Maternal asthma is associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts.

RATIONALE: Asthma in pregnancy is associated with respiratory diseases in the offspring. OBJECTIVE: To investigate if maternal asthma is associated with lung function in early life. METHODS: Data on lung function measured at 5-6 weeks of age were combined from two large birth cohorts: the Bern Infant Lung Development (BILD) and the Australian Breathing for Life Trial (BLT) birth cohorts conducted at three study sites (Bern, Switzerland; Newcastle and Sydney, Australia). The main outcome variable was time to reach peak tidal expiratory flow as a percentage of total expiratory time(tPTEF:tE%). Bayesian linear hierarchical regression analyses controlling for study site as random effect were performed to estimate the effect of maternal asthma on the main outcome, adjusting for sex, birth order, breast feeding, weight gain and gestational age. In separate adjusted Bayesian models an interaction between maternal asthma and sex was investigated by including an interaction term. MEASUREMENTS AND MAIN RESULTS: All 406 BLT infants were born to mothers with asthma in pregnancy, while 193 of the 213 (91%) BILD infants were born to mothers without asthma. A significant interaction between maternal asthma and male sex was negatively associated with tPTEF:tE% (intercept 37.5; estimate: -3.5; 95% credible interval -6.8 to -0.1). Comparing the model posterior probabilities provided decisive evidence in favour of an interaction between maternal asthma and male sex (Bayes factor 33.5). CONCLUSIONS: Maternal asthma is associated with lower lung function in male babies, which may have lifelong implications on their lung function trajectories and future risk of wheezing and asthma.

Effect of breastfeeding duration on lung function, respiratory symptoms and allergic diseases in school-age children.

BACKGROUND: A positive effect of breastfeeding on lung function has been demonstrated in cohorts of children with asthma or risk for asthma. We assessed the impact of breastfeeding on lung function and symptoms at the age of 6 years in an unselected, healthy birth cohort. METHODS: We prospectively studied healthy term infants from the Bern-Basel Infant Lung Development (BILD) cohort from birth up to 6 years. Any breastfeeding was assessed by weekly phone calls during the first year of life. Risk factors (eg, smoking exposure, parental history of allergic conditions, and education) were obtained using standardized questionnaires. The primary outcomes were lung function parameters measured at 6 years of age by spirometry forced expiratory volume in 1 second, body plethysmography (functional residual capacity [FRCpleth ], the total lung capacity [TLCpleth ], and the effective respiratory airway resistance [Reff ]) and fractional exhaled nitric oxide (FeNO). Secondary outcomes included ever wheeze (between birth and 6 years), wheeze in the past 12 months, asthma, presence of allergic conditions, atopic dermatitis, rhinitis, and positive skin prick test at the age of 6 years. RESULTS: In 377 children the mean breastfeeding duration was 36 weeks (SD 14.4). We found no association of breastfeeding duration with obstructive or restrictive lung function and FeNO. After adjustment for confounders, we found no associations of breastfeeding duration with respiratory symptoms or the presence of allergic conditions. CONCLUSION: This study found no evidence of an association between breastfeeding and comprehensive lung function in unselected healthy children with long-term breastfeeding. Our findings do not support the hypothesis that the duration of breastfeeding has a direct impact on lung function in a healthy population with low asthmatic risk.

Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry.

Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge. Among all the different analytical techniques available to interrogate exhaled breath, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) offers a number of advantages (e.g., real-time, yet wide, metabolome coverage) that makes it ideal for untargeted and targeted studies. However, so far, SESI-HRMS has relied mostly on lab-built prototypes, making it difficult to standardize breath sampling and subsequent analysis, hence preventing further developments such as multi-center clinical studies. To address this issue, we present here a number of new developments. In particular, we have characterized a new SESI interface featuring real-time readout of critical exhalation parameters such as CO2, exhalation flow rate, and exhaled volume. Four healthy subjects provided breath specimens over a period of 1 month to characterize the stability of the SESI-HRMS system. A first assessment of the repeatability of the system using a gas standard revealed a coefficient of variation (CV) of 2.9%. Three classes of aldehydes, namely 4-hydroxy-2-alkenals, 2-alkenals and 4-hydroxy-2,6-alkedienals-hypothesized to be markers of oxidative stress-were chosen as representative metabolites of interest to evaluate the repeatability and reproducibility of this breath analysis analytical platform. Median and interquartile ranges (IQRs) of CVs for CO2, exhalation flow rate, and exhaled volume were 3.2% (1.5%), 3.1% (1.9%), and 5.0% (4.6%), respectively. Despite the high repeatability observed for these parameters, we observed a systematic decay in the signal during repeated measurements for the shorter fatty aldehydes, which eventually reached a steady state after three/four repeated exhalations. In contrast, longer fatty aldehydes showed a steady behavior, independent of the number of repeated exhalation maneuvers. We hypothesize that this highly molecule-specific and individual-independent behavior may be explained by the fact that shorter aldehydes (with higher estimated blood-to-air partition coefficients; approaching 100) mainly get exchanged in the airways of the respiratory system, whereas the longer aldehydes (with smaller estimated blood-to-air partition coefficients; approaching 10) are thought to exchange mostly in the alveoli. Exclusion of the first three exhalations from the analysis led to a median CV (IQR) of 6.7 % (5.5 %) for the said classes of aldehydes. We found that such intra-subject variability is in general much lower than inter-subject variability (median relative differences between subjects 48.2%), suggesting that the system is suitable to capture such differences. No batch effect due to sampling date was observed, overall suggesting that the intra-subject variability measured for these series of aldehydes was biological rather than technical. High correlations found among the series of aldehydes support this notion. Finally, recommendations for breath sampling and analysis for SESI-HRMS users are provided with the aim of harmonizing procedures and improving future inter-laboratory comparisons. Graphical abstract.