1,721,136 research outputs found

    Clinical Interpretation of Efficacy Outcomes in Pharmacological Studies on Triple Fixed-Dose Combination Therapy for Uncontrolled Asthma: Assessment of IRIDIUM and ARGON Studies

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    : The IRIDIUM and ARGON studies provided positive findings concerning the benefits of the once-daily triple mometasone furoate/indacaterol/glycopyrronium (MF/IND/GLY) fixed-dose combination (FDC) for the treatment of uncontrolled asthma, at the least by a strict statistical point of view. In the IRIDIUM study patients received medium-dose (MD) or high-dose (HD) MF/IND/GLY or MF/IND oncex daily or HD fluticasone/salmeterol (FLU/SAL) twice daily; in the ARGON study patients received MD or HD MF/IND/GLY once daily or HD FLU/SAL twice daily + tiotropium (TIO) once daily. Since a detailed interpretation of clinical results has not yet been performed, we provided the clinical interpretation of efficacy outcomes resulting from the IRIDIUM and ARGON studies according to the currently available minimal clinically important difference (MCID) thresholds. The triple MF/IND/GLY FDC elicited beneficial clinically relevant effects compared to active comparators in asthmatic patients, according to the levels of ICS doses, by generally achieving and overcoming the MCID. The level of clinical benefit was usually greater in patients treated with HD-MF/IND/GLY compared to those treated with MD-MF/IND/GLY. Overall, HD-MF/IND/GLY induced greater clinically relevant benefits even when compared to HD-FLU/SAL + TIO. Considering that a balanced triple MF/IND/GLY FDC with MD ICS resulted as effective as HD-MF/IND in preventing moderate or severe exacerbations, thus triple ICS/LABA/LAMA FDCs with MD ICS should be considered for the treatment not only of uncontrolled asthma but also for those patients suffering from less severe forms of disease with airflow limitation as well as a possible as-needed therapeutic option

    The interplay between diabetes mellitus and chronic obstructive pulmonary disease. An overview

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    : Chronic Obstructive Pulmonary Disease and Diabetes Mellitus are common and chronic disorders. Chronic Obstructive Pulmonary Disease is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities and it is considered currently the fourth leading cause of death worldwide. Diabetes Mellitus is a systemic disease characterized by a chronic hyperglycemia associated with inflammation and oxidative stress. The relationship between the two conditions is not completely understood and conflicting results are reported in the literature. Many studies have investigated the mechanisms through with the respiratory disease is associated with an increased risk of metabolic condition or whether the incidence risk of Chronic Obstructive Pulmonary Disease in individuals affected by Diabetes Mellitus is higher. The link between the two chronic conditions has relevant implications in the management of patients affected by the both of them. Respiratory patients should be screened for Diabetes Mellitus as a frequent comorbidity of lung disease since therapeutic options should be assessed about risk-to-benefit ratios associated with the indication for the steroid use. Furthermore, the role of hyperglycemia on pulmonary function (e.g. infection or inflammatory processes) should be evaluated in Diabetes Mellitus. Finally, in presence of both diseases potential treatment interactions should be considered. In this overview we explored the common aspects of both clinical chronic illnesses and investigated the interplay between the two conditions

    Small airways in asthma: from bench-to-bedside

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    INTRODUCTION: Historically, asthma was considered a disease predominantly of the large airways, but gradually small airways have been recognized as the major site of airflow obstruction. Small airway dysfunction (SAD) significantly contributes to the pathophysiology of asthma and it is present across all asthma severities. Promising pre-clinical findings documented enhanced beneficial effects of combination therapies on small airways compared to monocomponents, thus it was questioned whether this could translate into further clinical implications from bench-to-bedside. The aim of this review was to systematically assess the state of the art of small airway involvement in asthma, especially in response to different pharmacological treatments acting on the respiratory system.EVIDENCE ACQUISITION: A comprehensive literature search was performed in MEDLINE for randomized controlled trials (RCTs) characterizing the impact on small airways of different pharmacological treatments acting on the respiratory system. The results were extracted and reported via qualitative synthesis.EVIDENCE SYNTHESIS: Overall, 63 studies were identified from the literature search, whereas 23 RCTs met the inclusion criteria. Evidence confirms that both drug particle size and the type of inhalation devices represent two of the most important variables for an effective peripheral lung distribution.CONCLUSIONS: Despite the numerous methodological tools to detect SAD, there is still no gold standard diagnostic method to assess small airways, especially in severe asthma. Further research should be directed to improve primary and secondary prevention strategies by supporting the combined approach of different non-invasive techniques for an early detection of peripheral abnormalities and optimization of asthma therapy

    Expert guidance on the management and challenges of long-COVID syndrome: a systematic review

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    Introduction: Long-COVID is a condition characterized by the permanence of symptoms beyond 4 weeks after an initial infection. It affects 1 out of 5 people and is loosely related to the severity of acute infection and pathological mechanisms, which are yet to be understood. Areas covered: This article looks at currently available and under-studied therapies for long-COVID syndrome. It particularly gives focus to ongoing trials and reviews the underlying mechanisms. A comprehensive literature search was performed on PubMed and clincaltrial.gov of clinical trials concerning the management of long-COVID syndrome. Expert opinion: 'Long-COVID' syndrome is a new emergency characterized by several symptoms such as fatigue, dyspnea, cognitive and attention disorders, sleep disorders, post-traumatic stress disorder, muscle pain, and concentration problems. Despite the many guidelines available to date, there are no established treatments of long-COVID. Pharmacological research is studying known drugs that act on the reduction or modulation of systemic inflammation, or innovative drugs used in similar pathologies. Rehabilitation now seems to be the safest treatment to offer, whereas we will have to wait for the pharmacological research trials in progress as well as plan new trials based on a better understanding of the pathogenic mechanisms

    Potential Drawbacks of ICS/LABA/LAMA Triple Fixed-Dose Combination Therapy in the Treatment of Asthma: A Quantitative Synthesis of Safety Profile

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    INTRODUCTION: Inhaled corticosteroid/long-acting β(2)-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) fixed-dose combination (FDC) is currently recommended as controller option at asthma Step 4 and as preferred treatment at asthma Step 5, but no research investigated the potential drawbacks of this therapeutic option in a large asthmatic population. Thus, the aim of this study was to quantify the potential drawbacks of triple FDC therapy in asthma. METHODS: A pairwise meta-analysis was performed according to PRISMA-P guidelines to assess the risk of overall serious adverse events (SAEs), cardiovascular SAEs, and pneumonia reported as SAE in asthmatic patients treated with ICS/LABA/LAMA FDC vs ICS/LABA FDC. A pooled analysis was performed to calculate the frequency of SAEs. RESULTS: Data from 7204 asthmatic patients were extracted from the CAPTAIN, IRIDIUM, TRIMARAN, and TRIGGER studies. Triple FDC vs ICS/LABA FDC did not increase the risk of total SAEs (RR 0.99 95% CI 0.83–1.18) and cardiac SAEs (RR 0.74 95% CI 0.39–1.40), whereas the sensitivity analysis performed to resolve heterogeneity resulted in increased risk of vascular SAEs (RR 3.23 95% CI 1.05–9.90, P<0.05). The level of ICS dose did not modulate the risk of pneumonia, in any case pneumonia was the most frequent SAE (0.57%). These results were not affected by significant risk of bias. CONCLUSION: Triple FDC is a safe pharmacological therapy in severe asthmatic patients; it is characterized by a favourable safety profile and few potential drawbacks, namely, the increased risk of vascular SAEs, that certainly are worthy of future investigations
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