lungsjukdom Kroniskt tobstruktiv lungsjukdom

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1 Kroniskt obstruktiv lungsjukdom Kroniskt tobstruktiv lungsjukdom Alf Tunsäter Föreläsning T och sök KOL-rekommendationer Definition av KOL Kroniskt obstruktiv lungsjukdom (KOL) är en inflammatorisk luftrörs-/lungsjukdom, som oftast är en följd av kronisk tobaksrökning KOL manifesterar sig som sänkt FEV 1 /VC-kvot vid spirometri. Försämringstakten av FEV 1 är ofta långsam KOL är i de allra flesta fall möjlig att förebygga och kan även behandlas med gynnsam effekt Lungfunktionsnedsättningen karakteriseras av att patienten aldrig uppnår normalvärden vare sig spontant eller efter behandling. Extrapulmonella manifestationer är vanliga. Svenska läkemedelsverkets rekommendationer 2009 Chronic obstructive pulmonary disease - pathogenesis Emphysema - centrilobular Bronchiolitis Location of COPD Bronchiolitis Some pathogenetic mechanisms in COPD Bacteria Virus Mucous secretion Emphysema Vasculitis Macrophage Increased expression of inflammatory genes MMP TNF-α Lymphocyte IL-17 Bronchiolitis 4 histone acetylation histone deacetylase Peroxinitrate - - O 2 + NO Antiproteases inos IL-8 GRO-α Neutrophil TNF-α LTB-4 IL-1β IL-8 Proteases Emphysema 1

2 Other inflammatory cells involved in COPD development Mast cells Br Local inflammatory response COPD - local and systemic inflammation Paricles from e g smoke IL-8 Fibrocytes Balancing parenchyma destruction TGFβ-depedent PA Systemic inflammatory response GMCSF, IL-6 Cytokines Leucocytes och thrombocytes IL1-β, TNF- Endothelial activation IL-6, IL1-β Acute phase proteins Vascular disease Efter Eeden 2006 Risk Factors for COPD Diagnosis of COPD Nutrition Infections Socio-economic status SYMPTOMS cough sputum shortness of breath EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution Aging Populations 9 SPIROMETRY Förekomst i Sverige Ovanlig före 40-årsåldern - ökar starkt med stigande ålder. Dödligheten i KOL är betydande - drygt 3000 dödsfall/år. Överlevnaden starkt beroende av ålder och FEV 1 och av komplikationer såsom patologiska blodgaser, ödem och undernäring. Samtidig kardiovaskulär sjukdom försämrar överlevnaden. Förekomsten av KOL i Sverige lika bland kvinnor och män Sjukvårdskonsumtionen till följd av KOL är numera högre bland kvinnor. När bör KOL misstänkas? Exponering för luftrörsskadliga ämnen, främst cigarettrök, Ålder över 45 år samt något av följande Luftvägssymtom som hosta, slemproduktion, andfåddhet eller pip i bröstet Återkommande bronkitepisoder eller långvariga förkylningar Nedsatt prestationsförmåga Lungröntgenbild som inger misstanke om KOL Känd hjärtsjukdom med andfåddhet och nedsatt prestationsförmåga 2

3 Diagnostik - spirometri Ökat luftflödesmotånd som kvarstår efter inandning av bronkdilaterare FEV 1 /VC Management of Stable COPD Assess and Monitor COPD: Spirometry Spirometry should be performed after the administration of an adequate dose of a shortacting inhaled bronchodilator to minimize variability. A post-bronchodilator FEV 1 /FVC < 0.70 (<0.65 if age >65) confirms the presence of airflow limitation that is not fully reversible. Where possible, values should be compared to age-related normal values to avoid overdiagnosis of COPD in the elderly. 14 KOL-utveckling Aldrig rökt eller 100 icke känslig för rök 75 Rökare med känslighet för rök 50 Slutade vid 45 Invaliditet 25 Död Slutade vid Ålder Svårighetsgrad Beror på spirometriresultat - efter fastställt kvotkriterium FEV 1 /VC <0.7(0.65) Stadium 1 FEV 1 >80% förv. Stadium 2 FEV % förv Stadium 3 FEV % förv. Stadium 4 FEV 1 <30% förv. och övrig påverkan hör till stadium 4 Svår kronisk hypoxi låg oxygenhalt i blodet Kronisk hyperkapni hög koldioxidhalt i blodet Cirkulationspåverkan (t ex perifera ödem eller takykardi). Låg kroppsvikt. BMI <21 Fletcher and Peto 1977 Differential Diagnosis: COPD and Asthma Systemic effects of COPD COPD Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow limitation ASTHMA Onset early in life (often childhood) Symptoms vary from day to day Symptoms at night/early morning Allergy, rhinitis, and/or eczema also present Family history of asthma Largely reversible airflow limitation Systemic inflammation Nutritional abnormalities and weight loss Skeletal muscle dysfunction Osteoporosis Cardiovascular effects Neurological effects Infectious disease tuberculosis? Evaluate systemic disease manifestations! 3

4 What does an exacerbation mean to a patient? Decline in lung function 1,2 Greater anxiety 3 Increased symptoms (I.e. breathlessness) 6 Worsening quality of life 45 4,5 Social withdrawal More exacerbations 6,7 Increased risk of mortality 8 1. Garcia-Aymerich J et al Increased risk of hospitalisation 1,2 2. Donaldson D et al Gore JM et al Seemungal T et al Pauwels Pet al Seemungal T et al Garcia-Aymerich J et al Anto JM et al * Acute esacerbations of COPD prior to entry to study requiring hospital management Soler-Cataluna et al Thorax 2005 ERS/ATS definition(2004) An event in the natural course of the disease characterised by a change in the patient s baseline dyspnoea, cough and/or sputum beyond day to day variability sufficient to warrant a change in management Celli B et al Eur Respir J 2004:23: ERS/ATS (2004) Severity grading(arbitrary) Level 1: Treated at home Level 2: Requires hospitalisation Level 3: Develops respiratory failure Celli B et al Eur Respir J 2004:23: Symptoms during an exacerbation Shortness of breath Prevention improving immune functionn Cough Chest tightness Night-time awakenings Calverley PM et al Eur Respir J 2005:26:

5 Viral and bacterial causes Bacteria Haemophilus influezae, Moraxella catharalis Streptococci, Pneumococci Virus Rhinovirus, respiratory syncytial virus, influensa A and B Flu vaccianation in COPD 125 patients randomised to vaccine or placebo relative risk [RR], 0.24, [p 0.005]; vaccine effectiveness 76% Wongsurakiat P et al Chest 2004:125: Management of Stable COPD Reduce Risk Factors: Key Points Prevention non-pharmacological n treatment Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD. Smoking cessation is the single most effective and cost effective intervention in most people to reduce the risk of developing COPD and stop its progression (Evidence A). 28 ASK ADVISE ASSESS ASSIST Brief Strategies to Help the Patient Willing to Quit Smoking Systematically identify all tobacco users at every visit. Strongly urge all tobacco users to quit. Determine willingness to make a quit attempt. Aid the patient in quitting. ARRANGE Schedule follow-up contact. Management of Stable COPD Reduce Risk Factors: Smoking Cessation Counseling delivered by physicians significantly increases quit rates over self-initiated strategies. A brief (3-minute) period of counseling to urge a smoker to quit results in smoking cessation rates of 5-10%. Pharmacotherapies for smoking cessation are available and is recommended when counseling is not sufficient to help patients quit smoking. 30 5

6 Management of Stable COPD Reduce Risk Factors: Indoor/Outdoor Air Pollution Reducing the risk from indoor and outdoor air pollution requires a combination of public policy and protective steps taken by individual patients. Reduction of exposure to smoke from biomass fuel, particularly among women and children, is a crucial goal to reduce the prevalence of COPD worldwide. 31 Therapy at Each Stage of COPD I: Mild II: Moderate III: Severe FEV 1 /FVC < 70% FEV FEV 1 /FVC < 70% 1 /FVC < 70% 30% < FEV 1 < 50% < FEV FEV 1 > 80% 1 < 80% 50% predicted predicted predicted Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Pharmacotherapy: Symptomatic IV: Very Severe FEV 1 /FVC < 70% FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long term oxygen if chronic respiratory failure. Consider surgical treatments Profylactic against exacerbations Effect on mortality of oxygen treatment NOTT-trial >18 h/24h >15 h/24h MRC-trial >15 h/24h Long-term oxygen treatment Reduces hospitalisations Given on strict indications pao2 < h/day No oxygen Ann Int Med 1980:93: Lancet 1981:93: Rehabilitation Effect of rehabilitation is well established Physiotherapy Muscular training Dietic measures Coping strategies Rehabilitation randomised controlled trial Griffiths TL et al Lancet 2000:355:

7 Bronchodilators - LABA Decreaseing symptoms Prevention pharmacological treatment and effect on exacerbations Formoterol one study 30 % reduction in exacerbation frequency (Rossi A Chest 2002:121: ) Others have not shown an effect Salmeterol TRISTAN shows 20 % recuction in exacerbation rate, 29 % reduction in oral steroid courses (Calverley PM et al Lancet 2003:361:449-56) TORCH Bronchodilators symptomatic and profylactic effects Tiotropium n=497 Placebo n=506 Dusser D et al. Eur Respir J 2006; 27: year study Decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Inhaled corticosteroids EUROSCOP - The yearly rate of severe exacerbations (estimated from courses of oral corticosteroids) was reduced in the budesonide group versus placebo group by 37% (0.05 versus 0.07, p=0.002), corresponding to a yearly exacerbation rate ratio of 0.63 (95% CI ). Löfdahl CG et al Eur Respir J ; 29: Inhaled corticosteroids ISOLDE exacerbations reduced 25 % (Fluticasone vs. Placebo) (Burge PS BMJ 2000:320: ) TRISTAN 20% reduction with fluticasone (Calverley PM et al Lancet 2003:361:449-56) TORCH Combination ICS and LABA TRISTAN fluticasone and salmeterol reduced exacerbation 25 % Budesonide and formoterol reduced 24 % in two studies (Szafranski et al Eur Respir J 2003:21:74-81, Calverley PM et al Eur Respir J 2003:22:912-19) 7

8 TORCH 6112 patients followed for 3 years randomised to Placebo Fluticasone 500 μg x 2 Salmeterol 50 μg x 2 combination Moderate and severe exacerbations 1,2 1 0,8 0,6 0,4 0,2 0 Placebo Salmeterol Fluticasone Combination TORCH Calverley PM et al New Engl J Med 2007;356: ,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 Oral corticosteroids Placebo Salmeterol Fluticasone Combination TORCH Hospitalisations TORCH n.s n.s n.s Cardio-ischemic events in COPD patients effect of inhaled corticosteroids EUROSCOP patients followed for 3 years Without cardiac disease at randomisation 60 new events in 49 patients: 31/582 in placebo and 18/592 in budesonide group (p<0.05) Post-hoc study showing a preventive effect on cardioiscemic events with inhaled corticosteroids in COPD Löfdahl CG et al ERJ 2007:29(6):

9 Conclusions Knowledge on pathogenetic mechanims is increasing Diagnosis dependent on spirometry Smoking cessation!! Symptomatic and preventive treatment Several interventions can prevent exacerbations in COPD Influensa-vaccination Pneumococcal vaccination (?) LTOT (?) Rehbilitation Pharmacologic treatment Bronchodilators Inhaled corticosteroids Combination treatment 9