Nasal and Otologic Effects of Experimental Influenza a Virus Infection

Abstract

Past studies showed that experimental rhinovirus colds in adults resulted in eustachian tube dysfunction and abnormal middle ear pressures. In the present study, the symptoms and pathophysiologic findings accompanying experimental influenza viral infection were documented. A total of 33 healthy adult volunteers were intranasally challenged with an influenza A/Kawasaki/86 (H1N1) virus and cloistered over a 9-day postchallenge period to monitor for evidence of infection, signs and symptoms of illness, and the extent and frequency of pathophysiologic responses of the nose, eustachian tube, and middle ear. Results showed a protective effect of high (> or = 16) prechallenge specific hemagglutination-inhibition antibody titer on the rate of infection and the magnitude and extent of provoked symptoms and pathophysiologic findings. Infected subjects with low (< 16) prechallenge serum antibody titers (n = 21) developed significant respiratory illness. These subjects also had objectively measurable increases in nasal secretion production, and decreased nasal patency and mucociliary clearance rates. More than 80% of the infected subjects developed eustachian tube dysfunction, and approximately 80% had middle ear underpressures of less than -100 mm H2O on study days 4 and 5. Five of 21 infected subjects with low prechallenge antibody titers had otoscopic evidence of otitis media with effusion. These results support a causal role for viral upper respiratory tract infection in the pathogenesis of otitis media, possibly mediated by the early development of eustachian tube dysfunction and abnormal middle ear pressure.

Influenza virus inhibits amiloride-sensitive Na+channels in respiratory epithelia

“…Given that the concentration range over which influenza virus inhibits epithelial Na ϩ channels (Fig. 1e) is 10-to 1,000-fold lower than the viral concentrations measured in the nasal turbinates and lungs of mice infected for 3-4 days with influenza (38)(39)(40)(41) and the role of these channels in controlling the amount of fluid in the respiratory tract (4,42), the present findings provide an explanation for the accumulation of fluid in the respiratory tract that is a feature of influenza infections (11,(13)(14)(15)(16). The role of epithelial Na ϩ channels in maintaining the middle ear cavities free of fluid (43,44) suggests that downregulation of Na ϩ channel activity may also underlie the known association between influenza infections and otitis media (11,45).…”

“…Disordered fluid balance across the respiratory mucosa is also a major feature of respiratory infections. Influenza infections, even by the attenuated viruses used in live vaccines (10), are frequently accompanied by rhinorrhea (10,11) and the accumulation of fluid in the eustachian tubes and middle ear (11,12). Furthermore, fluid accumulation in the respiratory tract is an early feature of many severe respiratory infections in both humans (13,14) and animals (15,16).…”

Rhinovirus infection induces mucus hypersecretion

“…Subjects scored eight symptoms (5)(6)(7)27). The sum of sneezing, congestion, and rhinorrhea replies was termed the nasal score.…”

“…Increases in the volume of nasal secretions combined with virus-induced impairments in mucociliary clearance may lead to local pooling of virus-laden secretions in the nasopharynx (6,32). The combination of mucins plus plasma fibrinogen may generate thick mucus ''clots.''…”

Viruslar ve Akut Otitis Media

“…Erişkin deneklere intranazal rhinovirus verilmesiyle %50-80 oranında östaki disfonksiyonu ve %30-50 oranında negatif orta kulak basıncı oluştuğu gösterilmiştir (35)(36)(37). İnflu-enza A virus verilmesiyle erişkin deneklerin %80'den fazlasında östaki disfonksiyonu oluştuğu saptanmıştır (38)(39). İnsanlarda yapılan klinik araştırmalarla viral enfeksiyona yanıt olarak nazofarenkste histamin, bradikinin, IL-1, IL-6, IL-8, lö-kotrien C4 ve tümör nekrozis faktör gibi inflamatuvar mediatörlerin arttığı saptanmıştır (27-30, 40, 41).…”