2021, Número 4
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Medicina & Laboratorio 2021; 25 (4)
Diagnóstico microbiológico en lavado broncoalveolar. Revisión de la literatura
Alzate-Rincón CM, Loaiza-Díaz N, Aguilar Y
Idioma: Español
Referencias bibliográficas: 88
Paginas: 675-693
Archivo PDF: 225.02 Kb.
RESUMEN
El lavado broncoalveolar (LBA) se describió hace aproximadamente 50
años, y desde ese momento se ha venido empleando cada vez con más frecuencia,
llegando a ser uno de los métodos de elección para hacer el diagnóstico microbiológico
de las infecciones respiratorias bajas, pues facilita la identificación de
patógenos oportunistas y no oportunistas. Su uso se incrementó paralelamente
con el número de pacientes inmunocomprometidos, sobre todo a causa del SIDA
y los trasplantes, situaciones en las que con frecuencia los pacientes padecen infecciones
pulmonares por gérmenes oportunistas. El LBA es un procedimiento
seguro que permite obtener muestras que aportan información amplia de las características
celulares y microbiológicas del tracto respiratorio inferior. Para garantizar
su utilidad es fundamental que la recolección, transporte, almacenamiento y
procesamiento de las muestras sean óptimos. El análisis de las muestras se hace
por técnicas convencionales para identificación de microorganismos, como son
las tinciones y el aislamiento en medios de cultivo, y por otros métodos tales como
la inmunofluorescencia, pruebas inmunológicas para la detección de antígenos y
anticuerpos, y pruebas de biología molecular. En la presente revisión, se hace una
actualización sobre el procedimiento de obtención, almacenamiento y transporte
de las muestras de LBA, así como de las técnicas de diagnóstico microbiológico
más utilizadas para identificar los principales agentes infecciosos asociados con
enfermedades del tracto respiratorio inferior.
REFERENCIAS (EN ESTE ARTÍCULO)
Patel PH, Antoine M, Ullah S. Bronchoalveolarlavage. Treasure Island (FL): StatPearls Publishing; 2021. Acceso 11 de abril de 2021. Disponibleen https://www.ncbi.nlm.nih.gov/books/NBK430762/.
Escribano-Montaner A, Moreno-Galdó A.Técnicas fibrobroncoscópicas especiales: lavadobroncoalveolar, biopsia bronquial y biopsiatransbronquial. An Pediatr 2005;62:352-366.https://doi.org/10.1157/13073249.
Fagon JY, Chastre J, Domart Y, Trouillet JL,Pierre J, Darne C, et al. Nosocomial pneumoniain patients receiving continuous mechanicalventilation. Prospective analysis of 52episodes with use of a protected specimenbrush and quantitative culture techniques. AmRev Respir Dis 1989;139:877-884. https://doi.org/10.1164/ajrccm/139.4.877.
Michavila IA, Núñez NR, Alvarez JL, SánchezMM. Broncoscopia. Técnicas diagnósticas. In:Soto Campos G, ed. Manual de Diagnósticoy Terapéutica en Neumología. 1a ed. Madrid,España: Asociación de Neumología y CirugíaTorácica del Sur (NEMOSUR); 2005. p. 113–124.
Cacho-Calvo JB, Meseguer-Peinado MA, Oliver-Palomo A, Puig-de la Bellacasa J. Procedimientosen Microbiología Clínica. Diagnósticomicrobiológico de las infecciones bacterianasdel tracto respiratorio inferior. Madrid, España:Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica; 2007. Acceso 15de marzo de 2021. Disponible en https://www.seimc.org/contenidos/documentoscientificos/procedimientosmicrobiologia/seimc-procedimientomicrobiologia25.pdf.
Fernández-Bussy S, Labarca G, Zagolin M,Oyonarte M, Isamit D, Jalilie A, et al. Complicacionesasociadas a la broncoscopía flexible:análisis de registro post-procedimiento. RevMéd Chile 2014;142:299-304.
Terkawi RS, Altirkawi KA, Terkawi AS,Mukhtar G, Al-Shamrani A. Flexible bronchoscopyin children: Utility and complications. Int JPediatr Adolesc Med 2016;3:18-27. https://doi.org/10.1016/j.ijpam.2015.12.003.
Miller JM, Binnicker MJ, Campbell S, CarrollKC, Chapin KC, Gilligan PH, et al. A guide toutilization of the microbiology laboratory fordiagnosis of infectious diseases: 2018 updateby The Infectious Diseases Society of Americaand the American Society for Microbiology.Clin Infect Dis 2018;67:e1-e94. https://doi.org/10.1093/cid/ciy381.
Sánchez-Romero MI, García-Lechuz MoyaJM, González López JJ, Orta Mira N. Recogida,transporte y procesamiento general de lasmuestras en el laboratorio de Microbiología.Enferm Infecc Microbiol Clin 2019;37:127-134.https://doi.org/10.1016/j.eimc.2017.12.002.
Somoza N, Torà M. Seguridad biológica en lapreservación y el transporte de muestras biológicasobtenidas en el ámbito de las enfermedadesrespiratorias y destinadas a la investigación.Arch Bronconeumol 2009;45:187-195.https://doi.org/10.1016/j.arbres.2009.02.001.
Bergner LM, Orton RJ, da Silva Filipe A,Shaw AE, Becker DJ, Tello C, et al. Usingnoninvasive metagenomics to characterizeviral communities from wildlife. MolEcol Resour 2019;19:128-143. https://doi.org/10.1111/1755-0998.12946.
Chamberlain DW, Braude AC, Rebuck AS. Acritical evaluation of bronchoalveolar lavage.Criteria for identifying unsatisfactory specimens.Acta Cytol 1987;31:599-605.
Ettensohn DB, Jankowski MJ, Duncan PG,Lalor PA. Bronchoalveolar lavage in the normalvolunteer subject. I. Technical aspects andintersubject variability. Chest 1988;94:275-280.https://doi.org/10.1378/chest.94.2.275.
Davis GS, Giancola MS, Costanza MC, LowRB. Analyses of sequential bronchoalveolar lavagesamples from healthy human volunteers.Am Rev Respir Dis 1982;126:611-616.
Thomson RB, Jr. Laboratory diagnosisof respiratory infections. Curr Opin InfectDis 1999;12:115-119. https://doi.org/10.1097/00001432-199904000-00002.
Jourdain B, Joly-Guillou ML, Dombret MC,Calvat S, Trouillet JL, Gibert C, et al. Usefulnessof quantitative cultures of BAL fluid fordiagnosing nosocomial pneumonia in ventilatedpatients. Chest 1997;111:411-418. https://doi.org/10.1378/chest.111.2.411.
Meduri GU, Baselski V. The role of bronchoalveolarlavage in diagnosing nonopportunisticbacterial pneumonia. Chest 1991;100:179-190.https://doi.org/10.1378/chest.100.1.179.
Castella J, Ancochea J, Llorente L, Puzo C, SanchisJ, Sueiro A, et al. Lavado broncoalveolar.Arch Bronconeumol 1997;33:515-526. https://doi.org/10.1016/S0300-2896(15)30534-2.
Norman FF, Chamorro S, Braojos F, López-Miranda E, Chamorro J, González I, et al.Strongyloides in bronchoalveolar lavage fluid:Practical implications in the COVID-19 era. JTravel Med 2021. https://doi.org/10.1093/jtm/taab114.
Fischer PU, Weil GJ. North American paragonimiasis:epidemiology and diagnostic strategies.Expert Rev Anti Infect Ther 2015;13:779-786. https://doi.org/10.1586/14787210.2015.1031745.
González Á, Tobón ÁM. Infecciones micóticasoportunistas en pacientes con VIH/SIDA. Infectio2006;10:279-287.
Decré D, Barbut F, Petit JC. [Role of the microbiologylaboratory in the diagnosis of nosocomialdiarrhea]. Pathol Biol (Paris) 2000;48:733-744.
O'Horo JC, Thompson D, Safdar N. Is theGram stain useful in the microbiologic diagnosisof VAP? A meta-analysis. Clin Infect Dis2012;55:551-561. https://doi.org/10.1093/cid/cis512.
Rea-Neto A, Youssef NC, Tuche F, BrunkhorstF, Ranieri VM, Reinhart K, et al. Diagnosis ofventilator-associated pneumonia: a systematicreview of the literature. Crit Care 2008;12:R56.https://doi.org/10.1186/cc6877.
Papazian L, Klompas M, Luyt CE. Ventilatorassociatedpneumonia in adults: a narrativereview. Intensive Care Med 2020;46:888-906. https://doi.org/10.1007/s00134-020-05980-0.
Corrales-Ramírez LC, Caycedo-Lozano L.Principios físicoquímicos de los colorantes utilizadosen microbiología. Nova 2020;18:73-100.https://doi.org/10.22490/24629448.3701.
Rosati LA, Leslie KO. 6 - Lung infections. In:Leslie KO, Wick MR, eds. Practical PulmonaryPathology: A Diagnostic Approach. 2nd ed.Philadelphia: W.B. Saunders; 2011. p. 137-211.https://doi.org/10.1016/B978-1-4160-5770-3.00006-7.
Acharya B, Acharya A, Gautam S, Ghimire SP,Mishra G, Parajuli N, et al. Advances in diagnosisof tuberculosis: an update into moleculardiagnosis of Mycobacterium tuberculosis.Mol Biol Rep 2020;47:4065-4075. https://doi.org/10.1007/s11033-020-05413-7.
Ahmad M, Ibrahim WH, Sarafandi SA, ShahzadaKS, Ahmed S, Haq IU, et al. Diagnosticvalue of bronchoalveolar lavage in the subset ofpatients with negative sputum/smear and mycobacterialculture and a suspicion of pulmonarytuberculosis. Int J Infect Dis 2019;82:96-101.https://doi.org/10.1016/j.ijid.2019.03.021.
Rincón-Caballero OL, Cano-Romero MA, Aristizábal-Bernal BH. Diagnóstico de tuberculosispulmonar en lavado broncoalveolar: desempeñode la PCR en comparación con las pruebas microbiológicasde rutina. Med Lab 2017;23:475-484. https://doi.org/10.36384/01232576.26.
Sanabria-Delgado EV. Evaluación del desempeñode la prueba Xpert Mtbd/Rif® para ladetección de tuberculosis en un hospital públicode Bucaramanga. Bogotá D.C.: UniversidadCES; 2018. Acceso 15 de marzo de 2021. Disponibleen http://repository.urosario.edu.co/handle/10336/18047.
Trujillo DE, Ortiz S, Pérez O, Cortés CA, CarrilloJA. Abscesos cerebrales por Nocardia spp.en una paciente inmunocompetente. Biomédica2020;40:27-33. https://doi.org/10.7705/biomedica.4925.
Bautista H, Lizarazo J. Nocardiosis diseminadaen una paciente VIH negativa. A propósito de uncaso de difícil tratamiento. Acta Neurol Colomb2015;31:267-273.
Guarner J, Brandt ME. Histopathologic diagnosisof fungal infections in the 21st century. ClinMicrobiol Rev 2011;24:247-280. https://doi.org/10.1128/cmr.00053-10.
Wheat LJ, Azar MM, Bahr NC, Spec A, RelichRF, Hage C. Histoplasmosis. Infect Dis Clin NorthAm 2016;30:207-227. https://doi.org/10.1016/j.idc.2015.10.009.
López CE. Dimorfismo y patogenia de Histoplasmacapsulatum. Rev Argent Microbiol2006;38:235-242.
Centers for Disease Control and Prevention(CDC). Pneumocystis pneumonia. Fungal diseases.Atlanta, USA: Centers for Disease Control and Prevention; 2020. Acceso 18 de abrilde 2021. Disponible en https://www.cdc.gov/fungal/diseases/pneumocystis-pneumonia/index.html.
Rapidmicrobiology. Gomori's methenaminesilver staining kit for fungi detection. Ireland:Rapid Test Methods Ltd, Sigma-Aldrich Corp;2010. Acceso 13 de abril de 2021. Disponibleen https://www.rapidmicrobiology.com/news/gomoris-methenamine-silver-staining-kit-forfungi-detection.
Muñoz CO, Cano LE, González A. Deteccióne identificación de Histoplasma capsulatumpor el laboratorio: de los métodos convencionalesa las pruebas moleculares. Infectio2010;14:s145-s158.
Maniscalchi-Badaoui MT, Lemus-Espinoza D.Mecanismos de evasión de Histoplasma capsulatumen los fagocitos. Rev Soc Ven Microbiol2006;26:6-13.
Cuervo-Maldonado SI, Gómez-Rincón JC,Rivas P, Guevara FO. Actualización en aspergilosiscon énfasis en aspergilosis invasora. Infectio2010;14:131-144. https://doi.org/10.1016/S0123-9392(10)70131-4.
Rodiño J, Rincón N, Aguilar YA, Rueda ZV, HerreraM, Vélez LA. Diagnóstico microscópico deneumonía por Pneumocystis jirovecii en muestrasde lavado broncoalveolar y lavado orofaríngeode pacientes inmunocomprometidos conneumonía. Biomédica 1969;31:222-231. https://doi.org/10.7705/biomedica.v31i2.307.
Raju K. Evolution of Pap Stain. Biomed Res Ther2016;3:6. https://doi.org/10.7603/s40730-016-0006-8.
Ullmann AJ, Aguado JM, Arikan-AkdagliS, Denning DW, Groll AH, Lagrou K, et al.Diagnosis and management of Aspergillusdiseases: executive summary of the 2017ESCMID-ECMM-ERS guideline. Clin MicrobiolInfect 2018;24 Suppl 1:e1-e38. https://doi.org/10.1016/j.cmi.2018.01.002.
Cuenca-Estrella M, Bassetti M, Lass-Flörl C,Rácil Z, Richardson M, Rogers TR. Detectionand investigation of invasive mould disease. JAntimicrob Chemother 2011;66 Suppl 1:i15-24. https://doi.org/10.1093/jac/dkq438.
Cruz R. [Laboratory guidelines for diagnosis of invasivefungal disease caused by filamentous fungi].Rev Chilena Infectol 2014;31:173-179. https://doi.org/10.4067/s0716-10182014000200008.
Mantadakis E. Pneumocystis jirovecii pneumoniain children with hematological malignancies:Diagnosis and approaches to management.J Fungi (Basel) 2020;6:331. https://doi.org/10.3390/jof6040331.
Hayden RT, Uhl JR, Qian X, Hopkins MK,Aubry MC, Limper AH, et al. Direct detectionof Legionella species from bronchoalveolar lavageand open lung biopsy specimens: comparisonof LightCycler PCR, in situ hybridization,direct fluorescence antigen detection,and culture. J Clin Microbiol 2001;39:2618-2626. https://doi.org/10.1128/jcm.39.7.2618-2626.2001.
Fernández-Cruz A, Magira E, Heo ST, EvansS, Tarrand J, Kontoyiannis DP. Bronchoalveolarlavage fluid cytology in culture-documentedinvasive pulmonary aspergillosis in patientswith hematologic diseases: Analysis of 67 episodes.J Clin Microbiol 2018;56. https://doi.org/10.1128/jcm.00962-18.
Roży A, Duk K, Szumna B, Skrońska P, GawrylukD, Chorostowska-Wynimko J. Effectivenessof PCR and immunofluorescence techniquesfor detecting human cytomegalovirus inblood and bronchoalveolar lavage fluid. AdvExp Med Biol 2016;921:21-26. https://doi.org/10.1007/5584_2016_246.
Davidson KR, Ha DM, Schwarz MI, Chan ED.Bronchoalveolar lavage as a diagnostic procedure:a review of known cellular and molecularfindings in various lung diseases. J Thorac Dis2020;12:4991-5019.
Musher B, Fredricks D, Leisenring W, BalajeeSA, Smith C, Marr KA. Aspergillus galactomannanenzyme immunoassay and quantitativePCR for diagnosis of invasive aspergillosis withbronchoalveolar lavage fluid. J Clin Microbiol2004;42:5517-5522. https://doi.org/10.1128/jcm.42.12.5517-5522.2004.
Jacobs JA, Stobberingh EE, CornelissenEIM, Drent M. Detection of Streptococcuspneumoniae antigen in bronchoalveolar lavagefluid samples by a rapid immunochromatographicmembrane assay. J Clin Microbiol2005;43:4037-4040. https://doi.org/10.1128/JCM.43.8.4037-4040.2005.
Scharmann U, Verhasselt HL, Kirchhoff L, BuerJ, Rath PM, Steinmann J, et al. Evaluation of twolateral flow assays in BAL fluids for the detectionof invasive pulmonary aspergillosis: A retrospectivetwo-centre study. Mycoses 2020;63:1362-1367. https://doi.org/10.1111/myc.13176.
Barrera-Ramírez L, Drago-Serrano M, Pérez-Ramos J, Sainz Espuñes T, Zamora A, Gómez-Arroyo F, et al. Citometría de flujo: vínculo entrela investigación básica y la aplicación clínica.Rev Inst Nal Enf Resp Mex 2004;17:42-55.
McKinnon KM. Flow cytometry: An overview.Curr Protoc Immunol 2018;120:5.1.1-5.1.11.https://doi.org/10.1002/cpim.40.
Alvarez-Barrientos A, Arroyo J, Cantón R,Nombela C, Sánchez-Pérez M. Applicationsof flow cytometry to clinical microbiology. Clinicalmicrobiology reviews 2000;13:167-195.https://doi.org/10.1128/CMR.13.2.167.
Huang W, Berube J, McNamara M, SaksenaS, Hartman M, Arshad T, et al. Lymphocytesubset counts in COVID-19 patients: Ameta-analysis. Cytometry A 2020;97:772-776.https://doi.org/10.1002/cyto.a.24172.
Mok JH, Eom JS, Jo EJ, Kim MH, Lee K, KimKU, et al. Clinical utility of rapid pathogenidentification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometryin ventilated patients with pneumonia:A pilot study. Respirology 2016;21:321-328.https://doi.org/10.1111/resp.12677.
Ullberg M, Lüthje P, Mölling P, Strålin K,Özenci V. Broad-range detection of microorganismsdirectly from bronchoalveolar lavagespecimens by PCR/Electrospray Ionization-MassSpectrometry. PLoS One 2017;12:e0170033.https://doi.org/10.1371/journal.pone.0170033.
Ragupathi NKD, Bakthavatchalam YD,Mathur P, Pragasam AK, Walia K, Ohri VC,et al. Plasmid profiles among some ESKAPEpathogens in a tertiary care centre in southIndia. Indian J Med Res 2019;149:222-231.https://doi.org/10.4103/ijmr.IJMR_2098_17.
Li Y, Sun B, Tang X, Liu YL, He HY, Li XY, et al.Application of metagenomic next-generationsequencing for bronchoalveolar lavage diagnosticsin critically ill patients. Eur J Clin MicrobiolInfect Dis 2020;39:369-374. https://doi.org/10.1007/s10096-019-03734-5.
Pendleton KM, Erb-Downward JR, Bao Y,Branton WR, Falkowski NR, Newton DW, etal. Rapid pathogen identification in bacterialpneumonia using real-time metagenomics. AmJ Respir Crit Care Med 2017;196:1610-1612.https://doi.org/10.1164/rccm.201703-0537LE.
Young JC, Chehoud C, Bittinger K, BaileyA, Diamond JM, Cantu E, et al. Viral metagenomicsreveal blooms of anelloviruses in therespiratory tract of lung transplant recipients.Am J Transplant 2015;15:200-209. https://doi.org/10.1111/ajt.13031.
Schneeberger PHH, Prescod J, Levy L,Hwang D, Martinu T, Coburn B. Microbiotaanalysis optimization for human bronchoalveolarlavage fluid. Microbiome 2019;7:141.https://doi.org/10.1186/s40168-019-0755-x.
Jahromi R, Avazpour A, Jahromi M, AlaviJ. COVID-19 with positive bronchoalveolarlavage fluid but negative nasopharyngealand oropharyngeal swabs: A case report andinsights. Indian J Case Reports 2020;6:380-382. https://doi.org/10.32677/IJCR.2020.v06.i07.010.
Baron A, Hachem M, Tran Van Nhieu J, BotterelF, Fourati S, Carteaux G, et al. Bronchoalveolarlavage in patients with COVID-19with invasive mechanical ventilation for acuterespiratory distress syndrome. Ann Am ThoracSoc 2021;18:723-726. https://doi.org/10.1513/AnnalsATS.202007-868RL.
Kadmon G, Levy I, Mandelboim M, NahumE, Stein J, Dovrat S, et al. Polymerase-chainreaction-based diagnosis of viral pulmonaryinfections in immunocompromised children.Acta Paediatr 2013;102:e263-268. https://doi.org/10.1111/apa.12207.
Ogimi C, Waghmare AA, Kuypers JM, Xie H,Yeung CC, Leisenring WM, et al. Clinical significanceof human coronavirus in bronchoalveolarlavage samples from hematopoietic cell transplantrecipients and patients with hematologicmalignancies. Clin Infect Dis 2017;64:1532-1539. https://doi.org/10.1093/cid/cix160.
Bogoch, II, Andrews JR, Zachary KC, HohmannEL. Diagnosis of influenza from lowerrespiratory tract sampling after negative upperrespiratory tract sampling. Virulence 2013;4:82-84. https://doi.org/10.4161/viru.22466.
Hogan C, Caya C, Papenburg J. Rapid andsimple molecular tests for the detection of respiratorysyncytial virus: a review. Expert Rev MolDiagn 2018;18:617-629. https://doi.org/10.1080/14737159.2018.1487293.
Linssen CF, Jacobs JA, Stelma FF, van MookWN, Terporten P, Vink C, et al. Herpes simplexvirus load in bronchoalveolar lavage fluidis related to poor outcome in critically ill patients.Intensive Care Med 2008;34:2202-2209.https://doi.org/10.1007/s00134-008-1231-4.
Kerschner H, Jaksch P, Zweytick B, Puchhammer-Stöckl E. Detection of human cytomegalovirusin bronchoalveolar lavage fluid of lungtransplant recipients reflects local virus replicationand not contamination from the throat. JClin Microbiol 2010;48:4273-4274. https://doi.org/10.1128/jcm.01197-10.
Gámez SS, Ruiz MP, Navarro Marí JM. Infecciónpor citomegalovirus humano. Enferm InfeccMicrobiol Clin 2014;32:15-22.
Schmitt BH, Sloan LM, Patel R. Real-time PCRdetection of Mycoplasma pneumoniae in respiratoryspecimens. Diagn Microbiol Infect Dis2013;77:202-205. https://doi.org/10.1016/j.diagmicrobio.2013.07.016.
Patterson C, Lipman M, Mack D, McHugh T.Who gets a laboratory positive diagnosis ofMycoplasma pneumoniae: A 10-year retrospectiveanalysis. Clin Infect Pract 2021;10:100070.https://doi.org/10.1016/j.clinpr.2021.100070.
Kumar S, Kashyap B, Kumar S, Kapoor S. Diagnosticutility of serology and polymerase chain reactionfor detection of Mycoplasma pneumoniaeand Chlamydophila pneumoniae in paediatriccommunity-acquired lower respiratory tract infections.Indian J Med Microbiol 2020;38:152-156.https://doi.org/10.4103/ijmm.IJMM_20_145.
González-Bertolín I, Ochoa-Fernández BM,Bloise I, de Ceano-Vivas-La Calle M, Ruíz-Domínguez JA. PCR urgente de Bordetella enlactantes menores de 3 meses, una herramientaútil en el servicio de urgencias pediátricas.Enferm Infecc Microbiol Clin 2021;39:174-178.https://doi.org/10.1016/j.eimc.2020.04.008.
Tsao TC, Chen CH, Hong JH, Hsieh MJ, TsaoKC, Lee CH. Shifts of T4/T8 T lymphocytes fromBAL fluid and peripheral blood by clinical gradein patients with pulmonary tuberculosis. Chest2002;122:1285-1291. https://doi.org/10.1378/chest.122.4.1285.
Perng CL, Chen HY, Chiueh TS, Wang WY,Huang CT, Sun JR. Identification of non-tuberculousmycobacteria by real-time PCR coupledwith a high-resolution melting system. JMed Microbiol 2012;61:944-951. https://doi.org/10.1099/jmm.0.042424-0.
Balajee SA, Marr KA. Phenotypic and genotypicidentification of human pathogenic aspergilli.Future Microbiol 2006;1:435-445. https://doi.org/10.2217/17460913.1.4.435.
Guegan H, Robert-Gangneux F. Moleculardiagnosis of Pneumocystis pneumonia in immunocompromisedpatients. Curr Opin InfectDis 2019;32:314-321. https://doi.org/10.1097/qco.0000000000000559.
Vasconcellos I, Dalla Lana DF, PasqualottoAC. The role of molecular tests in the diagnosisof disseminated histoplasmosis. J Fungi2019;6. https://doi.org/10.3390/jof6010001.
Dethlefsen L, McFall-Ngai M, Relman DA.An ecological and evolutionary perspective onhuman-microbe mutualism and disease. Nature2007;449:811-818. https://doi.org/10.1038/nature06245.
Leo S, Gaïa N, Ruppé E, Emonet S, Girard M,Lazarevic V, et al. Detection of bacterial pathogensfrom broncho-alveolar lavage by nextgenerationsequencing. Int J Mol Sci 2017;18.https://doi.org/10.3390/ijms18092011.
Hahn A, Warnken S, Pérez-Losada M, FreishtatRJ, Crandall KA. Microbial diversity withinthe airway microbiome in chronic pediatric lungdiseases. Infect Genet Evol 2018;63:316-325.https://doi.org/10.1016/j.meegid.2017.12.006.
Lee SH, Sung JY, Yong D, Chun J, Kim SY,Song JH, et al. Characterization of microbiomein bronchoalveolar lavage fluid of patients withlung cancer comparing with benign mass likelesions. Lung Cancer 2016;102:89-95. https://doi.org/10.1016/j.lungcan.2016.10.016.
Gao M, Wang K, Yang M, Meng F, Lu R,Zhuang H, et al. Transcriptome analysis ofbronchoalveolar lavage fluid from children withMycoplasma pneumoniae pneumonia revealsnatural killer and t cell-proliferation responses.Front Immunol 2018;9:1403. https://doi.org/10.3389/fimmu.2018.01403.