Mucins and Asthma : Are We Headed to the Revolutionary Road?

Mucus represents the first line of defense of our respiratory tract and mucociliary clearance is essential for maintaining the homeostasis of airway epithelium. The latter mechanisms are altered in asthma and mucus plugging of proximal and distal airways is the main cause of death in cases of fatal asthma. Starting from the influential review performed by Luke R. Bonser and David J. Erle in 2017, we discuss the latest evidence in terms of mucins regulation and potential treatment of mucus hypersecretion and tissue remodeling in severe asthma

Automated Experimental Modal Analysis of Bladed Wheels with an Anthropomorphic Robotic Station

Experimental modal analysis is challenging when the component has a highly three-dimensional shape, since a great number of measurement points are needed with accurate positioning. An anthropomorphic robotic station is proposed to automate this analysis, specifically on bladed wheels. This provides a reliable control of the spot location and of the beam orientation of a Laser Doppler Vibrometer. The modal frequencies were obtained along with the vibrational shapes and their spatial resolution was managed by exploiting the programming flexibility of the robotic station. The SAFE diagram was easily obtained by measuring a single point for each sector, and an extension of this diagram was demonstrated for the splitter blade wheels. The use of multiple measurement points, for each wheel sector, significantly improved the characterization of the modes having the same number of nodal diameters, hence the same shape coordinate on the SAFE diagram

Early consensus management for non-ICU acute respiratory failure SARS-CoV-2 emergency in Italy : from ward to trenches

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Modello di tenuta della flangia bullonata, senza guarnizione, mediante l'analogia della meccanica della frattura di una fessura parzialmente aperta

I compressori centrifughi di elevate dimensioni non permettono l'utilizzo di guarnizioni deformabili, per cui le due meta della flangia di connessione sono forzate mediante bullonatura e la tenuta e affidata al contatto completo delle due superfici. La previsione della pressione di perdita e un aspetto di progetto di notevole interesse per questa tecnologia. L'azione della pressione interna sollecita la separazione delle superfici della flangia, che invece e contrastata dall'azione di serraggio dei bulloni. Il presente lavoro propone un modello per prevedere la condizione di perdita, basato sulla meccanica della frattura. Dato che le due superfici della flangia sono semplicemente a contatto, esse costituiscono una vera e propria fessura parzialmente aperta. Come ben noto il fattore di intensificazione di una fessura parzialmente aperta e nullo. Imponendo che le due superfici siano parzialmente separate ad una distanza fino al bordo del foro del bullone (che offre un canale di fuoriuscita per il fluido in pressione), e imponendo la condizione di fattore di intensificazione nullo, e possibile determinare la pressione di perdita, analiticamente, mediante la tecnica delle "weight functions" (o "funzioni peso"). Il presente lavoro riporta una positiva validazione del modello proposto mediante sia simulazione numerica sia risultati sperimentali in piena scala e in scala ridotta. Il modello analitico proposto offre uno strumento di progetto di immediata implementazione per comparare diverse geometrie di flangia bullonata

Helmet CPAP to Treat Acute Hypoxemic Respiratory Failure in Patients with COVID-19 : a Management Strategy Proposal

Since the beginning of March 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 13,000 deaths in Europe, almost 54% of which has occurred in Italy. The Italian healthcare system is experiencing a stressful burden, especially in terms of intensive care assistance. In fact, the main clinical manifestation of COVID-19 patients is represented by an acute hypoxic respiratory failure secondary to bilateral pulmonary infiltrates, that in many cases, results in an acute respiratory distress syndrome and requires an invasive ventilator support. A precocious respiratory support with non-invasive ventilation or high flow oxygen should be avoided to limit the droplets' air-dispersion and the healthcare workers' contamination. The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia. It can also limit the room contamination, improve comfort for the patients, and allow for better clinical assistance with long-term tolerability. However, the initiation of a CPAP is not free from pitfalls. It requires a careful titration and monitoring to avoid a delayed intubation. Here, we discuss the rationale and some important considerations about timing, criteria, and monitoring requirements for patients with COVID-19 respiratory failure requiring a CPAP treatment

The airways' mechanical stress in lung disease: Implications for COPD pathophysiology and treatment evaluation

The airway epithelium stretches and relaxes during the normal respiratory cycle, and hyperventilation exaggerates this effect, resulting in changes in lung physiology. In fact, stretching of the airways influences lung function and the secretion of airway mediators, which in turn may cause a potentially injurious inflammatory response. This aim of the present narrative review was to illustrate the current evidence on the importance of mechanical stress in the pathophysiology of lung diseases with a particular focus on chronic obstructive pulmonary disease (COPD) and to discuss how this may influence pharmacological treatment strategies. Overall, treatment selection should be tailored to counterpart the effects of mechanical stress, which influences inflammation both in asthma and COPD. The most suitable treatment approach between a long-acting \u3b22-agonists/long-acting antimuscarinic-agonist (LABA/LAMA) alone or with the addition of inhaled corticosteroids should be determined based on the underlying mechanism of inflammation. Noteworthy, the anti-inflammatory effects of the glycopyrronium/indacaterol combination on hyperinflation and mucociliary clearance may decrease the rate of COPD exacerbations, and it may synergistically improve bronchodilation with a double action on both the cyclic adenosine monophosphate (cAMP) and the acetylcholine pathways

Fatigue fracture surface investigations with a 3D optical profiler

In this paper a set of specimens, used for the critical distance determination, are investigated with a non-contact 3D optical profiler. The fatigue fracture surfaces of both plain and V-notched specimens, under axial (mode I) and torsional (mode III) loadings are observed, investigating steel 42CrMo4+QT and aluminium alloy 7075-T6. The fatigue fracture profiles are compared to be previously obtained critical distances, both for mode I and mode III. The stage I to stage II transition was found at a smaller size than the axial critical distance, for the steel, while for the torsional load a local plateau at the nucleation was observed. The fracture surface of the axial loading was instead much irregular at the scale of the mode I critical distance, for the aluminium alloy, resembling a not concluded stage I, while again a relatively flat surface was observed for the mode III loading

The effect of a multidisciplinary approach for smoking cessation in patients with Crohn's disease : results from an observational cohort study

Introduction: Cigarette smoking is the most important risk factor for Crohn's disease (CD). The effectiveness of smoking cessation programs (SCPs) in patients with CD is still poorly understood. Methods: This was a retrospective, observational, single-centre, cohort study of 136 active smokers with mean age 55 years (SD=11), 58% males, including 27 (19.8%) patients with CD who entered the multidisciplinary SCP of the Luigi Sacco University Hospital of Milan from January 2017 through January 2019. A pulmonologist was responsible for the clinical and pharmacological management, while a psychiatrist and a psychologist conducted the counselling and assessed the motivation to quit, anxiety and depression using the Brief Psychiatric Rating Scale (BPRS) and the nicotine dependence with the Fagerstr\uf6m test. Patients were defined as quitters after 12 months. Results: Demographic and clinical characteristics, and Fagerstr\uf6m score, did not differ in patients with and without CD. At baseline, patients with CD had a higher BPRS (median: 27, IQR: 22-32; vs 25 and 22-28.5; p=0.03), and a lower motivation to quit score (median: 10, IQR: 9-13; vs 14 and 12-15; p<0.001). After 12 months, the quitting rate of smokers with CD was significantly lower (14.8% vs 36.7%; p<0.022) and the chance of quitting was negatively associated with the baseline BPRS (r=-0.256; p<0.003). Varenicline and nicotine replacement therapy tended to be less effective in patients with CD. Conclusions: The lower efficacy of SCPs in patients with CD might be secondary to a higher prevalence of anxiety and depression. Psychological issue recognition and support should be enhanced to increase SCP effectiveness in CD

Tetracyclines in COVID-19 patients quarantined at home: Literature evidence supporting real-world data from a multicenter observational study targeting inflammatory and infectious dermatoses

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID-19 outbreak, several dermatological patients contracted SARS-CoV-2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID-19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21-67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID-19 outpatients with mild symptoms

Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD

It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance. Formoterol, salmeterol and oxitropium have been recommended for maintenance therapy in COPD patients, but their effect on DH has only been assessed for salmeterol. The aim of the present study was to compare the acute effect of four inhaled bronchodilators (salbutamol, formoterol, salmeterol and oxitropium) and placebo on forced expiratory volume in one second, inspiratory capacity, forced vital capacity and dyspnoea in COPD patients. A cross-over, randomised, double-blind, placebo-controlled study was carried out on 20 COPD patients. Patients underwent pulmonary function testing and dyspnoea evaluation, in basal condition and 5, 15, 30, 60 and 120 min after bronchodilator or placebo administration. The results indicate that in chronic obstructive pulmonary disease patients with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory capacity after bronchodilator administration, which correlated closely with the improvement of dyspnoea sensation at rest. For all bronchodilators used, inspiratory capacity reversibility should be tested at 30 min following the bronchodilator. On average, formoterol elicited the greatest increase in inspiratory capacity than the other bronchodilators used, though the difference was significant only with salmeterol and oxitropium. The potential advantage of formoterol needs to be tested in a larger patient population