bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailored therapy for severe asthma
Authors: Menzella Francesco , Lusuardi Mirco , Galeone Carla , Zucchi Luigi
Published: January 2020

Patients with severe asthma or COPD have often a suboptimal symptom control due to inadequate treatment. A better understanding of pathogenetic mechanisms, phenotypes, endotypes and the new technologies available in the fields of molecular biology and immunogenetics have made it possible to synthesize specific monoclonal antibodies virtually able to interact with any target antigen, or to open a way for new therapeutic target options. At the moment, the only biologic drug available in clinical practice is omalizumab. To overcome the limits of omalizumab, the research has focused on new monoclonal antibodies presenting higher avidity for IgE (e.g. ligelizumab and lumiximab) and ability to interact also with low affinity IgE receptor (FcεRII). At present, many new biological drugs with different mechanisms of action and targets are matter of research. It is very important to identify the asthmatic phenotype in order to select the most appropriate drug for the individual patient. The most promising agents are targeted against cytokines of Th2 pattern and related receptors, such as IL-2 (daclizumab) and IL-13 (lebrikizumab) or IL-5 in patients with hypereosinophilia (mepolizumab, reslizumab and benralizumab). Other interesting drugs have as a target TNF-α or its soluble receptor (infliximab, golimumab and etanercept) or IL-1 (canakinumab), a cytokine with an important systemic proinflammatory action. Finally, the discovery of increased levels of C5a in the airways of asthmatic patients has led to the synthesis of a specific monoclonal antibody (eculizumab). Further help should come from the identification of biomarkers that can guide in choosing the best treatment for the individual patient, such as IgE for omalizumab or periostin for lebrikizumab.
Peripheral muscle strength and functional capacity in patients with moderate to severe asthma
Authors: Ramos Elisangela , Franco de Oliveira Luis Vicente , Borghi Silva Audrey , Peres Costa Ivan , Ferrari Correa João Carlos , Costa Dirceu , Alves Vera Lucia , Donner Claudio F. , Stirbulov Roberto , Arena Ross , Malosa Sampaio Luciana
Published: January 2020

Background: The adequate control of asthma includes the absence of nocturnal symptoms, minimal use of medication, normal or nearly normal lung function and no limitations to physical activity. The choice of a more sedentary lifestyle can lead to physical de-conditioning, thereby aggravating asthma symptoms and increasing the risk of obesity.

Methods: This study aimed at performing a battery of function-related assessments in patients with asthma and comparing them to a healthy control group. A prospective, transversal and case–control study was designed. It was set up at Santa Casa de Misericórdia Hospital – Sao Paulo and Nove de Julho University on a population of outpatients. Subjects of the study were patients affected by moderate to severe asthma. A case–control study was carried out involving 20 patients with moderate to severe asthma and 15 healthy individuals (control group). All participants underwent body composition analysis (BMI and BIA) and a controlled walk test (Shuttle test), resistance muscle test (1RM) and answered a physical activity questionnaire (IPAQ). The group with asthma also answered a questionnaire addressing the clinical control of the illness (ACQ).

Results: In comparison to the control group (unpaired Student’s t-test), the patients with asthma had a significantly higher BMI (31.09 ± 5.98 vs. 26.68 ± 7.56 kg/m2) and percentage of body fat (38.40 ± 6.75 vs. 33.28 ± 8.23%) as well as significantly lower values regarding distance traveled on the walk test (369 ± 110 vs. 494 ± 85 meters) and metabolic equivalents (3.74 ± 0.87 vs. 4.72 ± 0.60). A strong correlation was found between the distance completed and peripheral muscle strength (r: 0.57, p < 0.05) and METs (Metabolic equivalents – minutes/week) and peripheral muscle strength of 1RM (r: 0.61, p = 0.009).

Conclusions: The individuals with asthma had lower functional capacity and levels of physical activity as well as a higher percentage of body fat compared to healthy individuals. This suggests that such patients have a reduced physical performance stemming from a sedentary lifestyle. Despite the existence of few studies reporting moderate to severe asthmatic patients and functional capacity assessment, it is clear that the assessment presented in the current study is a valid and accessible tool in clinical practice.
Rethinking the withholding/withdrawing distinction: the cultural construction of “life-support” and the framing of end-of-life decisions
Authors: Barilan Yechiel M.
Published: January 2020

This paper is a theoretical and empirically informed examination of the naturalist distinction between withholding and withdrawing life-support. Drawing on the history of mechanical ventilation and on a recent Israeli law containing a novel approach to disconnecting life-support at the end of life, it is argued that the design of machines predicates the division line between “active” and “passive” interventions, and that the distinction itself might be morally self-defeating. Informed by insights from moral psychology, behavioral economics and philosophies of technology, the paper warns against the placement of this old distinction at the heart of the moral and legal regulation of life-support at the end of life.
Medical malpractice, defensive medicine and role of the “media” in Italy
Authors: Toraldo Domenico M. , Vergari Ughetta , Toraldo Marta
Published: January 2020

Background: For many years until now, Italy has been subjected to an inconsistent and contradictory media campaign. On one hand the “media” present us with bold and reassuring messages about the progress of medical science; on the other hand they are prone to kneejerk criticism every time medical treatment does not have the desired effect, routinely describing such cases as glaring examples of “malasanità”, an Italian word of recent coinage used to denote medical malpractice. Newspaper reports of legal proceedings involving health treatment are frequently full of errors and lack any scientific basis.

Data sources: The published data confirm the unsustainably high number of lawsuits against doctors and medical structures, accompanied by demands for compensation arising from true or alleged medical errors or mistakes blamed on the work of health structures.

Conclusions and implications: Currently Italian citizens have a greater awareness of their right to health than in the past, and patients’ expectations have risen. A discrepancy is emerging between the current state of medical science and the capacities of individual doctors and health structures. Lastly, there is a need for greater monitoring of the quality of health care services and a greater emphasis on health risk prevention.
Invasive candidiasis presenting multiple pulmonary cavitary lesions on chest computed tomography
Authors: Yasuda Yuichiro , Tobino Kazunori , Asaji Mina , Yamaji Yoshikazu , Tsuruno Kosuke
Published: January 2020

We herein report a case of invasive candidiasis presenting rare findings on chest computed tomography (CT). The chest CT scan showed multiple small cavitary lesions and nodules with surrounding ground-glass opacity, and also bilateral pleural effusion. Although this CT finding is thought as specific for pulmonary aspergillosis, two sets of blood culture specimens were drawn which yielded Candida albicans  in our case. Antifungal therapy was started and the chest CT findings showed a remarkable improvement. To our knowledge, this is the first case report describing multiple pulmonary cavitary lesions in invasive candidiasis.
Research on psychosocial aspects of asthma in the Arab world: a literature review
Authors: Al-Khateeb Anas J. , Al-Khateeb Jamal M.
Published: January 2020

The importance of psychosocial factors in the management of bronchial asthma has long been recognized. This paper offers a review of research published in the English language related to psychosocial aspects of bronchial asthma in Arab countries. Several databases (PubMed, Science Direct, Springer Link, ERIC, and PsychInfo) were searched using the following keywords: bronchial asthma, Arab countries, Algiers, Bahrain, Comoros, Djibouti, Egypt, Iraq, Jordan, Kuwait, Lebanon, Libya, Mauritania, Morocco, Oman, Palestine (West Bank, Gaza), Qatar, Saudi Arabia, Syria, Tunisia, Sudan, Somalia; United Arab Emirates, and Yemen. Thirty-two studies were conducted in 9 Arab countries. Almost all studies found were published in the last fourteen years with an apparent increasing rate in the last five years. In descending order, these studies addressed: knowledge of and attitudes toward asthma, quality of life, behavioral and emotional problems and factors related to academic achievement. The main results of the studies reviewed were: (a) physicians’, school staff’s, and parents’ knowledge of and attitudes toward asthma were generally unsatisfactory, (b) in-service asthma education programs significantly impacted parent and staff knowledge and attitudes, and asthma management practices, (c) quality of life in children and adolescents was significantly adversely affected by asthma, (d) asthma was a common cause of school absenteeism, and had a significant negative impact on academic achievement of students, and (e) students with asthma had significantly higher rates of behavioral and emotional difficulties compared to students without asthma. The paper concludes with a discussion about the implications of these results and a call for further research in this area.
Beirut Air Pollution and Health Effects - BAPHE study protocol and objectives
Authors: Nakhlé Myriam Mrad , Farah Wehbeh , Ziade Nelly , Abboud Maher , Coussa-Koniski Marie-Louise , Annesi-Maesano Isabella
Published: January 2020

Background: Recent studies investigating the health effects of air pollution have proven an existing impact aroundand below international air quality guidelines and standards. These studies were based on accessible data from official registers managed by public authorities. The protocol followed in BAPHE project is described; its benefits and disadvantages are presented and discussed in this paper.

Methods: Based on the review of several international studies we developed a custom made approach in BAPHE (Beirut Air Pollution and Health Effects) project in order to analyze the short term health effects of air pollution taking into consideration the lack of data availability from official sources.

Results: PM2.5 and PM10 concentrations were measured in Beirut for the period starting from the 1st of January 2012 to the 31st of December 2012. The annual average concentrations of PM10 and PM2.5 exceeded WHO’s annual average limits by 150 % and 200 %, respectively. Health data for 11,567 individuals were collected over 12 months. A variation of hospital admission causes was observed by age categories and gender.

Conclusions: This article presents a simple protocol and the descriptive results of its application in the frame of an eco-epidemiological study in Lebanon. We believe that this work is not only important on a local scale, but it could be helpful for environmental epidemiological studies in other countries.
Effects of Laminaria japonica polysaccharides on airway inflammation of lungs in an asthma mouse model
Authors: Lin Rongjun , Liu Xiaomei , Meng Yan , Xu Mei , Guo Jianping
Published: January 2020

Background: Asthma is a serious chronic inflammatory disease affecting 300 million people worldwide. This aim of this study to investigate the anti-inflammatory and anti-asthmatic effects of Laminaria japonica extract in the ovalbumin (OVA)-induced mouse asthma model.

Methods: A mouse asthma model was established in SPF Kunming mice by OVA-sensitization followed by inhalation of aerosol allergen for two weeks. Laminaria japonica polysaccharides (LJPS) were given by gavage feeding at 50 mg/kg/day during OVA inhalation challenge period, and their effect on asthma was compared with the standard treatment of Budesonide inhalation. The total inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF) were determined. Histopathological changes in lung tissue were studied and scored to determine the degree of inflammation. Levels of IL-12, IL-13, and TGF-β1 in BALF as well as serum levels of IgE were measured. Expressions of IL-12, IL-13, and TGF-β1 in lung tissues were assessed.

Results: Highly inflammatory lungs infiltrated with significant increased eosinophils were observed in OVAinduced asthmatic mice. The OVA treated mice presented with a lower level of IL-12 and higher levels of IL-13 and TGF-β1 in BALF and lung tissues, as well as an increased level of the serum IgE. Treatment with LJPS (Group B) significantly decreased the numbers of eosinophils in the BALF (P<0.05) and alleviated lung inflammation compared to the untreated asthma mice (Group A). It also reduced the serum IgE levels, increased expression of IL-12, and decreased the expression of IL-13 and TGF-β1 in BALF and lung (Both P < 0.05) compared with the group A.

Conclusions: LJPS can significantly inhibit airway inflammation of asthmatic mice, adjust the balance of cytokines, and improve the pulmonary histopathological condition. Our data suggested that LJPS might be a potential therapeutic reagent for allergic asthma.
Nasal High-flow versus non-invasive ventilation in stable hypercapnic COPD: a preliminary report
Authors: Bräunlich Jens , Seyfarth Hans-Jürgen , Wirtz Hubert
Published: January 2020

Background: There are no data available about effectiveness of Nasal High-flow (NHF)in chronic respiratory insufficiency. Methods: Eleven COPD patients with stable hypercapnia were adjusted to NHF-system with a flow of 20 l/min. After six weeks patients were switched to non-invasive ventilation (NIV) for another six weeks period. Results: NHF led to significant decreases in resting pCO2. Between the devices we found no differences in pCO2 levels. Conclusions: NHF may thus be an alternative treatment device in stable hypercapnic COPD patients.
Does additional antimicrobial treatment have a better effect on URTI cough resolution than homeopathic symptomatic therapy alone? A real-life preliminary observational study in a pediatric population
Authors: Zanasi Alessandro , Cazzato Salvatore , Mazzolini Massimiliano , Ierna Carla Maria Sofia , Mastroroberto Marianna , Nardi Elena , Morselli-Labate Antonio Maria
Published: January 2020

Background. The effectiveness of a homeopathic syrup on cough has been demonstrated in an adult population in a previous double-blind randomized study. The present prospective observational study investigated children affected by wet acute cough caused by non-complicated URTIs, comparing those who received the homeopathic syrup versus those treated with the homeopathic syrup plus antibiotic. Objectives. The aims were: 1) to assess whether the addition of antibiotics to a symptomatic treatment had a role in reducing the severity and duration of acute cough in a pediatric population, as well as in improving cough resolution; 2) to verify the safety of the two treatments.

Methods. Eighty-five children were enrolled in an open study: 46 children received homeopathic syrup alone for 10 days and 39 children received homeopathic syrup for 10 days plus oral antibiotic treatment (amoxicillin/clavulanate, clarithromycin, and erythromycin) for 7 days. To assess cough severity we used a subjective verbal category-descriptive (VCD) scale.

Results. Cough VCD score was significantly (P < 0.001) reduced in both groups starting from the second day of treatment (−0.52 ± 0.66 in the homeopathic syrup group and −0.56 ± 0.55 in children receiving homeopathic syrup plus oral antibiotic treatment). No significant differences in cough severity or resolution were found between the two groups of children in any of the 28 days of the study. After the first week (day 8) cough was completely resolved in more than one-half of patients in both groups. Two children (4.3 %) reported adverse effects in the group treated with the homeopathic syrup alone, versus 9 children (23.1 %) in the group treated with the homeopathic syrup plus antibiotics (P = 0.020).

Conclusions. Our data confirm that the homeopathic treatment in question has potential benefits for cough in children as well, and highlight the strong safety profile of this treatment. Additional antibiotic prescription was not associated with a greater cough reduction, and presented more adverse events than the homeopathic syrup alone.
DNA damage and cellular abnormalities in tuberculosis, lung cancer and chronic obstructive pulmonary disease
Authors: Gonçalves da Silva Andréa Lúcia , Bresciani Maribel Josimara , Karnopp Thaís Evelyn , Weber Augusto Ferreira , Ellwanger Joel Henrique , Pêgas Henriques João Antonio , De Moura Valim Andréia Rosane , Gonçalves Possuelo Lia
Published: January 2020

Background: Tuberculosis (TB), Lung Cancer (LC) and Chronic Obstructive Pulmonary Diseases (COPD) affect millions of individuals worldwide. Monitoring of DNA damage in pathological situations has been investigated because it can add a new dimension to clinical expression and may represent a potential target for therapeutic intervention. The aim of this study was to evaluate DNA damage and the frequency of cellular abnormalities in TB, LC and COPD patients by comparing them to healthy subjects.

Methods: The detection of DNA damage by a buccal micronucleus cytome assay was investigated in patients with COPD (n = 28), LC (n = 18) and TB (n = 22) and compared to control individuals (n = 17).

Results: The COPD group had a higher frequency of apoptotic cells compared to TB and LC group. The TB group showed a higher frequency of DNA damage, defect in cytokinesis, apoptotic and necrotic cells. Patients with LC had low frequency of chromosomal aberrations than TB and COPD patients.

Conclusion: COPD patients showed cellular abnormalities that corresponded to cell death by apoptosis and necrosis, while patients with TB presented defects in cytokinesis and dysfunctions in DNA repair that resulted in the formation of micronucleus (MN) besides apoptotic and necrotic cells. Patients with COPD, TB and LC had a low frequency of permanent DNA damage.
Acceptability and preference of three inhalation devices assessed by the Handling Questionnaire in asthma and COPD patients
Authors: Dal Negro Roberto W. , Povero Massimiliano
Published: January 2020

Background: The patients’ criteria of preference for inhalation devices can affect the extent of their adherence to treatment and outcomes. Aim of this study was to assess and compare the patients’ preference and acceptability (PPA) for Breezhaler and Genuair (both Dry Powder Inhalers), and for Respimat (a Soft Mist Inhaler) in asthma and COPD out-patients by means of the Handling Questionnaire. Methods: The Handling Questionnaire is a validated instrument which allows the investigation of different domains of PPA; it also takes into account the patients’ age and gender, together with their previous experience with the inhalation devices and their previous education approach to them. Differences in terms of preference, acceptance and usability were assessed by linear and logistic regressions in order to evaluate factors influencing the proper actuation. Results and Discussion: Data from 333 patients were collected: Genuair and Respimat were the most liked and perceived as the easiest to use at glance by patients, but also as the least problematic according to the patients’ and nurse’s judgments. Mean number of attempts for achieving the first effective actuation was the highest with Breezhaler (2.6 vs 1.6; p <0.0001). Linear regressions showed that longer the explanation, higher was the number of attempts to the first proper actuation (0.58 additional attempts every 10 s increase in the first explanation, p <0.0001). Devices requiring less manoeuvres for the actuation were used properly after less attempts (0.38 increase in the number of attempts every additional manoeuvres, p <0.0001). Respimat proved to be the most indicated in COPD patients since it was the most liked and its successful rate at first attempt was the highest. Logistic regressions confirmed these data. Previous experience with DPIs and/or MDIs did not affect the patient preference and acceptability, independently whether suffering from asthma or COPD. Conclusions: Substantial differences are existing in patient’s preference and acceptability for inhalation devices, mainly related to the handling and the understanding of the different devices.
The BODECOST Index (BCI): a composite index for assessing the impact of COPD in real life
Authors: Dal Negro Roberto W. , Celli Bartolome R.
Published: January 2020

Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive condition which is characterized by a dramatic socio-economic impact. Several indices were extensively investigated in order to asses the mortality risk in COPD, but the utilization of health care resources was never included in calculations. The aim of this study was to assess the predictive value of annual cost of care on COPD mortality at three years, and to develop a comprehensive index for easy calculation of mortality risk in real life.

Methods: COPD patients were anonymously and automatically selected from the local institutional Data Base. Selection criteria were: COPD diagnosis; both genders; age ≥ 40 years; availability of at least one complete clinical record/year, including history; clinical signs; complete lung function, therapeutic strategy, health BODE index; Charlson Comorbidity Index, and outcomes, collected at the first visit, and over the following 3-years. At the first visit, the health annual cost of care was calculated in each patient for the previous 12 months, and the survival rate was also measured over the following 3 years. The hospitalization and the exacerbation rate were implemented to the BODE index and the novel index thus obtained was called BODECOST index (BCI), ranging from 0 to 10 points. The mean cost for each BCI step was calculated and then compared to the corresponding patients’ survival duration. Parametrical, non parametrical tests, and linear regression were used; p < 0.05 was accepted as the lower limit of significance.

Results: At the first visit, the selected 275 patients were well matched for all variables by gender. The overall mortality over the 3 year survey was 40.4 % (n = 111/275). When compared to that of BODE index (r = 0.22), the total annual cost of care and the number of exacerbations showed the highest regression value vs the survival time (r = 0.58 and r = 0.44, respectively). BCI score proved strictly proportional to both the cost of care and the survival time in our sample of COPD patients.

Discussion: BCI takes origin from the implementation of the BODE index with the two main components of the annual cost of care, such as the number of hospitalizations and of exacerbations occurring yearly in COPD patients, and their corresponding economic impact. In other words, higher the BCI score, shorter the survival and higher the cost, these trends being strictly linked.

Conclusions: BCI is a novel composite index which helps in predicting the impact of COPD at 3 years in real life, both in terms of patients’ survival and of COPD economic burden.
Differentiation of respiratory epithelium in a 3-dimensional co-culture with fibroblasts embedded in fibrin gel
Authors: Jockenhoevel Stefan , Albers Stefanie , Thiebes Anja Lena , Gessenich Kai L. , Cornelissen Christian G.
Published: January 2020

Background: Tracheal tissue engineering is a promising option for the treatment of tracheal defects. In a previous study we proved the suitability of fibrin gel as a scaffold for tracheal tissue engineering. This study investigates whether the differentiation of respiratory epithelium can be increased by culturing epithelial cells in a three dimensional system containing fibroblasts embedded into fibrin gel. Methods: Respiratory epithelial cells were isolated from porcine trachea, seeded onto a fibrin gel and kept in air-liquid-interface culture for 33 days. Morphology as well as pan-cytokeratin, MUC5AC and claudin-1 expression of cells cultured on pure fibrin gel were compared to culture on gels containing fibroblasts. Results: After two weeks, cells seeded on pure fibrin gel were multilayered, showed hyperproliferation and dedifferentiation. Co-cultured cells built up a pseudostratified epithelium. The differentiation and organization of epithelial structure improved with respect to time. After four weeks, morphology of the co-cultured respiratory epithelium resembled native tracheal epithelium. Immunohistochemistry showed that respiratory epithelium co-cultured with fibroblasts had an increasing similarity of pan-cytokeratin expression compared to native trachea. Cells cultured without fibroblasts differed in pan-cytokeratin expression from native trachea and did not show any improvement of differentiation. Immunohistochemical staining of MUC5AC and claudin-1 proved seeded cells being respiratory epithelial cells. Conclusions: This study indicates that adding fibroblasts to fibrin gel positively influences the differentiation of respiratory epithelium.
Increased expression of A Proliferation-Inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?
Authors: Owen Caroline A. , Polverino Francesca , Laucho-Contreras Maria , Quintero Joselyn Rojas , Divo Miguel , Pinto-Plata Victor , Sholl Lynette , De-Torres Juan P. , Celli Bartolome R.
Published: January 2020

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients.

Methods: Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers. The percentage of B cells, alveolar macrophages (AMs) and polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells (AECs) that stained positively for APRIL was quantified using epi-fluorescence microscopy and image analysis software.

Results: The percentage of APRIL-expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC or NSC (p < 0.03 for all comparisons). The percentage of APRIL-expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC alone than in patients with COPD alone. The percentage of APRIL-expressing AECs (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05 for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs cells was similar in NSC and SC.

Conclusion: The percentage of APRIL-expressing B cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or control subjects. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.
Need of education for dry powder inhaler storage and retention – a patient-reported survey
Authors: Norderud Lærum Birger , Telg Gunilla , Stratelis Georgios
Published: January 2020

Background: Dry powder inhalers (DPIs) are the most commonly used devices in asthma treatment in the Nordic countries. As new DPIs become available, patients are likely to be exposed to more than one type of device, with variable optimal handling. The aim was to examine real life storage and retention of multidose DPIs in patients with asthma. Methods: This patient-reported survey on real life storage and retention of DPIs included asthma patients using multidose DPIs. Basic patient characteristics, information on inhaler use and storage, check of expiry date, and concurrent inhaler use was examined using an on line questionnaire. Results: A total of 738 patients were included with a median age of 41 years, out of which 83 % were women. Sixty-three per cent reported storage conditions pre-defined as risk locations for their maintenance inhaler and 38 % of the responding patients had more than one maintenance inhaler in use at the same time. Two thirds of the study population checked inhaler expiry date less than monthly or not at all. Use after expiry date was frequently reported. Two thirds of the patients had not received information on DPI storage, either from their doctor and/or nurse or at the pharmacy. Conclusions: This patient reported survey indicates that two thirds of the patients store their inhaler devices in suboptimal conditions, and only a minority had received instruction regarding inhaler handling. Non awareness of inhalers’ expiry dates and use of more than one maintenance inhaler simultaneously was common. As inhaler mishandling may impact device functionality, improved communication and patient education is needed.
Prospective study of the efficacy of antibiotics versus antitussive drugs for the management of URTI-related acute cough in children
Authors: Zanasi Alessandro , Lanata Luigi , Saibene Federico , Fontana Giovanni , Dicpinigaitis Peter V. , Venier Valentina , De Blasio Francesco
Published: January 2020

Background: Acute cough is one of the most frequent symptoms prompting a visit to a health care provider, usually following a viral upper respiratory tract infection (URTI). The disproportionate use of antibiotics in children with URTIs, recently highlighted in the medical literature, could lead to associated side effects, without any beneficial effect. Although an early, albeit inappropriate, antibiotic prescription increases parental satisfaction, URTIs are predominantly viral infections and are generally self-limiting. Therefore the aim of this study was to analyze the effectiveness of antibiotics compared to symptomatic drugs (central and peripheral antitussives) on URTI-related cough in a pediatric population. Methods: This is a prospective observational study of 330 children who required pediatric consultation for acute cough. Severity, frequency and type of cough were assessed at baseline and after 6 days of treatment (antitussives n = 123, antibiotics n = 89 or combination of them n = 38) or no treatment (n = 80). The outcome of cough management after 6 days was analyzed in terms of resolution, improvement, no change or worsening of symptoms. Study assessments were performed using a standardized questionnaire administered to parents. Results: Between children treated with antitussives or antibiotics, there was a statistically significant difference in the resolution of cough. Moreover, if considering peripheral antitussives, the resolution of cough was significantly higher with antitussives than with antibiotics (p < 0.01). There was no difference in cough resolution between children treated with antitussives and those receiving a combination of antibiotics and antitussives, either central and peripheral antitussives. Conclusion: Antibiotics are generally not useful nor appropriate in treating acute cough due to the common cold. Furthermore, inappropriate antibiotic use introduces the possibility of adverse side effects as well as promotion of antibiotic resistance. The findings of the present study suggest that antitussives, especially peripherally acting agents, represent an effective treatment option for acute pediatric cough caused by URTIs.
Sarcoidosis with prevalent and severe joint localization: a case report
Authors: Moccia Livio G. , Castaldo Sabrina , Sirignano Emanuela , Napolitano Maddalena , Barra Enrica , Sanduzzi Alessandro
Published: January 2020

Background: Sarcoidosis is a systemic granulomatous disease of unknown origin, characterized by the formation of granulomas without central necrosis. Each organ and tissue can be affected by the disease, but in most cases mainly the lungs and mediastinal lymph nodes but also skin, heart, eyes and joints are involved, the latter are mainly the metacarpophalangeal joints and bone lesions are often associated with involvement of the overlying skin. The diagnosis is often of exclusion, based on clinical and radiological suspicion, and should be confirmed by biopsy, although in each case it is necessary to exclude other possible causes of granulomatosis, including infections by mycobacteria. Here it is reported a case of particularly aggressive sarcoidosis with primitive involvement of the small joints of the hands and feet, and mediastinal lymph nodes. Case presentation: The subject, a man, 60 years old, born in Morocco but living in Italy for many years, presented important involvement of bone structures and soft periarticular tissue, and was affected by the formation of granulomas without “caseum necrosis”. The painful symptoms and the skin ulceration had led to surgical amputation of the distal phalanges of most fingers of his hands and feet, but with subsequent resurgence of lesions in acral locations after surgery. The PET/CT scan showed an amount of radiotracer in mediastinal lymph nodes, while the lymph nodes sampled by TBNA were normal and the CD4/CD8 ratio was less than 3 in the bronchoalveolar lavage. We ruled out any possible infectious cause, including mycobacterial infection (both tubercular and atypical), so the patient was treated with systemic corticosteroids, with an excellent clinical and radiological response. Conclusions: Such a case shows how the disease can have variable expressions, without primitive lung involvement; therefore, it should be necessary to consider any possible, unpredictable localization of the disease.
Asthma-related deaths
Authors: D’Amato Gennaro , Vitale Carolina , Molino Antonio , Stanziola Anna , Sanduzzi Alessandro , Vatrella Alessandro , Mormile Mauro , Lanza Maurizia , Calabrese Giovanna , Antonicelli Leonardo
Published: January 2020

Despite major advances in the treatment of asthma and the development of several asthma guidelines, people still die of asthma currently. According to WHO estimates, approximately 250,000 people die prematurely each year from asthma. Trends of asthma mortality rates vary very widely across countries, age and ethnic groups. Several risk factors have been associated with asthma mortality, including a history of near-fatal asthma requiring intubation and mechanical ventilation, hospitalization or emergency care visit for asthma in the past year, currently using or having recently stopped using oral corticosteroids (a marker of event severity), not currently using inhaled corticosteroids, a history of psychiatric disease or psychosocial problems, poor adherence with asthma medications and/or poor adherence with (or lack of) a written asthma action plan, food allergy in a patient with asthma. Preventable factors have been identified in the majority of asthma deaths. Inadequate education of patients on recognising risk and the appropriate action needed when asthma control is poor, deficiencies in the accuracy and timing of asthma diagnosis, inadequate classification of severity and treatment, seem to play a part in the majority of asthma deaths. Improvements in management, epitomized by the use of guided self-management systems of care may be the key goals in reducing asthma mortality worldwide
Personality and unachieved treatment goals related to poor adherence to asthma medication in a newly-developed adherence questionnaire – a population-based study
Authors: Axelsson Malin , Ekerljung Linda , Lundbäck Bo , Lötvall Jan
Published: January 2020

Background: Health-care professionals have a responsibility to be attentive to patients’ adherence behavior but it could be difficult to identify poor adherence in the context of clinical practice. Assessment of personality could be used to identify individuals who are in need for support with their adherence behavior. To our knowledge, existing adherence questionnaires are not based on individuals reflecting asthmatics in the general population and there is limited research describing adherence with asthma medication in relation to personal goals with the treatment. The aim was to develop and validate an adherence questionnaire in adult individuals with asthma from the general population and to assess adherence in relation to personality traits and goals with the asthma medication using the developed questionnaire. Methods: The study was conducted in three phases: 1. A preliminary postal 46-item questionnaire was refined after psychometric testing (n = 157). 2. The questionnaire was validated (n = 104). 3. The developed adherence questionnaire was analyzed in relation to personality traits and achieved goals with the asthma medication. Adult respondents with physician diagnosed asthma using asthma medications were selected from the population-based West Sweden Asthma Study. The respondents completed the Neuroticism, Extraversion and Openness to Experience Five-Factor Inventory and the Medication Adherence Report Scale and stated their goals with the asthma medication. Data were analyzed using t-tests, correlations, multiple regression and principal component analysis. Results: A final questionnaire was developed consisting of ten items organized in three subscales - “medication routines”, “self-adjusting the medication” and “concerns about side-effects”. Two of the subscales - “medication routines” and “self-adjusting the medication” – were associated with the Medication Adherence Report Scale. The subscale “medication routines” was associated with the personality traits – Conscientiousness and Neuroticism and unachieved goals with the asthma medication. Conclusions: The developed questionnaire appears to be useful for measuring adherence to asthma medication in adult individuals with asthma. The study suggests that both individual differences and personal treatment goals need to be addressed in efforts to promote adherence to asthma medication treatment.
DNA damage and repair capacity in lymphocyte of chronic obstructive pulmonary diseases patients during physical exercise with oxygen supplementation
Authors: Gonçalves da Silva Andréa Lúcia , Karnopp Thaís Evelyn , Ferreira Weber Augusto , Goulart Cassia da Luz , Scheneiders Paloma de Borba , Cardoso Dannuey Machado , Carvalho Lisiane Lisboa , Ellwanger Joel Henrique , Possuelo Lia Gonçalves , Rosane de Moura Valim Andréia
Published: January 2020

Background: We hypothesized that the use of oxygen supplementation during aerobic exercise induces less DNA damage than exercise alone. The aim of this study is to assess the level of DNA damage induced by physical exercise with and without oxygen supplementation in chronic obstructive pulmonary diseases (COPD) patients. Methods: Peripheral blood was collected before and after aerobic exercise in two conditions: (I) aerobic exercise without oxygen supplementation (AE group) and (II) with oxygen supplementation (AE-O2 group). Lymphocytes were collected to perform the alkaline version of the Comet Assay. To assess the susceptibility to exogenous DNA damage, the lymphocytes were treated with methyl methanesulphonate (MMS) for 1-h or 3-h. After 3-h treatment, the percentage of residual damage was calculated assuming the value of 1-h MMS treatment as 100%. Results: AE group showed lower induced damage (1 h of MMS treatment) and consequently less DNA repair compared to AE-O2 group. AE-O2 group showed an increase in the induced DNA damage (1 h of MMS treatment) and an increased DNA repair capacity. Within the AE-O2 group, in the post-exercise situation the induced DNA damage after 1 h of MMS treatment was higher (p = 0.01) than in the pre-exercise. Conclusion: COPD patients who performed physical exercise associated with oxygen supplementation had a better response to DNA damage induced by MMS and a better DNA repair when compared to the condition of physical exercise without oxygen supplementation.Trial registration: UNISC N374.298. Registered 04 JUN 2013 (retrospectively registered).
Bibliometric analysis of worldwide publications on multi-, extensively, and totally drug – resistant tuberculosis (2006–2015)
Authors: Sweileh Waleed M. , AbuTaha Adham S. , Sawalha Ansam F. , Al-Khalil Suleiman , Al-Jabi Samah W. , Zyoud Sa'ed H.
Published: January 2020

Background: The year 2015 marked the end of United Nations Millennium Development Goals which was aimed at halting and reversing worldwide tuberculosis (TB). The emergence of drug resistance is a major challenge for worldwide TB control. The aim of this study was to give a bibliometric overview of publications on multi-, extensively, and totally drug-resistant TB. Methods: Scopus database was used to retrieve articles on multidrug resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) tuberculosis for the study period (2006–2015). The number of publications, top productive countries and institutions, citation analysis, co-authorships, international collaboration, active authors, and active journals were retrieved and analyzed. Results: A total of 2260 journal articles were retrieved. The mean ± SD citations per article was 7.04 ± 16.0. The h-index of retrieved data was 76. The number of publications showed a three – fold increase over the study period compared with less than two – fold increase in tuberculosis research during the same study period. Stratified by number of publications, the United States of America ranked first while Switzerland ranked first in productivity per 100 million people, and South Africa ranked first in productivity stratified per one trillion Gross Domestic Product. Three of the High Burden Countries (HBC) MDR-TB (India, China, and South Africa) were present in top productive countries. High percentage of international collaboration was seen among most HBC MDR-TB. Except for Plos One journal, most active journals in publishing articles on MDR, XDR, TDR-TB were in infection – related fields and in general medicine. Top 20 cited articles were published in prestigious journal such as Lancet and New England Journal of Medicine. The themes in top 20 cited articles were diverse, ranging from molecular biology, diagnostic tools, co-infection with HIV, and results of new anti-TB drugs. Conclusion: Publications on MDR, XDR and TDR – TB are increasing in the past decade. International collaboration was common. Many low resourced African and Asian countries will benefit from research leading to new diagnostic and screening technology of TB. The exchange of expertise, ideas and technology is of paramount importance in this field.
Ventilator-associated pneumonia or ventilator-induced pneumonia
Authors: Khan Zahid Hussain , Ceriana Piero , Donner Claudio F.
Published: January 2020

Ventilator-associated pneumonia currently in vogue seems to have some pitfalls as far as the nomenclature is concerned and thus it imparts an erroneous impression to the reader. As the driving force is in fact the ventilator, the phraseology should preferably be changed to ventilator-induced pneumonia to convey the in depth meaning of the term thus evading the terminology currently in practice. A new and emerging paradigm dealing with all side effects of mechanical ventilation can be helpful to solve this etymological conflict.
Implementation of GOLD consensus report in real life: results from the Velletri-Lariano (VELA) cohort
Authors: De Filippi G. , Lallini M. , De Riggi G. , Marchetti G. , Dimartino C.M. , Russetti A.M. , Ferrari E. , Pistelli R. , Magnoni M.S. , Riparbelli M. , Rizzi A. , Angeletti P.
Published: January 2020

Background: COPD is one of the leading causes of morbidity and mortality. Pharmacotherapy improves quality of life and reduces exacerbations although low adherence with prescribed treatments may represent a barrier to optimal disease management. The first objective of this paper is to report the distribution of COPD patients according to GOLD categories, in a sample of patients from a cohort study in an area of the Latium region in Italy. The second objective is to evaluate the agreement between the distributions of severity obtained from the HCPs and the experts included in the study board (Board). Methods: COPD patients were given a card to collect demographic and clinical data at baseline. Information in those cards was independently evaluated by HCPs and Board to include each patient into one of the four GOLD categories. Results: In a sample of 187 stable COPD patients, 59% male, mean age 70 year, the distribution of GOLD categories according to the Board was: 6% A, 34% B, 2% C, and 58% D. A discrepancy in GOLD classification was observed between the study board and field-based HCPs, regarding more than 50% of the patients, with a clear trend to underestimate the frequency of patients in D level (21%) and to overestimate the frequency in C level (21%). Conclusions: These results describe for the first time the distribution of COPD patients in an Italian cohort according to the GOLD categories, with the highest frequencies in levels B and D. The misclassification from HCPs may impact the therapeutic approach and the clinical outcomes.
Instant velocity and consistency of emitted cloud change by the different levels of canister filling with Metered Dose Inhalers (MDIs), but not with Soft Mist Inhalers (SMIs): a bench study
Authors: Dal Negro Roberto W. , Longo Pietro , Villanis Ziani Orestepaolo , Bonadiman Luca , Turco Paola
Published: January 2020

Background: Inhalation is the preferred route for respiratory drug delivery, but several factors contribute to the variability of the respirable dose fraction. Instant velocity and the dynamic characteristics of the droplet cloud represent crucial factors. Aim was to measure and compare the instant velocity and the consistency of emitted cloud from five different MDIs (A - Salbutamol sulphate 100mcg, GSK; B - Salbutamol sulphate 100mcg, Valeas; C - Salmeterol xinafoate/Fluticasone propionate 25/125mcg, GSK; D - Formoterol fumarate/Bechlomethasone propionate 6/100mcg, Chiesi; E - Formoterol fumarate/Fluticasone dipropionate 5/125mcg, Mundipharma) and one SMI (Tiotropium bromide 5mcg, Boehringer Ingelheim), at different distance from the nozzle and canister filling. Methods: Measurements were made at 90, 50, and 10% of canister filling, and at 5, 10, and 20 cm from the nozzle, for a total of 972 puffs. A high speed video photography protocol was adopted and high speed cameras (1.200 frames/ sec.) were used. Data were acquired by means of specialized softwares. Temperature, humidity, and vibrations occurrence were strictly controlled during measurements. Statistics: Anova and p < 0.05 were accepted as the minimum significance level. Results: MDIs generated different Instant velocities: MDI B generated the highest, while MDI A the lowest. As expected, velocity decreased in proportion to the distance from the nozzle. Except with MDI C, instant velocity decreased significantly over the first 50% of canister emptying, but dropped by >33% at 90% of emptying with all other MDIs (p < 0–037; p < 0.001; p < 0.005, and p < 0.001, respectively). Instant velocity was extremely lower (p < 0.001) and constant for all levels of canister filling (p = ns) with SMI. All MDIs had a very fast jet phase, ranging 0.01–0.03 s at 10 cm, and 0.03–0.05 s at 20 cm from the nozzle, without any significant difference from each other (p= ns). MDIs generated a cloud similarly tight (p = ns) at 10 and 20 cm from the nozzle, while it was extremely wider and constant with the SMI (p = 0–001). Also the cloud turbulence was minimized during the SMI emission. Discussion and Conclusions: MDIs are characterized by a substantial variability in both their instant velocity and consistency of the emitted cloud at different levels of canister filling. SMI generates a much slower soft mist cloud which is constantly homogeneous and independent of canister emptying. These peculiarities assessed at bench are suggesting a higher dose consistency and a much more effective therapeutic performance also in real life.