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Association of Serum Vitamin D (25OHD) Level with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Islam, S, Sarkar, NK, Mujahid, AA, Bennoor, KS, Hossain, SS, Attar, MM, Jahan, R, Hossain, MA, Chowdhury, HA, Ali, L
Mymensingh medical journal : MMJ. 2019;(2):441-448
Abstract
Acute exacerbations of COPD is characterized by a change in the patients baseline dyspnoea, cough and/or sputum that is beyond normal day to day differences and guides to a change in standard medications in a patient with COPD. Vitamin D influences the innate & adaptive immune system, and exerts pleiotropic antimicrobial and anti-inflammatory responses. Vitamin D deficiency is frequent among COPD patients but its contributory role in disease exacerbations is widely debated. This study was aimed to assess relationship between reduced serum vitamin D (25-OHD) level with COPD severity and acute exacerbation. This observational cross-sectional study was carried out in the department of Respiratory Medicine, NIDCH, Mohakhali, Dhaka, Bangladesh from October 2016 to September 2017. Consecutive 80 hospital admitted patients with acute exacerbation of chronic obstructive pulmonary disease diagnosed on the basis of clinical history & pulmonary function tests and 78 age & sex matched controls were investigated for serum vitamin D (25-OHD) level. Among the COPD patients, 37% had Vitamin D deficiency (<20ng/ml) and 28.75% had Vitamin D insufficiency (20-29ng/ml). Mean vitamin D (25-OHD) level of COPD patients (25.82±10.62ngm/ml) was found to be significantly lower than healthy controls (32.57±11.32ngm/ml). Vitamin D deficiency was found, by Pearson correlation test, to be significantly associated with severity of COPD. Multivariate analysis showed that age (in years), FEV1 (percent predicted), frequent exacerbators (≥2 in the last year), and smoking (>40 pack year) were significantly associated with Vitamin D deficiency. Acute exacerbation of chronic obstructive pulmonary disease patients was found to have vitamin D deficiency and vitamin D deficiency was significantly associated with severity of COPD. Vitamin D deficiency was also associated with frequent disease exacerbation.
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Meta-analysis of vitamin D and lung function in patients with asthma.
Liu, J, Dong, YQ, Yin, J, Yao, J, Shen, J, Sheng, GJ, Li, K, Lv, HF, Fang, X, Wu, WF
Respiratory research. 2019;(1):161
Abstract
BACKGROUND There is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients. METHODS Major databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5. RESULTS This quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = - 0.1, 95% CI = - 0.11 to - 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = - 10.02, 95% CI = - 11 to - 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults. CONCLUSIONS Our meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.
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The P2-receptor-mediated Ca2+ signalosome of the human pulmonary endothelium - implications for pulmonary arterial hypertension.
Hennigs, JK, Lüneburg, N, Stage, A, Schmitz, M, Körbelin, J, Harbaum, L, Matuszcak, C, Mienert, J, Bokemeyer, C, Böger, RH, et al
Purinergic signalling. 2019;(3):299-311
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Abstract
Dysfunction of the pulmonary endothelium is associated with most lung diseases. Extracellular nucleotides modulate a plethora of endothelial functions in the lung such as vessel integrity, vasodilatation, inflammatory, and thrombotic responses as well as survival and DNA repair, mostly via Ca2+ signaling pathways. However, a comprehensive analysis of the molecular components of the underlying P2 receptor-mediated Ca2+ signaling pathways in the lung has not been conducted so far. Therefore, our aim was to identify the principal P2 receptor Ca2+ signalosome in the human pulmonary endothelium and investigate potential dysregulation in pulmonary vascular disease. Comparative transcriptomics and quantitative immunohistochemistry were performed on publicly available RNA sequencing and protein datasets to identify the specific expression profile of the P2-receptor Ca2+ signalosome in the healthy human pulmonary endothelium and endothelial cells (EC) dysfunctional due to loss of or defective bone morphogenetic protein receptor (BMPR2). Functional expression of signalosome components was tested by single cell Ca2+ imaging. Comparative transcriptome analysis of 11 endothelial cell subtypes revealed a specific P2 receptor Ca2+ signalosome signature for the pulmonary endothelium. Pulmonary endothelial expression of the most abundantly expressed Ca2+ toolkit genes CALM1, CALM2, VDAC1, and GNAS was confirmed by immunohistochemistry (IHC). P2RX1, P2RX4, P2RY6, and P2YR11 showed strong lung endothelial staining by IHC, P2X5, and P2Y1 were found to a much lesser extent. Very weak or no signals were detected for all other P2 receptors. Stimulation of human pulmonary artery (HPA) EC by purine nucleotides ATP, ADP, and AMP led to robust intracellular Ca2+ signals mediated through both P2X and P2Y receptors. Pyrimidine UTP and UDP-mediated Ca2+ signals were generated almost exclusively by activation of P2Y receptors. HPAEC made dysfunctional by siRNA-mediated BMPR2 depletion showed downregulation of 18 and upregulation of 19 P2 receptor Ca2+ signalosome genes including PLCD4, which was found to be upregulated in iPSC-EC from BMPR2-mutant patients with pulmonary arterial hypertension. In conclusion, the human pulmonary endothelium expresses a distinct functional subset of the P2 receptor Ca2+ signalosome. Composition of the P2 receptor Ca2+ toolkit in the pulmonary endothelium is susceptible to genetic disturbances likely contributing to an unfavorable pulmonary disease phenotype found in pulmonary arterial hypertension.
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Zinc intoxication induces ferroptosis in A549 human lung cells.
Palmer, LD, Jordan, AT, Maloney, KN, Farrow, MA, Gutierrez, DB, Gant-Branum, R, Burns, WJ, Romer, CE, Tsui, T, Allen, JL, et al
Metallomics : integrated biometal science. 2019;(5):982-993
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Abstract
Zinc (Zn) is an essential trace metal required for all forms of life, but is toxic at high concentrations. While the toxic effects of high levels of Zn are well documented, the mechanism of cell death appears to vary based on the study and concentration of Zn. Zn has been proposed as an anti-cancer treatment against non-small cell lung cancer (NSCLC). The goal of this analysis was to determine the effects of Zn on metabolism and cell death in A549 cells. Here, high throughput multi-omics analysis identified the molecular effects of Zn intoxication on the proteome, metabolome, and transcriptome of A549 human NSCLC cells after 5 min to 24 h of Zn exposure. Multi-omics analysis combined with additional experimental evidence suggests Zn intoxication induces ferroptosis, an iron and lipid peroxidation-dependent programmed cell death, demonstrating the utility of multi-omics analysis to identify cellular response to intoxicants.
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Course of lung function in children with cystic fibrosis in their first 3 years of life.
Balinotti, JE, Chang, DV, Lubovich, S, Rodríguez, V, Zaragoza, S, Escobar, N, Kofman, C, Pérez, GL, Ardiles, V, Teper, A
Archivos argentinos de pediatria. 2019;(5):323-329
Abstract
INTRODUCTION The early prevention of respiratory complications in children with cystic fibrosis is determining for a longer survival. The implementation of lung function tests in the first months of life allows to detect respiratory involvement, even in asymptomatic children. OBJECTIVE To assess the course of lung function in children with cystic fibrosis in their first 3 years of life and identify the factors affecting it. POPULATION AND METHODS Observational, retrospective, analytical study. Children younger than 36 months with at least 2 lung function tests were included. RESULTS Between 2008 and 2016, 48 patients were included; 85 % of them had been diagnosed by newborn screening. The first lung function test was done at 5 months old. The median Z-score of maximal flow at functional residual capacity was -0.05 (interquartile range: -1.09 to 1.08). The median change in the maximal flow Z-score between tests was -0.32 (interquartile range: -1.11 to 0.25), p = 0.045. Patients with Staphylococcus aureus respiratory infections, especially methicillin-resistant SA, evidenced a greater deterioration of lung function compared to those without infection. Neither sex nor the type of genetic mutation were associated with the course of lung function. Nutritional recovery throughout the study was really good. CONCLUSION Lung function in children with cystic fibrosis worsens progressively during their first 3 years of life. These findings are associated with Staphylococcus aureus respiratory infections.
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Enteral Nutrition Tolerance And REspiratory Support (ENTARES) Study in preterm infants: study protocol for a randomized controlled trial.
Cresi, F, Maggiora, E, Borgione, SM, Spada, E, Coscia, A, Bertino, E, Meneghin, F, Corvaglia, LT, Ventura, ML, Lista, G, et al
Trials. 2019;(1):67
Abstract
BACKGROUND Respiratory distress syndrome (RDS) and feeding intolerance are common conditions in preterm infants and among the major causes of neonatal mortality and morbidity. For many years, preterm infants with RDS have been treated with mechanical ventilation, increasing risks of acute lung injury and bronchopulmonary dysplasia. In recent years non-invasive ventilation techniques have been developed. Showing similar efficacy and risk of bronchopulmonary dysplasia, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) have become the most widespread techniques in neonatal intensive care units. However, their impact on nutrition, particularly on feeding tolerance and risk of complications, is still unknown in preterm infants. The aim of the study is to evaluate the impact of NCPAP vs HHHFNC on enteral feeding and to identify the most suitable technique for preterm infants with RDS. METHODS A multicenter randomized single-blind controlled trial was designed. All preterm infants with a gestational age of 25-29 weeks treated with NCPAP or HHHFNC for RDS and demonstrating stability for at least 48 h along with the compliance with inclusion criteria (age less than 7 days, need for non-invasive respiratory support, suitability to start enteral feeding) will be enrolled in the study and randomized to the NCPAP or HHHFNC arm. All patients will be monitored until discharge, and data will be analyzed according to an intention-to-treat model. The primary outcome is the time to reach full enteral feeding, while parameters of respiratory support, feeding tolerance, and overall health status will be evaluated as secondary outcomes. The sample size was calculated at 141 patients per arm. DISCUSSION The identification of the most suitable technique (NCPAP vs HHHFNC) for preterm infants with feeding intolerance could reduce gastrointestinal complications, improve growth, and reduce hospital length of stay, thus improving clinical outcomes and reducing health costs. The evaluation of the timing of oral feeding could be useful in understanding the influence that these techniques could have on the development of sucking-swallow coordination. Moreover, the evaluation of the response to NCPAP and HHHFNC could clarify their efficacy as a treatment for RDS in extremely preterm infants. TRIAL REGISTRATION ClinicalTrials.gov, NCT03548324 . Registered on 7 June 2018.
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Seasonal variations in objectively assessed physical activity among people with COPD in two Nordic countries and Australia: a cross-sectional study.
Hoaas, H, Zanaboni, P, Hjalmarsen, A, Morseth, B, Dinesen, B, Burge, AT, Cox, NS, Holland, AE
International journal of chronic obstructive pulmonary disease. 2019;:1219-1228
Abstract
Purpose: Seasons and weather conditions might influence participation in physical activity and contribute to differences between countries. This study aimed at investigating whether there were differences in physical activity levels between Norwegian, Danish and Australian people with chronic obstructive pulmonary disease (COPD), and establishing if any variations in physical activity were attributable to seasons. Patients and methods: A cross-sectional study where study subjects were people with COPD who participated in two separate clinical trials: the iTrain study (Norway, Denmark, and Australia) and the HomeBase study (Australia). Physical activity was objectively assessed with an activity monitor; variables were total energy expenditure, number of daily steps, awake sedentary time, light, and moderate-to-vigorous intensity physical activity. Differences in physical activity between countries and seasons were compared, with adjustment for disease severity. Results: In total, 168 participants were included from Norway (N=38), Denmark (N=36) and Australia (N=94). After controlling for disease severity, time spent in awake sedentary time was greater in Danish participants compared to the other countries (median 784 minutes/day [660-952] vs 775 minutes/day [626-877] for Norwegians vs 703 minutes/day [613-802] for Australians, P=0.013), whilst time spent in moderate to vigorous physical activity was lower (median 21 minutes/day [4-73] vs 30 minutes/day [7-93] for Norwegians vs 48 minutes/day [19-98] for Australians, P=0.024). Participants walked more during summer (median 3502 [1253-5407] steps/day) than in spring (median 2698 [1613-5207] steps/day), winter (median 2373 [1145-4206] steps/day) and autumn (median 1603 [738-4040] steps/day), regardless of geography. The median difference between summer and other seasons exceeded the minimal clinically important difference of 600 steps/day. However, the differences were not statistically significant (P=0.101). Conclusion: After controlling for disease severity, Danish participants spent more time in an awake sedentary state and less time in moderate to vigorous physical activity than their counterparts in Norway and Australia. People with COPD increased their physical activity in summer compared to other seasons. Weather conditions and seasonal variations may influence outcomes in clinical trials and health registries measuring physical activity over time, irrespective of the interventions delivered, and should be taken into account when interpreting results.
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Lung Ultrasound for Critically Ill Patients.
Mojoli, F, Bouhemad, B, Mongodi, S, Lichtenstein, D
American journal of respiratory and critical care medicine. 2019;(6):701-714
Abstract
Point-of-care ultrasound is increasingly used at the bedside to integrate the clinical assessment of the critically ill; in particular, lung ultrasound has greatly developed in the last decade. This review describes basic lung ultrasound signs and focuses on their applications in critical care. Lung semiotics are composed of artifacts (derived by air/tissue interface) and real images (i.e., effusions and consolidations), both providing significant information to identify the main acute respiratory disorders. Lung ultrasound signs, either alone or combined with other point-of-care ultrasound techniques, are helpful in the diagnostic approach to patients with acute respiratory failure, circulatory shock, or cardiac arrest. Moreover, a semiquantification of lung aeration can be performed at the bedside and used in mechanically ventilated patients to guide positive end-expiratory pressure setting, assess the efficacy of treatments, monitor the evolution of the respiratory disorder, and help the weaning process. Finally, lung ultrasound can be used for early detection and management of respiratory complications under mechanical ventilation, such as pneumothorax, ventilator-associated pneumonia, atelectasis, and pleural effusions. Lung ultrasound is a useful diagnostic and monitoring tool that might in the near future become part of the basic knowledge of physicians caring for the critically ill patient.
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Speckle tracking quantification of lung sliding for the diagnosis of pneumothorax: a multicentric observational study.
Duclos, G, Bobbia, X, Markarian, T, Muller, L, Cheyssac, C, Castillon, S, Resseguier, N, Boussuges, A, Volpicelli, G, Leone, M, et al
Intensive care medicine. 2019;(9):1212-1218
Abstract
PURPOSE Lung ultrasound is used for the diagnosis of pneumothorax, based on lung sliding abolition which is a qualitative and operator-dependent assessment. Speckle tracking allows the quantification of structure deformation over time by analysing acoustic markers. We aimed to test the ability of speckle tracking technology to quantify lung sliding in a selected cohort of patients and to observe how the technology may help the process of pneumothorax diagnosis. METHODS We performed retrospectively a pleural speckle tracking analysis on ultrasound loops from patients with pneumothorax. We compared the values measured by two observers from pneumothorax side with contralateral normal lung side. The receiver operating characteristic (ROC) curve was constructed to evaluate the performance of maximal pleural strain to detect the lung sliding abolition. Diagnosis performance and time to diagnosis between B-Mode and speckle tracking technology were compared from a third blinded observer. RESULTS We analysed 104 ultrasound loops from 52 patients. The area under the ROC curve of the maximal pleural strain value to identify lung sliding abolition was 1.00 [95%CI 1.00; 1.00]. Specificity was 100% [95%CI 93%; 100%] and sensitivity was 100% [95%CI 93%; 100%] with the best cut-off of 4%. Over 104 ultrasound loops, the blinded observer made two errors with B-Mode and none with speckle tracking. The median diagnosis time was 3 [2-5] seconds for B-Mode versus 2 [1-2] seconds for speckle tracking (p = 0.001). CONCLUSION Speckle tracking technology allows lung sliding quantification and detection of lung sliding abolition in case of pneumothorax on selected ultrasound loops.
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Improved lung function at age 6 in children born very preterm and fed extra protein post-discharge.
Toftlund, LH, Agertoft, L, Halken, S, Zachariassen, G
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019;(1):47-54
Abstract
BACKGROUND In very preterm-born children, alveolar maturation is challenged and lung function is often compromised during childhood. So far, very few studies have focused on type of early nutrition and lung function in children born preterm. METHODS This study is a 6 years follow-up of 281 very preterm-born infants (VPI) with a gestational age (GA) <32 + 0 weeks. Infants breastfed at discharge from hospital were randomized to unfortified (UHM) or fortified (FHM) mother's (human) milk, whereas those not breastfed received a preterm formula (PF). The intervention lasted until 4 months corrected age. At 6 years of age fractional exhaled nitric oxide (FeNO), airway resistance and occlusion measurements with reversibility were performed. Data on predisposition to asthma and allergy as well as possible allergic symptoms of the child were obtained with questionnaires. RESULTS Outcome data was fully or partially available on 160 (66.9%) of 239 children. This included 49 (30.6%) children fed UHM, 58 (36.3%) fed FHM and 53 (33.1%) fed PF. Successful FeNO measurements were obtained in 119 (74.4%) children and airway resistance measurements in 160. FeNO results were not significantly different between feeding groups. Children fed a protein-enriched diet (FMH/PF) had the lowest, for example, best, airway resistance; FHM-fed had lower values than UHM-fed (P = 0.042) before, and PF-fed had significantly lower values than UHM-fed after beta-2-agonist inhalation (P = 0.050). The tendency of lower airway resistance when protein enriched were the same in gender-specific analyses. In SGA children, the same tendency was found between PF- and UHM-fed (P = 0.007 before and P = 0.046 after beta-2-agonist inhalation). All values were within reference limits. CONCLUSIONS Lung function in very preterm-born children may improve when fed a protein-enriched nutrition post-discharge.