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PubMed2003

Infectious etiology of bronchiolitis obliterans: the respiratory viruses connection - myth or reality?

A variety of viruses, such as the influenza viruses A and B, the human respiratory syncytial virus, the parainfluenza viruses, and the adenoviruses, cause seasonal respiratory tract infections in young children and adults. Also, studies indicate that these viruses are an important group of pathogens in pediatric and adult lung transplant recipients. More importantly, accumulating data on these infections among lung transplant patients suggest that these illnesses may have immediate and long-term implications for the function of the transplanted lung, including the development of bronchiolitis obliterans. This is important because patient survival and allograft function in lung transplantation remain limited by the development of bronchiolitis obliterans. Models of lung transplantation indicate that respiratory viral infections cause acute and chronic airway damage after transplantation. The mechanism leading to allograft damage by respiratory viruses may be related to the production of alloreactive cytokines such as interleukin (IL)-1, tumor necrosis factor, IL-6 and IL-8 during viral replication. Current clinical data are suggestive of a possible role for respiratory viruses in the development of bronchiolitis obliterans, but further control studies are required to evaluate the significance of respiratory virus infections as a causal factor in the development of bronchiolitis obliterans in lung transplantation.

Bronchiolitis Obliterans↗
PubMed2001

Leucocyte populations in respiratory syncytial virus-induced bronchiolitis.

OBJECTIVES: To enumerate the cellular composition of the airways in infants with acute bronchiolitis. METHODOLOGY: Cells were obtained by airway lavage from the upper and lower airway and the peripheral blood of infants with respiratory syncytial virus (RSV)+ bronchiolitis, RSV- bronchiolitis and age-matched controls. RESULTS: Neutrophils are the predominant cells present in the upper and lower airway. Neutrophils are present at a higher number/unit volume in the airway than in the peripheral blood. CONCLUSIONS: Neutrophils, being the dominant cellular infiltrate into the airway, are likely to contribute to the pathophysiology of bronchiolitis. Therapies targeted at limiting neutrophil influx or neutrophil-mediated damage in the airway may have a therapeutic role.

Bronchiolitis, Viral↗
PubMedDate not supplied

Long and short-term effect of prednisolone in hospitalized infants with acute bronchiolitis.

OBJECTIVE: To assess long and short-term effect of prednisolone in hospitalized infants with bronchiolitis. METHODOLOGY: A randomized and controlled trial was carried out at the Federal University of Rio Grande, Rio Grande-RS, Brazil. Twenty-eight patients were randomly allocated prednisolone (1 mg/kg/day for 5 days) plus standard care, and 24 patients allocated standard care alone. The primary endpoint was the prevalence of post-bronchiolitis wheezing at 1, 3, 6 and 12 months after hospital discharge. The secondary endpoints were: length of hospital stay, duration of oxygen therapy and time to clinical improvement during the hospitalization. RESULTS: There were no significant differences between the prednisolone and control group in the prevalence of post-bronchioltis wheezing at 1 month (73.1 vs 83.3%, P = 0.5), 3 months (73.1 vs 79.2%, P = 0.7), 6 months (65.4 vs 66.7%, P = 0.9) and 12 months (50.0 vs 58.3%, P = 0.5) after hospital discharge. No reduction was observed in the prednisolone group, compared with the control group, in terms of length of hospital stay (6.0 vs 5.0 days, P = 0.7), duration of oxygen therapy (24.0 vs 24.0 h, P = 0.4) and time to clinical resolution (4.0 vs 4.0 days, P = 0.8). CONCLUSIONS: Prednisolone has no significant effect on reducing the prevalence of post-bronchiolitis wheezing and on improving the acute course of illness in hospitalized infants with bronchiolitis.

Acute Disease↗
PubMed2001

A comparison of nested polymerase chain reaction and immunofluorescence for the diagnosis of respiratory infections in children with bronchiolitis, and the implications for a cohorting strategy.

Cohorting bronchiolitis patients infected with respiratory syncytial virus (RSV) and/or influenza viruses is paramount in preventing cross-infection of these viruses in hospital. Nested polymerase chain reaction (nPCR) was compared with immunofluorescence (IF) for the detection of RSV subtypes A and B in children with suspected bronchiolitis. Co-infection with influenza A(H3N2), Chlamydia spp. and picornavirus/rhinovirus was also investigated using molecular techniques.A total of 50 nasopharyngeal secretions collected from babies admitted with bronchiolitis in the month of January 2000, comprising IF RSV positive (N= 27) and RSV negative (N= 23) specimens, were tested for both RSV subtypes, influenza A(H3N2), Chlamydia spp. and picornavirus/rhinovirus by nPCR. Nested PCR detected 28 specimens positive for RSV (RSV A = 20, RSV B = 8), which was two more than detected by IF. Influenza A(H3N2) was detected in three specimens, Chlamydia trachomatis in one, and picornavirus in 11, of which nine were confirmed to be rhinovirus by nPCR. Dual infection was detected in five cases using nPCR. Nested PCR proved useful in detecting RSV and influenza A(H3N2) infections missed by IF, and also other respiratory tract pathogens not routinely investigated. The clinical implications and risk of cross-infection with potentially virulent viruses due to inaccurate results from insensitive techniques, highlights the need for molecular assays such as nPCR to be employed as a routine method of investigation, provided as part of the laboratory service. Cohorting of patients with clinical bronchiolitis should continue, whilst awaiting laboratory confirmation.

Bronchiolitis↗
PubMed2000

Feeding efficiency and respiratory integration in infants with acute viral bronchiolitis.

OBJECTIVE: To examine the effects of bronchiolitis on feeding efficiency and respiratory integration. STUDY DESIGN: We studied 21 infants with bronchiolitis and 21 bottle-fed healthy infants who formed a comparison group. Repeat evaluations of half the bronchiolitis group were performed during recovery. During each feeding study we measured the duration and frequency of sucking, the frequency of single and multiple swallows, the respiratory rate, the postswallow respiratory direction, and the suck and swallow volumes. RESULTS: The infants with bronchiolitis devoted significantly less time to sucking than their healthy peers (P <.05), and the mean suck volume was reduced. Although the frequency of swallowing was slightly higher, the volume of milk consumed per swallow was almost half the amount consumed by the comparison group (P <.01). Coordination of breathing with swallowing was also less effective (P <.01). CONCLUSION: Although most aspects of feeding are less efficient during periods of respiratory illness, others are preserved or recover rapidly. Coordination of breathing during feeding is also significantly impaired.

Acute Disease↗
PubMed2001

Macrophage inflammatory protein-1alpha (not T helper type 2 cytokines) is associated with severe forms of respiratory syncytial virus bronchiolitis.

It has been suggested that the pathogenesis of respiratory syncytial virus (RSV) infection is related to the development of T helper (Th) type 2 cytokine responses. The presence of Th1 and Th2 cytokines and the chemokines macrophage inflammatory protein (MIP)-1alpha and monocyte chemotactic protein (MCP)-1 were assessed by ELISA in nasopharyngeal secretions of infants with RSV infection. Infants with mild bronchiolitis had increased Th1 cytokines and reduced Th2 cytokines, compared with infants with upper respiratory tract illness alone. Severe bronchiolitis was characterized by a more balanced Th1-Th2 response that did not differ from that of infants with upper respiratory tract illness alone. In contrast, MIP-1alpha was markedly increased in infants with severe bronchiolitis. MIP-1alpha and MCP-1 levels also were inversely related to oxygen saturation (P<.005). Thus, the severity of RSV bronchiolitis appears to be related more to chemokine release than to Th2 cytokine production.

Bronchiolitis↗
PubMed2003

Variants of the chemokine receptor CCR5 are associated with severe bronchiolitis caused by respiratory syncytial virus.

Respiratory syncytial virus (RSV) bronchiolitis is characterized by intense inflammation of the airways, and high levels of proinflammatory cytokines and chemokines can be found in respiratory secretions of affected infants. Important among these chemokines are RANTES (regulated on activation, normal T cell-expressed and -secreted) and macrophage inflammatory-protein alpha, MIP-1alpha, both of which show correlation with severe RSV bronchiolitis. It is not clear whether high levels of these chemokines are important in disease pathogenesis, and this study addresses this question by studying genetic variants of their major receptor, CC chemokine receptor 5. Results from both a case-control and family-based genetic-association analysis show that the -2459G and -2554T variants are associated with severe RSV bronchiolitis (P=.01). It is proposed that these CCR5 variants influence the inflammatory response, and these data provide further evidence of the important role that host genetic variability plays in the determination of disease severity in RSV bronchiolitis.

Bronchiolitis, Viral↗
PubMed2002

Aerosols in bronchiolitis.

Bronchiolitis is a common illness of the lower respiratory tract affecting infants that has considerable short and long-term morbidity and occasional mortality. It is the commonest cause of hospitalization for respiratory infection in early childhood, and the seasonal nature of the illness places considerable strain on health care resources during the bronchiolitis season. The youngest infants and those with preexisting cardiorespiratory disease are particularly at risk of severe illness. The treatment of infants with bronchiolitis is largely supportive. There are no therapies that have been proven to reduce the length of the hospitalization or intensive care stay. This paper will review the clinical course of bronchiolitis and discuss the aerosolized therapies that have been proposed for its treatment.

Administration, Inhalation↗
PubMed2006

Effects of subchronic and chronic exposure to ambient air pollutants on infant bronchiolitis.

Ambient air pollutant exposure has been linked to childhood respiratory disease, but infants have received little study. The authors tested the hypotheses that subchronic and chronic exposure to fine particulate matter (particulate matter < or = 2.5 microm in aerodynamic diameter (PM2.5)), nitrogen dioxide, carbon monoxide, and ozone increases risk of severe infant bronchiolitis requiring hospitalization. Study subjects were derived from linked birth-hospital-discharge records of infants born in 1995-2000 in the South Coast Air Basin of California. Cases with a hospital discharge for bronchiolitis in infancy were matched to 10 age- and gestational-age-matched controls. Exposures in the month prior to hospitalization (subchronic) and mean lifetime exposure (chronic) referenced to the case diagnosis date were assessed on the basis of data derived from the California Air Resources Board. In conditional logistic regression, only subchronic and chronic PM2.5 exposures were associated with increased risk of bronchiolitis hospitalization after adjustment for confounders (per 10-microg/m3 increase, adjusted odds ratio = 1.09 (95% confidence interval: 1.04, 1.14) for both). Ozone was associated with reduced risk in the single-pollutant model, but this relation did not persist in multipollutant models including PM2.5. These unique US data suggest that infant bronchiolitis may be added to the list of adverse effects of PM2.5 exposure.

Air Pollutants↗
PubMed1986

Is bronchiolitis in infancy an antecedent of chronic lung disease in adolescence and adulthood?

Acute bronchiolitis in infancy appears to be associated with persistence of wheezing or subsequent asthma in later life. Chest imaging techniques have demonstrated persistent structural lung damage such as atelectasis, bronchiectasis, and obliterative bronchiolitis among survivors of the more severe forms of bronchiolitis. In addition, in a significant number of survivors without demonstrable structural damage, pulmonary function studies have revealed a spectrum of disturbances including air-trapping, reduced air flow at low lung volumes, hypoxemia (all indicating disease in the small airways), and bronchial hyperreactivity. However, it has not yet been proven definitively whether the relationship between severe bronchiolitis in infancy and chronic obstructive lung disease is causal or noncausal. Further prospective clinical studies are needed to resolve this question.

Acute Disease↗
PubMed1989

Expression of MHC antigens in normal human lungs and transplanted lungs with obliterative bronchiolitis.

Immunocytochemical techniques have been used to investigate the expression of common determinants of class I, common determinants of class II and DR, DP, and DQ antigens on frozen sections from twenty normal donor lungs, three lungs resected due to carcinoma and nine lungs removed from heart/lung recipients who were undergoing retransplant due to obliterative bronchiolitis. In all lungs, alveolar macrophages expressed common determinants of class I and class II, as well as DR, DP and DQ antigens. In normal lung, class I was expressed on all vascular endothelium, all tracheal epithelium and most, but not all, bronchiolar epithelium. Class II was always expressed on tracheal epithelium, but expression on bronchiolar epithelium and vascular endothelium was variable and sometimes absent. In lungs from transplant patients with severe obliterative bronchiolitis, vascular endothelium, in addition to expressing class I, now consistently expressed class II. Epithelium from trachea, bronchioles, and alveoli also consistently expressed class I and class II. To conclude, there is enhanced expression of class II antigens on endothelial and epithelial cells from lungs with obliterative bronchiolitis.

Bronchi↗
PubMed1991

Risk factors for obliterative bronchiolitis in heart-lung transplant recipients.

Obliterative bronchiolitis is the major cause of death of long-term survivors of heart-lung transplantation. Of our first 75 patients who have received heart-lung transplantation, 38 have been followed for a year or longer. Eight patients developed clinical evidence of obliterative bronchiolitis within 15 months of transplantation, of whom four died with postmortem confirmation of extensive obliterative bronchiolitis, interstitial and pleural fibrosis, and vascular sclerosis in the heart and lungs. One further patient died before one year after chronic rejection. All nine patients had evidence on transbronchial biopsy of submucosal fibrosis and vascular sclerosis. Twelve of our remaining patients have shown similar areas of lung fibrosis on transbronchial biopsy, and the other eighteen are well and without fibrosis on transbronchial biopsy. Studies of the 274 biopsies obtained from 38 patients confirmed rejection on 182 occasions with more frequent, more persistent, and more severe rejection in the chronic rejection group than in the without-fibrosis or lung fibrosis groups. Opportunistic infection resulted in pneumonia on 19 occasions, and were most commonly found in lung fibrosis patients. We conclude that obliterative bronchiolitis is the likely outcome in patients with early, poorly controlled, severe rejection.

Adult↗
PubMed2004

An artificial neural network ensemble to predict disposition and length of stay in children presenting with bronchiolitis.

BACKGROUND: Artificial neural networks apply complex non-linear functions to pattern recognition problems. An ensemble is a 'committee' of neural networks that usually outperforms single neural networks. Bronchiolitis is a common manifestation of viral lower respiratory tract infection in infants and toddlers. OBJECTIVE: To train artificial neural network ensembles to predict the disposition and length of stay in children presenting to the Emergency Department with bronchiolitis. METHODS: A specifically constructed database of 119 episodes of bronchiolitis was used to train, validate, and test a neural network ensemble. We used EasyNN 7.0 on a 200 Mhz pentium PC with a maths co-processor. The ensemble of neural networks constructed was subjected to fivefold validation. Comparison with actual and predicted dispositions was measured using the kappa statistic for disposition and the Kaplan-Meier estimations and log rank test for predictions of length of stay. RESULTS: The neural network ensembles correctly predicted disposition in 81% (range 75-90%) of test cases. When compared with actual disposition the neural network performed similarly to a logistic regression model and significantly better than various 'dumb machine' strategies with which we compared it. The prediction of length of stay was poorer, 65% (range 60-80%), but the difference between observed and predicted lengths of stay were not significantly different. CONCLUSION: Artificial neural network ensembles can predict disposition for infants and toddlers with bronchiolitis; however, the prediction of length of hospital stay is not as good.

Bronchiolitis↗
PubMed2004

A validated clinical model to predict the need for admission and length of stay in children with acute bronchiolitis.

OBJECTIVE: To develop and validate a logistic regression model to predict need for admission and length of hospital stay in children presenting to the Emergency Department with bronchiolitis. SETTING: Two children's hospitals in Dublin, Ireland. METHODS: We reviewed 118 episodes of bronchiolitis in 99 children admitted from the Emergency Department. Those discharged within 24 h by a consultant/attending paediatrician were retrospectively categorized as suitable for discharge. We then validated the model using a cohort of 182 affected infants from another paediatric Emergency Department in a bronchiolitis season 2 years later. In the validation phase actual admission, failed discharge, and age less than 2 months defined the need for admission. RESULTS: The model predicted admission with 91% sensitivity and 83% specificity in the validation cohort. Age [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.76-0.97], dehydration (OR 2.54, 95% CI 1.34-4.82), increased work of breathing (OR 3.39, 95% CI 1.29-8.92) and initial heart rate above the 97th centile (OR 3.78, 95% CI 1.05-13.57) predicted the need for admission and a longer hospital stay. CONCLUSION: We derived and validated a severity of illness model for bronchiolitis. This can be used for outcome prediction in decision support tools or severity of illness stratification in research/audit.

Acute Disease↗
PubMed1998

Constrictive (obliterative) bronchiolitis.

Constrictive bronchiolitis (CB), also termed in lung transplant patients obliterative bronchiolitis, is inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles with resultant narrowing of their lumens. CB is found in a variety of settings, most often as a complication of lung and heart-lung transplantation (affecting 34% to 39% of patients, usually in the first 2 years after transplantation) and bone marrow transplantation, but also in rheumatoid arthritis, after inhalation of toxic agents such as nitrogen dioxide, after ingestion of certain drugs such as penicillamine and ingestion of the East Asian vegetable Sauropus androgynous, and as a rare complication of adenovirus, influenza type A, measles, and Mycoplasma pneumoniae infections in children. In lung transplants, CB is the single most important factor leading to death thereafter. In one study, the overall mortality rate was 25%. However, at the same time, 87% of patients who were asymptomatic and diagnosed solely by transbronchial biopsy had resolution or stabilization of disease. Decreases in FEV1 from baseline can be used to clinically support CB in transplant patients; the term bronchiolitis obliterans syndrome is used to denote this clinical dysfunction, and a grading system has been established for it that is now widely used in the literature. Significant risk factors for the development of CB in lung transplants include alloantigen-dependent and -independent mechanisms. In the former group are late acute rejection and HLA mismatches at the A loci; in the latter are ischemia/reperfusion injuries to airways that result from the transplantation surgery and cytomegalovirus infection.

Biopsy↗
PubMed2003

Erythropoietin therapy in children with bronchiolitis and anemia.

OBJECTIVE: Critically ill children with bronchiolitis often require red blood cell transfusions. Anemia normally results in increased circulating erythropoietin concentrations; however, critical illness has been associated with a blunted erythropoietin response. Treatment with erythropoietin decreases the need for red blood cell transfusion in several disease states. We hypothesized that critically ill children with bronchiolitis and anemia would have a circulating erythropoietin deficiency and that treatment with exogenous erythropoietin would increase reticulocyte count and hematocrit and reduce red blood cell transfusion requirements. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Children's hospital. PATIENTS: Critically ill children with bronchiolitis, anemia, and respiratory failure. Anemia was defined as a hematocrit >2 SD below normal for age. INTERVENTION: Patients were randomized to one of two groups. In the erythropoietin group, patients received daily intravenous erythropoietin. In the control group, patients received daily intravenous placebo. Both groups were treated with elemental iron. MEASUREMENTS AND MAIN RESULTS: Blood for complete blood count, reticulocyte count, and ferritin and erythropoietin concentration was obtained at admission and discharge. Red blood cell transfusions were administered to patients with a persistent oxygen requirement and a hematocrit of <25%. Outcome variables included number of red blood cell transfusions, change in reticulocyte count, ferritin values, and circulating erythropoietin values between groups. Forty-four patients completed the study (mean 3.1 +/- 0.6 months), with a baseline hematocrit of 27.6 +/- 0.5%, ventilator days of 8.2 +/- 0.6, and pediatric intensive care unit length of stay of 9.8 +/- 0.6 days. There were no significant baseline demographic differences between the control and erythropoietin groups. Ten of 22 (45%) children in the erythropoietin group required red blood cell transfusion compared with 11 of 22 (50%) in the control group (p = nonsignificant). The increase in reticulocyte count was greater in the erythropoietin group compared with the control group (2.1 +/- 0.3% to 4.7 +/- 0.7%, p = .003 vs. 2.1 +/- 0.3% to 2.7 +/- 0.5%, p = nonsignificant). CONCLUSIONS: Despite a favorable reticulocyte and circulating erythropoietin response, red blood cell transfusion requirements were not significantly diminished by erythropoietin treatment in children with bronchiolitis and respiratory failure. Erythropoietin cannot be routinely recommended for this patient population.

Anemia↗
PubMed2003

Utility of sepsis evaluation in infants 90 days of age or younger with fever and clinical bronchiolitis.

OBJECTIVE: To identify the clinical utility of obtaining blood, urine and cerebrospinal fluid for bacterial culture among febrile infants <90 days of age with clinical bronchiolitis. DESIGN: Retrospective chart review from 1995 to 2000. SETTING: Urban emergency department of a tertiary children's hospital. PARTICIPANTS: All infants <90 days of age presenting with fever and clinical bronchiolitis. MAIN OUTCOME MEASURES: Result of the cultures of blood, urine and cerebrospinal fluid. RESULTS: Of 3051 (11%) febrile infants, 329 met criteria for clinical bronchiolitis. Blood for culture was obtained from 309 (94%), urine for culture was obtained from 273 (83%) and cerebrospinal fluid for culture was obtained from 200 (61%). One hundred eighty-seven (57%) infants had all 3 specimens sent for culture. No cases of bacteremia [0%; 95% confidence interval (CI), 0, 1.1%] or meningitis (0%; 95% CI 0, 1.8%) occurred among these infants. However, 6 infants (2%; 95% CI 0.8, 5.7%), all male, had a culture of urine consistent with infection (4 Escherichia coli, 1 Staphylococcus aureus, 1 viridans streptococci). CONCLUSION: The risk of bacteremia or meningitis among infants <90 days with fever and bronchiolitis is low in this age group. The risk of urinary tract infection in this age group is also low, but not negligible, at 2%.

Anti-Bacterial Agents↗
PubMed2006

The interrater reliability of a validated bronchiolitis severity assessment tool.

BACKGROUND: We previously constructed and tested a bronchiolitis severity assessment tool in 2 independent hospitals. The model uses age, work of breathing, dehydration and tachycardia to successfully predict disease severity. OBJECTIVE: To prospectively measure the interrater reliability of a bronchiolitis severity assessment tool and of its component variables. DESIGN: Prospective observational survey. SETTING: A county teaching hospital emergency department serving a mixed urban and rural population with an emergency medicine residency program in 2-3-4 format. SUBJECTS: Thirty-two physicians evaluated a convenience sample of children aged less than 18 months presenting to the emergency department with a clinical diagnosis of bronchiolitis during a single season. METHODS: Two physicians independently examined each patient. Each physician completed a physical examination template that included the variables used in the severity assessment tool. Interrater agreement was measured for the variables work of breathing and dehydration and for the tool as a whole using a weighted kappa statistic. RESULTS: One hundred and forty-six cases were enrolled. Twenty-five were dropped for incomplete data collection. The actual weighted agreement on overall classification was 92%; expected, 73%, kappa = 0.676; P < 0.0001. The actual weighted agreement for dehydration was at 95%; expected, 92%, kappa = 0.305; P = 0.0001. The agreement for work of breathing was 95%; expected, 86%; kappa = 0.611; P < 0.0001. The overall model showed better interrater reliability than its individual components. CONCLUSIONS: Overall interrater reliability for this bronchiolitis severity assessment tool is substantial.

Bronchiolitis↗