Clinical research showed that asthma control is an achievable target. However, real-life observations suggest that a significant proportion of patients suffer from symptoms and report lifestyle ...limitations with a considerable burden on patient’s quality of life. The achievement of asthma control is the result of the interaction among different variables concerning the disease pattern and patients’ and physicians’ knowledge and behaviour. The failure in asthma control can be considered as the result of the complex interaction among different variables, such as the role of guidelines diffusion and implementation, some disease-related factors (i.e., the presence of common comorbidities in asthma such as gastroesophageal reflux disease (GERD), sleep disturbances and obstructive sleep apnea (OSA), and rhinitis) or patient-related factors (i.e., adherence to treatment, alexithymia, and coping strategies). Asthma control may be reached through a tailored treatment plan taking into account the complexity of factors that contribute to achieve and maintain this objective.
Explainable Artificial Intelligence (XAI) is becoming a disruptive trend in healthcare, allowing for transparency and interpretability of autonomous decision-making. In this study, we present an ...innovative application of a rule-based classification model to identify the main causes of chronic cough-related quality of life (QoL) impairment in a cohort of asthmatic patients. The proposed approach first involves the design of a suitable symptoms questionnaire and the subsequent analyses via XAI. Specifically, feature ranking, derived from statistically validated decision rules, helped in automatically identifying the main factors influencing an impaired QoL: pharynx/larynx and upper airways when asthma is under control, and asthma itself and digestive trait when asthma is not controlled. Moreover, the obtained if-then rules identified specific thresholds on the symptoms associated to the impaired QoL. These results, by finding priorities among symptoms, may prove helpful in supporting physicians in the choice of the most adequate diagnostic/therapeutic plan.
Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of ...evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs.
The reviews of this paper are available via the supplemental material section.
Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's ...medical management.The aim of the current expert consensus report is to provide a "state-of-the-art" review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors.
Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the ...immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.
Although bronchodilators are the cornerstone in chronic obstructive pulmonary disease (COPD) therapy, the treatment with a single-agent bronchodilator may not provide adequate symptoms control in ...COPD. The combination of drugs with different mechanisms of action may be more effective in inducing bronchodilation and preventing exacerbations, with a lower risk of side-effects in comparison with the increase of the dose of a single molecule. Several studies comparing the triple therapy with the association of long-acting ß2 agonist (LABA)/inhaled corticosteroid (ICS) or long-acting muscarinic antagonist (LAMA)/LABA reported improvement of lung function and quality of life. A significant reduction in moderate/severe exacerbations has been observed with a fixed triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) in a single inhaler. The TRILOGY, TRINITY and TRIBUTE studies have provided confirming evidence for a clinical benefit of triple therapy over ICS/LABA combination treatment, LAMA monotherapy and LABA/LAMA combination, with prevention of exacerbations being a key finding. A pooled post hoc analysis of the published clinical studies involving BDP/FF/G fixed combination demonstrated a reduction in fatal events in patients treated with ICS-containing medications, with a trend of statistical significance hazard ratio = 0.72, 95% confidence interval (CI) 0.50–1.02, p = 0.066, that becomes significant if we consider reduction in fatal events for non-respiratory reasons (hazard ratio = 0.65, 95% CI 0.43–0.97, p = 0.037). In conclusion, a fixed combination of more drugs in a single inhaler can improve long-term adherence to the therapy, reducing the risk of exacerbations and hospital resources utilization. The twice a day administration may provide a better coverage of night, particularly in COPD patients who are highly symptomatic. The inhaled extrafine formulation that allows drug deposition in both large and small – peripheral – airways, is the value added.
The European Respiratory Biologics Forum gathered participants from 21 countries in Madrid, Spain, to discuss the management and treatment of severe asthma in the era of biologics. The current ...insights on the pathophysiology of severe asthma were discussed, as well as the role of respiratory biologics in clinical practice and strategies for eliminating chronic use of oral corticosteroids. The participants also highlighted the key challenges in identifying patients with severe asthma based on phenotypes, biomarkers and treatable traits, and the existing problems in patient referral to specialist care. The monitoring of treatment was debated and the need for a change towards precision medicine and personalised care was emphasised throughout the meeting. This review provides a summary of the discussions and highlights important concerns identified by the participants regarding the current management of severe asthma.
Abstract Background Conflicting findings exist on the benefit of withdrawal of inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD). We performed a quantitative synthesis in ...order to assess real impact of ICS discontinuation in COPD patients. Methods We carried out a meta-analysis via random-effects model on the available clinical evidence to evaluate the effect of ICS discontinuation in COPD. Randomized clinical trials and observational real-life studies investigating the effects of ICS withdrawal on the risk of COPD exacerbation, lung function (forced expiratory volume in 1 s FEV1 ) and quality of life (St. George's Respiratory Questionnaire SGRQ) were identified by searching from published studies and repository databases. Results ICS withdrawal did not significantly (P > 0.05) increase the overall rate of COPD exacerbation, although a clinically important increased risk of severe exacerbation was detected (Relative Risk >1.2). ICS withdrawal significantly (P < 0.001) impaired both lung function (−30 ml FEV1 ) and quality of life (+1.24 SGRQ units), although in a non-clinically important manner. The time to the first exacerbation was significantly (P < 0.05) shorter in the patients who discontinued ICS. Conclusions The discrepancy between statistical analysis and clinical interpretation of this meta-analytic evaluation demonstrates the strong clinical need in understanding what is the real impact of ICS withdrawal in COPD. ICS discontinuation is a complex procedure that requires a well planned and tailored strategy. Further well designed studies on withdrawal of ICS should be performed by clustering COPD patients with regard to the phenotype characteristics, rate of exacerbations/year, decline of lung function, and quality of life.
Despite high rates of vaccination, pertussis resurgence has been reported worldwide in recent years, including in Italy, especially in older adults.
Chronic obstructive pulmonary disease (COPD) is a ...respiratory disease associated with progressive inflammation of the respiratory tract. Regional population studies have shown the prevalence of COPD in Italy to be approximately 15% with an age-dependent increase in proportion of COPD cases.
Emerging data shows that individuals with COPD are at high risk of contracting pertussis. Furthermore, those who develop pertussis could experience exacerbation of their pre-existent COPD and further susceptibility to other infections.
Immunization programs in Italy currently recommend a decennial reduced-antigen-content diphtheria-tetanus-acellular pertussis booster vaccine dose for adults. Active measures to encourage booster vaccination, especially for high-risk adults such as those with COPD, could positively impact pertussis morbidity and the associated healthcare burden.
The interplay between different neuropsychiatric conditions, beyond dementia, in the presence of a diagnosis of cancer in older adults may mediate patients' fitness and cancer-related outcomes. Here, ...we aimed to investigate the presence of depression, sleep disturbances, anxiety, attitude, motivation, and support in older adults receiving a diagnosis of cancer and the dimension of frailty in order to understand the magnitude of the problem.
This review provides an update of the state of the art based on references from searches of PubMed between 2000 and June 2021.
The evidence obtained underscored the tight association between frailty and unfavorable clinical outcomes in older adults with cancer. Given the intrinsic correlation of neuropsychiatric disorders with frailty in the realm of cancer survivorship, the evidence showed they might have a correlation with unfavorable clinical outcomes, late-life geriatric syndromes and higher degree of frailty.
The identification of common vulnerabilities among neuropsychiatric disorders, frailty, and cancer may hold promise to unmask similar shared pathways, potentially intercepting targeted new interventions over the spectrum of cancer with the delivery of better pathways of care for older adults with cancer.
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