interleukin-8 and Respiratory-Sounds

Respiratory syncytial virus (RSV) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma. Because azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model, demonstration of similar effects in human subjects might provide a strategy for the prevention of postbronchiolitis recurrent wheezing.. We sought to investigate whether azithromycin treatment during RSV bronchiolitis reduces serum and nasal lavage IL-8 levels and the occurrence of postbronchiolitis recurrent wheezing.. We performed a randomized, double-masked, placebo-controlled proof-of-concept trial in 40 otherwise healthy infants hospitalized with RSV bronchiolitis who were treated with azithromycin or placebo for 14 days. IL-8 levels were measured in nasal lavage fluid and serum on randomization, day 8, and day 15 (nasal lavage only). The occurrence of wheezing episodes was assessed monthly over the ensuing 50 weeks.. Compared with placebo, azithromycin treatment did not reduce serum IL-8 levels at day 8 (P = .6) but resulted in a greater decrease in nasal lavage fluid IL-8 levels by day 15 (P = .03). Twenty-two percent of azithromycin-treated participants experienced at least 3 wheezing episodes compared with 50% of participants in the placebo group (P = .07). Azithromycin treatment resulted in prolonged time to the third wheezing episode (P = .048) and in fewer days with respiratory symptoms over the subsequent year in comparison with placebo (36.7 vs 70.1 days, P = .01).. In this proof-of-concept study azithromycin treatment during RSV bronchiolitis reduced upper airway IL-8 levels, prolonged the time to the third wheezing episode, and reduced overall respiratory morbidity over the subsequent year.

Topics: Azithromycin; Bronchiolitis, Viral; Disease Progression; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Nasal Lavage Fluid; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Treatment Outcome

In cystic fibrosis (CF), the inflammatory process contributes to progressive lung tissue damage. Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects.. To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF.. Twenty-six patients aged 6 to 18 years were recruited to this 20-week, randomized, double-blind, placebo-controlled, crossover trial. Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment. Before and after treatment, findings from spirometry, whole-body plethysmography, and the clinical wheezing and cough scales were evaluated. At the same time, serum and sputum samples were obtained for the measurement of eosinophil cationic protein, interleukin 10 (IL-10), IL-8, and myeloperoxidase levels.. Twenty-three patients completed the study. Compared with placebo use, montelukast treatment significantly improved forced expiratory volume in I second, peak expiratory flow, and forced expiratory flow between 25% and 75% and significantly decreased cough and wheezing scale scores (P < .001 for all). There were no significant changes in vital capacity, thoracic gas volume, airway resistance, and residual volume after treatment. Compared with placebo use, montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8, decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (P < .001 for all).. Montelukast may have measurable anti-inflammatory properties in patients with CF.

Topics: Acetates; Adolescent; Airway Resistance; Anti-Asthmatic Agents; Child; Cough; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Eosinophil Cationic Protein; Female; Forced Expiratory Volume; Humans; Interleukin-10; Interleukin-8; Male; Peroxidase; Quinolines; Respiratory Sounds; Sputum; Sulfides; Treatment Outcome

Infection with rhinovirus (RV) is a major risk factor for disease exacerbations in patients with allergic asthma. This study analysed a broad set of cytokines in the noses of children and adults with asthma during RV infection in order to identify immunophenotypes that may link to virus-induced episodes.. Nasal wash specimens were analysed in children (n = 279 [healthy, n = 125; stable asthma, n = 64; wheeze, n = 90], ages 2-12) who presented to a hospital emergency department, and in adults (n = 44 [healthy, n = 13; asthma, n = 31], ages 18-38) who were experimentally infected with RV, including a subset who received anti-IgE. Cytokines were measured by multiplex bead assay and data analysed by univariate and multivariate methods to test relationships to viral load, allergic status, airway inflammation, and clinical outcomes.. Analysis of a core set of 7 cytokines (IL-6, CXCL8/IL-8, IL-15, EGF, G-CSF, CXCL10/IP-10 and CCL22/MDC) revealed higher levels in children with acute wheeze versus those with stable asthma or controls. Multivariate analysis identified two clusters that were enriched for acutely wheezing children; one displaying high viral load ("RV-high") with robust secretion of CXCL10, and the other displaying high IgE with elevated EGF, CXCL8 and both eosinophil- and neutrophil-derived mediators. Broader assessment of 39 cytokines confirmed that children with acute wheeze were not deficient in type 1 anti-viral responses. Analysis of 18 nasal cytokines in adults with asthma who received RV challenge identified two clusters; one that was "RV-high" and linked to robust induction of anti-viral cytokines and anti-IgE; and the other associated with more severe symptoms and a higher inflammatory state featuring eosinophil and neutrophil factors.. The results confirm the presence of different immunophenotypes linked to parameters of airway disease in both children and adults with asthma who are infected with RV. Such discrepancies may reflect the ability to regulate anti-viral responses.

Topics: Adolescent; Adult; Asthma; Chemokine CXCL10; Child; Child, Preschool; Cluster Analysis; Cytokines; Enterovirus Infections; Epidermal Growth Factor; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-15; Interleukin-6; Interleukin-8; Picornaviridae Infections; Respiratory Sounds; Rhinovirus; Young Adult

We aimed to use serum metabolomics to discriminate infants with severe respiratory syncytial virus (RSV) bronchiolitis who later developed subsequent recurrent wheezing from those who did not and to investigate the relationship between serum metabolome and host immune responses with regard to the subsequent development of recurrent wheezing. Fifty-one infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed for up to the age of 3 years. Of them, 24 developed subsequent recurrent wheezing and 27 did not. Untargeted serum metabolomics was performed by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS/MS). Cytokines were measured by multiplex immunoassay. Difference in serum metabolomic profiles was observed between infants who developed recurrent wheezing and those who did not. L-lactic acid level was significantly higher in infants with recurrent wheezing than those without. Pyrimidine metabolism, glycerophospholipid metabolism, and arginine biosynthesis were identified as the most significant changed pathways between the two groups. Moreover, L-lactic acid level was positively associated with serum CXCL8 level. This exploratory study showed that differential serum metabolic signatures during severe RSV bronchiolitis in early infancy were associated with the development of subsequent recurrent wheezing in later childhood.

Topics: Bronchiolitis; Child, Preschool; Chromatography, High Pressure Liquid; Cytokines; Female; Follow-Up Studies; Humans; Infant; Interleukin-8; Lactic Acid; Male; Metabolomics; Pyrimidines; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Serum; Tandem Mass Spectrometry

Laryngomalacia is a common cause of stridor in infants and is associated with laryngopharyngeal reflux (LPR). Although pepsin in operative supraglottic lavage specimens is associated with severe laryngomalacia, detection of pepsin in oral secretions has not been demonstrated in an outpatient setting.. Children <2 years old with laryngomalacia diagnosed by flexible laryngoscopy and children without stridor were selected. Oral secretion samples were obtained in clinic from all subjects. Pepsin, IL-1β, and IL-8 enzyme-linked immunosorbent assays were performed to determine presence of LPR.. Sixteen laryngomalacia and sixteen controls were enrolled. Pepsin was detected more frequently in oral secretions of patients with laryngomalacia (13/16) than in controls (2/16;. Pepsin in saliva appears to be associated with laryngomalacia, suggesting a role for salivary pepsin as a noninvasive marker of LPR in patients with laryngomalacia. Future studies will determine the utility of this test in laryngomalacia.

Topics: Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-1beta; Interleukin-8; Laryngomalacia; Laryngopharyngeal Reflux; Laryngoscopy; Male; Pepsin A; Respiratory Sounds; Saliva

Early interactions between respiratory viruses and microbiota might modulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis.. Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed up until the age of 3 years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively.. Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3 years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P = .003), CXCL8 (P = .004), CCL5 (P = .029), IL-6 (P = .004), and IL-13 (P < .001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r = 0.246, P = .037) level, and that of Moraxella was associated with IL-6 level (r = 0.236, P = .046) and IL-10 level (r = 0.266, P = .024).. Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood.

Topics: Asthma; Beijing; Bronchiolitis; Child, Preschool; Female; Humans; Immunity; Infant; Interleukin-10; Interleukin-13; Interleukin-8; Male; Microbiota; Prospective Studies; Recurrence; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory System; RNA, Ribosomal, 16S; Sputum

To distinguish between first wheeze and asthma in early childhood, we investigated respiratory viruses and cytokine/chemokine profiles among patients with first wheeze and established asthma.. We enrolled children with acute exacerbations of wheezing (17 first wheeze and 32 asthma) and 11 controls (no wheezing) aged between 10 months and 6 years. Nasal aspirates were obtained, and virus detection was performed with antigenic assay kits and/or RT-PCR. Serum 27 cytokines/chemokines were assayed by a multi-cytokine detection system.. Rhinovirus and respiratory syncytial (RS) virus were dominant in acute exacerbations of asthma. However, many types of viruses were isolated in first wheeze. Serum IL-8 and IL-12 values were significantly higher in first wheeze than in acute asthma or the controls. IL-5 and IP-10 levels in acute asthma and first wheeze cases were higher than in the controls. Both of them were significantly higher in cases of acute asthma than in convalescence stage of asthma cases. Only IP-10 was significantly higher in first wheeze than in convalescence stage of first wheeze cases.. Different profiles in virus detection and production of IL-8 and IL-12 might distinguish between first wheeze and childhood asthma.

Topics: Asthma; Child; Child, Preschool; Disease Progression; Eosinophils; Female; Humans; Infant; Interleukin-12; Interleukin-8; Leukocyte Count; Male; Neutrophils; Respiratory Sounds; Respiratory Syncytial Viruses; Rhinovirus

Hospitalization with bronchiolitis is linked to the development of early childhood chronic wheeze and asthma. Viral etiology and severity of inflammation are potential contributing factors. Previously we observed reduced airway neutrophil infiltration in breastfed bronchiolitic infants, with a corresponding reduction in disease severity. This study aimed to examine whether respiratory viral etiology and co-infection alters the pattern of neutrophil influx, and the inflammatory mediator profile, resulting in epithelial damage in bronchiolitis.. Nasopharyngeal aspirates (NPAs) collected from hospitalized infants were assessed for viruses, soluble protein, cellular infiltrate, interleukin (IL)-6, -8, and myeloperoxidase (MPO).. NPAs were collected from 228 bronchiolitic and 14 non-bronchiolitic infants. In the bronchiolitic cohort, human rhinovirus was most prevalent (38%), followed by respiratory syncytial virus (36%), adenovirus (10%), and human metapneumovirus (6%), with 25% positive for viral co-infections and 25% negative for all screened viruses. Viral-induced bronchiolitis was associated with increased cellular infiltrate and protein, above control, and virus-negative infants (P < 0.05). Cellular infiltrate correlated to IL-6, -8, and MPO (r = 0.331, 0.669, and 0.661; P < 0.01). Protein, IL-6, -8, and MPO differed significantly between viral groups; however, the majority of marker values for all groups fall within an overlapping, indistinguishable range, precluding their use as biomarkers of viral etiology. No significant difference was found between single and viral co-infections for any parameter.. Bronchiolitic infants presenting with a detectable respiratory virus during hospitalization demonstrated elevated markers of airway tissue inflammation and injury. In this cohort, viral etiology did not discernibly modulate chemokine-mediated neutrophil infiltration and activation. Pediatr Pulmonol. 2017;52:238-246. © 2016 Wiley Periodicals, Inc.

Topics: Adenoviridae; Adenoviridae Infections; Breast Feeding; Bronchiolitis; Bronchiolitis, Viral; Coinfection; Female; Humans; Immunoassay; Infant; Inflammation; Interleukin-6; Interleukin-8; Male; Metapneumovirus; Nasopharynx; Neutrophil Infiltration; Neutrophils; Paramyxoviridae Infections; Peroxidase; Picornaviridae Infections; Polymerase Chain Reaction; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Rhinovirus; Severity of Illness Index

Airway epithelial cells (AEC) are key contributors to immune function in the lungs but little is known about their role and function in children.. Having previously established that nasal AEC mediator release correlates with that of bronchial AEC, we assessed AEC responses in children with and without a history of wheeze.. Nasal AEC cultures were established from children (0.6-14.9 years) undergoing elective surgical procedures under general anaesthetic categorised as atopic asthmatic (n = 12), virus-induced wheeze (n = 8) or children without wheeze (n = 32). Mediator release by AEC monolayers at passage 2 was determined by cytometric bead array assay or ELISA.. Unstimulated AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. There were no group differences in AEC release of VEGF, RANTES, MMP-9 or TIMP-1. After stimulation with the pro-inflammatory cytokines IL-1β and TNFα, AEC from children with current wheeze produced significantly less IL-8, IL-6 and MCP-1 than children without wheeze. Release of G-CSF, VEGF, MMP-9 and TIMP-1 did not differ between the wheeze and control group. There were no differences in mediator release between subjects with atopic asthma and those with virus-induced wheeze or between atopic and non-atopic controls. On multivariate analysis, wheeze was the only significant predictor of AEC mediator release.. Intrinsic differences in AEC from children with a history of wheeze may reflect a defect in cytokine production in vivo or an altered state of differentiation in vitro, independent of atopic status.

Topics: Adolescent; Asthma; Chemokine CCL2; Chemokine CCL5; Child; Child, Preschool; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Humans; Infant; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Respiratory Mucosa; Respiratory Sounds; Tissue Inhibitor of Metalloproteinase-1; Vascular Endothelial Growth Factor A

Topics: Azithromycin; Bronchiolitis, Viral; Female; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

Topics: Azithromycin; Bronchiolitis, Viral; Female; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes.. The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument.. IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03).. This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.

Topics: CTLA-4 Antigen; Female; Follow-Up Studies; Gene-Environment Interaction; Genotype; Humans; I-kappa B Kinase; I-kappa B Proteins; Infant; Infant, Newborn; Interleukin-4 Receptor alpha Subunit; Interleukin-8; Male; Mannose-Binding Lectin; MAP Kinase Kinase Kinase 1; NF-KappaB Inhibitor alpha; Picornaviridae Infections; Polymorphism, Single Nucleotide; Recurrence; Respiratory Sounds; Rhinovirus; Risk Factors; Toll-Like Receptor 3; Vascular Endothelial Growth Factor A

As antenatal environment may influence the development of atopy-predisposing immune response, cord blood cytokine productions may be an important predictor for wheezing. We investigated cord blood cytokines in a prospective birth cohort, intensively monitored for wheezy infant outcome at 1 yr. Cord blood serum samples from 269 children were assayed for interleukin (IL)-1beta, -2, -4 to -8, -10, -12 (p70), -13, and -17, interferon-gamma, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1, and macrophage inflammatory protein-1beta. Associations between family histories, antenatal and perinatal factors, cord blood cytokine concentrations, and wheezy infant outcomes (wheezing more than two times) were analyzed. In cord blood sera from 269 children, there were associations between high levels of IL-6, -8 and G-CSF concentrations, and cesarean section. Data at 1 yr were obtained from 213 infants, including 33 wheezy infants. Risk of wheezing was related to gestational age, birth weight, cesarean section, and maternal eczema, but not to bacterial/viral infection during pregnancy, maternal asthma, maternal smoking, or paternal history. High level of cord blood IL-8 concentration had a significant association with wheezy infant outcomes at 1 yr (p = 0.025). By using multivariate logistic regression analysis, birth weight [odds ratio(OR) = 0.998, 95% confidence interval (CI) = 0.997-1.000] and maternal eczema (OR = 5.356, 95% CI = 1.340-21.41), but no other factors, were significant predictors of wheezy infants. Birth weight, gestational age, and maternal history were important risk factors for wheezing in the first year of life. Several cord blood cytokine productions were influenced by cesarean section, and IL-8 may be a predictor for recurrent wheezing at 1 yr.

Topics: Cohort Studies; Cytokines; Female; Fetal Blood; Granulocyte Colony-Stimulating Factor; Humans; Infant; Interleukin-6; Interleukin-8; Logistic Models; Male; Multivariate Analysis; Prospective Studies; Protein Array Analysis; Respiratory Sounds; Risk Factors

Persistent wheeze in childhood is associated with airway inflammation. The present study investigated relationships between polymorphisms in inflammatory genes, exposure to tobacco smoke and furred pets and risk of recurrent wheeze in children. Within a birth cohort of 101,042 children we identified 1111 eighteen month old cases with recurrent wheeze and 735 wheeze-free controls among 11942 children recruited in the Copenhagen area. Polymorphisms in IL-4R, IL-8, IL-13, SPINK5, and CD14 were genotyped. Interviews at gestational wks 12 and 30, and at age 6 and 18 months included questions on number of episodes with wheeze (18 months), exposure to tobacco smoke and pet-keeping. Recurrent wheeze was defined as at least four episodes of wheeze before the child was 18 months old. There was a statistically significant association between the IL-13 Arg144Gln polymorphism and risk of recurrent wheeze (p = 0.01). Furthermore, there was a statistically significant interaction between this polymorphism and exposure to tobacco smoke during pregnancy, though this was probably a chance finding. There were no other statistically significant effects of the polymorphisms or interactions with exposure to tobacco smoke in relation to the risk of recurrent wheeze. Polymorphisms in IL-8 affected the association between pet-keeping and risk of wheeze. Polymorphisms in inflammation genes might affect the association between environmental exposures and risk of recurrent wheeze in early childhood.

Topics: Animals; Animals, Domestic; Environmental Exposure; Female; Humans; Infant; Inflammation; Interleukin-13; Interleukin-8; Polymorphism, Genetic; Pregnancy; Prenatal Exposure Delayed Effects; Recurrence; Respiratory Sounds; Smoking

Sulfur mustard (SM) is a blistering chemical agent which has short and long term toxicity against many organs. The respiratory tract is one of the main targets, and is the most disabling long term complication of SM. Inflammatory mediators especially IL-8 and IL-6 play the primary role in the various chronic pulmonary diseases. Sardasht-Iran Cohort Study (SICS) was designed to evaluate immunological and molecular parameters in SM exposed people 20 years after exposure. In the present study, the association of the serum levels of IL-8, IL-6, C reactive protein (CRP) and rheumatoid factor (RF) with long term pulmonary involvement was evaluated. There were 348 exposed and 120 control participants. The clinical evaluations were done for all subjects and Spirometry was performed according to American Thoracic Society Criteria. Severity of pulmonary involvement was assessed by Global Initiative for chronic Obstructive Lung Disease (GOLD) classification. The serum levels of IL-8, IL-6 and RF were assessed by ELISA assay. CRP was assessed by photometric method. The serum levels of IL-8 and IL-6 significantly decreased in the SM exposed participants compared to the control group. There were no significant associations between the serum levels of IL-8 and pulmonary symptoms (chronic cough, sputum, hemoptysis, and dyspnea), pulmonary findings (crackles, rales, and wheezing) as well as spirometry parameters. IL-6 was associated with wheezing and CRP was associated with wheezing and rales in SM exposed group. We concluded the serum levels of these inflammatory mediators probably do not have any major role in pathogenesis and persistence of pulmonary complications and do not reflect the degree of severity of pulmonary involvement following SM exposure.

Topics: C-Reactive Protein; Chemical Warfare Agents; Cohort Studies; Cough; Dyspnea; Humans; Interleukin-6; Interleukin-8; Iran; Mustard Gas; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Respiratory Sounds; Rheumatoid Factor; Time Factors

Respiratory syncytial virus (RSV) infects nearly all children under two years of age. It is not understood why some develop serious bronchiolitis. Whether there is a genetic component is not known. The nature of the association between RSV bronchiolitis and subsequent wheezing remains unknown. interleukin-8 (IL-8) is a potent neutrophil chemokine and activator, which plays a role in virus-induced wheezing diseases. The purpose of this study was to assess the genetic association between the IL-8 gene promoter -251A/T polymorphism and RSV bronchiolitis and post-bronchiolitis wheezing in children.. Totally 320 children who were hospitalized for bronchiolitis together with positive immunofluorescence for RSV were recruited in this study from Jan. 2002 to Jan. 2004. A group of 272 healthy children were enrolled as controls. The age of these children ranged from 1 to 12 months. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify the polymorphism at position-251 of the IL-8 promoter in RSV bronchiolitis and control groups. The total IL-8 and IgE concentrations in serum samples were measured by enzyme-linked immunosorbent assay (ELISA). The patients with RSV bronchiolitis were followed up in order to analyze the occurrence of wheezing post-bronchiolitis.. (1) Both A allele and T allele were detected at -251 of the IL-8 promoter; the prevalence of the A allele in RSV bronchiolitis group was 45.6%, as compared with 37.7% in normal group. The prevalence of IL-8-251A allele was significantly different between the two groups (P < 0.05). (2) For genotypes T/T, A/T, A/A in RSV bronchiolitis, level of serum IL-8 were (17 +/- 6) ng/L, (21 +/- 7) ng/L, (24 +/- 9) ng/L, respectively, the difference was significant among the three genotypes (P < 0.01). (3) The prevalence of the A allele in the group who wheezed after the episode of RSV bronchiolitis was 54.6%, as compared with 35.8% in the group who had bronchiolitis but did not go on to wheeze. The prevalence of IL-8-251A allele was significantly different between the two groups (P < 0.05).. Polymorphism of IL-8 promoter-251A/T was associated with susceptibility to RSV bronchiolitis in children. The association of IL-8-251A with severe RSV bronchiolitis is most marked in the children who go on to wheeze.

Topics: Adolescent; Alleles; Bronchiolitis; Child; Child, Preschool; Chromosome Mapping; Enzyme-Linked Immunosorbent Assay; Female; Genetic Predisposition to Disease; Genotype; Humans; Infant; Interleukin-8; Male; Polymorphism, Genetic; Respiratory Sounds; Respiratory Syncytial Virus Infections

The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL-8-promoter region is associated with susceptibility to severe bronchiolitis.. The purpose of this study was to assess the association between wheezing post-bronchiolitis and the genetic variant of IL-8 gene.. We collected data from 134 children who had suffered from bronchiolitis, enrolled in our previous study. The occurrence of wheezing post-bronchiolitis was recorded from a questionnaire sent by post. The association between the genotype and wheezing phenotype was assessed by family-based and case-control approaches.. Family-based association showed that the IL-8 variant was transmitted significantly more often than expected in the children who wheezed after the episode of bronchiolitis (transmission=56%, P=0.02). This effect was not observed in the group of children who had bronchiolitis but did not go on to wheeze. Moreover, the variant was significantly more frequent in post-bronchiolitis wheezers compared with the general population (odds ratio=1.6, 95% confidence interval 1.0-2.6).. These preliminary results suggest that there is a genetic predisposition to wheeze following severe RSV bronchiolitis.

Topics: Alleles; Bronchiolitis, Viral; Case-Control Studies; Chi-Square Distribution; Child; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness.. The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil-driven inflammation was associated with EVW.. Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL-8, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP).. There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (-1.1, 2.2)x10(4)/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (-8.2, 14.5)%, respectively, P<0.01); however, this increase did not correlate with lower respiratory tract symptom scores. IL-8 increased in both the upper and lower respiratory tracts in both EVW and control subjects with colds, the largest change being seen on day 4 in the sputum of those with EVW (mean difference from baseline (95% confidence interval) 2.5 (0.55-4.46) ng/mL). Only modest changes were seen in IFN-gamma and no changes were seen in IL-5 or ECP. None of the results was influenced by the atopic status of the subjects in either group.. EVW wheeze is characterized by neutrophilic inflammation in both the upper and lower respiratory tracts without eosinophilia (even in atopic subjects). IL-8 is likely to be an important chemokine in this process. Symptoms and airway responsiveness were correlated with change in neutrophils.

Topics: Common Cold; Enzyme-Linked Immunosorbent Assay; Eosinophils; Forced Expiratory Volume; Humans; Inflammation; Interleukin-8; Nasal Mucosa; Respiratory Sounds; Respiratory Tract Infections; Sputum

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)-6, IL-8, IL-11, and interferon-gamma (IFN-gamma) levels in nasopharyngeal aspirates (NPA) from non-asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL-11 in NPA from asthmatic children were significantly higher than those from non-asthmatic children with RSV infection, and RSV infection enhanced the IL-11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL-6 than that of children with IFAV infection. There was little difference in the IL-8 and IFN-gamma levels between asthmatic and non-asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL-11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL-6 production in RSV infection compared with IFAV infection.

Topics: Asthma; Biomarkers; Bronchiolitis, Viral; Child Welfare; Child, Preschool; Cytokines; Female; Humans; Infant; Infant Welfare; Influenza A virus; Influenza, Human; Inhalation; Interferon-gamma; Interleukin-11; Interleukin-6; Interleukin-8; Male; Nasopharynx; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Statistics as Topic

Both virus-mediated damage to airway tissues and induction of pro-inflammatory cytokines such as interleukin-8 (IL-8) could contribute to symptom severity during viral respiratory infections in children. To test the hypothesis that IL-8 contributes to the pathogenesis of respiratory symptoms during naturally acquired respiratory viral infections in children, nasal wash samples collected from infants with acute viral infections (n = 198) or from healthy uninfected infants (n = 31) were analysed for IL-8. Nasal wash IL-8 was positively related to age in uninfected children (rs = 0.36, p < 0.05). Respiratory syncytial virus (RSV) infection caused more severe respiratory symptoms compared to infections with influenza A, parainfluenza viruses, or rhinoviruses. In addition, RSV, parainfluenza and rhinovirus infections increased levels of IL-8 in nasal lavage fluid, and there were some differences in the ability of the viruses to induce IL-8 production (RSV>influenza, p < 0.05). Finally, there were significant correlations between nasal wash IL-8 levels and symptom scores during infections with rhinovirus (rs = 0.56, p < 0.001) or influenza A (rs = 0.45, p < 0.05), but not with parainfluenza virus or RSV. These findings provide evidence of a close relationship between the generation of IL-8 and symptoms during acute community-acquired infections with rhinovirus or influenza A. In contrast, for RSV and parainfluenza infections, factors in addition to IL-8 production appear to contribute to the generation of clinical symptoms.

Topics: Age Factors; Fluorescent Antibody Technique, Direct; Humans; Infant; Infant Welfare; Infant, Newborn; Influenza A virus; Influenza, Human; Interleukin-8; Nasal Lavage Fluid; Picornaviridae Infections; Prospective Studies; Respiratory Hypersensitivity; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Rhinovirus; Severity of Illness Index; Statistics as Topic

It has been shown previously that airway eosinophils characterize childhood asthma and neutrophils contribute to the pathophysiology of both infantile wheezing and asthma. Therefore, eosinophil cationic protein (ECP) and interleukin-8 (IL-8) levels in bronchoalveolar lavage fluid (BALF) from asthmatics (n = 16) and infantile wheezers (n = 30) were analyzed as markers of eosinophil- and neutrophil-mediated inflammation. To aid the interpretation, a control group of children (n = 10) with no lower airway pathology were included. Disease severity was assessed by using a symptom score. Surprisingly, no significant difference was found in IL-8 or ECP levels among asthma, infantile wheeze, and control groups. Asthma was characterized by: a correlation between ECP levels and eosinophil counts (r = 0.618, p = 0.014); a correlation between neutrophil number and IL-8 levels (r = 0.747, p = 0.002); and increasing IL-8 levels with symptom score (p = 0.03). In infantile wheezers, IL-8 levels were poorly related to neutrophil number but were significantly increased when neutrophils were > 10%. Although detectable levels were found in all but one symptomatic infant, IL-8 concentrations did not reflect the symptom score in infantile wheeze. ECP was unexpectedly correlated to neutrophil percentages (Rho = 0.832, p = 0.001), and a threshold of ECP>20 ng/ml was associated with persistent symptoms in these infantile wheezers. Hence, in accordance with BALF cellularity, activation of eosinophils was suggested by raised levels of ECP in childhood asthma, but not in infantile wheeze. Neutrophil-mediated inflammation appeared to better reflect the severity of asthma than that of infantile wheeze. Although its meaning remains to be elucidated, ECP was suggested to be a helpful indicator of persistent infantile wheeze. However, its utility as a marker predicting ongoing asthma remains to be established.

Topics: Adolescent; Asthma; Biomarkers; Blood Proteins; Bronchoalveolar Lavage Fluid; Bronchoscopy; Child; Child, Preschool; Eosinophil Granule Proteins; Female; Humans; Infant; Inflammation Mediators; Interleukin-8; Male; Respiratory Sounds; Ribonucleases

We determined RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin-8 (IL-8) concentrations, and total white blood cell (WBC) and differential counts in nasal wash samples from rhinovirus-infected infants presenting with wheezing or acute upper respiratory illness alone and compared them with those from healthy infants. RANTES concentrations were significantly greater in acute samples from wheezy patients than in those from patients with acute upper respiratory illness only, or in control samples. IL-8 concentrations and WBC and neutrophil counts were significantly greater in acute samples from wheezy infants and patients with upper respiratory illness alone than in control samples, but they did not differ significantly between the 2 patient groups.

Topics: Chemokine CCL5; Chemokines; Child, Preschool; Humans; Infant; Interleukin-8; Leukocyte Count; Nasal Lavage Fluid; Picornaviridae Infections; Respiratory Sounds; Respiratory Tract Diseases; Rhinovirus