Lung Transplantation and Survival in Children with Cystic Fibrosis

Theodore G. Liou, M.D., Frederick R. Adler, Ph.D., David R. Cox, Ph.D., and Barbara C. Cahill, M.D.

ABSTRACT

Background The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain.

Methods We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis.

Results A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection was associated with a trend toward decreased survival, regardless of whether the patient underwent transplantation. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 283 patients had a significant risk of harm, 102 patients had an insignificant benefit, and 124 patients had an insignificant risk of harm associated with lung transplantation.

Conclusions Our analyses estimated clearly improved survival for only 5 of 514 patients on the waiting list for lung transplantation. Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality-of-life benefit from lung transplantation.

Phenotype and Course of Hutchinson–Gilford Progeria Syndrome

Melissa A. Merideth, M.D., M.P.H., Leslie B. Gordon, M.D., Ph.D., Sarah Clauss, M.D., Vandana Sachdev, M.D., Ann C.M. Smith, M.A., Monique B. Perry, M.D., Carmen C. Brewer, Ph.D., Christopher Zalewski, M.A., H. Jeffrey Kim, M.D., Beth Solomon, M.S., Brian P. Brooks, M.D., Ph.D., Lynn H. Gerber, M.D., Maria L. Turner, M.D., Demetrio L. Domingo, D.D.S., Thomas C. Hart, D.D.S., Jennifer Graf, M.S., James C. Reynolds, M.D., Andrea Gropman, M.D., Jack A. Yanovski, M.D., Ph.D., Marie Gerhard-Herman, M.D. Francis S. Collins, M.D., Ph.D., Elizabeth G. Nabel, M.D., Richard O. Cannon, III, M.D., William A. Gahl, M.D., Ph.D., and Wendy J. Introne, M.D.

ABSTRACT

Background Hutchinson–Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. The genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription.

Methods We enrolled 15 children between 1 and 17 years of age, representing nearly half of the world's known patients with Hutchinson–Gilford progeria syndrome, in a comprehensive clinical protocol between February 2005 and May 2006.

Results Clinical investigations confirmed sclerotic skin, joint contractures, bone abnormalities, alopecia, and growth impairment in all 15 patients; cardiovascular and central nervous system sequelae were also documented. Previously unrecognized findings included prolonged prothrombin times, elevated platelet counts and serum phosphorus levels, measured reductions in joint range of motion, low-frequency conductive hearing loss, and functional oral deficits. Growth impairment was not related to inadequate nutrition, insulin unresponsiveness, or growth hormone deficiency. Growth hormone treatment in a few patients increased height growth by 10% and weight growth by 50%. Cardiovascular studies revealed diminishing vascular function with age, including elevated blood pressure, reduced vascular compliance, decreased ankle–brachial indexes, and adventitial thickening.

Conclusions Establishing the detailed phenotype of Hutchinson–Gilford progeria syndrome is important because advances in understanding this syndrome may offer insight into normal aging. Abnormal lamin A (progerin) appears to accumulate with aging in normal cells. (ClinicalTrials.gov number, NCT00094393 [ClinicalTrials.gov] .)

Etanercept Treatment for Children and Adolescents with Plaque Psoriasis

Amy S. Paller, M.D., Elaine C. Siegfried, M.D., Richard G. Langley, M.D., Alice B. Gottlieb, M.D., Ph.D., David Pariser, M.D., Ian Landells, M.D., Adelaide A. Hebert, M.D., Lawrence F. Eichenfield, M.D., Vaishali Patel, Pharm.D., M.S., Kara Creamer, M.S., Angelika Jahreis, M.D., Ph.D., for the Etanercept Pediatric Psoriasis Study Group

ABSTRACT

Background Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis.

Methods In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label etanercept. At week 36, 138 patients underwent a second randomization to placebo or etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physician's global assessment of clear or almost clear of disease, and safety assessments.

Results At week 12, 57% of patients receiving etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P<0.001). A significantly higher proportion of patients in the etanercept group than in the placebo group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and a physician's global assessment of clear or almost clear (53% vs. 13%) at week 12 (P<0.001).> 36, after 24 weeks of open-label etanercept, rates of PASI 75 were 68% and 65% for patients initially assigned to etanercept and placebo, respectively. During the withdrawal period from week 36 to week 48, response was lost by 29 of 69 patients (42%) assigned to placebo at the second randomization. Four serious adverse events (including three infections) occurred in three patients during treatment with open-label etanercept; all resolved without sequelae.

Conclusions Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819 [ClinicalTrials.gov] .)

Severe Anemia in Malawian Children

Job C.J. Calis, M.D., Kamija S. Phiri, M.D., E. Brian Faragher, Ph.D., Bernard J. Brabin, F.R.C.P.C.H., Imelda Bates, M.D., Luis E. Cuevas, M.D., Rob J. de Haan, Ph.D., Ajib I. Phiri, M.D., Pelani Malange, M.Sc., Mirriam Khoka, B.Sc., Paul J.M. Hulshof, M.Sc., Lisette van Lieshout, Ph.D., Marcel G.H.M. Beld, Ph.D., Yik Y. Teo, Ph.D., Kirk A. Rockett, Ph.D., Anna Richardson, B.Sc., Dominic P. Kwiatkowski, F.R.C.P., Malcolm E. Molyneux, F.R.C.P., and Michaël Boele van Hensbroek, M.D.

ABSTRACT

Background Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.

Methods We conducted a case–control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.

Results Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD^{–202/–376} genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B₁₂ deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.

Conclusions There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.

Severe Anemia in Malawian Children

Job C.J. Calis, M.D., Kamija S. Phiri, M.D., E. Brian Faragher, Ph.D., Bernard J. Brabin, F.R.C.P.C.H., Imelda Bates, M.D., Luis E. Cuevas, M.D., Rob J. de Haan, Ph.D., Ajib I. Phiri, M.D., Pelani Malange, M.Sc., Mirriam Khoka, B.Sc., Paul J.M. Hulshof, M.Sc., Lisette van Lieshout, Ph.D., Marcel G.H.M. Beld, Ph.D., Yik Y. Teo, Ph.D., Kirk A. Rockett, Ph.D., Anna Richardson, B.Sc., Dominic P. Kwiatkowski, F.R.C.P., Malcolm E. Molyneux, F.R.C.P., and Michaël Boele van Hensbroek, M.D.

ABSTRACT

Background Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.

Methods We conducted a case–control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.

Results Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD^{–202/–376} genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B₁₂ deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.

Conclusions There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.

Shared Genetic Causes of Cardiac Hypertrophy in Children and Adults

Hiroyuki Morita, M.D., Heidi L. Rehm, Ph.D., Andres Menesses, M.D., Barbara McDonough, R.N., Amy E. Roberts, M.D., Raju Kucherlapati, Ph.D., Jeffrey A. Towbin, M.D., J.G. Seidman, Ph.D., and Christine E. Seidman, M.D.

ABSTRACT

Background The childhood onset of idiopathic cardiac hypertrophy that occurs without a family history of cardiomyopathy can portend a poor prognosis. Despite morphologic similarities to genetic cardiomyopathies of adulthood, the contribution of genetics to childhood-onset hypertrophy is unknown.

Methods We assessed the family and medical histories of 84 children (63 boys and 21 girls) with idiopathic cardiac hypertrophy diagnosed before 15 years of age (mean [±SD] age, 6.99±6.12 years). We sequenced eight genes: MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3, MYL2, and ACTC. These genes encode sarcomere proteins that, when mutated, cause adult-onset cardiomyopathies. We also sequenced PRKAG2 and LAMP2, which encode metabolic proteins; mutations in these genes can cause early-onset ventricular hypertrophy.

Results We identified mutations in 25 of 51 affected children without family histories of cardiomyopathy and in 21 of 33 affected children with familial cardiomyopathy. Among 11 of the 25 children with presumed sporadic disease, 4 carried new mutations and 7 inherited the mutations. Mutations occurred predominantly (in >75% of the children) in MYH7 and MYBPC3; significantly more MYBPC3 missense mutations were detected than occur in adult-onset cardiomyopathy (P<0.005).> contractile function correlated with familial or genetic status. Cardiac transplantation and sudden death were more prevalent among mutation-positive than among mutation-negative children; implantable cardioverter–defibrillators were more frequent (P=0.007) in children with family histories that were positive for the mutation.

Conclusions Genetic causes account for about half of presumed sporadic cases and nearly two thirds of familial cases of childhood-onset hypertrophy. Childhood-onset hypertrophy should prompt genetic analyses and family evaluations.

Hypothermia Therapy after Traumatic Brain Injury in Children

James S. Hutchison, M.D., Roxanne E. Ward, B.A., Jacques Lacroix, M.D., Paul C. Hébert, M.D., M.H.Sc., Marcia A. Barnes, Ph.D., Desmond J. Bohn, M.B., Peter B. Dirks, M.D., Steve Doucette, M.Sc., Dean Fergusson, Ph.D., Ronald Gottesman, M.D., Ari R. Joffe, M.D., Haresh M. Kirpalani, M.B., M.Sc., Philippe G. Meyer, M.D., Kevin P. Morris, M.D., David Moher, Ph.D., Ram N. Singh, M.D., Peter W. Skippen, M.D., for the Hypothermia Pediatric Head Injury Trial Investigators and the Canadian Critical Care Trials Group

ABSTRACT

Background Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown.

Methods In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5°C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0°C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months.

Results A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1±1.2°C and 36.9±0.5°C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001)> group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups.

Conclusions In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com] .)

Long-Term Medical and Social Consequences of Preterm Birth

Dag Moster, M.D., Ph.D., Rolv Terje Lie, Ph.D., and Trond Markestad, M.D., Ph.D.

ABSTRACT

Background Advances in perinatal care have increased the number of premature babies who survive. There are concerns, however, about the ability of these children to cope with the demands of adulthood.

Methods We linked compulsory national registries in Norway to identify children of different gestational-age categories who were born between 1967 and 1983 and to follow them through 2003 in order to document medical disabilities and outcomes reflecting social performance.

Results The study included 903,402 infants who were born alive and without congenital anomalies (1822 born at 23 to 27 weeks of gestation, 2805 at 28 to 30 weeks, 7424 at 31 to 33 weeks, 32,945 at 34 to 36 weeks, and 858,406 at 37 weeks or later). The proportions of infants who survived and were followed to adult life were 17.8%, 57.3%, 85.7%, 94.6%, and 96.5%, respectively. Among the survivors, the prevalence of having cerebral palsy was 0.1% for those born at term versus 9.1% for those born at 23 to 27 weeks of gestation (relative risk for birth at 23 to 27 weeks of gestation, 78.9; 95% confidence interval [CI], 56.5 to 110.0); the prevalence of having mental retardation, 0.4% versus 4.4% (relative risk, 10.3; 95% CI, 6.2 to 17.2); and the prevalence of receiving a disability pension, 1.7% versus 10.6% (relative risk, 7.5; 95% CI, 5.5 to 10.0). Among those who did not have medical disabilities, the gestational age at birth was associated with the education level attained, income, receipt of Social Security benefits, and the establishment of a family, but not with rates of unemployment or criminal activity.

Conclusions In this cohort of people in Norway who were born between 1967 and 1983, the risks of medical and social disabilities in adulthood increased with decreasing gestational age at birth.

GAD Treatment and Insulin Secretion in Recent-Onset Type 1 Diabetes

Johnny Ludvigsson, M.D., Ph.D., Maria Faresjö, Ph.D., Maria Hjorth, M.Sc., Stina Axelsson, M.Sc., Mikael Chéramy, M.Sc., Mikael Pihl, M.Sc., Outi Vaarala, M.D., Ph.D., Gun Forsander, M.D., Ph.D., Sten Ivarsson, M.D., Ph.D., Calle Johansson, M.D., Agne Lindh, M.D., Nils-Östen Nilsson, M.D., Jan Åman, M.D., Ph.D., Eva Örtqvist, M.D., Ph.D., Peter Zerhouni, M.Sc., and Rosaura Casas, Ph.D.

ABSTRACT

Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age.

Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 µg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied.

Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (–0.21 vs. –0.27 nmol per liter [–0.62 vs. –0.81 ng per milliliter], P=0.045), as did stimulated secretion measured as the area under the curve (–0.72 vs. –1.02 nmol per liter per 2 hours [–2.20 vs. –3.08 ng per milliliter per 2 hours], P=0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response.

Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981 [ClinicalTrials.gov] .)

Preemptive Use of High-Dose Fluticasone for Virus-Induced Wheezing in Young Children

Francine M. Ducharme, M.D., Chantal Lemire, M.D., Francisco J.D. Noya, M.D., G. Michael Davis, M.D., Nathalie Alos, M.D., Hélène Leblond, M.D., Cheryl Savdie, M.Sc., Jean-Paul Collet, M.D., Ph.D., Lyudmyla Khomenko, Ph.D., Georges Rivard, M.D., and Robert W. Platt, Ph.D.

ABSTRACT

Background Although virus-induced wheezing is common in preschool-age children, optimal management remains elusive. We examined the efficacy and safety of preemptive treatment with high-dose fluticasone in reducing the severity of recurrent virus-induced wheezing in children.

Methods We randomly assigned 129 children who were 1 to 6 years of age to receive 750 µg of fluticasone propionate (ex-valve [manufacturer-measured] dose) or placebo twice daily, beginning at the onset of an upper respiratory tract infection and continuing for a maximum of 10 days, over a period of 6 to 12 months. The primary outcome was rescue oral corticosteroid use. Secondary outcomes included symptoms, use of β₂-agonists, acute care visits, hospitalizations, discontinuation of the study drug, change in growth and bone mineral density, basal cortisol level, and adverse events.

Results Over a median period of 40 weeks, 8% of upper respiratory tract infections in the fluticasone group led to treatment with rescue systemic corticosteroids, as compared with 18% in the placebo group (odds ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were treated with fluticasone, as compared with those who were given placebo, had smaller mean (±SD) gains from baseline in height (6.23±2.62 cm [unadjusted value]; z score, –0.19 ±0.42 vs. 6.56±2.90 cm [unadjusted value]; z score, 0.00±0.48; difference between groups in z score from baseline to end point, –0.24 [95% CI, –0.40 to –0.08]) and in weight (1.53±1.17 kg [unadjusted value]; z score, –0.15±0.48 vs. 2.17±1.79 kg [unadjusted value]; z score, 0.11±0.43; difference between groups in z score from baseline to end point, –0.26 [95% CI, –0.41 to –0.09]). There were no significant differences between the groups in basal cortisol level, bone mineral density, or adverse events.

Conclusions In preschool-age children with moderate-to-severe virus-induced wheezing, preemptive treatment with high-dose fluticasone as compared with placebo reduced the use of rescue oral corticosteroids. Treatment with fluticasone was associated with a smaller gain in height and weight. Given the potential for overuse, this preventive approach should not be adopted in clinical practice until long-term adverse effects are clarified. (ClinicalTrials.gov number, NCT00238927 [ClinicalTrials.gov] .)

Oral Prednisolone for Preschool Children with Acute Virus-Induced Wheezing

Jayachandran Panickar, M.D., M.R.C.P.C.H., Monica Lakhanpaul, M.D., F.R.C.P.C.H., Paul C. Lambert, Ph.D., Priti Kenia, M.B., B.S., M.R.C.P.C.H., Terence Stephenson, D.M., F.R.C.P.C.H., Alan Smyth, M.D., F.R.C.P.C.H., and Jonathan Grigg, M.D., F.R.C.P.C.H.

ABSTRACT

Background Attacks of wheezing induced by upper respiratory viral infections are common in preschool children between the ages of 10 months and 6 years. A short course of oral prednisolone is widely used to treat preschool children with wheezing who present to a hospital, but there is conflicting evidence regarding its efficacy in this age group.

Methods We conducted a randomized, double-blind, placebo-controlled trial comparing a 5-day course of oral prednisolone (10 mg once a day for children 10 to 24 months of age and 20 mg once a day for older children) with placebo in 700 children between the ages of 10 months and 60 months. The children presented to three hospitals in England with an attack of wheezing associated with a viral infection; 687 children were included in the intention-to-treat analysis (343 in the prednisolone group and 344 in the placebo group). The primary outcome was the duration of hospitalization. Secondary outcomes were the score on the Preschool Respiratory Assessment Measure, albuterol use, and a 7-day symptom score.

Results There was no significant difference in the duration of hospitalization between the placebo group and the prednisolone group (13.9 hours vs. 11.0 hours; ratio of geometric means, 0.90; 95% confidence interval, 0.77 to 1.05) or in the interval between hospital admission and signoff for discharge by a physician. In addition, there was no significant difference between the two study groups for any of the secondary outcomes or for the number of adverse events.

Conclusions In preschool children presenting to a hospital with mild-to-moderate wheezing associated with a viral infection, oral prednisolone was not superior to placebo. (Current Controlled Trials number, ISRCTN58363576 [controlled-trials.com] .)