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Objective: Nocturnal symptoms are common in the asthmatic population, reflecting an exaggerated airway narrowing overnight due to several factors; it is questioned to what extent the awakenings documented in the clinical assessment of asthma control are due to the disease itself or to comorbidities. To answer this question, we aimed to evaluate to what proportion rhinitis, gastroesophageal reflux and the likelihood of being affected by OSAS were related to poor asthma control, by means of ACT evaluation., Methods: Asthmatics attending the outpatient clinic were enrolled and administered the following questionnaires: ACT, Total 5 Symptom Score, GERD Impact Scale, Pittsburgh Sleep Quality Index and the Sleep Disorders Questionnaire., Results: One-hundred consecutive patients (M/F: 42/58, mean age 52 ± 15 years) were recruited. According to the ACT findings, 14 asthmatics resulted as fully controlled (FC, ACT equal to 25), 55 partially controlled (PC, 25 < ACT >19) and 31 as uncontrolled (UC, ACT <19). GERD was not associated with the ACT score neither did rhinitic symptomatology. On the other hand, the PSQI scores appeared to significantly increase with the lack of symptom control: FC, 2.0 (1-4); PC, 3.5 (2-5); UC, 6.6 (4-8) ( p  = 0.002). The SA-SDQ questionnaire results significantly increased with the loss of asthma control: FC, 11.0 (9-12); PC, 12.5 (10-14); UC, 15.1 (14-16) ( p  = 0.005)., Conclusions: These results confirm and extend previous findings showing that there is a higher likelihood that underlying unknown sleep disturbances worsen asthma control, suggesting that a more comprehensive assessment is necessary to clarify the cause of nocturnal symptoms in asthma.

Purpose: This article illustrates the replication of asthma and COPD conditions in a laboratory setting and the potential applications of this methodology., Introduction: Biologic drugs have been shown to enhance the treatment of severe asthma and COPD. Monoclonal antibodies against specific targets have dramatically changed the management of these conditions. Although the inflammatory pathways of asthma and COPD have already been clearly outlined, alternative mechanisms of action remain mostly unexplored. They could provide additional insights into these diseases and their clinical management., Aims: In vivo or in vitro models have thus been developed to test alternative hypotheses. This study describes sophisticated ex vivo models that mimic the response of human respiratory mucosa to disease triggers, aiming to narrow the gap between laboratory studies and clinical practice., Results: These models successfully replicate crucial aspects of these diseases, such as inflammatory cell presence, cytokine production, and changes in tissue structure, offering a dynamic platform for investigating disease processes and evaluating potential treatments, such as monoclonal antibodies. The proposed models have the potential to enhance personalized medicine approaches and patient-specific treatments, helping to advance the understanding and management of respiratory diseases.

Background and Objective: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function., Results: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV 1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively)., Conclusion: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Rationale: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control., Objectives: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control., Methods: In this cross-sectional study, we assessed real-world data using the MASK-air ® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma., Measurement and Main Results: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma., Conclusions: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control., (© 2024 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Introduction and Objectives: Chronic respiratory diseases are associated with an increased risk of cardiovascular diseases (CVD); however, it is unknown whether some respiratory diseases are at higher risk than others. In this perspective, head-to-head studies comparing bronchiectasis and chronic obstructive pulmonary disease (COPD) are encouraged. We explored whether the prevalence of cardiovascular risk factors (diabetes mellitus and hyperlipidemia) and cardiovascular comorbidity (systemic hypertension, ischemic heart diseases, cardiac arrhythmia, stroke) are different in these two diseases., Methods: The present retrospective case-control study aimed to compare patients with bronchiectasis with age and sex-matched individuals with COPD. A total of 63 patients with bronchiectasis and 63 with COPD were retained for analysis., Results: Patients with bronchiectasis had a lower risk of systemic hypertension (OR 0.42 (C.I. 0.20 to 0.87)) and diabetes mellitus (OR 0.28 (C.I. 0.09 to 0.81)). In contrast, ischemic heart diseases, cardiac arrhythmia, stroke, and hyperlipidemia did not differ between the two groups. Logistic regression analysis showed that age, male sex, and COPD remain independent risk factors for having at least one condition of a composite index including the above-mentioned CVD and CV risk factors. In detail, a patient with COPD has a risk of 4.648 times (C.I. 1.48 to 15.78) for having at least one CVD compared with a patient with bronchiectasis., Conclusions: The current findings suggest that subjects with bronchiectasis may experience lower cardiovascular risk than those with COPD. Larger studies are needed to confirm this preliminary observation and its clinical implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite the worldwide recommendations for influenza immunisation, vaccination coverage for patients exposed to the highest risk of severe complications is still far from the optimal target. The need to take advantage of alternative methods to provide vaccination is essential. This study presents a hospital-based strategy which offers influenza vaccination to inpatients at discharge. This study was conducted during the 2022-2023 influenza season at the University Hospital of Palermo. A questionnaire was administered to identify the determinants for the acceptance of influenza vaccination in the frail population. Overall, 248 hospitalised patients were enrolled, of which 56.1% were female and 52.0% were over 65 years of age. The proportion of patients vaccinated against influenza during hospitalisation was 62.5%, an increase of 16% in influenza vaccination uptake among frail people in comparison with the previous influenza season (46.8% vaccinated during the 2021-22 influenza season). Factors significantly associated with vaccination acceptance were the following: to have received influenza vaccine advice from hospital healthcare workers (OR = 3.57, p = 0.001), to have been previously vaccinated for influenza (OR = 3.16 p = 0.005), and to have had a low level of education (OR = 3.56, p = 0.014). This study showed that offering influenza vaccination to hospitalised patients could be an effective strategy to increase vaccination coverage in the most vulnerable population, and these findings could be useful for planning and improving future influenza vaccination campaigns.

Background: The current definition of severe eosinophilic asthma (SEA) super-responders to biologic treatment does not include patients with other eosinophil-based comorbidities. Although eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess super-responder features in real-life patients with SEA and EGPA treated with mepolizumab and benralizumab., Methods: We enrolled 39 patients with SEA and EGPA eligible for treatment with mepolizumab or benralizumab. Super-responder assessment was performed considering oral corticosteroid (OCS) cessation, lack of exacerbations, forced expiratory volume in 1 s and Asthma Control Test (ACT) improvement., Results: Super-responders showed worse clinical baseline characteristics than non-super-responder patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of super-responders was consistent only considering a 12-month course of monoclonal antibody, lacking sensitivity in earlier evaluations., Conclusion: Mepolizumab and benralizumab are safe and effective in patients with EGPA and SEA, since a consistent proportion of patients show a super-response after 12 months of treatment. Further studies will address specific criteria for super-responder assessment in these patients., Competing Interests: Conflict of interest: A. Portacci reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. Conflict of interest: N. Crimi reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Sanofi. Conflict of interest: A. Benfante reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Sanofi. Conflict of interest: M. Triggiani reports consulting fees from AstraZeneca, GlaxoSmithKline and Novartis. Conflict of interest: G. Scioscia reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Sanofi. Conflict of interest: A. Detoraki reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Sanofi, Novartis and Lofarma. Conflict of interest: G. Valenti reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline and Sanofi. Conflict of interest: N. Scichilone reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. Conflict of interest: G. Pelaia reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Chiesi, Sanofi, Guidotti, Menarini and Novartis. Conflict of interest: C. Crimi reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Sanofi, Menarini, ResMed and Fisher&Paykel. Conflict of interest: G.E. Carlagnano reports grants or contracts from AstraZeneca, Chiesi, GlaxoSmithKline, Sanofi and Grifols; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Sanofi; and support for attending meetings and/or travel from Astrazeneca, Menarini and Chiesi., (Copyright ©The authors 2023.)

Background: COVID-19 is an infectious disease caused by a Coronavirus in humans, namely SARS-CoV-2, which has quickly become a global pandemic. The infection is responsible for a severe form of pneumonia, which may lead to lung failure and death. Among the therapeutic strategies, the antiviral agent remdesivir has become one of the most used drugs. The current literature reports a causal correlation between remdesivir administration and the incidence of cardiovascular effects. We aimed to further investigate this relationship, by exploring the association between the use of remdesivir and the onset of bradyarrhythmic disorders., Methods: We reviewed medical records, blood exams and chest imaging of 85 patients with COVID-19 pneumonia (M/F: 57/28, age: 61±12 years) admitted between September 2020 and May 2021 to the Division of Respiratory Diseases in Palermo, Italy., Results: We found a significant correlation between treatment with remdesivir and the occurrence of bradycardia, lasting for at least 3 days, which returned to normal values after the discontinuation of the drug. A significant reduction in heart rate (HR) was observed in the days following remdesivir administration (L. ratio 47.4, P<0.0001) in 24 patients (HR on the first day of observation: 75±14 bpm; at discharge: 72±14 bpm). Cardiac events occurred more frequently in subjects with extensive pulmonary involvement (greater than 50% of the total parenchyma, as assessed by chest CT)., Conclusions: We suggest to carefully monitor the administration of the drug in patients with risk factors for arrhythmic or cardiovascular events.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia., Objective: To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months., Methods: We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed., Results: 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p< 0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab ( p< 0.0001), while benralizumab depleted both eosinophils ( p< 0.0001) and basophils ( p <0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients., Conclusions: These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA., Competing Interests: AP has received speaker fees from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. AB has received speaker fees from AstraZeneca, GlaxoSmithKline, and Sanofi. MT has received speaker and consultancy fees from Novartis, AstraZeneca and GlaxoSmithKline. GSc has received speaker fees from AstraZeneca, GlaxoSmithKline, and Sanofi. AD has received speaker fees from Sanofi, AstraZeneca, GlaxoSmithKline, Novartis, Lofarma. GV has received speaker fees from GlaxoSmithKline, and Sanofi. NC has received speaker and lecturer fees from AstraZeneca, GlaxoSmithKline and Sanofi. NS has received speaker fees from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. GP has received speaker and lecturer fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Guidotti, Menarini, Novartis and Sanofi. GC has received grants from AstraZeneca, GlaxoSmithKline, Chiesi, Sanofi and Grifols; has received speaker and lecturer fees from AstraZeneca, GlaxoSmithKline, and Sanofi; has received supports for attending meetings from AstraZeneca, Menarini and Chiesi. CC has received speaker fees from ResMed, Fisher&Paykel, Sanofi, AstraZeneca, GlaxoSmithKline and Menarini. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor EH declared a past co-authorship with the authors SN, RC, CP, AB, MT, GS, MC, AD, NC, NS, GP, GC and CC., (Copyright © 2023 Nolasco, Portacci, Campisi, Buonamico, Pelaia, Benfante, Triggiani, Spadaro, Caiaffa, Scioscia, Detoraki, Valenti, Papia, Tomasello, Crimi, Scichilone, Pelaia, Carpagnano and Crimi.)

Purpose of Review: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the most severe forms of asthma has been an object of discussion. Indeed, it is not clear whether asthma is among the risk factors for the occurrence of severe coronavirus disease 2019 (COVID-19) disease, or rather it plays a protective role against the worsening of the respiratory involvement in the SARS-CoV-2 infection. On the other hand, the extent to which coronavirus infection may trigger asthma attacks is still partly unknown. The current investigation aims at reviewing the available literature on the topic to address factors influencing this relationship., Recent Findings: Based on recent observations, it is likely that type 2 inflammation plays a protective role against SARS-CoV-2 infection and disease. In particular, asthmatics show different expression of angiotensin-converting enzyme2 (ACE2) and Transmembrane protease, serine 2 (TMPRSS2) that are responsible for a reduced risk of infection as well as lower risk of hospitalization. Interestingly, studies showed a safe profile of inhaled corticosteroids and biological drugs in SARS-CoV-2 infection. In addition, inhaled corticosteroid could play a protective role against worsening of asthma., Summary: The current findings suggest that current treatment for asthma should be maintained to avoid severe exacerbations. Severe asthmatics under biological treatment should continue their medications, and be encouraged to receive COVID-19 vaccines., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation., Objective: To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence., Methods: Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP., Results: Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01)., Conclusion: Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pelaia, Benfante, Busceti, Caiaffa, Campisi, Carpagnano, Crimi, D’Amato, Foschino Barbaro, Maglio, Minenna, Nolasco, Paglino, Papia, Pelaia, Portacci, Ricciardi, Scichilone, Scioscia, Triggiani, Valenti, Vatrella and Crimi.)

Introduction: Asthma is commonly considered a disease of younger ages; however, it is not infrequent to pose a diagnosis of the disease in older individuals. Although current recommendations do not distinguish between young and old asthmatics in terms of diagnostic and therapeutic approaches, asthma in the elderly may present with peculiar features that contribute to complicate its management., Areas Covered: The current review focuses on the challenges that arise when approaching an older individual with suspected asthma. Age-associated changes of the lung may complicate the diagnostic approach. Measurement of the forced expiratory volume in the first 6 s (FEV6) in an easier and faster alternative to FVC estimation, and residual volume should always be assessed. Older individuals are often affected by concomitant diseases, both age- and drug-related, that need to be considered when approaching elderly asthmatics, since they can affect the efficacy of the treatment as well as the control of the disease., Expert Opinion: The potential drug to drug interaction should be routinely investigated, and documented in medical records. The effect of aging on the response to pharmacological therapy in older asthmatics should be explored. Therefore, the need of a multidisciplinary and multidimensional approach to the elderly asthmatics is strongly encouraged.

The "Blood pressure levels, clinical features and markers of subclinical cardiovascular Damage of Asthma patients" (BADA) study is aimed at defining the cardiovascular risk profile and the markers of subclinical and clinical vascular and cardiac damage in asthmatic patients. Very few studies have assessed asthmatic patients without concomitant heart disease through a transthoracic echocardiogram. The goal of the present study is to investigate the prevalence of morphology and/or function changes in the cardiac chambers of a sample of 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP "P. Giaccone" of the University of Palermo, and the results obtained were compared with those of a control group without respiratory or cardiovascular diseases. Patients with asthma showed a marked and widespread involvement of the four cardiac chambers compared with the controls: enlargement of the two atria, greater left ventricular remodeling with interventricular septal thickening, increased indexed left ventricular mass with a significantly greater percentage of patients with overt left ventricular hypertrophy, worse left ventricular diastolic function proven by the significant difference in the E/A ratio, and worse right ventricular systolic function with global right ventricular dysfunction estimated by the Myocardial Performance Index (Tei Index). Multivariate regression analysis, after adjustment for essential hypertension, hypertension severity, diabetes, Body Mass Index, and creatinine clearance, seems to indicate that the indexed left ventricular mass, right atrial volume, and right ventricular Tei index (but not left ventricular hypertrophy) correlate significantly with asthma, severe asthma, and FEV 1 (and to a lesser extent with asthma duration). No correlation is apparent between inhaled therapy (ICS, SABA) and myocardial involvement. These results seem to confirm that a more in-depth cardiovascular evaluation in patients with chronic respiratory disease allows the identification of unrecognized cardiovascular involvement. A transthoracic echocardiogram performed in asthmatic patients without clinically overt signs or symptoms of cardiovascular impairment has identified some features indicative of an early subclinical cardiac impairment not found in the control group. These findings, considering also the higher frequency of hypertension in the asthma group, deserve further validation in the future.

MASK-air ® , a good practice of the DG Santé, has been fully validated in allergic rhinitis, but little is known about its applicability to asthmatics. We explored whether the MASK-air ® application is applicable to patients with severe asthma. Severe asthmatics were proposed to use the MASK-air ® application for 6 months, along with best practice treatment. Treatment of the patients was not changed based on the application results. The evolution of the visual analogue scales (VAS) for asthma, shortness of breath, rhinitis, conjunctivitis, work, and sleep was monitored using MASK-air ® . Adherence to MASK-air ® and to the asthma treatment was also checked. Thirteen patients reported on 1229 days of MASK-air ® use. The average application adherence was 51.8% (range: 19.7-98.9%). There was no correlation between application and medication adherence. Highly variably trends were found for the VAS for asthma. Five patients had over 90% well-controlled days, four had well- or moderately controlled asthma (with up to 20% uncontrolled days), one patient had moderately controlled asthma with approximately 20% uncontrolled days, and one patient had 80% uncontrolled days. Highly significant correlations were found for the VAS for asthma, and other patients reported VASs for work, dyspnea, sleep, and rhinitis. MASK-air ® can be used in patients with severe asthma. VAS asthma appears to be an interesting patient-reported outcome highly correlated with dyspnea and impacts on work. Adherence to the application was better than that for rhinitis, but it needs to be improved.

SARS-CoV-2 pandemic has contributed to implement telemedicine, allowing clinicians to follow the patient remotely, therefore minimizing the risk of any exposure to positive COVID-19 patients. We summarize the approaches adopted to treat and monitor severe asthmatic patients during the lockdown phase of the pandemic. Our experience supports the strategy that every effort should be made to minimize patient contact with the health-care system, planning a pathway that allows patients to receive appropriate medical care and continue the biological therapies, thus preventing the loss of disease control and acute severe exacerbations., (Copyright © 2021. Published by Elsevier Ltd.)

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.

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.

Background: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes., Objective: To identify SEA sub-phenotypes with differential responsiveness to benralizumab., Methods: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV 1 % predicted, nasal polyposis, bronchiectasis)., Results: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients)., Conclusions: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

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.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects around 60% of patients with severe eosinophilic asthma (SEA). Benralizumab was recently approved for SEA add-on treatment., Objective: To assess the real-world effectiveness of benralizumab in SEA with or without CRSwNP., Methods: We conducted a multicenter observational study, including patients with SEA treated with benralizumab for 24 weeks in 12 Italian specialized facilities. Asthma exacerbations, Asthma Control Test (ACT), lung function, oral corticosteroid (OCS) dosage, and eosinophil and basophil count in peripheral blood were recorded at baseline and after 4, 12, and 24 weeks. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Mackay scores were assessed at baseline and after 24 weeks in SEA+CRSwNP., Results: A total of 137 patients with late-onset SEA were included; 57.7% (79 of 137) showed the copresence of CRSwNP. Overall, severe asthma exacerbations decreased from 4 (3-6) to 0 (0-2) (P < .0001) after 24 weeks of treatment, and significant improvements were observed as early as 4 weeks in ACT score, OCS dosage, forced expiratory volume in the 1st second (FEV 1 )%, FEV 1 (L), forced vital capacity (FVC)%, FEV 1 /FVC% (P < .0001), and forced expiratory flow between 25% and 75% of FVC (FEF 25-75 )% (P = .0022). Eosinophils and basophils in peripheral blood were rapidly depleted. In patients with SEA+CRSwNP, SNOT-22 decreased from 46 (39.5-64.5) to 32 (19-46) (P < .0001). Furthermore, in comparison with SEA, they showed enhanced responses with regard to ACT minimal clinically important difference (P = .0387), FEV 1 % (P = .017), FEV 1 (L) (P = .02), and FEF 25-75 % (P = .0362)., Conclusions: These real-world data suggest that benralizumab can represent a valid add-on therapeutic option for patients with SEA, especially with comorbid CRSwNP., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 IOP Publishing Ltd.)

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., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Benralizumab can be utilized as add-on biological treatment of severe eosinophilic asthma. However, so far only a few real-life studies have been published with regard to the use of this anti-IL-5 receptor humanized monoclonal antibody., Objective: The primary aim of this multicenter observational investigation has been to assess the therapeutic effects of benralizumab in patients with severe uncontrolled, corticosteroid refractory eosinophilic asthma. The secondary objective was to evaluate the efficacy of benralizumab with regard to positive or negative skin prick test (SPT)., Methods: Clinical, functional, and laboratory parameters were evaluated in order to verify the therapeutic actions of benralizumab in atopic and non atopic subjects with difficult-to-treat eosinophilic asthma. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity., Results: After 6 months of add-on biological therapy with benralizumab, our 111 patients experienced a marked improvement of their severe eosinophilic asthma, expressed by significant changes in asthma exacerbation rate, prednisone intake, daily use of short-acting β 2 -adrenergic agonists (SABA), asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score (56 patients), forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), blood eosinophil count, blood basophil count (59 patients), and fractional exhaled nitric oxide (FeNO) levels (39 patients). In addition, significantly more effective outcomes were detected in patients with positive SPT, when compared to subjects with negative SPT, only in regard to asthma exacerbation number, ACT score, and daily SABA utilization. No significant correlation was found between serum IgE concentrations and each of all measured parameters., Conclusion and Clinical Relevance: Taken together, the results of this real-world study indicate that in both allergic and non-allergic subjects benralizumab can be used as a valuable pharmacotherapeutic option for add-on biological therapy of severe eosinophilic asthma, regardless of SPT positivity or negativity., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 Pelaia et al.)

Pneumonia of unknown origin in tracheostomised patient https://bit.ly/3hZHBA0., Competing Interests: Conflict of interest: C. Arena has nothing to disclose. Conflict of interest: F. Scaduto has nothing to disclose. Conflict of interest: S. Principe has nothing to disclose. Conflict of interest: A. Benfante has nothing to disclose. Conflict of interest: R. Messina has nothing to disclose. Conflict of interest: A. La Sala has nothing to disclose. Conflict of interest: L. Serafino Agrusa has nothing to disclose. Conflict of interest: A. Martorana has nothing to disclose. Conflict of interest: D. Cabibi has nothing to disclose. Conflict of interest: P. Solidoro has nothing to disclose. Conflict of interest: N. Scichilone has nothing to disclose., (Copyright ©ERS 2020.)

Background: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects., Methods: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM)., Results: The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group ( p : 0.012). Reduced level of FEV 1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension ( p : 0.0002), higher day SBP levels ( p : 0.003), higher day DBP levels ( p : 0.03), higher 24 h-SBP levels ( p : 0.005) and higher 24h-DBP levels ( p : 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29-11.1)., Conclusions: hypertension is highly prevalent in asthma; the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives.

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the "International Course on Severe Asthma" that took place in Palermo, Italy, on May 10-11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient's needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.

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.

The increase in life expectancy together with better care of rheumatoid arthritis (RA) has led to higher proportions of elderly individuals with RA. This has challenged the treatment of the disease in older aged patients, usually characterized by comorbid conditions and polypharmacy. Overall, the lung involvement in RA is present in up to 80% of patients, depending on the assessment tools used, and interstitial abnormalities are among the most common; when present, interstitial lung disease (ILD) worsens the prognosis of RA, and is the second most common cause of mortality. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis of the lung. Therefore, ILD tends to occur more frequently in older patients with RA. The age at onset of RA distinguishes patients as having young-onset RA (YORA, < 60 years) or late-onset RA (LORA, > 60 years); the latter are characterized by more severe features of the disease and higher rates of lung involvement. The most frequent RA-related ILD radiological pattern is usual interstitial pneumonia (UIP); this includes peripheral and basal predominant reticulation and honeycombing with or without associated traction bronchiectasis. Patients with the UIP pattern are usually older and have more rapid decline in lung function and a worse prognosis. Treatment with corticosteroids in elderly patients carries the risk of adverse effects, such as osteoporosis, infections, diabetes, peptic ulcers, and cataract. The use of disease-modifying antirheumatic drugs (DMARDs) is generally well-tolerated by the elderly. The current narrative review aims at elucidating the association between ILD and RA in older individuals.

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 FEV 1 , 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 FEV 1 , 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 < 0.001). Age did not significantly affect the efficacy of anti-IL-5/IL-5R mABs with respect to the change in FEV 1 (coefficient -7.15, P = 0.190); however, in high Eos subjects this improvement tended to be less evident in the more advanced age ranges (coefficient -15.18, P = 0.087). In addition, anti-IL-5/IL-5R mABs reduced ACQ score (P < 0.001 vs. placebo), SGRQ score (P < 0.001 vs. placebo), Total Asthma Symptom Score (P < 0.05 vs. placebo), and the use of oral glucocorticoids (P < 0.001 vs. placebo)., Conclusions: Age does not negatively affect the efficacy of anti-IL-5/IL-5R mABs. These findings support the use of anti-IL-5/IL-5R mABs in asthmatics of different age ranges., (© 2019 The Author(s).)

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.

Introduction: The treatment of asthma in older ages follows the recommendations of international guidelines for the management of asthma in younger ages, although older age has always represented an exclusion criterion for eligibility to pharmacological trials. This poses a clinical challenge when deciding whether elderly severe asthmatics are candidates for biological drugs., Areas Covered: The current article has a narrative structure to review the current literature on efficacy and safety of novel pharmacological drugs against immunoglobulins and interleukins that mediate and orchestrate the main inflammatory pathways in severe asthma, in order to explore whether older subjects (i.e. > 65 years of age) are included., Expert Opinion: Asthma in older ages is not a rare entity, and loss of symptom control is common in most advanced ages. Current evidence from randomized clinical trials (RCTs) on the safety of biological drugs in elderly asthmatics is scarce and does not allow drawing definitive conclusions. An urgent call for studies specifically designed for elderly populations is needed, with the purpose to assess the efficacy and safety of target biological therapies in advanced ages. We envision the design of large multi-center clinical trials to decide whether and when geriatric population could benefit from biological therapies.

Background: Asthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis. In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins. Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL. In our previous study, we found a positive correlation between forced expiratory volume 1 s (FEV 1 ) % predicted and larger LDL particles (LDL-1), and an inverse correlation between FEV 1 % predicted and sdLDL (LDL-3) in mild, untreated asthmatics. Although LDL appear to be important modulators of inflammation, data on their clinical implications are still lacking., Objective: The aim of the study is to investigate whether LDL subclasses correlate with the severity of asthma, assuming that the atherogenic and most pro-inflammatory LDL contribute to ignite and perpetuate the airway inflammatory processes., Methods: The study was conducted in one visit, and included clinical and lung functional assessments, as well as measurements of serum concentrations of the LDL subclasses. Non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL subclasses, with the LipoPrint © System (Quantimetrix Corporation, Redondo Beach, CA, USA). LDL subclasses were distributed as seven bands (LDL-1 to LDL-7), LDL-1 and -2 being defined as large LDL (least pro-inflammatory), and LDL-3 to 7 defined as sdLDL (most pro-inflammatory)., Results: 70 asthmatics under inhaled treatment (M/F: 35/35) were enrolled; 10 healthy subjects (M/F: 3/7) served as controls. In the asthmatic group, FEV 1 % predicted was 81 ± 22% (mean ± SD), vital capacity (VC) % predicted was 97 ± 18%, and FEV 1 /FVC was 0.68 ± 0.1. The mean asthma control test (ACT) score was 18 ± 5. LDL-1 were significantly lower in asthmatics as compared to controls (18 ± 4% vs. 22 ± 4%, p = 0.008). On the contrary, LDL-2 (12 ± 4% vs. 12 ± 5%) and LDL-3 (3 ± 3% vs. 2 ± 2%) were not statistically different between the two groups; smaller subclasses were undetectable. To comply with the design of the study, subjects were classified according to their degree of severity into the 5 Global Initiative for Asthma (GINA) steps: Step 1 (M/F: 4/3, 44 ± 12 yrs), Step 2 (M/F: 1/2, 37 ± 11 yrs), Step 3 (M/F: 12/7, 47 ± 12 yrs), Step 4 (M/F: 8/15, 54 ± 12 yrs), and Step 5 (M/F: 7/9, 56 ± 9 yrs). None of the LDL subclasses showed significant differences between classes of severity: LDL-1 were 16.1 ± 5.6% in Step 1, 18 ± 2.8% in Step 2, 16.7 ± 3.7% in Step 3, 18 ± 3.3% in Step 4, and 19.5 ± 3.2% in Step 5 (p = NS); LDL2 were 14 ± 3.6%, 15 ± 3.4%, 12.4 ± 5.3%, 12.7 ± 4.4% and 11.3 ± 4.2%, respectively (p = NS); LDL3 were 5 ± 5.2%, 4.4 ± 2.6%, 3.3 ± 3.6%, 3.2 ± 2.6% and 2.4 ± 1.8%, p = NS. Finally, no relationship was detected between LDL subclasses and lung function parameters as well as the ACT scores., Conclusions: The current findings confirm a role of LDL as a potential biomarker in the diagnostic process for asthma, and suggest that LDL cannot be used as marker of severity of the disease., (Copyright © 2018. Published by Elsevier Ltd.)

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 (FEV 1 ): 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 (FEV 1 ≤ or >50% predicted) or air trappers versus non air trappers (Residual Volume, RV ≥ or <120% predicted) the CASIS score remained unchanged (for FEV 1 : 37 ± 23 versus 33 ± 25, respectively, p = 0.61; for RV: 30 ± 20 versus 40 ± 23, p = 0.16). Sleep disturbances due to COPD symptoms are associated with heterogeneity of airway constriction, possibly reflecting peripheral airway dysfunction.

We tested the hypothesis that dynamic hyperinflation develops in severe asthmatic subjects during exercise. Changes in inspiratory capacity (IC) were measured during the 6-min walk test (6MWT) in severe asthmatic subjects compared with chronic obstructive pulmonary disease (COPD) subjects with a similar degree of bronchial obstruction. We assessed whether changes in IC were associated with changes in dyspnoea perception. 27 severe asthmatic subjects (10 males and 17 females) and 43 COPD subjects (35 males and eight females) were recruited. The two groups performed similarly in the 6MWT (p=0.90). At the end of the test, the Borg score increased significantly in both groups (mean difference: for asthmatic subjects 1.7±1.6; p<0.0001; for COPD subjects 3.1±1.9; p<0.0001). IC measured at the beginning of 6MWT was not different between groups (2.25±0.47 L in asthmatic subjects versus 2.38±0.60 L in COPD subjects; p=0.32) and decreased in both groups (mean difference: for asthmatic subjects 0.160 L; p=0.02; for COPD subjects 0.164 L; p<0.0001). However, changes in IC were significantly associated with changes in the Borg score in the COPD group (r 2 =0.17; p=0.006), but not in the asthma group (r 2 =0.06; p=0.20). In severe asthmatic subjects, IC significantly drops during the 6MWT to the same extent as COPD subjects with a similar degree of lung impairment, indicating the development of dynamic hyperinflation. Contrary to COPD, in asthmatic subjects the occurrence of dynamic hyperinflation was not associated with changes in dyspnoea perception., Competing Interests: Conflict of interest: None declared.

Background: Interstitial lung disease (ILD) complicates the course of systemic sclerosis (SSc), representing the main cause of death in these patients. The identification of parameters that can predict the early onset and progression of ILD in SSc represents an unmet need in clinical practice. The study was designed to explore whether the surfactant proteins (SP) A and D may be used as noninvasive tools for the early identification of ILD in SSc. Alveolar exhaled nitric oxide (NO) was investigated as a surrogate marker of distal inflammation., Methods: Unselected consecutive subjects newly diagnosed with scleroderma and subjects free of respiratory and systemic diseases were recruited. All patients underwent clinical, lung functional, radiological and biological assessments., Results: 15 individuals affected by SSc (M/F: 3/12), and 10 healthy subjects (M/F: 3/7) participated to the study. The serum SP-D values were 115.3±81.36 ng/mL in SSc subjects and 32±11.9 ng/mL in healthy controls (P=0.004). The concentrations of serum SP-A were not statistically different between groups. Serum SP-D inversely correlated with FEV1% predicted (rs=-0.29; P=0.004), FVC% predicted (rs=-0.20; P=0.02) and DLCO% predicted (rs=-0.36; P=0.001). Alveolar NO concentrations were significantly different between SSc and control subjects (6.5±2.9 ppb vs. 2.2±1.3 ppb, respectively; P=0.001), and positively associated with the levels of serum SP-D (r=0.60, P=0.03)., Conclusions: These findings suggest that, in patients with scleroderma, SP-D and exhaled alveolar NO could represent novel non-invasive markers of early detection and activity of lung involvement.

Proceedings of the European Seminars in Respiratory Medicine course, Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD, held in Taormina, Italy, on 3-4 March, 2017.

Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular morbidity and mortality. Arterial stiffness and endothelial dysfunction index are validated surrogate cardiovascular markers and are increased in subjects with COPD. We tested whether increased arterial stiffness and endothelial dysfunction occur in symptomatic smokers with no evidence of bronchial obstruction. Clinical and lung functional assessments were conducted in smoker subjects with chronic respiratory symptoms and in COPD patients. Pulse wave velocity (PWV), aortic augmentation index (AIx) and reactive hyperaemia index (RHI) were measured to estimate the cardiovascular risk. 48 smokers (male n=37, female n=11; mean age 70±8.4 years) were studied. Smokers with respiratory symptoms without bronchial obstruction (n=13) did not differ from COPD patients (n=35) in terms of mean±sd PWV (12±3.2 m·s -1 versus 14±3.8 m·s -1 ; p=0.10), aortic AIx (25.2±11.8% versus 24.8±9.7%, p=0.89) and RHI (1.66±1.49 versus 1.62±1.43; p=0.79). The current investigation shows that the cardiovascular risk occurs in smokers with respiratory symptoms in the absence of bronchial obstruction. These findings need to be confirmed in larger populations in order to inform the design of intensive preventive programmes., Competing Interests: Conflict of interest: None declared

Introduction: Asthma and COPD are under-diagnosed and undertreated in adult populations, mainly due to the discrepancy between guideline recommendations and clinicians' practices. One of the reasons of this discrepancy is the difficulty encountered in real life in sharing the management of chronic respiratory diseases between general practitioners (GPs) and respiratory physicians., Methods: An explorative, population-based investigation was performed to test whether, and to what extent, an active collaboration between GPs and pulmonologists increases the diagnosis and proper treatment of chronic obstructive airway diseases. The "COPD action" involved an in-house intervention by pulmonologists who trained GPs on how to diagnose the disease and interpret the spirometry, yielding a final agreed diagnosis., Results: A total of 210 subjects (M/F: 156/54; age: 62.5 ± 13.8, mean ± SD) were consecutively invited by 20 GPs and classified in a) healthy, b) symptomatic with no airway obstruction, and 3) affected by chronic respiratory diseases. 11% of previously defined "healthy" subjects were diagnosed with COPD, and symptomatic subjects were diagnosed with asthma (20%) or COPD (23%). In addition, in those who already carried a diagnosis of chronic respiratory diseases as judged by GPs, the diagnosis of COPD decreased significantly after respiratory specialist intervention (p = 0.001), in favor of asthma and chronic bronchitis. Furthermore, following the clinical and lung function assessments performed by the respiratory physicians, changes in inhaled treatments were statistically significant for each therapeutic category (test-retest reliability: r = 0.42; p < 0.001)., Conclusion: In conclusion, the collaboration between GPs and pulmonologists based on a pro-active approach to the individuals attending the primary care offices followed by an in-house intervention by specialists may largely improve the diagnosis and management of chronic respiratory diseases., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources., Aim: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting., Method: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society., Results: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients)., Conclusions: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Age represents an exclusion criterion in randomized clinical trials designed to test the efficacy and safety of inhaled drugs in asthma. As a consequence, data on efficacy and safety of inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combinations in elderly asthmatics are scanty. Older age is associated with an increased proportion of comorbid conditions; in addition, all organ functions undergo a process of senescence, thus reducing their ability to metabolize the agents. Overall, these age-associated conditions may variably, and often unpredictably, affect the metabolism and excretion of respiratory drugs. However, pharmacological treatment of asthma does not follow specific recommendations in the elderly. In the elderly, the ICS/LABA combinations may carry an increased risk of local indesiderable effects, primarily due to the lack of coordination between activation of the device and inhalation, and systemic adverse events, mainly due to the greater amount of active drug that is available because of the age-associated changes in organ functions as well as drug-to-drug and drug-to-concomitant disease interactions. The extra-fine formulations of ICSs/LABAs, which allow for a more favorable drug deposition in the lungs at a reduced dose, may contribute to overcome this issue. This review revises the efficacy and safety of treatment with ICSs/LABAs, focusing on the main pharmacodynamic and pharmacokinetic properties of the drugs and highlighting the potential risks in the elderly asthmatic population., Competing Interests: The authors report no conflicts of interest in this work.

Asthma in older populations is characterized by frequent comorbid conditions, which increase the risk of side effects and of detrimental interactions between respiratory and non-respiratory drugs. These observations lead to the need to manage asthma in older populations by applying a multidimensional assessment and a multidisciplinary treatment; therefore, we favor the use of the 'geriatric' term to define asthma in the elderly. Geriatric asthma is a complex disease, which may not necessarily imply that it is also complicated, although the two conditions may often coexist. On this basis, the switch from an organ-driven management to the holistic approach may be the key factor to attain optimal control of the disease in this age range. The current review discusses the age-related factors affecting asthma treatment in the oldest individuals, such as the comorbid conditions, and age-related changes of metabolism and excretion that can impair the efficacy and safety of drugs.

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that share a condition of chronic inflammation of the airways and bronchial obstruction. In clinical settings, it is not rare to come across patients who present with clinical and functional features of both diseases, posing a diagnostic dilemma. The overlap condition has been termed asthma-COPD overlap syndrome (ACOS), and mainly occurs in individuals with long-standing asthma, especially if they are also current or former smokers. Patients with ACOS have poorer health-related quality of life and a higher exacerbation rate than subjects with asthma or COPD alone. Whether ACOS is a distinct nosological entity with genetic variants or rather a condition of concomitant diseases that overlap is still a matter of debate. However, there is no doubt that extended life expectancy has increased the prevalence of asthma and COPD in older ages, and thus the probability that overlap conditions occur in clinical settings. In addition, age-associated changes of the lung create the basis for the two entities to converge on the same subject. ACOS patients may benefit from a stepwise treatment similar to that of asthma and COPD; however, the proposed therapeutic algorithms are only speculative and extrapolated from studies that are not representative of the ACOS population. Inhaled corticosteroids are the mainstay of therapy, and always in conjunction with long-acting bronchodilators. The potential heterogeneity of the overlap syndrome in terms of inflammatory features (T helper-1 vs. T helper-2 pathways) may be responsible for the different responses to treatments. The interaction between respiratory drugs and concomitant diseases should be carefully evaluated. Similarly, the effect of non-respiratory drugs, such as aspirin, statins, and β-blockers, on lung function needs to be properly assessed.

Key Points: Asthma in the elderly can be difficult to identify due to modifications of its clinical features and functional characteristics.Several comorbidities are associated with asthma in the elderly, and this association differs from that observed in younger patients.In clinical practice, physicians should treat comorbidities that are correlated with asthma (i.e. rhinitis or gastro-oesophageal reflux), assess comorbidities that may influence asthma outcomes (i.e. depression or cognitive impairment) and try to prevent comorbidities related to -'drug-associated side-effects (i.e. cataracts, arrhythmias or osteoporosis)."Geriatric asthma" should be the preferred term because it implies the comprehensive and multidimensional approach to the disease in the older populations, whereas "asthma in the elderly" is only descriptive of the occurrence of the disease in this age range., Educational Aims: To present critical issues in performing differential diagnosis of asthma in the elderly.To offer the instrument to implement the management of asthma in the most advanced ages. Asthma is a chronic airway disease that affects all ages, but does this definition also include the elderly? Traditionally, asthma has been considered a disease of younger age, but epidemiological studies and clinical experience support the concept that asthma is as prevalent in older age as it is in the young. With the ever-increasing elderly population worldwide, the detection and proper management of the disease in old age may have a great impact from the public health perspective. Whether asthma in the elderly maintains the same characteristics as in young populations is an interesting matter. The diagnostic process in older individuals with suspected asthma follows the same steps, namely a detailed history supported by clinical examination and laboratory investigations; however, it should be recognised that elderly patients may partially lose reversibility of airway obstruction. The correct interpretation of spirometric curves in the elderly should take into account the physiological changes in the respiratory system. Several factors contribute to delaying the diagnosis of asthma in the elderly, including the age-related impairment in perception of breathlessness. The management of asthma in advanced age is complicated by the comorbidities and polypharmacotherapy, which advocate for a comprehensive approach with a multidimensional assessment. It should be emphasised that older age frequently represents an exclusion criterion for eligibility in clinical trials, and current asthma medications have rarely been tested in elderly asthmatics. Ageing is associated with pharmacokinetic changes of the medications. As a consequence, absorption, distribution, metabolism and excretion of antiasthmatic medications can be variably affected. Similarly, drug-to-drug interactions may reduce the effectiveness of inhaled medications and increase the risk of side-effects. For this reason, we propose the term "geriatric asthma" be preferred to the more generic "asthma in the elderly".

Historically, asthma has been envisioned as a disease of younger ages. This has led to the assumption that respiratory symptoms suggestive of asthma occurring in older ages are to be attributed to conditions other than asthma, mainly COPD. Old observational reports and new epidemiological studies confirm that asthma is as frequent in older as it is in younger populations. Nevertheless, under-recognition, misdiagnosis and under-treatment are still relevant issues. The characterization of asthma in the aged suffers from the fact that there has been very little original research in this field. Indeed, geriatric asthma is often excluded from clinical trials because of age and comorbidities. The current review paper revises the areas that need to be elucidated, and highlights the gaps in the management of this condition. It follows that a multidimensional management is advocated for elderly asthmatics to evaluate the severity and establish the complexity of the disease. We suggest that the term "geriatric" asthma should be preferred to "senile" asthma, which is confined to the age-related changes in the lung, or the more generic "asthma in the elderly", which is only descriptive of the prevalence in specific age groups.

There is limited information on the efficacy and safety of bronchial thermoplasty (BT) in real life . We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age: 54.6 ± 2.9 years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of 3.96 ± 1.1 to 4.5 ± 1.2 and 5.5 ± 0.6 after 6 and 12 months of treatment; p = 0.0007) and in the ACQ score (from 2.77 ± 0.8 to 1.83 ± 1.2 and 1.5 ± 0.8 after 6 and 12 months; p < 0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period ( p < 0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics in real life settings.