Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits.

Rationale:In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.

In utero smoke exposure and role of maternal and infant glutathione s-transferase genes on airway responsiveness and lung function in infancy.

RATIONALE: Xenobiotics in the maternal circulation are capable of crossing the placental barrier so a reduction in the mother and fetus's detoxification ability due to genetic variation in the glutathione S-transferases (GSTs) could expose the fetus to higher levels of toxins. OBJECTIVES: To investigate the interactive effects of maternal smoking during pregnancy with maternal and infant GST genotypes on airway responsiveness (AR) and lung function in infancy. METHODS: GSTT1, GSTP1 and GSTM1 were genotyped in infants and mothers, in utero smoke exposure was evaluated by questionnaire, AR was assessed by histamine challenge and Vmax(FRC) was measured using the rapid thoracoabdominal compression technique. We investigated the interactive effects of maternal smoking during pregnancy with maternal and infant GST genes on AR and lung function at 1, 6, and 12 months and longitudinally throughout the first year. MEASUREMENTS AND MAIN RESULTS: Infant and/or maternal GSTT1 nonnull was associated with reduced AR at 12 months and throughout the first year and increased Vmax(FRC) at 6 months. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(FRC) at 6 months. In infants exposed to in utero smoke, infant and/or maternal GSTT1 nonnull was associated with reduced AR at 1 month and throughout the first year and increased Vmax(FRC) throughout the first year. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(FRC) at 6 months. CONCLUSIONS: GST genes may be especially important during fetal development as they may modify, through proficient detoxification, the effects of in utero maternal smoke exposure on AR and lung function in infants.

Lung deposition of 99mTc-radiolabeled albuterol delivered through a pressurized metered dose inhaler and spacer with facemask or mouthpiece in children with asthma.

BACKGROUND: Research on the use of a pressurized metered dose inhaler (pMDI) with spacer (pMDI/spacer) in children has indicated oral inhalation via the spacer mouthpiece is more efficient than the combination of oral and nasal inhalation that occurs when a pMDI/spacer is used with a facemask. Changes in pMDI formulations and developments in spacer and facemask designs have highlighted the need for new comparative studies of spacer use, particularly focusing on the age at which children can be taught to transition from use of a pMDI/spacer with facemask to use of the spacer mouthpiece. METHODS: Twelve children aged 3-5 years (7 males) with stable asthma were recruited. Of these, 10 children (6 males) completed both arms of the study. A transmission scan of each compliant subject was taken using a 37 MBq (99m)Tc flood source. Actuations (2-3) of a (99m)Tc-radiolabeled albuterol pMDI were administered through an antistatic spacer (OptiChamber Diamond) via either a facemask (medium LiteTouch facemask), or the spacer mouthpiece. The subject's inhalation pattern was simultaneously recorded using a pMDI Datalogger, and narrative data relating to tolerance and compliance were documented. Anterior and posterior planar scintigraphic scans were taken immediately after aerosol administration. RESULTS: Mean (SD) lung deposition (% total dose) was 18.1 (9.1)% with the facemask and 22.5 (7.9)% with the spacer mouthpiece (p>0.05). Peripheral lung deposition (expressed as peripheral:central (P:C) ratio) was higher in 7 out of 10 children with the facemask compared with the spacer mouthpiece: 1.3 (0.26) vs. 1.2 (0.35); (p=0.11). Head and neck deposition was higher with use of the facemask compared with the spacer mouthpiece: 19.7 (10.6)% vs. 10.8 (5.3)% (p=0.011). CONCLUSIONS: Lung deposition achieved using the spacer with facemask was higher than previously reported, with a difference of only 4.4% of total dose measured compared to the deposition with mouthpiece. This may be due to a combination of factors including pMDI formulation, and use of an antistatic spacer with a flexible, well-fitting facemask.