Exhaled nitric oxide is not reduced in infants with cystic fibrosis (original) (raw)
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Lower exhaled nitric oxide in infants with Cystic Fibrosis compared to healthy controls
Journal of Cystic Fibrosis
Exhaled nitric oxide (FE NO) is a well-known, non-invasive airway biomarker. In patients with Cystic Fibrosis (CF) FE NO is decreased. To understand if reduced FE NO is primary related to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction or an epiphenomenon of chronic inflammation, we measured FE NO in 34 infants with CF prior to clinical symptoms and in 68 healthy controls. FE NO was lower in CF compared to controls (p = 0.0006) and the effect was more pronounced in CF infants without residual CFTR function (p b 0.0001). This suggests that FE NO is reduced in CF early in life, possibly associated with underlying CFTR dysfunction.
Alveolar, but not bronchial nitric oxide production is elevated in cystic fibrosis
Pediatric Pulmonology, 2007
Exhaled nitric oxide (NO) remains a promising non-invasive marker for measuring inflammation in lung diseases. In cystic fibrosis (CF), exhaled NO measured at a single expiratory flow has been found to be normal or low. However, this measure cannot localize the anatomical site of NO production. The aims of this study were to apply a multiple-flow NO analysis to compare alveolar NO concentration and bronchial NO flux in CF children with healthy controls. Twenty-two children with CF and 17 healthy controls had exhaled NO measured at four different expiratory flows to calculate bronchial NO flux and alveolar NO concentration. Median (range) alveolar NO concentration was 2.2 (0.6-5.6) ppb for children with CF and 1.5 (0.4-2.6) ppb for healthy controls. Median (range) bronchial NO flux was 445 (64-1,256) pL/sec for children with 913) pL/sec for healthy controls. Children with CF had a significantly higher alveolar NO concentration, but no significant difference in bronchial NO flux compared to healthy children. In conclusion, children with CF have increased alveolar NO production, but not bronchial NO flux compared to healthy controls. The distal airway is a major site of inflammation in CF, and measuring alveolar NO may be a marker of distal inflammation in this disease.
Extended Nitric Oxide Measurements in Exhaled Air of Cystic Fibrosis and Healthy Adults
Lung, 2009
In cystic fibrosis (CF) lung disease, exhaled nitric oxide (FeNO) is not raised, but rather is normal or even decreased when measured at a single expiratory flow. FeNO measurements at several flow rates allow differentiation between alveolar and bronchial nitric oxide (NO) production. Extended FeNO measurements therefore should be useful to localize the FeNO deficit in CF airways. FeNO was measured in stable CF adults with moderate lung disease and in healthy controls. Bronchial NO fluxes (J(NO,Br)) and alveolar NO concentrations (C(Alv)) were calculated from FeNO measurements at flow rates of 100, 150 and 200 ml/s using a method previously described. Thirty-two adults were included in the study, 12 of whom had CF. CF adults had significantly lower FeNO values at all flow rates. The median J(NO,Br) was significantly lower in CF adults than in healthy controls [0.31 nl/s (range = 0.11-0.63) vs. 0.70 nl/s (0.27-3.52); P < 0.001], while the median C(Alv) was similar in both groups [1.7 ppb (0.3-3.9) vs. 1.2 (0.1-5.2)]. Pulmonary NO exchange did not differ significantly between subgroups of CF patients with and without chronic Pseudomonas aeruginosa infection. No significant correlation was detectable between FEV(1)/VC and J(NO,Br) and C(Alv), respectively. Extended FeNO measurements can separate alveolar and bronchial NO outputs in CF adults. The lower FeNO in adults with moderate to severe CF lung disease is likely to be the result of lower bronchial NO output.
Exhaled nitric oxide in paediatric asthma and cystic fibrosis
Archives of Disease in Childhood, 1996
Nitric oxide (NO) is present in exhaled air ofhumans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be usefil in non-invasive diagnosis and monitoring of inflammatory airway diseases. (Arch Dis Child 1996;75:323-326)
Pediatric Allergy and Immunology, 2008
Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate (EBC) acidity, nitrite, nitrate, hydrogen peroxide (H2O2), 8-isoprostane, Th1/Th2 cytokines] to indicate (exacerbations of) CF; and (ii) the ability of these non-invasive IM to indicate CF disease severity. In 98 children (48 CF/50 controls), exhaled nitric oxide was measured using the NIOX, and condensate was collected using a glass condenser. In CF interferon (IFN-γ) and nitrite concentrations were significantly higher, whereas exhaled nitric oxide levels were significantly lower compared with controls (3.3 ± 0.3 pg/ml, 2.2 ± 0.2 μm, 10.0 ± 1.2 p.p.b. vs. 2.6 ± 0.2 pg/ml, 1.4 ± 0.1 μm, 15.4 ± 1.4 p.p.b. respectively). Using multivariate logistic regression models, the presence of CF was best indicated by 8-isoprostane, nitrite and IFN-γ [sensitivity 78%, specificity 83%; area under receiver operating characteristic curve (AUC) 0.906, p < 0.001]. An exacerbation of CF was best indicated by 8-isoprostane and nitrite (sensitivity 40%, specificity 97%, AUC curve 0.838, p = 0.009). Most indicative biomarkers of CF severity were exhaled nitric oxide, and condensate acidity (sensitivity 96%, specificity 67%; AUC curve 0.751, p = 0.008). In this cross-sectional study, the combination of different exhaled IM could indicate (exacerbations of) CF, and severity of the disease in children. Longitudinal data are necessary to further confirm the role of these markers for the management of CF in children.
Journal of Cystic Fibrosis, 2003
Background: Lack of standardisation for the measurement of exhaled nitric oxide (NO) (FE ) has resulted in conflicting data NO in cystic fibrosis (CF). The aim of this study was to assess whether FE is a useful non-invasive marker of lung disease in CF NO by assessing the effect of intravenous (IV) antibiotics on FE . Methods: FE was measured on line, according to recently NO NO published ERSyATS guidelines, using a chemiluminescence analyser together with pulmonary function in 14 CF children prior to and following a course of IV antibiotics. Results: There was a significant improvement in mean (S.E.M.) % FEV from 60.0 1 (6.3) to 68.0 (5.4) (P-0.05) and mean (S.E.M.) % FVC from 66.3 (5.5) to 75.1 (4.9) (P-0.01). FE increased significantly NO from median (range) 5.8 (2.0-14.3) to 9.2 ppb (0.8-25.1) (P-0.05). There was no correlation between FE and lung function. NO Subgroup analysis on those with chronic Pseudomonas aeruginosa infection (ns6) demonstrated no significant change in FE . NO Conclusions: Using a flow of 50 mlys, FE increases following admission for IV antibiotic treatment in children with CF but NO does not correlate with lung function. It is not a useful marker of lung diseases in CF, which has implications for clinical practice.
Journal of Comprehensive Pediatrics, 2019
Background: Exhaled nitric oxide (FeNO) in cystic fibrosis (CF) patients is reduced when compared with healthy people, and it has now been found that FeNO has a relative association with airway clearance index. Studies have shown the role of some infections in changing the FeNO level; however, the role of respiratory infections in FeNO has not yet been thoroughly studied. Objectives: The objective of this study was to investigate the possibility of FeNO usage to monitor the infections in CF patients. Methods: This cross-sectional case-control study was conducted on CF patients between the age of five to 18 with positive sputum culture, through simple non-random census method. FeNO levels were measured in 30 healthy children and 30 CF children with positive sputum culture. CF patients were treated by antibiotic therapy for two weeks; in the case offending negative sputum culture, the FeNO level was re-measured. FeNO levels were re-evaluated in 13 patients after four weeks. Results: There was no statistical difference between both groups in terms of age and weight. The level of FeNO in CF patients was significantly lower than in healthy children (22.1 ± 10.1 versus 30.0 ± 11.0 in the control group and P = 0.003). In 27 children, two weeks after administration of antibiotic therapy, sputum culture was negative. The mean of FeNO in these patients was 16.4 ± 5.5 at the time of the negative sputum culture, which was significantly lower than FeNO before starting the treatment. (P: 0.003). The mean FeNO was 13.0 ± 7.41 in 13 patients who were re-measured four weeks after starting the treatment. There was no significant difference between FeNO level two weeks after treatment and four weeks after starting treatment (P: 0.292). Patients with pseudomona sputum culture were not significantly different from those with non-pseudomona sputum culture in terms of primary FeNO and FeNO changes after the treatment (P value: 0.084 and 0.094, respectively). Conclusions: However, in our study, FeNO was decreased after administration of antibiotic treatment in CF patients, but according to the sample size and conflicting or similar results in other studies, currently, FeNO levels cannot be used as a way of monitoring the treatment of infection in CF patients.
Lung function in infants with cystic fibrosis
Thorax, 1988
Lung function was measured in 28 infants with cystic fibrosis and repeated in 17 of the infants during the first year of life. Thoracic gas volume (TGV) and specific airway conductance (sGaw) were measured plethysmographically and maximum forced expiratory flow at functional residual capacity (VmaxFRC) was derived from the partial expiratory flow-volume curve. At the time of the initial evaluation respiratory function was correlated with the clinical condition of the infants but not with age. There was a good correlation between sGaw and VmaxFRC when both were expressed as percentages of the predicted normal values. On the basis of the normal range for sGaw the infants were divided into two groups. Group A (n = 9), who had normal sGaw, were younger and had a lower clinical score and normal VmaxFRC and TGV values. Group B (n = 19), who had low sGaw, had increased TGV and decreased VmaxFRC. There was no correlation with age for any measure of lung function for the population as a whole. Repeat testing was undertaken at intervals in 17 representative infants. In most of these infants the relation between sGaw and VmaxFRC was maintained; there was no evidence that VmaxFRC was affected before sGaw. There was no functional evidence that the earliest changes in cystic fibrosis occur in small airways, as reflected by changes in VmaxFRC in infancy.
Nitric oxide metabolites in cystic fibrosis lung disease
Archives of Disease in Childhood, 1998
Although the activity of nitric oxide (NO) synthases are increased in lung tissue of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have recently been found to be decreased in cystic fibrosis. This could either be due to reduced NO formation or metabolism of NO within airway fluids. In this study, the stable NO metabolites, nitrate and nitrite, were determined in the saliva and sputum of 18 stable cystic fibrosis patients, 21 cystic fibrosis patients during a pulmonary exacerbation, and in saliva and endotracheal secretions of normal controls. Median saliva concentrations of NO metabolites (nitrate plus nitrite) were 704 µmol/l (95% confidence interval (CI) 419 to 1477) in stable cystic fibrosis patients, 629 µmol/l (95% CI 382 to 1392) in cystic fibrosis patients presenting with pulmonary exacerbation, and 313 µmol/l (95% CI 312 to 454) in controls. Median sputum NO metabolite concentration in stable cystic fibrosis was 346 µmol/l (95% CI 311 to 504). This was not significantly diVerent from cystic fibrosis patients presenting with pulmonary exacerbation (median 184 µmol/l, 95% CI 249 to 572), but significantly higher than in endotracheal secretions of controls (median 144 µmol/l, 95% CI 96 to 260). Sputum NO metabolite concentration in cystic fibrosis pulmonary exacerbation significantly increased during antibiotic treatment. A positive correlation was observed between sputum NO metabolites and lung function in stable cystic fibrosis, suggesting less airway NO formation in cystic fibrosis patients with more severe lung disease. These data indicate that decreased exhaled NO concentrations in cystic fibrosis patients may be due to retention and metabolism of NO within the airway secretions. However, sputum NO metabolites are not a useful marker of airway inflammation in cystic fibrosis lung disease.