Abstract

BackgroundIncreased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus) also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection.MethodsLung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old) and adult (6–12 week old) cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph.ResultsAdult cotton rats had significantly greater tidal volume (TV), and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh) during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult) cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals.ConclusionWhile respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume) is increased in the infant animals only. This is likely to be a consequence of greater lung elastance in the very young animals. This model replicates many respiratory features of humans and consequently may be a useful tool to investigate new strategies to treat respiratory disease in influenza-infected infants.

Highlights

  • Increased respiratory rate is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital

  • At a set respiratory rate, tidal volume (TV) and dynamic compliance (Cdyn) increased with age; resistance and pleural pressure in the lower airway decreased with age (Figure 1)

  • Our results show an age-dependent decrease in dynamic lung elastance; this correlates with the inability of adult influenzainfected cotton rats to maintain equivalent tidal volume in the presence of airway obstruction

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Summary

Introduction

Increased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus) results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. The highest infection and hospitalization rates are observed in infants and young children [1]. Among this group, hospitalization rates are inversely related to the age of the child, being highest in those younger than 6 months. Epidemiologic studies indicate that children with certain chronic conditions including asthma, and otherwise healthy children younger than 24 months are at high-risk of being hospitalized after influenza infection. There is still no influenza vaccine licensed for use in infants younger than 6 months and there are no antivirals licensed for the treatment of influenza in infants younger than 1 year of age

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