Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis

Kroesbergen, A.; Bel, Elisabeth H.; Hop, Wim C. J.; Jongste, Johan C. de

doi:10.1034/j.1399-3003.1999.14d24.x

Cited by 32 publications

(22 citation statements)

References 13 publications

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“…Other inflammatory airway diseases such as asthma are associated with increased production of NO (5). Another report demonstrates that the inducible production of the cytokine RANTES is also reduced in CF epithelial cells (6).…”

Section: Introductionmentioning

confidence: 99%

In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic fibrosis epithelium

Kelley¹,

Elmer²

2000

J. Clin. Invest.

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Inducible nitric oxide synthase-2 (NOS2) expression has been shown to be reduced in cystic fibrosis (CF) epithelial cells. Reduced NOS2 expression is unexpected, given the inflammatory nature of CF airway disease, and is an indication that cell-signaling mechanisms necessary for proper NOS2 regulation are probably altered in CF epithelium. Therefore, we examined the expression levels of regulatory factors necessary for NOS2 expression in CF epithelium and showed that IFN regulatory factor-1 (IRF-1) is necessary for full NOS2 expression. Mice lacking IRF-1 expression have diminished epithelial NOS2 expression, as well as reduced NO-dependent chloride transport across the nasal epithelia. Furthermore, IRF-1 protein expression is reduced in nasal and intestinal epithelial cells from CF mice, suggesting a possible mechanism for the CF-related reduction of epithelial NOS2 expression. Active signal transducer and activator of transcription-1 (Stat1) is necessary for both NOS2 and IRF-1 expression. We found that protein levels of Stat1 were increased in CF cells, but that the active phosphorylated form of Stat1 was bound to the protein inhibitor of activated Stat1 (PIAS1). We propose that increased levels of PIAS1 diminish certain cell-signaling pathways, resulting in reduced IRF-1 and NOS2 expression in CF epithelial cells.

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Section: Introductionmentioning

confidence: 99%

In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic fibrosis epithelium

Kelley¹,

Elmer²

2000

J. Clin. Invest.

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“…, Rudolph Inc.) with an individually standardized flow rate of 20% of the subject's vital capacity per second, as described previously in detail [24,25]. A biofeedback display provided visual guidance for the subject to maintain the exhalation flow at the target level.…”

Section: Nitric Oxide Measurementmentioning

confidence: 99%

Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment

Jöbsis

Raatgeep²,

Schellekens³

et al. 2000

Eur Respir J

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Cystic fibrosis (CF) patients characteristically have severe chronic airway inflammation associated with bacterial infection. A noninvasive marker of airway inflammation could be a useful guide to treatment of CF lung disease. The aim of this study was to assess whether measurement of hydrogen peroxide (H2O2) and nitric oxide (NO) in exhaled air can serve to monitor the effect of treatment with antibiotics in CF‐children with acute infective pulmonary exacerbations. Sixteen CF‐patients (mean age 12.3 yrs) with exacerbation of their lung infection were treated with intravenous antibiotics in an uncontrolled study. During treatment, H2O2 in exhaled air condensate was measured twice a week. In addition, serial NO measurements were performed in nine patients. During antibiotic treatment the median H2O2 concentration in exhaled air condensate decreased significantly from 0.28 µM (range 0.07–1.20 µM) to 0.16 µM (range 0.05–0.24 µM, p=0.002) and the mean forced expiratory volume in one second significantly increased from 55% predicted to 75% pred (p=0.001). In individual subjects, changes of H2O2 and FEV1 between pairs of serial measurements correlated weakly (p=0.08). Data on exhaled NO were inconclusive; exhaled NO did not change systematically during treatment. It is concluded that cystic fibrosis patients with an acute pulmonary exacerbation have abnormally high concentrations of hydrogen peroxide, but not of nitric oxide, in exhaled air, which decrease during intravenous antibiotic treatment. Further controlled studies should establish if exhaled hydrogen peroxide, may serve as a noninvasive parameter of airway inflammation to guide antibiotic treatment in cystic fibrosis lung disease.

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“…Measurements were performed in accordance with international recommendations for on-line NO measurements previously described in the European Respiratory Society Task Force Report (4). The children exhaled at six targeted flow rates (10,20,50,100,200, and 500 mL/s). We used the Aerocrine NO system (Aerocrine AB, Stockholm, Sweden), including the CLD 77 AM chemiluminescence analyzer from Eco Physics AG for on-line NO measurements and monitoring of pressure.…”

Section: Subjectsmentioning

confidence: 99%

Evaluation of Exhaled Nitric Oxide in Schoolchildren at Different Exhalation Flow Rates

Pedroletti

2002

Pediatric Research

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Nitric oxide (NO) in exhaled air is believed to reflect allergic inflammation in the airways. Measured levels of exhaled NO vary with the exhaled flow rate, which therefore must be standardized. The aim of this study was to estimate the optimal exhalation flow rate when measuring NO in exhaled air. We studied 15 asthmatic children (8-18 y) with elevated NO levels and 15 age-matched controls and focused on how the quality of the NO curve profile, the discriminatory power, and the reproducibility were influenced by the exhalation flow rate. We used an on-line system for NO measurements at six different exhalation flow rates in the interval of 11-382 mL/s. The fraction of exhaled nitric oxide (FENO) was highly flow-dependent as was expected. Intermediate flow rates yielded a flat and stable NO plateau and were considerably easier to interpret than those obtained at the highest and lowest flow rates. The ratio of FENO between asthmatics and controls was lower at higher flow rates and a considerable overlap in NO values was demonstrated at all flow rates except 50 mL/s. The reproducibility was much lower at more extreme flow rates and was best at 50 mL/s. We conclude that a target exhalation flow rate of approximately 50 mL/s is to be preferred using the single-breath method for on-line NO measurements in schoolchildren. The presence of nitric oxide (NO) in exhaled air was first reported in 1991 (1) and soon after, it was discovered that asthmatics have higher levels of exhaled NO compared with controls (2, 3). These findings have evoked great interest because monitoring the fraction of expired NO (FENO) may be useful in the management of asthma (4), especially in children, for whom noninvasive methods are preferable (5).It has been shown that NO is mainly synthesized in the epithelial layer in the conducting airways (6 -8). This being the case, the concentration of NO in exhaled air will be highly dependent on exhalation flow rate (9 -11). Thus, there is a need to standardize the NO measurements, particular with respect to flow rate. However, previous (4) and current (12) recommendations on exhalation flow rate have not been based on experimental data, but are compromises based on practical/technical issues.We therefore investigated the quality of the exhaled NO curve profile, the reproducibility, and the discriminatory power of the NO values at six different exhalation flow rates in a sample of asthmatic schoolchildren with elevated levels of NO and age-matched controls. MATERIALS AND METHODS Subjects.Fifteen children (aged 8 -18, mean 14 y), three girls and twelve boys, with asthma and elevated NO levels (Ͼ10 ppb at exhalation flow rate 150 mL/s) were recruited from the Allergy clinic at Astrid Lindgren Children's Hospital, Karolinska Hospital.Thirteen of these children had atopic asthma and were sensitized to furred pets, pollen, or house dust mite. Atopy was evaluated by skin prick testing. Five subjects were steroidnaive. Mean dose of inhaled steroids was 305 g/d in steroidtreated patients. A brief structured i...

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Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis

Cited by 32 publications

References 13 publications

In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic fibrosis epithelium

In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic fibrosis epithelium

Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment

Evaluation of Exhaled Nitric Oxide in Schoolchildren at Different Exhalation Flow Rates

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