Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations

Background: Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality. Stable COPD patients often have lower airway bacterial colonisation which may be an important stimulus to airway inflammation and thereby modulate exacerbation frequency. Methods: Twenty nine patients with COPD (21 men, 16 current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in 1 second (FEV1) 1.06 (0.41) l, FEV1 % predicted 38.7 (15.2)%, FEV1/FVC 43.7 (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards for symptoms and peak flow over 18 months. Exacerbation frequency rates were determined from diary card data. Induced sputum was obtained from patients in the stable state, quantitative bacterial culture was performed, and cytokine levels were measured. Results: Fifteen of the 29 patients (51.7%) were colonised by a possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%), Pseudomonas aeruginosa (20%). The presence of lower airway bacterial colonisation in the stable state was related to exacerbation frequency (p=0.023). Patients colonised by H influenzae in the stable state reported more symptoms and increased sputum purulence at exacerbation than those not colonised. The median (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00 (2.00–2.65) compared with 2.00 (1.00–2.00) in those not colonised (p=0.03). The occurrence of increased sputum purulence at exacerbation per patient was 0.92 (0.56–1.00) in those colonised with H influenzae and 0.33 (0.00–0.60) in those not colonised (p=0.02). Sputum interleukin (IL)-8 levels correlated with the total bacterial count (rho=0.459, p=0.02). Conclusion: Lower airway bacterial colonisation in the stable state modulates the character and frequency of COPD exacerbations.

[1]  T. Seemungal,et al.  Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[2]  X. Busquets,et al.  Enhanced neutrophil response in chronic obstructive pulmonary disease , 2001, Thorax.

[3]  T. Murphy,et al.  Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review , 2001, Clinical Microbiology Reviews.

[4]  B. Grant,et al.  Airway inflammation and etiology of acute exacerbations of chronic bronchitis. , 2000, Chest.

[5]  T. Seemungal,et al.  Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease , 2000, The European respiratory journal.

[6]  R. Stockley,et al.  Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. , 2000, The American journal of medicine.

[7]  R. Lutter,et al.  Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease. , 2000, American journal of respiratory and critical care medicine.

[8]  R. Stockley,et al.  Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care , 2000, Thorax.

[9]  R. Stockley,et al.  Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. , 2000, Chest.

[10]  T. Seemungal,et al.  Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. , 2000, American journal of respiratory and critical care medicine.

[11]  T. Seemungal,et al.  Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations , 2000, Thorax.

[12]  A. Torres,et al.  Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. , 1999, The European respiratory journal.

[13]  J. Ruiz,et al.  Risk factors for lower airway bacterial colonization in chronic bronchitis. , 1999, The European respiratory journal.

[14]  J. Pijoan,et al.  Predisposing factors to bacterial colonization in chronic obstructive pulmonary disease. , 1999, The European respiratory journal.

[15]  P. Hiemstra,et al.  Neutrophil serine proteinases and defensins in chronic obstructive pulmonary disease: effects on pulmonary epithelium. , 1998, The European respiratory journal.

[16]  T. Seemungal,et al.  Comparison of spontaneous and induced sputum for investigation of airway inflammation in chronic obstructive pulmonary disease , 1998, Thorax.

[17]  L. Fabbri,et al.  Severity of airflow limitation is associated with severity of airway inflammation in smokers. , 1998, American journal of respiratory and critical care medicine.

[18]  T. Seemungal,et al.  Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[19]  L. Fabbri,et al.  Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. , 1997, American journal of respiratory and critical care medicine.

[20]  C. Agustí,et al.  Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study. , 1997, The European respiratory journal.

[21]  J. G. Douglas,et al.  Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease. , 1997, Thorax.

[22]  L. Fabbri,et al.  Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. , 1996, Thorax.

[23]  L. Fabbri,et al.  Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar lavage. , 1995, American journal of respiratory and critical care medicine.

[24]  J. Vestbo,et al.  Chronic mucus hypersecretion in COPD and death from pulmonary infection. , 1995, The European respiratory journal.

[25]  R. Davies,et al.  Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF-alpha and expression of ICAM-1 in cultured human bronchial epithelial cells. , 1994, The European respiratory journal.

[26]  C. Roberts,et al.  Arterialised earlobe blood gas analysis: an underused technique. , 1994, Thorax.

[27]  I. Phillips Cowan and Steel's Manual for the Identification of Medical Bacteria , 1993 .

[28]  S. T. Cowan,et al.  Cowan and Steel's manual for the identification of medical bacteria , 1993 .

[29]  T. Murphy,et al.  Bacterial infection in chronic obstructive pulmonary disease. , 1992, The American review of respiratory disease.

[30]  S. Mostafa,et al.  Essentials in clinical microbiology , 1991 .

[31]  R. Stockley,et al.  Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. , 1991, American journal of respiratory cell and molecular biology.

[32]  G. Taylor,et al.  Effect of bacterial products on neutrophil migration in vitro. , 1990, Thorax.

[33]  L. van Alphen,et al.  Endogenous and exogenous reinfections by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence. , 1990, The Journal of infectious diseases.

[34]  D. Staunton,et al.  A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses , 1989, Cell.

[35]  L. van Alphen,et al.  Changes in outer membrane proteins of nontypable Haemophilus influenzae in patients with chronic obstructive pulmonary disease. , 1988, The Journal of infectious diseases.

[36]  Adler Kb,et al.  Bacteria associated with obstructive pulmonary disease elaborate extracellular products that stimulate mucin secretion by explants of guinea pig airways. , 1986 .

[37]  K. Adler,et al.  Bacteria associated with obstructive pulmonary disease elaborate extracellular products that stimulate mucin secretion by explants of guinea pig airways. , 1986, The American journal of pathology.

[38]  R. Crystal,et al.  Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers. , 1983, The American review of respiratory disease.

[39]  D. Musher,et al.  Bacterial adherence to pharyngeal cells during viral infection. , 1980, The Journal of infectious diseases.

[40]  R. Kanner,et al.  Interactions between Viruses and Bacteria in Patients with Chronic Bronchitis , 1976, The Journal of infectious diseases.

[41]  M. Sande,et al.  Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody. , 1975, The Journal of infectious diseases.