Pediatric Investigators Collaborative Network on Infections in Canada Study of Respiratory Syncytial Virus-associated Deaths in Pediatric Patients in Canada, 2003-2013.

Background: Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are <0.5%, but up to 37% in patients with underlying medical conditions. The objective of this study was to characterize factors associated with deaths among children hospitalized with RSV infection in Canadian pediatric centers. Methods: A retrospective case series of children aged ≤18 years with RSV-associated deaths at centers affiliated with the Pediatric Investigators Collaborative Network on Infections in Canada from 2003­2013, inclusive, was performed [corrected]. Cases were identified using RSV-specific International Classification of Diseases codes to capture deaths where a diagnosis of RSV infection was present. Results: Eleven centers reported 79 RSV-associated deaths. RSV was regarded as primarily responsible for death in 32 cases (40.5%). Median age at death was 11 months (range, <1 month to 16 years). Thirty-nine patients (49.4%) were male. Fourteen patients (17.7%) had no known risk factors for severe RSV infection. Healthcare-associated RSV infections (HAIs) accounted for 29 deaths (36.7%), with RSV judged to be the primary cause of death in 9 of these cases. Conclusions: RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs.

'Rational use of high-flow therapy in infants with bronchiolitis. What do the latest trials tell us?' A Paediatric Research in Emergency Departments International Collaborative perspective.

Bronchiolitis is the most common reason for infants to be hospitalised. Over the past decade, the use of high-flow nasal cannulae (HFNC) therapy has increased markedly and it is now utilised not only in the intensive care unit setting but in general paediatric wards and emergency departments. The aim of this systematic review was to summarise and critique the current evidence-base for the use of HFNC in infants with bronchiolitis. We searched Ovid Medline, OvidEmbase, PubMed, Cinahl, Cochrane Library, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials for systematic reviews and randomised controlled trials of HFNC therapy in infants with bronchiolitis from 1 January 2000 to 27 June 2018. We identified four randomised controlled trials (n = 1891) of HFNC in infants with bronchiolitis: three of these studies involved infants treated in emergency departments and inpatient paediatric wards in Spain, Australia and New Zealand, and one study involved infants treated in paediatric intensive care units in France. The findings of this review suggest that HFNC should be used as a rescue treatment for hypoxaemic infants who have not responded to standard sub nasal oxygen therapy. The use of HFNC for work of breathing in the absence of hypoxaemia, and severe disease, is not currently supported by the evidence, and should only be considered in the context of an appropriate research trial.

Predictors of Critical Care and Mortality in Bronchiolitis after Emergency Department Discharge.

OBJECTIVES: To identify the epidemiologic predictors and stratify the risk of critical care unit (CCU) admission or death in bronchiolitis following emergency department discharge. This information has not yet been explored. STUDY DESIGN: A population-based cohort study using Ontario-wide demographic and healthcare databases linked at the individual level. We assessed all infants with bronchiolitis discharged home from all emergency departments in Ontario, Canada, 2003-2014. Targeted information included plausible demographic and clinical predictors of CCU admission/death within 14 days of emergency department discharge. Using multivariable logistic regression analyses, we identified independent predictors of this outcome and stratified the outcome risk by the type of multivariable predictor. RESULTS: Of 34 270 study infants, 102 (0.3%) were admitted to CCU or died after discharge. Predictors of CCU admission/death were: comorbidities (OR 5.33; 95% CI 2.82-10.10), younger age [months] (OR 1.47; 95%CI 1.33-1.61), low income (OR 1.53; 95% CI 1.01-2.34), younger gestational age [weeks] (OR 1.14; 95%CI 1.06-1.22), and emergent presentation (Canadian Triage and Acuity Scale 2) at the index visit (OR 1.55, 95% CI 1.03-2.33). The absolute event risk of CCU admission/death in infants with versus without comorbidities were 1.5% versus 0.26%, respectively (P < .001). The odds of these outcomes in infants with comorbidities plus ≥2 other predictors were 25 times higher than in infants without predictors (OR 25.1, 95% CI 11.4-55.3). CONCLUSIONS: Infants with comorbidities plus other predictors discharged from the emergency department with bronchiolitis are at considerable risk of subsequent CCU admission and death. These risk factors should augment current clinical and social considerations determining patient disposition.

Characteristics of children admitted to intensive care with acute bronchiolitis.

To assess factors associated with outcome in children admitted to paediatric intensive care (PIC) with bronchiolitis. A retrospective study of children admitted to the PICU at St Mary's Hospital, London with bronchiolitis over a 6-year period (2011-2016). All bronchiolitis admissions < 2 years were included. Data collected particularly noted risk factors for severity, demographics, microbiology and outcome. We compared respiratory syncytial virus (RSV) with non-RSV status. Multivariate analysis was performed. Two hundred seventy-four patients were identified. Median age was 60 days (IQR 28-150 days), 63% were male, 90% were invasively ventilated and 42% were previously healthy. Pre-existing co-morbidities were present in 38%. The most frequently isolated pathogens were RSV (60%) and rhinovirus (26%). Co-infection was present in 45%, most commonly with RSV, rhinovirus and bacterial pathogens. Median length of stay (LOS) was 6 days (IQR 4.75-10). Younger age, prematurity, RSV, co-infection and co-morbidity were identified as significant risk factors for prolonged LOS. Six children died. Five of these had documented co-morbidities. CONCLUSION: RSV causes more severe bronchiolitis than other viruses. Nearly half of children admitted to PICU with RSV were previously healthy. Current guidelines for immunoprophylaxis of RSV bronchiolitis should be re-considered. What is Known: • Bronchiolitis is one of the most common reasons for unplanned PICU admission. The most common virus causing bronchiolitis is RSV • Bronchiolitis severe enough to require admission to PICU is associated with frequent morbidity but has low mortality. What is New: • RSV causes more severe bronchiolitis than other viruses. • Nearly half of all children admitted to PICU with RSV were previously healthy.

Antibiotics for bronchiolitis in children under two years of age.

BACKGROUND: Bronchiolitis is a serious, potentially life-threatening respiratory illness commonly affecting babies. It is often caused by respiratory syncytial virus (RSV). Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia or respiratory failure. Nevertheless, they are often used. OBJECTIVES: To evaluate the effectiveness of antibiotics for bronchiolitis in children under two years of age compared to placebo or other interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 6), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register, and the Database of Abstracts of Reviews of Effects, MEDLINE (1966 to June 2014), EMBASE (1990 to June 2014) and Current Contents (2001 to June 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics to placebo in children under two years diagnosed with bronchiolitis, using clinical criteria (including respiratory distress preceded by coryzal symptoms with or without fever). Primary clinical outcomes included time to resolution of signs or symptoms (pulmonary markers included respiratory distress, wheeze, crepitations, oxygen saturation and fever). Secondary outcomes included hospital admissions, length of hospital stay, readmissions, complications or adverse events and radiological findings. DATA COLLECTION AND ANALYSIS: Two review authors independently analysed the search results. MAIN RESULTS: We included seven studies with a total of 824 participants. The results of these seven included studies were often heterogeneous, which generally precluded meta-analysis, except for deaths, length of supplemental oxygen use and length of hospital admission.In this update, we included two new studies (281 participants), both comparing azithromycin with placebo. They found no significant difference for length of hospital stay, duration of oxygen requirement and readmission. These results were similar to an older study (52 participants) that demonstrated no significant difference comparing ampicillin and placebo for length of illness.One small study (21 participants) with higher risk of bias randomised children with proven RSV infection to clarithromycin or placebo and found a trend towards a reduction in hospital readmission with clarithromycin.The three studies providing adequate data for days of supplementary oxygen showed no difference between antibiotics and placebo (pooled mean difference (MD) (days) -0.20; 95% confidence interval (CI) -0.72 to 0.33). The three studies providing adequate data for length of hospital stay, similarly showed no difference between antibiotics (azithromycin) and placebo (pooled MD (days) -0.58; 95% CI -1.18 to 0.02).Two studies randomised children to intravenous ampicillin, oral erythromycin and control and found no difference for most symptom measures.There were no deaths reported in any of the arms of the seven included studies. No other adverse effects were reported. AUTHORS' CONCLUSIONS: This review did not find sufficient evidence to support the use of antibiotics for bronchiolitis, although research may be justified to identify a subgroup of patients who may benefit from antibiotics. Further research may be better focused on determining the reasons that clinicians use antibiotics so readily for bronchiolitis, how to reduce their use and how to reduce clinician anxiety about not using antibiotics.

Clinical outcomes of children with acute asthma and pneumonia in Mulago hospital, Uganda: a prospective study.

BACKGROUND: Little attention has been paid to asthma in 'under-fives' in Sub-Saharan Africa. In 'under-fives', acute asthma and pneumonia have similar clinical presentation and most children with acute respiratory symptoms are diagnosed with pneumonia according to the WHO criteria. The mortality associated with acute respiratory diseases in Uganda is high but improving, dropping from 24% in 2004 to 11.9% in 2012. We describe the immediate clinical outcomes of children with acute asthma and pneumonia and document the factors associated with prolonged hospitalization and mortality. METHODS: We enrolled 614 children aged 2 to 59 months with acute respiratory symptoms presenting at the emergency paediatric unit of Mulago hospital. Clinical histories, physical examination, blood and radiological tests were done. Children with asthma and bronchiolitis were collectively referred to as 'Asthma syndrome'. Hospitalized children were monitored every 12 hours for a maximum of 7 days. Survival analysis was done to compare outcome of children with asthma and pneumonia. Cox regression analysis was done to determine factors associated with prolonged hospitalization and mortality. RESULTS: Overall mortality was 3.6%. The highest case fatality was due to pneumocystis jirovecii pneumonia (2/4) and pulmonary tuberculosis (2/7). None of the children with asthma syndrome died. Children with 'asthma syndrome' had a significantly shorter hospital stay compared to those with pneumonia (p<0.001). Factors independently associated with mortality included hypoxemia (HR = 10.7, 95% CI 1.4- 81.1) and severe malnutrition (HR = 5.7, 95% CI 2.1- 15.8). Factors independently associated with prolonged hospitalization among children with asthma syndrome included age less than 12 months (RR = 1.2, 95% CI 1.0-1.4), hypoxemia (RR = 1.4, 95% CI 1.2-1.7), and severe malnutrition (RR = 1.5 95% CI 1.3-1.8). Similar factors were associated with long duration of hospital stay among children with pneumonia. CONCLUSION: This study identified a sharp decline in acute respiratory mortality compared to the previous studies in Mulago hospital. This may be related to focus on and treatment of asthma in this study, and will be analysed in a later study. Bacterial pneumonia is still associated with high case fatality. Hypoxemia, severe malnutrition, and being an infant were associated with poor prognosis among children with acute asthma and pneumonia and need to be addressed in the management protocols.

Epidemiology of hospitalization for acute bronchiolitis in children: differences between RSV and non-RSV bronchiolitis.

We study the clinical, management and outcome differences between respiratory syncytial virus (RSV) positive and negative bronchiolitis. A retrospective review of the medical records of children ≤ 2 years of age with acute bronchiolitis between January 1995 and December 2006 was done. There were 2,384 patients hospitalized for acute bronchiolitis, and 1,495 (62.7%) were RSV infections. Overall, hospitalization rate was 55/1,000 admissions. Mortality occurred in 0.08% of cases. Bronchiolitis due to RSV was more frequent from November to March (97%). RSV bronchiolitis had longer hospital stays (6 vs. 5 days, P<0.0001), higher risk of intensive care unit (ICU) admission (OR 2.7; 95%CI 1.87-3.9) and more oxygen use (OR 2.2; 95%CI 1.8-2.6). Infants < 2 months had longer median hospital stay (6 vs. 5 days, P <0.0001) and higher risk of ICU admission (OR 3.4; 95%CI 2.5-4.6). Prematures of < 32 gestational weeks, congenital heart disease, and atelectasis/condensation were the main risk factors for ICU admission in both RSV and non-RSV bronchiolitis. The introduction of palivizumab in prematures diminished hospitalization for RSV bronchiolitis, oxygen need, length of hospital stay and mechanical ventilation. In conclusion, this study supports that RSV bronchiolitis seems to be a more severe disease than that caused by other viruses.

Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome.

The outcome and cause of death of each lung disease directly associated with rheumatoid arthritis (RA-LD) have been poorly investigated. A retrospective study was conducted of 144 patients with RA-LD, in whom the median follow-up period after the initial visit for a respiratory examination was 4.5 yrs. A total of 57 patients were identified with usual interstitial pneumonia (UIP), 31 with bronchiectasis, 16 with nonspecific interstitial pneumonia (NSIP), 11 with bronchiolitis, five with organising pneumonia (OP), five with diffuse alveolar damage (DAD) and 19 with combined disease. The 5-yr survival rates were 36.6% in the UIP group, 87.1% in the bronchiectasis group, 93.8% in the NSIP group, 88.9% in the bronchiolitis group, 60.0% in the OP group and 20.0% in the DAD group. Survival of patients with DAD was worse than that of patients with UIP. Overall, survival of patients with UIP was worse than that of patients with bronchiectasis, NSIP or bronchiolitis. Of the 144 patients, 71 (49.3%) died, of whom 58 (81.7%) died due to respiratory lesions. Of patients with RA-LD, patients with DAD experienced the highest mortality, and the survival of patients with UIP was worse than that of patients with NSIP.

Associations between mortality and prolonged exposure to elevated particulate matter concentrations in East Asia.

Previous epidemiological studies regarding mortality and particulate matter with an aerodynamic diameter of <10µm (PM10) have considered only absolute concentrations of PM10 as a risk factor. However, none have evaluated the durational effect of multi-day periods with high PM10 concentrations. To evaluate the durational effect (i.e., number of days) of high PM10 concentrations on mortality, we collected data regarding 3,662,749 deaths from 28 cities in Japan, South Korea, and China (1993-2009). Exposure was defined as consecutive days with daily PM10 concentrations ≥75µg/m3. A Poisson model was used with duration as the variable of interest, while controlling for daily PM10 concentrations, meteorological variables, seasonal trends, and day of the week. The increase in mortality risk for each additional consecutive day with PM10 concentrations ≥75µg/m3 was 0.68% in Japan (95% confidence interval [CI]: 0.35-1.01%), 0.48% in South Korea (95% CI: 0.30-0.66%), and 0.24% in China (95% CI: 0.14-0.33%). The annual average maximum number of consecutive days with high PM10 in Japan (2.40days), South Korea (6.96days), and China (42.26days) was associated with non-accidental death increases of 1.64% (95% CI: 1.31-1.98%), 3.37% (95% CI: 3.19-3.56%), and 10.43% (95% CI: 10.33-10.54%), respectively. These findings may facilitate the planning of public health interventions to minimize the health burden of air pollution.

The role of mean platelet volume in the early detection of acute bronchiolitis: A prospective study.

INTRODUCTION AND OBJECTIVE: Acute bronchiolitis might be associated with morbidity and mortality in infants. The aim of this study was to evaluate the role of mean platelet volume (MPV) in the prediction of acute bronchiolitis. METHOD: One hundred and eighty-four of these infants were diagnosed with acute bronchiolitis and 100 were healthy children. The ability of MPV, C-reactive protein (CRP), white blood cell (WBC) count, and lymphocyte values to predict all bronchiolitis groups and the control group was examined by receiver operating characteristic (ROC) curve and their respective areas under the curves (AUC) with 95% confidence intervals. RESULTS: Patients with acute bronchiolitis had higher MPVs than their healthy counterparts (P < 0.001). However, there was no difference statistically significant in MPVs among all bronchiolitis groups (P = 0.239). ROC curve analysis suggested that MPV level cut-off point for making the prediction of acute bronchiolitis was 6.0 fL, with a sensitivity and specificity of 90% and 28%, respectively. Our results clearly indicated that AUCs for the MPV, CRP, WBC, and lymphocyte were statistically significant for bronchiolitis groups versus the control group. However, AUC values for MPV were the lowest. CONCLUSIONS: These findings suggest that the MPV might be a predictive value for the diagnosis of acute bronchiolitis. However, the predictive capacity of the CRP is better than that of others. Observational studies with a larger group to evaluate the clinical significance of MPV are necessary to predict acute bronchiolitis.

Respiratory bronchiolitis-interstitial lung disease: long-term outcome.

BACKGROUND: The clinical and physiologic features of respiratory bronchiolitis (RB)-interstitial lung disease (ILD) have been previously described; however, the natural history and outcome have not been systematically evaluated. The majority of published reports consider RB-ILD to be a nonprogressive ILD that clinically improves with smoking cessation and antiinflammatory treatment. In this study, we sought to determine the outcome of RB-ILD patients with and without smoking cessation and with and without corticosteroid therapy. METHODS: Thirty-two RB-ILD cases confirmed by surgical lung biopsy were identified from a prospectively enrolled cohort of subjects with ILD. Initial and follow-up data on symptoms, physiology, treatment, and outcome were collected and analyzed. RESULTS: Kaplan-Meier analysis revealed that at least 75% of RB-ILD patients survived > 7 years after diagnosis. Clinical improvement occurred in only 28% of cases, and physiologic improvement occurred in 10.5% of cases. One patient died of progressive ILD, and two patients died of non-small cell lung cancer. While physiologic improvement was limited to those who had ceased smoking, corticosteroids and/or other immunosuppressive therapy had little effect on symptoms or physiology. CONCLUSIONS: This study shows that prolonged survival is common in RB-ILD. However, symptomatic and physiologic improvement occurs in only a minority of patients, and neither smoking cessation nor immunosuppressive therapy is regularly associated with clinically significant benefit.

Are leukotriene inhibitors useful for bronchiolitis? / ¿Tienen utilidad los inhibidores de leucotrienos en bronquiolitis?

Bronchiolitis is a prevalent disease in children under two years of age, which carries significant morbidity and mortality. However, there is controversy regarding the optimal therapeutic management. Leukotriene inhibitors have been proposed as an alternative, although its efficacy is not clear yet. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified two systematic reviews comprising six trials addressing the question of this article. We extracted data, combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded leukotriene inhibitors might not decrease mortality levels on bronchiolitis patients and it is not clear whether they decrease length of hospital stay. They might reduce recurrent wheezing, but the certainty of the evidence is low, and they increase adverse effects.

Population-based Analysis of Bronchiolitis Epidemiology in Valencia, Spain.

BACKGROUND: There is a lack of European epidemiologic population-based studies on bronchiolitis and respiratory syncytial virus (RSV) bronchiolitis including both hospitalizations and primary care attendance. METHODS: A retrospective cohort of all children born between 2009 and 2012 was followed from birth to 2 years of age using population and health databases. We searched for global bronchiolitis (International Classification of Diseases, 9th revision, Clinical Modification codes 466.1, 466.11 and 466.19) and RSV bronchiolitis (code 466.11 and code 466.19 with positive RSV test) in the first appearance either in primary care or in hospitalization databases. A preterm subcohort (International Classification of Diseases, 9th revision, Clinical Modification codes 765) was also analyzed. RESULTS: The cohort consisted of 198,223 children of whom 41,479 were diagnosed of bronchiolitis (incidence rate 16.4/100 children <2 years per year). Of those, 5390 were hospitalized with the majority of hospitalizations occurring at <6 months of age (incidence rate of 5.2/100 children <6 months per year) and 3106 of the hospitalizations were RSV positive (incidence rate 3.2/100 children <6 months per year). RSV hospitalizations were 26% longer than non-RSV. In preterm infants, hospitalization incidence was more than double, and the mean length of hospitalization was 29% longer. CONCLUSIONS: Most (87%) bronchiolitis cases are managed in primary care offices. Approximately 2 out of every 10 children <2 are diagnosed of bronchiolitis, 3 out of every 100 are hospitalized and 1.6 out of every 100 are hospitalized with RSV bronchiolitis in our cohort. Infants between 2 and 10 weeks constitute a risk group for severe bronchiolitis.

Respiratory Syncytial Virus Bronchiolitis in Children up to 5 Years of Age in Spain: Epidemiology and Comorbidities: An Observational Study.

This epidemiological survey in Spain estimates the burden of respiratory syncytial virus (RSV) infection in children up to 5 year of age during a 15-year period (1997-2011). Observational retrospective survey was conducted by reviewing data of the National Surveillance System for Hospital Data, including >98% of Spanish hospitals. All hospitalizations related to RSV infection for children up to 5 years, reported during 1997-2011 period, were analyzed. Codes were selected by using the International Classification of Diseases 9th Clinical Modification 466.0-466.19, 480.1, and 079.6. A total of 326,175 and 286,007 hospital discharges for children up to 5 and 2 years of age were reported during the study period. The annual incidence was 1072 and 2413 patients per 100,000, respectively. The average length of hospital stay was 5.7 (standard deviation 8.2) days. Four hundred forty-six deaths were reported; of those, 403 occurred in children <2 years and 355 (80%) occurred in children <12 months of age. Hospitalization and mortality rates were significantly higher in boys and decrease significantly with age. The higher rate of hospitalization and mortality rates were found in the first year of life. Annual average cost for National Health Care System was € 47 M with a mean hospitalization cost of €2162. The average length of hospitalization and costs were significantly higher in high-risk children. RSV infections in children up to 5 year of age still pose a significant health threat in Spain, especially in the infants. The development of preventive, diagnostic, and therapeutic guidelines focused in children with comorbidities may help reduce the hospital and economic burden of the disease.

Immunomodulatory activity and effectiveness of macrolides in chronic airway disease.

The use of troleandomycin as adjunctive therapy for the treatment of patients with corticosteroid-dependent asthma first suggested an immunomodulatory effect of the macrolide antibiotics. This led to studies of the macrolides in other chronic airway diseases, such as diffuse panbronchiolitis (DPB), a disease occurring primarily in East Asia. The use of macrolides for the therapy of patients with DPB has led to dramatic improvements in pulmonary function and prolonged survival. Similar benefits have been documented in Japanese studies of bronchiectasis, chronic bronchitis, and sinobronchial syndrome. Clinical and pathologic similarities between DPB and cystic fibrosis (CF) led to the investigation of macrolides for the treatment of CF. Data now suggest that persons with CF will benefit from macrolide therapy. In vitro and in vivo studies suggest that macrolides may inhibit the pulmonary influx of neutrophils, inhibit the release of proinflammatory cytokines, protect the epithelium from bioactive phospholipids, and improve the transportability of airway secretions. The immunomodulatory effects of the macrolides also may be beneficial for the treatment of other chronic inflammatory conditions.

Risk factors for bronchiolitis-associated deaths among infants in the United States.

BACKGROUND: Risk factors for bronchiolitis deaths have not been described on a national level. We examined the epidemiology of and identified risk factors for bronchiolitis-associated deaths among infants in the United States. METHODS: Multiple cause-of-death and linked birth/infant death data for 1996 through 1998 were used to examine bronchiolitis-associated infant deaths. Risk factors were assessed by comparing infants who died with bronchiolitis and surviving infants. RESULTS: During 1996 through 1998 there were 229 bronchiolitis infant deaths, resulting in an average annual infant mortality rate of 2.0 per 100 000 live births. The majority (55%) of infant deaths occurred among infants ages 1 through 3 months. The bronchiolitis mortality rate was highest among infants weighing <1500 g at birth (VLBW) as compared with infants weighing 1500 to 2499 g (LBW) and > or =2500 g at birth (29.8, 6.4 and 1.3 per 100 000 live births, respectively). Sixty-three percent of bronchiolitis deaths were among infants weighing > or =2500 g. VLBW and LBW infants remained at an increased risk of dying with bronchiolitis after controlling for other risk factors. Other risk factors included increasing birth order, low 5-min Apgar score, young maternal age, unmarried mother and tobacco use during pregnancy. CONCLUSIONS: VLBW and LBW infants are at increased risk of dying with bronchiolitis, even when taking into account other risk factors. Although infants weighing <2500 g at birth are at increased risk for dying with bronchiolitis, the majority of bronchiolitis deaths occur among infants of normal birth weight.

Long-term results of lung volume reduction surgery.

OBJECTIVE: Lung volume reduction surgery (LVRS) is effective in the short and intermediate term for the improvement of pulmonary function and subjective symptoms in selected patients with advanced emphysema. The purpose of this study was to examine the long-term functional results of LVRS and to investigate which subgroups would benefit in terms of long-term survival. METHODS: All records of the patients who underwent LVRS between 1994 and, 1998 at our hospital were reviewed. RESULTS: Eighty-eight consecutive patients underwent LVRS during the period. There were 62 men and 26 women with an average age of 56.1 years (range 34-72 years). Eleven patients with alpha1-antitrypsin deficiency were included. The perioperative mortality rate (<90 days) was 2.3% (n=2). Total lung capacity (7.5+/-0.3 l) and residual volume (4.8+/-0.3 l) at 3 years remained lower than baseline (9.2+/-0.2 l, 6.5+/-0.2 l, each) (P<0.001). The mean forced expiratory volume in 1 s (FEV(1)) at 3 years (0.86+/-0.08 l) was higher than baseline (0.78+/-0.02 l), but the difference did not reach statistical significance. The FEV(1) of the patients with alpha1-antitrypsin deficiency and of those with respiratory bronchiolitis returned to baseline at one year after LVRS and showed further deterioration. Overall survival rate at 5 years was 71.0% with the mean length of follow-up of 54.2 months. The survival difference was statistically significant between patients with preoperative FEV(1) >or=28.5% and those with FEV(1)<28.5% (P=0.0152). CONCLUSIONS: The improvement of total lung capacity and residual volume persisted long after the operation. Patients with alpha1-antitrypsin deficiency and those with bronchiolitis showed early deterioration of the lung function. Patients with higher preoperative FEV(1) had a survival benefit. The favorable long-term survival might justify LVRS for the treatment of selected patients with severe emphysema.

Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and meta-analysis.

BACKGROUND: Viral bronchiolitis is the leading cause of respiratory failure among infants in the United States. Currently, the mainstay of treatment is supportive care. The effectiveness of treatments used for mechanically ventilated infants with bronchiolitis is unclear. OBJECTIVE: To evaluate the strength of the evidence supporting the use of currently available treatments for critically ill infants with bronchiolitis. DATA SOURCE: We searched PubMed, citations of relevant articles, personal files, and conference proceedings, and we contacted experts in the field. STUDY SELECTION: Randomized, controlled trials evaluating any therapy for bronchiolitis that included children in an intensive care unit. DATA EXTRACTION: Two reviewers independently extracted data and assessed methodologic quality. DATA SYNTHESIS: A total of 2,319 citations were screened, and 16 randomized, controlled trials were included. There were three trials of surfactant, three of ribavirin, three of immune globulin, three of systemic corticosteroids, and one each of vitamin A, interferon, erythropoietin, and heliox. A meta-analysis of the three surfactant studies showed a strong trend toward a decrease in duration of mechanical ventilation of 2.58 days (95% confidence interval, -5.34 to 0.18 days; p =.07) and a significant decrease of 3.3 intensive care unit days (95% confidence interval, -6.38 to -0.23 days; p =.04). A meta-analysis of the three systemic corticosteroid studies showed no overall effect on duration of mechanical ventilation when all three trials were combined (-0.62 day; 95% confidence interval, -2.78 to 1.53 days; p =.57). We identified one published meta-analysis of three ribavirin studies showing a significant decrease in ventilator days with ribavirin (-1.2 days; 95% confidence interval, -0.2 to -3.4 days; p =.2). CONCLUSIONS: Currently, there are no clearly effective interventions available to improve the outcome of critically ill infants with bronchiolitis. Surfactant seems to be a promising intervention, and corticosteroids or ribavirin may also be beneficial.

Diffuse panbronchiolitis complicated with thymoma: a report of 2 cases with literature review.

OBJECTIVE: Diffuse panbronchiolitis, a distinct clinical entity of unknown etiology, has been reported originally and primarily in Japanese and rarely in non-Japanese populations. Macrolide therapy is effective for this once dismal disease. Diffuse panbronchiolitis complicated with thymoma is uncommon; only 2 cases have been reported to date. The aims of this study were to describe the clinical profiles, assess the response to macrolide therapy, and to discuss the possible pathogenesis of diffuse panbronchiolitis in this setting. METHODS: The clinical profiles, macrolide therapy response of diffuse panbronchiolitis complicated with encapsulated thymoma in 2 histologically confirmed cases were described and discussed with the 2 cases reported in the literature: one complicated with encapsulated thymoma, another with invasive thymoma. RESULTS: Of the 2 cases, both had negative PPD skin testing and abnormal serum levels of various immunoglobulins, 1 had positive anti-nuclear antibody, but none had elevated cold hemagglutinin titers, and both had an excellent response to macrolide therapy. Of the 2 cases reported in the literature, both had negative PPD or tuberculin skin testing, 1 had severe hypogammaglobulinemia, 1 had elevated IgA, 1 had positive anti-DNA, 1 had elevated cold hemagglutinin titers, but both died of respiratory failure in spite of macrolide therapy in 1 case. CONCLUSIONS: Prognosis for diffuse panbronchiolitis complicated with thymoma may depend on the nature of the thymoma and on the disease course. Macrolide therapy is also effective if administered early in the disease course and if the thymoma is cured. Immunological factors may play an important role in the pathogenesis of diffuse panbronchiolitis in this setting.

Lower airway disease caused by respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants and young children. Most infections due to RSV are mild and do not require hospitalization. RSV causes both upper respiratory tract infections as well as lower respiratory tract infections. Infants with underlying disease states like bronchopulmonary dyslasia, congenital heart disease and prematurity appear more prone to develop severe infection and have a higher incidence of hospitalization. The exact pathogenesis of RSV is not well understood. The mortality associated with primary RSV infection in healthy children is estimated to be between .005% to .02%. In hospitalized children the mortality rate is estimated to be from 1% to 3%. Several treatment modalities in the form of bronchodilators, corticosteroids, ribavirin, intravenous immune gammaglobulin and antibiotics are available. Studies have failed to show the true beneficial effect of any of the above treatment modalities. Supportive care is only needed. The best treatment is the supportive care in the form of oxygen and fluids and close monitoring of the vital signs including oxygen saturation.