Download Infection In COPD

Infection in COPD
Pulmonology Subspeciality Rounds
(12/11/2008)
Dr.Krock
Dr.Vysetti
Review Article
Infection in the Pathogenesis and Course of
Chronic Obstructive Pulmonary Disease
Sanjay Sethi, M.D., and Timothy F. Murphy, M.D.
N Engl J Med
Volume 359(22):2355-2365
November 27, 2008
Outline
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Historical Perspective
Exacerbations
 Bacteria as a Cause of Exacerbations
 Viruses as a Cause of Exacerbations
 Interaction of Viruses and Bacteria
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Chronic Infection in COPD
 Bacterial Colonization and Inflammation
 Other Evidence of Chronic Infection
 Other Chronic Infections
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Mechanisms of Chronic Infection in COPD
 Innate Lung Defense
 The Vicious Circle
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Antibiotics in COPD
Future Directions
Historical Perspective..Causes for
exacerbation.
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1950’s and 1960’s repeated airway infection and hypersecretion
of mucus.
Tobacco smoke.
Frequency of bacterial isolation from sputum found similar in
stable COPD and during exacerbations.
Insufficient evidence to support role of bacteria.
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Antibiotic therapy in exacerbations of chronic obstructive
pulmonary disease. Ann Intern Med. 1987 Feb.
In the past two decades.. New molecular, cellular, and
immunologic techniques used to study host–pathogen
interactions have led to a reexamination of the role of infection in
chronic obstructive pulmonary disease (COPD).
► There is now considerable evidence that infection plays a major
role in the pathogenesis and clinical course of COPD.
► A vicious circle of infection and inflammation is thought to lead to
exacerbations of the disease
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Microbial Pathogens in COPD
Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365
Exacerbations…Bacteria as a cause..
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Clinical manifestations from the direct effects of viruses and bacteria and from
the host response.
Bacterial Role…Controversy in literature.
Bronchoscopic sampling with the use of a Protected Specimen Brush yields
reliable specimens from the lower airways.
50% of exacerbations are caused by bacteria.
Purulent sputum during an exacerbation is highly correlated with the presence
of bacteria in the lower respiratory tract.
? Bacterial Load as a cause.(Am J of Res CC May 2007,Ref No.6)
Bacterial Infection of the lower respiratory tract represents a dynamic complex
process and acquisition of new strain plays a central role in pathogenesis(Ref
no.7).
Not All Strains Cause Exacerbations.
Host FactorsImpairement of Immunity,Previous Immunologic exp
Implicated.
Proposed Model of the Pathogenesis of Bacterial Exacerbations in COPD
Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365
Viruses as a cause…
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Difficult to estimate the proportion of exacerbations by viruses.
Studies relying on cultures-Underestimate & studies relying on
PCR overestimate the role.
Most Common->Rhinoviruses
Most Severe Influenza.
Recently recognisedRSV and Human metapneumovirus.
When Viruses and Bacteria both cause-Exacerbations are very
Severe.
Chronic Infection
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Airways of COPD pts chronically colonised with respiratory
pathogens with no acute symptoms.
Significance:Even in stable COPD pts colonizations associated
with host inflammatory and immune response.
Airway inflammation related to colonization if neutrophilic with
IL-8 as the major mediator.
IL-8 and Neutrophils play a key role in the development of the
COPD.
Associated with increased sputum production and worsening
airflow obstruction
Colonization(smoldering infection) induced inflammation probably
contributes to the progression of the disease.
Supported by Pathologic and Radiologic Evidence
The Vicious-Circle Hypothesis of Infection and Inflammation in COPD
Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365
Antibiotics In COPD
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Antibiotics –Rx of mod-Severe exacerbations when purulent
sputum is present.
Predictive Factors for poor clinical outcomes.
Stratified Approach based on GOLD(2008) and Canadian
guidelines for management of acute exacerbations of chronic
bronchitis(2003)
Choice of Antibiotic Evidence ?
(Chest 2007)Metaanalysis of RCT’s comparing first line Vrs
Second line Antibiotics for Acute exacerbations of Chronic
Bronchitis.Second line more effective.
Algorithm for Antibiotic Treatment in Patients with Acute Exacerbations of COPD
Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365
Out Patient
In Patient
Ongoing trials and Future Research..
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Usefulness of Intermittent Pulsed Rx with Antibiotics or
Antiinflammatory action of antibiotics in treatment of
exacerbations.
More understanding of environmental factors,viruses and
bacteria in the pathogenesis of COPD exacerbations.
Questions…
1.
Which one of the following factors causes most
exacerbations of chronic obstructive pulmonary disease
(COPD)?
A. Air pollution.
B. Change in temperature.
C. Change in humidity.
D. Infection.
Q2
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Which one of the following viruses is most commonly
associated with infectious exacerbations of COPD?
A. Adenovirus.
B. Coronavirus.
C. Parainfluenza virus
D. Rhinovirus.
Q3
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Which one of the following mediators plays a major role
in inducing airway inflammation related to bacterial
colonization?
A. Endothelin-2.
B. Interleukin-8.
C. Phospholipase A3.
D. Prostaglandin E2.
Q4
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Antibiotics are especially beneficial for the treatment of
moderate and severe exacerbations of COPD in which
one of the following circumstances?
A : Purulent sputum is a presenting symptom.
B : The duration of symptoms exceeds 72 hours.
C : The patient has diabetes.
D : The patient is febrile.
Q5
5.What are the most prevalent bacterial pathogens in the
lungs of patients with COPD?
A.H.Influenza and Pseudomonas aeruginosa
B.M.catarrhalis
C.S.pneumonia.
Q6
Is it appropriate to start antibiotics for an acute
exacerbation of COPD?
Not Beneficial for Mild exacerbation.
Initial Antibiotic choice (before any specific infectious agent is
identified) based on the pts age ,risk factors,FEV1,No of
exacerbations per year, recent antibiotic exposure and presence
of cardiac disease.
THANK YOU !!