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Protected-Specimen Brush Technique in the Diagnosis of Ventilator-Associated Pneumonia^*

^* From the University of Cincinnati Medical Center, Cincinnati, OH.

	Introduction

TOP Introduction Qualifications for Inclusion in... Risks Conclusion

 
The protected-specimen brush (PSB) technique has been used for almost 20 years in diagnosing pneumonia,¹ and the technique has been refined for VAP. Of the many studies, those included in our analysis met certain criteria.

The 42 studies reviewed were identified through a MEDLINE search and presented primary data of bronchoscopy samples from patients receiving mechanical ventilation. All studies had rigorous clinical criteria for the diagnosis of pneumonia, including response to antibiotics, that were independent of the results of PSB or BAL procedures. The review methodology for this section is described in Dr. Steven H. Woolf’s section on the search of the literature.

Independent nonbronchoscopic diagnostic criteria were required to ensure that there were no derivative data.¹⁰⁸ Five studies compared PSB sampling to the use of specimens obtained immediately after autopsy as the final criteria for diagnosis. The remaining 13 studies used clinical assessment, response to antibiotics, and histologic data, including eventual autopsy information, when available. Of the 846 patients evaluated, pneumonia was diagnosed in 287.

The quality of the PSB technique used in making the diagnosis was not described in detail for most of the studies in Table 14 and Table 15 .

Assessing the quality of the PSB sample involves examining a cell sample and looking directly at a brush sample. The problem is that two brush samples have to be obtained, since the slide could contaminate the culture results. Using the PSB technique allows for assessment of the quality of the sample, because the presence of squamous epithelial cells indicates that the sample is unacceptable. In one study, this was looked for and was found in some cases, but the number of unacceptable specimens was not given.¹⁰⁹ In two studies, Gram’s stain was found to be sensitive and fairly specific in the identification of bacteria. It provides information within the first 24 h of the procedure, which is useful.^109,110

As noted above, 5 of the 18 studies used autopsy data from VAP patients as a "gold standard." Obviously, this does not provide information about patients who did not die. The other studies did not have histologic confirmation of the final diagnosis in all patients.

None of the studies included a PSB procedure on every patient in the ICU. Entry criteria for all patients required either a clinical suspicion of pneumonia or availability of autopsy studies. One study¹⁸ had autopsy confirmation of the diagnosis, but the bronchoscopy had been performed up to 3 days before death.

Among other factors contributing to variability are the skill of the health-care worker performing the procedure. It is not clear how much skill is required, but suctioning through the catheter before brushing may interfere with the results.¹¹¹ Few studies specify that the secretions were cleared out with a separate bronchoscope before the PSB sample was taken.²⁶ Also, where and what to brush is poorly defined.⁸⁵ Other problems include the selection of patients to undergo the procedure and the lack of standard protocols for therapy, such as the selection of prior antibiotics and the use of empirical therapy pending the results of the cultures. Because clinical outcome is often used in assessing the PSB technique, the use of antibiotics pending the culture result can influence the study outcome.

	Qualifications for Inclusion in the Tables

TOP Introduction Qualifications for Inclusion in... Risks Conclusion

 
Studies
The 18 studies covered were published from 1984 to 1995 and used semiquantitative culture results for the PSB sample. All studies used the technique described for patients not receiving ventilator support.¹ A standard method of bronchoscopy and handling of specimens was published in 1992,^112–114 but was not significantly different from the methodology used in the studies.

How Were Patients Enrolled?
All studies apparently enrolled patients prospectively, although two studies^24,25 do not make this clear. Although the studies were prospective, none included all ICU patients. Most studies also were limited by the ability to perform the procedure. Some studies stated that patients were enrolled only during daytime.⁹⁹ Most others probably followed this practice.

Description of the Population
The studies can be divided into two groups. The first includes patients who died while receiving mechanicalventilation. Bronchoscopy and autopsy were performed on these patients in the immediate postmortem period.^20,41,99 There were no other selection criteria, so pneumonia was not necessarily suspected prior to autopsy. One study compared the results in ventilator-assisted patients with and without clinically suspected pneumonia.¹³ The rest of the studies report results in patients studied because of the clinical suspicion of pneumonia. One study analyzed findings in patients who had bronchoscopy for possible pneumonia then underwent autopsy within 72 h.¹⁸

Were the Test Results and the Reference Standard Assessed by Investigators Unaware of the Results of the Other Investigators?
In all patients studied during life, the results from the PSB procedure affected long-term treatment.^{13,16,18,21,26,40,45,85,103,115–117} Clinical response was one of the criteria for defining pneumonia in all studies except for the one that used autopsy.¹⁸ The four studies in which postmortem bronchoscopy and autopsy were performed^20,29,41,99 did not have that bias. The fact that the results from the autopsy studies were similar to those from the clinical studies supports the results of the latter.

Were Methods of Performing the Tests Described Adequately?
Overall, the authors provided sufficient details on methodology. As noted, the PSB technique has remained virtually unchanged for years. In the one study using two bronchoscopes (the first used to suction the airways, and the second used without suction) on all patients,⁸⁵ the results were not significantly different from those of other studies. One study found that it did not matter which segment of the lung was brushed.¹¹⁸

Criteria Used to Assess the Quality of the Sample
One article discussed the examination of the bush sample for the presence of cells.¹⁰⁹ Technically, this may not be feasible, because dilution of the sample relies on the vigorous agitation of the brush in a solution immediately after sampling.^1,85 The Gram’s stain may provide an early guide to therapy.^25,109

Study Design
The most common study design selected patients suspected of having VAP who could undergo bronchoscopy. One study was limited to patients with localized infiltrates, so that an unaffected lobe could be analyzed.²⁶ One study included patients who had no clinical suspicion of pneumonia.¹³ One postmortem study examined bronchoscopy results obtained within 3 days before death.¹⁸ The remaining postmortem studies compared only the specimens obtained after death.

Antibiotics
Antibiotic therapy is a significant variable in the assessment of a diagnostic technique. In three studies, patients were not receiving any antibiotics.^24,26,100 Others studies attempted to study only patients who had not undergone a recent change in antibiotic therapy.^41,99 In the rest of the studies, patients took antibiotics for varying periods. Since most patients with VAP are already taking antibiotics at the time of bronchoscopy, this remains an unresolved dilemma.

Reference Standard
Table 14 discusses the reference standards for each study. The postmortem studies used histology reports and culture results.^{18,20,29,41,99} In the clinical studies, the most common criteria were response to therapy or the identification of an alternative diagnosis. In many studies, some patients died and underwent postmortem examination. The autopsy results did not change the clinical impression to any degree.

Sensitivity
The sensitivity of the studies varied from about 33 to 36%^20,41 to > 95%.^29,40 This wide range cannot be explained by diagnostic criteria alone. The lowest²⁰ and highest²⁹ sensitivities were in autopsy studies. As noted above, the recommended cutoff of 10³ cfu/mL⁸⁵ is arbitrary. In one series looking at the reproducibility of results for the brush technique, 25% of the results were discordant.²⁷ The median sensitivity of brush sampling for all studies was 67%.

Specificity
The calculated specificity, shown in Table 14 , ranged from 50%⁴¹ to 100%,^{16,24,26,45,100,103,116,117} with a median specificity of 95%. The PSB may be more specific than sensitive.

Likelihood Ratio
Table 14 also includes the calculated likelihood ratios (LRs), based on sensitivity and specificity. Since several studies reported the PSB procedure to be highly specific, the likelihood that a positive finding would mean pneumonia was quite high. The median LR was 16. Only one study reported an LR of < 1,⁴¹ and several studies reported ratios of > 50 based on a 100% specificity.^{16,24,26,100,103,116,117} In the one study reporting an LR of < 1, all patients were receiving antibiotics and only three patients had recently changed antibiotics.⁴¹ Since histology studies were the criteria for diagnosis, it is not clear whether a negative result for a PSB culture and a positive result of a histologic examination may indicate a treated, but not resolved, case of pneumonia.

Comparison to Other Techniques
Fourteen studies were direct comparisons between PSB and other invasive diagnostic techniques, usually BAL.^{13,18,20,24,28,41,93,99,100,103,116} None of the studies comparing the PSB and BAL techniques convincingly showed a benefit for one over the other, although BAL was generally more sensitive and PSB more specific. It is not clear that these tests are complimentary.

The other studies compared PSB with relatively less invasive techniques, such as aspiration samples,^13,20,118 blind BAL,^20,45 and nonprotected brush.¹¹⁷ The comparisons showed little difference between the techniques.

	Risks

TOP Introduction Qualifications for Inclusion in... Risks Conclusion

 
The reports are strangely silent regarding complications from the PSB procedure. Bronchoscopy in the patient receiving mechanical ventilation is associated with significant risks, but it is not clear that the brush technique adds to the risk.

	Conclusion

TOP Introduction Qualifications for Inclusion in... Risks Conclusion

 
Despite the wide array of studies and the use of high-quality diagnostic techniques in several studies to determine the cause of pneumonia, sensitivity ranged from 33 to 100% and specificity ranged from 50 to 100%. Overall, PSB appears more specific than sensitive in diagnosing VAP. In a patient with suspected VAP and a positive result of testing a PSB sample, the LR of VAP appears to be much > 1.

	Footnotes

 
Abbreviations: LR = likelihood ratio; PSB = protected-specimen brush; VAP = ventilator-associated pneumonia

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