Paula Fernández Martínez

Background/Objectives: Real-world evidence on dupilumab-induced clinical remission on treatment and on the predictors of complete response in severe uncontrolled asthma (SUA) is still limited. Methods: We conducted a single-centre ambispective uncontrolled observational study including 152 adults with SUA who started dupilumab. Lung function, type-2 (T2) biomarkers, patient-reported outcomes, exacerbations, oral corticosteroid (OCS) use, emergency-department (ED) visits and hospitalisations were compared between baseline and last follow-up. Response was graded with FEOS and EXACTO. Independent predictors of complete response (EXACTO = 1) were explored by multivariable logistic regression. Results: Mean age was 50 ± 12 years, 67.1% were women, baseline FEV1 was 82 ± 22% predicted, blood eosinophils were 612 ± 577 cells/µL and FeNO was 55 ± 46 ppb. After 21 ± 8 months, ACT improved from 15.7 to 23.3, ACQ-5 from 4.0 to 0.35, mini-AQLQ from 2.18 to 4.53, SNOT-22 from 52 to 16, and FEV1 by 275 ± 180 mL (all p < 0.001). Annual exacerbations decreased from 7.9 to 0.7, ED visits from 3.17 to 0.28, hospitalisations from 0.71 to 0.08, and maintenance OCS use from 11.8% to 3.9%. According to EXACTO, 95 patients (62.5%) achieved complete response/super-response. Independent predictors were higher baseline FEV1, higher eosinophil count, allergic rhinitis, rhinosinusitis with nasal polyps and atopic dermatitis, whereas prior OCS bursts and higher FeNO were inversely associated. Model discrimination was adequate (AUC = 0.91). Conclusions: Dupilumab achieved clinical remission on treatment in almost two-thirds of patients with SUA and markedly reduced healthcare utilisation. A T2-comorbidity-rich profile identified patients with the highest probability of complete response.

Background/Objectives: Chronic home oxygen therapy—long-term oxygen therapy (LTOT)—improves survival and quality of life in chronic respiratory failure when used ≥15 h/day, but adherence is frequently suboptimal and specific patient-reported outcome measures (PROMs) are scarce. To develop, validate and apply a specific PROM for patients on LTOT. Methods: A prospective observational cohort study was conducted at San Juan de Alicante University Hospital (April 2024–December 2025) following a four-stage process: conceptual framework definition and expert workshop, content validation and item reduction, cognitive interviews with pilot reliability testing (n = 25), and field application to 120 consecutive chronic LTOT users. The LTOT-PROM was designed to capture the patient-perceived impact attributable to LTOT during the previous 4 weeks. Internal consistency was assessed with Cronbach’s α and test–retest reproducibility with the intraclass correlation coefficient (ICC). Results: The final instrument comprises 15 scored items in two dimensions—Daily Activity (9 items) and Adverse Effects (6 items)—plus one ambulatory-only mobility item excluded from the total score. Cronbach’s α was 0.814 (95% CI 0.681–0.906) for Daily Activity, 0.743 (95% CI 0.548–0.872) for Adverse Effects and 0.808 (95% CI 0.677–0.902) for the total scale; total ICC(A,1) was 0.890 (95% CI 0.767–0.950). Among the 120 patients (62 men, 58 women; mean age 78 ± 13 years; mean therapy duration 40 ± 32 months), 68% reported reduced effort for daily activities, 66% reported a reduction in dyspnoea and 67% reported improved self-confidence; 49% reported morning airway dryness and 7% abandoned the equipment due to nasal dryness or rhinitis. Conclusions: The LTOT-PROM is a brief, reliable and reproducible oxygen-specific instrument for assessing the recent patient-perceived impact of LTOT in routine clinical practice. Further studies should evaluate structural validity, external validity and the relationship between LTOT-PROM scores and objective adherence measures. The construct was predefined as the patient-perceived impact attributable to LTOT during a standardised 4-week recall window, and cognitive interviews confirmed that respondents interpreted the items as experienced benefit/burden during that period rather than as week-to-week symptom change.

Background: Tobacco-related small-airway dysfunction (SAD) may precede spirometric obstruction. The single-breath nitrogen washout (SBW N₂) captures ventilation heterogeneity and may detect early peripheral airway involvement through the phase III slope (ΔN₂/L) and closing volume (CV). Aim: To describe SBW N₂ indices in smokers with preserved spirometry, examine their relationship with cumulative smoking exposure, and contextualise results against published reference (healthy predicted) values. Methods: Cross-sectional study of current smokers (n=90) with preserved spirometry (pre-bronchodilator FEV1/FVC ≥0.70). Spirometry followed SEPAR criteria and SBW N₂ followed ERS/ATS recommendations. Associations with pack-years were assessed by Pearson correlations and linear regression. In the absence of a concurrently recruited healthy control group, SBW N₂ outcomes were also expressed as percent-predicted using published reference equations (ΔN₂/L and CV/VC in males aged 30–70 years). To explore sex-related differences in ventilation heterogeneity, we compared key characteristics and size-independent functional indices between men and women (spirometry as % predicted and ratios) and fitted a multivariable OLS model for ΔN₂/L adjusting for pack-years, age and BMI. Results: Mean age was 42 (11) years and mean smoking exposure 29.01 (16.95) pack-years. Mean ΔN₂/L was 2.674 (1.424) %N2•L⁻¹ and correlated significantly with pack-years (r=0.452, p<0.0001), as did CV/VC (r=0.389, p=0.00015). In external-reference comparisons, ΔN₂/L in males aged 30–70 years (n=42) was markedly elevated (327.1 (165.7)% predicted; p<0.0001), with 83.3% exceeding the proposed ULN (180% predicted). In multivariable regression adjusting for pack-years, age and BMI, male sex remained independently associated with higher ΔN₂/L (β=+0.946 %N2•L⁻¹; 95% CI 0.400 to 1.492; p<0.001). Conclusions: SBW N₂ indices—particularly ΔN₂/L—show a dose–response relationship with smoking burden and are markedly abnormal relative to healthy predicted values, even in smokers with preserved spirometry. These findings support SBW N₂ as a sensitive tool for detecting early peripheral SAD before spirometric obstruction becomes apparent. Sex-related differences in ΔN₂/L persisted after adjustment for smoking exposure and anthropometrics, suggesting that sex should be considered when extrapolating male-based reference contextualisation to women.

Background: Tezepelumab has demonstrated efficacy in severe uncontrolled asthma (SUA), although real-world evidence remains limited. Methods: We included patients with SUA who completed at least 6 months of treatment. Lung function, eosinophil counts, IgE, FeNO, comorbidities, and changes in asthma control were assessed using ACT, ACQ, the VAS, and quality of life (AQLQ), as well as severe exacerbations (hospital admissions and emergency visits), oral corticosteroid (OCS) courses, OCS withdrawal/dose reduction, and reductions in maintenance and reliever medication. Response was evaluated using the FEOS and EXACTO scales. Baseline (T0) and 6-month (T6) outcomes were compared in the overall cohort and according to T2-high (eosinophilic/allergic) vs. T2-low phenotype. Results: A total of 33 patients were analyzed (58 ± 12 years; 94% women), with a high burden of comorbidities (88%), mainly rhinosinusitis (79%), obesity (41%), and smoking (37%). Of these, 45.5% had received prior biologic therapy. All patients were on high-dose ICS + LABA, frequently with LAMA and other controllers; 30% were on maintenance OCS. In the previous year, 49% had been hospitalized, 97% had attended the emergency department, and 100% required OCS courses. After 10 ± 3 months, the overall group showed significant improvement in VAS, ACT, ACQ, and AQLQ (p < 0.001), with a reduction in eosinophils, but no significant change in FEV1%. Severe exacerbations, emergency visits, hospitalizations, and OCS courses decreased markedly (p < 0.001). Among 10 patients on maintenance OCS, OCS were discontinued in 7 and reduced in 3; maintenance/reliever medication was also reduced. The T2-high phenotype showed a higher likelihood of “complete response” (52% vs. 17% in non-T2), although “good response” predominated in non-T2; this difference was significant (p = 0.04). Conclusions: Tezepelumab improved asthma control and reduced healthcare utilization and corticosteroid use in both T2 and non-T2 patients, achieving clinical remission in 40%, with better outcomes in T2.