Biomedical subjects

P N Lesouef

Publications and source records attributed to P N Lesouef.

3 recordsLinked to original sources

PubMed1999

Polymorphisms in the beta2-adrenoreceptor gene are associated with decreased airway responsiveness.

BACKGROUND: There are a number of candidate genes thought to play a role in the development of asthma. Polymorphisms at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamic acid) of the beta2-adrenoreceptor (B2AR) gene are known to be functionally relevant and have been associated with more severe forms of asthma, nocturnal asthma and decreased airway responsiveness in asthmatic subjects. OBJECTIVE: To determine if these polymorphisms contribute to the development of asthma by investigating the associations between the polymorphisms at amino acid positions 16 and 27 of the B2AR gene and asthma-related parameters in a large, phenotypically well-characterized population which was unselected for asthma. METHODS: Subjects (n = 332) were characterized using physiological assessments, immuno-logical data and information obtained from questionnaire. PCR was used to generate a 229 base pair fragment spanning the mutations of interest. Genotype was determined using allele-specific oligonucleotide hybridization and confirmed in 10% of the samples by direct sequencing. Multivariate analysis of the association between genotype and phenotype was then undertaken. RESULTS: Homozygotes for Glu27 were significantly less responsive to histamine than Gln27 homozygotes. In addition, Arg16 homozygotes were more likely to 'wheeze during a cold', in comparison with Gly16 homozygotes. However, there was no association between either polymorphism and physician-diagnosed asthma, eczema, skin reactivity to common allergens or total and specific serum IgE levels. The two polymorphisms were found to be in significant linkage disequilibrium. CONCLUSION: The polymorphism at position 27 was associated with decreased airway responsiveness in the study population and the polymorphism at position 16 was associated with increased wheeze during respiratory infection, but neither was associated with physician-diagnosed asthma or any of the other variables considered.

Adolescent↗

PubMed1993

Fast versus slow ventilation for neonates.

To investigate the effect of ventilation rate on respiratory mechanics, 21 neonates ventilated in the neonatal period for various reasons were studied while being ventilated at 30 and 80 breaths/min. Dynamic respiratory system elasticity (ERS), dynamic respiratory system resistance (RRS), and alveolar pressure at end expiration (EEP) were calculated by using multilinear regression to fit the equation of motion of a linear single-compartment model. Technically satisfactory data were obtained from 13 neonates. With the fast ventilation rate, tidal volume and RRS decreased by a mean of 41.3% (p < 0.01) and 17.5% (p < 0.01), respectively, ERS and EEP increased by a mean of 8.3% (p < 0.05) and 22.2% (p < 0.01), respectively. Fast ventilation produced a shorter effective time constant during expiration, limiting the changes in EEP and, hence, in end-expiratory lung volume. The same changes in respiratory mechanics were also observed in neonates who did not show an increase in EEP even at high frequency. These neonates had a high elastance and time constant short enough to ensure adequate lung emptying. These results suggest that the respiratory mechanics of ventilated neonates are frequency dependent and that neonates with higher ERS, such as those with hyaline membrane disease, can cope with fast rate ventilation without developing dynamic hyperinflation.

Anthropometry↗

PubMed1984

Passive respiratory mechanics in newborns and children.

When the Hering-Breuer reflex is used to relax the respiratory muscles, the passive compliance (Crs), resistance (Rrs), and time constant (Trs) of the respiratory system can be measured from the subsequent expiration. We used this method to assess 22 newborns with respiratory illness. Passive expirations were also recorded in 6 paralyzed, ventilated children. Using a simple slide valve, airway occlusion pressure was measured from a face mask or endotracheal tube, and expiratory flow was measured from a pneumotachygraph. In all subjects, there was a linear function of expiratory flow versus its integral, volume; by extrapolating the linear function to zero flow and zero volume (i.e., initial volume at time zero) Crs, Rrs, and Trs could be calculated; Crs was significantly reduced in mechanically ventilated versus spontaneously breathing infants, and Rrs was significantly higher in intubated versus extubated infants. During passive expiration in newborns, inspiration occurred at a volume above passive functional residual capacity. The passive expiratory flow-volume technique is simple, noninvasive, and appears to provide accurate measurements of respiratory mechanics in the newborn and in paralyzed children.

Child, Preschool↗