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Allergy & Asthma Advocate: Fall 2005
Airway Remodeling: Why taking care of asthma is importantBy Eugenia Hahn, MD and Iftikhar Hussain, MD Asthma is a chronic disease of reversible airway obstruction with symptoms of wheezing, coughing, shortness of breath, and chest tightness. Airway obstruction occurs when increased mucus secretions block airflow in the lungs and when smooth muscles which line the airways constrict. In susceptible individuals, various triggers such as upper respiratory illness, animal dander, mold, and pollen, lead to recurrent episodes of asthma exacerbations. Airway inflammation is an underlying mechanism that makes these individuals susceptible to various triggers. In patients with severe asthma with persistent chronic symptoms, anti-inflammatory treatment, such as inhaled corticosteroids and leukotriene modifiers, is inadequate. In these patients, irreversible airway obstruction may have developed due to alterations in airway structure, loosely termed as airway remodeling. In addition, lung function, measured as the ability to move air in and out of the lungs, is found to be reduced. Airway remodeling is an ongoing repair process in reaction to inflammation. In asthma, the body has activated a process in attempt to repair the lungs as a response to persistent inflammation, resulting in lasting structural changes. In asthmatic patients, the epithelial layer, the lining of the airway, has undergone structural and functional changes, which may contribute to airway remodeling. In response to injury, the epithelial layer releases proinflammatory molecules, growth factors, and other enzymes. Experts believe that various changes in the epithelial injury-repair cycle in response to inflammation and injury can lead to structural alterations in the airway. It is unclear exactly what aspects of the cycle are altered: the ability to turn off the repair process when completed, the ability to decrease the quantity of proinflammatory molecules, or the ability to decrease the effects of proinflammatory molecules. Structural changes have been described in the airways of asthmatic patients. These changes include increased airway wall thickness involving smooth muscle and collagen, increased mucous glands and mucus production, and increased airway vascularity. The correlation between these findings and asthma severity has not been consistent. Experts believe the structural changes may be the reason why some patients with severe asthma are poorly responsive to corticosteroids. The relationship between inflammation and remodeling are interdependent. Animal models have shown that prolonged allergen exposure can increase smooth muscle and increase mucus production. These findings suggest that allergen exposure can contribute to airway remodeling. Prospective studies have shown that in asthma patients, inhaled corticosteroids had an initial beneficial effect on symptoms and airway function, but these effects were not sustained long term. Since airway remodeling is thought to be the result of persistent underlying inflammation, there are ongoing studies to evaluate the use of inhaled corticosteroids in children in the development of asthma. Prospective studies on the development of asthma and clinical studies would give insight about the role of inflammation in the development of asthma and the effects of inhaled corticosteroids on lung function. Finally, the etiology of airway inflammation is unclear and may be a result of the complex interplay between genetic predisposition, environmental factors, and deregulation of the immune responses. Although genetics play a role in the risk of developing asthma, the increase in prevalence in the last thirty years is too large, rapid, and widespread to be caused by a genetic mechanism. Epidemiological studies have identified environmental influences upon susceptible individuals as potential triggers for the development and persistence of asthma. Some experts theorize that airway inflammation and remodeling may be due to increased susceptibility to injury and may occur simultaneously instead of a result of multiple exacerbations. This model suggests that environmental factors, whether it is allergens, viruses, or other airway irritants, play a dominant role in inducing airway remodeling. So, who is at risk? Evidence has shown that the duration of asthma correlates with decline in lung function. Compared to healthy subjects, patients with asthma have an accelerated decline in lung function, but all patients will not have a uniform decline. In addition, studies have shown that children with persistent symptoms and airway obstruction at younger age predicts a greater decline in lung function over time. The number of asthma exacerbations has been associated with greater decline in lung function. Treatments for asthma may play a significant role by reducing asthma exacerbations resulting in slowing the decline in lung function. The role of treating asthma Ongoing research studies are evaluating the genetic and environmental factors of asthma, looking at the relationship between these two main factors. Understanding this complex relationship would help elucidate the mechanisms behind the development of asthma and would give rise to novel therapeutic agents that may alter the course of asthma. In addition, these studies would help identify individuals who are at risk for developing asthma and allow appropriate therapies to be initiated to prevent the progression of asthma. |
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