Severe Exacerbations Research Articles

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.

Outcomes of a dexamethasone-prednisone combination treatment course for status asthmaticus

Objectives Dexamethasone has become the standard of care for pediatric patients with status asthmaticus in the emergency department (ED) setting. Inpatient providers often must decide between continuing the second dose of dexamethasone or transitioning to prednisone. The effectiveness of receiving dexamethasone followed by prednisone (combination therapy) compared to only prednisone or dexamethasone remains unclear. This study compares patient characteristics and ED reutilization/hospital readmission outcomes of dexamethasone, prednisone, and combination therapy for inpatient asthma management. Methods A retrospective study was conducted at our tertiary children’s hospital of children aged 2 to 18 years hospitalized between March 2016 and December 2018 with a primary discharge diagnosis of asthma, reactive airway disease, or bronchospasm. The differences between steroid groups were compared using Fisher’s exact or Chi-square tests for categorical variables, and a Kruskal-Wallis test for continuous variables. A multivariable logistic regression was performed to analyze ED reutilization and hospital readmission rates. Results 1697 subjects met inclusion criteria. 115 (6.8%) patients received dexamethasone, 597 (35.2%) received prednisone, and 985 (58.0%) received combination therapy. Patients prescribed combination therapy had a lower exacerbation severity than patients prescribed prednisone, but higher severity than patients prescribed dexamethasone (p < .001, p = .001, respectively). Dexamethasone and combination therapy were not associated with increased 30-day ED reutilization/hospital readmissions compared to prednisone (p > .05). Conclusions In our study, most patients hospitalized for status asthmaticus received combination therapy. Despite the differences in severity between steroid groups, outcomes of combination therapy and dexamethasone monotherapy, as measured by frequency of ED reutilizations/hospital readmissions, are comparable to prednisone monotherapy.

Variation in Triage to Pediatric vs Adult ICUs Among Adolescents and Young Adults With Asthma Exacerbations

BackgroundOver 90,000 children and adults in the United States are hospitalized with an asthma exacerbation annually, and between 5-34% of these hospitalizations include an admission to an intensive care unit (ICU). It is unclear how adolescent and young adults with severe asthma exacerbations are triaged in the inpatient setting between pediatric (PICUs) and adult ICUs. Using a large multicenter United States cohort, we characterized how hospitals triage adolescents and young adults with asthma exacerbations between PICUs and adult ICUs. Research QuestionHow do hospitals across the United States triage adolescents and young adults with asthma exacerbations between PICUs and adult ICUs? Study Design and MethodsThis was a retrospective cohort study from 2016 to 2022 using the enhanced-claims PINC AI database. Participants were patients aged 12-26 hospitalized with asthma exacerbation and admitted to a PICU or adult ICU. We used nested hierarchical multivariable regression models to quantify changes in the intraclass correlation coefficient (a measure of variation in triage decisions attributable to hospital of admission after accounting for covariables). ResultsAnalyses included 3,946 admissions from 93 hospitals. Stratified by age, the percent of patients admitted to PICUs dropped by 26.9% between age 17 to age 18. In the nested models, the ICC had a large decrease going from the empty model (28.7%) to the age-adjusted model (4.5%) but was similar between the age-adjusted and fully adjusted model (3.4%). InterpretationAmong adolescents and young adults with asthma exacerbations, age ≤18 years was a strong determinant of PICU triage. Further research is needed to understand differences in asthma care and outcomes between PICUs and adult ICUs, as well as how intermediate care units affect triage decision-making from wards and the emergency department.

Suboptimal Peak Inspiratory Flow in Patients Hospitalized for COPD Exacerbation: Prevalence and Predictive Factors.

Introduction: Despite the importance of an adequate peak inspiratory flow (PIF) during inhaled therapy in patients with COPD, the available evidence in patients with severe exacerbations and their evolution after admission is limited. We conducted this study to evaluate the PIF during an exacerbation, its variability, and predictors of suboptimal PIF. Material and Methods: A prospective study that included patients admitted for COPD exacerbation. Clinical, demographic, and functional variables were recorded. Using the In-Check DIAL G16®, PIF without resistance (PIF-nr) and that obtained by simulating the resistance of the patients' usual inhalers (PIF) were determined within the first 48 hours of admission and prior to discharge; also assessed during a stable phase in a subgroup of patients. The results were compared and, through a multivariate study, the factors related to a suboptimal PIF were analyzed. Results: A total of 137 patients were included; 27% were women and the mean age was 69.4 ± 9.8 years. Moreover, 30.8% of the participants with dry powder inhalers had a suboptimal PIF at admission and it was independently associated with female sex (odds ratio [OR] = 8.635; 95% confidence interval [CI] [2.007, 37.152]; p < 0.01) and forced expiratory volume in the 1st second (FEV1) (OR = 0.997; 95% CI: [0.995, 0.999]; p = 0.04). At discharge, suboptimal PIF reduced to 17% (p < 0.01). PIF-nr increased from the time of admission to the stable phase. Conclusion: One third of COPD patients admitted with a severe exacerbation had a suboptimal PIF, being female sex and lower FEV1 independent predictors. PIF-nr improved progressively after the exacerbation.

Early and late effects of volatile sedation with sevoflurane on respiratory mechanics of critically ill COPD patients

BackgroundThe objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation.MethodsProspective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint.ResultsSixteen patients were enrolled and were sedated for 126 h(61–228) in the propofol group and 207 h(171–216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8–21.6) in the propofol group and 20.4cmH2O/l/s(18.6–26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176–290) in the propofol group and 73 ml(35–126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1–3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups.ConclusionsIn critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.

Outcomes among patients with chronic obstructive pulmonary disease after recovery from COVID-19 infection of different severity

While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95–10.15, p < 0.001) and 6.77 (95% CI = 2.08–22.00, p = 0.001) respectively. Patients with severe COVID-19 infection had significantly increased risks of increase in severe COPD exacerbation frequency with adjusted odds ratios of 4.73 (95% CI = 1.55–14.41, p = 0.006) non-COVID-19 respiratory mortality from COPD exacerbation or pneumonia with adjusted hazard ratio of 11.25 (95% CI = 2.98–42.45, p < 0.001). After recovery from COVID-19, worsening of COPD control from worsening of dyspnea, increase in severe exacerbation frequency to non-COVID-19 respiratory mortality (COPD exacerbation and pneumonia) was observed among patients with severe COVID-19. Mild to moderate COVID-19 was also associated with symptomatic deterioration.

Clinic-Functional Assessment of Hemoglobin Desaturation by Oxygen in 6-Minute Walk Test Among Patients with Bronchial Asthma

The main purpose of the study is to assess the prevalence and clinical significance of hemoglobin desaturation by oxygen during the 6-minute walk exercise test in patients with bronchial asthma. Material and methods: 75 patients with exacerbation of mixed (48 %) and allergic (52 %) bronchial asthma were examined. Research explored following methods: collecting complaints and anamnesis, physical examination, spirometry, CO-metry of exhaled air to determine carboxyhemoglobin, transcutaneous 2-wave pulse oximetry (at rest and during 6-minute walk exercise test) with spectral analysis and correction for COHb. 6-minute walk exercise test was performed after relief of asthma exacerbation (before discharge from the hospital), assessing the desaturation-distance ratio (the ratio of the area of oxygen desaturation of hemoglobin to the 6-minute walk exercise test distance), O2-GAP index, the dynamics of fatigue and dyspnea before and after 6-minute walk exercise test. In smoking patients (n = 36, 48 %), the smoker index was calculated. Based on oximetry results during the 6-minute walk exercise test, patients were divided into “desaturators” (n = 28, 37 %) and “non-desaturators” (n = 47, 63 %). Results. The findings of the research illustrated that hemoglobin desaturation by oxygen, detected by reducing SpO2 to &lt; 90 % during 6-minute walk exercise test, was associated with the severity of this disease exacerbation, more pronounced impairment of pulmonary ventilation and blood oxygenation, and the demand for longer hospitalization. The prevalence of tobacco smoking and the magnitude of the smoker index in both groups were identical but in “desaturators” we found a higher prevalence of the combination of asthma and COPD compared to “non-desaturators.” The “desaturators” had significantly higher level of desaturation-distance ratio and increased demand for additional oxygen flow to maintain SpO2 at ≥ 88 % during a 6-minute walk test, which indicates a higher “oxygen price” of physical activity in this group of patients. Conclusion. Thus, the high prevalence of the phenomenon of hemoglobin oxygen desaturation during 6-minute walk exercise test in patients with asthma and associated clinic-functional disorders supports the feasibility and clinical significance of conducting a stress test with a 6-minute walk not only in COPD patients, but also in bronchial asthma patients.

A Nationwide Cohort Study of Delta and Omicron SARS-CoV-2 Outcomes in Vaccinated Individuals With Chronic Lung Disease

BackgroundIndividuals with chronic-lung-disease (CLD) are more susceptible to respiratory viral infections; however, there is significant heterogeneity in the literature on CLD and COVID-19 outcomes. Data is lacking on outcomes with newer variants (eg. Omicron) and in vaccinated/boosted populations. Research QuestionWhat are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission, in a highly vaccinated/boosted population-based cohort? Study Design and MethodsOutcomes of Delta/Omicron SARS-CoV-2 infection in a highly vaccinated/boosted cohort of adult Singaporeans with CLD (including asthma, chronic-obstructive-pulmonary-disease [COPD], bronchiectasis and pulmonary fibrosis) were contrasted against matched population controls. Calendar time-scale Cox regressions were used to compare risk of infection, COVID-19-related hospitalizations and severe COVID-19 disease, adjusting for sociodemographic factors/comorbidities. ResultsOverall, 68,782 individual patients with CLD and 534,364 matched population controls were included. 92.7% of CLD patients were boosted by the end of the Omicron wave. Compared with controls, higher risk of SARS-CoV-2 infection, COVID-19-related hospitalization and severe COVID-19 was observed amongst patients with CLD during both Delta (infection: adjusted-hazards-ratio, aHR=1.22[1.17-1.28]; hospitalization: aHR=1.76[1.61-1.92]; severe-COVID-19: aHR=1.75[1.50-2.05]) and Omicron waves (infection: aHR=1.15[1.14-1.17]; hospitalization: aHR=1.82[1.74-1.91]; severe-COVID-19: aHR=2.39[2.18-2.63]). During Omicron, significantly higher risk of infection, hospitalization and severe-COVID-19 was observed amongst patients with asthma (severe-COVID-19: aHR=1.31[1.10-1.55]) and COPD (severe-COVID-19: aHR=1.36[1.12-1.66]) compared with controls. Severe exacerbation (requiring hospitalization) in the preceding year was associated with higher risk of poorer outcomes (Delta-severe-COVID-19: aHR=9.84[6.33-15.28]; Omicron-severe-COVID-19: aHR=19.22[15.35-24.06]). Risk was attenuated in the boosted group, with numerically lower HRs against hospitalization/severe-COVID-19 in the 4-dose group compared with the 3-dose group. InterpretationIncreased risk of COVID-19-related hospitalization and severe-COVID-19 was observed amongst patients with CLD compared with matched population controls, during Delta/Omicron predominance. Boosting attenuated serious COVID-19 outcomes.

Prescription patterns and effectiveness of medications for chronic obstructive pulmonary disease: A retrospective study of real-world settings.

This study aimed to define real-world prescription patterns in Korea and compare the effectiveness of chronic obstructive pulmonary disease (COPD) medications. We used national claims data provided by the Health Insurance Review and Assessment Service in Korea and examined patients who were first diagnosed with COPD and started treatment between May 1, 2017, and April 30, 2018, with no change in drug regimen. Among 30,784 patients with COPD, long-acting β2 agonist (LABA) combined with long-acting muscarinic antagonist (LAMA) (32.7%), inhaled corticosteroid-LABA (ICS-LABA) (25.6%), LAMA (18.3%), ICS (5.8%), or LABA (4.6%) were prescribed as the first-choice inhalers. The use of LABA-LAMA (hazard ratio [HR], 0.248-0.584), LAMA (HR, 0.320-0.641), ICS-LABA (HR, 0.325-0.643), and xanthine (HR, 0.563-0.828) significantly reduced the total and severe exacerbation rates compared with no use of each medication. However, the use of ICS or LABA individually did not yield such effects. The continued use of LABA-LAMA, LAMA, and ICS-LABA showed a significant effect on exacerbation rate, whereas the long-term use of ICS, LABA, and xanthine did not. Moreover, some high doses of ICS-LABA did not show significant effects. This real-world study revealed that LAMA and/or LABA could be the first choice of therapy, as recommended by recent guidelines. However, ICS, xanthine, and high-dose ICS-LABA are still being prescribed frequently as first-line drugs in Korea.

The effectiveness of long-term respiratory support in a patient after pneumonectomy

Respiratory support for chronic respiratory failure in the last stages is widely used, most often in patients with end-stage COPD. It has been proven that the development of chronic hypercapnic respiratory failure is associated with an increasing in exacerbations, increased hospitalization rates, and an acceleration of the time before subsequent decompensation. Also hypercapnia isa determining factor in mortality. Effective treatment method of hypercapnic insufficiency is non-invasive ventilation. Long-term non-invasive ventilation improves daytime hypercapnia, quality of life, increases the period until the next severe exacerbation and survival of patients with COPD. Patients with COPD have different phenotypes and various comorbid diseases, which which may be challenging while choosing method of respiratory support and assessing the effectiveness of this treatment method. There is lack of data on long-term non-invasive respiratory support for patients with COPD after pneumonectomy in chronic period. Most of publications dedicated for early post-operative period after pneumonectomy. The purpose of this publication is to present a case of successful long-term non-invasive ventilation combined with oxygen therapy in a patient with COPD and bronchiectasis of a single lung. Stages of management of hypoxemic and subsequently developed hypercapnic chronic respiratory failure are reflected. We demonstrate experience of successful long-term ambulatory non-invasive ventilation in a patient with chronic hypercapnic respiratory failure as a result of COPD and pneumonectomy was demonstrated. Observation study showed feasibility of combined respiratory support in outpatient settings for patient with COPD of a single lung and a history of pneumonectomy.

The role of anti-IgE therapy in achieving remission of bronchial asthma

Bronchial asthma is one of the most common respiratory diseases, and follows a severe clinical course in 10% of patients. 70–80% of patients with severe asthma have signs of type 2 (T2) inflammation, which is clinically defined as an increase in blood and airways eosinophil counts. The emergence of genetically engineered biological drugs has made it possible to review the purpose of asthma therapy, that is, achieving remission instead of disease control, which includes managing the symptoms, absence of exacerbations, stabilization of functional parameters and normalization of biomarkers in the absence of therapy with systemic glucocorticoids. Clinical studies have shown that therapy with genetically engineered biological drugs can reduce the frequency of asthma exacerbations, decrease the need for maintenance therapy with systemic glucocorticoids, relieve symptoms, improve quality of life, which results in achieving a disease remission in 19.6–31.6% of patients. Predictors of suboptimal response to biological therapy were a high body mass index, admission to the intensive care unit and a history of severe asthma exacerbations, as well as initially more severe clinical manifestations of the disease. The most pronounced effect of omalizumab therapy was observed in patients with atopic severe asthma showing symptoms and exacerbations that are clinically associated with allergic sensitization confirmed by positive results of skin prick testing and (or) identification of serological allergen-specific IgE, elevated levels of T2 biomarkers. This publication presents the latest data on asthma remission: the concept, basic criteria, as well as the role of genetically engineered biological drugs in achieving a remission.

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.

SABA prescriptions and asthma management practices in Singapore: results from a cross-sectional, observational SABINA III study

ObjectivesTo evaluate asthma characteristics and treatment patterns, including short-acting β2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study.DesignCross-sectional,...

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.

Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.

Type 2 Inflammation and Asthma in Children: A Narrative Review

Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, such as blood eosinophils and/or fractional exhaled nitric oxide. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low to medium doses of inhaled corticosteroids. However, in a small but significant proportion of children, asthma remains uncontrolled despite maximum conventional treatment, with an increased risk of severe exacerbations. In this review, we focus on the role of type 2 inflammation and allergic processes in children with asthma, together with evidence of the efficacy of available treatment options for those who experience severe symptoms.

Risk of severe cardiovascular events following COPD exacerbations: results from the EXACOS-CV study in Spain

Introduction and objectivesThis real-world study—the first of its kind in a Spanish population—aimed to explore severe risk for cardiovascular events and all-cause death following exacerbations in a large cohort of patients with chronic obstructive pulmonary disease (COPD). MethodsWe included individuals with a COPD diagnosis code between 2014 and 2018 from the BIG-PAC health care claims database. The primary outcome was a composite of a first severe cardiovascular event (acute coronary syndrome, heart failure decompensation, cerebral ischemia, arrhythmia) or all-cause death following inclusion in the cohort. Time-dependent Cox proportional hazards models estimated HRs for associations between exposed time periods (1-7, 8-14, 15-30, 31-180, 181-365, and >365 days) following an exacerbation of any severity, and following moderate or severe exacerbations separately (vs unexposed time before a first exacerbation following cohort inclusion). ResultsDuring a median follow-up of 3.03 years, 18 901 of 24 393 patients (77.5%) experienced ≥ 1 moderate/severe exacerbation, and 8741 (35.8%) experienced the primary outcome. The risk of a severe cardiovascular event increased following moderate/severe COPD exacerbation onset vs the unexposed period, with rates being most increased during the first 1 to 7 days following exacerbation onset (HR, 10.10; 95%CI, 9.29-10.97) and remaining increased >365 days after exacerbation onset (HR, 1.65; 95%CI, 1.49-1.82). ConclusionsThe risk of severe cardiovascular events or death increased following moderate/severe exacerbation onset, illustrating the need for proactive multidisciplinary care of patients with COPD to prevent exacerbations and address other cardiovascular risk factors.

Efficacy and safety of weekend cyclosporine treatment as maintenance therapy for preventing frequent disease exacerbations in moderate to severe chronic plaque psoriasis patients - A retrospective cohort study.

Background Psoriasis is a chronic, inflammatory, systemic disease with predominant manifestations in the skin and joints impairing patient's quality of life. A proportion of patients have frequent severe disease exacerbations requiring repeated systemic treatments. There is a scarcity of literature evaluating the role of systemic maintenance therapy in psoriasis patients in preventing such frequent disease flares. Objective To evaluate the efficacy and safety of weekend cyclosporine treatment (WCT) as maintenance therapy in moderate to severe chronic plaque psoriasis patients for the prevention of frequent disease exacerbations. Methods In this retrospective cohort study, 22 psoriasis patients with a history of frequent disease exacerbations (≥ 3 in the last 1 year) who were administered WCT (group A) were compared with the same number of matched patients (age and gender) not on WCT or any systemic maintenance therapy (group B). Results Four patients (18.2%) in group A had disease exacerbations which was significantly lower (p = 0.00, Fisher's exact test) as compared to 21 patients (95.5%) in group B during the study period. Also, patients in group A had significantly lower number of overall exacerbations [mean ± SD: 0.23 ± 0.53 vs 2.95 ± 1.43) p = 0.00, Mann-Whitney U test] as compared to group B. Four (9.1%) patients in group A encountered adverse effects (acneiform eruptions - two, mild gingival hyperplasia - one, myalgia - one) as compared to three (acneiform eruptions - two, headache - one) in group B (p = 1.00). Conclusion WCT significantly reduced the number of disease exacerbations and is a safe and effective mode of maintenance therapy in such subset of psoriasis patients.

Real-world characteristics of patients with asthma initiating fluticasone furoate/umeclidinium/vilanterol single-inhaler triple therapy in Japan

BackgroundReal-world data assessing characteristics of patients with asthma initiating inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy in Japan are limited. MethodsDescriptive, observational study of patients with asthma aged ≥15 years newly initiating single- or multiple-inhaler triple therapy (SITT: fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI], SITT: indacaterol/glycopyrronium bromide/mometasone furoate [IND/GLY/MF] or MITT) or ICS/LABA using JMDC/Medical Data Vision (MDV) health insurance databases from February 2021–February 2022 (first prescription date: index date). Patients were assigned to three non-mutually exclusive cohorts: A) new FF/UMEC/VI initiators; B) new FF/UMEC/VI, IND/GLY/MF, or MITT initiators; C) new FF/UMEC/VI, IND/GLY/MF, MITT or ICS/LABA initiators as initial maintenance therapy (IMT). Patient characteristics were assessed descriptively for 12-months pre-treatment initiation (baseline period). ResultsCohort A: among new FF/UMEC/VI initiators, 12.8% and 0.1% (JMDC) and 21.7% and 0.9% (MDV) of patients had ≥1 moderate and severe exacerbation; 52.0% (JMDC) and 79.2% (MDV) had ICS/LABA use. Cohort B: most patients initiated FF/UMEC/VI and IND/GLY/MF over MITT (JMDC: 91.3% vs 8.7%; MDV: 67.8% vs 32.2%), with fewer exacerbations and lower rescue medication use. Cohort C: a greater proportion of FF/UMEC/VI initiators as IMT experienced a moderate exacerbation at index versus ICS/LABA initiators as IMT (JMDC: 17.8% vs 10.7%; MDV: 8.0% vs 5.1%). ConclusionsPatient characteristics were generally similar between treatment groups; SITT initiators had fewer exacerbations and lower rescue medication use than MITT initiators, represented by the greater proportion of IMT among SITT versus MITT initiators. Physicians may have prescribed triple over dual therapy as IMT in response to an exacerbation.