Fig. 4. Mucolytic treatment disrupts mucus plugging.

a AB-PAS stained lungs obtained after methacholine dose response tests show mucin glycoproteins obstructing airspaces in vehicle (Veh, n = 8 biological replicates) treated mice that are disrupted by mucolytic treatment (Tx, n = 7 biological replicates). Scale bars, 500 μm (low power) and 25 μm (high power). b–j Calculated mucus volumes (b, e, h), mean fractional occlusion (c, f, i), and heterogeneous plugging (d, g, j) were significantly decreased in AOE-challenged mice receiving mucolytic (Tx, magenta, n = 7 biological replicates) compared to controls (Veh, cyan, n = 8 biological replicates). Mucolytic treatment significantly reduced obstruction across all airways (b–d), and this effect was most prevalent in bronchi (e–g). Although total mucus volume in bronchioles was low (h), occasional mucus aggregates were obstructive and are sensitive to TCEP treatment (i, j). Data in b, c, e, f, h, and i are means ± sem on scatter plots, with p-values shown and significance (*) indicating p < 0.05 by two-tailed Mann–Whitney U-test. Cumulative frequency distributions in d, g, and h show percentages of airways demonstrating occlusion, with circles and error bars identifying means ± sem, and “*” demonstrating significance by t-test using a two-stage step-up method at a 5% false discovery rate. Source data are provided as a Source Data file.