Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Applying graph theory to improve the quality of scientific evidence from textual information: Neural injuries after gynaecologic pelvic surgery for genital prolapse and urinary incontinence.

AIMS: To provide the overall rate for all types of neurologic iatrogenic injuries during urogynaecologic surgery from textual data. METHODS: Systematic research focused on complications of gynaecologic surgery and neurologic injuries in abstracts. Keywords concerning complications (cluster A), unspecific; neurologic issues (cluster B); surgery (generic words) (cluster C); specific gynaecologic operations (cluster D); and specific gynaecologic operations for pelvic organ prolapse and urinary incontinence (cluster E) were extracted. Associations among clusters of keywords were assessed by using multiple runs of text-mining software Semantic Brand Score (SBS, https://semanticbrandscore.com/#primary). Association scores were converted into probabilities. The rate of neurologic complications in urogynaecologic surgery was calculated ("a priori" probability) by applying Bayes' theorem. Textual estimates of neurological injuries in urogynaecologic surgery are 0.035554 (95% confidence intervals 0.019607-0.0515001; no quantitative data were found). To test if the probability calculated on textual information was the same as quantitative data reports ("a posteriori" probability), the rate of neurologic complication of all gynaecologic surgery was calculated using a meta-analytics approach and was compared with the textual analysis value. RESULTS: The rate of neurologic complications in gynaecologic surgery after meta-analytic data synthesis has been 0.016489 (95% confidence intervals 0.012163-0.022320), which is equal to the textual estimate (0.016889, 95% confidence intervals 0.019607-0.051501). Therefore, 0.035554 is a reliable likelihood to observe a neurologic complication in urogynaecologic surgery. CONCLUSION: Iatrogenic nerve injuries in urogynaecologic surgery are higher than whole gynaecologic surgery. Text-mining software SBS and probability conversion can provide reliable answers from overall scholars' opinions on unsolved clinical questions when better evidence is lacking.

Future Perspectives of Revaluating Mild COPD.

In 2020, COPD was the third leading cause of death worldwide. Lung function is central for the diagnosis of this disease, and COPD severity is still partially classified based on airflow obstruction, which can range from "mild" (GOLD 1 group, FEV1 ≥80% predicted) to "very severe" (GOLD 4, FEV1 <30% predicted). However, the term "mild COPD" needs to be carefully analyzed. Several studies have shown that even in the presence of a mild obstruction, patients can have significant symptoms, physiological deterioration, evidence of emphysema, and suffer from recurrent exacerbations. Small airways pathology significantly correlates with the presence of symptoms, and it has been demonstrated that the onset of bronchiolitis occurs earlier than that of emphysema. These damages have long been known to not be detectable with conventional tests, and exclusive reliance on spirometry is not enough to adequately study and stage a patient with "mild COPD." Therefore, early identification of COPD is of utmost importance in the light of modifying the natural course of the disease. However, patients with early lung damage are yet to be included and studied in interventional clinical trials.

Joint Statement on the Role of Respiratory Rehabilitation in the COVID-19 Crisis: The Italian Position Paper.

Due to the exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian health care system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians were coming from different specialties (intensivists or pneumologists and infectiologists), while respiratory therapists and nurses have been recruited to work on and on without rest. However, due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions. The presentation of this paper is the result of a consensus promoted by the Italian societies of respiratory health care professionals who contacted pulmonologists directly involved in the treatment and rehabilitation of COVID-19. The aim was to formulate the more proper and common suggestions to be applied in different hospital settings in offering rehabilitative programs and physiotherapy workforce planning for COVID-19 patients. Two main areas of intervention were identified: organization and treatment, which are described in this paper to face the emergency.

Italian suggestions for pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process.

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

Management of Chronic Respiratory Failure in Interstitial Lung Diseases: Overview and Clinical Insights.

Interstitial lung diseases (ILDs) may be complicated by chronic respiratory failure (CRF), especially in the advanced stages. Aim of this narrative review is to evaluate the current evidence in management of CRF in ILDs. Many physiological mechanisms underlie CRF in ILDs, including lung restriction, ventilation/perfusion mismatch, impaired diffusion capacity and pulmonary vascular damage. Intermittent exertional hypoxemia is often the initial sign of CRF, evolving, as ILD progresses, into continuous hypoxemia. In the majority of the cases, the development of CRF is secondary to the worsening of the underlying disease; however, associated comorbidities may also play a role. When managing CRF in ILDs, the need for pulmonary rehabilitation, the referral to lung transplant centers and palliative care should be assessed and, if necessary, promptly offered. Long-term oxygen therapy is commonly prescribed in case of resting or exertional hypoxemia with the purpose to decrease dyspnea and improve exercise tolerance. High-Flow Nasal Cannula oxygen therapy may be used as an alternative to conventional oxygen therapy for ILD patients with severe hypoxemia requiring both high flows and high oxygen concentrations. Non-Invasive Ventilation may be used in the chronic setting for palliation of end-stage ILD patients, although the evidence to support this application is very limited.

[Rehabilitation medicine and appropriateness criteria: between chronicity, multi-morbidity and complexity]. / La medicina riabilitativa e i criteri di appropriatezza: tra cronicità, multimorbilità e complessità.

SUMMARY: In the last two decades, population aging has led to a substantial increase in the number of people living with moderate-to-severe disability and, consequently, an increased demand for rehabilitation care. It is estimated that, currently, 2.8 million people live with severe disability in Italy. Although greater access to rehabilitation care is required to meet the needs of disabled patients, the capacity to provide rehabilitation has not changed over the last years and fails to meet current rehabilitation needs. Efforts should be devoted for aligning the capacity to provide rehabilitation care to the increased demand for rehabilitation care.

Relative lymphocyte count as an indicator of 3-year mortality in elderly people with severe COPD.

BACKGROUND: Prognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD. METHODS AND RESULTS: This is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26-2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03-2.58, p = 0.038). CONCLUSIONS: Low relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD.

Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.

BACKGROUND: Interstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs. METHODS: A literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017). RESULTS: In managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out. Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients' therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF. CONCLUSIONS: Despite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients' management, possibly leading to improved outcomes. However, further studies are warranted.

Improvements in Lung Diffusion Capacity following Pulmonary Rehabilitation in COPD with and without Ventilation Inhomogeneity.

BACKGROUND: Lung diffusing capacity (DLCO) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify DLCO parameters is unknown. OBJECTIVES: To investigate changes in DLCO and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD. METHODS: This was a prospective, observational, multicentric study. Patients were evaluated before and after a standardized 3-week PR program. Functional assessment included body plethysmography, DLCO, transfer factor (KCO) and alveolar volume (VA), gas exchange, the 6-min walking test (6MWT) and exercise-related dyspnea. Patients were categorized according to the severity of airflow limitation and presence of ventilation inhomogeneity, identified by a VA/TLC <0.8. RESULTS: Two hundred and fifty patients completed the study. Baseline forced expiratory volume in 1 s (FEV1) % predicted (mean ± SD) was 50.5 ± 20.1 (76% males); 137 patients had a severe disease. General study population showed improvements in 6MWT (38 ± 55 m; p < 0.01), DLCO (0.12 ± 0.63 mmol × min-1 kPa-1; p < 0.01), lung function and dyspnea. Comparable improvements in DLCO were observed regardless of the severity of disease and the presence of ventilation inhomogeneity. While patients with VA/TLC <0.8 improved the DLCO increasing their VA (177 ± 69 ml; p < 0.01), patients with VA/TLC >0.8 improved their KCO (8.1 ± 2.8%; p = 0.019). The latter had also better baseline lung function and higher improvements in 6MWT (14.6 ± 6.7 vs. 9.0 ± 1.8%; p = 0.015). Lower DLCO at baseline was associated with lower improvements in 6MWT, the greatest difference being between subjects with very severe and mild DLCO impairment (2.7 ± 7.4 vs. 14 ± 2%; p = 0.049). CONCLUSIONS: In COPD patients undergoing a PR program, different pathophysiological mechanisms may drive improvements in DLCO, while ventilation inhomogeneity may limit improvements in exercise tolerance.

Analysis of the fungal microbiome in exhaled breath condensate of patients with asthma.

BACKGROUND: The presence of virus and bacteria in the airways of subjects with asthma is common and seems to be associated with a deterioration due to the disease. The microbiologic study of airways in asthma is foreseen by guidelines with induced sputum that is often ineffective and contraindicated in severe asthma. AIM: To analyze the fungal microbiome in the exhaled breath condensate (EBC) of subjects with asthma by evaluating a possible correlation with anthropometric and asthma severity data. METHODS: We enrolled 47 consecutive subjects with asthma (28 with atopic asthma and 19 with nonatopic asthma) and 20 controls. Enrolled subjects underwent EBC and sputum collection. Fungal microbiome was assessed by culture on EBC and sputum samples by using Czapek yeast extract agar. RESULTS: A fungal colonization in the EBC of 70% of enrolled subjects with asthma was detected (none detected in the controls). An overlap of fungal microbiome in EBC and sputum was observed (100% of overlap). Fungal colonization was higher in subjects without atopic, obesity, and severe and uncontrolled asthma. CONCLUSION: When considering the high morbidity and mortality of patients with severe asthma in whom we found an important fungal airways colonization, we support the use of the analysis of exhaled fungal microbiome in these subjects.

Predictors of Mortality in Patients with COPD and Chronic Respiratory Failure: The Quality-of-Life Evaluation and Survival Study (QuESS): A Three-Year Study.

UNLABELLED: Previous studies sought to identify survival or outcome predictors in patients with COPD and chronic respiratory failure, but their findings are inconsistent. We identified mortality-associated factors in a prospective study in 21 centers in 7 countries. Follow-up data were available in 221 patients on home mechanical ventilation and/or long-term oxygen therapy. MEASUREMENTS: diagnosis, co-morbidities, medication, oxygen therapy, mechanical ventilation, pulmonary function, arterial blood gases, exercise performance were recorded. Health status was assessed using the COPD-specific SGRQ and the respiratory-failure-specific MRF26 questionnaires. Date and cause of death were recorded in those who died. Overall mortality was 19.5%. The commonest causes of death were related to the underlying respiratory diseases. At baseline, patients who subsequently died were older than survivors (p = 0.03), had a lower forced vital capacity (p = 0.03), a higher use of oxygen at rest (p = 0.003) and a worse health status (SGRQ and MRF26, both p = 0.02). Longitudinal analyses over a follow-up period of 3 years showed higher median survival times in patients with use of oxygen at rest less than 1.75 l/min and with a better health status. In contrast, an increase from baseline levels of 1 liter in O2 flow at rest, 1 unit in SGRQ or MRF26, or 1 year increase in age resulted in an increase of mortality of 68%, 2.4%, 1.3%, and 6%, respectively. In conclusion, the need for oxygen at rest, and health status assessment seems to be the strongest predictors of mortality in COPD patients with chronic respiratory failure.

Italian registry of patients with alpha-1 antitrypsin deficiency: general data and quality of life evaluation.

Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy. In a period spanning 18 years (1996-2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection.

Non-invasive mechanical ventilation in patients with diffuse interstitial lung diseases.

BACKGROUND: To evaluate noninvasive ventilation (NIV) in diffuse interstitial lung diseases (DILD) patients with acute respiratory failure (ARF) according to baseline radiological patterns and the etiology of ARF. METHODS: In a multicenter, observational, retrospective study, consecutive DILD patients undergoing NIV because of an episode of ARF were evaluated in six Italian high dependency units. Three groups of patients were identified based on the etiology of ARF: those with pneumonia (Group A), those with acute exacerbation of fibrosis, (Group B) and those with other triggers (Group C). Clinical failure was defined as any among in-hospital mortality, endotracheal intubation and extra-corporeal membrane oxygenation use. RESULTS: Among the 60 patients enrolled (63% males; median age: 71 years), pneumonia (42%) and acute exacerbation of fibrosis (39%) were the two most frequent causes of ARF. A significant increase of PaO2/FiO2 ratio during NIV treatment was detected in Group A (p = 0.010), but not in Group B. No significant difference in PaO2/FiO2 ratio, PaCO2 and pH values during NIV treatment was detected in patients with a radiological pattern of usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). 22 patients (37%) suffered for a clinical failure. No significant differences in the study outcome were detected in Group A vs. Group B, as well as among patients with a radiological pattern of UIP vs. NSIP CONCLUSIONS: NIV treatment should be individualized in DILD patients with ARF according to the etiology, but not the baseline radiological pattern, in order to improve oxygenation.

Long-term inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease, cardiovascular disease, and a recent hospitalised exacerbation: The ICSLIFE pragmatic, randomised controlled study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD. METHODS: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death. RESULTS: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events. CONCLUSIONS: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia.

Cognitive Deficits among Individuals Admitted to a Post-Acute Pneumological Rehabilitation Unit in Southern Italy after COVID-19 Infection.

(1) Background: We investigated the differences in the neuropsychological profile as well as the pneumological and motor functions in two groups of patients admitted to rehabilitation who received different respiratory support during their COVID-19 infection. (2) Methods: Group-1 (n = 18; 15 male, median age 67.5) consisted of patients who received non-invasive mechanical ventilation; Group-2 (n = 19; 16 male, median age 63) consisted of patients who received invasive mechanical ventilation. All patients underwent a neuropsychological assessment including Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (R-BANS) to evaluate the patients' cognition. Depression and anxiety were also measured at admission and discharge to rehabilitation. (3) Results: At admission, patients impaired at MMSE were 44% in Group-1 and 5% in Group-2, while patients impaired at FAB were 88% in Group-1 and 26% in Group-2. Wilcoxon's effect size revealed meaningful differences between groups for FAB, R-BANS global score, immediate and delayed memory, and attention-coding task, with Group-2 performing better than Group-1 across all measures. At discharge, 52% of the 25 patients re-assessed still had mild to moderate cognitive deficits, while 19% had depression and 35% had anxiety. (4) Conclusions: Patients who received oxygen therapy experienced higher levels of acute and chronic stress compared to those who benefitted from invasive mechanical ventilation. Despite patients showing a meaningful improvement at discharge, cognitive impairment persisted in a great number of patients; therefore, long-term neuropsychological follow-up and treatment for COVID-19 patients are recommended.

Mortality in obstructive sleep apnea syndrome (OSAS) and overlap syndrome (OS): The role of nocturnal hypoxemia and CPAP compliance.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are two chronic diseases that afflict many individuals worldwide with negative effects on health that may overlap in Overlap Syndrome (OS). The aim of our study was to investigate the differences in mortality between OSAS alone and OS and the risk factors involved. METHODS: The study was conducted on patients with OSAS or OS diagnosis that completed 15-year follow-up between 2005 and 2023. Of these, the clinical, functional, sleep and survival data were registered and analysed. Risk factors were found by regression analysis. RESULTS: 501 patients (428 OSAS and 73 OS) were enrolled. Patients with OS had higher mortality than OSAS (p < 0,001). The morality risk factors for the overall population found were age >65 years (odds ratio (OR) = 10.69 (95%CI 3,85-29,69), p < 0,001) and low forced-expiratory volume in 1-s (FEV1) (OR = 10.18 (95%CI 2,32-44,68), p = 0,002). In patients with OSAS, age and nocturnal hypoxemia (NH) (OR = 2.41 (95%CI 1,07-5,41), p = 0,03) were risk factors, while adherence to nighttime positive airway pressure (PAP) reduced mortality (OR = 0,36 (95%CI 0,15-0,83), p = 0,017). Multivariate analysis confirmed age and FEV1 as risk factors in OS. Conversely, the risk factors for the overall population under 65 years were NH, which is confirmed in patients with OSAS alone (OR = 4,72 (95%CI 1,07-20,77), p = 0,04) in whom, on the other hand, PAP compliance reduced the mortality risk. CONCLUSIONS: The study suggests that NH is a risk factor for all-cause mortality in sleep disorders by excluding the age; conversely, nighttime PAP improves the survival.

MiRNA and Exosomal miRNA as New Biomarkers Useful to Phenotyping Severe Asthma.

Severe asthma (SA) is a chronic inflammatory disease of the airways. Due to the extreme heterogeneity of symptoms, new biomarkers are currently needed. MiRNAs are non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In biological fluids, miRNAs are contained within exosomes, vesicles capable of giving miRNAs considerable stability and resistance to degradation by RNAses. The main function attributed to the exosomes is intercellular communication. The goal of our study was to analyze intracellular and exosomal miRNAs in order to demonstrate their potential use as non-invasive biomarkers of asthma by showing, in particular, their role in SA. We detected miRNAs by qRT-PCR in both serum and serum-derived-exosomes of asthmatic patients and healthy controls. The levels of almost all analyzed intracellular miRNAs (miR-21, miR-223, and let-7a) were greater in asthmatic patients vs. healthy control, except for miR-223. In detail, miR-21 was greater in SA, while let-7a increased in mild-to-moderate asthma. On the other hand, in exosomes, all analyzed miRNAs were higher in SA. This study identified a series of miRNAs involved in SA, highlighting their potential role in asthma development and progression. These results need validation on a larger cohort.