Osteoarthritis year in review 2022: imaging.

PURPOSE: This narrative review summarizes original research focusing on imaging in osteoarthritis (OA) published between April 1st 2021 and March 31st 2022. We only considered English publications that were in vivo human studies. METHODS: The PubMed, Medline, Embase, Scopus, and ISI Web of Science databases were searched for "Osteoarthritis/OA" studies based on the search terms: "Radiography", "Ultrasound/US", "Computed Tomography/CT", "DXA", "Magnetic Resonance Imaging/MRI", "Artificial Intelligence/AI", and "Deep Learning". This review highlights the anatomical focus of research on the structures within the tibiofemoral, patellofemoral, hip, and hand joints. There is also a noted focus on artificial intelligence applications in OA imaging. RESULTS: Over the last decade, the increasing trend of using open-access large databases has reached a plateau (from 17 to 37). Compositional MRI has had the most prominent use in OA imaging and its biomarkers have been used in the detection of preclinical OA and prediction of OA outcomes. Most noteworthy, there has been an accelerated rate of publications on the implications of artificial intelligence, used in developing prediction models and performing trabecular texture analysis, in OA imaging (from 17 to 154). CONCLUSIONS: While imaging has maintained its key role in OA research, publication trends have shown an emphasis on the integration of AI. During the past year, MRI has maintained the highest prevalence in usage while US and CT remain as readily available modalities. Finally, there has been a notable uptake in the development and validation of AI techniques used to perform texture analysis and predict OA progression.

Imaging in Osteoarthritis.

Osteoarthritis (OA) is the most frequent form of arthritis with major implications on both individual and public health care levels. The field of joint imaging, and particularly magnetic resonance imaging (MRI), has evolved rapidly due to the application of technical advances to the field of clinical research. This narrative review will provide an introduction to the different aspects of OA imaging aimed at an audience of scientists, clinicians, students, industry employees, and others who are interested in OA but who do not necessarily focus on OA. The current role of radiography and recent advances in measuring joint space width will be discussed. The status of cartilage morphology assessment and evaluation of cartilage biochemical composition will be presented. Advances in quantitative three-dimensional morphologic cartilage assessment and semi-quantitative whole-organ assessment of OA will be reviewed. Although MRI has evolved as the most important imaging method used in OA research, other modalities such as ultrasound, computed tomography, and metabolic imaging play a complementary role and will also be discussed.

Osteoarthritis year in review 2019: imaging.

OBJECTIVE: To provide a narrative review of original articles on osteoarthritis (OA) imaging published between April 1, 2018 and March 30, 2019. METHODS: All original research articles on OA imaging published in English between April 1, 2018 and March 30, 2019 were identified using a PubMed database search. The search terms of "Osteoarthritis" or "OA" were combined with the search terms "Radiography", "X-Rays", "Magnetic Resonance Imaging", "MRI", "Ultrasound", "US", "Computed Tomography", "Dual Energy X-Ray Absorptiometry", "DXA", "DEXA", "CT", "Nuclear Medicine", "Scintigraphy", "Single-Photon Emission Computed Tomography", "SPECT", "Positron Emission Tomography", "PET", "PET-CT", or "PET-MRI". Articles were reviewed to determine relevance based upon the following criteria: 1) study involved human subjects with OA or risk factors for OA and 2) study involved imaging to evaluate OA disease status or OA treatment response. Relevant articles were ranked according to scientific merit, with the best publications selected for inclusion in the narrative report. RESULTS: The PubMed search revealed a total of 1257 articles, of which 256 (20.4%) were considered relevant to OA imaging. Two-hundred twenty-six (87.1%) articles involved the knee joint, while 195 (76.2%) articles involved the use of magnetic resonance imaging (MRI). The proportion of published studies involving the use of MRI was higher than previous years. An increasing number of articles were also published on imaging of subjects with joint injury and on deep learning application in OA imaging. CONCLUSION: MRI and other imaging modalities continue to play an important role in research studies designed to better understand the pathogenesis, progression, and treatment of OA.

Are contrast-enhanced and non-contrast MRI findings reflecting synovial inflammation in knee osteoarthritis: a meta-analysis of observational studies.

OBJECTIVE: To determine the correlation between knee synovitis assessed on contrast-enhanced (CE) and non-contrast enhanced (NCE) magnetic resonance imaging (MRI) with histology in patients with knee osteoarthritis. METHODS: A comprehensive literature search was performed, and related articles published through July 2018 were extracted. Spearman correlation coefficients of MRI-based scores with histology reports were pooled using random effects model. To evaluate presence of publication bias, Egger test was performed. RESULTS: Of 2377 identified records, eight studies consisting of 246 MRI exams were included. Two studies reported results of dynamic CE (DCE)-MRI examinations (81 knees) and two studies reported results of NCE-MRI. There were moderate positive correlations between CE-MRI scores and macroscopic (r = 0.53 (95% Confidence Interval (CI):0.37-0.66), P < 0.001) as well as microscopic (r = 0.56 (0.39-0.69), P < 0.001) histology. DCE-MRI were strongly correlated (r = 0.71 (0.58-0.80), P-value<0.001), with microscopic histology reports, while the correlation for NCE-MRI was low positive (r = 0.44 (0.20-0.63), P < 0.001). Meta-regression analysis showed that pooled correlation coefficients of DCE-MRI were significantly higher than CE-MRI (Slope = 0.29, SE = 0.13, P-value = 0.02). CE-MRI were also correlated with inflammatory infiltrate (r = 0.42), while the correlations for cell number of synovial lining (r = 0.27) and level of fibrosis (r = 0.29, P < 0.001) were very low. CONCLUSION: Static and dynamic CE-MRI evaluation of knee synovitis were positively correlated with macroscopic and microscopic features of synovial membrane inflammation. Among the features of synovial tissue inflammation, CE-MRI scores correlated best with the inflammatory infiltrates of synovial tissue. Paucity of current evidence warrants further studies to assess performance of NCE-MRI on determining knee synovitis.

Deep learning risk assessment models for predicting progression of radiographic medial joint space loss over a 48-MONTH follow-up period.

OBJECTIVE: To develop and evaluate deep learning (DL) risk assessment models for predicting the progression of radiographic medial joint space loss using baseline knee X-rays. METHODS: Knees from the Osteoarthritis Initiative without and with progression of radiographic joint space loss (defined as ≥ 0.7 mm decrease in medial joint space width measurement between baseline and 48-month follow-up X-rays) were randomly stratified into training (1400 knees) and hold-out testing (400 knees) datasets. A DL network was trained to predict the progression of radiographic joint space loss using the baseline knee X-rays. An artificial neural network was used to develop a traditional model for predicting progression utilizing demographic and radiographic risk factors. A combined joint training model was developed using a DL network to extract information from baseline knee X-rays as a feature vector, which was further concatenated with the risk factor data vector. Area under the curve (AUC) analysis was performed using the hold-out test dataset to evaluate model performance. RESULTS: The traditional model had an AUC of 0.660 (61.5% sensitivity and 64.0% specificity) for predicting progression. The DL model had an AUC of 0.799 (78.0% sensitivity and 75.5% specificity), which was significantly higher (P < 0.001) than the traditional model. The combined model had an AUC of 0.863 (80.5% sensitivity and specificity), which was significantly higher than the DL (P = 0.015) and traditional (P < 0.001) models. CONCLUSION: DL models using baseline knee X-rays had higher diagnostic performance for predicting the progression of radiographic joint space loss than the traditional model using demographic and radiographic risk factors.

Association of patella alta with worsening of patellofemoral osteoarthritis-related structural damage: data from the Osteoarthritis Initiative.

OBJECTIVES: To determine the association between Insall-Salvati ratio (ISR), a measure of patella alta, and worsening of Magnetic Resonance Imaging (MRI)-based osteoarthritis (OA)-related patellofemoral joint structural damages over 24-month in participants of the Osteoarthritis Initiative (OAI). DESIGN: Using weighted random sampling method, we selected a sample of 500 knees (from 1,677 knees with available baseline and 24-months MRI OA Knee Score (MOAKS) measurements), which is OAI-representative regarding knee OA-related factors (i.e., baseline age, sex, body mass index (BMI), and radiographic Kellgren-Lawrence grading). The ISR was measured in all enrolled knees using baseline sagittal 3T-MRI plane by three radiologists. Baseline and 24-month MOAKS variables for patellofemoral bone marrow lesions (BMLs), cartilage damages, and osteophytes were extracted, and the associations between ISR and 24-month worsening of these 3T-MRI features were evaluated using multivariable regression models. After computing receiver operating characteristic curves, the optimal cutoff point of ISR for indicating worsening of patellofemoral OA was determined. P-values were adjusted for multiple comparisons and false discovery rate (FDR) adjusted P-values were reported. RESULTS: In this longitudinal analysis, 24-month worsening of BML (odds ratio [OR] (95% confidence interval [95% CI]):11.18 (3.35-39.6), adjusted-p-value:<0.001) and cartilage scores (OR:7.39 (1.62-34.71), adjusted-p-value:0.042) in lateral patella was associated with higher baseline ISR. However, higher ISR was not statistically associated with medial patellar or medial and lateral trochlear BML or cartilage scores worsening. We determined the optimal cutoff point of ISR≥1.14 (95% CI: 1.083-1.284) for predicting lateral patellofemoral OA-related structural damages worsening over 24-months (sensitivity:73.73%; specificity: 66.67%). CONCLUSIONS: Given the uncertainly surrounding the results, our overall findings suggest that ISR could be considered as a predictor of lateral patellofemoral OA-related structural damages worsening with the optimal cutoff point of ≥1.14 using knee sagittal MRI measurements.

Tibiofibular syndesmosis in asymptomatic ankles: initial kinematic analysis using four-dimensional CT.

AIM: To evaluate the reliability of ankle syndesmotic measurements and their changes during active motion using four-dimensional computed tomography (4DCT) examination in asymptomatic ankles. MATERIALS AND METHODS: 4DCT was performed on both ankles of patients with signs and symptoms of unilateral ankle instability. Ankles from the asymptomatic side of 10 consecutive patients were included in this analysis. Five ankle syndesmotic measurements were adopted from the available literature and performed by two fellowship-trained foot and ankle surgeons: (1) syndesmotic anterior distance (SAD); (2) syndesmotic posterior distance (SPD); (3) syndesmotic translation (ST); (4) syndesmotic tibiofibular angle (STFA); and (5) ankle tibiofibular angle (ATFA). A Monte Carlo simulation was also performed to obtain exact p-values with 99% confidence intervals. RESULTS: Excellent interobserver reliability was observed among the two readers for four out of five measurements (intra-class correlation coefficients [ICC]: 0.767-0.995, p<0.001-0.020). The ICC values for SAD were not statistically significant (ICC=0.548 and 0.569 for dorsi and plantarflexion respectively, p=0.1). Among the five measurements, only ST measurements had significant changes during active motion (median [interquartile range] for change: -0.70 mm [-1.6-0.10]; p=0.012). Of the above measurements, only the ST measurements demonstrated a negative linear association with the tibiocalcaneal angle during active motion (beta=-2.5, p=0.04). CONCLUSIONS: Reliable quantitative kinematic assessment of ankle syndesmosis can be performed using 4DCT examination. Syndesmotic measurements remain unchanged during ankle motion except for the syndesmotic translation, which tends to decrease during plantar flexion.

Osteoarthritis year in review 2017: updates on imaging advancements.

OBJECTIVE: This narrative review covers original research publications related to imaging advancements in osteoarthritis (OA) published in the English language between 1st April 2016 and 30th April 2017. METHODS: Relevant human studies (excluding pre-clinical and in vitro studies), were searched and selected from PubMed database using the search terms of "osteoarthritis (OA)" in combination with "radiography", "magnetic resonance imaging (MRI)", "computed tomography (CT)", "ultrasound", "positron emission tomography (PET)," "single-photon emission computed tomography (SPECT)," and "scintigraphy". The included studies were sorted according to their relevance, novelty, and impact. Original research articles with both imaging advancements and novel clinical information were discussed in this review. RESULTS: A large portion of the published studies were focused on MRI-based semi-quantitative and quantitative (morphological and structural) metrics of the knee joint to assess OA-related structural damages. New imaging technologies, such as PET, have been investigated for OA diagnosis and characterization, the delineation of predictive factors for OA progression, and to monitor the treatment responses. CONCLUSION: Advanced imaging modalities play a pivotal role in OA research, and make a significant contribution to our understanding of OA diagnosis, pathogenesis, risk stratification, and prognosis.

Bisphosphonates intake and its association with changes of periarticular bone area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: To determine the association between bisphosphonate treatment with the change of periarticular bone area and three-dimensional (3D) shape in participants of the Osteoarthritis Initiative (OAI) study. DESIGN: Using propensity score (PS) matching method in females, 48 bisphosphonate users and 105 non-users, who were matched for osteoarthritis (OA) and osteoporosis (OP) related factors were included. Baseline and 24-month magnetic resonance imaging (MRI)-based periarticular bone area and 3D shape measurements were used. The association between bisphosphonate intake and 24-month interval changes of the periarticular bone area and 3D shape were evaluated using paired Wilcoxon signed rank test. We used conditional logistic regression models for determining the association between bisphosphonate intake and periarticular bone change, defined using the standard deviation of difference (SDD) and reliable change index (RCI) methods. P-values have been adjusted for multiple comparisons using Benjamini & Hochberg procedure and false discovery rate (FDR)-adjusted P-values were reported. RESULTS: The 24-month interval increases in the periarticular bone area in medial side of tibia were significantly greater in non-users than users (FDR-adjusted P-value: 0.002). There was an approaching significance trend for lower medial tibial periarticular bone area expansion in bisphosphonate users in comparison with non-users (For 1SDD change, odds ratio 95% confidence interval (OR (95% CI)): 0.514 (0.271-0.975), FDR-adjusted P-value: 0.085) (For 1.96RCI change, OR (95% CI): 0.552 (0.309-0.986), FDR-adjusted P-value: 0.085). CONCLUSIONS: Bisphosphonate intake was associated with a reduction in the odds (approaching but not achieving significance) of expansion periarticular bone area, specifically in the medial tibial sub-region.

Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients.

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.

Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative.

OBJECTIVES: To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). DESIGN: Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic +) and 173 referent (Analgesic -) subjects were included. Analgesic + and - subjects had analgesics in all and none of their visits, respectively. Analgesic + and - subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic + and - subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. RESULTS: Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic + and 15 among Analgesic - subjects (P = 0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic + and 12 among Analgesic - subjects (P = 0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic + subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. CONCLUSIONS: Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR.

Role of physical activity in cartilage damage progression of subjects with baseline full-thickness cartilage defects in medial tibiofemoral compartment: data from the Osteoarthritis Initiative.

OBJECTIVE: To assess the association between physical activity and cartilage damage progression in medial tibiofemoral compartment (MTFC) using 2-year follow-up magnetic resonance imaging (MRI) in subjects with denuded areas of subchondral bone (dABs) at the central weight-bearing medial femur (cMF) at baseline MRI examination. METHODS: One hundred subjects from the Osteoarthritis Initiative (OAI) progression cohort with dABs at the cMF at 3T MRI at baseline (51% men; mean age 62.2 years, range 45-79) were included. Sagittal 3D dual-echo steady-state with water excitation images were used to assess 2-year MTFC cartilage change. Associations between 2-year average Physical Activity Scale for the Elderly (PASE) and 2-year MTFC cartilage change were assessed by linear regression analysis. Subgroup analyses were performed. RESULTS: No associations between PASE and 2-year MTFC cartilage change were observed in the entire cohort. Similarly, in the subgroup with cartilage loss during the 2 years, the non-refuted confidence intervals for the regression coefficients were tightly clustered around the null value (regression coefficients for: mean cMF.ThCtAB = -0.00059; 98.75% CI: -0.00130 to 0.00012), cMF.dAB% = 0.02176; 98.75% CI: -0.02514 to 0.06865, Mean MT.ThCtAB = -0.00013; 98.75% CI: -0.00064 to 0.00038, MT.dAB% = 0.02543; 98.75% CI: -0.01485 to 0.06571. CONCLUSION: In the entire group of subjects with dABs at the cMF at baseline, no association between physical activity and 2-year MTFC cartilage change was detected. Due to the limited sample size of our study, small-sized effects may not have been detected in our study.

Association of mucoid degeneration of anterior cruciate ligament with knee meniscal and cartilage damage.

OBJECTIVE: To assess the prevalence of anterior cruciate ligament (ACL) mucoid degeneration in patients referred for routine knee magnetic resonance (MR) imaging, and its association with age and structural joint damage. METHOD: Four independent radiologists assessed 413 consecutive knee MR examinations for the presence of a normal or ruptured ACL, or ACL mucoid degeneration. Knees with ACL mucoid degeneration were frequency matched by age, sex, and MR field strength with consecutive control knees with a normal ACL (1:2 ratio). Differences in meniscal and cartilage damage of the tibiofemoral compartments, as determined by the Whole-Organ MR Imaging Score (WORMS) system, were compared by Mann-Whitney U tests. Multivariable logistic regression analysis identified the association of ACL mucoid degeneration with severe MTFC cartilage damage (WORMS≥5). RESULTS: Patients with ACL mucoid degeneration (n = 36; 36% males; median age 55.5 years, range: 26-81) were older than patients with a normal (P < 0.001) or ruptured ACL (P < 0.001), without sex predilection (P = 0.76), and were more frequently diagnosed at 3 T (12%) compared to 1.5 T (2%). Knees with ACL mucoid degeneration had statistically significantly more medial meniscal (P < 0.001) and central and posterior medial tibiofemoral compartment (MTFC) cartilage (P < 0.001) damage compared with control knees (n = 72), but there were no differences in patients ≤50 years (P = 0.09 and 0.32, respectively). In multivariable logistic regression, severe MTFC cartilage damage (WORMS≥5) was significantly associated with ACL mucoid degeneration (odds ratio 4.09, 95% confidence interval 1.29-12.94, P = 0.016). CONCLUSION: There is a strong association between ACL mucoid degeneration and cartilage damage in the central and posterior MTFC, especially in patients >50 years.

Assessment of image quality in soft tissue and bone visualization tasks for a dedicated extremity cone-beam CT system.

OBJECTIVE: To assess visualization tasks using cone-beam CT (CBCT) compared to multi-detector CT (MDCT) for musculoskeletal extremity imaging. METHODS: Ten cadaveric hands and ten knees were examined using a dedicated CBCT prototype and a clinical multi-detector CT using nominal protocols (80 kVp-108mAs for CBCT; 120 kVp- 300 mAs for MDCT). Soft tissue and bone visualization tasks were assessed by four radiologists using five-point satisfaction (for CBCT and MDCT individually) and five-point preference (side-by-side CBCT versus MDCT image quality comparison) rating tests. Ratings were analyzed using Kruskal-Wallis and Wilcoxon signed-rank tests, and observer agreement was assessed using the Kappa-statistic. RESULTS: Knee CBCT images were rated "excellent" or "good" (median scores 5 and 4) for "bone" and "soft tissue" visualization tasks. Hand CBCT images were rated "excellent" or "adequate" (median scores 5 and 3) for "bone" and "soft tissue" visualization tasks. Preference tests rated CBCT equivalent or superior to MDCT for bone visualization and favoured the MDCT for soft tissue visualization tasks. Intraobserver agreement for CBCT satisfaction tests was fair to almost perfect (κ ~ 0.26-0.92), and interobserver agreement was fair to moderate (κ ~ 0.27-0.54). CONCLUSION: CBCT provided excellent image quality for bone visualization and adequate image quality for soft tissue visualization tasks. KEY POINTS: • CBCT provided adequate image quality for diagnostic tasks in extremity imaging. • CBCT images were "excellent" for "bone" and "good/adequate" for "soft tissue" visualization tasks. • CBCT image quality was equivalent/superior to MDCT for bone visualization tasks.

Evaluation of pisotriquetral motion pattern using four-dimensional CT: initial clinical experience in asymptomatic wrists.

AIM: To characterise the normal motion pattern of the pisotriquetral (PT) joint during wrist extension and flexion, as well as observer performance of measurements using four-dimensional (4D)-computed tomography (CT) acquisitions and double-oblique multiplanar reconstruction (MPR) technique in asymptomatic contralateral joints of patients with unilateral wrist pain. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act (HIPAA)-compliant institutional review board-approved study, 4D-CT was performed on the asymptomatic contralateral wrists of 10 patients (mean age: 46 years; M/F: 6/4) for comparison to the symptomatic side. Two independent observers defined the "oblique-sagittal" plane for PT joint measurements. Measurements were obtained for the anteroposterior (AP) interval and craniocaudal (CC) excursion during the extension-flexion arc of wrist motion. RESULTS: The median (interquartile range) of the AP interval was 0.65 mm (0.55-1 mm) in extension, 1.1 mm (0.8-1.82 mm) in the neutral position, and 4.65 mm (2.07-5.87 mm) in flexion. Likewise, the median of the CC excursions in asymptomatic wrists were 0 mm in extension, 0.27 mm (0-0.37 mm) in the neutral position, and 0.28 mm (0.18-0.31 mm) in flexion. The AP interval measurements obtained at wrist flexion were larger than measurements obtained at wrist extension. There was a strong consistency in AP interval difference measurements between the two observers (ICC=0.80; p<0.01); however, CC excursion difference measurements did not reach the significance threshold between the two observers (ICC=0.40; p=0.11). CONCLUSION: PT joint kinematics in asymptomatic wrists demonstrates an increase in AP interval and CC excursion during wrist flexion. MPR techniques provide good interobserver agreements for AP interval measurements. The reported intervals for asymptomatic joints can be used as a reference for asymptomatic wrists.

Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort.

BACKGROUND: Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. OBJECTIVE: We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. METHODS: A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. RESULTS: We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze.