Ceramide and sphingosine-1 phosphate in COPD lungs

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215892
Author(s):  
Evgeny V Berdyshev ◽  
Karina A Serban ◽  
Kelly S Schweitzer ◽  
Irina A Bronova ◽  
Andrew Mikosz ◽  
...  

Studies of chronic obstructive pulmonary disease (COPD) using animal models and patient plasma indicate dysregulation of sphingolipid metabolism, but data in COPD lungs are sparse. Mass spectrometric and immunostaining measurements of lungs from 69 COPD, 16 smokers without COPD and 13 subjects with interstitial lung disease identified decoupling of lung ceramide and sphingosine-1 phosphate (S1P) levels and decreased sphingosine kinase-1 (SphK1) activity in COPD. The correlation of ceramide abundance in distal COPD lungs with apoptosis and the inverse correlation between SphK1 activity and presence of emphysema suggest that disruption of ceramide-to-S1P metabolism is an important determinant of emphysema phenotype in COPD.

2020 ◽  
Vol 2 (1) ◽  
pp. 01-06
Author(s):  
González Helena

Objective: To define the correlation between the Fat Free Mass Index (FFMI), the muscle function, degree of airflow obstruction, the respiratory symptoms and the number of exacerbations during the last year in patients with Chronic Obstructive Pulmonary Disease (COPD). Methods: Prospective and cross-sectional study of subjects older than 40 years with a clinical diagnosis of COPD who underwent measurement of the FFMI and muscular function to determine if these were correlated with the variables of severe COPD. Results: 55 patients Participated in the study. The FFMI was below 32.7% (n=18) and the strength diminished in 56.4% (n=31). In the sample, we found a direct and significant correlation between the FFMI and the FEV1* (predicted %), (p= 0,045). When analyzed by sex, men had a direct correlation between FFMI and the FEV1*(predicted %), (p=0,019), an inverse correlation between FFMI and the spirometric classification of the Global Initiative Obstructive Lung Disease (GOLD) (p=0,008) and between the muscular function and the symptoms (p=0, 03). In women no significant correlation was found. Conclusions: The conditions in mass and the muscular function were correlated with clinical variables and pulmonary function in men, but not in women. We did not find a correlation between corporal composition and the number of exacerbations.


2020 ◽  
Author(s):  
Haiyue Liu ◽  
Zhenyu Liang ◽  
Nannan Cao ◽  
Xilan Tan ◽  
Zuheng Liu ◽  
...  

AbstractBackgroundLittle is known about airway mycobiome, and its relationship with bacterial microbiome in chronic obstructive pulmonary disease (COPD).MethodsHere we report the first simultaneous characterization of sputum bacterial and fungal microbiome in 84 stable COPD and 29 healthy subjects, using 16S ribosomal DNA and fungal internal transcribed spacer DNA sequencing.ResultsAscomycota predominated over Basidiomycota in fungal microbiome both in COPD patients and healthy controls. Meyerozyma, Candida, Aspergillus and Schizophyllum were most abundant at the genus level. There was a significant inverse correlation between bacterial and fungal microbial diversity, both of which altered in opposite directions in COPD patients versus controls, and in frequent versus non-frequent exacerbators. An enhanced bacterial-fungal ecological interaction was observed in COPD patients, which was characterized by higher proportion of co-occurrence intrakingdom interactions and co-exclusive interkingdom interactions. In COPD, four mutually co-occurring fungal operational taxonomic units (OTUs) in Candida palmioleophila, Aspergillus and Sordariomycetes exhibited co-exclusive relationships with other fungal OTUs, which was specifically present in frequent exacerbators but not in non-frequent exacerbators. Conversely, the mutual co-occurrence interactions between bacterial OTUs in Rothia mucilaginosa, Streptococcus, Veillonella and Prevotella, showed up in non-frequent exacerbators but not in frequent exacerbators. The perturbed bacterial-fungal interactions in COPD were associated with increased airway inflammatory mediators such as IL-6 and IL-8.InterpretationThe disruption of airway bacterial-fungal community balance, characterized by the loss of commensal bacterial taxa and enriched pathogenic fungal taxa, is implicated in COPD. The airway mycobiome is an important cofactor mediating COPD pathogenic infection and host inflammation.Clinical Trial Registrationwww.clinicaltrials.gov (NCT 03240315).


Author(s):  
Shishirakumar A. Goudar ◽  
Virendra Chandrashekhar Patil

There is an overlap of risk factors between heart disease and COPD like cigarette smoking, sedentary lifestyle and old age. The economic burden of COPD is also very high. It is now proven that the only strategy which can reduce COPD incidence is cessation of smoking. The Aim of the present research is to study the Two-dimensional transthoracic Echocardiography (TTE) findings in patients with chronic obstructive pulmonary disease (COPD).The method is that all the enrolled patients were subjected to chest radiography, pulmonary function test, Two-dimensional transthoracic echocardiogram and Doppler study, according to the standard protocol. The findings in our study are consistent with previous studies about the COPD. Total 111(60.7%) of the patients had echocardiographic evidence of pulmonary hypertension and 83(45.4%) of the patients in this study had evidence of cor pulmonale.  We found significant difference between the duration of smoking and severity of the disease based on FEV1 values (p= 0.005). A significant moderate inverse correlation existed between pack years of smoking and FEV1 scores. (r= - 0.379, P < 0.001).


Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5873-5882 ◽  
Author(s):  
Marie-Noëlle Raymond ◽  
Christine Bole-Feysot ◽  
Yoshiko Banno ◽  
Zahra Tanfin ◽  
Philippe Robin

Uterine leiomyomas, or fibroids, are the most common tumors of the myometrium. The ELT3 cell line, derived from Eker rat leiomyoma, has been successfully used as a model for the study of leiomyomas. We have demonstrated previously the potent mitogenic properties of the peptidic hormone endothelin (ET)-1 in this cell line. Here we investigated the antiapoptotic effect of ET-1 in ELT3 cells. We found that 1) serum starvation of ELT3 cells induced an apoptotic process characterized by cytochrome c release from mitochondria, caspase-3/7 activation, nuclei condensation and DNA fragmentation; 2) ET-1 prevented the apoptotic process; and 3) this effect of ET-1 was fully reproduced by ETB agonists. In contrast, no antiapoptotic effect of ET-1 was observed in normal myometrial cells. A pharmacological approach showed that the effect of ET-1 on caspase-3/7 activation in ELT3 cells was not dependent on phosphatidylinositol 3-kinase, ERK1/2, or phospholipase D activities. However, inhibitors of sphingosine kinase-1 (SphK1), dimethylsphingosine and threo-dihydrosphingosine, reduced the effect of ET-1 by about 50%. Identical results were obtained when SphK1 expression was down-regulated in ELT3 cells transfected with SphK1 small interfering RNA. Furthermore, serum starvation induced a decrease in SphK1 activity that was prevented by ET-1 without affecting the level of SphK1 protein expression. Finally, sphingosine 1-phosphate, the product of SphK activity, was as efficient as ET-1 in inhibiting serum starvation-induced caspase-3/7 activation. Together, these results demonstrate that ET-1 possesses a potent antiapoptotic effect in ELT3 cells that involves sphingolipid metabolism through the activation of SphK1.


2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.


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