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Response of normal infants to inhaled histamine
P N Lesouëf1, G C Geelhoed, D J Turner
1Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia.
Insights
Infants as young as 3 months exhibit bronchial hyperresponsiveness (BHR) to histamine. This suggests BHR may be innate, with later factors influencing its persistence.
Area of Science:
- Pediatric Pulmonology
- Respiratory Physiology
Background:
- Nonspecific bronchial hyperresponsiveness (BHR) is a hallmark of asthma.
- The developmental origins of BHR in infants remain unclear.
- Genetic and environmental factors are suspected contributors to BHR development.
Purpose of the Study:
- To investigate the presence of BHR to histamine in normal infants.
- To determine if BHR can be detected in early infancy.
Main Methods:
- Studied twelve infants (3-18 months) with no prior significant respiratory illness.
- Measured respiratory function using maximal flow at functional residual capacity (VmaxFRC) via forced expiratory flow-volume technique.
- Administered inhaled histamine in doubling concentrations (0.125 to 8 g.L-1).
Main Results:
- All infants demonstrated BHR to histamine, with a mean response concentration of 1.4 g.L-1.
- Histamine inhalation caused transient increases in respiratory rate and decreases in oxygen saturation (SaO2).
- Post-histamine forced expiratory flow-volume curves became concave in all infants.
Conclusions:
- Bronchial hyperresponsiveness to histamine is demonstrable in normal infants.
- Findings support the hypothesis that humans may be born with BHR.
- Subsequent genetic or environmental influences may determine the persistence or resolution of BHR.
Abstract:
The age at which nonspecific bronchial hyperresponsiveness (BHR) is first seen in humans is unknown, though both genetic and environmental factors have been implicated in its development. The current study aimed to establish whether BHR to histamine can be demonstrated in normal infants. Twelve infants, mean age of 7.8 months (range, 3 to 18 months), were studied. None had any history of a previous significant respiratory illness. Respiratory function was monitored using the maximal flow at function residual capacity (VmaxFRC) obtained with the forced expiratory flow-volume technique. Histamine was inhaled in doubling concentrations from 0.125 to 8 g.L-1. A greater than 30% fall in VmaxFRC was considered a response. All infants responded to histamine, the geometric mean concentration for their response being 1.4 g.L-1. Associated transient changes for the group were an increase in respiratory rate (p less than 0.02) and a fall in SaO2 (p less than 0.001). Forced expiratory flow-volume curves were concave in all infants after the last dose of histamine. We speculate that humans are born with "bronchial hyperresponsiveness" and that genetic or environmental factors determine which infants lose it thereafter.