Comorbiditi in BPOC

Comorbiditi n BPOCObezitatea, Sd. Metabolic, Diabetul zaharatDr. Roxana Nicoleta SilisteClinica de Medicina InternaSpitalul Clinic ColteaComorbiditi n BPOC

Babb et al. Am J Respir Crit Care Med, 2008 BPOC i obezitateaInteractiune complexa:Simptome asemanatoareAfectare functie respiratorie prin mecanisme diferiteCeea ce implica exacerbari mai frecvente, cresterea consumului de bronhodilatatoare la acesti pacienti380% dintre bv. cu ind de chirurgie bariatric au dispnee la efort1Pacienii cu IMC30 kg/mp si dispnee au un consum crescut de oxigen i o crestere a travaliului respirator (n absena modificarilor funcionale resp. / a decondiionrii c-v) 2,3Deteriorarea funciei musc. respiratorii prin scderea FFM (fat free mass)4Obezitatea i simptomele respiratorii 1. Gibson GJ et al. Thorax 20002. Kress et al. Am J of Critacal Resp care 20083. Babb et al. Am J Respir Crit Care Med, 20084. Franssen FME et al. Thorax 2008 FFM=fat free mass1. Gibson GJ. Thorax 20002. Kress et al. Am J of Critacal Resp care 20083. Babb et al.4.4Obezitatea i simptomele respiratorii Franssen et al. Thorax, 2008

FFM=fat free mass5Obezitatea i mecanica respiratorie

Cresterea in greutatee si a IMC este asociata cu scaderea volumelor pulmonare si tulb ventilatorie de tip restrictiv. Cresterea IMC duce la scaderea in special a FVC dar si VEMS, PEF, FEF 25-75% fara a afecta semnificativ IT. Obezitatea morbida duce si la scaderea VR si a CPT.6Scade complianta cutiei toraciceCreste travaliul musc. respiratoriiCreste rezistenta in caile aerieneGrasimea periviscerala intraabdominala impiedica miscarile diafragmului scade expansiunea pulmonara anomalii ventilatie-perfuzieObezitatea i mecanica respiratorieImportanta dispozitia grasimii toraco-abdominale7Obezitate- apnee in somn- sd obezitate hipoV-BPOCObezitateApnee n somnSOHBPOC cu hipercapnie obezitate (sd overlap)Obezitatea i inflamaia

Overview of the complex interplay between obesity-inflammation-metabolic syndrome: metabolic overload impacts on adipose tissue, leading to organelle stress with production of ROS and adipokines, as well as activation of kinases that potentiate the transcription of inflammatory genes and interfere with insulin signaling. Hyperthrophy facilitates rupture of adipocytes which attract and activate macrophages that markedly reinforce the inflammatory process through further production of ROS and inflammatory cytokines. Production of adiponectin, an anti-inflammatory cytokine, is reduced. Increase of FFA concentration, namely, SFA, coming both from feeding and adipose tissue overflow, accumulates in the liver, among other organs. Fat accumulation in the liver leads to overproduction of LDLs and, together with IL-6, of CRP. NAFLD is a frequent consequence of these metabolic dysregulations, and all this impacts on insulin sensitivity. SFA activates TOLL-like receptors in adipocytes, contributing to the activation of the inflammatory response. Fat has also effects on intestinal permeability and on the microbiota, with systemic inflammatory consequences. Most excess metabolites and cytokines produced throughout these processes converge on insulin resistance, a central characteristic of the metabolic syndrome. AP-1: activator protein-1; CRP: C-reactive protein; FFA: free (nonesterified) fatty acids; IL-n: interleukins; IKK: inhibitor of NF-B kinase; IL-6: interleukin-6; Int: intestine; IR: insulin resistance; JNK: c-Jun N-terminal kinase; LDL: low density lipoprotein; M: microbiota; NAFLD: nonalcoholic fatty liver disease; NF-B: nuclear factor B; OxS: oxidative stress; ROS: reactive oxygen species; PKC: protein kinase C; SFA: saturated fatty acids; TAG: triacylglycerols; TLR: TOLL-like receptors; TNFalpha: tumour necrosis factor alpha.9Expresia tisular de citokine i rec la pacieni cu BPOC

Skybba P et al. Mediators of Inflammation, 2010 10Obezitate- inflamaie- funcie respiratorie

Sin DD. Thorax 200011Obezitatea i COPDBPOCInflamaie bronicInflamaie sistemicObezitateaCrete volumul adipocit cu reducere perfuzie localHipoxie adipocitEliberare mediatori ai inflamScadere funcie pulmonaraHipoxie sistemicSedentarismFFM=fat free mass12Exist receptori pentru leptin i adiponectin la nivelul es pulmonar1Crete expresia rec. de leptin la niv mucoasei bronice n inflamaie i obstrucie 2Adiponectina reduce inflamaia alergen-indus la nivelul mucoasei bronice, dar valorile serice crescute se coreleaz cu un prognostic mai prost la bolnavii subponderali cu BPOC 3Interaciunea esut adipos-plmn1. Bruno A. et al. Eur Resp Journal 20052. Vernooy J et al. Thorax 20093. Shore S. Journal of Alergy and Clin Immunology 20061. Bruno A. et al. European Respiratory Journal 20052. Vernooy J et al. Thorax 20093. Shore S Journal of Alergy and Clin Immunology 20064. 13

Interaciunea esut adipos-plmnObezitatea i severitatea BPOC

Bruno A. et al. Eur Resp Journal 2005Leptin positive cells are directly correlated with Global Initiative of Chronic Obstructive Lung Disease (GOLD) stages. Gold 0: n=15; Gold 1: n=11; Gold 2: n=7; Gold 3: n=9. Kendall au test: 0.57; p