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The individualities of bronchioles of the upper and middle lobes in the lung of guinea pig.

The bronchiole variation found in Guinea pigs is important for our understanding of the individualities of the upper lobe and middle lobe bronchioles. The upper lobe bronchiole of the Guinea pig can be divided into three sorts, namely, the well developed, ill developed and completely absent ones. Generally the right lung as the upper lobe bronchiole, while the left lung lacks the upper lobe bronchiole in many cases.

Animals↗

Identification of serous-like cells in the surface epithelium of human bronchioles.

The conductive airways of the mammalian lung are lined by several morphologically distinct cell types, both ciliated and non-ciliated. Of the non-ciliated secretory cells, mucous (goblet), Clara and neuroendocrine cells have been identified in adult human bronchiolar epithelium but, thus far, the serous cell has not. We have examined human membranous and respiratory bronchioles from macroscopically normal peripheral lung (n = 5 cases). For ultrastructural studies, a minimum of five nucleated, non-ciliated cell profiles, containing electron-dense secretory granules, were selected at random from both bronchiolar levels in each case, such that a total of 60 cells was examined. Data from the computer-aided image analysis of the cells indicated that two populations existed, differing in both granule area and granule number per cell p < 0.0005 by discriminant analysis. By visual inspection, the cells fell neatly into two groups: those which, were predominantly serous-like in type, and those which were "Clara". In the membranous bronchioles, serous-like cells had a mean(SEM) granule area per cell of 3.67(0.62) microns 2 and Clara cells 0.47(0.07) microns 2 (p < 0.001). Also, in the membranous bronchiole, the mean(SEM) number of granules in serous-like cells was 40(4.7) and in Clara cells 10(1.1) (p < 0.001). At the respiratory bronchiolar level, the corresponding means were similar to those of the membranous bronchioles and, likewise, serous and Clara cells were significantly different. Thus, our data, indicate that serous cells are present in the adult human bronchiole.

Aged↗

Histology of childhood bronchiolitis obliterans.

Childhood bronchiolitis obliterans (CBO) is an uncommon disease characterized by persistent signs and symptoms of obstructive respiratory disease after an acute bronchiolar injury. It is considered to be a complication of viral infection, most often of adenovirus, and is usually classified as a constrictive-type bronchiolitis obliterans (BO). Few reports have described its histology. We present the histopathological features of 34 pediatric patients with a diagnosis of BO, comprising 30 open lung biopsies (OLB), 2 lobectomies, and 2 autopsies. Quantitative analysis was performed on the OLB to better characterize the morphological changes observed in these lungs. Of 37 patients, 25 were male and 9 were female, ranging from 7 months to 15 years of age. Airway diameter in terminal bronchioles varied from 50-600 microm. Ninety-seven percent of the CBO were of constrictive type, with variable degrees of airway obstruction. Chronic inflammation in the bronchioles was mild in 63% of the patients. Aggregates of foamy macrophages, mucostasis, and bronchiectasis appeared in, respectively, 93%, 40%, and 30% of the biopsies. There was more hyperinflation than atelectasis (40.1% and 24.3%, respectively). Lobectomies and autopsies showed more severe bronchiolar obliteration, associated with bronchiectasis. The results show that CBO is characterized histologically mainly by a constrictive pattern, with variable degrees of inflammation and airway obliteration. Secondary signs of airway obstruction are invariably present. Mild histological changes may predominate and should be carefully evaluated by the pathologist.

Adolescent↗

Human metapneumovirus in children with bronchiolitis or pneumonia in New Zealand.

OBJECTIVES: To confirm the presence of human metapneumovirus (hMPV) in New Zealand and establish its prevalence in selected paediatric patient groups. METHODS: Nasopharyngeal swabs were collected in two separate paediatric studies enrolling children clinically diagnosed with either bronchiolitis or pneumonia and tested for hMPV by polymerase chain reaction. RESULTS: Nucleic acid detection tests demonstrated 5.3% of paediatric bronchiolitis cases were positive for hMPV RNA and 2.7% of children admitted with pneumonia tested positive for hMPV RNA. CONCLUSIONS: The presence of hMPV in New Zealand has been confirmed in two selected paediatric patient groups, namely children diagnosed with bronchiolitis and pneumonia. These results indicate that hMPV is associated with a minority of cases of bronchiolitis or pneumonia in this patient group.

Bronchiolitis↗

Inpatient care for uncomplicated bronchiolitis: comparison with Milliman and Robertson guidelines.

CONTEXT: Bronchiolitis is the most common lower respiratory tract infection in infancy. A recent Centers for Disease Control and Prevention report confirmed that hospitalization rates for bronchiolitis have increased 2.4-fold from 1980 to 1996. Controversies exist about optimal treatment plans. Milliman and Robertson recommend ambulatory care management; in case of hospitalization, the recommended length of stay is 1 day. OBJECTIVES: To relate actual practice variation for infants admitted with uncomplicated bronchiolitis to Milliman and Robertson's recommendations. DESIGN: Prospective observational study. SETTING: General care wards of 8 pediatric hospitals of the Child Health Accountability Initiative during the winter of 1998-1999. PATIENTS: First-time admissions for uncomplicated bronchiolitis in patients not previously diagnosed as having asthma and who were younger than 1 year. MAIN OUTCOME MEASURES: Respiratory rate, monitored interventions, attainment of discharge criteria goals, and length of stay. RESULTS: Eight hundred forty-six patients were included in the final analysis: 85.7% were younger than 6 months, 48.5% were nonwhite, and 64.1% were Medicaid recipients or self-pay. On admission to the hospital, 18.3% of the infants had respiratory rates higher than higher than 80 breaths per minute, 53.8% received supplemental oxygen therapy, and 52.6% received intravenous fluids. These proportions decreased to 1.9%, 33.8%, and 20.3%, respectively, 1 day after admission, and to 0.7%, 20.1%, and 8.6%, respectively, 2 days after admission. The average length of stay was 2.8 days (SD, 2.3 days). CONCLUSIONS: Milliman and Robertson's recommendations do not correspond to practice patterns observed at the hospitals participating in this study; no hospital met the Milliman and Robertson recommended 1-day goal length of stay. Administration of monitored intervention persisted past the second day of hospitalization.

Ambulatory Care↗

Diagnosis and testing in bronchiolitis: a systematic review.

BACKGROUND: The diagnosis of bronchiolitis is based on typical history and results of a physical examination. The indications for and utility of diagnostic and supportive laboratory testing (eg, chest x-ray films, complete blood cell counts, and respiratory syncytial virus testing) are unclear. OBJECTIVES: To review systematically the data on diagnostic and supportive testing in the management of bronchiolitis and to assess the utility of such testing. DESIGN: In conjunction with an expert panel, we generated admissibility criteria and derived relevant terms to search the literature published from 1980 to November 2002 in MEDLINE and the Cochrane Collaboration Database of Controlled Clinical Trials. Trained abstractors completed detailed data collection forms for each article. We summarized the data in tables after performing data integrity checks. RESULTS: Of the 797 abstracts identified, we present evidence from 82 trials that met our inclusion criteria (17 are primary articles on diagnosis of bronchiolitis and 65are reports of treatment or prevention trials). Numerous studies demonstrate that rapid respiratory syncytial virus tests have acceptable sensitivity and specificity, but no data show that respiratory syncytial virus testing affects clinical outcomes in typical cases of the disease. Seventeen studies presented chest x-ray film data. Abnormalities on chest x-ray films ranged from 20% to 96%. Insufficient data exist to show that chest x-ray films reliably distinguish between viral and bacterial disease or predict severity of disease. Ten studies included complete blood cell counts, but most did not present specific results. In one study, white blood cell counts correlated with radiologically defined disease categories of bronchiolitis. CONCLUSIONS: A large number of studies include diagnostic and supportive testing data. However, these studies do not define clear indications for such testing or the impact of testing on relevant patient outcomes. Given the high prevalence of this disease, prospective studies of the utility of such testing are needed and feasible.

Bronchiolitis↗

Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations.

BACKGROUND: Infants hospitalized with bronchiolitis are frequently monitored with a pulse oximeter. However, there is little consensus on an acceptable lower limit of oxygenation. No previous studies have examined how the use of pulse oximetry and supplemental oxygen therapy affects length of stay. OBJECTIVE: To determine the extent to which bronchiolitis hospitalizations are prolonged by a perceived need for supplemental oxygen based on pulse oximetry readings. Design and Patients Retrospective case series of subjects younger than 2 years who were hospitalized with bronchiolitis at an academic medical center. Two investigators independently reviewed the hospitalization records of 73 infants and determined at what point an infant met all discharge criteria except oxygenation. We then calculated the extent to which hospitalizations were prolonged by a perceived need for supplemental oxygen therapy based on pulse oximetry readings alone. RESULTS: Sixty-two infants met inclusion criteria. There was high interrater reliability in determining whether hospitalizations were prolonged (kappa = 0.75). In 16 (26%) of 62 patients (95% confidence interval, 15%-37%), the hospitalization was prolonged because of oxygenation concerns. Length of stay was prolonged an average of 1.6 days (range, 1.1-2.0 days) per hospitalization for these 16 patients, or 0.4 day (range, 0.2-0.6 day) per hospitalization for all 62 patients. CONCLUSIONS: Hospitalizations of some infants with bronchiolitis are prolonged by a perceived need for supplemental oxygen therapy based on pulse oximetry readings. Further investigation into outcomes of different levels and durations of oxygen desaturation is needed and would have the potential to reduce practice variability and shorten the length of stay.

Age Distribution↗

The clinical efficacy of nebulized racemic epinephrine and albuterol in acute bronchiolitis.

OBJECTIVE: To investigate whether nebulized racemic epinephrine or albuterol improves respiratory distress in infants with acute bronchiolitis. DESIGN: A randomized, placebo-controlled, double-blind study. SETTING: A university hospital providing primary hospital care for all pediatric patients in a defined area. PATIENTS: One hundred consecutive infants younger than 24 months treated in the hospital for acute bronchiolitis. INTERVENTION: The patients received two inhalations at 30-minute intervals: racemic epinephrine followed by physiologic saline (REP group; n = 24), albuterol followed by physiologic saline (AP group; n = 27), physiologic saline followed by racemic epinephrine (PRE group; n = 24), and physiologic saline followed by albuterol (PA group; n = 25). All patients received intramuscular epinephrine 60 minutes after the beginning of the study. MAIN OUTCOME MEASURES: Oxygen saturation, respiratory rate, and two clinical scores were used: one based on wheezing and retractions (Respiratory Distress Assessment Instrument) and the other based on changes in wheezing, retractions, and respiratory rate (Respiratory Assessment Change Score). MAIN RESULTS: During the study, there were no significant differences among the four groups in clinical scores, oxygen saturations, and respiratory rates. Mean Respiratory Distress Assessment Instrument scores improved significantly within the REP, PRE, and AP groups 15 minutes after the first inhalation. In only the REP group, which received racemic epinephrine, the confidence limits did not overlap. A comparison of paired data of each patient revealed that the difference in Respiratory Assessment Change Score was significant between racemic epinephrine and physiologic saline, but not between albuterol and physiologic saline. Intramuscular epinephrine significantly improved Respiratory Distress Assessment Index scores in those groups treated earlier with racemic epinephrine (REP and PRE groups). No significant adverse effects were seen in any group or at any phase of the study. CONCLUSIONS: Elimination of hypoxia by supplemental oxygen and moistening of inspired air relieve the symptoms of acute bronchiolitis. Nebulized racemic epinephrine and albuterol are safe and useful in the treatment of acute bronchiolitis. Improvements in symptom scores at 15 minutes favor the use of racemic epinephrine. As the action of epinephrine is short, the effect can be increased by repeated inhalations.

Acute Disease↗

Efficacy of bronchodilator therapy in bronchiolitis. A meta-analysis.

OBJECTIVE: To determine if bronchodilators are efficacious in treating bronchiolitis. DATA SOURCES: A search of bibliographic databases (MEDLINE, Excerpta Medica, and Reference Update) for bronchiolitis and albuterol or ipratropium bromide, or adrenergic agents or bronchodilator agents. Reference lists were also used. STUDY SELECTION: Randomized, placebo-controlled trials of bronchodilator treatment in bronchiolitis were selected by 2 investigators. Fifteen of 89 identified publications met the selection criteria. DATA EXTRACTION: Investigators independently abstracted data for 3 outcomes: clinical score, oxygen saturation, and hospitalization. Clinical score was measured as a dichotomous variable (score +/- improved) or continuous variable (average score). DATA SYNTHESIS: For primary analysis, data were pooled from 8 trials of children with first-time wheezing. The effect size for average score was -0.32 (95% confidence interval [CI], -0.54 to -0.11; P < .01), favoring treatment; the relative risk for score +/- improved was 0.76 (95% CI, 0.60 to 0.95; P = .02), favoring treatment. Bronchodilators had no effect on hospitalization (relative risk, 0.85; 95% CI, 0.47 to 1.53; P = .58), but co-interventions may have been administered prior to this outcome. The results for oxygen saturation were too varied to allow pooling of the results. Secondary analyses were performed on 4 outpatient trials of children with first-time wheezing, 7 trials in which only nebulized beta-agonists were used, and on all 15 trials identified. The results were similar, but the data varied more. CONCLUSION: Bronchodilators produce modest short-term improvement in clinical features of mild or moderately severe bronchiolitis.

Albuterol↗

Increased airway reactivity in human RSV bronchiolitis in the guinea pig is not due to increased wall thickness.

Bronchiolitis due to the respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in the first year of life. It has been suggested that RSV infection may cause subsequent asthma, but a mechanism for this relationship has not been demonstrated. Studies examining the presence of airway reactivity in infants with RSV bronchiolitis are limited by our inability to administer provocative agents such as histamine to such ill infants. This makes a small animal model of this condition a useful tool in which to investigate the pathophysiology of RSV bronchiolitis. We, therefore, evaluated airway responsiveness in vivo and airway morphometric changes in 20 guinea pigs infected by instilling 4,000 plaque-forming units of human RSV virus onto the nasal mucosa under halothane anaesthesia, while 20 control animals received an equivalent volume of sterile cell culture medium. Six days following instillation, 10 infected animals and 10 controls underwent measurements of pulmonary resistance (RL) following increasing doses of inhaled acetylcholine (Ach). These guinea pigs were then sacrificed and the lung and heart removed en bloc for morphometric studies. There were no differences in baseline RL between infected and control groups. At Ach concentrations of 15 and 50 mg/mL, RSV-infected animals had higher RL values than controls (P < 0.05). Fourteen days following RSV instillation no differences in Ach responses were detected in the 10 infected and 10 control animals studied. To determine whether the increase in airway reactivity 6 days after RSV instillation was associated with changes in airway wall morphometry, 125 airways (69 infected, 56 control) were studied. Analysis of wall area, wall area internal to the smooth muscle, or smooth muscle area standardized by the internal perimeter of the airway showed no significant differences between the infected and control airways. These results demonstrated that airway hyperresponsiveness correlated with previously reported histologic changes of acute bronchiolitis 6 days after guinea pigs were infected with human RSV, but neither hyperresponsiveness nor histological changes persisted following resolution of the primary infection. The increased airway reactivity and the previously observed histological changes seen at day 6 following infection was not due to increased airway wall thickness.

Acetylcholine↗

Nasopharyngeal eosinophil cationic protein in bronchiolitis: relation to viral findings and subsequent wheezing.

A prospective 4-month follow-up of children hospitalized with bronchiolitis revealed that high concentrations of eosinophil cationic protein (ECP) in nasopharyngeal aspirates (NPA) are predictive of wheezing after bronchiolitis. In the 29 patients who received no anti-inflammatory therapy the median concentration of NPA ECP was 882 ng/g in those with physician-diagnosed wheezing (P = 0.02). The NPA ECP concentration of the whole study group of 88 children with and without subsequent hospital admissions for wheezing were 531 and 299 ng/g, respectively (P = 0.02). At entry the children with negative viral findings had significantly higher concentrations of respiratory tract ECP than those with positive viral findings (515 vs. 240 ng/g; P = 0.01). The concentration of ECP in respiratory secretions decreased significantly after bronchiolitis (P = 0.01) provided that no new viral or mycoplasmal infection occurred. NPA ECP values decreased in relation to time regardless of whether anti-inflammatory therapy was used or not. Children with high concentrations of respiratory tract ECP seemed to benefit from anti-inflammatory therapy with nebulized cromolyn sodium or budesonide; both drugs significantly decreased the number of subsequent physician-diagnosed bronchial obstruction (P = 0.0006), and they tended to decrease the number of hospital admissions for wheezing (P = 0.08). Our results suggest that high concentrations of ECP in respiratory tract secretions in children with bronchiolitis reflect the presence of eosinophilic inflammation also seen in asthma.

Acute Disease↗

Differential detection of rhinoviruses and enteroviruses RNA sequences associated with classical immunofluorescence assay detection of respiratory virus antigens in nasopharyngeal swabs from infants with bronchiolitis.

To define the role of enteroviruses and human rhinoviruses as etiological agents in childhood bronchiolitis, clinical aspirates from 84 infants admitted to hospital with symptoms of obstructive bronchiolitis were tested by picornavirus RT-PCR assay, adenovirus PCR assay and classical immunofluorescence antigen detection of common respiratory viral agents. Respiratory syncytial viruses (A&B) were detectable in 45 of 84 (53.6%) nasopharyngeal aspirates from infants with bronchiolitis, whereas coronaviruses, influenza viruses, and parainfluenza viruses were not detectable in the same samples. Adenoviruses were detectable by PCR in 11 of 84 (13.1%) nasopharyngeal swabs. By using a picornavirus RT-PCR assay followed by a differential molecular hybridisation, rhinovirus and enterovirus RNA sequences were detected in 16 of 84 (19%) and in 10 of 84 (11.9%) of the nasopharyngeal swabs tested. Positive human rhinovirus or enterovirus RT-PCR assay, however, was the only evidence of respiratory infection in 8 of 84 (9.5%) and in 7 of 84 (8.33%) of the studied patients. Respiratory syncytial viruses, human rhinoviruses, adenoviruses, and enteroviruses occur in dual infections detected in 18 of 84 (21.4%) respiratory samples tested. The median duration of stay in hospital was not significantly different between the patients demonstrating a single viral infection and those with a dual viral infection (6.22 +/- 2.07 vs. 5. 04 +/- 0.95 days; P > 0.05). In summary, combination of molecular and classical detection assays of common viruses can be used to demonstrate enterovirus and human rhinovirus respiratory infection in childhood bronchiolitis, and provides an improved approach to obtain new insights into concomitant viral respiratory tract infection in infants.

Antigens, Viral↗

Bronchodilators for bronchiolitis.

OBJECTIVES: Bronchiolitis is an acute, highly communicable lower respiratory tract infection. Bronchodilators are commonly used in the management of bronchiolitis in North America, but not in the United Kingdom. The objective of this review was to assess the effects of bronchodilators for bronchiolitis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Reference Update, reference lists of articles, and the files of two of the authors up to June 1998. SELECTION CRITERIA: Randomised trials comparing bronchodilators with placebo in the treatment of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Unpublished data were requested from authors when necessary. MAIN RESULTS: In eight trials with 394 children, 46% demonstrated an improved clinical score with bronchodilators compared to 75% with placebo (odds ratio for no improvement 0.29, 95% confidence interval 0.19 to 0.45). However, the inclusion of studies that enrolled people with recurrent wheezes may have biased these results in favour of bronchodilators. Bronchodilator recipients did not show improvement in measures of oxygenation, the rate of hospitalisation (18% versus 26%, odds ratio 0.70, 95% confidence interval 0.36 to 1.35) or duration of hospitalisation (weighted mean difference 0.12, 95% confidence interval -0.3 to 0.5). REVIEWER'S CONCLUSIONS: Bronchodilators produce modest short-term improvement in clinical scores. This small benefit must be weighed against the costs of these agents.

Bronchiolitis↗

Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old.

BACKGROUND: Acute bronchiolitis is the leading causes of medical emergencies during winter in children younger than two years of age. Chest physiotherapy is thought to assist infants in the clearance of secretions and decrease ventilatory effort. OBJECTIVES: To determine the efficacy and safety of chest physiotherapy in infants aged less than 24 months old with acute bronchiolitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004) which contains the Acute Respiratory Infection Group's specialised register; MEDLINE (January 1966 to June 2004); EMBASE (1990 to June 2004); PASCAL; SCISEARCH; LILACS; and Cumulative Index to the Nursing & Allied Health Literature (CINAHL) (1982 to May 2004). SELECTION CRITERIA: Randomised controlled trails (RCTs) in paediatric patients younger than twenty four months old in which chest physiotherapy was compared against no intervention or against another type of physiotherapy. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted the data. Primary outcome was a severity clinical score. Secondary outcomes were length of hospital stay, duration of oxygen supplementation, and the use of bronchodilators and steroids. MAIN RESULTS: Three clinical trials met the inclusion criteria. All evaluated vibration and percussion techniques in postural drainage positions compared to no intervention. The study population were hospitalised infants with a clinical diagnosis of acute bronchiolitis, although one study included only infants who required nasogastric tube feeding or intravenous fluids. None of the other included trails observed any differences in the severity of the clinical score at day five or during each of the five days of the trial or until discharge, length of hospital stay, or oxygen requirements between chest physiotherapy group and control. AUTHORS' CONCLUSIONS: Based on the results of three RCTs, chest physiotherapy using vibration and percussion techniques does not reduce length of hospital stay, oxygen requirements, or improve the severity clinical score in infants with acute bronchiolitis that are not under mechanical ventilation, and who do not have any other co-morbidity. Chest physiotherapy using forced expiratory technique needs to be evaluated by clinical research.

Acute Disease↗

Lung function and bronchial responsiveness in children who had infantile bronchiolitis.

A number of studies have shown that children who had infantile bronchiolitis are at increased risk of recurrent episodes of wheezing. A genetic predisposition to atopy is mentioned in some studies and is contested by others. Lung function abnormalities and increased bronchial responsiveness (BR) have been described after infantile bronchiolitis. We investigated children who had had the clinical syndrome of bronchiolitis during infancy and compared them with asthmatic and healthy children of the same age regarding bronchial caliber, smooth muscle tone, and responsiveness to histamine. Lung function was measured by forced oscillometry. We found that most children with current symptoms had either decreased baseline bronchial caliber, increased bronchial smooth muscle tone, or increased BR. These patients are comparable to mild asthmatics. The children without current symptoms are comparable to healthy children in these respects. Recurrent respiratory symptoms after bronchiolitis should be regarded as mild asthma and treated as such.

Asthma↗

Airway responsiveness in infants following bronchiolitis.

Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis.

Acute Disease↗

Lymphocytic inflammation in childhood bronchiolitis obliterans.

Childhood bronchiolitis obliterans (CBO) is an infrequent, severe disorder characterized by persistent obstructive respiratory symptoms after an acute episode of bronchiolitis. The viral etiology is most common, and adenovirus is the most frequently identified causative agent. Pathologically, the disease is characterized as constrictive type BO, with variable degrees of chronic inflammation and fibrosis in the bronchioles. The nature of the cellular infiltrate is largely unknown, and its characterization may provide better understanding of the disease and offer clues for therapy. Therefore, the aim of the present study was to characterize the inflammatory infiltrate in the bronchioles of 23 open lung biopsies of children with CBO and to compare this to the infiltrate in histologically normal airways. Our results show that CD3+ T cells were the most frequent cell type observed in CBO, with a predominance of the CD8+ T-cell subtype. When compared to the control group, there was a larger number of CD8+, CD4+, CD20+, granzyme B+, and perforin+ lymphocytes in the CBO group. Further studies are needed to address the role of different cell types in the development of CBO.

Adolescent↗

Validation of a pediatric caregiver diary to measure symptoms of postacute respiratory syncytial virus bronchiolitis.

Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization. To date, there is no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis. We report on the reliability, validity, and responsiveness of the bronchiolitis caregiver diary (BCD) of symptoms and healthcare utilization associated with postacute RSV. The BCD measures four symptoms (daytime cough, wheeze, trouble breathing, and nighttime cough), healthcare utilization, and rescue medication for worsening of lung symptoms. Data from the 4-week treatment period of the reported prospective, placebo-controlled trial of montelukast for treatment of postacute RSV were used to assess reliability (internal consistency and test-retest), construct validity (cross-sectional and longitudinal correlations), discriminant validity (known-groups analyses), and responsiveness. The primary outcome of this study was the percentage of symptom-free days (SFD). The secondary outcome was a composite symptom score (CSS; average of daytime cough, wheezing, and trouble breathing). Cronbach's alpha of 0.85 indicated that the four symptoms were internally consistent, supporting a unidimensional scale structure. Test-retest reliabilities for the percentage of SFD and CSS were above the recommended cut point of 0.70. Cross-sectional and longitudinal correlations were sizeable and statistically significant, demonstrating construct validity. Hypothesized known-group differences were statistically significant in the appropriate direction. Responsiveness analyses indicated moderate effect sizes for percentage of SFD. In conclusion, the BCD provides a valid, reliable, and responsive tool for the assessment of symptoms of postacute RSV-induced bronchiolitis, capable of measuring moderate effect sizes, and demonstrating responsiveness to therapy.

Bronchiolitis, Viral↗