Pulmonary Cytomegalovirus - Bronchoalveolar Lavage Diagnosis

11/21/2005

Question:  How accurate is the bronchoalveolar lavage diagnosis of pulomonary cytomegalovirus infection?

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15108232.ui or 12736722.ui or 9645997.ui or 9554626.ui or 8859202.ui or 8772406.ui or 8648201.ui or 7874946.ui

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PubMed recovery search string (copy and paste into PubMed search entry panel)

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15108232[PMID] OR 12736722[PMID] OR 9645997[PMID] OR 9554626[PMID] OR 8859202[PMID] OR 8772406[PMID] OR 8648201[PMID] OR 7874946[PMID]

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Unique Identifier [PMID]: 15108232

Authors: Gupta RK. Naran S. Lallu S. Fauck R.

Institution: Cytology Unit, Department of Laboratory Services, Wellington Hospital and School of Medicine, Wellington, New Zealand. raj.gupta@xtra.co.nz

Title: Cytodiagnosis of simultaneous pulmonary infection due to cytomegalovirus and pneumocystis carinii in a sample of bronchoalveolar lavage.

Source: Diagnostic Cytopathology. 30(5):341, 2004 May.

Publication Type: Case Reports. Journal Article.

<2>

Unique Identifier [PMID]: 12736722

Authors: Ohyashiki JH. Nagate A. Ojima T. Abe K. Yamamoto K. Ohyashiki K.

Institution: Intractable Diseases Research Center, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan. junko@hh.iij4u.or.jp

Title: Quantification of human cytomegalovirus using bronchoalveolar lavage cells in pulmonary complications associated with hematologic neoplasia.

Source: International Journal of Molecular Medicine. 11(6):779-83, 2003 Jun.

Abstract: Human cytomegalovirus (CMV) has been recognized as a frequent pathogen involved in interstitial pneumonia (IP), and CMV-IP is a severe and life-threatening complication in the immunocompromised patients. The use of real-time PCR in molecular diagnostics has increased to the point where it is now accepted as the gold standard for detecting a wide variety of templates including viruses. Therefore, we developed a rapid quantification system of CMV using a LightCycler in order to clarify the possible role of CMV reactivation in patients with hematologic neoplasia showing pulmonary complications. Sixty-nine bronchoalveolar lavage fluid (BALF) specimens were obtained from consecutively treated patients showing interstitial shadow including 20 patients with hematologic neoplasia. First, we determined the viral burden in BAL cells from healthy volunteers, idiopathic interstitial pneumonia (IIP) and sarcoidosis. CMV copy numbers in samples obtained from healthy volunteers, IIP and sarcoidosis, were less than 10(2) copies per 1 microg of DNA, whether or not BAL cells were composed of high percentage of lymphocytes. Among 20 patients with hematologic neoplasia analyzed, two specimens obtained from leukemia patients with pulmonary alveolar proteinosis, two from GvHD, one with CMV interstitial pneumonia and one with Hodgkin's disease had high level of CMV viral DNA. Our results suggest that measurement of CMV genomes in BAL cells using real-time PCR may be useful not only to understand the involvement of CMV in systematic respiratory tract disease but also in management of the care of respiratory complications in hematologic neoplasia.

Publication Type: Journal Article. Validation Studies.

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Unique Identifier [PMID]: 9645997

Authors: de la Hoz RE. Byrne SK. Hayashi S. Sherlock C. Cook D. Hogg JC.

Institution: University of British Columbia Respiratory Medicine Program, St. Paul's Hospital, Vancouver, Canada.

Title: Diagnosis of cytomegalovirus infection in HIV-infected patients with respiratory disease.

Source: Clinical & Diagnostic Virology. 10(1):1-7, 1998 May 1.

Abstract: BACKGROUND: The role of the cytomegalovirus (CMV) in the respiratory morbidity and mortality of HIV-infected patients remains unclear. This is due in part to difficulties in making an accurate and rapid diagnosis. There has been a limited number of studies, often with few or no AIDS patients, on the use of DNA-DNA in situ hybridization (ISH) and polymerase chain reaction to diagnose CMV respiratory infection directly on bronchoalveolar fluid samples. OBJECTIVES: To compare the centrifugation culture (CC), ISH, and nested-primer polymerase chain reaction (npPCR) techniques (npPCR) techniques on bronchoalveolar fluid for the diagnosis of respiratory CMV infection. STUDY DESIGN: Samples were obtained prospectively from a group of 35 HIV-infected homosexual men evaluated for pneumonia at a university hospital. Sensitivity, specificity, and predictive values of the three techniques were measured and compared, using the conventional roller tube cell culture (CRTC) as the gold standard. RESULTS: Sensitivity, specificity, positive and negative predictive values were as follows: 86%, 86%, 90%, and 80% for the CC; 5%, 100%, 100%, and 41% for ISH; and 86%, 57%, 75%, and 73% for npPCR. Of the six false positive samples by npPCR, two were positive by CC (none by ISH). If the latter were considered true positives, the specificity and positive predictive values of npPCR would increase to 67% and 83%, respectively. CONCLUSIONS: CC appeared to be the best of the three techniques compared in this study for diagnosis of respiratory CMV infection in HIV-infected patients. The sensitivity and predictive values of DNA-DNA ISH were very poor. Results with npPCR were acceptable, and this technique may be considered in situations when rapid diagnosis of CMV infection is necessary.

Publication Type: Journal Article.

<4>

Unique Identifier [PMID]: 9554626

Authors: Uberti-Foppa C. Lillo F. Terreni MR. Puglisi A. Guffanti M. Gianotti N. Lazzarin A.

Institution: Department of Infectious Diseases, IRCCS San Raffaele Hospital and University of Milan, Milano, Italy.

Title: Cytomegalovirus pneumonia in AIDS patients: value of cytomegalovirus culture from BAL fluid and correlation with lung disease.

Source: Chest. 113(4):919-23, 1998 Apr.

Abstract: OBJECTIVES: To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs postmortem lung histopathology in detecting CMV pneumonia, and to correlate the BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung tissue of AIDS patients. DESIGN: Retrospective analysis of 434 BALs and 40 autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months. PATIENTS AND METHODS: The 40 patients who died within 20 days of undergoing BAL were divided on the basis of histopathologic findings into subjects with and without CMV-IB in the lung tissue. The relationship between the BAL viral dose and CMV lung infection was evaluated by counting the early antigen (CMV-EA) positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue. RESULTS: The predictive value of BAL virus isolation for the diagnosis of CMV pneumonia was 61% for positive and 100% for negative results. The patients with the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a moderate and small number, the CMV-EA counts were, respectively, from 11 to 700 and 2 to 300. Among the patients surviving up to 10 months after the BAL index sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in those with positive and 7% in those with negative cultures. CONCLUSIONS: BAL CMV cultures from AIDS patients have a very high negative and relatively low positive predictive value for CMV pneumonia. The presence and replication of CMV in the lung may lead to systemic dissemination as suggested by the higher probability of CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree of lung damage.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 8859202

Authors: Humphrey D. Brown M.

Institution: University of South Florida, USA.

Title: Respiratory distress in a patient with skin lesions.

Source: Hospital Practice (Office Edition). 31(10):33-4, 1996 Oct 15.

Publication Type: Case Reports. Journal Article.

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Unique Identifier [PMID]: 8772406

Authors: Stead JA. Thomas J.

Institution: Department of Pathology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown, USA.

Title: Rapid microscopic detection of cytomegalovirus and PCP in bronchoalveolar lavage specimens.

Source: West Virginia Medical Journal. 92(4):197-8, 1996 Jul-Aug.

Abstract: This article describes how bronchoalveolar lavage specimens can be screened rapidly and inexpensively for Pneumocystis carinii and cytomegalovirus infections with materials available in any hospital laboratory.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 8648201

Authors: Boivin G. Olson CA. Quirk MR. Kringstad B. Hertz MI. Jordan MC.

Institution: Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.

Title: Quantitation of cytomegalovirus DNA and characterization of viral gene expression in bronchoalveolar cells of infected patients with and without pneumonitis.

Source: Journal of Infectious Diseases. 173(6):1304-12, 1996 Jun.

Abstract: Cytomegalovirus (CMV) is often present in bronchoalveolar lavage (BAL) fluid of immunosuppressed patients without CMV pneumonitis. The amount of viral DNA within BAL cells of patients with definite CMV pneumonitis and of viral shedders was quantitated by polymerase chain reaction (PCR) and the extent of CMV gene expression within BAL cells was defined by reverse transcription - PCR. No viral DNA was detected in 6 viral shedders, and 12 had low copy numbers (mean, 72 copies/10(5) BAL cells; median, 20) compared with numbers in pneumonitis patients (267,580 and 57,000, respectively). When CMV intranuclear inclusions were absent within BAL cells of patients with pneumonitis, copy numbers (mean, 9362; median, 7110) were still significantly higher than among shedders. Expression of viral glycoprotein H mRNA was detected in BAL cells of all 11 pneumonitis patients tested but in 0 of 18 viral shedders. Thus, high-grade infection and viral replication within BAL cells are integral features of CMV pneumonitis but not viral shedding.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 7874946

Authors: Hayner CE. Baughman RP. Linnemann CC Jr. Dohn MN.

Institution: Department of Internal Medicine, University of Cincinnati Medical Center, OH 45267-0564.

Title: The relationship between cytomegalovirus retrieved by bronchoalveolar lavage and mortality in patients with HIV.[see comment].

Comments Comment in: Chest. 1995 Mar;107(3):595-7; PMID: 7874921, Comment in: Chest. 1996 Sep;110(3):863; PMID: 8797447

Source: Chest. 107(3):735-40, 1995 Mar.

Abstract: STUDY OBJECTIVE: To evaluate mortality over 6 months of patients with HIV with cytomegalovirus (CMV) cultured from bronchoalveolar lavage (BAL) compared with those without CMV and to assess the significance of CMV cytologic study, CD4+ counts, and coexistent Pneumocystis carinii pneumonia. DESIGN: Retrospective evaluation of HIV-infected patients undergoing bronchoscopy with BAL. The 40 most recent HIV-positive patients undergoing bronchoscopy with BAL were included for each of three categories: CMV by cytologic study; CMV by culture only; and CMV absent. Patients for whom survival status at 6 months was unknown were excluded from analysis. SETTING: University hospital, tertiary care center. PATIENTS: Group 1 consisted of 36 patients with positive CMV culture and cytologic study and group 2 consisted of 38 patients with only a positive culture for CMV. Group 3 consisted of 40 patients with no evidence of CMV by BAL. RESULTS: On comparison of the groups, there was no difference in 3-week survival (from date of bronchoscopy). There was a statistically significant increase in mortality in group 1 patients compared with group 3 patients at both 3 and 6 months. Between groups 2 and 3, there was a difference in mortality that approached but did not reach significance at 3 months but did at 6 months. The mortality in group 1 at 3 months = 28%, at 6 months = 47%, whereas mortality in group 2 at 3 months = 26% and at 6 months = 45%. Group 3 had a 3-month mortality of 10% and a 6-month mortality of 15%. While those patients with positive CMV cytologic study had lower mean CD4+ counts, within the group, CD4+ counts were no different between the 3-month survivors and nonsurvivors (survivors, CD4/mm3 median = 38 [0 to 141]; and nonsurvivors, CD4/mm3 median = 16 [3 to 224]). Coinfection with P carinii did not increase mortality at 3 months. CONCLUSIONS: The CMV retrieved by BAL in HIV-infected patients was associated with significantly greater 3- and 6-month mortality. The CMV cytologic study did not predict a higher mortality and the difference in mortality between patients with and without CMV in BAL fluid was not directly attributed to lower CD4+ counts or P carinii coinfection.

Publication Type: Journal Article.