Introduction: The relationship between asthma and obstructive sleep apnea (OSA) is a widely debated topic in the scientific literature with the controversy surrounding the bi-directional nature of the correlation.Case presentation: We report the case of a 59-year-old male being affected by severe allergic eosinophilic asthma and severe OSA (apnea-hypopnea index [AHI] 32 ev·hr-1).  Due to a clinical worsening of asthma (aggravation of dyspnea, chest constriction and night-time respiratory symptoms), despite the optimal therapy for asthma and recurrent administration of systemic corticosteroids, we have added-on treatment with benralizumab (monoclonal anti-interleukin 5 antibody). After eight months, the patient reported an improvement in asthma control (asthma control test [ACT]= 25 points), in pulmonary function and a good control of nocturnal symptoms of both diseases (i.e., wheezing, snoring, etc.). Then, the follow-up polysomnography (PSG) was performed resulting in a high reduction of OSA severity (~18% AHI) even if obstructive events persisted and almost resolution of nocturnal hypoxemia. So, a trial with positive airway pressure (PAP) was proposed to the patient, who declined.Conclusions: In consideration of our experience, we suggest that the nocturnal profile of patients with severe asthma should be always studied by a sleep investigation to prevent the negative effects of interaction with OSA. However, further studies on larger samples are needed to better understand the pathophysiological mechanisms underlying the beneficial effects of benralizumab on obstructive events during sleep.

Severe asthma patients’ life is heavily influenced by the disease, which has impact on personal and professional choices or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative “Patients insight meeting” was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient’s experience of his/her disease that need to be included in severe asthmatics’ management strategy.

To assess the presence of journal policies discouraging inappropriate author’s self-citation (A-SC) in “Respiratory System” journals, we evaluated submission guidelines of “Respiratory System” journals included in Journal-Citation Reports 2020 (Clarivate Analytics®) for presence of policies on A-SC and its impact on journals’ self-citation (J-SC) rate and impact factor (IF). We found that 14.3% of journals (n=8/56) reported policies on inappropriate A-SC. The median IF was not different in “Respiratory System” journals with (3.6; IQR:2.3) vs without A-SC policies (3.1; IQR:3.0; p=0.41). The J-SC rate was not influenced by presence of A-SC policies (p=0.83). Fully open-access (n=14) and traditional (n=42) journals had no differences in IF (3.3; IQR:1.5 vs 3.1; IQR:3.4, respectively; p=0.77) and J-SC rate (4.5%; IQR:5.6 vs 6.2%; IQR:8.4, respectively; p=0.38). The majority of “Respiratory System” journals do not have policies discouraging A-SC. The presence of such policies is not associated with changes in IF or J-SC rate.

Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. It demonstrated its efficacy in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting.Methods: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils >150 cells/ml and/or FeNO >25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV1 and ACT.Results: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 vs mean ACT post 19.17±4.45; p<0.01), so as FEV1% (mean FEV1% pre 62.58±15.73 vs mean FEV1% post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 vs median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 vs median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV1, and eight patients (67%) had a positive MCID for ACT.Conclusions: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV1, reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and lets a complete outpatient assessment. Further real-life studies with a longer follow-up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.

Greater understanding of molecular pathophysiology has led to the recognition that an excessive type 2 inflammatory response is at the basis of the pathophysiology of several inflammatory diseases including atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). Given the availability of biological agents that can permit management of specific disease endotypes, this reinforces the need for detailed characterization of these diseases through a multidisciplinary approach. Herein, these three conditions are briefly overviewed and practical guidance for a multidisciplinary approach to management is presented. Since type 2 inflammation is suppressed by steroids, drugs such as glucocorticoids have long been the workhorse of medical therapy. However, steroids have well-known local and systemic adverse effects, especially when used at high doses over prolonged periods of time, which is problematic when treating chronic diseases such as AD, asthma, and CRSwNP. Moreover, a substantial proportion of patients remain refractive to therapy. In the attempt to overcome these limitations, greater understanding of the molecular mechanisms of type 2 inflammation have led to the development of targeted biological drugs such as dupilumab, a fully human monoclonal antibody that targets the α chain of the IL-4 receptor. Dupilumab represents a unique therapy for type 2 inflammatory diseases and to date is the only therapy approved for AD, asthma, and CRSwNP. In terms of multidisciplinary management of type 2 inflammatory conditions, the main healthcare professionals involved include a dermatologist, pneumologist or allergologist, and ENT specialist. The model proposed herein takes into account the complex management of patients with type 2 inflammatory conditions and the new biological agents available. A multidisciplinary team can provide a central point for patient management, improve outcomes and specialist referrals, reduce costs, and guarantee that the most appropriate therapeutic decisions are made, as well as aid in management of adverse events. The multidisciplinary model should be structured and dedicated, but at the same time simple and flexible in order to not risk slowing down the patient's care. At present, it is believed that a structured multidisciplinary approach is currently the best means to optimize care of patients with type 2 inflammatory conditions.

Background: Chronic obstructive pulmonary disease (COPD) is a generic term identifying a condition characterized by variable changes in peripheral airways and lung parenchyma. Standard spirometry cannot discriminate the relative role of conductive airways inflammatory changes from destructive parenchymal emphysema changes. The aim of this study was to quantify the emphysema component in COPD by a simple parameter (the Emphysema Severity Index - ESI), previously proved to reflect CT-assessed emphysema.Methods: ESI was obtained by fitting the descending limb of MEFV curves by a fully automated procedure providing a 0 to 10 score of emphysema severity. ESI was computed in COPD patients enrolled in the CLIMA Study.Results: the vast majority of ESI values ranged from 0 to 4, compatible with no-to-mild/moderate emphysema component. A limited proportion of patients showed ESI values >4, compatible with severe-to-very severe emphysema. ESI values were greatly dispersed within each GOLD class indicating that GOLD classification cannot discriminate emphysema and conductive airways changes in patients with similar airflow limitation. ESI and diffusing capacity (DLCO) were significantly correlated (p<0.001). However, the great dispersion in their correlation suggests that ESI and DLCO reflect partially different anatomo-functional determinants in COPD.Conclusions: airflow limitation has heterogenous determinants in COPD. Inflammatory and destructive changes may combine in CT densitometric alterations that cannot be detected by standard spirometry. ESI computation from spirometric data helps to define the prevailing pathogenetic mechanism underlying the measured airflow limitation. ESI could be a reliable advancement to select large samples of patients in clinical or epidemiological trials, and to compare different pharmacological treatments.

Thunderstorm-triggered asthma (TA) can be defined as the occurrence of acute asthma attacks immediately following a thunderstorm during pollen seasons. Outbreaks have occurred across the world during pollen season with the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for allergicpatients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed atopic patients with IgE-mediated sentitization to pollen allergens. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen but also other pollens such as Parietaria and moulds in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which can be followed by a late inflammatory phase. There is evidence that, during pollen season, thunderstorms can induce allergic asthma outbreaks, sometimes also severe asthma crisis and sometimes deaths in patients suffering from pollen allergy. It has been observed that changes in the weather such as rain or humidity may induce hydratation of pollen grains during pollen seasons and sometimes also their fragmentation which generates atmospheric biological aerosols carrying allergens. Asthma attacks are induced for the high concentration at ground level of pollen grains which may release allergenic particles of respirable size after rupture by osmotic shock. In other words, it is a global health problem observed in several cities and areas of the world that can strike without sufficient warning, inducing sometimes severe clinical consequences also with deaths of asthma patients. Due to constant climate change, future TA events are likely to become more common, more disastrous and more unpredictable, as a consequence it is important to have deep knowledge on this topic to prevent asthma attacks. Other environmental factors, such as rapid changes in temperature and agricultural practices, also contribute to causing TA.

The aim of this study was to compare the number of the Pediatric Emergency Department (PED) visits for young allergic patients with respiratory or cutaneous symptoms during the first wave of the coronavirus disease 19 (COVID-19) pandemic in 2020 with the same period in 2019, evaluating the percentage of positive cases to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We carried out a retrospective analysis using data from young patients who visited the PED with cutaneous or respiratory symptoms in the period from 20th February to 12th May of the years 2020 and 2019. Data on allergy and COVID-19 nasal swab were also collected. We observed eleven (28.2%) PED visits for allergic patients with respiratory or cutaneous symptoms for the period from 20th February to 12th May of the year 2020 and ninety-three (31.8%) PED visits for the same time frame of the year 2019 (p=0.645). Only a two-month-old child out of 39 patients with non-allergic respiratory or cutaneous symptoms resulted positive for SARS-CoV-2. Specifically, we found for all the PED visits: 21 (7.2%) in 2019 vs 2 (5.1%) in 2020 for patients with urticaria/angioedema or atopic dermatitis (p=0.634); 3 (1.0%) in 2019 vs 3 (7.7%) in 2020 for patients with anaphylaxis (p=0.003); 19 (6.5%) in 2019 vs 2 (5.1%) in 2020 for those with asthma (p=0.740); 11(3.8%) in 2019 vs 1(2.6%) in 2020 for those with lower respiratory diseases, excluding asthma (p=0.706); 39(13.4%) in 2019 vs 3 (7.7%) in 2020 for those with upper respiratory diseases (URDs) (p=0.318). We also showed a substantial decrease (~80%) in all PED visits compared with the same time frame in 2019 (absolute number 263 vs 1211, respectively). Among all the PED visits a significant reduction was mostly found for URDs [155 (12.8%) in 2019 vs 17 (6.5%) in 2020; p=0.045)]. The total number of PED visits for allergic patients with respiratory or cutaneous symptoms dropped precipitously in 2020. It is very tricky to estimate whether it was a protective action of allergy or the fear of contagion or the lockdown or a reduction in air pollution that kept children with allergy from visiting the PED. Further studies are needed to better understand the impact of underlying allergies on COVID-19 susceptibility and disease severity.

Background: Biological drugs have been recognized as a breakthrough in the treatment of severe refractory asthma. This retrospective real-life observational study aims to evaluate the effect of add-on benralizumab on lung function, exacerbation rate, oral corticosteroids (OCS) reduction and asthma control questionnaire (ACQ) score after 52 weeks.Methods: In this observational study, a cohort of 18 patients with  severe eosinophilic asthma (SEA) according to the ERS / ATS and GINA 2020 classifications, with reference to the Pulmonology Unit of the Azienda USL - IRCCS, Reggio Emilia, Italy, were enrolled from 1 September 2019 to 31 August 2020. For each patient, the following data were collected: demographic data (age, sex, age of onset of asthma, history of smoking and atopy); comorbidity; clinical data (lung function, exacerbations, emergency room visits and hospitalizations); asthma control questionnaire (ACQ); biomarkers (blood eosinophil count and total serum IgE); asthma control drugs as high-dose inhaled corticosteroids / long-acting beta-adrenoceptor agonists (ICS / LABA), long-acting muscarinic antagonists (LAMA), leukotriene receptor antagonists (LTRA), theophylline, OCS. The benralizumab 30 mg treatment schedule was based on the currently recommended dosing regimen.Results: After end-of-treatment (EOT), a complete weaning of all patients from OCS was confirmed. After 26 weeks, the number of exacerbations decreased from 2.90 to 0.05 (p<0.0001), hospitalizations and ACQ score decreased from 3.37 to 0.97 (p<0.0001). At EOT, the number of exacerbations was unchanged, while no hospitalizations had occurred. Overall, lung function markedly improved over the study period. After 52 weeks, the increase in FEV1 from baseline was 26.8% (p=0.0002). The subset of patients with nasal polyposis (NP) had an increase of nearly 50% (1008 ml)  and patients with blood eosinophils count (BEC) greater than 500 cells/μl showed an increase of 68% (1081 ml) in FEV1 at EOT.Conclusions: The notable improvement in respiratory function is a significant result in this study and it is much higher than what has emerged to date. This result, together with the OCS sparing effect and the excellent clinical control of asthma, makes benralizumab a reliable and safe therapeutic option for SEA.

Often, in supporting patients suffering from severe respiratory diseases with mechanical ventilation, obstacles are encountered due to pulmonary and/or thoracic alterations, reductions in the ventilable lung parenchyma, increases in airway resistance, alterations in thoraco-pulmonary compliance, advanced age of the subjects. All this involves difficulties in finding the right ventilation parameters and an adequate driving pressure to guarantee sufficient ventilation. Therefrom, new mechanical ventilation techniques were sought that could help overcome the aforementioned obstacles. A new mode of mechanical ventilation is being presented, i.e., a Positive + Negative Synchronized Ventilation (PNSV), characterized by the association and integration of two pulmonary ventilators; one acting inside the chest with positive pressures and one externally with negative pressure. The peculiarity of this combination is the complete synchronization, which takes place with specific electronic modifications. The PNSV can be applied both in a completely non-invasive and invasive way and, therefore, be used both in acute care wards and in ICU. The most relevant effect found, due to the compensation of opposing pressures acting on the chest, is that, during the entire inspiratory act created by the ventilators, the pressure at the alveolar level is equal to zero even if adding together the two ventilators’ pressures; thus, the transpulmonary pressure is doubled. The application of this pressure for 1 hour on elderly patients suffering from severe acute respiratory failure, resulted in a significant improvement in blood gas analytical and clinical parameters without any side effects. An increased pulmonary recruitment, including posterior lung areas, and a reduction in spontaneous ventilatory rate have also been demonstrated with PNSV. This also paves the way to the search for the best ventilatory treatment in critically ill or ARDS patients. The compensation of intrathoracic pressures should also lead, although not yet proven, to an improvement in venous return, systolic and cardiac output. In the analysis of the study in which this method was applied, the total transpulmonary pressure delivered was the sum of the individual pressures applied by the two ventilators. However, this does not exclude the possibility of reducing the pressures of the two machines to modulate a lower but balanced total transpulmonary pressure within the chest.

Asthma is a chronic disease characterized by significant morbidities and mortality, with a large impact on socio-economic resources and a considerable burden on health-care systems. In the standard care of asthma, inhaled corticosteroids (ICS) associated with long-acting β-adrenoceptor agonists (LABA) are a reliable and often cost-effective choice, especially if based on the single inhaler therapy (SIT) strategy; however, in a subset of patients it is not possible to reach an adequate asthma control. In these cases, it is possible to resort to other pharmacologic options, including corticosteroids (OCS) or biologics. Unfortunately, OCS are associated with important side effects, whilst monoclonal antibodies (mAbs) allow excellent results, even if far more expensive. Up to now, the economic impact of asthma has not been compared with equivalent indicators in several studies. In fact, a significant heterogeneity of the cost analysis is evident in literature, for which the assessment of the real cost-effectiveness of asthma therapies is remarkably complex. To maximize the cost-effectiveness of asthma strategies, especially of biologics, attention must be paid on phenotyping and identification of predictors of response. Several studies were included, involving comparative analysis of drug treatments for asthma, comparative analysis of the costs and consequences of therapies, measurement and evaluation of direct drug costs, and the reduction of health service use. The initial research identified 389 articles, classified by titles and abstracts. A total of 311 articles were excluded as irrelevant and 78 articles were selected. Pharmacoeconomic studies on asthma therapies often report conflicting data also due to heterogeneous indicators and different populations examined. A careful evaluation of the existing literature is extremely important, because the scenario is remarkably complex, with an attempt to homogenize and interpret available data. Based on these studies, the improvement of prescriptive appropriateness and the reduction of the use of healthcare resources thanks to controller medications and to innovative therapies such as biologics partially reduce the economic burden of these treatments. A multidisciplinary stakeholder approach can also be extremely helpful in deciding between the available options and thus optimizing healthcare resources.

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by necrotizing eosinophilic granulomatous inflammation that frequently involves the respiratory tract (90% of cases). Asthma in EGPA is systematically severe and often refractory to common treatment, it is corticosteroid resistant and can often anticipate the onset of systemic vasculitis by many years. A release of cytokines necessary for the activation, maturation and survival of eosinophils, such as IL-4, IL-5 and IL-13 occurs in the activated Th-2 phenotype. In particular, IL-5 level is high in active EGPA and its inhibition has become a key therapeutic target. Oral glucocorticoids (OCS) are effective treatment options but unfortunately, frequent relapses occur in many patients and they lead to frequent side effects. As for now, there are currently no official recommendations on doses and treatment schedules in the management of EGPA.Case presentation: In this article, we describe the case of a man with EGPA, severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), with poor asthma and CRSwNP control despite OCS and mepolizumab treatment. Respiratory and vasculitis symptoms improved markedly after therapeutic switch to benralizumab. During the treatment, in addition to clinical effects, we witnessed a depletion of blood eosinophils, as well as an improvement in both pulmonary function tests, CT scan and skin lesions present initially. Conclusions: While there are many studies confirming the efficacy of benralizumab in EGPA, the most interesting aspect of our report is that efficacy was confirmed in a patient previously unresponsive to mepolizumab, known to be effective in EGPA.

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit.Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching.Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in nontreated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission.Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation.
  
 *Modena Covid-19 Working Group (MoCo19): Intensive Care Unit: Massimo Girardis, Alberto Andreotti, Emanuela Biagioni, Filippo Bondi, Stefano Busani, Giovanni Chierego, Marzia Scotti, Lucia Serio, Annamaria Ghirardini, Marco Sita, Stefano De Julis, Lara Donno, Lorenzo Dall’Ara, Fabrizio Di Salvo, Carlotta Farinelli, Laura Rinaldi, Ilaria Cavazzuti, Andrea Ghidoni, Antonio Buono, Elena Ferrari, Daniela Iseppi, Anna Maria Ardito, Irene Coloretti, Sophie Venturelli, Elena Munari, Martina Tosi, Erika Roat, Ilenia Gatto, Marco Sarti.Immuno-Lab: Andrea Cossarizza, Caterina Bellinazzi, Rebecca Borella, Sara De Biasi, Anna De Gaetano, Lucia Fidanza, Lara Gibellini, Anna Iannone, Domenico Lo Tartaro, Marco Mattioli, Milena Nasi, Annamaria Paolini, Marcello Pinti. Infectious Disease Unit: Cristina Mussini, Giovanni Guaraldi, Marianna Meschiari, Alessandro Cozzi-Lepri, Jovana Milic, Marianna Menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Vanni Borghi, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Luca Corradi. Respiratory Diseases Unit: Enrico Clini, Roberto Tonelli, Riccardo Fantini, Ivana Castaniere, Luca Tabbì, Giulia Bruzzi, Chiara Nani, Fabiana Trentacosti, Pierluigi Donatelli, Maria Rosaria Pellegrino, Linda Manicardi, Antonio Moretti, Morgana Vermi, Caterina Cerbone.Virology and Molecular Microbiology Unit: Monica Pecorari, William Gennari, Antonella Grottola, Giulia Fregni Serpini.

Background: Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes.Methods: To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). We compared this global score with the ranking of European countries in terms of death number per million persons.Results: The ranking of the AAT*air pollution global risk score matched the ranking of the countries in terms of the observed COVID-19 deaths per 1M inhabitants namely in the case of the first European countries:  Belgium, UK, Spain, Italy, Sweden, France. We observed parallelism between the number of COVID deaths and the AAT*air pollution global risk in Europe. AAT anti-protease, immune-modulating and coagulation-modulating activities may explain this finding, although very speculatively.Conclusions: Even if further studies taking into account genetic background, population density, temporal dynamics of individual epidemics, access to healthcare, social disparities and immunological response to SARS-CoV2 are needed, our preliminary observation, urges to open a discussion on gene-environment interactions in COVID-19.

Background: The performance of DPIs depends on several physiological (patient-dependent) and technological (device-dependent) factors. The inspiratory airflow rate is the only active force generated and operating in the system for inducing the required pressure drop and eliciting the resistance-induced turbulence needed to disaggregate the powder through the device. The present study aimed to investigate in the most prevalent respiratory disorders whether and at what extent the inspiratory airflow rate achievable when inhaling through a DPIs’ simulator reproducing different intrinsic resistance regimens (low, mid, and high resistance) is affected by peculiar changes in lung function and/or can be predicted by any specific lung function parameter.Methods: The inspiratory airflow rate was assessed in randomized order by the In-Check DIAL G16 at low, mid, and high resistance regimens in a sample of consecutive subjects at recruitment. Independent predictors of the probability to achieve the expected inhalation airflow rate were investigated by means of a multivariate logistic regression model, specific to the disease.Results: A total of 114 subjects were recruited (asthmatics n=30; COPD n=50, restrictive patients n=16, and normal subjects n=18). The mean values of the expected inspiratory airflow rate achieved proved significantly different within the groups (p<0.0001), independently of sex and age. In asthmatics and in COPD patients, the mid-resistance regimen proved highly associated with the highest mean values of airflow rates obtained. Low- and high-resistance regimens were significantly less likely to consent to achieve the expected level of inspiratory airflow rate (OR<1 in all comparisons). Restrictive patients performed the lowest airflow rates at the low-resistance regimen (p<0.01). Unlike FEV1, RV in asthmatics (OR=1.008); RV and IRaw in COPD (OR=0.587 and OR=0.901, respectively), and FIF and TLC in restrictive patients (OR=1.041, and OR=0.962, respectively) proved the only sensitive predictors of the inspiratory airflow rate achievable at the different resistive regimens.Conclusions: The intrinsic resistive regimen of DPIs can play a critical role.  The patients’ lung function profile also affects the extent of their inhalation airflow rate. Some specific lung function parameters (such as: FIF; RV; IRaw; TLC, but not FEV1) may be regarded as specific predictors in real-life. In order to optimize the DPI choice, further to the device’s technology, also the current patients’ lung function should be properly investigated and carefully assessed.

Dear Editor, We have carefully read the comments by Adiletta and colleagues...

We have read with interest the letter from D’Amato et al. entitled “Preventive home therapy for symptomatic patients affected by COVID-19 and followed by teleconsultations”....

In this paper we present our experience on the treatment at home of Covid+ symptomatic patients. One hundred and eighty-two subjects (111 men and 71 women) aged from 32 to 71 years have been consecutively followed at home in telemedicine from 1st September to 24th December 2020. We were informed almost twice daily in morning and evening about body temperature, symptoms (cough, shortness of breath or difficulty breathing, fatigue, muscle of body aches, headache, loss of taste or smell, sore throat, congestion or runny nose, nausea and vomiting, diarrhea), oxygen saturation measured by digital pulse oximetry and blood pressure. Our protocol of treatment was based on early use of prednisone (25 mg in the morning and 12.5 mg in the afternoon) and low molecular weight heparin (4000 UI one or two times daily) initiated just after the positivity of molecular nasopharyngeal test (about 3-4 days as mean time after initiation of symptomatology and not after 7-8 days as suggested by other protocols) and oxygen therapy when necessary. Antibiotics such as azithromycin for six days was added. It is always recommended to associate lansoprazole 30 mg to prevent gastric hemorrhages and potassium and magnesium supplements. This treatment scheme was able to reduce the risk of hospitalization as only 4 patients needed to be admitted to the Hospital, and only two in subintensive department. After negativeness of molecular nasopharyngeal test, patients were invited for a thoracic computerized tomography and laboratory evaluation of d-dimer and other data of inflammation to show eventual lung interstitial involvement characteristic of Covid-19.

Evidence-based management of bronchial asthma and wheezing in children and adults recommends the employment of inhaled corticosteroids (ICSs). Difficulty in using some inhalation devices for ICS delivery, such as pressurized metered-dose and dry-powder inhalers, is common among young children and in the elderly, and for that reason, they are replaced with nebulizers. We reviewed comparative studies that evaluated funisolide with other ICSs currently available on the market, including beclomethasone dipropionate, fluticasone propionate, and budesonide. Moreover, we assessed the physicochemical properties of these ICSs in determining drug fate in the lung. Data indicate that the flunisolide output in respirable particles by any type of pneumatic nebulizer (traditional, open breath or breath-enhanced) is superior to the output of other ICSs. This is principally attributed to the higher water solubility of flunisolide. Furthermore, in vivo simulation studies demonstrate that the intersubject variability of the inhaled dose among asthmatic children was much greater for suspensions of fluticasone propionate and beclomethasone dipropionate than for those of flunisolide. The physicochemical properties and pharmacokinetic profile of flunisolide favor its employment in nebulization.

The novel coronavirus called “Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2) caused an outbreak in December 2019, starting from the Chinese city of Wuhan, in the Hubei province, and rapidly spreading to the rest of the world. Consequently, the World Health Organization (WHO) declared that the coronavirus disease of 2019 (COVID-19) can be characterized as a pandemic. During COVID-19 several immunological alterations have been observed: in plasma of severe patients, inflammatory cytokines are at a much higher concentration (“cytokine storm”). These aspects are associated with pulmonary inflammation and parenchymal infiltrates with an extensive lung tissue damage in COVID-19 patients. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials (RCTs) for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments are currently being evaluated worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. As for ventilatory strategies, at the moment there are still no consistent data published about the different approaches and how they may influence disease progression. What will probably represent the real solution to this pandemic is the identification of a safe and effective vaccine, for which enormous efforts and investments are being put in place. This review will summarize the state-of-the-art of COVID-19 current treatment options and those potentially available in the future, as well as high flow oxygen therapy and non-invasive mechanical ventilation approaches.

The recent Coronavirus disease 19 (COVID-19) pandemic, first in China and then also in Italy, brought to the attention the problem of the saturation of Intensive Care Units (ICUs). Almost all previous reports showed that in ICU less than half of patients were treated with invasive mechanical ventilation (IMV) and the rest of them with non-invasive respiratory support. This highlighted the role of respiratory intensive care units (RICUs), where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support, avoiding ICU admission. In this report, we describe baseline characteristics and clinical outcomes of 97 patients with moderate to severe respiratory failure due to COVID-19 admitted to the RICU of the Policlinico of Bari from March 11th to May 31st 2020. In our population, most of the subjects were male (72%), non-smokers (76%), with a mean age of 69.65±14 years. Ninety-one percent of patients presented at least one comorbidity and 60% had more than two comorbidities. At admission, 40% of patients showed PaO2/FiO2 ratio between 100 and 200 and 17% showed Pa02/FiO2 ratio <100. Mean Pa02/FiO2 ratio at admission was 186.4±80. These patients were treated with non-invasive respiratory support 40% with CPAP, 38% with BPAP, 3% with HFNC, 11% with standard oxygen therapy or with IMV through tracheostomy (patients in step down from ICU, 8%). Patients discharged to general ward (GW) were 51%, 30% was transferred to ICU and 19% died. To the best of our knowledge, this is one of the few described experiences of patients with respiratory failure due to COVID-19 treated outside the ICU, in a RICU. Outcomes of our patients, characterized by several risk factors for disease progression, were satisfactory compared with other experiences regarding patients treated with non-invasive respiratory support in ICU. The strategical allocation of our RICU, between ED and ICU, might have positively influenced clinical outcomes of our patients.

Background: To date, the effects of COVID-19 pneumonia on health-related quality of life (HRQoL) and dyspnea are unknown.Methods: In a real-life observational study, 20 patients with COVID-19-related pneumonia received usual care plus erdosteine (300 mg twice daily) for 15 days after hospital discharge following local standard operating procedures. At discharge (T0) and on Day 15 (T1), participants completed the St George’s Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale of dyspnoea during daily activity, the BORG scale for dyspnoea during exertion, and Visual Analogue Scale (VAS) for dyspnoea at rest. Paired t-tests compared scores at T0 and T1.Results: The mean (SD) SGRQ total score decreased from 25.5 (15.5) at T0 to 16.9 (13.2) at T1 (p<0.01); 65% of patients achieved a clinically important change of ≥4 points. SGRQ domain scores (symptoms, activity, and impact) were also significantly reduced (all p<0.01). The mean (SD) VAS score decreased from 1.6 (1.7) to 1.4 (2.5); p<0.01. The mean mMRC score decreased significantly (p=0.031) and 30% of patients achieved a clinically important change of ≥1 point. The mean (SD) Borg score increased from 12.8 (4.2) to 14.3 (2.4); p<0.01.Conclusion: The present proof of concept study is the first to report HRQoL in patients with COVID-19. During 15 days after hospital discharge, patients reported significant improvements in HRQoL and dyspnoea at rest and during daily activities.

On behalf of the coauthors and with much regret, I must retract our publication entitled "Determinants of self-reported adherence to inhaler therapy in patients with chronic obstructive pulmonary disease", published in Multidisciplinary Respiratory Medicine 2020;15:654 DOI: https://doi.org/10.4081/mrm.2020.654
 The reason for the retraction is a complaint by MMAS Research LLC because of the breaching of the IRS Morisky Widget License.
 Prof. Caterina BuccaRetired Professor of Respiratory MedicineDept. Medical SciencesUniversity of TurinItaly

Thunderstorm asthma is a rare event: in this letter we describe two cases observed during the same month of 2018 at an Italian Emergency department, assessed by the same medical team and according to the same methodology and approach. Given the infrequency of such a phenomenon and the debate around its nature, frequency, and - at times - existence, we strongly believe it is important for all specialists who observe such cases to report them, building an evidence base to expand its knowledge and understanding.