Expression profiling of miRNA-145 and miRNA-338 in serum and sputum of patients with COPD, asthma, and asthmaâCOPD overlap syndrome phenotype

Background and objectives: A new phenotype with overlapping characteristics between asthma and chronic obstructive pulmonary disease (COPD) called asthmaâCOPD overlap syndrome (ACOS) is emerging among inflammation diseases. To date, there is no agreement on specific criteria to define this syndrome, and the current guidelines are insufficient to classify the analogy and differences between overlap and COPD or asthma phenotypes. It would be necessary to identify new biomarkers able to identify these diseases clearly. Thus, the aim of this study was to identify a serum and supernatant of sputum microRNA (miRNA) expression profile of miRNA-145 and miRNA-338 in patients with asthma (n=13), COPD (n=31), and ACOS (n=8) and controls (n=7). Methods: The expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). For statistical analysis, the ANOVA test, KruskalâWallis test, MannâWhitney U-test, and Spearmanâs rank correlation were used. Results: The main finding of this work is that the expression of miRNA-338 is higher in the supernatant of different obstructive diseases than in peripheral blood, while miRNA-145 is higher only in the supernatant of asthma patients. The expression of both selected miRNAs is higher in the supernatant of asthma and COPD patients than in controls. Conclusion: Differences in sputum miRNA expression profile were observed between patients with ACOS and asthma or COPD, which underline the potential role of miRNA as a biomarker that is able to discriminate patients with ACOS, asthma, and COPD

Dysphagia in non-intubated patients affected by COVID-19 infection

Purpose Patients affected by COVID-19 are assumed to be at high risk of developing swallowing disorders. However, to our best knowledge, data on the characteristics and incidence of dysphagia associated with COVID-19 are lacking, especially in non-intubated patients. Therefore, we investigated the onset of swallowing disorders in patients with laboratory-confirmed COVID-19 infection who have not been treated with invasive ventilation, in order to evaluate how the virus affected swallowing function regardless of orotracheal intubation. Methods We evaluated 41 patients admitted to the COVID department of our Hospital when they had already passed the acute phase of the disease and were therefore asymptomatic but still positive for SARS-CoV-2 RNA by RT-PCR. We examined patients' clinical history and performed the Volume-Viscosity Swallow Test (VVST). Each patient also answered the Swallowing Disturbance Questionnaire (SDQ). After 6 months, we performed a follow-up in patients with swallowing disorders. Results Eight of 41 patients (20%) presented with dysphagia symptoms during hospitalization and 2 of them (25%) still presented a SDQ high score and swallowing disorders with liquid consistency after 6 months. Conclusion Non-intubated patients can experience various grades of swallowing impairment that probably directly related to pulmonary respiratory function alterations and viral direct neuronal lesive activity. Although these symptoms show natural tendency to spontaneous resolution, their impact on a general physical impaired situation should not be underestimated, since it can adversely affect patients' recovery from COVID-19 worsening health outcomes

Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients

Abstract Background Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. Methods In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC 100% - FEF 25–75% Results Treatment with extrafine BDP/FF(200/6 μg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. Conclusions Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 μg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP

Prevalence of comorbidities in patients with obstructive sleep apnea syndrome, overlap syndrome and obesity hypoventilation syndrome

Sleep-disordered breathing causes a burden to the sufferer, the health care system and the society. Most studies have focused on obstructive sleep apnea (OSA); however, the prevalence of comorbidities in patients affected by overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) has not been carefully evaluated

Impact of CT Scan Phenotypes in Clinical Manifestations, Management and Outcomes of Hospitalised Patients with COVID-19

COVID-19 is such a heterogeneous disease that a one-size-fits-all approach is not recommended, so the management of patients has been based on their clinical and laboratory characteristics. We therefore investigated possible homogeneous groups presenting similar features of lung involvement based on chest CT and laboratory results. We designed a study to identify a possible correlation between CT scan phenotypes, laboratory exams, and clinical outcomes. We retrospectively analysed 120 adult patients with COVID-19 5who underwent chest CT scan during hospitalisation, between March and December 2020 at our COVID-19 Hospital in two different wards: Respiratory Intensive Care Unit (RICU) and Intensive Care Unit (ICU). The analysis of CT scans resulted in the identification of three radiological phenotypes by two blinded pulmonologists (Cohen's κ = 0.9 for Phenotype 1, 0.9 for Phenotype 2 and 0.89 for Phenotype 3), in accordance with what previously described by Robba et al. “Phenotype 1” (PH1) is characterised by modest interstitial oedema with presentation on chest CT of diffuse ground glass opacities (GGO). “Phenotype 2” (PH2) shows predominant consolidation at lung lobes. “Phenotype 3” (PH3) shows a typical CT pattern of moderate-to-severe ARDS, with alveolar oedema. Based on our results, we could hypothesise that phenotype 2 shows a different trend from all the others and would seem to be more related to a coagulopathy, although we cannot exclude the hypothesis that one phenotype evolves from the other. Further studies might focus on the predictive role of D-dimer, and its cut-offs, in delineating the PH2 patients, that could require an early CT scan to avoid excessive pressure support and finally prevent VILI. To further understand the exact basis of the different CT scan phenotype, a longer longitudinal analysis of clinical and laboratory features (e.g., timing of weaning, pressures and FiO2 delivered) in each phenotype and a comparison among them is needed

Use of narrative medicine to identify key factors for effective doctor–patient relationships in severe asthma

Background: In this project the authors use a narrative medicine (NM) approach to assess the promotion of trust in the relationship between physicians and their asthma patients. Methods: Following a NM educational course for physicians, a research was carried out in which at least 5 written narratives (parallel charts) for each participating physician were collected and qualitatively analysed according to Bury's classification and the Grounded Theory. Results: The results of this study were of speculative and clinical interest. In particular, 66 participants wrote 314 narratives (246 on adult and 68 on paediatric patients). As a result of applying the NM approach, when the relationships remained problematic, many physicians wrote with a moral style about their adult (67%), and paediatric patients (33%) - especially in cases of asthmatic children's or adolescents' overprotective or absent families (40%) -. On the contrary, physicians who were able to listen to their patients with empathy (35%) made more shared decisions with patients, even with those they initially had a bad relationship. The used words of welcome, interest and acceptance were promoting patients' trust that lead to restoring their activities in 45% of cases, according to physicians self-reporting. Conclusions: These approaches of NM are useful in daily clinical practice, with the goal of improving the quality of life (QOL) of patients with severe asthma, even in cases in which the doctor-patient relationship isn't initially good

Pretreatment rate of decay in forced vital capacity predicts long-term response to pirfenidone in patients with idiopathic pulmonary fibrosis.

Pirfenidone reduces functional decline and disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF). However, response to treatment is highly heterogeneous. In this study, we evaluated whether response to pirfenidone is influenced by the pre-treatment rate of forced vital capacity (FVC) decline. Fifty-seven IPF patients were categorized as rapid (RP) or slow progressors (SP) based on whether their FVC decline in the year preceding pirfenidone treatment was > or <10% predicted. Patients were followed-up every 6 months and up to 24 months following institution of pirfenidone treatment. In the entire population, pirfenidone reduced significantly the rate of FVC decline from 222 ml/yr to 68 ml/yr at 12 month (p<0.01) and 86 ml/yr at 24 month (p=0.04) follow-up. In RP, the reduction of FVC decline was evident at 6 months (706 ml/yr pre-treatment vs 35 ml/yr; p<0.01) and maintained, though to a lesser degree, at 12 (105 ml/yr; p< 0.01) and 24 months (125 ml/yr; p<0.02). Conversely, among SP the reduction in FVC decline was not significant at any of the time points analyzed. Pirfenidone reduces significantly the rate of FVC decline in patients with IPF. However, the beneficial effect is more pronounced and long-lasting in patients with rapidly progressive disease

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. Methods: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. Results: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia