The American Journal of the Medical Sciences, 1999
Over the past several decades, a number of surgical techniques have been developed for the treatm... more Over the past several decades, a number of surgical techniques have been developed for the treatment of chronic obstructive pulmonary disease. Many of these procedures have been abandoned because of lack of efficacy and/or high morbidity and mortality. At the present time, lung transplantation, reduction pneumoplasty for giant bullous emphysema, and lung volume reduction sur-From the
Lipid profile alterations have been observed in patients with coronavirus disease 2019 (COVID-19)... more Lipid profile alterations have been observed in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting total, HDL, and LDL-cholesterol, and triglyceride concentrations in hospitalized patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January 2020 and January 2021, for studies describing lipid concentrations, COVID-19 severity, and survival status (PROSPERO registration number: CRD42021253401). Twenty-two studies in 10,122 COVID-19 patients were included in the meta-analysis. Pooled results showed that hospitalized patients with severe disease or non-survivor status had significantly lower total cholesterol (standardized mean difference, SMD = −0.29, 95% CI −0.41 to −0.16, p < 0.001), LDL-cholesterol (SMD = −0.30, 95% CI −0.41 to −0.18, p < 0.001), and HDL-cholesterol (SMD = −0.44, 95% CI −0.62 to −0.26, p < 0.001), but not triglyceride (SMD = 0.04, 95% CI −0.10 to −0.19, p = 0.57), concentrations compared to patients with milder disease or survivor status during follow up. Betweenstudy heterogeneity was large-to-extreme. In sensitivity analysis, the effect size of different lipid fractions was not affected when each study was in turn removed. The Begg's and Egger's t-tests did not show evidence of publication bias, except for studies investigating LDL-cholesterol. In meta-regression, significant associations were observed between the SMD of LDL-cholesterol and age and hypertension, and between the SMD of triglycerides and study endpoint and aspartate aminotransferase. In our systematic review and meta-analysis, lower total, HDL, and LDL-cholesterol, but not triglyceride, concentrations were significantly associated with COVID-19 severity and Zinellu et al. Lipids and COVID-19 mortality. Cholesterol concentrations might be useful, in combination with other clinical and demographic variables, for risk stratification and monitoring in this group. Systematic Review Registration: PROSPERO registration number: CRD42021253401.
Measure of lung dielectric proprieties in patients with idiopathic pulmonary fibrosis: Correlation with clinical, radiological and pulmonary functional parameters
International Journal of Chronic Obstructive Pulmonary Disease, Dec 1, 2016
The pathophysiology of chronic obstructive pulmonary disease (COPD) includes persistent airflow l... more The pathophysiology of chronic obstructive pulmonary disease (COPD) includes persistent airflow limitation, altered gas exchange, and enhanced chronic inflammatory response. According to disease severity in individual patients, exacerbations and comorbidities frequently occur. The overall nocturnal and daily symptoms have a strong impact on patient quality of life and clinical outcomes. Bronchodilators, by targeting two important aspects of COPD pathophysiology, ie, bronchoconstriction and lung hyperinflation, are the mainstay of therapy for COPD. Aclidinium bromide in particular is an anticholinergic molecule, approved for maintenance bronchodilator treatment of stable COPD, that combines high antimuscarinic activity with strong kinetic selectivity for the M3 receptor subtype. Moreover, the elevated plasma clearance of aclidinium has been related to low systemic bioavailability and low incidence of anticholinergic adverse events, whereas the reduced residence time at M2 receptors provides good cardiovascular safety. Altogether, these characteristics result in a high safety and tolerability profile. This review aims to reappraise the contribution of symptoms and of the level of quality of life determinants on COPD severity and to evaluate how therapeutic strategies with aclidinium may positively impact on these specific determinants of disease severity.
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterize... more Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterized by usually progressive development of airflow obstruction that is not fully reversible. While most patients will experience symptoms throughout the day or in the morning upon awakening, many patients do not experience their symptoms as constant but report variability in symptoms during the course of the day or over time. Symptom variability adversely affects patients' health status and increases the risk of COPD exacerbations. Methods: We examined data from the literature on symptom variability and control in patients with COPD, with focus on the use of inhaled bronchodilator therapy with long-acting muscarinic antagonist agents (LAMA) plus long-acting b 2-agonists (LABA); in particular twice-daily fixed-dose combination LAMA/LABA therapy with aclidinium/formoterol. Results: Correct diagnosis and assessment of COPD requires comprehensive clinical and functional evaluation and consideration of individual needs to support the clinical decisions necessary for effective long-term management. Combining bronchodilators from different and complementary pharmacological classes with distinct mechanisms of action can increase the magnitude of bronchodilation as opposed to increasing the dose of a single bronchodilator. Conclusions: The use of inhaled bronchodilator therapy with LAMA/LABA fixed-dose combinations in patients with stable COPD is supported by current evidence. This treatment approach provides robust effects on lung function and symptom control and may improve patients' adherence to treatment. Administration of the long-acting bronchodilators aclidinium and formoterol as twice daily fixed-dose aclidinium/formoterol 400/12 mg has the potential to control symptoms throughout the 24 h in patients with stable moderate-to-severe COPD.
Respiratory muscles are both cause and targ e t of respiratory failure. Some neuro-m u s c u l a ... more Respiratory muscles are both cause and targ e t of respiratory failure. Some neuro-m u s c u l a r diseases are cause of pump failure and hypoxemia even with a normal lung. On the other hand in case of chronic lung failure re s p i r atory muscles have a lower perf o rmance because of a lower oxygen feeding. Physiology and pathophysiology of muscular function can help in understanding both 1) mechanisms of "substitution" of muscular pump in case of fatigue with mechanical ventilation and 2) training of a weak muscle with rehabilitation.
Understanding whether the ABCD GOLD classification method is informative with respect to the spir... more Understanding whether the ABCD GOLD classification method is informative with respect to the spirometric classification of severity in predicting mortality of patients with chronic obstructive pulmonary disease (COPD) is subject of debate. The results of a study performed on a sample of the Norwegian population (HUNT2) were recently published. Such data showed the inferiority of ABCD classification in predicting mortality compared to the spirometric classification, which was considered the gold standard up to the 2011 version of GOLD guidelines. This result is not in line with the results of other studies that have shown the equivalence of the two classifications. The new GOLD classification seemed to be a step forward for what concerns understanding patient's needs, but it seems clear that the insertion of a single clinical variable to the spirometric data may not be exhaustive in describing all the phenomena related to a heterogeneous disease such as COPD. The publication of the HUNT study provides an opportunity to analyze how the evidence has been produced, which scientific speculations it offers, what considerations could be drawn and what further research would be appropriate.
[Fluticasone propionate in the treatment of airway inflammations (asthma and rhinitis)]
PubMed, Aug 1, 2003
Inflammation is the pathogenetic basis of many airway diseases like asthma and rhinitis. This pro... more Inflammation is the pathogenetic basis of many airway diseases like asthma and rhinitis. This provides the rationale for a therapy with antiinflammatory drugs like inhaled corticosteroids (ICS), which are able to suppress the underlying pathologic processes, ensuring an effective control of the disease and improving patients's quality of life. Within ICS, fluticasone is endowed of a potent antiinflammatory activity, due to its high affinity for the the glucocorticoid receptor (allowing the use of 50% of the dose of other ICS) and of a negligible oral bioavailability (<1%), indicating a low potential for systemic exposure. Due to its high therapeutical index, fluticasone can be used in the management of severe asthma or other airway diseases at doses devoid of relevant unwanted systemic effects. Scientific literature has broadly demonstrated its efficacy and safety, even at high doses and in the long term use.
Bronchial asthma, in adults and children, is a major health problem, with prevalence rates rangin... more Bronchial asthma, in adults and children, is a major health problem, with prevalence rates ranging from 4% to 7% in western Europe. Observational studies suggest that in Italy, like in the other countries, asthma is poorly controlled: most patients report frequent symptoms and limitation to daily activities; the utilization of healthcare resources (hospitalization, emergency room visits, unscheduled urgent care visit) is high. Recent international guidelines (GINA) for asthma management, together with an up-date by NIH, point to the primary role of inhaled corticosteroids for the control of the disease. Early interention with anti-inflammatory drugs is important, also in pre-school children with frequent or persistent symptoms, in order to prevent irreversible structural alterations of the airways and to improve long-term prognosis. In the presence of more severe asthma, inhaled corticosteroids can be associated with long-acting beta2-agonists bronchodilators. These 2 drug classes target different and complementary aspects of the pathophysiology of asthma (inflammation and bronchial obstruction) in a synergistic manner, i.e. by mutual potentiation of their pharmacological activity. Thus, combination therapy may optimize beneficial actions, allowing a more effective control of asthma.
Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of ... more Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airw... more Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, with the involvement of many inflammatory cells and mediators. Traditionally, this inflammation is thought to spread to a systemic level, thus inducing damage of different organs. However, other pathogenetic mechanisms could take part to the above-described process, and some open questions need to be solved. Due to the burden and increasing prevalence of COPD, the opportunity to find biomarkers that can potentially be useful in identifying individuals with the disease, or better, prior to symptoms onset, to diagnose and properly manage the respiratory symptoms, as well as to evaluate the response to treatment and to select specific subtypes of patients for tailored treatments is strongly advocated. Several mediators, enzymes, hormones and cells have been claimed to adhere to this objective. Moreover, the presence of comorbid or concomitant diseases can variably influence the concentration of specific biomarkers in samples of individuals with COPD, and age-related functional and structural changes (inflammaging) can further confuse the biological pattern. Several observations have been performed in the last decades; nevertheless, no biomarker is currently considered as satisfying all the above-mentioned issues. The "Evaluation of COPD longitudinally to identify predictive surrogates and points (ECLIPSE)" study has specifically explored the possibility to identify novel biomarkers that correlate with clinically relevant COPD subtypes and with markers of disease progression. Among the thirty-four biomarkers considered, 15 resulted to be increased in COPD patients rather than in smoker and non-smoker controls. Specific lung proteins such as CC-16 and SPD are promising in detecting lung damage, exacerbation susceptibility or responsiveness to treatment. The ECLIPSE findings confirm that, to date, the use of a single biomarker is not sufficient, but the combination of novel biomarkers with the already existing tools could improve our skills in optimizing treatment of COPD patients.
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