Exacerbations Of Disease In Patients Research Articles

P452 Serum Amyloid A for Predicting Surgery and Disease Exacerbation in Patients with Newly Diagnosed Crohn’s Disease

Abstract Background Crohn's disease (CD) is characterized by relapsing-remitting course with highly heterogenous prognosis, ranging from quiescent disease to complicated course with stricturing, penetrating or need of abdominal surgery. Identifying biomarkers that determine their disease course can enable implementing more aggressive preventive strategies. Serum amyloid A (SAA) has been demonstrated to involve in the pathogenesis of Crohn’s disease (CD); however, its prognostic value is still uncertain. This study was determined to explore the prognostic value of SAA for CD-related surgery and disease exacerbation in newly diagnosed CD. Methods We conducted a retrospective cohort study and recruited newly-diagnosed CD patients at the First Affiliated Hospital of Sun Yat-sen University. Level of SAA was detected at diagnosis. The primary outcome was CD-related surgery. The secondary outcome was disease exacerbation, defining as newly developed structuring or penetrating lesions. Association between variables and outcome was evaluated through Kaplan–Meier method and Cox proportional hazard regression analysis. For continuous variables, the optimal cutoff values were determined by using the survminer R package in the analysis of primary outcome. The prognostic model was developed by cox proportional-hazards model. Concordance-index (c-index) was used to assess the predictive ability of the prognostic model. Results During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease exacerbation events were documented. After adjustment, a 14% higher risk for surgery (adjusted hazard ratio, aHR [95% confidence interval]: 1.14 [1.05–1.23]; p=0.001) and a 12% higher risk for disease exacerbation (1.12 [1.05–1.19]; p<0.001) were observed with a 100-unit increase in SAA level. Patients with SAA levels ≥89.2 mg/L had aHRs of 2.08 [1.31–3.28] and 1.72 [1.22–2.41] for CD-related surgery and disease exacerbation, respectively. The association between SAA and outcomes was assessed as linear by the restricted cubic spline. Adding SAA into the model including known risk factors, including age at diagnosis ≥40 years, disease behavior, disease location, and initial biological treatment, led to significant improvement in its predictive ability for surgery (net reclassification index and integrated discrimination index, p<0.001) and disease exacerbation (net reclassification index and integrated discrimination index, p<0.001). Sensitivity analyses showed robust results. Conclusion Our study shows that higher serum SAA level at diagnosis was associated with poorer prognosis, including risk of surgery and disease exacerbation. And prognostic models based on SAA and known risk factors could better predict prognosis.

A radiomics based approach using adrenal gland and periadrenal fat CT images to allocate COVID-19 health care resources fairly

BackgroundThe value of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied extensively. We assess the value of radiomics features from the adrenal gland and periadrenal fat CT images in predicting COVID-19 disease exacerbation.MethodsA total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed a 3D V-net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted.ResultsThe auto-segmentation framework yielded a dice value 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.717, 0.716, 0.736, 0.760, and 0.833 in the validation set. FM and RN had better predictive efficacy than CM (P < 0.0001) in the training set. RN showed that there was no significant difference in the validation set (mean absolute error [MAE] = 0.04) and test set (MAE = 0.075) between predictive and actual results. Decision curve analysis showed that if the threshold probability was between 0.4 and 0.8 in the validation set or between 0.3 and 0.7 in the test set, it could gain more net benefits using RN than FM and CM.ConclusionsRadiomics features extracted from the adrenal gland and periadrenal fat CT images are related to disease exacerbation in patients with COVID-19.

Evaluation of Medication Exposure on Exacerbation of Disease in Patients With Myasthenia Gravis.

In patients with myasthenia gravis (MG), worsening of symptoms poses a risk of respiratory failure which can be precipitated by medication use. Although purported, the risks associated with administration of certain medications are not fully elucidated. Thus, clinical decision support involving a best practice alert was executed to caution providers of drug-disease interactions when ordering a potentially harmful medication. We performed an analysis of the alert overrides with subsequent medication exposure to determine the incidence of MG exacerbations. This retrospective chart-review evaluated adult patients with MG at 2 large academic medical centers via electronic health records between November-2019 and November-2021 who received a medication following override of the clinical decision support tool. The primary outcome was proportion of patient encounters complicated by myasthenic exacerbations after potentially harmful medication administration. Secondary outcomes included changes in motor strength, length of stay, discharge disposition, unplanned level-of-care escalations, and changes to immunosuppressant therapy following medication administration. A total of 70 orders were assessed in 38 patients across 55 encounters. Medications administered during these encounters included macrolides, fluoroquinolones, β-blockers, calcium channel blockers, and magnesium sulfate. Exacerbation of disease occurred in 7 patient encounters (12.7%) and occurred after intravenous magnesium or intravenous labetalol. In 5/7 events, at least 1 other risk factor associated with a myasthenic exacerbation was present. Of the medications reported to potentially worsen MG, intravenous labetalol and intravenous magnesium were the 2 agents associated with myasthenic exacerbations with a higher incidence in patients harboring additional risk factors.

Real-World Treatment Patterns and Switching Following Moderate/Severe Chronic Obstructive Pulmonary Disease Exacerbation in Patients with Commercial or Medicare Insurance in the United States.

There is limited literature regarding real-world treatment patterns of patients with COPD, particularly since the introduction of once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol in 2017. Here, we evaluated treatment patterns of patients with COPD before and after a COPD exacerbation. Retrospective, descriptive study using medical and pharmacy claims data and enrollment information from the Optum® Clinformatics® Data Mart database. Patients aged ≥40 years with ≥1 COPD exacerbation on or after September 18, 2017 were included. The index date was the last day of the first COPD exacerbation (ie day of visit for a moderate exacerbation or discharge date for a severe exacerbation). The baseline period was 12 months prior to index and the follow-up period (≥3 months) spanned from index until the earliest of health plan disenrollment, end of data availability (September 30, 2020), or death. Treatment patterns were evaluated during baseline and follow-up, with a focus on medication switching in the 90 days pre- and post-index. COPD exacerbations were identified in 307,727 patients (125,942 severe; 181,785 moderate). Mean age at index was 72.8 years; 56.3% were female. Before and after first exacerbation, 37.7% and 48.2% of patients used ≥1 controller medication, respectively. In the 90 days pre-index, ICS, LABA, and LAMA medications were used by 27.5% of patients. Of these users, 64.3% remained on the same medication class, 21.7% discontinued, and 14.1% switched medication in the 90 days post-index. Among switchers, 44.0% switched to triple therapy. Most common switches were ICS/LABA to ICS/LABA/LAMA (20.7%) and LAMA to ICS/LABA/LAMA (16.4%). Many COPD exacerbations occur among patients not on controller medications. Although the percentage of patients receiving a controller medication increased following a first exacerbation, it remained below 50%. Of patients receiving controller medications pre-exacerbation, only a small proportion escalated to triple therapy post-exacerbation.

16S rRNA-Based Microbiota Profiling Assists Conventional Culture Analysis of Airway Samples from Pediatric Cystic Fibrosis Patients.

16S-based sequencing provides broader information on the respiratory microbial community than conventional culturing. However, it (often) lacks species- and strain-level information. To overcome this issue, we used 16S rRNA-based sequencing results from 246 nasopharyngeal samples obtained from 20 infants with cystic fibrosis (CF) and 43 healthy infants, which were all 0 to 6 months old, and compared them to both standard (blind) diagnostic culturing and a 16S-sequencing-informed "targeted" reculturing approach. Using routine culturing, we almost uniquely detected Moraxella catarrhalis, Staphylococcus aureus, and Haemophilus influenzae (42%, 38%, and 33% of samples, respectively). Using the targeted reculturing approach, we were able to reculture 47% of the top-5 operational taxonomical units (OTUs) in the sequencing profiles. In total, we identified 60 species from 30 genera with a median of 3 species per sample (range, 1 to 8). We also identified up to 10 species per identified genus. The success of reculturing the top-5 genera present from the sequencing profile depended on the genus. In the case of Corynebacterium being in the top 5, we recultured them in 79% of samples, whereas for Staphylococcus, this value was only 25%. The success of reculturing was also correlated with the relative abundance of those genera in the corresponding sequencing profile. In conclusion, revisiting samples using 16S-based sequencing profiles to guide a targeted culturing approach led to the detection of more potential pathogens per sample than conventional culturing and may therefore be useful in the identification and, consequently, treatment of bacteria considered relevant for the deterioration or exacerbation of disease in patients like those with CF. IMPORTANCE Early and effective treatment of pulmonary infections in cystic fibrosis is vital to prevent chronic lung damage. Although microbial diagnostics and treatment decisions are still based on conventional culture methods, research is gradually focusing more on microbiome and metagenomic-based approaches. This study compared the results of both methods and proposed a way to combine the best of both worlds. Many species can relatively easily be recultured based on the 16S-based sequencing profile, and it provides more in-depth information about the microbial composition of a sample than that obtained through routine (blind) diagnostic culturing. Still, well-known pathogens can be missed by both routine diagnostic culture methods as well as by targeted reculture methods, sometimes even when they are highly abundant, which may be a consequence of either sample storage conditions or antibiotic treatment at the time of sampling.

Comparative Ethics of Modern Payment Models

Comparative Ethics of Modern Payment Models

Association of &lt;i&gt;VEGF&lt;/i&gt; gene rs699947 and rs2010963 polymorphisms with vascular endothelial growth factor levels in the blood serum of children with lupus nephritis

The growth factor genes VEGF and TGFB1 are involved in the normal functioning of the kidneys, and some polymorphic loci of these genes determine a genetic predisposition to the autoimmune diseases, including systemic lupus erythematosus (SLE) and its dangerous complication, lupus nephritis (LN). The products of these genes, in particular, the vascular endothelial growth factor protein and the transforming growth factor β1 protein are used in clinical practice as markers of endothelial dysfunction for early diagnosis of kidney pathology. However, the relationship between the expression of these proteins and the genotypes/alleles of the polymorphic loci of these genes has not been studied enough, which requires clarification of this issue for the child population of Belarus. In this work, we analyzed the associations of the TGFB1 (rs1800469) and VEGF (rs699947 and rs2010963) gene genotypes with the concentration of their products in the blood serum of patients with LN during exacerbation and remission of the disease. The study did not find a significant relationship between polymorphic variants of the TGFB1 gene (rs1800469) and levels of its product in the blood. An association has been established between the rs699947 and rs2010963 polymorphic variants of the VEGF gene and the serum concentration of the gene product in pediatric patients with LN during exacerbation. It was found that the homozygous minor genotype AA of the polymorphic locus rs699947 and the group of genotypes GC + CC containing at least one minor allele of the locus rs2010963 are associated with higher levels of the gene product in the blood serum of children with LN during disease exacerbation (p &lt; 0.001 and p = 0.036, respectively). Thus, VEGF polymorphic variants associated with an increased concentration of the gene product in the blood serum during disease exacerbation can be considered as markers of the risk of disease exacerbation in patients with LN.

Influence of the environment on ragweed pollen and their sensitizing capacity in a mouse model of allergic lung inflammation.

Common ragweed (Ambrosia artemisiifolia) is an invasive plant with allergenic pollen. Due to environmental changes, ragweed pollen (RWP) airborne concentrations are predicted to quadruple in Europe by 2050 and more than double allergic sensitization of Europeans by 2060. We developed an experimental RWP model of allergy in BALB/c mice to evaluate how the number of RWP and how RWP collected from different geographical environments influence disease. We administered RWP six times over 3 weeks intranasally to the mice and then evaluated disease parameters 72 h later or allowed the mice to recover for at least 90 days before rechallenging them with RWP to elicit a disease relapse. Doses over 300 pollen grains induced lung eosinophilia. Higher doses of 3,000 and 30,000 pollen grains increased both eosinophils and neutrophils and induced disease relapses. RWP harvested from diverse geographical regions induced a spectrum of allergic lung disease from mild inflammation to moderate eosinophilic and severe mixed eosinophilic-neutrophilic lung infiltrates. After a recovery period, mice rechallenged with pollen developed a robust disease relapse. We found no correlation between Amb a 1 content, the major immunodominant allergen, endotoxin content, or RWP structure with disease severity. These results demonstrate that there is an environmental impact on RWP with clinical consequences that may underlie the increasing sensitization rates and the severity of pollen-induced disease exacerbation in patients. The multitude of diverse environmental factors governing distinctive patterns of disease induced by RWP remains unclear. Further studies are necessary to elucidate how the environment influences the complex interaction between RWP and human health.

Effects of Muscle Energy Technique and Joint Manipulation on Pulmonary Functions, Mobility, Disease Exacerbations, and Health-Related Quality of Life in Chronic Obstructive Pulmonary Disease Patients: A Quasiexperimental Study.

Chronic obstructive pulmonary disease (COPD) is primarily a disease of the lungs; however, extrapulmonary comorbidities like rib cage stiffness, decreased thoracic spine mobility, postural changes, and skeletal muscle dysfunctions also coexist. Muscle energy technique (MET) and joint manipulation (JM) may help alleviate these musculoskeletal problems. This study was aimed at evaluating the effectiveness of MET and JM on pulmonary functions, dyspnea, chest wall mobility, disease exacerbations, and health-related quality of life in COPD patients. A total of 16 patients (7 women and 9 men) suffering from COPD between the ages of 35 and 65 years participated in the study. Pretest-posttest quasiexperimental design was used. MET was applied to the sternocleidomastoid, anterior scalene, pectoralis major muscles, and at the C4-C6 level of the cervical spine. Maitland JM was performed in the thoracic region at the intervertebral, costovertebral, and costotransverse joints. The treatment intervention lasted for 3 weeks. FEV1/FVC, maximum inspiratory pressure (MIP), SpO2, modified Borg dyspnea scale (MBDS), COPD assessment test (CAT), mMRC dyspnea scale, BODE index, right and left hemidiaphragm excursion, and chest wall expansion at T4 and T10 levels were the outcome measures. Significant improvement (p < 0.05) was observed in FEV1/FVC, MIP, SpO2, MBDS, CAT, mMRC dyspnea scale, BODE index, and chest expansion at T4 and T10 levels. Only for the hemidiaphragm excursion, no significant (p > 0.05) improvement was observed. Combined application of MET to accessory respiratory muscles and cervical spine and JM to thoracic spine improved pulmonary functions, chest wall mobility, and health-related quality of life and reduced dyspnea and disease exacerbations in patients with mild to moderate COPD.

Effects of anti-SARS-CoV-2 vaccination on safety and disease exacerbation in patients with Behçet syndrome in a monocentric cohort.

AimVaccination represents a cornerstone in mastering the coronavirus disease 2019 (COVID‐19) pandemic. There is a paucity of data regarding the safety of COVID‐19 vaccines in patients with rheumatic diseases such as Behçet syndrome (BS). The present study aimed to investigate the side‐effects and post‐vaccine disease exacerbation rates of COVID‐19 vaccines in a BS cohort.MethodsWe retrospectively evaluated 450 BS patients followed in our clinic who met the criteria of the International Study Group. COVID‐19 vaccination status, type of vaccine received (Pfizer‐BioNTech vs CoronaVac), post‐vaccine side‐effects and exacerbations were evaluated by interviewing patients over the phone or face to face. Behçet's Disease Current Activity Form (BDCAF) scores were calculated for BS symptoms before and after vaccination.ResultsIn all, 287 patients received at least one dose of the COVID‐19 vaccine. Of the total number of COVID‐19 vaccines (n = 639), 379 (59%) were Pfizer‐BioNTech vaccines and 257 (41%) were CoronaVac vaccines. The number of side‐effects after first, second, third and fourth vaccine doses were 151 (52.6%), 135 (49.4%), 29 (42.6%), and 3 (30%), respectively. BS exacerbation after first, second, third, and fourth vaccine doses were 151 (52.6%), 135 (49.4%), 16 (23.5%), and 3 (30%), respectively. Injection site pain/swelling was the most common side‐effect at all vaccine doses followed by fatigue and arthralgia.ConclusionCOVID‐19 vaccines are well tolerated in patients with BS, and more side‐effects develop after mRNA vaccines. Regardless of the vaccine type, exacerbations after the COVID‐19 vaccine are common, predominantly mucocutaneous and articular involvement, and exacerbations in the form of other organ involvement are rare.

Cluster analysis of nasal cytokines during rhinovirus infection identifies different immunophenotypes in both children and adults with allergic asthma.

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

Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation.

Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.

Unsupervised Cluster Analysis of Nasal Cytokines During RV Infection Identifies Distinct Immunophenotypes in Both Children and Adults with Allergic Asthma

Infection with rhinovirus (RV) is a major risk factor for disease exacerbations in patients with allergic asthma. In this study we sought to identify nasal cytokine immunophenotypes that link to virus-induced episodes in children and adults.

Use of azurocidin (heparin binding protein) and interleukin-1ß as prognostic indicators in COVID-19 patients

Objective: Considering the published manuscripts on this subject, it is thought that IL-1B and azurocidin may be diagnostic and prognostic factors in severe COVID-19 disease. This study aimed to determine whether azurocidin and IL-1β are useful biomarkers and are associated with disease exacerbation in patients needing advanced treatment options. Material and Method: Our study was performed retrospectively. The data of a total of 291 patients followed in the hospital due to COVID-19 were collected. Among these patients, 66 randomly selected patients were included in this study. The control group consisted of 24 healthy individuals referred to the infectious disease outpatient clinic who weren’t no diagnosis of COVID-19 infection or any other infection. After the samples were taken into tubes without anticoagulant, they were kept at room temperature for 30 min. Afterwards, it was centrifuged at 1000xg for 15 min at +4° according to the instructions of the ELISA kit we used. The remaining serum was transferred to Eppendorf tubes and stored at −80° throughout this study. Results: A statistically significant strong positive correlation was determined between IL1β and azurocidin. A statistically significant weak positive correlation was found between IL1β and CRP, ferritin and neutrophil count, weak negative correlation with albumin, and moderately strong positive correlation with leukocyte count. Moreover, a statistically significant weak positive correlation was found between azurucidin and CRP, ferritin, and neutrophil counts. Conclusion: Azurocidin and IL-1β may serve as a potential therapeutic target for patients at risk of developing systemic multi-organ failure, with improved patient prognosis and prevention of death in severely ill patients. Although these results may contribute to the improvement of the follow-up and treatment of the patients and reduce mortality rates, there is a need for randomized controlled studies with a larger number of patients to be performed in the future.

P16‐24: Clinical impact of sarcopenia on chemotherapy‐triggered exacerbation of interstitial lung disease in patients with non‐small cell lung cancer

P16‐24: Clinical impact of sarcopenia on chemotherapy‐triggered exacerbation of interstitial lung disease in patients with non‐small cell lung cancer

A Radiomics Based Approach Using Adrenal Gland and Periadrenal Fat CT Images to Fairly Allocate COVID-19 Health Care Resources

Background: COVID-19 disease severity is associated with endocrine system. We hypothesis radiomics features from the adrenal gland and periadrenal fat CT images can assess possibilities of disease exacerbation.Methods: A total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed 3D V-Net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted.Findings: The auto-segmentation framework yielded a dice value of 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.717, 0.716, 0.736, 0.760, and 0.833, respectively in the validation set. FM and RN had better predictive efficacy than CM (P Interpretation: Radiomics features extracted from adrenal gland and periadrenal fat CT images are related to disease exacerbation in patients with COVID-19.Funding Information: The study was supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT320003）; The Science and Technology Foundation of Guizhou Province (QKHPTRC[2019]5803); The Guiyang Science and Technology Project (ZKXM[2020]4); Beijing Medical and Health Foundation (YWJKJJHKYJJ-B20261CS) and Chongqing Science and Health Joint Medical Research Project (2021MSXM052).Declaration of Interests: The authors have declared that no conflict of interest exists.Ethics Approval Statement: This multicenter study was approved by the ethics committees of all participating hospitals (2020,NO.01). Because of its retrospective nature, the need to obtain informed consent in advance was waived. The study was performed according to the principles of the declaration of Helsinki.

Effect of Inhaled Corticosteroid Withdrawal on Chronic Obstructive Pulmonary Disease Exacerbations in Patients Taking Triple Therapy at Baseline.

PurposeIn the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β2-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk. However, many patients were not taking triple therapy before study participation. This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.Patients and MethodsThe effect of ICS withdrawal on moderate/severe exacerbation risk in the subgroup of WISDOM patients taking triple therapy before enrolling in the study was evaluated in this post hoc analysis. Additionally, the effect of ICS withdrawal in patients with a history of ≥2 exacerbations in the previous year and various blood eosinophil counts was assessed.ResultsOverall, 39.0% (n=970: ICS continuation, 479; ICS withdrawal, 491) of the WISDOM trial population were taking triple therapy at screening. Baseline characteristics were generally similar between groups. Moderate/severe exacerbation risk between the ICS withdrawal and continuation groups (hazard ratio [HR], 1.05; 95% confidence interval [CI]: 0.89–1.25) was not increased in patients taking triple therapy at screening versus the overall trial population (HR [95% CI]: 1.06 [0.94–1.19]). However, in patients with a history of ≥2 exacerbations, exacerbation risk (HR [95% CI]) increased nominally with blood eosinophil count from 1.07 [0.81–1.41] (≥100 cells/μL) to 1.45 [0.58–3.60] (≥400 cells/μL).ConclusionConsistent with results from the overall WISDOM trial population, ICS withdrawal did not increase exacerbation risk in patients taking triple therapy at screening. Patients with a history of frequent exacerbations and higher blood eosinophil counts could benefit from continuation of ICS-based therapy.

A242 EXERCISE AND PHYSICAL ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND RECOMMENDATIONS

Abstract Background Inflammatory bowel disease (IBD) is a chronic life-long condition affecting 0.25% of the North American population. Childhood onset IBD is particularly aggressive, with disease often characterised by poor growth, severe unpredictable abdominal pain and frequent school absences. Treatment involves lifelong medications, which do not always resolve symptoms and carry increased cumulative risks of infections, malignancy, or other adverse effects. Exercise has been suggested as a method of ameliorating some of the symptoms associated with IBD. To date, few studies have investigated the role of exercise and physical activity in paediatric IBD patients. Aims We conducted a systematic review assessing the role of exercise and physical activity in paediatric IBD. Methods This Level III systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. An electronic database search of Pubmed, Google Scholar, and Cochrane used the search terms “(physical activity or exercise), (Inflammatory Bowel Disease), and (children or paediatric)”. Of the 1458 articles identified during the two rounds of review, only 21 articles met final inclusion criteria. Results Three main themes emerged from the review: 1) prescriptive exercise and physical activity ameliorated symptoms IBD and improved physical well-being, 2) patients who actively engage in exercise and physical activity show improved markers of inflammation and decreased future risk of disease, 3) exercise and physical activity improves the mental health and well-being of paediatric IBD patients. The results recommended 30–60 minutes, 6 times per week of mild to moderate aerobic exercise activity. It was noted that vigorous and high intensity exercise was well-tolerated by most IBD patients. Further, exercise prescription should be tailored to individual needs. Conclusions Exercise and physical activity improves mental and physical health and well-being of paediatric IBD patients, including decreasing the risk of future disease exacerbation in patients with mild to moderate disease activity. Clinicians and practitioners should consider actively prescribing exercise and physical activity to IBD patients as part of a standard treatment algorithm. Funding Agencies None

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Meta-analysis of macrolide maintenance therapy for prevention of disease exacerbations in patients with noncystic fibrosis bronchiectasis.

Macrolide maintenance treatment remains controversial for patients with noncystic fibrosis (non-CF) bronchiectasis, we performed a meta-analysis to estimate the benefits and safety of macrolides therapy in adults and children with non-CF bronchiectasis. PubMed, Embase, the Cochrane Library, and Web of Science databases were searched for all the randomized controlled trials of macrolides for treating non-CF bronchiectasis. The primary outcome was improvement of bronchiectasis exacerbations. Secondary outcomes included adverse events and macrolide resistance. A total of 10 studies involving 602 patients were included in the analysis. Pooled results showed that macrolide therapy significantly reduced the number of patients who suffered from exacerbations (RR = 1.56, 95% CI = 1.14-2.14, P = .006, I = 72%), number of patients who experienced at least 3 exacerbations (RR = 0.55, 95% CI = 0.39-0.77, P = .0005, I = 40%), average exacerbations per patient during the observation time (SMD = -0.69, 95% CI = -1.06 to -0.32, P = .0002, I = 60%), and bronchiectasis exacerbation-related admissions (RR = 0.46, 95% CI = 0.23-0.96, P = .04, I = 0%). Specified subgroup analyses of the number of patients free from exacerbations were further performed; macrolide therapy showed a significant benefit in both children (RR 5.03, 95% CI 2.02-12.50, P = .0005, I = 45%) and adults (RR = 1.66, 95% CI = 1.37-2.02, P < .00001, I = 79%); azithromycin showed a significant reduction on the number of patients who suffered from exacerbations (RR = 2.25, 95% CI = 1.67-3.02, P < .00001, I = 0%), was different from erythromycin (RR = 1.33, 95% CI = 0.92-1.94, P = .13, I = 0%) and roxithromycin (RR = 1.14, 95% CI = 0.97-1.35, P = .11, I = 0%). The pooled results also showed no higher risk of adverse events (RR = 0.98, 95% CI = 0.85-1.13, P = .80, I = 8%), even a lower risk of severe adverse events (RR = 0.53, 95% CI = 0.33-0.85, P = .009, I = 0%). However, a higher risk of macrolide resistance (RR = 3.59, 95% CI 2.6-4.96, P < .00001, I = 0%) was observed. For both children and adults with non-CF bronchiectasis, macrolide maintenance therapy can effectively reduce bronchiectasis exacerbations, especially for patients with more frequent exacerbations and needing hospital treatment. Azithromycin was more effective than other macrolides. Macrolide maintenance therapy did not increase the risk of adverse events, but may increase the risk of macrolide resistance.