invited commentary

1
33. Cunha BA. Cytomegalovirus pneumonia: community- acquired pneumonia in immunocompetent hosts. Infect Dis Clin North Am 2010;24:147–58. 34. Chiche L, Forel JM, Roch A, et al. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med 2009;37:1850 –7. 35. Jaber S, Chanques G, Borry J, et al. Cytomegalovirus infec- tion in critically ill patients: associated factors and conse- quences. Chest 2005;127:233– 41. 36. Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 2008;300:413–22. 37. Simon CO, Seckert CK, Dreis D, Reddehase MJ, Grzimek NK. Role for tumor necrosis factor alpha in murine cytomeg- alovirus transcriptional reactivation in latently infected lungs. J Virol 2005;79:326 – 40. 38. Cook CH, Zhang Y, Sedmak DD, Martin LC, Jewell S, Ferguson RM. Pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice. Crit Care Med 2006;34:842–9. 39. Hummel M, Abecassis MM. A model for reactivation of CMV from latency. J Clin Virol 2002;25:123–36. 40. Sinclair J, Sissons P. Latency and reactivation of human cytomegalovirus. J Gen Virol 2006;87:1763–79. INVITED COMMENTARY The article by D’Journo and colleagues [1] is a prospec- tive study about the molecular detection of microorgan- isms in distal airways of patients undergoing major lung resection for lung cancer. The samples were taken from the resected specimen through guided bronchoalveolar lavage (BAL) or tissue biopsy. Microbiologic analysis was undertaken through a standardized protocol of DNA and RNA extraction for polymerase chain reaction (PCR) sequencing and amplification. Among the 87 consecutive patients included in the study, 13 (15%) had a PCR-positive test for cytomegalo- virus (CMV). No tests resulted positive for encapsulated bacteria. A higher frequency of respiratory complications developed in these positive patients compared with neg- ative patients. In particular, their rate of postoperative pneumonia was as high as 31% vs 8% in the negative patients. PCR positivity remained an independent signif- icant factor associated with postoperative respiratory complications after multivariable analysis. The authors concluded that a culture-independent molecular evaluation can be a reliable biologic marker for early detection of patients at high risk for pulmonary complications. The possibility to detect patients at risk for postoperative respiratory events at the time of their operation by using a relatively inexpensive test with sufficient sensitivity and specificity appears intriguing. The analysis, however, has some limitations. Thus, the results need to be interpreted with caution, and no definitive conclusion should be inferred by this work. As honestly admitted by the authors, the sample size was relatively small. Even worse, the number of events was small— only 27 pulmonary complications—making the final multivariable model (including the three predictors) likely overfitted. The inclusion of sputum retention and atelectasis in the list of respiratory complications is questionable. In fact, the link between CMV colonization and atelectasis appears far-fetched. The data on pneumonia are cer- tainly more logical; however, this complication occurred in only 10 patients, 4 of whom had PCR-positive findings. Of the 13 PCR-positive patients, pneumonia occurred in 3, and only 1 of them had postoperative polymicrobial bronchoscopic samples that were positive. The associa- tion between PCR-CMV positivity and postoperative pulmonary infection therefore remains still unclear. To complicate further the matter, no concomitant sam- ple was taken from the larger airways at the time of the operation. It would have been interesting to know if there was an association between distal lung viral infection and proximal airway bacterial infection. Nevertheless, the concept of latent viral infection activation due to an immunosuppressive effect of the operation or cancer status leading to postoperative pulmonary dysfunction and secondary pneumonia is provocative and warrants further investigation. Among the open questions are: What is the clinical implication of this analysis? How should we manage the PCR-CMV–positive patients? Should we individualize their antimicrobial prophylaxis? If so, which drugs should be used if the results of most of the postoperative bronchoscopic samples were negative? Should we then use antiviral agents? The authors must be commended for their vision and for their inspiring contribution. Hopefully, they will ex- pand and refine their analysis to clarify the outstanding issues of this important contribution. Alessandro Brunelli, MD Division of Thoracic Surgery Ospedali Riuniti Ancona Via Conca 1 60020 Ancona, Italy e-mail: [email protected] Reference 1. D’Journo XB, Bittar F, Trousse D, et al. Molecular detection of microorganisms in distal airways of patients undergoing lung cancer surgery. Ann Thorac Surg 2012;93;413–22. 422 D’JOURNO ET AL Ann Thorac Surg AIRWAYS COLONIZATION IN LUNG CANCER SURGERY 2012;93:413–22 © 2012 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2011.10.008 GENERAL THORACIC

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Page 1: Invited Commentary

422 D’JOURNO ET AL Ann Thorac SurgAIRWAYS COLONIZATION IN LUNG CANCER SURGERY 2012;93:413–22

GEN

ERA

LT

HO

RA

CIC

33. Cunha BA. Cytomegalovirus pneumonia: community-acquired pneumonia in immunocompetent hosts. Infect DisClin North Am 2010;24:147–58.

34. Chiche L, Forel JM, Roch A, et al. Active cytomegalovirusinfection is common in mechanically ventilated medicalintensive care unit patients. Crit Care Med 2009;37:1850–7.

35. Jaber S, Chanques G, Borry J, et al. Cytomegalovirus infec-tion in critically ill patients: associated factors and conse-quences. Chest 2005;127:233–41.

36. Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus

reactivation in critically ill immunocompetent patients.JAMA 2008;300:413–22.

in only 10 patients, 4 of whom had PCR-positive findings.

© 2012 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

37. Simon CO, Seckert CK, Dreis D, Reddehase MJ, GrzimekNK. Role for tumor necrosis factor alpha in murine cytomeg-alovirus transcriptional reactivation in latently infectedlungs. J Virol 2005;79:326–40.

38. Cook CH, Zhang Y, Sedmak DD, Martin LC, Jewell S,Ferguson RM. Pulmonary cytomegalovirus reactivationcauses pathology in immunocompetent mice. Crit Care Med2006;34:842–9.

39. Hummel M, Abecassis MM. A model for reactivation ofCMV from latency. J Clin Virol 2002;25:123–36.

40. Sinclair J, Sissons P. Latency and reactivation of humancytomegalovirus. J Gen Virol 2006;87:1763–79.

INVITED COMMENTARY

The article by D’Journo and colleagues [1] is a prospec-tive study about the molecular detection of microorgan-isms in distal airways of patients undergoing major lungresection for lung cancer. The samples were taken fromthe resected specimen through guided bronchoalveolarlavage (BAL) or tissue biopsy. Microbiologic analysis wasundertaken through a standardized protocol of DNA andRNA extraction for polymerase chain reaction (PCR)sequencing and amplification.

Among the 87 consecutive patients included in thestudy, 13 (15%) had a PCR-positive test for cytomegalo-virus (CMV). No tests resulted positive for encapsulatedbacteria. A higher frequency of respiratory complicationsdeveloped in these positive patients compared with neg-ative patients. In particular, their rate of postoperativepneumonia was as high as 31% vs 8% in the negativepatients. PCR positivity remained an independent signif-icant factor associated with postoperative respiratorycomplications after multivariable analysis.

The authors concluded that a culture-independentmolecular evaluation can be a reliable biologic markerfor early detection of patients at high risk for pulmonarycomplications. The possibility to detect patients at risk forpostoperative respiratory events at the time of theiroperation by using a relatively inexpensive test withsufficient sensitivity and specificity appears intriguing.

The analysis, however, has some limitations. Thus, theresults need to be interpreted with caution, and nodefinitive conclusion should be inferred by this work. Ashonestly admitted by the authors, the sample size wasrelatively small. Even worse, the number of events wassmall—only 27 pulmonary complications—making thefinal multivariable model (including the three predictors)likely overfitted.

The inclusion of sputum retention and atelectasis inthe list of respiratory complications is questionable. Infact, the link between CMV colonization and atelectasisappears far-fetched. The data on pneumonia are cer-tainly more logical; however, this complication occurred

Of the 13 PCR-positive patients, pneumonia occurred in3, and only 1 of them had postoperative polymicrobialbronchoscopic samples that were positive. The associa-tion between PCR-CMV positivity and postoperativepulmonary infection therefore remains still unclear.

To complicate further the matter, no concomitant sam-ple was taken from the larger airways at the time of theoperation. It would have been interesting to know if therewas an association between distal lung viral infection andproximal airway bacterial infection. Nevertheless, theconcept of latent viral infection activation due to animmunosuppressive effect of the operation or cancerstatus leading to postoperative pulmonary dysfunctionand secondary pneumonia is provocative and warrantsfurther investigation.

Among the open questions are: What is the clinicalimplication of this analysis? How should we manage thePCR-CMV–positive patients? Should we individualizetheir antimicrobial prophylaxis? If so, which drugsshould be used if the results of most of the postoperativebronchoscopic samples were negative? Should we thenuse antiviral agents?

The authors must be commended for their vision andfor their inspiring contribution. Hopefully, they will ex-pand and refine their analysis to clarify the outstandingissues of this important contribution.

Alessandro Brunelli, MD

Division of Thoracic SurgeryOspedali Riuniti AnconaVia Conca 160020 Ancona, Italye-mail: [email protected]

Reference

1. D’Journo XB, Bittar F, Trousse D, et al. Molecular detection ofmicroorganisms in distal airways of patients undergoing lung

cancer surgery. Ann Thorac Surg 2012;93;413–22.

0003-4975/$36.00doi:10.1016/j.athoracsur.2011.10.008