Infection in COPD

1. Infection in COPD Pulmonology Subspeciality Rounds (12/11/2008) Dr.Krock Dr.Vysetti

2. Review ArticleInfection 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

3. Outline • Historical Perspective • Exacerbations • Bacteria as a Cause of Exacerbations • Viruses as a Cause of Exacerbations • Interaction of Viruses and Bacteria • Chronic Infection in COPD • Bacterial Colonization and Inflammation • Other Evidence of Chronic Infection • Other Chronic Infections • Mechanisms of Chronic Infection in COPD • Innate Lung Defense • The Vicious Circle • Antibiotics in COPD • Future Directions

4. Historical Perspective..Causes for exacerbation. • 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.

5. 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

6. Microbial Pathogens in COPD Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365

7. Exacerbations…Bacteria as a cause.. • 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.

8. Proposed Model of the Pathogenesis of Bacterial Exacerbations in COPD Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365

9. Viruses as a cause… • 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.

10. Chronic Infection • 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

11. The Vicious-Circle Hypothesis of Infection and Inflammation in COPD Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365

12. Antibiotics In COPD • 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.

13. Algorithm for Antibiotic Treatment in Patients with Acute Exacerbations of COPD Sethi S, Murphy T. N Engl J Med 2008;359:2355-2365

14. Out Patient

15. In Patient

16. Ongoing trials and Future Research.. • 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.

17. Questions… • 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.

18. Q2 • Which one of the following viruses is most commonly associated with infectious exacerbations of COPD? A. Adenovirus. B. Coronavirus. C. Parainfluenza virus D. Rhinovirus.

19. Q3 • 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.

20. Q4 • 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.

21. 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.

22. 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.

23. THANK YOU !!