[Chronic obstructive pulmonary disease (COPD): eosinophilia and novel drug therapies]. / Chronisch-obstruktive Lungenerkrankung (COPD) ­ Eosinophilie und neue Arzneimitteltherapien.

BACKGROUND: The phenotyping of chronic obstructive pulmonary disease (COPD) has increasingly gained attention in recent years, as it leads to new and individualized therapeutic concepts. OBJECTIVE: The aim is to provide an overview of the heterogeneity of COPD and to summarize current drug therapy concepts, particularly in the context of eosinophilic airway inflammation. DATA: Several prospective, randomized, placebo-controlled studies have shown a reduction in exacerbations and overall mortality with inhaled triple therapy using an inhaled corticosteroid and dual bronchodilation. The higher the eosinophils in the blood, the greater the expected effect. In addition, a reduction in exacerbations with biologics in COPD with eosinophilia has been demonstrated for dupilumab. Eosinophil-guided therapy for acute exacerbations is the subject of current research. CONCLUSION: For COPD without exacerbations, dual bronchodilation forms the basis of inhaled therapy. With exacerbations, inhaled triple therapy is indicated for patients with a blood eosinophil count of ≥ 300/µl. This type of treatment may also be useful when eosinophils are between 100 and 300/µl. Therapy with dupilumab is a possible option for the eosinophilic phenotype in the near future.

Evaluation of the Quality of ED Management for Patients with COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with exacerbations and high risk of serious outcomes. Our goal was to determine the appropriateness of the ED management of COPD exacerbations. METHODS: This observational cohort study incorporated a health records review and included COPD exacerbation cases seen at two large academic EDs. We included all patients with the primary diagnosis of COPD exacerbation. From the electronic medical record, demographic and clinical data were abstracted, and the Ottawa COPD Risk Score (OCRS) was calculated for each. Short-term serious outcomes (SSO) included ICU admission, intubation, myocardial infarction, non-invasive positive pressure ventilation (NIV), and death at 30 days. Cases were judged for appropriateness of treatment according to explicit indications and standards developed a priori. RESULTS: We enrolled 500 cases with mean age 71.9, female 51.2%, admitted 50.2%, and death 4.4%. The calculated OCRS score was >2 for 70.8% of patients. The treatments provided were inhaled beta-agonists (82.6%), inhaled anticholinergics (76.6%), corticosteroids (75.2%), antibiotics (71.0%), oxygen (63.8%), NIV (8.8%) and intubation (0.6%). Overall, 50.0% of cases were judged to have had inadequate management due to missing treatments. Specifically, the proportion of missing treatments were inhaled beta agonist (17.0%), inhaled anticholinergic (22.6%), corticosteroids (24.4%), antibiotics (12.8%), and NIV (2.0%). CONCLUSIONS: Adequate treatment of COPD exacerbation was lacking in 50.0% of patients in these two large academic EDs. Concerning were the number of patients not receiving corticosteroids or antibiotics. Implementation of explicit treatment standards should lead to improved patient care of this common and serious condition.

Obstructive Sleep Apnea Effects on Chronic Airway Disease Exacerbations-Missed Opportunities for Improving Outcomes in Chronic Obstructive Pulmonary Disease and Asthma.

In patients with chronic obstructive pulmonary disease (COPD) and asthma, exacerbations determine the natural history of both diseases. Patients with both respiratory diseases who suffer from obstructive sleep apnea (OSA) as a comorbidity (overlap syndromes) have a higher risk of exacerbations and hospitalization. In cases of OSA/COPD and OSA/asthma, continuous positive airway pressure treatment is indicated. Adequate adherence to therapy appears to reduce exacerbations and their severity, especially in OSA/COPD overlap. However, there is a lack of randomized trials that definitively demonstrate this evidence.

Comparison of BAP65, DECAF, PEARL, and MEWS Scores in Predicting Respiratory Support Need in Hospitalized Exacerbation of Chronic Obstructive Lung Disease Patients.

OBJECTIVE: Prognostic models aid clinical practice with decision-making on treatment and hospitalization in exacerbation of chronic obstructive lung disease (ECOPD). Although there are many studies with prognostic models, diagnostic accuracy is variable within and between models. SUBJECTS AND METHODS: We compared the prognostic performance of the BAP65 score, DECAF score, PEARL score, and modified early warning score (MEWS) in hospitalized patients with ECOPD, to estimate ventilatory support need. RESULTS: This cross-sectional study consisted of 139 patients. Patients in need of noninvasive or invasive mechanical ventilation support are grouped as ventilatory support groups (n = 54). Comparison between receiver operating characteristic curves revealed that the DECAF score is significantly superior to the PEARL score (p = 0.04) in discriminating patients in need of ventilatory support. DECAF score with a cutoff value of 1 presented the highest sensitivity and BAP65 score with a cutoff value of 2 presented the highest specificity in predicting ventilatory support need. Multivariable analysis revealed that gender played a significant role in COPD exacerbation outcome, and arterial pCO2 and RDW measurements were also predictors of ventilatory support need. Within severity indexes, only the DECAF score was independently associated with the outcome. One-point increase in DECAF score created a 1.43 times higher risk of ventilatory support need. All severity indexes showed a correlation with age, comorbidity index, and dyspnea. BAP65 and DECAF scores also showed a correlation with length of stay. CONCLUSION: Objective and practical classifications are needed by clinicians to assess prognosis and initiate treatment accordingly. DECAF score is a strong candidate among severity indexes.

Changes in disease burden and treatment reality in patients with severe asthma.

BACKGROUND: Biologics are clinically available for patients with severe asthma, but changes in asthma control over time are unknown. We examined changes in disease burden and treatment in severe asthma patients. METHODS: This retrospective study used a Japanese health insurance database (Cross Fact) and included patients aged ≥16 years treated continuously with an inhaled corticosteroid (ICS) for a diagnosis of asthma in each calendar year from 2015 to 2019. Severe asthma was defined as annual use of high-dose ICS plus one or more asthma controller medications four or more times, oral corticosteroids for ≥183 days, or biologics for ≥16 weeks. Changes in asthma exacerbations, prescriptions, and laboratory testing were examined. RESULTS: Demographic characteristics were similar throughout the study. The number and proportion of patients with severe asthma among those with asthma increased (2724; 15.3% in 2015 vs 4485; 19.0% in 2019). The proportion of severe asthma patients with two or more asthma exacerbations decreased from 24.4% to 21.5%. Odds ratios (95% confidence interval) of ≥2 asthma exacerbations in each year compared with 2015 were 0.96 (0.85-1.08) in 2016 and 0.86 (0.76-0.97) in 2017, with significant reductions observed in subsequent years. Short-acting beta agonists and oral corticosteroid prescriptions for asthma exacerbations decreased and long-acting muscarinic antagonist and biologic prescriptions for maintenance treatment increased. CONCLUSIONS: This study showed improvements in disease burden and treatment in severe asthma patients. There remains an unmet medical need for patients with severe asthma, given the proportion who continue to have asthma exacerbations.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Management of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in Hospitalized Patients From Admission to Discharge: A Comprehensive Review of Therapeutic Interventions.

Chronic obstructive pulmonary disease (COPD) is a common and debilitating condition that often necessitates hospitalization for exacerbations. Since COPD exacerbations can cause significant morbidity and mortality, managing them is crucial for patient care. Effective management of COPD exacerbations is essential to prevent complications, as COPD exacerbations are associated with increased healthcare costs and decreased quality of life. This review aims to comprehensively discuss the management of COPD exacerbations, covering various pharmacologic and non-pharmacologic strategies. These include inhaled bronchodilators, systemic steroids, antibiotics, invasive and non-invasive ventilation, oxygen therapy, smoking cessation, immunization with pneumococcal vaccine, inhalers at discharge, pulmonary rehabilitation, long-term oxygen therapy (LTOT), ambulatory oxygen therapy, short-burst oxygen therapy, extracorporeal membrane oxygenation (ECMO), lung volume reduction surgery (LVRS), endobronchial procedures, and lung transplant. It is drawn upon various sources, including clinical studies, systemic reviews, and observational studies, to provide a comprehensive overview of current practices and identify areas for future research and innovation in managing COPD exacerbations. Addressing these areas of interest can improve patient outcomes and quality of life.

Investigating the role of uric acid and uric acid-to-creatinine ratio as a predictive factor of chronic obstructive pulmonary disease exacerbation in 2019.

INTRODUCTION: Serum uric acid has been suggested as an independent marker of oxidative metabolism in chronic obstructive pulmonary disease (COPD), a disease with significant social, health, and economic burden. Therefore, we aimed to investigate the role of this factor in COPD exacerbation. METHODS: We investigated 20- to 70-year-old patients who were admitted due to COPD exacerbation (acute phase) or presented to the pulmonary clinic for follow-up (non-acute phase). Correlation of uric acid and uric acid-to-creatinine ratio (UCR) with multiple factors and their predictive performance for more exacerbations and acute phase of COPD was investigated (receiver operating characteristic [ROC] analysis). RESULTS: Overall, 63 patients were enrolled in this study, of whom 79.4% were men. Acute-phase group encompassed 79.4% of the population with a greater rate of heavy smoking and average exacerbation in a year (p-value = 0.009 and <0.001). The mean of uric acid and UCR was 5.6 (SD, 2.35) and 4.4 (SD, 1.9) in the total population, respectively, and were significantly higher in the acute phase and patients with frequent exacerbations (FE ≥ 3 exacerbations a year), p-value <0.05. The area under the curve (AUC) of ROC analysis showed a high performance of uric acid and UCR for predicting acute phase (0.84 [95%CI, 0.73-0.96] and 0.86 [0.74-0.98]), FE (0.72 [0.60-0.85] and 0.75 [0.63-0.87]), and FE among acute-phase patients (AUC, 0.63 [0.46-0.79] and 0.66 [0.50-0.81], respectively). CONCLUSION: Uric acid and UCR could be invaluable predictors of frequent exacerbation and the acute phase of COPD. Therefore, they might be applicable in evaluating the severity and progress of the disease.

Physical Activity Profiles among Patients Admitted with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

People with hospitalised acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exhibit low levels of physical activity (PA) and increased risks of future exacerbations. While methods to objectively measure and express PA are established for people with stable COPD, less clarity exists for people during AECOPD. Further, the relationship between PA during AECOPD and clinically relevant outcomes remains uncertain. The purpose of the study was to evaluate how much PA (step count and intensity) people accumulate during hospitalised AECOPDs, and the effect of accumulated inpatient PA (expressed via differing metrics) on length of stay (LOS), PA recovery, and readmission risk. This study was a secondary analysis of prospective observational cohort data collected with Actigraph wActiSleep-BT devices from patients with AECOPD in a Melbourne hospital from 2016 to 2018. Step counts and PA intensity throughout the hospital admission and at one-month follow-up were collected and analysed. Sixty-eight participants were recruited for inpatient measurement, and 51 were retained for follow-up. There were no significant changes in step count or intensity across the inpatient days, but 33/51 (65%) of participants demonstrated a clinically meaningful improvement in steps per day from 3817.0 to 6173.7 at follow-up. Participants spent most time sedentary and in light PA, with both PA metrics demonstrating significant influences on LOS and follow-up PA intensity, but with generally low explanatory power (R2 value range 7-22%). Those who had LOS < 5 days spent significantly less time sedentary and more time in light PA than those with LOS ≥ 5 days (p < 0.001 for both). Time spent sedentary or in light PA appears to be the most promising metric to associate with clinically relevant outcomes related to recovery following AECOPD. These findings can inform future clinical practice for the evaluation of inpatient PA to better establish its role in the clinical management of patients with AECOPD.

Association Between Rome Classification Among Hospitalized Patients With COPD Exacerbations and Short-Term and Intermediate-Term Outcomes.

BACKGROUND: Recently, the Rome proposal updated the definition of exacerbation of COPD (ECOPD). However, such severity grade has not yet demonstrated intermediate-term clinical relevance. RESEARCH QUESTION: What is the association between the Rome severity classification and short-term and intermediate-term clinical outcomes? STUDY DESIGN AND METHODS: We retrospectively grouped hospitalized patients with ECOPD according to the Rome severity classification (ie, mild, moderate, severe). Baseline, clinical, microbiologic, gas analysis, and laboratory variables were collected. In addition, data about the length of hospital stay and mortality (in-hospital and a follow-up time line from 6 months until 3 years) were assessed. RESULTS: Of the 347 hospitalized patients, 39% were categorized as mild, 31% were categorized as moderate, and 30% were categorized as severe. Overall, patients with severe ECOPD had an extended length of hospital stay. Although in-hospital mortality was similar among groups, patients with severe ECOPD presented a worse prognosis in all follow-up time points. The Kaplan-Meier curves show the role of the severe classification in the cumulative survival at 1 and 3 years (Gehan-Breslow-Wilcoxon test, P = .032 and P = .004, respectively). The multivariable Cox regression analysis showed a higher risk of death at 1 year when patients presented a severe (hazard ratio, 1.99; 95% CI, 1.49-2.65) or moderate grade (hazard ratio, 1.47; 95% CI, 1.10-1.97) compared with a mild grade. Older patients (aged ≥ 80 years), patients requiring long-term oxygen therapy, or patients reporting previous ECOPD episodes had a higher mortality risk. A BMI between 25 and 29 kg/m2 was associated with a lower risk. INTERPRETATION: The Rome classification makes it possible to discriminate patients with a worse prognosis (severe or moderate) until a 3-year follow-up.

Serum vitamin D levels can be predictive of psoriasis flares up after COVID-19 vaccination: a retrospective case control study.

Introduction: Many patients with chronic inflammatory dermatosis such as psoriasis usually ask about the safety of COVID-19 vaccination and if it would affect the course of their disease. Indeed, many case reports, case series and clinical studies, reporting psoriasis exacerbation following vaccination against COVID-19, were published during the pandemic. Also, many questions arise regarding the existence of exacerbating factors of these flare ups, including environmental triggers such as the insufficiency of vitamin D levels. Methods: This is a retrospective study that measures alterations in psoriasis activity and severity index (PASI) not exceeding 2 weeks after the first and second dose of COVID-19 vaccinations in the reported cases and assesses whether such changes have any association with patients' vitamin D levels. We retrospectively reviewed the case records of all patients with a documented flare up after COVID-19 vaccination in our department as well as those who did not, during a year. Results: Among them, we found 40 psoriasis patients that had reported vitamin D levels in the form of 25-hydroxy-vitamin D within 3 weeks after vaccination, including 23 with exacerbation and 17 without exacerbation. Performing χ2 and t-test controls for psoriasis patients with and without flare-ups, a statistically significant dependence emerged in the seasons of summer [χ2(1) = 5.507, p = 0.019], spring [χ2(1) = 11.429, p = 0.001] and in the categories of vitamin D [χ2(2) = 7.932, p = 0.019], while the mean value of vitamin D for psoriasis patients who did not have exacerbation (31.14 ± 6.67 ng/mL) is statistically higher [t(38) = 3.655, p = 0.001] than the corresponding value of psoriasis patients who had an exacerbation (23.43 ± 6.49 ng/mL). Discussion: This study indicates that psoriasis patients with insufficient (21-29 ng/mL) or inadequate (<20 ng/mL) levels of vitamin D are more prone to postvaccination aggravation of the disease while vaccination in summer, a period with the most extent photo-exposition, can be a protective factor.

Cardiovascular Autonomic Function and Incident Chronic Obstructive Pulmonary Disease Hospitalizations in Atherosclerosis Risk in Communities.

Rationale: The autonomic nervous system extensively innervates the lungs, but its role in chronic obstructive pulmonary disease (COPD) outcomes has not been well studied. Objective: We assessed relationships between cardiovascular autonomic nervous system measures (heart rate variability [HRV] and orthostatic hypotension [OH]) and incident COPD hospitalization in the multicenter ARIC (Atherosclerosis Risk In Communities) study. Methods: We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals between baseline (1987-1989) autonomic function measures (HRV measures from 2-minute electrocardiograms and OH variables) and incident COPD hospitalizations through 2019. Adjusted analyses included demographic data, smoking status, lung function, comorbidities, and physical activity. We also performed analyses stratified by baseline airflow obstruction. Results: Of the 11,625 participants, (mean age, 53.8 yr), 56.5% were female and 26.3% identified as Black. Baseline mean percentage predicted forced expiratory volume in 1 second was 94 ± 17% (standard deviation), and 2,599 participants (22.4%) had airflow obstruction. During a median follow-up time of 26.9 years, there were 2,406 incident COPD hospitalizations. Higher HRV (i.e., better autonomic function) was associated with a lower risk of incident COPD hospitalization. Markers of worse autonomic function (OH and greater orthostatic changes in systolic and diastolic blood pressure) were associated with a higher risk of incident COPD hospitalization (hazard ratio for the presence of OH, 1.5; 95% confidence interval, 1.25-1.92). In stratified analyses, results were more robust in participants without airflow obstruction at baseline. Conclusions: In this large multicenter prospective community cohort, better cardiovascular autonomic function at baseline was associated with a lower risk of subsequent hospitalization for COPD, particularly among participants without evidence of lung disease at baseline.

Characteristics and outcomes of patients with chronic obstructive pulmonary disease admitted to the intensive care unit due to acute hypercapnic respiratory failure.

BACKGROUND: The study aimed to describe the clinical course, outcomes, and prognostic factors of chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure. METHODS: This retrospective study involved patients with acute hypercapnic respiratory failure due to COPD of any cause admitted to the intensive care unit (ICU) for non-invasive or invasive mechanical ventilation (IMV) support between December 2015 and February 2020. RESULTS: One hundred patients were evaluated. The main causes of acute hypercapnic respiratory failure were bronchitis, pneumonia, and heart failure. The patients' mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 23.0±7.2, and their IMV rate was 43%. ICU, in-hospital, and 90-day mortality rates were 21%, 29%, and 39%, respectively. Non-survivors had more pneumonia, shock within the first 24 hours of admission, IMV, vasopressor use, and renal replacement therapy, along with higher APACHE II scores, lower admission albumin levels and PaO2/ FiO2 ratios, and longer ICU and hospital stays than survivors. Logistic regression analysis identified APACHE II score (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.017-1.317; P=0.026), admission PaO2/FiO2 ratio (OR, 0.989; 95% CI, 0.978-0.999; P=0.046), and vasopressor use (OR, 8.827; 95% CI, 1.650-47.215; P=0.011) as predictors of ICU mortality. APACHE II score (OR, 1.099; 95% CI, 1.021-1.182; P=0.011) and admission albumin level (OR, 0.169; 95% CI, 0.056-0.514; P=0.002) emerged as predictors of 90-day mortality. CONCLUSIONS: APACHE II scores, the PaO2/FiO2 ratio, vasopressor use, and albumin levels are significant short-term mortality predictors in severely ill COPD patients with acute hypercapnic respiratory failure.

The Clinical Association between Aspergillus fumigatus and Respiratory Outcomes in Adolescents and Adults with Cystic Fibrosis.

Rationale: The clinical significance of Aspergillus fumigatus (Af) detection in the absence of allergic bronchopulmonary aspergillosis in cystic fibrosis (CF) airways remains unclear. Yet, some clinicians initiate antifungal therapy for Af-positive respiratory cultures out of concern for infection in people with CF. Objectives: To determine the association between the presence of Af and respiratory outcomes in individuals with CF. Methods: We conducted a prospective longitudinal cohort study of 206 adults and adolescents (age 14 yr and older) with CF and collected sputum for selective fungus culture. We assessed clinical outcome measurements, including patient-reported outcomes (measured by the Cystic Fibrosis Questionnaire-Revised), spirometry, and number of pulmonary exacerbations (PEx) for a 1-year period. We used mixed-effects linear models to determine the association between positive Af culture results, defined as Af detection in sputum culture at the study visit, with both respiratory domain score and forced expiratory volume in 1 second (FEV1) percent predicted, adjusted for confounders. Mixed-effects Poisson regression models were employed to examine the association between positive Af culture results and PEx events. We explored the association between Af history, defined as Af detection at baseline or within 2 years of enrollment, and respiratory outcomes. Results: Af prevalence was 10.3% (95% confidence interval [CI], 6.8, 15.7) at baseline. Forty-eight (23.3%; 95% CI, 17.7, 29.7) participants had at least one Af-positive culture result during the study period. Positive Af culture result was not associated with lower respiratory domain score. However, Af history was associated with a 6.48-point lower respiratory domain score, reflective of worse respiratory quality of life (95% CI, -11.96, -0.99; P = 0.02). Positive Af culture result was associated with a 2.54% lower FEV1 percent predicted (95% CI, -4.64, -0.44; P = 0.02) and a 1.71-fold increase in severe PEx incidence (95% CI, 1.05, 2.76; P = 0.03). Conclusions: Positive Af culture result was not associated with lower patient-reported, respiratory-related quality of life. Yet, positive Af culture result was associated with both lower FEV1 percent predicted and increased frequency of severe PEx warranting intravenous antibiotics in adolescents and adults with CF. Future studies are required to better understand the direct role of Af in lung disease progression in CF.

A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation.

Purpose: The disease burden of severe asthma patients stratified by type 2 (T2) biomarkers is not well studied in large patient samples, especially for T2-low severe asthma patients. Using a Japanese medical record database, we investigated disease and economic burdens in T2-high and T2-low severe asthma patients. Patients and Methods: Data of severe asthma patients (receiving high-dose inhaled corticosteroids and additional asthma-related controller medications or oral corticosteroids [OCS] prescription [≥183 days] during the 1-year baseline period) were analyzed in the Real World Data database, comprising electronic medical records from Japanese medical institutions. Severe asthma patients were stratified into a T2-high population with higher eosinophils (≥150 cells/µL) and/or higher total immunoglobulin E (IgE, ≥75 IU/mL) or a T2-low population with lower eosinophils (<150 cells/µL) and lower total IgE (<75 IU/mL). The incidence of asthma exacerbation events and drug costs were analyzed for each population. Different T2 thresholds were explored, including eosinophil count 300 cells/µL and/or IgE 150 IU/mL. Results: Of the 732 severe asthma patients, 599 (81.8%) patients had T2-high type, and 133 (18.2%) had T2-low type. Proportions of the T2-high patients (30.6%) with asthma exacerbations, defined as a composite outcome, including OCS burst, injectable steroid use, and hospitalization, were similar to those of T2-low type (34.6%). The annual drug cost was similar between T2-high (175,487 JPY) and T2-low (165,322 JPY) populations. Conclusion: In this large-scale study, both T2-high and T2-low severe asthma patients in Japan were shown to have a high disease burden and high economic burden, suggesting an unmet treatment need.

Abdominal X-Ray Findings of Patients With Crohn's Disease Presenting With Acute Abdominal Pain.

OBJECTIVES: The primary objective of this study is to describe the most common radiological findings found on abdominal X-rays of patients with Crohn's disease (CD) presenting with acute abdominal pain. METHODS: A cross-sectional study was conducted at a tertiary care hospital in Riyadh. Data from CD patients who presented with acute abdominal pain between December 2016 and December 2021 was analyzed. A total of 144 abdominal X-rays met the inclusion and exclusion criteria and were included in the study. The medical records of patients who had the X-rays were subsequently reviewed for the presence or absence of follow-up imaging studies. RESULTS: Of the 144 abdominal X-ray studies, 54 (37.5%) had positive findings, while 90 (62.5%) were unremarkable. The most common category of findings was small bowel findings (32.6%), acute complications (32.6%), followed by extraintestinal findings (2.7%), and colonic findings (1.35%). About 29.2% of the abdominal X-rays had subsequent follow-up imaging done. The multivariate logistic binary regression analysis demonstrated that males had an odds ratio of 2.25 of undergoing follow-up imaging compared to females (p = 0.049). CONCLUSION:  The non-specific findings found on the majority of the abdominal X-rays may indicate that it is of limited diagnostic value in this patient population. However, they play an integral role in ruling out acute complications in CD patients presenting with abdominal pain and exhibiting disease activity.

Combined proteomics and single cell RNA-sequencing analysis to identify biomarkers of disease diagnosis and disease exacerbation for systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease for which there is no cure. Effective diagnosis and precise assessment of disease exacerbation remains a major challenge. Methods: We performed peripheral blood mononuclear cell (PBMC) proteomics of a discovery cohort, including patients with active SLE and inactive SLE, patients with rheumatoid arthritis (RA), and healthy controls (HC). Then, we performed a machine learning pipeline to identify biomarker combinations. The biomarker combinations were further validated using enzyme-linked immunosorbent assays (ELISAs) in another cohort. Single-cell RNA sequencing (scRNA-seq) data from active SLE, inactive SLE, and HC PBMC samples further elucidated the potential immune cellular sources of each of these PBMC biomarkers. Results: Screening of the PBMC proteome identified 1023, 168, and 124 proteins that were significantly different between SLE vs. HC, SLE vs. RA, and active SLE vs. inactive SLE, respectively. The machine learning pipeline identified two biomarker combinations that accurately distinguished patients with SLE from controls and discriminated between active and inactive SLE. The validated results of ELISAs for two biomarker combinations were in line with the discovery cohort results. Among them, the six-protein combination (IFIT3, MX1, TOMM40, STAT1, STAT2, and OAS3) exhibited good performance for SLE disease diagnosis, with AUC of 0.723 and 0.815 for distinguishing SLE from HC and RA, respectively. Nine-protein combination (PHACTR2, GOT2, L-selectin, CMC4, MAP2K1, CMPK2, ECPAS, SRA1, and STAT2) showed a robust performance in assessing disease exacerbation (AUC=0.990). Further, the potential immune cellular sources of nine PBMC biomarkers, which had the consistent changes with the proteomics data, were elucidated by PBMC scRNAseq. Discussion: Unbiased proteomic quantification and experimental validation of PBMC samples from two cohorts of patients with SLE were identified as biomarker combinations for diagnosis and activity monitoring. Furthermore, the immune cell subtype origin of the biomarkers in the transcript expression level was determined using PBMC scRNAseq. These findings present valuable PBMC biomarkers associated with SLE and may reveal potential therapeutic targets.

Incidence of community acquired lower respiratory tract disease in Bristol, UK during the COVID-19 pandemic: A prospective cohort study.

Background: The emergence of COVID-19 and public health measures implemented to reduce SARS-CoV-2 infections have both affected acute lower respiratory tract disease (aLRTD) epidemiology and incidence trends. The severity of COVID-19 and non-SARS-CoV-2 aLRTD during this period have not been compared in detail. Methods: We conducted a prospective cohort study of adults age ≥18 years admitted to either of two acute care hospitals in Bristol, UK, from August 2020 to November 2021. Patients were included if they presented with signs or symptoms of aLRTD (e.g., cough, pleurisy), or a clinical or radiological aLRTD diagnosis. Findings: 12,557 adult aLRTD hospitalisations occurred: 10,087 were associated with infection (pneumonia or non-pneumonic lower respiratory tract infection [NP-LRTI]), 2161 with no infective cause, with 306 providing a minimal surveillance dataset. Confirmed SARS-CoV-2 infection accounted for 32% (3178/10,087) of respiratory infections. Annual incidences of overall, COVID-19, and non- SARS-CoV-2 pneumonia were 714.1, 264.2, and 449.9, and NP-LRTI were 346.2, 43.8, and 302.4 per 100,000 adults, respectively. Weekly incidence trends in COVID-19 aLRTD showed large surges (median 6.5 [IQR 0.7-10.2] admissions per 100,000 adults per week), while other infective aLRTD events were more stable (median 14.3 [IQR 12.8-16.4] admissions per 100,000 adults per week) as were non-infective aLRTD events (median 4.4 [IQR 3.5-5.5] admissions per 100,000 adults per week). Interpretation: While COVID-19 disease was a large component of total aLRTD during this pandemic period, non- SARS-CoV-2 infection still caused the majority of respiratory infection hospitalisations. COVID-19 disease showed significant temporal fluctuations in frequency, which were less apparent in non-SARS-CoV-2 infection. Despite public health interventions to reduce respiratory infection, disease incidence remains high. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?

Background and Aim: There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods: In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results: Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion: Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.