Fast real-time moment-ratio analysis of multibreath nitrogen washout in children

To apply real-time moment-ratio analysis to multibreath N2-washout curves (MBNW) from children, a new processor-controlled device was constructed. Flow and fractional N2 concentration (FN2) were each sampled by 200 Hz. An electromagnetic triple-valve system, with an instrumental dead space of 36 ml and a valve resistance of 0.3 cmH2O . l-1 . s, was connected in series with a pneumotachograph and an N2 analyzer (Ohio 720) placed next to the mouthpiece. A FORTRAN/MACRO program on a PDP 11/23 computer enabled measurement of inspiratory and expiratory flow and FN2 sampling by a 12-bit analog-to-digital converter. The fast real-time digital processing of the N2 and flow signals incorporated filtering, delay compensation, and corrections for the effects of changes in gas composition and temperature. MBNW dynamics of the lungs were studied in 17 healthy and 28 asthmatic children and in 16 patients with cystic fibrosis, evaluating the moment ratios of the washout curves as indices of the ventilation characteristics. Intrasubject variability of the moment ratios (m1/m0, m2/m0) and determination of functional residual capacity (FRC) varied between 6.3 and 14.7% (depending on which parameter is considered) and was comparatively lower than other indices previously investigated in adults. In addition, the sensitivity of the moment ratios for discriminating different stages of ventilation inhomogeneity was superior to other indices. m2/m0 is closely related to the simultaneously measured airway resistance, and the ratio between cumulative expired volume and FRC is correlated with the ratio between residual volume and total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glycosylation of sputum mucins is altered in cystic fibrosis patients

Cystic fibrosis (CF) is characterized by chronic lung infection and inflammation, with periods of acute exacerbation causing severe and irreversible lung tissue damage. We used protein and glycosylation analysis of high-molecular mass proteins in saline-induced sputum from CF adults with and without an acute exacerbation, CF children with stable disease and preserved lung function, and healthy non-CF adult and child controls to identify potential biomarkers of lung condition. While the main high-molecular mass proteins in the sputum from all subjects were the mucins MUC5B and MUC5AC, these appeared degraded in CF adults with an exacerbation. The glycosylation of these mucins also showed reduced sulfation, increased sialylation, and reduced fucosylation in CF adults compared with controls. Despite improvements in pulmonary function after hospitalization, these differences remained. Two CF children showed glycoprotein profiles similar to those of CF adults with exacerbations and also presented with pulmonary flares shortly after sampling, while the remaining CF children had profiles indistinguishable from those of healthy non-CF controls. Sputum mucin glycosylation and degradation are therefore not inherently different in CF, and may also be useful predictive biomarkers of lung condition.     

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening

Background

In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.

Methods

Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M₁/M₀ and M₂/M₀, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.

Results

Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M₂/M₀ but not LCI or M₁/M₀. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.

Conclusion

These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.     

Insulin-like growth factor-1, leptin, body composition, and clinical status interactions in children with cystic fibrosis

BACKGROUND/AIMS: Children with cystic fibrosis (CF) are of increased risk of reduced fat body mass (FBM) and lean body mass (LBM). Serum concentrations of insulin-like growth factor-1 (IGF-1)and leptin could be markers of LBM and/or FBM depletion. To evaluate the relationships between disease activity, body composition, IGF-1 and leptin concentrations in CF children. METHODS: A cross-sectional study with 26 CF children aged 5.0-15.5 years and 33 healthy controls, mean age 9.4 years. Body composition was evaluated by dual-energy X-ray absorptiometry. Fasting blood samples were analyzed for leptin, IGF-1 and IGFBP-3. RESULTS: FBM standard deviation score (SDS; CF boys -0.02 +/- 0.88 vs. 0.78 +/- 0.65, p < 0.01; CF girls -0.37 +/- 1.15 vs. 0.70 +/- 0.97, p < 0.05), leptin concentration (CF boys 2.07 +/- 0.79 vs. 3.07 +/- 1.28 ng/ml, p < 0.05; CF girls 2.71 +/- 0.86 vs. 5.00 +/- 2.95 ng/ml, p < 0.05) and IGF-1SDS (CF boys -1.43 +/- 1.50 vs. -0.32 +/- 0.88, p < 0.05; CF girls -0.66 +/- 1.66 vs. 0.64 +/- 0.57, p < 0.01) were lower in CF children compared to controls. Shwachman score was the strongest predictor of lean body mass (R = 0.63). Leptin levels explain 60% of the variability in FBM. CONCLUSION: Serum concentrations of IGF-1 and leptin are decreased in children with CF and are associated with clinical conditions and body composition.     

Longitudinal associations of adiposity with adult lung function in the Childhood Determinants of Adult Health (CDAH) study

Childhood BMI has been reported to be positively associated with adult lung function. The aim of this study was to investigate the effect of childhood BMI on young adult lung function independently of the effects of lean body mass (LBM). Clinical and questionnaire data were collected from 654 young Australian adults (aged 27-36 years), first studied when age 9, 12, or 15 years. Adult lung function was measured by forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC ratio, and the forced expiratory flow in the middle 50% of FVC (FEF(25-75)). BMI and LBM were derived from anthropometric measures at baseline (1985) and at follow-up (2004-2006). Multivariable models were used to investigate the effect of age and sex standardized BMI in childhood on adult lung function, before and after adjustment for LBM. Adult adiposity had a strong deleterious effect on lung function, irrespective of childhood BMI, and adjustment for childhood LBM eliminated any apparent beneficial effect of childhood BMI on adult FEV(1) or FVC. This suggests that the beneficial effect of increased BMI in childhood on adult FEV(1) and FVC observed in previous longitudinal studies is likely to be attributable to greater childhood LBM not adiposity. Obese children who become obese adults can expect to have poorer lung function than those who maintain healthy weight but large deficits in lung function are also likely for healthy weight children who become obese adults. This highlights the importance of lifetime healthy weight maintenance.     

Plasma C-type natriuretic peptide levels in healthy children

C-type natriuretic peptide (CNP) is assuming increasing importance in cardiovascular disease, and in adults its plasma levels are related to clinical and functional disease severity. Data are scarce regarding the reference values for CNP in infancy. Aim of this study was to assess the reference intervals for CNP in human healthy newborns and infants. Plasma CNP was measured in 121 healthy children divided into: 41 newborns (age 0-3 days), 24 newborns (4-30 days), 22 infants (1-12 months) and 32 children (1-12 years). A group of 32 healthy adult subjects (age 64 ± 1 years) was also studied. CNP was measured by a specific radioimmunoassay. Between- and within-assay variability resulted ≤ 30 and 20%, respectively and analytical sensitivity 0.77 ± 0.05 pg/tube. Plasma CNP resulted significantly higher in children than in adult subjects (13.6 ± 1.2 pg/ml vs. 7.4 ± 1.0 pg/ml, p=0.030). When the results were analyzed as a function of the age the reference intervals for plasma CNP resulted: 11.6 ± 2.1 pg/ml for newborns (0-3 days), 16.4 ± 3.7 pg/ml for newborns (4-30 days), 15.4 ± 2.7 pg/ml for infants (1-12 months), 13.6 ± 2.3 pg/ml for children (1-12 years) [p=0.01 newborns (4-30 days) vs. adults; p=0.03 infants (1-12 months) vs. adults]. CNP showed the highest concentrations after 12h of life with a peak between 4 and 5 days of life and with a progressive decline afterwards. According to these data at least five different reference intervals for CNP determinations should be used. These observations may be helpful for future clinical application of CNP in human children.     

Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.     

Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients

BackgroundDisorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients.MethodsWe investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges.ResultsSubclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function.ConclusionDramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately.     

Reference percentiles for FEV1 and BMI in European children and adults with cystic fibrosis

ABSTRACT: BACKGROUND: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. METHODS: 34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI. RESULTS: FEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). CONCLUSION: The CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.     

Relationship between maximal expiratory flows and lung volumes in growing humans

We examined airway vs. lung parenchymal growth, as inferred from maximal expiratory flows (MEF) and lung volumes (V), respectively, to determine whether the interindividual variability of airway size (inferred from MEF) changes during lung growth and whether a young child with large (or small) airways for his parenchymal size (inferred from V) maintains relatively large (or small) airways for his lung size as he grows to adulthood. Serial measurements of MEF and V were obtained from a cohort of healthy 6- to 27-yr-old males (n = 26) and females (n = 21) over a period of 18 yr. Data were analyzed using logarithmic transformation of the power law equation, MEF = aVb, to fit a regression line to each subject's data points. These growth trajectories were satisfactorily modeled as parallel lines with 20-30% variability of their y-intercepts, indicating that substantial intersubject variability of MEF relative to V is present in early childhood and remains constant during growth. The results further indicate that MEF does track V during lung growth. We conclude that dysanapsis originates in early childhood.     

High Peripheral Blood Th17 Percent Associated with Poor Lung Function in Cystic Fibrosis

People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4⁺ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months–53 years old) and 78 healthy controls (2–61 years old) were analyzed for Th1 (IFN-γ⁺), Th2 (IL-4⁺), Th17 (IL-17⁺), Treg (FOXP3⁺), IL-10⁺ and TGF-β⁺ CD4⁺ cells. We observed higher proportions of Treg, IL-10⁺ and TGF-β⁺ CD4⁺ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-β⁺% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.     

Foot mechanics during the first six years of independent walking

Recognition of the changes during gait that occur normally as a part of growth is essential to prevent mislabeling those changes from adult gait as evidence of gait pathology. Currently, in the literature, the definition of a mature age for ankle joint dynamics is controversial (i.e., between 5 and 10 years). Moreover, the mature age of the metatarsophalangeal (MP) joint, which is essential for the functioning of the foot, has not been defined in the literature. Thus, the objective of the present study explored foot mechanics (ankle and MP joints) in young children to define a mature age of foot function. Forty-two healthy children between 1 and 6 years of age and eight adults were measured during gait. The ground reaction force (GRF), the MP and ankle joint angles, moments, powers, and 3D angles between the joint moment and the joint angular velocity vectors (3D angle α(M.ω)) were processed and compared between four age groups (2, 3.5, 5 and adults). Based on statistical analysis, the MP joint biomechanical parameters were similar between children (older than 2 years) and adults, hinting at a quick maturation of this joint mechanics. The ankle joint parameters and the GRFs (except for the frontal plane) showed an adult-like pattern in 5-year-old children. Some ankle joint parameters, such as the joint power and the 3D angle α(M.ω) still evolved significantly until 3.5 years. Based on these results, it would appear that foot maturation during gait is fully achieved at 5 years.     

Systemic Inflammation in Young Adults Is Associated with Abnormal Lung Function in Middle Age

Background

Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain.

Methodology/Principal Findings

We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV₁) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV₁ (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30–1.75) for fibrinogen and 1.35 (95% CI: 1.14–1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV₁. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08–2.16).

Conclusion/Significance

Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00005130","term_id":"NCT00005130"}}NCT00005130     

Low abundance of sweat duct Cl- channel CFTR in both healthy and cystic fibrosis athletes with exceptionally salty sweat during exercise

To understand potential mechanisms explaining interindividual variability observed in human sweat sodium concentration ([Na(+)]), we investigated the relationship among [Na(+)] of thermoregulatory sweat, plasma membrane expression of Na(+) and Cl(-) transport proteins in biopsied human eccrine sweat ducts, and basal levels of vasopressin (AVP) and aldosterone. Lower ductal luminal membrane expression of the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR) was observed in immunofluorescent staining of sweat glands from healthy young adults identified as exceptionally "salty sweaters" (SS) (n = 6, P < 0.05) and from patients with cystic fibrosis (CF) (n = 6, P < 0.005) compared with ducts from healthy young adults with "typical" sweat [Na(+)] (control, n = 6). Genetic testing of healthy subjects did not reveal any heterozygotes ("carriers") for any of the 39 most common disease-causing CFTR mutations in the United States. SS had higher baseline plasma [AVP] compared with control (P = 0.029). Immunostaining to investigate a potential relationship between higher plasma [AVP] (and sweat [Na(+)]) and ductal membrane aquaporin-5 revealed for all groups a relatively sparse and location-dependent ductal expression of the water channel with localization primarily to the secretory coil. Availability of CFTR for NaCl transport across the ductal membrane appears related to the significant physiological variability observed in sweat salt concentration in apparently healthy humans. At present, a heritable link between healthy salty sweaters and the most prevalent disease-causing CFTR mutations cannot be established.     

Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis

Inflammation plays a critical role in lung disease progression in cystic fibrosis (CF). This inflammatory process is dominated by a neutrophil influx in the airways. To determine whether the accumulation of neutrophils in the airways of CF patients is associated with an altered function, we analyzed the capacity of neutrophils isolated from the lung compartment and the blood to release the major neutrophil pro- and anti-inflammatory cytokines IL-8 and IL-1-receptor antagonist (ra) spontaneously and in the presence of LPS. Comparison of cytokine production by blood neutrophils from CF patients and from control subjects showed significantly increased IL-8 and decreased IL-1ra release by CF neutrophils. Comparison of cytokine production by airway and blood neutrophils from CF patients also documented distinct profiles: the spontaneous release of IL-8 and IL-1ra by airway neutrophils was significantly higher than that from blood neutrophils. Culture in the presence of LPS failed to further enhance cytokine production. Analysis of the effect of dexamethasone confirmed the difference in the responsiveness of lung and blood neutrophils in CF. Used at a concentration effective in reducing IL-8 production by blood neutrophils, dexamethasone (10(-6) M) was unable to repress secretion of IL-8 by airway neutrophils. In addition, comparison of cytokine production by airway neutrophils from children with CF and children with dyskinetic cilia syndrome also documented distinct profiles of secretion. These results are consistent with a dysregulated cytokine production by lung and blood neutrophils in CF. They provide support to the hypothesis that not only the CF genotype but also the local environment may modify the functional properties of the neutrophils.     

Model simulations of gas mixing and ventilation distribution in the human lung

A new lung model that incorporates intra-acinar diffusion- and convection-dependent inhomogeneities (DCDI) and interregional and intraregional convection-dependent inhomogeneities (CDI) is described. The model is divided into two regions, each containing two subunits. Each of the four subunits in the model consists of a multi-branch-point structure, based on the anatomic data from Haefeli-Bleuer and Weibel (Anat. Record 220: 401-414, 1988). The subunit turnover (TO), i.e., the ratio of subunit tidal to resting volume, and the flow sequences (FS) between the subunits are used as model parameters. The model simulates the normalized alveolar slope (Sn), Fowler and Bohr dead space (VDF and VDB), and alveolar mixing efficiency (AME) as a function of breath number (n) during a multiple-breath N2 washout (MBNW). For the first breath of the MBNW, these indexes are poorly sensitive to the TO distribution or FS between the subunits. However, as the washout proceeds, the n dependence of both Sn and VDB becomes markedly distinct for simulations with different TO and FS. VDF increases only slightly with n during the MBNW for a large range of TO and FS combinations, and AME is independent of FS. Comparison of published experimental observations with model simulations gave a consistent picture of ventilation maldistribution in the human lung. MBNW simulations in conditions of weightlessness, which will be performed shortly in Spacelab, suggest that it will be possible to evaluate quantitatively the intraregional elastic inhomogeneities in the human lung.     

Can glutamine and growth hormone promote protein anabolism in children with cystic fibrosis?

To determine whether recombinant human growth hormone (rhGH), glutamine (GLN) or a combination of both agents can enhance protein synthesis in cystic fibrosis (CF) patients, six 9.6 +/- 0.5-year-old prepubertal children (4 M, 2 F) with CF and stable lung disease with undernutrition (weight/height <50th percentile) or delayed growth (height <5th percentile) received stable isotope infusions, in the postabsorptive state and on 4 separate study days: (a) at baseline, and after a 4-week treatment with either, (b) oral GLN (0.7 g/kg/day), (c) rhGH (0.3 mg/kg/week, SC), or (d) both GLN and rhGH. Four-hour infusions of (13)C-leucine were used to assess leucine appearance rate (Ra, an index of protein breakdown), oxidation (Ox), and non-oxidative leucine disposal (NOLD, an index of protein synthesis). Results are expressed as changes (%) from baseline:We conclude that in children with CF: (1) due to high inter-subject variability, oral glutamine does not significantly enhance protein gain; (2) rhGH has significant anabolic effects which are mediated by stimulation of protein synthesis, and (3) glutamine does not enhance the effect of rhGH.     

Effect of Different Breathing Aids on Ventilation Distribution in Adults with Cystic Fibrosis

Background and objectives

We investigated the effect of different breathing aids on ventilation distribution in healthy adults and subjects with cystic fibrosis (CF).

Methods

In 11 healthy adults and 9 adults with CF electrical impedance tomography measurements were performed during spontaneous breathing, continuous positive airway pressure (CPAP) and positive expiratory pressure (PEP) therapy randomly applied in upright and lateral position. Spatial and temporal ventilation distribution was assessed.

Results

The proportion of ventilation directed to the dependent lung significantly increased in lateral position compared to upright in healthy and CF. This effect was enhanced with CPAP but neutralised with PEP, whereas the effect of PEP was larger in the healthy group. Temporal ventilation distribution showed exactly the opposite with homogenisation during CPAP and increased inhomogeneity with PEP.

Conclusions

PEP shows distinct differences to CPAP with respect to its impact on ventilation distribution in healthy adults and CF subjects EIT might be used to individualise respiratory physiotherapy.     

Evidence for a Cystic Fibrosis Enteropathy

BackgroundPrevious studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use.MethodsSixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts.ResultsSerum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use.ConclusionThis study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance.