bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal Adsorption in Biomass: Fundamentals and Application
Authors: Canuto M.F.C. Silva , Ferreira J. Morais , Silva S.W.C. Araújo , de Sousa Conrado Líbia , Alsina Odelsia Leonor Sánchez , Silva F.L.H.
Published: January 2020

In this chapter the adsorption fundamentals using biomass as adsorbents in the removal of metallic ions are presented. The research as shows the importance of many factors that affects the adsorption, such as the biomass superficial area, system temperature, pH, initial concentration of the metal, biomass amount and status (living or dead). The study was directed at the approach of two applications using Saccharomyces cerevisiae yeast in the adsorption of Cd2+ metal ions. In the first application it is discussed the influence of the pH of the medium and the biomass status (living or dead) in the adsorption of Cd2+, in batch. In the second application, it was studied the adsorption of Cd2+metallic ions through the Saccharomyces cerevisiae yeast immobilized in chitosan, in fixed bed, where the influence inlet mass flow rate and the initial effluent concentration on the adsorption capacity and percentage of Cd2+ ions removal are evaluated.The studies realized are supported by statistical analysis with 95% confidence intervals.
Small GTPase ARF6 Is a Coincidence-Detection Code for RPH3A Polarization in Neutrophil Polarization
Authors: Ren Chunguang , Yuan Qianying , Jian Xiaoying , Randazzo Paul A. , Tang Wenwen , Wu Dianqing
Published: January 2020

Cell polarization is a key step for leukocytes adhesion and transmigration during leukocytes’ inflammatory infiltration. Polarized localization of plasma membrane (PM) phosphatidylinositol-4-phosphate (PtdIns4P) directs the polarization of RPH3A, which contains a PtdIns4P binding site. Consequently, RPH3A mediates the RAB21 and PIP5K1C90 polarization, which is important for neutrophil adhesion to endothelia during inflammation. However, the mechanism by which RPH3A is recruited only to PM PtdIns4P rather than Golgi PtdIns4P remains unclear. By using ADP-ribosylation factor 6 (ARF6) small interfering RNA, ARF6 dominant-negative mutant ARF6(T27N), and ARF6 activation inhibitor SecinH3, we demonstrate that ARF6 plays an important role in the polarization of RPH3A, RAB21, and PIP5K1C90 in murine neutrophils. PM ARF6 is polarized and colocalized with RPH3A, RAB21, PIP5K1C90, and PM PtdIns4P in mouse and human neutrophils upon integrin stimulation. Additionally, ARF6 binds to RPH3A and enhances the interaction between the PM PtdIns4P and RPH3A. Consistent with functional roles of polarization of RPH3A, Rab21, and PIP5K1C90, ARF6 is also required for neutrophil adhesion on the inflamed endothelial layer. Our study reveals a previously unknown role of ARF6 in neutrophil polarization as being the coincidence-detection code with PM PtdIns4P. Cooperation of ARF6 and PM PtdIns4P direct RPH3A polarization, which is important for neutrophil firm adhesion to endothelia.
Pyruvate Kinase M2 Promotes Expression of Proinflammatory Mediators in House Dust Mite–Induced Allergic Airways Disease
Authors: van de Wetering Cheryl , Aboushousha Reem , Manuel Allison M. , Chia Shi B. , Erickson Cuixia , MacPherson Maximilian B. , van der Velden Jos L. , Anathy Vikas , Dixon Anne E. , Irvin Charles G. , Poynter Matthew E. , van der Vliet Albert , Wouters Emiel F. M. , Reynaert Niki L. , Janssen-Heininger Yvonne M. W.
Published: January 2020

Asthma is a chronic disorder characterized by inflammation, mucus metaplasia, airway remodeling, and hyperresponsiveness. We recently showed that IL-1–induced glycolytic reprogramming contributes to allergic airway disease using a murine house dust mite model. Moreover, levels of pyruvate kinase M2 (PKM2) were increased in this model as well as in nasal epithelial cells from asthmatics as compared with healthy controls. Although the tetramer form of PKM2 converts phosphoenolpyruvate to pyruvate, the dimeric form of PKM2 has alternative, nonglycolysis functions as a transcriptional coactivator to enhance the transcription of several proinflammatory cytokines. In the current study, we examined the impact of PKM2 on the pathogenesis of house dust mite–induced allergic airways disease in C57BL/6NJ mice. We report, in this study, that activation of PKM2, using the small molecule activator, TEPP46, augmented PKM activity in lung tissues and attenuated airway eosinophils, mucus metaplasia, and subepithelial collagen. TEPP46 attenuated IL-1β–mediated airway inflammation and expression of proinflammatory mediators. Exposure to TEPP46 strongly decreased the IL-1β–mediated increases in thymic stromal lymphopoietin (TSLP) and GM-CSF in primary tracheal epithelial cells isolated from C57BL/6NJ mice. We also demonstrate that IL-1β–mediated increases in nuclear phospho-STAT3 were decreased by TEPP46. Finally, STAT3 inhibition attenuated the IL-1β–induced release of TSLP and GM-CSF, suggesting that the ability of PKM2 to phosphorylate STAT3 contributes to its proinflammatory function. Collectively, these results demonstrate that the glycolysis-inactive form of PKM2 plays a crucial role in the pathogenesis of allergic airways disease by increasing IL-1β–induced proinflammatory signaling, in part, through phosphorylation of STAT3.
B Cell Endosomal RAB7 Promotes TRAF6 K63 Polyubiquitination and NF-κB Activation for Antibody Class-Switching
Authors: Yan Hui , Fernandez Maria , Wang Jingwei , Wu Shuai , Wang Rui , Lou Zheng , Moroney Justin B. , Rivera Carlos E. , Taylor Julia R. , Gan Huoqun , Zan Hong , Kovalskyy Dmytro , Liu Dongfang , Casali Paolo , Xu Zhenming
Published: January 2020

Upon activation by CD40 or TLR signaling, B lymphocytes activate NF-κB to induce activation-induced cytidine deaminase and, therefore, Ig class switch DNA recombination, as central to the maturation of the Ab and autoantibody responses. In this study, we show that NF-κB activation is boosted by colocalization of engaged immune receptors, such as CD40, with RAB7 small GTPase on mature endosomes, in addition to signals emanating from the receptors localized on the plasma membrane, in mouse B cells. In mature endosomes, RAB7 directly interacts with TRAF6 E3 ubiquitin ligase, which catalyzes K63 polyubiquitination for NF-κB activation. RAB7 overexpression in Cd19+/creRosa26fl-STOP-fl-Rab7 mouse B cells upregulates K63 polyubiquitination activity of TRAF6, enhances NF-κB activation and activation-induced cytidine deaminase induction, and boosts IgG Ab and autoantibody levels. This, together with the extensive intracellular localization of CD40 and the strong correlation of RAB7 expression with NF-κB activation in mouse lupus B cells, shows that RAB7 is an integral component of the B cell NF-κB activation machinery, likely through interaction with TRAF6 for the assembly of “intracellular membrane signalosomes.”
Calcitriol Regulates the Differentiation of IL-9–Secreting Th9 Cells by Modulating the Transcription Factor PU.1
Authors: Vyas Shachi Pranjal , Hansda Arman Kunwar , Kaplan Mark H. , Goswami Ritobrata
Published: January 2020

Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been associated with various autoimmune diseases. Th9 cells are implicated in the pathogenesis of numerous autoimmune diseases. Thus, we investigated the role of calcitriol (active metabolite of vitamin D) in the regulation of Th9 cell differentiation. In this study, we have unraveled the molecular mechanisms of calcitriol-mediated regulation of Th9 cell differentiation. Calcitriol significantly diminished IL-9 secretion from murine Th9 cells associated with downregulated expression of the Th9-associated transcription factor, PU.1. Ectopic expression of VDR in Th9 cells attenuated the percentage of IL-9–secreting cells. VDR associated with PU.1 in Th9 cells. Using a series of mutations, we were able to dissect the VDR domain involved in the regulation of the Il9 gene. The VDR–PU.1 interaction prevented the accessibility of PU.1 to the Il9 gene promoter, thereby restricting its expression. However, the expression of Foxp3, regulatory T cell–specific transcription factor, was enhanced in the presence of calcitriol in Th9 cells. When Th9 cells are treated with both calcitriol and trichostatin A (histone deacetylase inhibitor), the level of IL-9 reached to the level of wild-type untreated Th9 cells. Calcitriol attenuated specific histone acetylation at the Il9 gene. In contrast, calcitriol enhanced the recruitment of the histone modifier HDAC1 at the Il9 gene promoter. In summary, we have identified that calcitriol blocked the access of PU.1 to the Il9 gene by reducing its expression and associating with it as well as regulated the chromatin of the Il9 gene to regulate expression.
LOS SENTIDOS DE PERTENENCIA DE LOS JÓVENES QUE PARTICIPAN EN EL MOVIMIENTO MASORTÍ EN LA CIUDAD AUTÓNOMA DE BUENOS AIRES. PERCEPCIONES SOBRE EL MOVIMIENTO Y LA “COMUNIDAD”
Authors: Lerner Vanesa Cynthia
Published: January 2020

En este artículo se analizan los sentidos de pertenencia de los jóvenes que  participan en el movimiento masortí en la Ciudad Autónoma de Buenos Aires en la actualidad. Sus percepciones sobre el movimiento masortí en general y sobre su “comunidad” en particular muestran que no siempre existe una relación lineal entre ambos. Para ello se utilizó una metodología cualitativa, valiéndose del enfoque interpretativo. Por medio de observaciones participantes y de 32 entrevistas semi-estructuradas en profundidad realizadas entre febrero de 2016 y septiembre de 2017 se pudo evidenciar el modo en que las dinámicas de centralización y descentralización del movimiento masortí inciden en sus construcciones identitarias.
Cough variant asthma and atopic cough
Authors: Magni Chiara , Chellini Elisa , Zanasi Alessandro
Published: January 2020

Chronic cough has been reported to be the fifth most com- mon complaint seen by primary care physicians in the world, the third in Italy. Chronic cough in non-smoking, non-treated with ACE-inhibitor adults with normal chest radiogram could be a symptom of asthma and can be sub-classified into: cough-variant asthma, atopic cough, and eosinophilic bron- chitis. This review discusses the differential diagnosis of these three disorders.
Role of quantitative CT in predicting postoperative FEV1 and chronic dyspnea in patients undergoing lung resection
Authors: Papageorgiou Chrysovalantis V. , Antoniou Dimosthenis , Kaltsakas Georgios , Koulouris Nikolaos G.
Published: January 2020

Lung resection is the mainstay of treatment in patients with early stage non-small cell lung cancer. However, lung cancer patients often suffer from comorbidities and the respiratory reserve should be carefully evaluated preoperatively in order to avoid postoperative complications. Forced expiratory vol- ume in 1 second (FEV1) is considered to be an index that depicts the patient’s respiratory efficacy and its prediction has a key role in the preoperative evaluation of lung cancer patients with impaired lung function. Prediction of postoperative FEV1 is currently possible with the use of perfusion radionuclide lung scanning. Quantitative CT is the analysis of data acquired during nor- mal chest CT scan using the system’s software. By applying a dual threshold of -500 to -910 Hounsfield Units, functional lung volumes are estimated and postoperative FEV1 can be predicted by reducing the preoperative measurement by the fraction of the part to be resected. Studies have shown that preoperative predictions correlate well with the actual postoperative measurements. Additionally, quantitative CT results are in good agreement with perfusion scintigraphy predictions. Newer radiological techniques such as perfusion MRI and co-registered SPECT/CT have also been used in the preoperative evaluation with similar results. In conclusion, chest CT which is obligatory for staging, can be used for quantitative analysis of the already available data. It is technically simple, providing an accurate prediction of postoperative FEV1. Thus, quantitative CT appears to be a useful tool in the preoperative evaluation of lung cancer patients undergoing lung resection.
Qualitative aspects of exertional dyspnea in patients with restrictive lung disease
Authors: Laveneziana Pierantonio
Published: January 2020

Restrictive lung disease is a broad term encompassing a num- ber of conditions in which lung volumes are reduced. Dyspnea is a common clinical manifestation of restrictive lung disease and frequently becomes a prominent and disabling symptom that undermines patients’ ability to function and engage in activities of daily living (especially in those with more advanced restriction). Effective management of this disabling symptom awaits a better understanding of its underlying physiology. In recent decades, our understanding of the mechanisms of dyspnea in restrictive lung disease has been improved by a small, but significant, body of research. One approach to the study of dyspnea is to identify the major qualitative dimensions of the symptom in an attempt to uncover different underlying neurophysiologic mechanisms. This article will review the existing literature on the intensity and qualitative dimensions of dyspnea during exercise in patients with restrictive lung disease. The main focus will be on interstitial lung disease (ILD), since it is the prototypical restrictive disease.
Does urban asthma exist? How climatic changes and urban air pollution intervene on asthma and respiratory allergy
Authors: Annesi-Maesano Isabella
Published: January 2020

In his important article, Gennaro D’Amato pro- vides elements that contribute to reply to two burn- ing questions of the present time. How bad is the fact of living in a city for asthma and, more gener- ally, for respiratory allergy? And to what extent [...]
Effects of climatic changes and urban air pollution on the rising trends of respiratory allergy and asthma
Authors: D'Amato Gennaro
Published: January 2020

Over the past two decades there has been increasing interest in studies regarding effects on human health of climate changes and urban air pollution. Climate change induced by anthropogenic warming of the earth’s atmosphere is a daunt- ing problem and there are several observations about the role of urbanization, with its high levels of vehicle emissions and other pollutants, and westernized lifestyle with respect to the rising frequency of respiratory allergic diseases observed in most industrialized countries. There is also evidence that asthmatic subjects are at increased risk of developing exacerbations of bronchial obstruction with exposure to gaseous (ozone, nitrogen diox- ide, sulfur dioxide) and particulate inhalable components of air pollution.

A change in the genetic predisposition is an unlikely cause of the increasing frequency in allergic diseases because genetic changes in a population require several generations. Consequently, environmental factors such as climate change and indoor and outdoor air pollution may contribute to explain the increasing frequency of respiratory allergy and asthma. Since concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increas- ing frequency of allergic respiratory diseases and bronchial asthma. Scientific societies such as the European Academy of Allergy and Clinical Immunology, European Respiratory Society and the World Allergy Organization have set up committees and task forces to produce documents to focalize attention on this topic, calling for prevention measures.
Renal transplant improves pulmonary hypertension in patients with end stage renal disease
Authors: Bozbas Serife Savas , Kanyilmaz Suleyman , Akcay Sule , Bozbas Huseyin , Altin Cihan , Karacaglar Emir , Muderrisoglu Haldun , Haberal Mehmet
Published: January 2020

Background: Pulmonary hypertension (PH) is present in a sig- nificant proportion of patients with end stage renal disease (ESRD) and is of prognostic importance. Data on the effect of renal transplant on PH is very limited. In this study, the aim was to examine the effect of renal transplant on systolic pul- monary artery pressure (SPAP) determined by Doppler echocardiography.

Methods: Analysis was performed on the records of 500 con- secutive patients who underwent renal transplant at our cen- ter between the years 1999 to 2008. The prevalence of PH in the preoperative assessment period was established. Patients were diagnosed as having PH when measured SPAP values were > 35 mm Hg.

Results: Pulmonary hypertension was detected in 85 of the 500 (17%) patients under pre-transplant evaluation. At post-transplant follow up Doppler echocardiographic exam- ination was performed on 50 of the 85 patients. After exclu- sion of 8 cases (1 due to massive pulmonary thromboem- boli; 7 due to graft failure requiring dialysis therapy) analy- ses were performed on 42 patients who had undergone both pre- and post-transplant echocardiographic examination. Mean SPAP at pre-transplant evaluation was 45.9 ± 8.8 mm Hg and in 6 (14.3%) cases SPAP was above 50 mm Hg. Compared to pre-transplant values, a significant decrease was observed in mean SPAP values in an average of 53 months of postoperative follow up (41.8 ± 7.4 mm Hg vs. 45.9 ± 8.8 mm Hg, p < 0.0001).

Conclusion: These findings indicate that patients with ESRD accompanied by PH may benefit from renal transplant. Further research is required for more concrete conclusions to be drawn on this subject.
Persistence of systemic inflammation in COPD in spite of smoking cessation
Authors: Invernizzi Giovanni
Published: January 2020

Cigarette smoking, which exposes the lung to high concentrations of reactive oxygen species (ROS), is the major risk factor for chronic obstructive pul- monary disease (COPD). ROS are responsible for lipid peroxidation, protein oxidation [...]
Photoacoustic technique: a new method for measuring the rheologic properties of human bronchial mucus
Authors: De Oliveira Luis V.F. , De Faria Jr. Newton S. , Garcia Gonzaga Napoleone Fernanda M. , Ingraci Barboza Marcelo A. , Studart Leitão Filho Fernando S. , De Mattos Luiz C. , Donner Claudio F. , Barja Paulo R.
Published: January 2020

Patients affected by obstructive pulmonary diseases exhibit typical characteristics of airway mucus hypersecretion, including sputum production, in- creased luminal mucus, goblet cell hyperplasia and submucosal gland hypertrophy. The mucociliary system is a sophisticated defense mechanism to maintain the homeostasis of the respiratory tract by means of the bronchial mucus transport, the process in which airway mucus together with substances trapped within are moved out of the lungs. In the end, the mucus together with the substances trapped within are swallowed or coughed up. It is an impor- tant defense mechanism of the human body. [...]
Does asthma control as assessed by the asthma control test reflect airway inflammation?
Authors: Bora Mine , Alpaydin Aylin Ozgen , Yorgancioglu Arzu , Akkas Gizem , Isisag Aydın , Coskun Aysın Sakar , Celik Pınar
Published: January 2020

Background and aims: The treatment of asthmatic patients is particularly focused on the control of symptoms as well as functional and inflammatory parameters. In our study, we investigated the relationship between the asthma control test (ACT) which evaluates symptoms and airway inflammation and functional parameters.

Materials and methods: Stable asthmatic patients admitted to our pulmonary outpatient clinic were enrolled in the study consecutively and underwent the ACT, pulmonary function tests and methacholine bronchial provocation test (MBPT). Additionally, fractional exhaled nitric oxide level (FeNO) and induced sputum cell distribution were assessed. All these parameters were re-evaluated at the third month after adjusting medications of the patients according to baseline ACT scores.

Results: Of the 101 patients screened, we analyzed 83 who proceeded to the follow up visit. At the baseline visit, 8 were totally controlled, 36 partially controlled and 39 uncontrolled according to ACT. At the follow up visit, 10 were totally controlled, 39 partially controlled and 34 uncontrolled. Comparison of the two visits in terms of all parameters revealed significant reductions only in the percentages of patients with MBPT positivity (p = 0.029) and FeNO levels > 20 ppb (p = 0.025) at follow up. The percentages of patients with FeNO > 20 ppb, MBPT positivity, induced sputum eosinophilia or induced sputum neutrophilia did not show significant differences between totally controlled, partially controlled and uncontrolled groups at both baseline and follow up visits.

Conclusion: Although the ACT scores did not show significant correlations with the airway inflammation parameters tested in this study, a marked reduction in the percentage of patients with MBPT positivity and FeNO > 20 ppb at follow up may suggest the importance of the control concept in the management of asthma.
Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages
Authors: Huang Quan-Yong , Chen Yu-Chuan , Liu Shui-Ping
Published: January 2020

Background: Alcohol abuse is involved in the pathogenesis of multiple organ disorders; the underlying mechanism is incompletely understood. The ubiquitin editing enzyme A20 is involved in regulating activities in the cell. Suppression of A20 is suggested as one factor in the initiation of  inflammation. This study investigates the mechanism by which chronic alcohol consumption modulates the levels of ubiquitin editing enzyme A20 in macrophages and further contributes to induce endothelial barrier dysfunction in the lung.

Methods: Mice were gavage-fed with 40% alcohol daily for 0- 3 weeks. Airway macrophages were collected by lung lavage. Expression of ubiquitin editing enzyme A20 in isolated macrophages was assessed at both mRNA and protein levels. The endothelial barrier function of the lung was evaluated by the Evans blue method.

Results: Mice treated with alcohol for 3 weeks showed an increase in cell infiltration in the lung in response to exposure to peptidoglycan; over 80% of the infiltrated cells were macrophages. Furthermore, we observed that A20 level was suppressed in macrophages of mice treated with alcohol; the levels of tumor necrosis factor, interleukin-6 and nuclear factor kappa B in macrophage were increased. In addition, the endothelial barrier function of the lung was compromised, showing excessive infiltration of Evans blue in the lung indicating lung edema. Pretreatment with synthesized A20 inhibited alcohol-induced lung endothelial barrier dysfunction.

Conclusions: We conclude that chronic alcohol ingestion disturbs the endothelial barrier function in the lung by modulating macrophage properties. Increase in A20 in the cell may have potential for the treatment of inflammatory disorders.
Re-admissions to hospital and patient satisfaction among patients with chronic obstructive pulmonary disease after telemedicine video consultation - a retrospective pilot study
Authors: Saleh Safaa , Larsen Jan Petter , Bergsåker-Aspøy Johannes , Grundt Heidi
Published: January 2020

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of acute hospital admissions. The main object of our study was to evaluate the effects of telemedicine video-consultation (TVC) on the frequency of hospital re-admissions due to COPD exacerbations. Our secondary aim was to assess the impact of TVC on the length of re-admission stays within 6 and 12 months follow up after TVC. Patient satisfaction was also evaluated.

Methods: The study was a retrospective observational study of COPD patients who after hospital discharge or during outpatient treatment for acute COPD exacerbations, were monitored for 2 weeks by TVC at home by a specialist nurse at the hospital during a pilot project period. Retrospectively, we compared the frequencies (chi-square test) and durations of hospital re-admissions (paired t-test) due to COPD exacerbations within 6 and 12 months follow up after TVC to comparable events 6 and 12 months prior to TVC.

Results: Among 99 patients followed for 6 months after TVC, 56 were followed for totally 12 months. The number of patients re-admitted and the number of re-admissions due to COPD exacerbations were not reduced within 6 or 12 months post-TVC, as compared to 6 and 12 months pre-TVC. The mean length of re-admission stays within 12 months post-TVC was markedly reduced as compared to pre-TVC. Patients hospitalised the last 6 and 12 months pre-TVC, had significantly shorter re-admission stays, p = 0.033 and p = 0.001, respectively. Patient satisfaction was high.

Conclusion: Despite the failure to demonstrate reduced frequency of re-admissions within 6 and 12 months post-TVC, the re-admission length within 12 months post-TVC was markedly reduced as compared to pre-TVC. The patient satisfaction was high. Future prospective, randomised, controlled trials must be performed before TVC can be recommended in COPD management.
Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection
Authors: Ostermann Carola , Linde Susanna , Siegling-Vlitakis Christiane , Reinhold Petra
Published: January 2020

Background: Chlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aims at quantifying and differentiating pulmonary dysfunction and acid–base imbalances induced by Cp.

Methods: Forty-two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls shaminoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and FRC (functional residual capacity) measurement were applied to spontaneously breathing animals. Variables of acid–base status were assessed in venous blood using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach.

Results: Both obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. Although disorders in respiratory mechanics lasted for 8–11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume (−25%) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10%. Minute ventilation increased significantly (+50%) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2–3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid–base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2–10 dpi), a negative acute-phase marker, resulted in a decrease in the sum of non-volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects of decreased strong ion difference (SID), mediated by the interplay between hypochloraemia (alkalotic effect) and hyponatraemia (acidic effect).

Conclusions: This bovine model was found to be suitable for studying pathophysiology of respiratory Cp infection and may help elucidating functional host-pathogen interactions in the mammalian lung.
Audit on the appropriateness of integrated COPD management: the “ALT-BPCO” project
Authors: Nardini Stefano , Cicchitto Gaetano , De Benedetto Fernando , Donner Claudio F. , Polverino Mario , Sanguinetti Claudio M. , Visconti Alberto , The ALT-BPCO Group And on behalf of
Published: January 2020

Background: Non communicable chronic diseases (including respiratory ones) are the leading cause of deathand disability. To cope with them we need to redesign the health system, improving primary prevention, screening, and outpatient services, while fully integrating different branches of the health service. The Italian Ministry of Health published extended guidelines on integrated COPD management (COPD-GL) in 2010. In2011 a condensed version was produced. These documents define appropriateness of management regarding both the specialist and the health service.

Methods: An internal audit on how clinical practice conforms to COPD-GL standards was implemented in one Italian region involving 29 respiratory units (RU) (65.8% of the total regional RU): data were collected from the clinical database at time zero and after 6 months. In the meantime, specialists of RU underwent education on COPD-GL.

Results: At time zero, significant gaps between current practice and recommendations emerged both in medical practice (mean agreement 25%) and in the health organization (48%). At month 6 the gaps were reduced more in clinical practice (60.7%) than in organization (54.7%).

Conclusions: It is easier to resolve the gaps in specialist clinical practice than the organizational gaps, changing which is the politicians’ task. Correcting specialists’ inappropriateness may be worthless if this is not accompanied by improvement of the organizational obstacles. The search for appropriateness should not be limited only to specialists or to a strict control of drug prescription but should include all the organizational aspects. Implementation of COPD-GL calls for actions on the part of both specialists and the health system.
CAT correlates positively with respiratory rate and is a significant predictor of the impact of COPD on daily life of patients: a cross sectional study
Authors: Becker Cíntia , Schäfer Janaína , Carvalho Lisiane L. , Vitiello Isabel P. , Da Silva Andréa L.G.
Published: January 2020

Background: The pathophysiological changes of COPD tend to worsen with progression, triggering limiting symptoms and implying the decrease in the activities of daily living and quality of life. The COPD Assessment Test (CAT) is a questionnaire designed to measure the impact of COPD on the health status. The aim of this study was to evaluate the impact of the disease through the CAT in a Brazilian sample of COPD patients and to correlate symptoms at rest with the CAT score in these patients.

Methods: Study of cases with COPD patients was conducted by pulmonary rehabilitation program (RP). Respiratory rate (RR) and symptoms (dyspnea by Modified Borg Scale Dyspnea Index; symptoms by CAT) were analyzed at the beginning of the RP.

Results: The study analyzed 28 COPD patients, both genders, age 65.93 ± 7.84 years and many patients ranging from severe and very severe disease. The majority of patients were rated by CAT with low impact-disease (n = 13/46, 4%); medium (n = 11/39, 3%) and the high impact-diseases were observed in a few subjects (n = 4/14.3%). The difference between all CAT scores was significant, p = 0.000. There was a positive correlation between respiratory rate and CAT scores impact-level (r = 0.585, p = 0.001). The results obtained by the Borg Scale revealed a high presence of symptoms in these COPD patients but no association with CAT.

Conclusion: The CAT is a sensitive tool to assess the current health status of COPD patients, and in Southern Brazil it is positively correlated with respiratory rate.
A novel biomarker in the diagnosis of parapneumonic effusion: neutrophil gelatinase-associated lipocalin
Authors: Gümüs Aziz , Ozkaya Sevket , Ozyurt Songul , Cınarka Halit , Kirbas Aynur , Sahin Unal
Published: January 2020

Background: The protein neutrophil gelatinase-associated lipocalin (NGAL) is a mediator synthesized and released by neutrophils. Its physiological function is as yet unclear. Levels in blood increase in several inflammatory diseases. High serum values indicate poor prognosis for several diseases. Pleural effusion may appear as the result of various pathologies. The most common cause is heart failure (HF). Other common causes include parapneumonic (PPE) and malignant (MPE) pleural effusions, and pulmonary embolism. Tubercular effusion (TE) is commonly encountered in Turkey and similar developing countries. The purpose of this study was to investigate the effectiveness of NGAL, a current inflammation marker, in discriminating between different etiological diseases that cause pleural effusion.

Methods: The study was performed at the Recep Tayyip Erdoğan University Faculty of Medicine Chest Diseases Clinic. One hundred patients were included in the study, 25 with parapneumonic effusion, 25 with heart failure-related effusion, 25 with tubercular effusion and 25 with cancer-related effusion. NGAL was measured in patients’ serum and pleural fluids.

Results: Serum NGAL levels in PPE (171 ± 56 ng/ml) were significantly higher (p < 0.001) than those in HF (86 ±31 ng/ml), CA (103 ± 42 ng/ml) and TE (63 ± 19 ng/ml). Pleural NGAL levels were also significantly higher in PPE compared to HF, MPE and TE (p < 0.001). Serum NGAL levels exhibited a positive correlation with white blood cell (WBC), neutrophil, C-reactive protein (CRP), sedimentation, serum LDH, creatinine, pleural leukocyte and pleural neutrophil numbers. The most significant correlation was between NGAL level and WBC (p < 0.001, r = 0.579). Both serum and pleural NGAL levels are highly effective in differentiating patients with PPE from those without PPE (AUC: 0.910 and 0.790, respectively).

Conclusions: NGAL can be used in the diagnosis of diseases with an acute inflammatory course. Serum and pleural NGAL levels can differentiate PPE from other diseases causing pleural fluid with high sensitivity and specificity.
The association of human leukocyte antigen polymorphisms with disease severity and latency period in patients with silicosis
Authors: Dogan Hasan , Akgun Metin , Araz Omer , Ucar Elif Yilmazel , Yoruk Ozgur , Diyarbakir Eda , Atis Omer , Akdemir Fatih , Acemoglu4 Hamit , Pirim Ibrahim
Published: January 2020

Background: Denim sandblasting may cause silicosis as a result of free crystalline silica inhalation. Its pathogenesis remains unclear, but autoimmunity may play a role in the development of silicosis. The present study aimed to investigate the relationships between human leukocyte antigen (HLA) and the severity and latency period of silicosis.

Methods: 48 silicotic patients in the Eastern part of Turkey were classified according to their latency period and disease severity. The distribution of HLAs according to disease severity and latency period was assessed.

Results: A23 (7.5%), B49 (7.5%), and B51 (25%) were more common in the mild group than in the severe group, and B55 (8.9%) and DR4 (17.9%) were more common in the severe group than in the mild one. Only B51 was significantly more common in the mild group than in the severe one (25%, n = 10 vs. 7.1%, n = 4; p = 0.016).

Conclusions: This study suggests that HLA antigens may play a particular role in the severity of silica-induced lung disease, but there was no association between HLA and progression time of the disease.
The ethics of forgoing life-sustaining treatment: theoretical considerations and clinical decision making
Authors: Welie Jos V.M. , Ten Have Henk A.M.J.
Published: January 2020

Withholding or withdrawing a life-sustaining treatment tends to be very challenging for health care providers, patients, and their family members alike. When a patient’s life seems to be nearing its end, it is generally felt that the morally best approach is to try a new intervention, continue all treatments, attempt an experimental course of action, in short, do something. In contrast to this common practice, the authors argue that in most instances, the morally safer route is actually to forgo life-sustaining treatments, particularly when their likelihood to effectuate a truly beneficial outcome has become small relative to the odds of harming the patient. The ethical analysis proceeds in three stages. First, the difference between neglectful omission and passive acquiescence is explained. Next, the two necessary conditions for any medical treatment, i.e., that it is medically indicated and that consent is obtained, are applied to life-sustaining interventions. Finally, the difference between withholding and withdrawing a life-sustaining treatment is discussed. In the second part of the paper the authors show how these theoretical- ethical considerations can guide clinical-ethical decision making. A case vignette is presented about a patient who cannot be weaned off the ventilator post-surgery. The ethical analysis of this case proceeds through three stages. First, it is shown that and why withdrawal of the ventilator in this case does not equate assistance in suicide or euthanasia. Next, the question is raised whether continued ventilation can be justified medically, or has become futile. Finally, the need for the health care team to obtain consent for the continuation of the ventilation is discussed.
INDACO project: COPD and link between comorbidities, lung function and inhalation therapy
Authors: Fumagalli Giorgio , Fabiani Fabrizio , Forte Silvia , Napolitano Massimiliano , Balzano Giovanni , Bonini Matteo , De Simone Giuseppe , Fuschillo Salvatore , Pentassuglia Antonella , Pasqua Franco , Alimonti Pietro , Carlone Stefano
Published: January 2020

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by respiratory and extrarespiratory components referring both to systemic complications of COPD, like skeletal muscle myopathy, weight loss and others, and frequently associated comorbidities, interesting various organs and systems (cardiovascular diseases, malignancies, osteoporosis, diabetes, etc.). These comorbidities may increase the rate of hospitalization of COPD patients and have a huge effect on the outcomes of the respiratory disease. Inhalation therapy of COPD with bronchodilators and steroid is primary driven by airflow obstruction, symptoms like dyspnoea, and acute exacerbations. INDACO project has been developed in 2013 to assess the prevalence and type of comorbidities in COPD patients referred to the outpatient wards of some hospitals in Central and South Italy and a preliminary report has recently been published. In the present study, after widening that database, we evaluate the prevalence of comorbidities and the relationships between comorbidities and sex, age, symptoms, lung function and inhalation therapy in COPD patients.

Methods: In each enrolled patient, anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for Chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI) were recorded.

Results: We collected data of 569 patients (395 males and 174 females, mean age 73 ± 8.5 yrs). The prevalence of patients with comorbidities was 81.2%. Overall number of comorbidities was not related to airflow obstruction and age, but to acute exacerbation of COPD, dyspnoea measured with MRC scale, and male gender. A subgroup analysis revealed that ischaemic heart disease was predominant in males, whereas mood disorders in females. The use of a more complex (multi-drug) inhalation therapy was related with bronchial obstruction measured by FEV1/FVC (p for trend = 0.003) and number of comorbidities (p for trend = 0.001). In multivariate analysis, only airflow obstruction and number of comorbidities were determinant of complexity of therapy, but not MRC and acute exacerbation of COPD. However, the statistical model reached an extreme low degree of significance (r^2 = 0.07).

Conclusions: Our study showed a high prevalence of comorbidities in COPD, with some differences related to gender. Number of comorbidities and airflow obstruction represent the determinant of inhalation therapy prescription. Dyspnoea and acute exacerbation of COPD, unlikely suggested by guidelines, are not significant drivers of therapy in the real life setting of our study.
Reviewer acknowledgement 2014
Authors: De Benedetto Fernando , Donner Claudio F. , Sanguinetti Claudio M.
Published: January 2020

Contributing reviewers

 

The editors of Multidisciplinary Respiratory Medicine would like to thank all of our reviewers who have contributed to the journal in Volume 9 (2014).
Recommendations for the early diagnosis of COPD: the AIMAR view
Authors: Celli Bartolome R.
Published: January 2020

Chronic obstructive pulmonary disease (COPD) has the dubious distinction of being one of the few major causes of death that continues to rise in the United States and the world. In that sense, its prevention, early diagno- sis when clinically present, and finally its appropriate treatment should constitute a priority item in today’s health care agenda. [...]
Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 2007–2010
Authors: Kurth Laura , Hnizdo Eva
Published: January 2020

Background: Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988–1994 to 2007–2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restrictive pattern rather than the age-defined American Thoracic Society (ATS)/European Respiratory Society (ERS) lower limit of normal (LLN) criteria, which may lead to misclassification.

Methods: Spirometry measurements from NHANES data for the 1988–1994 and 2007–2010 periods were analyzed to estimate the age-standardized prevalence of a restrictive pattern on spirometry and the change in prevalence over time for adults aged 20–79. A restrictive pattern was defined based on ATS/ERS LLN criteria as FEV1/FVC > LLN and FVC < LLN, and a moderate to more severe restrictive pattern was further evaluated using FEV1 < 70% predicted. The associations between demographic and other individual risk factors for restrictive lung impairment were examined using multivariable logistic regression models for the two consecutive time periods.

Results: The overall age-standardized prevalence of restrictive pattern decreased significantly from 7.2% (1988–1994) to 5.4% (2007–2010) (p = 0.0013). The prevalence of moderate to more severe restrictive pattern also decreased significantly from 2.0% to 1.4% (p = 0.023). Factors positively associated with restrictive pattern on spirometry included age, female sex, white race, lower education, former and current smoking, and comorbidities including doctor-diagnosed cardiovascular disease, doctor-diagnosed diabetes, and abdominal obesity.

Conclusions: The overall prevalence of restrictive pattern and moderate to more severe restrictive pattern decreased between the 1988–1994 and 2007–2010 survey periods despite a population increase in the proportion of comorbidities associated with restrictive pattern (i.e. diabetes and abdominal obesity). This suggests a decline in individual risk factors for restrictive pattern and a need for future research.
Recurrent lung atelectasis from fibrin plugs as a very early complication of bronchial thermoplasty: a case report
Authors: Facciolongo Nicola , Menzella Francesco , Lusuardi Mirco , Piro Roberto , Galeone Carla , Castagnetti Claudia , Cavazza Alberto , Carbonelli Cristiano , Zucchi Luigi , Salsi Pier Paolo
Published: January 2020

Background: Bronchial thermoplasty (BT) is a new therapeutic option for severe refractory asthma not controlled despite high dose inhaled corticosteroids plus long-acting bronchodilators and omalizumab in selected cases. Risk of pulmonary atelectasis after BT in severe asthma has been described in literature, but no details have been reported on the possible mechanisms of the complication.

Case presentation: A 49-year-old male with severe uncontrolled asthma was referred to BT. One hour after the first procedure, acute respiratory failure occurred with PaO2/FiO2 < 300. A CT scan showed atelectasis of the right lower and middle lobes. A new bronchoscopy was performed under non-invasive ventilation; the right lower and middle lobe bronchus were occluded by bronchus-shaped plugs, that were very difficult to remove despite repeated saline washings and fragmentation with forceps. The patient had a rapid resolution of respiratory failure. Four weeks later, 6 hours after the second session of BT, severe bronchospasm occurred with respiratory failure. Chest X-Ray showed atelectasis of the left lower lobe, prompting to perform a new flexible bronchoscopy on non-invasive ventilation. The exam showed again a plug occluding the left lower lobar bronchus, removed with forceps and washings. The histological analysis of the plugs demonstrated the massive presence of fibrin with mucus debris, rare Charcot-Leyden crystals, scattered macrophages, neutrophils, eosinophils and bronchial epithelial cells.

Conclusion: The originality of our case report is related to the recurrence of bronchial plugging with lobar atelectasis within one and five hours respectively, after two sequential BT procedures. At the histological evaluation the bronchial plugs appeared very different from the typical mucoid asthma plugs, being composed prevalently by fibrin. It can be hypothesized that intense thermal stimulation of the bronchial mucosa may represent a strong boost for inflammation in susceptible patients, with microvascular alteration induced directly by heat or through the release of mediators. Although in severe asthma a risk of atelectasis from the classical asthma mucoid plugs may be expected, the peculiarity of our case resides in the formation of fibrin plugs whose direct correlation with BT should be considered.
The impact of abdominal adiposity measured by sonography on the pulmonary function of pre-menopausal females
Authors: Rasslan Zied , Stirbulov Roberto , Saad Junior Roberto , Tercio Curia Sergio , Da Conceição Lima Carlos Alberto , Araújo Perez Eduardo , Fernandes Oliveira Ezequiel , Donner Claudio F. , Franco Oliveira Luis Vicente
Published: January 2020

Background: The Body Mass Index (BMI) is a widely used parameter to study obesity; however it does not assess the distribution of body adiposity. Ultrasonography is a reliable method of measuring subcutaneous (SAT), visceral (VAT) and Total adipose tissue of the abdomen (TAT) to determine the influence of abdominal fat on pulmonary function by directly measuring abdominal adipose tissue.

Methods: Eighty pre-menopausal, non-smoker, sedentary females with no history of pulmonary disease were subdivided into three groups: 25 normal-weight, 28 overweight, 27 obese. Absolute and predictive spirometric values were obtained: FVC, FEV1, FEV1/FVC, IC, ERV.

Results: A positive correlation between increased %IC and decreased %ERV was observed with increased BMI (p < 0.02; 0.001 respectively); %FVC, %FEV1 and %ERV decreased significantly as SAT (p = 0.01, p = 0.02; p < 0.001) and TAT (p = 0.01, p = 0.03, p < 0.001) increased, whereas VAT was negatively correlated only with %ERV (p < 0.001). Increments of 5 mm in TAT, VAT and SAT were followed by a reduction of 0.83 %, 0.81 %, 1.90 % in %FVC, respectively, as well as a reduction of 4.25 %, 4.31 % and 9.44 % in %ERV, respectively.

Conclusions: Subcutaneous abdominal adipose tissue deposition in obese females has a greater negative influence on pulmonary function than visceral adipose tissue deposition.