131,021 research outputs found
Lung pathophysiology in patients with long COVID-19: one size definitely does not fit all
No full textDespite reduced resting lung volumes and D LCO, patients with long COVID and dyspnoea have similar physiological response to exercise to healthy subjects. D LCO impairment can marginally explain heterogeneity of complex syndromes such as long COVID. https://bit.ly/40j4aX6
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
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
Role of nebulized glycopyrrolate in the treatment of chronic obstructive pulmonary disease
No full textPierachille Santus,1 Dejan Radovanovic,1 Andrea Cristiano,1 Vincenzo Valenti,2 Maurizio Rizzi1 1Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Division of Respiratory Diseases, “L. Sacco” Hospital, ASST Fatebenefratelli Sacco, Milan, Italy; 2Department of Health Bioscience, University of Milan – Respiratory Unit, Policlinico di San Donato, IRCCS – San Donato Milanese, Milan, Italy Abstract: In the upcoming years, the proportion of elderly patients with chronic obstructive pulmonary disease (COPD) will increase, according to the progressively aging population and the increased efficacy of the pharmacological treatments, especially considering the management of chronic comorbidities. The issue to prescribe an appropriate inhalation therapy to COPD patients with significant handling or coordination difficulties represents a common clinical experience; in the latter case, the choice of an inadequate inhalation device may jeopardize the adherence to the treatment and eventually lead to its ineffectiveness. Treatment options that do not require particular timing for coordination between activation and/or inhalation or require high flow thresholds to be activated should represent the best treatment option for these patients. Nebulized bronchodilators, usually used only in acute conditions such as COPD exacerbations, could fulfill this gap, enabling an adequate drug administration during tidal breathing and without the need for patients’ cooperation. However, so far, only short-acting muscarinic antagonists have been available for nebulization. Recently, a nebulized formulation of the inhaled long-acting muscarinic antagonist glycopyrrolate, delivered by means of a novel proprietary vibrating mesh nebulizer closed system (SUN-101/eFlow®), has progressed to Phase III trials and is currently in late-stage development as an option for maintenance treatment in COPD. The present critical review describes the current knowledge about the novel nebulizer technology, the efficacy, safety, and critical role of nebulized glycopyrrolate in patients with COPD. To this end, PubMed, ClinicalTrials.gov, Embase, and Cochrane Library have been searched for relevant papers. According to the available results, the efficacy and tolerability profile of nebulized glycopyrrolate may represent a valuable and dynamic treatment option for the chronic pharmacological management of patients with COPD. Keywords: glycopyrrolate, glycopyrronium, nebulizer, COPD, antimuscarinic, devic
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
Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study
No full textPatients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 μg/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 μg/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes’ function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results
Plethysmographic measurement of intrinsic PEEP in stable COPD patients at rest
No full textBackground: In stable chronic obstructive pulmonary disease (COPD), intrinsic positive end-expiratory pressure (PEEPi) due to tidal expiratory flow-limitation (FL) is responsible for the increase in work of breathing and for adverse haemodynamic effects. PEEPi during spontaneous breathing can be only measured invasively with the esophageal balloon technique (ES).
Aims: To obtain a non-invasive estimation of PEEPi in stable COPD patients using a commercially available plethysmograph (PEEPipl) and to compare it with existing data on PEEPi obtained with ES (PEEPies) [Haluszka, J. et al. Am Rev Respir Dis 1990; 141:1194-97;Dal Vecchio, L. et al. Eur Respir J 1990; 3:74-80].
Methods: Stable mild to very severe COPD patients performed body-plethysmography before and after bronchodilation (BD) according to current guidelines. PEEPipl was calculated by converting into alveolar pressure the shift volume measured at the end of a spontaneous tidal expiration. FL was assessed with the negative expiratory pressure method.
Results: 62 COPD patients were enrolled (mean±SD 72±7 years; 40 males). At baseline patients with FL (N=35) exhibited a higher PEEPipl than those with no FL (0.8±0.4 vs 0.3±0.2 cmH2O, P<0.01). After BD PEEPipl decreased (P=0.01) similarly in both groups (-12% vs -15%). As previously documented for PEEPies, PEEPipl was correlated with FEV1 (R=-0.597), vital capacity (R=-0.541), inspiratory capacity (R=-0.521) and residual volume (R=0.489), all P<0.01. However, PEEPipl and changes post-BD were lower than previously reported for PEEPies (2.4±1.5 cmH2O and -60%).
Conclusions: Although further implementations are necessary, the non invasive assessment of PEEPi by means of plethismography appears achievable
Acute effects of long acting bronchodilators on small airways detected in COPD patients by single breath N2 test and lung P-V curve
No full textSmall airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence, the acute effects of tiotropium (18 μg) and indacaterol (150 μg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (mean age (SD): 70±7 years; 82% males) with moderate to very severe COPD. Patients underwent body-plethysmography, arterial blood gas-analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single breath nitrogen test (SBN) and transpulmonary pressure-volume curve (PL-V), before and one hour after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the GOLD scale, and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (-5±4% and -2.5±2.1%, both P<0.001), with an increase in both slope and height of phase IV, and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3±3 mmHg and 2±2%, both P<0.001); their changes negatively correlated with those of phase III slope (r=-0.659 and r=-0.454, both P<0.01). The vital capacity (VC) increased substantially but the PL-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small airways damage and positively affect gas exchange
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