ABSTRACT Inflammation in the small airways might contribute to incomplete asthma disease control ... more ABSTRACT Inflammation in the small airways might contribute to incomplete asthma disease control despite intensive treatment in some subgroups of patients. Exhaled NO (FeNO) is a marker of inflammation in asthma and the estimated NO contribution from small airways (CalvNO ) is believed to reflect distal inflammation. Recent studies recommend adjustments of CalvNO for trumpet model and axial diffusion (TMAD-adj). This study aimed to investigate the clinical correlates of CalvNO , both TMAD-adjusted and unadjusted.
The fraction of exhaled nitric oxide (FeNO) is an established marker of airway inflammation in as... more The fraction of exhaled nitric oxide (FeNO) is an established marker of airway inflammation in asthma. Nasal nitric oxide (nNO) has initially been regarded as a promising marker of inflammation of nasal mucosa. However, due to its dual origins, paranasal sinuses and nasal mucosa, the clinical use of nNO is controversial. There is an inflammatory link between inflammation in the upper and lower airways within the united airways' paradigm, but the study of the clinical value of nNO in asthma has been limited. The objective of this study is to analyse nNO in asthmatics and its relationship to FeNO, bronchial hyperresponsiveness, allergic sensitization and asthma control. A total of 371 children and young adults from an asthma cohort were included in this study, which performed measurements of nNO (through aspiration at 5 mL s(-1)), FeNO, bronchial responsiveness to methacholine, blood eosinophil count (B-Eos) and IgE sensitization. The asthma control test (ACT) and a questionnaire regarding medical treatment, symptoms of asthma, rhinitis and chronic rhinosinusitis were completed by all subjects. An association was found between higher nNO levels and increased bronchial responsiveness (p < 0.001), FeNO (p < 0.001) and B-Eos (p = 0.002). Sensitization to furry animals related to higher levels of nNO (p < 0.001). Subjects with poorly controlled asthma (ACT < 15) had lower levels of nNO than subjects with a higher ACT score (619 ± 278 ppb, versus 807 ± 274 ppb, p = 0.002). Loss of smell showed the strongest association with lower nNO levels among the upper airway symptoms recorded. In patients with asthma, nNO was positively correlated with exhaled NO, bronchial responsiveness and asthma control. This study suggests clinical utility of nNO in subjects with asthma, but in order to get better understanding of the nNO determinants, simultaneous mapping of upper airway comorbidities by clinical examination is appropriate.
Development of atopic disease was prospectively studied in 148 children from birth to the age of ... more Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (> = 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350 AU/l than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.
We recently reported an independent association between IgE sensitization to food allergens and i... more We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population-based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization. FeNO, airway responsiveness, blood eosinophil count (B-Eos) and IgE sensitization to food allergens and aeroallergens were determined in 408 subjects with asthma, aged 10-34 years. Asthmatics had higher prevalence of IgE sensitization against all allergens than controls (P < 0.001). Mite, pollen, furry animal, mould and food sensitizations were each associated with increased FeNO, airway responsiveness and B-Eos in asthmatics. IgE sensitization to mould, furry animals and food allergens was independently related to FeNO (all P < 0.05) after adjustment for age, sex, height, smoking history and medication. IgE sensitization to mould (P < 0.001) and furry animals (P = 0.02) was related to airway responsiveness in a similar model. Finally, IgE sensitization to mould (P = 0.001), furry animals (P < 0.001) and food allergens (P < 0.001) was independently related to B-Eos. Independent effects of IgE sensitization to aeroallergens (furry animals and mould) and food allergens were found on both local and systemic markers of inflammation in asthma. The finding regarding food IgE sensitization is novel, and a clinical implication might be that even food sensitization must be assessed to fully understand inflammation patterns in asthma.
Component-resolved allergy diagnostics enables the detection of crossreactive or species-specific... more Component-resolved allergy diagnostics enables the detection of crossreactive or species-specific allergen components. This study analysed Immunoglobulin E (IgE) profiles to single allergen components in relation to bronchial inflammation in severe childhood asthma. Ninety-five schoolchildren were assessed, 39 with controlled mild-to-moderate asthma and 56 uncontrolled severe asthmatics. Allergen components (n = 111) of food allergens, pollen and perennial aeroallergens were analysed using an immunosolid-phase allergen chip. Blood eosinophils (10(9) × l(-1)), bronchial inflammation (FeNO, ppb), lung function (FEV(1)%) and bronchial hyper-responsiveness (BHR) (dose-response slope of methacholine challenge) were measured. A specific IgE response to more than three animal-derived components--lipocalin (nMus m 1, rEqu c 1, Fel d 4, rCan f 1, 2), kallikrein (rCan f 5) and secretoglobin (rFel d 1)--was more common among severe asthmatics compared to children with controlled asthma (n = 14 vs n = 3, P = 0.030). These subjects also displayed higher blood eosinophils (0.65 vs 0.39, P = 0.021), higher Fractional exhaled nitric oxide (38 ppb vs 25 ppb, P = 0.021) and increased BHR (112 vs 28, P = 0.002) compared to other severe asthmatics positive to fewer lipocalin/kallikrein/secretoglobin components. Among all sensitized subjects, there were correlations between specific IgE levels for rFel d 4 and nMus m 1 (r = 0.751, P ≤ 0.001) and for rFel d 4 and rEqu c 1 (r = 0.850, P ≤ 0.001). Multi-sensitization towards lipocalin, kallikrein and secretoglobin components is associated with increased bronchial inflammation in severe asthmatics. In addition, crossreactive patterns were observed between different lipocalin components.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Jan 27, 2015
The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increase... more The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. The aim was to identify allergen components useful to diagnose sesame allergic children with the goal to reduce the number of OFCs needed. Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S) and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the be...
IgE-sensitization to hazelnut is common, especially in birch endemic areas. However, its clinical... more IgE-sensitization to hazelnut is common, especially in birch endemic areas. However, its clinical significance often needs to be confirmed by a food challenge. To evaluate the clinical significance of IgE-antibodies to hazelnut components and basophil allergen threshold sensitivity (CD-sens) to hazelnut, in relation to double-blind placebo-controlled food-challenge (DBPCFC) in children with a suspected hazelnut allergy. Forty children underwent a DBPCFC. CD-sens to hazelnut as well as IgE-antibodies to hazelnut and its components Cor a 1, Cor a 8, Cor a 9 and Cor a 14 were analyzed. Serum tryptase was measured before, during and after DBPCFC. Eight children had a positive DBPCFC and all of them had a high CD-sens value to hazelnut. Of the 32 children that passed the DBPCFC, 31 were very low or negative in CD-sens. A positive DBPCFC corresponded with significantly higher CD-sens values (median 8.9, range 3.3-281) compared to children negative in challenge (median 0.05, range 0-34.7, P < 0.0001). Children positive in challenge also had higher levels of IgE-ab to Cor a 9 and Cor a 14 (P < 0.01 and P < 0.001, respectively) compared with those with a negative challenge. In relation to the results from DBPCFC the sensitivity of CD-sens and IgE-ab to Cor a 14 was excellent (100%) and the specificity was very high (> 97% and >94%; respectively). Five of the eight patients positive at challenge showed an increase in tryptase >20% compared to tryptase base line levels. CD-sens and component resolved diagnostics to hazelnut, used separately or in combination may improve the diagnostic accuracy and safety and reduce over-diagnosis of hazelnut allergy. This article is protected by copyright. All rights reserved.
The marked rise in allergies during the past decade has been increasingly perceptible for school ... more The marked rise in allergies during the past decade has been increasingly perceptible for school personnel. A quarter of Swedish parents of children with allergies are unsatisfied with the school environment and how the schools are organized around their children. The Association of School Physicians has, together with six other medical, teaching and patient organizations, developed written guidelines for the management of asthma and allergies in Swedish schools. The aim was to regulate the responsibility of the school and its personnel for students with asthma and allergies, and to strengthen safety arrangements within schools. A secondary aim was to describe how the curriculum, teaching equipment, excursions, and other school activities, could be arranged appropriately and safely for students with asthma and allergies. Five-hundred copies of the document were circulated to all of Sweden's municipalities, county councils and pediatric departments. There was general agreement re...
The number of police reports on child assault shows an increasing trend during the last two decad... more The number of police reports on child assault shows an increasing trend during the last two decades in Sweden. The purpose of this article is to present possible explanations. Increased awareness of child abuse, legislative reforms, changes in attitudes toward corporal punishment and violence in general, and changed routines within schools can explain the increasing trend in police reporting. An actual increase in the rate of child abuse is possible but less likely. Reports of increasingly violent behavior among young people must be taken seriously.
ABSTRACT Inflammation in the small airways might contribute to incomplete asthma disease control ... more ABSTRACT Inflammation in the small airways might contribute to incomplete asthma disease control despite intensive treatment in some subgroups of patients. Exhaled NO (FeNO) is a marker of inflammation in asthma and the estimated NO contribution from small airways (CalvNO ) is believed to reflect distal inflammation. Recent studies recommend adjustments of CalvNO for trumpet model and axial diffusion (TMAD-adj). This study aimed to investigate the clinical correlates of CalvNO , both TMAD-adjusted and unadjusted.
The fraction of exhaled nitric oxide (FeNO) is an established marker of airway inflammation in as... more The fraction of exhaled nitric oxide (FeNO) is an established marker of airway inflammation in asthma. Nasal nitric oxide (nNO) has initially been regarded as a promising marker of inflammation of nasal mucosa. However, due to its dual origins, paranasal sinuses and nasal mucosa, the clinical use of nNO is controversial. There is an inflammatory link between inflammation in the upper and lower airways within the united airways' paradigm, but the study of the clinical value of nNO in asthma has been limited. The objective of this study is to analyse nNO in asthmatics and its relationship to FeNO, bronchial hyperresponsiveness, allergic sensitization and asthma control. A total of 371 children and young adults from an asthma cohort were included in this study, which performed measurements of nNO (through aspiration at 5 mL s(-1)), FeNO, bronchial responsiveness to methacholine, blood eosinophil count (B-Eos) and IgE sensitization. The asthma control test (ACT) and a questionnaire regarding medical treatment, symptoms of asthma, rhinitis and chronic rhinosinusitis were completed by all subjects. An association was found between higher nNO levels and increased bronchial responsiveness (p < 0.001), FeNO (p < 0.001) and B-Eos (p = 0.002). Sensitization to furry animals related to higher levels of nNO (p < 0.001). Subjects with poorly controlled asthma (ACT < 15) had lower levels of nNO than subjects with a higher ACT score (619 ± 278 ppb, versus 807 ± 274 ppb, p = 0.002). Loss of smell showed the strongest association with lower nNO levels among the upper airway symptoms recorded. In patients with asthma, nNO was positively correlated with exhaled NO, bronchial responsiveness and asthma control. This study suggests clinical utility of nNO in subjects with asthma, but in order to get better understanding of the nNO determinants, simultaneous mapping of upper airway comorbidities by clinical examination is appropriate.
Development of atopic disease was prospectively studied in 148 children from birth to the age of ... more Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (> = 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350 AU/l than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.
We recently reported an independent association between IgE sensitization to food allergens and i... more We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population-based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization. FeNO, airway responsiveness, blood eosinophil count (B-Eos) and IgE sensitization to food allergens and aeroallergens were determined in 408 subjects with asthma, aged 10-34 years. Asthmatics had higher prevalence of IgE sensitization against all allergens than controls (P < 0.001). Mite, pollen, furry animal, mould and food sensitizations were each associated with increased FeNO, airway responsiveness and B-Eos in asthmatics. IgE sensitization to mould, furry animals and food allergens was independently related to FeNO (all P < 0.05) after adjustment for age, sex, height, smoking history and medication. IgE sensitization to mould (P < 0.001) and furry animals (P = 0.02) was related to airway responsiveness in a similar model. Finally, IgE sensitization to mould (P = 0.001), furry animals (P < 0.001) and food allergens (P < 0.001) was independently related to B-Eos. Independent effects of IgE sensitization to aeroallergens (furry animals and mould) and food allergens were found on both local and systemic markers of inflammation in asthma. The finding regarding food IgE sensitization is novel, and a clinical implication might be that even food sensitization must be assessed to fully understand inflammation patterns in asthma.
Component-resolved allergy diagnostics enables the detection of crossreactive or species-specific... more Component-resolved allergy diagnostics enables the detection of crossreactive or species-specific allergen components. This study analysed Immunoglobulin E (IgE) profiles to single allergen components in relation to bronchial inflammation in severe childhood asthma. Ninety-five schoolchildren were assessed, 39 with controlled mild-to-moderate asthma and 56 uncontrolled severe asthmatics. Allergen components (n = 111) of food allergens, pollen and perennial aeroallergens were analysed using an immunosolid-phase allergen chip. Blood eosinophils (10(9) × l(-1)), bronchial inflammation (FeNO, ppb), lung function (FEV(1)%) and bronchial hyper-responsiveness (BHR) (dose-response slope of methacholine challenge) were measured. A specific IgE response to more than three animal-derived components--lipocalin (nMus m 1, rEqu c 1, Fel d 4, rCan f 1, 2), kallikrein (rCan f 5) and secretoglobin (rFel d 1)--was more common among severe asthmatics compared to children with controlled asthma (n = 14 vs n = 3, P = 0.030). These subjects also displayed higher blood eosinophils (0.65 vs 0.39, P = 0.021), higher Fractional exhaled nitric oxide (38 ppb vs 25 ppb, P = 0.021) and increased BHR (112 vs 28, P = 0.002) compared to other severe asthmatics positive to fewer lipocalin/kallikrein/secretoglobin components. Among all sensitized subjects, there were correlations between specific IgE levels for rFel d 4 and nMus m 1 (r = 0.751, P ≤ 0.001) and for rFel d 4 and rEqu c 1 (r = 0.850, P ≤ 0.001). Multi-sensitization towards lipocalin, kallikrein and secretoglobin components is associated with increased bronchial inflammation in severe asthmatics. In addition, crossreactive patterns were observed between different lipocalin components.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Jan 27, 2015
The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increase... more The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. The aim was to identify allergen components useful to diagnose sesame allergic children with the goal to reduce the number of OFCs needed. Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S) and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the be...
IgE-sensitization to hazelnut is common, especially in birch endemic areas. However, its clinical... more IgE-sensitization to hazelnut is common, especially in birch endemic areas. However, its clinical significance often needs to be confirmed by a food challenge. To evaluate the clinical significance of IgE-antibodies to hazelnut components and basophil allergen threshold sensitivity (CD-sens) to hazelnut, in relation to double-blind placebo-controlled food-challenge (DBPCFC) in children with a suspected hazelnut allergy. Forty children underwent a DBPCFC. CD-sens to hazelnut as well as IgE-antibodies to hazelnut and its components Cor a 1, Cor a 8, Cor a 9 and Cor a 14 were analyzed. Serum tryptase was measured before, during and after DBPCFC. Eight children had a positive DBPCFC and all of them had a high CD-sens value to hazelnut. Of the 32 children that passed the DBPCFC, 31 were very low or negative in CD-sens. A positive DBPCFC corresponded with significantly higher CD-sens values (median 8.9, range 3.3-281) compared to children negative in challenge (median 0.05, range 0-34.7, P < 0.0001). Children positive in challenge also had higher levels of IgE-ab to Cor a 9 and Cor a 14 (P < 0.01 and P < 0.001, respectively) compared with those with a negative challenge. In relation to the results from DBPCFC the sensitivity of CD-sens and IgE-ab to Cor a 14 was excellent (100%) and the specificity was very high (> 97% and >94%; respectively). Five of the eight patients positive at challenge showed an increase in tryptase >20% compared to tryptase base line levels. CD-sens and component resolved diagnostics to hazelnut, used separately or in combination may improve the diagnostic accuracy and safety and reduce over-diagnosis of hazelnut allergy. This article is protected by copyright. All rights reserved.
The marked rise in allergies during the past decade has been increasingly perceptible for school ... more The marked rise in allergies during the past decade has been increasingly perceptible for school personnel. A quarter of Swedish parents of children with allergies are unsatisfied with the school environment and how the schools are organized around their children. The Association of School Physicians has, together with six other medical, teaching and patient organizations, developed written guidelines for the management of asthma and allergies in Swedish schools. The aim was to regulate the responsibility of the school and its personnel for students with asthma and allergies, and to strengthen safety arrangements within schools. A secondary aim was to describe how the curriculum, teaching equipment, excursions, and other school activities, could be arranged appropriately and safely for students with asthma and allergies. Five-hundred copies of the document were circulated to all of Sweden's municipalities, county councils and pediatric departments. There was general agreement re...
The number of police reports on child assault shows an increasing trend during the last two decad... more The number of police reports on child assault shows an increasing trend during the last two decades in Sweden. The purpose of this article is to present possible explanations. Increased awareness of child abuse, legislative reforms, changes in attitudes toward corporal punishment and violence in general, and changed routines within schools can explain the increasing trend in police reporting. An actual increase in the rate of child abuse is possible but less likely. Reports of increasingly violent behavior among young people must be taken seriously.
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