Severe Bronchiolitis Research Articles

Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze.

BackgroundInfants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro‐stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.MethodsWe obtained peripheral blood from 166 infants hospitalized with their first episode of RSV‐confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin‐10, interferon‐γ, tumor necrosis factor‐α (TNF‐α), IL‐4, and IL‐5 production by in vitro anti‐CD3/CD28‐ and anti‐CD3/CD46‐activated CD4+ T cells, and percentage of peripheral Treg (CD4+CD25hiFoxp3hi) cells were measured by flow cytometry. Wheezing was assessed every 6 months. Recurrent wheezing was defined as three or more episodes following the initial RSV bronchiolitis.ResultsSixty‐seven percent (n = 111) of children had wheezing after their initial RSV infection, with 30% having recurrent wheezing. The percentage of peripheral Treg (CD4+CD25hiFoxp3hi) cells was not significantly different between the wheezing groups. Decreased TNF‐α production from anti‐CD3/CD28− and anti‐CD3/CD46− activated CD4+ T cells was observed in the recurrent wheezers, compared with nonwheezers (p = .048 and .03, respectively). There were no significant differences in the GZB+ CD4+ T cells and production of other inflammatory cytokines between these groups.ConclusionsWe demonstrated lower TNF‐α production by in vitro stimulated CD4+ T cells during severe RSV bronchiolitis in children that subsequently developed recurrent wheezing, compared with children with no subsequent wheeze. These findings support the role of CD4+ T cell immunity in the development of subsequent wheezing in these children.

A Polymorphism in the Catalase Gene Promoter Confers Protection against Severe RSV Bronchiolitis.

Respiratory syncytial virus (RSV) infection is associated with oxidative lung injury, decreased levels of antioxidant enzymes (AOEs), and the degradation of the transcription factor NF-E2-related factor 2 (NRF2), a master regulator of AOE expression. Single nucleotide polymorphisms (SNPs) in AOE and NRF2 genes have been associated with various lung disorders. To test whether specific NRF2 and/or AOE gene SNPs in children with RSV lower respiratory tract infection were associated with disease severity, one hundred and forty one children <24 month of age with bronchiolitis were assessed for seven AOE and two NRF2 SNPs, and data were correlated with disease severity, which was determined by need of oxygen supplementation and intensive care support. One SNP in the promoter region of the catalase gene, rs1001179, which is associated with higher enzyme expression, was significantly underrepresented (p = 0.01, OR 0.38) among patients with moderate to severe RSV bronchiolitis, suggesting a protective effect against disease severity. Our results suggest that increasing catalase expression/activity could exert a protective role in the context of RSV infection and represent a potential novel therapeutic target to ameliorate viral-induced lung disease.

Acute bronchiolitis in children

Bronchiolitis is the most common respiratory disease in children below 2 years of age. Primarily, the disease is caused by viral infection (respiratory syncytial virus), mainly in the month from November to April. Climate and environment both influence the season and severity of bronchiolitis. Forty percent infants are affected in 1st year of life. Diagnosis of the bronchiolitis is mainly clinical though various definitions have been suggested by different groups. Laboratory investigations including reverse transcription polymerase chain reaction, chest X-ray, and others do not contribute in diagnosing the disease. There is no effective treatment available and mortality is also low with bronchiolitis.

Konvansiyonel Tedaviye Cevapsız Ağır Akut Bronşiyolitli İnfantlarda “Yüksek Akımlı Nazal Oksijen” Tedavisinin Vital Bulgular Üzerine Etkisi

Konvansiyonel Tedaviye Cevapsız Ağır Akut Bronşiyolitli İnfantlarda “Yüksek Akımlı Nazal Oksijen” Tedavisinin Vital Bulgular Üzerine Etkisi

Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the most common viral pathogens. It is especially dangerous for newborns and young children. In some cases it could lead to severe bronchiolitis, pneumonia with hospitalization or even a lethal outcome. Despite decades of investigation of RSV biology, effective and safe therapeutics are still under development. Certain natural peptides have been found to exhibit antiviral activity against respiratory viruses, but their implementation is limited by low stability in biological media. One of the current approaches to enhance the peptide therapeutic opportunities is chemical synthesis of peptide dendrimers with hyperbranched structures. Taking into account the recent data of bioactive cationic and helical regions of natural peptides and the structure features of nucleolin identified as an RSV cellular receptor, the main goal of this study was to design relatively short linear and dendrimeric cationic peptides and to test their antiviral activity against RSV. As a result 3 linear cationic peptides and 4 peptide dendrimers were synthesized and compared with known LL-37 (cathelicidin family) and anti-F0 monoclonal antibodies in terms of cytotoxicity and antiviral activity. Their affinity to the supposed molecular target - nucleolin (C23) - was estimated in silico by molecular docking analysis. Four synthesized peptides demonstrated a cytotoxic effect, two of them were even more cytotoxic than LL-37, which could be explained by a combination of a high amount of positive charge and amphipathicity. Contrariwise, non-hydrophobic dendrimer peptides did not exhibit cytotoxicity in mammalian cells in the studied concentration range. Two of the seven synthesized peptides, LTP (dendrimer) and SA-35 (linear), used in this study had a stronger antiviral effect than natural peptide LL-37, and three others showed slightly lower activity than anti-F0 monoclonal antibodies. The data obtained in this study suggest that evenly distributed positive charge, and low or medium amphipathicity play a key role in the antiviral activity of the studied peptides. Moreover, the calculated free energy values of the peptide/nucleolin complex for the most active peptides supported the idea that the peptide ability of nucleolin interaction promotes the anti-RSV properties of the molecules.

Clinical profile and course of children with postinfectious bronchiolitis obliterans from a tertiary care hospital.

Background:Postinfectious bronchiolitis obliterans (PIBO) is a chronic obstructive lung disease with scanty information in literature on etiology, clinical profile, treatment, and outcome.Objective:The objective of the study is to describe the clinical profile and course of children diagnosed with PIBO.Methods:A chart review of children below 18 years of age diagnosed as PIBO over the past 9 years was carried out. Details of clinical profile, laboratory investigations, imaging, treatment received, and outcome were recorded.Results:Eight children (boys 4) with PIBO were identified. Median (interquartile range [IQR]) age at the first episode of acute severe bronchiolitis such as illness and diagnosis of PIBO was 15 (6, 23.5) and 30 (16.5, 60) months, respectively, indicating a delay in diagnosis. The most common symptoms were recurrent episodes of cough (100%), fast breathing (100%), wheezing (87.5%), and fever (62.5%). Median (IQR) number of hospitalizations and episodes of antibiotic use prior to diagnosis were 2.5 (2, 5.5) and 2 (2, 4), respectively. Three (37.5%) children received mechanical ventilation during previous hospitalizations. Chest computed tomography revealed mosaic attenuation in 8 (100%), ground-glass opacities in 2 (25%), and bronchial wall thickening in 2 (25%). After diagnosis, 7 received oral steroids, 7 received hydroxychloroquine, 5 received azithromycin, and 2 received azathioprine. The median (IQR) duration of follow-up (n = 6) was 6 (1.5, 9.5) months. Median (IQR) number of pulmonary exacerbations in follow-up was 2 (1, 5).Conclusion:PIBO is still an under-recognized entity with substantial delay in diagnosis and unnecessary use of antibiotics. Clinical course with imaging findings may help to diagnose and manage this entity.

Signal inhibitory receptor on leukocytes (SIRL)-1 and leukocyte- associated immunoglobulin-like receptor (LAIR)-1 regulate neutrophil function in infants

During severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.

Frequency of pleural effusion in acute bronchiolitis and its effect on prognosis

Aim: To analyze the frequency of pleural effusion and theeffect on prognosis in children with acute bronchiolitis.&#x0D; Methods: A total of 69 infants aged 1-24 months with acute bronchiolitis were studied between September 2009 and December 2010. All patients’age, sex, breastfeeding duration, exposure to smoking, history of using vitamin D, symptoms duration, physical examination and laboratory findings were recorded. Bronchiolitis score and predisposing factors that influence the disease process were determined. Thorax ultrasonography was carried out in all patients, who were evaluated on the 3rd and 7th day of the treatment.&#x0D; Results: Mean age of patients (43 boys, 26 girls) was 11.97 ± 0.69 months (median 11 months). Breastfeeding duration was 8.26 ± 0.56 months (median 8 months). According to bronchiolitis score, 52 patients (75.4%) had mild and moderate bronchiolitis and 17 (24.6%) had severe bronchiolitis; 34 patients (49.2%) had pleural effusion. There was no relation between pleural effusion and symptoms. Frequency of pleural effusion was significantly higher in patients with risk factors.&#x0D; Conclusions: This study demonstrated that most of the acute bronchiolitis cases in the infants studied were accompanied by pleural effusion. Pleural effusion in acute bronchiolitis had no effects on prognosis.

Lung T-Cell Profile Alterations are Associated with Bronchiolitis Obliterans Syndrome in Cystic Fibrosis Lung Transplant Recipients.

The contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6months post-LTx) and follow-up (most recent bronchoscopy-clinical or surveillance per protocol). Comparing BOS to No BOS cohorts, significant differences were found in CD4+ T-cell frequency [17.4 (12.5, 28.2) vs 46.6 (44.4, 48.4), p = 0.003] and CD8+ T-cell frequency [65.6 (62.8, 75.3) vs 39.2 (32.2, 43.3), p = 0.014], respectively. The mean difference of the CD4:CD8 ratio was 0.87 units lower (95% CI - 1.44 to - 0.30, p = 0.006) than patients without BOS, while the median difference of the CD4:CD8 ratio was 0.92 units lower (95% CI - 1.83 to - 0.009, p = 0.048). Therefore, our results suggest that T-cell profiles measured through flow cytometry of BALF in the CF LTx population are associated with the development of severe BOS. Further work is needed in larger patient populations to validate our findings and to determine if this is useful for recipients who underwent LTx for other indications.

Elevated Levels of Type 2 Respiratory Innate Lymphoid Cells in Human Infants with Severe Respiratory Syncytial Virus Bronchiolitis.

Rationale: Studies of the immune responses at the site of respiratory syncytial virus (RSV) infection are sparse despite nearly five decades of research into understanding RSV disease.Objectives: To investigate the role of mucosal innate immune responses to RSV and respiratory viral load in infants hospitalized with the natural disease.Methods: Cytokines, viral load, and type 2 innate lymphoid cell (ILC2) levels in nasal aspirates, collected within 24 hours of enrollment, from infants hospitalized with RSV infection were quantified.Measurements and Main Results: RSV severity in infants was categorized based on admission to the general ward (moderate) or the pediatric ICU (severe). Evaluable subjects included 30 patients with severe and 63 patients with moderate disease (median age, 74 d; range, 9-297 d). ILC2s were found in the nasal aspirates of patients with severe disease (0.051% of total respiratory CD45+ cells) to a significantly greater extent than in patients with moderate disease (0.018%, P = 0.004). Levels of IL-4, IL-13, IL-33, and IL-1β were significantly higher in nasal aspirates of patients with severe disease compared with those of patients with moderate disease. Factors associated with disease severity were gestational age (odds ratio, 0.49; 95% confidence interval, 0.29-0.82; P = 0.007) and IL-4 (odds ratio, 9.67; 95% confidence interval, 2.45-38.15; P = 0.001).Conclusions: This study shows, for the first time, that elevated levels of ILC2s is associated with infant RSV severity. The findings highlight the dominance of type-2 responses to RSV infection in infants and suggest an important role of ILC2 in shaping the immune response early during RSV infection.

Urinary club cell protein 16 (CC16): Utility of its assay during acute bronchiolitis.

Acute bronchiolitis is responsible for high morbidity in infants. Club cell protein 16 kDa (CC16) is a major pneumoprotein secreted by club cells of the bronchial epithelium and eliminated by the renal pathway. CC16 seems to be a biomarker of epithelial damage in asthma. However, its value as a marker of acute bronchiolitis severity and later recurrent wheezing are uncertain, especially the value of its urinary assay for this purpose. A prospective, observational, analytical study was conducted at Clermont‐Ferrand University Hospital to correlate serum CC16 level with clinical severity of bronchiolitis in hospitalized infants aged less than 1 year. We analyzed correlations between serum and urinary CC16, CC16 levels and Wainwright score, immediate morbidity due to bronchiolitis, causal viruses, and recurrent wheezing 1 year after inclusion. In 166 infants, serum CC16 did not correlate with acute bronchiolitis severity (P = .49), but urinary CC16 did (P < .001). In multivariate analysis, urinary CC16 correlated mainly with urinary retinol binding protein (RBP; r = 0.70; P < .001). The logCC16u/logRBPu ratio correlated significantly with severity (P = .02). CC16 levels were not correlated with recurrent wheezing at 1 year. Urinary CC16 could be a useful biomarker in acute bronchiolitis for specific indications. This noninvasive assay would be particularly useful in the young infant population. Several factors must be taken into account in its interpretation, mainly tubular function. Further studies are needed to assess these factors.

Association between multiple respiratory viral infections and pediatric intensive care unit admission among infants with bronchiolitis

BackgroundIt is unclear whether multiple respiratory viral infections are associated with more severe bronchiolitis requiring pediatric intensive care unit (PICU) admission. We aimed to identify the association between multiple respiratory viral infections and PICU admission among infants with bronchiolitis. MethodsWe performed a 1:1 case-control study enrolling previously healthy full-term infants (≤12 months) with bronchiolitis admitted to the PICU as cases and those to the general pediatric ward as controls from 2015 to 2017. Multiplex polymerase chain reaction (PCR) was used for detection of the respiratory viruses. We summarized the characteristics of infants admitted to the PICU and the general pediatric unit. Multivariable logistic regression analysis was used to fit the association between multiple respiratory viral infections (≥2 strains) and PICU admission. ResultsA total of 135 infants admitted to the PICU were compared with 135 randomly selected control infants admitted to the general pediatric unit. The PICU patients were younger (median: 2.2 months, interquartile range: 1.3–4.2) than the general ward patients (median: 3.2 months, interquartile range: 1.6–6.4). Respiratory syncytial virus (74.1%), rhinovirus (28.9%), and coronavirus (5.9%) were the most common viruses for bronchiolitis requiring PICU admission. Patients with bronchiolitis admitted to the PICU tended to have multiple viral infections compared with patients on the general ward (23.0% vs. 10.4%, P<0.001). In the multivariable logistic regression analysis, bronchiolitis with multiple viral infections was associated with higher odds of PICU admission (adjusted odds ratio: 2.56, 95% confidence interval: 1.17–5.57, P=0.02). ConclusionInfants with multiviral bronchiolitis have higher odds of PICU admission compared with those with a single or nondetectable viral infection.

Clinical and Paraclinical Characteristics of Severe Bronchiolitis in Children From 2 Months to 12 Months at the Children's Hospital 1 in Ho Chi Minh City - Vietnam

Clinical and Paraclinical Characteristics of Severe Bronchiolitis in Children From 2 Months to 12 Months at the Children's Hospital 1 in Ho Chi Minh City - Vietnam

Factors predicting length of stay in bronchiolitis.

Despite advances in medical knowledge, the treatment of viral bronchiolitis is mainly supportive. Antiviral therapies are being investigated in clinical trials. Identifying population-attributable risk factors for RSV hospitalization may help prioritizing targeted treatment. To utilize MDClone, a data acquisition tool, to examine factors associated with the risk of hospitalization and length of stay (LOS) in bronchiolitis. A single tertiary medical center retrospective study. Infants discharged with a diagnosis of bronchiolitis between January 2001 and March 2019 were included. Demographic, clinical, laboratory, microbiologic parameters and co-morbidities were collected. Correlations with the risk of hospitalization and LOS were examined. A total of 4793 infants with bronchiolitis, 3851 (80.3%) previously healthy, were seen; 975 visited emergency room only; 3311 were hospitalized in pediatric wards and 507 required pediatric intensive care unit. O2 saturation, age and fever correlated with the risk of hospitalization (OR=0.703, p<0.0001, OR=0.4, p=0.024 and OR=2.388, p<0.0001, respectively). Saturation, fever, gestational age and birth weight correlated with LOS (r=-0.283, p=0.000; r=0.16, p=0.000; r=-0.12, p=0.00; and r=-0.117, p=0.00, respectively). Rates of hospitalization were higher (81.1% vs. 75.6%, p=0.0008) and LOS was longer (median 2.97 vs. 2.73 days, p<0.001) in Arabs than in Jews. In a multivariate model, saturation, fever, gestational age and age predicted LOS. Saturation and ethnicity predicted LOS for previously healthy infants. Prematurity and cardiac anomalies increased LOS (p=0.016 and p<0.0001, respectively). Population-based data may enable predicting disease severity and LOS in bronchiolitis. Focusing on children at greatest risk may aid targeting new therapies.

Increased Moraxella and Streptococcus species abundance after severe bronchiolitis is associated with recurrent wheezing

BackgroundThe role of the airway microbiome in the development of recurrent wheezing and asthma remains uncertain, particularly in the high-risk group of infants hospitalized for bronchiolitis.ObjectiveWe sought to examine the relation of the nasal microbiota at bronchiolitis-related hospitalization and 3 later points to the risk of recurrent wheezing by age 3 years.MethodsIn 17 US centers researchers collected clinical data and nasal swabs from infants hospitalized for bronchiolitis. Trained parents collected nasal swabs 3 weeks after hospitalization and, when healthy, during the summer and 1 year after hospitalization. We applied 16S rRNA gene sequencing to all nasal swabs. We used joint modeling to examine the relation of longitudinal nasal microbiota abundances to the risk of recurrent wheezing.ResultsAmong 842 infants hospitalized for bronchiolitis, there was 88% follow-up at 3 years, and 31% had recurrent wheezing. The median age at enrollment was 3.2 months (interquartile range, 1.7-5.8 months). In joint modeling analyses adjusting for 16 covariates, including viral cause, a 10% increase in relative abundance of Moraxella or Streptococcus species 3 weeks after day 1 of hospitalization was associated with an increased risk of recurrent wheezing (hazard ratio [HR] of 1.38 and 95% high-density interval [HDI] of 1.11-1.85 and HR of 1.76 and 95% HDI of 1.13-3.19, respectively). Increased Streptococcus species abundance the summer after hospitalization was also associated with a greater risk of recurrent wheezing (HR, 1.76; 95% HDI, 1.15-3.27).ConclusionsEnrichment of Moraxella or Streptococcus species after bronchiolitis hospitalization was associated with recurrent wheezing by age 3 years, possibly providing new avenues to ameliorate the long-term respiratory outcomes of infants with severe bronchiolitis.

Risk factors for severe bronchiolitis among children in the emergency department at Sultan Qaboos University Hospital

Background and Aim: Bronchiolitis is an acute viral lower respiratory tract infection. It is a common disease among children below 2 years old, resulting in frequent presentation to the emergency department and occasionally admission1 . For proper management of such patients, studying the disease spectrum and the risk factors is important2 . The aim of this study was to investigate the demographics and risk factors for severe bronchiolitis in children (0–2 years old), in the emergency department (ED) at Sultan Qaboos University Hospital (SQUH). Methods: We conducted a retrospective cohort study, including children ( < 2 years old), who came to the ED with a presentation suggestive of bronchiolitis. We reviewed the charts for a two-year period (January 2015–December 2016). Demographic and baseline characteristics were gathered from electronic medical records and then analyzed. We categorized patients into severe and non-severe bronchiolitis according to the guidelines set by the New South Wales (NSW) Ministry of Health in Australia in 2012 for the “Acute Management of Bronchiolitis in Infants and Children”3 . Therefore, in our study children who were considered to have severe bronchiolitis had one of the following: unwell appearance, apneas, severe tachypnea (>70 breaths/min), bradypnea ( < 30 breaths/min), moderate to severe grunting, cyanosis, pallor, oxygen saturation < 90% in air (or < 92% in O2), tachycardia (>180 beats/min) and difficulty in feeding (taking less than 50% of normal feed).We investigated the following risk factors to predict severe bronchiolitis: maternal age, birth weight, prematurity ( < 37 weeks of gestational age), age < 12 weeks, congenital heart defects, congenital respiratory diseases, immunodeficiency, and global developmental delay. We described the cohort using descriptive statistics and performed a logistic regression analysis to determine the risk factors for severe bronchiolitis. Results: Of the 235 children with bronchiolitis, 133 had severe bronchiolitis while 102 had the non-severe form of the disease, with a greater percentage of males than females in both groups. The majority of children with severe bronchiolitis were in the age < 3 months group (32%), while the least was in the ≥ 12 months age group (10%). There was a trend toward statistically significant results for the following factors: chronological age < 12 weeks (OR = 2.67, 95% CI = 0.89–2.67), congenital cardiac diseases (OR = 2.12, 95% CI = 0.85–5.30) and congenital respiratory diseases (OR = 1.86, 95% CI = 0.80–4.27).The following factors were associated with severe bronchiolitis using stepwise logistic regression: increased heart rate (OR = 1.046, 95% CI = 1.026 – 1.066), decreased SpO2 (OR = 0.890, 95% CI = 0.827 - 0.957), male gender (OR = 2.248, 95% CI = 1.105 – 4.573), irritability (OR = 2.209, 95% CI = 1.024 – 4.769) and global developmental delay (OR = 3.5, 95% CI = 1.0 – 12.537). Conclusion: Multiple factors were associated with severe bronchiolitis and three were trending toward significant association including the younger age group, presence of congenital heart and respiratory diseases4. Low saturation, tachycardia and irritability were both part of the diagnostic criteria for severity and risk factors which confirms the clinical importance of these factors. Further investigations with a prospective study and a bigger sample size are required to confirm our findings and find other associated factors.

High-flow nasal cannula oxygen therapy in children: a clinical review.

High-flow nasal cannula (HFNC) is a relatively safe and effective noninvasive ventilation method that was recently accepted as a treatment option for acute respiratory support before endotracheal intubation or invasive ventilation. The action mechanism of HFNC includes a decrease in nasopharyngeal resistance, washout of dead space, reduction in inflow of ambient air, and an increase in airway pressure. In preterm infants, HFNC can be used to prevent reintubation and initial noninvasive respiratory support after birth. In children, flow level adjustments are crucial considering their maximal efficacy and complications. Randomized controlled studies suggest that HFNC can be used in cases of moderate to severe bronchiolitis upon initial low-flow oxygen failure. HFNC can also reduce intubation and mechanical ventilation in children with respiratory failure. Several observational studies have shown that HFNC can be beneficial in acute asthma and other respiratory distress. Multicenter randomized studies are warranted to determine the feasibility and adherence of HFNC and continuous positive airway pressure in pediatric intensive care units. The development of clinical guidelines for HFNC, including flow settings, indications, and contraindications, device management, efficacy identification, and safety issues are needed, particularly in children.

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients.

BackgroundSingle-nucleotide polymorphisms (SNPs) that impact on the differential expression of interleukin 28B (IL28B) are implicated in the progression of viral-induced diseases. In this prospective longitudinal cohort study, we evaluated the association between IL28B SNPs rs12979860 and rs8099917 and the clinical outcome of bronchiolitis in pediatric patients.MethodsA total of 682 infants suffering from bronchiolitis, categorized based on the final clinical outcome as mild or severe, were genotyped for IL28B SNPs rs12979860 and rs8099917.ResultsWhen infants were categorized exclusively based on the final clinical outcome, no association was established between IL28B SNPs and the severity of bronchiolitis. However, when stratified by sex, the homozygotes for the minor alleles of rs12979860 (T) and rs8099917 (G) were associated with a mild disease in girls but not in boys.ConclusionSNPs rs12979860 and rs8099917 correlate with the severity of bronchiolitis and display a sex bias, where GG rs8099917 and TT rs12979860 genotypes are associated with a mild disease in girls but not in boys. These findings suggest that innate immunity and female sex links with the outcome of the diseases induced by respiratory viruses, such as RSV.

Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis

PurposeThe aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam. MethodsIn the study were included 49 critically ill children of both genders (from 0 to 130 weeks of age) with severe acute bronchiolitis hospitalised in intensive care units. Nonlinear mixed effects modelling approach was applied for data analyses and simulations. ResultsThe final model is a two-compartment model that includes the effects of body weight using allometric scaling with fixed exponents and maturation of clearance. For a typical subject, scaled to the adult body weight of 70 kg, population pharmacokinetic values were estimated at 8.52 L/h for clearance (when maturation function was 1), 25.5 L/h for intercompartmental clearance, and 5.71 L and 39.8 L for the volume of the central and peripheral compartment, respectively. Based on the final model, maturation reaches 50% of the adult clearance in 45.9 weeks of postmenstrual age. The influence of gender, ABCB1 genotype and biochemical parameters on midazolam clearance was not detected. Results of simulations indicate the need for reduced dosing in certain groups of patients in order to maintain plasma concentrations of midazolam within recommended values. ConclusionsThe developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam.

Cold Weather Viruses.

1. Asif Noor, MD* 2. Theresa Fiorito, MD* 3. Leonard R. Krilov, MD*,† 1. *Department of Pediatrics, Children's Medical Center, NYU Winthrop Hospital, Mineola, NY 2. †Department of Pediatrics, State University of New York, Stony Brook School of Medicine, Stony Brook, NY * Abbreviations: AAP: : American Academy of Pediatrics Adv: : adenovirus CDC: : Centers for Disease Control and Prevention FDA: : Food and Drug Administration hMPV: : human metapneumovirus PCR: : polymerase chain reaction PIV: : parainfluenza virus RSV: : respiratory syncytial virus RV: : rhinovirus Clinicians must learn to identify viral infections in children during the winter months and must practice caution with the use of unnecessary medications in such cases. Recognition of the clinical pattern of viral infection (eg, bronchiolitis) in conjunction with judicious use of viral tests (either office-based immunoassays or newer molecular tests) may assist in epidemiological monitoring, cohorting patients in the hospital, withholding unnecessary therapies, and providing a definitive diagnosis. After completing this article, readers should be able to: 1. Review the epidemiological aspects and clinical signs and symptoms of common cold weather viruses. 2. Recognize situations in which viral testing is indicated. 3. Recognize situations in which treatment is indicated. In early November you are evaluating a 9-month-old boy born at 33 weeks of gestation. The infant presents with 2 days of fevers (101°F–102°F [38.3°C–38.8°C]), copious rhinorrhea, and 1 day of coughing with difficulty breathing. He is otherwise feeding well and has had adequate urination. His 4-year-older sister has an upper respiratory tract infection. On physical examination, the infant has a respiratory rate of 45 breaths/min without chest wall retractions. On auscultation there is good air entry with scattered rhonchi bilaterally. What is the most appropriate next step in management? 1. Obtain respiratory syncytial virus (RSV) and influenza antigen testing. 2. Obtain a chest radiograph to look for focal infiltrate. 3. Provide supportive care with nasal …