Aerosolized agents for airway clearance in cystic fibrosis

Southern, Kevin W; Clancy, John; Ranganathan, Sarath

doi:10.1002/ppul.24306

Cited by 14 publications

(13 citation statements)

References 49 publications

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“…It facilitates excretion of water and toxic materials of tubular epithelial cells. Mannitol is also indicated as add-on maintenance therapy for improving pulmonary function in cystic fibrosis patients [ 27 ]. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, which allows easier mucociliary clearance [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Untargeted metabolomics reveals alternations in metabolism of bovine mammary epithelial cells upon IFN-γ treatment

et al. 2023

BMC Vet Res

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Background IFN-γ is a pleiotropic cytokine that has been shown to affect multiple cellular functions of bovine mammary epithelial cells (BMECs) including impaired milk fat synthesis and induction of malignant transformation via depletion of arginine, one of host conditionally essential amino acids. But the molecular mechanisms of these IFN-γ induced phenotypes are still unknown. Methods BMECs were treated with IFN-γ for 6 h, 12 h, and 24 h. The metabolomic profiling in BMECs upon IFN-γ induction were assessed using untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolomic analysis. Key differentially expressed metabolites (DEMs) were quantified by targeted metabolomics. Results IFN-γ induction resulted in significant differences in the contents of metabolites. Untargeted analysis identified 221 significantly DEMs, most of which are lipids and lipid-like molecules, organic acids and derivatives, organ heterocyclic compounds and benzenoids. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEMs were enriched in fructose and mannose metabolism, phosphotransferase system (PTS), β-alanine metabolism, arginine and proline metabolism, methane metabolism, phenylalanine metabolism, and glycolysis/gluconeogenesis. Quantification of selected key DEMs by targeted metabolomics showed significantly decreased levels of D-(-)-mannitol, argininosuccinate, and phenylacetylglycine (PAG), while increased levels in S-hydroxymethylglutathione (S-HMG) and 2,3-bisphospho-D-glyceric acid (2,3-BPG). Conclusions These results provide insights into the metabolic alterations in BMECs upon IFN-γ induction and indicate potential theoretical basis for clarifying IFN-γ-induced diseases in mammary gland.

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Section: Discussionmentioning

confidence: 99%

Untargeted metabolomics reveals alternations in metabolism of bovine mammary epithelial cells upon IFN-γ treatment

et al. 2023

BMC Vet Res

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“…Guidelines generally do not provide recommendations on which to start first. Since these agents have different mechanisms of action, it is possible benefit from the use of more than one at the same time [ 34 ]. We think that the choice of the inhalation mucolytic therefore requires careful clinical evaluation and sharing with patients and their families, having considered all available options.…”

Section: Discussionmentioning

confidence: 99%

Hypertonic saline in people with cystic fibrosis: review of comparative studies and clinical practice

et al. 2021

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Cystic fibrosis (CF) is a multisystem disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. These cause a reduced secretion of chloride, a marked absorption of sodium and, therefore, of water, through the epithelium, resulting in the formation of thickened secretions in organs such as lung or pancreas. These viscous secretions lead to airway obstruction, chronic infection and inflammation resulting in progressive lung damage, bronchiectasis and eventual respiratory failure. Although the average life expectancy has increased over the last 30 years, lung disease is the most common cause of death in people with CF. For these reasons, the improvement of sputum clearance is a major therapeutic aim in CF and early initiation of airway clearance is widely recommended and implemented. Symptomatic mucolytic therapy today is mainly based on inhalation of DNase, hypertonic saline or mannitol, in combination with physiotherapy. Mucolytic agents break down the gel structure of mucus and therefore decrease its elasticity and viscosity, reducing the pulmonary exacerbation frequency and to improve and stabilize lung function. Nevertheless, high quality studies comparing these mucolytic drugs are still few, and the individual experiences of patients and caregivers explain the high variability of their use globally. This review will summarize the current knowledge on hypertonic saline in the treatment of CF lung disease. Furthermore, we report the real-world prescription of inhaled mucolytic agents in CF.

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“…It elevates plasma osmolality, which enhances flow from the extravascular to the intravascular space. Interestingly, inhaled mannitol was also indicated by the Food and Drug Administration (FDA) in the treatment of cystic fibrosis in the lung [ 11 , 12 ].…”

Section: The Most Popular Hyperosmotic Agentsmentioning

confidence: 99%

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

Dąbrowski

Siwicka-Gieroba

Robba

et al. 2021

JCM

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Hyperosmotic therapy is commonly used to treat intracranial hypertension in traumatic brain injury patients. Unfortunately, hyperosmolality also affects other organs. An increase in plasma osmolality may impair kidney, cardiac, and immune function, and increase blood–brain barrier permeability. These effects are related not only to the type of hyperosmotic agents, but also to the level of hyperosmolality. The commonly recommended osmolality of 320 mOsm/kg H2O seems to be the maximum level, although an increase in plasma osmolality above 310 mOsm/kg H2O may already induce cardiac and immune system disorders. The present review focuses on the adverse effects of hyperosmolality on the function of various organs.

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Aerosolized agents for airway clearance in cystic fibrosis

Cited by 14 publications

References 49 publications

Untargeted metabolomics reveals alternations in metabolism of bovine mammary epithelial cells upon IFN-γ treatment

Untargeted metabolomics reveals alternations in metabolism of bovine mammary epithelial cells upon IFN-γ treatment

Hypertonic saline in people with cystic fibrosis: review of comparative studies and clinical practice

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

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