and indirect costs accounting for 62.5% and 37.5%, respectively. COPD exacerbations were responsible for 32% of total costs (€1,512). Key exacerbation-related cost drivers were hospitalization (€830) and intensive care unit (ICU) admission costs (€454), jointly accounting for 85% of total exacerbation costs. Annual maintenance phase costs were estimated at €835, with pharmaceutical treatment accounting for 77% (€639.9). Patient time costs were estimated at €146 per year. The average number of sick days per year was estimated at 16.9, resulting in productivity losses of €968. Caregiver’s costs were estimated at €806 per year.ConclusionThe management of COPD in Greece is associated with intensive resource use and significant economic burden. Exacerbations and productivity losses are the key cost drivers. Cost containment policies should focus on prioritizing treatments that increase patient compliance as these can lead to reduction of exacerbations, longer maintenance phases, and thus lower costs.

The need for non-invasive assessment of airway inflammation is imperative, since inflammatory airway diseases, such as asthma and COPD, are characterized by variation in their clinical presentation throughout their course. Exhaled breath condensate (EBC) collection represents a rather appealing method that can be used to conveniently and noninvasively collect a wide range of volatile and non-volatile molecules from the respiratory tract, without affecting airway function or inflammation. Although promising, EBC is currently used only as a research tool, due to the lack of appropriate standardization and the absence of reference values. A large number of mediators of inflammation, oxidative and nitrosative stress, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. This review focuses mainly on the presentation of the above biomarkers in asthma as well as on the effect of various factors on their concentrations. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results up-to-date, the introduction of EBC in everyday clinical practice requires the work-out of some methodological pitfalls, the standardization of EBC collection, and finally the identification of a reliable biomarker which is reproducible, has normal values and provides information for the underlying inflammatory process and the response to treatment. So far none of the parameters studied in EBC fulfils the aforementioned requirements.