Long-Term Efficacy of Mepolizumab at 3 Years in Patients with Severe Asthma: Comparison with Clinical Trials and Super Responders.

The efficacy mepolizumab in severe asthmatic patients is proven in the literature. Primarily to study the effect of mepolizumab on exacerbations, steroid dependence, and the continuation of efficacy in the long term. Secondarily to evaluate the effect of the drug on nasal polyps. Analyzing data from SANI (Severe Asthma Network Italy) clinics, we observed severe asthmatic patients treated with mepolizumab 100 mg/4 weeks, for a period of 3 years. 157 patients were observed. Exacerbations were reduced from the first year (-84.6%) and progressively to 90 and 95% in the second and third ones. Steroid-dependent patients decreased from 54% to 21% and subsequently to 11% in the second year and 6% in the third year. Patients with concomitant nasal polyps, assessed by SNOT-22, showed a 49% reduction in value from baseline to the third year. The study demonstrated the long-term efficacy of mepolizumab in a real-life setting.

IL-13 and idiopathic pulmonary fibrosis: Possible links and new therapeutic strategies.

The recent advances in the knowledge of immunological aspects of many pulmonary diseases, allowed to identify cells, biological functions, cytokines, and receptors that are preferentially involved in each disease. This is the case of asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The role of IL-13 is strictly related, via complex signaling pathways, to eosinophil recruitment and activation, to mucus secretion, periostin generation and to fibrogenic processes (which are part of the remodeling process). These peculiar roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary Fibrosis, and consequently of its antagonists in the treatment of such disease. We review herein the immunological roles of IL-13 in asthma and IPF, and the currently ongoing attempts to treat IPF by IL-13 antagonism strategies.

CD4(+)CD25(high)CD127(-) regulatory T-cells in COPD: smoke and drugs effect.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction and its pathogenesis remains largely misunderstood. Local changes of regulatory T-cell populations in the lungs of COPD patients have been demonstrated although data concerning their pathologic role are contrasting. The aim of our study was to evaluate the relative percentage of regulatory T-cells in the peripheral blood of current and former smoker subjects, affected or not by COPD. Furthermore, the effect of different concentrations of budesonide and formoterol, on regulatory T-cells has been investigated. METHODS: T regulatory lymphocytes were isolated and assessed as CD4(+)CD25(high)CD127(-) cells by flow cytometry and cultured for 48 hours in the absence or in the presence of budesonide and/or formoterol at different doses. RESULTS: CD4(+)CD25(high)CD127(-) regulatory T-cells percentage was significantly reduced in COPD patients, both current and former smokers, with respect to volunteers. Furthermore, CD4(+)CD25(high)CD127(-) cells of COPD patients showed a not statistically significant response to drugs compared to healthy subjects. DISCUSSION: Our results evidenced a different behaviour of CD4(+)CD25(high)CD127(-) Treg cells in COPD patients after in vitro treatments. CONCLUSIONS: Based on our data, we suggested a possible role of CD4 CD25(high)CD127 T-cells in COPD pathogenesis.

Psychological aspects in asthma: do psychological factors affect asthma management?

Despite the regular treatment with inhaled corticosteroids (ICS) or ICS plus long-acting beta2-agonists, permits to control de majority of asthmatics, a significant proportion of patients does not respond to this treatment. This review was aimed to explore the role of psychological factors associated to the unsuccessful fulfilment of optimal levels of asthma control, especially in patients suffering from severe asthma. The results of a Medline search were 5510 articles addressed to different psychological key concepts, constructs and variables. This review will highlight how some selected psychological factors may have a burden on asthma management. Evidences are now available about the link between asthma (in terms of severity and control), some psychological aspects (subjective perception, alexithymia, coping style) and mental health (anxiety, depression). Taking into account this most probably bidirectional influence, a screening of mental symptoms and psychological aspects related to asthma, could lead to plan appropriate interventions to better control asthma and to improve the patient's well-being.

Chronic obstructive pulmonary disease patient well-being and its relationship with clinical and patient-reported outcomes: a real-life observational study.

BACKGROUND: Quality of life is an umbrella concept that refers to all aspects of a person's life, including health status and well-being. While health status measure focuses on the impact of the disease on physical functioning, well-being represents the self-representation of the emotional states related to the disease itself. OBJECTIVES: The objective of this study was to evaluate the psychological well-being and its determining factors in a real-life chronic obstructive pulmonary disease (COPD) population and to evaluate if patients with a different well-being differ in illness perception, health status and alexithymia. METHODS: Psychological well-being (Psychological General Well-Being Index), health status (SF-36), illness perception (Illness Perception Questionnaire), alexithymia (Toronto Alexithymia Scale), as well as clinical parameters were assessed in COPD out-patients. RESULTS: One hundred and sixty-four patients, with a mean forced expiratory volume in 1 s of 58.5%, were recruited. Forty percent of them had a moderately/severely impaired well-being, not correlated with forced expiratory volume in 1 s and the Charlson index value but significantly with the Medical Research Council score (p = 0.0001) that appeared to be the dominant factor. Patients with impaired well-being showed a different illness perception in terms of correct identification of symptoms, disease consequences, emotional representation and confidence in treatment compared with those having a positive well-being. The latter presented a lower alexithymia prevalence and a better health status. CONCLUSIONS: In order to minimize the disease-negative effects on patients' lives, assessment of well-being and its determining factors, as well as planning specific behavioural, educational and therapeutic interventions seem to be relevant and useful.

Disability in COPD and its relationship to clinical and patient-reported outcomes.

OBJECTIVE: To assess the presence of disability in chronic obstructive pulmonary disease (COPD) patients and its relationships with disease severity, comorbidities, and patient-reported outcomes. RESEARCH DESIGN AND METHOD: COPD outpatients completed validated questionnaires designed to investigate illness perception, well-being, quality of life, and stress, while physicians collected data concerning disability, dyspnea, and comorbidities (Charlson Index). RESULTS: Of 164 patients, 37.3% exhibited a degree of disability and 67.7 % of them reported the loss of at least one relevant function in daily life (mean 2.34 ± 2.41). Although disability was associated with disease severity (χ(2) = 8.292; p < 0.016), disability was present to some degree in all disease stages and in 44.9% of patients with moderate COPD. Barthel Index scores were related to MRC scores (r = 0.529; p < 0.001), GOLD stage (r = 0.223; p < 0.006), and Charlson Index (r = 0.163; p < 0.032). Disabled patients had a lower mean FEV(1) value (50.96 ± 20.99 vs. 65.00 ± 23.63; p < 0.001) than self-sufficient patients (p < 0.001). The stepwise regression analysis showed that the MRC score was the most relevant factor in inducing COPD patient disability (F = 56.5; p = 0.001). Compared to self-sufficient patients, disabled patients reported lower levels of well-being and health status, increased levels of distress, and a different illness perception. CONCLUSIONS: Disability can be identified in each disease stage, with dyspnea serving as the most relevant inducing factor. Since disability substantially impacts patient perception of and experience with COPD, its presence must be taken into account during disease management. The cross-sectional nature of the study and the characteristics of the sample size represent a limitation in the possibility to generalize the results.