BackgroundMany human epidemiologic studies demonstrate that maternal asthma confers greater risk of asthma to offspring than does paternal disease. However, a handful have shown the opposite. Given this disparity, a meta-analysis is necessary to determine the veracity and magnitude of the “maternal effect.”Methodology/Principal FindingsWe screened the medical literature from 1966 to 2009 and performed a meta-analysis to compare the effect of maternal asthma vs. paternal asthma on offspring asthma susceptibility. Aggregating data from 33 studies, the odds ratio for asthma in children of asthmatic mothers compared with non-asthmatic mothers was significantly increased at 3.04 (95% confidence interval: 2.59–3.56). The corresponding odds ratio for asthma in children of asthmatic fathers was increased at 2.44 (2.14–2.79). When comparing the odds ratios, maternal asthma conferred greater risk of disease than did paternal asthma (3.04 vs. 2.44, p = 0.037). When analyzing the studies in which asthma was diagnosed by a physician the odds ratios were attenuated and no significant differences were observed (2.85 vs. 2.48, N = 18, p = 0.37). Similarly, no significant differences were observed between maternal and paternal odds ratios when analyzing the studies in which the patient population was 5 years or older (3.15 vs. 2.60, p = 0.14). However, in all cases the trend remained the same, that maternal asthma was a greater risk factor for asthma than paternal.Conclusions/SignificanceThe results show that maternal asthma increases offspring disease risk to a greater extent than paternal disease.

Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control ''inert'' titanium dioxide (TiO 2 ) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle-or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to ''inert'' TiO 2 . In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO 2 and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO 2 . Neonates of mothers exposed to TiO 2 (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy exposure to both ''inert'' TiO 2 and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.

Little is known about how prenatal maternal stress (PNMS) influences risks of asthma in humans. In this small study, we sought to determine whether disaster-related PNMS would predict asthma risk in children. In June 1998, we assessed severity of objective hardship and subjective distress in women pregnant during the January 1998 Quebec Ice Storm. Lifetime asthma symptoms, diagnoses, and corticosteroid utilization were assessed when the children were 12 years old (N = 68). No effects of objective hardship or timing of the exposure were found. However, we found that, in girls only, higher levels of prenatal maternal subjective distress predicted greater lifetime risk of wheezing (OR = 1.11; 90% CI = 1.01–1.23), doctor-diagnosed asthma (OR = 1.09; 90% CI = 1.00–1.19), and lifetime utilization of corticosteroids (OR = 1.12; 90% CI = 1.01–1.25). Other perinatal and current maternal life events were also associated with asthma outcomes. Findings suggest that stress during pregnancy opens a window for fetal programming of immune functioning. A sex-based approach may be useful to examine how prenatal and postnatal environments combine to program the immune system. This small study needs to be replicated with a larger, more representative sample.

BackgroundEpidemiologic evidence suggests that chronic stress may alter susceptibility to air pollution. However, persistent spatial confounding between these exposures may limit the utility of epidemiologic methods to disentangle these effects and cannot identify physiologic mechanisms for potential differential susceptibilities.ObjectivesUsing a rat model of social stress, we compared respiratory responses to fine concentrated ambient particles (CAPs) and examined biological markers of inflammation.MethodsTwenty-four 12-week-old male Sprague-Dawley rats were randomly assigned to four groups [stress/CAPs, stress/filtered air (FA), nonstress/CAPs, nonstress/FA]. Stress-group animals were individually introduced into the home cage of a dominant male twice weekly. Blood drawn at sacrifice was analyzed for immune and inflammatory markers. CAPs were generated using the Harvard ambient particle concentrator, which draws real-time urban ambient fine particles, enriching concentrations approximately 30 times. CAPs/FA exposures were delivered in single-animal plethysmographs, 5 hr/day for 10 days, and respiratory function was continuously monitored using a Buxco system.ResultsStressed animals displayed higher average C-reactive protein, tumor necrosis factor-α, and white blood cell counts than did nonstressed animals. Only among stressed animals were CAPs exposures associated with increased respiratory frequency, lower flows, and lower volumes, suggesting a rapid, shallow breathing pattern. Conversely, in animals with elevated CAPs exposures alone, we observed increased inspiratory flows and greater minute volumes (volume of air inhaled or exhaled per minute).ConclusionsCAPs effects on respiratory measures differed significantly, and substantively, by stress group. Higher CAPs exposures were associated with a rapid, shallow breathing pattern only under chronic stress. Blood measures provided evidence of inflammatory responses. Results support epidemiologic findings that chronic stress may alter respiratory response to air pollution and may help elucidate pathways for differential susceptibility.