Lung epithelial permeability and inhaled furosemide: added dimensions in asthmatics

Bhure, Shraddha; Bhatt, B. M.; Mistry, Sonal; Pednekar, Suhas; Chari, V. V.; Desai, Sheetal; Joshi, J. M.; Pai-Dhungat, Asha

doi:10.1007/s12149-009-0275-z

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…This is supported by observations of impaired barrier function in poorly controlled asthma (3,19). Further support was obtained in studies of direct exposure of cultured epithelial cells to HDM fecal pellets or extract.…”

Section: Discussionsupporting

confidence: 54%

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The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

Turi

Ellis

Wattie

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionsupporting

confidence: 54%

“…Surprisingly, early observations did not demonstrate significant impairment of barrier function in asthmatic compared with healthy control subjects (7,20). However, recent studies have demonstrated significant impairment of airway barrier function in poorly controlled pediatric and adult asthmatic patients (3,19).…”

mentioning

confidence: 96%

The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

Turi

Ellis

Wattie

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Notably, growing evidence suggests that metabolic derangement leads to airway dysfunction through the underlying mechanism of epithelial damage and airway smooth muscle proliferation [37]. Moreover, it was reported that metabolic derangement is a high risk factor for insulin resistance, metabolic syndrome, diabetes and childhood obesity [38].…”

Section: Discussionmentioning

confidence: 99%

Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation

Yang

Zhang

et al. 2017

Basic Clin Pharma Tox

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Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic reprogramming associated with a combination treatment of inhaled budesonide and salbutamol in asthmatic children.Glucocorticoids and beta2 agonists represent the most important and frequently used drugs for symptom control in asthmatic children during acute exacerbation [1,2]. Current guidelines recommend the combined use of glucocorticoids and beta2 agonists as the preferred therapy for asthmatic children during acute exacerbation [3,4]. The glucocorticoid and beta2 agonist therapies are effective at controlling airway inflammation, reducing asthma symptoms, decreasing airway hyper-responsiveness and reducing the frequency and severity of exacerbations as well as asthma mortality. Despite their undoubted effectiveness and safety, there is still no consensus about the resulting metabolic derangements, including the development of dyslipidaemia, insulin resistance, glucose intolerance, diabetes, central adiposity and skeletal muscle wasting [5][6][7].Both glucocorticoids and beta2 agonists have the potential to influence glucose, lipid and protein...

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“…Alternatively, monitoring the distribution of intratracheally instilled tracer molecules may provide a method for repeated measurement of airway epithelium permeability (29). We have recently developed a mouse model of Tc-DTPA imaging using single-photon emission computed tomography that allows us to determine the lung clearance of tracer over time as a functional measurement and indirect marker of airway permeability, as has been done in humans (11). A limitation of this technique is that it is unable to discriminate between changes in airway or alveolar epithelial permeability.…”

Section: Methodsmentioning

confidence: 99%

“…The structural changes in asthmatic airway epithelium have recently been associated with increased epithelial permeability in functional studies examining technetium-labeled diethylenetriamine pentaacetate (Tc-DTPA) clearance (11). In patients with chronic persistent asthma, inhaled Tc-DTPA displays a shorter half-life in the lungs, suggesting increased permeability as com-…”

mentioning

confidence: 99%

Modeling Asthma in Mice

Hirota

Hackett²,

Inman³

et al. 2011

Am J Respir Cell Mol Biol

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Clinical reports of areas of damaged airway epithelium associated with shed epithelial cells in bronchoalveolar lavage fluid, aberrant epithelial repair processes, and altered cytokine and growth factor release have highlighted some fundamental differences between the airway epithelium in individuals with and without asthma. However, the consequences of these epithelial changes are not clearly defined, and may be difficult to assess in the clinic. In this Review, we answer the two questions. (1) What in vivo models and methods have been used to inform us about airway epithelium damage, repair, and immune responses? Our response focuses on genetic influences as well as allergen exposure, environmental/chemical, and mechanical models. (2) How can we improve on existing mouse models to understand changes in airway epithelium biology in asthma? In answering the second question, we include exciting recent studies that have combined multiple exposure methods and/or epithelium-centric outcome measurements. By addressing these two questions, we propose that future interrogation of epithelial responses of both existing and nascent mouse models may provide greater understanding of the mechanisms underlying airway inflammation and remodeling in asthma with hope of generating novel therapeutic targets.

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Lung epithelial permeability and inhaled furosemide: added dimensions in asthmatics

Cited by 16 publications

References 26 publications

The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation

Modeling Asthma in Mice

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