Objective. To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants. Methods. A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and similar to 93% received all five scheduled injections. Results. Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups. Conclusions. Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BFD.

Home apnea/bradycardia monitoring is frequently used in the management of infants at increased risk for sudden infant death syndrome (SIDS). However, some infants have died despite evaluation by infant apnea programs, and the benefits of home monitoring remain unproven. To determine the SIDS rate and risk factors of infants evaluated by infant apnea programs, 31 apnea programs and ten home monitor vendors in California were surveyed. Eleven (35%) of the apnea programs and four (40%) of the vendors responded. Information was obtained on 26 infants who died. Thirteen (50%) deaths were due to SIDS. Abnormal sleep studies did not predict death. Fifteen infants died despite a recommendation for home monitoring. Seven deaths occurred in association with technical errors or noncompliance with monitoring. Four deaths were due to nonaccidental trauma. The apnea programs evaluated 3,406 infants during a 5-year period; 1,841 had monitoring recommended. Term infants with apnea, subsequent siblings of SIDS victims, and infants evaluated at referral centers were more likely to have monitoring recommended than premature infants with apnea or infants evaluated at nonreferral centers (P less than .0001). Infants who had monitoring recommended were at equal risk of dying of SIDS as those who did not.

In order to assess diurnal variation of flow-volume curves and to determine whether small airways are involved in the diurnal variation of pulmonary function in asthmatic children, we studied eight asthmatics who were attending an asthma summer camp. Spirometry and maximal expiratory flow-volume curves with air and a helium-oxygen mixture were obtained in the morning and afternoon over a 10-day period. We found that significant increases in maximal expiratory flows at all lung volumes occurred in the afternoon. However, the increase in flows with helium (helium response) was unchanged from morning to afternoon. These results suggest that both large and small airways are involved in the diurnal variation of pulmonary function in asthmatic children.

IDIOPATHIC FIBRINOUS MEDIASTINITIS is rarely encountered in pediatric practice. The natural history and course of this process have been described in relatively few children. ~-6 We have had a patient with this entity who presented with an extrinsic bronchial compression causing massive multilobar atelectasis. CASE HISTORY A 41/2-year-old black boy was referred to The Children's Center of The Johns Hopkins Hospital for evaluation of collapse of the right middle and right lower lobes of unknown duration (Fig. 1). The patient had been in his usual state of good health until three months prior to admission when he developed a dry hacking cough. During the subsequent three months, his nonproductive cough gradually increased, especially at night. Noisy respiration, decreased activity, and elevated respiratory rate were noted in the month prior to admission. There was no history of choking or any acute febrile illness in the past six months. The review of systems was negative. His past medical history and family history were unremarkable. Physical examination revealed a tachypneic, well-nourished black boy. The only abnormal physical findings were in the thorax. The right lower lung field was dull to percussion, with no audible breath sounds. High-pitched inspiratory and expiratory rhonchi were heard just above the area of consolidation. Examination of the left lung was normal. Laboratory findings included: hemoglobin 9.4 gm/dl, hematocrit 28%, white blood cell count 11,800/mm 3 with 67% segmented neutrophils, 24% lymphocytes, 2% atypical lymphocytes, 5%

A double-blind controlled trail of anti-Pseudomonas chemotherapy was carried out in 24 exacerbations of pulmonary disease in patients with cystic fibrosis. Fifteen exacerbations were treated with oxacillin plus sisomicin and carbenicillin (treatment group); nine were treated with oxacillin alone (control group). The planned length of treatment was 14 days. The difference between the failure rate in the treatment group (3/15) and the control group (7/9) was statistically significant (P less than 0.015). The difference in improvement of forced expiratory volume in 1 second was also significant (P less than 0.025). At the end of the study, Pseudomonas aeruginosa was still present in the sputum of all nine patients in the control group, but was not isolated from six of the 15 patients in the treatment group. The data suggest a beneficial role for anti-Pseudomonas chemotherapy in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis.

Twenty children with respiratory disease ingested 500 muCi of Tc-99m sulfur colloid orally, and scintigrams of the thorax were obtained to determine whether pulmonary aspiration of gastric contents could be detected. The children ranged in age from 1 mo to 14 yr; 13 were 8 mo of age or younger. Children were studied at 5 min and 4 hr after ingestion of Tc-99m sulfur colloid using a high sensitivity computer oscilloscope to record 100K-count images. Additional images were obtained after the children had slept overnight. Five children (25%) showed definite pulmonary accumulation of activity; four of these also had a barium swallow and three showed either pulmonary aspiration of barium or moderately severe gastroesophageal reflux. Oral ingestion of Tc-99m sulfur colloid provides a noninvasive means for diagnosing pulmonary aspiration under physiologic conditions in infants and children.

At sea level, it appears that oxygen desaturation does not occur in normal children at night and that the desaturation that occurs in moderately severe asthmatic children with therapeutic levels of theophylline does not approach dangerously low levels.

A child with congenital atresia of the apical posterior bronchus was followed from birth. The obstructed segment, ventilated through collateral pathways, was documented to be aerated by day 6. At 10 yr of age, the anomalous and adjacent normal segments were resected because of respiratory symptoms. Preoperatively, pulmonary function studies showed a mild obstructive ventilatory defect. Postoperatively, although asymptomatic, the patient's obstruction persisted. Collateral resistance (Rcoll) measured between the atretic and adjacent normal segments of the resected lung was comparable to Rcoll in young adults, but markedly greater than Rcoll for emphysematous lungs. Pathologic examination revealed gross emphysematous changes in the anomalous segment. We conclude that collateral pathways exist early in life and that ventilation of lung distal to congenitally absent airways is slow and may contribute to the development of emphysema; we speculate that this lesion should be resected early in life to permit optimal growth and development of the remaining lung.

Forty-four children (mean age 9.6 years) with a history of an allergic reaction(s) to an insect sting and with positive insect venom skin tests were studied. IgE antibodies (RAST) to honeybee phospholipase A and to yellow jacket venom were found in the sera of 78% and 77%, respectively, of these patients. The patients were immunized with the appropriate venoms over a 15-week course and most were then subjected to an in-hospital sting; there was a 3% reaction rate (1/37). Clinical protection as associated with a fivefold increase in anti-venom IgG. Five patients did not develop a significant increase in IgG antibody and they were treated more vigorously; four were stung subsequently without reaction. Two patients did not react when stung in the field; positive identification of the culprit insect was obtained. Twenty patients were re-stung after one year of maintenance therapy; there was a single mild, delayed reaction. Immunotherapy also increased the IgE antibody against venom 3.7-fold at three months; after one year of therapy the IgE antibody level had decreased but was still 40% greater than at the outset. Immunotherapy was associated with a 25% incidence of local pain and swelling and a 6% incidence of systemic reactions. We conclude that venom therapy in children is safe and effective. The indications for initiating immunotherapy require further definition.

The cardiac function of 21 patients with cystic fibrosis was studied using radionuclides and M-mode echocardiography. The patients (mean age 13.2 years, range 4 to 27) had a wide range of clinical and pulmonary function abnormalities (mean Shwachman-Kulczycki score 62.1). Decreased right ventricular ejection fraction was found in 13 of 18 patients (72%); an additional four patients had abnormal septal motion on ECHO. Left ventricular ejection fraction was abnormal at rest in four patients (19~ an additional four patients had borderline low L VEF. The L V pre-ejection period to ejection time ratio increased significantly (i.e, worsening L V performance) with deterioration of S-K score, chest radiograph score, and forced expiratory volume in 1 second Three of eight patients with normal LVEF at rest had an abnormal response to supine bicycle exercise: L VEF fell in two patients and was unchanged in one. Thus evidence of L V dysfunction was observed in seven of 21 (33%) of the patients," four at rest and in three only during exercise.

Chronic mucocutaneous candidiasis (CMCC) is a clinical syndrome characterized by persistent and recurrent Candida albicans infections of the mucous membranes and skin often associated with immunodeficiency. In order to gain insight into the frequency and severity of non-candidal infections in children with CMCC, four patients with CMCC are described in detail and 60 previously reported cases are reviewed. Fifty percent of children with CMCC had significant infections with other fungi, bacteria and viruses. Recurrent bacterial pneumonias and bronchiectasis were a major cause of morbidity and mortality. In addition, there were a large number of infections, in both the lung and other sites, due to opportunistic organisms. Thus the clincial syndrome of CMCC includes not only mucocutaneous candidiasis, endocrine failure and autoimmune phenomena, but patients with CMCC also show a remarkable susceptibility to non-candidal infections. These non-candidal infections represent a serious cause of morbidity for patients with CMCC.