Severe Acute Exacerbation Research Articles

Association of systemic corticosteroid use with prognosis of patients with acute exacerbations of chronic obstructive pulmonary disease in the intensive care unit: a propensity score-matched cohort study

BackgroundSystemic corticosteroid has been recommended for the treatment of severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Little is known about the use of systemic corticosteroid in patients admitted to intensive care units (ICU) since most of previous trials excluded these critically ill patients.MethodsWe conducted a matched cohort study based on the Medical Information Mart in Intensive Care-IV database. Patients with AECOPD in ICUs were included. Patients in the exposure group should be intravenously administrated with methylprednisolone or treated with oral prednisone within 24 h after ICU admission. The propensity score matching and multivariable analyses were used to adjust for covariates. The primary outcome was 28-day mortality, and secondary outcomes included ICU mortality, in-hospital mortality, the duration of ICU stay, and mechanical ventilation. Subgroup analyses for the primary outcome were performed according to age, sex, type of corticosteroid, type of ICU admission, type of mechanical ventilation, and co-morbidities/complications.ResultsThe entire cohort and the matched cohort included 763 and 412 patients, respectively. In the matched cohort, the use of systemic corticosteroid had no impact on 28-day mortality (OR: 1.00, 95% CI: 0.61–1.64, P = 1.000). The results kept consistent in all subgroups. Additionally, systemic corticosteroid showed no benefits on ICU mortality, in-hospital mortality, the length of ICU stay, and the duration of mechanical ventilation.ConclusionsThe results of this study do not support routine use of systemic corticosteroid in patients with AECOPD admitted to ICUs.

Identification of Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease Subgroups by Machine Learning Implementation in Electronic Health Records.

Acute exacerbations of COPD (AECOPD) are heterogeneous. Machine learning (ML) has previously been used to dissect some of the heterogeneity in COPD. The widespread adoption of electronic health records (EHRs) has led to the rapid accumulation of large amounts of patient data as part of routine clinical care. However, it is unclear whether the implementation of ML in EHR-derived data has the potential to identify subgroups of AECOPD. Determine whether ML implementation using EHR data from severe AECOPD requiring hospitalization identifies relevant subgroups. This study used two retrospective cohorts of patients with AECOPD (non-COVID-19 and COVID-19) treated at Yale-New Haven Hospital (YNHHS). K-means clustering was used to identify patient subgroups. We identified three subgroups in the non-COVID cohort (n=1,736). Each subgroup had distinct clinical characteristics. The reference subgroup was the largest (n=904), followed by cardio-renal (n = 548) and eosinophilic (n=284). The eosinophilic subgroup had milder severity of AECOPD, including a shorter hospital stay (p<0.01). The cardio-renal subgroup had the highest mortality during (5%) and in the year after hospitalization (30%). Validation of the severe AECOPD classifier in the COVID-19 cohort recapitulated the characteristics seen in the non-COVID cohort. AECOPD subgroups in the COVID-19 cohort had different IL-1 beta, IL-2R, and IL-8 levels (FDR ≤ 0.05. These specific leukocyte and cytokine profiles resulted in inflammatory differences between the AECOPD subgroups based on C-reactive protein levels. Incorporating ML with EHR-data allows the identification of specific clinical and biological subgroups for severe AECOPD.

The rs6967330 minor allele in CDHR3 is a significant risk factor for severe acute exacerbations in CRS.

Acute exacerbations of chronic rhinosinusitis (AECRS) are commonly triggered by rhinovirus (RV) infections with secondary bacterial infections. Risk factors for AECRS are not well understood. To determine if carriers of the minor allele rs6967330 (AA/AG) in the Cadherin related family member 3 (CDHR3) gene have an increased risk for RV infections in AECRS in vivo and identify CDHR3 genotype-dependent host responses to RV infection in differentiated nasal airway liquid interface (ALI) cultures ex vivo. We performed a prospective year-long study of adult subjects with chronic rhinosinusitis (CRS) by rs6967330 genotype (AA/AG, n=16; GG, n=38). We contacted subjects every 2 weeks, and if they reported AECRS clinical data were collected. ALI cultures of adults with CRS (AG/AA,n=19; GG,n=19) were challenged with RV-A and RV-C. We measured viral copy numbers at 4- and 48-hours post-infection and RNA transcriptomes and cytokines at 48 hours post infection. Subjects with the minor allele had significantly higher rates of RV and bacterial infections than those with the major allele. ALI minor allele cultures had higher viral copy numbers of RV-A and RV-C after 48 hours compared to the major allele. Differentially expressed genes (DEG) and pathways identified an upregulation of IL-10 and IL4/13 pathways and a significant downregulation of toll like receptor (TLR) pathways in the minor allele cultures after RV-A and RV-C infection. Unsupervised hierarchical analysis of all DEGs suggest that allergic rhinitis had an additive effect on this response. The rs6967330 minor allele is associated with increased RV-A and RV-C replication, downregulation of TLR-mediated responses and increased T2-type and cytokine and chemokine responses during RV infection.

Dynamic changes in quality of life in older patients with chronic obstructive pulmonary disease: a 7-year follow up

Purposes: Chronic obstructive pulmonary disease (COPD) is a major cause of the rapid decline of health-related quality of life (HRQoL), associated with accelerated frailty in older populations. This study aimed to analyse the long-term dynamic changes of HRQoL and the predictive factors for the rapid decline of HRQoL in older patients with COPD.MethodsOverall 244 patients with COPD, aged ≧ 65 years from one medical centre were enrolled between March 2012 and July 2020. Further, we prospectively assessed HRQoL scores with utility values, using EuroQol Five-Dimension (EQ-5D) questionnaires. Additionally, long-term dynamic changes in HRQoL were analysed using the Kernel smoothing method and examined the factors contributing to the deterioration of HRQoL using a linear mixed effects model.ResultsOlder patients with COPD with forced expiration volume (FEV1) < 50% of prediction entered the phase of rapid and continuous decline of HRQoL ~ 2 years after enrolment, but patients with FEV1 ≥ 50% of prediction without rapidly declined HRQoL during 7 years follow up. Therefore, FEV1 < 50% of prediction is a novel predictor for the rapid decline of HRQoL. The course of rapidly declining HRQoL occurred, initially in the usual activities and pain/discomfort domains, followed by the morbidity, self-care, and depression/anxiety domains ~ 2 and 4 years after enrolment, respectively. The mixed effects model indicated that both FEV1 < 50% of prediction and a history of severe acute exacerbation (SAE) requiring hospitalisation were contributing factors for deterioration in HRQoL .ConclusionsBoth FEV1 < 50% of prediction and exacerbations requiring hospitalisation were contributing factors for the deterioration of HRQoL in long-term follow up. Additionally, FEV1 < 50% of prediction was a novel predictor for patients entering the phase of rapid decline of HRQoL.

Suppression of the DNA repair enzyme NEIL2 promotes persistent inflammation and genomic damage in subjects with stable COPD and during severe exacerbations.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that is an independent risk factor for lung cancer. NEIL2, a DNA glycolase involved in DNA repair during transcription, has also been associated with an increased incidence of malignancies in humans. NEIL2 knockout mouse models have demonstrated increased inflammation and oxidative DNA damage in the lungs after exposure to an inflammatory insult, but data are lacking regarding NEIL2 function in individuals with stable COPD and during severe acute exacerbations of COPD (AECOPD). We investigated whether NEIL2 levels and oxidative DNA damage to the transcribed genome are altered in individuals with stable COPD and AECOPD. The study was conducted at a single center in the US. Eligible subjects underwent a one-time 30 cc venous blood draw. The population consisted of 50 adults: 16 with stable COPD, 11 hospitalized for AECOPD, and 23 volunteers. We analyzed blood leukocytes for NEIL2 mRNA and DNA damage by RT-qPCR and LA-qPCR, respectively, in all groups. Plasma levels of seven biomarkers, CXCL1, CXCL8, CXCL9, CXCL10, CCL2, CCL11 and IL-6, were analyzed in the COPD groups using a magnetic bead panel (Millipore®). The NEIL2 mRNA levels were lower in individuals with stable COPD and AECOPD than in controls (0.72 for COPD, p = 0.0289; 0.407 for AECOPD, p = 0.0002). The difference in NEIL2 mRNA expression between the stable COPD group and AECOPD group was also statistically significant (p < 0.001). The fold change in DNA lesions per 10 kb of DNA was greater in the stable COPD (9.38, p < 0.0008) and AECOPD (15.81, p < 0.0004) groups than in the control group. The difference in fold change was also greater in the AECOPD group versus stable COPD p < 0.0236). Biomarker levels were not significantly different between the COPD groups. NEIL2 levels were correlated with plasma eosinophil levels in the stable COPD group (r = 0.737, p < 0.0027). NEIL2 mRNA levels are significantly reduced in COPD subjects and are associated with increased DNA damage and inflammation. These results reveal a mechanism that promotes persistent airway inflammation and oxidative genomic damage and increases the risk of malignancy in this population.

Severe Acute Motor Exacerbations (SAME) across Metabolic, Developmental and Genetic Disorders.

Acute presentation of severe motor disorders is a diagnostic and management challenge. We define severe acute motor exacerbations (SAME) as acute/subacute motor symptoms that persist for hours-to-days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing/dysphagia). Phenomenology includes dystonia, choreoathetosis, combined movement disorders, weakness, and hemiplegic attacks. SAME can develop in diverse diseases and can be preceded by triggers or catabolic states. Recent descriptions of SAME in complex neurodevelopmental and epileptic encephalopathies have broadened appreciation of this presentation beyond inborn errors of metabolism. A high degree of clinical suspicion is required to identify appropriately targeted investigations and management. We conducted a comprehensive literature analysis of etiologies. Reported triggers are described and classified as per pathophysiological mechanism. A video of six cases displaying multiple SAME with diverse outcomes is provided. We identified 50 different conditions that manifest SAME, some associated with developmental regression. Etiologies include disorders of metabolism: energy substrate, amino acids, complex molecules, vitamins/cofactors, minerals, and neurotransmitters/synaptic vesicle cycling. Non-metabolic neurodegenerative and genetic disorders that present with movement disorders and epilepsy can additionally manifest SAME. A limited number of triggers are grouped here, together with an approach to investigations and general management strategies. Several neurogenetic and neurometabolic disorders manifest SAME. Identifying triggers can help in certain cases narrow the differential diagnosis and guide the expeditious application of targeted therapies to minimize adverse developmental and neurological consequences. This process may inform pathogenesis and eventually improve our understanding of the mechanisms that lead to the development of SAME. © 2024 International Parkinson and Movement Disorder Society.

Predictive score for in-hospital mortality in patients with severe acute exacerbations of COPD

Predictive score for in-hospital mortality in patients with severe acute exacerbations of COPD

The Impact of Malnutrition on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: The Predictive Value of the Mini Nutritional Assessment (MNA) versus Acute Exacerbations in Patients with Highly Complex COPD and Its Clinical and Prognostic Implications.

Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. This was a prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had a normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear regression models showed that the MNA score was associated with dyspnea and respiratory symptom severity, assessed by the Modified British Medical Research Council (mMRC) scale and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1, and with poorer QoL, as assessed by the EQ-5D-3 questionnaire. Competing risk analysis according to nutritional status based on the MNA Total Score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with sub-hazard ratios of 3.08 (1.40-6.80), p = 0.015, and 4.64 (1.71-12.55), p = 0.0002, respectively. Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Effect of soluble dietary fiber plus synbiotics on nutrition status, tolerance of enteral nutrition, and intestinal barrier function in elderly patients with severe acute exacerbation of severe chronic obstructive pulmonary disease on enteral nutrition

Effect of soluble dietary fiber plus synbiotics on nutrition status, tolerance of enteral nutrition, and intestinal barrier function in elderly patients with severe acute exacerbation of severe chronic obstructive pulmonary disease on enteral nutrition

Entecavir vs. tenofovir disoproxil fumarate in the treatment of chronic hepatitis B patients with severe acute exacerbation.

The efficacy of different nucleos(t)ide analogs in the treatment of chronic hepatitis B virus (CHB) with severe acute exacerbation (SAE) remained unclear. Thus, this study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients having CHB with SAE. We analyzed consecutive patients with treatment-naive CHB receiving TDF (n = 36) or ETV (n = 65) for SAE. The primary endpoint was overall mortality or receipt of liver transplantation (LT) by 24 weeks. The secondary endpoints are the comparison of ETV vs. TDF influences on renal function and virological and biochemical responses at 4, 12, 24, and 48 weeks. The baseline characteristics were comparable between the two groups. By 24 weeks, 8 (22%) patients in the TDF group and 10 (15%) patients in the ETV group had either died (n = 15) or received LT (n = 3) ( P = 0.367). Cox-regression multivariate analysis revealed age ( P = 0.003), baseline international normalized ratio of prothrombin time ( P = 0.024), and early presence of hepatic encephalopathy ( P = 0.003) as independent factors associated with mortality or LT. The two groups of patients achieved comparable biochemical and virological responses at 48 weeks. No significant difference was found in the estimated glomerular filtration rate (eGFR) between the TDF and the ETV groups. However, a significant reduction in the eGFR at 48 weeks, as compared with the baseline, was found in each group. TDF and ETV achieved similar short-term clinical outcomes and treatment responses in CHB patients with SAE.

Assessment of phosphatemia at admission to the intensive care unit to predict mechanical ventilation among patients with acute exacerbation of chronic obstructive pulmonary disease: a retrospective cohort study.

Hypophosphatemia has been reported to impair diaphragmatic function in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the role of dysphosphatemia at admission [plasmatic phosphate concentration at intensive care unit (ICU) admission (T0-Ph)] to the ICU and respiratory outcomes among patients with severe acute COPD exacerbation. We aimed to assess the value of T0-Ph as a predictive factor of invasive mechanical ventilation (MV) during ICU stay. We retrospectively included consecutive patients admitted to the ICU for a severe acute exacerbation of COPD between May 2015 and December 2018. Logistic multivariate regression analysis was performed to identify association between T0-Ph and the need for invasive MV during the ICU stay. We included 198 patients of whom 132 (67%) were male. The median age was 70 [interquartile range (IQR), 61-77] years. Nine (4.5%) patients died in the ICU. Median T0-Ph was significantly higher among patients requiring invasive MV as compared to non-intubated patients [1.23 (IQR, 1.07-1.41) and 1.09 (IQR, 0.91-1.27) mmol/L; P=0.005]. By multivariate analysis, pneumonia [odds ratio (OR) =6.42; 95% confidence interval (CI): 2.78-15.96; P<0.0001) and a history of intubation (OR =3.33; 95% CI: 0.97-11.19; P=0.05) were independently associated with the need for invasive MV, whereas T0-Ph was not (OR =1.75; 95% CI: 0.72-4.44; P=0.22). T0-Ph was significantly higher in patients requiring invasive MV. However, T0-Ph was not associated with the need for invasive MV in multivariate analysis.

Development of a novel cell-free DNA fragmentomics assay for monitoring disease progression in real-time for stage IV cancer patients.

e14544 Background: Advances in oncology have improved treatment response rates and overall survival. Many treatments, even targeted therapies, can fail to deliver an initial response to stage IV patients. We aimed to evaluate cfDNA as a biomarker of non-response to therapy in metastatic cancer. Methods: Blood samples were prospectively collected in Streck tubes at baseline and 12 - 21 days after initiating treatment, along with detailed clinical data, including imaging assessments captured in a cohort of metastatic non-small-cell lung (50), small-cell lung (8), breast (21), and colorectal (51) cancer study participants. To determine the fragmentation pattern of the DNA in the patient plasma, cfDNA was extracted using QIAamp Circulating Nucleic ACID Kit (Qiagen). cfDNA fragment concentrations were quantitated using two multiplexed qPCR assays on a QuantStudio 5. Primers and probes for the qPCR assay were designed using the high copy number retrotransposons Alu and SVA, represented across all 23 chromosomes. The two assays were performed on each specimen: an &gt;80bp, &gt;265bp and internal positive control (IPC) assay and an &gt;105bp, &gt;265bp with IPC assay. Following analytic validation of the assays, specimens from all participants were analyzed. The results from both assays were combined and merged with the clinical results and statistically analyzed. Results: 130 patients were included in the analysis. The qPCR assays work across all tumor and therapy types analyzed. A logit regression model was developed which calculates the likelihood that a patient’s cancer is progressing. The area under the ROC is 0.93 with a p-value of &lt;0.001. Results clustered above the logit value of 0.65 (n=15) are all progressors by imaging (PPV=100.0%). All logit values below 0.045 (n=69) are non-progressors by imaging (NPV=0.0%). Bootstrap resampling (1,000 iterations) suggests a 99.3% PPV at the 0.9 logit cut point. Healthy subjects (9) and patients with a variety of conditions (33) known to create elevated fragmented levels of cfDNA were also analyzed to determine which patients are not appropriate patients for the assay. Results indicate patients with following conditions within 10 days of a blood draw should be excluded: stroke, myocardial infarction, severe acute autoimmune event, and severe acute COPD exacerbation; and patients treated with a chemotherapy agent (i.e., methotrexate) within 10 days of a blood draw. Conclusions: These data support the value of a blood-based biopsy test for evaluating cancer cfDNA. cfDNA fragment assay is applicable to lung, colorectal, and breast cancer, and is agnostic to any mutation status. The cfDNA fragment analysis is a promising biomarker to monitor patient treatment and save time and the expense of clinically ineffective therapies, allowing the medical oncologist to evaluate the response to therapy in real-time and provide the best care possible for the patient.

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD

BackgroundAccumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.MethodsThe study designs of AERIFY-1 and AERIFY-2 are described in this article.DiscussionThe primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimabversusplacebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40–85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.

Acute Myocardial Infarction in Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Surviving Case

Background: COPD is characterized by chronic respiratory symptoms with progressive, irreversible structural abnormalities and impaired lung function. Previously, COPD was known as a condition that only affected the airways and lungs, but recent studies have revealed the incidence of cardiovascular disease in this population as the prevalence increased.Case: A 68-year-old male came to the emergency room fully conscious, complaining of shortness of breath since the afternoon. A physical examination detected tachypnea, desaturation of oxygen, and additional breath sounds in both lungs. Blood gas analysis with the result of respiratory acidosis supported the diagnosis of AECOPD (acute exacerbations of chronic obstructive pulmonary disease), impending type II respiratory failure, cor-pulmonale. During the treatment in the intensive unit, the physicians recognized deteriorating conditions as unconsciousness, unstable vital signs, and ST-T segment changes on the ECG with an elevated cardiac marker. Other medications (antiplatelet, LMWH, and statin) were given immediately. The patient’s condition improved. On the ninth day of the treatments, the patient was discharged home.Discussion: Acute exacerbations of COPD have a higher risk of developing ischemic heart disease with varying underlying mechanisms (atherosclerosis process and oxygen supply-demand imbalance). Understanding the numerous pathways that contribute to AMI (acute myocardial infarction) in COPD will help physicians determine the therapy.Conclusion: Based on this case, the ECG and cardiac enzymes warrant immediate evaluation, as must symptoms, vital signs, clinical findings, and other changes. Delays in case finding and treatment can worsen the prognosis.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol

BackgroundChronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture.Methods/designThis is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period.DiscussionThis study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Profile of adult patients hospitalized for asthma exacerbation

A variable proportion of patients presenting to the emergency department (ED) with acute asthma require admission to hospital. Previous studies have identified select factors associated with admission following ED presentation .However, patients hospitalized for AEs are highly heterogeneous and remain largely unexplored.This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.

Clonal Hematopoiesis of Indeterminate Potential Is Associated with Current Smoking Status and History of Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

There is limited data regarding the clinical outcomes of clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical significance of CHIP as a COPD biomarker. This retrospective study was conducted on patients with COPD who were enrolled prospectively in the Seoul National University Hospital Airway Registry from January 2013 to December 2019 and underwent pulmonary function and blood tests. We evaluated the CHIP score according to smoking status and severity of airflow obstruction. We analyzed next-generation sequencing data to detect CHIP in 125 patients with COPD. Current smokers had a higher prevalence of CHIP in combination of DNMT3A, TET2, and PPM1D (DTP), DNA methyltransferase 3 alpha (DNMT3A), and protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) genes than in never- or ex-smokers. CHIP of DTP and DNMT3A genes was significantly associated with current smokers (adjusted odds ratio [aOR], 2.80; 95% confidence interval [CI], 1.01 to 7.79) (aOR, 4.03; 95% CI, 1.09 to 14.0). Patients with moderate-to-severe airflow obstruction had a higher prevalence of CHIP in most of the explored genes than those with mild obstruction, although the difference was not statistically significant. CHIP in ASXL transcriptional regulator 1 (ASXL1) genes was significantly associated with history of mild, severe, and total acute exacerbation. Given that CHIP in specific genes was significantly associated with current smoking status and acute exacerbation, CHIP can be considered as a candidate biomarker for COPD patients.

Risk of exacerbation and mortality in asthma: a 10-year retrospective financial database analysis of the Hungarian Health Insurance Fund

IntroductionAsthma is the most prevalent obstructive pulmonary disease, with drastically improved treatment options over the past decades. However, there is still a proportion of patients with suboptimal level of asthma...

Chronic obstructive pulmonary disease trajectory: severe exacerbations and dynamic change in health-related quality of life

BackgroundThe life trajectory of chronic obstructive pulmonary disease (COPD) remains unknown.Patients and methodsWe collected data from two populations. In the first cohort, we recruited 375 patients with COPD from our...

P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic era

Abstract Background Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear. Methods A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p&amp;lt;0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223). Conclusion 8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.