Elena Proietti

Normative data for lung function and exhaled nitric oxide in unsedated healthy infants

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean±sd age of 5.1±0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow–volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5–10 acceptable interruption resistance (Rint) measurements. Acceptable measurements were obtained in ≤285 infants with high variability. Mean values were 7.48 mL·kg−1 (95% limits of agreement 4.95–10.0 mL·kg−1) for tidal volume, 14.3 ppb (2.6–26.1 ppb) for eNO, 23.9 mL·kg−1 (16.0–31.8 mL·kg−1) for functional residual capacity, 6.75 (5.63–7.87) for lung clearance index and 3.78 kPa·s·L−1 (1.14–6.42 kPa·s·L−1) for Rint. In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

A Prospective Study of the Impact of Air Pollution on Respiratory Symptoms and Infections in Infants

RATIONALE There is increasing evidence that short-term exposure to air pollution has a detrimental effect on respiratory health, but data from healthy populations, particularly infants, are scarce. OBJECTIVES To assess the association of air pollution with frequency and severity of respiratory symptoms and infections measured weekly in healthy infants. METHODS In a prospective birth cohort of 366 infants of unselected mothers, respiratory health was assessed weekly by telephone interviews during the first year of life (19,106 total observations). Daily mean levels of particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3) were obtained from local monitoring stations. We determined the association of the preceding weeks pollutant levels with symptom scores and respiratory tract infections using a generalized additive mixed model with an autoregressive component. In addition, we assessed whether neonatal lung function influences this association and whether duration of infectious episodes differed between weeks with normal PM10 and weeks with elevated levels. MEASUREMENTS AND MAIN RESULTS We found a significant association between air pollution and respiratory symptoms, particularly in the week after respiratory tract infections (risk ratio, 1.13 [1.02-1.24] per 10 μg/m(3) PM10 levels) and in infants with premorbid lung function. During times of elevated PM10 (>33.3 μg/m(3)), duration of respiratory tract infections increased by 20% (95% confidence interval, 2-42%). CONCLUSIONS Exposure to even moderate levels of air pollution was associated with increased respiratory symptoms in healthy infants. Particularly in infants with premorbid lung function and inflammation, air pollution contributed to longer duration of infectious episodes with a potentially large socioeconomic impact.

Volumetric Capnography in Infants with Bronchopulmonary Dysplasia

OBJECTIVES To assess the feasibility of using volumetric capnography in spontaneously breathing small infants and its ability to discriminate between infants with and without bronchopulmonary dysplasia (BPD). STUDY DESIGN Lung function variables for 231 infants (102 term, 52 healthy preterm, 77 BPD), matched for post-conceptional age of 44 weeks, were collected. BPD was defined as supplemental oxygen requirement at 36 weeks post-menstrual age. Tidal breath-by-breath volume capnograms were obtained by mainstream capnography. The capnographic slope of phase II (SII) and slope of phase III (SIII) were calculated and compared between study groups. The effect of BPD, tidal volume (VT), respiratory rate (RR), and prematurity on the magnitude of the slopes was assessed. RESULTS SII was steeper in infants with BPD (100 ± 28/L) compared with healthy preterm (88 ± 22/L; P = .007) and term infants (79 ± 18/L; P < .001), but this finding was attributed to differences in VT, RR, and gestational age. SIII was steeper in the BPD group (26.8 ± 14.1/L) compared with healthy preterm (16.2 ± 6.2/L; P < .001) and term controls (14.8 ± 5.4/L; P < .001). BPD was a significant predictor of SIII independently of VT, RR, and gestational age. The ability of SIII to discriminate between BPD and controls was significantly higher compared with lung clearance index (area under the curve 0.83 vs 0.56; P < .001). CONCLUSIONS Volumetric capnography may provide valuable information regarding functional lung alterations related to BPD and might be considered as an alternative to more involved lung function techniques for monitoring chronic lung disease during early infancy.

Validation of multiple-breath washout equipment for infants and young children.

The new ATS/ERS consensus report recommends in vitro validation of multiple‐breath inert gas washout (MBW) equipment based on a lung model with simulated physiologic conditions. We aimed to assess accuracy of two MBW setups for infants and young children using this model, and to compare functional residual capacity (FRC) from helium MBW (FRCMBW) with FRC from plethysmography (FRCpleth) in vivo.

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms. The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data. In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child. Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm. Infant lung function tests do not help to predict symptoms in preterms but show early pathophysiological alterations http://ow.ly/uyJpW

Air pollution modelling for birth cohorts: a time-space regression model.

BackgroundTo investigate air pollution effects during pregnancy or in the first weeks of life, models are needed that capture both the spatial and temporal variability of air pollution exposures.MethodsWe developed a time-space exposure model for ambient NO2 concentrations in Bern, Switzerland. We used NO2 data from passive monitoring conducted between 1998 and 2009: 101 rural sites (24,499 biweekly measurements) and 45 urban sites (4350 monthly measurements). We evaluated spatial predictors (land use; roads; traffic; population; annual NO2 from a dispersion model) and temporal predictors (meteorological conditions; NO2 from continuous monitoring station). Separate rural and urban models were developed by multivariable regression techniques. We performed ten-fold internal cross-validation, and an external validation using 57 NO2 passive measurements obtained at study participant’s homes.ResultsTraffic related explanatory variables and fixed site NO2 measurements were the most relevant predictors in both models. The coefficient of determination (R2) for the log transformed models were 0.63 (rural) and 0.54 (urban); cross-validation R2s were unchanged indicating robust coefficient estimates. External validation showed R2s of 0.54 (rural) and 0.67 (urban).ConclusionsThis approach is suitable for air pollution exposure prediction in epidemiologic research with time-vulnerable health effects such as those occurring during pregnancy or in the first weeks of life.

Sigh‐induced changes of breathing pattern in preterm infants

Sighs are thought to play an important role in control of breathing. It is unclear how sighs are triggered, and whether preterm birth and lung disease influence breathing pattern prior to and after a sigh in infants. To assess whether frequency, morphology, size, and short‐term variability in tidal volume (VT) before, during, and after a sigh are influenced by gestational age at birth and lung disease (bronchopulmonary dysplasia, BPD) in former preterm infants and healthy term controls measured at equivalent postconceptional age (PCA). We performed tidal breathing measurements in 143 infants during quiet natural sleep at a mean (SD) PCA of 44.8 (1.3) weeks. A total of 233 sighs were analyzed using multilevel, multivariable regression. Sigh frequency in preterm infants increased with the degree of prematurity and severity of BPD, but was not different from that of term controls when normalized to respiratory rate. After a sigh, VT decreased remarkably in all infants (paired t‐test: P < 0.001). There was no major effect of prematurity or BPD on various indices of sigh morphology and changes in VT prior to or after a sigh. Short‐term variability in VT modestly increased with maturity at birth and infants with BPD showed an earlier return to baseline variability in VT following a sigh. In early infancy, sigh‐induced changes in breathing pattern are moderately influenced by prematurity and BPD in preterm infants. The major determinants of sigh‐related breathing pattern in these infants remain to be investigated, ideally using a longitudinal study design.

Response of cord blood cells to environmental, hereditary and perinatal factors: A prospective birth cohort study

Background Many studies investigating the impact of individual risk factors on cord blood immune cell counts may be biased given that cord blood composition is influenced by a multitude of factors. The aim of this study was to comprehensively investigate the relative impact of environmental, hereditary and perinatal factors on cord blood cells. Methods In 295 neonates from the prospective Basel-Bern Infant Lung Development Cohort, we performed complete blood counts and fluorescence-activated cell sorting scans of umbilical cord blood. The associations between risk factors and cord blood cells were assessed using multivariable linear regressions. Results The multivariable regression analysis showed that an increase per 10μg/m3 of the average nitrogen dioxide 14 days before birth was associated with a decrease in leukocyte (6.7%, 95% CI:-12.1,-1.0) and monocyte counts (11.6%, 95% CI:-19.6,-2.8). Maternal smoking during pregnancy was associated with significantly lower cord blood cell counts in multiple cell populations. Moreover, we observed sex differences regarding eosinophilic granulocytes and plasmacytoid dendritic cells. Finally, significantly increased numbers of cord blood cells were observed in infants exposed to perinatal stress. Cesarean section seems to play a significant role in Th1/Th2 balance. Conclusions Our results suggest that all three: environmental, hereditary and perinatal factors play a significant role in the composition of cord blood cells at birth, and it is important to adjust for all of these factors in cord blood studies. In particular, perinatal circumstances seem to influence immune balance, which could have far reaching consequences in the development of immune mediated diseases.

Glucocorticoid metabolites in newborns: A marker for traffic noise related stress?

BACKGROUND Traffic noise has been associated with an increased risk for several non-auditory health effects, which may be explained by a noise-induced release of stress hormones (e.g. glucocorticoids). Although several studies in children and adults have indicated an increased secretion of glucocorticoids after exposure to noise, information regarding newborns is scarce. OBJECTIVES To investigate the association between residential exposure to road traffic noise and postnatal stress response, as assessed by the concentration of glucocorticoids at five weeks of age. METHODS Residential noise exposure was estimated for each infant based on spatially detailed modeled data. Adjusted multivariable linear regression models were used to estimate the association between noise exposure and the concentration of nine glucocorticoid metabolites measured in urine of 165 infants from a prospective birth cohort in Bern, Switzerland. Noise exposure (Lden, dB) was categorized into tertiles: low (reference), medium and high. RESULTS Indications of a positive association were found between high road traffic noise and cortisol (% change relative to the reference: 12.1% [95% confidence interval: -10.3, 40.1%]) and cortisone (22.6% [-1.8, 53.0%]), but just the latter was borderline significant. Borderline significant associations were also found between downstream metabolites and higher road traffic noise levels; associations were found to be both positive (i.e. for β-cortolone (51.5% [-0.9, 131.5%])) and negative (i.e. for α-cortolone (-18.3% [-33.6, 0.6%]) and tetrahydrocortisol (-23.7% [-42.8, 1.9%])). CONCLUSIONS Our findings suggest a potential association between exposure to higher road traffic noise levels and changes in glucocorticoid metabolism in early postnatal life. A possible physiological relevance and associations with short- and long-term adverse health effects in a larger study population need to be further investigated.

Lactate dehydrogenase concentration in nasal wash fluid indicates severity of rhinovirus-induced wheezy bronchitis in preschool children.

The clinical course of rhinovirus (RV)-associated wheezing illnesses is difficult to predict. We measured lactate dehydrogenase concentrations, RV load, antiviral and proinflammatory cytokines in nasal washes obtained from 126 preschool children with RV wheezy bronchitis. lactate dehydrogenase values were inversely associated with subsequent need for oxygen therapy. lactate dehydrogenase may be a useful biomarker predicting disease severity in RV wheezy bronchitis.