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Rationale: Asthma in children generally starts as being mild but may progress to being severe and may stay severe for unknown reasons. Objectives: To identify factors in childhood that predict the persistence of severe asthma in late adolescence and early adulthood. Methods: The CAMP (Childhood Asthma Management Program) is, to our knowledge, the largest and longest asthma trial to date; it includes 1,041 children aged 5–12 years with mild to moderate asthma. We evaluated 682 program participants with analyzable data in late adolescence (age, 17–19 yr) and early adulthood (age, 21–23 yr). Measurements and Main Results: To best capture the cases of severe asthma, a status of severe asthma was defined by using criteria from the American Thoracic Society and the National Asthma Education and Prevention Program. Logistic regression with stepwise elimination was used to analyze the clinical features, biomarkers, and lung function that are predictive of the persistence of severe asthma. In late adolescence and early adulthood, 12% and 19% of the participants had severe asthma, respectively; only 6% at both time points had severe cases. For every 5% decrease in the postbronchodilator FEV(1)/FVC ratio in childhood, the odds of the persistence of severe asthma increased by 2.36-fold (95% confidence interval [CI], 1.70–3.28; P

Evidence from longitudinal cohort studies demonstrates that wheezing that begins in early life and continues into the school years generally persists into adulthood. This persistent wheezing is associated with lung function deficits and airways hyperresponsiveness that appear to be established in the first few years of life. Allergic sensitization early in life, early-life infection with rhinovirus, or colonization with any of a number of bacteria have been associated with increased risk of persistent wheeze. Early life, whether in utero or in the first few years of life, presents a window of vulnerability during which airway injury results in persistent airways dysfunction. Available data further suggest that a second such window of vulnerability might be present in the preadolescent and adolescent years. Lung function growth patterns established by age 6 years generally continue into early adulthood to middle adulthood, typically leaving groups of subjects with wheezing that persists into or relapses during adulthood with a mean FEV 1 of about 10% of predicted value less than their peers who do not wheeze. Subgroups of patients with persistent asthma, however, can have progressive decreases in lung function and enter adulthood with even lower lung function. The concern exists that these deficits in lung function apparent in early adulthood might put subjects at risk for the later development of chronic obstructive pulmonary disease.

Inhaled corticosteroids, when properly used, can offer considerable protection against asthma-related morbidity. However, adherence to prescribed inhaled steroids among children is low and rates differ markedly by population. The lowest rates of adherence and highest rates of morbidity are among inner-city and low income populations.To describe the design of a school-based clinical trial in a largely minority population that is examining the efficacy of a school-based intervention intended to increase adherence to daily inhaled corticosteroids.The supervised asthma therapy study is a two-group randomized longitudinal trial. Children were randomly assigned to either school-based supervised asthma therapy or parent supervised asthma therapy. Children were followed longitudinally for 15 months. The primary outcome of the study is the time-averaged difference between the two groups in the percentage of children experiencing at least one asthma exacerbation each month.A web-based data collection system was designed to capture data at school. A total of 295 students, recruited from community and school sites, who attended one of 36 urban elementary schools enrolled in the study and 290 were randomized. The average age of the students was 10.0 years (sd=2.1), 91% were African American, 8% were white, and 1% were of other racial groups. 57% of students were male. The study has been recently completed and results are being analyzed.Intervention studies requiring daily medication supervision and daily data collection can be successfully conducted within the elementary school environment.

Importance Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. Objective To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. Design, Setting, and Participants Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. Interventions Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. Main Outcomes and Measures The primary outcome measure was change in forced expiratory volume in the first second (FEV 1 ) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. Results Mean changes in prebronchodilator FEV 1 over 24 weeks were 0.03 L (95% CI, −0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, −0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different ( P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, −3.48 ppb [95% CI, −5.99 to −0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, −1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL ( P Conclusions and Relevance Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. Trial Registration clinicaltrials.gov Identifier:NCT01052116

Few studies have examined how developing obesity in early adulthood affects the course of asthma.We analyzed lung function and asthma impairment and risk among nonobese children with asthma, comparing those who were obese in young adulthood with those who remained nonobese.We carried out the post hoc analysis of 771 subjects with mild to moderate asthma who were not obese (pediatric definition, body mass index [BMI]95th percentile) when enrolled in the Childhood Asthma Management Program at ages 5-12 years. The subjects were then followed to age 20 years or more. For visits at ages 20 years or more, spirometry values as percent predicted and recent asthma symptom scores and prednisone exposure were compared between 579 subjects who were nonobese at all visits and 151 who were obese (adult definition of BMI ≥ 30 kg/m(2)) on at least 1 visit (median number of visits when obese = 4, IQR 2-7).Compared with participants who were nonobese (BMI 23.4 ± 2.6 kg/m(2)), those who became obese (BMI 31.5 ± 3.8 kg/m(2)) had significant decreases in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (P.0003) and FEV1 (P = .001), without differences in FVC (P = .15) during visits at ages 20 years or more. For each unit increase of BMI, FEV1 percent predicted decreased by 0.29 (P = .0009). The relationship between BMI and lung function was not confounded by sex or BMI at baseline. Asthma impairment (symptom scores) and risk (prednisone use) did not differ between the 2 groups.Becoming obese in early adulthood was associated with increased airway obstruction, without impact on asthma impairment or risk.

In a double-blind, double-placebo, randomized crossover study, we compared the effects of 6 wk of treatment with the anti-inflammatory drug nedocromil sodium (16 mg/day) with 6 wk of treatment with the bronchodilator drug albuterol (800 micrograms/day) in 29 adults with allergic asthma. After 3 and 6 wk of treatment with nedocromil sodium, patients were significantly less hyperresponsive to propranolol (p = 0.002 and p = 0.02) and almost significantly less hyperresponsive to histamine (p = 0.071 and p = 0.065). FEV1 and FVC percent predicted tended to be higher, morning PEF values increased significantly (p = 0.038 and p = 0.03), and diurnal and day-to-day PEF variation decreased (p = 0.03 and p = 0.093, p = 0.005 and p = 0.096, respectively) with nedocromil sodium treatment compared with albuterol treatment. Almost all symptoms (daytime and nighttime asthma, wheezing, shortness of breath) and the additional bronchodilator use were significantly reduced with nedocromil sodium treatment compared with albuterol treatment. Treatment with the anti-inflammatory drug nedocromil sodium was shown to be superior to treatment with the bronchodilator drug albuterol. The patient's clinical situation may deteriorate when beta 2-agonists are used continuously. Nedocromil sodium has good clinical effect, and it may serve as a first-line choice for antiinflammatory therapy in asthma.

Objective. To determine the incidence of cardiotoxicity in infants and children who receive continuous nebulized albuterol (CNA) for bronchospasm. Design. Prospective, case series. Setting. A university pediatric intensive care and pediatric subacute units. Patients. Nineteen infants and children who received CNA for at least 24 hours. Interventions. None. Measurements. Creatinine phosphokinase (CK) was measured at the time of admission and then at 12,24,48, and 72 hours while the patient received CNA. Isoenzyme CK-MB fractions were measured if CK concentration was ≥250 IU/L. One electrocardiogram was obtained for each patient during CNA treatment. All patients had continuous cardiac monitoring during continuous nebulization therapy. Main results. Creatinine phosphokinase levels remained within normal limits for 16 patients during CNA treatment. Three patients had elevated CK and in two CK-MB fractions were elevated at one measurement. None of the electrocardiograms showed evidence of ischemia and no arrhythmias were noted during CNA therapy, even in the patients with elevated CK-MB fractions. Conclusions. Continuous albuterol therapy appears to be safe in our patient population as there was no significant evidence of cardiotoxicity. The significance of the transient elevation of CK-MB without other evidence of cardiotoxicity remains to be determined.

Beagle puppies infected with both canine parainfluenza virus type 2 (CPI2) and Bordetella bronchiseptica (Bb) develop more severe acute bronchiolitis and airways hyperresponsiveness than do those infected with CPI2 or Bb alone. The aim of our study was to characterize the inflammatory response associated with airway hyperresponsiveness, and to determine whether the inflammatory cell response of bronchoalveolar lavage fluid (BALF) reflected changes in the bronchioles in this model. We investigated 25 beagle puppies (ages 76 +/- 5 days, mean +/- SEM) in four groups: controls (n = 6), or puppies inoculated with both CPI2 and Bb (CPI2-Bb) (n = 11), with only CPI2 (n = 4), or only Bb (n = 4). The puppies were killed 3-4 days after inoculation, the lungs excised, the intermediate lobe lavaged, and BALF and the bronchiolar wall tissue examined for neutrophils and other inflammatory cells. Control puppies had no evidence of inflammation. However, the CPI2-Bb puppies had developed cough and rhinitis, positive cultures for CPI2 and Bb, and a neutrophilic cellular response in both the bronchioles and the BALF. Puppies inoculated with only CPI2 or Bb had milder illnesses and no significant bronchiolar and BALF neutrophilic response. For all groups, the severity of bronchiolar wall inflammation correlated with the total number of BALF inflammatory cells, and bronchiolar wall neutrophil counts correlated with the percentage of neutrophils in the BALF. The illness and the airway hyperresponsiveness observed in the CPI2-Bb group were associated with airway neutrophilia. Our studies support the hypothesis that neutrophils are associated with airway dysfunction in this model, and the use of BALF to study the process.

OBJECTIVE: Population-based asthma detection is a potential strategy to reduce asthma morbidity in children; however, the burden of respiratory symptoms and health care use among children identified by case detection is not well known. METHODS: Data come from a school-based asthma case detection validation study of 3539 children. Respiratory symptoms, emergency department (ED) visits, and hospitalizations were assessed by questionnaire for children whose case detection result and physician study diagnosis agreed. RESULTS: Physician evaluation of 530 case detection results yielded 420 cases of agreement (168 children with previously diagnosed asthma, 39 with undiagnosed asthma, and 213 without asthma). Children with previously diagnosed asthma were more likely to be male (P < .0001). No differences in severity were observed in children with previously and undiagnosed asthma (P = .31). Children with undiagnosed asthma reported less frequent daytime and nighttime symptoms than children with previously diagnosed asthma but more than those without asthma (P < .0001). The proportion of children with at least 1 respiratory-related ED visit in the past year was 32%, 3%, and 3% for those with previously diagnosed, undiagnosed, and no asthma, respectively (P < .0001). The proportion with at least 1 respiratory-related hospitalization was 8%, 0%, and 0%, respectively (P < .0001). There were no differences in nonrespiratory ED visits (P = .93). CONCLUSIONS: Despite similar physician-rated severity, children with undiagnosed asthma reported significantly less frequent respiratory symptoms and health care use than children with previously diagnosed asthma. These findings suggest that the potential health gains from case detection may be smaller than expected.

Background Much has been done to promote population-based childhood asthma screening; however, concerns remain regarding its cost-effectiveness. Objectives To conduct a cost-effectiveness analysis of school-based asthma screening strategies. Methods A 5 health state Markov approach (symptom-free, symptom, exacerbation recovery, emergency department, and hospitalization day) was used to evaluate school-based screening in a simulated population of urban elementary-age school children. Two questionnaire and 2 multistage strategies incorporating spirometry or spirometry with exercise testing were evaluated from the societal perspective by using 365 daily cycles. The outcome was 2006 dollars per quality-adjusted life year (QALY). Results The most efficient strategy identified children with previously diagnosed but poorly controlled asthma at a cost of $150,000 per QALY (95% CI, $65,800-$318,000). Uncertainty surrounding the cost-effectiveness estimate was primarily a result of the symptom day preference weight estimate (44%), the probability of confirmation after screening (17%), the adequacy of asthma control in the population (9%), and the estimated treatment effect on symptoms (6%). Screening generated an additional 21 symptom-free day equivalents per child identified with previously diagnosed but not well controlled asthma and led to $85.55, $12.36, and $2.58 in additional screening, daily treatment, and indirect costs and $5.01 less in emergency department and hospitalization costs. Conclusion Population-based asthma screening is not cost-effective at $50,000 per QALY and has only a 20% chance of being cost-effective at $100,000 per QALY. The most efficient approach is to screen for previously diagnosed but poorly controlled asthma. Linking screening with better treatment, and long-term adherence strategies might yield future cost-effective approaches.

Self-monitoring of symptoms or peak flow monitoring (PFM) is recommended for all asthma patients and is commonly included in asthma management plans. Limited data are available documenting PFM outcomes in school settings.Three hundred twenty-three urban children with persistent asthma were enrolled in a school-based study that implemented an internet-based asthma monitoring and data collection system. The mean age of the children was 10.0 (SD 2.1) years; 57% were male and 91% were African American. Children logged in daily to an internet-based program to record their asthma symptoms and PFM reading. Teachers logged in daily to confirm the PFM readings. School staff responsible for student health reported actions taken for low PFM readings.A total of 12,245 child reports were completed; 98% (n = 11,974) had corresponding teacher reports, confirming the peak flow meter readings reported by the children. The prevalence of reported asthma symptoms varied across PFM readings; the highest prevalence occurred in the setting of red zone readings, with intermediate prevalence in the setting of yellow zone readings, and lowest prevalence in the setting of green zone readings. The actions reported in response to children's symptoms and peak flow results similarly varied; however, instances of no action were reported in the setting of yellow and red zone readings. When comparing the "worst days" of children who had ever had a red or yellow PFM reading with those of children who only had exhibited green, there was a nonsignificant trend toward fewer symptoms in the green-only group. Additionally, there was a nonsignificant trend toward a greater likelihood of being sent to the office or school nurse with greater symptoms in the setting of a yellow or red zone reading.On the whole, peak flow readings tended to correspond to asthma disease activity. However, the data indicate that school staff may be more inclined to take action based on their own perceptions of a child's asthma or respond to children's subjective reports of asthma symptoms rather than using a more objective measure of disease activity provided by a peak flow meter.

OBJECTIVE. We aimed to determine the effectiveness of school-based supervised asthma therapy in improving asthma control. The primary hypothesis was that the supervised-therapy group would have a smaller proportion of children experiencing an episode of poor asthma control each month, compared with those in the usual-care group.METHODS. Children were eligible if they had physician-diagnosed persistent asthma, the need for daily controller medication, and the ability to use a dry-powder inhaler and a peak flowmeter. The trial used a 2-group, randomized, longitudinal design with a 15-month follow-up period. A total of 290 children from 36 schools were assigned randomly to either school-based, supervised therapy or usual care. Ninety-one percent of the children were black, and 57% were male. The mean age was 11 years (SD: 2.1 years). An episode of poor asthma control was defined as ≥1 of the following each month: (1) an absence from school attributable to respiratory illness/asthma; (2) average use of rescue medication >2 times per week (not including preexercise treatment); or (3) ≥1 red or yellow peak flowmeter reading.RESULTS. Two hundred forty children completed the study. There were no differences in the likelihood of an episode of poor asthma control between the baseline period and the follow-up period for the usual-care group. For the supervised-therapy group, however, the odds of experiencing an episode of poor asthma control during the baseline period were 1.57 times the odds of experiencing an episode of poor asthma control during the follow-up period. Generalized estimating equation modeling revealed a marginally significant intervention–time period interaction, indicating that children in the supervised-therapy group showed greater improvement in asthma control.CONCLUSIONS. Supervised asthma therapy improves asthma control. Clinicians who have pediatric patients with asthma with poor outcomes that may be attributable to nonadherence should consider supervised therapy.

Histamine hyperresponsiveness with viral bronchiolitis may depend on previous exposures to viruses or to other pathogens. We studied 32 outbred beagle puppies 80 to 155 days of age who were raised in isolation and who were specific pathogen-free. Puppies were inoculated with canine parainfluenza type 2 (CPI2, n = 8), Bordetella bronchiseptica (Bb, n = 7), or both CPI2 and Bb (CPI2-Bb, n = 9). Control puppies (C, n = 8) were not inoculated. The puppies were anesthetized with sodium thiopental (5 mg/kg) and chloralose (80 mg/kg) and were ventilated mechanically. Lung resistance (RL), dynamic lung compliance (Cdyn), functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured 3 days prior to inoculation (Day -3), on the day of inoculation (Day 0), and on Days 3-4, 6, 8-10, and 12-14 after inoculation. Histamine responsiveness was measured as: (1) the concentration of histamine base that increased RL to 150% (PC 150% RL) or decreased Cdyn to 75% (PC 75% Cdyn) of the response to saline (RL sal and Cdyn sal, respectively), and (2) the change in RL or Cdyn after inhalation of 11 mg/ml of histamine when compared with RL sal and Cdyn sal. On Day 0 there were no significant (p greater than 0.05) differences among groups with regard to age-corrected weights, FRC, RL, Cdyn, or histamine responsiveness. Control puppies remained healthy, and their pulmonary function and histamine responsiveness did not change. CPI2-Bb puppies increased RL and decreased FRC on Day 3-4, and were moderately ill and histamine-hyperresponsive on Day 3-4 and on Day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Health literacy was assessed in pediatric asthma caregivers attending a university-based clinic. The medical provider's perception of caregiver health literacy was also examined. Eighty-six percent of the caregivers had adequate health literacy, 4% and 10% had marginal and inadequate health literacy, respectively. Health literacy was significantly higher for caregivers who were younger (p = 0.039) and had a higher level of education (p = 0.037). An agreement analysis revealed moderate agreement between provider perception of caregiver's health literacy and measured health literacy (Kappa = 0.51). The results suggest that medical providers may not accurately assess caregivers' actual health literacy level.

Objective. The purpose of this study was to validate a 3-stage asthma case-detection procedure for elementary school-aged children.Methods. The study was performed in 10 elementary schools in 4 inner-city school systems, with a total enrollment of 3539 children. Results of the case-detection procedure were compared with the diagnosis of an asthma specialist study physician, to determine the sensitivity and specificity of the case-detection procedure.Results. Ninety-eight percent of children returned the asthma symptoms questionnaires, and 79% of those children consented to additional testing. Results indicated that the 3-stage procedure had good validity, with sensitivity, specificity, and predictive value of 82%, 93%, and 93%, respectively. A 2-stage procedure using questionnaires and spirometry had similar validity, with sensitivity, specificity, and predictive value of 78%, 93%, and 93%, respectively. However, given the time and expense associated with the 2- or 3-stage procedure and the difficulty of obtaining physician follow-up evaluation of the case-detection diagnosis, schools may prefer to use a 2-item questionnaire that has a lower sensitivity (66%) but higher specificity (96%) and predictive value (95%).Conclusions. Case-detection programs are generally well received by school personnel and can identify children with unrecognized or undiagnosed disease, as well as those with a current diagnosis but poorly controlled disease. This study yields substantial information regarding the validity, yield, and specific types of children who might be identified with the use of such procedures. For the choice of the method of case detection used in a school, the strengths and weaknesses of each procedure, as well as the resources available for case detection, physician referral, and follow-up procedures, must be considered.

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9–12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CPI2, n = 7). We compared their acute responses to puppies infected with CPI2 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12–14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CPI2 group, CPI2 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CPI2 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CPI2 group. Airway histamine responsiveness in the CAV2-CPI2 group increased during infection with CPI2 and was similar to that observed with CAV2 alone. In contrast, infection with CPI2 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CPI2 group in comparison to CPI2 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CPI2 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI. Pediatr Pulmonol 1991; 10:236–243.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Beagle puppies develop bronchiolar inflammation and histamine hyperresponsiveness with canine adenovirus type 2 (CAV2) infections. We determined the distribution of bronchiolar lesions and correlated inflammation with virions and bronchoalveolar lavage fluid (BALF) cytology. Nineteen beagle puppies were inoculated with tissue culture fluid (control puppies, n = 8), or CAV2 (CAV2, n = 11). The puppies had clinical assessments and measurements of lung resistance (RL), and dynamic compliance (Cdyn) immediately before inoculation (Day zero) and 3 days later (Day 3). The puppies were killed on Day 3, the lungs were removed, and the right intermediate lobe was lavaged. The BALF was assessed for total and differential cell counts. Bronchiolar inflammation was quantitated by bronchiolar inflammation scores (BIS). CAV2 was localized by immunofluorescent antibody staining and electron microscopy. The control puppies remained healthy. The CAV2 puppies had positive cultures for CAV2, respiratory symptoms, and generalized necrotizing bronchiolitis. Alveolar inflammation was quantitatively less prominent than bronchiolar inflammation, and RL and Cdyn were unchanged. The BALF neutrophilia correlated with the BIS. CAV2 was present within bronchiolar epithelium, alveolar epithelial type 2 cells, neutrophils, and macrophages. CAV2 was not found in airways smooth muscles or nerves, nor in any noninflamed tissues of CAV2 puppies or in control animals. Our data suggest that acute CAV2 in beagle puppies produces an inflammation of most bronchioles. Intracellular CAV2 was found in bronchiolar epithelium, macrophages, neutrophils, and alveolar epithelial type 2 cells. Bronchiolar inflammation was reflected in BALF cytology. We conclude that bronchiolar inflammation as indicated by BIS and BALF cytology is related temporarily to histamine hyperresponsiveness in our beagle puppies.

We studied the effects of acute smoke exposure on lung permeability, eicosanoids, and inflammatory cell activity. Thirty-five New Zealand white rabbits were anesthetized, paralyzed, and exposed to 60 tidal volume breaths of diesel fuel-polycarbonate plastic smoke or sham smoke within 10 min. At 1 h postexposure the rabbits were killed and their lungs were removed for bronchoalveolar lavage (BAL) or pathologic procedures. Smoke exposure caused decreases in technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, mol. wt. 492 Da) biological half-life (t1/2), BAL plasminogen activator, and BAL leukotriene B4 (LTB4). In addition, alveolar macrophage acid phosphatase enzyme activity increased in smoke-exposed rabbits. The leukotriene synthesis inhibitor, piriprost (U-60,257), given before smoke exposure, caused attenuation of the changes in 99mTcDTPA uptake and plasminogen activator, swelling of type I alveolar cell epithelium, a large increase in lung inflammatory cells, and decreases in BAL LTB4, prostaglandin E2 (PGE2), and TxB2 (stable metabolite of thromboxane, TxA2). We conclude that changes in alveolar-capillary barrier permeability and plasminogen activator activity occur within 1 h after exposure to smoke and may play an early role in the inflammatory process associated with smoke inhalation injury. Furthermore, piriprost attenuates the smoke-induced increase in alveolar-capillary barrier permeability and decrease in plasminogen activator activity and causes a swelling of type I alveolar epithelium. However, our data suggest that neither lung eicosanoids or the alveolar macrophage lysis process plays a major role in the smoke-induced increase in alveolar-capillary barrier permeability.

Acute infection with canine adenovirus was studied in 23 specific pathogen-free outbred beagle puppies (median age = 78 days, range = 67 to 86 days) to determine its effects on pulmonary function and airway responsiveness to aerosolized histamine. The following groups were studied: uninoculated (n = 6, Control); inoculated with canine adenovirus type 2 (CAV2) (n = 11, Infected); and subclinical spontaneous infection with CAV2 (n = 6, Subclinical). While anesthetized with chloralose and mechanically ventilated, lung function and responsiveness to aerosolized histamine were measured 3 days before inoculation (Day -3), the day of inoculation (Day 0), and 3 to 4 (Day 3-4), 6 (Day 6), 8 to 10 (Day 8-10), and 12 to 14 (Day 12-14) days after inoculation. Histamine responsiveness was assessed by calculating the provocation concentration of histamine diphosphate to increase lung resistance (RL) to 150% (PC 150% RL), or decrease dynamic lung compliance (Cdyn) to 75% (PC 75% Cdyn) of the response to saline [RL(sal) and Cdyn(sal), respectively]. Arterial blood gases, functional residual capacity (FRC), specific static lung compliance (spCst), RL, Cdyn, and histamine responsiveness were not significantly different on Day 0 among the groups (p greater than 0.05). Control and Subclinical puppies remained healthy, had a mean weight gain of 0.7 kg, and did not change their histamine responsiveness during the study period. Infected puppies developed moderate to severe clinical illnesses, had poor weight gain, and were histamine hyperresponsive on Days 3-4 and 6. One infected puppy died on Day 3-4, and two died on Day 6 of their illness.(ABSTRACT TRUNCATED AT 250 WORDS)

This is a multiauthored series on a wide variety of lung diseases that affect children. Almost all of the authors are well known in the field of pediatric pulmonology. Unfortunately, the book's chapters are poorly integrated and reflect the multiple writing styles of the authors. Many of the topics are handled superficially. Another problem is that considerable attention is given to the discussion of obstructive airway diseases when the focus of the book is on restrictive lung diseases. Little or no attention is given to the pathogenesis of interstitial lung disease or the epidemiologic aspects of restrictive lung disease. In general, the discussions of theory are also limited. The series would have been improved if the publication was limited to one volume that focused on interstitial lung diseases, including natural history, treatment, and unanswered research questions. It would have also been strengthened if the chapters had been better integrated. The

Campomelic dysplasia is a generalized disorder of cartilaginous growth and development, leading to early death from pulmonary insufficiency. We describe the airway dynamics as observed bronchoscopically in two affected infants. Both infants demonstrated anatomic compromise of the upper airway and diffuse laryngotracheobronchomalacia. Additionally, both had a characteristically small, bell-shaped thoracic cage. The abnormal airway dynamics produced serious inspiratory and expiratory obstruction in these infants and, in combination with the restrictive chest wall defect, led rapidly to the development of respiratory failure. While palliative procedures such as tracheostomy may temporarily improve airway dynamics, future respiratory tract insults may prove fatal. Pediatr Pulmonol 1987; 3:364–367.