November 28, 2004

Colonization of Dental Plaques*: A Reservoir of Respiratory Pathogens for Hospital-Acquired Pneumonia in Institutionalized Elders

Study objectives: Poor dental hygiene has been linked to respiratory pathogen colonization in residents of long-term care facilities. We sought to investigate the association between dental plaque (DP) colonization and lower respiratory tract infection in hospitalized institutionalized elders using molecular genotyping.

Methods: We assessed the dental status of 49 critically ill residents of long-term care facilities requiring intensive care treatment. Plaque index scores and quantitative cultures of DPs were obtained on ICU admission. Protected BAL (PBAL) was performed on 14 patients who developed hospital-acquired pneumonia (HAP). Respiratory pathogens recovered from the PBAL fluid were compared genetically to those isolated from DPs by pulsed-field gel electrophoresis.

Measurements and results: Twenty-eight subjects (57%) had colonization of their DPs with aerobic pathogens. Staphylococcus aureus (45%) accounted for the majority of the isolates, followed by enteric Gram-negative bacilli (42%) and Pseudomonas aeruginosa (13%). The etiology of HAP was documented in 10 patients. Of the 13 isolates recovered from PBAL fluid, nine respiratory pathogens matched genetically those recovered from the corresponding DPs of eight patients.

Conclusions: These findings suggest that aerobic respiratory pathogens colonizing DPs may be an important reservoir for HAP in institutionalized elders. Future studies are needed to delineate whether daily oral hygiene in hospitalized elderly would reduce the risk of nosocomial pneumonia in this frail population. (CHEST 2004; 126:1575-1582)

Key words: dental plaque; elderly; nursing home; oral hygiene; pneumonia

Abbreviations: ADL = activity of daily living; APACHE = acute physiologic and chronic health evaluation; DP = dental plaque; EDTA = ethylenediaminetetraacetic acid; HAP = hospital-acquired pneumonia; PBAL = protected BAL: PFGE = pulsed-field gel electrophoresis

A number of studies have indicated a higher prevalence of nosocomial and Gram-negative enteric bacilli pathogens in institutionalized elderly patients with severe pneumonia.1,2 The propensity of this frail population to succumb to these organisms has led investigators to suspect the oral cavity to be a source of these pathogens. Because colonization of the pharyngeal mucosa by respiratory pathogens is thought to be a transient phenomenon,3 it has been suggested that dental plaques (DPs) may serve as reservoir for these pathogens, especially in those high-risk patients with poor oral hygiene.

The bacterial DP complex is a dynamic system that comprises the extracellular matrix and oral bacteria. It occupies the subgingival and supragingival surfaces of the teeth but may also extend to dental prostheses. Numerous factors minimize the colonization of DPs by aerobic pathogens. The physicochemical properties of the dental surface, the enzymatic salivary contents, and the presence of local Ig^sup 4^ act as a defense barrier against the attachment of these bacteria. However, the lack of oral hygiene, the decline in activity of daily thing (ADL), and the presence of polypharmacy-related xerostomia in institutionalized elders disturb the delicate equilibrium between tooth structure and oral fluids, thus providing favorable conditions for the proliferation of these pathogens.

We hypothesized that the colonization of the DPs of nursing home residents with aerobic respiratory pathogens acts as a reservoir for lower respiratory tract infection in subjects requiring hospitalisation. We designed a prospective study to assess the prevalence of the plaque colonization of institutionalized critically ill elderly patients by aerobic respiratory pathogens, and to determine the clonal relationship between these pathogens and those recovered from the lower respiraton tract of patients who developed hospital-acquired pneumonia (HAP).


Study Population

The study was conducted prospectively in our critical care unit, in a hospital affiliated with the University of Buffalo. After obtaining approval from the Institutional Review Board, all nursing home patients requiring mechanical ventilation were considered for enrollment if an informed consent could be obtained from the next of kin. Patients were excluded from the study if the patient had any of the following conditions: (1) clinical suspicion of pneumonia on ICU admission or within 72 h after ICU admission: (2) severe thrombocytopenia (ie, platelet count,. 2 weeks, or the use of cyclophosphamide, azathioprine, or cyclosporine). Edentulous patients who had no dentures also were not eligible for participation.

Data Collection

Demographic data that were collected included age, gender, ADL score,5 comorbid illnesses, Charlson index score,6 and acute physiology and chronic health evaluation (APACHE) II score.7

Oral Examination and Plaque Samplings

Oral examinations and microbiological samplings were conducted by a single examiner on admission to the ICU. Oral examination included the plaque index score8 and enumeration of the number of remaining teeth. The plaque index is a measure of the debris deposited around and between teeth. It is the major cause of tooth decay and gingivitis. The plaque index was performed for the following six teeth: the upper right first molar (tooth 3); upper right central incisor (tooth 8); upper left first bicuspid (tooth 12); lower left first molar (tooth 19); lower left central incisor (tooth 24); and lower right first bicuspid (tooth 28). The amount of plaque seen on the tooth or dentures, if applicable, was given a score ranging from 0 to 3 (0, no plaque noted; 1, 50% of the denture surface covered with plaque/debris. The plaque index score was the average of the scores obtained from the six teeth. For those patients who were missing any of the index teeth, the remaining teeth that were closest to the missing teeth were scored.

After isolating the tooth with cotton rolls, the tooth surface was gently dried with a sterile gauze to avoid contamination by saliva. Supragingival plaques were removed using sterile periodontal curettes and were placed in sterile vials containing 1 mL Ringer solute transport medium. The buccal mucosa was sampled subsequently by rubbing the oropharyngeal cavity with a sterile cotton swab. The samples were vortexed for 5 min and serially diluted in sterile normal saline solution. Of each dilution, 100 L was inoculated on chocolate agar and MacConkey agar, and was incubated at 37C in 5% CO2 for 72 h. All colonies were subcultured and identified by standard methods.9 *Respiratory pathogens were considered to be present if one of the following organisms was isolated from any of the oral samples: Staphylococcus aureus; Streptococcus pneumoniae; Haemophilus influenzae; Moraxella catarrhalis; Klebsiella pneumoniae; Serratia marcescens; Proteus mirabilis; Escherichia coli; Enterobacter cloacae; or Psudomonas aeruginosa. DPs were considered to be colonized if ≥ 1.0% of the total cultivable flora were identified as respiratory pathogens.10

Assesment of Lower Respiratory Tract Infection

Enrolled subjects were observed daily for signs and symptoms of HAP. The criteria for suspected pneumonia included the development of new radiographic infiltrate compatible with pneumonia and the presence of two or more of the following criteria: (1) purulent endotracheal aspirates; (2) temperature of >30C or 12,000 cells/L, and/or left shift or leukopenia of

Isolation of Chromosomal DNA

Bacterial isolates of the same species isolated from the BAL samples and from the DP samples were harvested by centrifugation (7,000g for 15 min), were washed once in sodium chloride-Tris- ethylenediaminetetraacetic acid (EDTA) buffer (0.1 mol/L NaCl, 10 mmol/L Tris-HCl [pH 8.0], and 1 mmol/L EDTA), and were resuspended in 567 L Tris-EDTA buffer (10 mmol/L Tris and 1 mmol/L EDTA [pH 8.0]), 30 L 10% sodium dodecyl sulfate, and 30 L 2 mg/mL proteinase K. The samples were mixed and incubated at 37C for 1 h. A total of 100 L 5 mol/L NaCl and 80 L cetyltrimethyl-ammonium bromide/NaCl solution were added, and were incubated for 10 min at 65C. The samples then were extracted three times with equal volumes of buffer- saturated phenol-chloroform-isoamyl alcoh\ol (25:24:1) and three times with chloroform-isoamyl alcohol (24:1). DNA was precipitated by the addition of 0.6 volumes isopropanol and was centrifuged in a microcentrifuge for 30 min. The DNA precipitate was rinsed once with 0.5 mL 70% ethanol. The ethanol was removed after centrifugation for 15 min, the DNA vacuum was dried for 30 min, and then was resuspended in 100 L distilled water.

Pulsed-Field Gel Electrophoresis

Similar aerobic respiratory pathogens isolated from DPs and lower respiratory tract were subjected to pulsed-field gel electrophoresis (PFGE). Genomic DNA for PFGE was performed (CHEF Mapper XA system; Bio-Rad Laboratories, Inc; Hercules, CA) as described previously.11 The chromosomal DNA was digested at 37C for 6 h with corresponding restriction endonucleases. Restriction fragments underwent electrophoresis in 1% chromosomal-grade agarose (Bio-Rad Laboratories, Inc). The electrophoretic conditions were as follows: initial switch time, 2.16 s; final switch time, 54.17 s; run time, 22 h; angle, 120; gradient, 6.0 V/cm; temperature, 14C; and ramping factor, linear. The PFGE patterns were analyzed with computer software (Molecular Analyst; Bio-Rad Laboratories, Inc). The PFGE patterns were compared by the unweighted pair group method with arithmetic averages with the Dice coefficient of similarity.12 The interpretation of the DNA fragments was made based on the guidelines proposed by Tenover and colleagues.13 In brief, isolates were designated to be genetically indistinguishable if their restriction patterns had the same number of bands and if these bands appeared to be the same size. Isolates were considered to be closely related or possibly related when the patterns of two of them differed by no more than three bands (ie, a single genetic event) or by four to six bands (ie, two independent genetic events), respectively. Two isolates were considered to be unrelated if their PFGE patterns differed by changes that were consistent with three or more independent genetic events (generally, seven or more band differences).

Statistical Analysis

Data were analyzed using a statistical software package (NCSS 2000; NCSS Statistical Analysis System; Kaysville, UT). The results were expressed as the mean SD. Continuous variables were compared using the Student t test for normally distributed variables and the Mann-Whitney test for non-normally distributed variables. Proportions were compared using the χ^sup 2^ test with Yates correction, or the Fisher exact test when necessary. A p value of


Study Population

Forty-nine institutionalized elderly patients requiring mechanical ventilation met the inclusion criteria, including 22 male patients (45%) and 27 female patients (Fig 1). Reasons for ICU admission included congestive heart failure (7 patients), cerebrovascular accident (9 patients), septic shock (12 patients), COPD exacerbation (7 patients), and others (14 patients). Fourteen patients (29%) developed clinical evidence of HAP. The clinical characteristics of the study population on admission to the ICU are summarized in Table 1. The mean duration of mechanical ventilation before the occurrence of HAP was 11.6 4.3 days. The burden of comorbidities, the ADL score, and the severity of illness were comparable between those who developed HAP and those who did not. Sixteen of the 35 patients (46%) in the non-HAP group received initial antimicrobial therapy on admission to the ICU compared to 7 of 14 patients (50%) who developed HAP (p = 0.9). The antimicrobial therapy consisted of monotherapv in 13 patients, including an aminopenicillin agent/β-lactamase inhibitor (four patients), a flouroquinolone (seven patients), or a third-generation cephalosporin (two patients). Ten patients had a combination of either an aminopenicillin/β-lactamase inhibitor plus an aminoglycoside (six patients), a flouroquinolone or a third- generation cephalosporin plus metronidazole (three patients), or a flouroquinolone plus an aminoglycoside (one patient).

FIGURE 1. Flow chart of the study population.

Table 1-Characteristics of the Study Population*

Table 2-Characteristics of Subjects With Colonized and Noncolonized DPs*

Dental Assessment

All patients were examined on the first day of admission to the ICU. Indicators of oral health are presented in Table 1. Both groups had evidence of poor oral hygiene, as indicated by the high plaque index score and the high frequency of DP colonization with respiratory pathogens. Yet, patients who had dentures (11 patients) had significantly lower plaque indexes (1.65 0.29 vs 2.28 0.43. respectively; p

Table 3-The Spectrum of Respiratory Pathogens Isolated From DPs and PBAL Fluid of Those With and Without Clinical Suspicion for HAP

A comparison of those patients who were colonized with respiratory pathogens and those deemed to be not be colonized revealed no difference in terms of age, comorbidities, or the length of time spent in the chronic care facilities (Table 2). However, colonized subjects had significantly lower functional status and a worse mean plaque index than noncolonized subjects. There was also a trend toward a higher incidence of HAP in the colonized group, but the difference did not reach statistical significance.

Microbial Assessment

Overall, 33 respiratory pathogens were identified from the DPs (Table 3). Eleven isolates were recovered from those who had clinical evidence of HAP and 22 from those who were deemed not to have HAP. S aureus (45%) accounted for the majority of the isolates, followed by enteric Gram-negative bacilli (42%) and P aeruginosa (13%). Polymicrobial colonization was noted in five patients and comprised the following combinations: S aureus and E coli; S aureus and K pneumoniae; K pneumoniae and E coli; S aureus and P aeruginosa; and S aureus and E coli. Of interest, 9 of the 15 S aureus isolates were methicillin-resistant. There was no association between any of the respiratory pathogens with the demographic characteristics or with any of the oral indexes.

Comparably, 36 respiratory isolates were recovered from the oropharyngeal cavity (Table 3). The concordance of bacterial cultures between DPs and the oropharyngeal cavity was observed in 20 patients. Four of those 20 patients developed clinical suspicion for HAP. The isolates were composed of S aureus (two patients), E coli (one patient), and S aureus plus P aeruginosa (one patient).

The etiology of HAP could be documented in 10 of the 14 patients who underwent PBAL (Table 3). Thirteen isolates were identified, with mixed infection present in three patients. The polymicrobial isolates consisted of the following combinations: H influenzae and E cloacae; S aureus and P aeruginosa; and S aureus and K pneumoniae.


Nine respiratory pathogens isolated from eight patients with microbiologically verified HAP matched those recovered from DPs. These included S aureus (five patients), E coli (one patient), E cloacae (one patient), and P aeruginosa (two patients). One patient had two pathogens (S aureus and P aeruginosa) isolated from both the DP and PBAL fluid. All matching pathogens displayed similar antimicrobial susceptibility profiles (Table 4). Following PFGE, 16 isolates were considered to be genetically indistinguishable (Fig 2- 5). One strain of S aureus was classified as closely related.

Table 4-Antimicrobial Susceptibility Profile of the Nine DNA- Matched Pathogens*

FIGURE 2. DNA patterns of S aureus isolates obtained from PBAL fluid and DP after macrorestriction with SmaI. LL = lamda ladder; QC = quality control.


We have shown the following in this study: (1) that colonization of DPs with aerobic respiratory pathogens is highly prevalent in institutionalized critically ill elderly patients; (2) that S aureus and Gram-negative enteric bacilli accounted for the majority of DP colonization by respiratory pathogens; and (3) that DPs can be a reservoir of respiratory pathogens responsible for HAP in hospitalized elderly patients.

FIGURE 3. DNA patterns of E coli isolates obtained from PBAL fluid and DP after macrorestriction with NotI. See the legend of Figure 2 for abbreviations not used in the text.

FIGURE 5. DNA patterns of E cloacae isolates obtained from PBAL fluid and DP after macrorestriction with SpeI. See the legend of Figure 2 for abbreviations not used in the text.

The colonization of DPs with respiratory pathogens has been shown to occur in elderly patients residing in the community as well in chronic care facilities.14 However, while DP colonization of community dwellers is considered to be transient in nature, the occurrence of colonization in the DPs of institutionalized elders is well-established. Russell and colleagues14 recruited a group of elderly residents of chronic care facilities and performed a complete oral examination, including characterization of the respiratory pathogens. Compared to an age-matched, gender-matched, and race-matched outpatient control group, the chronic care facility subjects had significantly higher plaque scores and were more likely to be colonized with respiratory pathogens. In their analysis, 25% of the patients residing in long-term facilities were colonized with respiratory pathogens compared to 57% in our study. The disparity in the frequency of DP colonization is attributed to the lower functional status and the higher burden of comorbidities of our participants. Yet, our results corroborate the findings of Russell and colleagues14 in terms of the pathogens isolated from DPs. Both studies identified S aureus, enteric Gram-negative bacilli (ie, E coli and E cloacae), and P aeruginosa as the predominant respiratory pathogens present in institutionalized elders. Although we ha\ve excluded subjects who had received antimicrobial therapy within 60 days of enrollment into the study, we speculate that the increased prevalence of S aureus and enteric Gram-negative bacilli in DPs is likely to be attributed to prior treatment with antibiotics in the nursing homes.15,16

FIGURE 4. DNA patterns of P aeruginosa isolates obtained from PBAL fluid and DP after macrorestriction with XbaI. See the legend of Figure 2 for abbreviations not used in the text.

A possible link between poor hygiene and an increased incidence of pneumonia in institutionalized elders has been suggested previously,17-19 but the link between dental colonization and lower respiratory tract infection has never been firmly established. In a retrospective analysis of 358 veterans, aged ≥ 55 years, who were prospectively enrolled, Terpenning and coworkers18 demonstrated a significant association between the presence of dental decay, periodontal pathogens, and the risk of pneumonia. Similarly, Mojon and others19 showed a greater 1-year incidence of respiratory tract infection among dentate elderly subjects with high plaque scores and those with generalized oral disease. Our data were consistent with the trend toward a higher incidence of pneumonia in those with poor dental hygiene, although a link between oral hygiene and pneumonia ought not to be inferred because the study was not powered to show statistical significance. Nevertheless, this investigation is the first, to our knowledge, to confirm the association between the colonization of DPs and lower respiratory infection in institutionalized patients using molecular genotyping.

It may be argued that dental culture might reflect mere oropharyngeal colonization, with bacterial pathogens just covering the tooth surface. While this scenario is plausible, we think that this possibility is highly unlikely. Samplings of the DPs were obtained from the supragingival third of the tooth after the tooth surface was dried with a sterile gauze to avoid contamination with saliva. Moreover, previous studies17,20 have shown the accuracy of such a sampling technique in measuring bacterial aerobic and anaerobic plaque colonization without contamination. Although we found a high agreement of colonization between DPs and the oropharyngeal cavity, four patients who developed microbiologically proven HAP had no evidence of oropharyngeal colonization on hospital admission. This sequence suggests that DP colonization preceded oropharyngeal colonization and acted as a potential reservoir for lower respiratory7 tract infection. It is worthy to mention that Fourrier and colleagues17 used an arbitrary threshold of ≥ 10^sup 3^ colony-forming units/mL for a plaque culture to be characterized as being colonized with an aerobic pathogen. In the present study, we chose a cutoff value based on the hypothesis that if a bacterium is considered to represent at least 1% of the plaque at a given site, it has most likely entered into a stable relationship with the host by virtue of its numerical dominance.10 This definition is more likely to capture the dynamic equilibrium of the bacterial DP ecosystem.

The clonality of dental and respiratory bacteria yields significant weight for the need of routine dental care in long-term care facilities. Control of the accumulation of plaque on the teeth and dentures of these residents, however, is challenging because health-care providers in residential homes give little assistance with tooth and denture cleaning,21 even if training and education are provided.22 Several preventive interventions have been tested in older nursing home residents to improve dental health. In a 2-year prospective study, Yoneyama and coworkers23 randomized 417 residents of 11 nursing homes to an oral care group and to a no-oral care group. In the oral care group, a health-care provider cleaned patients' teeth after each meal. In addition, a dental hygienist administered professional care once weekly to the oral group. During follow-up, the relative risk of death attributable to pneumonia decreased significantly in those patients who received oral care compared to the no-oral care group. Simons and coworkers24 have shown that the mastication of two pellets of chewing gums containing xylitol and chlorhexidine twice daily for 15 min over a period of > 12 in residential homes produced significant improvements in stomalogic health compared to a control group that did not chew gum.

In summary, we have proven that respiratory pathogens colonizing DPs are implicated in lower respiratory tract infections of hospitalized institutionalized elders. Further studies are needed to investigate the relationship between the burden of dental disease and the incidence of respiratory events. Meanwhile, it is advocated that active programs be instituted by all health-care practitioners to enhance the access of institutionalized elders to dental care sendees and to improve daily oral hygiene.

* From the Department of Medicine (Drs. El-Solh, Pietrantoni. Bhat, Okada, and Aquilina, and Ms. Berbary), Division of Pulmonary, Critical Care, and Sleep Medicine. School of Medicine and Biomedical Sciences, and the Department of Periodontics and Endodontics (Dr. Zambon), School of Dental Medicine, University at Buffalo, Buffalo, NY.

This study was supported by a grant from the American Lung Association of New York (AAE).


1 El-Solh A. Sikka P, Ramadan F, et al. Etiology of severe pneumonia in the very elderly. Am J Respir Grit Care Med 2001; 163:645-651

2 El-Solh A, Aquilina T, Dhillon R, et al. Impact of invasive strategy on management of antimicrobial treatment failure in institutionalized older people with severe pneumonia. Am J Respir Crit Care Med 2002; 166:1038-1043

3 Irwin RS, Whitaker S, Pratter MR, et al. The transiency of oropharyngeal colonization with Gram-negative bacilli in residents of a skilled nursing facility. Chest 1982; 81:31-35

4 Gibbons RJ. Bacterial adhesion to oral tissues: a model for infectious diseases. J Dent Res 1989: 68:750-760

5 Katz S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged-the index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963; 185:94-99

6 Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidiry in longitudinal studies: development and validation. J Chronic Dis 1987; 40:373-383

7 Knaus WA, Draper EA, Wagner DP, et al. APACHE II a severity of disease classification system. Crit Care Med 1985; 13:818-829

8 Silness J. Loe H Periodontal disease in pregnancy: II. Correlation between oral hygiene and periodontal conditions. Acta Odontol Scand 1964: 24:747-759

9 Balows A, Harsler WJ. Manual of clinical microbiology. 5th ed. Washington. DC: American Society for Microbiology, 1991; 209-553

10 Loesche WJ. Ecology of the oral flora. In: Nisengard RJ, Newman MG. eds. Oral microbiology and immunology. Toronto. ON. Canada: WB Sannders, 1988; 308

11 Maslow J. Slutsky AM, Arbeit RD. Application of pulse-field gel electrophoresis to molecular epidemiology. In: Persing DH, Smith TF, Tenover FC, et al. eds. Diagnostic molecular microbiology: principles and applications. Washington, DC: American Society lor Microbiology, 1993: 563-572

12 Romling U. Grothues D, Heuer T, et al. Physical genome analysis of bacteria. Electrophoresis 1992; 13:626-631

13 Tenoyer F. Arbeit K, Goering R, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-gel field electrophoresis: criteria tor bacteria] strain typing. J Clin Microbiol 1995:33:2233-2239

14 Russell S. Boylan R. Kaslick R. et al. Respiratory pathogen colonization of the dental plaque of institntionalized elders. Spec Care Dentist 1999: 19:128-134

15 Rams TE. Babalola OO. Slots J. Subgingival occurrence of enteric rods, yeasts and staphylococci after systemic doxycycline therapy. Oral Microbiol Immunol 1990; 5:166-168

16 Heluvuo H, Hakkarainen K, Paunio K. Changes in the prevalence of subgingival enteric rods, staphylococci and veasts after treatment with penicillin and erythromycin. Oral Microbiol Imunol 1993; 8:75-79

17 Fourrier F. Duvivier B. Boutigny H. et al. Colonization of dental plague, a source of nosocomial infections in intensive care unit patients. Grit Care Med 1998; 26:301-308

18 Terpenning M, Taylor GW. Lopatin DE, et al. Aspiration pneumonia: dental and oral risk factors in an older veteran population. J Am Geriatr Soc 2001; 49:557-563

19 Mojon P, Budtz-Jorgenson E. Michel JP. et al. Oral health and history of respiratory tract infection in frail institutionalized elders. Gerontology 1997: 14:9-16

20 Slots J, Rams TE, Litsgarten MA. Yeasts, enteric rods and pseudomonales in the subgingival flora of severe adult periodontitis. Oral Microhiol Immunol 1988; 3:47-52

21 Simons D. Kidds EA, Beighton D. Oral health of elderly occupants in residential homes [letter]. Lancet 1999; 353: 1761

22 Simons D, Baker P, Jones B. et al. An evaluation of oral health training programme for carers of the elderly in residential homes. Br Dent J 2000; 188:206-210

23 Yoneyama T, Yoshida M, Ohrui T. et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002; 50:430-433

24 Simons D, Brailsford SR, Kidd EA. et al. The effect of medicated chewing gums on oral health in frail older people: a 1- year clinical trial. J Am Geriatr Soc 2002; 50:1348-1353

Ali A. El-Solh, MD, MPH, FCCP; Celestino Pietrantoni, DO; Abid Bhat, MD; Mifue Okada, MD; Joseph Zambon, DDS, PhD; Alan Aquilina, MD, FCCP; and Eileen Berbary, RN

Manuscript received November 14, 2003; revision accepted April 8, 2004.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

Correspondence to: Ali A. El Solh, MD, MPH, FCCP, Division of Pulmonary, Critical Care, and Sleep Medicine, Erie County Medical Center, 462 Grider St, Buffalo\, NY 14215; e-mail: [email protected]

Copyright American College of Chest Physicians Nov 2004