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| 2. |
- Kalm-Stephens, Pia, 1959-, et al.
(författare)
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Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents
- 2020
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Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 55:3, s. 571-579
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Kalm-Stephens, Pia, 1959-
(författare)
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Development of allergic and respiratory symptoms in adolescence and early adulthood : Risk factors and gender differences
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma and allergic diseases have increased in prevalence for several decades and affect a substantial number of individuals in everyday life, as well as their families and public healthcare resources. Subjects with asthma report impaired self-rated health. Fractional exhaled nitric oxide (FeNO) is a marker of type 2 inflammation in the airways and higher levels may precede the development of allergic and respiratory disease.Aims: To investigate the development of allergic and respiratory symptoms in adolescence and early adulthood, and related baseline risk factors. Further, to study self-rated health in young adults with reported asthma.Methods: A total of 959 schoolchildren completed a standardized respiratory questionnaire and underwent lung function and FeNO measurements at baseline (12–15 years; early adolescence). Four (late adolescence) and sixteen (early adulthood) years later, 921 (96%) and 502 (52%) of these individuals completed a similar questionnaire. A total of 491 subjects participated in all three examinations. Nineteen clinically assessed non-asthmatic subjects with elevated FeNO and 28 control subjects with low FeNO and without symptoms of asthma or allergy in early adolescence were identified. Their FeNO, IgE sensitization, airway responsiveness, and inflammatory markers in blood and sputum were measured.Results: The main finding was that higher FeNO in early adolescence was associated with an increased risk of developing allergic symptoms to cat and dog, but not pollen allergens, during adolescence. Gender-stratified data showed that obesity at baseline in girls and an atopic constitution in boys were associated with increased risk of developing wheeze during adolescence. The prevalence of asthma and wheeze had increased in early adulthood, but the increase was significant only in females. Reduced lung function at baseline in females and higher FeNO in males were associated with an increased risk of incident asthma sixteen years later. The increase in allergic symptoms during this period was significant but without sex differences. Asthmatic females rated their health worse than non-asthmatic females, a difference not observed in males. Non-asthmatic adolescents with higher FeNO at baseline were to a higher extent sensitized, had more reactive airways, higher blood eosinophil counts, and lower systemic activation of neutrophils, compared with controls.Conclusions: It is important to detect risk factors for the development of allergic and respiratory diseases at an early stage to optimize health and wellbeing. Gender differences in respiratory development, associated risk factors, and treatment of respiratory symptoms must be taken into account.
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| 4. |
- Kalm-Stephens, Pia, 1959-, et al.
(författare)
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Different baseline characteristics are associated with incident wheeze in female and male adolescents
- 2020
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 109, s. 2324-2331
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Kalm-Stephens, Pia, 1959-, et al.
(författare)
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Incidence of asthma between adolescence and adulthood : early risk factors and gender differences
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Several studies have shown gender differences in the prevalence of asthma at various ages. The aim was to investigate the development of respiratory symptoms between adolescence and adulthood in relation to baseline risk factors and gender, and the effect on self-rated health. Methods: In the study Screening project asthma in schools, adolescents aged 12–15 years answered a standardised respiratory questionnaire (ISAAC) and underwent measurements of fractional exhaled nitric oxide (FeNO) and lung function (FEV1) at baseline. Two follow-ups with similar questionnaires were performed after four and 16 years, with 491 subjects participating in all three examinations. Results: The prevalence rates of asthma and wheeze were unchanged after four years, but had increased after 16 years; the increase was significant for females only. A more continuous increase in allergic symptoms showed no gender difference. The adjusted odds ratio [aOR (95% confidence interval)] for the development of asthma was 4.11 (1.27, 13.24) times higher in females with reduced FEV1 and 1.13 (1.06, 1.20) times higher in males with higher FeNO at baseline. Females, but not males, with asthma, rated their health as poor to a higher extent than individuals without asthma at the last follow-up, 20.0% vs. 7.7% (p < 0.01). Conclusions: An increased prevalence of respiratory symptoms was seen primarily between late adolescence and young adulthood, and was significant for females but not males. To optimise health and wellbeing, gender differences in asthma development, associated risk factors, and treatment of respiratory symptoms, must be considered.
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| 6. |
- Kalm-Stephens, Pia, 1959-, et al.
(författare)
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Sex differences in baseline risk factors for the incidence of asthma between early adolescence and young adulthood
- 2021
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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068 .- 1698-0808. ; 33:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several studies have shown sex differences in the prevalence of asthma and a relationship to age. The aim of the present study was to prospectively investigate the development of asthma, wheeze, rhinitis and allergic symptoms, between adolescence and adulthood. Furthermore, to determine if sex modifies the associations between baseline risk factors and incidence of asthma in early adulthood.METHODS: In the study Screening Project Asthma in Schools(SPAIS), adolescents aged 12-15 years answered a standardised respiratory questionnaire (ISAAC) and underwent measurements of fractional exhaled nitric oxide (FeNO) and lung function (FEV1) at baseline. Two follow-ups with similar questionnaires were performed after four and 16 years, with 491 subjects participating in all three examinations.RESULTS: The prevalence of asthma and wheeze were unchanged after four years, but had increased after 16 years. However, the increase was significant only for females. A more continuous increasein rhinitis and allergic symptoms showed no difference between the sexes. Sex interaction analysis showed that higher FeNO (p = 0.01) and family asthma (p = 0.02) increased the risk of incident asthma for males but not for females.CONCLUSION: An increased prevalence of respiratory symptoms was seen primarily between late adolescence and young adulthood, and was significant for females but not males. Allergic risk factors in early adolescence for incident asthma in early adulthood were confirmed in males but not in females. Awareness of these sex differences in the development of symptoms, and the associated risk factors, are important in clinical practice.
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| 7. |
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| 8. |
- Zetterquist, Wilhelm, et al.
(författare)
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Oral bacteria : the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis
- 2009
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 103:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Heijkenskjöld-Rentzhog, Charlotte, et al.
(författare)
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New method for single-breath fraction of exhaled nitric oxide measurement with improved feasibility in preschool children with asthma
- 2015
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 26:7, s. 662-667
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Janson, Christer, et al.
(författare)
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Risk factors associated with allergic and non-allergic asthma in adolescents
- 2007
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Ingår i: Clinical Respiratory Journal. - : Wiley. - 1752-6981 .- 1752-699X. ; 1:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 11. |
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| 12. |
- Kalm-Stephens, Pia, et al.
(författare)
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Elevated exhaled nitric oxide in adolescents is associated with incident allergic symptoms : a prospective cohort study
- 2019
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Ingår i: Journal of investigational allergology & clinical immunology. - : ESMON Publicidad. - 1018-9068 .- 1698-0808. ; 29:3, s. 231-238
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Tidskriftsartikel (refereegranskat)abstract
- Background: The fraction of exhaled nitric oxide (FeNO) is a marker of type-2 inflammation in the airways and elevated FeNO may precede development of allergic disease. The aim of the present study was to investigate the association between elevated FeNO and the development of allergic symptoms.Methods: A total of 959 adolescents from a general population answered, together with their parents, a standardized questionnaire, performed lung function and FeNO measurements at a baseline visit. Four years later, 921 of these subjects (96%) completed a to a great extent same version of the baseline questionnaire.Results: Adolescents with self-reported incident allergic symptoms to cat (n = 50) or dog (n = 33) had higher baseline FeNO (p < 0.001) than subjects without allergic symptoms to cat and dog at either time point (n = 776 and n = 838, respectively). Adolescents with incident allergic symptoms to pollen did not have elevated baseline FeNO. The adjusted odds ratio [aOR (95% confidence interval)] for incident allergic symptoms to cat was 4.2 (2.2, 8.0) times higher if FeNO was > 75th percentile (vs. < 75th percentile) at baseline. This was consistent after exclusion of subjects with reported asthma, wheeze or rhinitis at baseline [aOR (95% CI) 8.6 (3.0, 24.1)].Conclusion: Elevated FeNO in adolescents related to an increased risk of developing allergic symptoms to cat and dog, but not pollen allergens, within four years.
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| 13. |
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| 14. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Increased exhaled nitric oxide predicts new-onset rhinitis and persistent rhinitis in adolescents without allergic symptoms
- 2012
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 42:3, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: The fraction of nitric oxide in exhaled air (FENO) is increased in rhinitis and asthma. We have previously suggested that elevated FENO levels in the absence of asthma symptoms may be a sign of 'early asthma'. In the present study, we hypothesize that elevated exhaled NO levels may also precede rhinitis symptoms.Objective: To investigate in a cohort of adolescents whether or not increased exhaled NO levels at the age of 13-14 years predicted new-onset or persistent rhinitis within a 4-year period.Methods: A total of 959 randomly selected adolescents (13-14 years) completed a questionnaire on respiratory symptoms at baseline and follow-up, 4 years later. Exhaled NO was measured at baseline. After exclusion of subjects with asthma diagnosis or asthma symptoms at baseline, 657 participants were eligible for the present study.Results: Higher FENO levels at baseline were associated with increased risk for new-onset (P = 0.009) and persistent rhinitis (P = 0.03) within a 4-year period. The risk of new-onset rhinitis was 2.32 (1.23, 4.37) [OR (95% CI)] times higher if FENO > 90th percentile of the group without rhinitis at baseline. This increased risk for new-onset rhinitis was significant [2.49 (1.24, 5.01)] after excluding subjects with allergic symptoms. The risk of persistent rhinitis was 5.11 (1.34, 19.57) times higher if FENO > 90th percentile of the group without rhinitis at baseline.Conclusion: Elevated exhaled nitric oxide levels predicted incident and persistent rhinitis in this population-based study of adolescents. Moreover, these findings were consistent after excluding subjects with allergic symptoms. Thus, it appears that elevation of exhaled NO precedes airway symptoms and predicts development of rhinitis in subjects without allergic symptoms or family history of allergic disease.
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| 15. |
- Salomonsson, Maya, et al.
(författare)
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Circulating mast cell progenitors correlate with reduced lung function in allergic asthma
- 2019
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 49:6, s. 874-882
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundStudies 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.ObjectivesTo 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.MethodsBlood 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.ResultsAllergic 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.ConclusionElevated 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.
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