Apr 15, 2014 - BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, et al. Efficacy .... Sanders DB, Li Z, Rock MJ, Brody AS, Farrell PM. The sensitivity of lung.
EDITORIALS in infection control practitioner time (2, 5, 10). The electronic minute-to-minute monitoring of ventilator settings used in the study of Klouwenberg and colleagues demonstrates potential problems with this as well (4). They correlated a variety of algorithms for their minute-to-minute data with prospectively defined VAP. Their primary analysis was incorrect in that it used the lowest recorded FIO2/PEEP for any duration of time. The official CDC definition for “minimal daily PEEP or FIO2 used for surveillance is the lowest setting during a calendar day that is maintained for at least 1 hour” (11). So the author’s “sustained settings rule” is actually the correct analysis for the current VAC algorithm, but the results are essentially the same as their primary analysis (although the individual patients identified may differ). That may not be true for centers with different ventilatory strategies (9). So has the VAE surveillance algorithm delivered on any of the proposed benefits (2)? Clearly, with properly programmed electronic surveillance, the VAE algorithms will decrease infection control practitioner time commitment. Reliability for between-hospital comparisons is questionable, whereas intrahospital comparisons may be valid (9). However, the actual clinical entity being compared is unclear, and therefore its use for quality improvement is questionable. The study of Klouwenberg and colleagues confirms others’ findings that VAEs poorly correlate with VAP (4, 9). A VAC “bundle” to address all the multiple potential causes, including variability resulting from the original disorder leading to mechanical ventilation, will be difficult to design. So with VAE surveillance, we do not know what we are detecting or what to do about it, but we can detect it faster and easier. If VAE surveillance is subsequently linked to public reporting or pay-for-performance, the Newtonian-predicted reaction will be manipulation of ventilatory strategy to minimize VAEs without resultant clinical benefit. The missing factor of this equation is better diagnostics. Once these are available, we can enter the quantum mechanics era of VAP prevention. n Author disclosures are available with the text of this article at www.atsjournals.org. Richard G. Wunderink, M.D. Division of Pulmonary and Critical Care Medicine Northwestern University Feinberg School of Medicine Chicago, Illinois
References 1. Klompas M. Interobserver variability in ventilator-associated pneumonia surveillance. Am J Infect Control 2010;38:237–239. 2. Magill SS, Klompas M, Balk R, Burns SM, Deutschman CS, Diekema D, Fridkin S, Greene L, Guh A, Gutterman D, et al. Developing a new, national approach to surveillance for ventilator-associated events. Crit Care Med 2013;41:2467–2475. 3. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388–416. 4. Klouwenberg PMCK, van Mourik MSM, Ong DSY, Horn J, Schultz MJ, Cremer OL, Bonten MJM. Electronic implementation of a novel surveillance paradigm for ventilator-associated events: feasibility and validation. Am J Respir Crit Care Med 2014;189: 947–955. 5. Klompas M, Kleinman K, Platt R. Development of an algorithm for surveillance of ventilator-associated pneumonia with electronic data and comparison of algorithm results with clinician diagnoses. Infect Control Hosp Epidemiol 2008;29:31–37. 6. Klompas M. Complications of mechanical ventilation—the CDC’s new surveillance paradigm. N Engl J Med 2013;368: 1472–1475. 7. Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:1864–1869. 8. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371:126–134. 9. Muscedere J, Sinuff T, Heyland DK, Dodek PM, Keenan SP, Wood G, Jiang X, Day AG, Laporta D, Klompas M; Canadian Critical Care Trials Group. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 2013;144:1453–1460. 10. Klompas M, Kleinman K, Khan Y, Evans RS, Lloyd JF, Stevenson K, Samore M, Platt R; CDC Prevention Epicenters Program. Rapid and reproducible surveillance for ventilator-associated pneumonia. Clin Infect Dis 2012;54:370–377. 11. Centers for Disease Control and Prevention CfDCa. Ventilatorassociated event (VAE) [accessed 2014 Mar 5]. Available from: http://www.cdc.gov/nhsn/PDFs/pscManual/10-VAE_FINAL.pdf
Copyright © 2014 by the American Thoracic Society
Seeing Is Believing: Imaging Early Lung Disease in Cystic Fibrosis The progression of lung disease in cystic fibrosis (CF) begins early in life, and a major challenge in the field has been detecting and quantifying these early changes. This challenge extends both to clinical practice, where abnormal findings may dictate additional treatments, and to quantifying response to interventions in the research setting. There is clearly a need for better ways to objectively assess early lung disease in CF. Seeing is believing, and the impact of progressive lung destruction is readily observed in routine chest radiographs of adults Editorials
with CF. Similarly, recent data suggest that abnormalities seen on a rigorously scored chest radiograph in older children and adolescents correlate well with structural abnormalities seen on computed tomography (CT) scans, perhaps better than they correlate with other markers of disease progress, such as spirometry (1, 2). In contrast, some data have suggested that CT scans are superior for detecting structural abnormalities, especially in infants and young children (3), leading to wider use in this age group (4–7). These efforts using CT scanning have resulted in especially 883
EDITORIALS valuable longitudinal data of the progress of CF-related lung damage in early childhood, as well as the identification of factors associated with such progression. However, as is also well recognized, there are limits to the routine use of CT scanning that are primarily related to risks of exposure to ionizing radiation required for image generation. This severely limits the frequency at which scans can be performed, especially in the research setting. Furthermore, we have limited data at present to indicate that such imaging in young children would be a robust and sensitive outcome measure for detecting intervention-related improvements. These shortcomings have spurred significant interest in the possible utility of magnetic resonance imaging (MRI) techniques, and newly developed MR sequences, for imaging lung disease in young children with CF. In this issue of the Journal, Wielp¨utz and colleagues (pp. 956–965) present important data that further support a role for this approach (8). The MRI techniques used here are especially well suited for assessing perfusion, bronchial wall thickening, and mucus plugging, and thus seem particularly well suited to CF, where inflammation leading to bronchial wall thickening and mucus plugging due to impaired mucociliary clearance are prominent features. These data demonstrate the impressively detailed information that MRI is able to display, and provide clear further evidence that CF-related pathology is present in infancy. MRI was also able to differentiate abnormalities in subjects with CF that are fundamentally different than those in other suppurative diseases, like pneumonias. In addition, most areas of mucous plugging coincided with perfusion defects, thus suggesting sensitivity to ventilation/perfusion matching. The ability to identify substantive changes in image characteristics over the course of treatment for a pulmonary exacerbation suggests potential utility as an objective outcome measure, especially in infants and younger children who are unable to perform spirometry. An intriguing future possibility is the correlation of mucus plugging seen by MRI and elevations in lung clearance index as an indication of ventilation inhomogeneity (9). This is particularly interesting, as lung clearance index can be performed in young children without the need for sedation. Even though the use of MRI to gain this additional detail avoids the radiation of CT scans, the use of MRI in this setting is not completely without risks. As scan times averaged 15–20 minutes in a loud and claustrophobic setting within a magnet, most, if not all, infants and younger children will require sedation to remain calm and sufficiently still during the imaging process. In fact, the MRI morphology score is potentially confounded by this need for sedation, which can impair mucus clearance, although the observed sensitivity of the MRI morphology score to therapy for pulmonary exacerbation argues against such confounding in the comparison of ill versus well states. Several additional questions remain. These cross-sectional data do not address whether the increased mucus plugs and associated perfusion abnormalities are stable or transient. These data also do not address if transient plugging may be exacerbated by sedation or relieved by chest physiotherapy, hypertonic saline inhalation, and/or other airway clearance maneuvers. Addressing these questions will require assessment of the repeatability over short time periods (i.e., days) of the scans and morphology scores in infants and children with CF who are well. Such studies of repeatability will also be needed for this technique to be useful as an outcome 884
measure for interventional trials for clinically stable infants and children in their baseline state of health. Unfortunately, because of the requirement for repeated sedation, such studies may be difficult to accomplish. Several questions also arise with regard to the potential clinical use of this technique. First, the aforementioned issue of repeatability must be addressed, as the utility of diagnostic tests hinges on such repeatability. For example, if there are significant changes in the morphology score as a result of airway clearance, standardized protocols for performing the test will at least need to take this into account. It is also unclear how much such data may influence medical decision making. Although some CF centers presently perform annual CT scans with sedation in young children to monitor disease progress, it is not clear how these scans influence care decisions. In addition, there are now clear data that both CT scanning and MRI techniques demonstrate the common presence of CF-related pathology, such that a reasonable clinician could assume that such pathology is there and increase aggression of care without routinely performing the scan(s). Empirically increased aggression of care, which will likely improve outcomes, may be especially appropriate given the cost of MRI. This cost, as well as the need for sedation, also suggests that such MRI scans may be done occasionally at most, and perhaps not to monitor changes due to clinical intervention. The thought-provoking data of Wielp¨utz and colleagues (8) clearly support the notion that airway and lung disease in CF starts early, and that the nature of this lung disease is fundamentally different than other suppurative lung diseases of childhood. We look forward to the important discussion of how these data will inform how we study and care for infants and young children with CF. n Author disclosures are available with the text of this article at www.atsjournals.org. Stamatia Alexiou, M.D. Ronald C. Rubenstein, M.D., Ph.D. Division of Pulmonary Medicine and Cystic Fibrosis Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania and Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania
References 1. Sanders DB, Li Z, Brody AS, Farrell PM. Chest computed tomography scores of severity are associated with future lung disease progression in children with cystic fibrosis. Am J Respir Crit Care Med 2011;184:816–821. 2. Sanders DB, Li Z, Rock MJ, Brody AS, Farrell PM. The sensitivity of lung disease surrogates in detecting chest CT abnormalities in children with cystic fibrosis. Pediatr Pulmonol 2012;47:567–573. 3. Demirkazik FB, Ariyurek ¨ OM, Ozçelik U, Goçmen ¨ A, Hassanabad HK, Kiper N. High resolution CT in children with cystic fibrosis: correlation with pulmonary functions and radiographic scores. Eur J Radiol 2001; 37:54–59. 4. Sly PD, Brennan S, Gangell C, de Klerk N, Murray C, Mott L, Stick SM, Robinson PJ, Robertson CF, Ranganathan SC; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF). Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009;180:146–152. 5. Mott LS, Park J, Gangell CL, de Klerk NH, Sly PD, Murray CP, Stick SM; Australian Respiratory Early Surveillance Team for Cystic Fibrosis Study Group. Distribution of early structural lung changes due to
American Journal of Respiratory and Critical Care Medicine Volume 189 Number 8 | April 15 2014
EDITORIALS cystic fibrosis detected with chest computed tomography. J Pediatr 2013;163:243–248.e1–e3. 6. Mott LS, Park J, Murray CP, Gangell CL, de Klerk NH, Robinson PJ, Robertson CF, Ranganathan SC, Sly PD, Stick SM; AREST CF. Progression of early structural lung disease in young children with cystic fibrosis assessed using CT. Thorax 2012;67:509–516. 7. 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. 8. Wielp utz ¨ MO, Puderbach M, Kopp-Schneider A, Stahl M, Fritzsching E, Sommerburg O, Ley S, Sumkauskaite M, Biederer J, Kauczor H-U, et al. Magnetic resonance imaging detects changes in
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structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 2014;189: 956–965. 9. Subbarao P, Stanojevic S, Brown M, Jensen R, Rosenfeld M, Davis S, Brumback L, Gustafsson P, Ratjen F. Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis: a pilot study using inhaled hypertonic saline. Am J Respir Crit Care Med 2013;188:456–460.
Copyright © 2014 by the American Thoracic Society
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