Frequent Exacerbations Research Articles

The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study

Background: There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear. Methods: Patients aged ≥20 years with suspected COP were prospectively enrolled between June 2018 and December 2022. Among the enrolled patients, those diagnosed with COP based on computed tomography (CT) and bronchoalveolar lavage (BAL) findings were compared between the IPAF and non-IPAF groups. Results: A total of 56 patients were enrolled in this study. Of these, 30 were diagnosed with COP and included in the analysis. Clinical and serological features were positive in two and six patients, respectively. Each feature was exclusive, and eight patients (26.7%) were diagnosed with IPAF. There were no differences between the IPAF and non-IPAF groups in terms of clinical features, including BAL findings, laboratory data, CT findings, and clinical course. During the one-year follow-up period, the frequency of COP exacerbation did not differ between the IPAF and non-IPAF groups, and no cases of systemic autoimmune disease or death occurred in either group. Conclusions: The COP characteristics of the IPAF and non-IPAF groups are similar in all aspects, and distinguishing between the two groups may be of little significance.

Correlation Between Vitamin E Levels and Cholesterol, Vitamin D, and Frequency of Pulmonary Exacerbations in Children With Cystic Fibrosis

Correlation Between Vitamin E Levels and Cholesterol, Vitamin D, and Frequency of Pulmonary Exacerbations in Children With Cystic Fibrosis

Wide possibilities of topical therapy in the treatment of patients with infectious and inflammatory diseases of the pharynx

Despite medical advances, infectious and inflammatory upper respiratory diseases are the most common groups of diseases among outpatients. Viruses induce acute respiratory diseases in most patients; however, bacterial and “atypical” pathogens can cause exacerbations of chronic diseases such as adenoiditis, tonsillitis, pharyngitis and others. Prescribing etiotropic drugs to patients with infectious and inflammatory diseases of the pharynx can reduce the effectiveness of the therapy due to the growth of antimicrobial resistance. Increasing etiotropic drug resistance of some pathogens requires the selection of alternative agents for patients with infectious and inflammatory diseases of the pharynx. The non-specific prophylaxis of the latter is aimed to activate inner defense mechanisms using bacterial lysates (BL). Based on a review of the literature, the article discusses the features of the use and clinical effectiveness of topical BL in infectious and inflammatory diseases of the pharynx. BL are an important supplementation to the standard therapy regimen for inflammatory upper respiratory diseases, which contributes to the restoration of the immune response autoregulation, a reliable decrease in the frequency and duration of acute forms and exacerbations of chronic upper respiratory diseases, and reduced use of antibiotics and antipyretics. Evidence of possible mechanisms to correct immunity in infectious and inflammatory diseases of the pharynx, as well as a review of the clinical effectiveness of the medicine was demonstrated by example of Imudon. Its beneficial use to treat disease in the acute period is associated with its focal action on the infectious and inflammatory lesions. The drug is effective at any stage of the disease and can be used for prophylactic purposes due to activation of mucosal immunity in the respiratory tract. The high efficiency of Imudon is determined by its ability to activate phagocytosis and production of specific immunoglobulins by plasma cells, which reduces the risk of relapses and chronicity of the disease.

Long-term oxygen treatment in chronic respiratory failure

Chronic respiratory failure (CRF) is the leading cause of mortality in patients with pulmonary diseases. One of the key treatments for CRF is long-term oxygen therapy (LTOT). The main purpose of LTOT is to improve the quality of life, increase physical performance, reduce the frequency of exacerbations and mortality of patients. It is recommended to use oxygen therapy for at least 15–16 hours a day, and if there is no effect, increase this time to 24 hours. Indications for LTOT have remained unchanged for a long time. The decision on the appointment of LTOT should be based on three-fold results of the gas composition of arterial blood, and the assessment of gas exchange parameters can be made only after stabilization of the condition (3–4 weeks after exacerbation). It is also worth considering the possibility of hypercapnia in patients and the likelihood of aggravation of the patient’s condition due to oxygen-induced hypercapnia and respiratory acidosis. Despite the existence of numerous studies concerning the use of LTOT, most of them have been conducted on patients with COPD, which creates the need for a deeper study of the effectiveness of this method in patients with other diseases. The use of long-term oxygen therapy has a positive effect on the quality of life, physical performance, the frequency of exacerbations, hospitalizations and patient survival. There are various methods of oxygen delivery, which allows the use of LTOT not only at rest, but also when moving the patient over long distances. It is important to note that in addition to prescribing LTOT, patients need to change their lifestyle, stop smoking, and receive adequate drug therapy for the underlying disease.

The DOSE index in chronic obstructive pulmonary disease: evaluating healthcare costs

Background and objectivesThe DOSE index, which incorporates Dyspnea, Obstruction, Smoking, and Exacerbations, is a widely used tool for assessing the severity and prognosis of Chronic Obstructive Pulmonary Disease (COPD). In addition to risk assessment, it has potential clinical utility in predicting healthcare costs, which are primarily driven by exacerbations. While several indices, such as the BODE (Body-mass index, Obstruction, Dyspnea, Exercise) and ADO (Age, Dyspnea, Obstruction) indices, exist for risk prediction, there is a lack of dedicated tools for forecasting healthcare costs. This study explores the potential of the DOSE index compared to other indices, including BODE, ADO, and the Charlson Comorbidity Index (CCI), for this purpose.Materials and methodsThis cross-sectional retrospective study analyzed data from 396 COPD cases. We examined associations between the DOSE index, BODE index, ADO index, CCI, and healthcare costs, including hospitalizations and emergency room treatments. Healthcare costs were categorized as direct medical expenses.ResultsSignificant associations were observed between the DOSE index and various healthcare parameters. DOSE quartiles showed strong correlations with outpatient visits (p = 0.013) and outpatient medical expenses (p = 0.011). In addition, hospitalization frequency, duration, and associated costs were significantly correlated with higher DOSE quartiles (p < 0.001). A significant difference was found when comparing DOSE quartiles between patients with high (CCI ≥ 3) and low (CCI < 3) comorbidity scores (p = 0.018). The DOSE index outperformed other indices, likely due to its inclusion of exacerbations, a key driver of healthcare costs.ConclusionThe DOSE index demonstrates potential in predicting healthcare costs, particularly due to its inclusion of exacerbation frequency. This study highlights the importance of considering exacerbations alongside traditional risk factors for more accurate cost forecasting in COPD management. Our findings suggest that the DOSE index may be a valuable tool in both clinical and economic assessments of COPD patients, though further research is warranted to validate these findings in larger datasets.

Pediatric physiotherapy management of airway clearance therapy and exercise: Data from the Australian Bronchiectasis Registry.

Regular airway clearance techniques (ACTs) and exercise are recommended for children with bronchiectasis, but current clinical practice and their predictors are unknown. We aimed to describe current use of ACTs and exercise among Australian children with bronchiectasis and identify associated predictors. Physiotherapy-specific data of 397 children (median age = 8 were extracted from the Australian Bronchiectasis Registry. A multivariate analysis was undertaken to identify predictors associated with the use of regular ACTs and physical exercise. Regular ACTs were undertaken by 118 (30%) children while 192 (48%) engaged in regular exercise. Physical exercise was the most common ACT modality (n = 83, 20%). The likelihood of regular ACT increased in children whose sputum isolated Pseudomonas aeruginosa (OR = 3.88, 95% CI 1.69-8.89) and was 50% higher for every respiratory exacerbation in the previous 12-months that required hospitalization (OR = 1.50, 95% CI 1.15-1.95). For every year older in age, children had increased odds of engaging in physical exercise (OR = 1.21, 95% CI 1.08-1.34) or using an ACT device (OR = 1.21, 95% CI 1.05-1.34). Regular exercise was twice as likely in the presence of bibasal bronchiectasis (OR = 2.43, 95% CI 1.14-5.16), yet less likely in those with ≥1 hospitalizations in the previous 12-months (OR = 0.76, 0.95% CI 0.57-1.03). Approximately one-third of children with bronchiectasis undertake regular ACTs while physical exercise was undertaken in approximately one in two children. Age, frequent respiratory exacerbations requiring hospitalization and the extent of disease are predictors of undertaking regular ACTs and exercise. Identification of these factors may assist in tailoring ACT, exercise and ACT modality prescription in clinical practice.

Factors influencing the initiation of biologic therapy in children with severe asthma: Results of the pediatric asthma noninvasive diagnostic approaches (PANDA) study.

Despite the availability of biologics for severe pediatric asthma, real-life studies reporting on drivers behind initiating biologics and their alignment with the Global Initiative for Asthma (GINA) recommendations are lacking. We performed analysis within the pediatric asthma noninvasive diagnostic approaches study, a prospective cohort of 6- to 17-year-old children with severe asthma. Information was collected on demographic factors, symptom control, treatment, comorbidities, and diagnostic tests from medical records and questionnaires. We divided patients into "starters" or "nonstarters" based on the clinical decision to initiate biologics and performed multivariate logistic regression analysis to identify drivers behind initiating therapy. Additionally, we assessed patient suitability for biologics according to key factors in the GINA recommendations: Type 2 inflammation, frequency of exacerbations, and optimization of treatment adherence. In total, 72 children (mean age 11.5 ± 3.0 years, 65.3% male) were included (13 starters). Initiation of biologics was associated with a higher GINA treatment step (adjusted odds ratio's [aOR] = 5.0, 95%CI 1.33-18.76), steroid toxicity (aOR = 21.1, 95%CI 3.73-119.91), frequency of exacerbations (aOR = 1.6, 95%CI 1.10-2.39), improved therapy adherence (aOR = 1.7, 95%CI 1.10-2.46), Caucasian ethnicity (aOR = 0.20, 95%CI 0.05-0.80), ≥1 allergic sensitization (aOR = 0.06, 95%CI 0.004-0.97), and allergic rhinitis (aOR = 0.13, 95%CI 0.03-0.65). Furthermore, steroid toxicity was identified as an important factor for deviation from the current recommendations on biologic prescription. We identified multiple drivers and inhibitors for initiating biologics, and showed the clinical need for biologics in severe pediatric asthmatics suffering from steroid toxicity. These findings may help refine asthma management guidelines.

Early treatment response to mepolizumab predicts clinical remission in severe eosinophilic asthma

Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA). We questioned whether early response to mepolizumab could predict future asthma remission, and sought to identify the best predictor of treatment response to mepolizumab for achieving remission. The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the Asthma Control Questionnaire (ACQ)-5, oral corticosteroid (OCS) dose, exacerbation frequency, and post-bronchodilator FEV1. Clinical remission, assessed at 12 months, was defined as ACQ-5 ≤1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve (AUC) for internal validation. We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and post-bronchodilator FEV1 at 6 months was more predictive of achieving remission than measures at 3 months. ACQ-5 score at 6 months had the highest optimism-corrected AUC of 0.778 [95% CI: 0.719-0.833]. ACQ-5 score <1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, while ACQ-5 score <0.75 had a specificity of 84.7%. ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, where treatment response is assessed at 6 months to predict clinical remission.

Biomarkers for house dust mite subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy (AIT) has demonstrated clinical efficacy in patients with allergic asthma. However, there is little information on biomarkers to evaluate the effect of house dust mite (HDM) subcutaneous immunotherapy (SCIT) on allergic asthma. ObjectiveTo evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SCIT. Methods139 patients with asthma sensitized to HDM were recruited, 75 subjects received SCIT as an add-on therapy to drug treatment, and 64 subjects received drug treatment alone. Spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total IgE (TIgE), serum specific IgE for HDM, and frequency of exacerbations (ACT scores) were measured at baseline, 6 months, and 12 months. The relationship between biomarkers and pulmonary function improvement was investigated. ResultsSCIT demonstrated a significant reduction in FeNO, serum IL-25 and ACT scores at 6 months and significantly improved airflow limitation at 12 months compared to pharmacotherapy. The changes in FEV1 were dramatically correlated with changes in blood eosinophils ( r =-0.35, P=0.002), FeNO ( r =-0.57, P＜0.0001), serum IL-25 ( r =-0.68, P＜0.0001) and ACT scores( r =0.562, P＜0.0001). The multivariate regression analysis revealed that the changes in serum IL-25 concentration and FeNO were independently associated with an increase in FEV1 (r2 = 0.514, P < 0.05, respectively) in patients with allergic asthma treated with HDM SCIT. ConclusionsAdding HDM SCIT to pharmacotherapy reduced serum IL-25 and FeNO and improved pulmonary function in allergic asthma. Serum IL-25 and FeNO may be useful biomarkers for predicting HDM SCIT in allergic asthma, even in the absence of significant improvement in airflow limitation.

Modeling severe uncontrolled asthma: transitioning away from health states

BackgroundModels developed to date to simulate long-term outcomes of asthma have been criticized for lacking granularity and ignoring disease heterogeneity. ObjectiveTo propose an alternative approach to modeling asthma and apply it to model long-term outcomes in a population with moderate-to-severe type 2 asthma (patients with raised fractional exhaled nitric oxide or eosinophils) and treated with conventional therapy. MethodsA discretely integrated condition event (DICE) approach was adopted, simulating individual profiles with asthma over patients’ lifetime in terms of exacerbations, asthma-related death, and death unrelated to asthma. The timing of these events is dependent on profile characteristics including lung function, asthma control, exacerbation history, and other baseline characteristics or contextual factors. Predictive equations were derived from a clinical trial to model time to exacerbation, change in asthma control, lung function, and utility. Real-world studies were used to supplement data gaps. Outcomes evaluated included life expectancy, quality-adjusted life-years (QALY), number of exacerbations, and lung function over time. ResultsAverage annual rates of severe and moderate exacerbations were 1.82 and 3.08 respectively, with rates increasing over time. Lung function declined at a higher rate compared with the general population. Average life expectancy was 75.2 years, compared with 82.4 years in a matched general population. The majority of life-years were spent with uncontrolled asthma and impaired lung function. ConclusionPatients with moderate-to-severe type 2 asthma and a history of exacerbations suffer from frequent exacerbations and reduced lung function and life expectancy. Capturing multiple conditions to simulate long-term outcomes in patients with asthma may provide more realistic projections of exacerbation rates.

Oscillometry defined small airways dysfunction as a treatable trait in asthma.

The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called 'treatable traits' has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extra-pulmonary, and behavioral traits affecting asthma control. In this review article we examine the literature on small airways dysfunction as a potential treatable trait in persistent asthma. Pointedly, we discuss whole- and intra-breath oscillometry as well as the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.

Severe Uncontrolled Asthma: A Longitudinal Retrospective Study Illustrating the Experience of the Pulmonology Clinic of Târgu-Mureș, Romania.

Introduction: Severe uncontrolled asthma (SUA) affects approximately 5% of asthma patients, leading to frequent exacerbations, reduced lung function, and lower quality of life. Recent biologic therapies target specific inflammatory pathways, offering new options for SUA. Objective: This study aimed to evaluate clinical characteristics, treatment outcomes, and biomarkers in patients with SUA treated with biologics (Omalizumab, Benralizumab, and Dupilumab) at our clinic. Material and Methods: A six-month retrospective longitudinal study was conducted on 28 patients aged 36-83 years with SUA. Patients were divided into three groups: Omalizumab (n = 4), Benralizumab (n = 18), and Dupilumab (n = 6). Lung function tests and biomarkers such as eosinophil and IgE levels were measured over 3-month periods (T0, T1, and T2). Asthma control was assessed using asthma control tests (ACT), and non-parametric statistical methods were applied. Results: The median patient age was 64 years, with 75% showing elevated eosinophil counts (>300 cells/µL). Benralizumab significantly improved lung function (p < 0.05) and ACT scores (p < 0.001), reducing eosinophil counts to zero (p < 0.001). Patients on Dupilumab and Omalizumab showed improved asthma control (p < 0.05) and reduced exacerbations, albeit to a lesser extent (p > 0.05). Conclusions: Biologics, particularly Benralizumab and Dupilumab, improved asthma control, lung function, and quality of life in SUA patients, with improved ACT scores and spirometry values. Some patients remained poorly controlled, emphasizing the need for personalized treatment and regular biomarker monitoring. Multidisciplinary management and lifestyle changes are critical for better outcomes in SUA.

Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS

IntroductionNeutrophilic asthma has been suggested to be a clinically distinct phenotype characterized by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results.We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls.AimTo examine if neutrophilic inflammation, either in sputum or blood, is more prevalent in asthma and whether it correlates with disease severity.MethodsATLANTIS included 773 asthma patients, with blood collected from 767 (99%) and sputum from 228 patients (30%). Data were available from 244 healthy controls, all providing blood and 126 (52%) providing sputum. Asthma patients were characterized including parameters of large and small airways disease at baseline and after 6- and 12-months follow-up. Sputum and blood neutrophilia were defined as values exceeding the upper quartile in asthma patients.ResultsThe prevalence of sputum neutrophilia did not differ between asthma patients and healthy controls. Asthma patients with sputum neutrophilia did not display more severe symptoms, large or small airways disease, or more frequent exacerbations. Blood neutrophilia was more common in asthma and associated with higher BMI, female sex, current smoking and systemic corticosteroid use. Patients with blood neutrophilia had a statistically significant, but small, increase in RV/TLC. Blood neutrophilia was not associated with large or small airways disease, or exacerbation risk.ConclusionSputum and blood neutrophilia do not define a distinct clinical phenotype in asthma.

Effect of disabling biventricular pacing in patients with left ventricular assist device and cardiac resynchronization therapy

Abstract Introduction Taking into account the mechanism of the left ventricular assist device (LVAD) function, the cardiac resynchronization therapy (CRT) seems to be unnecessary and, according to the current reports, the left ventricular lead (LVL) should be disabled. However, observation of the patients suggests that deactivation of the left ventricle (LV) pacing leads to deterioration of the patients condition and progression of the heart failure (HF) symptoms. Purpose The study aimed to determine differences in survival of the patients with LVAD and maintained or disabled CRT, including patients subjected to heart transplantation, as well differences in left and right ventricle function, kidneys and liver condition, NTproBNP value, subjective exercise tolerance and frequency of HF exacerbation before and after CRT deactivation. Methods The study group involved 55 patients with LVAD and CRT devices, including 11 patients with disabled LV pacing. The statistical analysis concerned the comparison of groups with and without biventricular stimulation as well results within the group with disabled LVL before and after its deactivation. Analyzed data included laboratory results, echocardiographic parameters, number of HF exacerbation episodes and exercise tolerance by NYHA classification. Results Total CRT period did not differ in group with maintained and disabled CRT [24 (12-36)months vs. 30 IQR(12-48)months respectively; p=0,74]. The median period of CRT deactivation was 30 IQR(12-48) months after LVAD implantation. Time from LVAD implantation to heart transplantation differed significantly between patients with and without CRT [20 IQR(9-32)months vs. 49,5 IQR(46,5-62)months respectively; p=0,003]. LV disabling was connected with a significant increase of NTproBNP [3072 IQR(2287-6636) pg/ml vs. 2133 IQR(1618-3437) pg/ml before LVL deactivation; p=0,009), without an aggravation of the exercise intolerance by NYHA classification (p=0,11) or total number of HF exacerbation episodes (p=0,72). Lack of LV pacing was not related to change of concentration of creatinine (p=0,13), AST (p=0,89, ALT (p=0,5), bilirubin (p=0,06) and albumin (p=0,69) before and after LV deactivation. Comparison of echocardiographic parameters with and without CRT did not demonstrate significant differences in LV ejection fraction (p=0,37), LV end-diastolic diameter (p=0,33), TAPSE (p=0,72) and tricuspid regurgitation degree (p=0,39). Death-free survival from LVAD implantation has not differed in patients with and without CRT(p=0,08), similarly like death-free survival from heart transplantation (p=0,56), however with tendency to better outcome of patients with CRT till 12 months after the heart transplant. Conclusion CRT does not improve general health condition as well death-free survival in LVAD recipients, including patients subjected to heart transplantation, however with tendency to better outcome of patients with CRT till 12 months after the heart transplant.Death-free surival after LVADDeath-free survival after transplant

Stability of severe asthma phenotypes

Introduction. Severe asthma (SA) is a heterogeneous disease with several phenotypes. There are lack of data about its stability.Aim. To assess stability of SA phenotypes in adult patients during 5 years follow-up.Materials and methods. Prospective study included 117 adult outpatients with allergic SA, 51 severe asthmatics with aspirin-induced disease, 59 patient with persistent airflow limitation (PAL) and 35 patients with SA and concomitant COPD, 65 steroid-dependent severe asthmatics and 89 patients with SA and frequent (≥2 per year) exacerbations. Spirometry and bronchodilator reversibility testing were carried out; fractional exhaled nitric oxide (FeNO) was measured; hypersensitivity to common inhalant allergens (skin prick and blood specific IgE testing) and peripheral blood eosinophil counts were estimated. Asthma control and asthma-related quality of life were assessed by using ACQ-5 and SGRQ questionnaire.Results. During 5-year prospective study stability of aspirin-induced SA and SA with COPD was 100%. Allergic phenotype was stable in 81% of SA cases and in patients with changed atopic status we revealed worsening of symptoms and accelerated lung function decline. Stability of SA phenotype with PAL without COPD was 86% and steroid-dependent SA was stable in 55% of cases. After 5 years of treatment frequent exacerbations remained in 28% of severe asthmatics.Conclusion. The most stable phenotypes of SA were aspirin-induced and asthma with concomitant COPD. Less stable were allergic SA, steroid-dependent SA and phenotype with persistent airflow limitation. The least stable was SA phenotype with frequent exacerbations.

Eosinophil count testing in patients with asthma varies by healthcare provider type in the US: a retrospective study

BackgroundPatients with asthma with an eosinophilic phenotype may be eligible for additional treatment options to improve disease control; however, the prevalence and frequency of eosinophil testing is unknown. This study assessed blood eosinophil count testing prevalence in patients with asthma by exacerbation frequency and healthcare provider (HCP) type.MethodsThis was a retrospective, longitudinal, real-world study (GSK ID: 214470) utilizing the Merative Explorys® Universe electronic health records database. Eligible patients had ≥ 2 asthma diagnostic codes (January 2016–December 2018) (Index date: first asthma diagnosis). Outcomes included patient demographics and clinical characteristics (12 months pre-index [baseline]), and prevalence of blood eosinophil count testing, stratified by exacerbation frequency (infrequent exacerbations [< 2]) or frequent exacerbations [≥ 2] or primary HCP (Allergist/Pulmonologist, a primary care physician [PCP] or other HCP) during the 12 months post-index (follow-up).ResultsOf 400,254 patients included (mean age: 51.2 years; 70.8% female), the most common provider type at baseline was a PCP (76.8%). A higher proportion of patients with frequent exacerbations had blood eosinophil count tests at baseline (55.4–69.5%) and follow-up (67.9–75.1%), compared with patients with infrequent exacerbations (55.5–63.7%, 62.4–67.3%). Significantly more patients in the Allergist/Pulmonologist subgroup had ≥ 1 blood eosinophil count test result compared with patients in the PCP subgroup at both baseline (59.9% vs. 50.7%; p < 0.001) and follow-up (59.0% vs. 56.2%; p < 0.001). In the total population, the mean (SD) number of tests ordered was 3.4 (5.3) and 4.1 (6.4) during the baseline and follow-up periods, respectively. A greater mean number of tests were ordered for patients with frequent exacerbations, most apparently in the Allergist/Pulmonologist subgroup during baseline and follow-up (7.4 vs. 4.9). For patients with frequent exacerbations and blood eosinophil count test results, the mean (SD) number of tests ranged from 3.1 (4.6) to 5.8 (8.3) at baseline and 5.1 (8.5) to 7.4 (10.6) during follow-up.ConclusionsThe prevalence of blood eosinophil count testing in patients with asthma remains suboptimal. Routine blood eosinophil count testing should be considered by HCPs for patients with asthma to increase identification of the eosinophilic asthma phenotype, which may inform the decision to advance to targeted biologic therapy.

Aspergillus serology and clinical outcomes in patients with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)

IntroductionAspergillus sp. cause diverse clinical manifestations in bronchiectasis including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS) and raised IgG indicating exposure or infection with Aspergillus. Research QuestionWhat is the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis? MethodsBronchiectasis patients enrolled into the EMBARC registry from 2015 to 2022 with laboratory testing for Aspergillus lung disease (total IgE, specific IgE to Aspergillus or Aspergillus skin test, IgG to Aspergillus and blood eosinophil counts) were included for analysis. Modified-ISHAM-ABPA working group criteria (2021) were used to define ABPA. Results9953 patients were included. 608 (6.1%) were classified as having ABPA, 570 (5.7%) showed Aspergillus sensitization, 806 (8.1%) had raised Aspergillus-specific IgG without sensitisation, 184 (1.8%) were both sensitised to Aspergillus and had raised Aspergillus-specific IgG and 619 (6.2%) had eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72.0% had negative Aspergillus serology. Patients with ABPA, Aspergillus sensitization, and raised Aspergillus-specific IgG had more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG had higher exacerbation frequency and more severe exacerbations. Aspergillus sensitization associated with increased exacerbations and hospitalisations only in patients not receiving inhaled corticosteroids. InterpretationAspergillus lung disease is common in bronchiectasis. Raised IgG to Aspergillus is associated with significantly worse outcomes while ABPA and Aspergillus sensitization are associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use.

Gene expression responses of CF airway epithelial cells exposed to elexacaftor/tezacaftor/ivacaftor (ETI) suggest benefits beyond improved CFTR channel function.

The combination of elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) reverses the primary defect in Cystic Fibrosis (CF) by improving CFTR mediated Cl- and HCO3- secretion by airway epithelial cells (AEC), leading to improved lung function and less frequent exacerbations and hospitalizations. However, studies have shown that CFTR modulators like ivacaftor, a component of ETI, has numerous effects on CF cells beyond improved CFTR channel function. Because little is known about the effect of ETI on CF AEC gene expression we exposed primary human AEC to ETI for 48 hours and interrogated the transcriptome by RNA-seq and qPCR. ETI increased CFTR Cl- secretion, and defensin gene expression (DEFB1) an observation consistent with reports of decreased bacterial burden in the lungs of people with CF (pwCF). ETI decreased MMP10 and MMP12 gene expression, suggesting that ETI may reduce proteolytic induced lung destruction in CF. ETI also reduced the expression of the stress response gene heme oxygenase (HMOX1). qPCR analysis confirmed DEFB1, HMOX1, MMP10 and MMP12 gene expression results observed by RNA-seq. Gene pathway analysis revealed that ETI decreased inflammatory signaling, cellular proliferation and MHC Class II antigen presentation. Collectively, these findings suggest that the clinical observation that ETI reduces lung infections in pwCF is related in part to drug induced increases in DEFB1, and that ETI may reduce lung damage by reducing MMP10 and MMP12 gene expression. Moreover, pathway analysis also identified several other genes responsible for the ETI induced reduction in inflammation observed in pwCF.

Economic burden of short-acting beta-2 agonist (SABA) overuse among asthma patients in Türkiye: a cost analysis with respect to the updated GINA treatment recommendations.

This cost of illness study aimed to determine economic burden of short-acting β2-agonist (SABA) overuse in Türkiye from payer perspective with respect to the updated GINA 2022 treatment recommendations. A total of 3,034,879 asthma patients comprised the study population, via estimations extrapolated from the Türkiye arm of the global SABINA III study. The economic burden (costs related to the drug use and severe exacerbations) was compared in subgroups of overall (≥ 0 canisters/year) vs. GINA-recommended (0-2 canisters/year, hypothetical population) SABA use and in subgroups of appropriate use (0-2 canisters/year, real population) vs. overuse (≥ 3 canisters/year) of SABA with extrapolation of SABINA Türkiye data to the Türkiye asthma population. Recommended SABA use was predicted to prevent 127,505 of 157,512 severe exacerbations per year in mild asthma patients and 2,668,916 of 3,262,800 severe exacerbations per year in moderate-severe asthma patients. Annual cost burden of not applying recommended SABA use (overall [≥ 0 canisters/year] vs. GINA-recommended [0-2 canisters/year] SABA use) in mild asthma and moderate-severe asthma patients was calculated to be €20.43 million and €427.65 million in terms of severe exacerbations, and to be €829,352 and €7.20 million in terms of drug costs, respectively. The total annual economic burden arising from not applying recommended SABA use was estimated to be €456.11 million. Appropriate use (0-2 canisters/year) vs. overuse (≥ 3 canisters/year) of SABA was associated with decreased frequency of severe exacerbations per year in mild asthma (from 129,878 to 27,634) and moderate-severe asthma (from 2,834,611 to 428,189) patients. SABA overuse in mild and moderate-severe asthma patients was estimated to yield an additional annual cost of €16.38 million and €385.59 million, respectively in terms of severe exacerbations, and a total €11.30 million additional drug cost. The overall annual economic burden arising from SABA overuse was estimated to be €413.27 million. The estimated annual total economic burden arising from not applying recommended SABA use (€456.11 million) and SABA overuse (€413.27 million) with respect to the updated GINA 2022 treatment recommendations indicates the substantial cost burden of SABA overuse to the Turkish National Health System, corresponding up to 26% of the total direct cost of asthma reported in our country.

Efficacy and safety of cladribine tablets in multiple sclerosis in real-world clinical practice

Cladribine has a well-defined activity against lymphocytes, leading to their selective depletion.Objective: to determine the efficacy and safety of cladribine in the treatment of multiple sclerosis (MS) in real-world clinical practice.Material and methods. The study involved 82 patients (57 women and 25 men, mean age 36.4±9.3 years) with a disease duration of 2.2±1.5 years. Seven (9%) patients had secondary progressive MS (SPMS), 6 (7%) had rapidly progressive MS (RPMS) and 69 (84%) had highly active MS (HAMS). According to the instructions for use, oral therapy with cladribine was administered in two short courses (up to 10 days per year) to achieve a long-term effect on the immune system. The dose of cladribine was calculated based on the body weight.Results. The average frequency of exacerbations per year before starting therapy was 1.6, while it decreased to 0.2 during cladribine therapy. An exacerbation was observed in 18 patients (22%) at the end of the first course of cladribine treatment and in one patient (2.6%) after the second treatment course. Thus, the number of exacerbations decreased by 78% after the first year of treatment and by 97.4% after the second year of treatment. The mean EDSS score was 3.2±2.5 points before the start of treatment, 3.6±2.5 points after the first course of treatment and 3.4±2.5 points after the second course (p&gt;0.05). MRI results showed a decrease in disease activity by 83% after the first course of cladribine therapy and by 97.4% after the second course. No serious adverse events occurred in any of the patients.Conclusion. We demonstrated efficacy and safety of cladribine in real-life clinical practice in MS patients with frequent exacerbations and rapid disability progression (SPMS, RPMS, HAMS).