High-Flow Nasal Cannula System in Respiratory Failure Associated with Interstitial Lung Diseases: A Systematic Review and Narrative Synthesis.

Background: High-flow nasal cannula (HFNC) therapy has emerged as a promising treatment modality for interstitial lung disease (ILD)-related respiratory failure. This systematic review aims to evaluate the efficacy and safety of HFNC therapy in patients with ILDs. Methods: A comprehensive literature search was conducted using major electronic databases to identify relevant studies investigating the use of HFNC therapy in ILD patients with respiratory failure. Outcome measures of interest included improvements in oxygenation, dyspnea relief, respiratory rate control, hospital length of stay, and mortality. Results: Twelve studies were analyzed with an overall population of 715 patients included. Idiopathic Pulmonary Fibrosis (IPF) was the most prevalent type of ILD. Evaluated clinical settings were acute (7 studies), chronic (2 studies), and end-stage (3 studies) ILDs. The HFNC as a support for acute respiratory failure seems not inferior to non-invasive ventilation while offering better comfort and patient's perception. Poor data are available about use in chronic/long-term or rehabilitative settings. In end of life/palliative care, an HFNC might improve quality of life. Despite the promising results, further research is warranted to establish optimal HFNC protocols, identify patient subgroups most likely to benefit, and explore long-term outcomes. Conclusions: Overall, the HFNC appears to be a valuable therapeutic option for managing respiratory failure in ILD patients, offering potential improvements in oxygenation and symptom relief.

The Role of SARS-CoV-2 Nucleocapsidic Antigen and Krebs von den Lungen 6 Serum Levels in Predicting COVID-19 Pneumonia Outcome.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a significant threat worldwide, with severe cases leading to hospitalization and death. This study aims to evaluate the potential use of serum nucleocapsid antigen (NAg) and Krebs von den Lungen-6 glycoprotein (KL-6) as biomarkers of severe COVID-19 and to investigate their correlation with clinical, radiological, and biochemical parameters. METHODS: This retrospective study included 128 patients with confirmed SARS-CoV-2 infection admitted to a Neapolitan hospital in Italy between October 2020 and July 2021. Demographic, clinical, and laboratory data were collected, including serum levels of NAg and KL-6. The Chung et al. Computed Tomography Severity Score (TSS) was used to assess the severity of pneumonia, and outcomes were classified as home discharge, rehabilitation, and death. Statistical analyses were performed to compare Group I (home discharge and rehabilitation) and Group II (death, sub-intensive care, and ICU stay) based on demographic data, laboratory parameters, and TSS. RESULTS: Group II patients showed worse outcomes with higher levels of NAg, KL-6, and inflammatory markers, including interleukin-6 (IL-6), interleukin-2 receptor (IL-2R), and adrenomedullin. TSS was also significantly higher in Group II, with a positive correlation between TSS and NAg and KL-6 levels. Group I patients had higher values of hemoglobin (Hb) and platelets (PLT), while Group II patients had higher values of C-reactive protein (CRP), procalcitonin (PCT), D-Dimer, and glycemia. No significant difference was observed in gender distribution. CONCLUSIONS: Serum NAg and KL-6 levels are potential biomarkers of severe COVID-19 pneumonia, with higher levels indicating greater inflammation and organ damage. NAg may help identify infected patients at an increased risk of severe COVID-19 and ensure their admission to the most appropriate level of care. KL-6 may help predict interstitial lung damage and the severity of clinical features. Further studies are needed to establish a decision-making cut-off for these biomarkers in COVID-19.

Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention.

Interstitial lung diseases comprise a heterogenous range of diffuse lung disorders, potentially resulting in pulmonary fibrosis. While idiopathic pulmonary fibrosis has been recognized as the paradigm of a progressive fibrosing interstitial lung disease, other conditions with a progressive fibrosing phenotype characterized by a significant deterioration of the lung function may lead to a burden of significant symptoms, a reduced quality of life, and increased mortality, despite treatment. There is now evidence indicating that some common underlying biological mechanisms can be shared among different chronic fibrosing disorders; therefore, different biomarkers for disease-activity monitoring and prognostic assessment are under evaluation. Thus, understanding the common pathways that induce the progression of pulmonary fibrosis, comprehending the diversity of these diseases, and identifying new molecular markers and potential therapeutic targets remain highly crucial assignments. The purpose of this review is to examine the main pathological mechanisms regulating the progression of fibrosis in interstitial lung diseases and to provide an overview of potential biomarker and therapeutic options for patients with progressive pulmonary fibrosis.

The Unveiled Triad: Clinical, Radiological and Pathological Insights into Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is a diffuse parenchymal lung disease (DLPD) characterized by complex interstitial lung damage with polymorphic and protean inflammatory aspects affecting lung tissue targets including small airways, the interstitium, alveolar compartments and vascular structures. HP shares clinical and often radiological features with other lung diseases in acute or chronic forms. In its natural temporal evolution, if specific therapy is not initiated promptly, HP leads to progressive fibrotic damage with reduced lung volumes and impaired gas exchange. The prevalence of HP varies considerably worldwide, influenced by factors like imprecise disease classification, diagnostic method limitations for obtaining a confident diagnosis, diagnostic limitations in the correct processing of high-resolution computed tomography (HRCT) radiological parameters, unreliable medical history, diverse geographical conditions, heterogeneous agricultural and industrial practices and occasionally ineffective individual protections regarding occupational exposures and host risk factors. The aim of this review is to present an accurate and detailed 360-degree analysis of HP considering HRCT patterns and the role of the broncho-alveolar lavage (BAL), without neglecting biopsy and anatomopathological aspects and future technological developments that could make the diagnosis of this disease less challenging.

Cardiovascular Risk Associated with Alpha-1 Antitrypsin Deficiency (AATD) Genotypes: A Meta-Analysis with Meta-Regressions.

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.

The Evolving Concept of the Multidisciplinary Approach in the Diagnosis and Management of Interstitial Lung Diseases.

BACKGROUND: Interstitial lung diseases (ILDs) are a group of heterogeneous diseases characterized by inflammation and/or fibrosis of the lung interstitium, leading to a wide range of clinical manifestations and outcomes. Over the years, the literature has demonstrated the increased diagnostic accuracy and confidence associated with a multidisciplinary approach (MDA) in assessing diseases involving lung parenchyma. This approach was recently emphasized by the latest guidelines from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association for the diagnosis of ILDs. METHODS: In this review, we will discuss the role, composition, and timing of multidisciplinary diagnosis (MDD) concerning idiopathic pulmonary fibrosis, connective tissue disease associated with ILDs, hypersensitive pneumonia, and idiopathic pneumonia with autoimmune features, based on the latest recommendations for their diagnosis. RESULTS: The integration of clinical, radiological, histopathological, and, often, serological data is crucial in the early identification and management of ILDs, improving patient outcomes. Based on the recent endorsement of transbronchial cryo-biopsy in idiopathic pulmonary fibrosis guidelines, an MDA helps guide the choice of the sampling technique, obtaining the maximum diagnostic performance, and avoiding the execution of more invasive procedures such as a surgical lung biopsy. A multidisciplinary team should include pulmonologists, radiologists, pathologists, and, often, rheumatologists, being assembled regularly to achieve a consensus diagnosis and to review cases in light of new features. CONCLUSIONS: The literature highlighted that an MDA is essential to improve the accuracy and reliability of ILD diagnosis, allowing for the early optimization of therapy and reducing the need for invasive procedures. The multidisciplinary diagnosis of ILDs is an ongoing and dynamic process, often referred to as a "working diagnosis", involving the progressive integration and re-evaluation of clinical, radiological, and histological features.

Clinical impact of COVID-19 on tuberculosis.

During COVID-19 pandemic, a lot of diseases suffered from a limited access to health care services, owing to the use of resources, both technical and financial, mainly directed towards such a dramatic outbreak. Among these, tuberculosis (TB) has been one of the most penalized, with a huge delay both in diagnosis and in start of treatment, with a consequential dramatic increase in morbidity and mortality. COVID-19 and tuberculosis share similar common pathogenetic pathways, and both diseases affect primarily the lungs. About the impact of TB on COVID-19 severity and mortality, data are unclear and literature reports are often conflicting. Certainly, considering the management of coinfected patients, there are pharmacokinetic interactions between several drugs used for the therapy of SARS-CoV-2 infection and the treatment of TB.

Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions.

BACKGROUND: Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19. 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. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684. RESULTS: Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: -2.31%; 95% CI: -3.19, -1.44; p < 0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: -1.73%; 95% CI: -3.04, -0.41; p = 0.010). Interestingly, when considering studies separately based on enrolment within or after 3 months of symptom onset, results were further confirmed in both short- (MD: -2.20%; 95% CI: -3.35, -1.05; p < 0.0001) and long-term follow-up (MD: -2.53%; 95% CI: -4.19, -0.86; p = 0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: -2.09; p = 0.037). CONCLUSIONS: Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.Key messagesThe mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated.Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist.Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19.

Association between COVID-19 and Sick Leave for Healthcare Workers in a Large Academic Hospital in Southern Italy: An Observational Study.

Studies have shown that the pandemic has led to an increase in sick leave periods among healthcare workers (HCWs); however, this might have changed over time considering increase in vaccination coverage and change in COVID-19 variant predominance. Therefore, we conducted an observational study to evaluate whether the type of symptoms and the duration of sick leave period for healthcare workers working in a large university hospital in the South of Italy changed between January 2021 and January 2022; 398 cases of COVID-19 were identified for a total of 382 subjects involved. A total of 191 subjects answered the questionnaire about symptoms; of these, 79 had COVID-19 during the period from March 2020 until February 2022. The results showed a decrease of about 1.2 days in sick leave period for each quarter without finding significant differences in the perception of symptoms. It is possible to hypothesize a contribution from the Omicron variant to the decrease in sick leave period in the last quarter, from vaccination coverage, from optimization of COVID-19 management, and from change in the regulations for the assessment of positivity.

A Phase II Study on the Effect of Taurisolo® Administered via AEROsol in Hospitalized Patients with Mild to Moderate COVID-19 Pneumonia: The TAEROVID-19 Study.

BACKGROUND: Polyphenols are the largest class of bioactive compounds in plants, which are synthesized as secondary metabolites. In the last few years, interesting studies have demonstrated the efficacy of polyphenols against coronavirus infections. METHODS: we conducted a phase II multicentric clinical trial (TAEROVID-19) during the first wave of the COVID-19 pandemic in order to assess the safety and feasibility of Taurisolo® aerosol formulation in hospitalized patients suffering from SARS-CoV-2 pneumonia. RESULTS: we observed a rapid decline of symptoms and a low rate of intensive care in patients treated with Taurisolo®, with a faster decline of symptoms. CONCLUSIONS: This is the first trial assessing the safety and feasibility of Taurisolo® aerosol formulation. We could argue that this treatment could act as an add-on therapy in the treatment of COVID-19 patients, owing to both its anti-inflammatory and antioxidant effects. Further controlled trials are needed, which may be of interest to evaluate the compound's efficacy.

Correlation between clinical-functional parameters and number of lobes involved in non-cystic fibrosis bronchiectasis.

BACKGROUND: Currently, the prognosis of bronchiectasis is based on different prognostic indicators, like BSI and FACED score, founded on clinical-demographic, functional and radiological criteria. Both scoring systems include the number of lobes involved in bronchiectasis, which represents an adverse prognostic index. Our study aimed to investigate the prognostic role of the clinical-functional parameters and the number of involved lobes ratio in adult bronchiectasis. METHODS: The study was conducted on 52 patients diagnosed with non-cystic fibrosis bronchiectasis (NCFB) between 2015 and 2017 who attended the Pneumology Unit of Monaldi Hospital in Naples, Italy. Correlations between clinical- functional parameters (BMI, smoking history, number of exacerbations in the previous year, spirometry, DLCO, ABG test, and 6MWT) and number of involved lobes were investigated. RESULTS: At baseline, the number of exacerbations in the previous year had a statistically significant association with the number of involved lobes. Furthermore, at baseline, the radiological criterion was also negatively associated with some functional parameters (FEV1/FVC ratio e FEF25-75%). Statistical significance was lost during the follow up, demonstrating the effectiveness of the therapy. CONCLUSIONS: Imaging extension represents a promising biomarker of disease severity as well as a helpful follow up tool for non-Cystic Fibrosis bronchiectasis (NCFB).

Alpha-1-Antitrypsin Deficiency and Bronchiectasis: A Concomitance or a Real Association?

Alpha-1-antitrypsin deficiency (AATd) is a hereditary disease, mainly characterized by early onset and the lower lobes' predominant emphysema. Bronchiectasis is characterized by dilatation of the bronchial wall and a clinical syndrome whose features are a cough, sputum production and frequent respiratory exacerbations. In the literature, there are many papers concerning these two clinical entities, but there is still a lot of debate about a possible association between them, in particular about the frequency of their association and causal links. The aim of this short communication is to show the literature reports about the association between AATd and bronchiectasis to establish the state of the art and possible future developments in this research field.