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Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients.

An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65% +/- 4% at 1 month, 54% +/- 4% at 3 months, 45% +/- 4% at 1 year, 38% +/- 5% at 2 years, and 36% +/- 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65% +/- 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89 +/- 0.13 L early after retransplantation to 1.80 +/- 0.15 L at 1 year and 1.54 +/- 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients.

ABO Blood-Group System↗

Bronchiolitis obliterans with pemphigus vulgaris and Castleman's disease of hyaline-vascular type: an autopsy case analyzed by computer-aided 3-D reconstruction of the airway lesions.

We have experienced an autopsy case of a 20-year-old woman with bronchiolitis obliterans, pemphigus vulgaris, and Castleman's disease. The affected bronchioles showed almost the same histology as previously described. But, the number of the lesions seemed too small to cause her death of respiratory insufficiency. We also wondered whether or not some normal routes to the peripheral pulmonary tissues remained. After reviewing many histological sections from both lungs, one tissue block was chosen to make semiserial sections, and computer-aided three-dimensional (3-D) reconstruction analysis was performed. The 3-D reconstruction clearly showed two points: (1) Obstructive lesions developed within very narrow segments of bronchioles (0.4 to 0.7 mm in diameter; restricted to two to three generations) sparing terminal and respiratory bronchioles. This could explain the paucity of bronchiolar lesions that appeared on random sections; (2) All the affected bronchioles showed a high degree (up to 80-90%) of luminal stenosis. No intact routes to the periphery were left. Thus, respiratory insufficiency in this case became quite understandable.

Adult↗

Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the most prevalent acute wheezing disorder in infants and is associated with recurrent wheeze and asthma in childhood. Interleukin 9, a type 2 cytokine has been proposed as a key cytokine in susceptibility to asthma. We aimed to investigate whether interleukin 9 was produced in the lungs of infants with severe RSV disease and if found, from which cells it originated. METHODS: We did 150 non-bronchoscopic bronchoalveolar lavages during the course of ventilation in 24 term infants and 21 preterm infants ventilated for RSV bronchiolitis. We also did 10 bronchoalveolar lavages on the day of intubation in 10 control infants ventilated for non-respiratory causes. We measured pulmonary interleukin 9 mRNA and protein in samples from all groups. We used immunostaining to identify the cells that produce interleukin 9. FINDINGS: Interleukin 9 mRNA expression, which persisted over the course of ventilation, was noted in all infants with bronchiolitis. Three of the control group also showed interleukin 9 mRNA expression. Median interleukin 9 protein concentration on day 1 (1.9 microg/L [range 0.1-36.2]) was significantly greater in term infants with bronchiolitis than either preterm infants (0.4 microg/L [0.1-2.9]; p<0.05) or the control group (0.7 microg/L [0.4-2.5]; p<0.05). There was a trend for interleukin 9 protein concentrations in term, but not preterm infants to decrease over time. Immunostained cell smears showed that most interleukin 9 expression in bronchoalveolar lavage was by neutrophils. INTERPRETATION: In term infants with RSV bronchiolitis, we noted large amounts of interleukin 9 mRNA and interleukin 9 protein. Neutrophils seem to be the main source of this type 2 cytokine. Interleukin 9 production by neutrophils may contribute to the pathogenesis of RSV disease. These findings may be relevant to other disease processes in the lung where neutrophils are the predominant inflammatory cell type.

Acute Disease↗

Bronchiolitis.

Bronchiolitis is a distressing, potentially life-threatening respiratory condition that affects young babies. Around 2-3% of all infants younger than 1 year are admitted to hospital with bronchiolitis, usually during the seasonal epidemic. The majority of these infants are infected with respiratory syncytial virus and all have an intense inflammatory response in their airways. Although most infants recover, they have an increased risk of recurrent wheezing. Although bronchiolitis is common, little is known about what causes infants to be susceptible. Diagnostic interventions have little effect on clinical outcome, and apart from supportive measures, there is no specific treatment. Bronchiolitis therefore presents an intriguing clinical conundrum and a major challenge to researchers. High quality clinical studies are needed to clarify assessment of disease severity and criteria for hospital admission, particularly the use of pulse oximetry and chest radiography. Careful mapping of the inflammatory pathways in the pathogenesis of bronchiolitis should lead to development of new therapies to alleviate symptoms.

Antibodies, Monoclonal↗

Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis and bronchiolitis obliterans.

BACKGROUND: Cases of paraneoplastic pemphigus (PNP) have been reported associated with various lymphoproliferative malignancies and benign Castleman tumors, with the most severe course and fatal outcome seen in patients with bronchiolitis obliterans. OBJECTIVE: The aim was to establish immunologic associations by coexistence of Castleman tumor, myasthenia gravis, and bronchiolitis obliterans and to evaluate the treatment modalities. METHODS: Clinical studies included computed tomography of the mediastinum, computed tomography and magnetic resonance imaging of the abdominal cavity, and quantitative electromyography. Direct and indirect immunofluorescence on various substrates, immunoblot analysis, immunoprecipitation, and specific enzyme-linked immunosorbent assay using recombinant desmogleins (Dsg) were performed as immunologic assays. RESULTS: Direct and indirect immunofluorescence including rat bladder showed intercellular antibodies. Immunoblotting disclosed antibodies to envoplakin (210 kd protein) and periplakin (190 kd protein); in addition, immunoprecipitation detected antibodies to desmoplakin I (250 kd protein). Antibodies to Dsg3 (pemphigus vulgaris antigen) were detected by specific enzyme-linked immunosorbent assay. Myasthenia gravis was controlled by drugs; however, mucocutaneous changes were not fully responsive to corticosteroids and cyclophosphamide pulses, cyclosporine, and intravenous immunoglobulins. The surgical removal of Castleman tumor did not change the course of the disease. The fatal outcome was the result of bronchiolitis obliterans that occurred after the surgery and was only transitionally controlled by plasmapheresis. CONCLUSION: This is the first case of paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis, and bronchiolitis obliterans. Despite a benign character of the tumor the patient died, as do all patients with bronchiolitis obliterans. Massive plasmapheresis has only a transient effect. We confirmed the presence of antibodies to Dsg 3, in addition to the set of specific paraneoplastic pemphigus antibodies against various proteins of plakin family.

Adult↗

[Bronchiolitis caused by influenza type A virus. An emerging infectious disease].

OBJECTIVES: To prospectively study the emergence and diagnostic problems of bronchiolitis caused by influenza A virus among children durign the 1999-2000 influenza epidemic. MATERIALS AND METHODS: Negative respiratory syncitial virus (RSV) specimens (ELISA dot-blot) were seeded in the MDCK cell line for the isolation of influenza A virus, by the shell-vial technique. Vials were revealed by indirect immunofluorescence with antibodies directed against the influenza A virus nucleoprotein (Monofluookit IA, Pasteur Diagnostics). The clinical and epidemiologic features of patients with viral recovery were studied. A theoretical cost/benefit study was performed on the usefulness of the rapid antigenic detection of the influenza A virus. RESULTS: A total of 117 cases of respiratory infection caused by influenza A virus were detected. In 62 cases (52.9%) the diagnosis was bronchiolitis. Of them, 80.6% of cases were aged less than 6 years. Subtype H3N2 predominated in all respiratory infections, paticularly in bronchiolitis. During the 1999-2000 season, a significant emergence of bronchiolitis caused by influenza A virus was observed (week 3, 30% cases of influenza A versus 24% of RSV). The cost/benefit study disclosed that the antigenic detection of RSV and influenza A virus in all respiratory specimens would amount up to 30.83 Euros/specimen. CONCLUSIONS: During the last influenza epidemic, an emergence of bronchiolitis caused by influenza A virus among children was observed and confirmed. Based upon this observation, a dual strategy should be followed. On the one hand, a prophylactic approach (immunization of pregnant women); on the other hand, a diagnostic approach with a rapid antigenic detection of the influenza A virus.

Bronchiolitis↗

[Constrictive bronchiolitis obliterans. Apropos of a case].

INTRODUCTION: Constrictive bronchiolitis obliterans is defined histologically as obliteration of the lumina of bronchioles by inflammatory tissue elements and progressive destruction of bronchioles, eventually replaced by fibrotic tissue. Most of the cases, which are not associated with either solid organ or bone marrow transplantation, occur in the development of rheumatoid arthritis. EXEGESIS: We present the case of a 73-year-old woman who developed severe constrictive bronchiolitis obliterans without readily identifiable cause, rapidly fatal despite corticosteroid therapy. The patient had antinuclear antibodies (titer 1/1024) and antiphospholipid antibodies, but there was no anti-DNA, anti-ENA or anti-beta 2GPI antibodies. Tests for rheumatoid factor were negative. Cryoglobulinemia was present (monoclonal IgM Kappa). CONCLUSION: In this case, constrictive bronchiolitis obliterans was associated with serologic abnormalities and cryoglobulinemia. However, were was no clinical evidence of connective tissue disease.

Aged↗

[Prospective regional study of an epidemic of respiratory syncytial virus (RSV) bronchiolitis].

UNLABELLED: This prospective study was designed to identify risk factors associated with admission in pediatric intensive care units (PICU) among infants hospitalized for treatment of RSV induced bronchiolitis. This study was population-based and was conducted in Burgundy, a French region with 1,800,000 inhabitants where passive immunoprophylaxis for RSV bronchiolitis was not set up at the time of the study. RESULTS: From December 1st 1999 to April 30th 2000, 484 infants were hospitalized for RSV bronchiolitis in Burgundy: 19.6% were born prematurely (gestational age [GA] below 37 weeks) and at admission, 68.3% had a postnatal age below six months (mean = 5 +/- 5.9 months; median value = 3 months). The duration of hospitalization was 7.3 +/- 12.4 days (median value = 6 days). Among the 484 infants, 31 (6.4%) needed admission in PICU, eight needed mechanical ventilation (1.7%) and one died (0.2%). Univariate analysis identified anamnestic risk factors associated with admission in PICU: prematurity; low birth weight; past history of neonatal respiratory distress syndrome (RDS); mechanical ventilation for RDS treatment; bronchopulmonary dysplasia (BPD) and congenital heart disease. Multivariate analysis identified three independent factors associated with an increased risk for admission in PICU: GA below 32 weeks; RDS and congenital heart disease. CONCLUSION: This study suggests that population at risk for severe RSV bronchiolitis with PICU admission should include all very preterm infants with RDS whatever the outcome of RDS (with or without BPD). These epidemiological data could be helpful to set up indications for passive immunoprophylaxis of RSV induced bronchiolitis.

Antibodies, Monoclonal↗

[Chest radiograph in bronchiolitis: is it always necessary?].

BACKGROUND: The routine use of chest radiograph in infants with bronchiolitis increases health costs and can often unnecessarily expose the patient to radiation. OBJECTIVES: To evaluate the prevalence of infiltrate/atelectasis in infants younger than 2 years who presented to the emergency department with bronchiolitis, to assess whether patient management is changed after viewing the chest radiograph and to determine which clinical variables can accurately identify children with normal radiographs, with a view to reducing unnecessary radiological investigations. PATIENTS AND METHODS: From October 2003 to December 2004, infants aged < 24 months evaluated in the emergency department of the Severo Ochoa Hospital (Madrid) with a diagnosis of bronchiolitis were included in this study. The variables registered were age, sex, time since onset, respiratory rate, temperature, asymmetry on auscultation, oxygen saturation and the virus identified. A chest radiograph was obtained and the need for admission was evaluated before and after obtaining the results. RESULTS: Two hundred fifty-two infants were included, of which 50 % were aged less than 5 months. Infiltrate/atelectasis was identified in 14.3 % (95 % CI: 10.1-18.5; kappa coefficient: 0.64). Patients with infiltrate/atelectasis were 2.5 times more likely to have a temperature of > or = 38 degrees C (p: 0.004), O2 saturation of < 94 % (p: 0,006) and to be admitted before the results of chest radiograph were known. No differences were found between children with and without infiltrate in age at presentation, sex, disease duration, respiratory rate or identified virus. Patient management was modified in 30 % of patients with infiltrate/ atelectasis. Patients with a temperature of < 38 degrees and O2 saturation of > 94 % had a 92 % probability of normal chest radiograph. CONCLUSIONS: Most infants presenting with bronchiolitis had a normal chest radiograph. Temperature >or = 38 degrees and O2 saturation < 94 % were significantly associated with infiltrate/atelectasis. In most infants with bronchiolitis, the absence of fever and hypoxia are good predictors of normal chest radiographs.

Bronchiolitis, Viral↗

Epidemiology and aetiology of acute bronchiolitis in Hong Kong infants.

The epidemiological, clinical and virological features of 1220 children with acute bronchiolitis admitted to the Prince of Wales Hospital, Hong Kong, from 1985 to 1988 are reported. They accounted for 6.6% of total paediatric admissions and provided a case incidence of bronchiolitis requiring admission to hospital of approximately 21 per 1000 children 0-24 months of age. The clinical course and outcome was in general benign. The average hospital stay was 5 days and there were no deaths. Ten per cent of patients were repeatedly admitted to hospital with recurrent wheezing after discharge. Two infants developed bronchiolitis obliterans. Respiratory syncytial virus (RSV) was shown by direct immunofluorescence, virus culture and serology to be the commonest cause of acute bronchiolitis in Hong Kong. Other aetiological agents included parainfluenza and influenza viruses, adenoviruses, and Mycoplasma pneumoniae. In contrast to western countries, a seasonal variation of bronchiolitis was found with a peak incidence in the summer months. The significance of these observations is discussed.

Acute Disease↗

Epidemiology of respiratory syncytial virus bronchiolitis in hospitalized infants in Greece.

New therapies have been introduced for the prophylaxis and treatment of respiratory syncytial virus (RSV) infection in recent years. The aim of the study was to determine the epidemiological and clinical characteristics of infants hospitalized with bronchiolitis in our area. All patients under 1 year of age admitted with acute bronchiolitis during four consecutive RSV seasons from February 1, 1997 to June 30, 2000 were enrolled in the study. The records of patients admitted during the first season were reviewed retrospectively while the rest were followed prospectively. A total of 636 infants with bronchiolitis were admitted and RSV infection was documented in 61% of those tested. Admission to intensive care unit (ICU) was required for 6.2% of them and was more common in premature infants (26%) (p < 0.001). Case fatality rate was 0.7% (overall 0.3%). RSV bronchiolitis accounted for about 12% of all infant admissions during the 5 months of the yearly outbreak. Patients with documented RSV infection had a more severe illness with a higher ICU admission rate (6 vs. 1%, p = 0.008) and longer duration of hospitalization (mean 6.3 vs. 5.3 days, p < 0.001) compared to those who tested negative. Although none of the patients had a positive blood culture on admission a considerable number of them (210/636, 33%) were treated with antibiotics. RSV infection has a significant impact on infant morbidity in our settings which is more serious among those born prematurely. Documentation of RSV infection may be a marker of more severe illness in infants hospitalized with bronchiolitis. Antibiotic use has to be restricted since the occurrence of a serious bacteraemic illness on admission is a very rare event.

Anti-Bacterial Agents↗

Obliterative bronchiolitis after lung transplantation: a fibroproliferative disorder associated with platelet-derived growth factor.

Fibroproliferative disorders are characterized by accumulations of mesenchymal cells and connective tissue in critical locations, leading to organ dysfunction. We examined the role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative bronchiolitis, a fibroproliferative process that occurs after lung transplantation and results in small airway occlusion. Bronchoalveolar lavage fluid from obliterative bronchiolitis patients significantly stimulated fibroblast migration, whereas fluid from patient controls did not. Quantitation by radioligand binding assay demonstrated increased concentrations of PDGF in lavage fluid from obliterative bronchiolitis patients (patients, 104 +/- 26.9 pM; controls, 8.4 +/- 6.9 pM; P < 0.01). Heparin affinity, gel filtration, and Western blot analysis confirmed the presence of PDGF in lavage fluid. Immunohistochemical and in situ hybridization studies of histologic sections and bronchoalveolar lavage cells suggest that alveolar macrophages are one cellular source. Prospective evaluation of sequential bronchoalveolar lavage samples from a patient who developed obliterative bronchiolitis demonstrated markedly increased PDGF concentrations before the onset of irreversible airflow obstruction. These findings are consistent with a role for PDGF in the fibroproliferative changes observed in obliterative bronchiolitis.

Adult↗

T cell subset analysis in peripheral blood of children with RSV bronchiolitis.

Respiratory syncytial virus (RSV) bronchiolitis is partially an immune-mediated disease in which RSV-specific T cells play a predominant role. The peripheral blood T cell response was studied in patients with RSV bronchiolitis in order to detect evidence for T cell redistribution during natural RSV infection and if so, which subsets are involved. 18 patients with RSV bronchiolitis and 13 control patients were studied. The white blood cell count, the number of T cells and T cell subsets in blood on admission and after 1 week were measured. The absolute count of natural killer cells and gamma delta + T cells on admission were significantly lower in RSV patients in comparison with the control group. During the course of RSV bronchiolitis CD8+ T cells and IL-2 receptor-positive T cells increased significantly. In the ventilated patients the total lymphocytes and the number of T cells and several T cell subsets with surface molecules compatible with an activation state of the cell were decreased in comparison with the non-ventilated RSV patients on admission. During RSV bronchiolitis, consistent shifts in T cell subsets can be demonstrated in the peripheral blood compatible with redistribution from the circulation probably towards the lungs. These findings are more pronounced in patients with severe disease.

Antigens, CD↗

Socioeconomic environmental factors and hospitalization for acute bronchiolitis during infancy.

UNLABELLED: Bronchiolitis is a major cause of hospitalization during infancy. The aim of this study was to evaluate the influence of socioeconomic factors on the hospitalization of infants with bronchiolitis. All infants below 1 y of age living in the city of Malmö, Sweden, and hospitalized at the University Hospital. Malmö, owing to bronchiolitis during the years 1998 and 1999 were identified. The bronchiolitis hospitalization rates (BHRs) were determined for the infants living in each of the 10 different administrative residential areas of Malmö and correlated with socioeconomic factors (percentage of immigrants, per capita income, unemployment rate and households receiving social benefit) in the respective residential areas. The severity of the disease on admission and during hospital care was assessed by comparing oxygen saturation, days with supplemental oxygen and length of stay. BHR varied more than fourfold between the 10 residential areas. BHR varied significantly with per capita income and the percentage of immigrants. Infants living in the area with the highest social burden were hospitalized almost twice as often as those from the rest of the city, but the severity of disease was similar. CONCLUSION: The association between socioeconomic factors and hospitalization indicates that these factors may have a significant influence on the hospitalization rate in bronchiolitis during infancy.

Acute Disease↗

Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979-1997.

A 1985 estimate that 4500 respiratory syncytial virus (RSV)-associated deaths occur annually among US children has not been updated using nationally representative data. Thus, 1979-1997 multiple cause-of-death records for children <5 years old listing bronchiolitis, pneumonia, or any respiratory tract disease were examined. Deaths among children associated with any respiratory disease declined from 4631 in 1979 to 2502 in 1997. During the 19-year study period, 1806 bronchiolitis-associated deaths occurred (annual mean, 95 deaths; range, 66-127 deaths). Of these deaths, 1435 (79%) occurred among infants <1 year old. Congenital heart disease, lung disease, or prematurity was listed in death records of 179 (9.9%), 99 (5.5%), and 76 (4.2%) children dying with bronchiolitis, respectively. By applying published proportions of children hospitalized for bronchiolitis or pneumonia who were RSV-infected to bronchiolitis and pneumonia deaths, it was estimated that < or =510 RSV-associated deaths occurred annually during the study period, fewer than previously estimated.

Bronchiolitis↗

Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.

Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.

Adult↗

Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in infants is characterized by a massive neutrophilic infiltrate into the airways. Chemokines direct migration of leukocytes and contribute to the pathogenesis of RSV disease. However, little is known about pulmonary chemokine responses to RSV in humans. Our aim was to characterize the production of chemokines in the lungs of infants with RSV bronchiolitis and how this production changes over time. METHODS: Chemokine mRNA and the concentration of chemokines were measured in nonbronchoscopic bronchoalveolar lavage (BAL) samples from infants with RSV bronchiolitis and from control infants. In infants with RSV bronchiolitis, changes in the concentrations of chemokines during the 7 days after intubation and between the days of intubation and extubation were examined. RESULTS: The production of chemokines within the lower respiratory tract was shown in all patients with RSV bronchiolitis. CXC chemokines (particularly CXCL10/interferon-inducible protein 10 and CXCL8/interleukin-8) were found to be the most abundant, but CC chemokines (CCL2/monocyte chemotactic protein 1 and CCL3/macrophage inflammatory protein-1 alpha) were also present. Concentrations of some of these chemokines remained elevated over the course of the illness, whereas others decreased steadily. No differences in the concentrations were found between the days of intubation and extubation. CONCLUSIONS: CXC chemokines predominate within the RSV-infected lung. Much of this response comes from inflammatory cells within the lower respiratory tract. Chemokine response patterns vary over time, possibly indicating different cellular sources for individual chemokines in the RSV-infected lung.

Bronchiolitis↗

Observer variation in detecting the radiologic features associated with bronchiolitis.

Chest radiographs are commonly obtained to assess children for bronchiolitis, both to corroborate the diagnosis and to exclude other diagnostic possibilities. Their utility in this setting has not previously been examined. Using a blinded, randomized study design, we examined the interobserver and intraobserver variation in the detection of the radiologic features of bronchiolitis from the chest radiograph using "weighted kappa" statistics. This observer variation was compared with that found by other authors for other diagnoses. We also determined the reported presence of these radiologic features in radiographs from patients with bronchiolitis as compared with normal controls. Our study showed acceptable interobserver (kappa = 0.40-0.66) and intraobserver agreement (kappa = 0.50-0.78) on the radiologic features of bronchiolitis relative to other diagnoses. We demonstrated a higher reported presence of these accepted radiologic features in patients with bronchiolitis as compared to controls. Although kappa statistics are widely used in studies of observer variation, "weighted kappa" has received little attention in the radiologic literature. This statistical analysis allows observers to equivocate on the presence or absence of a feature and therefore allows the format of observer variation studies to simulate more closely the normal clinical setting.

Bronchiolitis, Viral↗