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BackgroundEffectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for 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.

Objective: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. Methods: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. Results: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. Conclusions: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.

COVID-19 modified the healthcare system. Nasal-pharyngeal swab (NPS), with real-time reverse transcriptase-polymerase (PCR), is the gold standard for the diagnosis; however, there are difficulties related to the procedure that may postpone it. The study aims to evaluate whether other elements than the PCR-NPS are reliable and confirm the diagnosis of COVID-19. This is a cross-sectional study on data from the Lung Unit of Pavia (confirmed) and at the Emergency Unit of Palermo (suspected). COVID-19 was confirmed by positive NPS, suspected tested negative. We compared clinical, laboratory and radiological variables and performed Logistic regression to estimate which variables increased the risk of COVID-19. The derived ROC-AUCcurve, assessed the accuracy of the model to distinguish between COVID-19 suspected and confirmed. We selected 50 confirmed and 103 suspected cases. High Reactive C-Protein (OR: 1.02; CI95%: 0.11–1.02), suggestive CT-images (OR: 11.43; CI95%: 3.01–43.3), dyspnea (OR: 10.48; CI95%: 2.08–52.7) and respiratory failure (OR: 5.84; CI95%: 1.73–19.75) increased the risk of COVID-19, whereas pleural effusion decreased the risk (OR: 0.15; CI95%: 0.04–0.63). ROC confirmed the discriminative role of these variables between suspected and confirmed COVID-19 (AUC 0.91). Clinical, laboratory and imaging features predict the diagnosis of COVID-19, independently from the NPS result.

Severe asthma is a heterogeneous disease with different phenotypes based on clinical, functional or inflammatory parameters. In particular, the eosinophilic phenotype is associated with type 2 inflammation and increased levels of interleukin (IL)‐4, IL‐5 and IL‐13). Monoclonal antibodies that target the eosinophilic inflammatory pathways (IL‐5R and IL‐5), namely mepolizumab, reslizumab, and benralizumab, are effective and safe for severe eosinophilic asthma. Eosinophils threshold represents the most indicative biomarker for response to treatment with all three monoclonal antibodies. Improvement in asthma symptoms scores, lung function, the number of exacerbations, history of late‐onset asthma, chronic rhinosinusitis with nasal polyposis, low oral corticosteroids use and low body mass index represent predictive clinical markers of response. Novel Omics studies are emerging with proteomics data and exhaled breath analyses. These may prove useful as biomarkers of response and non‐response biologics. Moreover, future biomarker studies need to be undertaken in paediatric patients affected by severe asthma. The choice of appropriate biologic therapy for severe asthma remains challenging. The importance of finding biomarkers that can predict response continuous an open issue that needs to be further explored. This review describes the clinical effects of targeting the IL‐5 pathway in severe asthma in adult and paediatric patients, focusing on predictors of response and non‐response.

Background The SARS-CoV-2 pandemic has changed the health-care systems around the world in a remarkable way. We describe the strategies adopted to cope with the limitations imposed by the pandemic to the access to health care by patients diagnosed with idiopathic Pulmonary Fibrosis (IPF). Material and methods We conducted a retrospective observational analysis including IPF patients under antifibrotic drugs (nintedanib and pirfenidone) that accessed to the Outpatient clinic of the University of Palermo, Italy. Patients received a phone number and an email address in case of any urgency and a virtual meeting was settled up monthly. Results 40 patients (M/F: 30/10) were followed up, 33 under nintedanib treatment, 7 under pirfenidone . Among patients under nintedanib, 1 patient reported high fever (T max 39 °C) and purulent sputum with no sign of infections, 1 had hemoptysis that was spontaneously resolved. 2 patients accessed to the emergency department for the worsening of dyspnea; 5 patients had diarrhea that resolved with symptomatic drugs in few days. 3 patients had an increase of alkaline phosphatase levels, leading to the withdrawal of the antifibrotic drug for 15 days, and subsequent normalization of the plasmatic levels. Among patients under pirfenidone, one subject had an increase of ferritin serum levels with no symptoms. The remaining subjects were in stable clinical conditions. None of the patients reported hospitalization or exacerbations, and did not experience antifibrotic withdrawal. Conclusions We were able to demonstrate that by implementing alternative ways to monitor the disease, patients did not incur in increased rates of acute exacerbations or higher frequency of side effects and antifibrotic treatment withdrawal.

Breath analysis using eNose technology can be used to discriminate between asthma and COPD patients, but it remains unclear whether results are influenced by smoking status. We aim to study whether eNose can discriminate between ever- vs. never-smokers and smoking &lt, 24 vs. &gt, 24 h before the exhaled breath, and if smoking can be considered a confounder that influences eNose results. We performed a cross-sectional analysis in adults with asthma or chronic obstructive pulmonary disease (COPD), and healthy controls. Ever-smokers were defined as patients with current or past smoking habits. eNose measurements were performed by using the SpiroNose. The principal component (PC) described the eNose signals, and linear discriminant analysis determined if PCs classified ever-smokers vs. never-smokers and smoking &lt, 24 h. The area under the receiver–operator characteristic curve (AUC) assessed the accuracy of the models. We selected 593 ever-smokers (167 smoked &lt, 24 h before measurement) and 303 never-smokers and measured the exhaled breath profiles of discriminated ever- and never-smokers (AUC: 0.74, 95% CI: 0.66–0.81), and no cigarette consumption &lt, 24h (AUC 0.54, 95% CI: 0.43–0.65). In healthy controls, the eNose did not discriminate between ever or never-smokers (AUC 0.54, 95% CI: 0.49–0.60) and recent cigarette consumption (AUC 0.60, 95% CI: 0.50–0.69). The eNose could distinguish between ever and never-smokers in asthma and COPD patients, but not recent smokers. Recent smoking is not a confounding factor of eNose breath profiles.

The spread of the SARS-CoV-2 infection among population has imposed a re-organization of healthcare services, aiming at stratifying patients and dedicating specific areas where patients with suspected COVID-related respiratory disease could receive the necessary health care assistance while waiting for the confirmation of the diagnosis of COVID-19 disease. In this scenario, the pathway defined as a “grey zone” is strongly advocated. We describe the application of rules and pathways in a regional context with low diffusion of the infection among the general population in the attempt to provide the best care to respiratory patients with suspected COVID-19. To date, this process has avoided the worst-case scenario of intra-hospital epidemic outbreak.

Objective: Management of asthma includes monitoring of inhaler technique and level of adherence to treatment. Both factors could be influenced by high frequency of switching inhaler devices. We explored whether switching inhalers is an independent predictive factor of exacerbations. Methods: Data were collected from 2015 to 2017 from the outpatient clinic of asthma at the University of Palermo, Italy. This observational study consisted of two phases: Phase 1 included subjects of at least three visits in the previous year who reported the frequency of inhalers switched; Phase 2 included subjects of at least two visits during the second year, and the rate of switches and exacerbations was recorded. We included adult (24–84 years old) mild/moderate asthmatics under regular inhaled treatment; uncontrolled asthma was defined as poor symptom control, exacerbations (≥2/year) requiring oral corticosteroids (OCS), or serious exacerbations (≥1/year) requiring hospitalization. Results: A total of 109 records were retrieved for the analysis. A significant correlation between the rate of switches in Phase 1 and exacerbations in Phase 2 was found (p = 0.001). Age and the rates of exacerbations in Phase 1 were also independently associated with a higher number of exacerbations in Phase 2 (p < 0.0001). The multivariate regression model showed that the numbers of switches, as well as exacerbations in Phase 1, were independently correlated to the number of exacerbations in Phase 2 (p = 0.003). Conclusions: The frequency of switching inhalers independently affects the risk of exacerbations in asthma. These results imply that changing inhaler requires careful management in clinical practice.

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.

Urinary incontinence (UI) is defined as a loss of bladder control and is characterized by the complaint of any involuntary leakage of urine. Evidence suggests that the prevalence of UI is higher in subjects with chronic obstructive pulmonary disease (COPD) than in age-matched controls in both sexes. UI is classified as stress, urge, and mixed, and has a considerable impact on quality of life. However, the prevalence of UI in individuals with COPD is mostly unexplored in clinical research and often underestimated in clinical practice. Interestingly, although the involuntary leakage of a small amount of urine during coughing (e.g., stress UI) is among the most plausible causes of UI in patients with COPD, its importance has been questioned by some researchers. Moreover, UI as a respiratory drug-related adverse effect is largely overlooked; only a few randomized controlled trials have reported the presence of urinary symptoms, mainly as urinary retention due to anticholinergic agents. In this narrative review, we explored whether, and to what extent, UI occurs in COPD individuals, and what the proposed actions to improve this condition are. We found that the association between UI and COPD is largely unexplored, mostly because UI tends to be attributed to older age. We infer that the prevalence of UI in individuals with chronic respiratory symptoms is often underestimated in clinical practice. The misinterpretation of urinary symptoms as related to the respiratory condition can delay diagnostic and therapeutic approaches. The use of simple self-administered questionnaires to assess the presence of UI is encouraged.

Background: Healthcare decisions made on the basis of insufficient evidence may potentially have ineffective or even harmful consequences. The proportion of older ages (over 65 years) in randomized controlled trials (RCTs) for severe asthma is not enough to establish whether anti-IL-5/IL-5R therapies are equally effective in the elderly as in younger subjects. Methods: In order to assess the relationship between age and the efficacy of anti-IL-5 monoclonal antibodies (mABs) with respect to the risk of exacerbations and changes in FEV1, a meta-regression analysis via random-effect method was carried out by plotting the effect estimates (outcome variables) resulting from the pairwise meta-analysis with the age of asthmatic subjects (explanatory variable). A comprehensive literature search was performed for pivotal RCTs on the effects of anti-IL-5/IL-5R in severe asthma, with the following keywords: “asthma and mepolizumab”, “asthma and reslizumab” and “asthma and benralizumab”. The study was restricted to “clinical trials”, “age over 65” and “humans”. Data were checked for age, exacerbation rates, changes from baseline in FEV1, and blood eosinophil (Eos) count. Secondary outcomes included inhaled and oral medication use, clinical scores and quality of life. Results: A total of 10 studies were analysed. Age did not modulate the efficacy of anti-IL-5/IL-5R treatment against the risk of exacerbation neither in the overall population (coefficient −0.007, P = 0.89), nor in patients with high blood Eos count (coefficient 0.075, P = 0.30). The blood Eos level drove the efficacy of anti-IL-5/IL-5R mABs against the risk of exacerbation regardless of age (coefficient −0.27, P

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.