COPD (Chronic Obstructive Lung Disease) DEFINITION OF COPD • •COPD is a common, preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation (PERSISTENT OBSTRUCTION) • •Due to airway and/or alveolar • abnormalities, usually caused by • significant exposure to noxious • particles or gases. • • GOLD 2020 report • CHRONIC BRONCHITIS •Clinical and epidemiological term • •Defined as a persistent cough and sputum production for at least 3 months per year for 2 consecutive years • •NO bronchial obstruction (compared to COPD) • •Can proceed to COPD EPIDEMIOLOGY - worldwide -po r.2000- provedeno 6 rozsáhlých randomizovaných studií, nejčastěji citovaná je studie BOLD -Důvod- potřeba dokumentů o prevalenci CHOPN - - r.2000 – CHOPN 5.nejcastejsi pricinou umrti - prevalencne studie ukazuju velku heterogenitu v zavislosti od zadania zakladnych hodnot (radilogie, spiro, klinika, symptomy) -Adeloyle, 2015 (systematicky prehled a metaanalyzy) na zaklade BOLD a inych velkych epidemiologickych studii sa predpoklada 384mil. CHOPN v r.2010 -Celosvetova prevalencia CHOPN 1990-2010 narast 118% Blizky vychod, Afrika 102% -GBDS 2015, Lancet 2017 hovorí o celosvetovém narustu prevalence o 44% ve srovnáni s r.1990 EPIDEMIOLOGY • • •Global Burden Of Disease Study (Mathers, 1990) - 1990 6th most common cause of death - 2002 5th most common cause of death - 2015 4th most common cause of death – 3.2 million patients died (5% of worldwide deaths) - 2020 3rd most common cause of death •90% of all COPD deaths are in low and middle income countries § ¡ ¡ WHO 2012 – TOP 10 causes of death • l MORTALITY - Czech Republic - 32.8 pts. / 100 000 (Czech Republic 2017) - Prevalence 8% 324% RISK FACTORS Host factors Exposure Genetic factors (A1AT deficiency) Advanced age Bronchial hyperreactivity (bronchial asthma) Smoking Occupational exposure to dusts and chemicals Exposure to fumes from burning fuel Air pollution Recurrent respiratory infections (respiratory illnesses in childhood) l l PATOPHYSIOLOGY • •Inflammnation (macrophages + neutrophils -> EMPHYSEMA + MUCUS HYPERSECRETION + AIRWAY REMODELLING + OXIDATIVE STRESS) • •Oxidative + carbonyl stress (ROS, RNS -> airway + lung damage + extrapulmonary effects) • •Protease-antiprotease imbalance (in favour of protease -> proteolysis -> EMPHYSEMA + MUCUS HYPERSECRETION + AIRWAY REMODELLING) • RNS = reactive nitrogen species ROS = reactive oxidant species Neutrophil elastase, cathepsin G, and proteinase-3 Mucous gland hyperplasia (as seen in the images below) is the histologic hallmark of chronic bronchitis. Airway structural changes include atrophy, focal squamous metaplasia, ciliary abnormalities, variable amounts of airway smooth muscle hyperplasia, inflammation, and bronchial wall thickening. Damage to the endothelium impairs the mucociliary response that clears bacteria and mucus. Inflammation and secretions provide the obstructive component of chronic bronchitis. Neutrophilia develops in the airway lumen, and neutrophilic infiltrates accumulate in the submucosa. The respiratory bronchioles display a mononuclear inflammatory process, lumen occlusion by mucus plugging, goblet cell metaplasia, smooth muscle hyperplasia, and distortion due to fibrosis. These changes, combined with loss of supporting alveolar attachments, cause airflow limitation by allowing airway walls to deform and narrow the airway lumen. In contrast to emphysema, chronic bronchitis is associated with a relatively undamaged pulmonary capillary bed. The body responds by decreasing ventilation and increasing cardiac output. This V/Q mismatch results in rapid circulation in a poorly ventilated lung, leading to hypoxemia and polycythemia. Eventually, hypercapnia and respiratory acidosis develop, leading to pulmonary artery vasoconstriction and cor pulmonale. With the ensuing hypoxemia, polycythemia, and increased CO2 retention, these patients have signs of right heart failure and are known as "blue bloaters." Emphysema Emphysema is a pathologic diagnosis defined by permanent enlargement of airspaces distal to the terminal bronchioles. This leads to a dramatic decline in the alveolar surface area available for gas exchange. Furthermore, loss of alveoli leads to airflow limitation by 2 mechanisms. First, loss of the alveolar walls results in a decrease in elastic recoil, which leads to airflow limitation. Second, loss of the alveolar supporting structure leads to airway narrowing, which further limits airflow. PATOPHYSIOLOGY (2) •Pathologic changes in COPD occur in: • §Large airways (bronchial obstruction) § §Small „peripheral“ airways (bronchiolitis obliterans) § §Lungs (emphysema -> dynamic hyperinflation) § §Pulmonary capillary bed (hypoxic pulmonary vasoconstriction or/and destruction of the alveolar–capillary bed due to emphysema -> right-sided heart failure - „cor pulmonale“) § §Systemic manifestation (cachexy, osteoporosis…) Emphysematous destruction and small airway inflammation Emphysematous destruction and small airway inflammation often are found in combination in individual patients, leading to the spectrum that is known as COPD. When emphysema is moderate or severe, loss of elastic recoil, rather than bronchiolar disease, is the dominant mechanism of airflow limitation. By contrast, when emphysema is mild, bronchiolar abnormalities are most responsible for the majority of the deficit in lung function. Although airflow obstruction in emphysema is often irreversible, bronchoconstriction due to inflammation accounts for some reversibility. Airflow limitation is not the only pathophysiologic mechanism by which symptoms occur. Dynamic hyperinflation Lung volumes, particularly dynamic hyperinflation, have also been shown to play a crucial role in the development of dyspnea perceived during exercise. In fact, the improvement in exercise capacity brought about by several treatment modalities, including bronchodilators, oxygen therapy, lung volume reduction surgery (LVRS), and maneuvers learned in pulmonary rehabilitation, is more likely due to delaying dynamic hyperinflation rather than improving the degree of airflow obstruction. Additionally, hyperinflation (defined as the ratio of inspiratory capacity to total lung capacity [IC/TLC]) has been shown to predict survival better than forced expiratory volume in 1 second (FEV1). 11 17099 PATOPHYSIOLOGY (3) PATOPHYSIOLOGY COPD vs BRONCHIAL ASTHMA Výsledek obrázku pro chopn astma HISTOPATHOLOGY OF COPD/ASTHMA Asthma bronchiale – subepithelial fibrosis COPD – peribronchial fibrosis SYMPTOMS ¡Shortness of breath (dyspnea) - persistent - worsened over time - worsened by exercise - worsened by respiratory infections ¡ ¡ ¡Chronic cough ¡ ¡Chronic sputum production PHYSICAL EXAMINATION § §Auscultation- wheezes, „silent“ chest § §Barrel chest (due to lung emphysema) § §Central cyanosis § §Cor pulmonale- peripheral edema, neck vein distention, hepatomegaly BARREL CHEST http://image.slidesharecdn.com/howtomanageacaseofacuteexacerbationofcopd-151119173956-lva1-app6891/ 95/acute-exacerbation-of-copd-12-638.jpg?cb=1447955089 LUNG FUNCTION TESTING • • •Spirometry is needed for COPD diagnosis • - NOT FULLY reversible obstruction • - Bronchodilator test negative • - Bronchoprovocation test negative • - Fractional exhaled nitric oxide (FeNO) normal • • • • •Chlumský a kol. Doporučený postup pro interpretaci základních vyšetření plicních funkcí – AKTUALIZACE 2013. Dostupný na www.pneumologie.cz • • DIF.DG.CHOPN a ASTHMA DIF.DG.CHOPN a ASTHMA – reverzibilita/ireverzibilita DIAGNOSIS of COPD • • Symptoms cough sputum dyspnea Exposure to risk factors smoking occupational hazards frequent infections Obstruction on spirometry !!! COPD classification according to spirometry (‘GOLD 1-4’) I. mild FEV1/VCmax < 70% FEV1 >80%nh II. moderate FEV1/VCmax < 70% FEV1 50-80%nh III. severe FEV1 + FEV1/VCmax 30-50%nh IV. very severe FEV1 + FEV1/VCmax < 30%nh Koblížek, Chlumský (ed.). Doporučený postup ČPFS pro diagnostiku a léčbu stabilní CHOPN. Dostupný na www.pneumologie.cz FENOTYPY CHOPN – česká cesta GOLD 1-4 + A-D + fenotypy LÉČBA CHOPN • SNIZIT SYMPTOMY - Relieve symptoms - Improve exercise tolerance - Improve health status SNIZIT RIZIKO EXACERBACI - Prevent disease progression - Prevent and treat exacerbations - Reduce mortality LÉČBA CHOPN * pro všechny symptomatické pacienty FARMAKOLOGICKÁ LĚČBA •Anticholinergika (LAMA) + beta2-mimetika (LABA) • - lék 1.volby (výjimka IKS u CHOPN/Asthma overlap) • • • - preferováno INHALAČNÍ podání léků • • - preferovány dlouhodobě (12-24hod) působící léky • (LAMA, LABA) nežli krátkodobě působící (SAMA, SABA) • • - kombinace LAMA + LABA s výhodou • - u těžších forem CHOPN, symptomat.pacientů • • - monoterapie IKS není doporučována 4. • LAMA/LABA - Lepsia BD, lepsia compliance při rovnakych alebo mensich NU • •Inhalační kortikosteroidy • - překryv CHOPN+ ASTHMA, četné exacerbace • •Inhibitory PDE-4 (ROFLUMILAST) • - fenotyp bronchitický + četné exacerbace • - protizánětlivý účinek (ovlivnění Neu zánětu) • •Substituce alfa-1-antitrypsinu • - fenotyp emfyzematicky s deficitem alfa-1-AT • • FARMAKOLOGICKÁ LĚČBA Kortikosteroidy -improves symptoms -lung function -QoL -reduces the frequency of exacerbations in COPD patients with an FEV1 < 60% predicted -Neovlivňují dlouhodobou mortalitu a deklinaci plicních funkcí, vyšší riziko iPDE-4 -Menej jako 50% ATB - Snížení počtu exacerbací (něktěré NE, některé zase ANO) •Moderní mukolytika (ERDOSTEIN a N-ACETYLCYSTEIN ) • - fenotyp bronchitický, bronchiektazie + četné exacerb. • - mukomodulační + antibakteriální + antioxidační účinky + • ↑účinnosti ATB • • Metylxantiny (TEOFYLIN) • - fenotyp emfyzematický, CHOPN/AB • - malý BD účinek (+), stimulace dechového centra • •Antileukotrieny (MONTELUKAST) • - fenotyp CHOPN/AB • • § • • FARMAKOLOGICKÁ LĚČBA N-acetylcystein - obecně efekt mukolytik pro BD je malý - CHOPN léčený IKS – redukce počtu AE (ale jenom u GOLD 2), není vplyv na QoL Teofylin - některé studie ukazají malý symptomatický a BD efekt - účinek TEOF + SALMETEROL proti placebu CHIRURGICKÁ LÉČBA §bulektomie, volumredukční operace p 3.KROK – BSK volumredukce http://www.floridamd.com/wp-content/uploads/2013/02/pulm-1-Small.jpg Výsledek obrázku pro endobronchial volume reduction coils http://jtd.amegroups.com/article/viewFile/3159/html/21846 http://www.interventionalbronchoscopy.co.uk/Research/Entries/2013/6/3_RESET_STUDY_files/shapeimage_ 1.png LÉČBA TERMINÁLNÍ CHOPN ¡ • ¡ ¡ ¡ ¡DDOT ¡Domácí neinvazivní ventilace - NIV (HI-NIV) - CHOPN + hyperkapnické respirační selhání (GOLD 4D) - CHOPN + OSAS ¡Transplantace plic § DDOT Cílem DDOT je zlepšení kvality života, tolerance zátěže a snížení morbidity, včetně snížení potřeby hospitalizací, a mortality LONG TERM OXYGEN THERAPY (LTOT) § §Přítomnost chronické respirační insuficience • - hodnota pO2 < 8.0 kPa § •Nutný pozitivní kyslíkový test, event. 6-MWT • §Kontraindikace • - negativní kyslíkový test, 6-MWT • - vzestup pCO2 při kyslíkovém testu • - kuřák, asociál • • • • • LTOT – OXYGEN TEST Kapalný O2 / Koncentrátor O2