Purpose:Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods:This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV1) or percent predicted peak expiratory flow rate (ppPEFR) ≥80%, and no long-term oral corticosteroid (LTOCS) use. Results:A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤0.001), no exacerbations (p<0.001), well- or partly controlled asthma (p=0.047), a ppFEV1 or ppPEFR ≥80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion:Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.

Background:Reversal of methacholine induced bronchoconstriction (MIB) is routinely achieved by administering 200 mcg salbutamol via pressurized metered dose inhaler (pMDI). The propellant in the inhaler (hydrofluoroalkane-134a) contributes to greenhouse gas emissions, negatively impacting the environment. One alternative to delivering bronchodilator would be using the Aerogen® Solo vibrating mesh nebulizer (VMN). Using the VMN to deliver methacholine during MCT as well as bronchodilator after MCT could reduce the carbon footprint of testing by eliminating pMDI inhaler use. The current study compared bronchodilator reversal of MIB via pMDI to that of VMN. Methods:Sixteen individuals exhibiting airway hyperresponsiveness to methacholine completed a double blind, double dummy, placebo controlled, randomized, three-way crossover study. At each visit, participants underwent MCT followed by administration of placebo or salbutamol (200 mcg) via pMDI or VMN. Lung function and heart rate measurements were captured before and at 5, 10, 15, 30, 45 and 60 minutes after treatment administration. Results:Pre MCT FEV1 did not differ between the three treatment arms (RM ANOVA p = 0.741). When corrected for repeated measures, the reduction in FEV1 after MCT (30.5%, 27.4% and 24.8% for placebo, pMDI and VMN, respectively) was similar across groups. Mean FEV1 values after administration of salbutamol via pMDI or VMN were significantly greater than after placebo at all timepoints (RM ANOVA p < 0.001) with no significant difference between methods of salbutamol administration. Mean heartrate did not differ between treatments before or after treatment. Conclusion:Use of the VMN for delivering salbutamol to reverse MIB is feasible. Doing so adds functionality to the use of this nebulizer for performing methacholine bronchoprovocation and reduces the negative environmental impact of pMDI inhalers.

This review article explores the methacholine challenge test (MCT), a bronchoprovocation technique used to assess airway hyperresponsiveness (AHR), a hallmark of asthma. The article begins by tracing the historical development of the MCT, including early studies that established its clinical relevance in diagnosing asthma. The physiological mechanisms underlying AHR are discussed, with emphasis on how these contribute to bronchoconstriction. The article also highlights advances in MCT methodology, clinical utility in ruling out asthma, factors that influence the interpretation of MCT results, and limitations of the test. Finally, the review suggests future directions for improving MCT.

Background Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma. Methods Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed. Results 46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference - 5.81%, 95% CI - 10.69 -- 0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively. Conclusion Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.

Background House dust mite (HDM) induces greater responses than other allergens during allergen bronchoprovocation (ABP) testing. The two standardized methods for reporting results of ABP tests are the maximal percent fall in forced expiratory volume in one second (FEV 1, max ; %) and the area under the FEV 1 vs time curve (AUC; %FEV 1 x min). The relationship between these methods has not been previously investigated. Aims We aimed to measure the correlation between FEV 1, max and AUC during the early asthmatic response (EAR) and the late asthmatic response (LAR), and to determine if the EAR recovery period for HDM would be longer than other allergens (cat, grass, horse, and ragweed). Methods We retrospectively calculated the AUC and correlation between FEV 1, max and AUC during the EAR (0-2 h) and LAR (3-7 h) for each allergen. We compared EAR (0-3 h) and LAR (3-7 h) FEV 1, max , AUC and absolute difference in FEV 1, max to the most recovered FEV 1 (FEV 1, min ). We performed pairwise comparisons of correlation and slope values using Fischer’s r to z transformation and t-tests, respectively. AUC and absolute differences in FEV 1, max and FEV 1, min were compared using a one-way ANOVA test, followed by a post-hoc Scheffe test. Results Correlation between the FEV 1, max and AUC during the EAR (0-2 h) (n = 221) was 0.807, and was 0.798 during the LAR (3-7 h) (n = 157 of 221), (difference p = 0.408). The EAR (0-3 h) AUC and FEV 1, max did differ between allergens (both p < 0.0001) but the LAR (3-7 h) AUC and FEV 1, max did not (p = 0.548 and 0.824, respectively). HDM did not have a larger AUC or FEV 1, max , than all other allergens during the EAR (0-3 h) or the LAR (3-7 h) . The absolute difference between the FEV 1, max and FEV 1, min during the EAR (0-3 h) did not differ between allergens (p = 0.180). Conclusion The FEV 1, max and AUC for both the EAR (0-2 h) and LAR (3-7 h) had excellent correlation, with no significant difference. Thus, significant bronchoconstriction will likely result in a longer recovery period. There was no evidence of delayed EAR (0-3 h) recovery following HDM challenges, so HDM did not induce a larger response compared to all the other allergens examined. Registration: Not registered. This is not a clinical trial. (This study is a retrospective analysis of data collected during several registered trials.)

BackgroundThymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma.MethodsThis was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18–60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once-daily inhaled ecleralimab or placebo. Primary end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV1) during the late asthmatic response (LAR) measured by area under the curve (AUC3–7h) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide (FENO) were secondary and exploratory end-points.Results28 subjects were randomised to ecleralimab (n=15) or placebo (n=13). On day 84, ecleralimab significantly attenuated LAR AUC3–7hby 64% (p=0.008), LAR% by 48% (p=0.029), and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC0–2h(p=0.097) and EAR% (p=0.105).FENOlevels were significantly reduced from baseline throughout the study (p<0.05), except at 24 h post-allergen (day 43 and day 85). Overall, ecleralimab was safe and well tolerated.ConclusionEcleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation, and was safe in subjects with mild atopic asthma.

While static mechanical forces govern resting lung volumes, dynamic forces determine tidal breathing, airflow, and changes in airflow and lung volume during normal and abnormal breathing. This section will examine the mechanisms, measurement methodology, and interpretation of the dynamic changes in airflow and lung volume that occur in health and disease. We will first examine how the total work of breathing can be described by the parameters of the equation of motion, which determine the pressure required to move air into and out of the lung. This will include a detailed description of airflow characteristics and airway resistance. Next, we will review the changes in pressure and flow that determine maximal forced inspiration and expiration, which result in the maximal flow-volume loop and the clinically important forced expired volume in 1 second. We will also assess the mechanisms and interpretation of bronchodilator responsiveness, dynamic hyperinflation, and airways hyperresponsiveness.

Abstract Introduction Up to 80% of autistic children experience sleep disturbances. Sleep hygiene guidelines advise patients to maintain consistent bedtimes and waketimes for the purpose of regulating one’s circadian rhythm. However, the relationship between bedtime and waketime variability and sleep outcomes in autistic children is unclear, and so the current study examines these associations. Methods One hundred thirty autistic children (Mage = 8.81 yrs, SD = 1.92 yrs, range = 6-12 yrs, 71% male) completed two weeks of daily sleep diaries with parental assistance and concurrently wore actigraphic wrist watches (Actiwatch-2, Respironics). Rest intervals in Actiware software were set using visual inspection while referencing self-reported bed/waketime. Boundaries of rest intervals were defined as the time when the child first attempted sleep to the time when the child vacated bed. Subjective and objective estimates of bedtime, waketime, total wake time during attempted sleep periods, and total sleep time were obtained. Bayesian multi-level models obtained individual estimates of average variability in bedtime and waketime. Multiple linear regressions were then used to examine associations between subjective and objective bedtime and waketime variability and total wake time and total sleep time, controlling for age and average levels of bed/waketime variability. Models were separated out by subjective/objective sleep outcomes (i.e., subjective waketime variability predicting subjective total sleep time). Results Greater objective waketime variability was associated with less objective total sleep time (B=-38.80, p<.001, partial eta-squared = .071). Greater subjective waketime variability was associated with longer subjective total wake time (B = 18.58, p=.02, partial eta-squared = .058) and shorter subjective total sleep time (B=-70.60, p<.001, partial eta-squared = 0.227). Conclusion While results do not possess causal implications, greater subjective and objective waketime variability are associated with poorer sleep outcomes in autistic children. Effect sizes ranged from approximately medium to large. Results suggest that bedtime variability may not be related to sleep outcomes in autistic children. Future studies should examine whether reductions in waketime variability mediate the effect of behavioral insomnia interventions on improved sleep in autistic children. Support (if any) MU Research Board Grant (McCrae, PI); Department of Defense Autism Research Program (McCrae, PI; W81XWH2010399); Thompson Center for Autism and Neurodevelopmental Disorders.

"The “ABCs” of DEGs in Airway Hyperresponsiveness." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –

Abstract Introduction Arousal dysregulation (over- or under-arousal) and executive functioning (EF) difficulties are positively correlated and often experienced by autistic children. Arousal and task performance (e.g., EF) are connected, such that there is an optimal arousal level for an optimal performance and arousal dysregulation reduces task performance. Up to 80% of autistic children experience sleep problems, and sleep problems are positively correlated with arousal dysregulation and EF difficulties. Thus, sleep may moderate the relationship between arousal and EF in autistic children. Given that sleep is modifiable through behavioral sleep treatment, it is important to better understand these relationships in autistic children. This study examined whether subjective and objective sleep moderated the relationship between HRV and EF among autistic children. Methods Children with autism spectrum disorder (N=65), verbal IQ >70, and parent reported sleep complaints (Mage=8.95, SD=2.01, range 6-12; 74% male) completed 14 days of sleep diaries (with parental assistance) and actigraphy, Holter Monitoring (8-mins at rest), and the Connor’s Continuous Performance Test (CPT)-III (ages 8+) or Connor’s Kiddie CPT-II (ages 4-7.11). Multiple regressions (SPSS PROCESS) examined whether sleep (subjective/objective wake after sleep onset-WASO, total sleep time-TST) moderated associations between arousal (standard deviation of normal-to-normal R-R-intervals-SDNN, proportion of adjacent R-R intervals differing by >50 ms-PNN50) and EF (CPT-perseverations, omissions, commissions). Analyses controlled for age. Results Objective WASO moderated associations between SDNN and CPT-perseverations (R2=.27, p=.03). At highest WASO, higher SDNN was associated with greater perseverations, t(1,65)=5.00, p=.029. Subjective TST moderated associations between PNN50 and CPT-perseverations (R2=.32, p=.01). At highest TST, higher PNN50 was associated with greater perseverations t(1,65)=4.27, p=.04. Conclusion When autistic children sleep more and have greater sleep fragmentation, EF may suffer (i.e., greater response repetition) if arousal is not high enough. While our finding for sleep fragmentation (indicative of poor sleep) is consistent with existing literature, that for greater sleep (indicative of better sleep) is not. This suggests the relationships amongst these constructs are complex in autism, and more research using longitudinal and experimental methodology and perhaps even examining other aspects of TST (e.g., variability) are needed. Support (if any) DOD Autism Research Program (McCrae, PI; W81XWH2010399); NIAMS (R01AR055160/R01AR005160- S1; P1,McCrae).

The alarmin cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 are epithelial cell-derived mediators that contribute to the pathobiology and pathophysiology of asthma. Released from airway epithelial cells exposed to environmental triggers, the alarmins drive airway inflammation through the release of predominantly T2 cytokines from multiple effector cells. The upstream positioning of the alarmins is an attractive pharmacological target to block multiple T2 pathways important in asthma. Blocking the function of TSLP inhibits allergen-induced responses including bronchoconstriction, airway hyperresponsiveness, and inflammation, and subsequent clinical trials of an anti-TSLP monoclonal antibody, tezepelumab, in asthma patients demonstrated improvements in lung function, airway responsiveness, inflammation, and importantly, a reduction in the rate of exacerbations. Notably, these improvements were observed in patients with T2-high and with T2-low asthma. Clinical trials blocking IL-33 and its receptor ST2 have also shown improvements in lung function and exacerbation rates; however, the impact of blocking the IL-33/ST2 axis in T2-high versus T2-low asthma is unclear. To date, there is no evidence that IL-25 blockade is beneficial in asthma. Despite the considerable overlap in the cellular functions of IL-25, IL-33, and TSLP, they appear to have distinct roles in the immunopathology of asthma.

Abstract Introduction Fatigue is related to various adverse health outcomes. Mean levels of some common sleep variables, such as total sleep time (TST), sleep onset latency (SOL), and wake after sleep onset (WASO), have been associated with fatigue. However, intraindividual variability (IIV) of sleep parameters might play an independent role in sleep’s relationship with fatigue. Understanding fatigue is particularly important for parents of children with autism spectrum disorder (ASD) given fatigue's negative associations with positive parenting and implementation of child interventions. This preliminary study examined linear associations between subjective sleep IIV and mean fatigue levels in parents of children on the autism spectrum. Methods The sample included 66 parents who expressed interest in a behavioral treatment sleep study for their school-aged children diagnosed with ASD (6-12 years old; NCT04545606). All parents (Mage=37.03, SD=6.53; 91% female) completed daily electronic diaries over a two-week baseline period. Daily fatigue rating was collected using a visual analog scale (0-100) and averaged within individuals. Within-individual standard deviations of subjective TST, SOL, and WASO were calculated to estimate IIV. Data were analyzed in R (v4.1.2) using multiple linear regression models controlling for participant age, gender, and individual sleep parameter means. Results Bivariate correlations between sleep variable IIV and average fatigue indicated a positive association between TST variability and average fatigue, r(64)=0.33, p<0.01. Multiple regression analyses showed that greater IIV of TST was associated with higher average fatigue (β=0.14, 95%CI [0.01, 0.27], sr2=0.06, p=0.041). No significant associations were found between average fatigue level and IIV of WASO or SOL. Conclusion Results suggest that greater TST variability may be one factor independently contributing to higher fatigue levels in parents of children on the autism spectrum, which warrants further examination of sleep variability in this population. Future research could explore IIV of additional sleep parameters, fatigue IIV as an outcome, alternative methods of sleep measurement, and study designs that address causation. Increased insight into these connections might inform the importance of considering sleep interventions for both children and parents, and potential subsequent treatment benefits. Support (If Any) MU Research Board Grant (McCrae, PI); Department of Defense Autism Research Program (McCrae, PI; W81XWH2010399).

PURPOSE The purpose of this scoping review was to identify existing clinical and basic science knowledge surrounding the effect of muscarinic receptor antagonism on allergen-induced airway responses to inform future clinical research in this area. METHODS Multiple advanced searches were performed using the National Library of Medicine PubMed search engine. Each search began with two terms; for example, "atropine and asthma" or "tiotropium and airway inflammation". Results were then further refined to include terms such as "allergen" or "ovalbumin (OVA)". Abstracts of refined searches were reviewed for relevance to allergic asthma and allergen-induced airway responses including the early and late asthmatic responses, airway inflammation and tissue remodelling. There was no restriction regarding publication date. Reference lists of selected papers were also reviewed for relevant publications. RESULTS Nine human clinical trial publications and fourteen animal model publications were identified. In humans, single dose atropine (n=4), ipratropium (n=4) or oxitropium (n=1) administered pre-challenge produced equivocal effects on allergen-induced early asthmatic responses as reported but favored inhibition in eight of nine studies after re-analyses. Animal model investigations (n=14) showed mostly favorable results, especially with respect to airway inflammation and tissue remodelling, although two studies were negative, and one study showed a worsening in allergen induced airway inflammation following muscarinic receptor antagonism. CONCLUSION Existing human and animal model data suggest muscarinic receptor antagonism may be beneficial in preventing allergen induced airway responses in those with allergic asthma. Additional human research utilizing current standardized methodologies is required.

Long-acting muscarinic antagonists (LAMAs) have been approved as an add-on treatment for moderate-to-severe asthma—tiotropium as an individual inhaler and umeclidinium as a combination inhaler. Data from ovalbumin-sensitized and challenged animals treated with muscarinic antagonists, including tiotropium, reveal reductions in inflammatory markers and allergen-associated changes. 1 Ohta S Oda N Yokoe T Tanaka A Yamamoto Y Watanabe Y et al. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy. 2010; 40: 1266-1275 Crossref PubMed Scopus (122) Google Scholar ,2 Kistemaker LEM Bos IST Menzen MH Maarsingh H Meurs H Gosens R. Combination therapy of tiotropium and ciclesonide attenuates airway inflammation and remodeling in a guinea pig model of chronic asthma. Respir Res. 2016; 17: 13 Crossref PubMed Scopus (37) Google Scholar Inhaled muscarinic antagonists may, therefore, protect the airways of patients with allergic asthma through both bronchodilators (ie, decrease the early asthmatic response [EAR]) and anti-inflammatory action (ie, decrease type 2 [T2] eosinophilic airway inflammation). Single-dose short-acting muscarinic antagonists (eg, ipratropium) partially inhibit allergen-induced EARs in human studies. 3 Cockcroft DW Ruffin RE Haargreave FE. Effect of Sch1000 in allergen-induced asthma. Clin Allergy. 1978; 8: 361-372 Crossref PubMed Scopus (35) Google Scholar ,4 Orehek J Gayrard P Ch Grimaud Charpin J. Allergen-induced bronchoconstriction in asthma: antagonistic effect of a synthetic anticholinergic drug (author's transl)]. Bull Physiopathol Respir (Nancy). 1975; 11: 193-201 PubMed Google Scholar There are no human data on LAMA efficacy against allergen-induced asthmatic responses. Here, we report the results of a pilot investigation of the efficacy of regular use of tiotropium on the allergen-induced EAR and T2 eosinophilic airway inflammation.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review.

Introduction: Loss of bronchoprotection against direct and indirect acting stimuli following regular use of inhaled beta2-agonists occurs with both short and long-acting formulations. Comparatively little is known about the development of tolerance following regular use of inhaled muscarinic receptor antagonists. Two investigations with the short-acting muscarinic receptor antagonist ipratropium bromide have reported no tolerance after regular use against inhaled methacholine. To our knowledge, there are no data regarding loss of bronchopro-tection following regular use of long-acting muscarinic receptor antagonist. We therefore looked at the effect of daily dosing with tiotropium on methacholine induced bronchoconstriction in a population of mild asthmatics.Methods: We performed a randomized, double-blind, placebo-controlled cross-over study comparing tiotropium Respimat (R) 5 mu g to placebo in adult asthmatics. Each treatment arm began with baseline methacholine challenge followed immediately by treatment administration. One hour later a post treatment methacholine challenge was performed. Participants dosed daily (two puffs) at home for the next six days and returned to the lab on Day 8 for a final dose of treatment 1 h prior to methacholine challenge.Results: The average doubling dose increase in methacholine PD20 following a single dose of tiotropium was 3.9 doubling doses whereas that following placebo was 0.93 (p = 0.003). After regular use, methacholine PD20 was further increased to 6.4 doubling doses following tiotropium whereas that following placebo decreased by 0.57 doubling doses (p < 0.001).Conclusion: LAMA are indicated for use as add-on monotherapy or in triple therapy combination for poorly controlled asthma. It may be reassuring to know therefore, that regular use does not result in loss of broncho-protection like that which occurs with beta2-agonist bronchodilators.

Allergen inhalation challenges (AICs) are widely used in research to assess airway responses to allergen exposure and predict the therapeutic effectiveness of various medications.1 The characteristics of early asthmatic response (EAR) and late asthmatic response (LAR) are often described in general terms.2-4 Original research findings focus on mean data. We are not aware of any data objectively documenting the responses of individual participants, and it is important to acknowledge that mean data do not accurately reflect the range of individual responses and the relevant safety implications of performing AICs. We therefore sought to directly characterize the timing, magnitude, and recovery characteristics of the EAR and LAR with an emphasis on individual responses.

Introduction: CSJ117 is a potent neutralizing antibody fragment against human Thymic stromal lymphopoietin (TSLP).