Differences in tidal breathing between infants with chronic lung diseases and healthy controls

BACKGROUND: The diagnostic value of tidal breathing (TB) measurements in infants is controversially discussed. The aim of this study was to investigate to what extent the breathing pattern of sleeping infants with chronic lung diseases (CLD) differ from healthy controls with the same postconceptional age and to assess the predictive value of TB parameters. METHODS: In the age of 36–42 postconceptional weeks TB measurements were performed in 48 healthy newborns (median age and weight 7d, 3100 g) and 48 infants with CLD (80d, 2465 g)) using the deadspace-free flow-through technique. Once the infants had adapted to the mask and were sleeping quietly and breathing regularly, 20–60 breathing cycles were evaluated. Beside the shape of the tidal breathing flow-volume loop (TBFVL) 18 TB parameters were analyzed using ANOVA with Bonferroni correction. Receiver-operator characteristic (ROC) curves were calculated to investigate the discriminative ability of TB parameters. RESULTS: The incidence of concave expiratory limbs in CLD infants was 31% and significantly higher compared to controls (2%) (p < 0.001). Significant differences between CLD infants and controls were found in 11/18 TB parameters. The largest differences were seen in the mean (SD) inspiratory time 0.45(0.11)s vs. 0.65(0.14)s (p < 0.0001) and respiratory rate (RR) 55.4(14.2)/min vs. 39.2(8.6)/min (p < 0.0001) without statistically significant difference in the discriminative power between both time parameters. Most flow parameters were strongly correlated with RR so that there is no additional diagnostic value. No significant differences were found in the tidal volume and commonly used TB parameters describing the expiratory flow profile. CONCLUSION: The breathing pattern of CLD infants differs significantly from that of healthy controls. Concave TBFVL and an increased RR measured during quiet sleep and under standardized conditions may indicate diminished respiratory functions in CLD infants whereas most of the commonly used TB parameters are poorly predictive

Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: Longitudinal assessment during the first 15 months of corrected age

<p>Abstract</p> <p>Background</p> <p>Very low birth weight (VLBW) infants (< 1,500 g) with bronchopulmonary dysplasia (BPD) develop lung damage caused by mechanical ventilation and maturational arrest. We compared functional lung development after discharge from hospital between VLBW infants with and without BPD.</p> <p>Methods</p> <p>Comprehensive lung function assessment was performed at about 50, 70, and 100 weeks of postmenstrual age in 55 sedated VLBW infants (29 with former BPD [O₂supplementation was given at 36 weeks of gestational age] and 26 VLBW infants without BPD [controls]). Mean gestational age (26 vs. 29 weeks), birth weight (815 g vs. 1,125 g), and the proportion of infants requiring mechanical ventilation for ≥7 d (55% vs. 8%), differed significantly between BPD infants and controls.</p> <p>Results</p> <p>Both body weight and length, determined over time, were persistently lower in former BPD infants compared to controls, but no significant between-group differences were noted in respiratory rate, respiratory or airway resistance, functional residual capacity as determined by body plethysmography (FRC_pleth), maximal expiratory flow at the FRC (V'max _FRC), or blood gas (pO₂, pCO₂) levels. Tidal volume, minute ventilation, respiratory compliance, and FRC determined by SF6 multiple breath washout (representing the lung volume in actual communication with the airways) were significantly lower in former BPD infants compared to controls. However, these differences became non-significant after normalization to body weight.</p> <p>Conclusions</p> <p>Although somatic growth and the development of some lung functional parameters lag in former BPD infants, the lung function of such infants appears to develop in line with that of non-BPD infants when a body weight correction is applied. Longitudinal lung function testing of preterm infants after discharge from hospital may help to identify former BPD infants at risk of incomplete recovery of respiratory function; such infants are at risk of later respiratory problems.</p

Early Lung Function Testing in Infants with Aortic Arch Anomalies Identifies Patients at Risk for Airway Obstruction

BACKGROUND: Aortic arch anomalies (AAA) are rare cardio-vascular anomalies. Right-sided and double-sided aortic arch anomalies (RAAA, DAAA) are distinguished, both may cause airway obstructions. We studied the degree of airway obstruction in infants with AAA by neonatal lung function testing (LFT). PATIENTS AND METHODS: 17 patients (10 RAAA and 7 DAAA) with prenatal diagnosis of AAA were investigated. The median (range) post conception age at LFT was 40.3 (36.6-44.1) weeks, median body weight 3400 (2320-4665) g. Measurements included tidal breathing flow-volume loops (TBFVL), airway resistance (R(aw)) by bodyplethysmography and the maximal expiratory flow at functional residual capacity (V'(max)FRC) by rapid thoracic-abdominal compression (RTC) technique. V'(max)FRC was also expressed in Z-scores, based on published gender-, age and height-specific reference values. RESULTS: Abnormal lung function tests were seen in both RAAA and DAAA infants. Compared to RAAA infants, infants with DAAA had significantly more expiratory flow limitations in the TBFVL, (86% vs. 30%, p<0.05) and a significantly increased R(aw) (p = 0.015). Despite a significant correlation between R(aw) and the Z-score of V'(max)FRC (r = 0.740, p<0.001), there were no statistically significant differences in V'(max)FRC and it's Z-scores between RAAA and DAAA infants. 4 (24%) infants (2 RAAA, 2 DAAA) were near or below the 10(th) percentile of V'(max)FRC, indicating a high risk for airway obstruction. CONCLUSION: Both, infants with RAAA and DAAA, are at risk for airway obstruction and early LFT helps to identify and to monitor these infants. This may support the decision for therapeutic interventions before clinical symptoms arise

The effect of maternal anthropometric characteristics and social factors on gestational age and birth weight in Sudanese newborn infants

<p>Abstract</p> <p>Background</p> <p>In Africa low birth weight (LBW) (<2500 g), is the strongest determinant of infant morbidity and mortality. The aim of this study was to quantify the effect of maternal anthropometry, education and socio-economic status on gestational age and birth weight.</p> <p>Methods</p> <p>In 1000 Sudanese mothers with singleton births, anthropometric measurements (weight, height, mid-arm circumference) and newborn birth weight were taken within 24 hours of delivery. Furthermore, maternal education and socio-economic status were recorded. The effect of these maternal variables on gestational age and birth weight was investigated by receiver operating characteristic (ROC) curves and by multivariate logistic regression analysis.</p> <p>Results</p> <p>Although maternal height was significantly correlated (p = 0.002) with gestational age, we did not find maternal characteristics of value in determining the risk for preterm birth. Birth order was the strongest determinant of birth weight compared to other maternal characteristics. The LBW rate of first born babies of 12.2% was nearly twice that of infants of multiparous mothers. Maternal age and all maternal anthropometric measurements were positively correlated (p < 0.001) with birth weight. A maternal height of <156 cm, a maternal weight of <66 kg, a maternal mid arm circumference of <27 cm and years of education of ≤ 8 years were found to increase the relative risk of LBW but this was statistically significant only in the case of maternal height. Maternal age and BMI had no statistically significant effect on determining the risk for LBW. The social class did not affect the birth weight, while the number of years of education was positively correlated with birth weight (p = 0.01). The LBW rate decreased from 9.2% for ≤ 8 years of education to 6.0% for >12 years of education.</p> <p>Conclusion</p> <p>Birth order and maternal height were found to be the most important maternal parameters which influences birth weight and the risk for LBW. The duration of maternal education and not social class was found to significantly affect the risk for LBW.</p

A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality

Background: Accurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria. Methods: 50MBWtest occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic). Results: Using qualitative criteria, 46/168 trials were rejected: 16.6%were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53– 0.83%) to (κ 0.73–0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis. Conclusions: The application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes

Persistently Elevated Right Ventricular Index of Myocardial Performance in Preterm Infants with Incipient Bronchopulmonary Dysplasia

OBJECTIVES: Elevated pulmonary vascular resistance occurs during the first days after birth in all newborn infants and persists in infants at risk for bronchopulmonary dysplasia (BPD). It is difficult to measure in a non-invasive fashion. We assessed the usefulness of the right ventricular index of myocardial performance (RIMP) to estimate pulmonary vascular resistance in very low birth weight infants. STUDY DESIGN: Prospective echocardiography on day of life (DOL) 2, 7, 14, and 28 in 121 preterm infants (median [quartiles] gestational age 28 [26]-[29] weeks, birth weight 998 [743-1225] g) of whom 36 developed BPD (oxygen supplementation at 36 postmenstrual weeks). RESULTS: RIMP derived by conventional pulsed Doppler technique was unrelated to heart rate or mean blood pressure. RIMP on DOL 2 was similar in infants who subsequently did (0.39 [0.33-0.55]) and did not develop BPD (0.39 [0.28-0.51], p = 0.467). RIMP declined steadily in non-BPD infants but not in BPD infants (DOL 7: 0.31[0.22-0.39] vs. 0.35[0.29-0.48], p = 0.014; DOL 14: 0.23[0.17-0.30] vs. 0.35[0.25-0.43], p<0.001; DOL 28: 0.21[0.15-0.28] vs. 0.31 [0.21-0.35], p = 0.015). CONCLUSIONS: In preterm infants, a decline in RIMP after birth was not observed in those with incipient BPD. The pattern of RIMP measured in preterm infants is commensurate with that of pulmonary vascular resistance

Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis

INTRODUCTION: Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. METHODS: 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. RESULTS: From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). CONCLUSION: There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI

Lung Volume, Breathing Pattern and Ventilation Inhomogeneity in Preterm and Term Infants

BACKGROUND: Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. METHODOLOGY/PRINCIPAL FINDINGS: We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. CONCLUSIONS: Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process

A Trigger Enzyme in Mycoplasma pneumoniae: Impact of the Glycerophosphodiesterase GlpQ on Virulence and Gene Expression

Mycoplasma pneumoniae is a causative agent of atypical pneumonia. The formation of hydrogen peroxide, a product of glycerol metabolism, is essential for host cell cytotoxicity. Phosphatidylcholine is the major carbon source available on lung epithelia, and its utilization requires the cleavage of deacylated phospholipids to glycerol-3-phosphate and choline. M. pneumoniae possesses two potential glycerophosphodiesterases, MPN420 (GlpQ) and MPN566. In this work, the function of these proteins was analyzed by biochemical, genetic, and physiological studies. The results indicate that only GlpQ is an active glycerophosphodiesterase. MPN566 has no enzymatic activity as glycerophosphodiesterase and the inactivation of the gene did not result in any detectable phenotype. Inactivation of the glpQ gene resulted in reduced growth in medium with glucose as the carbon source, in loss of hydrogen peroxide production when phosphatidylcholine was present, and in a complete loss of cytotoxicity towards HeLa cells. All these phenotypes were reverted upon complementation of the mutant. Moreover, the glpQ mutant strain exhibited a reduced gliding velocity. A comparison of the proteomes of the wild type strain and the glpQ mutant revealed that this enzyme is also implicated in the control of gene expression. Several proteins were present in higher or lower amounts in the mutant. This apparent regulation by GlpQ is exerted at the level of transcription as determined by mRNA slot blot analyses. All genes subject to GlpQ-dependent control have a conserved potential cis-acting element upstream of the coding region. This element overlaps the promoter in the case of the genes that are repressed in a GlpQ-dependent manner and it is located upstream of the promoter for GlpQ-activated genes. We may suggest that GlpQ acts as a trigger enzyme that measures the availability of its product glycerol-3-phosphate and uses this information to differentially control gene expression