91 research outputs found
Immunological and genetic determinants of pulmonary outcome in school aged children
Background: The prevalence of respiratory disorders in children has steadily increased over the past decades to such an extent that asthma is now the most common chronic disease of childhood. Childhood asthma resembles a complex syndrome rather than a single disease, and includes many wheeze phenotypes, making its diagnosis challenging. Most likely, it is not a single risk factor that determines whether a child develops asthma, but several risk factors (e.g. environmental, immunological, genetic, onset of respiratory symptoms) that each make small contributions to the development of the disease. Already infancy, lung function tests are available to assess airway disease. These tests are predominantly used in patients with Cystic Fibrosis (CF), for whom preservation of normal lung function is crucial. Despite recent advances in lung function testing, several methodological issues remain unanswered. Higher quality tests are required in order to effectively study the various risk factors involved in the development of complex airway diseases
Aim: The first aim was to describe methodological issues during infant lung function testing in order to improve their quality. The second aim was to study different risk factors for asthma development, and to investigate their association with respiratory diseases during childhood.
Methods: The study was conducted within the prospective Basel-Bern infant lung development (BILD) cohort, a population-based cohort of unselected infants of Central-European origin. The survey collects prenatal data via standardized interviews and cord blood samples for the assessment of immunological and genetic information. During the first year of life, research nurses call the parents weekly to assess the occurrence of respiratory symptoms. Pulmonary function tests, as well as measurement of fractional exhaled nitric oxide (FeNO) to assess airway inflammation, are completed at 5 weeks of age, and again at 6 years of age during follow-up.
Results: We provided specific recommendations on how to improve outcomes from infant lung measurements. Furthermore, we measured airway obstruction using the interrupter technique (Rint) in unsedated infants shortly after birth, and were able to show that measurements were feasible but had a high variability. We compared Rint between term and preterm infants, and found that Rint was higher, and variability of Rint lower, in term-born infants. We assessed FeNO in healthy newborn infants, and in infants with CF. FeNO at birth had no predictive value for asthma development at school age. In CF patients, FeNO at birth was lower compared to matched healthy controls.
We could also show that polymorphisms in the chitinase 3-like 1 (CHI3L1) gene encoding YKl-40 were associated with asthma at 6 years. There was some indication that increased YKL-40 levels at birth may also be involved in the development of airway disease. We also developed a novel method to characterize the time series of prospectively assessed respiratory symptom scores during infancy. This method assesses symptom dynamics in an observer-independent manner. Using this method, we were able to identify a high-risk phenotype, which was predominantly male, and contained more infants exposed to maternal asthma, and environmental tobacco smoke. This phenotype was also at increased risk for asthma and atopy at school age.
Conclusions: Infant lung function is useful to study airway disease at an early age, and outcomes can be improved by applying minimal changes in analyses algorithms. Assessment of airway obstruction in infants is feasible, but measurements require careful interpretation due to the high variability. We found some indication that FeNO levels early in life are determined by environmental factors and the child’s genetic profile. In CF patients, FeNO after birth was associated with the severity of the genetic mutation. In healthy infants, FeNO levels early in life seem to be influenced by environmental exposures.
Our findings contribute additional, relevant knowledge on asthma risk factors and their association with respiratory symptoms from birth through school age. We found associations between genetics and the immunological status at birth with asthma at school age. The development of asthma may also depend on respiratory symptoms early in life. We could show that the pattern of symptom deterioration and recovery during the first year of life determines whether or not a child has persistent wheezing until school age
CFTR genotype and maximal exercise capacity in cystic fibrosis: a cross-sectional study
RATIONALE: Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with CF may present an important determinant of aerobic exercise capacity in CF. Previous studies on the relationship between CFTR genotype and aerobic exercise capacity are scarce and contradictory.
OBJECTIVES: This study was designed to explore factors influencing aerobic exercise capacity, expressed as peak oxygen consumption (VO2peak) with a specific focus on CFTR genotype in children and adults with CF.
METHODS: In an international, multicenter cross-sectional study we collected data on CFTR genotype and cardiopulmonary exercise tests (CPET) in patients with CF eight years and older. CFTR mutations were classified into functional classes I-V.
RESULTS: The final analysis included 726 patients (45% females, age 8 to 61 years, FEV1 16 to 123 % predicted) from 17 CF centers in North America, Europe, Australia and Asia whom all had both valid maximal CPET and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (VO2peak, 77.3±19.1 % predicted), but values were comparable among different CFTR classes. Using linear regression analysis adjusted for relevant confounders, lung function and body mass index, but not CFTR genotype were the main predictors of VO2peak.
CONCLUSIONS: We conclude that lung disease severity and reduced nutritional status rather than CFTR genotypes are the major determinants of aerobic exercise capacity in patients with CF
Feasibility of nasal NO screening in healthy newborns
BACKGROUND
Nasal nitric oxide (nNO) measurement is recommended as a first line screening test for primary ciliary dyskinesia (PCD). While reliable velum- and non-velum-closure techniques exist for preschool children and older individuals, no data are available for neonates.
AIMS
To determine feasibility of nNO screening and nNO concentration in healthy newborns in the first week of life.
METHODS
Nasal NO was analyzed in tidal breathing during natural sleep using a CLD-88 sp NO analyzer (chemoluminescence sensor) and a NIOX MINO (electrochemical sensor). Test success and nNO concentration were determined and compared between the two devices.
RESULTS
Nasal NO was measured in 62 healthy neonates within the first week of life. Feasibility of nNO measurement was 100% for at least one nostril and 85.5% for both nostrils using the chemoluminescence device, but significantly lower with the electrochemical device (85.5% and 53.2%; p < .001). Median nNO concentration was 38 ppb (interquartile range, 27-55; range, 9-100) with the ECOMEDICS device and 23 (15-33, 8-59) with the NIOX MINO (p < .001), with a trend towards higher values for older subjects. None of the subjects exceeded nNO levels of 100 ppb.
CONCLUSION
Measurement of nNO using a chemoluminescence device is highly feasible in newborns during natural sleep. However, nNO levels are considerably lower compared to the published data for older individuals and in the range of a PCD reference group of infants between 4 and 8 weeks of age, potentially resulting in a great overlap with subjects with PCD in this age group. Therefore, screening for PCD using nasal NO might not be useful in the first week of life. Upon clinical suspicion, other diagnostic tests such as high-speed video analysis of the cilia should be applied
Validation of computerized wheeze detection in young infants during the first months of life
Background Several respiratory diseases are associated with specific
respiratory sounds. In contrast to auscultation, computerized lung sound
analysis is objective and can be performed continuously over an extended
period. Moreover, audio recordings can be stored. Computerized lung sounds
have rarely been assessed in neonates during the first year of life. This
study was designed to determine and validate optimal cut-off values for
computerized wheeze detection, based on the assessment by trained clinicians
of stored records of lung sounds, in infants aged <1 year. Methods Lung sounds
in 120 sleeping infants, of median (interquartile range) postmenstrual age of
51 (44.5–67.5) weeks, were recorded on 144 test occasions by an automatic
wheeze detection device (PulmoTrack®). The records were retrospectively
evaluated by three trained clinicians blinded to the results. Optimal cut-off
values for the automatically determined relative durations of inspiratory and
expiratory wheezing were determined by receiver operating curve analysis, and
sensitivity and specificity were calculated. Results The optimal cut-off
values for the automatically detected durations of inspiratory and expiratory
wheezing were 2% and 3%, respectively. These cutoffs had a sensitivity and
specificity of 85.7% and 80.7%, respectively, for inspiratory wheezing and
84.6% and 82.5%, respectively, for expiratory wheezing. Inter-observer
reliability among the experts was moderate, with a Fleiss’ Kappa (95%
confidence interval) of 0.59 (0.57-0.62) for inspiratory and 0.54 (0.52 -
0.57) for expiratory wheezing. Conclusion Computerized wheeze detection is
feasible during the first year of life. This method is more objective and can
be more readily standardized than subjective auscultation, providing
quantitative and noninvasive information about the extent of wheezing
Age and body mass index affect fit of spirometry Global Lung Function Initiative references in schoolchildren.
Background
References from the Global Lung Function Initiative (GLI) are widely used to interpret children's spirometry results. We assessed fit for healthy schoolchildren.
Methods
LuftiBus in the School was a population-based cross-sectional study undertaken in 2013-2016 in the canton of Zurich, Switzerland. Parents and their children aged 6-17 years answered questionnaires about respiratory symptoms and lifestyle. Children underwent spirometry in a mobile lung function lab. We calculated GLI-based z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow for 25-75% of FVC (FEF25-75) for healthy White participants. We defined appropriate fit to GLI references by mean values between +0.5 and -0.5 z-scores. We assessed whether fit varied by age, body mass index, height and sex using linear regression models.
Results
We analysed data from 2036 children with valid FEV1 measurements, of whom 1762 also had valid FVC measurements. The median age was 12.2 years. Fit was appropriate for children aged 6-11 years for all indices. In adolescents aged 12-17 years, fit was appropriate for FEV1/FVC z-scores (mean±sd -0.09±1.02), but not for FEV1 (-0.62±0.98), FVC (-0.60±0.98) and FEF25-75 (-0.54±1.02). Mean FEV1, FVC and FEF25-75 z-scores fitted better in children considered overweight (-0.25, -0.13 and -0.38, respectively) than normal weight (-0.55, -0.50 and -0.55, respectively; p-trend <0.001, 0.014 and <0.001, respectively). FEV1, FVC and FEF25-75 z-scores depended on both age and height (p-interaction 0.033, 0.019 and <0.001, respectively).
Conclusion
GLI-based FEV1, FVC, and FEF25-75 z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision-making, research and international comparison
Age and body mass index affect fit of spirometry Global Lung Function Initiative references in schoolchildren
BACKGROUND: References from the Global Lung Function Initiative (GLI) are widely used to interpret children's spirometry results. We assessed fit for healthy schoolchildren.
METHODS: LuftiBus in the School was a population-based cross-sectional study undertaken in 2013-2016 in the canton of Zurich, Switzerland. Parents and their children aged 6-17 years answered questionnaires about respiratory symptoms and lifestyle. Children underwent spirometry in a mobile lung function lab. We calculated GLI-based z-scores for forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC and forced expiratory flow for 25-75% of FVC (FEF) for healthy White participants. We defined appropriate fit to GLI references by mean values between +0.5 and -0.5 z-scores. We assessed whether fit varied by age, body mass index, height and sex using linear regression models.
RESULTS: We analysed data from 2036 children with valid FEV measurements, of whom 1762 also had valid FVC measurements. The median age was 12.2 years. Fit was appropriate for children aged 6-11 years for all indices. In adolescents aged 12-17 years, fit was appropriate for FEV/FVC z-scores (mean±sd -0.09±1.02), but not for FEV (-0.62±0.98), FVC (-0.60±0.98) and FEF (-0.54±1.02). Mean FEV, FVC and FEF z-scores fitted better in children considered overweight (-0.25, -0.13 and -0.38, respectively) than normal weight (-0.55, -0.50 and -0.55, respectively; p-trend <0.001, 0.014 and <0.001, respectively). FEV, FVC and FEF z-scores depended on both age and height (p-interaction 0.033, 0.019 and <0.001, respectively).
CONCLUSION: GLI-based FEV, FVC, and FEF z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision-making, research and international comparison
Possible effects of left pulmonary artery stenting in single ventricle patients on bronchial area, lung volume and lung function
BACKGROUND
Left pulmonary artery (LPA) stenting is often required in single ventricle (SV) patients. Due to their close anatomical relationship an LPA stent could potentially compress the left main bronchus (LMB). We assessed the impact of LPA stenting on bronchial size, pulmonary volumes, and lung function in a cohort of SV patients.
METHODS
Forty-nine patients underwent cardiovascular magnetic resonance (CMR) and 36 spirometry 11 (8-15) years after Fontan. All patients were free of respiratory symptoms. LPA stents were inserted in 17 (35%) patients at 8.8 (3.4-12.6) years. Area/shape of the main bronchi (n = 46) and lung volumes (n = 47) were calculated from CMR-ZTE images for each lung and transformed in right-to-left (r/l) ratio and indexed for BSA. The effect of early stent insertion (prior to stage III) was analyzed.
RESULTS
Patients with LPA stent had larger r/l ratio for main bronchus area (p < 0.001) and r/l ratio difference for lung volumes was slightly larger in patients with early stenting. A trend toward a deformation of LMB shape in patients with LPA stent and toward a higher prevalence of abnormal spirometry in patients with early stent implantation was observed.
CONCLUSIONS
In this cohort of patients, early insertion of LPA stents seems to relate with smaller LMB sizes and a trend toward smaller left lung volume and higher prevalence of impaired lung function. Whether these findings are caused by the stent or, at least to a certain degree, present prior to the implantation needs to be verified
Agreement of parent- and child-reported wheeze and its association with measurable asthma traits
Objectives
In epidemiological studies, childhood asthma is usually assessed with questionnaires directed at parents or children, and these may give different answers. We studied how well parents and children agreed when asked to report symptoms of wheeze and investigated whose answers were closer to measurable traits of asthma.
Methods
LuftiBus in the school is a cross-sectional survey of respiratory health among Swiss schoolchildren aged 6–17 years. We applied questionnaires to parents and children asking about wheeze and exertional wheeze in the past year. We assessed agreement between parent–child answers with Cohen's kappa (k), and associations of answers from children and parents with fractional exhaled nitric oxide (FeNO) and forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC), using quantile regression.
Results
We received questionnaires from 3079 children and their parents. Agreement was poor for reported wheeze (k = 0.37) and exertional wheeze (k = 0.36). Median FeNO varied when wheeze was reported by children (19 ppb, interquartile range [IQR]: 9–44), parents (22 ppb, IQR: 12–46), both (31 ppb, IQR: 16–55), or neither (11 ppb, IQR: 7–19). Median absolute FEV1/FVC was the same when wheeze was reported by children (84%, IQR: 78–89) and by parents (84%, IQR: 78–89), lower when reported by both (82%, IQR: 78–87), and higher when reported by neither (87%, IQR: 82–91). For exertional wheeze findings were similar. Results did not differ by age or sex.
Conclusion
Our findings suggest that surveying both parents and children and combining their responses can help us to better identify children with measurable asthma traits
Evaluation of the double-tracer gas single-breath washout test in a pediatric field study.
BACKGROUND
The early-life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren.
RESEARCH QUESTION
Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBW derived ventilation inhomogeneity estimate in unselected schoolchildren?
STUDY DESIGN AND METHODS
In this prospective cross-sectional field study, a mobile lung function-testing unit visited participating schools in Switzerland. We applied DTG-SBW, fraction of exhaled nitric oxide (FeNO), and spirometry measurements. The DTG-SBW is based on tidal inhalation of helium (He) and sulfur-hexafluoride (SF6) and the phase III slope (SIIIHe-SF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors anthropometrics, presence of wheeze (i.e. parental report of ≥ 1 episode of wheeze in the prior year), FeNO, forced expiratory volume in the first second (FEV1), and FEV1/forced vital capacity (FVC).
RESULTS
In 1782 children, 5223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1449 (81.3%) children, coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 (21.2%) children, wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze as compared to those without and remained associated with wheeze after adjusting for age and BMI in a multi-variable linear regression model. SIIIHe-SF6 was not associated with FeNO, FEV1, and FEV1/FVC.
INTERPRETATION
The DTG-SBW is feasible in a pediatric field study setting. On the population level, age, body composition and wheeze are independent predictors of peripheral airway function in unselected schoolchildren. The variation of the DTG-SBW possibly constrains its current applicability on the individual level
Evaluation of the Double-Tracer Gas Single-Breath Washout Test in a Pediatric Field Study
BACKGROUND: The early life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren.
RESEARCH QUESTION: Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBWderived ventilation inhomogeneity estimate in unselected schoolchildren?
STUDY DESIGN AND METHODS: In this prospective cross-sectional field study, a mobile lung function testing unit visited participating schools in Switzerland. We applied DTG-SBW, fraction of exhaled nitric oxide (FENO), and spirometry measurements. The DTG-SBW is based on tidal inhalation of helium and sulfur-hexafluoride, and the phase III slope (SIIIHeSF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors of anthropometrics, presence of wheeze (ie, parental report of one or more episode of wheeze in the prior year), FENO, FEV1, and FEV1/FVC.
RESULTS: In 1,782 children, 5,223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1,449 children (81.3%); the coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 children (21.2%), wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze
compared with those without and remained associated with wheeze after adjusting for age and BMI in a multivariable linear regression model. SIIIHe-SF6 was not associated with FENO, FEV1, and FEV1/FVC.
INTERPRETATION: The DTG-SBW is feasible in a pediatric field study setting. On the population level, age, body composition, and wheeze are independent predictors of peripheral airway function in unselected schoolchildren. The variation of the DTG-SBW possibly constrains its current applicability on the individual level
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