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Semin Respir Crit Care Med 2005; 26(2): 192-203
DOI: 10.1055/s-2005-869538
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pathogenesis and Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Sanjay Sethi1 , 2
  • 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, University at Buffalo SUNY, Buffalo, New York
  • 2Department of Veterans Affairs, Western New York Healthcare System, Buffalo, New York
Further Information

Publication History

Publication Date:
27 April 2005 (online)

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ABSTRACT

Once thought to be a mere nuisance, exacerbations are now recognized as a major contributor to the morbidity and mortality associated with chronic obstructive pulmonary disease. This recognition has led to research using new investigative tools that has substantially enhanced our understanding of the pathogenesis of exacerbations. Several overlapping etiologies can precipitate the symptom complex of an exacerbation. Treatment of exacerbations requires the use of several therapeutic modalities with the goal of restoring the patient to baseline. Results of recent clinical trials and observational studies have allowed a refinement of the approach to treatment of exacerbations. These include a rational, stratified approach to the use of antibiotics and several trials substantiating the use of systemic corticosteroids. Relapse or failure rates of 20 to 33% have been described in the treatment of acute exacerbation, with these treatment failures contributing substantially to the costs associated with exacerbations. Improved treatment based on enhanced understanding and good clinical evidence should lead to better outcomes in this common clinical entity.

KEYWORDS

Chronic obstructive pulmonary disease - exacerbation - pathogenesis - antibiotics

REFERENCES

  • 1 Mapel D W, Hurley J S, Frost F J, Petersen H V, Picchi M A, Coultas D B. Health care utilization in chronic obstructive pulmonary disease: a case-control study in a health maintenance organization.  Arch Intern Med. 2000;  160 2653-2658
    CrossrefPubMedGoogle Scholar
  • 2 Fabbri L M, Hurd S S. Global strategy for the diagnosis, management and prevention of COPD: 2003 update.  Eur Respir J. 2003;  22 1-2
    CrossrefPubMedGoogle Scholar
  • 3 Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations.  Chest. 2000;  117(5 suppl 2) 398S-401S
    CrossrefPubMedGoogle Scholar
  • 4 Sethi S, Evans N, Grant B JB, Murphy T F. Acquisition of a new bacterial strain and occurrence of exacerbations of chronic obstructive pulmonary disease.  N Engl J Med. 2002;  347 465-471
    CrossrefPubMedGoogle Scholar
  • 5 Saetta M, Turato G, Maestrelli P, Mapp C E, Fabbri L M. Cellular and structural bases of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  163 1304-1309
    PubMedGoogle Scholar
  • 6 White A J, Gompertz S, Stockley R A. Chronic obstructive pulmonary disease, VI: The aetiology of exacerbations of chronic obstructive pulmonary disease.  Thorax. 2003;  58 73-80
    CrossrefPubMedGoogle Scholar
  • 7 Sethi S. New developments in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease.  Curr Opin Infect Dis. 2004;  17 113-119
    CrossrefPubMedGoogle Scholar
  • 8 Sethi S, Muscarella K, Evans N, Klingman K L, Grant B JB, Murphy T F. Airway inflammation and etiology of acute exacerbations of chronic bronchitis.  Chest. 2000;  118 1557-1565
    CrossrefPubMedGoogle Scholar
  • 9 Gompertz S, O'Brien C, Bayley D L, Hill S L, Stockley R A. Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.  Eur Respir J. 2001;  17 1112-1119
    CrossrefPubMedGoogle Scholar
  • 10 Zhu J, Qiu Y S, Majumdar S et al.. Exacerbations of bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants.  Am J Respir Crit Care Med. 2001;  164 109-116
    PubMedGoogle Scholar
  • 11 Balbi B, Bason C, Balleari E et al.. Increased bronchoalveolar grnulocytes and granulocyte-macrophage colony-stimulating factor during exacerbations of chronic bronchitis.  Eur Respir J. 1997;  10 846-850
    PubMedGoogle Scholar
  • 12 Saetta M, Di Stefano A, Maestrelli P et al.. Airway eosinophilia in chronic bronchitis during exacerbations.  Am J Respir Crit Care Med. 1994;  150(6 Pt 1) 1646-1652
    PubMedGoogle Scholar
  • 13 Stockley R A. The role of proteinases in the pathogenesis of chronic bronchits.  Am J Respir Crit Care Med. 1994;  150 S109-S113
    PubMedGoogle Scholar
  • 14 Wouters E F. Chronic obstructive pulmonary disease, V: Systemic effects of COPD.  Thorax. 2002;  57 1067-1070
    CrossrefPubMedGoogle Scholar
  • 14a Saetta M, Di Stefano A, Maestrelli J P et al.. Airway eosinophilia in chronic bronchitis during exacerbations.  Am J Respir Crit Care Med. 1994;  150 1646-1652
    PubMedGoogle Scholar
  • 14b Crooks S W, Bayley D L, Hill S L, Stockley R A. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4.  Eur Respir J. 2000;  15 274-280
    CrossrefPubMedGoogle Scholar
  • 14c Biernacki W A, Kharitonov S A, Barnes P J. Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD.  Thorax. 2003;  58 294-298
    CrossrefPubMedGoogle Scholar
  • 14d Bhowmik A, Seemungal T A, Sapsford R J, Wedzicha J A. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations.  Thorax. 2000;  55 114-120
    CrossrefPubMedGoogle Scholar
  • 14e Stockley R A, O'Brien C, Pye A, Hill S L. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD.  Chest. 2000;  117 1638-1645
    CrossrefPubMedGoogle Scholar
  • 14f Agusti A G, Villaverde J M, Togores B, Bosch M. Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease.  Eur Respir J. 1999;  14 523-528
    CrossrefPubMedGoogle Scholar
  • 14g Roland M, Bhowmik A, Sapsford R J et al.. Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease.  Thorax. 2001;  56 30-35
    CrossrefPubMedGoogle Scholar
  • 15 Wedzicha J A, Seemungal T A, MacCallum P K et al.. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.  Thromb Haemost. 2000;  84 210-215
    PubMedGoogle Scholar
  • 16 Dev D, Wallace E, Sankaran R et al.. Value of C-reactive protein measurements in exacerbations of chronic obstructive pulmonary disease.  Respir Med. 1998;  92 664-667
    PubMedGoogle Scholar
  • 17 Ohtoshi T, Takizawa H, Okazaki H et al.. Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro.  J Allergy Clin Immunol. 1998;  101 778-785
    PubMedGoogle Scholar
  • 18 Devalia J L, Rusznak C, Herdman M J, Trigg C J, Tarraf H, Davies R J. Effect of nitrogen dioxide and sulphur dioxide on airway response of mild asthmatic patients to allergen inhalation.  Lancet. 1994;  344 1668-1671
    CrossrefPubMedGoogle Scholar
  • 19 Rudell B, Blomberg A, Helleday R. Bronchoalveolar inflammation after exposure to diesel exhaust: comparison between unfiltered and particle trap filtered exhaust.  Occup Environ Med. 1999;  56 527-534
    PubMedGoogle Scholar
  • 20 Garcia-Aymerich J, Tobias A, Anto J M, Sunyer J. Air pollution and mortality in a cohort of patients with chronic obstructive pulmonary disease: a time series analysis.  J Epidemiol Community Health. 2000;  54 73-74
    PubMedGoogle Scholar
  • 21 Sunyer J, Saez M, Murillo C, Castellsague J, Martinez F, Anto J M. Air pollution and emergency room admissions for chronic obstructive pulmonary disease: a 5-year study.  Am J Epidemiol. 1993;  137 701-705
    PubMedGoogle Scholar
  • 22 Sunyer J, Schwartz J, Tobias A, Macfarlane D, Garcia J, Anto J M. Patients with chronic obstructive pulmonary disease are at increased risk of death associated with urban particle air pollution: a case-crossover analysis.  Am J Epidemiol. 2000;  151 50-56
    PubMedGoogle Scholar
  • 23 Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis.  Chest. 2000;  117 380S-385S
    CrossrefPubMedGoogle Scholar
  • 24 Hirschmann J V. Do bacteria cause exacerbations of COPD?.  Chest. 2000;  118 193-203
    CrossrefPubMedGoogle Scholar
  • 25 Murphy T F, Sethi S, Niederman M S. The role of bacteria in exacerbations of COPD: a constructive view.  Chest. 2000;  118 204-209
    CrossrefPubMedGoogle Scholar
  • 26 Sethi S, Murphy T F. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review.  Clin Microbiol Rev. 2001;  14 336-363
    CrossrefPubMedGoogle Scholar
  • 27 Chastre J, Fagon J-Y, Bornet-Lesco M et al.. Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia.  Am J Respir Crit Care Med. 1995;  152 231-240
    CrossrefPubMedGoogle Scholar
  • 28 Monso E, Ruiz J, Rosell A et al.. Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush.  Am J Respir Crit Care Med. 1995;  152 1316-1320
    PubMedGoogle Scholar
  • 29 Fagon J-Y, Chastre J, Trouillet J-L et al.. Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis.  Am Rev Respir Dis. 1990;  142 1004-1008
    PubMedGoogle Scholar
  • 30 Soler N, Torres A, Ewig S et al.. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.  Am J Respir Crit Care Med. 1998;  157 1498-1505
    CrossrefPubMedGoogle Scholar
  • 31 Pela R, Marchesani F, Agostinelli C et al.. Airways microbial flora in COPD patients in stable clinical conditions and during exacerbations: a bronchoscopic investigation.  Monaldi Arch Chest Dis. 1998;  53 262-267
    PubMedGoogle Scholar
  • 32 Bandi V, Apicella M A, Mason E et al.. Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis.  Am J Respir Crit Care Med. 2001;  164 2114-2119
    PubMedGoogle Scholar
  • 33 Gump D W, Phillips C A, Forsyth B R, McIntosh F K, Lamborn K R, Stouch W H. Role of infection in chronic bronchitis.  Am Rev Respir Dis. 1976;  113 465-473
    PubMedGoogle Scholar
  • 34 McHardy V U, Inglis J M, Calder M A, Crofton J W. A study of infective and other factors in exacerbations of chronic bronchitis.  Br J Dis Chest. 1980;  74 228-238
    CrossrefPubMedGoogle Scholar
  • 35 Gog J R, Grenfell B T. Dynamics and selection of many-strain pathogens.  Proc Natl Acad Sci USA. 2002;  99 17209-17214
    CrossrefPubMedGoogle Scholar
  • 36 Sethi S, Wrona C, Grant B, Murphy T. Strain‐specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2004;  169 448-453
    PubMedGoogle Scholar
  • 37 Bakri F, Brauer A L, Sethi S, Murphy T F. Systemic and mucosal antibody response to Moraxella catarrhalis following exacerbations of chronic obstructive pulmonary disease.  J Infect Dis. 2002;  185 632-640
    CrossrefPubMedGoogle Scholar
  • 38 Abe Y, Murphy T F, Sethi S et al.. Lymphocyte proliferative response to P6 of Haemophilus influenzae is associated with relative protection from exacerbations of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2002;  165 967-971
    PubMedGoogle Scholar
  • 39 Aaron S D, Angel J B, Lunau M et al.. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  163 349-355
    PubMedGoogle Scholar
  • 40 White A J, Gompertz S, Bayley D L et al.. Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis.  Thorax. 2003;  58 680-685
    CrossrefPubMedGoogle Scholar
  • 41 Rohde G, Wiethege A, Borg I et al.. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.  Thorax. 2003;  58 37-42
    CrossrefPubMedGoogle Scholar
  • 42 Tan W C, Xiang X, Qiu D, Ng T P, Lam S F, Hegele R G. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease.  Am J Med. 2003;  115 272-277
    CrossrefPubMedGoogle Scholar
  • 43 Seemungal T A, Harper-Owen R, Bhowmik A, Jeffries D J, Wedzicha J A. Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease.  Eur Respir J. 2000;  16 677-683
    CrossrefPubMedGoogle Scholar
  • 44 Lieberman D, Gelfer Y, Varshavsky R, Dvoskin B, Leinonen M, Friedman M G. Pneumonic vs nonpneumonic acute exacerbations of COPD.  Chest. 2002;  122 1264-1270
    CrossrefPubMedGoogle Scholar
  • 45 von Hertzen L, Alakarppa H, Koskinen R et al.. Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease.  Epidemiol Infect. 1997;  118 155-164
    CrossrefPubMedGoogle Scholar
  • 46 Blasi F, Damato S, Cosentini R et al.. Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment.  Thorax. 2002;  57 672-676
    CrossrefPubMedGoogle Scholar
  • 47 Lieberman D, Lieberman D, Ben-Yaakov M et al.. Serological evidence of Mycoplasma pneumoniae infection in acute exacerbation of COPD.  Diagn Microbiol Infect Dis. 2002;  44 1-6
    CrossrefPubMedGoogle Scholar
  • 48 Mogulkoc N, Karakurt S, Isalska B et al.. Acute purulent exacerbation of chronic obstructive pulmonary disease and Chlamydia pneumoniae infection.  Am J Respir Crit Care Med. 1999;  160 349-353
    PubMedGoogle Scholar
  • 49 Miyashita N, Niki Y, Nakajima M, Kawane H, Matsushima T. Chlamydia pneumoniae infections in patients with diffuse panbronchiolitis and COPD.  Chest. 1998;  114 969-971
    PubMedGoogle Scholar
  • 50 Karnak D, Beng-sun S, Beder S, Kayacan O. Chlamydia pneumoniae infection and acute exacerbation of chronic obstructive pulmonary disease (COPD).  Respir Med. 2001;  95 811-816
    PubMedGoogle Scholar
  • 51 Hahn D L, Golubjatnikov R. Smoking is a potential confounder of the Chlamydia pneumoniae-coronary artery disease association.  Arterioscler Thromb. 1992;  12 945-947
    PubMedGoogle Scholar
  • 52 Beaty C D, Grayston J T, Wang S P, Kuo C C, Reto C S, Martin T R. Chlamydia pneumoniae, strain TWAR, infection in patients with chronic obstructive pulmonary disease.  Am Rev Respir Dis. 1991;  144 1408-1410
    CrossrefPubMedGoogle Scholar
  • 53 Blasi F, Legnani D, Lombardo V M et al.. Chlamydia pneumoniae infection in acute exacerbations of COPD.  Eur Respir J. 1993;  6 19-22
    PubMedGoogle Scholar
  • 54 Smith C B, Golden C, Kanner R, Renzetti Jr A D. Association of viral and Mycoplasma pneumoniae infections with acute respiratory illness in patients with chronic obstructive pulmonary diseases.  Am Rev Respir Dis. 1980;  121 225-232
    PubMedGoogle Scholar
  • 55 Sethi S. Acute exacerbations of COPD: a “multipronged” approach.  J Respir Dis. 2002;  23 217-255
    PubMedGoogle Scholar
  • 56 Bach P B, Brown C, Gelfand S E, McCrory D C. Management of acute exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence.  Ann Intern Med. 2001;  134 600-620
    PubMedGoogle Scholar
  • 57 Balter M S, La Forge J, Low D E, Mandell L, Grossman R F. Canadian guidelines for the management of acute exacerbations of chronic bronchitis.  Can Respir J. 2003;  10(Suppl B) 3B-32B
    PubMedGoogle Scholar
  • 58 Murphy T F, Sethi S. Chronic obstructive pulmonary disease: role of bacteria and guide to antibacterial selection in the older patient.  Drugs Aging. 2002;  19 761-775
    CrossrefPubMedGoogle Scholar
  • 59 Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis.  JAMA. 1995;  273 957-996
    CrossrefPubMedGoogle Scholar
  • 60 Sachs A PE, Koeter G H, Groenier K H, van der Waaij D, Schiphuis J, Jong B M. Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice.  Thorax. 1995;  50 758-763
    CrossrefPubMedGoogle Scholar
  • 61 Nouira S, Marghli S, Belghith M, Besbes L, Elatrous S, Abroug F. Once-daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial.  Lancet. 2001;  358 2020-2025
    CrossrefPubMedGoogle Scholar
  • 62 Allegra L, Blasi F, de Bernardi B, Cosentini R, Tarsia P. Antibiotic treatment and baseline severity of disease in acute exacerbations of chronic bronchitis: a reevaluation of previously published data of a placebo-controlled randomized study.  Pulm Pharmacol Ther. 2001;  14 149-155
    PubMedGoogle Scholar
  • 63 Anthonisen N R, Manfreda J, Warren C PW, Hershfield E S, Harding G KM, Nelson N A. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease.  Ann Intern Med. 1987;  106 196-204
    CrossrefPubMedGoogle Scholar
  • 64 Sethi S. Bacteria in exacerbations of chronic obstructive pulmonary disease: phenomenon or epiphenomenon?.  Proc Am Thorac Soc.. 2004;  1 109-114
    PubMedGoogle Scholar
  • 65 Wilson R, Schentag J J, Ball P, Mandell L. A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes.  Clin Ther. 2002;  24 639-652
    CrossrefPubMedGoogle Scholar
  • 66 Spencer S, Jones P W. Time course of recovery of health status following an infective exacerbation of chronic bronchitis.  Thorax. 2003;  58 589-593
    CrossrefPubMedGoogle Scholar
  • 67 Wilson R, Allegra L, Huchon G et al.. Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis.  Chest. 2004;  125 953-964
    CrossrefPubMedGoogle Scholar
  • 68 Ball P, Harris J M, Lowson D, Tillotson G, Wilson R. Acute infective exacerbations of chronic bronchitis.  Q J Med. 1995;  88 61-68
    PubMedGoogle Scholar
  • 69 Dewan N A, Rafique S, Kanwar B et al.. Acute exacerbation of COPD: factors associated with poor treatment outcome.  Chest. 2000;  117 662-671
    CrossrefPubMedGoogle Scholar
  • 70 Miravitlles M, Murio C, Guerrero T. Factors associated with relapse after ambulatory treatment of acute exacerbations of chronic bronchitis. DAFNE Study Group.  Eur Respir J. 2001;  17 928-933
    CrossrefPubMedGoogle Scholar
  • 71 Groenewegen K H, Schols A M, Wouters E F. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD.  Chest. 2003;  124 459-467
    CrossrefPubMedGoogle Scholar
  • 72 Adams S G, Melo J, Luther M, Anzueto A. Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD.  Chest. 2000;  117 1345-1352
    CrossrefPubMedGoogle Scholar

Sanjay SethiM.D 

VA WNY Healthcare System (151)

3495 Bailey Ave., Buffalo, NY 14215

Email: ssethi@buffalo.edu