Severe Asthma Patients Research Articles

Comparison of clinical remission criteria for severe asthma patients receiving biologic therapy

BackgroundThe concept of remission on biological treatment has been suggested as a therapeutic target for patients with severe asthma, composed of 1. no chronic use of systemic steroids, 2. no exacerbations, 3. minimal symptoms, and 4. optimized lung function, for a significant time. However, the criteria for remission are not clearly defined. ObjectiveOur objective was to compare different criteria for remission in subjects receiving biologicals for severe asthma. MethodsA cross-sectional study of adult subjects who receive a stable regimen of a biological for severe asthma for at least 6-months. We compared the proportion of subjects who fulfilled different specific criteria in the four domains, as well as those who achieved different composite outcome measures of clinical remission. ResultsOf 39 subjects, 28 were females (71.8%), mean age 60.4. Twelve were current or past smokers (30.8%). Twelve had prior different biological treatment (30.8%), and 3/39 had more than one previous treatment (7.7%). Current biological included mepolizumab 12/39 (30.8%), dupilumab 11/39 (28.2%), benralizumab 10/39 (25.6%), omalizumab 5/39 (12.8%), reslizumab 1/39 (2.6%). Different specific criteria were achieved in 39–80% of subjects, being highest for no chronic steroid use and lowest for symptoms control and lung function. Overall remission was obtained by 20–41%, depending on definition, with significant variability in agreement between different sets of remission criteria (Cohen's kappa 0.33–0.89). ConclusionClinical remission is achievable in real-world severe asthmatics on biological therapies. The core criteria for remission should be better defined.

Understanding Differential Response to Biologic Therapies in Severe Asthma: Retrospective study

Severe asthma, characterized by airway inflammation and debilitating symptoms, poses a significant challenge to millions of people worldwide. Traditional treatments for treating severe cases are limited, leading to the emergence of biologic therapies as promising alternatives. This retrospective cohort study from a tertiary hospital in Dubai aimed to explore the differential response to biologics in severe asthma patients and identify predictors of treatment outcomes. The baseline characteristics of 129 severe asthma patients receiving biologic therapy were analyzed, revealing a greater incidence of allergic diseases among responders. Multivariate Cox regression analysis revealed that early-onset asthma, urticaria, and rhinosinusitis (p =0.027, 0.037, and <0.001, respectively) were predictors of a positive treatment response. Compared with non-responders, responders demonstrated improved asthma control, reduced exacerbations, and decreased oral corticosteroid usage. Despite the limitations inherent in retrospective studies, our findings underscore the significant clinical benefits of biologic therapy in severe asthma patients. Tailored treatment strategies based on patient characteristics and biologic class could optimize outcomes in this population, emphasizing the importance of personalized medicine in managing severe asthma. Further research into predictive biomarkers and larger cohort studies are warranted to validate these findings and enhance treatment efficacy in severe asthma management.

Healthcare Resource Utilisation of Severe Uncontrolled T2low and Non-T2low Asthma in Finland During 2018-2021.

Patients with asthma and low levels of type 2 inflammatory biomarkers (T2 low) have limited effective treatment options. Such biomarkers include eg blood eosinophils (b-eos) and fractional exhaled nitric oxide (FeNO). The healthcare resource utilisation (HCRU) of severe uncontrolled T2 low asthma remains unexplored. Thus, this study aimed to estimate the HCRU of T2 low and non-T2 low severe uncontrolled asthma patients using real-world data in Finland. Adult patients with an asthma diagnosis during baseline (2012-2017) at the pulmonary department of Turku University Hospital were included and followed during 2018-2021, or until death. Total HCRU costs and respiratory-related HCRU costs were evaluated. The main drivers for the HCRU and costs were assessed with gamma and negative binomial regression models. Of the severe uncontrolled asthma patients with T2 status available, 40% (N=66) were identified with T2 low and 60% (N=103) with non-T2 low asthma. The average cumulative cost per patient was similar in patients with T2 low compared with non-T2 low, with all-cause costs cumulating in four years of follow-up to 37,524€ (95% CI: 27,160, 47,888) in T2 low compared to 34,712€ (25,484, 43,940) in non-T2 low. The corresponding average cumulative respiratory-related costs were 5178€ (3150, 7205) in T2 low compared to 5209€ (4104, 6313) in non-T2 low. Regression modelling identified no differences between the T2-status groups when assessing all-cause healthcare costs per patient-year (PPY). On the other hand, the regression modelling predicted more inpatient days PPY for severe uncontrolled patients with T2 low status compared to the patients with non-T2 low status. Patients with uncontrolled severe T2 low asthma use equal healthcare resources as corresponding non-T2 low patients. This study brought new insights into the HCRU of severe uncontrolled asthma patients per T2 status, which has not previously been investigated.

Assessment of Tenascin C levels in the serum of patients with bronchial asthma

Asthma is a heterogeneous disease that affects a large proportion of the global population and is distinguished by airway hyperresponsiveness to direct and indirect stimulations. It is a multifactorial disease that is triggered by heredity and environmental causes. Tenascin C (TNC) is an extracellular matrix glycoprotein that promotes inflammatory cell migration from the interstitium to the airways. Stimulation of TNC is through cytokines from T helper 2 (Th2) cells, in addition, it proliferates within basement membranes of the airways in asthmatic patients. This study aimed to determine whether serum TNC can be used as a novel biomarker for asthma diagnosis and to evaluate the association between serum TNC measurement and asthma severity. This case-control study included 64 patients with mild to severe bronchial asthma, diagnosed according to GINA 2022, referred to the Allergy and Clinical Immunology outpatient clinic at Ain Shams University Hospital, and 64 normal subjects as controls. Serum TNC levels were measured by ELISA. Serum TNC levels were significantly higher among bronchial asthma patients than controls (p ˂0.001). The sensitivity of serum TNC measurement in the diagnosis of bronchial asthma was 93.75%, the specificity 60.94%, and the negative predictive value 90.7%. Besides, a significant relation was found between serum TNC levels and the severity of bronchial asthma (p=0.004), as elevated serum TNC levels were the highest among severe asthmatic patients. In conclusion, the results gained in this study revealed that serum TNC level could be proposed as a potential biomarker for the diagnosis of bronchial asthma and a potential predictor of disease severity.

Scoping review on severe asthma: Cytokines, cells, triggers and multi-omics approaches

<abstract> <p>Severe asthma (SA) is a refractory condition that does not respond well to conventional treatments. Patients with SA have heterogenetic endotypes. Endotypes for SA can be classified as type 2 cytokine-high and type 2 cytokine-low. The condition can also be classified as eosinophilic, neutrophilic, mixed, and paucigranulocytic SA. Abnormalities in T<sub>H</sub>1 and T<sub>H</sub>17 cytokines can be present in some SA patients. Innate lymphoid cells, airway smooth muscle cells, and lung epithelial cells have important roles in the disease. Viral infections, bacterial infections, fungal infections, smoking, allergens, and pollutants are major triggers that determine the severity of the disease. Biologics have been proven to be effective for some type 2 high patients. Multi-omics approaches, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, have identified many novel genes or molecules that could serve as biomarkers or potential therapeutic targets for SA. Investigations of the mechanisms of novel genes and molecules will help us understand the condition and find new treatment means for SA in the future.</p> </abstract>

The Path to Diagnosis of Severe Asthma-A Qualitative Exploration.

Severe asthma poses a significant health burden in those with the disease, therefore a timely diagnosis can ensure patients receive specialist care and appropriate medication management. This study qualitatively explored the patient experience of adult Australians with severe asthma regarding specialist referral, to identify potential opportunities to streamline the process of severe asthma diagnosis and treatment and optimise referral pathways. Adults currently being treated with medication for severe asthma were invited to participate in this study. Participants were interviewed and asked to describe initial diagnosis of their asthma or severe asthma, and how they came to be referred to secondary care. Interviews were transcribed verbatim, coded by two members of the research team and thematically analysed. Thirty-two people completed the study; 72% were female. Mean interview length was 33 minutes. The major themes generated were patient-related factors contributing to seeking a severe asthma diagnosis; perceptions of health care provision; diagnosis of severe asthma and the referral journey.Key findings were that both patient and healthcare provider attitudes contributed to participants' willingness to seek or receive a referral, and referral to respiratory specialists was often delayed. Contributing factors included a mismatch between patient expectations and general practice, lack of continuity of primary care, and a lack of patient understanding of the role of the respiratory specialist. Timely severe asthma diagnosis in Australia appears to be hampered by an absence of a clear referral process, lack of general practitioner (GP) knowledge of additional treatment options, underutilisation of pharmacists, and multiple specialists treating patient comorbidities. Directions for future research might include interviewing healthcare providers regarding how well the referral process works for severe asthma patients, and researching the time between referral and when a patient sees the respiratory specialist.

Eosinophil to lymphocyte ratio may predict OCS reduction and change in quality of life (AQLQ) resulting from asthma biological treatment

Objectives Simple clinical parameters that could be helpful in choice of monoclonal antibodies and prediction of their effectiveness are being sought. The aim was to assess if neutrophil-to-lymphocyte, eosinophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict outcomes of biologic therapy for severe asthma. Methods Retrospective, single-center study including severe asthma patients treated with three different biologics. The blood ratios were assessed at initiation of treatment (point 0) and after six months (point 1). The chi-square test was used to analyze differences in nominal variables. Quantitative variables were compared by Student’s t-test, Mann–Whitney U or Wilcoxon signed-rank tests. Results 53 patients with severe asthma were included, among them 21 patients (40%) treated with omalizumab and 32 patients (60%) with mepolizumab or benralizumab. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios did not change during six-month-course of biological treatment. Eosinophil-to-lymphocyte ratio was higher at the point 0 (p = 0.016) in the group treated with anti-eosinophils than in the omalizumab group and lower at the point 1 (p = 0.006). In the anti-eosinophil group this ratio decreased between points 0 and 1 (p < 0.001). In the omalizumab group there was an inverse correlation between the initial ratio and oral corticosteroid dose reduction (rs = −0,67). In the a/eos group there were significant correlations between initial ratio and age (rs = 0.36), and ACQ (rs = −0.4) and ACQ (rs = 0.41) measured at the point 1. Conclusions Pretreatment eosinophil-to-lymphocyte ratio may predict oral corticosteroid dose reduction resulting from omalizumab treatment and change in quality of life and asthma control resulting from anti-IL-5 and IL-5R treatment.

Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling

Dysregulation of IL-17A is closely associated with airway inflammation and remodeling in severe asthma. However, the molecular mechanisms by which IL-17A is regulated remain unclear. Here we identify epithelial sirtuin 6 (SIRT6) as an epigenetic regulator that governs IL-17A pathogenicity in severe asthma. Mice with airway epithelial cell-specific deletion of Sirt6 are protected against allergen-induced airway inflammation and remodeling via inhibiting IL-17A-mediated inflammatory chemokines and mesenchymal reprogramming. Mechanistically, SIRT6 directly interacts with RORγt and mediates RORγt deacetylation at lysine 192 via its PPXY motifs. SIRT6 promotes RORγt recruitment to the IL-17A gene promoter and enhances its transcription. In severe asthma patients, high expression of SIRT6 positively correlates with airway remodeling and disease severity. SIRT6 inhibitor (OSS_128167) treatment significantly attenuates airway inflammation and remodeling in mice. Collectively, these results uncover a function for SIRT6 in regulating IL-17A pathogenicity in severe asthma, implicating SIRT6 as a potential therapeutic target for severe asthma.

A five-gene qPCR signature can classify type 2 asthma comparably to microscopy of induced sputum from severe asthma patients

ABSTRACT Asthma is a heterogenous disease characterized by airway inflammation and variable expiratory airflow limitation resulting in variable respiratory symptoms. Characterization of airway inflammation is important to choose the optimal treatment for severe asthma patients eligible for biological treatment. However, counting cells in induced sputum samples are a time-consuming process, highly dependent on personal skills. Replacing eosinophil and neutrophil cell counting with qPCR for transcripts of selected mast cell, and basophil genes may provide more reproducible results. Aims The objective of this study was to compare qPCR with microscopy in asthma endotyping. Methods A qPCR method measuring five mast cell/basophil genes was applied on induced sputum samples from 30 severe asthma patients and compared with microscopy. Target gene Ct-values (CPA3, GATA2, HDC, MS4A2, TPSAB1/TPSB2) were referenced to household β-actin Ct values as a measure of relative mRNA abundance of the target in each sample. Target/β-actin-ratios in eosinophilic and non-eosinophilic groups determined by microscopy with an eosinophil threshold of 3% in 400 cells were compared using Mann–Whitney U Test. Spearman´s correlations were used to test for correlation between targets vs. FENO and targets vs. blood eosinophil counts. Results The study demonstrated a statistical difference in relative mRNA abundance for four mast cell/basophil specific genes. CPA3, GATA2, HDC and MS4A2 were elevated in eosinophilic asthma versus non-eosinophilic asthma patients. The study found that GATA2, CPA3, MS4A2 and TPSAB1/TPSB2 transcripts are positively correlated with FENO. Neither the five mast cell genes nor the five-gene signature correlated with blood eosinophils. The five-gene signature with a target/β-actin-ratio cut-off ≥2 generated sensitivity = 87%, specificity = 94%, NPV = 88% and PPV = 92% compared to microscopy. Conclusion This study confirms the contribution of mast cells in the pathogenesis of EA and suggests that mast cell mRNA markers could be one of the biomarkers used to identify EA

The Medico-Legal Aspects of Non-Traumatic Subdural Haemorrhage

In this case study, we describe a case of a subdural haemorrhage in an acutely severe asthmatic patient in a suspicious circumstance. A woman in her early 40s came to the emergency department with an acute asthmatic exacerbation. The autopsy showed subdural hemorrhage in the parieto-temporal area and slightly congested, overinflated lungs with mucus plugs and a thickened bronchiolar wall. This case report emphasizes the medicolegal aspect of the presence of subdural haemorrhage in an asthmatic patient who died in a suspicious circumstance.

Patient-reported outcome measures in severe asthma: an expert consensus

Objective The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. Methods Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs’ relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). Results Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. Conclusion This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management.

Expert consensus on management of pain, agitation and related issues in adult patients with critical respiratory diseases

As patients with critical respiratory diseases suffer from the discomfort of disease, frequent medical and nursing procedures, and the noise disturbance of the ICU environment, it is necessary to implement analgesia and sedation to reduce their negative stress and oxygen consumption. Special emphasis will be placed on the clinical practice of analgesia, sedation and rehabilitation in critically ill patients with respiratory diseases, as different pathophysiological features of the respective pulmonary diseases are presented, such as severe asthma and acute exacerbations of chronic obstructive pulmonary disease, as well as the exclusive situations during respiratory therapy, such as recruitment maneuvers, bedside bronchoscopy and operation of extracorporeal membrane oxygenators. To standardize the prevention and management of pain, agitation, delirium, immobility, and sleep disturbance in adult patients with critical respiratory diseases, the Chinese Thoracic Society and Critical Care Medicine Group of Chinese Association of Chest Physicians, Chinese Medical Doctor Association organized pulmonary and critical care experts to discuss 19 important issues and ultimately provided 20 recommendations based on the best available evidence.Assessment, prevention and management of pain should be prioritized before the administration of continuous infused sedatives in all patients with critical respiratory diseases. Bundles that include multiple strategies of non-pharmacological interventions to prevent and manage delirium and sleep disruption are encouraged. For the patients with stable respiratory and hemodynamic status, early mobility and exercise could be safe and beneficial. Respiratory drive control by addressing patient and ventilator factors should be the priority before administration of analog-sedation protocol in the ARDS patients. Deep sedation could be necessary in the early stage of ARDS with high respiratory drive, and during the recruitment maneuver, prone position and measurement of the respiratory mechanics. Maintaining spontaneous breathing with a lower level of sedation is recommended in COPD patients on invasive mechanical ventilation, while a deeper level of sedation, even with a short course of neuromuscular blockade, may be beneficial among severe asthma patients with high peak airway pressure. Pharmacokinetic alterations in patients with critical respiratory diseases during ECMO support are complicated as varied factors are involved, including ECMO circuit factors, drug factors, and patient factors. Therefore, the dosage of analgesics and sedatives should be adjusted according to the target of analog-sedation protocol in the respective disease.

Peripheral neutrophils and oxidative stress-associated molecules for predicting the severity of asthma: a cross-sectional study based on multidimensional assessment.

This study aims to explore the relationship between the severity of asthma and neutrophils and related oxidative stress-associated molecules in peripheral blood and induced sputum. A total of 67 subjects were included in this study, namely, 25 patients with severe asthma and 42 patients with non-severe asthma. Clinical data, induced sputum and peripheral blood were collected. Lung function and molecules related to oxidative stress in induced sputum and peripheral blood of asthma patients were detected. The relationship between neutrophils and asthma severity was analyzed. HDAC2 mRNA and protein expression levels and HDAC2 activity were also analyzed. Multivariate logistic regression was performed to select statistically significant variables. The absolute value of neutrophils and percentage of neutrophils were higher in the severe asthma patients. These two values were used to predict the severity of asthma by ROC analysis, with the best cutoff values being 4.55 × 109/L (sensitivity 83.3%, specificity 64.0%) and 55.15% (sensitivity 54.8%, specificity 88.0%). The ROS concentration of neutrophils in the induced sputum samples and the 8-iso-PGF2α concentration in the peripheral blood samples were higher in the severe asthma group (P = 0.012; P = 0.044), whereas there was reduced HDAC2 protein activity in PBMCs (P < 0.001). A logistic equation and a nomogram were created to give a precise prediction of disease severity. Oxidative stress is increased in severe asthma patients. Peripheral blood neutrophils and 8-iso-PGF2α can be used as biomarkers to predict the severity of asthma. A prediction model was created for evaluating asthma severity.

An examination of factorial invariance of the Asthma Control Questionnaire among adults with severe asthma

Background The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown. Methods Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed. Results A one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p&lt;0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p&lt;0.01)and increased with age (p&lt;0.01). Reliability of the instrument was high (over 88%) in all subgroups studied. Conclusion The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.

EE101 Assessing the Cost-Effectiveness of Introducing Benralizumab in the Treatment of Severe Uncontrolled Eosinophilic Asthma Patients in Prince Sultan Military Medical City (PSMMC) - Kingdom of Saudi Arabia (KSA)

EE101 Assessing the Cost-Effectiveness of Introducing Benralizumab in the Treatment of Severe Uncontrolled Eosinophilic Asthma Patients in Prince Sultan Military Medical City (PSMMC) - Kingdom of Saudi Arabia (KSA)

HSD44 Healthcare Resource Utilization of Severe Eosinophilic Asthma Patients Treated With Benralizumab in Real-Life: Results From the Portuguese BETREAT Study

HSD44 Healthcare Resource Utilization of Severe Eosinophilic Asthma Patients Treated With Benralizumab in Real-Life: Results From the Portuguese BETREAT Study

AIM2 participates in house dust mite (HDM)-induced epithelial dysfunctions and ovalbumin (OVA)-induced allergic asthma in infant mice

Objective: Allergen sensitization and high rates of concomitant allergic diseases are characteristic of severe pediatric asthma. The present study was aimed to explore the mechanism of allergic asthma via bioinformatics and experiment investigation. Methods: The GSE27011 dataset contained the expression profiles of normal and pediatric asthma white blood cells was downloaded for analyzing the different expression genes and function enrichment. The allergic asthma model in infant mice was established by ovalbumin (OVA) stimulation. The cellular model was established by house dust mite (HDM)-stimulation in human bronchial epithelial cells. The absent in melanoma 2 (AIM2) knockdown was achieved by intranasal lentivirus injection or cell infection. The bronchoalveolar lavage fluid (BALF) was collected for cell counting and ELISA assessment of cytokines. Lung tissues were collected for HE staining and immunohistochemical (IHC) staining. Real-time PCR and immunoblotting were used for the determination of key gene expressions in mouse and cell models. Results: upregulation of AIM2 gene expression was observed in pediatric asthma patients based on GSE27011 and OVA-induced infant mouse allergic asthma model. AIM2 knockdown ameliorated OVA caused elevation in airway hyper-responsiveness (AHR), elevation in cell quantities (eosinophils, neutrophils, lymphocytes), and levels of cytokines (IL-4, IL-13, TNF-α, and OVA-specific IgE) in BALF. Moreover, AIM2 knockdown relieved OVA-caused histopathological alterations in mouse lungs, up-regulation of AIM2 levels, and NOD1 and receptor-interacting protein 2 (RIP2) protein levels, as well as p65 phosphorylation. In the cell model, AIM2 knockdown partially ameliorated HDM-induced epithelial dysfunctions by promoting cell viability, down-regulating inflammatory cytokines levels, and decreasing the protein levels of AIM2, NOD1, RIP2, and phosphorylated p65. Conclusion: AIM2 participates in HDM-induced epithelial dysfunctions and OVA-induced allergic asthma progression. AIM2 could be a promising target for pediatric allergic asthma treatment regimens, which warrants further in vivo investigations.

Comparison of Long-term Response and Remission to Omalizumab and Anti-IL-5/IL-5R Using Different Criteria in a Real-life Cohort of Severe Asthma Patients

BackgroundEvaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission. ObjectivesTo ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission. MethodsA multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria. ResultsThe study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06–1.23; p<0.001), admissions at ICU (2.69; 1.30–5.56; p=0.01), high count of SAE (1.21; 1.03–1.42; p=0.02) before biologic treatment. High FEV1% (0.96; 0.95–0.98; p<0.001), a high ACT score (0.93; 0.88–0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29–0.91; p=0.02) showed strong associations with achieving clinical remission. ConclusionA substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons.

Predictors of persistent poor control and validation of ASSESS score: Longitudinal 5-year follow-up of severe asthma cohort

BackgroundLongitudinal predictors of persistent poor asthma control in severe asthma (SA) cohort remain scarce. The predictive value of the asthma severity scoring system (ASSESS) and their validation in the SA cohort outside the original study and in the Asian population is unknown. ObjectiveTo determine the 5-year longitudinal outcome of SA patients and validate the use of ASSESS score in predicting future outcomes in SA. MethodsProspective longitudinal observational study of patients with severe asthma (SA) attending the multidisciplinary specialist SA clinic from 2011 to 2021. The number of exacerbations and asthma control tests (ACT) were recorded yearly for 5 consecutive years. ASSESS score was computed at baseline, and the area under the receiving operating characteristics curve (AUC) for predicting persistent poor asthma control was generated. ResultsOf the 489 patients recruited into the study, 306 patients with 5-year follow-up data were analyzed. Seventy-three percent had Type-2 inflammation (T2) with increased overall exacerbations over 5 years (rate ratio (RR) 2.55, 95% CI 1.31-4.96, p=0.006) relative to non-T2 SA. In the multivariate model, bronchiectasis, gastroesophageal reflux disease (GERD) and ACT<20, were significantly associated with persistent poor asthma control over 5 -years. ASSESS scores were good at predicting persistent poor asthma control with an AUC of 0.71 (95% CI 0.57-0.84). ConclusionBronchiectasis and GERD are predictors for persistent poor asthma control and targeted traits for precision medicine in SA. The ASSESS score has a good prediction for persistent poor asthma control over 5 years.

Application of Omalizumab Combined with Enteral Nutrition in Treating Severe Allergic Asthma

To investigate the influence of omalizumab combined with enteral nutrition in treating severe allergic asthma, 102 patients in our hospital from May 2020 to May 2023 were retrospectively included, followed by dividing into a control group and a study group. The control group received only budesonide formoterol, and the study group accepted budesonide formoterol, omazumab, and an oral enteral hypernutrient polymer. After therapy, the asthma control test score, mini-asthma quality of life questionnaire score, hemoglobin level, serum total protein level, serum total immunoglobulin E level, forced expiratory volume in one second, forced expiratory volume in one second predicted, CD3+, CD4+, and CD4+/CD8+ in the study group presented higher than the control group, while CD8+, fractional concentration of exhaled nitric oxide level, and percentage of eosinophils in blood were lower. No difference was observed in the incidence of adverse reactions between the two groups (P = 0.34). To sum up, enteral nutrition combined with omalizumab can effectively inhibit airway inflammation, improve lung function, and promote the quality of life of severe allergic asthma patients with high safety, which opens a new way of biologically targeting therapy for asthma.