Effects of high-flow nasal therapy on swallowing function: a scoping review.

Background: High-flow nasal therapy is widely used in patients with respiratory failure in different clinical settings, but the effect of high-flow nasal therapy on respiratory-swallow coordination is unknown. Understanding this relationship is crucial, considering the necessity for patients to maintain adequate nutrition during daytime high-flow nasal therapy. This scoping review aims to synthesise available data on the effects of high-flow nasal therapy flow rates on swallowing function and the possible risk of aspiration during treatment, focusing on knowledge and evidence gaps. Methods: PubMed, Scopus, Web of Science and Google Scholar databases were searched from inception to 30 May 2023 for studies reporting data on swallowing assessment in healthy adults or patients with acute or chronic respiratory failure receiving high-flow nasal therapy. Data on study design, patients' characteristics and quality outcomes were extracted. Results: Eight studies were included, four including cohorts of healthy volunteers (n=148) and four including patients with acute or chronic respiratory failure (n=151). Study designs, patient populations and quality outcome measures were heterogeneous. Two studies indicated improvement while four articles showed impairment in swallowing function during high-flow nasal therapy; two studies showed that patients' overall clinical picture and underlying medical conditions influenced swallowing-breathing coordination rather than high-flow nasal therapy per se. Conclusion: This scoping review found limited and controversial evidence on the impact of high-flow nasal therapy on swallowing function. Remarkably, methods for swallowing function assessment were quite heterogeneous. Additional research is required to test the effect of high-flow nasal therapy on respiratory-swallowing coordination.

Asthma remission one, none and one-hundred thousand: the relevance of the patient's view.

OBJECTIVE: Achieving remission in severe asthma holds paramount importance in elevating patient quality of life and reducing both individual and societal burdens associated with this chronic condition. This study centers on identifying pivotal patient-relevant endpoints through standardized, reproducible methods, while also developing a patient-centric definition of remission, essential for effective disease management. METHODS: A discrete choice experiment (DCE) was conducted to assess patients' perceptions on the four primary criteria for defining severe asthma remission, as outlined by the SANI survey. Additionally, it investigated the correlation between these perceptions and improvements in the doctor-patient therapeutic alliance during treatment decision-making. RESULTS: 249 patients (70% aged between 31-60, 59% women and 82% without other pathologies requiring corticosteroids) prioritize the use of oral corticosteroids (OCS, 48%) and the Asthma Control Test (ACT, 27%) in defining their condition, ranking these above lung function and exacerbations. This preference for OCS stems from its direct role in treatment, tangible tracking, immediate symptom relief, and being a concrete measure of disease severity compared to the less predictable and quantifiable exacerbations. CONCLUSIONS: This study explores severe asthma remission from patients' perspectives using clinician-evaluated parameters. The DCE revealed that most patients highly value OCS and the ACT, prefer moderate improvement, and avoid cortisone cycles. No definitive preference was found for lung function status. Integrating patient-reported information with professional insights is crucial for effective management and future research. Personalized treatment plans focusing on patient preferences, adherence, and alternative therapies aim to achieve remission and enhance quality of life.

Pharmacological treatment in Idiopathic Pulmonary Fibrosis: current issues and future perspectives

Idiopathic pulmonary fibrosis (IPF) represents a fibrotic interstitial lung disease characterized by uncertain etiology and poor prognosis. Over the years, the path to effective treatments has been marked by a series of advances and setbacks. The introduction of approved antifibrotic drugs, pirfenidone and nintedanib, marked a pivotal moment in the management of IPF. However, despite these advances, these drugs are not curative, although they can slow the natural progression of the disease. The history of drug therapy for IPF goes together with the increased understanding of the pathogenic mechanisms underlying the disease. Based on that, current research efforts continue to explore new therapies, possible personalized treatment strategies, drug combinations, and potential biomarkers for diagnosis and prognosis. In this review, we outline the route that led to the discover of the first effective therapies, ongoing clinical trials, and future directions in the search for more effective treatments.

Melatonin Enhances Neural Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.

Diagnostic delay in bronchiectasis: an Italian perspective.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Distance follow-up by a remote medical care centre improves adherence to CPAP in patients with obstructive sleep apnoea over the short and long term.

BACKGROUND: Adherence to continuous positive air pressure (CPAP) in patients with obstructive sleep apnoea (OSA) has remained invariably low over the last decades. Remote monitoring of the nocturnal CPAP treatment, within telemedicine (TM)-based follow-up programs, in these patients has been suggested as a potential tool to improve adherence and release the workload of sleep units. The aim of this study was therefore to assess whether a follow-up program carried out by a Remote Medical Care Centre (RMCC), outside the sleep unit, improves adherence to CPAP in the short and long term in patients with OSA. METHODS: In this pilot protocol, we enrolled 37 patients starting CPAP in our Sleep Centre (SC). After three months of standard care in our SC, patients initiated a six-month remote follow-up carried out by the RMCC, functioning as an intermediary between patients and SC. Monthly reports and indication for face-to-face visits were sent to the SC for six months. After this period patients returned to usual care for one year. Results were compared with those obtained in 38 patients (controls) followed with usual care over the same time range. RESULTS: Mean nightly use of CPAP increased from 3.2 ± 2.4 h pre-RMCC to 5.2 ± 1.9 h post-RMCC (p < 0.0001). Nights/month of CPAP use improved from 19.8 ± 9.2 to 25.2 ± 2.5 (p < 0.05) and nights/month with CPAP use >4 h from 12.5 ± 10 to 21.03 ± 8.9 (p < 0.05). This improvement remained stable after 12 months from the return of patients to usual care. No significant changes in CPAP use were observed in controls over the time. CONCLUSION: A six-month follow-up through a remote facility can significantly improve adherence to CPAP in the short and long term. This pilot study provides a solid base for the design of multicentre randomized trials focusing on new models which are able to increase the long-term efficacy of TM programs.

The Pattern and Progression of "Usual" Interstitial Pneumonia with Autoimmune Features: Comparison with Patients with Classic Interstitial Pneumonia with Autoimmune Features and Idiopathic Pulmonary Fibrosis.

BACKGROUND: We proposed the term "UIPAF" to define patients with Usual Interstitial Pneumonia (UIP) associated with only one domain of the classification called "Interstitial Pneumonia with Autoimmune Features" (IPAF). The objective of this study was to evaluate the clinical presentation and prognosis of UIPAF patients, compared with two cohorts, composed of IPAF and idiopathic pulmonary fibrosis (IPF) patients, respectively. METHODS: The patients were enrolled as IPAF, UIPAF, or IPF based on clinical, serological, and radiological data and evaluated by a multidisciplinary team. RESULTS: We enrolled 110 patients with IPF, 69 UIPAF, and 123 IPAF subjects. UIPAF patients were similar to IPAF regarding autoimmune features, except for the prevalence of Rheumatoid Factor in UIPAF and anti-SSA in IPAF. A similar proportion of the two cohorts progressed toward a specific autoimmune disease (SAD), with differences in the kind of SAD developed. The real-life management and prognosis of UIPAF patients proved to be almost identical to IPF. CONCLUSIONS: UIPAF shared with IPAF similar autoimmune features, suggesting the opportunity to be considered IPAF, excluding the morphological domain by the classification. However, the real-life management and prognosis of UIPAF are similar to IPF. These data suggest a possible modification in the therapeutic management of UIPAF.

Images in Sarcoidosis: new section of our Journal.

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Use of Remdesivir in Patients Hospitalized for COVID-19 Pneumonia: Effect on the Hypoxic and Inflammatory State.

Remdesivir is one of the most attractive options for patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). The aim of our study was to evaluate the effect of remdesivir on the hypoxic and inflammatory state in patients with moderate to severe COVID-19. We retrospectively enrolled 112 patients admitted for COVID-19 pneumonia, requiring low-flow oxygen, 57 treated with remdesivir plus standard of care (SoC) and 55 treated only with SoC that were similar for demographic and clinical data. We evaluated changes in hypoxemia and inflammatory markers at admission (Day 0) and after 5 days of treatment (Day 5) and the clinical course of the disease. From Day 0 to Day 5, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) increased from 222 ± 62 to 274 ± 97 (p < 0.0001) in the remdesivir group and decreased from 223 ± 62 to 183 ± 76 (p < 0.05) in the SoC group. Interleukine-6 levels decreased in the remdesivir (45.9 to 17.5 pg/mL, p < 0.05) but not in the SoC group. Remdesivir reduced the need for ventilatory support and the length of hospitalization. In conclusion, compared to standard care, remdesivir rapidly improves hypoxia and inflammation, causing a better course of the disease in moderate to severe COVID-19.

Histogram-based analysis in progressive pulmonary fibrosis: relationships between pulmonary functional tests and HRCT indexes.

OBJECTIVES: To investigate relationships between histogram-based high-resolution CT (HRCT) indexes and pulmonary function tests (PFTs) in interstitial lung diseases. METHODS: Forty-nine patients having baseline and 1-year HRCT examinations and PFTs were investigated. Histogram-based HRCT indexes were calculated; strength of associations with PFTs was investigated using Pearson correlation. Patients were divided into progressive and non-progressive groups. HRCT indexes were compared between the two groups using the U-test; within each group, baseline and follow-up Wilcoxon analysis was performed. Receiver operating characteristic analysis was used for predicting disease progression. RESULTS: At baseline, moderate correlations were observed considering kurtosis and diffusion capacity of the lungs for carbon monoxide (DLCO) (r = 0.54) and skewness and DLCO (r = 0.559), whereas weak but significant correlations were observed between forced vital capacity and kurtosis (r = 0.368, p = 0.009) and forced vital capacity and skewness (r = 0.391, p = 0.005). Negative correlations were reported between HAA% and PFTs (from r = -0.418 up to r = -0.507). At follow-up correlations between quantitative indexes and PFTs were also moderate, except for high attenuation area (HAA)% -700 and DLCO (r = -0.397). In progressive subgroup, moderate and strong correlations were found between DLCO and HRCT indexes (r = 0.595 kurtosis, r = 0.672 skewness, r=-0. 598 HAA% -600 and r = -0.626 HAA% -700). At follow-up, we observed significant differences between the two groups for kurtosis (p = 0.029), HAA% -600 (p = 0.04) and HAA% -700 (p = 0.02). To predict progression, ROC analysis reported sensitivity of 90.9% and specificity of 51.9% using a threshold value of δ kurtosis <0.03. CONCLUSION: At one year, moderate correlations suggest that progression could be assessed through HRCT quantification. ADVANCES IN KNOWLEDGE: This study promotes histogram-based HRCT indexes in the assessment of progressive pulmonary fibrosis.

Effect of Nintedanib in Patients with Progressive Pulmonary Fibrosis in Subgroups with Differing Baseline Characteristics.

INTRODUCTION: In the INBUILD trial in patients with progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (IPF), nintedanib slowed the rate of decline in forced vital capacity (FVC; mL/year) over 52 weeks compared with placebo. We assessed the efficacy of nintedanib across subgroups in the INBUILD trial by baseline characteristics. METHODS: We assessed the rate of decline in FVC over 52 weeks and time to progression of interstitial lung disease (ILD) (absolute decline from baseline in FVC % predicted > 10%) or death over the whole trial in subgroups based on sex, age, race, body mass index (BMI), time since diagnosis of ILD, FVC % predicted, diffusing capacity of the lungs for carbon monoxide (DLco) % predicted, composite physiologic index (CPI), GAP (gender, age, lung physiology) stage, use of anti-acid therapy and use of disease-modifying antirheumatic drugs (DMARDs) at baseline. RESULTS: The effect of nintedanib versus placebo on reducing the rate of decline in FVC over 52 weeks was consistent across the subgroups by baseline characteristics analysed. Interaction p values did not indicate heterogeneity in the treatment effect between these subgroups (p > 0.05). Over the whole trial (median follow-up time ∼19 months), progression of ILD or death occurred in similar or lower proportions of patients treated with nintedanib than placebo across the subgroups analysed, with no heterogeneity detected between the subgroups. CONCLUSIONS: In the INBUILD trial, no heterogeneity was detected in the effect of nintedanib on reducing the rate of ILD progression across subgroups based on demographics, ILD severity or use of anti-acid therapy or DMARDs. These data support the use of nintedanib as a treatment for progressive pulmonary fibrosis. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02999178.

Clinical and Prognostic Significance of p-ANCA Positivity in Idiopathic Pulmonary Fibrosis: A Retrospective Observational Study.

Perinuclear Anti Neutrophil Cytoplasmic Antibody (p-ANCA) is a serological marker of Microscopic Polyangiitis (MPA), a vasculitis associated with lung involvement potentially mimicking Idiopathic Pulmonary Fibrosis (IPF). In this study, we evaluated the role of p-ANCA in predicting clinical evolution and prognosis in a cohort of IPF patients. In this observational, retrospective, case-control study, we compared 18 patients with an IPF diagnosis and p-ANCA positivity with 36 patients with seronegative IPF, matched for age and sex. IPF patients with and without p-ANCA showed similar lung function decline during the follow-up, but IPF p-ANCA+ showed better survival. Half of IPF p-ANCA+ patients were classified as MPA for the development of renal involvement (55%) or skin signs (45%). The progression towards MPA was associated with high levels of Rheumatoid Factor (RF) at baseline. In conclusion, p-ANCA, mainly when associated with RF, could predict the evolution of Usual Interstitial Pneumonia (UIP) towards a definite vasculitis in patients, with a better prognosis compared with IPF. In this view, ANCA testing should be included in the diagnostic workup of UIP patients.

Clinical Presentation of Connective Tissue Disease Patients with and without Interstitial Lung Disease: A Retrospective Study.

BACKGROUND: Connective tissue diseases (CTDs) are responsible for about 20% of interstitial lung disease (ILD) cases, but their diagnosis in a pulmonary unit (PU) is not always straightforward due to a heterogeneous clinical picture. OBJECTIVES: The aim of this study was to evaluate the clinical presentation of rheumatoid arthritis (RA) and CTD-ILD cases diagnosed in PU, compared to RA and CTD patients diagnosed in a rheumatologic unit (RU). METHODS: Patients with RA, systemic sclerosis (SSc), primary SjÓ§gren's syndrome (pSS), and idiopathic inflammatory myopathy were retrospectively enrolled from an RU and a PU designated to manage ILD during a period from January 2017 to October 2022. The classification of CTD-PU was carried out in a multidisciplinary setting, including the same rheumatologists that diagnosed CTD in the RU. RESULTS: ILD-CTD-PU patients were prevalently male and older. Progression from undifferentiated CTD to a specific condition was more common in ILD-CTD-PU, and those patients generally obtained a lower score on specific classification criteria. RA-PU patients resembled polymyalgia rheumatica in 47.6% of cases, also showing a greater proportion of typical joint deformities (p = 0.02). SSc-PU patients showed a usual interstitial pneumonia pattern in 76% of cases and, compared with SSc-RU, were more commonly seronegative (p = 0.03) and generally lacked fingertip lesions (p = 0.02). The majority of the diagnoses of pSS-PU were in patients with previously diagnosed ILD, in which seropositivity and sicca syndrome developed during follow-up. CONCLUSIONS: CTD-ILD patients diagnosed in the PU show severe lung involvement and a nuanced autoimmune clinical picture.

An update on lateral flow immunoassay for the rapid detection of SARS-CoV-2 antibodies.

Over the last three years, after the outbreak of the COVID-19 pandemic, an unprecedented number of novel diagnostic tests have been developed. Assays to evaluate the immune response to SARS-CoV-2 have been widely considered as part of the control strategy. The lateral flow immunoassay (LFIA), to detect both IgM and IgG against SARS-CoV-2, has been widely studied as a point-of-care (POC) test. Compared to laboratory tests, LFIAs are faster, cheaper and user-friendly, thus available also in areas with low economic resources. Soon after the onset of the pandemic, numerous kits for rapid antibody detection were put on the market with an emergency use authorization. However, since then, scientists have tried to better define the accuracy of these tests and their usefulness in different contexts. In fact, while during the first phase of the pandemic LFIAs for antibody detection were auxiliary to molecular tests for the diagnosis of COVID-19, successively these tests became a tool of seroprevalence surveillance to address infection control policies. When in 2021 a massive vaccination campaign was implemented worldwide, the interest in LFIA reemerged due to the need to establish the extent and the longevity of immunization in the vaccinated population and to establish priorities to guide health policies in low-income countries with limited access to vaccines. Here, we summarize the accuracy, the advantages and limits of LFIAs as POC tests for antibody detection, highlighting the efforts that have been made to improve this technology over the last few years.

Targeting intracellular pathways in idiopathic inflammatory myopathies: A narrative review.

In recent decades, several pieces of evidence have drawn greater attention to the topic of innate immunity, in particular, interferon (IFN) and Interleukin 6 in the pathogenesis of idiopathic inflammatory myopathies (IIM). Both of these molecules transduce their signal through a receptor coupled with Janus kinases (JAK)/signal transducer and activator of transcription proteins (STAT). In this review, we discuss the role of the JAK/STAT pathway in IIM, evaluate a possible therapeutic role for JAK inhibitors in this group of diseases, focusing on those with the strongest IFN signature (dermatomyositis and antisynthetase syndrome).

Myositis-Specific and Myositis-Associated Antibodies in Fibromyalgia Patients: A Prospective Study.

Fibromyalgia (FM) is a common rheumatologic disorder characterised by widespread muscular pain. Myalgia is also a common clinical feature in Connective Tissue Disease (CTD), and FM should be studied for the concomitant presence of a CTD. The aim of this study is to evaluate the prevalence of Myositis-Specific and Myositis-Associated Antibodies (MSA/MAA) in a cohort of FM patients. We enrolled 233 consecutive FM patients (defined according to the 2016 criteria) that did not report clinical signs of autoimmune disorders and followed them for at least one year. The patients were tested for MSA/MAA with immunoblotting. FM patients were seropositive for Antinuclear Antibodies (ANA) in 24% of cases, for MSA in 9%, and for MAA in 6%. A specific diagnosis of CTD was made in 12 patients (5.2%), namely, 5 cases of primary Sjögren's Syndrome and 7 of Idiopathic Inflammatory Myopathy. Seropositive patients showed clinical features similar to those who were seronegative at baseline. A CTD diagnosis was associated with ANA positivity (p = 0.03, X2 4.9), the presence of a speckled pattern (p = 0.02, X2 5.3), positivity for MAA (p = 0.004, X2 8.1), and MSA (p = 0.003, X2 9.2). In conclusion, a non-negligible proportion of FM patients may be seropositive for MSA/MAA, and that seropositivity might suggest a diagnosis of CTD.

Nocturnal nasal high-flow oxygen therapy in elderly patients with concomitant chronic obstructive pulmonary disease and obstructive sleep apnea.

PURPOSE: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is known as "overlap syndrome" (OS). Patients with OS are usually older than patients with OSA alone, suffer from more profound oxygen desaturation during the obstructive events often accompanied by sustained nocturnal hypoventilation. Although oxygen-enriched positive airway pressure (PAP) is the treatment of choice in these patients, this therapy is often poorly tolerated particularly by the elderly. The aim of this study was to assess the usefulness of nocturnal oxygen therapy via nasal high flow (NHF-OT) as a possible alternative to PAP in patients with OS. METHODS: Patients > 65 years old with OS and nocturnal respiratory failure (time spent below SaO2 90% (T90) > 30%) had cardio-respiratory monitoring performed at baseline, during NHF-OT, or during conventional oxygen therapy (COT). RESULTS: A total of 40 patients were enrolled in the study. NHF-OT significantly reduced the apnea-hypopnea index (AHI) in all patients compared to baseline and COT. The mean basal AHI was 25.4 ± 8.6. During COT and NHF-OT, the AHI was 19.4 ± 7 and 5.4 ± 4.6, respectively (P < 0.001) and 19 patients reached an AHI < 5 during NHF-OT. The mean nocturnal SaO2% was 86.2 ± 2.6 at baseline and at equivalent FiO2 it significantly increased to 91.8 ± 2.4 during COT and to 93.9 ± 2.5 during NHF-OT (P < 0.001). The T90% was 48.7 ± 20.1 at baseline, 16.8 ± 11.7 during COT, and 8.8 ± 8.0 during NHF-OT (P < 0.001). CONCLUSIONS: In elderly patients with OS, nocturnal treatment with NHF-OT significantly reduces obstructive episodes and improves oxygenation. As the treatment is generally well tolerated compared to PAP, NHF-OT may be a possible alternative therapy in this subgroup of patients.