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

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

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

The evidence on tiotropium bromide in asthma: from the rationale to the bedside

Severe and poorly controlled asthma still accounts for a great portion of the patients affected. Disease control and future risk management have been identified by international guidelines as the main goals in patients with asthma. The need for new treatment approaches has led to reconsider anticholinergic drugs as an option for asthma treatment. Tiotropium is the first anticholinergic drug that has been approved for children and adults with poorly controlled asthma and is currently considered as an option for steps 4 and 5 of the Global Initiative for Asthma. In large randomized clinical trials enrolling patients with moderate to severe asthma, add-on therapy with tiotropium has demonstrated to be efficacious in improving lung function, decreasing risk of exacerbation and slowing the worsening of disease; accordingly, tiotropium demonstrated to be non inferior compared to long acting beta-agonists in the maintenance treatment along with medium to high inhaled corticosteroids. In view of the numerous ancillary effects acting on inflammation, airway remodeling, mucus production and cough reflex, along with the good safety profile and the broad spectrum of efficacy demonstrated in different disease phenotypes, tiotropium can represent a beneficial alternative in the therapeutic management of poorly controlled asthma. The present extensive narrative review presents the pharmacological and pathophysiological basis that guided the rationale for the introduction of tiotropium in asthma treatment algorithm, with a particular focus on its conventional and unconventional effects; finally, data on tiotropium efficacy and safety. from recent randomized clinical trials performed in all age categories will be extensively discussed

Management of severe COPD exacerbations : focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide

The major determinant of the decline in lung function, quality of life, and the increased mortality risk in patients with COPD is represented by severe acute exacerbations of the disease, that is, those requiring patients' hospitalization, constituting a substantial social and health care burden in terms of morbidity and medical resource utilization. Different long-term therapeutic strategies have been proposed so far in order to prevent and/or reduce the clinical and social impact of these events, the majority of which were extrapolated from trials initially focused on the effect of long-acting muscarinic antagonist and subsequently on the efficacy of long-acting \u3b22-agonists in combination or not with inhaled corticosteroids. The option to employ all three classes of molecules combined, despite the limited amount of evidence in our possession, represents a choice currently proposed by international guidelines; however, current recommendations are often based mainly on observational studies or on the results of secondary outcomes in randomized controlled trials. The present narrative review evaluates the available trials that investigated the efficacy of inhaled therapy to prevent COPD exacerbations and especially severe ones, with a particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide fixed dose combination, which is the first treatment that comprises all the three drug classes, specifically tested for the prevention of moderate and severe COPD exacerbations