1164
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
5. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ, Van de Heyning PH. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013; 22:348–355. Copyright ª 2013 by the American Thoracic Society
Importance of Onsite Cytopathology at Endobronchial Ultrasound To the Editor:
We read with interest the article by Navani and colleagues (1), which demonstrates well that samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA) can be used to subtype and genotype non–small cell lung cancer (NSCLC). However, we are keen to point out that their techniques used to obtain the sample may not necessarily be delivering the best yields for further investigations. In contrast to the authors, we use rapid onsite evaluation by a cytopathologist (ROSE) to help triage samples, which is effective both for tuberculosis (TB) molecular diagnostics and culture and for optimal cancer immunophenotyping and molecular diagnostics. In their study, 241 patients with either “lymphoid cells only” or insufficient sample seen in the cell block (i.e., a nondiagnostic aspirate) were thought not to have cancer by EBUS-TBNA. Of these, 69 (w1 in 3) went on to have a diagnosis of cancer within 6 months. In this “nondiagnostic” group, we believe ROSE should play a pivotal role. ROSE enables continued sampling of the nodes until a diagnosis is achieved on a direct smear. Further sampling is then possible to ensure adequate material for immunocytochemistry (ICC), and genotyping is taken. In contrast, in the current study there was no bedside analysis, and only one section of the cell block was examined. Of the lung cancer cases in this study, 23% (101 of 434) had a final diagnosis of NSCLC-not otherwise specified (NOS). Of this group, only 52% had ICC performed. Given that ICC is the one variable identified in this study that predicts the category NSCLC-NOS, all samples ideally should have ICC. In our institution, all EBUSTBNA samples diagnosed as NSCLC would generally go on to have ICC, and if adenocarcinoma is seen on morphological stains, then epidermal growth factor receptor analysis is requested. The samples we obtain using ROSE are bedside smeared and stained with DiffQuick and then the liquid needle washing samples are cytospun for the ICC slides and the remainder prepared as a cell block. Using ROSE in our center, of 352 patients undergoing an EBUS procedure, 102 patients were suspected of having NSCLC (unpublished data). Of these, 28 did not have a diagnosis of malignancy on EBUS. Three of these patients were referrals from peripheral hospitals and were lost to follow-up; three patients had a diagnosis of NSCLC by bronchial biopsy or transbronchial biopsy in the same procedure as EBUS; 20 were true negatives with an alternative diagnosis; and two patients went on to have malignancy over a 6-month period. Overall this gives a false-negative rate of 9.1%. Of our 74 patients with malignant cells diagnosed at EBUS, 24 were given a label of NSCLC-NOS on Diff-Quik staining at the bedside. However, the final diagnosis of NSCLC-NOS was only given in two patients or 3% of the 61 malignant cases that were lung cancers. Nineteen of the 24 NSCLC-NOS cases had ICC, which in one case did not help define the cancer beyond NSCLC-NOS. Three patients had a specific diagnosis of a nonlung primary after ICC. Of the five cases that did not have ICC, one patient had ICC performed on cells from a bronchoalveolar lavage performed at the time; two patients had a morphological diagnosis * Joint first authors.
VOL 188
2013
of squamous cell carcinoma, which was made on Giemsa staining of the direct preparations and Papanicolaou staining of the needle washings, both of which give more detail than Diff-Quik staining; and two patients were left with a diagnosis of NSCLC-NOS. Rossi emphasized the role of the pathologist in optimizing the use of tumor material for diagnostic purposes and ideally leaving remaining tissue for research (2). We argue that this role should begin at the bedside. First, the pathologist can ensure that the amount of tissue sampled is maximized by directing the endoscopist to resample the most successful target. Second, the bedside diagnosis prevents material being sent for inappropriate auxiliary investigations such as TB polymerase chain reaction and culture. Furthermore, only 197 of 1047 nodes sampled were from stations 10 and 11 in this study, with the majority being from stations 7 and 4R, where the average node size was large (.2 cm), and therefore less likely to benefit from ROSE as these stations and node sizes are more accessible. The node stations less frequently sampled were smaller and less well-represented in this study but are likely to benefit more from ROSE. Further studies are needed to compare the adequacy of sampling and triaging for diagnostics with and without ROSE, before deciding on specific methodologies. Therefore, at this stage, centers using ROSE should audit their own practice before deciding that no ROSE is required. Author disclosures are available with the text of this letter at www.atsjournals.org.
Clare Elizabeth Honor Craig, B.M.B.Ch.* Melissa Wickremasinghe, M.B.B.S., Ph.D.* Lydia Finney, M.B.B.Ch., B.Sc. Corrina B. Wright, M.B.B.Ch.B.A.O. Matthew Berry, M.B.B.Chir., Ph.D. Onn Min Kon, M.B.B.S., M.D. Imperial College Healthcare NHS Trust London, United Kingdom References 1. Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Vandana J, Munavvar M, Ng BN, Rassl DM, Falzon M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012;185:1316–1322. 2. Rossi G. Wanted: lung cancer pathologists. Am J Respir Crit Care Med 2013;187:450. Copyright ª 2013 by the American Thoracic Society
Reply: Optimum Performance of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration From the Authors:
We thank Dr. Craig and colleagues for their interest in our article on the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens for the phenotyping and genotyping of non–small cell lung cancer (1). Dr. Craig and colleagues raise the issue of the value of rapid onsite evaluation (ROSE) by a cytopathologist and suggest that the techniques used in our article may not be yielding the best results for our patients. We disagree. Dr. Craig and colleagues overstate clinical conclusions based on a single-center retrospective uncontrolled series and choose to omit available published data from randomized controlled trials of ROSE. Furthermore, their assertion that ROSE may be superior to no ROSE is not supported by the selected data they present. The
Correspondence
sensitivity of EBUS-TBNA with ROSE in their institution was 90.9% and therefore not different from the sensitivity reported using EBUSTBNA in our article. They state that all non–small cell lung cancer– not otherwise specified (NSCLC-NOS) samples in their institution have immunocytochemistry (ICC) performed. However, in their illustrative retrospective cohort, only 19 of 24 NSCLC-NOS cases underwent ICC, implying that 21% of cases of NSCLC-NOS were inadequate for further testing despite ROSE. In our multicenter study of 774 patients, 101 had a diagnosis of NSCLC-NOS and in only 6 patients was immunohistochemistry not possible. Dr. Craig and colleagues unfortunately also do not refer to the randomized controlled trials of ROSE that also do not support its routine use. Even in patients undergoing conventional TBNA, the presence of ROSE does not appear to improve yield (2). In a randomized controlled trial of patients undergoing EBUS-TBNA with and without ROSE, the sensitivity was not significantly different between the arms (3). Dr. Craig and colleagues also suggest that the presence of malignant cells in one lymph node station as assessed by ROSE can preclude further investigation of other diagnoses such as tuberculosis in other lymph node stations. This is certainly not our practice in our high-tuberculosis-prevalence region (4). Dr. Craig and colleagues suggest some potential advantages of ROSE. They omit that it may improve the negative predictive value of a negative EBUS sample; however, they also do not include any potential disadvantages that must also be considered. For example, the process of ROSE will use up vital tissue that could be better used for further tumor characterization in the laboratory. The number of passes submitted to the pathologist in the room before a lymph node is labeled as benign is unknown, and the risk of false-positive diagnoses in the bronchoscopy suite must also be clarified. The cost-effectiveness of ROSE is also unknown; however, the number of cases reported by a pathologist in an EBUS session is less than if the equivalent time was spent in the cytology laboratory. Routine use of ROSE will have enormous impact on pathology service provision and costs to the United Kingdom National Health Service. Dr. Craig and colleagues’ analysis of our data (225 patients with “lymphoid cells only” on EBUS-TBNA) also highlights a key point surrounding terminology of EBUS-TBNA samples. Dr. Craig and colleagues refer to this group of patients with lymphoid cells only or an inadequate sample as the “nondiagnostic” group. We believe this is an unhelpful and inaccurate term and should be restricted to the group of patients where EBUS-TBNA has provided an insufficient sample only. Lymphoid cells only may be entirely diagnostic of a reactive lymph node, which was the final diagnosis in 71% in this group. We currently classify these results as negative, appreciating that this negative result may be diagnostic (true negative) or a false negative if malignancy is subsequently confirmed. We agree with the authors that when a phenotypic diagnosis is not clear on initial assessment, ICC plays an important role in subtyping, and it is also our routine practice that this is performed as well as epidermal growth factor receptor mutation testing where appropriate. In addition to the tests routinely used in Dr. Craig and colleagues’ institution, we routinely analyze adenocarcinomas for the EML4-ALK gene rearrangement and are about to embark on multiplex testing of lung cancers, with a view to aiding recruitment to early-phase clinical trials. This emphasizes the pressure that specimens from EBUS-TBNA are likely to be subjected to in the future and highlights that using specimen at the bedside for ROSE may not be the best use of lung cancer tissue. The evidence is not currently available to suggest that ROSE is effective or cost-effective, and therefore, we do not agree with Dr. Craig and colleagues’ conclusion that availability of ROSE should be default. Although we agree that ROSE is helpful in the learning phase of the procedure (5), a recommendation for
1165
routine use of ROSE will add to the already high capital costs of embarking on EBUS-TBNA and may deter further centers from being commissioned. Finally, we agree that all EBUS-TBNA services should be subject to audit with a review of service specifications if standards are not being met. Author disclosures are available with the text of this letter at www.atsjournals.org.
Neal Navani, M.B.B.S., M.A., M.Sc., Ph.D. Sam M. Janes, M.B.B.S., M.Sc., Ph.D. University College London Hospital London, United Kingdom and University College London London, United Kingdom
References 1. Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Jeebun V, Munavvar M, Ng BJ, Rassl DM, Falzon M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012;185:1316–1322. 2. Trisolini R, Cancellieri A, Tinelli C, Paioli D, Scudeller L, Casadei GP, Parri SF, Livi V, Bondi A, Boaron M, et al. Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial. Chest 2011;139:395–401. 3. Oki M, Saka H, Kitagawa C, Kogure Y, Murata N, Adachi T, Ando M. Rapid on-site cytologic evaluation during endobronchial ultrasoundguided transbronchial needle aspiration for diagnosing lung cancer: a randomized study. Respiration 2013;85:486–492. 4. Navani N, Molyneaux PL, Breen RA, Connell DW, Jepson A, Nankivell M, Brown JM, Morris-Jones S, Ng B, Wickremasinghe M, et al. Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study. Thorax 2011;66:889–893. 5. Navani N, Nankivell M, Nadarajan P, Pereira SP, Kocjan G, Janes SM. The learning curve for EBUS-TBNA. Thorax 2011;66:352–353. Copyright ª 2013 by the American Thoracic Society
Rhinovirus and Asthma: Reinfection, Not Persistence To the Editor:
Asthma and viruses share a strong relationship. Viruses are the major source of exacerbations, and rhinoviruses are most frequently detected, especially in patients with allergies (1, 2). Repeated rhinovirus detection has been demonstrated in patients with asthma, even in the stable state (3). Some authors have suggested that this may be due to persistent rhinovirus infection (4–6). Several studies have shown abnormalities in the innate immune response to viruses in patients with asthma, especially deficient IFN I and III production (7–9). Increased rhinovirus replication has also been suggested (7). Supported by a Socie´te´ Franc¸aise d’Allergologie grant, a Socie´te´ de Pneumologie de Langue Franc¸aise (Comite´ National des Maladies Respiratoires) grant, and a Conseil Re´gional du Nord-Pas de Calais grant. The study was approved by the Lille University Hospital ethics committee (CPP Nord Ouest IV, 2007A01425-48). Author Contributions: Conception and design: A. Deschildre, P.G., I.T.-L., I.E., A. Dewilde, G.P., and C.T. Performed the experiments: P.G., C.M., I.E., and A. Dewilde. Recorded data: A. Deschildre, C.M., C.T., and G.P. Analysis and interpretation: A. Deschildre, P.G., I.T.-L., I.E., and A. Dewilde. Drafting the manuscript for important intellectual content: A. Deschildre, I.E., C.M., P.G., and I.T.-L.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
5. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ, Van de Heyning PH. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013; 22:348–355. Copyright ª 2013 by the American Thoracic Society
Importance of Onsite Cytopathology at Endobronchial Ultrasound To the Editor:
We read with interest the article by Navani and colleagues (1), which demonstrates well that samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA) can be used to subtype and genotype non–small cell lung cancer (NSCLC). However, we are keen to point out that their techniques used to obtain the sample may not necessarily be delivering the best yields for further investigations. In contrast to the authors, we use rapid onsite evaluation by a cytopathologist (ROSE) to help triage samples, which is effective both for tuberculosis (TB) molecular diagnostics and culture and for optimal cancer immunophenotyping and molecular diagnostics. In their study, 241 patients with either “lymphoid cells only” or insufficient sample seen in the cell block (i.e., a nondiagnostic aspirate) were thought not to have cancer by EBUS-TBNA. Of these, 69 (w1 in 3) went on to have a diagnosis of cancer within 6 months. In this “nondiagnostic” group, we believe ROSE should play a pivotal role. ROSE enables continued sampling of the nodes until a diagnosis is achieved on a direct smear. Further sampling is then possible to ensure adequate material for immunocytochemistry (ICC), and genotyping is taken. In contrast, in the current study there was no bedside analysis, and only one section of the cell block was examined. Of the lung cancer cases in this study, 23% (101 of 434) had a final diagnosis of NSCLC-not otherwise specified (NOS). Of this group, only 52% had ICC performed. Given that ICC is the one variable identified in this study that predicts the category NSCLC-NOS, all samples ideally should have ICC. In our institution, all EBUSTBNA samples diagnosed as NSCLC would generally go on to have ICC, and if adenocarcinoma is seen on morphological stains, then epidermal growth factor receptor analysis is requested. The samples we obtain using ROSE are bedside smeared and stained with DiffQuick and then the liquid needle washing samples are cytospun for the ICC slides and the remainder prepared as a cell block. Using ROSE in our center, of 352 patients undergoing an EBUS procedure, 102 patients were suspected of having NSCLC (unpublished data). Of these, 28 did not have a diagnosis of malignancy on EBUS. Three of these patients were referrals from peripheral hospitals and were lost to follow-up; three patients had a diagnosis of NSCLC by bronchial biopsy or transbronchial biopsy in the same procedure as EBUS; 20 were true negatives with an alternative diagnosis; and two patients went on to have malignancy over a 6-month period. Overall this gives a false-negative rate of 9.1%. Of our 74 patients with malignant cells diagnosed at EBUS, 24 were given a label of NSCLC-NOS on Diff-Quik staining at the bedside. However, the final diagnosis of NSCLC-NOS was only given in two patients or 3% of the 61 malignant cases that were lung cancers. Nineteen of the 24 NSCLC-NOS cases had ICC, which in one case did not help define the cancer beyond NSCLC-NOS. Three patients had a specific diagnosis of a nonlung primary after ICC. Of the five cases that did not have ICC, one patient had ICC performed on cells from a bronchoalveolar lavage performed at the time; two patients had a morphological diagnosis * Joint first authors.
VOL 188
2013
of squamous cell carcinoma, which was made on Giemsa staining of the direct preparations and Papanicolaou staining of the needle washings, both of which give more detail than Diff-Quik staining; and two patients were left with a diagnosis of NSCLC-NOS. Rossi emphasized the role of the pathologist in optimizing the use of tumor material for diagnostic purposes and ideally leaving remaining tissue for research (2). We argue that this role should begin at the bedside. First, the pathologist can ensure that the amount of tissue sampled is maximized by directing the endoscopist to resample the most successful target. Second, the bedside diagnosis prevents material being sent for inappropriate auxiliary investigations such as TB polymerase chain reaction and culture. Furthermore, only 197 of 1047 nodes sampled were from stations 10 and 11 in this study, with the majority being from stations 7 and 4R, where the average node size was large (.2 cm), and therefore less likely to benefit from ROSE as these stations and node sizes are more accessible. The node stations less frequently sampled were smaller and less well-represented in this study but are likely to benefit more from ROSE. Further studies are needed to compare the adequacy of sampling and triaging for diagnostics with and without ROSE, before deciding on specific methodologies. Therefore, at this stage, centers using ROSE should audit their own practice before deciding that no ROSE is required. Author disclosures are available with the text of this letter at www.atsjournals.org.
Clare Elizabeth Honor Craig, B.M.B.Ch.* Melissa Wickremasinghe, M.B.B.S., Ph.D.* Lydia Finney, M.B.B.Ch., B.Sc. Corrina B. Wright, M.B.B.Ch.B.A.O. Matthew Berry, M.B.B.Chir., Ph.D. Onn Min Kon, M.B.B.S., M.D. Imperial College Healthcare NHS Trust London, United Kingdom References 1. Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Vandana J, Munavvar M, Ng BN, Rassl DM, Falzon M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012;185:1316–1322. 2. Rossi G. Wanted: lung cancer pathologists. Am J Respir Crit Care Med 2013;187:450. Copyright ª 2013 by the American Thoracic Society
Reply: Optimum Performance of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration From the Authors:
We thank Dr. Craig and colleagues for their interest in our article on the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens for the phenotyping and genotyping of non–small cell lung cancer (1). Dr. Craig and colleagues raise the issue of the value of rapid onsite evaluation (ROSE) by a cytopathologist and suggest that the techniques used in our article may not be yielding the best results for our patients. We disagree. Dr. Craig and colleagues overstate clinical conclusions based on a single-center retrospective uncontrolled series and choose to omit available published data from randomized controlled trials of ROSE. Furthermore, their assertion that ROSE may be superior to no ROSE is not supported by the selected data they present. The
Correspondence
sensitivity of EBUS-TBNA with ROSE in their institution was 90.9% and therefore not different from the sensitivity reported using EBUSTBNA in our article. They state that all non–small cell lung cancer– not otherwise specified (NSCLC-NOS) samples in their institution have immunocytochemistry (ICC) performed. However, in their illustrative retrospective cohort, only 19 of 24 NSCLC-NOS cases underwent ICC, implying that 21% of cases of NSCLC-NOS were inadequate for further testing despite ROSE. In our multicenter study of 774 patients, 101 had a diagnosis of NSCLC-NOS and in only 6 patients was immunohistochemistry not possible. Dr. Craig and colleagues unfortunately also do not refer to the randomized controlled trials of ROSE that also do not support its routine use. Even in patients undergoing conventional TBNA, the presence of ROSE does not appear to improve yield (2). In a randomized controlled trial of patients undergoing EBUS-TBNA with and without ROSE, the sensitivity was not significantly different between the arms (3). Dr. Craig and colleagues also suggest that the presence of malignant cells in one lymph node station as assessed by ROSE can preclude further investigation of other diagnoses such as tuberculosis in other lymph node stations. This is certainly not our practice in our high-tuberculosis-prevalence region (4). Dr. Craig and colleagues suggest some potential advantages of ROSE. They omit that it may improve the negative predictive value of a negative EBUS sample; however, they also do not include any potential disadvantages that must also be considered. For example, the process of ROSE will use up vital tissue that could be better used for further tumor characterization in the laboratory. The number of passes submitted to the pathologist in the room before a lymph node is labeled as benign is unknown, and the risk of false-positive diagnoses in the bronchoscopy suite must also be clarified. The cost-effectiveness of ROSE is also unknown; however, the number of cases reported by a pathologist in an EBUS session is less than if the equivalent time was spent in the cytology laboratory. Routine use of ROSE will have enormous impact on pathology service provision and costs to the United Kingdom National Health Service. Dr. Craig and colleagues’ analysis of our data (225 patients with “lymphoid cells only” on EBUS-TBNA) also highlights a key point surrounding terminology of EBUS-TBNA samples. Dr. Craig and colleagues refer to this group of patients with lymphoid cells only or an inadequate sample as the “nondiagnostic” group. We believe this is an unhelpful and inaccurate term and should be restricted to the group of patients where EBUS-TBNA has provided an insufficient sample only. Lymphoid cells only may be entirely diagnostic of a reactive lymph node, which was the final diagnosis in 71% in this group. We currently classify these results as negative, appreciating that this negative result may be diagnostic (true negative) or a false negative if malignancy is subsequently confirmed. We agree with the authors that when a phenotypic diagnosis is not clear on initial assessment, ICC plays an important role in subtyping, and it is also our routine practice that this is performed as well as epidermal growth factor receptor mutation testing where appropriate. In addition to the tests routinely used in Dr. Craig and colleagues’ institution, we routinely analyze adenocarcinomas for the EML4-ALK gene rearrangement and are about to embark on multiplex testing of lung cancers, with a view to aiding recruitment to early-phase clinical trials. This emphasizes the pressure that specimens from EBUS-TBNA are likely to be subjected to in the future and highlights that using specimen at the bedside for ROSE may not be the best use of lung cancer tissue. The evidence is not currently available to suggest that ROSE is effective or cost-effective, and therefore, we do not agree with Dr. Craig and colleagues’ conclusion that availability of ROSE should be default. Although we agree that ROSE is helpful in the learning phase of the procedure (5), a recommendation for
1165
routine use of ROSE will add to the already high capital costs of embarking on EBUS-TBNA and may deter further centers from being commissioned. Finally, we agree that all EBUS-TBNA services should be subject to audit with a review of service specifications if standards are not being met. Author disclosures are available with the text of this letter at www.atsjournals.org.
Neal Navani, M.B.B.S., M.A., M.Sc., Ph.D. Sam M. Janes, M.B.B.S., M.Sc., Ph.D. University College London Hospital London, United Kingdom and University College London London, United Kingdom
References 1. Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Jeebun V, Munavvar M, Ng BJ, Rassl DM, Falzon M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012;185:1316–1322. 2. Trisolini R, Cancellieri A, Tinelli C, Paioli D, Scudeller L, Casadei GP, Parri SF, Livi V, Bondi A, Boaron M, et al. Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial. Chest 2011;139:395–401. 3. Oki M, Saka H, Kitagawa C, Kogure Y, Murata N, Adachi T, Ando M. Rapid on-site cytologic evaluation during endobronchial ultrasoundguided transbronchial needle aspiration for diagnosing lung cancer: a randomized study. Respiration 2013;85:486–492. 4. Navani N, Molyneaux PL, Breen RA, Connell DW, Jepson A, Nankivell M, Brown JM, Morris-Jones S, Ng B, Wickremasinghe M, et al. Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study. Thorax 2011;66:889–893. 5. Navani N, Nankivell M, Nadarajan P, Pereira SP, Kocjan G, Janes SM. The learning curve for EBUS-TBNA. Thorax 2011;66:352–353. Copyright ª 2013 by the American Thoracic Society
Rhinovirus and Asthma: Reinfection, Not Persistence To the Editor:
Asthma and viruses share a strong relationship. Viruses are the major source of exacerbations, and rhinoviruses are most frequently detected, especially in patients with allergies (1, 2). Repeated rhinovirus detection has been demonstrated in patients with asthma, even in the stable state (3). Some authors have suggested that this may be due to persistent rhinovirus infection (4–6). Several studies have shown abnormalities in the innate immune response to viruses in patients with asthma, especially deficient IFN I and III production (7–9). Increased rhinovirus replication has also been suggested (7). Supported by a Socie´te´ Franc¸aise d’Allergologie grant, a Socie´te´ de Pneumologie de Langue Franc¸aise (Comite´ National des Maladies Respiratoires) grant, and a Conseil Re´gional du Nord-Pas de Calais grant. The study was approved by the Lille University Hospital ethics committee (CPP Nord Ouest IV, 2007A01425-48). Author Contributions: Conception and design: A. Deschildre, P.G., I.T.-L., I.E., A. Dewilde, G.P., and C.T. Performed the experiments: P.G., C.M., I.E., and A. Dewilde. Recorded data: A. Deschildre, C.M., C.T., and G.P. Analysis and interpretation: A. Deschildre, P.G., I.T.-L., I.E., and A. Dewilde. Drafting the manuscript for important intellectual content: A. Deschildre, I.E., C.M., P.G., and I.T.-L.
