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Definition COPD def- A disease state characterized by
air flow limitation that is not fully reversible It is expected to be the 3rd leading cause of
death by 2020Approximately 14 million Indians are
currently suffering form COPD
The Indian J Chest Dis & Allied Sciences 2001; 43:139-47
The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking.
RISK FACTORSSmoke from home cooking and heating fuelOccupational dust and chemicalsGender: More common in men. M:F ratio is
5%:2.7% (in India)Increasing ageOthers: Infection, nutrition and deficiency of
1 antitrypsin
PATHOPHYSIOLOGY Increased mucus production and reduced
mucociliary clearance - cough and sputum production
Loss of elastic recoil - airway collapse Increase smooth muscle tone Pulmonary hyperinflation Gas exchange abnormalities - hypoxemia
and/or hypercapnia
PATHOGENESIS
Classification
TREATMENTStable COPDAcute COPD
STABLE COPDSmoking cessationOxygen therapyBronchodilators- anticholinergics,beta
agonists, inhaled steroids, xanthines
Pharmacotherapy for Stable COPD
Bronchodilators Short-acting 2-
agonist – Salbutamol Long-acting 2-
agonist - Salmeterol and Formoterol
Anticholinergics – Ipratropium, Tiotropium
Methylxanthines - Theophylline
Steroids Oral – Prednisolone
Inhaled - Fluticasone, Budesonide
ACUTE EXACERBATIONBronchodilatorsAntibioticsGlucocorticoidsOxygen Ventilatory support
Management based on GOLD
JAMA sept 2008;300(12):1439-49.Sonal Singh, Yoon k, Curt D
Need for this meta analysisCOPD – 4TH leading cause of chronic
morbidity and mortality.
CV disease is an important cause of morbidity and mortality.
Need for this meta analysisGOLD guidance-small increase in
cardiovascular adverse events with anticholinergics
US FDA-possible increased risk of stroke(8/1000/yr vs 6/1000/yr)
No risk( chest 2006;130(6):1695-1703)
OBJECTIVEAscertain cardiovascular risks with long term
use of inhaled anticholinergics compared with control therapies in patients with COPD in RCTs.
ELIGIBLITY CRITERIAMore than 30 days of follow up
Diagnosis of COPD of any severity
Inhaled anticholinergics vs placebo or inhaled beta agonists and/or steroids
Cardiovascular events reported
STUDY SELECTION703 reports17 RCTs- 12 tiotropium,5 ipratropium5 long term trials(48weeks-5yrs)12 short term(6weeks-26weeks)
RESULTSPrimary outcome-increased risk of
MI(1.2%vs0.2%) Significantly increased risk of cardiovascular
death(0.9%vs0.5%) No significant increase in risk of
stroke(0.5%vs0.4%)
Secondary outcome- no significant increase in all cause mortality
Long term trials- increased risk of cardio vascular events(2.9%vs1.8%)
Short term trials-no statistically significant increase in cardiovascular event
NUMBER NEEDED TO HARMFor MI-174/yr (baseline event 10.9/1000)
For cardiovascular mortality-40/yr(31.9/1000)
MECHANISMCOPD- inflammatory cytokines
Inhaled tiotropium increases interleukin 8-destabilizes existing atherosclerotic plaques
CONCLUSSIONInhales anticholinergics used for >30 days
significantly increases the risk of cardiovascular events by approx.58%- long term trials
Then Why to use it?Number needed to treat for tiotropium to
prevent one COPD exacerbation is 21Versus number needed to harm -40 for
cardiovascular deaths and 174 for MITreatment modalities are limitedBaseline cardiovascular risks should be
evaluated.