John T. McBride

Aerosolized Ribavirin Treatment of Infants with Respiratory Syncytial Viral Infection: A Randomized Double-Blind Study

We evaluated a new antiviral agent, ribavirin, in the treatment of infants hospitalized with lower-respiratory-tract disease from respiratory syncytial virus. Ribavirin or placebo was administered to 33 infants in a double-blind manner by continuous aerosol for three to six days. Seventeen infants were treated with placebo, and 16 with ribavirin. By the end of treatment, infants receiving ribavirin had significantly greater improvement in their overall score for severity of illness, in lower-respiratory-tract signs, and in arterial oxygen saturation. Viral shedding was also diminished in the treated groups as compared with the placebo group. No side effects or toxicity were associated with the aerosol therapy. Isolates of respiratory syncytial virus obtained from the infants over the course of therapy showed no change in sensitivity to ribavirin.

Lung Growth and Airway Function after Lobectomy in Infancy for Congenital Lobar Emphysema

To characterize the outcome of lobectomy in infancy and the low expiratory flows which persist after lobectomy for congenital lobar emphysema, 15 subjects with this history were studied at age 8-30 yr. Total lung capacity was normal in all, but higher values (P < 0.05) were observed in nine subjects with upper lobectomy than in five subjects with right middle lobectomy. Ratio of residual volume to total lung capacity was correlated (P < 0.05) with the amount of lung missing as estimated from normal relative weights of the respective lobes. Xe(133) radiospirometry in eight subjects showed that the operated and unoperated sides had nearly equal volumes at total lung capacity, but that the operated side was larger than the unoperated side at residual volume. Perfusion was equally distributed between the two sides. Similar findings were detected radiographically in four other subjects. Forced expiratory volume in 1 s and maximal midexpiratory flow rate averaged 72 and 45% of predicted, respectively. Low values of specific airway conductance and normal density dependence of maximal flows in 12 subjects suggested that obstruction was not limited to peripheral airways. Pathologic observations at the time of surgery and morphometry of the resected lobes were not correlated with any test of pulmonary function. These data show that lung volume can be completely recovered after lobectomy for congenital lobar emphysema in infancy. The volume increase occurs on the operated side, and probably represents tissue growth rather than simple distension. The response to resection is influenced by the particular lobe resected and may be associated with decreased lung recoil near residual volume. Low expiratory flows in these subjects could be explained by several mechanisms, among which a disproportion between airway and parenchymal growth in infancy (dysanaptic growth) is most compatible with our data.

The Association of Acetaminophen and Asthma Prevalence and Severity

The epidemiologic association between acetaminophen use and asthma prevalence and severity in children and adults is well established. A variety of observations suggest that acetaminophen use has contributed to the recent increase in asthma prevalence in children: (1) the strength of the association; (2) the consistency of the association across age, geography, and culture; (3) the dose-response relationship; (4) the timing of increased acetaminophen use and the asthma epidemic; (5) the relationship between per-capita sales of acetaminophen and asthma prevalence across countries; (6) the results of a double-blind trial of ibuprofen and acetaminophen for treatment of fever in asthmatic children; and (7) the biologically plausible mechanism of glutathione depletion in airway mucosa. Until future studies document the safety of this drug, children with asthma or at risk for asthma should avoid the use of acetaminophen.

Predicting deterioration in previously healthy infants hospitalized with respiratory syncytial virus infection

Objective. To estimate the incidence of clinical deterioration leading to intensive care unit transfer in previously healthy infants with respiratory syncytial virus (RSV) infection hospitalized on a general pediatric unit and, to assess the hypothesis that history, physical examination, oximetry, and chest radiographic findings at time of presentation can accurately identify these infants. Study Design. A virology database was used to identify and determine the disposition of all children ≤1 year of age admitted to the Childrens Hospital at Strong (CHaS) with RSV infection during the 1985 to 1994 respiratory seasons. Index patients were all previously healthy, full-term infants admitted initially to the general inpatient services at CHaS or Rochester General Hospital, a second University of Rochester teaching hospital, whose clinical deterioration led to transfer to the pediatric intensive care unit (PICU). These infants were matched retrospectively (for year and date of infection, sex, chronologic age, and race) with two hospitalized controls who did not require PICU transfer. Chest radiographic findings, respiratory rate (RR), O2 saturation, and presence of wheezing at time of presentation to the emergency department (ED) were compared. Results. During the study years, 542 previously healthy, full-term infants were admitted to the general pediatric unit at CHaS with proven RSV infection. Ten (1.8%; 95% confidence interval, 0.9%, 3.4%) were transferred subsequently to the PICU, primarily for close monitoring of progressive respiratory distress. Data for these patients and 7 patients transferred from Rochester General Hospital to the PICU at the CHaS were compared with those for control patients. The mean RR in the ED (63 vs 50), and O2 saturation in the ED (88% vs 93%) were modestly abnormal in cases compared with controls. Wheezing on examination at time of presentation and chest radiographic findings did not differ between the two groups. A RR >80 and an O2saturation <85% at time of presentation each had a specificity >97% for predicting subsequent deterioration. Each parameter, however, had a sensitivity ≤30%. Conclusion. Clinical deterioration requiring PICU admission is an uncommon occurrence in previously healthy infants admitted to a general pediatric inpatient unit with RSV infection. Extreme tachypnea and hypoxemia were both associated with subsequent deterioration; however, only a small proportion of patients who clinically deteriorated presented in this way. The clinical usefulness of these parameters, therefore, is limited. respiratory syncytial virus, deterioration, healthy infants, prediction.

Sequelae of respiratory syncytial virus infections. A role for intervention studies.

The association between respiratory syncytial virus (RSV) infections in infancy and respiratory abnormalities later in life has been attributed both to a direct effect of the infection itself and to an inherent susceptibility. Observational studies do not allow a rigorous test of these hypotheses. Respiratory syncytial virus infection is universal in the first years of life and no uninfected control group exists. Randomized, controlled trials using new prophylactic agents such as vaccines or specific therapeutic agents will provide a powerful test of the relationship between RSV infection and long-term respiratory sequelae.

Normal pulmonary function measurements and airway reactivity in childhood after mild bronchiolitis

Concern about the long-term sequelae of bronchiolitis has been raised through studies of children hospitalized for bronchiolitis, but the long-term sequelae of mild bronchiolitis have not been studied. We assessed the hypothesis that 25 children with mild bronchiolitis (index subjects) were at greater risk for abnormalities of pulmonary function or airway reactivity to cold air between the ages of 8 and 12 years than were randomly selected, matched controls. There were no consistent differences in pulmonary function or airway reactivity between index and control groups. Airway hyperreactivity was found in five control subjects and three index subjects, and all children with symptomatic asthma were identified by cold air challenge. Our data suggest that children with a history of mild bronchiolitis are not at increased risk between ages 8 and 12 years for airway hyperreactivity or for abnormalities in pulmonary function.

Increase in admission threshold explains stable asthma hospitalization rates.

Background. Asthma morbidity and mortality has increased substantially in recent years, but asthma hospitalization rates among many geographic and sociodemographic groups have remained stable. Observations on asthma hospitalization rates and severity of acute episodes might provide valuable insight into the functioning of the health care system during this period of health care reform. Objective. To analyze changes between 1991 and 1995 in childhood asthma hospitalization rates and severity of acute episodes. Design and Methods. All 29 329 hospitalizations, including 2028 for asthma, for the 198 893 children (<19 years of age) in Monroe County (Rochester), New York, were studied during this 5-year period. Severity was determined by hospital record review on a 22% random sample. Using the worst oxygen saturation (Sao 2) during the first 24 hours of hospitalization as the primary index of severity, episodes were categorized as mild (0 to ≥95), moderate (90 to 94), or severe (<90). Results. Hospitalization rates are expressed as hospitalizations per 1000 child-years. The overall asthma hospitalization rate was 2.04 (95% confidence interval, 1.95–2.13). The overall annual asthma hospitalization rate remained relatively stable from 1991 (1.90) to 1995 (2.31), whereas the hospitalization rates for severe asthma rose 270%—from 0.57 to 1.55—during this period. Simultaneously, the hospitalization rates for mild asthma decreased from 0.26 to 0.12. As a proportion of all asthma hospitalizations between 1991 and 1995, severe episodes increased from 31.5% to 60.4%; conversely, mild episodes decreased from 14.1% to 4.7%. Conclusions. Severity increased significantly among children hospitalized for asthma while the overall asthma hospitalization rate remained stable. It seems that the health care system in this community has responded to an increase in severity of asthma by raising the severity threshold for admission.

Polyalveolar lobe: anatomic and physiologic parameters and their relationship to congenital lobar emphysema.

Polyalveolar lobe is one of the recently described pathological entities that can give rise to congenital lobar emphysema (CLE). In polyalveolar lobe, the total alveolar number as determined by microscopic point-counting of randomly taken lung sections is increased three to fivefold. The airways and arteries are normal for age in number, size and structure. Follow-up over 10-20 yr of patients operated upon for congenital lobar emphysema, including those of polyalveolar lobe etiology shows that these patients do well clinically. All patients have some pulmonary function abnormalities, specifically a decrease in airway conductance, and forced expiratory volume. It is not possible to distinguish patients with polyalveolar lobes from other CLE patients on the basis of pulmonary function data. All patients had normal lung volumes and vital capacities, despite losing 8%-20% of their pulmonary parenchyma. Based on compensatory lung growth, it may be preferable to operate earlier, rather than later in these cases.

Respiratory Syncytial Virus — From Chimps with Colds to Conundrums and Cures

Three and a half decades ago Morris et al.1 recovered from a chimpanzee with a cold a virus that had infected the entire colony and its handler. In subsequent years this contagious chimpanzee coryz...

Ventilatory chemosensitivity in parents of infants with sudden infant death syndrome

We measured ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia (CO2) using rebreathing techniques in 16 parents of infants with autopsy-confirmed sudden infant death syndrome (SIDS) and 18 control parents matched for age, sex, and body size. Response to ventilatory loading was assessed by repeating the CO2 test with an inspiratory flow-resistive load (16 cm H2O/L/sec). During loaded and unloaded CO2 tests, respiratory effort was also assessed by measuring the pressure generated in the first 0.1 second (P0.1) of the subsequent inspiratory effort after brief manual occlusion of the inspiratory line. Ventilatory responses of the parents of victims of SIDS to chemical and mechanical stimulation were not significantly different from those of control parents. Responses in both groups were similar to previously reported normal values. There was a linear increase in ventilation (VE) in response to hypercapnia and hypoxia and in P0.1 in response to hypercapnia. We found expected increases in P0.1/PCO2 and decreases in VE/PCO2 slopes during loaded breathing in all subjects, but no difference between groups. We conclude that parents of SIDS victims have normal ventilatory chemosensitivity and respiratory drive.