© 2004 American Thoracic Society
All Roses Are Flowers, But Not All Flowers Are RosesTo the Editor:We read the editorial by Drs. Cornfield and Haddad (1) on our article (2) with considerable interest. The editorial raises important issues, including the importance of accurate definitions for disease states, but it has several misconceptions and errors that we wish to clarify and correct. Drs. Cornfield and Haddad (1) refer to our study as a trial. Although the information was collected as part of a weaning trial, this article is not a report of a trial. It is a descriptive study across nine centers for 6 consecutive months of patients who were mechanically ventilated for more than 24 hours (2). Drs. Cornfield and Haddad (1) have used the term respiratory failure to refer specifically to acute respiratory distress syndrome (ARDS), which is incorrect. The editorial also incorrectly states that we were not specific in defining ARDS and that the incidence of ARDS was probably higher than reported. We defined ARDS as a PaO2/FIO2 ratio of 200 or less with bilateral infiltrates and no evidence of heart failure (2). Although 52% of our patients had a PaO2/FIO2 ratio of 200 or less during their stay, only 7.6% met the criteria for ARDS at 24 hours after admission. Timmons and colleagues (3) found that ARDS was found in only 39% of patients with acute hypoxemic respiratory failure, but they did not include any patient with acute ventilatory failure without hypoxia. Drs. Cornfield and Haddad stated: "Implicit in the objective of the trial is a goal of determining the normative incidence and natural history of respiratory failure in children" (1). We clearly stated that our objective was to describe those children receiving mechanical ventilation for greater than 24 hours across large pediatric referral centers in North America to determine the feasibility of conducting clinical trials to improve the health outcomes of this population (2). The editorial (1) also criticizes our exclusion criteria. We excluded these patients for the express purpose of defining a population in which clinical trials may be undertaken. Patients with pulmonary hypoplasia, bone marrow transplantation, and abnormal vascular tone may not be suitable candidates for a clinical trial of a therapy to improve outcomes from acute respiratory failure. There have been at least three major clinical trials in children with respiratory failure (4–6). Our exclusion criteria are consistent with published studies. Drs. Cornfield and Haddad (1) have criticized us for not including trauma patients. That is not correct. Trauma was reported in 30 patients (9.6%), and 25 had traumatic brain injury (2). In addition, they point out the difference in mortality rates between our study and that published in the literature (4–6). The studies on high-frequency oscillation and inhaled nitric oxide only included patients whose oxygenation index was greater than 13 and 15, respectively (4, 6). Clearly, these patients had severe disease. The surfactant study had an overall mortality of 11.9% for patients with an oxygenation index greater than 7 (5). Our lower mortality rate might have been secondary to inclusion criteria with a broad range of severity and to improved management strategies in an era of lung-protective ventilation. We disagree with the conclusion that the significance of the study is diminished. In fact, we would state that it is exactly the opposite for the following reasons. First, it defines a group of children who can be potentially enrolled in clinical trials. Second, it provides an estimate of the population size that can be studied. For example, it would not be feasible to conduct a randomized controlled trial in all children with respiratory failure using mortality as the primary outcome because the mortality is low, especially in infants with bronchiolitis, the single most common diagnosis in this population of children. If we focus on a subset of patients with a higher mortality rate, such as those requiring mechanical ventilation with a clinical diagnosis of ARDS after 24 hours of mechanical ventilation, such a study would have to enroll patients from multiple centers to achieve sufficient power. Third, the editorial (1) points out the heterogeneity in the population requiring acute mechanical ventilator support for more than 24 hours and shows that half of these children are younger than 1 year of age. We believe that our study (2) did meet its intended goal: to provide future clinical investigators an estimate for conducting clinical trials in children with acute respiratory failure. In addition, our study provides estimates of individual subsets of patients with acute respiratory failure who may be eligible for different clinical trials.
FOOTNOTES Conflict of Interest Statement: S.V., A.R., J.H., P.F., I.C., R.G., and P.L. have no declared conflict of interest. REFERENCES
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