Magnetomotive optical coherence elastography for relating lung structure and function in cystic fibrosis

AbstractBedside lung ultrasound (LUS) can play a role in the setting of the SarsCoV2 pneumonia pandemic. To evaluate the clinical and LUS features of COVID-19 in the ED and their potential prognostic role, a cohort of laboratory-confirmed COVID-19 patients underwent LUS upon admission in the ED. LUS score was derived from 12 fields. A prevalent LUS pattern was assigned depending on the presence of interstitial syndrome only (Interstitial Pattern), or evidence of subpleural consolidations in at least two fields (Consolidation Pattern). The endpoint was 30-day mortality. The relationship between hemogasanalysis parameters and LUS score was also evaluated. Out of 312 patients, only 36 (11.5%) did not present lung involvment, as defined by LUS score < 1. The majority of patients were admitted either in a general ward (53.8%) or in intensive care unit (9.6%), whereas 106 patients (33.9%) were discharged from the ED. In-hospital mortality was 25.3%, and 30-day survival was 67.6%. A LUS score > 13 had a 77.2% sensitivity and a 71.5% specificity (AUC 0.814; p < 0.001) in predicting mortality. LUS alterations were more frequent (64%) in the posterior lower fields. LUS score was related with P/F (R2 0.68; p < 0.0001) and P/F at FiO2 = 21% (R2 0.59; p < 0.0001). The correlation between LUS score and P/F was not influenced by the prevalent ultrasound pattern. LUS represents an effective tool in both defining diagnosis and stratifying prognosis of COVID-19 pneumonia. The correlation between LUS and hemogasanalysis parameters underscores its role in evaluating lung structure and function.

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Structure and Function of the CFTR Chloride Channel

Physiological Reviews ◽

10.1152/physrev.1999.79.1.s23 ◽

1999 ◽

Vol 79 (1) ◽

pp. S23-S45 ◽

Cited By ~ 647

Author(s):

DAVID N. SHEPPARD ◽

MICHAEL J. WELSH

Keyword(s):

Cystic Fibrosis ◽

Chloride Channel ◽

Atp Hydrolysis ◽

Current Knowledge ◽

Structure And Function ◽

Binding Domains ◽

Transporter Family ◽

Membrane Spanning ◽

And Function ◽

R Domain

Sheppard, David N., and Michael J. Welsh. Structure and Function of the CFTR Chloride Channel. Physiol. Rev. 79 , Suppl.: S23–S45, 1999. — The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ABC transporter family that forms a novel Cl− channel. It is located predominantly in the apical membrane of epithelia where it mediates transepithelial salt and liquid movement. Dysfunction of CFTR causes the genetic disease cystic fibrosis. The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. Here we review the structure and function of this unique channel, with a focus on how the various domains contribute to channel function. The MSDs form the channel pore, phosphorylation of the R domain determines channel activity, and ATP hydrolysis by the NBDs controls channel gating. Current knowledge of CFTR structure and function may help us understand better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters.

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Lung Structure And Function Relation In Elastase-Treated Rats: A Long-Term Follow Up Study

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6405 ◽

2012 ◽

Author(s):

Margit V. Szabari ◽

Jozsef Tolnai ◽

Balazs Maar ◽

Harikrishnan Parameswaran ◽

Elizabeth Bartolak-Suki ◽

...

Keyword(s):

Structure And Function ◽

Follow Up Study ◽

Lung Structure ◽

Long Term Follow Up ◽

And Function ◽

Function Relation

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Hyperinsulinemia adversely affects lung structure and function

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00091.2015 ◽

2016 ◽

Vol 310 (9) ◽

pp. L837-L845 ◽

Cited By ~ 28

Author(s):

Suchita Singh ◽

Manish Bodas ◽

Naveen K. Bhatraju ◽

Bijay Pattnaik ◽

Atish Gheware ◽

...

Keyword(s):

Insulin Treatment ◽

Epithelial Mesenchymal Transition ◽

Respiratory Health ◽

Structure And Function ◽

Intranasal Insulin ◽

Mesenchymal Transition ◽

Inhaled Insulin ◽

Lung Structure ◽

Prevalence Of Obesity ◽

And Function

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly ( P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

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Perinatal Inflammation Negatively Impacts Lung Structure And Function In Adult Mice

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1223 ◽

2012 ◽

Author(s):

Markus Velten ◽

Rodney D. Britt ◽

Kathryn M. Heyob ◽

Trent E. Tipple ◽

Lynette K. Rogers

Keyword(s):

Structure And Function ◽

Adult Mice ◽

Lung Structure ◽

And Function

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CT-Derived Pulmonary Vascular Volume And Lung Structure And Function In Humans

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2032 ◽

2012 ◽

Author(s):

Sarah Lau ◽

Courtney M. Wheatley ◽

Eric C. Wong ◽

Nicholas A. Cassuto ◽

Cori L. Daines ◽

...

Keyword(s):

Structure And Function ◽

Vascular Volume ◽

Lung Structure ◽

And Function

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A new Era of Personalized Medicine for Cystic Fibrosis – at Last!

Canadian Respiratory Journal ◽

10.1155/2015/921712 ◽

2015 ◽

Vol 22 (5) ◽

pp. 257-260 ◽

Cited By ~ 3

Author(s):

Bradley S Quon ◽

Pearce G Wilcox

Keyword(s):

Cystic Fibrosis ◽

Personalized Medicine ◽

Late Phase ◽

Structure And Function ◽

Clinical Development ◽

New Era ◽

High Throughput Drug Screening ◽

Cftr Protein ◽

And Function ◽

Screening Approaches

The gene responsible for cystic fibrosis (CF) was discovered 25 years ago. This breakthrough has enabled a sophisticated understanding of how various mutations lead to specific alterations in the structure and function of the CF transmembrane regulator (CFTR) protein. Until recently, all therapies in CF were focused on ameliorating the downstream consequences of CFTR dysfunction. High-throughput drug screening approaches have yielded compounds that can modify CFTR structure and function, thus targeting the basic defect in CF. The present article describes theCFTRmutational classes, reviews mutation-specific therapies currently in late-phase clinical development, and highlights research opportunities and challenges with personalized medicine in CF.

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