MbShea@PWP@English@UMCP

ABSTRACT: In obstructive lung diseases, such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD), patients experience an increase in the viscosity of their mucus. The subsequent inability to clear this highly viscoelastic mucus leads to chronic inflammation, recurrent infections, and the blockage of airways, which can all potentially lead to mortality. Clinicians currently rely on indirect measurements, such as spirometry measurements and disease symptoms (e.g. cough, wheezing), to evaluate patients with these obstructive lung diseases. However, these assessments do not address how the viscoelastic properties of mucus produced in the lungs of these patients may impact disease progression. Using particle tracking microrheology, we have previously shown that translational diffusion of polyethylene glycol (PEG) coated muco-inert nanoparticles (MIP) in mucus samples produced from patients with CF is correlated with disease severity. However, the technology required to perform these measurements is not available in clinical laboratories. Here, we show that the rotational diffusion of MIP, as measured by fluorescence polarization (FP) using pre-existing technology found in clinical laboratories, correlates with MIP translational diffusion. Additionally, we have developed formalism to estimate microviscosity from FP-based rotational diffusion measurements and validated this approach using glycerol:water mixtures and polymer solutions and hydrogels of known viscosity.
WC = 201

READER’S PROFILE: I imagine a reader, such as a professor in the field of rheology, being skeptical of this technique due to its perceived variability and lack of precision.

READER’S RESPONSE: This technique lacks the refinement or theoretical explanations of other rheological procedures such as particle tracking microrheology or dynamic light scattering. I question the ability of this procedure to accurately measure microrheology outside the short list of materials tested by the author. Furthermore, the author does not describe how they will account for the high variability experienced in clinical mucus samples associated with dilution by saliva or blood, which would lead to an underestimation of the true viscosity value.

R, can you address that reader comment in the Analysis and Discussion sections of the final piece?

Good work here and I am glad that this class supports you in sharing your important research.