Background Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. Objective We assessed which inflammatory mediators were released from bronchial epithelial cells ...(BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. Methods BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments. Results IFN-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 95% CI, 3.9-100.3). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction ( r = −0.8; P < .01). Conclusions IP-10 release is specific to acute virus-induced asthma. Clinical implications Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.
Increased body weight may influence airway inflammatory mechanisms.
To assess whether overweight-obesity (OW-O), evaluated as increased body mass index, is associated either with exhaled nitric oxide ...(eNO), a marker of airway inflammation, or with allergic sensitization in a large sample of children and adolescents.
A cross-sectional, epidemiological study was performed on a population sample of schoolchildren evaluating 708 subjects (age 10-16 years; BMI 13-39 kg/m(2)) by respiratory health questionnaire, skin prick tests, spirometry, and eNO measure.
Prevalence rates were: OW-O 16.4%, asthma ever (A) 11.9%, and rhinoconjunctivitis (RC) 14.8%. Asthma ever and allergic sensitization were significantly more frequent among OW-O (21.0 and 51.6%) than in non-OW-O (10.2 and 37.0%, respectively). The forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) ratio was not significantly different between OW-O and non-OW-O. Exhaled NO (median and interquartile range) was 15.3 (11.2-23.1) ppb in the overall sample, 20.3 (12.9-35.8) ppb among allergic subjects, and 13.9 (10.6-18.3) ppb among nonallergic subjects (P<.0001). No significant difference between OW-O and non OW-O subjects was found in eNO levels. Similarly, OW-O subjects with A or RC did not show significantly higher eNO levels than non-OW-O. In a logistic regression model, presence of allergic sensitization, A, and RC, and not OW-O, were significant predictors of increased eNO.
In children, OW-O was not associated with increased eNO levels, but it was an independent risk factor for asthma and allergic sensitization.
Background IL-13 is a key cytokine associated with the asthmatic phenotype. IL-13 signals via its cognate receptor, a complex of IL-13 receptor (IL-13R) α 1 chain with IL-4 receptor α; however, a ...second protein, IL-13Rα2, also binds IL-13. Recently a polymorphic variant of IL-13 (R110Q) has been shown to be associated with atopy. Objective To investigate the binding properties of this IL-13 variant to its cognate receptors. Methods We used surface plasmon resonance to measure the binding kinetics of R110Q to its receptors. Primary human fibroblasts were grown from endobronchial biopsies obtained from volunteers. Receptor levels were measured by fluorescence-activated cell sorting. Results There was no significant difference in the binding of R110Q with soluble human IL-13Rα1 compared with IL-13 (32 ± 5 nmol/L and 36 ± 7 nmol/L, respectively; P = .625). However, a small but significant difference was observed in the binding of R110Q to soluble human IL-13Rα2 compared with IL-13 (840 ± 87 pmol/L and 1.1 ± .05 nmol/L, respectively; P = .04). We observed that primary human lung fibroblasts expressed different levels of IL-13Rα2. Eotaxin release from fibroblasts expressing low IL-13Rα2 levels was significantly higher in response to R110Q compared with IL-13. This was not evident in cells that had high baseline IL-13Rα2 levels. Conclusion These results suggest that relatively small changes in functional properties of a ligand combined with variation in receptor levels in vivo can result in significant differences in responsiveness. Clinical implications Expression of R110Q and low IL-13Rα2 levels can result in important biological differences that may have clinical relevance in an atopic environment.
Background Asthma pathogenesis involves gene and environmental interactions. A disintegrin and metalloprotease 33 (ADAM33)/Adam33 is a susceptibility gene for asthma and bronchial hyperresponsiveness ...in human beings and mice. ADAM33 is almost exclusively expressed in mesenchymal cells, including mesenchymal progenitors in developing lungs. Objective Because maternal allergy is a risk factor for asthma, we hypothesized that an allergic environment affects ADAM33/Adam33 expression during human and mouse lung development. Methods Human embryonic/fetal lung (HEL) tissues were collected from first-trimester terminations of pregnancy. These were processed immediately or used for explant culture ± IL-13. MF1 mice or ovalbumin-sensitized A/J mice ( Bronchial hyperresponsivness (Bhr)1/Adam33 locus–positive) were time-mated and challenged with ovalbumin (A/J mice only) during pregnancy. Lungs were harvested at different times during gestation and post partum. ADAM33/Adam33 expression was analyzed by using reverse transcriptase quantitative polymerase chain reaction and Western blotting. Results ADAM33 mRNA was detectable in HELs in the pseudoglandular stage of development and showed a significant increase from 7 to 9 weeks postconception. IL-13 significantly suppressed ADAM33 mRNA in HEL explants. In developing murine lungs, Adam33 mRNA and protein expression increased significantly in the early pseudoglandular stage and showed another large increase post partum . In A/J mice, maternal allergy significantly suppressed Adam33 mRNA in lungs of newborn pups, whereas processed Adam33 protein increased and several smaller isoforms were detected. Conclusion Adam33 /Adam33 shows 2 significant increments in expression during lung morphogenesis, suggesting important developmental regulation. The ability of maternal allergy or exogenous IL-13 to suppress Adam33 / ADAM33 mRNA but enhance Adam33 processing suggests a gene-environment interaction that may be relevant for asthma pathogenesis.
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