Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness
| Autor: | Kenneth R. Lutchen, Heather L. Gillis |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pathology
medicine.medical_specialty Physiology Respiratory System Models Biological Constriction Airway resistance Physiology (medical) Internal medicine medicine Humans Respiratory system Asthma Lung Mucous Membrane business.industry Airway Resistance Total Lung Capacity Muscle Smooth respiratory system medicine.disease respiratory tract diseases medicine.anatomical_structure Cardiology medicine.symptom Bronchial Hyperreactivity business Airway Algorithms Respiratory tract Muscle contraction Muscle Contraction |
| Zdroj: | Journal of applied physiology (Bethesda, Md. : 1985). 86(6) |
| ISSN: | 8750-7587 |
| Popis: | Although airway remodeling and inflamation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflamation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction. |
| Databáze: | OpenAIRE |
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