(Chest. 2003;124:832-833.)
© 2003
American College of Chest Physicians
Immune Response to Fusobacterium nucleatum and Prevotella intermedia in the Sputum of Patients With Acute Exacerbation of Chronic Bronchitis*
Itzhak Brook, MD, MSc and
Edith H. Frazier, MSc
* From the Naval Medical Center, Bethesda, MD.
Correspondence to: Itzhak Brook, MD, MSc, 4431 Albemarle St NW, Washington DC 20016; e-mail: ib6{at}georgetown.edu
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Abstract
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Objective: To assess the role of anaerobic bacteria in acute exacerbation of chronic bronchitis (AECB).
Methods: The level of the Ig-A class to two organisms (Fusobacterium nucleatum and Prevotella intermedia) was determined in the sputum of 25 patients with AECB and 25 control patients. The presence and level of these antibodies were investigated by enzyme-linked immunosorbent assay.
Results: The median sputum antibody level for F nucleatum and P intermedia were significantly higher in patients with AECB as compared to control patients (p < 0.05). The IgA levels for F nucleatum was 3.5 times higher in patients with AECB and 3.8 times greater for P intermedia.
Conclusions: This study demonstrates for the first time an elevated sputum antibody titers in patients with AECB to F nucleatum and P intermedia.
Key Words: acute exacerbation of chronic bronchitis • Fusobacterium spp • immune response • Prevotella spp
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Introduction
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Antimicrobial therapy plays an important role in the management of acute exacerbation of chronic bronchitis (AECB), because bacteria may contribute to the perpetuation and exacerbation of the illness.1
The major organisms recovered from the sputum of patients with AECB are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.1
2
The role of anaerobic bacteria in AECB has never been studied before, although these organisms are the major colonizers of the oropharynx and have been implicated in upper and lower respiratory tract infections.3
Aspirates from patients with AECB contain several species of anaerobic bacteria4
; however, their contribution to the inflammatory process in AECB is unknown.
Elevated antibodies levels against potential pathogens are an accepted indication of past infection due to these organism.5
6
The purpose of this study was to investigate the role of anaerobic bacteria in AECB by measuring the antibodies of the Ig-A class to two organisms (Fusobacterium nucleatum and Prevotella intermedia) commonly recovered from sputum of patients with AECB. The presence of these antibodies was investigated by enzyme-linked immunosorbent assay (ELISA).
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Materials and Methods
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The study included 25 hospitalized patients, 20 men and 5 women. Their ages ranged from 39 to 78 years (average, 52 years). All patients had chronic bronchitis, as defined by the American Thoracic Society7
: recurrent productive cough most days for a minimum of 3 months in each of the 2 past years. They had symptoms consistent with AECB, specifically cough, substernal pain during respiration or cough, and fever. Two patients had mild airway obstruction, 11 patients had moderate airway obstruction, and 12 patients had severe airway obstruction.7
None received antimicrobial therapy in the 6 weeks prior to inclusion in the study; however, all had received numerous courses of antibiotics for AECB in the past 2 years. Other inclusion criteria included a sputum smear with < 10 squamous epithelial cells and > 25 leukocytes per low-power field. Sputum was also collected from 25 control patients of similar age and gender distribution who presented with lower respiratory tract infection but did not have AECB. These control specimens were sent to the laboratory for cultures for acid-fast organisms. All of these cultures showed no mycobacterial growth.
Immunologic Methods
Sputum IgA titers were measured by ELISA on two separate occasions by a modification of the method described by Ebersole et al.8
The assay was run twice, in a single run on each occasion. Isolates of the following bacteria served as sources of antigens: P intermedia American Type Culture Collection strain 25611 and F nucleatum American Type Culture Collection strain 25586. The processing of antigens and the ELISA test were previously described in detail.6
Statistical Analysis
The nonpaired t test and the median test9
were used to compare the data sets. For the purpose of the median test, the data were transformed to conform to the positive and negative control readings for each batch of 20 data values. The positive control reading was assigned an arbitrary value of 100 U, and the negative control reading was assigned a value of zero. Actual data values were then transformed as a straight-line adjustment between these two values.
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Results
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The median sputum antibody level for F nucleatum and P intermedia were significantly higher in patients with AECB as compared to control patients (p < 0.05) [Table 1
]. As determined by ELISA, the IgA levels for F nucleatum was 3.5 times higher in patients with AECB and 3.8 times greater for P intermedia.
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Table 1.. Sputum Levels for F nucleatum and P intermedia Units as Determined by ELISA in 25 Patients With AECB and 25 Control Patients*
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Discussion
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This study demonstrates for the first time an elevated antibody titers in the sputum of patients with AECB to F nucleatum and P intermedia. These two anaerobic organisms are known oral pathogens,3
and have been isolated as a predominant species in several other chronic respiratory tract infections, which included aspiration pneumonia, lung abscesses, chronic otitis media, retropharyngeal and peritonsillar abscesses, and bacteremia associated with these infections.3
Immune response against P intermedia can be detected in patients with non-group A hemolytic streptococci tonsillitis;6
and an immune response can also be detected against P intermedia and F nucleatum in patients who recovered from peritonsillar cellulitis or abscesses10
and infectious mononucleosis.11
Elevated antibody levels are an accepted indication of bacterial infection due to several microorganisms. A recent study5
illustrated elevated serum and sputum levels in patients with AECB to M catarrhalis signifying its potential role in this condition.
The elevated antibody levels in patients with AECB support the role of F nucleatum and P intermedia in this inflammatory process. Further studies of AECB are indicated to evaluate whether antibody titers to F nucleatum and P intermedia decrease following improvement or recovery, whether other aerobic and anaerobic organisms play a role in this condition, and whether antimicrobials directed at the eradication of F nucleatum and P intermedia as well as other organisms improve AECB and prevent recurrences and complications.
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Acknowledgements
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The authors thank the staffs of the Clinical Microbiology Laboratory Services at the Naval Medical Center, Bethesda, MD.
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Footnotes
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Abbreviations: AECB = acute exacerbation of chronic bronchitis; ELISA = enzyme-linked immunosorbent assay
The opinions and assertions contained herein are the private ones of the writers and are not to be construed as official or reflecting the views of the Navy Department or the Naval Service at large.
Received for publication September 5, 2002.
Accepted for publication February 13, 2003.
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References
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- Monso, E, Ruiz, J, Rosell, A, et al (1995) Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Car Med 152,1316-1320[Abstract]
- 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
- Brook, I Anaerobic bacteria in upper respiratory tract and other head and neck infections. Ann Otol Rhinol Laryngol 2002;111,430-440[ISI][Medline]
- Brook, I, Frazier, EH Bacteriology and ß-lactamase activity in acute exacerbation of chronic bronchitis. Int J Infect Dis 2001;5,74-77[CrossRef][Medline]
- Bakri, F, Brauer, AL, Sethi, S, et al Systemic and mucosal antibody response to Moraxella catarrhalis after exacerbations of chronic obstructive pulmonary disease. J Infect Dis 2002;185,632-640[CrossRef][ISI][Medline]
- Brook, I, Foote, PA, Slots, J, et al Immune response to Prevotella intermedia in patients with recurrent nonstreptococcal tonsillitis. Ann Otol Rhinol Laryngol 1993;102,113-116[ISI][Medline]
- American Thoracic society.. Standards for the diagnosis and care of patients with chronic obstructive pulmonary (COPD) and asthma. Am J Respir Dis 1987;136,225-244
- Ebersole, JL, Frey, DE, Taubman, MA, et al An ELISA for measuring serum antibodies to Actinobacillus actinomycetemcomitans. J Periodontal Res 1980;15,621-632[CrossRef][ISI][Medline]
- Conover, WJ Pediatric non-parametric statistics 2nd ed. 1980,171-178 John Wiley and Sons. New York, NY:
- Brook, I, Foote, PA, Slots, J Immune response to Fusobacterium nucleatum and Prevotella intermedia in patients with peritonsillar cellulitis and abscess. Clin infect Dis 1995;20,S220-S221
- Brook, I, de Leyva, F Immune response to Fusobacterium nucleatum and Prevotella intermedia in patients with infectious mononucleosis. J Med Microbiol 1996;44,131-134[ISI][Medline]
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Abstract
Introduction
