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A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation.

ABSTRACT: Bronchoalveolar lavage (BAL) has been a useful initial diagnostic tool in the evaluation of pulmonary complications after hematopoietic stem cell transplantation (HSCT); however, the diagnostic sensitivity, prevalence, and outcome after BAL versus lung biopsy (LB) in pediatric HSCT patients remains to be determined. We reviewed 193 pediatric HSCT recipients who underwent a total of 235 HSCTs. Sixty-five patients (34%) underwent a total of 101 BALs for fever, respiratory distress, and/or pulmonary infiltrates on chest radiograph and/or computed tomography scan. The 1-year probability of undergoing BAL was 43.0% after allogeneic stem cell transplantation (alloSCT) and 8.5% after autologous stem cell transplantation (autoSCT) (P = .001). Sixteen of the 193 patients (8%) patients underwent 19 LBs. The probability of undergoing LB at 1 year after HSCT was 9.3%. No grade III or IV adverse events related to either procedure were observed. Of the 101 BALs performed, 40% (n = 40) were diagnostic, with a majority revealing a bacterial pathogen. Among the 19 LBs performed, 94% identified an etiology. In multivariate analysis, myeloablative conditioning alloSCT conferred the highest risk of requiring a BAL (hazard ratio [HR],8.5; P = .0002). The probability of 2-year overall survival was 20.2% in patients who underwent BAL, 17.5% for patients who underwent biopsy, and 67.4% for patients who had neither procedure. In multivariate analysis, only the requirement of a BAL was independently associated with an increased risk of mortality (HR, 2.96; P < .0001). In summary, in this cohort of pediatric HSCT recipients, BAL and LB were used in approximately 35% and 8% of pediatric HSCTs with diagnostic yields of approximately 40% and 94%, respectively, and were both associated with poor long-term outcomes.

SUBMITTER: Qualter E

PROVIDER: S-EPMC4099252 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation.

Qualter Erin E Satwani Prakash P Ricci Angela A Jin Zhezhen Z Geyer Mark B MB Alobeid Bachir B Radhakrishnan Kavita K Bye Michael M Middlesworth William W Della-Letta Phyllis P Behr Gerald G Muniz Miguel M van de Ven Carmella C Harrison Lauren L Morris Erin E Cairo Mitchell S MS

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20140423 8

Bronchoalveolar lavage (BAL) has been a useful initial diagnostic tool in the evaluation of pulmonary complications after hematopoietic stem cell transplantation (HSCT); however, the diagnostic sensitivity, prevalence, and outcome after BAL versus lung biopsy (LB) in pediatric HSCT patients remains to be determined. We reviewed 193 pediatric HSCT recipients who underwent a total of 235 HSCTs. Sixty-five patients (34%) underwent a total of 101 BALs for fever, respiratory distress, and/or pulmonar ...[more]

PMID: 24769329

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Project description:BackgroundDifferentiating malignant lung tumors from benign pulmonary nodules is a great challenge. While the analysis of bronchoalveolar lavage fluid (BALF) is used for diagnosing infections and interstitial lung diseases, there is limited evidence to support its use for lung cancer diagnosis. This study aimed to interrogate the potential of using BALF cell-free DNA (cfDNA) to discriminate malignant lesions from benign nodules.MethodsFifty-three patients with solid pulmonary nodules (≤2 cm) were prospectively enrolled, including 21 confirmed with benign disease and 32 with malignant tumors. Mutations were profiled for 30 tumor tissues and 40 BALFs. Paired BALFs and plasma from 48 patients underwent DNA methylation profiling. A methylome-based classification model was developed for BALF and plasma separately.ResultsAmong the 30 patients with paired tissues and BALFs, 96.7% and 70% had alterations detected from their tissues (79 alterations) and BALFs (53 alterations), respectively. Using tissues as references, BALFs revealed 14 new alterations and missed 41. BALF mutation displayed a sensitivity of 71%, specificity of 77.8%, and accuracy of 72.5% in detecting lung cancer. BALF methylation achieved an accuracy of 81.3%, with both sensitivity and specificity being 81%. Plasma methylation showed a 66.7% sensitivity, 71.4% specificity, and 68.8% accuracy. BALF methylation also demonstrated 82.4% sensitivity in stage I patients. Parallel bronchoscopy, lavage cytology, and bronchial brushing demonstrated an inferior sensitivity of 23%, 3.1%, and 9.7%, respectively, compared with BALF methylation and mutation (P<0.0001).ConclusionsBALF cfDNA can serve as a liquid biopsy media for both mutation and methylation profiling, demonstrating better sensitivities in distinguishing small malignant tumors from benign nodules than conventional methods.KeywordsLung cancer diagnosis; pulmonary nodule; bronchoalveolar lavage fluid (BALF); methylation; genomic mutation.

Project description:We developed a rapid thermocycling, real-time detection (also known as real-time PCR) method for the detection of Legionella species directly from clinical specimens. This method uses the LightCycler (Roche Molecular Biochemicals, Indianapolis, Ind.) and requires approximately 1 to 2 h to perform. Both a Legionella genus PCR assay and Legionella pneumophila species-specific PCR assay were designed. A total of 43 archived specimens from 35 patients were evaluated, including 19 bronchoalveolar lavage (BAL) specimens and 24 formalin-fixed, paraffin-embedded open lung biopsy specimens. Twenty-five of the specimens were culture-positive for Legionella (9 BAL specimens and 16 tissue specimens). BAL specimens were tested by LightCycler PCR (LC-PCR) methods and by a direct fluorescent antibody (DFA) assay, which detects L. pneumophila serogroups 1 to 6 and several other Legionella species. Tissue sections were tested by the two LC-PCR methods, by DFA, by an in situ hybridization (ISH) assay, specifically designed to detect L. pneumophila, and by Warthin-Starry (WS) staining. The results were compared to the "gold standard" method of bacterial culture. With BAL specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by Legionella genus LC-PCR, 100 and 100%; Legionella genus detection by DFA assay, 33 and 100%; and L. pneumophila detection by L. pneumophila species-specific LC-PCR, 100 and 100%. With open lung biopsy specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by LC-PCR 68.8 and 100%; Legionella genus detection by DFA assay, 44 and 100%; Legionella genus detection by WS staining, 63 and 100%; L. pneumophila species-specific detection by LC-PCR, 17 and 100%; and L. pneumophila species-specific detection by ISH, 100 and 100%. The analytical sensitivity of both LC-PCR assays was <10 CFU/reaction. LC-PCR is a reliable method for the direct detection of Legionella species from BAL specimens. The Legionella genus LC-PCR assay could be performed initially; if positive, L. pneumophila species-specific LC-PCR could then be performed (if species differentiation is desired). The speed with which the LC-PCR procedure can be performed offers significant advantages over both culture-based methods and conventional PCR techniques. In contrast, for the methods evaluated, culture was the best for detecting multiple Legionella species in lung tissue. WS staining, Legionella genus LC-PCR, and L. pneumophila species-specific ISH were useful as rapid tests with lung tissue.

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A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation.

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A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation.

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