High-flow nasal cannula (HFNC) has recently emerged as a crucial therapeutic strategy for hypoxemic patients both in acute and chronic settings. Indeed, HFNC therapy is able to deliver higher fractions of inspired oxygen (FiO₂) with a heated and humidified gas flow ranging from 20 up to 60 L per minute, in a more comfortable way for the patient in comparison with Conventional Oxygen Therapy (COT). In fact, the flow keeps the epithelium of the airways adequately moisturized, thus positively affecting the mucus clearance. Finally, the flow is able to wash out the carbon dioxide in the dead space of the airways; this is also enhanced by a modest positive end-expiratory pressure (PEEP) effect. Recent evidence has shown applications of HFNC in exercise training and chronic settings with promising results. In this narrative review, we explored how HFNC might contribute to enhancing outcomes of exercise training and pulmonary rehabilitation among patients dealing with chronic obstructive pulmonary disease, interstitial lung diseases, and lung cancer.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible fibrotic disease whose natural history is characterised by a progressive worsening of the pulmonary function, exertional dyspnoea, exercise intolerance, reduced physical activity, and health-related quality of life (HRQOL) impairment. Pulmonary rehabilitation (PR) is a comprehensive, multi-disciplinary programme that uses a combination of strength training, teaching, counselling, and behaviour modification techniques to reduce symptoms and optimise functional capacity in patients with chronic lung disease. Based on the well-documented effectiveness of PR in chronic obstructive pulmonary disease (COPD), over the years supportive evidence of its benefits for other respiratory diseases has been emerging. Although the latest rehabilitation guidelines recognised PR’s efficacy for interstitial lung disease (ILD) and IPF in particular, this comprehensive approach remains underused and under-resourced. In this review, we will discuss the advantages and beneficial effects of PR on IPF, analysing its impact on exercise capacity, disease-related symptoms, cardiovascular outcomes, body composition, and HRQOL.

Background. Alpha-1 antitrypsin deficiency (AATD) can result in severe liver and respiratory disorders. The uninhibited elastase activity on the elastic tissue of arterial walls suggests that AATD may also impact vascular health. Thus, we performed a meta-analysis of the studies evaluating cardiovascular risk in individuals with AATD and non-AATD controls. Methods. A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differences between cases and controls were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The protocol was registered on PROSPERO under the identification number CRD42023429756. Results. The analysis of eight studies showed that, with a prevented fraction of disease of 15.0% and a corresponding OR of 0.779 (95%CI: 0.665–0.912; p = 0.002), a total of 24,428 individuals with AATD exhibited a significantly lower risk of ischemic heart disease compared to 534,654 non-AATD controls. Accordingly, given a prevented fraction of disease of 19.5%, a lower risk of acute myocardial infarction was documented when analyzing four studies on 21,741 cases and 513,733 controls (OR: 0.774; 95%CI: 0.599–0.999; p = 0.049). Sensitivity and subgroup analyses substantially confirmed results. Meta-regression models suggested that these findings were not influenced by AATD genotypes or prevalence of chronic obstructive pulmonary disease (COPD) among cases and controls, while higher differences in the prevalence of male sex (Z-score: 3.40; p < 0.001), hypertension (Z-score: 2.31; p = 0.021), and diabetes (Z-score: 4.25; p < 0.001) were associated with a lower effect size. Conclusions. Individuals with AATD may exhibit a reduced risk of ischemic heart disease, even in the presence of mild deficiency of the serine protease inhibitor. Although caution is warranted due to the observational nature of the data, future pharmacological and rehabilitation strategies should also take this controversial relationship into account.

Background: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods: Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results: A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23–4.45) in ICS users and 3.39% (IQR: 2.45–4.08) in ICS nonusers (p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23–4.45 to 4.77%; IQR: 3.25–5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45–4.08 to 5.04%; IQR: 3.98–6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions: Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy.

Background: The monocyte–phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F; mean age ± SD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169⁺ monocytes, conventional CD1c⁺ and CD141⁺ (namely cDC2 and cDC1), and plasmacytoid CD303⁺ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory-related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p < 0.0001). COVID-19 cases with absolute counts of CD169⁺ monocytes above the median value of 114.68/μL had significantly higher in-hospital mortality (HR 4.96; 95% CI: 1.42–17.27; p = 0.02). Interleukin (IL)-6 concentrations were significantly increased in COVID-19 patients (p < 0.0001 vs. controls), and negatively correlated with the absolute counts of circulating CD1c⁺ cDC2 (r = −0.29, p = 0.034) and CD303⁺ pDC (r = −0.29, p = 0.036) subsets. Viral genes were upregulated in patients with worse outcomes along with inflammatory mediators such as interleukin (IL)-1 beta, tumor necrosis-α (TNF-α) and the anticoagulant protein (PROS1). Conversely, surviving patients had upregulated genes related to inflammatory and anti-viral-related pathways along with the T cell membrane molecule CD4. Conclusions: Our results suggest that the dysregulated interplay between the different components of the MPS along with the imbalance between viral gene expression and host anti-viral immunity negatively impacts COVID-19 outcomes. Although the clinical scenario of COVID-19 has changed over time, a deepening of its pathogenesis remains a priority in clinical and experimental research.

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F ; mean ageSD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p