This cross-sectional emergency department study of 70 wheezing children and 59 control subjects (2 mo to 16 yr of age) examined the prevalence of respiratory viruses and their relationship to age, atopic status, and eosinophil markers. Nasal washes were cultured for respiratory viruses, assayed for respiratory syncytial virus (RSV) antigen, and tested for coronavirus and rhinovirus RNA using reverse transcription-PCR (RT-PCR). Also evaluated were eosinophil numbers and eosinophil cationic protein (ECP) in both nasal washes and serum, along with total IgE and specific IgE antibody in serum. Respiratory viruses were detected in 82% (18 of 22) of wheezing infants younger than 2 yr of age and in 83% (40 of 48) of older wheezing children. The predominant pathogens were RSV in infants (detected in 68% of wheezing subjects) and rhinovirus in older wheezing children (71%), and both were strongly associated with wheezing (p < 0.005). RSV was largely limited to wheezing children younger than 24 mo of age, but rhinovirus was detected by RT-PCR in 41% of all infants and in 35% of nonwheezing control subjects older than 2 yr of age. After 2 yr of age the strongest odds for wheezing were observed among those who had a positive RT-PCR test for rhinovirus together with a positive serum radioallergosorbent testing (RAST), nasal eosinophilia, or elevated nasal ECP (odds ratios = 17, 21, and 25, respectively). Results from this study demonstrate that a large majority of emergent wheezing illnesses during childhood (2 to 16 yr of age) can be linked to infection with rhinovirus, and that these wheezing attacks are most likely in those who have rhinovirus together with evidence of atopy or eosinophilic airway inflammation.

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Human rhinovirus (HRV) accounts for a significant portion of common-cold illness, with the peak incidence being in the early fall. Three hundred forty-six adults who had self-diagnosed colds of 48 h or less were enrolled in a study during September and October 1994 to determine the frequency and clinical course of HRV infections. Nasal wash specimens for viral culture and reverse transcription-PCR (RT-PCR) for HRV RNA and human coronavirus OC43 and 229E RNA detection were collected on enrollment, and participants recorded their symptoms twice daily for 14 days. Middle ear pressure (MEP) was measured with a digital tympanometer on days 1 and 7. Picornaviruses (224 HRV and 7 enterovirus isolates) were detected by culture in 67% (231 of 346) of the subjects. Among 114 samples negative by culture, HRV was detected by RT-PCR in 52 (46%) for an overall picornavirus infection rate of 82% (283 of 346 subjects). Among the remaining 62 negative samples, human coronavirus RNA was detected by RT-PCR in 5 patients, so that 288 (83%) of patients had documented viral infection. The first symptom noticed most often was sore throat (40%) in HRV culture-or PCR-positive patients and stuffy nose in HRV-negative patients (27%). No differences in symptom scores over time or in the presence of individual symptoms were noted between groups. The median duration of the cold episodes was 11 days in HRV culture-positive patients, 9.5 days in HRV RT-PCR-positive patients, and 11.5 days in HRVnegative patients. On enrollment, abnormal MEPs (<؊100 or >؉100 mm of H 2 O) were found for 21% of HRV culture-positive patients, 14% of HRV RT-PCR-positive patients, and 10% of HRV-negative patients. No important differences in the clinical course of HRV culture-positive, HRV culture-negative and RT-PCR-positive, or HRV-negative colds were found. These results represent the highest frequency of virologically confirmed natural colds to date and document the importance of rhinoviruses as the cause of colds during fall months.

These findings highlight the importance of common respiratory viruses, particularly HRV and RSV, in predisposing to and causing AOM in young children.

Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.