Journal of Asthma and Allergy最新文献

Purpose: With the advent of biological therapies, emerging concepts regarding establishing new targets in asthma management, such as disease modification, have entered the debate among the scientific community. The definitions that form the conceptual basis of this goal need to be agreed upon.

Methods: A multidisciplinary expert group was assembled as the steering committee. A systematic literature review was conducted to identify the scientific background for constructing appropriate definitions. Based on the literature review and the clinical experience of the experts, the committee built a list of statements that could be applied to establish the definition of disease modification in asthma. After that, a Delphi validation was performed to assess the appropriateness of the list of statements. The questionnaire included a total of 22 statements, divided into "Essential criteria for disease modification in asthma" (5 statements) and "Disease modification indicators and other considerations" (17 statements). Panelists used a 9-point Likert scale to measure agreement on each statement. The cut-off point for high consensus was defined as a minimum score of 7 and had to be reached by at least two-thirds of the experts.

Results: A total of 192 asthma experts voted on statements anonymously. Of those, 104 (54%) were Pneumologists, 65 (34%) were allergologists, and 23 (12%) were Pediatricians. An interim analysis of round 1 data was performed. All statements reached consensus on the first round, with a median score above 7 in all cases.

Conclusion: In conclusion, in this Delphi study, a large number of experts in the management of severe asthma from different specialties agreed on the clinical-functional and pathophysiological aspects to be considered in order to try to achieve disease modification.

Purpose: Omalizumab, the anti-IgE monoclonal antibody used to treat severe asthma, reduces asthma exacerbations, hospitalizations, and corticosteroid use. Although allergic asthma is a therapeutic target of omalizumab, omalizumab is not effective in all patients with severe allergic asthma and is not always available for long-term use. We retrospectively investigated factors related to long-term (≥2 years) use of omalizumab for severe asthma.

Patients and methods: Of the 116 patients treated with omalizumab for severe asthma at our hospital between 2009 and 2017, 82 were included in this retrospective analysis. Thirty-four were excluded because of adverse events, financial difficulties, or hospital transfers. The number of asthma exacerbations, unscheduled visits, corticosteroid doses, asthma control test scores, pulmonary function test results, and fractional exhaled nitric oxide levels were evaluated.

Results: The median age of the study population was 58 years, with 66% female and 26% taking regular oral corticosteroids. After 2 years of treatment, 52 responders were identified using the global evaluation of treatment effectiveness (GETE) score. Improvements in asthma control test scores, airflow limitation, exacerbations, and oral corticosteroid use were observed in the responders. Multivariate analysis revealed that a peripheral blood eosinophil count of ≥200 or a perennial antigen-specific IgE antibody positivity of ≥2 predicted a response at the 2-year mark. However, Kaplan-Meier analysis demonstrated that neither high eosinophil counts nor perennial antigen-specific IgE positivity influenced the prolongation of treatment beyond 2 years, and responders at 2 years underwent omalizumab treatment for a significantly longer period than non-responders (HR = 9.89, p < 0.001), with GETE at 2 years being the only predictor of long-term omalizumab use.

Conclusion: In this retrospective study the GETE after 2 years of omalizumab therapy emerged as the most meaningful predictor of the long-term effectiveness of omalizumab treatment in patients with severe asthma, highlighting the benefits of prolonged therapy in certain populations. These findings may guide future therapeutic strategies for severe asthma.

Purpose: To investigate the differential clinical significance of fractional concentration of exhaled nitric oxide measured at a flow rate of 200 mL/s (FENO₂₀₀) and concentration of nitric oxide in alveolar (CANO) in asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD Overlap (ACO).

Methods: A total of 178 patients were included, with 82 patients in asthma group, 47 patients in COPD group and 49 patients in ACO group. Data for demographic data, spirometry and exhaled nitric oxide were collected for comparative analysis, correlation analysis and discriminant canonical analysis.

Results: The values of FENO₂₀₀ in asthma, COPD and ACO groups were 11.0(7.0-22.3), 8.0(6.0-11.0) and 9.0(6.5-19.5) ppb, respectively. In the asthma group, FENO₂₀₀ exhibited negative correlations with FEV₁/FVC, MMEF and MEF50. No significant correlation was observed between CANO and pulmonary function parameters. In the COPD group, both FENO₂₀₀ and CANO showed negative correlation with pulmonary function parameters including FVC, FEV₁, PEF, MMEF, MEF75, MEF50. In the ACO group, FENO₂₀₀ demonstrated no significant correlation with pulmonary function parameters, while CANO was correlated with FEV₁, PEF, MMEF and MEF50. In COPD group, ΔFEV₁ in the bronchodilator test was correlated with FENO₂₀₀. As for the ACO group, ΔFEV₁ was correlated with CANO. In the discriminant canonical analysis, four parameters including gender, age, MEF75 and FENO₅₀ discriminated between the three groups of asthma, COPD and ACO.

Conclusion: In asthma, COPD and ACO, FENO₂₀₀ has demonstrated a robust correlation with CANO. Elevated FENO₂₀₀ levels are predominantly indicative of pulmonary function impairment in asthma and COPD, whereas elevated CANO levels are mainly correlated with pulmonary function impairment in COPD and ACO. Compared with FENO₂₀₀ and CANO, FENO₅₀ may have a better discriminatory ability in distinguishing asthma, COPD and ACO.

Background: Asthma is a health condition with worldwide relevance, evaluated based on the necessary treatment to control symptoms and exacerbations. Severe asthma is uncontrolled despite high doses of ICS-LABA and treatment for triggering factors. Severe eosinophilic asthma is characterized by an increase in eosinophils in the peripheral circulation, walls, and passages of the respiratory tract. Biologic treatments such as benralizumab have demonstrated effectiveness as aids in decreasing respiratory tract inflammation and improving the management of symptoms in patients living with asthma.

Objective: To assess the efficacy and safety of benralizumab as an add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts.

Methods: Observational, analytic and ambispective study in 21 patients diagnosed with severe eosinophilic asthma treated with benralizumab, to determine the treatment's effectiveness through the change in estimated respiratory function by spirometry through the forced expiratory volume in one second (FEV1) value, reduction in second controlling treatment, serum eosinophil reduction, change in the Asthma Control Test score and the Asthma Control Questionnaire test at 6 and 16 months of treatment.

Results: An average difference of 241.43 mL (±461.43) in FEV1 at 6 months was found, as well as an average FeNO reduction of 49.8 ppm and eosinophil reduction of 612.78 cells at 12 months of treatment, additionally, CSI requirements were reduced in 95% of patients.

Conclusion: Benralizumab improved respiratory function as well as key biomarkers such as eosinophil count, exhaled nitric oxide fraction (FeNO), which reflected in a decreased requirement of inhaled corticosteroids and improved symptom control.

Background: Patients with severe asthma (SA) benefit from biologic therapy substantially. However, the impact of smoking-related comorbidities remains unclear due to the exclusion of patients with ≥10 pack-years from asthma studies. Our aim was to examine the effects of emphysema on biologic treatment response in SA in this retrospective cohort study.

Methods: Pulmonary emphysema was examined using computed tomography. Patients with SA were included and divided into two groups based on emphysema quantity (≥5% or <5%). They received either anti-IgE (22.1%), anti-IL-5-(receptor) (52.3%), or anti-IL-4/IL-13 (25.6%) biologic therapy. Treatment response was assessed after 7.8 ± 2.5 months based on acute exacerbations (AE), oral corticosteroid (OCS) therapy, Asthma Control Test (ACT), forced expiratory volume in 1 second (FEV1) and using the Biologics Asthma Response Score (BARS).

Results: This study comprised 86 patients (mean age 56.1 ± 12.8 years; 54% female). Half (43, 50.0%) were never-smokers, half ex-smokers with an average of 26.9 ± 18.2 pack-years. Patients with ≥5% emphysema were more often ex-smokers (80% vs 41%, p=0.002), had poorer lung function (FEV1 median 1.3 [interquartile range: 1.0;1.6] vs 1.8[1-2;2.4] L, p=0.037), and more comorbid COPD (50% vs 21%, p=0.012). However, no significant differences were noted in treatment response regarding annualized AE rate (-2.5[-5;-1] vs -3.0[-5;-2] n/year, p=0.295) and OCS reduction (-4[-10;0] vs -5[-10;0] mg, p=0.691), ACT score (5[3;9] vs 4[0;9] points, p=0.579) or FEV1 improvement (0.03[-0.15;0.25] vs 0.23[-0.5;0.49] L, p=0.052), BARS (p=0.312), and remission rates (15.0% vs 19.7%, p=0.753).

Conclusion: In patients with severe asthma, those with comorbid emphysema show similar treatment response to biologic therapy. Therefore, suitable patients should not be denied biologics due to the presence of emphysema.

Background: Adenoid hypertrophy (AH) and allergic rhinitis (AR) are common pediatric diseases, seriously affecting the quality of life and growth of children. The recurrence rate of AH is higher for patients with than for those without concurrent AR. Allergen specific immunotherapy (AIT) is the only effective therapy for modifying the course of allergic diseases. This study sought to investigate the efficacy of AIT in preventing AH recurrence in patients with AR who underwent adenoidectomy.

Methods: This study included 134 children aged 5-12 years with concurrent AH and AR. They were separated into the subcutaneous immunotherapy (SCIT) group treated with a double-mite allergen preparation or the non-AIT group treated symptomatically with only medications. The adenoid/nasopharyngeal ratio at one year after adenoidectomy was used to assess AH recurrence. The Obstructive Sleep Apnoea Questionnaire (OSA-18), Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Visual Analogue Scale (VAS) were used to assess the severity of the sleep disorders and AR.

Results: This study included 62 and 72 children with concurrent AH and AR in the SCIT and non-AIT groups, respectively. The rate of recurrence in the SCIT group was significantly lower than that in the non-AIT group (4.84% vs.16.67%; P=0.030). The OSA-18, PRQLQ, and VAS scores were significantly lower for the SCIT than (P<0.001) for the non-AIT group after one year of treatment.

Conclusion: The findings suggest that AIT should be considered the preferred therapy for reducing postoperative recurrence of AH in children with concurrent AR following adenoidectomy, but further research is needed to confirm these findings in a larger population.

Background: Examining human coding and non-coding RNAs present in skin surface lipids (SSL-RNAs) offers a promising approach to understanding the physiological state of the skin. Benralizumab treatment can reduce exacerbations and improve symptom control and quality of life in patients with severe eosinophilic asthma. Although this treatment effectively depletes peripheral blood eosinophils, the impact of benralizumab on SSL-RNA remains completely unknown.

Objective: To investigate the effects of benralizumab treatment on SSL-RNA profiles in patients with severe asthma.

Methods: Skin samples were non-invasively collected from patients before and after one year of benralizumab treatment. Sixteen patients were enrolled, but the SSL-RNA analysis was only feasible for five patients due to collection challenges, mainly in female participants.

Results: Following benralizumab treatment, asthma symptoms, exacerbation rates, and lung function parameters improved. Peripheral blood eosinophils were completely depleted and serum eotaxin-1 levels increased. SSL-RNA analysis revealed differential expression of 134 genes, with significant downregulation of immune-related pathways and genes associated with neutrophilic inflammation.

Conclusion: These findings suggest a suppression of both type 2 and non-type 2 inflammation in response to benralizumab treatment, with potential implications for asthma management. However, the limitations of the study include a small sample size and challenges in sebum collection, particularly among female participants. Although the noninvasive nature of this sampling method makes it attractive for both research and clinical applications, additional studies are needed to fully investigate the potential of SSL-RNA analysis as a noninvasive biomarker to assess treatment response in asthma.

Purpose: Asthma is affecting 4-5% of all adults (10% of children) in Germany, ≥ half are inadequately controlled. In 2019 up to 54 thousand patients suffered from severe uncontrolled asthma, 52% were treated/co-treated by pneumonologists. 45% of them had continuous oral corticosteroid (OCS)- and short-acting β2-agonist (SABA) overuse for ≥2 years. The aim of the current study was to analyze the main treatments, escalation schemes and the adherence to the GINA recommendations.

Patients and methods: Retrospective analysis in 2021 based on data from January to December 2019 in Germany, using the IQVIA™ LRx prescription database and the IQVIA™ Disease Analyzer database containing anonymized electronic medical records as the main data sources.

Results: In 2019 25,200 patients with severe, uncontrolled asthma treated in a pneumonologist´s practice in Germany received GINA 3 (0,4%), GINA 4 (76%) or GINA 5 therapy (24%) during the study year compared to 59% GINA 5 therapy in the 5-10% (1,500-3,000) co-treated in a specialized outpatient department. In Pneumonologists` practices the most frequent choice in GINA 5 was OCS in 69% of patients (biologicals 37%, long-acting muscarinic antagonist (LAMA) 20%) compared to 66% biologicals, 55% OCS, and 25% LAMA in the outpatient department. 54,958 of 613,000 GINA 4/5 patients were treated with OCS, 9,725 even with doses above the so called "Cushing threshold" for prednisolone of 2700 mg/year. After introduction of a biological treatment, patients reduced their SABA prescriptions by 28%, OCS by 55%, and OCS overall exposure by 40%, one-third did not need OCS anymore.

Conclusion: In 75% of patients with uncontrolled asthma for ≥2 years therapy was not escalated beyond GINA 4 or low dose OCS was used as the most frequent add-on treatment in GINA 5 contradictory to treatment recommendations. Use of biologics reduced on demand rescue medication and OCS use.

Objective: To study the role of transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor receptor related factor 6 (TRAF6) in the progression of epithelial mesenchymal transformation (EMT) in allergic rhinitis (AR).

Methods: A total of 30 patients underwent nasal endoscopic surgery at our Hospital were selected for 15 patients in each group based on their allergy status. Inferior turbinate mucosa tissue was obtained and analyzed using immunohistochemical (IHC) tests, real-time quantitative PCR (qRT-PCR) detection, and Western blotting (WB) tests to measure TGF-β1, TRAF6, E-cadherin, Vimentin, and α-Smooth Muscle Actin (α-SMA) expression levels.

Results: The expression levels of TGF-β1, TRAF6, Vimentin, and α-SMA were significantly higher in the AR group compared to the control group as shown by IHC, qRT-PCR, and WB (P < 0.05). E-cadherin expression was significantly lower group than in the control group (P < 0.05). Protein expression of TGF-β1 showed significantly positive correlations with TRAF6 (r = 0.8188, P = 0.0002), α-SMA (r = 0.8076, P = 0.0003), and Vimentin (r = 0.6917, P = 0.0043). There was a significantly negative correlation between protein expression of TGF-β1 and E-cadherin (r = -0.8032, P = 0.0003). Protein expression of TRAF6 showed a significantly negative correlation with E-cadherin (r = -0.6405, P = 0.0101) but positive correlations with α-SMA (r = 0.5809, P = 0.0231) and Vimentin (r = 0.555, P = 0.0318).

Conclusion: TGF-β1, TRAF6, and EMT-related markers (Vimentin, α-SMA) were highly expressed in the nasal mucosa of AR patients. TGF-β1 and TRAF6 may be involved in the epithelial-mesenchymal transition in allergic rhinitis.