Respiratory syncytial virus infection in children with bronchopulmonary dysplasia.

Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia. A prospective study was done of the natural history of respiratory syncytial virus infection in 30 children less than 2 years of age with bronchopulmonary dysplasia who were in a home oxygen program. Surveillance to identify children with acute respiratory symptoms was done by weekly telephone interview. Symptomatic children were examined, oxygen saturation was determined by oximetry, and nasopharyngeal lavage fluid was collected for virus cultures and rapid respiratory syncytial virus antigen tests. During the 4-month study period (December to April), 27 children had one or more acute respiratory illnesses, and respiratory syncytial virus developed in 16/27 (59%). Passive smoking and greater than or equal to four members in the home increased the risk of symptomatic respiratory syncytial virus (P less than .01 and P less than .03, respectively). Of 16 children, 11 (69%) required hospitalization. Of the 11 hospitalized children with respiratory syncytial virus, nine were either still receiving oxygen at home or required oxygen therapy within the previous 3 months v none of five nonhospitalized children (P less than .005). Five of the hospitalized children were greater than 12 months of age and five had respiratory syncytial virus infection previously that had been confirmed by culture results. Hospitalizations were prolonged and complicated. Seven of 11 children were hospitalized for greater than 1 week; four were admitted to the intensive care unit; four were treated with ribavirin aerosol, and two needed mechanical ventilation. There were no deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory syncytial virus (RSV) infection in preterm infants and the protective effects of RSV immune globulin (RSVIG). Respiratory Syncytial Virus Immune Globulin Study Group.

OBJECTIVE: To evaluate the safety and efficacy of respiratory syncytial virus immune globulin (RSVIG) in the prevention of severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infants born prematurely with or without bronchopulmonary dysplasia (BPD). METHODS: Data from a prospective, blinded, randomized, multicenter trial during three consecutive RSV seasons involving 249 children. This analysis comprises 162 preterm children, of whom 102 had BPD. The 87 children with congenital heart disease (CHD) were excluded from this analysis. Children were randomized to receive monthly infusions of RSVIG 750 mg/kg (high dose), RSVIG 150 mg/kg (low dose), or no RSVIG: Results from the preterm infants with and without BPD who received RSVIG 750 mg/kg are contrasted with control infants who did not receive RSVIG: RESULTS: As compared with controls, high-dose RSVIG administration significantly reduced the incidences of RSV LRTI (P = .01) and moderate-to-severe LRTI (P = .006). RSV-associated hospitalization also was decreased (P = .06) as well as were total RSV-associated days in the intensive care unit (P = .05). Significantly fewer preterm infants developed severe RSV LRTI in the RSVIG group compared with controls (4/58 [7%] vs 14/58 [24%], respectively; P = .01). Adverse reactions occurred in 5% of RSVIG infusions. These were generally mild and included reversible fluid overload, transient fever, and decreases in oxygen saturation. There was one death unrelated to either RSV or RSVIG administration. CONCLUSIONS: Prophylaxis with RSVIG is safe and is currently the only effective means to prevent severe RSV LRTI in high-risk preterm infants.

Immunization of high-risk infants younger than 18 months of age with split-product influenza vaccine.

Influenza is an important cause of serious illness in very young children with cardiopulmonary disease. A 4-year study was conducted at two centers to assess immunogenicity and safety of influenza split-product vaccine in children aged 3 to 18 months with bronchopulmonary dysplasia and congenital heart disease. A total of 113 children were studied: 62 children 3 to 5 months of age and 51 children 6 to 18 months of age. Sera were drawn prior to first and second immunization and 3 weeks after second immunization and were tested by hemagglutination inhibition; protection was defined as greater than 1:32. Ninety-five children were surveyed for adverse reactions. Seroresponses were age and antigen specific. Best responses for all ages were to A/Mississippi (H3N2) (97%). Children older than 6 months of age had better seroresponses to A/Leningrad (H3N2) (73%, P less than .03) and B/Victoria (62%, P less than .02) than did children younger than 6 months of age. Seroconversion rates to the remaining antigens were low. Only 9% of children experienced adverse reactions; all but one were mild. The immunologic mechanisms responsible for preventing serious influenzal disease and more effective immunization strategies need to be defined for very young high-risk children.

Antibody responses to influenza B viruses in immunologically unprimed children.

The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children without appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.

Increased child abuse in families with twins.

Large families and inadequate spacing of children increase the risk of abuse. Twin births incorporate both of these factors, yet the association of twinning with subsequent abuse has not been explored. Forty-eight families with twins from St Vincent Hospital and Medical Center and Nashville General Hospital were compared with 124 single-birth families, matched for hospital of delivery, birth date, maternal age, race, and socioeconomic status. Three control (2.4%) and nine twin (18.7%) families were reported for maltreatment (P less than .001). Mothers of twins experienced greater previous parity than did control subjects (P less than .001). Twins also had significantly longer nursery stays (P less than .001), lower birth weights (P less than .001), and lower Apgar scores at one (P less than .01) and five (P less than .05) minutes. A regression analysis incorporating all of these variables, however, showed that twin status was most predictive of subsequent abuse.

Role of antibody and the use of respiratory syncytial virus immunoglobulin in the prevention of respiratory syncytial virus disease in preterm infants with and without bronchopulmonary dysplasia.

Respiratory syncytial virus (RSV) is the only viral respiratory pathogen that produces an annual epidemic of respiratory illness. Infants with cardiac disease or infants born prematurely with or without bronchopulmonary dysplasia are at increased risk of severe RSV disease. A recently developed RSV immunoglobulin (RSVIG) was studied to determine safety and efficacy in prevention of severe RSV disease in such children who are high risk for severe RSV illness. Results from this prospective, blinded trial involving 249 children (102 with broncho-pulmonary dysplasia, 87 with congenital heart disease and 60 who were born prematurely) indicate that high dose RSVIG reduced the incidence and severity of RSV lower respiratory tract infection. It is a safe and effective means of RSV prophylaxis in selected high risk children.

Safety and tolerance of palivizumab administration in a large Northern Hemisphere trial. Northern Hemisphere Expanded Access Study Group.

An Expanded Access Study was conducted to collect additional safety data on palivizumab. Preterm infants with or without bronchopulmonary dysplasia received palivizumab every 30 days during the respiratory syncytial virus season. Adverse events were low (6.9%) in the 565 subjects. Serious adverse events included hospitalization and 1 case of respiratory syncytial virus bronchiolitis not requiring hospitalization. This study reaffirms the safety and tolerability of palivizumab.

The role of RSV neutralizing antibodies in the treatment and prevention of respiratory syncytial virus infection in high-risk children.

Studies assessing the use of RSV immune globulin in the treatment of RSV illness are not yet completed. However, a large multicenter trial demonstrated that prophylaxis with RSV immune globulin was safe and efficacious in prevention of serious RSV disease in high-risk infants. Refinements in the practical application of RSVIG are needed, as intravenous lines are difficult to place and maintain in these fragile infants. With the development of concentrated polyclonal and/or effective monoclonal antibody preparations, it may be possible to immunize intramuscularly (Tempest et al., 1993; Barbas et al., 1992). The efficacy of RSV-specific monoclonal antibodies must still be defined, and the appropriate viral epitopes targeted. While these issues still need to be addressed, it is exciting to have finally produced a safe and effective way to prevent severe RSV disease in high-risk young children.

Comparison of nasopharyngeal washings and swab specimens for diagnosis of respiratory syncytial virus by EIA, FAT, and cell culture.

Respiratory secretions for viral diagnosis are often collected with nasopharyngeal (NP) swabs, although many laboratories recommend NP aspirates or washings. We compared results using NP washings and NP swabs in three diagnostic RSV tests, a rapid RSV EIA antigen test (Abbott Laboratories), an indirect fluorescent antibody test (FAT) with rabbit antiserum, and virus culture (HEp-2 cells). Paired samples were collected from 121 children with suspected RSV bronchiolitis or pneumonia. A minitip swap was passed into the nasopharynx for 10 sec, rotated and withdrawn. The opposite nares was irrigated with approximately 1 ml of saline and aspirated using a syringe and plastic feeding tube. Fifty-one children (42%) grew RSV in culture, 49 from NP washings versus 27 from NP swabs (p less than 0.001). Fifty-three (44%) were positive by FAT, 52 from NP washings versus 12 from NP swabs (p less than 0.001). Fifty-eight children (48%) had positive RSV EIA tests, 57 from NP washings versus 35 from NP swabs (p less than 0.001). Detection by EIA was more sensitive than culture regardless of the method of specimen collection. We conclude that NP washings are superior to NP swabs for RSV culture and rapid diagnosis by EIA or FAT.

Immunoprophylaxis and immunotherapy: role in the prevention and treatment of repiratory syncytial virus.

It is now apparent that neutralizing antibody may play an important role in ameliorating RSV lower repiratory tract illness. At the present time immunoprophylaxis and immunotherapy with polyclonal antibodies show the most promise in the prevention and treatment of RSV illness. Several questions remained to be answered. These include the practical application of IGIV in prevention and treatment of RSV illness. Intravenous lines are often difficult to place and maintain. With the further development of polyclonal or monoclonal antibodies it may be possible to immunize prospective donors and boost their anti RSV titers to the degree that a hyper-immune IGIV with sufficient antibody to be given intramuscularly could be produced. The role for RSV-specific monoclonal antibodies for disease prevention or treatment must be defined as well as the appropriatee viral epitopes to target. In the absence of a safe and effective vaccine, it is clear that, despite these questions passive immunotherapy and immunoprophylaxis offers the greatest hope for the prevention and treatment of RSV disease in high risk infants and children.

Respiratory syncytial virus prophylaxis--the story so far.

Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that infects nearly all children by the age of 2 years. It is responsible for significant morbidity and mortality worldwide among certain high-risk paediatric populations. Therapy is sub-optimal for RSV, thus treatment focuses on ameliorating symptoms. Since discovery of the virus in the 1950s, efforts have been ongoing to develop a safe and effective vaccine. These efforts have met with serious obstacles. Passive immunoprophylaxis presents a viable alternative to active immunization. In 1998, the genetically engineered humanized monoclonal antibody (palivizumab) was granted FDA (Food and Drug Administration) approval for prophylaxis of high-risk children in the United States; EMEA (European Agency for the Evaluation of Medicinal Products) approval followed in 1999 for Europe. It is now approved in over 45 countries worldwide. Palivizumab was shown to significantly reduce RSV-related hospitalizations in North America and Europe with few adverse effects. Clinical trial and outcomes data documenting experience with palivizumab to date continue to extend the initial safety and efficacy observations.

Room air challenge: prediction for successful weaning of oxygen-dependent infants.

OBJECTIVE: The objective of this study was to determine the time required for equilibration of oxygen saturation (SpO2) and the oxygen flow rate that might predict readiness for oxygen weaning to room air in preterm infants with improving bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a prospective longitudinal cohort study, conducted in the neonatal care unit and the neonatal high risk follow-up clinic. Seventeen preterm children with BPD (mean postconceptual age 39.9 [range 31.5 to 43.5] weeks) were enrolled. With the infants breathing room air, the SpO2 pulse and respiratory rates, and clinical status were monitored for 120 minutes. Factors that predicted a successful room air challenge were determined. Children successfully weaned were followed up for 6 months after discontinuation of oxygen therapy. RESULTS: A total of 20 room air challenges were done in 17 study infants. In most infants the lowest SpO2 value (mean 89.7%) was reached within the first 40 minutes. Infants with an SpO2 > or = 92% at 40 minutes continued to have values > or = 92% at 120 minutes (specificity, 100%; sensitivity, 42%). In all infants receiving oxygen flow rates < or = 20 ml/kg per minute an SpO2 > or = 92% was maintained after 40 and 120 minutes. Infants who were successfully weaned to room air showed maintenance of weight and height percentiles 6 months after discontinuation of oxygen therapy. One child was rehospitalized and oxygen support reinstituted because of viral pneumonia. CONCLUSIONS: An SpO2 value > or = 92% at 40 minutes best predicts readiness for oxygen weaning to room air in infants with improving BPD. Infants requiring oxygen flow rates < or = 20 ml/kg per minute are also likely to be weaned off oxygen support.

Twins and twin families. A practical guide to outpatient management.

Little has been written of a practical nature to guide the health professional in providing advice and support to families with twins in the practice setting. This article provides an overview of issues and concerns specific to twins and provides practical guidelines for caring for twins and their families.

Correlation of nasopharyngeal and conjunctival cultures with middle ear fluid cultures in otitis media. A prospective study.

Eighty children with acute otitis media (AOM) were prospectively studied to determine the correlation and clinical usefulness of nasopharyngeal (NP), conjunctival (CONJ), and middle ear fluid (MEF) cultures. NP cultures correlated more accurately with MEF (p less than 0.01) than did CONJ cultures (p less than 0.05) for both Streptococcus pneumoniae and Haemophilus influenzae (H. flu). The positive predictive value of NP cultures for positive MEF was only 47%, but the negative predictive value was 87 percent. NP cultures, therefore, appear to have significant predictive clinical value only when negative in identifying children likely to have sterile MEF. High correlation of NP, CONJ, and MEF in children with H. flu conjunctivitis (p less than 0.01) suggests that early systemic rather than topical antibiotic treatment for H. flu conjunctivitis in small children may avert subsequent occurrence of the "conjunctivitis-otitis" syndrome.

Telephone encounters in a university pediatric group practice. A 2-year analysis of after-hour calls.

The records of off-hours calls received by the University of Colorado Pediatric Group Practice from 4:30 p.m. throughout 8:00 a.m. weekdays and all day Saturday, Sunday, and holidays were audited. An answering service and pageboy system ensured 24-hour, 7-day-a-week accessibility through a single telephone number. The four practices received 2386 after-hours calls from November 1978 to October 1980. An average of 104 calls per month were received with approximately four calls per day on weekday evenings and six calls per day on Saturday, Sunday, and holidays. Five concerns accounted for 49 percent of all after hours calls: fever, vomiting and/or diarrhea, upper respiratory infection (URI), earache, and rash. While 75 percent of families made fewer than four calls per year, 4 percent made at least 12 calls per year, accounting for 18 percent of all calls. Families calling three or more times a month were defined as "frequent users" and accounted for 22 percent of a given month's calls. Most calls from the same families (55%) occurred within a 24-hour period and dealt chiefly with parental concerns about fever, vomiting and diarrhea, URIs, ear infection, accident, and rashes. The additional responsibility that residents assume in taking calls for the Pediatric Group Practice while on other off-hour assignments was not excessively demanding, and cost of the answering service was easily absorbed by group practice revenues.

Childhood asthma. Considerations in establishing treatment programs.

This article briefly discusses the natural history of asthma, evaluation strategies, patient education programs for asthmatics and their families, as well as monitoring techniques for outpatient management of the asthmatic child. This information should facilitate an aggressive comprehensive treatment program that will not only minimize symptomatic periods but maximize normalization of the patient's life-style.