CORRESPONDENCE in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med 2010;181:116–124. 5. Miller JD, Cox G, Vincic L, Lombard CM, Loomas BE, Danek CJ. A prospective feasibility study of bronchial thermoplasty in the human airway. Chest 2005;127:1999–2006. 6. Lee AM, Kirby M, Ohtani K, Candido T, Shalansky R, MacAulay C, English J, Finley R, Lam S, Coxson HO, et al. Validation of airway wall measurements by optical coherence tomography in porcine airways. PLoS One 2014;20:9:e100145.
Copyright © 2015 by the American Thoracic Society
Reply: Reduction of Airway Smooth Muscle Mass by Bronchial Thermoplasty in Patients with Severe Asthma
Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Marina Pretolani, Ph.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Pascal Chanez, M.D., Ph.D. Inserm CNRS U 1067, UMR 7733 Marseille, France Gabriel Thabut, M.D., Ph.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France
From the Authors: We appreciate the interest of Dr. Bonta and colleagues in our investigation into the effect of bronchial thermoplasty (BT) on airway smooth muscle mass (ASM) in patients with severe asthma. The first point raised by the authors is that although they confirm our observation of transient radiological abnormalities in the treated lobe after BT, they did not detect any abnormalities in the middle lobe. Ground-glass opacities in the middle lobe were noted after BT in only 7 of the 10 patients reported in our research letter (1). The hypothesis we put forward to explain these unexpected abnormalities is a diffusion of heat from the treated lobe through incomplete fissures. The latter are frequent and have been described by high-resolution computed tomography scan in a high proportion of cases (2). We agree with Dr. Bonta and colleagues that this explanation is purely speculative and may not explain at all, or even in part, the decrease in the ASM in the middle lobe observed after BT. In their second point, Dr. Bonta and colleagues suggest a scar effect as an alternative explanation for the decreased ASM in the middle lobe. Our patients were selected for BT on the basis of the increase in ASM. The latter was assessed on two biopsies collected in the middle lobe 2–4 weeks before the 10 biopsies that were performed just before BT. We did not find any major difference in values of ASM area when comparing the biopsies performed in the middle lobe at 1-month intervals. Therefore, we believe a scar effect after BT is very unlikely. We fully agree with our colleagues that a noninvasive technique such as optical coherence tomography (3) would be very useful to assess the effects of BT on the different airway structures, and particularly ASM, and are waiting with great interest for the results of the TASMA (Unravelling Targets of Therapy in Bronchial Thermoplasty in Severe Asthma) trial (ClinicalTrials.gov NCT 02225392). n Author disclosures are available with the text of this letter at www.atsjournals.org. Michel Aubier, M.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France
1208
and
Universite´ Paris Diderot Paris, France Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Marie-Pierre Debray, M.D. Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France and Assistance Publique des Hopitaux ˆ de Paris Paris, France Camille Taille, M.D., Ph.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Dominique Knap Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Fatima Hamidi Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France
American Journal of Respiratory and Critical Care Medicine Volume 191 Number 10 | May 15 2015
CORRESPONDENCE References 1. Pretolani M, Dombret MC, Thabut G, Knap D, Hamidi F, Debray MP, Taille C, Chanez P, Aubier M. Reduction of airway smooth muscle mass by bronchial thermoplasty in patients with severe asthma. Am J Respir Crit Care Med 2014;190:1452–1454. 2. Aziz A, Ashizawa K, Nagaoki K, Hayashi K. High resolution CT anatomy of the pulmonary fissures. J Thorac Imaging 2004;19:186–191. 3. Lee AM, Kirby M, Ohtani K, Candido T, Shalansky R, MacAulay C, English J, Finley R, Lam S, Coxson HO, et al. Validation of airway wall measurements by optical coherence tomography in porcine airways. PLoS One 2014;20:9:e100145.
Copyright © 2015 by the American Thoracic Society
Lung Cancer Screening: The Balance between Harm and Benefit To the Editor: We read with interest the concise review by Tanoue and colleagues (1) on lung cancer screening. In our opinion, there are some points that put too much weight on potential harms that are not based on any evidence. For example, the authors correctly state that the National Lung Screening Trial (NLST) did not have a protocol for nodule work-up, but they further speculate that although participants had the choice of having their nodules worked up at their local centers, most of them likely chose NLST centers to continue their diagnostic tests. In the transcripts of the Medicare Evidence Development & Coverage Advisory Committee meeting held on April 30, 2014 (2), Dr. Pinsky, an NLST investigator, stated that more than a third of the participants were screened at nonacademic sites, and he estimates that most of the diagnostic follow-up of individuals screened in academic centers was actually performed in local community centers. Regarding radiation dose, the authors quote a model that used 2 mSv as the average dose of a low-dose computed tomography (LDCT) scan and assumed follow-up of positive tests with full-dose CT scan (i.e., 8 mSv) (1). Furthermore, this model estimates that a participant will have a positive test every 2 years, with a total accumulated dose of 420 mSv over the course of 20–30 years. The average dose of a screening round in NLST was slightly below 1.5 mSv (2), and the International Early Lung Cancer Action Program, the longest and largest ongoing study on lung cancer screening, has shown that follow-up of positive screening tests can be done with LDCT, and usually with no more than three additional tests (at 3, 12, and 24 mo) (3). Thus, using technology already available that allows us to reduce the dose of an LDCT below 1 mSv, a full cycle of an initial positive LDCT and a 2-year follow-up can be achieved with an accumulated dose below 4 mSv. There is no evidence whatsoever to suggest a participant will have a positive test every 2 years. Quite to the contrary, positive rates decline significantly after the baseline round of screening. Finally, regarding who should be screened, most guidelines recommend screening for individuals who meet the NLST entry criteria. Obviously, these are the only criteria that have been tested in a randomized controlled trial, but there is no evidence that screening individuals with different criteria would not be effective. Evidence-based medicine followed too strictly can lead to absurd situations. For example, being strict about these criteria would not allow screening of a 45-year-old smoker with three or four Correspondence
first-degree relatives with lung cancer. Our group, in collaboration with Dr. David Wilson’s group from the Pittsburgh Lung Screening Study, has just published two articles in this same journal in which we propose rethinking the selection criteria. We believe criteria should be different for the baseline round of screening than the subsequent annual rounds (4). For the latter, information obtained from the LDCT scan (i.e., the presence of emphysema) to select individuals who should continue screening even without meeting NLST criteria may help reduce the number of LDCT scans needed to diagnose a single lung cancer while increasing the cancer detection rate. In addition, we present a score to help select patients with chronic obstructive pulmonary disease who have the highest risk of lung cancer who might benefit most from lung cancer screening (5). It is important to minimize harms and to study them in detail, but we should not forget that lung cancer screening reduces lung cancer mortality as no treatment or intervention has been able to achieve in the history of this disease. n Author disclosures are available with the text of this letter at www.atsjournals.org. Javier J. Zulueta, M.D. Juan P. de-Torres, M.D. Cl´ınica Universidad de Navarra Pamplona, Spain
References 1. Tanoue LT, Tanner NT, Gould MK, Silvestri GA. Lung cancer screening. Am J Respir Crit Care Med 2015;191:19–33. 2. Centers for Medicare & Medicaid Services. MEDCAC Meeting 4/30/2014 - Lung Cancer Screening with Low Dose Computed Tomography [accessed 2015 Mar 19]. Available from: http://www.cms.gov/ medicare-coverage-database/details/medcac-meeting-details.aspx? MEDCACId=68 3. Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS; International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763– 1771. 4. Sanchez-Salcedo P, Wilson DO, de-Torres JP, Weissfeld JL, Berto J, Campo A, Alcaide AB, Pueyo J, Bastarrika G, Seijo LM, et al. Improving selection criteria for lung cancer screening: the potential role of emphysema. Am J Respir Crit Care Med [online ahead of print] 10 Feb 2015; DOI: 10.1164/rccm.201410-1848OC. 5. de-Torres JP, Wilson DO, Sanchez-Salcedo P, Weissfeld JL, Berto J, Campo A, Alcaide AB, Garc´ıa-Granero M, Celli BR, Zulueta JJ. Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening Score. Am J Respir Crit Care Med 2015;191:285–291.
Copyright © 2015 by the American Thoracic Society
Reply From the Authors: We appreciate the thoughtful comments provided by Drs. Zulueta and de-Torres relating to our review on lung cancer screening (1). They raise the concern that the review puts too much emphasis on potential harms related to screening and that the main benefit of lung cancer screening is minimized. 1209
Copyright © 2015 by the American Thoracic Society
Reply: Reduction of Airway Smooth Muscle Mass by Bronchial Thermoplasty in Patients with Severe Asthma
Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Marina Pretolani, Ph.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Pascal Chanez, M.D., Ph.D. Inserm CNRS U 1067, UMR 7733 Marseille, France Gabriel Thabut, M.D., Ph.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France
From the Authors: We appreciate the interest of Dr. Bonta and colleagues in our investigation into the effect of bronchial thermoplasty (BT) on airway smooth muscle mass (ASM) in patients with severe asthma. The first point raised by the authors is that although they confirm our observation of transient radiological abnormalities in the treated lobe after BT, they did not detect any abnormalities in the middle lobe. Ground-glass opacities in the middle lobe were noted after BT in only 7 of the 10 patients reported in our research letter (1). The hypothesis we put forward to explain these unexpected abnormalities is a diffusion of heat from the treated lobe through incomplete fissures. The latter are frequent and have been described by high-resolution computed tomography scan in a high proportion of cases (2). We agree with Dr. Bonta and colleagues that this explanation is purely speculative and may not explain at all, or even in part, the decrease in the ASM in the middle lobe observed after BT. In their second point, Dr. Bonta and colleagues suggest a scar effect as an alternative explanation for the decreased ASM in the middle lobe. Our patients were selected for BT on the basis of the increase in ASM. The latter was assessed on two biopsies collected in the middle lobe 2–4 weeks before the 10 biopsies that were performed just before BT. We did not find any major difference in values of ASM area when comparing the biopsies performed in the middle lobe at 1-month intervals. Therefore, we believe a scar effect after BT is very unlikely. We fully agree with our colleagues that a noninvasive technique such as optical coherence tomography (3) would be very useful to assess the effects of BT on the different airway structures, and particularly ASM, and are waiting with great interest for the results of the TASMA (Unravelling Targets of Therapy in Bronchial Thermoplasty in Severe Asthma) trial (ClinicalTrials.gov NCT 02225392). n Author disclosures are available with the text of this letter at www.atsjournals.org. Michel Aubier, M.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France
1208
and
Universite´ Paris Diderot Paris, France Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Marie-Pierre Debray, M.D. Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France and Assistance Publique des Hopitaux ˆ de Paris Paris, France Camille Taille, M.D., Ph.D. Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Groupement Hospitalier Universitaire Nord Bichat-Claude Bernard Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Dominique Knap Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France Assistance Publique des Hopitaux ˆ de Paris Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France Fatima Hamidi Physiopathologie et Epidemiologie ´ des Maladies Respiratoires Paris, France Universite´ Paris Diderot Paris, France and Labex Inflamex and Departement ´ Hospitalo-Universitaire FIRE Paris, France
American Journal of Respiratory and Critical Care Medicine Volume 191 Number 10 | May 15 2015
CORRESPONDENCE References 1. Pretolani M, Dombret MC, Thabut G, Knap D, Hamidi F, Debray MP, Taille C, Chanez P, Aubier M. Reduction of airway smooth muscle mass by bronchial thermoplasty in patients with severe asthma. Am J Respir Crit Care Med 2014;190:1452–1454. 2. Aziz A, Ashizawa K, Nagaoki K, Hayashi K. High resolution CT anatomy of the pulmonary fissures. J Thorac Imaging 2004;19:186–191. 3. Lee AM, Kirby M, Ohtani K, Candido T, Shalansky R, MacAulay C, English J, Finley R, Lam S, Coxson HO, et al. Validation of airway wall measurements by optical coherence tomography in porcine airways. PLoS One 2014;20:9:e100145.
Copyright © 2015 by the American Thoracic Society
Lung Cancer Screening: The Balance between Harm and Benefit To the Editor: We read with interest the concise review by Tanoue and colleagues (1) on lung cancer screening. In our opinion, there are some points that put too much weight on potential harms that are not based on any evidence. For example, the authors correctly state that the National Lung Screening Trial (NLST) did not have a protocol for nodule work-up, but they further speculate that although participants had the choice of having their nodules worked up at their local centers, most of them likely chose NLST centers to continue their diagnostic tests. In the transcripts of the Medicare Evidence Development & Coverage Advisory Committee meeting held on April 30, 2014 (2), Dr. Pinsky, an NLST investigator, stated that more than a third of the participants were screened at nonacademic sites, and he estimates that most of the diagnostic follow-up of individuals screened in academic centers was actually performed in local community centers. Regarding radiation dose, the authors quote a model that used 2 mSv as the average dose of a low-dose computed tomography (LDCT) scan and assumed follow-up of positive tests with full-dose CT scan (i.e., 8 mSv) (1). Furthermore, this model estimates that a participant will have a positive test every 2 years, with a total accumulated dose of 420 mSv over the course of 20–30 years. The average dose of a screening round in NLST was slightly below 1.5 mSv (2), and the International Early Lung Cancer Action Program, the longest and largest ongoing study on lung cancer screening, has shown that follow-up of positive screening tests can be done with LDCT, and usually with no more than three additional tests (at 3, 12, and 24 mo) (3). Thus, using technology already available that allows us to reduce the dose of an LDCT below 1 mSv, a full cycle of an initial positive LDCT and a 2-year follow-up can be achieved with an accumulated dose below 4 mSv. There is no evidence whatsoever to suggest a participant will have a positive test every 2 years. Quite to the contrary, positive rates decline significantly after the baseline round of screening. Finally, regarding who should be screened, most guidelines recommend screening for individuals who meet the NLST entry criteria. Obviously, these are the only criteria that have been tested in a randomized controlled trial, but there is no evidence that screening individuals with different criteria would not be effective. Evidence-based medicine followed too strictly can lead to absurd situations. For example, being strict about these criteria would not allow screening of a 45-year-old smoker with three or four Correspondence
first-degree relatives with lung cancer. Our group, in collaboration with Dr. David Wilson’s group from the Pittsburgh Lung Screening Study, has just published two articles in this same journal in which we propose rethinking the selection criteria. We believe criteria should be different for the baseline round of screening than the subsequent annual rounds (4). For the latter, information obtained from the LDCT scan (i.e., the presence of emphysema) to select individuals who should continue screening even without meeting NLST criteria may help reduce the number of LDCT scans needed to diagnose a single lung cancer while increasing the cancer detection rate. In addition, we present a score to help select patients with chronic obstructive pulmonary disease who have the highest risk of lung cancer who might benefit most from lung cancer screening (5). It is important to minimize harms and to study them in detail, but we should not forget that lung cancer screening reduces lung cancer mortality as no treatment or intervention has been able to achieve in the history of this disease. n Author disclosures are available with the text of this letter at www.atsjournals.org. Javier J. Zulueta, M.D. Juan P. de-Torres, M.D. Cl´ınica Universidad de Navarra Pamplona, Spain
References 1. Tanoue LT, Tanner NT, Gould MK, Silvestri GA. Lung cancer screening. Am J Respir Crit Care Med 2015;191:19–33. 2. Centers for Medicare & Medicaid Services. MEDCAC Meeting 4/30/2014 - Lung Cancer Screening with Low Dose Computed Tomography [accessed 2015 Mar 19]. Available from: http://www.cms.gov/ medicare-coverage-database/details/medcac-meeting-details.aspx? MEDCACId=68 3. Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS; International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763– 1771. 4. Sanchez-Salcedo P, Wilson DO, de-Torres JP, Weissfeld JL, Berto J, Campo A, Alcaide AB, Pueyo J, Bastarrika G, Seijo LM, et al. Improving selection criteria for lung cancer screening: the potential role of emphysema. Am J Respir Crit Care Med [online ahead of print] 10 Feb 2015; DOI: 10.1164/rccm.201410-1848OC. 5. de-Torres JP, Wilson DO, Sanchez-Salcedo P, Weissfeld JL, Berto J, Campo A, Alcaide AB, Garc´ıa-Granero M, Celli BR, Zulueta JJ. Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening Score. Am J Respir Crit Care Med 2015;191:285–291.
Copyright © 2015 by the American Thoracic Society
Reply From the Authors: We appreciate the thoughtful comments provided by Drs. Zulueta and de-Torres relating to our review on lung cancer screening (1). They raise the concern that the review puts too much emphasis on potential harms related to screening and that the main benefit of lung cancer screening is minimized. 1209
