Onset of action of inhaled glucocorticoids on bronchial and alveolar nitric oxide output.

Fractional exhaled nitric oxide (FENO) is a marker of airway inflammation. Measuring FENO at multiple flow rates enables calculation of NO parameters: bronchial NO output (J awNO), bronchial wall (C awNO) and alveolar (C ANO) NO concentrations, and bronchial diffusion factor of NO (D awNO). FENO is known to rapidly reduce after the commencement of inhaled corticosteroid (ICS) treatment. However, little is known on the effect of ICS on the other NO parameters. We assessed (1) the onset of action of ICS treatment on the NO parameters and (2) whether the changes in bronchial NO output are due to changes in bronchial wall NO concentration or diffusion factor. FENO and other NO parameters were measured at baseline and after 1, 3 and 7 d of treatment with inhaled fluticasone propionate 250 µg b.i.d. in 23 allergic children with a history of asthma-like symptoms. There was a decrease in J awNO (from 680 (244/1791) (median (1st/3rd quartile)) to 357 (165/753) pl s-1, p < 0.001) and FENO50( from 13.8 (7.5/35) to 8.3 (5.36/17.0) ppb, p < 0.001) in 3 d from the first dose of ICS. Also, C awNO seemed to reduce after 3 d (from 171 (89/328) to 79 (54/157) ppb, p = 0.041), while D awNO remained unchanged. Furthermore, C ANO reduced during the 7 d treatment (from 3.0 (2.0/5.0) to 2.3 (1.9/2.6) ppb, p = 0.004). ICS treatment reduced FENO50 and J awNO rapidly and the decline was caused by decreased bronchial wall NO concentration while bronchial NO diffusion factor remained unchanged. These findings suggest that C awNO could be a more specific marker of airway inflammation and treatment response than J awNO or FENO50, which are both determined also by D awNO that seems to be resistant to the treatment with ICS.

Relation of bronchial and alveolar nitric oxide to exercise-induced bronchoconstriction in atopic children and adolescents.

BACKGROUND AND OBJECTIVE: Exercise challenge test is widely used in diagnostics and follow-up of childhood asthma, but the method is complex, time consuming, and expensive. In this study, we aimed to find out whether flow-independent nitric oxide (NO) parameters (bronchial NO flux [J'aw(NO)] and alveolar NO concentration [CA(NO)]) predict exercise-induced bronchoconstriction (EIB) in atopic children and adolescents with asthma-like symptoms. Also, the respective NO parameters corrected for axial backward diffusion (J'aw(NO) [TMAD] and CA(NO) [TMAD]) were calculated and included in the analysis. METHODS: Thirty patients (6-19 yr old) with confirmed atopy (positive skin prick tests or allergen-specific IgE) and asthma-like respiratory symptoms were included in the study. Before the current investigations, none of the patients had been diagnosed to have asthma and none were on inhaled corticosteroids. Exhaled NO was measured at multiple exhalation flow rates, and exercise challenge test was carried out. Bronchial NO flux and alveolar NO concentration were calculated according to the linear method with and without correction for axial backward diffusion. Sixty-six healthy school children served as controls. RESULTS: The patients were divided into two groups according to EIB. Patients with EIB (EIB+ group, n = 18) had enhanced bronchial NO output as compared to patients without EIB (EIB- group, n = 12); but the EIB- group did not differ from healthy controls. EIB+ group had also higher alveolar NO concentration than EIB- group and healthy controls, but EIB- group did not differ from healthy controls. When bronchial NO flux and alveolar NO concentration were corrected for axial diffusion, J'aw(NO) (TMAD) had equal difference as J'aw(NO) between the groups as expected. However, only EIB+ had higher CA(NO) (TMAD) than healthy controls, and the patient groups did not differ from each other. In patients, bronchial NO output correlated with the magnitude of exercise-induced change in PEF (r(s) = -0.388, p = 0.034), FEV(1) (r(s) = -0.395, p = 0.031), and FEF(50%) (r(s) = -0.431, p = 0.020), i.e., the higher the bronchial NO output, the larger the decrease in PEF/FEV(1) /FEF(50%) . Alveolar NO concentrations correlated with the change in FEV(1) (r(s) = -0.439, p = 0.015), FEF(50%) (r(s) = -0.454, p = 0.013), FEF(75%) (r(s) = -0.447, p = 0.017), and FVC (r(s) = -0.375, p = 0.045). For J'aw(NO) (TMAD), the correlations and p-values were equal to those of J'aw(NO) , but, interestingly, CA(NO) (TMAD) had no significant correlations with any of the exercise-induced changes in lung function. CONCLUSION: The results showed that in atopic children and adolescents, increased bronchial NO output as well as J'aw(NO) (TMAD) were associated with EIB, while alveolar NO concentration (but not CA(NO) [TMAD]) correlated with the degree of obstruction in smaller airways induced by exercise challenge.

Increased bronchial NO output in severe atopic eczema in children and adolescents.

Atopic children have an increased risk for asthma, which is preceded by bronchial inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess alveolar NO concentration and bronchial NO flux, which reflect inflammation in lung periphery and central airways, respectively. Exhaled breath condensate is another non-invasive method to measure lung inflammation. The purpose of the present study was to find out if the severity of atopic eczema is associated with lung inflammation that can be observed with these non-invasive tests. We studied 81 patients (7-22 yr old) with atopic eczema and increased wheat-specific IgE (>or=0.4 kUA/l) and no diagnosis of asthma. Exhaled NO was measured at multiple exhalation flow rates, and bronchial NO flux and alveolar NO concentration were calculated. Cysteinyl-leukotriene concentrations were measured in exhaled breath condensate. The patients were divided into two groups according to the severity of atopic eczema. Patients with severe atopic eczema had enhanced bronchial NO output as compared with patients with mild eczema (2.1 +/- 0.5 vs. 0.9 +/- 0.1, p = 0.003). No statistically significant differences in alveolar NO concentrations were found between the groups. In the whole group of patients, the bronchial NO output correlated positively with serum eosinophil protein X (r(s) = 0.450, p < 0.001), serum eosinophil cationic protein (r(s) = 0.393, p < 0.001), serum total IgE (r(s) = 0.268, p = 0.016) and with urine eosinophil protein X (r(s) = 0.279, p = 0.012), but not with lung function. Alveolar NO concentration correlated positively with serum eosinophil protein X (r(s) = 0.444, p < 0.001) and with serum eosinophil cationic protein (r(s) = 0.362, p = 0.001). Measurable cysteinyl-leukotriene concentrations in exhaled breath condensate were found only in one-third of the patients, and there were no differences between the two groups. The results show that increased bronchial NO output is associated with eosinophilic inflammation and severe atopic eczema in patients without established asthma.

No observed local immunological response at cell level after five years of oats in adult coeliac disease.

OBJECTIVE: Our earlier 5-year follow-up study produced the first evidence to show the long-term safety of oats as part of a coeliac diet. The objective of the present study was to clarify its applicability by analysing local cellular immunological responses after 5 years' consumption of oats by adult coeliac patients. MATERIAL AND METHODS: Forty-two coeliac patients took part in an earlier oats intervention study for 6-12 months. Twenty-two of these patients originally consumed oats as part of their gluten-free diet. During the 5-year follow-up 10 patients had felt uncertain about the safety of long-term consumption of oats and gave up this part of their diet. Finally, 12 of the 22 patients consumed oats for the whole 5-year period. The control group consisted of the remaining 20 coeliac patients using a strict, conventional, gluten-free diet without oats. Intraepithelial CD3, alphabetaTCR (alphabetaIEL) and gammadeltaTCR (gammadeltaIEL) T cells were counted after specific staining of small intestinal biopsy specimens. RESULTS: There were no differences in the densities of CD3, alphabetaIEL and gammadeltaIEL T cells between the oat and the control groups. CONCLUSIONS: Long-term use of oats included in the gluten-free diets of patients with coeliac disease does not stimulate an immunological response locally in the mucosa of the small intestine.

Alpha/beta intraepithelial lymphocytes, serum gliadin antibodies and allergy test positivity in children.

AIM: To determine whether the amount of alphabeta-positive intraepithelial lymphocytes (IELs) is connected to allergy test positivity in children with gastrointestinal symptoms and whether elevated serum gliadin antibodies have any role in the diagnosis. METHODS: Twenty-seven children suffering from gastrointestinal-symptoms in whom intestinal biopsies had previously been obtained via endoscopy or with capsule biopsy to exclude coeliac disease were included into the study. The other inclusion criteria were increased amounts of CD3 and alphabeta-positive IELs with normal amounts of gammadelta-positive IELs in duodenal or jejunal biopsy specimens. At the control visit, the children underwent a physical examination and parents filled in a questionnaire concerning gastrointestinal- and atopic symptoms. Skin prick- and patch tests were done and serum gliadin, endomysium, transglutaminase antibodies and specific IgEs were measured. RESULTS: Only nine children (33%) had at least one positive result in the allergy tests, the rest remaining test negative. In children with digestive symptoms, IgG-class gliadin antibody titres were higher than those of the non-symptomatic children. A significant correlation was found between IgG-class gliadin antibodies and total amount of alphabeta-positive IELs (p = 0.017). CONCLUSION: No positive skin test or specific IgE positivity for cereals in children with high intestinal T-cell densities was observed. The correlation between IgG-class gliadin antibodies and the total amount of alphabeta-TCR positive-cells is likely to be a reflection of local immune response of the gut.