Gelsolin Attenuates Neonatal Hyperoxia-Induced Inflammatory Responses to Rhinovirus Infection and Preserves Alveolarization.

Prematurity and bronchopulmonary dysplasia (BPD) increase the risk of asthma later in life. Supplemental oxygen therapy is a risk factor for chronic respiratory symptoms in infants with BPD. Hyperoxia induces cell injury and release of damage-associated molecular patterns (DAMPs). Cytoskeletal filamentous actin (F-actin) is a DAMP which binds Clec9a, a C-type lectin selectively expressed on CD103+ dendritic cells (DCs). Co-stimulation of Clec9a and TLR3 induces maximal proinflammatory responses. We have shown that neonatal hyperoxia (a model of BPD) increases lung IL-12+Clec9a+CD103+ DCs, pro-inflammatory responses and airway hyperreactivity following rhinovirus (RV) infection. CD103+ DCs and Clec9a are required for these responses. Hyperoxia increases F-actin levels in bronchoalveolar lavage fluid (BALF). We hypothesized that the F-actin severing protein gelsolin attenuates neonatal hyperoxia-induced Clec9a+CD103+ DC-dependent pro-inflammatory responses to RV and preserves alveolarization. We exposed neonatal mice to hyperoxia and treated them with gelsolin intranasally. Subsequently we inoculated the mice with RV intranasally. Alternatively, we inoculated normoxic neonatal mice with BALF from hyperoxia-exposed mice (hyperoxic BALF), RV and gelsolin. We analyzed lung gene expression two days after RV infection. For in vitro studies, lung CD11c+ cells were isolated from C57BL/6J or Clec9agfp-/- mice and incubated with hyperoxic BALF and RV. Cells were analyzed by flow cytometry. In neonatal mice, gelsolin blocked hyperoxia-induced Il12p40, TNF-α and IFN-γ mRNA and protein expression in response to RV infection. Similar effects were observed when gelsolin was co-administered with hyperoxic BALF and RV. Gelsolin decreased F-actin levels in hyperoxic BALF in vitro and inhibited hyperoxia-induced D103lo DC expansion and inflammation in vivo. Gelsolin also attenuated hyperoxia-induced hypoalveolarization. Further, incubation of lung CD11c+ cells from WT and Clec9agfp-/- mice with hyperoxic BALF and RV, showed Clec9a is required for maximal hyperoxic BALF and RV induced IL-12 expression in CD103+ DCs. Finally, in tracheal aspirates from mechanically ventilated human preterm infants the F-actin to gelsolin ratio positively correlates with FiO2, and gelsolin levels decrease during the first two weeks of mechanical ventilation. Collectively, our findings demonstrate a promising role for gelsolin, administered by inhalation into the airway to treat RV-induced exacerbations of BPD and prevent chronic lung disease.

Association of Adverse Hearing, Growth, and Discharge Age Outcomes With Postnatal Cytomegalovirus Infection in Infants With Very Low Birth Weight.

Importance: Studies suggest that postnatal cytomegalovirus (CMV) infection can lead to long-term morbidity in infants with very low birth weight (VLBW; <1500 g), including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and neurodevelopmental impairment. However, to date, the association of postnatal CMV with hearing, growth, and length of stay among VLBW infants is unknown. Objectives: To determine the risk for failed hearing screen, increased postnatal age at discharge, or decreased growth at discharge in VLBW infants with postnatal CMV infection compared with CMV-uninfected infants and to compare the risk for other major outcomes of prematurity, including BPD and NEC, in infants with and without postnatal CMV infection. Participants: This multicenter retrospective cohort study included VLBW infants from 302 neonatal intensive care units managed by the Pediatrix Medical Group from January 1, 2002, through December 31, 2016. Infants hospitalized on postnatal day 21 with a diagnosis of postnatal CMV and hearing screen results after a postmenstrual age of 34 weeks were included in the study population. Data were analyzed from December 11, 2017, to June 14, 2019. Main Outcomes and Measures: Infants with and without postnatal CMV infection were matched using propensity scores. Poisson and linear regression were used to examine the association between postnatal CMV and the risk of failed hearing screen, postnatal age at discharge, growth, BPD, and NEC. Results: A total of 304 infants with postnatal CMV were identified, and 273 of these infants (89.8%; 155 boys [56.8%]) were matched with 273 infants without postnatal CMV (148 boys [54.2%]). Hearing screen failure occurred in 45 of 273 infants (16.5%) with postnatal CMV compared with 25 of 273 infants (9.2%) without postnatal CMV (risk ratio [RR], 1.80; 95% CI, 1.14 to 2.85; P = .01). Postnatal CMV was also associated with an increased postnatal age at discharge of 11.89 days (95% CI, 6.72 to 17.06 days; P < .001) and lower weight-for-age z score (-0.23; 95% CI, -0.39 to -0.07; P = .005). Analysis confirmed an increased risk of BPD (RR, 1.30; 95% CI, 1.17 to 1.44; P < .001), previously reported on infants from this cohort from 1997 to 2012, but not an increased risk of NEC after postnatal day 21 (RR, 2.00; 95% CI, 0.18 to 22.06; P = .57). Conclusions and Relevance: These data suggest that postnatal CMV infection is associated with lasting sequelae in the hearing and growth status of VLBW infants and with prolonged hospitalization. Prospective studies are needed to determine the full effects of postnatal CMV infection and whether antiviral treatment reduces the associated morbidity.

Bronchopulmonary Dysplasia in Very Preterm Infants with Symptomatic Congenital Cytomegalovirus Infection: A Propensity Score-Matched Analysis.

OBJECTIVE: To assess whether symptomatic congenital cytomegalovirus infection (cCMV) is associated with bronchopulmonary dysplasia (BPD) and mortality in very preterm infants (gestational age ≤32 weeks). STUDY DESIGN: We performed a retrospective study using the Kids' Inpatient Database for 2003, 2006, 2009, and 2012. Diagnoses of BPD and symptomatic cCMV were determined using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among patients with in-hospital birth at ≤32 weeks of gestation, cases of symptomatic cCMV were matched with infants without cCMV using propensity score matching at 1:2 ratio. Outcomes of BPD and in-hospital mortality were assessed using conditional logistic regression. RESULTS: Of 204 818 in-hospital births with gestational age ≤32 weeks, we identified 208 cases of symptomatic cCMV, 177 of which underwent matching. Symptomatic cCMV was associated with higher odds of BPD (OR, 2.34; 95% CI, 1.41-3.87), but was not significantly associated with in-hospital all-cause mortality (OR, 1.18, 95% CI, 0.64-2.17). CONCLUSIONS: Symptomatic cCMV was associated with BPD but not with in-hospital mortality among very preterm infants. Further study is needed to determine the risk of BPD among infants with cCMV to allow for evaluation of possible preventive measures.

Prevalence of Congenital CMV Infection and Antiviral Therapy in Very-Low-Birth-Weight Infants: Observations of the German Neonatal Network.

BACKGROUND: To determine the prevalence of congenital CMV infection (cCMV) in very-low-birth-weight infants (VLBWI) and to evaluate epidemiological characteristics of VLBWI with antiviral therapy (AT). METHODS: CMV-specific PCR in umbilical cord tissue was performed (n=3330). Univariate analyses and logistic regression models were used to identify associations with outcome. RESULTS: 22/3330 VLBWI received AT (0.66%). 4 of these (0.12%) were PCR positive, with 2 VLBWI showing pathological screening for hearing loss. VLBWI with AT and negative PCR had significantly reduced mean birth weight (BW) and higher rates of small-for-gestational-age (SGA). Clinical sepsis, bronchopulmonary dysplasia (BPD), use of reserve antibiotics (RA) and treatment for retinopathy of prematurity were significantly increased. We further observed a higher need of transfusion of red blood cells (RBC), fresh frozen plasma and platelets. Logistic regression (controlled for gender, gestational age, SGA and BW) showed associations for AT and BPD (OR 3.4 [1.2-10.1], p=0.024), RA (OR 20.4 [4.2-98.9], p≤0.001), transfusions of RBC (OR 11.9 [1.3-105.7], p=0.026) and platelets (OR 8.7 [2.9-26.4], p≤0.001). DISCUSSION: All VLBWI with positive PCR received AT. We hypothesize from our data by assuming a postnatal aquired CMV infection in VLBWI with AT and negative PCR that VLBWI born SGA have a different risk profile. CONCLUSION: Further prospective studies concerning postnatal transmission should take VLBWI born SGA into account and should study the impact of infection on short- and long-term complications in this supposed vulnerable group.

Postnatal Cytomegalovirus Infection and the Risk for Bronchopulmonary Dysplasia.

IMPORTANCE: Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-birth-weight (VLBW) infants can cause pneumonitis and sepsislike illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown. OBJECTIVE: To investigate the association between postnatal CMV infection and bronchopulmonary dysplasia (BPD) and mortality in a large multicenter cohort of VLBW infants. DESIGN, SETTING, AND PARTICIPANTS: Conducted between October 2014 and June 2015, this propensity-matched retrospective cohort study involved 101,111 hospitalized VLBW (<1500 g) infants at 348 neonatal intensive care units in the United States from 1997 to 2012. We matched infants with postnatal CMV infection 1:1 to comparison infants using propensity scores, and we used Poisson regression to examine the effect of postnatal CMV on the combined risk for death or BPD at 36 weeks' postmenstrual age. To describe features of postnatal CMV infection, we extracted clinical and laboratory data from 7 days before until 7 days after infants met criteria for postnatal CMV. EXPOSURES: Postnatal CMV infection was defined as a diagnosis of CMV or detection of CMV from blood, urine, cerebrospinal fluid, or respiratory secretions on or after day of life 21. Infants with a CMV diagnosis or virologic detection of CMV prior to day of life 21 were not considered to have postnatal infection. MAIN OUTCOMES AND MEASURES: The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS: Of 101,111 infants, 328 (0.3%) had postnatal CMV infection. We matched a comparison infant to 303 CMV-infected infants (92%) for a final cohort of 606 infants. The median gestational age and birth weight of this cohort were 25 weeks and 730 g, respectively. Postnatal CMV infection was associated with an increased risk for death or BPD at 36 weeks' postmenstrual age (risk ratio, 1.21; 95% CI, 1.10-1.32) and BPD (risk ratio, 1.33; 95% CI, 1.19-1.50). Changes in cardiorespiratory status associated with postnatal CMV infection included a new requirement for vasopressor medications (9%; n = 29), intubation for mechanical ventilation (15%; n = 49), a new oxygen requirement (28%; n = 91), and death (1.2%; n = 4). CONCLUSIONS AND RELEVANCE: In VLBW infants, postnatal CMV infection was associated with increased risk for BPD. Further studies are needed to determine the role of preventive measures against CMV in this population.

Rhinovirus-induced airway cytokines and respiratory morbidity in severely premature children.

BACKGROUND: Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (<32 wks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and whether RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first 2 yrs of life. METHODS: We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0-2 yrs with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP, and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. RESULTS: The study comprised 214 children born full term (n = 108), preterm (n = 44) or severely premature (n = 62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/yr; IQR 2.8-4.8) and were more likely to have at least one pediatric intensive care unit admission during the first 2 yrs of life (OR 8.72; 95% CI 1.3-58.7; p = 0.02). CONCLUSIONS: Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first 2 yrs of life.

Congenital and perinatal cytomegalovirus lung infection.

BACKGROUND: Cytomegalovirus (CMV) pneumonitis may be severe, even lethal, following congenital infection or in premature infants with perinatal infection. OBJECTIVE: To review the epidemiological, pathogenetic, clinical and therapeutic features of prenatal and perinatal CMV lung diseases. METHODS: Evaluation of all published papers listed on PubMed describing CMV pneumonitis in infants. RESULTS: CMV is frequent and severe in immunosuppressed infants but infrequent in full-term neonates and occurs more frequently after perinatal than after congenital infection, particularly in premature infants. In premature infants, CMV infection is often protracted and causes a diffuse interstitial pneumonitis leading to fibrosis and bronchopulmonary dysplasia (BPD). Congenital CMV infection should also be considered in newborns with severe acute respiratory distress syndrome and refractory respiratory failure with progression to early chronic lung disease. The association between breast milk-transmitted CMV and development of cystic lung disease and Wilson-Mikity syndrome has also been reported. Data on the efficacy of antiviral therapy for infants with respiratory CMV diseases are lacking and only anecdotal case reports are available. CONCLUSIONS: Persistent CMV infection appears to cause a diffuse necrotizing pneumonitis with fibrosis leading to BPD, in both immunocompromised or preterm infants and, less frequently in immunocompetent infants. The role of antiviral therapy remains to be elucidated.

Functional genetic variation in NFKBIA and susceptibility to childhood asthma, bronchiolitis, and bronchopulmonary dysplasia.

Respiratory diseases are the most frequent chronic illnesses in babies and children. Although a vigorous innate immune system is critical for maintaining lung health, a balanced response is essential to minimize damaging inflammation. We investigated the functional and clinical impact of human genetic variants in the promoter of NFKBIA, which encodes IκBα, the major negative regulator of NF-κB. In this study, we quantified the functional impact of NFKBIA promoter polymorphisms (rs3138053, rs2233406, and rs2233409) on promoter-driven protein expression, allele-specific and total NFKBIA mRNA expression, IκBα protein expression, and TLR responsiveness; mapped innate immune regulatory networks active during respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia; and genotyped and analyzed independent cohorts of children with respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Genetic variants in the promoter of NFKBIA influenced NFKBIA gene expression, IκBα protein expression, and TLR-mediated inflammatory responses. Using a systems biology approach, we demonstrated that NFKBIA/IκBα is a central hub in transcriptional responses of prevalent childhood lung diseases, including respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Finally, by examining independent pediatric lung disease cohorts, we established that this immunologically relevant genetic variation in the promoter of NFKBIA is associated with differential susceptibility to severe bronchiolitis following infection with respiratory syncytial virus, airway hyperresponsiveness, and severe bronchopulmonary dysplasia. These data highlight the importance of negative innate immune regulators, such as NFKBIA, in pediatric lung disease and begin to unravel common aspects in the genetic predisposition to bronchopulmonary dysplasia, bronchiolitis, and childhood asthma.

Prospective evaluation of clinical scoring systems in infants with bronchiolitis admitted to the intensive care unit.

The objective of this investigation was to compare different scoring systems to assess the severity of illness in infants with bronchiolitis admitted to a tertiary paediatric intensive care unit (PICU). Over an 18-year period (1990-2007), infants with bronchiolitis aged up to 12 months and admitted to the PICU were prospectively scored using the Pediatric Risk of Mortality III (PRISM III) score, the Organ System Failure (OSF) score and the Acute Physiologic Score for Children (APSC) within 24 h. Infants were compared as to whether or not bronchiolitis was associated with respiratory syncytial virus (RSV). There was no difference between 113 RSV-positive and 80 RSV-negative infants regarding gestational age, birth weight, rate of premature delivery or bronchopulmonary dysplasia (BPD). The PRISM III score differed significantly between RSV-positive and RSV-negative cases (3.27 ± 0.39 vs. 1.96 ± 0.44, p = 0.006), as did the OSF score (0.56 ± 0.05 vs. 0.35 ± 0.06, p = 0.049) and the APSC (5.16 ± 0.46 vs. 4.1 ± 0.53, p = 0.048). All scores were significantly higher in the subgroup with mechanical ventilation (p < 0.0001). The mean time of ventilation was significantly higher in the RSV-positive group compared to the RSV-negative group (6.39 ± 1.74 days vs. 2.4 ± 0.47 days, p < 0.001). Infants suffering from RSV-positive bronchiolitis had higher clinical scores corresponding with the severity of bronchiolitis.

Value of herpes simplex virus type-specific serology: a case report.

Genital herpes, usually caused by herpes simplex virus type 2 (HSV-2), is one of the most common sexually transmitted diseases in humans. By contrast, intrauterine HSV-2 infections have been described rarely in the literature. Our report describes a case of neonate who was delivered after 30+2 gestational weeks by cesarean section. He presented with a respiratory distress syndrome resulting in broncho-pulmonary dysplasia. At the age of 6 weeks, a chorioretinal scar was detected. During the 4th month of age, the infant developed recurrent HSV-2 infection with nasal lesions. The retrospective type-specific serologic diagnosis revealed previous HSV-2 infection of the mother resulting in prenatal HSV-2 infection of the infant. In conclusion, intrauterine HSV-2 infections may be underrepresented since they may not be associated with severe congenital malformations and the diagnosis requires the use of HSV type-specific serologic methods not widely applied in microbiological laboratories.

Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands.

BACKGROUND: Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences. OBJECTIVE: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting. METHODS: A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands. RESULTS: The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting. CONCLUSION: Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.

School age outcome of hospitalisation with respiratory syncytial virus infection of prematurely born infants.

BACKGROUND: Hospitalisation due to respiratory syncytial virus (RSV) infection in the first 2 years after birth has been associated with increased healthcare utilisation and associated costs up to 5 years of age in children born prematurely at less than 32 weeks of gestation who developed bronchopulmonary dysplasia (BPD). A study was undertaken to determine whether hospitalisation due to RSV infection in the first 2 years was associated with increased morbidity and lung function abnormalities in such children at school age, and if any effects were influenced by age. METHODS: Healthcare utilisation and cost of care in years 5-7 were reviewed in 147 children and changes in healthcare utilisation between 0 and 8 years were assessed also using results from two previous studies. At age 8-10 years, 77 children had their lung function assessed and bronchial hyper-responsiveness determined. RESULTS: Children hospitalised with RSV infection (n = 25) in the first 2 years had a greater cost of care related to outpatient attendance than those with a non-respiratory or no admission (n = 72) when aged 5-7 years (p = 0.008). At 8-10 years of age, children hospitalised with RSV infection (n = 14) had lower forced expiratory volume in 0.75 s (FEV(0.75)) (p = 0.015), FEV(0.75)/forced vital capacity (p = 0.027) and flows at 50% (p = 0.034) and 75% (p = 0.006) of vital capacity than children hospitalised for non-RSV causes (n = 63). Healthcare utilisation decreased with increasing age regardless of RSV hospitalisation status. CONCLUSIONS: In prematurely born children who had BPD, hospitalisation due to RSV infection in the first 2 years is associated with reduced airway calibre at school age.

Human adenovirus and human cytomegalovirus infections in preterm newborns: no association with bronchopulmonary dysplasia.

Connatal infection with human adenovirus (HAdV) has been recently proposed as a cofactor for the development of bronchopulmonary dysplasia (BPD) in preterm infants [Couroucli et al. 2000 Pediatr Res 47:225-232]. In another study, BPD was associated with an increased incidence of human cytomegalovirus (HCMV) infection [Sawyer et al. 1987 Am J Dis Child 141:303-305]. During a 18-mo study period, we investigated tracheal aspirates or pharyngeal aspirates and urine samples collected during the first month of life from 66 preterm newborns with very low birth weight (< or =1.500 g) for replication-potent HAdV as well as for adenoviral and HCMV DNA by virus culture and qualitative DNA PCR. Thus, our study included not only prenatal but also peri- and postnatal infections. Thirty-seven percent (24/66) of infants developed BPD(1), as defined by persistent oxygen dependency at day 28 of life. Replication-potent HAdV and/or adenoviral DNA could be detected repeatedly in tracheal aspirates/pharyngeal aspirates and/or urine from 20% (13/66) of preterm infants. Seventeen percent (4/24) of infants in the BPD(1) group and 21% (9/42) of infants in the non-BPD group had an HAdV infection, indicating that in our study the very recently proposed association between HAdV infection of the lung and BPD could not be confirmed. For comparison, active HCMV infection was diagnosed in 18% (12/66) of infants, 3 of which developed HCMV disease. 29% (7/24) in the BPD(1) group and 12% (5/42) in the non-BPD group were positive for HCMV. Again, there was no statistically significant association between HCMV infection and BPD. In summary, our findings indicate that HAdV and HCMV infection are frequent in preterm newborns with very low birth weight; however, a causal association with the development of BPD seems unlikely.

Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease: a review of the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada.

OBJECTIVE: We wished to compare outcomes of respiratory syncytial virus (RSV) infection in children with bronchopulmonary dysplasia (BPD) with those with other pulmonary disorders: cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, and tracheoesophageal fistula. METHODS: Children with RSV infection hospitalized at seven Canadian pediatric tertiary care hospitals in 1993 through 1994 and 9 hospitals in 1994 through 1995 were enrolled and prospectively followed. This study is a secondary analysis of data from this prospective cohort. RESULTS: Of the 1516 patients enrolled the outcomes of 159 with preexisting lung disorders before RSV lower respiratory tract infection constitute this report. There were no significant differences among the 7 groups (BPD, cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, tracheoesophageal fistula, other) for the morbidity measures: duration of hospitalization, intensive care unit (ICU) admission, duration of ICU stay, mechanical ventilation and duration of mechanical ventilation. Patients using home oxygen were more likely to be admitted to the ICU than those who had never or previously used home oxygen (current 57.1%, past 23.8%, never 33.3%, P = 0.03). CONCLUSIONS: Children with other underlying diseases have morbidity similar to those with BPD. Prophylactic interventions against RSV should also be studied in these groups.

Safety and immunogenicity of a purified F protein respiratory syncytial virus (PFP-2) vaccine in seropositive children with bronchopulmonary dysplasia.

Respiratory syncytial virus (RSV) causes serious respiratory illness in preterm children with bronchopulmonary dysplasia. In a prospective randomized placebo-controlled trial, 21 children received one dose of PFP-2 (purified fusion [F] protein) vaccine or influenza vaccine (placebo). Children were followed for adverse reactions and RSV illness over two respiratory seasons. Sera were obtained for determination of IgG titers to RSV F protein and neutralizing antibody titers before and 1, 6, and 12 months after vaccination. Adverse reactions were few. Four-fold F protein rises occurred in 9 of 10 PFP-2 and 0 of 11 placebo recipients. Six PFP-2 recipients had low prevaccination neutralizing antibody titers (< 1:450); all had 4-fold rises. By 12 months, F protein and neutralizing antibody titers in all 21 children were similar. RSV illness occurred in 6 of 11 placebo versus 1 of 10 PFP-2 recipients (P = .06); 1 placebo child required hospitalization. PFP-2 vaccine appears safe and immunogenic and may protect children with bronchopulmonary dysplasia against serious RSV disease on reinfection.

Rhinovirus infection associated with serious lower respiratory illness in patients with bronchopulmonary dysplasia.

OBJECTIVE: To determine the characteristics of rhinovirus infection in patients with bronchopulmonary dysplasia. SUBJECTS AND METHODS: Between July 1, 1993, and July 1, 1995, 40 patients with bronchopulmonary dysplasia were identified. Viral cultures were obtained in ambulatory patients presenting with an acute respiratory illness requiring hospitalization or in hospitalized patients with a respiratory deterioration. When rhinovirus was isolated epidemiologic data were collected, and the characteristics of the illness, its severity and outcome were noted. Key features of rhinovirus and respiratory syncytial virus (RSV) bronchiolitis were compared. RESULTS: There were 8 cases of lower respiratory tract illness associated with rhinovirus infection in 6 infants (mean age, 7.1 +/- 4.1 months) and 1 child (age, 40 months), an incidence of 0.15 infection/patient year. The mean gestational age and birth weight of these patients were 27.3 (+/- 2.75) weeks and 853 (+/-341) g, respectively. There were 5 males. Four patients needed intensive care unit admission and 1 required mechanical ventilation. By comparison there were 13 cases of RSV bronchiolitis, an incidence of 0.25 infection/patient year. The 2 groups were similar epidemiologically and an equal proportion of patients with rhinovirus and RSV needed intensive care unit admission. A greater percentage of patients with RSV required mechanical ventilation (50% vs. 14%), but this difference was not statistically significant. Three cases of rhinovirus were nosocomial, and 1 infant had a second infection. Four patients required 5 hospitalizations caused by rhinovirus infection, and the mean duration of hospital stay was 11 days. All children had sustained worsening in their respiratory status after rhinoviral illness requiring additional therapy. CONCLUSIONS: Rhinovirus is a common and potentially serious lower respiratory pathogen in bronchopulmonary dysplasia patients. Rhinovirus infection has lasting pulmonary sequelae in these children.