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ABSTRACT: 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. Objective: 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 PM10, NO2 and O3 were obtained from local monitoring stations. We determined the association of the preceding week's 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 10µg/m³ PM10 levels) and in infants with premorbid lung function. During times of elevated PM10 (>33.3 µg/m³), duration of respiratory tract infections increased by 20% (95% CI: 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.
American Journal of Respiratory and Critical Care Medicine 04/2013; · 11.08 Impact Factor
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ABSTRACT: Multiple-breath washout (MBW)-derived lung clearance index (LCI) is a sensitive measure of ventilation inhomogeneity in patients with cystic fibrosis (CF), but LCI measurement is time consuming. We systematically assessed ways to shorten LCI measurements.In 68 school-aged children (44 with mild CF lung disease) three standard nitrogen (N(2)) MBWs were applied. We assessed repeatability and diagnostic performance of (1) LCI measured earlier from three MBW runs and (2) LCI measured at complete MBW (1/40th of starting N(2) concentration) from two runs only.Compared with the standard LCI from three complete MBW runs, the new LCI based on three N(2)MBW runs until 1/20th, or two complete runs until 1/40th, provided similar or better repeatability as well as sensitivity and specificity for CF lung disease. Alternative ways to measure LCI reduced test duration in children with CF by 30% and 41%, respectively.LCI measurements can be reliably shortened in children. These new MBW protocols may advance the transition of LCI from research into clinical settings.
Thorax 10/2012; · 6.84 Impact Factor
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Elisabeth Kieninger,
Florian Singer,
Caroline Tapparel,
Marco P Alves, Philipp Latzin,
Hui-Leng Tan,
Cara Bossley,
Carmen Casaulta,
Andrew Bush,
Jane C Davies,
Laurent Kaiser,
Nicolas Regamey
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ABSTRACT: ABSTRACT BACKGROUND: Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. OBJECTIVE: To assess in vivo the association of RV prevalence and load with anti-viral defense mechanisms, airway inflammation and lung function parameters in children with CF as compared to children with other chronic respiratory diseases and controls. METHODS: RV presence and load was measured by real-time RT-PCR in bronchoalveolar lavage (BAL) samples and related to anti-viral and inflammatory mediators measured in BAL and to clinical parameters. RESULTS: BAL samples were obtained from children with CF (n=195), non-CF bronchiectasis (n=40), asthma (n=29) and controls (n=35) at a median (IQR) age of 8.2 (4.0-11.7) years. RV was detected in 73 samples (24.4%). RV prevalence was similar between groups. RV load (median [IQR] x103 copies/mL) was higher in CF (143.0 [13.1-1530.0]), especially during pulmonary exacerbations, compared to asthmatics (3.0 [1.3-25.8], p=0.006) and controls (0.5 [0.3-0.5], p<0.001), but similar to non-CF bronchiectasis (122.1 [2.7-4423.5], p=NS). In children with CF, RV load was negatively associated with IFN-β/-λ, IL-r1a levels and FEV1, and positively with CXCL8 and CXCL10 levels. CONCLUSION: RV load in CF BAL is high, especially during exacerbated lung disease. Impaired production of anti-viral mediators may lead to the high RV burden in the lower airways of children with CF. Whether high RV load is a cause or a consequence of inflammation needs further investigation in longitudinal studies.1Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland; elisabeth.kieinger@insel.ch, florian.singer@insel.ch, marco.alves@dkf.unibe.ch, philipp.latzin@insel.ch, carmen.casaulta@insel.ch, nicolas.regamey@insel.ch2Department of Clinical Research, University of Bern, Bern, Switzerland; elisabeth.kieinger@insel.ch, marco.alves@dkf.unibe.ch, philipp.latzin@insel.ch, nicolas.regamey@insel.ch3Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland; Caroline.Tapparel@hcuge.ch, Laurent.Kaiser@sec.hcuge.ch4Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom, h.tan@imperial.ac.uk, carajbossley@hotmail.com, a.bush@imperial.ac.uk, j.c.davies@imperial.ac.ukCorresponding author: Nicolas Regamey, MD; Division of Respiratory Medicine, Department of Pediatrics, University Hospital, Inselspital, 3010 Bern, Switzerland Email: nicolas.regamey@insel.chFunding Sources: Supported by the Swiss National Science Foundation [PP00P3_123453/1 to N.R], the Fondazione Ettore e Valeria Rossi [long-time fellowship to E.K.] and the Austrian, German and Swiss Pediatric Respiratory Society [short-time fellowship to E.K].
Chest 09/2012; · 5.25 Impact Factor
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ABSTRACT: BACKGROUND: Although lung clearance index (LCI) is a sensitive indicator of mild cystic fibrosis (CF) lung disease, it is rarely measured due to lengthy protocols and the commercial unavailability of multiple-breath washout (MBW) setups and tracer gases. We used a newly validated, commercially available nitrogen (N(2) ) MBW setup to assess success rate, duration, and variability of LCI within a 20 min timeframe, during clinical routine. We also evaluated the relationship between LCI and other clinical markers of CF lung disease. METHODS: One hundred thirty six children (83 with CF) between 4 and 16 years were studied in a pediatric CF outpatient setting. One hundred eighteen out of 136 children were naïve to MBW. Within 20 min, each child was trained, N(2) MBW was performed, and LCI was analyzed. We assessed intra- and between-test reproducibility in a subgroup of children. RESULTS: At least one LCI was feasible in 123 (90%) children, with a mean (range) of 3.3 (1.2-6.4) min per test. Two or more measurements were feasible in 56 (41%) children. Comparing LCI in CF versus controls, LCI mean (SD) was 12.0 (3.9) versus 6.1 (0.9), and the intra- and inter-test coefficient of repeatability was 1.00 versus 0.81 and 0.96 versus 0.62, respectively. LCI was correlated with spirometry, blood gases, and Pseudomonas aeruginosa infection. CONCLUSIONS: Using available N(2) MBW equipment, LCI measurements are practical and fast in children. LCI is correlated with markers of CF lung disease. Longer timeframes would be required for triplicate N(2) MBW tests in inexperienced children. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.
Pediatric Pulmonology 08/2012; · 2.53 Impact Factor
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ABSTRACT: Abstract There is increasing evidence of the adverse impact of prenatal exposure to air pollution. This is of particular interest, as exposure during pregnancy-a crucial time span of important biological development-may have long-term implications. The aims of this review are to show current epidemiological evidence of known effects of prenatal exposure to air pollution and present possible mechanisms behind this process. Harmful effects of exposure to air pollution during pregnancy have been shown for different birth outcomes: higher infant mortality, lower birth weight, impaired lung development, increased later respiratory morbidity, and early alterations in immune development. Although results on lower birth weight are somewhat controversial, evidence for higher infant mortality is consistent in studies published worldwide. Possible mechanisms include direct toxicity of particles due to particle translocation across tissue barriers or particle penetration across cellular membranes. The induction of specific processes or interaction with immune cells in either the pregnant mother or the fetus may be possible consequences. Indirect effects could be oxidative stress and inflammation with consequent hemodynamic alterations resulting in decreased placental blood flow and reduced transfer of nutrients to the fetus. The early developmental phase of pregnancy is thought to be very important in determining long-term growth and overall health. So-called "tracking" of somatic growth and lung function is believed to have a huge impact on long-term morbidity, especially from a public health perspective. This is particularly important in areas with high levels of outdoor pollution, where it is practically impossible for an individual to avoid exposure. Especially in these areas, good evidence for the association between prenatal exposure to air pollution and infant mortality exists, clearly indicating the need for more stringent measures to reduce exposure to air pollution.
Journal of Aerosol Medicine and Pulmonary Drug Delivery 08/2012; · 2.20 Impact Factor
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ABSTRACT: Rhinovirus (RV) infections occur early and recurrently in life, imposing a significant burden of disease on infants and young children. They are the most frequent causative agents of both upper and lower respiratory tract infections in this age group and are associated with a broad variety of clinical outcomes, ranging from asymptomatic infections to severe respiratory disease requiring hospitalisation. In addition to their impact on short-term morbidity, RVs are also debated as important pathogens in the development of recurrent wheeze and/or asthma. Several studies in infants at high-risk for atopy and asthma and in hospitalised children have demonstrated that recurrent wheezing illnesses induced by RVs in early life are a risk factor for asthma development later in childhood. Underlying mechanisms, however, are poorly understood. The question whether RVs are directly involved in the development of childhood wheeze and asthma, or whether symptomatic RV infections only represent a proxy for infants prone to develop obstructive lung diseases, is still open. In this review we provide an overview on the role of RVs as important disease-causing agents from infancy to early childhood and discuss their contribution to the subsequent development of childhood wheeze and/or asthma.
European Respiratory Journal 06/2012; · 5.89 Impact Factor
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Oliver Fuchs,
Jon Genuneit, Philipp Latzin,
Gisela Büchele,
Elisabeth Horak,
Georg Loss,
Barbara Sozanska,
Juliane Weber,
Andrzej Boznanski,
Dick Heederik,
Charlotte Braun-Fahrländer,
Urs Frey,
Erika von Mutius
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ABSTRACT: Previous studies have demonstrated that children raised on farms are protected from asthma and allergies. It is unknown whether the farming effect is solely mediated by atopy or also affects nonatopic wheeze phenotypes.
We sought to study the farm effect on wheeze phenotypes and objective markers, such as lung function and exhaled nitric oxide, and their interrelation with atopy in children.
The GABRIEL Advanced Studies are cross-sectional, multiphase, population-based surveys of the farm effect on asthma and allergic disease in children aged 6 to 12 years. Detailed data on wheeze, farming exposure, and IgE levels were collected from a random sample of 8023 children stratified for farm exposure. Of those, another random subsample of 858 children was invited for spirometry, including bronchodilator tests and exhaled nitric oxide measurements.
We found effects of exposure to farming environments on the prevalence and degree of atopy, on the prevalence of transient wheeze (adjusted odds ratio, 0.78; 95% CI, 0.64-0.96), and on the prevalence of current wheeze among nonatopic subjects (adjusted odds ratio, 0.45; 95% CI, 0.32-0.63). There was no farm effect on lung function and exhaled nitric oxide levels in the general study population.
Children living on farms are protected against wheeze independently of atopy. This farm effect is not attributable to improved airway size and lung mechanics. These findings imply as yet unknown protective mechanisms. They might include alterations of immune response and susceptibility to triggers of wheeze, such as viral infections.
The Journal of allergy and clinical immunology 06/2012; 130(2):382-8.e6. · 9.17 Impact Factor
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ABSTRACT: In cystic fibrosis (CF) lung disease, tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and controls, and compared SBW between groups and with nitrogen multiple-breath washout (MBNW).Three SBW and MBNW were done in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIIIDTG), MBNW derived lung clearance index (LCI), and indices of acinar (Sacin) and conductive (Scond) ventilation inhomogeneity.SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIIIDTG differed between children with CF and controls, mean (SD) was -456.7 (492.8) and -88.4 (129.1) mg·mol.L(-1), respectively. Abnormal SIIIDTG was present in 36 (59%) of CF children. SIIIDTG was associated with LCI (r= -0.58), Sacin (r= -0.58), but not with Scond.In CF, steeply sloping SIIIDTG potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.
European Respiratory Journal 05/2012; · 5.89 Impact Factor
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ABSTRACT: Standards for online multiple-breath (mb) exhaled nitric oxide (eNO) measurements and studies comparing them with online single-breath (sb) eNO measurements are lacking, although eNOmb requires less cooperation in children at school age or younger.
Online eNOmb and eNOsb were measured in 99 healthy children and (in order to observe higher values) in 21 children with suspected asthma at a median age of 6.1 and 11.7 y, respectively. For eNOmb, we aimed for 20 tidal breathing maneuvers; eNOsb was measured according to standards. The two techniques were compared by standard methods after computing NO output or extrapolating eNOmb to the standard flow of 50 ml/s (eNOmb(50)).
Measurements were acceptable in 82 (eNOmb) and 81 (eNOsb) children. Paired data were available for 65 children. On a log-log scale, eNOmb(50) (geometric mean ± SD 13.1 ± 15.5 parts per billion, ppb) was correlated with eNOsb (12.5 ± 15.8 ppb), with r(2) = 0.87. The mean difference between eNOsb and eNOmb(50) was -0.7 ppb, with limits of agreement (LOAs) of 4.0 and -5.3 ppb.
Despite its correlation with eNOsb, the LOA range hampers eNOmb use in research, where exact values across the whole range are warranted. However, eNOmb might be an alternative tool especially at preschool age, when cooperation during measurements is crucial.
Pediatric Research 02/2012; 71(5):605-11. · 2.70 Impact Factor
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ABSTRACT: For reliable assessment of ventilation inhomogeneity, multiple-breath washout (MBW) systems should be realistically validated. We describe a new lung model for in vitro validation under physiological conditions and the assessment of a new nitrogen (N(2))MBW system.
The N(2)MBW setup indirectly measures the N(2) fraction (F(N2)) from main-stream carbon dioxide (CO(2)) and side-stream oxygen (O(2)) signals: F(N2) = 1-F(O2)-F(CO2)-F(Argon). For in vitro N(2)MBW, a double chamber plastic lung model was filled with water, heated to 37°C, and ventilated at various lung volumes, respiratory rates, and F(CO2). In vivo N(2)MBW was undertaken in triplets on two occasions in 30 healthy adults. Primary N(2)MBW outcome was functional residual capacity (FRC). We assessed in vitro error (√[difference](2)) between measured and model FRC (100-4174 mL), and error between tests of in vivo FRC, lung clearance index (LCI), and normalized phase III slope indices (S(acin) and S(cond)).
The model generated 145 FRCs under BTPS conditions and various breathing patterns. Mean (SD) error was 2.3 (1.7)%. In 500 to 4174 mL FRCs, 121 (98%) of FRCs were within 5%. In 100 to 400 mL FRCs, the error was better than 7%. In vivo FRC error between tests was 10.1 (8.2)%. LCI was the most reproducible ventilation inhomogeneity index.
The lung model generates lung volumes under the conditions encountered during clinical MBW testing and enables realistic validation of MBW systems. The new N(2)MBW system reliably measures lung volumes and delivers reproducible LCI values.
PLoS ONE 01/2012; 7(4):e36083. · 4.09 Impact Factor
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ABSTRACT: Exposure to air pollution increases the risk of Sudden Infant Death Syndrome and thus potentially influences control of breathing. This raises the question of whether tidal breathing parameters related to the control of breathing are influenced by atmospheric conditions and air pollution on the day of measurement (DOM).
In a prospective birth cohort study of 175 healthy term infants, we measured tidal breathing parameters including tidal volume, respiratory rate, minute ventilation, inspiratory time to total breath time (TI/Ttot), ratio of time to peak tidal expiratory flow to expiratory time (TPTEF/TE), and peak tidal inspiratory flow at the age of 4-5 weeks. We assessed the association of these tidal breathing parameters with postnatal environmental tobacco smoke exposure (ETS), local atmospheric parameters, pollution levels of nitrogen dioxide (NO2), ozone (O3), and airborne particles with an aerodynamic diameter B10mm (PM10) on the DOM using multiple linear regression analysis and adjusting for anthropometric data.
We found no consistent evidence of an association between atmospheric parameters, outside temperature and humidity, and tidal breathing parameters when adjusting for multiple testing. Anthropometric data (postconceptional age, length, and sex) were associated with control of breathing but not urban pollutant levels and ETS on the DOM.
Tidal breathing parameters, which are normally used to determine the maturational state of breathing control in infants, are influenced by anthropometric parameters. The acute effects of outside temperature and humidity, postnatal ETS, and outdoor air pollution levels on the DOM for the control of breathing were negligible in our study of healthy term infants.
Annals of Respiratory Medicine. 08/2011; 2(1):7-15.
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ABSTRACT: Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases. We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 08/2011; 10(6):487-90. · 3.19 Impact Factor
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ABSTRACT: Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown.
In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM₁₀), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders.
Mean (95%-CI) PM₁₀ exposure for the last 7 days of pregnancy was 18.3 (10.3-38.4 µg/m³). PM₁₀ exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found.
Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort.
PLoS ONE 01/2011; 6(8):e23130. · 4.09 Impact Factor
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International Journal of Epidemiology 01/2011; 41(2):366-76. · 6.41 Impact Factor
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Andreas Hector,
Michael S D Kormann,
Ines Mack, Philipp Latzin,
Carmen Casaulta,
Elisabeth Kieninger,
Zhe Zhou,
Ali Ö Yildirim,
Alexander Bohla,
Nikolaus Rieber,
Matthias Kappler,
Barbara Koller,
Ernst Eber,
Olaf Eickmeier,
Stefan Zielen,
Oliver Eickelberg,
Matthias Griese,
Marcus A Mall,
Dominik Hartl
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ABSTRACT: The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.
PLoS ONE 01/2011; 6(9):e24399. · 4.09 Impact Factor
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ABSTRACT: Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF(6)) and helium (He) using an ultrasonic flowmeter (USFM).
The tracer gas mixture contained 5% SF(6) and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart.
USFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF(6) and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%.
The USFM accurately measured relative changes in SF(6) and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF(6) and He washout patterns during tidal breathing.
PLoS ONE 01/2011; 6(3):e17588. · 4.09 Impact Factor
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ABSTRACT: Infants with chronic lung disease (CLD) have a capacity to maintain functional lung volume despite alterations to their lung mechanics. We hypothesize that they achieve this by altering breathing patterns and dynamic elevation of lung volume, leading to differences in the relationship between respiratory muscle activity, flow and lung volume. Lung function and transcutaneous electromyography of the respiratory muscles (rEMG) were measured in 20 infants with CLD and in 39 healthy age-matched controls during quiet sleep. We compared coefficient of variations (CVs) of rEMG and the temporal relationship of rEMG variables, to flow and lung volume [functional residual capacity (FRC)] between these groups. The time between the start of inspiratory muscle activity and the resulting flow (tria)--in relation to respiratory cycle time--was significantly longer in infants with CLD. Although FRC had similar associations with tria and postinspiratory activity (corrected for respiratory cycle time), the CV of the diaphragmatic rEMG was lower in CLD infants (22.6 versus 31.0%, p = 0.030). The temporal relationship of rEMG to flow and FRC and the loss of adaptive variability provide additional information on coping mechanisms in infants with CLD. This technique could be used for noninvasive bedside monitoring of CLD.
Pediatric Research 10/2010; 68(4):339-43. · 2.70 Impact Factor
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ABSTRACT: In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.
Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination.
PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes.
In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation.
Respiratory research 11/2009; 10:106. · 3.36 Impact Factor
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ABSTRACT: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis patients remains challenging, mainly owing to overlapping symptoms of the underlying lung disease with clinical symptoms of ABPA. In addition, a varying mixture of diagnostic criteria, including clinical status, radiological findings and immunological measurements, has led to confusion and differing recommendations. In order to help simplify as well as standardize the diagnostic criteria for ABPA, different serological markers have been evaluated in the last 20 years and their usefulness has been assessed in many clinical studies. This review presents current diagnostic criteria of ABPA, with a special focus on serum markers supporting the diagnosis and explains why the hunt for a serological marker for ABPA is still ongoing.
Expert Review of Molecular Diagnostics 04/2009; 9(2):157-64. · 4.86 Impact Factor
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ABSTRACT: 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.
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.
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.
PLoS ONE 02/2009; 4(2):e4635. · 4.09 Impact Factor
