Human Metapneumovirus (hMPV), has been recently isolated from children with acute respiratory tract infections (RTIs), including bronchiolitis, and classified in the Pneumovirinae subfamily within the Paramyxoviridae family.|Since most bronchiolitis studies fail to detect any viral pathogen in part of the samples, we sought for the presence of hMPV in a well characterized bronchiolitis cohort.|Nasal washes were obtained from 56 children admitted to the hospital for acute bronchiolitis. RNA extraction and subsequent RT-PCR were used to detect hMPV, and correlated the presence of the virus with clinical characteristics of the disease.|PCR revealed the presence of hMPV in 16% of bronchiolitis cases, whereas respiratory syncytial virus (RSV; 67.9%) was the most frequently encountered viral pathogen. hMPV was identified either as a unique viral pathogen or co-existed with RSV, with whom they shared a similar seasonal distribution. There were no differences in disease characteristics, either clinical or laboratory, between bronchiolitis cases where hMPV was present and those caused by RSV or other viral pathogens. These findings suggest that hMPV is a common and important causative agent in infants with bronchiolitis, with clinical characteristics similar to that of RSV.

Community-acquired pneumonia (CAP) in young children is most commonly associated with viral infections; however, the role of viruses in CAP of school-age children is still inconclusive.|Seventy-five school-age children hospitalized with CAP were prospectively evaluated for the presence of viral and bacterial pathogens. Nasopharyngeal washes were examined by polymerase chain reaction for viruses and atypical bacteria. Antibody assays to detect bacterial pathogens in acute-phase and convalescent-phase serum samples were also performed.|A viral infection was identified in 65% of cases. Rhinovirus RNA was detected in 45% of patients; infection with another virus occurred in 31%. The most common bacterial pathogen was Mycoplasma pneumoniae, which was diagnosed in 35% of cases. Chlamydia pneumoniae DNA was not detected in any patient; results of serological tests were positive in only 2 patients (3%). Mixed infections were documented in 35% of patients, and the majority were a viral-bacterial combination.|The high prevalence of viral and mixed viral-bacterial infections supports the notion that the presence of a virus, acting either as a direct or an indirect pathogen, may be the rule rather than the exception in the development of CAP in school-age children requiring hospitalization.

Respiratory syncytial virus (RSV) is a common cause of virus infection of the human respiratory tract during the first two years of life, with virtually all children experiencing at least one infection within this period. Although this usually leads to mild respiratory illness, some infants develop more severe disease (bronchiolitis, pneumonia, etc.) affecting the lower airways and frequently requiring hospitalisation. There is evidence that bronchiolitis hospitalisations have increased during the last two decades and many of the hospitalised children develop wheezing later in life. The immune response to the virus is probably a major factor in the development or the expression of the pathological phenotype. In particular, a bias towards type-2 cytokine responses seems to be associated with more severe disease, whereas a type-1 response leads to more effective viral clearance and milder illness. Although the virus by itself triggers a type-1 response, a preexisting type-1 deficiency may contribute to the severity of the disease. In that sense, RSV bronchiolitis may serve as a marker, reflecting predisposition of the individual for virus induced wheezing early in life and/or asthma later in life.

Several epidemiological studies using sensitive detection methodologies have confirmed that the majority of acute asthma exacerbations follow upper respiratory tract infections–common colds. Most of these colds are due to human rhinoviruses (RVs). RVs are able to reach and replicate in epithelial cells of the lower airways and can activate these cells to produce pro-inflammatory mediators. Under some circumstances, RVs can also become cytotoxic to the epithelium. Atopic asthmatic individuals produce less interferon-gamma and more interleukin-10 than normal subjects in response to RV infection. Symptom severity as well as viral shedding after experimental RV infection, is inversely correlated with 'atopic' status, expressed as the interferon-gamma to interleukin-5 ratio. Expression of co-stimulatory molecules on immune cells is also affected in atopic asthmatics, suggesting an aberrant immune response to RV that may lead to suboptimal viral clearance and viral persistence. Some of the above effects can be reversed in vitro by corticosteroids, second-generation antihistamines or anti-oxidants; however, the optimal strategy for treating acute asthma exacerbations requires further research at both mechanistic and clinical levels.

Respiratory syncytial virus (RSV) subtypes A and B are present either simultaneously or alternate during yearly epidemics. It is still not clear whether clinical severity of acute bronchiolitis differs between the two subtypes. Reverse transcription polymerase chain reaction was used to subtype RSV in previously healthy infants hospitalized with RSV bronchiolitis during a winter epidemic. A severity index based on heart rate, respiratory rate, wheezing, difficulty in feeding and oxygen saturation was calculated upon admission. Infants infected with RSV subtype-A were found to have a significantly higher (more severe) clinical score than those infected with RSV-B. There was no statistically significant difference in duration of hospitalization or need of intensive care. Boys and infants younger than 3 months of age were also more severely affected than girls or older infants, respectively. These results support the notion that RSV-A-induced bronchiolitis is more severe than RSV-B-induced one, in agreement with the majority of previously published studies.

Rhinoviruses are the most common precipitants of the common cold and have been associated with different infections of the respiratory tract, such as otitis media and sinusitis. They have also been implicated in the induction of acute asthma exacerbations, most of which are preceded by a common cold. Although in several occasions, mainly in immunocompromised hosts, severe lower respiratory tract infections have been attributed to rhinovirus infections, it is still unclear whether and to what extent these viruses contribute as pathogens in community-acquired pneumonia. Current mechanistic data suggest that rhinoviruses could be the cause of pneumonia in immunocompetent subjects. This notion is supported by epidemiological evidence, however, more clinical studies are needed to assess the actual burden.

Recurrent viral infections are frequently observed in children with atopic asthma. In this study we investigated the ability of the synthetic immunomodulator pidotimod to affect in vitro the phenotype and/or cytokine profile of blood cells in relation to atopic asthma. Peripheral blood mononuclear cells were isolated from 13 atopic asthmatic and 9 normal children and stimulated in culture with mitogen either in the presence or not of the drug. Expression of surface markers was evaluated by flow cytometry, and production of interleukin-4 and interferon-gamma was measured in supernatants. Pidotimod was able to down-regulate the expression of CD30 on cells from both atopic and normal subjects. Because CD30 has been associated with Th-2 cells, this observation supports the possibility of pidotimod being able to affect the Th-1/Th-2 balance in atopic asthma.