Virus-induced Wheezing Research Articles

Asthma in the community Observations by the Swiss Sentinel Surveillance Network over a ten year period (1988-1997)

Purpose: The overall prevalence and incidence of asthma attacks reported by primary care physicians (general practitioners, general internists and paediatricians) between 1988 and 1997 was assessed. Special attention was paid to the observation of seasonal patterns in different age groups of the consulting population.Methods: About 200 private practice physicians participated in the collection of data each year. Only data from doctors who reported 39 weeks or more each year were included in the analysis. Physicians were recruited on the basis of a stratification by geographic area, sociodemographic characteristics and speciality, with even distributions over the whole country. They represent about 3% of all family practitioners in Switzerland. Weekly attack rates per physician were investigated using time series analysis. Seasonal smoothing was used to visualise and explore the series.Results: Asthma attack rates (all ages) increased from 5.7 attacks per physician (0.18 per 100 consultations) in 1988/1989 to 11.8 (0.22 per 100 consultations) in 1994. The rates then decreased to 8.8 (0.19 per 100 consultations) in 1996 and rose to 10.4 (0.22 per 100 consultations) in 1997. Peak incidence occurred in June (particularly for the 5-16 years age group) and in November (particularly for the 0-4 years age group). Seasonality dwindled with increasing age. Attack rates were highest in January and July in the 46-65 years and above 65 years age groups. An August/September trough was repeatedly found in all age groups. First asthma attacks (registered since 1994) accounted for a third of all asthma attacks. Hospital admission rates, expressed as a percentage of attacks, were low by international standards.Conclusions: Sentinel practices in Switzerland are useful for measuring the asthma morbidity seen in the primary care setting. We observed a rising trend in asthma rates until 1994 and a fluctuating course until 1997. We believe that the temporal changes over time in asthma rates reflect societal changes, with a tendency to early therapeutic interventions by both patients and professionals. Differences in seasonal patterns signal the presence of environmental and age-related diagnostic effects which overlap with virus-induced wheezing, allergic asthma and bronchitis-related broncho-constrictive disorders.

Nonatopic wheezy children have reduced interferon-gamma.

Viruses cause asthmatic exacerbations in schoolchildren. We tested the hypothesis that children who wheezed with viral respiratory tract infections secrete higher levels of the type 1 cytokine interferon-gamma (IFN-gamma) in the peripheral circulation than children who had never wheezed. Blood was taken from 13 children (eight atopic) with episodic wheeze and 11 controls. CD4 and CD8 cells were separated from peripheral blood mononuclear cells and stimulated with phorbol 12-myrisate 13-acetate (PMA) and ionomycin for 24 h. IFN-gamma, IL-4, and IL-5 were measured in the supernatant by ELISA. IFN-gamma production by CD4 and CD8 cells was lower in children with a history of wheeze (CD4, P = 0.046; CD8, P = 0.037). These children were then analysed according to atopic status. CD4 and CD8 IFN-gamma production in nonatopic wheezy children was reduced (CD4, P=0.009; CD8, P=0.003). IFN-gamma production by atopic wheezy children was lower than by controls, but the differences were not significant (CD4, P = 0.2831; CD8, P = 0.1372). CD8 IL-5 was lower in children who wheezed (P=0.012). Release of IL-4 and IL-5 by CD4 cells did not differ between the three groups. We propose that defective IFN-gamma secretion by CD4 and CD8 cells may contribute to viral-induced wheeze in nonatopic children.

Increased production of IFN-γ and cysteinyl leukotrienes in virus-induced wheezing

Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction of IL-4, is believed to be important in the pathogenesis of allergic asthma. However, less is known about the cytokine response in virus-induced wheezing, which is a major cause of morbidity in asthma. Objective: We undertook this study to determine the magnitude of IFN-γ, IL-4 and IL-10, and leukotriene (LT) responses in infants and children with virus-induced wheezing. Methods: We measured the concentrations of IFN-γ, IL-4 and IL-10, and cysteinyl LTs in respiratory secretions of 82 infants and young children during acute episodes of virus-induced wheezing. Control subjects were 47 infants and children with uncomplicated upper respiratory infections and 18 normal healthy infants. Results: Ratios of IFN-γ to IL-4 were higher (due to increased quantities of IFN-γ) in subjects with wheezing than in those with upper respiratory infection alone ( P = .003). Quantities of LTs were also increased in wheezing subjects in comparison with those with upper respiratory infections ( P = .009). There was a significant correlation between measured concentrations of IFN-γ and LTs (correlation coefficient = .451, P = .007). Quantities of IL-4 were slightly suppressed in the wheezing groups. Conclusions: An imbalance favoring overproduction of IFN-γ appears to be associated temporarily with virus-induced wheezing. A possible mechanism is the enhanced release of LTs from eosinophils or mast cells after sensitization by IFN-γ. (J Allergy Clin Immunol 1999;103:630-6.)

VIRUS-INDUCED WHEEZING IN CHILDREN: Respiratory Syncytial Virus (RSV) and Rhinovirus

The strong association between infantile wheezing and respiratory tract infections caused by the respiratory syncytial virus (RSV) has been well established. In studies of older children, rhinovirus becomes the major virus associated with asthma. These relationships are outlined in the box on page 36. In the past, this relationship was more difficult to appreciate, because rhinovirus does not always grow well in culture. In addition, the linkage between asthma and atopy during childhood has raised the question whether viral infections alone can precipitate exacerbations of asthma. Use of the polymerase chain reaction (PCR) to measure viral nucleic acid material has provided the opportunity to study virus-induced wheezing among children in greater detail, and investigations of experimental rhinovirus infections in adults have demonstrated how this virus can augment both the early and late phase manifestations of airway hyperreactivity. This article reviews recent advances that have enhanced our understanding of virus-induced wheezing, along with new information indicating that interactions between viral infections and allergic inflammation may be critical to the pathogenesis of acute symptoms.

The cellular and mediator basis of asthma in relation to natural history

The cellular and mediator basis of asthma in relation to natural history

The Wheezing Infant

In summary, wheezing is a common manifestation of viral respiratory tract disease in infancy. The precise pathogenetic mechanisms of virus-induced wheezing and its sequelae are not clear, although recent reports about participation of the cellular and humoral immune systems are promising. Although therapies like those used to treat asthma are employed in the treatment of virus-induced wheezing in infancy, their efficacy remains controversial in bronchiolitis. Recently developed agents with antiviral properties are promising and the choice of any of these agents in a therapeutic regimen should be individualized. Antiviral agents during acute infections may modify the long-term sequelae. Clearly, much work needs to be done to elucidate pathogenetic mechanisms, and to develop new, safe, and effective anti-inflammatory agents for the therapy of these disorders.