Management of acute Management of acute

exacerbation of COPDexacerbation of COPD

Dr. Roland LeungDr. Roland Leung

MBBS MD FRACP FCCP FHKCP MBBS MD FRACP FCCP FHKCP

FHKAM (Medicine)FHKAM (Medicine)

Specialist in Respiratory MedicineSpecialist in Respiratory Medicine

�� What is COPD and its prevalence in Hong Kong?What is COPD and its prevalence in Hong Kong?

�� What are the precipitating factors for AECOPD?What are the precipitating factors for AECOPD?

�� How to manage?How to manage?

�� Prevention?Prevention?

AECOPD

COPDCOPD� COPD is a 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 lungs to noxious particles or gases.

The GOLD Workshop Report (Updated 2004)

Barnes PJ. NEJM 2000; 343 : 269-280.

Barnes PJ. NEJM 2000; 343 : 269-280.

O2-, H2O2, OH, ONOO-

Mucus secretionisoprostanes Plasma leak

NKκB

IL8 TNFα

Antiproteinases

↓SLPI α1-AT

↓↑proteolysis

Neutrophil

recruitment

Oxidative stress in COPD

Bronchoconstriction

Relationship between the severity of COPD and exhaled breath condensate levels of 8-isoprostane, monocyte chemoattractantprotein-1 (MCP-1) and growth related oncogene-αααα (GROαααα)

Ko FW et al. Proceedings of the American Thoracic Society 2005;2:A312.

Control Group 1 Group 2 COPD0

25

5060

110160

p<0.001

p<0.001p=0.048 p=0.016

Exh

ale

d c

on

cen

trati

on

of

8-I

so

pro

sta

ne (

pg

/ml)

Group1 : FEV1 ≥50% predicted

Group 2: FEV1<50% predicted

Level of GROα was lower in COPD patients than control subjects

(p=0.004)

Level of MCP-1 was higher in

subjects with more severe COPD

(FEV1 <50% predicted) when

compared to the less severe COPD

subjects (FEV1 ≥ 50% predicted)

2.8

5.8

7.7

3.1

0

1

2

3

4

5

6

7

8

Pre

vale

nce (%

)

History of

tuberculosis

Asthma Chronic

Bronchitis

Emphysema

Self-reported respiratory diseases

Random household telephone interview was conducted from Nov to Dec, 2003.

1522 Subjects with age ≥70 years were asked to complete a respiratory

questionnaire by Dow L et al. (Eur Respir J 1991;4:267-72.)

Prevalence of respiratory symptoms, common chronic respiratory diseases, atopy and bronchial hyperresponsiveness in elderly Chinese living in Hong Kong.

Ko FW et al. Respirology 2004; 9:A155.

In HK, COPD was the 5th leading cause of death, and accounted for at least 4% of

all public hospital acute admissions in 2003.

Acute exacerbations of COPD (AECOPD)Acute exacerbations of COPD (AECOPD)

� Defined by increased symptoms and worsening lung function

� In Hong Kong, COPD was the fourth leading cause of death, and accounted for 3% of all public hospital admissions in 2001

� Effect of COPD exacerbation– QOL (Seemungal TA et al. Am J Respir Crit Care Med 1998; 157:1418-22.)

– Lung function (Donaldson GC et al. Thorax 2002; 57:847-52.)

Factors related to AECOPDFactors related to AECOPD

� Infections: – bacterial, viral

� Environmental factors– such as air pollution, temperature, interruption of regular treatment

� Donaldson GC et al. Eur Respir J 1999;13:844-9.

� Jarad NA et al. Respir Med 1999; 93:161-6.

COPDCOPD

Smoking

Allergen

Infection(viral / bacterial)

Environmental Pollutants

Acute ExacerbationAcute Exacerbation

• Increase cough & sputum• Increase SOB• Increase purulence of sputum

GOLD guideline 2004

�= Fluticasone+sameterol

�= salmeterol alone

A=salmeterol, FEV1≥50%B=seretide, FEV1≥50%C=seretide, FEV1,<50%D=salmeterol, FEV1<50%

Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes

immediate and sustained disease deterioration: a

randomised controlled trialWouters EF et al for the , COSMIC (COPD and Seretide: a Multi-Center Intervention

and Characterization) Study Group

Thorax 2005;60:480–487.

AvsB, p=0.3CvsD, p=0.6

Seemungal T et al. Am J Respir Crit Care Med.

2001;164:1618-23.

Viruses

Bacteria in AECOPDBacteria in AECOPD

Pathogen Colonizationvs

Bandi V et al. Am J Respir Crit Care Med 2001; 164.:2114–2119

Role of bacteriaRole of bacteria

Sethi S et al. N Engl J Med 2002;347:465-71.

**

Sethi S et al. N Engl J Med 2002;347:465-71.

Small airways in

COPD

Hogg et al NEJM 2004:350:2645-53

Management of AECOPDManagement of AECOPD

�� Bronchodilator therapyBronchodilator therapy

�� Systemic corticosteroidSystemic corticosteroid

�� AntibioticAntibiotic

In some patients, controlled oxygen therapy and/or non-invasive positive pressure ventilation (NIPPV) may be beneficial.

More severe exacerbations may require invasive mechanical ventilation.

Acute managementAcute management��Short acting betaShort acting beta--2 agonist2 agonist

��Short acting antiShort acting anti--cholinergiccholinergic

�� Trials showing that use of MDI with spacer is Trials showing that use of MDI with spacer is as effective as using nebulizer.as effective as using nebulizer.

vs

N=156 (11th-29th Mar 2003)138 traceable to a single index case

20 doctors34 nurses15 allied health16 medical students

Device Selection and Outcomes of Aerosol Therapy: Evidence-Based Guidelines* American College of Chest Physicians/American College of Asthma, Allergy, and Immunology

Dolovich MB et al. CHEST 2005; 127:335–371

Systemic steroid Systemic steroid vsvs Placebo in AECOPDPlacebo in AECOPD

� ↓ treatment failures in 30 days� OR 0.48; 95%CI 0.34 to 0.68� Hazard Ratio 0.78; 95%CI 0.63 to 0.97� treat 9 patients (95%CI 6 to 14) with systemic steroid to avoid one treatment failure in this time

period� There was no significant difference in mortality

� Treatment benefit in early FEV1 (up to 72hrs)� weighted mean difference140mls (95%CI 80-200mls)

� Significant improvement in breathlessness and blood gases between 6 - 72 hrs

� Increase likelihood of an adverse drug reaction� OR 2.29; 95%CI 1.55 to 3.38� Overall one extra adverse effect occurred for every 6 people treated (95% CI 4 to 10)

Wood-baker RR et al. Cochrane Database Syst Rev. 2005;25:CD001288.

Prednisolone gp

� Lower rate of relapse at 30 days(27% vs 43%, P=0.05)

� greater improvements in FEV1 at 10 days (mean increase from baseline, 34% vs15%; P=0.007)

� Improvements in dyspnea

X health-related quality of life (P=0.14)

Discharged from A&E after COPDAE

10 days of prednisolone 40 mg/d

vsplacebo

Aaron SD et al. NEJM2003;348:2618-25.

Antibiotic treatmentAntibiotic treatment

““ Patients experiencing COPD exacerbations with

clinical signs of airway infection (e.g., increasedvolume and change of color of sputum, and/or fever)may benefit from antibiotic treatment (Evidence B).”

GOLD guideline 2004.

Local sceneLocal scene

Ko FW et al. Respiratory Medicine (2005) 99, 454–460

� 329 patients with 418 episodes of AECOPD

� Mean age = 74.4±8.3 yrs.

� Acute hospital length of stay = 7.3±6.5 days

� Presence of organisms in sputum had no association with the hospital length of stay and ICU

admissions

Ko FW et al. Respiratory Medicine (2005) 99, 454–460

0.0

5.0

10.0

15.0

20.0

25.0

30.0

H. i

nflu

enza

eP

. aer

ugin

osa

S. P

neum

onia

eM

. cat

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MR

SA

Aci

neto

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Ste

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Ent

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Coa

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oli

Pro

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All episodes of admission with routine sputum culture saved for investigation

were included. (n=146)

Figure 1: Bacterial flora in sputum of patients with acute exacerbation of COPD

and concomitant pneumonia

Bacteria in sputum

%

Ko FW et al. Internal Medical Journal 2005 In press

0.0

1.0

2.0

3.0

4.0

5.0

6.0

Mycobacterial TB Atypical mycobacterium

Mycobacteria

Perc

enta

ge

All episodes of admission with AFB culture saved for investigation were included.

(n=130)

Figure 2: Mycobacterial growth from sputum of patients with acute exacerbation

of COPD and concomitant pneumonia

Ko FW et al. Internal Medical Journal 2005 In press

Comparison of organisms found in sputum culture in different studies in patients with

COPDAE and concomitant pneumonia (Ko FW et al. Internal Medical Journal 2005 In press)

na1(1.5%)2 (1.4%)Proteus mirabilis

nana2 (1.4%)Coagulase negative Staphyloccus aureus

nana2 (1.4%)Enterobacter

1 (4.2%)na4 (2.7%)Acinetobacter calcocaceticus

1 (4.2%)na2 (1.4%)Escherichia coli

1 (4.2%)na2 (1.4%)Klebsiella pneumoniae

nana2 (1.4%)Stenotrophomonas maltophilia

nana4 (2.7%)MRSA

nana2 (1.4%)Klebsiella pneumoniae

nana5 (3.4%)Morexalla catarhalis

3 (12.5%)17 (25.4%)5 (3.4%)Streptococcus pneumoniae

na2(3.0%)8 (5.5%)Pseudomonas aeruginosa

3 (12.5%)6 (9.0%)38 (26.0%)Haemophilus influenzae

Liam#(n=24)

Torres et al*(n =67)

Current study

(n = 146)

na = data not available

* Torres et al. Am J Respir Crit Care Med 1996;154:1456-61.

# Liam CK, et al. Respirology 2001;6:259-64.

AECOPDAECOPD

– The choice of agents should reflect local patterns of antibioticsensitivity among S. pneumoniae, H. influenzae, and M. catarrhalis.

(Gold guideline 2004)(Gold guideline 2004)

betabeta--lactamaselactamase activity was found in 33.7% isolates activity was found in 33.7% isolates

of of HaemophilusHaemophilus influenzaeinfluenzae..

At least intermediate resistance to penicillin was identified inAt least intermediate resistance to penicillin was identified in

25% of 25% of Streptococcal Streptococcal pneumoniaepneumoniae isolates. isolates. Ko FW et al. Respiratory Medicine (2005) 99, 454–460

Hong Kong IMPACT guideline 2003:

Recommended therapy: PO/IV amoxicillin-clavulanate or ampicillin/sulbactam

Alternative therapy: cefotaxime or a new anti-Gram positive fluroquinolone

�� ATS guideline 2001ATS guideline 2001–– Both outpatients and inpatientsBoth outpatients and inpatients

�� ββ lactamlactam + + macrolide/doxyclinemacrolide/doxycline or respiratory or respiratory fluroquinolonefluroquinolone alonealone

�� IDSA guideline 2003IDSA guideline 2003–– OutpatientsOutpatients

�� No recent antibiotic Rx: No recent antibiotic Rx: macrolidemacrolide or or doxycylinedoxycyline

�� Recent Recent antibioitcantibioitc Rx: respiratory Rx: respiratory fluroquinolonefluroquinolone alone /an advanced alone /an advanced macrolidemacrolide + high dose + high dose amoxillinamoxillin/ advanced / advanced marcolidemarcolide + high dose + high dose amoxicillinamoxicillin--clavulanateclavulanate

–– InpatientsInpatients�� ββ lactamlactam + + macrolidemacrolide or respiratory or respiratory fluroquinolonefluroquinolone alonealone

AECOPD with concomitant pneumoniaAECOPD with concomitant pneumonia

Prospective, randomized, controlled trials have shown that the NIPPV is efficacious in

� AECOPD Bott J et al. Lancet 1993;341:1555-7.

Brochard et al. N Engl J Med 1995;333:817-22Wysocki et al. Chest 1995;107:761-8.

Kramer N et al. Am J Respir Crit Care Med 1995;151:1799-806.Plant PK et al. Lancet 2000 ;355:1931-5.

� acute cardiogenic pulmonary edema Bersten AD; et al. N Engl J Med 1991 ;325:1825-30.

Lin M et al. Chest 1995;107:1379-86.Mehta S et al. Crit Care Med 1997 ;25:620-8.

Masip J et al. Lancet 2000;356:2126-32.

� hypoxemic respiratory failureAntonelli M et al. N Engl J Med 1998;339:429-35.

Martin TJ et al. Am J Respir Crit Care Med 2000;161:807-13.Ferrer M et al. Am J Respir Crit Care Med 2003;168:1438-44.

� immunocompromised patientsAntonelli M et al. JAMA 2000;283:235-41.

Hilbert G et al. N Engl J Med 2001;344:481-7.

� adjunct to weaning in patients with COPDNava S et al. Ann Intern Med 1998;128:721-8.

Girault C et al. Am J Respir Crit Care Med 1999;160:86-92.

�� MetaanalysesMetaanalyses of of RCTsRCTs of NPPV in patients of NPPV in patients with acute respiratory failure have with acute respiratory failure have concluded that:concluded that:

–– NPPV reduces mortality, length of hospital NPPV reduces mortality, length of hospital stay, and the need for mechanical ventilationstay, and the need for mechanical ventilation

–– improvements appear to be greatest for improvements appear to be greatest for patients with AECOPD patients with AECOPD

Peter JV et al. Crit Care Med 2002;30:555-62.

Lightowler JV et al. BMJ 2003 ;326:185.

Ram FS et al. Cochrane Database Syst Rev 2003;(1):CD004104.

Ram FS et al. Cochrane

Database Syst Rev

2003;(1):CD004104.

Ram FS et al. Cochrane

Database Syst Rev

2003;(1):CD004104.

Ram FS et al. Cochrane

Database Syst Rev

2003;(1):CD004104.

NIPPV for treatment ofrespiratory failure due to AECOPD (Review)Ram FS et al. Cochrane Database Ram FS et al. Cochrane Database SystSyst Rev 2003;(1):CD004104.Rev 2003;(1):CD004104.

�� NIPPV NIPPV vsvs conventional careconventional care

–– ↓↓ rate of intubation by 30rate of intubation by 30--60%60%

–– ↓↓ mortality of 10 to 20 %mortality of 10 to 20 %

–– ↓↓ ICU length of stay (13 ICU length of stay (13 vsvs 32 32 days) days)

–– ↓↓ in hospital length of stay (23 in hospital length of stay (23 vsvs35 days)35 days)

Selection criteria for NIPPVSelection criteria for NIPPV� Moderate to severe dyspnea with use of accessory muscles

and paradoxical abdominal motion� Moderate to severe acidosis (pH ≤ 7.35) and hypercapnia

(PaCO2 > 6.0 kPa, 45 mm Hg)� RR > 25 breaths/min

Exclusion criteria � Respiratory arrest� Cardiovascular instability (hypotension,arrhythmias, myocardial

infarction)� Somnolence, impaired mental status, uncooperative patient� High aspiration risk; viscous or copious secretions� Recent facial or gastroesophageal surgery� Craniofacial trauma, fixed nasopharyngeal abnormalities

Pressure settingPressure setting�� Start with low pressure in spontaneous triggered mode with backuStart with low pressure in spontaneous triggered mode with backup ratep rate

�� Pressure limit ~8Pressure limit ~8--12cmH2O 12cmH2O inspiratoryinspiratory pressure, 3pressure, 3--5cm H2O expiratory 5cm H2O expiratory pressurepressure

�� Gradually increase Gradually increase inspiratoryinspiratory pressure (10 to 20cm H2O) as tolerated to pressure (10 to 20cm H2O) as tolerated to achieve alleviation of achieve alleviation of dyspnoeadyspnoea, decreased respiratory rate, increased tidal , decreased respiratory rate, increased tidal volume (~7volume (~7--10ml/kg), and good patient ventilator synchrony10ml/kg), and good patient ventilator synchrony

�� Provide O2 supplementation as needed to keep O2 >90%Provide O2 supplementation as needed to keep O2 >90%

�� Check for air leaks, adjust straps, mask fitting as neededCheck for air leaks, adjust straps, mask fitting as needed

�� Monitor occasional blood gases (within 1 to 2 hours) and then neMonitor occasional blood gases (within 1 to 2 hours) and then needededed

International Consensus Conferences in Intensive Care Medicine: Noninvasive Positive Pressure Ventilation in Acute Respiratory Failure

Am J Respir Crit Care Med 2001;163:283–291.

Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure

C M Chu et al. Thorax 2004;59:1020–1025.

GOLD guideline 2004

Prevention of AECOPD

?

Smoking cessation

the single most effective intervention

to reduce the risk of developing COPD

and slow its progression

Prevention of AECOPDPrevention of AECOPD

? Environment

√ Pulmonary rehabilitation

±/? Proper use of medications: long acting bronchodilator and inhaled corticosteroid

(Sin DD et al. JAMA. 2003;290:2301-12.)

√ Vaccination

*****vaccination****Elderly persons with chronic lung disease, influenza vaccination is associated with substantial

health benefits, including

�fewer outpatient visits

�fewer hospitalizations

�fewer deaths.

Nichol KL et al. Ann Intern Med. 1999;130:397-403.

Incidence of influenza-related ARI:

�28.1 per 100 person-yrs in the placebo gp

�6.8 per 100 person-yrs in the vaccine group

�RR 0.24 [p 0.005]; vaccine effectiveness, 76%

Influenza vaccination is highly effective regardless of the severity of COPD.

Wongsurakiat P et al. CHEST 2004; 125:2011–2020