CHRONIC OBSTRUCTIVE PULMONARY DISEASE Faizal Drissa Hasibuan
Bagian Penyakit Dalam Fak.KedokteranUniversitas YARSI J A K A R T A
GOLD (2002) Global Initiative for Chronic Obstructive Lung DiseaseWHO & NHLBIA disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lung to noxious particles of gasses.The major cause is smoking
Chronic Obstructive Pulmonary Disease (COPD)Spectrum of chronic respiratory diseases characterized by cough, sputum production, dyspnea, airflow limitation and impaired gas exchange.MORBIDITYMORTALITYDyspnea on exertionHRQoLIncidence worldwideChronic Obstructive BronchitisEmphysemaProgressiveExacerbations (acute & subacute symptoms)More frequent & severe
LUNG INFLAMMATIONNOXIOUSPARTICLEGASESCOPDOXIDATIVE STRESSPROTEINASE IMBALANCEHOST FACTORSANTI OXIDANTS[ environmental ]ANTI OXIDANTSANTI PROTEINASES[ genetic ]REPAIRMECHANISMREPAIRMECHANISMPATHOGENESIS OF COPD
ANTI PROTEASE ENZYME1-Antitrypsin
MacrophagesNeutrophilsCD8+ LymphocytesEosinophilsEpithelial cellsFibroblastsCELLSIL-8, GRO-1MCP-1, MIP-1GM-CSFEndothelinSubstance PNeutrophil elastaseCathepsinProteinase-3MMPsPROTEINASESMEDIATORS
MUCUS HYPERSECRETION
FIBROSIS
ALVEOLAR WALLDESTRUCTIONEFFECTSCELLS & INFLAMMATORY MEDIATORS IN COPD PATHOGENESIS
O2, H2O2OH, ONOO Antiproteinases SLPI 1-AT
ProteolysisANTIOXIDANTSGlutathione AnalogsVitamins C, EN-acetylsisteineNitrones [spin-trap] NF-KB
IL-8 TNF
NeutrophilrecruitmentISOPROSTANES Mucus secretion Plasma leakREACTIVE OXYGEN SPECIES IN COPD
Bronchoconstriction
ADRENERGIC & CHOLINERGIC ( MUSCARINIC ) RECEPTORSADRENERGICRECEPTORSCHOLINERGICRECEPTORS
SYMPTOMSCOUGHSPUTUMDYSPNEAEXPOSURE TORISK FACTORSTobacco SmokeOccupationIndoor / outdoorpollution12DIAGNOSISOF COPDSPIROMETRY3
Table 1. Elements necessary for the diagnosis of COPD.FEV1 < 84% and FEV1/VC < 88 or 89% of predicted values.Reversibility < 12% of predicted FEV1 by 2-sympathomimetic or anticholinergic drug.Continuous presence and verified on at least three occasions during the year.Patients is usually over 50 years of age.Usually a smoker and/or other environmental factors present.Often signs of emphysema (abnormal diffusion and radiology) Asthma Cystic fibrosisByssinosisBronchiectasisBronchiolitis obliteransChronic airways obstructionAdditional elementsDifferential diagnosis
Table 2. Clinical distinction between COPD and asthma (Modified according to Vermiere 1993).PatternCOPDAsthmaClinicalOnset at a young age-++Relatively sudden onset-++Smoker (now or previously)++++Atopy+++Eosinophilia/raised total IgE+++Recurrent dyspnoea and wheezing+++Nasal symptoms-++Basic abnormalitiesBronchial hyperresponsiveness+++++Reversibility rapid and/or complete-++Parenchymal destruction++-- = (almost) never; + = sometimes; ++ = frequently; +++ = (almost) always
COPDComplicationsSYSTEMICEFFECTOF COPDCARDIOVASCULARDISORDERHANDICAP / DISABILITYNUTRITIONALDISORDER
PSYCHOLOGICALFACTORANXIETY - DEPRESSIONSYSTEMICINFLAMMATORYRESPONSRESPIRATORYMUSCLEDISFUNCTION
GOALS OF COPD TREATMENTGLOBAL GOALSPREVENT DISEASE PROGRESSIVEREDUCE EXACERBATIONSIMPROVE QUALITY OF LIFEIMPROVE EXERCISE TOLERANCEREDUCE MORTALITYIMMEDIATE BENEFITSRELIEF OF SYMPTOMS[ BREATHLESSNESS ]LONG TERMGOALSSMOKINGCESSATIONSHORT TERM GOALS123
COPD MANAGEMENTPULMONARY REHABILITATIONPROGRAMMEESTABLISH DIAGNOSISASSESS SYMPTOMSSTOP SMOKINGHEALTHY LIFESTYLEIMMUNISATIONTREAT OBSTRUCTIONASSESS FOR HYPOXIABRONCHODILATORSLONG TERMOXYGEN THERAPY1234
COPDPHARMACOTHERAPYINHALED CORTICOSTEROIDSONLY FOR CONCOMITANTASTHMALONG TERMOXYGEN THERAPY[ SELECTED PATIENT ]ANTICHOLINERGICS[ TIOTROPIUM = AVAILABLE ]LABATHEOPHYLLINE[ ANTI INFLAMMATORY EFFECT ]BRONCHODILATORSNEW ANTIINFLAMMATORYTREATMENT NEEDEDTRIAL OF BUPROPIONNICOTINE REPLACEMENTSTOP SMOKING12345
OTHER TREATMENTIN COPDANTILEUCOTRIENTSPROPHYLACTICANTIBIOTICSNO EVIDENCEN-ACETYLCYSTEINEANTI INFLAMMATORYDRUGSINHALED CORTICOSTEROID ?ANTIOXIDANTSCARBOCYSTINEBROMHEXOLAMBROXOLMUCOLYTICS123
NONPHARMACOLOGICALMANAGEMENTEXERCISEPULMONARY REHABILITATIONAVOIDANCE OF POLLUTANTOBESITY&NUTRITIONALINTERVENTIONEDUCATIONSURGERYVACCINATIONPHYSIOTHERAPY12345768
Advances in Drug TherapyAnti smoking measuresNew bronchodilatorAntibioticsOxygenCorticosteroidsNonpharmacologic treatmentNon-invasive ventilationPulmonary rehabilitationLung-volume reduction surgeryNew treatmentMediator antagonistsNew anti inflammatory drugs (Phosphodiesterase 4)Drug deliveryFuture developmentMolecular genetic
BRONCHODILATORSFOR COPDIPRATROPIUM BROMIDEOXITROPIUM BROMIDETIOTROPIUM BROMIDEINHALEDANTICHOLINERGICSIPRATOPRIUM BROMIDE&SHORT ACTING INHALEDBETA 2 AGONISTSHORT ACTING INHALED BETA 2 AGONISTBETA 2AGONISTCOMBINATIONINHALER123THEOPHYLLINE4
BRONCHODILATORSIN COPDRELAXAIRWAY SMOOTHMUSCLEDECREASEDPLASMAEXUDATION ?DECREASEDINFLAMMATORYMEDIATORRELEASE ?IMPROVERESPIRATORYMUSCLEFATIGUE ?DECREASEDNEUROTRANSMITTERRELEASE ?12345
BRONCHODILATORSEFFECT IN COPDINCREASEDFEV1, FVC,PEF[ < 10 % ]DECREASEDHYPERINFLATIONDECREASEDDYSPNOEAIMPROVEDEXERCISETOLERANCEIMPROVED RESPIRATORY MUSCLE STRENGTH ?123
INHALEDCORTICOSTEROIDSIN COPDTREAT ASSOCIATED ASTHMACLINICALLY IRRELEVANT EFFECTON EXACERBATIONSNO EFFECTONPROGRESSIONOF DISEASEHIGH RISKOF ADVERSESYSTEMICEFFECTSEXPENSIVESHOULD NOT BERECOMMENDEDNO SIGNIFICANTEFFECT ONINFLAMMATION
TIOTROPIUMBROMIDESIGNIFICANTREDUCTIONINEXACERBATIONSSIGNIFICANTIMPROVEMENTIN LUNG FUNCTIONSUSTAINEDOVER 12 MONTHSSTATISTICALLYSIGNIFICANTIMPROVEMENTINBREATHLESSNESSSCORESTATISTICALLY SIGNIFICANTIMPROVEMENT IN HEALTH-RELATEDQUALITY OR LIFE SCORELONG ACTING ANTICHOLINERGIC
TIOTROPIUMBROMIDEPROLONGEDBLOCKADE OFM3 RECEPTORSUBTYPESIGNIFICANTLYREDUCES THE USEOF SHORT ACTINGBETA AGONISTSNO OTHERANTICHOLINERGICEFFENTSGREATER THANIPRATOPRIUMSAFE & WELL TOLERATED IN CLINICAL STUDYONLY SIGNIFICANT ADVERSE EVENT ISDRY MOUTHLONG ACTING ANTICHOLINERGICSAFETY
AntibioticsCOPDExacerbationsBacterial infections ?Antibiotic therapy has been linked to accelerated recoveryMost common organisms:Streptococcus pneumoniaeHaemophillus influenzaeBranhamella catarrhalisVirus Leong TK(2002) Tanjung A(2000)AntibioticsAmoxycillin CotrimoxazoleAmoxycillin -Clavulanic acidAlternativeNewer cephalosporinMacrolides (Azithromycin)Quinolone (Levofloxacin)Azithromycin (Zithromax) = Levofloxacin (Cravit ) (Tanjung A, 2000)
Long Term Oxygen TherapyThe long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival.
Pulmonary Rehabilitation ProgramAll COPD-patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.
*Adrenergic and muscarinic (cholinergic) receptorsAdrenergic receptorsThe a- and b-adrenergic receptor subtypes are found in different locations around the body.The a1-receptors are found mainly in the nerve/muscle junctions in the skin and smooth muscle. The a2-receptors are found mainly in pre- and post-synaptic nerve endings in skin and smooth muscle.The b1-receptors are found mainly in the heart muscle. The b2-receptors are found mainly in bronchial smooth muscle. Stimulation of a1-receptors causes vasoconstriction. Stimulation of of a2-receptors reduces the excitability of post-synaptic neurones.Stimulation of the b1-receptors increases heart rate and contractilityIn the respiratory system, stimulation of the b2-receptors on bronchial smooth muscle causes smooth muscle relaxation, resulting in bronchodilation. This is the point of action of the b2-agonist medications that stimulate b2-receptors, causing bronchodilatation.
Muscarinic (cholinergic) receptorsDifferent types of muscarinic receptors have been identified, of which three subtypes (M1, M2 and M3) are present in the bronchial airways of humans.The different subtypes have different regulatory functions.M1-receptors:Facilitate ganglionic transmission and enhance the cholinergic reflex.Located in the heart, parasympathetic ganglia, submucosal glands and alveolar walls.M2-receptors:Found on postganglionic cholinergic nerves.Inhibit acetylcholine release.Located in the postganglionic parasympathetic nerves.M3-receptors:Mediate bronchoconstriction and a mucus secretory response to acetylcholine and cholinergic nerve stimulation.Located in the smooth muscle of the airways, submucosal glands, endothelial cells and epithelium.
*BronchodilatorsEitherAct as agonists at beta receptorsorAct as antagonists at muscarinic receptors*BronchodilatorsEitherAct as agonists at beta receptorsorAct as antagonists at muscarinic receptors
