1,721,069 research outputs found
Prostaglandin D2 receptor antagonists in early development as potential therapeutic options for asthma
No full textINTRODUCTION:
Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that interfere with the innate inflammatory response in asthma have been identified. Promising preliminary results concern the signaling cascade promoted by prostaglandin D2 (PGD2) and its receptor antagonists.
AREAS COVERED:
The aim of this review is to provide the most recent clinical and preclinical data on the efficacy and safety of newly developed compounds for the treatment of allergic asthma. The authors will present an overview of the pathogenetic molecular mechanisms sustaining the chronic inflammatory response in asthma; the focus will be then directed on the mediators of the PGD2 pathway, the chemoattractant receptor-homologous molecule expressed on TH2 cells, and their latest antagonists developed.
EXPERT OPINION:
Bronchodilators and corticosteroids are not sufficient to achieve a satisfactory management of all asthmatic patients; the development of new specific treatments appears therefore essential. The good results in terms of cellular, functional and clinical outcomes, together with an acceptable safety of the CRTh2 antagonists represent a promising start for a tailored management of allergic asthma
Assessment of airway occlusion by single breath N2 test and deflation lung PL-V curve in healthy subjects and COPD patients
No full textCyclic airway closing and opening may induce lung injury in both normal and diseased lung. During tidal breathing this phenomenon occurs when closing volume (CV) exceeds the expiratory reserve volume. In humans, CV is currently assessed from the onset of phase IV of the single breath nitrogen test (CVSBN), but this method fails in severe chronic obstructive pulmonary disease (COPD) patients in whom phase IV can be absent, even if the amount of airway closure should be substantial. At present, no agreement exists whether an another potential indicator of airways closure, the inflection point on the transpulmonary pressure–volume curve (CVPL-V) can be used as a surrogate of CVSBN, when phase IV is not detectable. The comparison of CVSBN with CVPL-V assessed during the same slow deflation showed that both in healthy subjects and in COPD patients, when CVSBN was present, it coincided with CVPL-V. In the young subjects in whom CVSBN was absent, CVPL-V was not detectable, in accordance to the notion that in these subjects lung recoil can be high enough to prevent airway closure in the whole vital capacity range. On the other hand, in the COPD patients with no phase IV, CVPL-V was constantly present, as expected. These results suggest that measurement of CVPL-V is a reliable method for closing volume assessment in both normal and COPD subjects. In the latter group, the measurement of CVSBN can lead to heavily underestimate the extent of the airway collapse
Uso delle resistenze specifiche per la stima della risposta al broncodilatatore in pazienti BPCO
No full textNei pazienti affetti da broncopneumopatia cronica ostruttiva (BPCO), i broncodilatatori migliorano la funzione polmonare e alleviano la sintomatologia respiratoria nella misura in cui riducono la resistenza delle vie aeree durante la respirazione tidalica, prevenendo o riducendo l’iperinflazione dinamica (Barnes et al., 1981). Inoltre, la riduzione del tono broncomotore a livello delle piccole vie aeree può ridurre il volume residuo (RV) e aumentare la capacità vitale (VC).
Secondo le linee guida ATS/ERS (Pellegrino et al., 2005), un paziente BPCO risponde a un broncodilatatore se, dopo somministrazione del farmaco, l’aumento del volume espirato forzatamente in un secondo (FEV1) e/o della capacità vitale forzata (FVC) è uguale o maggiore del 12% del valore di controllo, e comunque uguale o maggiore di 200 ml.
Tuttavia è noto che a) FEV1 riflette solo parzialmente le resistenze polmonari (Pride, 1971;Skinner and Palmer, 1974), b) la misurazione di FEV1 e di FVC è ottenuta con una manovra di per sè in grado di modificare il calibro delle vie aeree (Barnes et al., 1981), c) FEV1 e FVC sono altamente correlate (Schermer et al., 2007), e d) le variazioni di FEV1 e di FVC nei pazienti BPCO di grado severo possono essere molto piccole (Deesomchok et al., 2010).
E’ possibile che le variazioni delle resistenze specifiche pletismografiche (sRAW), un parametro che riflette accuratamente le resistenze delle vie aeree periferiche (Bassiri et al., 1997), possano evidenziare l’azione dei broncodilatatori nei pazienti BPCO meglio di quanto possano fare le variazioni di FEV1 o di FVC
Airway occlusion assessed by single breath N2 test and lung P-V curve in healthy subjects and COPD patients
Full text linkPurpose To determine whether the analysis of the slow expiratory transpulmonary pressure–volume (PL-V) curve provides an alternative to the single-breath nitrogen test (SBN) for the assessment of the closing volume (CV). Methods SBN test and slow deflation PL-V curve were simultaneously recorded in 40 healthy subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test (CVSBN), whereas in the PL-V curve CV was identified by: a) deviation from the exponential fit (CVexp), and b) inflection point of the interpolating sigmoid function (CVsig). Results In the absence of phase IV, COPD patients exhibited a clearly discernible inflection in the PL-V curve. In the presence of phase IV, CVSBN and CVexp coincided (CVSBN/CVexp = 1.04 ± 0.04 SD), whereas CVsig was systematically larger (CVsig/CVexp = 2.1 ± 0.86). Conclusion The coincidence between CVSBN and CVexp, and the presence of the inflection in the absence of phase IV indicate that the deviation of the PL-V curve from the exponential fit reliably assesses CV
Varenicline and evaluated outcomes in smoking cessation programmes
No full textThe morbidity and mortality rates attributed to smoking are substantial and cigarette smoke remains the first preventable cause of premature death worldwide. Despite the knowledge of the adverse consequences of smoking, many smokers struggle to quit. Cigarette smoking is the primary cause of chronic obstructive pulmonary disease, and smoking cessation represents the most effective way of stopping its progression. Varenicline is one of the first-line smoking cessation aids recommended in many Clinical Practice Guidelines and its efficacy and safety have been demonstrated in several clinical trials. Varenicline has a unique mechanism of action and clinical trials support its use as an effective and generally well-tolerated therapy. This article reviews the clinical pharmacological trials on smoking cessation published in recent years on varenicline, with particular attention to the outcomes used in the studies. MedLine, the Cochrane database and Embase were evaluated. Almost all the trials have, as a primary endpoint, the abstinence from cigarettes at 9-12 weeks of treatment. Only one study considers lung function spirometric changes as a secondary endpoint. No study has evaluated lung function. This marker could be very important as a way of evaluating, objectively, an improvement in lung function, which correlates also with subjective parameters, as dyspnea and fatigue
A quantitative analysis of plethysmographic loops
No full textContrary to healthy subjects, in whom the relation between alveolar pressure (Palv) and flow (V̇) is linear, Palv-V̇ loops are often seen in chronic obstructive pulmonary disease (COPD) patients. These loops contain potentially relevant information about the physiopathological phenomena that characterize this disease, but, at present, no quantitative data during spontaneous breathing are available.
This study has characterized plethysmographic Palv-V̇ loops in terms of inspiratory (Ains), expiratory area (Aexp), and sense of rotation in 130 stable COPD patients at rest during spontaneous breathing. Relative to Ains, Aexp was larger (1.29±1.74 versus 0.39±0.33 cmH2O L s-1), and its sense of rotation was compatible with time-constants heterogeneity, air trapping, recruitment/derecruitment of lung units or expiratory flow-limitation.
Aexp correlated with indexes of flow-limitation (RS= -0.274, P<0.01 with forced expiratory volume in one second) and gas trapping (RS= 0.321, P<0.01 with the ratio of residual volume to total lung capacity), but not with indexes of uneven distribution of ventilation as the alveolar volume measured during the single breath carbon monoxide test (RS= -0.081, P=0.36).
These results suggest that in COPD patients breathing spontaneously at rest, expiratory looping appears primarily because of the presence of tidal expiratory flow-limitation and eventually gas trapping, rather than because of time-constants heterogeneity or recruitment/derecruitment
Bronchoscopy in sarcoidosis : union is strength
No full textSarcoidosis is a benign disease of unknown etiology that is characterized by the formation of noncaseating epithelioid cell granulomas. Although a multisystemic disease, it primarily affects the lung and the lymphatic system of the body. When a histological diagnosis is required, bronchoscopy is frequently employed because allows tissue sampling from several anatomic sources, such as airways, lung parenchyma and hilar/mediastinal nodes. Transbronchial lung biopsies (TBLB), endobronchial biopsies (EBB) and conventional transbronchial needle aspiration (cTBNA) have long been the only bronchoscopic techniques to diagnose sarcoid granulomas, until the advent of endobronchial ultrasound guided needle aspiration (EBUS-TBNA). This technique shows excellent yield in sampling mediastinal adenopathies with a higher sensitivity than the conventional technique in sarcoidosis as well. Furthermore, non controlled studies, demonstrated its diagnostic superiority than EBB and TBLB in stages I (hilar adenopathies only) and II (hilar lymph nodes and parenchymal infiltrations) thoracic sarcoidosis. In a recent study, Gupta et al., randomized 130 patients with suspected stage I and II disease to undergo EBUS-TBNA or cTBNA in conjunction with transbronchial and endobronchial biopsies. The Authors demonstrated that the yield of cTBNA added to EBB and TBLB is similar to EBUS-TBNA plus transbronchial biopsies, although ultrasound guided transbronchial needle aspiration shows the best single diagnostic efficacy. In this review article we aimed to discuss the findings by Gupta in the context of medical literature, highlighting the importance of adding nodal aspirations (with or without ultrasound guidance) with bronchial and transbronchial samples to gain the optimal sensitivity in obtaining histological confirmation. We finally pointed out the need for future studies to evaluate the potential role of rapid on-site evaluation (ROSE) of needle aspirates in reducing additional sampling and related costs and complications
Management of severe COPD exacerbations : focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide
Full text linkThe 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 β2-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
Tiotropium: what came after the UPLIFT study
No full textINTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive bronchial obstruction, and bronchodilators represent the maintenance therapeutic choice. Tiotropium is an anticholinergic drug that is proved to be safe, efficient and simple to handle; Respimat® technology was recently introduced as a new device for tiotropium administration. AREAS COVERED: This paper reviews clinical trials and meta-analyses, with tiotropium efficacy as a primary end point, found in MedLine, the Cochrane trials database and Embase. Only the literature published after the UPLIFT study has been considered. EXPERT OPINION: Data published after the UPLIFT study confirms the efficacy of tiotropium as maintenance COPD therapy and its capacity to reduce airflow obstruction, as well as lung hyperinflation. Nevertheless, there is a certain inhomogeneity in the definition and evaluation of COPD exacerbations, in lung functional parameters and quality-of-life assessment, and there has not always been a proper comparison between tiotropium and other long-acting bronchodilators. Respimat is comparable in efficacy to the HandiHaler®, using bioequivalent doses of tiotropium
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