Profiling severe asthma: Any relevance for age? An analysis from Severe Asthma Network Italy (SANI) cohort.

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study.

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

High-Flow Tracheal Oxygen for Tracheostomy Tube Removal in Lung Transplant Recipients.

(1) Background: Because of a complicated intraoperative course and/or poor recovery of graft function, approximately 15% of lung transplant (LT) recipients require prolonged mechanical ventilation (PMV) and receive a tracheostomy. This prospective study aimed to assess the effect of High-Flow Tracheal Oxygen (HFTO) on tracheostomy tube removal in LT recipients receiving PMV postoperatively. (2) Methods: The clinical course of 14 LT recipients receiving HFTO was prospectively evaluated and compared to that of 13 comparable controls receiving conventional oxygen therapy (COT) via tracheostomy. The study's primary endpoint was the number of patients whose tracheostomy tube was removed at discharge from an Intermediate Respiratory Care Unit (IRCU). (3) Results: Setting up HFTO proved easy, and it was well tolerated by all the patients. The number of patients whose tracheostomy tube was removed was significantly higher in the HFOT group compared to the COT group [13/14 vs. 6/13 (p = 0.0128)]. (4) Conclusions: HFTO is an effective, safe therapy that facilitates tracheostomy tube removal in LT recipients after weaning from PMV.

Continuitiy of care with ataluren in Duchenne Muscular Dystrophy patients with nonsense mutations after loss of ambulation. Personal experience.

Duchenne Muscular Dystrophy (DMD) includes predictable phases requiring dedicated standard treatments. Therapeutic strategies feature corticosteroids or the more recent gene therapy/stop codon read-through. Ataluren (Translarna®) is an oral drug promoting the readthrough of premature stop codons caused by nonsense mutation (nm) in order to produce full-length dystrophin. It was licensed by EMA in 2014 for ambulatory patients with nmDMD aged ≥ 5 years. Our aim is to report data on long-term ataluren use in Italian patients with nmDMD, with emphasis on continuity of the treatment after loss of ambulation (LoA). Four DMD patients aged between 16 and 24 years who lost ambulation between 12 and 14 years continued to take ataluren after LoA. The oldest patient, aged 24 years, is still taking a few steps. Even in those experiencing motor decline, PUL-test performances were stable and respiratory function satisfactory in all; two patients developed severe cardiomyopathy, stable in one. Therapeutic continuity with ataluren should be offered to all nmDMD patients after LoA given its favourable safety and efficacy profile. However, further research is recommended to identify additional clinically meaningful outcomes and treatment goals following LoA.

Geographical Overlap Between Alpha-1 Antitrypsin Deficiency and COVID-19 Infection in Italy: Casual or Causal? / Superposición geográfica entre la deficiencia de alfa-1 antitripsina y la infección por COVID-19 en Italia: casual o causal?

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