Background: Non-anemic iron deficiency (NAID) has been increasingly recognized as a potential factor affecting chronic obstructive pulmonary disease (COPD) outcomes. However, its prognostic role in COPD exacerbations and hospitalizations remains poorly understood. This study aimed to evaluate the prevalence of NAID in COPD patients, its impact on functional parameters, and its predictive value for exacerbations and hospitalizations. Methods: This prospective observational study included 238 patients with stable COPD and 60 age- and sex-matched smokers without COPD as a control group. NAID was defined as serum ferritin < 100 ng/mL or serum ferritin between 100 and 299 ng/mL with transferrin saturation < 20%. Clinical assessments included pulmonary function tests, 6 min walk distance (6MWD), handgrip strength, and fat-free mass index (FFMI). Patients were followed for 12 months to record moderate and severe COPD exacerbations. Cox regression analysis was used to determine the predictive value of NAID for exacerbations and hospitalizations. Results: NAID was present in 68.9% of COPD patients compared to 46.7% of smokers without COPD (p = 0.001). COPD patients with NAID had lower 6MWD (430 (330–500) m vs. 462 (390–510) m, p = 0.029), reduced FFMI (17.9 (15.5–20.2) kg/m² vs. 20.6 (17.6–22.6) kg/m², p < 0.001), and weaker handgrip strength (26 (22–33) kg vs. 34 (27–40) kg, p < 0.001) compared to non-NAID COPD patients. During the 12-month follow-up period, 140 patients developed moderate COPD exacerbations (107 in the NAID group), and 43 patients were hospitalized due to severe exacerbations (36 in the NAID group). Cox regression analysis showed that NAID was an independent predictor of moderate COPD exacerbations (HR 1.846, 95% CI 1.249–2.729, p = 0.002) and hospitalization (HR 2.537, 95% CI 1.129–5.703, p = 0.024) after adjusting for age, sex, lung function, and comorbidities. Conclusions: NAID is highly prevalent in COPD and is associated with worse exercise capacity, lower muscle mass, and increased exacerbation risk independently of sex and age. These findings suggest that NAID could be a valuable biomarker for risk stratification in COPD patients, warranting further research on potential therapeutic interventions targeting iron metabolism.

Inflammatory cell activation in asthma may lead to reactive oxygen species (ROS) overproduction with an imbalance between oxidant levels and antioxidant capacity, called oxidative stress (OS). Since particulate matter (PM) airborne exposure may also contribute to ROS generation, it is unclear whether PM contributes more to OS than inflammatory cell activation. In our ASTHMA-FENOP study, which included 44 asthma patients and 37 matched controls, we aimed to characterize OS using five serum markers: total ROS content, protein carbonyl content, oxidized low-density lipoprotein (OxLDL), 8-hydroxydeoxyguanosine, and glutathione. Volunteers wore personal samplers for 24 h, collecting fine and coarse PM fractions separately, and the oxidative potential (OP) was determined using two methods. We observed differences between asthmatic and non-asthmatic volunteers in some OS markers, such as OxLDL, with an adjusted mean difference of 50,059.8 ng/mL (p < 0.001). However, we did not find an association between higher PM-OP and increased systemic OS. This suggests that at our PM-OP exposure levels, OS generated by the inflammatory cells themselves is more relevant than that generated by airborne PM. This supports the idea that asthma is a heterogeneous disease at the molecular level, mediated by inflammatory cell activation, and that OS may have potential clinical implications.

With the rationale that the oxidative potential of particulate matter (PM-OP) may induce oxidative stress and inflammation, we conducted the ASTHMA-FENOP study in which 44 asthmatic patients and 37 matched controls wore a personal sampler for 24 h, allowing the collection of fine and coarse PM fractions separately, to determine PM-OP by the dithiothreitol (DTT) and ascorbic acid (AA) methods. The levels of Interleukin 6 (IL-6) and the IL-6/IL-10 ratio, as indicators of pro- and anti-inflammatory statuses, were determined by calculating the mean differences (MDs), odds ratios (ORs) and p-trends adjusted for sex, age, study level and body mass index. Positive associations for IL-6 levels in the form of adjusted MDs and ORs were obtained for all PM-OP metrics, reaching statistical significance for both OP-DTT and OP-AA in the fine fraction, with adjusted OR = 5.66; 95%CI (1.46 to 21.92) and 3.32; 95%CI (1.07 to 10.35), respectively, along with statistically significant dose–response patterns when restricting to asthma and adjusted also for clinical variables (adjusted p-trend = 0.029 and 0.01). Similar or stronger associations and dose–response patterns were found for the IL-6/IL-10 ratio. In conclusion, our findings on the effect of PM-OP on systemic inflammation support that asthma is a heterogeneous disease at the molecular level, with PM-OP potentially playing an important role.

Background: Our objective was to determine the stability of fractional exhaled nitric oxide (FENO) levels in a same group of asthma patients over three consecutive days, and whether the highest levels were found in patients with higher environmental exposure. Methods: Three consecutive FENOS were determined over three days in 41 adult asthma patients (25 women and 16 men) (Visits 2-4). All determinations were made with the same device by the same qualified person. Previously they wore a personal sampler for 24 hours (visit 1) collecting their fine and coarse particulate matter (PM) personal exposure. Finally, Oxidative potential (OP) of filters was determined by two methods: dithiothreitol and ascorbic acid. Results: The correlations were very high: rho spearman>0.95 also suggesting high stability in the repeated measures ANOVA results: F(2,0; 80)=0.205, p= 0.815; Partial Eta squared= 0.005. Higher OP was not associated with greater airway inflammation, finding non-significant negative mean differences adjusted for sex, age, asthma control test, test of Adherence to Inhalers, asthma severity and body mass index. Conclusions: FENO levels were very stable, so that their repetition would not be necessary, at least within the same week, neither in clinical practice nor in epidemiological studies such as our ASTHMA-FENOP study (Santibáñez M et al. Open Respir Arch 2023;5:100246). Higher OP does not seem to be associated with greater airway inflammation. It would be interesting to compare these results with a control group without asthma and therefore without inhaled corticosteroid treatment that could slow down the possible increase in FENO.

Background: The GALERNA study is a retrospective real-world observational study conducted across 21 hospitals in Spain, aiming to evaluate long-term clinical benefits and adherence to benralizumab in 255 adult patients with severe eosinophilic asthma (SEA) over a follow-up period of up to 144 weeks. Objectives: Primary objectives focused on assessing adherence to benralizumab, while secondary objectives included the description of severe asthma exacerbation rates, systemic corticosteroid (SCS) use, persistence to benralizumab, lung function, asthma control, and the proportion of patients achieving super-response or clinical remission. Data were collected at baseline (48 weeks prior to benralizumab initiation/index date), follow-up 1 (FUP1) (0–48 weeks), FUP2 (49–96 weeks), and FUP3 (97–144 weeks) after the index date. Results: At baseline, patients demonstrated a substantial disease burden characterised by impaired lung function, poorly controlled asthma, and frequent severe exacerbations. The results indicated high adherence rates to benralizumab, with 92.9% of patients receiving each of the prescribed doses of benralizumab at week 48 and 70.6% at week 144. Patients showed substantial and sustained clinical improvements, with a reduction in the proportion of individuals presenting at least one severe exacerbation from baseline to FUP3 and a 74% decrease in SCS use for the same period. Lung function also improved, with the proportion of patients achieving pre-bronchodilator FEV₁ ≥ 80% rising to 52% at 144 weeks. Furthermore, mean Asthma Control Test (ACT) scores increased to 20.5, with 68.5% of patients achieving well-controlled asthma (ACT ≥ 20). By the end of the study, 63.6% of patients achieved super-response and 39.1% showed clinical remission, with an overall benralizumab persistence of 79.8% during all follow-up periods. Conclusions: The GALERNA study provides compelling real-world evidence that benralizumab affords marked and sustained clinical benefits together with high long-term adherence in Spanish SEA patients, reinforcing its usefulness as a long-term therapeutic option in routine clinical practice.