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Roberta Pisi,1 Marina Aiello,1 Annalisa Frizzelli,1 Luigino Calzetta,1 Laura Marchi,1 Giuseppina Bertorelli,1 Giovanna Pisi,2 Alfredo Chetta1 1Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy; 2Department of Pediatrics, Cystic Fibrosis Center, University Hospital, Parma, ItalyCorrespondence: Luigino CalzettaDepartment of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Viale A. Gramsci, 14, Parma, 43126, ItalyEmail luigino.calzetta@unipr.itPurpose: Smoking-induced bronchiolitis with progressive small airway dysfunction (SAD) is a leading cause of chronic obstructive pulmonary disease. We investigated the value of using the impulse oscillometry system (IOS) to detect SAD in asymptomatic smokers with preserved spirometry.Patients and Methods: We included 75 asymptomatic smokers (37 females, mean age 47± 12 years, 26± 17 pack/year) with preserved spirometry [forced expiratory volume at 1st second (FEV1)/forced vital capacity (FVC) ≥ 0.70 and normal FVC] and 34 never-smokers (19 females, mean age 42± 15 years).Results: In smokers, pack/years were significantly related to spirometry and IOS parameters (p < 0.05). The values of the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were significantly and inversely related to the values of the ratio of forced expiratory volume in 3 and in 6 seconds (FEV3/FEV6) (p < 0.05). In addition, the percentage of heavy smokers (≥ 30 pack/year) with R5 – R20 > 0.07 kPa·s·L− 1, considered as IOS index of SAD, but not with FEV3/FEV6 less than a lower limit of normal, a spirometry index of SAD, was significantly higher than that of mild smokers (< 30 pack/year) and never-smokers (p < 0.05).Conclusion: This study demonstrates that IOS has the potential to detect SAD in asymptomatic heavy smokers with preserved spirometry and with FEV3/FEV6 values in the normal range. We confirm that IOS provides parameters which can complement traditional measurements of pulmonary function.Keywords: small airway dysfunction, impulse oscillometry system, spirometry, smokers, COPD

This study aims to analyze how the Technology Acceptance Model which consists of Percieved usefulness, Perceived Ease of use, Privacy and Security, and additional variable "Promotion Programs" affect behavior intention in using e-wallets or digital wallets in the current pandemic era. A total of 394 respondents aged 16-30 years old who use e-wallets in Yogyakarta were sampled in this study. The results using the SEM test show that perceived usefulness and behavioral intention have a significant effect. Meanwhile, Perceived Ease of use, Privacy and Security, and promotional programs are not significant on E-Wallets Usage.

Asthma is a very heterogeneous disease and since early childhood many classifications have been proposed according to phenotype and endotype. The phenotype includes the clinical features of asthma such as age of onset, triggers, comorbidities, response to treatment and evolution over time. The endotype is more difficult to define, includes the underlying immunopathological mechanisms of the disease and requires reliable biomarkers. A deep knowledge of phenotype and endotype of the patient may guide a tailored therapeutic approach. In this review the main phenotypes and endotypes of asthma acknowledged in children will be discussed.

Background: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. Objectives: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. Method: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. Results: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. Conclusions: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

Zygomatic implant rehabilitation is a challenging procedure that requires an accurate prosthetic and implant plan. The aim of this study was to evaluate the malar bone available for three-dimensional zygomatic implant placement on the possible trajectories exhibiting optimal occlusal emergence. After a preliminary analysis on 30 computed tomography (CT) scans of dentate patients to identify the ideal implant emergencies, we used 80 CT scans of edentulous patients to create two sagittal planes representing the possible trajectories of the anterior and posterior zygomatic implants. These planes were rotated clockwise on the ideal emergence points and three different hypothetical implant trajectories per zygoma were drawn for each slice. Then, the engageable malar bone and intra- and extra-sinus paths were measured. It was possible to identify the ideal implant emergences via anatomical landmarks with a high predictability. Significant differences were evident between males and females, between implants featuring anterior and those featuring posterior emergences, and between the different trajectories. The use of internal trajectories provided better bone engagement but required a higher intra-sinus path. A significant association was found between higher intra-sinus paths and lower crestal bone heights.

Knowledge on multiple interdependences between quality of life (QoL) and behavioural problems in relation to asthma severity and control is undetermined. The aims of the study were: (i) to assess the relationship of QoL and behavioural problems with asthma severity and control (ii) to predict children’s “abnormal/borderline” status with variation in QoL. For these purposes a multicenter case-control study on 47 Severe Asthma (SA) and 94 Moderate Asthma (MA) children was performed. The MIMIC approach was applied to investigate the effect of SA and non-controlled asthma (NC) on QoL and behavioural disorders. Logistic regression was used to estimate probabilities of having an “abnormal/borderline” status with variation in QoL. The MIMIC model showed that the magnitude of the effect of SA and NC was larger on QoL (β = −0.37 and β = −0.30, respectively) than on behavioural problems (β = 0.27). With regards to the probability of having a borderline status, in MA a QoL of 1 returned a probability of 0.81, whereas in SA a QoL of 1 returned a probability of 0.89. In conclusion, SA children are highly affected by impaired QoL and behavioural problems. The MIMIC model allowed us to obtain a comprehensive assessment of QoL and behavioural problems with asthma severity and control.

The purpose of this work was to study a new dry powder inhaler (DPI) of tobramycin capable to simplify the dose administration maneuvers to maximize the cystic fibrosis (CF) patient care in antibiotic inhalation therapy. For the purpose, tobramycin/sodium stearate powder (TobraPS) having a high drug content, was produced by spray drying, characterized and the aerodynamic behavior was investigated in vitro using different RS01 DPI inhalers. The aerosols produced with 28, 56 or 112 mg of tobramycin in TobraPS powder using capsules size #3, #2 or #0 showed that there was quasi linear relationship between the amount loaded in the device and the FPD. An in vivo study in healthy human volunteers showed that 3–6 inhalation acts were requested by the volunteers to inhale 120 mg of TobraPS powder loaded in a size #0 capsule aerosolized with a prototype RS01 device, according to their capability to inhale. The amount of powder emitted at 4 kPa pressure drop at constant air flow well correlated with the in vivo emission at dynamic flow, when the same volume of air passed through the device. The novel approach for the administration of 112 mg of tobramycin in one capsule could improve the convenience and adherence of the CF patient to the antibiotic therapy.

The problem of climate change is increasingly global and results in environmental damage due to the use of fossil energy in human activities. An increasing population will make energy consumption increase and can make things worse. Therefore, it is necessary to replace old energy with alternative energy that is more environmentally friendly and makes productivity effective and efficient. Renewable energy is pointed out as an alternative energy source that is environmentally friendly and the process is sustainable because it is always available in nature. Renewable energy is expected to increase the country's national income. This study aims to analyze the impact of renewable energy on economic growth in the Asia Pacific region as a whole. By using data from 2000-2015, panel data analysis in this study shows that Renewable Energy Consumption (REC) has a negative and significant relationship to economic growth, while renewable energy and combustible waste (CRW) has a significant and positive effect on economic growth.

The current work deals with multi-objective optimisations including financial merit factors in the multi- disciplinary conceptual design of a commercial aircraft with a specific focus on noise social cost. The results of optimisations using financial and performance-oriented objective functions have been analysed and combined in a multi-objective optimisation problem using a three-dimensional objective vector. The main novelty of the present work is the analysis of social cost noise fees effectiveness integrated in financial models embracing a wider group of stakeholders’ interests. The foundations of this research lie on the air traffic increase envisaged in the next decades and the contextual growth of the urban areas nearby airport facilities. This scenario requires the aeronautical industry to handle the environment challenge taking into account all the social and economic effects. Indeed, the consolidated technology has approached a saturation point, therefore breakthrough concepts and configurations are mandatory. This matter is addressed as a highly multi-disciplinary problem within conceptual design framework. The financial model proposed is shown to highlight the need of appropriate noise fees as instruments to push all stakeholders towards a technology radical renewal and encourage the aeronautical industry towards a shared strategy in the development of an eco-friendly commercial aviation system.

Introduction In the last decades, the large use of several effective vaccines has dramatically reduced the incidence of community acquired pneumonia (CAP) in infants and children. Moreover, the availability of new antibiotics effective against emerging resistant strains of bacteria has greatly improved the early and long-term prognosis of this disease. Areas covered The aim of this manuscript is to evaluate the burden of complicated CAP in pediatric age and to discuss its appropriate management. Expert opinion Complicated CAP remains a problem for children in industrialized and developing countries. A larger use of lung ultrasonography (US) as first diagnostic approach could significantly improve early identification of cases at higher risk of complications. Difficult to solve, is the problem of the use of an antibiotic therapy able to assure adequate control in all the CAP cases, including those at high risk of or with already established complications. All these findings reveal that control of the incidence of complicated CAP remains difficult and will not be significantly changed in the next few years. Any attempt to improve complicated CAP management must be made. Consensus documents on better definition of the use of corticosteroids, fibrinolytic agents and interventional procedures (including surgery) can allow us to reach this goal.

Background: The presence of interstitial pneumonia in coronavirus disease 2019 (COVID-19) patients, as diagnosed through laboratory, functional, and radiological data, provides potential predicting factors of pulmonary sequelae. Objectives: The objectives were the creation of a risk assessment score for pulmonary sequelae at high-resolution computed tomography (HRCT) through the assessment of laboratory data, lung function, and radiological changes in patients after the onset of COVID-19 interstitial pneumonia and the identification of predictive factors. Methods: We enrolled 121 subjects hospitalized due to COVID-19 pneumonia in our study. Clinical features, Charlson Comorbidity Index (CCI) score, HRCT score, and blood chemistry data at hospital admission, as well as HRCT score, pulmonary function testing values, exercise capacity by means of a 6-Minute Walk Test (6MWT), and dyspnea perception by the modified Medical Research Council (mMRC) at 4-month follow-up, were all recorded. The variables were elaborated in order to create a predictive model to identify patients at high risk of pulmonary sequelae at HRCT. Results: At the time of follow-up visit, 63% of patients had functional abnormality (diffusion lung capacity and/or total lung capacity 10%) at follow-up. The most revelatory COSeSco value that was found to intercept the highest sensitivity (100%) and specificity (77%) was 2. Conclusion: The COSeSco – comprising age, BMI, comorbidities, D-dimer, walking distance, and dyspnea perception – makes it possible to identify particularly at-risk COVID-19 patients who are likely to develop pulmonary sequelae assessed by HRCT.

Introduction In patients with chronic obstructive pulmonary disease (COPD), small airway dysfunction (SAD) is a key element and a functional consequence of the pathology. The exact role of SAD as a specific ‘pharmacological target’ represents an important research topic. Our objective was to ascertain whether an extra-fine formulation of beclomethasone dipropionate/formoterol fumarate (BDP/FF) NEXThaler® 100/6 μg b.i.d. could improve SAD and, consequently, the quality of life of COPD patients. Methods We enrolled COPD patients with severe airflow obstruction and at least one moderate exacerbation in the previous year, having started treatment with BDP/FF NEXThaler® for no more than 1 week. Patients underwent three visits: at the start of the treatment (V1), 6 weeks (V2), and 12 weeks later (V3). At each visit, we evaluated the fall in resistance from 5 to 20 Hz (R5–R20) and residual volume/total lung capacity (RV/TLC) ratio by impulse oscillometry, spirometry, and plethysmography. The COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also administered to assess the disease’s impact on quality of life. Results We enrolled 43 COPD patients (mean age 69 years, FEV1 43%). R5–R20 significantly changed from baseline [0.23 ± 0.09 kPa/(l/s)] to V2 [0.16 ± 0.09 kPa/(l/s)] and V3 [0.16 ± 0.08 kPa/(l/s)] (p

Bronchiolitis (BR), a lower respiratory tract infection mainly caused by respiratory syncytial virus (RSV), can be very severe. Presently, adequate nutritional support and oxygen therapy remain the only interventions recommended to treat patients with BR. For years, mild BR cases were treated with noninvasive standard oxygen therapy (SOT), i.e., with cold and poorly or totally non-humidified oxygen delivered by an ambient headbox or low-flow nasal cannula. Children with severe disease were intubated and treated with invasive mechanical ventilation (IMV). To improve SOT and overcome the disadvantages of IMV, new measures of noninvasive and more efficient oxygen administration have been studied. Bi-level positive air way pressure (BiPAP), continuous positive airway pressure (CPAP), and high-flow nasal cannula (HFNC) are among them. For its simplicity, good tolerability and safety, and the good results reported in clinical studies, HFNC has become increasingly popular and is now widely used. However, consistent guidelines for initiation and discontinuation of HFNC are lacking. In this narrative review, the role of HFNC to treat infants with BR is discussed. An analysis of the literature showed that, despite its widespread use, the role of HFNC in preventing respiratory failure in children with BR is not precisely defined. It is not established whether it can offer greater benefits compared to SOT and when and in which infants it can replace CPAP or BiPAP. The analysis of the results clearly indicates the need for multicenter studies and official guidelines. In the meantime, HFNC can be considered a safe and effective method to treat children with mild to moderate BR who do not respond to SOT.

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19.

INTRODUCTION The management and treatment of Chronic Obstructive Pulmonary Disease (COPD) are based on a cutoff point either of ≥ 10 on the COPD Assessment Test (CAT) or of ≥ 2 of the Medical Research Council (mMRC). Up to now, no study has assessed the equivalence between CAT and mMRC, as related to exercise tolerance in COPD. The aim of this study was to investigate as primary outcome the relationship between CAT and mMRC and maximal exercise capacity in COPD patients. We also evaluated as secondary outcome the agreement between CAT (≥ 10) and mMRC (≥ 2) to categorize patients according to their exercise tolerance. MATERIAL AND METHODS 118 consecutive COPD patients (39 females), aged between 47 and 85 years with a wide range of airflow obstruction and lung hyperinflation were studied. Maximal exercise capacity was assessed by cardiopulmonary exercise test. RESULTS CAT and mMRC scores were significantly related to VO2 peak (p

Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.

Although the etiology and disease mechanisms of asthma and alpha-1 antitrypsin deficiency (AATD) are distinct, several reports indicate that asthma is common in AATD patients, however the relations...

Functional outcome represents the most central objective of rehabilitation programs. Understanding which factors could affect functional status at discharge is crucial for the planning of appropriate treatments in both neurologic and orthopedic patients. The aim of this study was to investigate which clinical and demographic variables, collected at the patient's admission, could influence the functional outcome, assessed by the modified Barthel Index (mBI), at discharge.A retrospective study was conducted on a large cohort (n = 3548) of orthopedic and neurologic patients. Functional, demographic, and clinical records at patient admission and mBI score at discharge were collected. General linear model analysis was performed to assess the influence of these variables on functional outcome at discharge.The results reported a significant effect of mBI score at admission (P0.0001), age (P0.0001), and time from the acute event (P0.0001) on mBI score at discharge. Moreover, the disease type (neurologic or orthopedic) adjusted by sex (male or female) and presence of different impairments (cognitive and behavioral impairments) and complications (hypertension and cardiovascular diseases) significantly influenced mBI score at discharge (P0.05) (R2 = 0.497). No significant interactions between other factors were found (P0.05).Several prognostic factors should be considered when planning an appropriate tailored rehabilitation program.

The study of such a complex phenomenon as cancer, which depends on several but unexplored and unclear factors, needs new ways to visualize, analyze and combine different data both on species characteristics and genes function. To this respect, we propose a novel platform, named VarCopy, supporting visual Exploratory Data Analysis (EDA) in the context of Copy Number Variation (CNV) data. The platform will be publicly available as a web application soon, and is, to our best knowledge, the first tool allowing visual, interactive exploration and analysis of the CNV landscape of multiple species, allowing the identification of new target genes that might be useful for biomedical research.

Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF.

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. Objectives: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation. Methods: We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system. Results: The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (p = 0.014 and p = 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution. Conclusions: In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

Background Ivacaftor is an innovative treatment for CF. Ivacaftor monotherapy in a phase III trial for patients with F508del and a residual function (RF) mutation showed improvement in lung function. We evaluated the effectiveness and safety of ivacaftor in patients with severe CF carrying RF mutations. Methods Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use program. Data were collected 1 year before and 1 year after commencement of ivacaftor. Results Twenty-six patients received ivacaftor. The mean [standard deviation (SD)] percent predicted FEV1 significantly increased from 33.9% (8.3) before treatment to 44.0% (10.7) after 12 months of treatment (p Conclusions In patients with CFTR mutations that confer RF with severe lung disease, treatment with Ivacaftor is safe and results in a clinically significant improvement that was evident at 1 month and maintained at 12 months.

As alternative energy sources increase the proportion of intermittent energy supplies in power grids, coal-fired power plants have come to play an important role in flexible peak power regulation. The burner is the core of the pulverized-coal boiler, and so its performance greatly affects the ability to achieve stable combustion at low boiler loads and also determines the load adjustment range. A novel coal-igniting-fuel technology using intermediate frequency induction heating has been proposed as a means of obtaining better combustion stability at low and variable loads. This method involves the combustion of a small quantity of coal particles in the ignitor to form a central pilot flame that subsequently ignites the surrounding pulverized coal in the main burner to achieve stable combustion. The present work utilized numerical simulations and full-scale experiments to systematically investigate the coal ignition and combustion characteristics associated with this technology. The numerical results show that coal particles inside the ignitor are rapidly heated and ignited, after which the resulting flame is gathered and accelerated by the flame extension tube, thereby forming a pilot flame near the ignitor outlet. When applied to a direct current (DC) burner, this ignitor is able to ignite the primary coal/air flow in a timely manner to form a second high-temperature zone near the burner nozzle. Compared with the absence of an ignitor, the flame center area appears roughly 1.6 m ahead. In an experiment using a single ignitor, it is found that the induction heating coil can quickly heat coal particles, thereby generating a stable high-temperature heat source within 80 s. The application of this ignitor to a DC burner allows the rapid start of the burner at a low initial ambient temperature, and the load can be adjusted over wide ranges of 17.6% – 100% and 13.6% – 100% when burning Shenhua coal and Blended coal, respectively. The degree of coal burnout is found to gradually improve as the thermal load of the burner is increased, reaching a maximum of approximately 93% at full load.

Background The gait recovery is a realist goal in the rehabilitation of almost Stroke patients. Over the last years, the introduction of robotic technologies in gait rehabilitation of stroke patients has had a greatest interest. Objective The aim of this study was to evaluate efficacy of Robotic Gait Training (RGT) in chronic stroke patients. Methods Fourteen chronic stroke patients were divided into two groups. Six patients received RGT, eight patients received traditional gait rehabilitation. Patients were assessed with clinical scales, as well as with gait analysis, at the beginning and at the end of the treatment. Results Significant changes in some clinical scales for both the groups were detected. In the robotic group, patients showed higher percentage changes in the MRC scale (p = 0.020), in the 6MWT (p = 0.043) and in the Ashworth scale (hip: p = 0.008; knee: p = 0.043; ankle: p = 0.043) when compared with the traditional group. With respect to the gait analysis, we did not found any difference neither in the within-group analysis, nor in the between-group analysis. Conclusions Both rehabilitation treatments do not change the compensatory strategies in chronic patients but the RGT offers to the patients a more intensive and controlled gait training increasing the gait endurance and decreasing spasticity in the lower limb.

Unexpected events of breath, tone, and skin color change in infants are a cause of considerable distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and management of brief resolved unexplained events (BRUE)/apparent life-threatening events (ALTE) and to develop a shared protocol among hospitals and primary care pediatricians regarding hospital admission criteria, work-up and post-discharge monitoring of patients with BRUE/ALTE. For the study purpose, a panel of 54 experts was selected to achieve consensus using the RAND/UCLA appropriateness method. Twelve scenarios were developed: one addressed to primary prevention of ALTE and BRUE, and 11 focused on hospital management of BRUE and ALTE. For each scenario, participants were asked to rank each option from ‘1’ (extremely inappropriate) to ‘9’ (extremely appropriate). Results derived from panel meeting and discussion showed several points of agreement but also disagreement with different opinion emerged and the need of focused education on some areas. However, by combining previous recommendations with expert opinion, the application of the RAND/UCLA appropriateness permitted us to drive pediatricians to reasoned and informed decisions in term of evaluation, treatment and follow-up of infants with BRUE/ALTE, reducing inappropriate exams and hospitalisation and highlighting priorities for educational interventions.

Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations, affecting approximately 80,000 people worldwide. CF is a complex multi-organ monogenic autosomal recessive disorder caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the CFTR gene in 1989, more than 2000 mutations have been identified so far and about 240 can cause CF. Until recently, the treatment for CF was aimed to prevent and manage the manifestations of CFTR dysfunction, primarily recurrent pulmonary infections and pancreatic exocrine failure. Over the past few decades, the therapeutic approach to CF has been revolutionized by the development of a new class of small molecules called CFTR modulators that target specific defects caused by mutations in the CFTR gene. CFTR modulators have been shown to change profoundly the clinical course of the CF, leading to meaningful improvements in the lives of a large proportion of people of CF heterozygous for F508del, especially if started in young children. Further studies are needed to extend the use of triple CFTR modulation therapy also for young children in order to prevent the irreversible effects of the disease and for patients with very rare mutations with a personalized approach to treatment.

It is now well established that the healthy bronchial tree contains a microbiome distinct from that of the upper respiratory tract and that the lung microbiome may be dysregulated in individuals with a chronic respiratory disease, such as asthma. In addition, after birth, gut microbes interact with the host tissue, especially with the lymphatic tissue, thereby guaranteeing efficient immune activation. This review focuses on the available literature on the relationships between the gut microbiome, immune function and asthma in childhood, as well as the therapeutic strategies aimed at acting on the modulation of the microbiome.

A fixed-dose inhalation of a long-acting β-agonist (LABA) and inhaled corticosteroids (ICS) is commonly recommended for moderate to severe asthmatic patients not adequately controlled by an ICS only. In order to improve the patients' adherence and the control of disease there is a noteworthy interest for the next generation inhaled β adrenoreceptor agonists maintaining an over 24 hours bronchodilatation and used once-daily (ultra-LABAs). This review focuses on the currently available evidences on the clinical role of any single ultra-LABAs in the treatment of asthmatic patients. Areas covered: New ultra-LABAs have been developed in recent years for the treatment of asthma. In particular, several evidences in asthmatic patients include indacaterol, vilanterol, olodaterol, and abediterol. Expert opinion: Pharmacologically, all new ultra-LABAs considered have demonstrated a good ability to maintain a true bronchodilatation for over 24 hours and a good safety profile. This aspect could be a key point to improve the patient's perspective, the adherence to the treatment regimens and therefore the control of disease. At this time, however, limited data are available and no ultra-LABA+ICS may be recommended as preferred.

Introduction: Subjects affected by alpha-1 antitrypsin (AAT) deficiency are susceptible to develop both asthma and atopy, even if the link between these conditions and AAT deficiency has still to be defined. The aim of this study was to evaluate the relationship between SERPINA1 gene mutations linked with AAT deficiency and atopy in a sample of asthmatics. In addition, we evaluated the atopy characteristics, as related to the AAT deficiency, in a sample of atopic outpatients. Materials and Methods: We prospectively evaluated 55 asthmatic outpatients with and without atopy and 47 atopic outpatients with and without asthma with a serum concentration of AAT Results: In 25 out of 55 outpatients (45%), a gene mutation was demonstrated and 39 out of 55 (71%) were atopic. The percentage of the SERPINA1 gene mutations in asthmatics with atopy was significantly higher than that in non-atopic asthmatic patients (χ2= 6.5; p= 0.01). In this group, patients with gene mutations had higher values in RV/TLC ratio than those without (p=0.009). In the group of 47 atopic outpatients with and without asthma and gene mutations, the percentage with seasonal atopy was significantly higher in mutated ones (41% vs 10%, χ2= 5.4; p= 0.02). Conclusion: We showed that gene mutations linked to AAT deficiency are significantly associated to atopy in asthmatic patients. Furthermore, we provided evidence that gene mutations linked to AAT deficiency are associated to seasonal atopy.

Despite being a hallmark and an independent prognostic factor in several cardiopulmonary diseases, ventilatory efficiency—i.e., minute ventilation/carbon dioxide output relationship (V̇e/V̇co2)—has never been systematically explored in cystic fibrosis (CF). To provide a comprehensive frame of reference regarding measures of ventilatory efficiency in CF adults with normal to moderately impaired lung function and to confirm the hypothesis that V̇e/V̇co2is a sensitive marker of early lung disease. CF patients were divided into three groups, according to their spirometry: normal (G1), mild impairment (G2), and moderate impairment (G3) in lung function. All participants underwent incremental cardiopulmonary exercise testing on a cycle ergometer. Lowest V̇e/V̇co2ratio (nadir) and the slope and the intercept of the linear region of the V̇e/V̇co2relationship were contrasted in a two-center retrospective analysis, involving 72 CF patients and 36 healthy controls (HC). Compared with HC, CF patients had significantly higher V̇e/V̇co2nadir, slope, and intercept ( P < 0.001, P < 0.001, and P = 0.049, respectively). Subgroup analysis revealed significant differences in nadir ( P = 0.001) and slope ( P = 0.012) values even between HC and G1. Dynamic hyperinflation related negatively with slope ( P = 0.045) and positively with intercept ( P = 0.001), while no impact on nadir was observed. Ventilatory inefficiency is a clear feature of adults with CF, even among patients with normal spirometry. V̇e/V̇co2nadir seems to be the most reliable metric to describe ventilatory efficiency in CF adults. Further prospective studies are needed to clarify whether V̇e/V̇co2could represent a useful marker in the evaluation of early lung disease in CF.NEW & NOTEWORTHY This is the first study to investigate ventilatory efficiency in a cohort of adult cystic fibrosis (CF) patients with nonsevere lung disease. The finding of impaired ventilatory efficiency in patients with normal lung function confirms the higher sensitivity of exercise testing in detecting early lung disease compared with spirometry. Dynamic hyperinflation plays a significant role in determining the behavior of V̇e/V̇co2slope and intercept values with increasing lung function impairment. Apparently free from interference from mechanical constraints, V̇e/V̇co2nadir seems the most reliable parameter to evaluate ventilatory efficiency in CF adults.

Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678

Introduction In Cystic Fibrosis (CF), exercise ventilatory inefficiency and dynamic hyperinflation (DH) cause exercise limitation and induce poor exercise tolerance. High-resolution computed tomography (HRCT) of the lung can detect pulmonary abnormalities in CF patients. We aimed to identify the determinants of exercise ventilatory inefficiency and DH using HRCT-derived metrics. Methods Fifty-two adult CF patients were prospectively enrolled; all participants underwent cardio-pulmonary exercise test (CPET) and HRCT. Radiological impairment was evaluated by the Brody II scoring system. Slope and intercept of the minute ventilation/CO2 production (V’E/V’CO2) regression line and the ratio of inspiratory capacity/total lung capacity (IC/TLC) at rest and at peak of exercise were measured. Results Four groups of patients were identified based on the combination of ventilatory efficiency (Vef) or inefficiency (Vin) and the presence/absence of DH. Compared to other groups, CF adults with Vin and DH had worse functional status and higher total (T), bronchiectasis (B) and air trapping (AT) scores at HRCT. Significant correlations were found between V’E/V’CO2 intercept and V’E/V’CO2 slope (ρ − 0.455, p = 0.001) and between V’E/V’CO2 intercept and Δ inspiratory capacity (IC) (ρ − 0.334, p = 0.015). Regression analysis identified AT score (cut-off 7.9, odds ratio-OR 3.50) as the only independent predictor of Vin and T (cut-off 53.6, OR 4.98), B (cut-off 16.1, OR 4.88), airways wall thickening (AWT) (cut-off 13, OR 3.41), and mucous plugging (MP) scores (cut-off 11.7, OR 4.18) as significant predictors of DH. Conclusion In adult CF cohort, values of HRCT metrics are determinants of Vin (AT) and DH (T, B, AWT, MP).

Background: Patients with cystic fibrosis (CF) are at high risk of developing severe forms of viral respiratory infections. This study aimed at comparing symptoms and clinical course of SARS-CoV2 infection with other respiratory infections in patients with CF. Methods: We carried out a prospective multicentre cohort study within the Italian CF Society involving 32 CF centres following 6,597 patients. CF centres were contacted to collect baseline and follow-up data of all patients who had reported symptoms suggestive of COVID-19 or who had had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls). Results: Thirty patients were reported from the centres, 16 of whom tested positive and 14 negative. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms and their frequency were not significant different between groups. Eight cases (50%) were hospitalised but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation;none required ICU admission. All patients fully recovered without short-term sequelae. Changes in FEV1 (percent of predicted) after recovery were not significantly different between groups (median, interquartile range: 3.0%, –1.5, 5.5 among cases and –3.0%, –8.5, 6.3 among controls, P = 0.48). Conclusions: Symptoms and clinical course of SARS-CoV-2 infection in our patients was not significantly different from other respiratory infections. The clinical course of COVID-19 was relatively favourable, however CF patients with severely impaired respiratory function and organ transplant may develop complications and a negative outcome. The study is ongoing, and we are recruiting patients during the second wave of the pandemic.

Background Upper limb recovery is one of the main goals of post-stroke rehabilitation due to its importance for autonomy in Activities of Daily Living (ADL). Although the efficacy of upper limb Robot-assisted Therapy (RT) is well established in literature, the impact of the initial status of the patient on the effects of RT is still understudied. This paper aims to identify whether demographic, clinical and motor characteristics of stroke patients may influence the ability to independently perform ADL after RT. Methods A retrospective study was conducted on sixty stroke patients who conducted planar upper limb goal-directed tasks with the InMotion 2.0 robot. The RT was administered 5 days/week for 4 weeks and each session lasted 45 minutes. The primary outcome measure was the Modified Barthel Index (BI), dichotomized into favourable (BI ≥75) and unfavourable (BI

Inhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists (LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma.

Cystic fibrosis-related diabetes (CFRD) is associated with worsening of inflammation and infections, and the beginning of insulin treatment is debated.To verify high-mobility group box 1 protein (HMGB1) levels in CF patients according to glucose tolerance state, and analyze relationships with insulin secretion and resistance. To verify, in an in vitro model, whether HMGB1 gene expression and protein content were affected by insulin administration and whether these changes were dependent on CF transmembrane conductance regulator (CFTR) loss of function.Forty-three patients in stable clinical conditions and 35 age- and sex-matched controls were enrolled. Glucose tolerance was established in patients based on a 5 point oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FGIR), HOMA-IR index, whole-body insulin sensitivity index (WIBISI), and the areas under the curve for glucose (AUCG) and insulin (AUCI) were calculated. HMGB1 was assayed in serum, in cell lysates and conditioned media using a specific ELISA kit. For the in vitro study we used CFBE41o- cells, homozygous for the F508del mutation, and 16HBE14o- as non-CF control. HMGB1 gene expression was studied by real-time RT-PCR. Cells were stimulated with insulin at 2.5 and 5 ng/mL. The CFTR inhibitor 172 and CFTR gene silencing were used to induce CFTR loss of function in 16HBE14o- cells.HMGB1 levels were increased at onset of CFRD (5.04 ± 1.2 vs 2.7 ± 0.3 ng/mL in controls; P.05) and correlated with FGIR (R = +0.43; P = .038), and AUCI (R = +0.43; P = .013). CFTR loss of function in the 16HBE14o- cells increased HMGB1 and was lowered by insulin.HMGB1 was increased in CF patients with deranging glucose metabolism and showed relationships with indexes of glucose metabolism. The increase in HMGB1 was related to CFTR loss of function, and insulin lowered HMGB1. Further research is required to verify whether HMGB1 could potentially be a candidate marker of onset of CFRD and to establish when to start insulin treatment.

False aneurysm occurring after replacement of ascending aorta by a vascular prosthesis is a rare, but life-threatening complication. In spite of advances in endovascular techniques, surgery remains the treatment of choice in the majority of cases. We report the case of a huge pseudoaneurysm caused by late dehiscence of the right coronary ostium-aortic tubular graft anastomosis, occurred 30 years after replacement of aortic valve and ascending aorta by classical Bentall operation. A fistula originating from the aneurysmal sac extended across the sternum into the thoracic subcutaneous soft tissues and gave rise to a pulsatile mass well appreciable on the anterior chest wall. The surgical treatment, consisting of partial resection of the aortic tubular graft and sternal reconstruction was effective and uneventful.

Seven months after undergoing kidney transplantation, a 56-year-old woman presented with papules and ulcers in her right forearm. The patient received antibiotics for 8 months with limited improvement. Eleven months after symptom onset, she presented with acute arthritis in her left knee. Asynovial fluid culture yielded Mycobacterium tuberculosis, and a forearm ulcer biopsy showed granulomatous inflammation. After surgical fistulectomy and 12 months of tuberculosis treatment, she was cured. Chronic cutaneous ulcers and articular manifestations in TB are rare, but they should always be considered in the differential diagnosis for immunosuppressed patients. Surgical intervention and prolonged treatment might be necessary.

Introduction: Small airway dysfunction (SAD) is a pathophysiological characteristic of chronic obstructive pulmonary disease (COPD). Excess ventilation and dynamic hyperinflation (DH) are two main pathophysiological traits and limiting factors of COPD patients while exercising. We aimed to ascertain whether or not SAD, assessed by the multiple breath nitrogen washout (MBNW), may predict exercise ventilatory inefficiency and DH. Methods: Fifty stable COPD patients were prospectively studied and underwent MBNW and incremental cardio-pulmonary exercise test (CPET). Indices of conductive (Scond) and acinar (Sacin) ventilation heterogeneity as well as minute ventilation/CO2 production (VE/VCO2) linear relationship and the change in inspiratory capacity (IC) were analyzed. Results: Sacin was significantly and directly related to VE/VCO2 slope and inversely related to IC change and to peak O2 uptake (p

Our objective was to evaluate the efficacy of a standardised work-up in the diagnosis of pleural tuberculosis (TB) that included fibreoptic bronchoscopy and medical thoracoscopy. A consecutive series of 52 pleural TB patients observed during the period 2001–2015 was evaluated retrospectively. 20 females, mean (range) age 39.7 (18–74) years, and 32 males, mean (range) age 45.75 (21–83) years, were included (28 non-EU citizens (53.8%)). The diagnosis of TB infections was established by identification (using stains, culture or molecular tests) of Mycobacterium tuberculosis in the pleura, sputum and/or bronchial specimens, or by evidence of caseous granulomas on pleural biopsies. Patients with and without lung lesions were considered separately. The diagnostic yield of the microbiological tests on pleural fluid was 17.3% (nine out of 52 patients). Among the 18 patients with lung lesions, bronchial samples (washing, lavage or biopsy) were positive in 50% of cases (nine patients). Cultures of pleural biopsies were positive in 63% of cases (29 out of 46 patients); pleural histology was relevant in all patients. Without pleural biopsy, a diagnosis would have been reached in 15 out of 52 patients (28.6%) and in four of them only following culture at 30–40 days. An integrated diagnostic work-up that includes all the diagnostic methods of interventional pulmonology is required for a diagnosis of pleural TB. In the majority of patients, a diagnosis can be reached only with pleural biopsy., Diagnosis of tuberculous pleural effusion can be a challenge; medical thoracoscopy greatly increases accuracy http://ow.ly/EnY430gubm9