COPD Managing the Acute Phase and Preventing Readmissions

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1 COPD Managing the Acute Phase and Preventing Readmissions Professor Bill MacNee Centre for Inflammation Research Queen s Medical Research Institute and The Royal Infirmary of Edinburgh 4 th International Conference, Society for Acute Medicine, Edinburgh 7-8 October 2010

2 Stage IV Proportion of subjects (%) Stage III Stage II Reported exacerbations at baseline 75 60% Mean= % of Frequent Exacerbators in Year 1 and Year 2 were Frequent 50% Exacerbators in Year 3 Mean= % of patients having no exacerbations in Years 1 and Year 2 had no exacerbations in Year 3 30% Mean= >7 Number of exacerbations Hurst et al NEJM 2010 ;263:1128 Agustí A et al. Respir. Res. 2010;11:122

3 Univariate associations with exacerbations Top 10 (by Wald Chi-Square) OR 95%CI Exacerbation Last Year FEV 1 ( 100mL) SGRQ-C Total Score (+4 points) FEV 1 /FVC ratio ( 1 %) FACIT-F Fatigue Score (-1 unit) Emphysema LAA% (+5%) MRC Dyspnoea Score, MWD ( 50m) Serum Fibrinogen (+SD) CES-D Depression score (+1 unit) All p<0.001 Hurst et al NEJM 2010 ;263:1128

4 COPD Exacerbations : Mortality Mortality in exacerbations without respiratory failure 5-11%, with respiratory failure 11-26% 1 Mortality in the UK following admission for an exacerbations occurs in 14% of cases within 3 months 2 Prognostic indicators of death during follow-up: - low ph - peripheral oedema - residence in nursing home - age 70 years - unrecordable PEF - oxygen saturation 86% - assisted ventilation 1. Patil et al. Arch Intern Med 2003;163: Roberts et al. Thorax 2003;58:947

5 Investigating and managing exacerbations of COPD

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7 Exacerbations of COPD Differential diagnosis Patients with exacerbations who do not respond to treatment Pneumonia Asthma Congestive cardiac failure Pulmonary embolism Pneumothorax Cardiac arrhythmia MI 20.5% COPD patients unrecognised heart failure Rutten FH et al, Eur Heart J 2005;26: % of exacerbations are associated with unrecognised ACS McAlistair et al 2010 Jemtel et al JACC 2007;49:171

8 Exacerbations of COPD : Treatment Bronchodilators Cochrane review 3 studies comparing 2 agonist and anticholinergic 1 Both produced similar improvement in FEV 1 ( ml at 90 min) One study showed significant improvement in PaO 2 ( kpa) with anticholinergic compared with 2 agonist ( kpa) Several studies have assessed the addition of anticholinergic to 2 agonist all have found no further improvement in FEV 1 one study found shorter ER stays but no difference in admission rates 2 Meta-analysis comparing MDI and nebulised bronchodilators found no differences in their effect on FEV 1 3 Cochrane review 4 of methylxanthenes (4 randomised trials) show no improvement in FEV 1 symptoms, admission rates and an increase in side effects 1. Brown et al Cochrane data base Shrestha et al Ann Emerg Med Turner et al Arch Intern Med Barr et al Cochrane data base 2000

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10 Meta analysis of the use of antibiotics In exacerbations of COPD Favours control Favours antibiotics Elmes et al, 1957 Berry et al, 1960 Fear and Edwards, 1962 Elmes et al, 1965 Petersen et al, 1967 Beneficial effect in particularly in patients with low FEV 1 Allegra et al Pul Pharm Ther 2001;14:149 Bach et al Ann Intern Med 2001;134:600 Pines et al, 1972 Nicorta et al, 1982 Anthonisen et al, 1987 Jorgensen et al, 1992 Overall Sachs et al Thorax 1995;50:758 No relevant effect of antibiotics in exacerbations of COPD in primary care Effect size (SD Units) Saint et al. JAMA (1995)

11 ANTIBIOTICS IN EXACERBATIONS OF COPD Exacerbation = (n=362) Dyspnoea, sputum volume and purulence % success with :- Placebo Antibiotic GIVE SIMPLE ANTBIOTICS:- Aminopenicillin Macrolide- if penicillin allergy Tetracyline Follow local microbiological guidance 3 of above symptoms of above Consider cover for other organisms in patients with severe disease recurrant admissions 1 of above No bacteriology Antibiotic Resistance Outcome Measures Anthonisen Ann Int Med 1987;106:196

12 Corticosteroids in Exacerbations of COPD 7 Randomised placebo controlled trials Various doses (125 mg methyl prednisolone 6 hourly to 30mgprednisolone daily. Duration 8 2 weeks) FEV 1 (6 72 hrs) significantly improved over placebo. Weighted mean difference 120ml Fewer treatment failures Increase likelihood of adverse drug reaction

13 Change in FEV 1 after bronchodilation from baseline (%) Patients remaining in hospital (%) Randomised Controlled Trial of the Effect of Oral Corticosteroids in Exacerbations of COPD Prednisolone 30 mg 14 days n=29 Placebo n= ml/day Median LOS shortened by 2 days ml/day Length of stay in hospital (days) Time point of measurement Davies et al. Lancet (1999)

14 Acute on Chronic Respiratory Failure in ECOPD Factors associated with death Age Acidosis H+ ion 55nmol/l (ph 7.26) Survival unrelated to hypoxaemia or hypercapnia Normal ph Mortality 6.9% ph < Mortality 13.8% Hypotension Uraemia

15 BTS guideline for emergency oxygen use in adult patients

16 National COPD Audit High flow oxygen was associated with: Subsequent ventilatory support (22% vs 9%, p<0.001) and Higher in-hospital mortality (11.1% vs 7.2%, p<0.001) Use of relatively high flow rates of oxygen prior to and after admission where there is not only a significant relationship with the degree of admission acidosis but also adverse outcomes of need for ventilatory support and death

17 Exacerbations COPD: :Respiratory Failure Noninvasive intermittent positive pressure ventilation (NPPV) in acute exacerbations:- - improves blood gases and ph, - reduces in-hospital mortality, - decreases the need for invasive mechanical ventilation and intubation, - decreases the length of hospital stay National (Evidence COPD A) Audit Potential impact of delay in initiation of NIV after admission NPPV After optimal medical treatment and oxygen respiratory acidosis (ph <7.35) and / The group of patients for whom there exists an or excessive breathlessness persists evidence base for the effectiveness of NIV, those with a ph range of 7.26<7.35, form only a minority of those receiving NIV

18 Long-term trials in COPD Short acting anticholinergics Inhaled Corticosteroids (ICS) LHS Ipratropium N-Acetylcysteine Long Acting Beta2 Agonists/ICS EUROSCOP-1999 Budesonide ISOLDE-2000 Fluticasone BRONCUS N-Acetylcysteine Long Acting anticholinergic CCLS-1999 Budesonide LHS II-2000 Triamcinolone TORCH SALM + FP UPLIFT 2008 Tiotropium vs Control INSPIRE-2007 SALM + FP v tiotropium PDE4inhibitor 2009 Roflumilast vs Control

19 TOwards a Revolution in COPD Health TORCH: Salmeterol and fluticasone in COPD 6112 COPD patients FEV 1 60% SFC 2x 50/500 µg Salm 2x 50 µg FP 2x 500 µg Placebo [%] -10 SFC combination Exacerbations Mortality 3 years % p=0.052 Mortality Exacerbations % p<0.001 Calverley et al., NEJM 2007

20 Understanding Potential Long-term Impacts on Function with Tiotropium UPLIFT: Tiotropium 18µg vs placebo in COPD 5993 COPD patients FEV 1 45% pred Tiotropium 18µg Placebo usual respiratory medications allowed, (LABA/ICS 60%) 4 years 3 years Decline FEV1 [%] Exacerbations - 16% p<0.001 Mortality - 16% p=0.086 Exacerbations Mortality -30 Tashkin et al.,nejm 2008, Celli et al AJRCCM 2009

21 Single, double, or triple therapy for COPD? Pts 1 exac. [%] 60 Exacerbations p = n.s. 60 [n] Hospitalisations for COPD exacerbations p = Tio Tio + Salm Tio + Salm-FP Tio Tio + Salm Tio + Salm-FP Aaron et al., Ann Intern Med 2007

22 Treatment algorithm for inhaled therapies in the management of stable COPD Nice 2010

23 Long term erythromycin therapy is associated with decreased COPD Exacerbations n=109 Seemungal et al AJRCCM 2008

24 Pulmonary rehabilitation for COPD Improves exercise tolerance Improves breathlessness Improves quality of life Reduces re-admission to hospital with exacerbations of COPD

25 Reduction of hospitalisation in COPD : a disease specific self management intervention Kaplan-Meler curves for the probability of not being admitted to the hospital during 12-month follow-up Bourbeau et al Ann Intern Med 2003;163:585

26 Associations between statins and outcomes in COPD Dobler et al BMC Pulmonary Medicine 2009, 9:32

27 Tissue engineering- the future for chronic diseases?

28 COPD Managing the Acute Phase and Preventing Readmissions Key messages There is a high prevalence of co-morbidities in exacerbations of COPD which influence outcome Give oxygen therapy judiciously in exacerbations of COPD Provide non-invasive further exacrbation in those with respiratory acidosis Review treatment options to prevent further exacerbations

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32 Procalcitonin guided antimicrobial therapy Prospective, controlled, single center trial 208 consecutive hospitalized patients Randomized to: Standard therapy antibiotics per discretion of MD Procalcitonin driven therapy < 0.1 mg/l Antibiotics discouraged mg/l Antibiotics based on clinical condition > 0.25 mg/l Antibiotics encouraged Primary endpoint total antibiotic use Stolz et al. Chest 2007; 131:9

33 Procalcitonin guided antimicrobial therapy Procalcitonin therapy decreased antibiotic use from 72% to 40% (RR reduction 44%, p < ) No difference between groups in: Subsequent antibiotic use during six months Time to next AE COPD did not differ Clinical response, adverse events Stolz et al. Chest 2007; 131:9.

34 National COPD Audit

35 National COPD Audit

36 Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD In-hospital mortality was 5.2% Those receiving beta blockers (n = 142) were older and more frequently had cardiovascular disease than those who did not Beta blocker use was associated with reduced mortality (OR = 0.39; 95% CI 0.14 to 0.99) The use of beta blockers by inpatients with exacerbations of COPD is well tolerated and may be associated with reduced mortality Dransfield MT, Thorax. 2008

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39 Domiciliary non-invasive ventilation for recurrent acidotic exacerbations of COPD n=13 highly selected patients No home NIV With home NIV Mean age (years) 55 (7.5) M:F ratio 9:4 FEV 1 (clinic measurement) 0.58 (0.24) Mean arterial gas tensions on admission with acute exacerbation ph 7.31 (0.02) 7.31 (0.04) PCO 2 (kpa) 9.94 (0.86) 9.55 (1.26) PO 2 (kpa) 6.97 (0.66) 7.37 (2.15) Admissions 5 (3) 2 (2)* Total days in hospital 78 (51) 25 (25)** Duration of admissions (days) 17 (10) 8 (7)*** Days in ICU 2 (5) 0.3 (1) Outpatient appointments 5 (3) 4 (2) Data are expressed as mean (SD). *p=0.007; **p=0.004; ***p=0.03; Tuggey et al Thorax 2003;58:

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41 Mortality (%) National COPD Audit 2008 COPD Exacerbations : Mortality 1016 pts with severe COPD exacerbation (PaCO 2 > 6.5 kpa) 49% 43% 33% 20% 11% 0 Hospital stay 60 days 180 days 1 year 2 years Connors AF Jr et al. Am J Respir Crit Care Med. 1996;154:959-67

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43 National COPD Audit

44 National COPD Audit

45 187 AECOPD 139 other 48 Glasgow 24 Positive Troponin 115 Negative troponin 4 acute ECG Δ s Proportion (95 % CI) Score Method 3% (1 to 7), 2 had Chest Pain 3 equivocal ECG Δ s 5 % (2 to 10) 4 ST/T abnormalities Old ECG unavailable 8% (4 to 14) McAllisiter et al ERJ 2007

46 Exacerbations of COPD - Oxygen Therapy In patients with a history of COPD aged 50 years or more, do not give an FIO 2 > 28%,via a Venturi mask, or 2l/min via nasal prongs until the arterial gas tensions are known Check blood gases within 60 minutes of starting oxygen and within 60 minutes of a change in inspired oxygen If the PaO 2 is responding and the effect on H+ ion <55nmol/l, increase the inspired concentration of oxygen until the PaO 2 is above 7.5 kpa If the H+ ion rises >55nmol/l consider alternative strategies

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