Small airway inflammation and extrafine inhaled corticosteroids plus long-acting beta2-agonists formulations in chronic obstructive pulmonary disease

Abstract Objectives To summarize the evidence of small airways involvement in chronic obstructive pulmonary disease (COPD) pathophysiology, and to evaluate the efficacy of extrafine formulations of inhaled corticosteroids (ICS) in combination with long-acting beta2-agonists (LABAs) in the treatment of COPD. Data source A search of the PubMed database was conducted using the keywords "COPD", "small airways", "inflammation" and "extrafine formulation." The search was limited to entries published in English before August 2016. Only studies conducted in humans were considered. Study selection Publications were included on the basis of relevance. Results COPD is a common preventable and treatable disease, characterized by persistent and progressive airflow limitation. With improved understanding of COPD pathophysiology, small airways (internal diameter Conclusion There is an urgent need for improved and reliable techniques for small airways assessment in order to detect early damage, disease progression and response to treatment. Evidence from randomized clinical trials supports the benefits of extrafine ICS/LABA formulations in COPD, real world studies are necessary to confirm this

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

Pain Catastrophizing in Childhood Migraine: An Observational Study in a Tertiary Headache Center

Background: Migraine is the most common cause of primary headache in children leading to a decrease in the quality of life. During the last decade, pain catastrophizing construct became a major focus of interest in the study and treatment of pain.Aim of the study:To evaluate pain catastrophizing in episodic and chronic migraine children and adolescents selected in a tertiary headache Center.To test whether the children's pain catastrophizing might be associated (a) with the frequency of attacks and disability (b) with psychopathological aspects (c) with allodynia and total tenderness score as symptom of central sensitization.To test the best discriminating clinical variables and scores between episodic and chronic migraine, including pain catastrophizing.Methods: We conducted a cross sectional observational study on consecutive pediatric patients affected by migraine. We selected 190 headache patients who met the diagnostic criteria for Migraine without aura, Migraine with aura and Chronic migraine. We submitted all children to the Child version of the Pain Catastrophizing Scale (PCS-C), and to the disability scale for migraine (PedMIDAS), general quality of life estimated by children (PedsQL) and parents (PedsQL-P), anxiety and depression (SAFA-A; SAFA-D) scales. We also evaluated headache frequency and the presence and severity of allodynia and pericranial tenderness.Results: No difference was detected in Total Pain Catastrophizing score (PCS-C) between chronic and episodic migraine groups (ANOVA F = 0.59, p = 0.70); the PedMIDAS, the PedsQL-P for physical functioning and the Total Tenderness Score were discriminant variables between episodic and chronic migraine. The PCS-C was not correlated with migraine related disability as expressed by Ped MIDAS, but it was significantly correlated with general low quality of life, allodynia, pericranial tenderness, anxiety, and depression.Conclusion: Pain catastrophizing seems a mental characteristic of a clinical phenotype with psychopathological traits and enhanced expression of central sensitization symptoms. This clinical profile causes general decline in quality of life in the child judgment, with a probable parents' underestimation. In childhood age, it would not be a feature of chronic migraine, but the possibility that it could predict this evolution is consistent and worthy of further prospective evaluation

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

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

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

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

Changes in sputum composition during 15min of sputum induction in healthy subjects and patients with asthma and chronic obstructive pulmonary disease

SummaryIntroductionThe use of sputum induction by inhalation of hypertonic saline to study the cellular and biochemical composition of the airways allows noninvasive sampling of the airways content and identification of markers of airways inflammation.ObjectiveThe present study aimed to identify possible changes in the cellular composition of induced sputum between samples obtained sequentially (three periods of 5min each) during one sputum induction. Moreover, difference between these samples and the mixed one (mixture of samples obtained after 5, 10 and 15min of induction) was investigated.MethodsForty-six subjects (10 healthy volunteers, 12 patients with chronic obstructive pulmonary disease (COPD) and 24 patients with asthma) (mean age 53.0±14.0yr, forced expiratory volume in one second (FEV1) 71.8±19.0% pred) produced sputum after three consecutive 5min periods of hypertonic (4.5%) saline inhalation. Stained cytospins from the three periods separately and from the mixed sample were produced and analyzed.ResultsThe mean percentage of neutrophils, eosinophils, lymphocytes and epithelial cells did not change significantly in samples obtained consecutively after 5, 10 and 15min of the induction procedure. There was no significant difference in the cellular composition of samples obtained after 5, 10 and 15min of induction and the cellular composition of the mixed sample (P=0.06).ConclusionThe separate analysis of induced sputum from three consecutive sampling and the mixed sample did not demonstrate significant changes in their cellular composition. Fifteen minutes induction procedure with the fixed concentration of hypertonic saline and processing of the mixed sample can be recommended for clinical settings and clinical trials

SARS-CoV-2 Gamma and Delta Variants of Concern Might Undermine Neutralizing Activity Generated in Response to BNT162b2 mRNA Vaccination

The Delta variant raised concern regarding its ability to evade SARS-CoV-2 vaccines. We evaluated a serum neutralizing response of 172 Italian healthcare workers, three months after complete Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer) vaccination, testing their sera against viral isolates of Alpha, Gamma and Delta variants, including 36 subjects with a previous SARS-CoV-2 infection. We assessed whether IgG anti-spike TRIM levels and serum neutralizing activity by seroneutralization assay were associated. Concerning Gamma variant, a two-fold reduction in neutralizing titres compared to the Alpha variant was observed, while a four-fold reduction of Delta virus compared to Alpha was found. A gender difference was observed in neutralizing titres only for the Gamma variant. The serum samples of 36 previously infected SARS-CoV-2 individuals neutralized Alpha, Gamma and Delta variants, demonstrating respectively a nearly three-fold and a five-fold reduction in neutralizing titres compared to Alpha variant. IgG anti-spike TRIM levels were positively correlated with serum neutralizing titres against the three variants. The Comirnaty vaccine provides sustained neutralizing antibody activity towards the Alpha variant, but it is less effective against Gamma and even less against Delta variants