EDITORIALS communities. In the study by Madan and colleagues, Moraxella and Corynebacterium spp. were found only in low relative abundance, whereas Streptococcus spp. was present in higher relative abundance (9). In conclusion, this longitudinal study indicates that infants with CF acquire a distinct nasopharyngeal microbiota, even before intervention with antimicrobials, compared with healthy infants, suggesting that innate differences in the host (e.g., CF transmembrane conductance regulator dysfunction) drive some of these early alterations. Antibiotics are used early and frequently in CF, and may have the unintended consequence of shifting the microbiota toward a less “healthy” structure. Chronic S. aureus prophylactic treatment for this age group continues to be debated, and future investigations of this approach should include microbiota analyses (17). The relationship between upper airway microbiota and development of lower respiratory tract infection, inflammation, and structural lung disease in CF is not yet clear and will need further study, as do alternative approaches such as probiotics, encouraging longer breastfeeding, or more judicious use of antimicrobials. n Author disclosures are available with the text of this article at www.atsjournals.org. Edith T. Zemanick, M.D., M.S.C.S. Department of Pediatrics University of Colorado School of Medicine Aurora, Colorado Claire Wainwright, M.B.B.S., M.D. Department of Respiratory and Sleep Medicine Lady Cilento Children’s Hospital South Brisbane, Queensland, Australia and School of Medicine University of Queensland Brisbane, Queensland, Australia
ORCID IDs: 0000-0002-7507-9337 (E.T.Z.); 0000-0001-8389-3809 (C.W.).
References 1. Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM; AREST CF Investigators. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013;368:1963–1970. 2. Stick SM, Brennan S, Murray C, Douglas T, von Ungern-Sternberg BS, Garratt LW, Gangell CL, De Klerk N, Linnane B, Ranganathan S, et al.; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening. J Pediatr 2009;155:623–628.e1. 3. Razvi S, Quittell L, Sewall A, Quinton H, Marshall B, Saiman L. Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005. Chest 2009;136:1554–1560.
4. Caverly LJ, Zhao J, LiPuma JJ. Cystic fibrosis lung microbiome: opportunities to reconsider management of airway infection. Pediatr Pulmonol 2015;50:S31–S38. 5. Zhao J, Schloss PD, Kalikin LM, Carmody LA, Foster BK, Petrosino JF, Cavalcoli JD, VanDevanter DR, Murray S, Li JZ, et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci USA 2012;109:5809–5814. 6. Stressmann FA, Rogers GB, van der Gast CJ, Marsh P, Vermeer LS, Carroll MP, Hoffman L, Daniels TW, Patel N, Forbes B, et al. Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience. Thorax 2012;67:867–873. 7. Rosenfeld M, Emerson J, Accurso F, Armstrong D, Castile R, Grimwood K, Hiatt P, McCoy K, McNamara S, Ramsey B, et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr Pulmonol 1999;28:321–328. 8. Zemanick ET, Wagner BD, Robertson CE, Stevens MJ, Szefler SJ, Accurso FJ, Sagel SD, Harris JK. Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods. Ann Am Thorac Soc 2015;12:221–229. 9. Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, Moore JH, Guill MF, Morrison HG, Sogin ML, et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. MBio 2012;3:3. 10. Biesbroek G, Bosch AA, Wang X, Keijser BJ, Veenhoven RH, Sanders EA, Bogaert D. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med 2014;190:298–308. 11. Faden H. Monthly prevalence of group A, B and G Streptococcus, Haemophilus influenzae types E and F and Pseudomonas aeruginosa nasopharyngeal colonization in the first two years of life. Pediatr Infect Dis J 1998;17:255–256. 12. Velazquez-Guadarrama ´ N, Martinez-Aguilar G, Galindo JA, Zuñiga G, Arbo-Sosa A. Methicillin-resistant S. aureus colonization in Mexican children attending day care centres. Clin Invest Med 2009;32:E57–E63. 13. Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, Holt BJ, Hales BJ, Walker ML, Hollams E, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 2015;17:704–715. 14. Taylor L, Corey M, Matlow A, Sweezey NB, Ratjen F. Comparison of throat swabs and nasopharyngeal suction specimens in non-sputum-producing patients with cystic fibrosis. Pediatr Pulmonol 2006;41:839–843. 15. Prevaes SM, de Winter-de Groot KM, Janssens HM, de Steenhuijsen Piters WA, Tramper-Stranders GA, Wyllie AL, Hasrat R, Tiddens HA, van Westreenen M, van der Ent CK, et al. Development of the nasopharyngeal microbiota in infants with cystic fibrosis. Am J Respir Crit Care Med 2016;193:504–515. 16. Bogaert D, Keijser B, Huse S, Rossen J, Veenhoven R, van Gils E, Bruin J, Montijn R, Bonten M, Sanders E. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS One 2011;6:e17035. 17. Smyth A. Prophylactic antibiotics in cystic fibrosis: a conviction without evidence? Pediatr Pulmonol 2005;40:471–476.
Copyright © 2016 by the American Thoracic Society
Bridge or Abyss: Extracorporeal Membrane Oxygenation for Acute Respiratory Failure in Interstitial Lung Disease Interstitial lung disease (ILD) defines an entity or a syndrome of chronic alterations of lung parenchyma characterized by inflammation and/or fibrosis (1, 2). ILD can be induced by defined conditions such as pneumonia or fibrosis. It can be classified as 474
idiopathic if a predisposing factor cannot be identified or if the underlying pathophysiology is not totally understood. A multidisciplinary approach allows a definitive diagnosis, and reasonable progress with respect to pharmacological treatment
American Journal of Respiratory and Critical Care Medicine Volume 193 Number 5 | March 1 2016
EDITORIALS options has been made for some of the underlying conditions (1, 3–5). However, regardless of the underlying condition, acute exacerbations of ILD leading to acute respiratory failure requiring mechanical ventilation are still associated with a poor outcome (6, 7). Mechanical ventilation (MV) makes any patient prone to the risk for ventilator-induced lung injury (8), which in patients with ILD may cause irreversible deterioration of the underlying disease process and lead to a fatal outcome if lung transplantation cannot be performed (7, 9, 10). There are two potential rationales for the use of extracorporeal membrane oxygenation (ECMO), First of all, extracorporeal lung support might allow one to reduce the invasiveness of MV (11), and therefore minimize the risk of “triggering” fatal deterioration of the underlying chronic process. Second, ECMO might bridge the period necessary for registering the patient for a lung transplant, possibly obtaining a suitable organ (12–14). In this issue of the Journal, Trudzinski and colleagues (pp. 527–533) report the findings of a retrospective single-center analysis of patients with ILD suffering from severe acute respiratory failure who have been treated either with conventional MV alone or with ECMO combined with MV or noninvasive respiratory support (15). Patients were eligible for ECMO if the acute cause of deterioration and acute respiratory failure was rated as potentially reversible. ECMO therapy was provided regardless of whether the patient was already listed for lung transplantation or not. Patients were not considered for ECMO if their prognosis was poor and existing comorbitdies represented contraindications for lung transplantation. The patients included in this analysis were treated with ECMO either because of hypoxemic respiratory failure, in which conventional ventilation, even with injurious ventilator settings, such as plateau pressures above 35 cm H2O (highest plateau pressure . 55 cm H2O) failed to ensure adequate gas exchange with consequent hypoxemia and severe respiratory acidosis, or if noninvasive respiratory support (e.g., high-flow oxygen) was not sufficient to prevent intubation and invasive ventilation. In the latter cases, ECMO was applied as “awake ECMO,” which represents an evolving technique to bridge patients if there are no contraindications for transplantation (14, 16). Trudzinski and colleagues analyzed 21 patients with ILD who had received ECMO therapy. One of the main findings was a high mortality rate in those patients receiving ECMO, who, for whatever reason, did not receive a lung transplant. In contrast, in those patients suffering from acute respiratory failure who met the criteria for transplantation, the time gain opened the opportunity to receive an organ. Of the 21 patients who were placed on ECMO, 33% either received a lung transplant (n = 6) or were discharged alive without transplantation (n = 1). Although mortality is high in this group of severely ill patients, one can assume that it would been closer to 100% without ECMO support. In the end, six of the eight patients, whose transferal from another hospital was facilitated by ECMO, were not considered for lung transplantation. Because these patients had not been evaluated for transplantation before the acute respiratory failure, ECMO had, at least, made this a possibility. However, the high percentage of patients whose transfer was ultimately futile is worrisome. The supplemental data that provide additional information for each single case reveal that making a decision against or in favor of potentially live-sustaining measures such as ECMO was extremely difficult. This finding and the time receiving mechanical ventilation before being considered Editorials
for transferal and initiation of ECMO therapy underlines the urgent need for the early consultation of an experienced ECMO center to minimize the rate of futile treatments. Such a center should either perform lung transplantations itself or work closely together with such an institution. Acute respiratory failure in ILD has a poor outcome without lung transplantation. The data of Trudzinski and colleagues give an important indication that, at least in their study patient group, ECMO was unable to prevent the irreversible progression of the underlying disease when it was established according to the inclusion criteria and at the time used in their study. As a consequence, the rationale to use ECMO in patients with ILD to prevent further ILD progression seems questionable, to say the least. Moreover, the rationale and option to use ECMO as a bridge to transplant seems to only work for those patients who have already been considered for lung transplantation, and in whom transplantation was ultimately realized. Using ECMO to “win time” apparently offers no benefit for those patients in whom transplantation is, for whatever reason, not a realistic option. As a consequence, the use of ECMO in patients with ILD who do not qualify for lung transplantation is likely to increase the burden and the suffering for the patients and their relatives without offering a realistic chance of a benefit. As the decision to initiate ECMO must frequently be made under obvious time pressure, the data presented here strongly support obtaining an objective and comprehensive picture of a patient as best as one can with the available knowledge before starting. This is to keep the number of patients who start ECMO and then have it judged a futile treatment as low as possible. The data presented by Trudzinski and colleagues represent a small but important piece in the puzzle of the reasonable indications for, and potential benefits and possible futility of initiating, ECMO therapy. The study does not so much gives definitive answers in terms of robust assistance in evidence-based decision making but, instead, helps one to ask the right questions and to think the proper thoughts. To preserve and further develop ECMO as the lifesaving tool that it is, and not an instrument for preventing dignified dying, one must ensure a thorough evaluation and indication before initiation, the correct implementation with a continuous reevaluation of the therapeutic goals, and the readiness to terminate ECMO therapy if the defined and agreed-upon goals can no longer be achieved. The publication of Trudzinski and colleagues might help make ECMO a bridge for life and save the patient, the family, and the whole caregiving team from the abyss. n
Author disclosures are available with the text of this article at www.atsjournals.org. Onnen Moerer, M.D. Michael Quintel, M.D. Department of Anaesthesiology, Emergency and Intensive Care Medicine Georg-August-University Gottingen ¨ Gottingen, ¨ Germany
References 1. Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, Brozek JL, Collard HR, Cunningham W, Homma S, et al.; American Thoracic Society; European Respiratory society; Japanese Respiratory Society; Latin American Thoracic Association.
475
EDITORIALS An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 2015;192:e3–e19. 2. Cottin V. Interstitial lung disease. Eur Respir Rev 2013;22:26–32. 3. Wilson KC, Raghu G. The 2015 guidelines for idiopathic pulmonary fibrosis: an important chapter in the evolution of the management of patients with IPF. Eur Respir J 2015;46:883–886. 4. Cottin V, Richeldi L. Neglected evidence in idiopathic pulmonary fibrosis and the importance of early diagnosis and treatment. Eur Respir Rev 2014;23:106–110. 5. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/ JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824. 6. Mallick S. Outcome of patients with idiopathic pulmonary fibrosis (IPF) ventilated in intensive care unit. Respir Med 2008;102: 1355–1359. 7. Gaudry S, Vincent F, Rabbat A, Nunes H, Crestani B, Naccache JM, Wolff M, Thabut G, Valeyre D, Cohen Y, et al. Invasive mechanical ventilation in patients with fibrosing interstitial pneumonia. J Thorac Cardiovasc Surg 2014;147:47–53. 8. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med 2014;370:980. 9. Fernandez-P ´ erez ´ ER, Yilmaz M, Jenad H, Daniels CE, Ryu JH, Hubmayr RD, Gajic O. Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease. Chest 2008;133:1113–1119.
10. Baydur A. Mechanical ventilation in interstitial lung disease: which patients are likely to benefit? Chest 2008;133:1062–1063. 11. Terragni P, Ranieri VM, Brazzi L. Novel approaches to minimize ventilator-induced lung injury. Curr Opin Crit Care 2015;21:20–25. 12. Hoopes CW, Kukreja J, Golden J, Davenport DL, Diaz-Guzman E, Zwischenberger JB. Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation. J Thorac Cardiovasc Surg 2013;145:862–867, discussion 867–868. 13. Hayanga AJ, Aboagye J, Esper S, Shigemura N, Bermudez CA, D’Cunha J, Bhama JK. Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy in the management of rapidly advancing pulmonary disease. J Thorac Cardiovasc Surg 2015;149:291–296. 14. Inci I, Klinzing S, Schneiter D, Schuepbach RA, Kestenholz P, Hillinger S, Benden C, Maggiorini M, Weder W. Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review. Transplantation 2015;99:1667–1671. 15. Trudzinski FC, Kaestner F, Schafers ¨ H-J, Fahndrich ¨ S, Seiler F, Bohmer ¨ P, Linn O, Kaiser R, Haake H, Langer F, et al. Outcome of patients with interstitial lung disease treated with extracorporeal membrane oxygenation for acute respiratory failure. Am J Respir Crit Care Med 2016;193:527–533. 16. Lehr CJ, Zaas DW, Cheifetz IM, Turner DA. Ambulatory extracorporeal membrane oxygenation as a bridge to lung transplantation: walking while waiting. Chest 2015;147:1213–1218.
Copyright © 2016 by the American Thoracic Society
Just Say No! Smoking Abstinence Works Lung cancer still remains the leading cause of cancer death in the United States, more than 50 years after the original Surgeon General’s report. In addition, diseases are continuing to be added to the list of risks from smoking, including renal failure, intestinal ischemia, and hypertensive heart disease (1). Smoking cessation, and better yet, lifelong abstinence, remain the best approaches to lowering this dreadful toll (2). Public health measures in the United States are continuing to lower the prevalence of adult smoking, and a current encouraging estimate from the Centers for Disease Control and Prevention for 2014 is a prevalence of 16.8% in the civilian, noninstitutionalized population that is willing to be interviewed (3). Data collection on e-cigarette use began in 2014, and prevalence is estimated at 3.7%. There are now 5 million fewer smokers, at 40.0 million smokers, down from 45 million smokers in 2005. Those individuals aged 65 years or older have the lowest smoking rate, at 8.5%, but this has not changed recently. Unfortunately, the persistence of smoking is seen most commonly in lower socioeconomic groups; for example, the prevalence of smoking in those on Medicaid is estimated to be 29.1%. Screening of high-risk current or former smokers for lung cancer with three annual low-dose computerized tomography (LDCT) scans has been shown to reduce lung cancer mortality by 20% in the definitive NLST (National Lung Screening Trial) (4). There has been a concern that screening may lead to a sense of false reassurance and might encourage smoking resumption or discourage cessation. In this issue of the Journal, Tanner and colleagues (pp. 534–541) review available data from the NLST to assess the effect of smoking abstinence at entry into the study with
476
subsequent mortality (5). Reassuringly, lower mortality is seen for those who have the longest periods of smoking abstinence. Furthermore, coupling smoking abstinence with lung cancer screening with LDCT results in even a further decline in lung cancer mortality. There was, on average, a 9% annual decline in lung cancer mortality for each year of smoking abstinence coupled with screening. Fifteen years of smoking cessation at time of trial entry and LDCT screening led to a lung cancer mortality risk reduction of 38%. A subset of the NLST was analyzed comprising non-Hispanic white and non-Hispanic black individuals (47,902 vs. 2,361, respectively), with 24,190 current and 26,073 former smokers. The full NLST data set does not have information about smoking cessation or persistence during the trial, which limited the analysis to some extent. Information at study entry, including standard demographic, smoking, and comorbid conditions, was assessed. Nonlinear effects of pack-years and quit-years were assessed through quadratic forms of the two variables. Time to lung cancerspecific and overall mortality were the outcomes of interest. The lowest hazard rates for lung cancer mortality were seen in those who smoked the least and had the longest duration of smoking cessation at trial entry. Of importance, this effect was lessened by increasing pack-year history. Current smokers at trial entry were more likely to be African American and less educated. Reassuringly, however, the benefit of smoking cessation was more pronounced among African Americans. Black former smokers, which included 794 individuals at trial entry, had a hazard rate for lung cancer mortality of
American Journal of Respiratory and Critical Care Medicine Volume 193 Number 5 | March 1 2016
ORCID IDs: 0000-0002-7507-9337 (E.T.Z.); 0000-0001-8389-3809 (C.W.).
References 1. Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM; AREST CF Investigators. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013;368:1963–1970. 2. Stick SM, Brennan S, Murray C, Douglas T, von Ungern-Sternberg BS, Garratt LW, Gangell CL, De Klerk N, Linnane B, Ranganathan S, et al.; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening. J Pediatr 2009;155:623–628.e1. 3. Razvi S, Quittell L, Sewall A, Quinton H, Marshall B, Saiman L. Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005. Chest 2009;136:1554–1560.
4. Caverly LJ, Zhao J, LiPuma JJ. Cystic fibrosis lung microbiome: opportunities to reconsider management of airway infection. Pediatr Pulmonol 2015;50:S31–S38. 5. Zhao J, Schloss PD, Kalikin LM, Carmody LA, Foster BK, Petrosino JF, Cavalcoli JD, VanDevanter DR, Murray S, Li JZ, et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci USA 2012;109:5809–5814. 6. Stressmann FA, Rogers GB, van der Gast CJ, Marsh P, Vermeer LS, Carroll MP, Hoffman L, Daniels TW, Patel N, Forbes B, et al. Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience. Thorax 2012;67:867–873. 7. Rosenfeld M, Emerson J, Accurso F, Armstrong D, Castile R, Grimwood K, Hiatt P, McCoy K, McNamara S, Ramsey B, et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr Pulmonol 1999;28:321–328. 8. Zemanick ET, Wagner BD, Robertson CE, Stevens MJ, Szefler SJ, Accurso FJ, Sagel SD, Harris JK. Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods. Ann Am Thorac Soc 2015;12:221–229. 9. Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, Moore JH, Guill MF, Morrison HG, Sogin ML, et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. MBio 2012;3:3. 10. Biesbroek G, Bosch AA, Wang X, Keijser BJ, Veenhoven RH, Sanders EA, Bogaert D. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med 2014;190:298–308. 11. Faden H. Monthly prevalence of group A, B and G Streptococcus, Haemophilus influenzae types E and F and Pseudomonas aeruginosa nasopharyngeal colonization in the first two years of life. Pediatr Infect Dis J 1998;17:255–256. 12. Velazquez-Guadarrama ´ N, Martinez-Aguilar G, Galindo JA, Zuñiga G, Arbo-Sosa A. Methicillin-resistant S. aureus colonization in Mexican children attending day care centres. Clin Invest Med 2009;32:E57–E63. 13. Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, Holt BJ, Hales BJ, Walker ML, Hollams E, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 2015;17:704–715. 14. Taylor L, Corey M, Matlow A, Sweezey NB, Ratjen F. Comparison of throat swabs and nasopharyngeal suction specimens in non-sputum-producing patients with cystic fibrosis. Pediatr Pulmonol 2006;41:839–843. 15. Prevaes SM, de Winter-de Groot KM, Janssens HM, de Steenhuijsen Piters WA, Tramper-Stranders GA, Wyllie AL, Hasrat R, Tiddens HA, van Westreenen M, van der Ent CK, et al. Development of the nasopharyngeal microbiota in infants with cystic fibrosis. Am J Respir Crit Care Med 2016;193:504–515. 16. Bogaert D, Keijser B, Huse S, Rossen J, Veenhoven R, van Gils E, Bruin J, Montijn R, Bonten M, Sanders E. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS One 2011;6:e17035. 17. Smyth A. Prophylactic antibiotics in cystic fibrosis: a conviction without evidence? Pediatr Pulmonol 2005;40:471–476.
Copyright © 2016 by the American Thoracic Society
Bridge or Abyss: Extracorporeal Membrane Oxygenation for Acute Respiratory Failure in Interstitial Lung Disease Interstitial lung disease (ILD) defines an entity or a syndrome of chronic alterations of lung parenchyma characterized by inflammation and/or fibrosis (1, 2). ILD can be induced by defined conditions such as pneumonia or fibrosis. It can be classified as 474
idiopathic if a predisposing factor cannot be identified or if the underlying pathophysiology is not totally understood. A multidisciplinary approach allows a definitive diagnosis, and reasonable progress with respect to pharmacological treatment
American Journal of Respiratory and Critical Care Medicine Volume 193 Number 5 | March 1 2016
EDITORIALS options has been made for some of the underlying conditions (1, 3–5). However, regardless of the underlying condition, acute exacerbations of ILD leading to acute respiratory failure requiring mechanical ventilation are still associated with a poor outcome (6, 7). Mechanical ventilation (MV) makes any patient prone to the risk for ventilator-induced lung injury (8), which in patients with ILD may cause irreversible deterioration of the underlying disease process and lead to a fatal outcome if lung transplantation cannot be performed (7, 9, 10). There are two potential rationales for the use of extracorporeal membrane oxygenation (ECMO), First of all, extracorporeal lung support might allow one to reduce the invasiveness of MV (11), and therefore minimize the risk of “triggering” fatal deterioration of the underlying chronic process. Second, ECMO might bridge the period necessary for registering the patient for a lung transplant, possibly obtaining a suitable organ (12–14). In this issue of the Journal, Trudzinski and colleagues (pp. 527–533) report the findings of a retrospective single-center analysis of patients with ILD suffering from severe acute respiratory failure who have been treated either with conventional MV alone or with ECMO combined with MV or noninvasive respiratory support (15). Patients were eligible for ECMO if the acute cause of deterioration and acute respiratory failure was rated as potentially reversible. ECMO therapy was provided regardless of whether the patient was already listed for lung transplantation or not. Patients were not considered for ECMO if their prognosis was poor and existing comorbitdies represented contraindications for lung transplantation. The patients included in this analysis were treated with ECMO either because of hypoxemic respiratory failure, in which conventional ventilation, even with injurious ventilator settings, such as plateau pressures above 35 cm H2O (highest plateau pressure . 55 cm H2O) failed to ensure adequate gas exchange with consequent hypoxemia and severe respiratory acidosis, or if noninvasive respiratory support (e.g., high-flow oxygen) was not sufficient to prevent intubation and invasive ventilation. In the latter cases, ECMO was applied as “awake ECMO,” which represents an evolving technique to bridge patients if there are no contraindications for transplantation (14, 16). Trudzinski and colleagues analyzed 21 patients with ILD who had received ECMO therapy. One of the main findings was a high mortality rate in those patients receiving ECMO, who, for whatever reason, did not receive a lung transplant. In contrast, in those patients suffering from acute respiratory failure who met the criteria for transplantation, the time gain opened the opportunity to receive an organ. Of the 21 patients who were placed on ECMO, 33% either received a lung transplant (n = 6) or were discharged alive without transplantation (n = 1). Although mortality is high in this group of severely ill patients, one can assume that it would been closer to 100% without ECMO support. In the end, six of the eight patients, whose transferal from another hospital was facilitated by ECMO, were not considered for lung transplantation. Because these patients had not been evaluated for transplantation before the acute respiratory failure, ECMO had, at least, made this a possibility. However, the high percentage of patients whose transfer was ultimately futile is worrisome. The supplemental data that provide additional information for each single case reveal that making a decision against or in favor of potentially live-sustaining measures such as ECMO was extremely difficult. This finding and the time receiving mechanical ventilation before being considered Editorials
for transferal and initiation of ECMO therapy underlines the urgent need for the early consultation of an experienced ECMO center to minimize the rate of futile treatments. Such a center should either perform lung transplantations itself or work closely together with such an institution. Acute respiratory failure in ILD has a poor outcome without lung transplantation. The data of Trudzinski and colleagues give an important indication that, at least in their study patient group, ECMO was unable to prevent the irreversible progression of the underlying disease when it was established according to the inclusion criteria and at the time used in their study. As a consequence, the rationale to use ECMO in patients with ILD to prevent further ILD progression seems questionable, to say the least. Moreover, the rationale and option to use ECMO as a bridge to transplant seems to only work for those patients who have already been considered for lung transplantation, and in whom transplantation was ultimately realized. Using ECMO to “win time” apparently offers no benefit for those patients in whom transplantation is, for whatever reason, not a realistic option. As a consequence, the use of ECMO in patients with ILD who do not qualify for lung transplantation is likely to increase the burden and the suffering for the patients and their relatives without offering a realistic chance of a benefit. As the decision to initiate ECMO must frequently be made under obvious time pressure, the data presented here strongly support obtaining an objective and comprehensive picture of a patient as best as one can with the available knowledge before starting. This is to keep the number of patients who start ECMO and then have it judged a futile treatment as low as possible. The data presented by Trudzinski and colleagues represent a small but important piece in the puzzle of the reasonable indications for, and potential benefits and possible futility of initiating, ECMO therapy. The study does not so much gives definitive answers in terms of robust assistance in evidence-based decision making but, instead, helps one to ask the right questions and to think the proper thoughts. To preserve and further develop ECMO as the lifesaving tool that it is, and not an instrument for preventing dignified dying, one must ensure a thorough evaluation and indication before initiation, the correct implementation with a continuous reevaluation of the therapeutic goals, and the readiness to terminate ECMO therapy if the defined and agreed-upon goals can no longer be achieved. The publication of Trudzinski and colleagues might help make ECMO a bridge for life and save the patient, the family, and the whole caregiving team from the abyss. n
Author disclosures are available with the text of this article at www.atsjournals.org. Onnen Moerer, M.D. Michael Quintel, M.D. Department of Anaesthesiology, Emergency and Intensive Care Medicine Georg-August-University Gottingen ¨ Gottingen, ¨ Germany
References 1. Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, Brozek JL, Collard HR, Cunningham W, Homma S, et al.; American Thoracic Society; European Respiratory society; Japanese Respiratory Society; Latin American Thoracic Association.
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EDITORIALS An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 2015;192:e3–e19. 2. Cottin V. Interstitial lung disease. Eur Respir Rev 2013;22:26–32. 3. Wilson KC, Raghu G. The 2015 guidelines for idiopathic pulmonary fibrosis: an important chapter in the evolution of the management of patients with IPF. Eur Respir J 2015;46:883–886. 4. Cottin V, Richeldi L. Neglected evidence in idiopathic pulmonary fibrosis and the importance of early diagnosis and treatment. Eur Respir Rev 2014;23:106–110. 5. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/ JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824. 6. Mallick S. Outcome of patients with idiopathic pulmonary fibrosis (IPF) ventilated in intensive care unit. Respir Med 2008;102: 1355–1359. 7. Gaudry S, Vincent F, Rabbat A, Nunes H, Crestani B, Naccache JM, Wolff M, Thabut G, Valeyre D, Cohen Y, et al. Invasive mechanical ventilation in patients with fibrosing interstitial pneumonia. J Thorac Cardiovasc Surg 2014;147:47–53. 8. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med 2014;370:980. 9. Fernandez-P ´ erez ´ ER, Yilmaz M, Jenad H, Daniels CE, Ryu JH, Hubmayr RD, Gajic O. Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease. Chest 2008;133:1113–1119.
10. Baydur A. Mechanical ventilation in interstitial lung disease: which patients are likely to benefit? Chest 2008;133:1062–1063. 11. Terragni P, Ranieri VM, Brazzi L. Novel approaches to minimize ventilator-induced lung injury. Curr Opin Crit Care 2015;21:20–25. 12. Hoopes CW, Kukreja J, Golden J, Davenport DL, Diaz-Guzman E, Zwischenberger JB. Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation. J Thorac Cardiovasc Surg 2013;145:862–867, discussion 867–868. 13. Hayanga AJ, Aboagye J, Esper S, Shigemura N, Bermudez CA, D’Cunha J, Bhama JK. Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy in the management of rapidly advancing pulmonary disease. J Thorac Cardiovasc Surg 2015;149:291–296. 14. Inci I, Klinzing S, Schneiter D, Schuepbach RA, Kestenholz P, Hillinger S, Benden C, Maggiorini M, Weder W. Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review. Transplantation 2015;99:1667–1671. 15. Trudzinski FC, Kaestner F, Schafers ¨ H-J, Fahndrich ¨ S, Seiler F, Bohmer ¨ P, Linn O, Kaiser R, Haake H, Langer F, et al. Outcome of patients with interstitial lung disease treated with extracorporeal membrane oxygenation for acute respiratory failure. Am J Respir Crit Care Med 2016;193:527–533. 16. Lehr CJ, Zaas DW, Cheifetz IM, Turner DA. Ambulatory extracorporeal membrane oxygenation as a bridge to lung transplantation: walking while waiting. Chest 2015;147:1213–1218.
Copyright © 2016 by the American Thoracic Society
Just Say No! Smoking Abstinence Works Lung cancer still remains the leading cause of cancer death in the United States, more than 50 years after the original Surgeon General’s report. In addition, diseases are continuing to be added to the list of risks from smoking, including renal failure, intestinal ischemia, and hypertensive heart disease (1). Smoking cessation, and better yet, lifelong abstinence, remain the best approaches to lowering this dreadful toll (2). Public health measures in the United States are continuing to lower the prevalence of adult smoking, and a current encouraging estimate from the Centers for Disease Control and Prevention for 2014 is a prevalence of 16.8% in the civilian, noninstitutionalized population that is willing to be interviewed (3). Data collection on e-cigarette use began in 2014, and prevalence is estimated at 3.7%. There are now 5 million fewer smokers, at 40.0 million smokers, down from 45 million smokers in 2005. Those individuals aged 65 years or older have the lowest smoking rate, at 8.5%, but this has not changed recently. Unfortunately, the persistence of smoking is seen most commonly in lower socioeconomic groups; for example, the prevalence of smoking in those on Medicaid is estimated to be 29.1%. Screening of high-risk current or former smokers for lung cancer with three annual low-dose computerized tomography (LDCT) scans has been shown to reduce lung cancer mortality by 20% in the definitive NLST (National Lung Screening Trial) (4). There has been a concern that screening may lead to a sense of false reassurance and might encourage smoking resumption or discourage cessation. In this issue of the Journal, Tanner and colleagues (pp. 534–541) review available data from the NLST to assess the effect of smoking abstinence at entry into the study with
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subsequent mortality (5). Reassuringly, lower mortality is seen for those who have the longest periods of smoking abstinence. Furthermore, coupling smoking abstinence with lung cancer screening with LDCT results in even a further decline in lung cancer mortality. There was, on average, a 9% annual decline in lung cancer mortality for each year of smoking abstinence coupled with screening. Fifteen years of smoking cessation at time of trial entry and LDCT screening led to a lung cancer mortality risk reduction of 38%. A subset of the NLST was analyzed comprising non-Hispanic white and non-Hispanic black individuals (47,902 vs. 2,361, respectively), with 24,190 current and 26,073 former smokers. The full NLST data set does not have information about smoking cessation or persistence during the trial, which limited the analysis to some extent. Information at study entry, including standard demographic, smoking, and comorbid conditions, was assessed. Nonlinear effects of pack-years and quit-years were assessed through quadratic forms of the two variables. Time to lung cancerspecific and overall mortality were the outcomes of interest. The lowest hazard rates for lung cancer mortality were seen in those who smoked the least and had the longest duration of smoking cessation at trial entry. Of importance, this effect was lessened by increasing pack-year history. Current smokers at trial entry were more likely to be African American and less educated. Reassuringly, however, the benefit of smoking cessation was more pronounced among African Americans. Black former smokers, which included 794 individuals at trial entry, had a hazard rate for lung cancer mortality of
American Journal of Respiratory and Critical Care Medicine Volume 193 Number 5 | March 1 2016
