Tidal breathing affects airway responsiveness to methacholine.

Abstract Asthma is characterized by increased airway responsiveness and airway inflammation. Airway hyperresponsiveness may be caused by increased airway smooth muscle contractility or by a decrease in the mechanical load that opposes airway smooth muscle contraction. Under static conditions, the equilibrium between contractility and load will determine the final airway smooth muscle length and therefore airway caliber. Because of tidal breathing, however, lungs normally function under dynamic conditions where both airway contractility and opposing load are affected. The capability of tidal breathing to appropriately modulate airway function might be the mechanism that differentiates airways of asthmatics from those of normal subjects

The extracellular matrix of the lung and airway responsiveness in asthma.

Abstract The extracellular matrix is the main determinant of the structure and of mechanical behaviour of the lung. The extracellular matrix is also responsible for the mechanical interdependence between airway and parenchyma due to the alveolar attachments to the airways. Asthma is characterized by bronchial hyperresponsiveness, airway remodelling and inflammation, and an altered extracellular matrix may play a role in all these functional and structural abnormalities. The excessive airway narrowing observed in asthma may be related to the altered viscoelastic properties of lung parenchyma and airway wall, determining a decrease in the mechanical load opposing the airways' smooth muscle contraction. Indeed, an altered extracellular matrix deposition in asthma in humans, has been demonstrated. In addition, in the asthmatic lung, the matrix seems to contribute to airway inflammation, airway remodelling, and to those alterations of the smooth muscle function of the airway and morphology typical of asthma

Attenuation of induced bronchoconstriction in healthy subjects: effects of breathing depth.

The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (approximately 1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at approximately 80, approximately 90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V(part)) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V(part) and the increase in RV were significantly less when the depth of the five-breath series was progressively increased (P < 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V(part) (P < 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V(part), likely due to the different mechanisms that regulate airway closure and expiratory flow limitation

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy.

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy

Vitamin A deficiency alters the pulmonary parenchymal elastic modulus and elastic fiber concentration in rats

BACKGROUND: Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD) is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA) or remained unsupplemented. METHODS: Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh) by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion. RESULTS: VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS) rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98°, decreased in VAD and was not restored after 21 days of RA-treatment. CONCLUSION: Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways

Magnetic resonance imaging (MRI) in rectal cancer: a comprehensive review

Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience

Competing for Public Resources: Higher Education and Academic Research in Europe. A Cross-Sectoral Perspective

The chapter focuses on the increasing cross-sectoral competition for public resources between various types of public sector institutions in Europe and its implications for future public funding for both higher education and academic research. It views the major models of the institution of the modern (Continental) university and the major types of the modern institution of the state, and of the welfare state in particular, as traditionally closely linked (following Kogan et al., 2000; Kogan and Hanney, 2000; Becher and Kogan, 1992). Historically, in the post-war period in Europe, the unprecedented growth of welfare states and state-funded public services was paralleled by the unprecedented growth of public universities. The massification and universalization of higher education in Europe coincided with the growth of the welfare state in general. Currently, both processes in higher education are in full swing across Europe while welfare states are under the most far-reaching restructuring in their postwar history. The major implication is the fierce competition for public resources, studied in this chapter from a cross-sectoral perspective, in which the future levels of public funding for higher education in tax-based European systems are highly dependent on social attitudes towards what higher education brings to society and the economy, relative to what other claimants to the public purse can bring to them