Persistent adenoviral infection and chronic airway obstruction in children.

Abstract

Previous studies from several laboratories have established that adenovirus is a common cause of severe childhood bronchiolitis. The observation that children with an established history of bronchiolitis subsequently developed unremitting airways obstruction even after adequate steroid therapy led us to postulate that this bronchial obstruction might be due to persistence of an adenoviral infection. This hypothesis was tested by performing bronchoalveolar lavage (BAL) on a group of 34 children with a mean age of 5 yr (range, 14 mo to 14 yr) who showed an unfavorable response to standard corticosteroid and bronchodilator therapy. Analysis of cytospin preparations of BAL fluid at the light-microscopic level, using a monoclonal antibody to detect adenoviral antigens, demonstrated that capsid protein was present in 31 of 34 (94%) of the children examined. Limited repeat studies within 1 yr showed 6 of 8 (75%) were positive twice when tested on two occasions, and that three were positive in all occasions when sampled three times. Cultures of the BAL fluid were also positive for adenovirus in six of six cultures performed, indicating that the virus was in some cases replicating. Similar studies of control patients without persistent asthma showed no evidence of adenovirus. We conclude that persistent and/or latent adenoviral infection may contribute to the pathogenesis of childhood asthma in which there is an unfavorable response to steroid and bronchodilatation therapy.

Chronic cough and wheeze in children: do they all have asthma?

“…Whether this effect is due to parental smoking [15], air pollution [16], poor access to health care [17] or poor nutrition [18] is difficult to establish. Chronic lung damage resulting from early chest infections with such organisms as respiratory syncytial virus [19] or adenovirus [20] is also well described. Whatever the exact cause, it seems reasonable to assume that the combination of severe respiratory tract infections in early life and poor social conditions produces, in some children, chronic pulmonary inflammation that becomes self-perpetuating, and is manifested by a chronic productive cough with frequent exacerbations throughout childhood [21].…”

Histone acetylation and deacetylation: importance in inflammatory lung diseases

“…Therefore, the latent adenovirus infections described in COPD may contribute to the reduction in HDAC activity described in the peripheral lungs of these patients. Persistence of adenovirus infections has also been implicated in steroid resistance in children with asthma [85].…”

Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

“…54 Immunofluorescence and virus isolation assays were used to show that the majority of bronchoalveolar lavage specimens from children with chronic airway obstruction were infected with Ad, whereas control patients did not show signs of Ad infection. 55 One study showed that an equal proportion of patients who died of fatal asthma, asthmatic patients who died of other causes, and nonasthmatic patients who did not die of lung disease were positive for Ad DNA (by PCR) in lower airway secretions obtained at autopsy. 56 In a study of specimens obtained by nasopharyngeal swabs of normal and asthmatic children at least 3 weeks from their last respiratory infection, Marin et al 57 found that 5% (one out of 20) of normal but 78% (69 out of 88) of asthmatic samples were positive for Ad by PCR.…”