Background: Asthma is an international health problem of epidemic proportions that affects around 300 million people worldwide with an estimated 250,000 annual deaths. It is the most common chronic childhood disease, and affects 10% of children in the United States (1). The economic burden of the chronic effects of asthma in the United States is estimated to be over $50 billion per year (2).
The hallmark of asthma is hyperresponsiveness of the airway smooth muscle and fluctuating levels of airflow obstruction. Clinically, this manifests itself as repeated episodes of shortness of breath and wheezing, which can deteriorate to respiratory failure and death. The main culprit of airway obstruction is symptomatic airway narrowing due to the contraction …show more content…
A major problem in asthma are extended episodes of bronchospasm, where symptoms persist even when stimuli leading to it are removed. To explain this memory effect, several models have been proposed either based on purely mechanical effects (Lambert model) (32), or purely immunological mechanisms (33). Here, we present an in vitro model to perform mechanistic studies of bronchospasm, and propose a new hybrid mechanism based on the coupling between airway smooth-muscle contraction and activation of inflammatory pathways through mechanical stress in airway epithelial …show more content…
For 10-15%, who suffer from severe asthma, it is a life-threatening condition. Furthermore, the rate of asthma is expected to increase considerably, as communities around the world become more urbanized and adopt a western lifestyle. The major source of morbidity and mortality of asthma is airway obstruction, which often is due to actively constricted smooth muscle of the bronchi. Besides this constriction, what significantly contributes to the morbidity of asthma is also the relatively slow recovery from bronchospasms. A better understanding of the factors that contribute to the delayed relaxation of the airway smooth muscle cells has a potential for better treatment approaches to asthmatic conditions. We show that compressive stress levels in asthmatic airways can lead to sustained bronchospasm due to mechanical-stress regulated release of spasmogens by the airway epithelium, even upon removal of external stimuli that initially triggered the
The hallmark of asthma is hyperresponsiveness of the airway smooth muscle and fluctuating levels of airflow obstruction. Clinically, this manifests itself as repeated episodes of shortness of breath and wheezing, which can deteriorate to respiratory failure and death. The main culprit of airway obstruction is symptomatic airway narrowing due to the contraction …show more content…
A major problem in asthma are extended episodes of bronchospasm, where symptoms persist even when stimuli leading to it are removed. To explain this memory effect, several models have been proposed either based on purely mechanical effects (Lambert model) (32), or purely immunological mechanisms (33). Here, we present an in vitro model to perform mechanistic studies of bronchospasm, and propose a new hybrid mechanism based on the coupling between airway smooth-muscle contraction and activation of inflammatory pathways through mechanical stress in airway epithelial …show more content…
For 10-15%, who suffer from severe asthma, it is a life-threatening condition. Furthermore, the rate of asthma is expected to increase considerably, as communities around the world become more urbanized and adopt a western lifestyle. The major source of morbidity and mortality of asthma is airway obstruction, which often is due to actively constricted smooth muscle of the bronchi. Besides this constriction, what significantly contributes to the morbidity of asthma is also the relatively slow recovery from bronchospasms. A better understanding of the factors that contribute to the delayed relaxation of the airway smooth muscle cells has a potential for better treatment approaches to asthmatic conditions. We show that compressive stress levels in asthmatic airways can lead to sustained bronchospasm due to mechanical-stress regulated release of spasmogens by the airway epithelium, even upon removal of external stimuli that initially triggered the