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Characterization of airway mucus from a fatal case of status asthmaticus
K R Bhaskar1, D D O'Sullivan, S J Coles
1Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Abstract:
We used density gradient methods to analyze mucus recovered from the airways of a patient who died from status asthmaticus. At postmortem the mucus that plugged the length of the bronchial tree could only be removed by cutting with forceps. It was dispersed in cesium bromide (CsBr) and examined in the analytical ultracentrifuge. Surprisingly, no macromolecular component was seen in the buoyant density region typical of mucus glycoprotein (at 1.5 g/ml). The gelatinous material migrated to the region of lowest density, typical of lipids, and thin-layer chromatography indicated that besides neutral lipids, a variety of phospho- and glycolipids (including gangliosides) were present. The residue left after the lipid extraction contained all sugar components of mucus glycoprotein, and alkaline borohydride cleaved oligosaccharides three to 12 sugars long, indicating that the sugars were O-glycosidically linked as in mucus glycoproteins. Prior desulfation of the residue increased the number of oligosaccharides released by borohydride; analysis showed the presence in these of components (glucose, methylmannuronate) not present in epithelial glycoprotein. A trace component of high buoyant density was also present: Glucose was the predominant component in this, but glycoprotein sugars were also present. The above results suggest that in status asthmaticus plugging of the airways with mucus can occur even in the absence of typical epithelial glycoprotein and that lipids play a crucial role in such plugging.
Insights
Airway mucus in fatal asthma attacks is surprisingly lipid-rich, not glycoprotein-based. This lipid accumulation, rather than typical mucus glycoproteins, likely causes airway obstruction in status asthmaticus.
Area of Science:
- Biochemistry
- Pulmonary Medicine
- Pathology
Background:
- Status asthmaticus is a severe asthma exacerbation characterized by airway obstruction.
- Airway mucus plugging is a key feature of fatal asthma, but its composition is not fully understood.
Observation:
- Postmortem analysis of airway mucus from a patient with status asthmaticus was performed using density gradient ultracentrifugation.
- The mucus predominantly consisted of lipids, not the expected mucus glycoproteins.
Findings:
- Lipids, including neutral, phospho-, and glycolipids (gangliosides), were identified as the main component of the obstructive mucus.
- The remaining residue contained sugars characteristic of O-glycosidically linked mucus glycoproteins, but with unusual components like glucose and methylmannuronate after desulfation.
- A minor high-density component was also detected, primarily composed of glucose and some glycoprotein sugars.
Implications:
- Airway plugging in status asthmaticus may occur due to lipid accumulation rather than solely from epithelial mucus glycoproteins.
- Lipids play a critical role in the pathophysiology of severe airway obstruction during asthma attacks.
- Further research into the role of lipids in asthma mucus is warranted for potential therapeutic targets.