Search

BackgroundThe use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs.Materials and methodsWe performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies.ResultsPatients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids.ConclusionA large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

Asthma is a complex, heterogeneous disease that necessitates a proper patient evaluation to decide the correct treatment and optimize disease control. The recent introduction of new target therapies for the most severe form of the disease has heralded a new era of treatment options, intending to treat and control specific molecular pathways in asthma pathophysiology. Precision medicine, using omics sciences, investigates biological and molecular mechanisms to find novel biomarkers that can be used to guide treatment selection and predict response. The identification of reliable biomarkers indicative of the pathological mechanisms in asthma is essential to unravel new potential treatment targets. In this chapter, we provide a general description of the currently available -omics techniques, focusing on their implications in asthma therapy.

Individuals with Chronic Obstructive Pulmonary Disease (COPD) experience sleep disturbances due to the impact of respiratory symptoms on sleep quality. We explored whether sleep disturbances in COPD are linked to heterogeneity of airway constriction.The impact of breathing problems on sleep quality was measured in consecutive COPD outpatients with the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Impulse oscillometry technique (IOS) was employed to assess heterogeneity of airway constriction. Subjects with a previous or concomitant diagnosis of asthma or obstructive sleep apnea (OSA) were excluded.Fifty COPD subjects (M/F 40/10; age: 71 +/- 8 yrs, Body Mass Index (BMI): 26.2 +/- 4.7 kg/m(2), Forced Expiratory Volume in the first second (FEV1): 65 +/- 25% predicted; mean +/- SD) were enrolled. The mean CASIS score was 36 +/- 3.3, and the R5-R20 value was 0.2 +/- 0.15 kPa s L-1. The CASIS score was significantly higher in subjects with increased R5-R20 (>0.07 kPa s L-1) (39 +/- 24; p = 0.02) compared to normal R5-R20 (21 +/- 17). When subjects were categorized on the basis of lung function in severely versus non severely obstructed (FEV1 50% predicted) or air trappers versus non air trappers (Residual Volume, RV >= or

Surfactant decreases the surface tension of peripheral airways and modulates the immunological responses of the lung. The alterations of surfactant due to the airway inflammation suggest a role in the pathogenesis of asthma. We aim to test the hypothesis that serum levels of SP-A (Surfactant Protein A) and SP-D (Surfactant Protein-D) are altered in patients with mild asthma compared to healthy controls and those alterations are related to functional abnormalities of peripheral airways, which are an early marker of progression of asthma. In this pilot study, we recruited 20 mild asthmatics and 10 healthy controls. We measured serum SP-A and SP-D and all subjects underwent clinical, lung functional and biological assessments. Serum SP-D was significantly higher in asthmatics compared to healthy controls (mean (SD) values: 7.9(4.65) vs 3.31(1.71) ng ml(-1), p-value: 0.008). In the asthmatic group, serum SP-D was significantly correlated to CalvNO (alveolar NO concentration) (R-squared: 0.26; p-value: 0.014). These preliminary findings suggest that serum SP-D could be used as a lung-specific biomarker of small airways damage thus predicting the progression to the most severe forms of asthma.

Background: Patients on home continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) show large variability in compliance to treatment. Aim: To identify predictors of poor compliance, we evaluated compliance to treatment in patients with obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), and OSA-chronic obstructive pulmonary disease (COPD) overlap syndrome. Methods: We analyzed clinical and compliance data provided by a single home care provider, in 602 patients (n=442 OSA, males (M) 308; 38 OHS M=15, and 122 overlap M=111) on home CPAP/NIV in the province of Agrigento, Italy, after one year of treatment. The following variables were considered: age, body mass index (BMI), sex, diagnosis, type of prescribed ventilator, and common comorbidities. Results: Mean (±SD) age and BMI were: 64.6±11.9 yrs, and 34.4±7.3 kg/m2. CPAP was prescribed in 67.1%, AutoCPAP in 12.9%, Bilevel in 9.1%, and volume assured pressure support ventilation in 10.9% of the sample. Mean compliance to treatment was 4.7±2.7 h/day, with 64.3% of the patients showing good compliance (>4 h/night). Patients overestimated CPAP/NIV use by 0.5 h/night. Compliance was not affected by age, diagnosis, severity of sleep disordered breathing, type of ventilation or occurrence of comorbidities, with the exception of depression (p=0.05). BMI was higher in poorly compliant compared to compliant patients (p=0.02). When data were split by gender, compliance was OHS>OSAS>overlap in women (p 0.007); overlap>OSAS>OHS in men (p=0.013) Conclusions: A high degree of obesity and depression were associated with poor compliance to ventilatory treatment.

Background: Individuals with COPD experience sleep disturbances due to the impact of symptoms on quality of sleep. Aim: To test the hypothesis that, in COPD, sleep disturbances are linked to peripheral airway abnormalities. Methods: An investigational study is being performed at the University of Palermo, Italy. The impact of breathing problems on quality of sleep during the previous week is measured with the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Airway resistances by impulse oscillometry (IOS) assesses peripheral airway abnormalities. Lung function evaluation includes static and dynamic lung volume measurements. To rule out the risk of having obstructive sleep apnea, the Epworth Sleepness Scale (ESS) and nocturnal oximetry is performed. Results: To date, 29 COPD subjects (M/F: 25/4, age: 72±8 yrs, BMI: 26.3±4.5 kg/m2, FEV1: 65±11% predicted; mean±SD) have been enrolled. In this interim analysis, the CASIS score was 33 (range: 0-86), and R5-R20 was 0.16±0.09 kPasL-1. Subjects with abnormal peripheral airway resistances (R5-R20>0.07 kPasL-1) had a significantly higher CASIS score than those with R5-R20≤0.07 kPasL-1 (38.9±29 vs 16.6±16, respectively; p=0.049). The CASIS score was not associated with the degree of airway obstruction (FEV1≤50% and >50% predicted: 38±30 vs. 30±27, p=0.48), or the magnitude of air trapping (residual volume >120% and ≤120% predicted: 25±25 vs 39±27, p=0.22). EES and nocturnal oximetry were within normal ranges. Conclusions: Preliminary results indicate that a relationship exists between sleep disturbances due to COPD symptoms and peripheral airway abnormalities. The final analysis will allow better description of this association.

Pulmonary surfactant is a mixture of lipids and surfactant-specific proteins that covers the alveolar surface, as well as the terminal conducting airways, lowering the surface tension at the air–liquid interface during breathing. The involvement of pulmonary surfactant in the pathophysiology of asthma has been suggested. An interesting working hypothesis is that the surface tension of the peripheral airways is altered in asthma, because the inflammatory process affects the structure and function of surfactant, leading to excessive airway narrowing and features of air trapping. We explored whether serum levels of surfactant protein D (SP-D) in asthmatics are related to the severity of the disease. In addition, we aimed to assess whether serum SP-D correlated with functional abnormalities of peripheral airways.