• Contents
• Introduction Claude Lenfant
• Preface
• Contributors

Part I: Introduction

1. Definitions and Severity of Exacerbations
Stephen I. Rennard and Nancy Kline Leidy

• I. Introduction
• II. Definitions
• III. Standardizing Measurement of Exacerbations
• IV. Heterogeneity and Phenotypes of Exacerbations
• V. Summary
• References

2. Epidemiology of COPD Exacerbations
Andrea K. Johnston and David M. Mannino

• I. Introduction
• II. Methods
• III. Exacerbation Frequency
• IV. Frequent Vs. Infrequent Exacerbators
• V. Lung Function Impairment
• VI. Emergency Care
• VII. Hospitalizations
• VIII. Comorbidities
• IX. Mortality
• X. Conclusions
• References

3. Differential Diagnosis of COPD Exacerbations
Peter M. A. Calverley

• I. Introduction
• II. Clinical Features of COPD Exacerbations
• III. Principal Alternative Diagnoses
• IV. Clinical Approach to Differential Diagnosis
• V. Conclusion
• References

Part II: Mechanisms and Pathophysiology

4. Symptom Changes at COPD Exacerbation
Terence A. R. Seemungal

• I. Introduction
• II. Common Symptoms at Exacerbation
• III. Time Course of Symptom Changes
• IV. Physiological Basis of Dyspnea and Symptom Recovery
• V. The Concept of Recovery of Symptoms and Lung Function
• VI. Changes in Symptoms and Airway and Systemic Inflammation
• VII. Frequency of Symptom Changes and Recurrent Exacerbations
• VIII. Symptom Changes and New and Colonizing Strains of Bacteria
• IX. Symptom Changes and Viruses
• X. Symptom Changes and Environmental Factors
• XI. Symptoms and Treatment
• XII. Conclusion and Recommendations References

5. Airway Pathology at Exacerbations
Graziella Turato, Simonetta Baraldo, Kim Lokar-Oliani, Renzo Zuin, and Marina Saetta

• I. Introduction
• II. Airway Pathology During Exacerbations
• III. Summary
• References

6. Airway and Systemic Inflammatory Markers at Exacerbation
John R. Hurst

• I. Introduction
• II. Changes in Airway and Systemic Inflammatory Markers at Exacerbation of COPD
• III. Utility of Changes in Airway and Systemic Inflammatory Markers at Exacerbation of COPD
• IV. Summary
• Abbreviations
• References

7. Pathophysiology of Acute Exacerbations of COPD
Chris M. Parker and Denis E. O’Donnell

• I. Introduction
• II. Pulmonary Function
• III. Dynamic Hyperinflation
• IV. Effects on Gas Exchange
• V. Cardiovascular Effects
• VI. Mechanisms of Dyspnea During Exacerbation
• VII. Conclusions
• References

8. Systemic Consequences of COPD Exacerbations
Scott S. Wagers, Karin Groenewegen, and Emiel F. Wouters

• I. Introduction
• II. Systemic Inflammation and Oxidative Stress
• III. Skeletal Muscle Wasting
• IV. Exercise Intolerance
• V. Weight Loss
• VI. Osteoporosis
• VII. Diabetes
• VIII. Accentuated Thrombosis
• IX. Depression
• X. Summary
• References

9. Mechanisms of Respiratory Failure in COPD Exacerbations
Borja G. Cosio and Roberto Rodri´guez-Roisin

• I. Introduction
• II. Mechanisms of Hypoxemia and Hypercapnia
• III. Natural History of Hypoxemic Respiratory Failure
• IV. Effects of Oxygen Breathing
• V. Response to Bronchodilators
• VI. Response to Glucocorticoids
• VII. Conclusion
• References

10. Role of Respiratory Viral Infection at Exacerbation
J. K. Quint and Jadwiga A. Wedzicha

• I. Introduction
• II. Detection of Viruses
• III. Mechanisms of Virus-Induced Exacerbations and Host Response
• IV. Susceptibility to Viral Infection
• V. Rhinovirus
• VI. Coronavirus
• VII. Influenza and Parainfluenza
• VIII. Adenovirus
• IX. Respiratory Syncytial Virus
• X. Human Metapneumovirus
• XI. Viruses in Stable COPD
• XII. Summary
• References

11. Do Airway Bacteria Cause COPD Exacerbations?
Himanshu Desai and Sanjay Sethi

• I. Introduction
• II. Pathogenesis of Infectious COPD Exacerbations
• III. Role of Airway Bacteria in COPD Exacerbation
• IV. Conclusions
• References

12. Interactions of Airway Pathogens and Inflammatory Processes
Marco Contoli, Gaetano Caramori, Brunilda Marku, Alberto Papi, and Anita Pandit

• I. Introduction
• II. Pathogens and Inflammation
• III. Conclusion
• References

13. Comorbidity at Exacerbation of COPD
David McAllister, John Maclay, William Macnee, and Roberto Rabinovich

• I. Introduction
• II. Respiratory CoMorbidity
• III. Cardiovascular CoMorbidity
• IV. Anemia and Hyperglycemia
• V. Conclusion
• References

14. Environmental Causes of Exacerbations
Fanny WS Ko and David SC Hui

• I. Introduction
• II. Environmental Factors Associated with AECOPD
• III. Summary
• References

15. Exacerbations in Alpha-1-Antitrypsin Deficiency
R. A. Stockley

• I. Introduction
• II. Potential Role of the Neutrophil
• III. Proteinase Cascade
• IV. Alpha-1-Antitrypsin Deficiency
• V. Management
• References

16. Animal Models of COPD—Current Status of an Evolving Field
Paul J. Christensen, W. Bradley Fields, Christine M. Freeman, and Jeffrey L. Curtis

• I. Introduction
• II. Murine Models of COPD
• III. Genetic Models of Emphysema
• IV. Autoimmune and Other Murine Models not Involving CSE
• V. COPD Models in Nonmurine Species
• VI. Summary and Future Directions
• References

17. Comparison of Asthma and COPD Exacerbations
Joseph Footitt, Annemarie Sykes, Patrick Mallia, and Sebastian L. Johnston

• I. Introduction
• II. Epidemiology of Exacerbations
• III. Etiology of Exacerbations
• IV. Mechanisms of Exacerbations
• V. Pathophysiology of Exacerbations
• VI. Conclusion
• References

Part III: Impact of Exacerbations

18. Risk Factors for Hospital Admission
Judith Garcia-Aymerich

• I. Methodological Introduction
• II. Risk Factors of Hospital Admission for a COPD Exacerbation
• III. Conclusion
• References

19. Effect of Exacerbations on Disease Progression and Mortality
James J. P. Goldring and Gavin C. Donaldson

• I. Introduction
• II. Studies That Have Investigated the Effect of Exacerbations on Disease Progression
• III. Studies That Have Investigated the Mechanisms Behind FEV1 Decline in COPD Exacerbations
• IV. Evidence from Other Diseases That Lung Function Decline is Related to Infection and Inflammation
• V. Effects of Exacerbation on Mortality
• VI. Summary
• References

20. Health Economic Consequences of COPD Exacerbations
Marc Miravitlles

• I. Introduction
• II. Costs of COPD
• III. Economic Impact of Exacerbations
• IV. Conclusions
• References

Part IV: Management of the Acute Exacerbation

21. Use of Bronchodilators and Mucolytics at COPD Exacerbations
Wim Janssens and Marc Decramer

• I. Introduction
• II. Bronchodilators
• III. Mucolytics
• References

22. Corticosteroids in the Management of Acute Exacerbations
Dennis E. Niewoehner and Kathryn Rice

• I. Introduction
• II. Evidence for Clinical Efficacy
• III. Dose, Duration, and Route of Administration
• IV. Adverse Effects of Short-Term Systemic Corticosteroids
• V. Mechanisms of Response to Corticosteroids in COPD Exacerbations
• VI. Summary
• References

23. Antibiotic Therapy at COPD Exacerbations
Robert Wilson and Mitzi Nisbet

• I. Introduction
• II. Meta-Analysis of Placebo-Controlled Antibiotic Trials in COPD
• III. Bacterial Infection Causing Exacerbations of COPD
• IV. Aims of Antibiotic Therapy at Acute Exacerbations of COPD
• V. Current Guidelines for Antibiotic Treatment at COPD Exacerbations
• VI. Patient Characteristics Which Might Influence Choice of Antibiotic
• VII. Other Issues
• VIII. Length of Antibiotic Course and Dosage
• IX. Biomarkers
• X. Atypical Bacterial Infections
• XI. Viral and Bacterial Coinfection
• XII. Future Research
• References

24. Noninvasive Ventilatory Support in Acute Exacerbations of COPD
Stanley D. W. Miller and Mark W. Elliott

• I. Introduction
• II. NIV in Acute COPD
• III. NIV vs. IMV
• IV. Indications for NIV in AECOPD
• V. Where Should NIV be Given?
• VI. Contraindications
• VII. Choice of Ventilator Type
• VIII. Interfaces
• IX. Monitoring the Patient on NIV
• X. Predictors of Success and Outcome
• XI. Conclusion
• References

25. Invasive Mechanical Ventilation and Weaning at COPDExacerbation
Antonio Anzueto, Andre´s Esteban, and Fernando Frutos-Vivar

• I. Introduction
• II. Impact of Exacerbations on Mortality
• III. Physiological Impairment in Acute Respiratory Failure in Patients with COPD Exacerbation
• IV. Respiratory Failure and Supplemental Oxygen
• V. Weaning
• VI. Conclusion
• References

26. Oxygen Therapy and Exacerbations
A. G. Davison, Ronan O’Driscoll, and Luke Howard

• I. Introduction
• II. Blood Gas Pathophysiology in AECOPD
• III. Critical Hypoxemia in Normal Subjects
• IV. Levels of Hypoxemia Found in AECOPD
• V. Hypercapnia
• VI. Effect of Continuous High Concentrations of Oxygen in AECOPD
• VII. Effect of Intermittent Oxygen Therapy or Stopping Oxygen in AECOPD
• VIII. High-Flow Low-Concentration Oxygen Using a 24–28% Venturi Mask
• IX. Use of Nasal Cannulae (Prongs) to Provide Controlled Oxygen
• X. Recent Studies on AECOPD
• XI. Oxygen Alert Cards and 24 or 28% Venturi Masks for COPD
• Patients Who have had an Episode of Hypercapnic Respiratory Failure
• References

27. End-of-Life Issues and COPD Exacerbations
Anita K. Simonds

• I. Mortality and Morbidity of Severe Acute Exacerbations
• II. Symptom Burden
• III. Conclusions
• References

28. Novel Models of Care for COPD Exacerbations
Martyn R. Partridge

29. Physiotherapy at Exacerbation of COPD
Rachel Garrod and Christine Mikelsons

• I. Introduction
• II. Positioning
• III. Breathing Techniques
• IV. Early Pulmonary Rehabilitation
• V. Early Rehabilitation of Intubated Patients with COPD
• VI. Airway Clearance Therapies
• References

30. COPD Exacerbation and Pulmonary Rehabilitation
William D-C. Man and Michael I. Polkey

• I. Introduction
• II. PR in the Prevention of Acute Exacerbations
• III. PR in the Treatment of Acute Exacerbations
• IV. Summary
• References

Part V: Prevention of COPD Exacerbation

31. Pharmacological Prevention of COPD Exacerbations
Bianca Beghe´, Fabrizio Luppi, and Leonardo M. Fabbri

• I. Introduction
• II. Smoking Cessation
• III. Vaccines
• IV. Antioxidant and/or Mucolytic Agents
• V. Bronchodilators
• VI. Theophylline
• VII. Phosphodiesterase Inhibitors
• VIII. Inhaled Corticosteroids
• IX. Combination Therapy
• X. Importance of Comorbidities and Their Treatment
• XI. Conclusion
• References

32. Self-Management in Prevention and Early Intervention of Exacerbations
Jean Bourbeau, Erik W. M. A. Bischoff, and Maria Sedeno

• I. Introduction
• II. Self-Management in COPD
• III. Self-Management to Prevent Exacerbation
• IV. Self-Management and Early Treatment
• V. Practice Advice in Using an Action Plan
• VI. Conclusion
• VII. Needs for Research
• References

33. Immunological Interventions
Phillippa J. Poole

• I. Introduction
• II. Influenza Vaccination
• III. Pneumococcal Vaccination
• IV. Haemophilus Influenzae Vaccination
• V. Other Immunostimulants
• VI. Conclusion
• References

34. Oxygen Therapy and Home Mechanical Ventilation
Nathaniel Marchett i and Gerard J. Criner

• I. Introduction
• II. Oxygen Therapy
• III. Home Mechanical Ventilation
• IV. Conclusion
• References

Part VI: Issues for Studies of COPD Exacerbations

35. Design of Trials for COPD Exacerbations
Fernando J. Martinez, Meilan Han, and Jeffrey L. Curtis

• I. Introduction
• II. Therapeutic Trials of AECOPD
• III. Conclusions
• References

36. Statistical Considerations for COPD Exacerbation Trials
Shawn D. Aaron

• I. Introduction
• II. Distribution of the Data
• III. Approaches to Determining Rates
• IV. Counting Individual COPD Exacerbations
• V. Reporting Exacerbations
• VI. Summary
• References

37. Future Developments in Acute Exacerbations of COPD
Peter J. Barnes

• I. Introduction
• II. Inflammatory Mechanisms
• III. Novel Therapeutic Approaches
• IV. Conclusions and Future Directions
• References
• Index

• Jadwiga A. Wedzicha, Royal Free and University, London, UK
• Fernando J. Martinez, University of Michigan Medical Center
  Ann Arbor, MI, USA