Comorbidities and their impact on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex disease that is associated with devastating outcomes resulting from lung involvement and several comorbidities. Comorbidities could impact on symptomology, quality of life, the complications, the management, economic burden and the mortality of the disease. The importance of comorbidities originates from their impact on the outcome of COPD. The most frequent comorbidities in COPD are cardiovascular, endocrinological, musculoskeletal, phycological disorders and lung cancer. Almost 50% of the COPD patients have 3 or more comorbidities. The recent Global Initiative of Obstructive Lung Disease (GOLD) Guideline suggested proactive search and the treatment of the comorbidities. However, there is no certain evidence demonstrating that active treatment of comorbidities improve the outcomes of COPD. However, it is well known that several comorbidities such as cardiovascular disease and lung cancer have greater impact on mortality caused by COPD. Several studies have shown that Charlson Comorbidity index or more recenty COPD Specific Comorbidity Index (COTE) has been found to be related with mortality of COPD. This concise review intended to summarize the most frequent comorbidities in association with their impact on COPD

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10-12), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10-13). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10-15), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10-8). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy