Matti Korppi

Rhinovirus-induced wheezing in infancy—the first sign of childhood asthma?

Abstract Background: Although known as common causes of upper respiratory infections, rhinoviruses, enteroviruses, and corona-viruses are poorly studied as inducers of wheezing in infants, and their possible role in the development of childhood asthma has not been investigated. Objective: The purposes of this study were to assess the occurrence of RV, enterovirus, and coronavirus infections in wheezing infants and to evaluate the association of these viral findings with early school-age asthma. Methods: In 1999, outcome in relation to asthma was studied in 82 of 100 initially recruited children who had been hospitalized for wheezing in infancy during the period 1992-1993. In 2000, etiologic viral studies regarding the index episode of wheezing were supplemented by rhinovirus, enterovirus, and coronavirus detection by RT-PCR from frozen nasopharyngeal aspirates in 81 of the children for whom adequate samples were available. Of these children, 66 had participated in the follow-up in 1999. Results: Rhinoviruses were identified in 27 (33%) of the 81 children, enteroviruses in 10 (12%), and coronaviruses in none. Rhinoviruses were present as single viral findings in 22 (81%) of the 27 rhinovirus-positive cases, and rhinovirus infections were associated with the presence of atopic dermatitis in infancy. Enteroviruses were commonly encountered in mixed infections and had no association with atopy. As single viral findings, rhinoviruses were associated with the development of asthma (P = .047; odds ratio, 4.14; 95% CI, 1.02-16.77 versus rhinovirus-negative cases [by logistic regression adjusted for age, sex, and atopic dermatitis on entry)]. Conclusion: Our results present rhinoviruses as important inducers of wheezing even in infancy. The association with atopy and subsequent asthma calls for reevaluation of the role of rhinoviruses in the development of asthma. (J Allergy Clin Immunol 2003;111:66-71.)

Rhinovirus-associated wheezing in infancy: comparison with respiratory syncytial virus bronchiolitis.

Background: There is increasing evidence that rhinoviruses (RV) are able to cause lower airway infections and to induce wheezing in young children. There are few data on the clinical characteristics of RV infections in infants. Objective: The aim of the study was to compare clinical characteristics of infantile RV infection associated with wheezing and respiratory syncytial virus (RSV) bronchiolitis. Material and Methods: During a 22-month study period in 1992–1993, 100 children younger than 24 months old were hospitalized with respiratory tract infection-associated wheezing. Viral etiology was originally assessed by antibody and antigen assays. Etiologic studies were later supplemented by polymerase chain reaction for RVs (in 2000) and for RSV (in 2002), studied in frozen respiratory samples. There were 81 children with adequate determinations for both RVs and RSV. Twenty-six children had RV and 24 had RSV infection, and these 50 cases form the material of the present study. Atopic dermatitis, oxygen saturation, respiratory rates and clinical scores based on wheezing and retractions and total serum IgE concentrations and blood eosinophil counts were studied in all cases on admission. Results: The children with RV infection, compared with RSV patients, were older (median, 13 versus 5 months), presented more often with atopic dermatitis (odds ratio, 16.7; 95% confidence interval, 2.22–100) and blood eosinophilia (odds ratio, 2.22; 95% confidence interval, 1.04–50). The groups did not differ from each other with regard to total serum IgE. Oxygen saturation values were lower in children with RSV infection. There were no significant differences in respiratory rates or scores combining wheezing and retractions. Conclusion: RV-associated wheezing and RSV bronchiolitis, although having rather similar clinical characteristics, differ significantly with regard to age, presence of atopic dermatitis and eosinophilia during infection.

Aetiology of community-acquired pneumonia in children treated in hospital

Viral and bacterial antigen and antibody assays were prospectively applied to study the microbial actiology of community-acquired pneumonia in 195 hospitalised children during a surveillance period of 12 months. A viral infection alone was indicated in 37 (19%), a bacterial infection alone in 30 (15%) and a mixed viral-bacterial infection in 32 (16%) patients. Thus, 46% of the 69 patients with viral infection and 52% of the 62 patients with bacterial infection had a mixed viral and bacterial aetiology. Respiratory syncytial virus (RSV) was identified in 52 patients andStreptococcus pneumoniae in 41 patients. The next common agents in order were non-classifiedHaemophilus influenzae (17 cases), adenoviruses (10 cases) andChlamydia species (8 cases). The diagnosis of an RSV infection was based on detecting viral antigen in nasopharyngeal secretions in 79% of the cases. Pneumococcal infections were in most cases identified by antibody assays; in 39% they were indicated by demonstrating pneumococcal antigen in acute phase serum. An alveolar infiltrate was present in 53 (27%) and an interstitial infiltrate in 108 (55%) of the 195 patients. The remaining 34 patients had probable pneumonia. C-reactive protein (CRP), erythrocyte sedimentation rate and total white blood cell count were elevated in 25%, 40% and 36% of the patients, respectively, CRP was more often elevated in patients with bacterial infection alone than in those with viral or mixed viral-bacterial infections. No other correlation was seen between the radiological or laboratory findings and serologically identified viral, bacterial or mixed viralbacterial infections. By using a comprehensive serological panel, the causative agent could be found in over 50% of patients with pneumonia. We conclude that RSV and pneumococcus are the two most common organisms causing pneumonia in children. Our results suggest that mixed viral-bacterial aetiology is common in lower respiratory tract infections affecting children.

Bacterial coinfection in children hospitalized with respiratory syncytial virus infections

Clinical and bacterial findings were prospectively studied in 90 children hospitalized because of middle or lower respiratory tract infection caused by respiratory syncytial virus (RSV) during a surveillance period of 12 months. The results were compared with those of RSV-negative children hospitalized with identical indications during the 3 peak months of the RSV epidemic (N =91) or for the 3 months after the outbreak (N= 99). A high frequency of pneumonia and acute otitis media were found in both RSV-positive and RSV-negative children during the epidemic, but not in control patients after the epidemic. Bacterial infection, based on a significant rise of antibody titer and/or on detection of pneumococcal antigen in serum or urine, was observed in 39% of the children with RSV-negative children hospitalized during the epidemic and 8% after the epidemic. Our observations stress the role of RSV as a predisposing agent for secondary bacterial infection in the airways of children. The most common bacteria involved in the mixed RSV-bacterial infections were Streptococcus pneumoniae and Haemophilus influenzae, the latter being found only in pneumonic patients. The presence or absence of pneumonic or acute otitis media was not significantly correlated with evidence of pneumococcal infection. We conclude that a bacterial pathogen should be actively sought when managing patients with lower respiratory tract syndromes, especially in those who have evidence of RSV infection.

White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children

We evaluated the applicability of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and absolute neutrophil count (ANC), in the screening of pneumococcal (PNC) pneumonia in children. In 1981-1982, 161 children were treated for radiologically verified community-acquired pneumonia in the hospital during a period of 12 months. The Streptococcus pneumoniae aetiology of infection was studied by antigen, antibody and immune complex assays in acute and convalescent sera. In acute blood samples, CRP was measured by the immunonephelometric method, ESR by the Westergren method, WBC using an automatic cell counter, and thereafter the ANC was calculated after microscopic examination of peripheral smears. CRP and ESR were significantly higher in patients with alveolar (n=53) than in those with interstitial (n=108) pneumonia. CRP, ESR and ANC were significantly higher in PNC (n=29) than in viral (n=23) pneumonia. The values in mixed PNC and viral infections (n=17) were approximately midway between PNC and viral cases. All cases with serologic evidence of S. pneumoniae aetiology were combined (n=46) for calculation of diagnostic parameters. When a cut-off limit of 60 mg x L(-1) was used, CRP had a sensitivity of 26% and a specificity of 83% in the screening of PNC pneumonia. We conclude that C-reactive protein and erythrocyte sedimentation rate have a limited capacity to differentiate between pneumococcal and nonpneumococcal pneumonia. C-reactive protein is recommended as the first-line method of screening, and the value of 60 mg x L(-1) as the cut-off limit.

Moisture damage and childhood asthma - a population-based incident case-control study

Most previous studies on the association between moisture damage and asthma have been cross-sectional and relied on self-reported exposure and health. The present authors studied the association by carrying out careful home inspections among new, clinically determined cases of asthma and controls. New cases of asthma aged 12–84 months (n = 121) were recruited prospectively and matched for year of birth, sex and living area with two randomly selected population controls (n = 241). Trained engineers visited all homes. Both cases and controls had lived ≥75% of their lifetime or the past 2 yrs in their current home. Risk of asthma increased with severity of moisture damage and presence of visible mould in the main living quarters but not in other areas of the house. Cases more often had damage in their bedroom. Associations were comparable for atopic and nonatopic asthma and for children aged >30 months or ≤30 months. The present results, using standardised assessment of exposure and asthma, suggest that moisture damage and mould growth in the main living quarters are associated with the development of asthma in early childhood.

Incidence of community-acquired pneumonia in children caused by Mycoplasma pneumoniae: Serological results of a prospective, population-based study in primary health care

Objective:  The objective of the present study was to assess the incidence of community‐acquired pneumonia (CAP) in children caused by Mycoplasma pneumoniae.

Epidemiology of encephalitis in children. A prospective multicentre study

Abstract We found 175 cases with acute encephalitis in a population of 791,712 children aged 1 month – 15 years during a 2-year surveillance period in 1993–1994. The overall incidence was 10.5/100,000 child-years with the highest figure in children < 1 year of age, 18.4/100 000 child-years. The microbial diagnosis was considered proven or suggested in 110 cases (63%); varicella zoster, respiratory and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes simplex and rota viruses comprised 5% each. A clearcut change seems to have occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus associated encephalitides have been almost eliminated. Varicella zoster, respiratory, and enteroviruses have increased in frequency and occur in younger age groups. New causes were identified, especially Chlamydia pneumoniae and HHV-6. Our data should assist in making a specific diagnosis and defining appropriate antimicrobial therapy. ConclusionThe spectrum of encephalitis in children has changed due to vaccination programs. The incidence, however, appears to be about the same due to increasing frequency of other associated old and new microbes.

Wheezy babies--wheezy adults? Review on long-term outcome until adulthood after early childhood wheezing.

Population‐based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long‐term postbronchiolitis follow‐up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom‐free years.

In search of childhood asthma: questionnaire, tests of bronchial hyperresponsiveness, and clinical evaluation

Background: The definition or diagnosis of asthma is a challenge for both clinicians and epidemiologists. Symptom history is usually supplemented with tests of bronchial hyperresponsiveness (BHR) in spite of their uncertainty in improving diagnostic accuracy. Methods: To assess the interrelationship between respiratory symptoms, BHR, and clinical diagnosis of asthma, the respiratory symptoms of 1633 schoolchildren were screened using a questionnaire (response rate 81.2%) and a clinical study was conducted in a subsample of 247 children. Data from a free running test and a methacholine inhalation challenge test were available in 218 children. The diagnosis of asthma was confirmed by a paediatric allergist. Results: Despite their high specificity (>0.97), BHR tests did not significantly improve the diagnostic accuracy after the symptom history: area under the receiver operator characteristic (ROC) curve was 0.90 for a logistic regression model with four symptoms and 0.94 for the symptoms with free running test and methacholine inhalation challenge results. On the other hand, BHR tests had low sensitivity (0.35–0.47), whereas several symptoms had both high specificity (>0.97) and sensitivity (>0.7) in relation to clinical asthma, which makes them a better tool for asthma epidemiology than BHR. Conclusions: Symptom history still forms the basis for defining asthma in both clinical and epidemiological settings. BHR tests only marginally increased the diagnostic accuracy after symptom history had been taken into account. The diagnosis of childhood asthma should not therefore be overlooked in symptomatic cases with no objective evidence of BHR. Moreover, BHR should not be required for defining asthma in epidemiological studies.