COPD – Primary Care Update Andrew White & Charles Buckley

Definition of COPD ‘Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced inflammatory response in the airways and lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients’ Global initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines February 2013

Basics Mainly smoking related 2-4% of the adult population 4th leading cause of death (set to rise) 10% of all emergency admissions A major burden on NHS resources

Basics of evidence based management Stop smoking Flu and pneumonia immunisation Pulmonary rehabilitation Oxygen therapy for those with significant hypoxia Prompt treatment of exacerbations with steroids and antibiotics Inhalers????

COPD Value pyramid London Respiratory Team

Inhaled therapy Short acting bronchodilators Long acting bronchodilators What about inhaled corticosteroids?

Inhaled steroids in COPD No benefit in mild/moderate COPD – no effect of lung function or exacerbation rate (Vestbo, Lancet 1999) Lung Health Study showed “fewer visits to primary care physician” in triamcinalone treated group vs placebo (N Eng J Med 2000) Studies on more severe disease with FEV1 <50% predicted reported fewer exacerbations in those treated with steroids (Burge PS, BMJ 2000; Alsaeedi A, Am J Med 2002) Approx reduction of 30% Methods overestimated effect

Benefits if ICS in COPD? Some reduction in mild exacerbation with ICS/LABA vs LABA alone No reduction in hospital admissions NNT with Seretide 500 vs Salmeterol 50 alone = 14 to prevent 1 exacerbation (controversial) (Suissa, Thorax 2013)

Pneumonia and other adverse effects of ICS 70% increase in pneumonia requiring hospitalisation (Ernst P, 2007; Am J Resp Crit Care Med) 44 patients must be treated for 3 years to prevent 1 exacerbation vs 16 over 3 years to result in 1 pneumonia (Suissa, Thorax 2012) 34% relative risk of developing new onset diabetes and 34% risk of progressing to insulin dependence among those on oral hypoglycaemics. Risk of adrenal insufficiency greater in COPD patients.

Can we safely stop inhaled steroids in COPD Withdrawal of steroids results in increased exacerbations (Jarad NA Respir Med 1999; Choudhury AB Respir Res 2007) WISDOM trial showed no increased exacerbation rate in patients if the ICS was reduced in a stepwise fashion 500 FDP bd then 250 bd then 100 bd then stop. (Magnussen H, N Eng J Med 2014)

Azithromycin prophylaxis COLUMBUS trail: Azithromycin resulted in approximate 40% reduction in exacerbations compared to placebo (Uzun, Lancet Respiratory Medicine 2014) Albert et al found 17% reduction in exacerbations (N Engl J Med2011) Donath et al for 37% reduction in meta analysis (Respir Med 2013) BUT QT prolongation and some effects on hearing Strep pneumoniae macrolide resistance in Gloucestershire is double the national average.

Phenotypes Can better characterisation of COPD determine response to treatment?

FEV1 = 44% predicted FEV1/FVC = 0.51

FEV1 = 39% predicted FEV1/FVC = 0.42

COPD and FEV1 COPD defined by FEV1 and FEV1/FVC FEV1 correlates poorly with Breathlessness Exacerbations Health status Response to treatment Reversibility tests Do not reliably predict treatment response

COPD stage – traditional model

Patient* is now in one of four categories: GOLD guidelines 2013: Stable COPD: Combined assessment of symptoms + spirometry + exacerbation risk1 Figure 2.3: Association between symptoms, spirometric classification and future risk of exacerbation Patient* is now in one of four categories: A: Less symptoms, low risk B: More symptoms, low risk C: Less symptoms, high risk D: More symptoms, high risk * When identifying the Patient Group to which a patient belongs, if their level of risk is different between their GOLD grade and their exacerbation history assessment, choose the method indicating the highest risk 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (updated Feb 2013).

ICS+LABA and PDE4-inh. or Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy Patient Recommended First choice Alternative choice Other Possible Treatments A SAMA prn or SABA prn LAMA LABA SABA and SAMA Theophylline B LAMA and LABA SABA and/or SAMA C ICS + LABA LAMA and LABA or LAMA and PDE4-inh. or LABA and PDE4-inh. D and/or ICS + LABA and LAMA or ICS+LABA and PDE4-inh. or LAMA and PDE4-inh. Carbocysteine

COPD Phenotypes Chronic bronchitis and emphysema Pink puffer and blue bloater Newer concepts Asthma-COPD overlap syndrome (ACOS) Exacerbator phenotype 2 or more exacerbations/year Emphysema/hyperinflation phenotype

Asthma COPD Overlap Syndrome Patients fulfil spirometric definition of COPD Have a history of asthma diagnosed before age 40yrs Have less emphysema Have greater bronchial wall thickening Tend to exacerbate more Have greater eosinophilic airway inflammation Benefit from ICS

Lung Volume Reduction Treatment for hyperinflation related breathlessness in emphysema

Lung volumes in COPD/emphysema Normal Lung COPD/Emphysema Lung

Lung volume reduction

Endobronchial valves

Endobronchial valves

Lung volume reduction coil

Conclusion Influenza and pneumococcal vaccination and smoking cessation are the most cost effective interventions Pulmonary rehabilitation and long acting bronchodilators are both cost effective and complementary Oxygen for hypoxic patients Inhaled steroids only for those with coexistant “asthma”/ACOS and for those with frequent exacerbations not already controlled with LABA/LAMA Consider withdrawal of ICS in patients who should never have been put on it! Consider referral for younger, more severe and when there is diagnostic doubt or consideration for LVR.