Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality around the globe. Its main characteristics are persistent respiratory symptoms and progressive airflow limitation, both of which are driven by chronic inflammation. Despite the use of maximum bronchodilation and in selected patients inhaled corticosteroids (ICS), current therapies neither halt disease progression nor prevent exacerbations and loss of lung function. Recent research has focused on developing novel anti-inflammatory agents targeting specific pathways implicated in COPD pathogenesis, aiming to provide disease-modifying effects beyond symptomatic relief. Among these, inhaled phosphodiesterase 4 (PDE4) inhibitors and especially dual PDE3/4 inhibitors like ensifentrine have demonstrated promising anti-inflammatory and bronchodilator effects, with ensifentrine recently being added in our arsenal of treatment options. Additionally, biologic therapies targeting type 2 inflammation, particularly monoclonal antibodies (mAbs) focusing on interleukin-5 (IL-5) and interleukin-4/13 (IL-4/13) pathways have shown efficacy in reducing exacerbations in patients with eosinophilic COPD. Dupilumab, a mAb targeting IL-4/13, is the first biologic officially approved for COPD. Other strategies under investigation include Janus kinase (JAK) and mitogen-activated protein kinase (MAPK) inhibitors, chemokine receptor antagonists and agents targeting products of inflammatory cells such as matrix metalloproteinases (MMPs) and neutrophil elastase. While some novel compounds have failed to demonstrate clinical benefit or were discontinued due to futility, the constantly evolving therapeutic landscape highlights the importance of a personalized approach, based on inflammatory phenotypes. Ongoing and future trials could elucidate the role of these innovative agents in improving outcomes for COPD patients and may reshape standard management paradigms.

Background: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19. Aim: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness. Methods: In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN₂W). Results: CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010). Conclusions: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid–femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.

Background/Objectives: Cardiorespiratory complications are commonly reported among patients with long COVID-19 syndrome. However, their effects on exercise capacity remain inconclusive. We investigated the impact of long COVID-19 on exercise tolerance combining cardiopulmonary exercise testing (CPET) with resting echocardiographic data. Methods: Forty-two patients (55 ± 13 years), 149 ± 92 days post-hospital discharge, and ten healthy age-matched participants underwent resting echocardiography and an incremental CPET to the limit of tolerance. Left ventricular global longitudinal strain (LV-GLS) and the left ventricular ejection fraction (LVEF) were calculated to assess left ventricular systolic function. The E/e’ ratio was estimated as a surrogate of left ventricular end-diastolic filling pressures. Tricuspid annular systolic velocity (SRV) was used to assess right ventricular systolic performance. Through tricuspid regurgitation velocity and inferior vena cava diameter, end-respiratory variations in systolic pulmonary artery pressure (PASP) were estimated. Peak work rate (WRpeak) and peak oxygen uptake (VO₂peak) were measured via a ramp incremental symptom-limited CPET. Results: Compared to healthy participants, patients had a significantly (p < 0.05) lower LVEF (59 ± 4% versus 49 ± 5%) and greater left ventricular end-diastolic diameter (48 ± 2 versus 54 ± 5 cm). In patients, there was a significant association of E/e’ with WRpeak (r = −0.325) and VO₂peak (r = −0.341). SRV was significantly associated with WRpeak (r = 0.432) and VO₂peak (r = 0.556). LV-GLS and PASP were significantly correlated with VO₂peak (r = −0.358 and r = −0.345, respectively). Conclusions: In patients with long COVID-19 syndrome, exercise intolerance is associated with left ventricular diastolic performance, left ventricular end-diastolic pressure, PASP and SRV. These findings highlight the interrelationship of exercise intolerance with left and right ventricular performance in long COVID-19 syndrome.

Background: Stewart’s approach is known to have better diagnostic accuracy for the identification of metabolic acid–base disturbances compared to traditional methods based either on plasma bicarbonate concentration ([HCO₃⁻]) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid–base disorders using either Stewart’s or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid–base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome. Methods: This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU. Electronical files were used to retrieve data for arterial blood gases, serum electrolytes, and proteins and to derive [HCO₃⁻], BE, anion gap (AG), AG adjusted for albumin (AG_adj), strong ion difference, strong ion gap (SIG), and SIG corrected for water excess/deficit (SIG_corr). The acid–base status was evaluated in each patient using the BE, [HCO₃⁻], and physicochemical approaches. Results: We included 185 patients. The physicochemical approach detected more individuals with metabolic acid–base abnormalities than the BE and [HCO₃⁻] approaches (p < 0.001), and at least one acid–base disorder was recognized in most patients. According to the physicochemical method, 170/185 patients (91.4%) had at least one disorder, as opposed to the number of patients identified using the BE 90/186 (48%) and HCO₃ 62/186 (33%) methods. Regarding the derived acid–base status variables, non-survivors had greater AG_adj, (p = 0.013) and SIG_corr (p = 0.035) compared to survivors. Conclusions: The identification of hidden acid–base disturbances may provide a detailed understanding of the underlying conditions in patients and of the possible pathophysiological mechanisms implicated. The association of these acid–base abnormalities with mortality provides the opportunity to recognize patients at increased risk of death and support them accordingly.