Making a case for metallothioneins conferring cardioprotection in pulmonary hypertension.
Med Hypotheses. 2020 Jan 18;137:109572
Authors: Maarman GJ
Pulmonary hypertension (PH) is defined as elevated mean pulmonary artery pressure secondary to e.g. congenital heart disease and chronic obstructive pulmonary disease. It elevates right ventricular afterload that eventually leads to cor pulmonale and right heart failure. Experimental research has shown that cardioprotective strategies may improve morbidity and reduce mortality in PH patients. PH and consequent right heart failure are underpinned by dysregulated mitochondrial dynamics, and therefore mitochondrial regulators may be targeted as cardioprotective agents in PH. Mitochondrial regulators such as the metallothioneins (MTs) confer cardioprotection against several forms of heart/lung disease. Furthermore, MT expression is up or downregulated in biopsies or blood from patients with PH. However, despite the overwhelming evidence that MT has potential as cardioprotective agents in PH, MT-induced cardioprotection has not been tested in experimental models of PH. Therefore, it is necessary to evaluate the attributes of MTs that make them candidates for cardioprotection in PH. The hypothesis presented in this paper is that upregulation of cardiac MTs can confer cardioprotection in PH and associated right ventricular remodelling. Mainly due to their ability to detoxify the myocardium of excess heavy metals, scavenging of free radicals and modulation of mitochondrial dynamics. These processes are instrumental in the development of PH and right ventricular remodelling. With this hypothesis we propose that the upregulation of cardiac MTs can confer cardioprotection in PH by detoxifying the myocardium of heavy metals and improving cardiac mitochondrial efficiency (i.e. reducing ROS, reducing oxidative stress, and improving antioxidant capacity and improving mitochondrial respiration).
PMID: 31986470 [PubMed - as supplied by publisher]
Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue.
Clin Biomech (Bristol, Avon). 2020 Jan 09;73:162-165
Authors: Jammes Y, Stavris C, Charpin C, Rebaudet S, Lagrange G, Retornaz F
BACKGROUND: Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue.
METHODS: Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances.
FINDINGS: No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue.
INTERPRETATION: We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.
PMID: 31986462 [PubMed - as supplied by publisher]
Practical lessons in implementing frailty assessments for hospitalised patients with COPD.
BMJ Open Qual. 2020 Jan;9(1):
Authors: Chin M, Voduc N, Huang S, Forster A, Mulpuru S
PMID: 31986119 [PubMed - in process]
Morphological features of pulmonary fibrosis in workers occupationally exposed to alpha radiation.
Int J Radiat Biol. 2020 Jan 27;:1-32
Authors: Sychugov G, Azizova T, Osovets S, Kazachkov E, Revina V, Grigoryeva E
Purpose. The paper reports on a comparative analysis of biological specimens of lung tissues collected from workers with pulmonary fibrosis induced by internal exposure to plutonium alpha-particles (PuPF) and with etiologically different pulmonary fibrosis (non-PuPF) that developed as an outcome of a chronic obstructive pulmonary disease (COPD).Materials and methods. To perform histological examinations, lung tissues were sampled during autopsy. Six samples of various lung regions (the apical region, the lingula of the left lung, the inferior lobe) were collected from each donor. The resected tissue samples were fixed in 10% neutral-buffered formalin during 24 hours and embedded into paraffin blocks (FFPE). FFPE blocks with lung tissue specimens collected from 56 workers with PuPF, 34 workers with non-PuPF and 35 workers without any lung disease were used in the study. To perform microscopic examination, lung tissue specimens were hematoxylin and eosin stained. To examine the connective-tissue scaffold of lung stroma and identify foci of pulmonary fibrosis, the cut sections of paraffin blocks were stained by Van-Gizon's method (to assess the total volume of fibrosis-affected tissues); by Gomori's technique (to define the reticular scaffold of lung stroma), by Weigert's technique (to examine elastic fibers). Morphological patterns of all biological specimens were studied using immunohistochemistry. To fit the empirical data, the Weibull's model was used.Results and Conclusions. The study found qualitative and quantitative morphological features specific for PuPF compared to non-PuPF. The study demonstrated that hyper-production of collagen type V plays a key role in PuPF. The collagen type V content in fibrotic foci in lung tissue specimens from workers with PuPF was found to be increased.
PMID: 31985334 [PubMed - as supplied by publisher]
Device use errors with soft mist inhalers: A global systematic literature review and meta-analysis.
Chron Respir Dis. 2020 Jan-Dec;17:1479973119901234
Authors: Navaie M, Dembek C, Cho-Reyes S, Yeh K, Celli BR
Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD). Soft mist inhalers (SMIs) are devices that deliver bronchodilators. Although correct device use is paramount to successful medication delivery, patient errors are common. This global systematic literature review and meta-analysis examined device use errors with SMIs among patients with obstructive lung diseases. PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify studies published between 2010 and 2019 that met the following inclusion criteria: (a) English language; (b) a diagnosis of COPD, bronchitis, or emphysema; and (c) reported device use errors among adults receiving long-acting bronchodilator treatment with Respimat® SMI (i.e. Spiriva®, Stiolto®, Spiolto®, and Striverdi®). Descriptive statistics examined sociodemographics, clinical characteristics, and device use errors. Meta-analysis techniques were employed with random-effects models to generate pooled mean effect sizes and 95% confidence intervals (CIs) for overall and step-by-step errors. The I 2 statistic measured heterogeneity. Twelve studies (n = 1288 patients) were included in this meta-analysis. Eighty-eight percent of patients had COPD, and most had moderate/very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease spirometric stages II to IV). Aggregate results revealed that 58.9% (95% CI: 42.4-75.5; I 2 = 92.8%) of patients made ≥1 device use errors. Among 11 studies with step-by-step data, the most common errors were failure to (1) exhale completely and away from the device (47.8% (95% CI: 33.6-62.0)); (2) hold breath for up to 10 seconds (30.6% (95% CI: 17.5-43.7)); (3) take a slow, deep breath while pressing the dose release button (27.9% (95% CI: 14.5-41.2)); (4) hold the inhaler upright (22.6% (95% CI: 6.2-39.0)); and (5) turn the base toward the arrows until it clicked (17.6% (95% CI: 3.0-32.2)). Device use errors occurred in about 6 of 10 patients who used SMIs. An individualized approach to inhalation device selection and ongoing training and monitoring of device use are important in optimizing bronchodilator treatment.
PMID: 31984767 [PubMed - in process]
Comorbidity and stage at diagnosis among lung cancer patients in the US military health system.
Cancer Causes Control. 2020 Jan 27;:
Authors: Lin J, McGlynn KA, Nations JA, Shriver CD, Zhu K
PURPOSE: We investigated the association between comorbidities and stage at diagnosis among NSCLC patients in the US Military Health System (MHS), which provides universal health care to its beneficiaries.
METHODS: The linked data from the Department of Defense's Central Cancer Registry (CCR) and the MHS Data Repository (MDR) were used. The study included 4768 patients with histologically confirmed primary NSCLC. Comorbid conditions were extracted from the MDR data. Comorbid conditions were those included in the Charlson Comorbidity Index (CCI) and were defined as a diagnosis during a 3-year time frame prior to the NSCLC diagnosis. Multivariable logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) of late stage (stages III and IV) versus early stage (stages I and II) in relation to pre-existing comorbidities.
RESULTS: Compared to patients with no comorbidities, those with prior comorbidities tended to be less likely to have lung cancer diagnosed at late stage. When specific comorbidities were analyzed, decreased odds of being diagnosed at late stage were observed among those with chronic obstructive pulmonary disease (COPD) (adjusted OR 0.78, 95% CI 0.68 to 0.90). In contrast, patients with a congestive heart failure or a liver cirrhosis/chronic hepatitis had an increased likelihood of being diagnosed at late stage (adjusted OR 1.30, 95% CI 1.00 to 1.69 and adjusted OR 1.87, 95% CI 1.24 to 2.82, respectively).
CONCLUSIONS: Among NSCLC patients in an equal access health system, the likelihood of late stage at diagnosis differed by specific comorbid diseases.
PMID: 31984449 [PubMed - as supplied by publisher]
Annotating and detecting phenotypic information for chronic obstructive pulmonary disease.
JAMIA Open. 2019 Jul;2(2):261-271
Authors: Ju M, Short AD, Thompson P, Bakerly ND, Gkoutos GV, Tsaprouni L, Ananiadou S
Objectives: Chronic obstructive pulmonary disease (COPD) phenotypes cover a range of lung abnormalities. To allow text mining methods to identify pertinent and potentially complex information about these phenotypes from textual data, we have developed a novel annotated corpus, which we use to train a neural network-based named entity recognizer to detect fine-grained COPD phenotypic information.
Materials and methods: Since COPD phenotype descriptions often mention other concepts within them (proteins, treatments, etc.), our corpus annotations include both outermost phenotype descriptions and concepts nested within them. Our neural layered bidirectional long short-term memory conditional random field (BiLSTM-CRF) network firstly recognizes nested mentions, which are fed into subsequent BiLSTM-CRF layers, to help to recognize enclosing phenotype mentions.
Results: Our corpus of 30 full papers (available at: http://www.nactem.ac.uk/COPD) is annotated by experts with 27 030 phenotype-related concept mentions, most of which are automatically linked to UMLS Metathesaurus concepts. When trained using the corpus, our BiLSTM-CRF network outperforms other popular approaches in recognizing detailed phenotypic information.
Discussion: Information extracted by our method can facilitate efficient location and exploration of detailed information about phenotypes, for example, those specifically concerning reactions to treatments.
Conclusion: The importance of our corpus for developing methods to extract fine-grained information about COPD phenotypes is demonstrated through its successful use to train a layered BiLSTM-CRF network to extract phenotypic information at various levels of granularity. The minimal human intervention needed for training should permit ready adaption to extracting phenotypic information about other diseases.
PMID: 31984360 [PubMed]
Seeing the world through different lenses: activity registration differs between two validated accelerometers.
ERJ Open Res. 2020 Jan;6(1):
Authors: van der Molen MC, Hartman JE, Vanfleteren LEGW, Slebos DJ
Although accelerometers are extensively validated to estimate energy expenditure in patients with COPD, they show significant differences in non-worn time and type of activity registration http://bit.ly/32fa7WR.
PMID: 31984209 [PubMed]
Association of periodontal status with lung function in patients with and without chronic obstructive pulmonary disease visiting a medical hospital in Pune: A comparative study.
J Indian Soc Periodontol. 2020 Jan-Feb;24(1):67-71
Authors: Bomble N, Shetiya SH, Agarwal DR
Background: The relationship between oral health and systemic conditions has been increasingly debated over recent decades with one such discussion existing about oral hygiene and periodontitis with chronic obstructive pulmonary disease (COPD). Hence, a study was conducted to assess and compare the oral hygiene status and periodontal status of age and gender-matched participants with and without COPD and to correlate oral hygiene status and periodontal status with lung function status among them.
Materials and Methods: This hospital-based study included a study population of 117 participants (39 patients of COPD and 78 participants without COPD) 35-75 years of age with at least 20 natural teeth. Participant's demographic details and history of smoking were recorded. Lung function was recorded using a spirometer. Periodontal health was assessed by measuring Probing Pocket Depth (PPD), Clinical Attachment Loss (CAL), and Oral Hygiene Index (OHI) by a trained and calibrated examiner.
Results: Higher mean of PPD, CAL, and OHI is being reported in the present study with 4.07 versus 3.50, 0.58 versus 0.24, and 5.24 versus 3.60, respectively, among patients with and without COPD which was statistically significant. The risk of having COPD was 0.4 times more in participants having poor oral hygiene and 0.07 times more in patients smoking. Smoking and oral hygiene, as independent variables, have a significant influence on COPD which is a dependent variable. A weak correlation was found of poor oral hygiene and loss of attachment among participants with COPD.
Conclusion: Periodontitis and respiratory disease share a common risk factor, i.e., smoking. Smoking has a definite relation with periodontitis and COPD. Oral hygiene is significantly associated with increased risk for COPD when age and gender effects have been matched and when adjusted for smoking. However, no association was found of PPD with COPD.
PMID: 31983848 [PubMed]
The Clinical Implications of Triple Therapy in Fixed-Dose Combination in COPD: From the Trial to the Patient.
Arch Bronconeumol. 2020 Jan 23;:
Authors: López-Campos JL, Carrasco-Hernández L, Román Rodríguez L, Quintana-Gallego E, Carmona Bernal C, Alcázar Navarrete B
The emergence of a fixed-dose combination (FDC) of a long-acting β2-agonists (LABAS), a long-acting anticholinergic agent (LAMA), and an inhaled corticosteroid (ICS) in a single inhalation device has changed the approach to inhaled therapy. Although clinical trials describe the efficacy and safety of these FDCs, their use in daily clinical practice can present challenges for the clinician in two specific scenarios. In patients who are already receiving triple therapy via different devices, switching to FDCs could confer benefits by reducing critical errors in the management of inhalers, improving therapeutic adherence, and lowering costs, while maintaining the same clinical efficacy. In patients who are not receiving triple therapy in different devices and who require a change in treatment, triple therapy FDC has shown benefits in clinical trials. Although methodological differences among the trials advise against direct comparison, clinical results show good efficacy, but also considerable variability, and a number of clinical outcomes have yet to be explored. In the future, trials must be developed to complete clinical efficacy data. Real-world efficacy trials are needed, and studies must be designed to determine the profile of patients who present a greater therapeutic response to each FDC in order to pave to way towards more personalized treatment.
PMID: 31983474 [PubMed - as supplied by publisher]
Budesonide/formoterol therapy: effective and appropriate use in asthma and chronic obstructive pulmonary disease.
J Comp Eff Res. 2020 Jan 27;:
Authors: Mapel DW, Roberts MH, Davis J
Aim: Quality, real-world comparative effectiveness (CE) studies of asthma and chronic obstructive pulmonary disease therapy efficacy are scarce. We identified and evaluated peer-reviewed CE and appropriate-use evaluations of budesonide/formoterol combination (BFC) maintenance therapy. Materials & methods: Analyses were limited to retrospective, real-world utilization studies of BFC delivered by pressurized metered-dose inhalers. Results: In a CE study of BFC versus fluticasone/salmeterol combinations (FSC) in asthma, BFC users had fewer total exacerbations. In appropriate-use studies of asthma treatment, BFC patients were consistently more likely to meet treatment escalation recommendations. BFC comparisons with FSC or tiotropium for chronic obstructive pulmonary disease found differences in exacerbation rates and rescue inhaler use. Conclusion: We found available, good quality BFC CE and appropriate-use articles; however, all had limitations.
PMID: 31983228 [PubMed - as supplied by publisher]
[Lung volume reduction surgery for severe emphysema treatment].
Ugeskr Laeger. 2019 Feb 18;181(8):
Authors: Nodin E, Hansen HJ, Ravn J, Perch M
Lung volume reduction surgery (LVRS) is a treatment option for patients with severe emphysema. A multicentre randomised trial (NETT) found, that LVRS reduced symptoms from emphysema, and in selected patients with heterogen-ous emphysema it improved survival. Since NETT was performed, other studies have demonstrated positive outcomes, both symptomatic and for survival in previously classified high-risk patients. Post-operative mortality after LVRS is now negligible, which is often credited to minimally invasive techniques, greater experience with the patient group and improved operative equipment.
PMID: 30821241 [PubMed - indexed for MEDLINE]