bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutational status predicts the risk of thromboembolic events in lung adenocarcinoma
Authors: Ferrara Giovanni , Davidsson Elsa , Murgia Nicola , Ortiz-Villalón Cristian , Wiklundh Emil , Sköld Magnus , Kölbeck Karl Gustav
Published: January 2020

Background: Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR and rearrangement in the ALK genes identify specific subgroups of patients. Aim of this study was to investigate the role of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status on the risk of venous thromboembolism (VTE) in lung adenocarcinoma. Methods: A retrospective longitudinal design was used. Patients with lung adenocarcinoma diagnosed and undergoing a mutational analysis at the Karolinska University Hospital, Stockholm, Sweden between January 2009 and September 2015 were divided in three subgroups based on their mutational status (EGFR-, ALK-mutated, unexposed group). Event-free time for VTE was assessed using Cox regression analysis based on mutation status and treatment received. Results: Three hundred-ten patients were included. A VTE occurred in 70 (22.6%) patients. Mutation of EGFR was associated with a decreased risk of VTE (HR 0.46, 95% CI 0.23–0.94). Treatment with tyrosine kinase inhibitors (TKI) reduced the risk of VTE compared to other treatment strategies not including TKI (HR 0.42, 95% CI 0.29–0.79). Conclusions: Our study suggests that patients with lung adenocarcinoma bearing a EGFR-mutation have a decreased risk of VTE compared with patients with other forms of lung adenocarcinoma. Targeted therapy with TKI alone or in combination with other treatments seems to reduce the risk of VTE compared to other treatments not including TKI.
Erratum to: Recent advances in capsule-based dry powder inhaler technology
Authors: Lavorini Federico , Pistolesi Massimo , Usmani Omar S.
Published: January 2020

After publication of the article it was brought to our attention that resistance values of Breezahler (0.15 cmH2O/

L/min) and Handihaler (0.22 cmH2O/L/min) are incorrect.... [more]
Could eosinophilia predict clinical severity in nasal polyps?
Authors: Altun Eren , Aslan Figen , Paksoy Serpil , Turan Gulay
Published: January 2020

Background: Although nasal polyps are one of the most frequent diseases, their etiopathogenesis remains unclear. Since eosinophils are the main inflammatory cells in the substantial proportion of nasal polyp tissues, they are considered potentially responsible for the etiopathogenesis and prognosis of the disease. Aim of this study was to investigate the relation between mucosal and peripheral eosinophilia and their relation with disease severity in nasal polyps.

Methods: The study included 53 patients with nasal polyps who underwent endoscopic sinus surgery. Preoperative Lund-MacKay computed tomography (CT) scores and the Lund-Kennedy endoscopic scores of the patients were recorded. Nasal polyp tissues were stained with hematoxylin and eosin, eosinophil counts were performed using high-power field (HPF, 400×) under the light microscope, and the patients were grouped as those with high mucosal eosinophil count and those with low mucosal eosinophil count.

Results: The mean Lund-MacKay CT score and the mean Lund-Kennedy endoscopic score were higher in the patients with high mucosal eosinophil count than in those with low mucosal eosinophil count. Likewise, the mean Lund-MacKay CT score and the mean Lund-Kennedy endoscopic scores were significantly higher in the patients with high peripheral eosinophil count than in those with low peripheral eosinophil count (p < 0.05 for both). Moreover, the mean peripheral eosinophil count was significantly higher in the patients with high mucosal eosinophil count than in those with low mucosal eosinophil count (p < 0.05).

Conclusion: Mucosal and peripheral eosinophilia can be used as a marker to predict disease severity in nasal polyps.
Desmoplastic small round cell tumors of the pleura: a review of the clinical literature
Authors: Fois Alessandro Giuseppe , Pirina Pietro , Arcadu Antonella , Becciu Francesca , Manca Sandra , Marras Viviana , Canu Sara , Castagna Gaetano , Ginesu Giorgio Carlo , Zinellu Angelo , Paliogiannis Panagiotis
Published: January 2020

Desmoplastic small round cell tumor of the pleura is a rare malignancy, with only a few cases reported in the scientific literature. The aim of the present review is to discuss the demographic, pathological, clinical, and therapeutic features of this rare tumor. English-language articles published since 1989, when the first case of desmoplastic small round cell tumor of the pleura was described, were retrieved, and fifteen cases included in fourteen articles were revised. The mean age of the patients was 25.5 years, out of them 60% were males. Chest pain, pleural effusion, and dyspnea were the most common clinical manifestations, while chest roentgenogram and computed tomography were the imaging techniques most commonly used. Surgical biopsy was employed in 80% of the cases for diagnosis. A multidisciplinary approach consisting in a combination of surgery with chemotherapy and radiation therapy was adopted in most cases. Only two patients (13.3%) were alive at 3 years from diagnosis, reflecting the aggressiveness of the disease, and the poor outcomes of the treatments currently available. Desmoplastic small round cell tumors of the pleura are extremely aggressive and challenging to diagnose, because of their rarity and unspecific demographic, clinical, and radiological features. An in-depth knowledge of such features is necessary for the optimal management of patients with this rare malignancy.
Case-finding for alpha1-antitrypsin deficiency in Kazakh patients with COPD
Authors: Ferrarotti Ilaria , Zhumagaliyeva Ardak , Ottaviani Stefania , Greulich Timm , Gorrini Marina , Vogelmeier Claus , Karazhanova Ludmila , Nurgazina Gulmira , DeSilvestri Annalisa , Kotke Victor , Barzon Valentina , Zorzetto Michele , Corsico Angelo
Published: January 2020

Background: Alpha-1-antitrypsin deficiency (AATD) is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to screen for AATD in Kazakh patients with COPD using dried blood spot specimens.

Methods: The alpha1-antitrypsin (AAT) concentration was determined by nephelometry, PCR was used to detect PiS and PiZ alleles; and isoelectric focusing was used to confirm questionable genotype results and detect rare AAT variants.

Results: To this aim, 187 Kazakh subjects with COPD were recruited. Blood samples were collected as dried blood spot. Genotyping of 187 samples revealed 3 (1.6%) PI*MZ and 1 (0.53%) PI*MS, Phenotyping identified also two sample (1.1%) with phenotype PiMI. Allelic frequencies of pathological mutations Z, S and I resulted 0.8%, 0.3%, 0.5%, respectively, in COPD Kazakh population.

Conclusions: This study proved that AATD is present in the Kazakh population. These results support the general concept of targeted screening for AAT deficiency in countries like Kazakhstan, with a large population of COPD patients and low awareness among care-givers about this genetic condition.
Second lung malignancy and Richter syndrome in chronic lymphocytic leukemia: case report and literature review
Authors: Soussi Ghassen , Daboussi Selsabil , Mhamdi Samira , Moatemri Zied , Ghedira Hela , Aichaouia Chiraz , Khadhraoui Mohsen , El Mezni Faouzi , Cheikh Rezaik
Published: January 2020

Background: Chronic lymphocytic leukemia (CLL) is the most frequent lymphoproliferative disease. Transformation into Richter disease and occurrence of second malignancies involving the lungs are rare complications. The hallmarks of any thoracic involvement are still unknown. Case presentation: We report a case of a 56-year-old male patient, with history of tobacco smoking, who presented with recurrent hemoptysis, fatigue and weight loss. Physical examination was normal except a slightly enlarged supraclavicular lymph node. Chest x-ray revealed a mediastinal widening due to enlarged paratracheal nodes and a left parahilar infiltrate. Blood tests showed a hyperlymphocytosis and a biological inflammatory syndrome. CT scan showed bilateral mediastinal and axillary lymphadenopathy, as well as left supraclavicular lymphadenopathy, with a left upper lobe alveolar attenuation and a solitary contralateral pulmonary nodule. Examination of Virchow’s node and bone marrow biopsies confirmed metastasis of a pulmonary adenocarcinoma, as well as chronic lymphocytic leukemia with Richter’s transformation. The clinical course was unfavorable since the first days of therapy as the patient passed away in a matter of a few days. Conclusions: Steady surveillance of CLL patients and systematic screening for second solid tumors, particularly lung cancer, and Richter’s transformation seem to be relevant more than ever. Early diagnosis might help us understand the pathways leading to these complications and adapt therapy.
COPD management as a model for all chronic respiratory conditions: report of the 4th Consensus Conference in Respiratory Medicine
Authors: Nardini Stefano , De Benedetto Fernando , Sanguinetti Claudio M. , Bellofiore Salvatore , Carlone Stefano , Privitera Salvatore , Sagliocca Luciano , Tupputi Emmanuele
Published: January 2020

Background: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. Methods: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3–4 November 2016. Results and conclusions: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.
Nasal muco-ciliary transport time alteration: efficacy of 18B glycyrrhetinic acid
Authors: Passali Desiderio , Cappello Chiara , Passali Giulio Cesare , Cingi Cemal , Sarafoleanu Codrut
Published: January 2020

Background: Mucociliary clearance is the main self-clearing system of the nasal cavity and paranasal sinuses. This is a very important means of non specific defence against continuous organic and inorganic contamination conveyed by air. It works by trapping particles and microorganisms in the mucus and then by transporting the mucous film to the pharynx where it is eliminated with a cough or swallowed. Its congenital or acquired abnormalities are involved in the occurrence of widespread infectious and often severe nose and paranasal sinuses diseases; generally concerning the rhinopharyngealtubal district. Restoring mucociliary clearance of the nasal epithelium when altered thus represents a key therapeutic tool against rhinosinus chronic diseases. This study evaluates the clinical efficacy of the inhalation of a natural compound (Narivent® nasal spray) in chronic vasomotor rhinitis.

Methods: The study involved 79 patients suffering from chronic vasomotor rhinitis presenting an increased mucociliary clearance time. Patients were randomized into 2 groups: a first group of 49 subjects and a second group of 30 subjects. The first group was treated with a nasal spray (Narivent® nasal spray) (2 sprays per nostril twice a day) for 30 days. The second group was treated with a nasal spray containing isotonic solution in the same way and for the same period of the first group. Nasal Mucociliary transport time was measured in the patients of both groups before treatment, after 15 days of treatment, and at the end of the 30 days treatment.

Results: The study shows how one of the treatments carried out determines a major objective reduction of the mucociliary clearance time in the patients under examination, using the method which involves the use of an insoluble coloured tracer (vegetable carbon), bringing the values back within normal range. At the end of the study we objectivated an increase in the rate of mucociliary transport in 97.9% percentage of patients we enrolled.

Conclusions: This study shows the effectiveness of treatment with natural extracts with nasal mucosa restoring function in the treatment of chronic vasomotor rhinitis, a nasal inflammatory disease characterized by morphological and functional alteration of the normal nasal mucosa.
A pilot study with early adolescents: dealing with diet, tobacco and air pollution using practical experiences and biological markers
Authors: Marabelli Chiara , Munarini Elena , Lina Micaela , Mazza Roberto , Boffi Roberto , De Marco Cinzia , Ruprecht Ario , Angellotti Giorgia , Veronese Chiara , Pozzi Paolo , Bruno Eleonora , Gargano Giuliana , Cavalleri Adalberto , Garrone Giulia , Berrino Franco
Published: January 2020

Background: Tobacco use and the Western diet are two of the most important and investigated topics in relation to adolescents’ health. In addition, air pollution is a crucial subject for future generations. School is a key social environment that should promote healthy behaviors in children and adolescents. In this field many different programs have been conducted, with mixed results and effectiveness. Research data suggest that comprehensive and multicomponent approaches may have a greater effect on tobacco use and diet, especially when integrated into a community-wide approach. Methods: The present work describes a multi-area pilot study called “La Scuola della Salute” (the School of Health) with a focus on the methodological aspects of the intervention. In our study we assessed different web-based and practical experiences related to adolescents’ smoking and dietary behaviors and awareness of smoke-related air pollution. Furthermore, to make adolescents more conscious of smoking and dietary behaviors, we conducted experiential workshops that addressed smoking and environmental pollution, food education, and lifestyle. Teachers and school administrators were involved in the project. Results: At baseline we investigated dietary habits, tobacco use, and individual and social characteristics by means of lifestyle questionnaires. In addition, we collected anthropometric parameters and performance indicators such as exhaled carbon monoxide and urinary fructose to assess smoking and nutrition habits. At the end of the intervention lifestyle questionnaire and biological markers were collected again: knowledge about these topics was significantly improved, and the urinary fructose was able to estimate the levels of obesity in the classes. Conclusions: The integrated approach, combined with the use of biological markers, could be an innovative approach to the promotion of healthy lifestyles among adolescents, but further research is needed.
The patient needing prolonged mechanical ventilation: a narrative review
Authors: Ambrosino Nicolino
Published: January 2020

Background: Progress in management has improved hospital mortality of patients admitted to the intensive care

units, but also the prevalence of those patients needing weaning from prolonged mechanical ventilation, and of

ventilator assisted individuals. The result is a number of difficult clinical and organizational problems for patients,

caregivers and health services, as well as high human and financial resources consumption, despite poor long-term

outcomes. An effort should be made to improve the management of these patients. This narrative review

summarizes the main concepts in this field.

Main body: There is great variability in terminology and definitions of prolonged mechanical ventilation.

There have been several recent developments in the field of prolonged weaning: ventilatory strategies, use of

protocols, early mobilisation and physiotherapy, specialised weaning units.

There are few published data on discharge home rates, need of home mechanical ventilation, or long-term survival

of these patients.

Whether artificial nutritional support improves the outcome for these chronic critically ill patients, is unclear and

controversial how these data are reported on the optimal time of initiation of parenteral vs enteral nutrition.

There is no consensus on time of tracheostomy or decannulation. Despite several individualized, non-comparative

and non-validated decannulation protocols exist, universally accepted protocols are lacking as well as randomised

controlled trials on this critical issue. End of life decisions should result from appropriate communication among

professionals, patients and surrogates and national legislations should give clear indications.

Conclusion: Present medical training of clinicians and locations like traditional intensive care units do not appear

enough to face the dramatic problems posed by these patients. The solutions cannot be reserved to professionals

but must involve also families and all other stakeholders. Large multicentric, multinational studies on several aspects

of management are needed.
Influenza and influenza-like syndromes: the subjects’ beliefs, the attitude to prevention and treatment, and the impact in Italian general population
Authors: Dal Negro Roberto W. , Zanasi Alessandro , Turco Paola , Povero Massimiliano
Published: January 2020

Background: Influenza and influenza-like syndromes (I-LSs) are infectious diseases occurring on a seasonal basis

which can lead to upper (URTI) and lower respiratory tract illness (LRTI) of different severity. The approach to these disorders is unfortunately not uniform. Aim of the study was to investigate real-life people beliefs, the attitude to  their prevention and treatment, and their impact in general population.

Methods: A cross-sectional survey via Computer Assisted Telephone Interview (CATI) was carried out using a specific questionnaire investigating influenza episode rates, subjects behavior in case of influenza and I-LSs, and prescribed therapy.

Results: 1,202 subjects completed the questionnaire: median age was 46, 49% male, 20% active smokers. 57% of respondents experienced at least one episode of influenza or I-LS in the previous 12 months; episodes were usually homemanaged, shorter than 2 weeks and more frequent in fall and winter (73% of the total). GP resulted the first health-care option (56%); almost 3% of respondents referred to the emergency room, and hospitalization occurred in 1%. Mucolytics resulted the most prescribed drugs (55%) followed by antibiotics and aerosol therapy (37–38%). Even if more than 70% of subjects considered vaccination essential, only 14% received influenza vaccination yearly and almost 60% had never received vaccination. Approximately 36% of respondents regarded homeopathy (namely Oscillococcinum) as an helpful alternative because of perceived as safer.

Conclusions: Seasonal prevalence of I-LSs and influenza partially overlap. As virus identification is not a common procedure in daily practice, only a clinical discrimination is possible. Antibiotic prescription is still too high and largely inappropriate. Influenza vaccination is strongly encouraged, but different strategies are also used. Other approaches are receiving increasing attention in general population, and subjects’ willingness to spend out-of-pocket for effective remedies is also increasing. The discrepancy between subjects’ beliefs and health care actions likely reflects the insufficiency of institutional preventive strategies. In general, the approach to influenza and I-LSs appear variable and highly dependent of subjects’ and their GPs’ cultural beliefs.
Association of sleep quality with excessive daytime somnolence and quality of life of elderlies of community
Authors: Sá Brandão Glauber , Camelier Fernanda Warken Rosa , Callou Sampaio Antônia Adonis , Sá Brandão Glaudson , Soares Silva Anderson , Sá Brandão Freitas Gomes Glaucia , Donner Claudio F. , Franco Oliveira Luis Vicente , Camelier Aquiles Assunção
Published: January 2020

Background: The progressive increase in the elderly population contributes to the fact that studies on human aging have important attention of health professionals and government agents, since they present a great challenge regarding public health. Our objective is to characterize the profile of older people with poor sleep quality and analyze possible associations with excessive daytime somnolence, quality of life and functional mobility. Methods: This is a cross-sectional descriptive study, involving elderlies of the community, with the questionnaires Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, WHOQOL-OLD and application of the Timed Up and Go test - TUG. Descriptive statistics, Student’s t test for paired samples and Pearson’s correlation coefficient (p ≤ 0.05) were used. Results: We recruited 131 elderly people, predominantly female (87%); mean age 68 ± 7 years, low per capita income (84.8% ≤ 2 minimum wage), low education (86.3% ≤ 3 years of study), and mostly staying with relatives (67.9%), married (39.7%) or amassed (35.9%). Seventy-one percent of the sample is above normal weight, 90.1% of women have an abdominal circumference ≥ 80 cm and a high prevalence of chronic and psychosocial diseases was identified in the self-report, and the risk of obstructive sleep apnea in 38.2%. The mean PSQI, Epworth Sleepiness Scale, WHOQOL-OLD and TUG were equal to, respectively, 11.2 ± 3.2; 8.32 ± 2.2; 84.8 ± 10.2 and 8.97 ± 2. An association of sleep quality with excessive daytime somnolence and quality of life, while not with functional mobility, was observed. Conclusion: The results of the present study allowed to identify a sleep quality associated with excessive daytime somnolence and quality of life and also to characterize the profile of elders with poor sleep quality.
Criteria for enhancing mucus transport: a systematic scoping review
Authors: Pieterse Alison , Hanekom Susan D.
Published: January 2020

Background: Uncertainty exists regarding the physiological basis of physiotherapy strategies to facilitate mucus clearance. The aim of this review was to describe the physiological factors and intrinsic conditions that facilitate airway mucus transport. Method: A scoping review was performed. A systematic literature search of six databases was executed. Eligibility criteria were applied by two researchers to reach the aim of the review. Papers were identified independently by two reviewers on title, abstract and full-text level. Any discrepancies were discussed with a third reviewer. Results: The search identified 35 papers published between 1975 and 2015. These differed significantly in terms of outcome measures, measurement techniques and methodologies and included animal studies, laboratory investigations, and the use of small human samples. Nine key factors influencing mucus transport were identified. These include: temperature and humidity, bronchial perfusion, ATP, forced expiratory technique and cough, generation of oscillation, ventilation patterns/airflow, epithelial differences, mucus properties and positioning. Conclusion: This review provides a framework for factors/conditions influencing mucus transport. Existing physiotherapy strategies for augmentation of airway mucus clearance can now be evaluated against the framework and new modalities informed.
XII AIST 2018 Conference: “The thousand faces of cough: clinical and therapeutic updates”
Authors: Zanasi Alessandro , Morselli-Labate Antonio M. , Mazzolini Massimiliano , Mastroroberto Marianna , Dal Negro Roberto W. , Poliacek Ivan , Morice Alyn H. , Maio Sara , Viegi Giovanni , Koufman Jamie , Torresan Francesco , Ioannou Alexandros , Mandolesi Daniele , Liverani Elisa , Montale Amedeo , Bazzoli Franco , Baldi Fabio , Zompatori Maurizio , Fontana Giovanni A. , Kantar Ahmad , Dicpinigaitis Peter , Page Clive , Birring Surinder S. , Tursi Francesco
Published: January 2020

This paper summarizes the presentations submitted for publication of the 12th AIST National Congress (Associazione Italiana Studio Tosse/Italian Association for Cough Study) entitled “The thousand facets of cough. A clinical and therapeutic update”, which occurred last February 2nd-3rd, 2018 in Bologna (Italy). It summarizes the contributions from leading experts of the sector, who, as in the previous editions, also this year have analyzed a problem too often underestimated which still has many dark sides as regards both the diagnosis and the therapy of cough. The Scientific Committee has chosen topics that had less space in previous editions and these are topical subjects representing a concrete opportunity for learning and comparison of opinions, as well as indispensable elements for the correct management of the symptoms. Hereby we report the abstracts of the works submitted for publication in this Meeting report. The main topics have covered Cough relationship with nerve vagus, ATP, air pollution, GERD, imaging, COPD, pediatric and therapy. Of particular interest it is the preliminary data on cough hydration ratio that shows a highly significant correlation between dehydration and cough.
Asthma-like symptoms: is it always a pulmonary issue?
Authors: Piloni Davide , Tirelli Claudio , Di Domenica Rita , Conio Valentina , Grosso Amelia , Ronzoni Vanessa , Antonacci Filippo , Totaro Pasquale , Corsico Angelo G.
Published: January 2020

Background: Double aortic arch is a rare congenital and complete vascular ring around trachea and esophagus. It is usually diagnosed during infancy. The symptoms are generally related to respiratory and gastroesophageal tracts. Case presentation: A 20-year-old female patient was referred to our outpatient clinic for persistent dry cough. She had a history of an episode of inhalation of food bolus as an infant and recurrent bronchitis, anorexia and allergic bronchial asthma since the childhood. Since the beginning, an intrathoracic obstruction was suspected at pulmonary function tests. After 1 month of complete asthma treatment, the cough was unchanged and the spirometry confirmed the presence of an intrathoracic obstruction. Then, she underwent a chest CT with contrast medium, a contrast transthoracic echocardiography, a fiberbronchoscopy and an esophageal radiography with contrast medium. The final diagnosis was made and a double aortic arch was found. Conclusion: A careful observation of the flow/volume curve should always be guaranteed and the presence of congenital vascular anomalies should be suspected in case of difficult-to-treat asthma.
5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin
Authors: Bosio Matteo , Salvaterra Elena , Datturi Francesca , Morbini Patrizia , Zorzetto Michele , Inghilleri Simona , Tomaselli Stefano , Mangiarotti Patrizia , Meloni Federica , Cerveri Isa , Stella Giulia Maria
Published: January 2020

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM’s molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile. Methods: We here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis. Results: Within the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter. Conclusions: Mesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal.
The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models
Authors: Hahn Beth , Buikema Ami R. , Brekke Lee , Anderson Amy , Koep Eleena , Van Voorhis Damon , Sharpsten Lucie , Ray Riju , Stanford Richard H.
Published: January 2020

Background: Chronic obstructive pulmonary disease (COPD) is associated with high clinical and economic burden. Optimal pharmacological therapy for COPD aims to reduce symptoms and the frequency and severity of exacerbations. Umeclidinium/vilanterol (UMEC/VI) is an approved combination therapy for once-daily maintenance treatment of patients with COPD. This study evaluated the impact of delaying UMEC/VI initiation on medical costs and exacerbation risk. Methods: A retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 and 7/31/2016 was conducted using the Optum Research Database. The index date was the first COPD visit after UMEC/VI available on US formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12 months post-index, and categorized into 12 cohorts corresponding to month (30-day period) of UMEC/VI initiation (i.e. Months 1–12) post-index. The outcomes studied during the follow up period included COPD-related and all-cause medical costs, and risk of COPD exacerbations. Marginal structural models (MSM) were used to control for time-varying confounding due to changes in treatment and severity during follow up. Results: 2,200 patients initiating UMEC/VI were included in the study sample. Patients’ average age was 69.3 years, 49.9% were female and 69.7% were Medicare insured. Following MSM analysis, 12-month adjusted COPD-related medical costs increased by 2.9% (95% confidence interval [CI]: 0.1–5.9%; p = 0.044) for each monthly delay in UMEC/VI initiation, with a 37.4% higher adjusted cost for patients initiating UMEC/VI in Month 12 versus Month 1 ($13,087 vs. $9524). The 12-month adjusted all-cause medical costs increased by 2.8% (95% CI: 0.6–5.2%; p = 0.013) for each monthly delay, with a 36.1% higher adjusted cost for patients initiating UMEC/VI at Month 12 versus Month 1 ($22,766 vs. $16,727). The monthly risk of severe exacerbation was significantly higher in patients who had not yet initiated UMEC/VI than those who had (hazard ratio: 1.74; 95% CI: 1.35–2.23; p < 0.001). Conclusions: Prompt use of UMEC/VI following a physician visit for COPD appears to result in economic and clinical benefits, with reductions in medical costs and exacerbation risk. Additional research is warranted to assess the benefits of initiating UMEC/VI as a first-line therapy compared with escalation to UMEC/VI from monotherapies.
Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults
Authors: Giménez María-José , Aguilar Lorenzo , Granizo Juan José
Published: January 2020

Fifteen years after its licensure, this revision assesses the role of cefditoren facing the current pharmacoepidemiology of resistances in respiratory human-adapted pathogens (Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis). In the era of post- pneumococcal conjugate vaccines and in an environment of increasing diffusion of the ftsI gene among H. influenzae isolates, published studies on the cefditoren in vitro microbiological activity, pharmacokinetic/pharmcodynamic (PK/PD) activity and clinical efficacy are reviewed. Based on published data, an overall analysis is performed for PK/PD susceptibility interpretation. Further translation of PK/PD data into clinical/microbiological outcomes obtained in clinical trials carried out in the respiratory indications approved for cefditoren in adults (tonsillitis, sinusitis, acute exacerbation of chronic bronchitis and community-acquired pneumonia) is commented. Finally, the role of cefditoren within the current antibiotic armamentarium for the treatment of community respiratory tract infections in adults is discussed based on the revised information on its intrinsic activity, pharmacodynamic adequacy and clinical/bacteriological efficacy. Cefditoren remains an option to be taken into account when selecting an oral antibiotic for the empirical treatment of respiratory infections in the community caused by human-adapted pathogens, even when considering changes in the pharmacoepidemiology of resistances over the last two decades.
OSAS: its burden increases, not enough the awareness
Authors: Sanna Antonio , Lacedonia Donato
Published: January 2020

Obstructive sleep apnoea syndrome (OSAS) is a chronic disease that is widespread in the world and affects subjects of both sexes at all ages. The prevalence of moderate and severe OSAS is extraordinarily high, with values of 23.4% in women and 49.7% in men over 40 years old. [...]
Home exercise improves the quality of sleep and daytime sleepiness of elderlies: a randomized controlled trial
Authors: Sá Brandão Glauber , Sá Brandão Freitas Gomes Glaucia , Sá Brandão Glaudson , Callou Sampaio Antônia A. , Donner Claudio F. , Oliveira Luis V.F. , Camelier Aquiles Assunção
Published: January 2020

Background: Aging causes physiological changes which affect the quality of sleep. Supervised physical exercise is an important therapeutic resource to improve the sleep of the elderlies, however there is a low adherence to those type of programs, so it is necessary to implement an exercise program which is feasible and effective. The study aimed to test the hypothesis that a semi-supervised home exercise program, improves sleep quality and daytime sleepiness of elderlies of the community who present poor sleep quality.

Methods: This was a randomized controlled trial study, conducted from May to September 2017, in Northeastern Brazil, with elderlies of the community aging 60 years old or older, sedentary, with lower scores or equal to 5 at the Pittsburgh Sleep Quality Index (PSQI) and without cognitive decline. From one hundred ninety-one potential participants twenty-eight refused to participate, therefore, one hundred thirty-one (mean age 68 ± 7 years), and 88% female, were randomly assigned to an intervention group - IG (home exercise and sleep hygiene, n = 65) and a control group - CG (sleep hygiene only, n = 66). Sleep assessment tools were used: PSQI, Epworth sleepiness scaleA (ESS) and clinical questionnaire of Berlin. The level of physical activity has been assessed by means of International Physical Activity Questionnaire adapted for the elderly (IPAQ) and Mini-Mental State Examination for cognitive decline. All participants were assessed before and after the 12-week intervention period and, also, the assessors were blind.

Results: The IG showed significant improvement in quality of sleep with a mean reduction of 4.9 ± 2.7 points in the overall PSQI (p < 0.01) and in all its 7 components of evaluation (p < 0.05), and improvement of secondary endpoint, daytime sleepiness, a decline of 2.8 ± 2.2 points in the ESS (p < 0.01).

Conclusion: Our results suggest that semi-supervised home exercise is effective in improving the quality of sleep and self-referred daytime sleepiness of sedentary elderlies of the community who presented sleep disorders.
Clinical characteristics and outcomes of patients with severe acute respiratory infections (SARI): results from the Egyptian surveillance study 2010–2014
Authors: Hatem Ashraf , Mohamed Sherif , Elhassan Usama E. Abu , Ismael Eman A.M. , Rizk Magda S. , El-kholy Amany , El-Harras Mohamed
Published: January 2020

Background: Respiratory viral and atypical bacterial infections data in Egyptian patients are sparse. This study describes the clinical features and outcomes of patients with severe acute respiratory infections (SARI) in hospitalized patients in Egypt. Methods: SARI surveillance was implemented at Cairo University Hospital (CUH) during the period 2010–2014. All hospitalized patients meeting the WHO case definition for SARI were enrolled. Nasopharyngeal/oropharyngeal (NP/ OP) swabs were collected and samples were tested using RT-PCR for influenza A, B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza virus (PIV 1,2,3,4), adenovirus, bocavirus, coronavirus, enterovirus, rhinovirus, and atypical bacteria. Data were analyzed to calculate positivity rates for viral pathogens and determine which pathogens related to severe outcomes or resulted in death. Results: Overall, 1,075/3,207 (33.5%) cases had a viral etiology, with a mean age of 5.74 (±13.87) years. The highest rates were reported for RSV (485 cases, 45.2%), PIV (125, 11.6%), and adenovirus (105, 9.8%). Children had a higher viral rate (981, 91.2%) compared to 94 (8.8%) cases in adults. Patients with identified viruses had significantly lower rates for ICU admission, hospital stay, mechanical ventilation, and overall mortality than those without identified viruses. No infections were independently associated with severe outcomes. Conclusions: Viral pathogens were encountered in one-third of hospitalized adult and pediatric Egyptian patients with SARI, while atypical bacteria had a minor role. Highest rates of viral infections were reported for RSV, PIV, and adenovirus. Viral infections had neither negative impacts on clinical features nor outcomes of patients with SARI in our locality.
A case of airway aluminosis with likely secondary pleuroparenchymal fibroelastosis
Authors: Yabuuchi Yuki , Goto Hitomi , Nonaka Mizu , Tachi Hiroaki , Akiyama Tatsuya , Arai Naoki , Ishikawa Hiroaki , Hyodo Kentaro , Nemoto Kenji , Miura Yukiko , Hase Isano , Oh-ishi Shuji , Hayashihara Kenji , Saito Takefumi , Chonan Tatsuya
Published: January 2020

Background: Excessive inhalation of aluminium powder occasionally results in upper lobe predominant lung fibrosis, which is similar to idiopathic pleuroparenchymal fibroelastosis (IPPFE) and has been suggested to be secondary PPFE. Case presentation: A 67-year-old man who had worked in an aluminum-processing factory for 50 years visited our hospital complaining of exertional dyspnea. Chest computed tomography (CT) showed bilateral dense sub-pleural consolidation in the upper and middle lung fields, which was consistent with IPPFE; however, the possibility of secondary PPFE associated with aluminosis was not ruled out. Considering the patient’s critical condition, trans-bronchial lung biopsy (TBLB) rather than surgical lung biopsy was performed, with elemental analysis of the biopsied specimen. Unfortunately, the specimen obtained by TBLB did not contain alveolar tissue; therefore, pathological diagnosis of PPFE was not possible. However, radiographic findings were highly suggestive of PPFE. On elemental analysis, excessive amounts of aluminum were detected in the bronchiolar walls, establishing a diagnosis of airway aluminosis with likely secondary PPFE resulting from aluminium exposure. Conclusions: TBLB with elemental analysis might be useful in differentiating idiopathic PPFE from secondary causes in dust inhalation related disease, such as aluminosis. This case indicated that inhalation of aluminium might cause secondary PPFE, with attention needing to be paid to avoid further exposure.
Contribution of pulmonary function tests (PFTs) to the diagnosis and follow up of connective tissue diseases
Authors: Ciancio Nicola , Pavone Mauro , Torrisi Sebastiano Emanuele , Vancheri Ada , Sambataro Domenico , Palmucci Stefano , Vancheri Carlo , Di Marco Fabiano , Sambataro Gianluca
Published: January 2020

Introduction: Connective Tissue Diseases (CTDs) are systemic autoimmune conditions characterized by frequent lung involvement. This usually takes the form of Interstitial Lung Disease (ILD), but Obstructive Lung Disease (OLD) and Pulmonary Artery Hypertension (PAH) can also occur. Lung involvement is often severe, representing the first cause of death in CTD. The aim of this study is to highlight the role of Pulmonary Function Tests (PFTs) in the diagnosis and follow up of CTD patients. Main body: Rheumatoid Arthritis (RA) showed mainly an ILD with a Usual Interstitial Pneumonia (UIP) pattern in High-Resolution Chest Tomography (HRCT). PFTs are able to highlight a RA-ILD before its clinical onset and to drive follow up of patients with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO). In the course of Scleroderma Spectrum Disorders (SSDs) and Idiopathic Inflammatory Myopathies (IIMs), DLCO appears to be more sensitive than FVC in highlighting an ILD, but it can be compromised by the presence of PAH. A restrictive respiratory pattern can be present in IIMs and Systemic Lupus Erythematosus due to the inflammatory involvement of respiratory muscles, the presence of fatigue or diaphragm distress. Conclusions: The lung should be carefully studied during CTDs. PFTs can represent an important prognostic tool for diagnosis and follow up of RA-ILD, but, on their own, lack sufficient specificity or sensitivity to describe lung involvement in SSDs and IIMs. Several composite indexes potentially able to describe the evolution of lung damage and response to treatment in SSDs are under investigation. Considering the potential severity of these conditions, an HRCT jointly with PFTs should be performed in all new diagnoses of SSDs and IIMs. Moreover, follow up PFTs should be interpreted in the light of the risk factor for respiratory disease related to each disease.
Acute cough in Italian children: parents’ beliefs, approach to treatment, and the family impact
Authors: Dal Negro Roberto W. , Zanasi Alessandro , Turco Paola , Povero Massimiliano
Published: January 2020

Background: Acute cough is the most common symptom among children in primary care, but the impact of cough episodes was never investigated in Italian families. Methods: A cross-sectional telephone survey was conducted on a representative sample of Italian families, randomly selected from general population; a specific and validated questionnaire was used. Results: The sample (604 calls) was uniformby geographical distribution, and by children age and gender. Mean cough episode was 3.1/year, they were short lasting (only 4.7% > 2 weeks). Independent predictors of children cough episodes were parents’ active smoking habit and work (p < 0.05). The mean nursery/school absenteeism was mostly < 7 days, but of a 7–15-day duration in near 30% of cases. The pediatrician was contacted immediately only by 25% of parents and a second consultation (mostly a lung physician) usually occurred after 2–3 weeks of cough. Meanwhile, home/pharmacist suggested remedies were adopted in 50–70% of cases. Usual prescriptions were mucolytics (85.8%), antitussive agents (55.6%), non-steroideal anti-inflammatory drugs (33.8%), antibiotics (regularly or episodically 80%), and corticosteroids (systemic steroids in less than 50%, but via aerosol in more than 80% of cases). Moreover, pediatricians claimed to use homeopathic drugs regularly or episodically in almost 50%. The respondents’ willingness to spend out-of-pocket for an “effective remedy” against cough was of € 20 (>€ 30 in 18.4% of cases). Conclusions: Parents’ actions against cough episodes were variable, depending on their beliefs, smoking habit, and occupational status. The parents’ perceived efficacy of usual prescriptions is poor, and their willingness to pay out-ofpocket for an “effective remedy” against cough is high. The interest for alternative treatments is not negligible in these circumstances.
Ultrasound evaluation of diaphragmatic mobility in patients with idiopathic lung fibrosis: a pilot study
Authors: Boccatonda Andrea , Decorato Valentina , Cocco Giulio , Marinari Stefano , Schiavone Cosima
Published: January 2020

Background: Some previous works have tested LUS use in diagnosing and monitoring interstitial lung diseases. B-lines are main sonographic signs for interstitial diseases. Increasing evidences suggest that dyspnea and impaired exercise capacity in IPF patients can be related, at least in part, to respiratory muscle dysfunction, in particular to diaphragm functionality. Both B-mode and M-mode ultrasound techniques have been employed to assess diaphragm excursion (DE), which measures the distance that the diaphragm is able to move during the respiratory cycle. Methods: The main objective of this case-control study was to evaluate if differences exist between diaphragmatic excursions in IPF patients and in a control group of healthy subjects. Secondary objectives were to evaluate possible correlations among respiratory excursions, anthropometric parameters and respiratory function parameters. All patients performed spirometry and body plethysmography (PC). Diaphragm was examined by ultrasound imaging in B-MODE, and respiratory excursions were evaluated in M-MODE. Examination consisted of 3 measurements of the inspiratory phase at rest and after deep inspiration. Results: Twelve patients with IPF and 12 healthy subjects were enrolled. There were no significant differences between respiratory excursions in patients and controls during spontaneous breathing, while there was a statistically significant difference between the mean values of the deep respiratory excursion in the two groups (p value < 0.001). There was a positive correlation between respiratory excursion with normal breath and chest circumference in controls (p = 0.034; R = 0.614) and in patients (p = 0.032; R = 0.37), but this relationship was not found even in subjects in deep breathing. A positive correlation was found between FVC values and diaphragmatic motility both at rest and in deep breathing in fibrotic patients. Conclusions: Diaphragmatic mobility is lower in IPF patients than in healthy controls, especially during deep inspiration. The correlation between reduced FVC and diaphragmatic excursion values in IPF patients can be of interest, since it could represent an index of functional respiratory function performed by a non-invasive, low-cost, simple and reliable imaging technique, such as LUS.