Effects of Vitamin A Deficiency on Virus-Infected Airwa*

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Acute viral respiratory illnesses are a major cause of morbidity and mortality in children worldwide, but particularly in regions where vitamin A deficiency (VAD) is common. This proposal seeks to address the hypothesis VAD may promote bronchial hyperreactivity (BHR), particularly during and after an upper respiratory infection (URI). This may be accentuated in individuals with pre-existing asthma. The hypothesis will be addressed through two specific aims: (1) To determine whether sub-clinical VAD is associated with prolonged airway reactivity following acute respiratory tract illness in children with or without pre-existing asthma. (2) To establish whether VAD alters the characteristics of the inflammatory response to viral infection in the nasal cavity, which is an important determinant of bronchial hyperreactivity. Prevailing evidence indicates that the airway hyperresponsiveness, that follows acute upper respiratory illness, results from viral invasion of the lower respiratory tract, persistence of inflammatory cells and peptide mediators, and/or residual airway edema, which may be influenced by VAD. The analysis of airway hyperresponsiveness to histamine is a feasible, reliable, well-tolerated approach that can be used for serial measurements. The applicant has conducted a pilot study in Natal, RN, Brazil which indicated that sub- clinical vitamin-A deficiency exists in approximately 30% of the children encountered, and he has established a working collaboration with Brazilian scientists. Studies in children will be conducted in Natal, and subjects will be recruited during visits to the emergency hospital. The forced oscillatory technique will be used to measure total respiratory resistance during the acute and convalescent stages of acute viral respiratory illness in children ages 2 through 8 years. Viral infection will be documented by analysis of nasal lavage specimens using reverse-transcriptase polymerise chain reaction analysis. Vitamin- A nutriture will be assessed through a modified relative dose response test. The rate of normalization of respiratory resistance and airway hyperresponsiveness will be compared in individuals with or without viral upper respiratory tract infections, who have normal or diminished vitamin A stores. The second aim will evaluate how VAD alters the immunologic and inflammatory response of the nasal epithelium to viral infection. Studies will focus on cytokines and epithelial properties that are known to be altered by VAD and/or by viral infection, and are thought to influence bronchial hyperreactivity. These studies should help establish whether VAD is an important contributor to airway pathology following viral respiratory tract illnesses and illuminate some of the pathologic mechanisms that may be involved.