Rheology predicts sputum eosinophilia in patients with muco-obstructive lung diseases

Volpato, Mathilde; Vialaret, Jérôme; Hirtz, Christophe; Petit, Audrey; Suehs, Carey M.; Patarin, J.; Matzner-Løber, Éric; Vachier, Isabelle; Molinari, Nicolas; Bourdin, Arnaud; Charriot, Jeremy

doi:10.1016/j.bbrc.2022.07.025

Cited by 5 publications

(6 citation statements)

References 43 publications

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“…The asthma group was characterized by elastic and viscous moduli significantly higher (G ′ = 14.49 Pa•s, G ′′ = 3 Pa•s) than those of the COPD group (G ′ = 5.01 Pa•s; G ′′ = 1.45 Pa•s). Sputum eosinophil percentages were higher in the asthma group (1.02%) compared to the COPD (0.25%) group, and Spearman's correlation tests confirmed that G' and G" were positively correlated with MUC5AC protein concentration [172].…”

Section: Mucus In Asthmamentioning

confidence: 74%

“…TCEP treatment increased mean-squared displacement (MSD) values, decreased the viscoelasticity of mucus, caused rapid depolarization of mucins, and normalized the homogeneity and level of MSD such that they were similar to those of controls. Another study assessed the contribution of eosinophil and mucin content to mucus rheology from spontaneous unselected sputum samples harvested from patients with asthma and COPD [172]. The asthma group was characterized by elastic and viscous moduli significantly higher (G ′ = 14.49 Pa•s, G ′′ = 3 Pa•s) than those of the COPD group (G ′ = 5.01 Pa•s; G ′′ = 1.45 Pa•s).…”

Section: Mucus In Asthmamentioning

confidence: 99%

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Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

Abrami,

Biasin,

Tescione

et al. 2024

IJMS

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The respiratory mucus, a viscoelastic gel, effectuates a primary line of the airway defense when operated by the mucociliary clearance. In chronic respiratory diseases (CRDs), such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), the mucus is overproduced and its solid content augments, changing its structure and viscoelastic properties and determining a derangement of essential defense mechanisms against opportunistic microbial (virus and bacteria) pathogens. This ensues in damaging of the airways, leading to a vicious cycle of obstruction and infection responsible for the harsh clinical evolution of these CRDs. Here, we review the essential features of normal and pathological mucus (i.e., sputum in CF, COPD, and asthma), i.e., mucin content, structure (mesh size), micro/macro-rheology, pH, and osmotic pressure, ending with the awareness that sputum biomarkers (mucins, inflammatory proteins and peptides, and metabolites) might serve to indicate acute exacerbation and response to therapies. There are some indications that old and novel treatments may change the structure, viscoelastic properties, and biomarker content of sputum; however, a wealth of work is still needed to embrace these measures as correlates of disease severity in association with (or even as substitutes of) pulmonary functional tests.

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Section: Mucus In Asthmamentioning

confidence: 74%

Section: Mucus In Asthmamentioning

confidence: 99%

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

Abrami,

Biasin,

Tescione

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…For the variable “critical stress σc”, the threshold of 39 was determined based on a previously published ancillary study [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…The objective selection of a subpopulation of COPD patients, based on altered or unaltered sputum rheology (now easily quantifiable within minutes), would provide a more effective treatment algorithm than the current standard management. In patients with COPD, asthma, and non-CF bronchiectasis, our team recently demonstrated that sputum rheology (elastic modulus G’, viscous modulus G’’, and critical stress σc), was correlated with MUC5AC and MUC5B mucin content and sputum eosinophilia [ 25 ]. We have also shown that sputum rheology can predict sputum eosinophilia at a rate superior or equal to 1.25%, a value that correlated with exacerbations requiring corticosteroids and a reduction in FEV1 in the SPIROMICS cohort [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Sputum-Rheology-Based Strategy for Guiding Azithromycin Prescription in COPD Patients with Frequent Exacerbations: A Randomized, Controlled Study (“COPD CARhE”)

et al. 2023

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(1) Background: We have previously shown that sputum rheology can discriminate between patients with COPD and other muco-obstructive lung diseases, and that it is correlated with mucin content and sputum eosinophilia. We now hypothesize that it could be a more-accurate guide than clinical evaluation for the prescription of azithromycin to prevent exacerbations of COPD and to reduce exposure to antibiotics; (2) Methods: “COPD CaRhe” is a multicentric, randomized, controlled trial comparing outcomes in two parallel arms (36 vs. 36 patients). Patients will be recruited in the university hospitals of Montpellier, Bordeaux, and Toulouse, in France, and they should have a diagnosis of COPD with frequent exacerbations (≥3/year). Enrollment will occur during a routine visit to a respiratory department, and follow-up visits will occur every 3 months for a period of 1 year. At each visit, a 3-month prescription of azithromycin will be provided to those patients who obtain a score of <70 on the Cough and Sputum Assessment Questionnaire (CASA-Q) or a critical stress score of σc > 39 on a rheological assessment of sputum, depending upon their randomization group. The primary outcome will be the number of exacerbations of COPD; (3) Discussion: By using sputum rheology, the COPD CaRhe study may provide clinicians with an objective biomarker to guide the prescription of azithromycin while reducing the cumulative exposure to macrolides.

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“…Ex vivo samples can be obtained by expectoration when patients are able to produce sputum or more invasively by endotracheal collection, but the availability and reproducibility of samples are not guaranteed, and the collected volumes are very limited (in the order of 10 2 μL or less). In addition, mucus samples collected from patients are often infected or inflamed, , which makes them unsuitable for in vitro applications where sterile material may be needed. Because of these limitations, there is a great interest in developing a controlled mucus model able to replicate the mechanical properties and physicochemical interactions happening within native mucus.…”

Section: Introductionmentioning

confidence: 99%

Gastropod Slime-Based Gel as an Adjustable Synthetic Model for Human Airway Mucus

Milian,

Robert de Saint Vincent,

Patarin

et al. 2023

Biomacromolecules

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Airway mucus works as a protective barrier in the human body, as it entraps pathogens that will be later cleared from the airways by ciliary transport or by coughing, thus featuring the rheological properties of a highly stretchable gel. Nonetheless, the study of these physical barrier as well as transport properties remains limited due to the restricted and invasive access to lungs and bronchi to retrieve mucus and to the poor repeatability inherent to native mucus samples. To overcome these limits, we report on a biobased synthetic mucus prepared from snail slime and multibranched thiol cross-linker, which are able to establish disulfide bonds, in analogy with the disulfide bonding of mucins, and therefore build viscoelastoplastic hydrogels. The gel macroscopic properties are tuned by modifying the cross-linker and slime concentrations and can quantitatively match those of native sputum from donors with cystic fibrosis (CF) or non-cystic fibrosis bronchiectasis (NCFB) both in the small-and large-deformation regimes. Heterogeneous regimes were locally found in the mucus model by passive microrheology, in which both diffusive and nondiffusive motion are present, similar to what is observed in sputa. The biobased synthetic approach proposed in the present study thus allows to produce, with commercially available components, a promising model to native respiratory mucus regarding both mechanical and, to a lesser extent, physicochemical aspects.

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Rheology predicts sputum eosinophilia in patients with muco-obstructive lung diseases

Cited by 5 publications

References 43 publications

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

Sputum-Rheology-Based Strategy for Guiding Azithromycin Prescription in COPD Patients with Frequent Exacerbations: A Randomized, Controlled Study (“COPD CARhE”)

Gastropod Slime-Based Gel as an Adjustable Synthetic Model for Human Airway Mucus

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