Cysteinyl leukotriene receptor 1 expression identifies a subset of neutrophils during the antiviral response that contributes to postviral atopic airway disease.

BACKGROUND: Viral respiratory tract infections increase the risk of development and exacerbation of atopic disease. Previously, we demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of postviral atopic airway disease in mice. OBJECTIVE: We sought to determine whether human CD49d+ PMNs are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in human subjects and mice. METHODS: Sixty subjects (5-50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swabs for viral PCR were performed at enrollment and during convalescence. The Sendai virus mouse model was used to investigate the phenotype and functional relevance of CD49d+ PMNs. RESULTS: CD49d+ PMN frequency was significantly higher in nasal lavage fluid during acute respiratory symptoms in all subjects (2.9% vs 1.0%, n = 42, P < .001). In mice CD49d+ PMNs represented a "proatopic" neutrophil subset that expressed cysteinyl leukotriene receptor 1 (CysLTR1) and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in the first days of a viral respiratory tract infection was sufficient to reduce accumulation of CD49d+ PMNs in the lungs and development of postviral atopic airway disease. Similar to the mouse, human CD49d+ PMNs isolated from nasal lavage fluid during a viral respiratory tract infection expressed CysLTR1. CONCLUSION: CD49d and CysLTR1-coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease.

Heiner syndrome mimicking an immune deficiency.

Heiner syndrome is a rare but reversible non-IgE mediated hypersensitivity to cow's milk resulting in an atypical pulmonary disease in infants and young children. There isoften a delay in diagnosis in this disorder due to its unusual presentation with heterogeneous manifestations. Such infants usually have chronic or recurrent upper or lower respiratory tract symptoms, suggestive of recurring infections such as otitis media or pneumonia. The patchy infiltrates on chest x-ray are commonly mistaken for pneumonia, yet are refractory to antibiotictreatment. Systemic features such as fever, vomiting, diarrhea, and failure to thrive further contribute to the difficulty in making a prompt diagnosis. Only a few case reports have been published. We report a case of this unique milk-induced pulmonary syndrome in a hospitalized 12-month-old child, which illustrates the importance of considering this diagnosis in any child with unexplained lung infiltrates.