Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Time-resolved photoluminescence analysis of ceramic Ce:GAGG scintillators.

This paper introduces the characteristics and efficiency of post-treatment methods for enhancing the timing resolution of ceramic Ce:GAGG scintillators. The thermal annealing and surface treatments were included to analyze their impact on time-resolved photoluminescence (TRPL) and thermoluminescence (TL) characteristics. Optical properties were improved by suppressing nonradiative recombination due to the reduced surface defects, while heat-treatment removes traps as confirmed by TL measurements. TRPL decay characteristics revealed that samples treated with mechanical polishing followed by heat treatment exhibited the best scintillation performance, with a slow component of 272.3 ns. These findings will aid in developing techniques for improving the luminescence of other inorganic scintillators.

Improvement of phoswich detector-based ß+/γ-ray discrimination algorithm with deep learning.

BACKGROUND: Positron probes can accurately localize malignant tumors by directly detecting positrons emitted from positron-emitting radiopharmaceuticals that accumulate in malignant tumors. In the conventional method for direct positron detection, multilayer scintillator detection and pulse shape discrimination techniques are used. However, some γ-rays cannot be distinguished by conventional methods. Accordingly, these γ-rays are misidentified as positrons, which may increase the error rate of positron detection. PURPOSE: To analyze the energy distribution in each scintillator of the multilayer scintillator detector to distinguish true positrons and γ-rays and to improve the positron detection algorithm by discriminating true and false positrons. METHODS: We used Autoencoder, an unsupervised deep learning architecture, to obtain the energy distribution data in each scintillator of the multilayer scintillator detector. The Autoencoder was trained to separate the combined signals generated from the multilayer scintillator detector into two signals of each scintillator. An energy window was then applied to the energy distribution obtained using the trained Autoencoder to distinguish true positrons from false positrons. Finally, the performance of the proposed method and conventional positron detection algorithm was evaluated in terms of the sensitivity and error rate for positron detection. RESULTS: The energy distribution map obtained using the trained Autoencoder was proven to be similar to that of the simulated results. Furthermore, the proposed method demonstrated a 29.79% (+0.42%p) increase in positron detection sensitivity compared to the conventional method, both having an equal error rate of 0.48%. However, when both methods were set to have the same sensitivity of 1.83%, the proposed method had an error rate that was 25.0% (-0.16%p) lower than that of the conventional method. CONCLUSIONS: We proposed and developed an Autoencoder-based positron detection algorithm that can discriminate between true and false positrons with a smaller error rate than conventional methods. We verified that the proposed method could increase the positron detection sensitivity while maintaining a low error rate compared to the conventional method. If the proposed algorithm is implemented in handheld positron detection probes or cameras, diseases such as cancers can be more accurately localized in a shorter time compared with using traditional methods.

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study.

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Scintillation characteristics of chemically processed Ce:GAGG single crystals.

We investigated the correlation between the surface finish and luminescence properties of chemically polished cerium-doped single-crystal Gd3Al2Ga3O12 scintillators (Ce:GAGG), from the crystallographic perspective. The intrinsic defects in the crystals were identified via photoluminescence spectroscopy followed by scanning electron microscopy and X-ray diffraction to analyze their surface morphologies. Finally, the samples were individually wrapped with an enhanced specular reflector (ESR), coupled with a photomultiplier tube, placed inside a dark box, connected to a digitizer, and irradiated with a 137Cs radioactive source to evaluate the relative light (signal) output and energy resolution of each sample. The as-cut (rough) Ce:GAGG single-crystal samples, that were chemically polished with phosphoric acid at 190°C in air for 60 min, demonstrated a 33.1% increase in signal amplitude (light output to photosensor) and 2.4% (absolute value) improvement in energy resolution, which were comparable to those obtained for the mechanically polished sample. For these samples, the surface roughness was found to be ~430 nm, which was approximately half of that of the mechanically polished sample. The chemical polishing method used in this study is a cost-effective and straightforward technique to improve structural imperfections and can facilitate the treatment of inorganic scintillators with complex shapes and/or on a large scale.

Performance Comparison of CdTe:Na, CdTe:As, and CdTe:P Single Crystals for Solar Cell Applications.

We compared thermal stability, open-circuit voltage, short-circuit current, and fill factor values of single-crystal Cadmium telluride (CdTe) grown using the vertical Bridgman (VB) technique and doped with group V elements (phosphorus and arsenic), and group Ⅰ element (sodium), followed by an annealing process. The sodium-doped CdTe maintained a hole density of 1016 cm-3 or higher; after annealing for a long time, this decreased to 1015 cm-3 or less. The arsenic-doped CdTe maintained a hole density of approximately 1016 cm-3 even after the annealing process; however its bulk minority carrier lifetime decreased by approximately 10%. The phosphorus-doped CdTe maintained its properties after the annealing process, ultimately achieving a hole density of ~1016 cm-3 and a minority carrier lifetime of ~40 ns. The characteristics of a single-crystal solar cell were evaluated using a solar cell device that contained single-crystal CdTe with various dopants. The sodium-doped sample exhibited poor interfacial properties, and its performance decreased rapidly during annealing. The samples doped with group V elements exhibited stable characteristics even during long-term annealing. We concluded, therefore, that group V elements dopants are more suitable for CdTe single-crystal-based solar cell applications involving thermal stress conditions, such as space missions or extreme fabrication temperature environments.

Enhancement of the luminescent and optical properties of ceramic Ce:GAGG after surface treatment with phosphoric acid.

Surface modification of ceramic Ce-doped Gd3Al2Ga3O12 (Ce:GAGG) was performed by exposing small samples to anhydrous phosphoric acid (H3PO4) under different conditions (temperature and duration) to investigate the effects of chemical polishing treatment. When coupled to a photomultiplier tube (PMT) and used as a radiation detector, chemical treatment for 3 min at 190 °C improved the light (signal) output by 24.8% and energy resolution by 2.5% (percentage point), respectively. This can be attributed to a reduction in surface roughness that enhanced optical properties. Thus, chemical polishing could be a low-cost alternative to mechanical polishing especially for small or complex shaped ceramic scintillators.

Simultaneous Acquisition of Ultrasound and Gamma Signals with a Single-Channel Readout.

We propose an integrated front-end data acquisition circuit for a hybrid ultrasound (US)-gamma probe. The proposed circuit consists of three main parts: (1) a preamplifier for the gamma probe, (2) a preprocessing analog circuit for the US, and (3) a digitally controlled analog switch. By exploiting the long idle time of the US system, an analog switch can be used to acquire data of both systems using a single output channel simultaneously. On the nuclear medicine (NM) gamma probe side, energy resolutions of 18.4% and 17.5% were acquired with the standalone system and with the proposed switching circuit, respectively, when irradiated with a Co-57 radiation source. Similarly, signal-to-noise ratios of 14.89 and 13.12 dB were achieved when US echo signals were acquired with the standalone system and with the proposed switching circuit, respectively. Lastly, a combined US-gamma probe was used to scan a glass target and a sealed radiation source placed in a water tank. The results confirmed that, by using a hybrid US-gamma probe system, it is possible to distinguish between the two objects and acquire structural information (ultrasound) alongside molecular information (gamma radiation source).

Anxiety, depression, and stress in Korean patients with chronic urticaria.

BACKGROUND/AIMS: Emotional distress is thought to cause or maintain chronic urticaria (CU). We aimed to investigate the presence of anxiety, depression, and stress in Korean adult CU patients and to explore their potential impact on treatment. METHODS: We enrolled 79 CU patients and a disease control group comprising 39 persistent asthma patients. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate depression and anxiety. Stress and quality of life (QoL) were assessed by Stress Response Inventory and CU-QoL questionnaires. The sociodemographic and clinical data such as urticaria activity score (UAS-15, UAS-6) were obtained. RESULTS: The prevalence of depression and anxiety based on the HADS were 48.1% and 38.0%. Although the prevalence of anxiety didn't differ between the CU and asthma patients, depression was significantly more prevalent in the CU patients (48.1% vs. 28.2%). Stress tended to be lower in CU patients. Anxiety, depression, and stress exhibited negative correlations with QoL. Anxiety showed significant correlation with UAS-6 and pruritus-visual analog scale (VAS; r = 0.256, r = 0.272, p < 0.05, respectively); depression correlated with sleep difficulty-VAS (r = 0.261, p < 0.05). Stress was associated with UAS-15, UAS-6, pruritus-VAS, and sleep difficulty-VAS (r = 0.251, r = 0.317, r = 0.302, r = 0.258, p < 0.05, respectively). CONCLUSION: The current study first presented that Korean CU patients frequently have anxiety and depression, which affect their QoL and demonstrated that anxiety, depression, and stress had different effects on sleep difficulty, pruritus, and urticaria severity in Korean CU patients.

Inhibition of LFA-1/ICAM-1-mediated cell adhesion by stilbene derivatives from Rheum undulatum.

Six stilbenes were isolated from the methanol extract of Rheum undulatum rhizomes by bioactivity-guided fractionation. The structures of the compounds were determined by spectroscopic analysis ((1)H-, (13)C-NMR and MS), to be desoxyrhapontigenin (1), rhapontigenin (2), trans-resveratrol (3), piceatannol (4), piceatannol-3'-O-ß-D-glucopyranoside (5) and isorhapontin (6). Compounds 1-4 inhibited the direct binding between sICAM-1 and LFA-1 of the THP-1 cells in a dose-dependent manner with IC(50) values of 50.1, 25.4, 33.4 and 45.9 µM, respectively. On the other hand, the other compounds 5 and 6 with a glucose moiety in each molecule did not show any inhibitory activity in the cell adhesion assay (IC(50) values of >100.0 µM). Compounds 2, 3 and 4 also had an inhibitory effect on direct binding between sVCAM-1 and VLA-4 of THP-1 cells. This suggests that the stilbenes from Rheum undulatum rhizomes are good candidates for therapeutic strategies towards inflammation.

Chlamydophila pneumoniae inhibits corticosteroid-induced suppression of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion by human peripheral blood mononuclear cells.

Chlamydophila pneumoniae infection has been suggested to be associated with severe asthma characterized by persistent airway limitation, which may be related to airway remodelling. We investigated whether C. pneumoniae infection affected the secretion of metalloproteinase-9 (MMP9) and tissue inhibitor metalloproteinase-1 (TIMP1), and altered the responsiveness of inflammatory cells to corticosteroids. Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence or absence of C. pneumoniae. Secretion of both MMP9 and TIMP1 was strongly suppressed by dexamethasone treatment in uninfected cells. MMP9 secretion was also significantly inhibited by dexamethasone in C. pneumoniae-infected cells, but TIMP1 secretion was not; hence the MMP9 to TIMP1 ratio decreased. Interestingly, expression of human glucocorticoid receptor ß, which is believed to confer resistance to corticosteroids, was enhanced by dexamethasone treatment in C. pneumoniae-infected PBMCs. We conclude that C. pneumoniae infection may promote airway remodelling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids.

Hyperoxidized peroxiredoxins in peripheral blood mononuclear cells of asthma patients is associated with asthma severity.

AIMS: Oxidative stress is involved in the pathogenesis of asthma, and peroxiredoxins (PRDX) may be critical in controlling intracellular oxidative stress. The aim of this study was to evaluate expressions of PRDX and their hyperoxidized forms in asthmatic individuals. MAIN METHODS: The levels of expression of PRDX1, PRDX2, PRDX3, and PRDX6 and their hyperoxidized forms (PRDX-SO(3)) were measured in PBMCs from asthma patients and control subjects. In addition, cells from these subjects were treated with hydrogen peroxide (H(2)O(2)) and their intracellular concentrations of reactive oxygen species (ROS) were measured. KEY FINDINGS: The ratios of hyperoxidized to total PRDX (PRDX-SO(3/)PRDX) in PBMCs were significantly higher in asthma patients than in normal subjects and were correlated with disease severity, with the highest ratio seen in patients with severe asthma. Furthermore, H(2)O(2) treatment of PBMCs, particularly lymphocytes, increased intracellular ROS concentrations with greater and more persistent increases observed in cells from asthmatic than from control subjects. SIGNIFICANCE: Hyperoxidation of PRDX may serve as a biomarker of asthma severity and may predict enhanced susceptibility to oxidative stress load in PBMCs of asthmatics.

Airway Measurement for Airway Remodeling Defined by Post-Bronchodilator FEV1/FVC in Asthma: Investigation Using Inspiration-Expiration Computed Tomography.

PURPOSE: Airway remodeling may be responsible for irreversible airway obstruction in asthma, and a low post-bronchodilator FEV1/FVC ratio can be used as a noninvasive marker of airway remodeling. We investigated correlations between airway wall indices on computed tomography (CT) and various clinical indices, including post-bronchodilator FEV1/FVC ratio, in patients with asthma. METHODS: Volumetric CT was performed on 22 stable asthma patients who were taking inhaled corticosteroids. Airway dimensions were measured at four segmental bronchi using in-house software based on the full-width/half-maximum method. Parameters included luminal area, wall thickness (WT), wall thickness percentage (WT%), wall area percentage (WA%), bronchial-to-arterial diameter (BA) ratio on inspiration CT, airway collapsibility (AC), and air trapping index (ATI). Correlations were analyzed between CT parameters and clinical indices, including %FEV1, FEV1/FVC, FEF(25-75%), and post-bronchodilator FEV1/FVC ratio. RESULTS: Post-bronchodilator FEV1/FVC showed significant correlations with WT%, WT, BA ratio, AC, and ATI (r=-0.503, -0.576, 0.454, 0.475, and -0.610, respectively). WT showed negative correlations with FEV1/FVC and FEF(25-75%) (r=-0.431 and -0.581), and WT% was negatively correlated with %FEV1, FEV1/FVC, and FEF(25-75%) (r=-0.434, -0.431, and -0.540, respectively). WA% showed correlations with FEF(25-75%) and body mass index (r=-0.459 and 0.453). The BA ratio was positively correlated with %FEV1 (r=0.459) and FEF(25-75%) (r=0.479). AC showed strong positive correlation with FEV1/FVC (r=0.592), and ATI showed negative correlations with FEV1/FVC (r=-0.534) and FEF(25-75%) (r=-0.591). CONCLUSIONS: WT%, WT, BA ratio, and AC on inspiration and expiration CT are good indices for measuring airway remodeling defined by post-bronchodilator FEV1/FVC in stable asthma patients treated with inhaled corticosteroids.

Silver-stained fibrin zymography: separation of proteases and activity detection using a single substrate-containing gel.

A new zymogram method, silver-stained fibrin zymography, for separation of protease bands and activity detection using a single substrate gel, was developed. The method takes advantage of the nanoscale sensitivity of both zymography and silver staining. After SDS-PAGE in a gel containing fibrin, the gel was incubated in enzyme reaction buffer and the zymogram was silver-stained. Bands with protease activity were stained with silver in clear areas where the protein substrate had been degraded. The molecular sizes of proteases were accurately determined. Furthermore, proteases of high molecular weight were clearly and sharply resolved.

Chlamydophila pneumoniae enhances secretion of VEGF, TGF-beta and TIMP-1 from human bronchial epithelial cells under Th2 dominant microenvironment.

PURPOSE: Chlamydophila pneumoniae infection in the airways is thought to be associated with the pathogenesis of asthma, especially in non-atopic severe asthma with irreversible airway obstruction that may be related to airway remodeling. Here, we investigated whether C. pneumoniae infection enhances the secretion of critical chemical mediators for airway remodeling, such as VEGF, TGF-beta, and TIMP-1, in human bronchial epithelial cells (BECs) in a Th2-dominant microenvironment. METHODS: Human bronchial epithelial cells (BEAS-2B cells) were infected with C. pneumoniae strain TW183 and cultured in both a Th1-dominant microenvironment with INF-gamma and a Th2-dominant microenvironment with IL-4 or IL-13 added to the culture medium. The VEGF, TGF-beta, and TIMP-1 levels in the culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). The activation of NF-kappaB in each experimental condition was determined using an electrophoretic mobility shift assay. RESULTS: Chlamydophila pneumoniae-infected BECs showed enhanced secretion of VEGF, TGF-beta, and TIMP-1 compared with non-infected BECs. The levels of cytokines secreted from BECs were increased more when IL-13 was added to the culture medium. C. pneumoniae-infected BECs also showed increased NF-kappaB activation. CONCLUSIONS: These results suggest that C. pneumoniae plays a role in the pathogenesis of airway remodeling in asthma, revealing a Th2-dominant immune response. Further studies are required to clarify the precise mechanism of C. pneumoniae infection in airway remodeling.

Activity assay for nisin-like acidic bacteriocins using an optimal pH-conditioned gel matrix.

A new zymography for detecting nisin-like acidic bacteriocins was developed using a tricine-sodium dodecyl sulfate (SDS) gel and an acidic gel matrix (pH 4.0). After electrophoresis, proteins in the tricine gel were electrotransferred to an optimal pH-conditioned gel matrix (OP-CGM). The OP-CGM was overlaid with indicator cells (Bacillus cereus) embedded in nutrient broth soft agar (0.8%, w/v). Antibacterial activity shown as a growth inhibition using B. cereus was detected at approximately 3.8kDa. Because nisin is unstable in buffers at pH values over 6.0, the common electrophoretic systems, SDS-polyacrylamide gel electrophoresis and tricine gel, are not suitable for detection of nisin-like acidic bacteriocins.

Production of pure beta-glucan by Aureobasidium pullulans after pullulan synthetase gene disruption.

By disruption of the pullulan synthetase gene (pul) of Aureobasidium pullulans IMS822 KCTC11179BP, we constructed a mutant strain, A. pullulans NP1221, which produced a pure beta-glucan exopolysaccharide. The mutant NP1221 was white, whereas the wild-type strain produced a black dye. When we compared fermentation kinetics between wide-type and mutant strains, the mutant NP1221 did not produce pullulan. Substrate uptake rate and beta-glucan production were similar in both strains. However, the biomass yield of mutant NP1221 was 2.3-fold (9.2 g l(-1)) greater than that of wild-type.

Increased oxidative stress in the airway and development of allergic inflammation in a mouse model of asthma.

BACKGROUND: The exact pathogenic role of oxidative stress in the development of allergic airway inflammation is still largely unknown. OBJECTIVE: To investigate a possible link between increased pulmonary oxidative stress and the pivotal features of asthma during the mounting of an allergic inflammatory response. METHODS: To determine the relationship between oxidative stress and allergic inflammatory responses, we evaluated the sequential kinetics of oxidative stress in the lung, the development of airway inflammation, mucin hypersecretion, and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)-sensitized and challenged mouse with and without antioxidant. Parameters were measured at 9 points for more than 28 days, starting from the first day of OVA challenge with or without antioxidant treatment. The ratio of reduced to oxidized glutathione in the lungs and levels of intracellular reactive oxygen species (ROS) in the bronchial epithelium were serially measured. Bronchoalveolar lavage fluid cells, histopathologic features, and AHR were analyzed at the same time points. RESULTS: The reduced to oxidized glutathione ratio was reduced from immediately after OVA challenge to day 1, remained at this level until day 1, and rapidly recovered to the normal level after more than 2 days. Intracellular ROS levels in the bronchial epithelium followed similar kinetics. The inflammatory cells in bronchoalveolar lavage fluid reached a maximum of 3 days and decreased progressively thereafter. Histopathologic examination revealed that substantial airway inflammation persisted through day 28. The proportion of mucin-producing epithelial cells significantly increased after day 1, reached a maximum at day 3, and remained at this level until day 5. The AHR peaked on day 1 and normalized within 5 days. The pretreatment of antioxidant significantly reduced not only the increased ROS levels but also development of other phenotypes of asthma. CONCLUSION: These results indicate that increased oxidative stress in the lung precedes other pivotal phenotypes of allergic airway disease, suggesting a critical role for increased oxidative stress in the induction of allergic airway inflammation.