Rheological analysis of sputum from patients with chronic bronchial diseases

Abstract

Bronchial diseases are characterised by the weak efficiency of mucus transport through the lower airways, leading in some cases to the muco-obstruction of bronchi. It has been hypothesised that this loss of clearance results from alterations in the mucus rheology, which are reflected in sputum samples collected from patients, making sputum rheology a possible biophysical marker of these diseases and their evolution. However, previous rheological studies have focused on quasi-static viscoelastic (linear storage and loss moduli) properties only, which are not representative of the mucus mobilisation within the respiratory tract. In this paper, we extend this approach further, by analysing both quasi-static and some dynamic (flow point) properties, to assess their usability and relative performance in characterising several chronic bronchial diseases (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) and distinguishing them from healthy subjects. We demonstrate that pathologies influence substantially the linear and flow properties. Linear moduli are weakly condition-specific and even though the corresponding ranges overlap, distinct levels can be identified. This directly relates to the specific mucus structure in each case. In contrast, the flow point is found to strongly increase in muco-obstructive diseases, which may reflect the complete failure of mucociliary clearance causing episodic obstructions. These results suggest that the analysis of quasi-static and dynamic regimes in sputum rheology is in fact useful as these regimes provide complementary markers of chronic bronchial diseases.

Optimizations of In Vitro Mucus and Cell Culture Models to Better Predict In Vivo Gene Transfer in Pathological Lung Respiratory Airways: Cystic Fibrosis as an Example

“…At last, there are numerous recent studies concerning the search for rheological properties as characteristic markers of respiratory diseases [ 59 ]. From that point of view, characteristics of the rheological response in a non-linear regime (large deformation or flow regime) seem to be better biomarkers than the viscoelastic response in the linear regime [ 60 ].…”

Magnetic wire active microrheology of human respiratory mucus

“…To this end, macro and microrheological data from 23 sputum and mucus surveys were evaluated. [9][10][11]13,14,16,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] The nature, origin and references of the samples selected for this analysis are listed in ESI, † S9. From these reports, the elastic modulus G 0 (o), the loss modulus G 00 (o) and the complex modulus G Ã ðoÞ ¼ ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ffi G 0 ðoÞ 2 þ G 00 ðoÞ 2 p =o were compiled for cystic fibrosis sputum and healthy mucus.…”

“…[6][7][8] Besides it was shown recently that the elastic modulus of expectorated samples from patients with asthma, COPD and cystic fibrosis, when measured at large deformation increases in this order compared to healthy mucus, suggesting that rheology could be used as a biomarker for chronic bronchial disease. 9 Rheological measurements of human pulmonary mucus are however difficult to carry out. One reason is the minute quantity of sample available from healthy individuals or diseased patients, typically of the order of a few microliters.…”

“…To overcome the difficulty related to macrorheology volume requirement, researchers have focused on sputum samples. 7,9,11,13,14,18,[24][25][26][27][28][29][30][31] The sputum samples are generally obtained from patients with serious lung conditions, such as cystic fibrosis and COPD. The collection methods are invasive and present a risk of contamination with saliva or blood.…”

“…10,26 We compiled sputum and mucus rheology data coming from 23 surveys. [9][10][11]13,14,16,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] Data on cystic fibrosis sputum 7,9,13,14,24,[28][29][30][31]33 shows a gel-like behavior with the elastic modulus G 0 (o) larger than the loss modulus G 00 (o) over the frequency range 0.01-100 rad s À1 . At the angular frequency o = 1 rad s À1 , it is found that the averaged values of G 0 and G 00 for cystic fibrosis sputum are 4.4 AE 1.9 Pa and 3.0 AE 2.0 Pa, respectively, whereas its shear viscosity is estimated to be 67 AE 34 Pa s at a shear rate of 1 s À1 .…”