Different baseline characteristics are associated with incident wheeze in female and male adolescents.

AIM: To investigate the independent relationships between baseline characteristics and incident wheeze in adolescents, with particular regard to gender. METHODS: Adolescents (N = 959), aged 12-15 years, answered a standardised respiratory questionnaire and underwent height and weight measurements at baseline. Four years later, 96% of the subjects completed a similar questionnaire. The present study included the adolescents without self-reported wheeze at baseline (n = 795; 394 girls). RESULTS: The proportion of adolescents with obesity was higher among subjects with incident wheeze than among subjects who never reported wheeze: 19.1% vs 8.3%. When stratifying for gender, this difference was only found in girls. In stepwise logistic regression models (odds ratios [95% confidence interval]), obesity (2.84 [1.17-6.86]) and rhinitis (3.04 [1.53-6.03]) at baseline and current smoking (2.60 [1.16-5.82]) at follow-up were associated with incident wheeze in girls. For boys, FEV1 <-1.65 standard deviation (3.20 [1.04-9.79]), family asthma (3.16 [1.46-6.86]) and seasonal allergic symptoms (5.61 [2.56-12.27]) at baseline were independently associated with incident wheeze. CONCLUSION: Data stratified by gender showed that obesity in girls and an atopic constitution in boys were independently associated with increased risk of developing wheeze within four years.

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents.

OBJECTIVES: The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with elevated fractional exhaled nitric oxide (FeNO), a marker of type-2 inflammation in the airways. METHODOLOGY: A total of 959 subjects from a general population, aged 12 to 15 years, answered a standardised questionnaire and underwent FeNO measurements at a screening visit at school. Adolescents without asthma, who had elevated FeNO (FeNO100 > 15 ppb) (n = 19), and control subjects, with low FeNO (FeNO100 < 5 ppb) and without reported symptoms of asthma or allergy (n = 28), participated in a follow-up study where FeNO50 , airway responsiveness to methacholine (PD20 ), blood eosinophil counts, and serum neutrophil lipocalin (HNL) and myeloperoxidase (MPO) levels were measured. Questionnaire follow-ups were performed 4 and 16 years later. RESULTS: Airway responsiveness (PD20 : 6.94 [1.87, 11.39] vs 11.42 [6.33, 59.4] µmol; P < .05) and blood eosinophil counts (0.31 [0.20, 0.44] vs 0.13 [0.1, 0.22] 109 /L; P < .001) (geometric mean [95% CI]) were higher among cases than controls. A significant correlation between blood eosinophils and FeNO was found (rho = 0.41; P = .005). In contrast, serum HNL and MPO were lower in cases than controls (P < .05 both), and there was a negative correlation between HNL and FeNO (r = -0.31; P = .04). At both follow-ups, a higher proportion of subjects reported allergic symptoms compared with baseline (P = .02, P = .01). CONCLUSIONS: Elevated FeNO in nonasthmatic adolescents was associated with airway hyperresponsiveness, elevated blood eosinophil counts, and lower systemic activation of neutrophils.

Circulating mast cell progenitors correlate with reduced lung function in allergic asthma.

BACKGROUND: Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to the lung during acute allergic airway inflammation. The discovery of a corresponding human mast cell progenitor population in the blood has enabled to study the relation of circulating mast cell progenitors in clinical settings. OBJECTIVES: To explore the possible association between the frequency of mast cell progenitors in the blood circulation and allergic asthma, we assessed the relation of this recently identified cell population with asthma outcomes and inflammatory mediators in allergic asthmatic patients and controls. METHODS: Blood samples were obtained, and spirometry was performed on 38 well-controlled allergic asthmatic patients and 29 controls. The frequency of blood mast cell progenitors, total serum IgE and 180 inflammation- and immune-related plasma proteins were quantified. RESULTS: Allergic asthmatic patients and controls had a similar mean frequency of blood mast cell progenitors, but the frequency was higher in allergic asthmatic patients with reduced FEV1 and PEF (% of predicted) as well as in women. The level of fibroblast growth factor 21 (FGF-21) correlated positively with the frequency of mast cell progenitors, independent of age and gender, and negatively with lung function. The expression of FcεRI on mast cell progenitors was higher in allergic asthmatic patients and correlated positively with the level of total IgE in the controls but not in the asthmatic patients. CONCLUSION: Elevated levels of circulating mast cell progenitors are related to reduced lung function, female gender and high levels of FGF-21 in young adults with allergic asthma.

New method for single-breath fraction of exhaled nitric oxide measurement with improved feasibility in preschool children with asthma.

BACKGROUND: Respiratory societies recommend use of standardized methodologies for fraction of exhaled nitric oxide (FeNO) measurements in adults and children, but in preschoolers, feasibility remains a problem. The exhalation time needed to obtain steady-state FeNO is unclear. Our primary aim was to study the feasibility of an adapted single-breath FeNO method with age-adjusted exhalation times. We also studied the association between time to steady-state NO level and height, as well as FeNO in relation to asthma and current treatment with inhaled corticosteroids (ICS). METHODS: Sixty-three children aged 3-10 years performed FeNO measurements with a hand-held electrochemical device with a newly developed flow-control unit. Exhalation times were pre-adapted to age. Exhaled air was simultaneously sampled to a chemiluminescence analyzer to measure time to steady-state NO level. RESULTS: Eighty-one percent of the children achieved at least one approved measurement. From 4 years upwards, success rate was high (96%). Time to steady-state [NO] (median and interquartile range) was 2.5 s (2.4-3.5) at the age of 3-4 years and 3.5 s (2.7-3.8) at the age of 5-6 years. Height was associated with time to steady state (r(2) = 0.13, p = 0.02). FeNO (geometric mean [95% CI]) was higher in ICS-naïve asthmatic children (n = 19): 15.9 p.p.b. (12.2-20.9), than in both healthy controls (n = 8) 9.1 p.p.b. (6.6-12.4) and asthmatic subjects on treatment (n = 24) 11.5 p.p.b. (9.7-13.6). CONCLUSION: We found this adapted single-breath method with age-adjusted exhalation times highly feasible for children aged 4-10 years. ICS-naïve asthmatic children had FeNO levels under the current guideline cutoff level (20 p.p.b.), highlighting the importance of taking age into account when setting reference values.

Hypersensitivity and the working environment for allergy nurses in sweden.

Background. Allergy nurses are exposed to allergens and respiratory irritants, and there are no national guidelines addressing personnel safety when working with these agents. Objective. To investigate the prevalence of allergies, asthma, and hypersensitivity symptoms among allergy nurses and the use of protective equipment and measures when working with allergen concentrates and respiratory irritants. Methods. A questionnaire survey was performed among the members of the Swedish Association of Allergy Nurses. Results. Diagnosed asthma was reported by 17%, while 18% had allergy to pets, 28% had allergy to pollens, and 26% reported nasal symptoms. Fifty-one percent reported a history of asthma, allergic diseases, or hypersensitivity symptoms in their family. Exhaust ventilation was used by 24% during skin prick tests, 17% during allergen specific immunotherapy, and 33% when performing methacholine challenge tests. Tightly closed containers for disposable waste were used by 58% during skin prick tests, by 60% during immunotherapy, and by 40% during Pc provocation tests. Conclusion. Allergy nurses had a tendency to increased prevalence of lower respiratory symptoms, asthma, and allergic rhinitis and more than half of the nurses had a family history of asthma, allergic diseases, or hypersensitivity symptoms. Additional studies are needed to evaluate the validity of these results.

The fraction of NO in exhaled air and estimates of alveolar NO in adolescents with asthma: methodological aspects.

RATIONALE: This study investigated the oral contribution to exhaled NO in young people with asthma and its potential effects on estimated alveolar NO (Calv(NO) ), a proposed marker of inflammation in peripheral airways. Secondary aims were to investigate the effects of various exhalation flow-rates and the feasibility of different proposed adjustments of (Calv(NO) ) for trumpet model and axial diffusion (TMAD). METHODS: Exhaled NO at flow rates of 50-300 ml/sec, and salivary nitrite was measured before and after antibacterial mouthwash in 29 healthy young people (10-20 years) and 29 with asthma (10-19 years). Calv(NO) was calculated using the slope-intercept model with and without TMAD adjustment. RESULTS: Exhaled NO at 50 ml/sec decreased significantly after mouthwash, to a similar degree in asthmatic and healthy subjects (8.8% vs. 9.8%, P = 0.49). The two groups had similar salivary nitrite levels (56.4 vs. 78.4 µM, P = 0.25). Calv(NO) was not significantly decreased by mouthwash. Calv(NO) levels were similar when flow-rates between 50-200 or 100-300 ml/sec were used (P = 0.34 in asthmatics and P = 0.90 in healthy subjects). A positive association was found between bronchial and alveolar NO in asthmatic subjects and this disappeared after the TMAD-adjustment. Negative TMAD-adjusted Calv(NO) values were found in a minority of the subjects. CONCLUSIONS: Young people with and without asthma have similar salivary nitrite levels and oral contributions to exhaled NO and therefore no antibacterial mouthwash is necessary in routine use. TMAD corrections of alveolar NO could be successfully applied in young people with asthma and yielded negative results only in a minority of subjects.

Oral bacteria--the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis.

BACKGROUND: Nitrite in exhaled breath condensate (EBC) has been shown to be elevated in cystic fibrosis (CF), while exhaled nitric oxide (FENO) is paradoxically low. This has been argued to reflect increased metabolism of NO while its diffusion is obstructed by mucus. However, we wanted to study the possible influence of salivary nitrite and bacterial nitrate reduction on these parameters in CF patients by the intervention of an anti-bacterial mouthwash. METHODS: EBC and saliva were collected from 15 CF patients (10-43 years) and 15 controls (9-44 years) before and 5 min after a 30s chlorhexidine mouthwash, in parallel with measurements of FENO. Nitrite and nitrate concentrations were measured fluorometrically. RESULTS: EBC nitrite, but not nitrate, was significantly higher in the CF patients (median 3.6 vs 1.3 microM in controls, p<0.05) and decreased after mouthwash in both groups (3.6-1.4 microM, p<0.01; 1.3-0.5 microM, p<0.01). Salivary nitrite correlated significantly to EBC nitrite (r=0.60, p<0.001) and decreased correspondingly after chlorhexidine, whereas salivary nitrate increased. FENO was lower in CF and the difference between patients and controls was accentuated after mouthwash (5.4 vs 8.4 ppb in controls, p<0.05). CONCLUSION: EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.

Risk factors associated with allergic and non-allergic asthma in adolescents.

INTRODUCTION: Risk factors for asthma have been investigated in a large number of studies in adults and children, with little progress in the primary and secondary prevention of asthma. The aim of this investigation was to investigate risk factors associated with allergic and non-allergic asthma in adolescents. METHODS: In this study, 959 schoolchildren (13-14 years old) answered a questionnaire and performed exhaled nitric oxide (NO) measurements. All children (n = 238) with reported asthma, asthma-related symptoms and/or increased NO levels were invited to a clinical follow-up which included a physician evaluation and skin-prick testing. RESULTS: Asthma was diagnosed in 96 adolescents, whereof half had allergic and half non-allergic asthma. Children with both allergic and non-allergic asthma had a significantly higher body mass index (BMI) (20.8 and 20.7 vs. 19.8 kg/m(2)) (p < 0.05) and a higher prevalence of parental asthma (30% and 32% vs. 16%) (p < 0.05). Early-life infection (otitis and croup) [adjusted odds ratio (OR) (95% confidence interval (CI)): 1.99 (1.02-3.88) and 2.80 (1.44-5.42), respectively], pets during the first year of life [2.17 (1.16-4.04)], window pane condensation [2.45 (1.11-5.40)] and unsatisfactory school cleaning [(2.50 (1.28-4.89)] was associated with non-allergic but not with allergic asthma. CONCLUSION: This study indicates the importance of distinguishing between subtypes of asthma when assessing the effect of different risk factors. While the risk of both allergic and non-allergic asthma increased with increasing BMI, associations between early-life and current environmental exposure were primarily found in relation to non-allergic asthma.

Exhaled nitric oxide levels in school children in relation to IgE sensitisation and window pane condensation.

BACKGROUND: A positive relation between exhaled nitric oxide (NO) levels and allergen exposure has been found in some studies whereas there is less information on how non-allergen environmental factors influences exhaled NO. OBJECTIVE: To study the relationship between exhaled NO levels in schoolchildren in relation to IgE sensitisation and allergenic and non-allergenic environmental factors. METHOD: This study comprised 374 schoolchildren (13-14 years of age) who performed exhaled NO-measurements and skin prick tests. Exposure to allergens, respiratory infections, environmental tobacco smoke and home window pane condensation, the latter an indicator of high humidity and poor ventilation was evaluated through questionnaires. RESULTS: In IgE-sensitised children sensitisation to pets was a more important determinant of exhaled NO than sensitisation to pollen. Higher NO levels were found in cat-sensitised children with a cat or other furred pets at home compared to cat-sensitised children without pets (geometric mean, 24.0 vs. 13.9 ppb, P=0.03). Significantly higher exhaled NO levels were found in non-sensitised children that reported having a cold (5.7 vs. 3.8 ppb, P<0.001) or lived in homes with window pane condensation (7.1 vs. 4.4 ppb, P=0.01) than in non-sensitised children without a cold and window pane condensation, respectively. These associations were not found in children that were sensitised to inhalation allergens. CONCLUSION: Allergen exposure seems to be the most important determinant for exhaled NO levels in IgE-sensitised children whereas in non-sensitised children NO levels were associated with respiratory infections and home window pane condensation.