The epistolic response to other letters published in The New England Journal of Medicine 337 (2017), no. 19, pp. 1903-1905, as a result of the Review Article: B. Taylor Thompson, Rachel C. Chambers, Kathleen D. Liu, Acute Respiratory Distress Syndrome, The New England of Medicine 377, no. 6, (2017), pp. 562-572

Chambers, RC

Liu, KD

Thompson, BT

UCL Discovery

Correspondencen engl j med 377;19 nejm.org November 9, 2017 1903The authors reply: Eskazan speculates that a regimen using daunorubicin at a dose of 90 mg per square meter (with or without midostaurin) would lead to superior outcomes as compared with the regimen of daunorubicin at a dose of 60 mg per square meter plus midostaurin that was used in the CALGB 10603 trial. However, at the time that the trial was designed, neither the results showing the superiority of induction with daunorubicin at a dose of 90 mg per square meter as compared with 45 mg per square meter in FLT3-mutated AML1 nor those suggesting that the higher dose of this anthracycline might be better than 60 mg per square meter in FLT3-mutated AML2 were available. These cited data are derived from retrospective analyses that were not powered to show significant differences. With all the ca-veats involved in comparing one trial with an-other, the results with the induction of daunoru-bicin at a dose of 60 mg per square meter plus midostaurin in the CALGB 10603 trial were, if anything, slightly better than the results with a dose of 90 mg per square meter in the Eastern Cooperative Oncology Group 1900 (E1900) trial1 and the U.K. Medical Research Council AML17 trial.2A detailed analysis of the effect of NPM1 co-mutations on the outcome in each group of the CALGB 10603 trial is of interest. In the prelimi-nary trial, concurrent administration of midostau-rin and chemotherapy had neither a better side-effect profile nor better efficacy3 than the sequential schedule used in the CALGB 10603 trial. However, we agree that further exploration of midostaurin schedules and effects on target inhibition are warranted.Richard M. Stone, M.D.Dana–Farber Cancer Institute Boston, MA richard_stone@ dfci . harvard . eduRichard A. Larson, M.D.University of Chicago Medicine Chicago, ILHartmut Döhner, M.D.University Hospital of Ulm Ulm, GermanyDr. Larson reports receiving consulting fees from Bristol-My-ers Squibb, Ariad Pharmaceuticals, Celgene, and Pfizer and re-search funding from Astellas Pharma and Daiichi Sankyo. An updated disclosure form has been posted with the original arti-cle at NEJM.org. Since publication of their article, Dr. Stone re-ports having received consulting fees from Roche/Genentech and Astellas Pharma. No further potential conflict of interest relevant to this letter was reported.1. Luskin MR, Lee J-W, Fernandez HF, et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood 2016; 127: 1551-8.2. Burnett AK, Russell NH, Hills RK. Higher daunorubicin ex-posure benefits FLT3 mutated acute myeloid leukemia. Blood 2016; 128: 449-52.3. Stone RM, Fischer T, Paquette R, et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in young-er newly diagnosed adult patients with acute myeloid leukemia. Leukemia 2012; 26: 2061-8.DOI: 10.1056/NEJMc1711340Acute Respiratory Distress SyndromeTo the Editor: In their review of the acute re-spiratory distress syndrome (ARDS) (Aug. 10 issue),1 Thompson et al. recommend that pa-tients be placed in the prone position when the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao2:Fio2) is less than 120 mm Hg. However, the guidelines for the mechanical ventilation of patients with ARDS2 recommend this strategy for patients with severe ARDS, which the guidelines define as a Pao2:Fio2 of less than 100 mm Hg. Further-more, one of the inclusion criteria for a trial that showed a decrease in mortality with this maneuver was a Pao2:Fio2 of 150 mm Hg or less.3 In regard to neuromuscular blocking agents, Thompson et al. recommend the use of such drugs when the Pao2:Fio2 is less than 150 mm Hg. This statement is in agreement with the guide-lines for the use of neuromuscular blocking agents in critically ill patients,4 but the trial conducted by Papazian et al., which is cited by the authors, showed that these agents had a ben-eficial effect on survival at 90 days for patients with a baseline Pao2:Fio2 of less than 120 mm Hg.5 This finding has important clinical relevance, since the thresholds defined for the initiation of interventions, if unclear, may lead to inappro-priate exposure to these interventions or delays in their withdrawal, either of which may put patients at risk.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY COLLEGE LONDON on November 23, 2017. For personal use only. No other uses without permission.  Copyright © 2017 Massachusetts Medical Society. All rights reserved. T h e  n e w  e ngl a nd  j o u r na l  o f  m e dic i n en engl j med 377;19 nejm.org November 9, 20171904Valente Jaramillo-Rocha, M.D.University Health Network Toronto, ON, Canada valentejaramillo@ gmail . comNo potential conflict of interest relevant to this letter was re-ported.1. Thompson BT, Chambers RC, Liu KD. Acute respiratory dis-tress syndrome. N Engl J Med 2017; 377: 562-72.2. Fan E, Del Sorbo L, Goligher EC, et al. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: me-chanical ventilation in adult patients with acute respiratory dis-tress syndrome. Am J Respir Crit Care Med 2017; 195: 1253-63.3. Guérin C, Reignier J, Richard J-C, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368: 2159-68.4. Murray MJ, DeBlock H, Erstad B, et al. Clinical practice guide-lines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2016; 44: 2079-103.5. Papazian L, Forel J-M, Gacouin A, et al. Neuromuscular block-ers in early acute respiratory distress syndrome. N Engl J Med 2010; 363: 1107-16.DOI: 10.1056/NEJMc1711824To the Editor: Thompson et al. do not include drugs as a possible trigger for ARDS. For exam-ple, some of the drugs used to treat cancer, such as cytarabine, gefitinib, gemcitabine, vinblastine, and vincristine, are a well-recognized cause of ARDS.1,2 Amiodarone, infliximab, nitrofurantoin, verapamil, narcotics, and overdoses of salicylates have also been implicated as causes of ARDS. Overall, drugs are implicated in approximately 13% of patients with ARDS in the absence of other identified precipitating factors.3 Although for most drugs the exact mechanism of pulmo-nary toxicity has not been elucidated, direct, drug-induced damage of pulmonary vascular endothe-lial cells and alveolar epithelial cells has been suggested.2 Drug-induced ARDS should be con-sidered if the cause of lung injury is not evident.4 The diagnosis of drug-induced ARDS is based on a history of drug exposure, with a temporal rela-tion between the introduction of the drug and the onset of symptoms, and on the exclusion of other causes of acute lung injury. Treatment is based on timely withdrawal of the offending drug and the provision of supportive measures.Chaker Ben Salem, M.D.Pharmacovigilance Center Sousse, Tunisia bensalem . c@ gmail . comNo potential conflict of interest relevant to this letter was re-ported.1. Ben-Noun L. Drug-induced respiratory disorders: incidence, prevention and management. Drug Saf 2000; 23: 143-64.2. Lee-Chiong T Jr, Matthay RA. Drug-induced pulmonary edema and acute respiratory distress syndrome. Clin Chest Med 2004; 25: 95-104.3. Gibelin A, Parrot A, Maitre B, et al. Acute respiratory dis-tress syndrome mimickers lacking common risk factors of the Berlin definition. Intensive Care Med 2016; 42: 164-72.4. Ben Salem C, Hmouda H, Bouraoui K. Acute lung injury and acute respiratory distress syndrome. Lancet 2007; 370: 383-5.DOI: 10.1056/NEJMc1711824The authors reply: The official clinical practice guideline of the American Thoracic Society, the European Society of Intensive Care Medicine, and the Society of Critical Care Medicine strongly rec-ommends the use of the prone position in pa-tients with a Pao2:Fio2 of 100 mm Hg or less; this approach is supported by data showing a lower risk of death, as compared with the use of me-chanical ventilation in the supine position. How-ever, there was a lack of consensus regarding the use of the prone position in patients with a Pao2:Fio2 of 101 to 150 mm Hg owing to a “lower confidence in the balance between desirable as compared with undesirable outcomes in this sub-group of patients.”1As we noted in our review, a recent global survey of more than 29,000 patients who received mechanical ventilation showed that ARDS, even in its severest form, is underrecognized.2 The prone position was used in only 16.3% of patients recognized by clinicians as having severe ARDS (patients with a Pao2:Fio2 of less than 100 mm Hg), the subset in which the evidence of benefit is strongest and for which we have consensus. Ac-cordingly, increased recognition of ARDS and increased use of ventilation with patients in the prone position in the subset of patients with se-vere disease should be high priorities.1,2 We agree with Jaramillo-Rocha that thresholds should also guide the decision to change from the prone to the supine position at a Pao2:Fio2 of at least 150 mm Hg, measured approximately 4 hours after returning to ventilation in the supine posi-tion, with a positive end-expiratory pressure of 10 cm of water or less and an Fio2 of 0.6 or less, as reported by Guérin et al.3We agree that drug-induced lung disease should be considered when assessing a patient with ARDS and note this in Table 3 of our article, available at NEJM.org. We thank Ben Salem for drawing attention to this important clinical caveat.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY COLLEGE LONDON on November 23, 2017. For personal use only. No other uses without permission.  Copyright © 2017 Massachusetts Medical Society. All rights reserved. noticesn engl j med 377;19 nejm.org November 9, 2017 1905B. Taylor Thompson, M.D.Massachusetts General Hospital Boston, MA thompson . taylor@ mgh . harvard . eduRachel C. Chambers, Ph.D.University College London London, United KingdomKathleen D. Liu, M.D., Ph.D.University of California, San Francisco San Francisco, CASince publication of their article, the authors report no fur-ther potential conflict of interest.1. Fan E, Del Sorbo L, Goligher EC, et al. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: me-chanical ventilation in adult patients with acute respiratory dis-tress syndrome. Am J Respir Crit Care Med 2017; 195: 1253-63.2. Bellani G, Laffey JG, Pham T, et al. Noninvasive ventilation of patients with acute respiratory distress syndrome. Insights from the LUNG SAFE study. Am J Respir Crit Care Med 2017; 195: 67-77.3. Guérin C, Reignier J, Richard J-C, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368: 2159-68.DOI: 10.1056/NEJMc1711824Correspondence Copyright © 2017 Massachusetts Medical Society.instructions for letters to the editorLetters to the Editor are considered for publication, subject to editing and abridgment, provided they do not contain material that has been submitted or published elsewhere.Letters accepted for publication will appear in print, on our website at NEJM.org, or both. 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Box 1622, Parker, CO 80134; or call (303) 358-2797; or e-mail Jeanne.Cleary@ucdenver.edu; or see http://www.aspenlungconference.org.CARS 2018The congress will be held in Berlin, June 20–23. Deadline for submission of abstracts and papers is Jan. 10.Contact Mrs. Franziska Schweikert, CARS Conference Office, Klettgaustr. 20, 79790 Kuessaberg, Germany; or call (49) 7742-922 434; or e-mail office@cars-int.org; or see http://www.cars-int.org.UPDATE IN INTERNAL MEDICINE 2017The course will be offered in Boston, Dec. 3–9. It is jointly presented by Harvard Medical School and Beth Israel Deaconess Medical Center.Contact the Department of Continuing Education, Harvard Medical School, P.O. Box 825, Boston, MA 02117-0825; or call 617-384-8600; or e-mail ceprograms@hms.harvard.edu; or see http://www.updateinternalmedicine.com.ROOSEVELT ISLAND HISTORICAL SOCIETYThe Roosevelt Island Historical Society is seeking physi-cians who worked on the New York City island as students, interns, and residents to learn about their experiences. The is-land was known as Welfare Island until 1973.Contact Judith Berdy, Roosevelt Island Historical Society, 531 Main St., Roosevelt Island, NY 10044; or call (212) 688-4836; or e-mail rooseveltislandhistory@usa.com.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY COLLEGE LONDON on November 23, 2017. For personal use only. No other uses without permission.  Copyright © 2017 Massachusetts Medical Society. All rights reserved. 

Acute Respiratory Distress Syndrome: Response

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Acute Respiratory Distress Syndrome: Response

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