Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection.

Abstract

To study the cellular infiltrate that occurs within the airways of infants with respiratory syncytial virus bronchiolitis, samples of airways secretions were obtained by bronchial lavage from the lower respiratory tract of infants ventilated for this condition and from the upper airway of non-intubated infants with this disorder using nasopharyngeal aspirates.Cytospin samples were prepared so that differential cell counts could be performed on the cells obtained and alkaline phosphatase-antialkaline phosphatase immunocytochemical analysis of lymphocyte subsets was carried out using a panel of monoclonal antibodies, which included anti-CD3, anti-CD4, anti-CD8, anti-CD19, and anti-TcR-y.Results from the lower and upper airways were similar. Large numbers of inflammatory cells were obtained, of which neutrophils accounted for a median of 93%/o in the upper airway and 76% in the lower airway. The numbers of CD8 positive cells detected were small and consistently less than CD4 positive cells, median CD4:CD8 ratios being 22*5:1 and 15:1 for the lower and upper airways. CD19 positive cells were rarely observed and no y8 positive lymphocytes were detected.These results indicate that neutrophils probably play a major part in causing symptoms in these infants. They do not support the concept that excessive lymphocyte mediated cytotoxic activity is principally responsible for the pathology in respiratory syncytial virus bronchiolitis. (Arch Dis Child 1994; 71: 428-432) The respiratory syncytial virus is unique in its ability to cause yearly epidemics of respiratory disease.1 2 As a result almost all infants will have been infected by the virus by the second year of life and, of these, 05-2% develop acute bronchiolitis severe enough to be admitted to hospital. Results from studies using a formalin inactivated virus3 and other more recent attempts to produce a vaccine suggest that it is unlikely that we will be able to effectively prevent this distressing illness until the immunological mechanisms involved in the disease process, including those aspects conferring protection, are clarified.

The histopathology of fatal untreated human respiratory syncytial virus infection

“…Analysis of the cellular composition of bronchoalveolar lavage (BAL) fluid in acutely RSVinfected infants suggests that polymorphonuclear leukocytes play an important role in the response to acute RSV infection, at least in the airway and airspace compartments. 19,20 This is consistent with finding high levels of IL-8 in respiratory secretions of RSV-infected infants 21 or adults. 22 In the current cases, debris consisting of sloughed epithelium and macrophages with fibrin and minimal mucin was noted to fill airway lumens.…”

“…There were very few CD4 þ T cells present in the inflammatory infiltrates. The magnitude of lymphocytes in the peribronchiolar infiltrates contrasts sharply with a study of bronchial lavage samples, 19 in which CD3 þ T cells were not present in BAL fluid in infected infants. The prominence of CD8 þ T cells in the peribronchiolar and alveolar interstitial infiltrate is consistent with the correlation of CD8 þ T cells with virus clearance and illness in the murine model of RSV 29 and the bovine model of BRSV.…”

Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility

“…18 The increased abundance of mRNA from haplotype 2 is compatible with the observation that the concentration of IL-8 is correlated with severe disease 7 and that severely affected individuals have increased neutrophil infiltration in the lungs. 3,4 The effect of the haplotype on mRNA abundance appeared to be cell specific as it was observed in primary respiratory epithelial cells but was not seen in primary lymphocyte cells. Though the size of the difference in mRNA detected between the two haplotypes was modest (6%), it remains statistically significant and may be of biological importance for the following reasons.…”

“…2 IL-8 contributes to the activation and migration of neutrophils that characterize the inflammatory infiltrates seen in the airways of affected individuals. 3,4 IL-8 is present in nasal secretion 5 and tracheal aspirate 6 samples from patients with RSV infection. Moreover, the concentration of IL-8 transcript in nasopharyngeal secretions from affected infants is significantly associated with disease severity.…”

Chronic cough in children: bronchoalveolar lavage findings

“…These children may have recurrent viral infection as the underlying cause of cough since viral infections are known to induce neutrophilia e.g. in bronchial lavage and nasopharyngeal secretions from infants with respiratory syncytial virus infection [17]. Both healthy and asthmatic subjects have significantly increased induced sputum neutrophils during experimental rhinovirus-16 infection [18].…”