Publications by authors named "Anna S Pelkonen"

56 Publications

Overweight and exercise-induced bronchoconstriction - is there a link?

Pediatr Allergy Immunol 2021 Mar 8. Epub 2021 Mar 8.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The objective of this study was to evaluate the role of body mass index with regard to exercise performance, exercise-induced bronchoconstriction (EIB) and respiratory symptoms in 7-16-year-old children.

Methods: 1120 outdoor running exercise challenge test results of 7-16-year-old children were retrospectively reviewed. Lung function was evaluated with spirometry and exercise performance was assessed by calculating distance per 6 minutes from the running time and distance. Respiratory symptoms in the exercise challenge test were recorded and body mass index modified for children (ISO-BMI) was calculated for each child from height, weight, age, and gender according to the national growth references.

Results: Greater ISO-BMI and overweight were associated with poorer exercise performance (p<0.001). In addition, greater ISO-BMI was independently associated with cough (p=0.002) and shortness of breath (p=0.012) in the exercise challenge. However, there was no association between ISO-BMI and EIB or with wheeze during the exercise challenge.

Conclusion: Greater ISO-BMI may have a role in poorer exercise performance and appearance of respiratory symptoms during exercise, but not in EIB in 7-16-year-old children.
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http://dx.doi.org/10.1111/pai.13492DOI Listing
March 2021

Are Infants and Toddlers with Moderate-to-severe Atopic Dermatitis Undertreated? Experiences of a Finnish Tertiary Care Hospital.

Acta Derm Venereol 2021 Jan 5;101(1):adv00368. Epub 2021 Jan 5.

Department of Dermatology and Allergology, Helsinki University Hospital, FIN-00250 Helsinki, Finland.

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http://dx.doi.org/10.2340/00015555-3739DOI Listing
January 2021

Health-related quality of life in patients who had partaken in milk oral immunotherapy and comparison to the general population.

Allergy 2021 01 24;76(1):387-390. Epub 2020 Aug 24.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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http://dx.doi.org/10.1111/all.14525DOI Listing
January 2021

For hazelnut allergy, component testing of Cor a 9 and Cor a 14 is relevant also in birch-endemic areas.

Allergy 2020 11 26;75(11):2977-2980. Epub 2020 Jul 26.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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http://dx.doi.org/10.1111/all.14430DOI Listing
November 2020

Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze.

Clin Exp Allergy 2020 05 23;50(5):558-566. Epub 2020 Mar 23.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear.

Objective: To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing.

Methods: Inclusion criteria were as follows: full-term, 3-23 months of age; doctor -diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed.

Results: Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (P = .031).

Conclusions And Clinical Relevance: These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.
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http://dx.doi.org/10.1111/cea.13598DOI Listing
May 2020

Early bronchial inflammation and remodeling and airway hyperresponsiveness at school age.

Allergy 2020 07 11;75(7):1765-1768. Epub 2020 Feb 11.

Department of Allergy, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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http://dx.doi.org/10.1111/all.14198DOI Listing
July 2020

Serum chitinase-like protein YKL-40 is linked to small airway function in children with asthmatic symptoms.

Pediatr Allergy Immunol 2019 12 2;30(8):803-809. Epub 2019 Oct 2.

Department of Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Lung function impairment among asthmatic children begins in early life, and biomarkers for identifying this impairment are needed. The chitinase-like protein YKL-40 has been associated with asthma and lung function in adults, but studies in children have yielded conflicting results. We evaluated the potential of YKL-40 and other systemic biomarkers for identifying lung function deficits in children with asthmatic symptoms.

Methods: We determined the levels of serum YKL-40, periostin, and high-sensitivity C-reactive protein (hs-CRP) from the blood samples of 49 children with asthmatic symptoms. Lung function was assessed with impulse oscillometry (IOS) and spirometry, combined with an exercise challenge and a bronchodilator test. Fractional exhaled nitric oxide was measured at multiple flow rates.

Results: Serum levels of YKL-40 showed significant correlations with most IOS indices at baseline (P = .008-.039), but there was no association between YKL-40 and spirometry parameters. Neither periostin nor hs-CRP were associated with baseline lung function. Children with a significant response in either the exercise challenge or the bronchodilator test had increased serum levels of YKL-40 (P = .003) and periostin (P = .035). YKL-40 correlated significantly with the blood neutrophil count (r  = .397, P = .005) but was not associated with biomarkers of eosinophilic inflammation.

Conclusion: Serum YKL-40 is a potential biomarker for lung function deficits in children with asthmatic symptoms. These deficits appear to be focused on small airways and may remain undetected with spirometry.
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http://dx.doi.org/10.1111/pai.13119DOI Listing
December 2019

Young children with moderate-to-severe atopic dermatitis can be treated safely and effectively with either topical tacrolimus or mild corticosteroids.

Acta Paediatr 2020 03 7;109(3):550-556. Epub 2019 Oct 7.

University of Helsinki and Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland.

Aim: We collected evidence and safety data for topical tacrolimus in small children with atopic dermatitis (AD) and compared the usage with topical corticosteroid.

Methods: This was an interim analysis of 75 patients (55% female) at 1 year of an ongoing 3-year randomised open-label comparative follow-up study of topical tacrolimus vs corticosteroid treatment. One- to three-year-old children with moderate-to-severe eczema referred to the Skin and Allergy Hospital in Helsinki, Finland, were enrolled.

Results: Efficacy parameters, the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), transepidermal water loss (TEWL), eczema area, serum total immunoglobulin E (IgE) and the blood eosinophil count, showed improvement in both groups during the study. However, patients with signs of early sensitisation at baseline (elevated serum total IgE, elevated eosinophil count, positive prick tests or specific IgEs to aero or food allergens) had statistically significantly lower TEWL at the eczema site and a smaller eczema area at 12 months in the tacrolimus group. No severe adverse effects were seen during the treatment.

Conclusion: Children with AD and signs of early sensitisation appeared to benefit more from early tacrolimus than corticosteroid treatment. Small children may need stronger but nevertheless safe ointment options when treating moderate-to-severe AD.
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http://dx.doi.org/10.1111/apa.15001DOI Listing
March 2020

High-Dose Vitamin D Supplementation Does Not Prevent Allergic Sensitization of Infants.

J Pediatr 2019 06 20;209:139-145.e1. Epub 2019 Mar 20.

Helsinki University Hospital, Helsinki, Finland; Department of Allergy, University of Helsinki, Helsinki, Finland.

Objective: To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes.

Study Design: Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 μg (400 IU) or 30 μg (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated.

Results: We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 μg vitamin D compared with the 10 μg dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (≥100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39).

Conclusions: High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.
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http://dx.doi.org/10.1016/j.jpeds.2019.02.021DOI Listing
June 2019

Airway hyperresponsiveness in young children with respiratory symptoms: A five-year follow-up.

Ann Allergy Asthma Immunol 2019 May 2;122(5):492-497. Epub 2019 Mar 2.

Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland.

Background: Recurrent wheezing in early life is transient in most children. The significance of airway hyperresponsiveness (AHR) in persistence of respiratory symptoms from infancy to early childhood is controversial.

Objective: We evaluated whether AHR in wheezy infants predicts doctor-diagnosed asthma (DDA) or AHR at the age of 6 years.

Methods: Sixty-one wheezy infants (age 6-24 months) were followed up to the median age of 6 years. Lung function and AHR with methacholine challenge test were assessed at infancy and 6 years. The exercise challenge test was performed at the age of 6 years. Atopy was assessed with skin prick tests.

Results: At 6 years, 21 (34%) of the children had DDA. Children with DDA had higher logarithmic transformed dose-response slope (LOGDRS) to methacholine in infancy than children without DDA (0.047 vs 0.025; P = .033). Furthermore, AHR to methacholine in infancy and at 6 years were associated with each other (r = 0.324, P = .011). Children with exercise-induced bronchoconstriction (EIB) at 6 years were more reactive to methacholine in infancy than those without EIB (P = .019).

Conclusion: Increased AHR in symptomatic infants was associated with increased AHR, DDA, and EIB at median the age of 6 years, suggesting early establishment of AHR.
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http://dx.doi.org/10.1016/j.anai.2019.02.025DOI Listing
May 2019

Outcome of oral immunotherapy for persistent cow's milk allergy from 11 years of experience in Finland.

Pediatr Allergy Immunol 2019 05 18;30(3):356-362. Epub 2019 Feb 18.

Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland.

Background: The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow's milk allergy (CMA) were evaluated in an open-label, non-randomized study.

Methods: During the 11-year study, 296 children aged 5 years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data were collected at three time points: the post-buildup phase, 1 year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk-specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high-dose group consumed ≥2 dL of milk daily, while the failure group consumed <2 dL of milk or were on a milk-avoidance diet.

Results: Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed ≥2 dL of milk daily. The median follow-up time was 6.5 years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P < 0.001). Respiratory symptoms in the post-buildup phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P = 0.003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P = 0.01).

Conclusion: More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT.
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http://dx.doi.org/10.1111/pai.13025DOI Listing
May 2019

Small airway function in children with mild to moderate asthmatic symptoms.

Ann Allergy Asthma Immunol 2018 10 27;121(4):451-457. Epub 2018 Jul 27.

Pediatric Unit, Department of Allergy, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Clinical significance of small airway obstruction in mild pediatric asthma is unclear.

Objective: To evaluate small airway properties in children with mild to moderate asthmatic symptoms and the association of small airway function with asthma control and exercise-induced bronchoconstriction (EIB).

Methods: Children (5-10 years old) with recurrent wheezing (n = 42) or persistent troublesome cough (n = 16) and healthy controls (n = 19) performed impulse oscillometry (IOS), spirometry, and a multiple-breath nitrogen washout (MBNW) test. Exhaled nitric oxide (NO) was measured at multiple flow rates to determine alveolar NO concentration (Calv). Asthma control was evaluated with the Childhood Asthma Control Test (C-ACT), short-acting β-agonist (SABA) use within the past month, and asthma exacerbations within the past year.

Results: IOS, spirometry, and exhaled NO indexes that are related to small airway function differed between children with recurrent wheezing and healthy controls, whereas only forced expiratory flow at 25% to 75% of the forced vital capacity was associated with persistent cough. The MBNW indexes showed no difference between the groups. Among symptomatic children, conducting airway ventilation inhomogeneity and Calv were associated with asthma exacerbations (P = .03 and P = .002, respectively), and lung clearance index and Calv were associated with EIB (P = .04 and P = .004, respectively). None of the proposed small airway indexes was associated with the C-ACT score or SABA use.

Conclusion: Subtle changes were observed in the proposed small airway indexes of IOS, spirometry, and exhaled NO among children with mild to moderate recurrent wheezing. Small airway dysfunction, expressed as ventilation inhomogeneity indexes and Calv, was also associated with asthma exacerbations and EIB.
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http://dx.doi.org/10.1016/j.anai.2018.07.026DOI Listing
October 2018

Nocturnal Heart Rate Variability Spectrum Characterization in Preschool Children With Asthmatic Symptoms.

IEEE J Biomed Health Inform 2018 09 17;22(5):1332-1340. Epub 2017 Nov 17.

Asthma is a chronic lung disease that usually develops during childhood. Despite that symptoms can almost be controlled with medication, early diagnosis is desirable in order to reduce permanent airway obstruction risk. It has been suggested that abnormal parasympathetic nervous system (PSNS) activity might be closely related with the pathogenesis of asthma, and that this PSNS activity could be reflected in cardiac vagal control. In this work, an index to characterize the spectral distribution of the high frequency (HF) component of heart rate variability (HRV), named peakness ($\wp$), is proposed. Three different implementations of $\wp$, based on electrocardiogram (ECG) recordings, impedance pneumography (IP) recordings and a combination of both, were employed in the characterization of a group of preschool children classified attending to their risk of developing asthma. Peakier components were observed in the HF band of those children classified as high-risk ( $p < 0.005$), who also presented reduced sympathvoagal balance. Results suggest that high-risk of developing asthma might be related with a lack of adaptability of PSNS.
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http://dx.doi.org/10.1109/JBHI.2017.2775059DOI Listing
September 2018

Abnormal lung function at preschool age asthma in adolescence?

Ann Allergy Asthma Immunol 2018 05 6;120(5):520-526. Epub 2018 Mar 6.

Department of Allergology, Skin and Allergy Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.

Background: Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate.

Objective: This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence.

Methods: Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests.

Results: Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage.

Conclusion: Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence.
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http://dx.doi.org/10.1016/j.anai.2018.03.002DOI Listing
May 2018

Wheat oral immunotherapy was moderately successful but was associated with very frequent adverse events in children aged 6-18 years.

Acta Paediatr 2018 05 6;107(5):861-870. Epub 2018 Feb 6.

Department of Allergy, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.

Aim: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies.

Methods: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units.

Results: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions.

Conclusion: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy.
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http://dx.doi.org/10.1111/apa.14226DOI Listing
May 2018

Small airway oscillometry indices: Repeatability and bronchodilator responsiveness in young children.

Pediatr Pulmonol 2017 10 18;52(10):1260-1267. Epub 2017 Aug 18.

Pediatric Unit of the Department of Allergy, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: The impulse oscillometry (IOS) indices absolute and relative difference between respiratory resistance at 5 and 20 Hz (R5-20 and R5-20%, respectively) and the area under the reactance curve (AX) are postulated to reflect small airway function. Data on their cutoff values to evaluate bronchodilator responsiveness (BDR) or between-visit changes after interventions are limited in young children.

Methods: We evaluated the BDR of 103 healthy children aged 2-7 years, who received either salbutamol (n = 84) or placebo (n = 19) in order to determine cutoff values for BDR of R5-20, R5-20%, and AX. We then determined the repeatability within and between two IOS measurements 7-14 days apart in young children aged 4-8 years with asthmatic symptoms (n = 43), including cutoff values for significant between-visit changes.

Results: The investigated IOS parameters showed marked BDR (fifth percentile cutoff of 75-110% of the baseline value) in healthy children, whereas no significant changes were seen after inhalation of placebo. The agreement within the triplicate IOS measurement was excellent (ICC > 0.80), and the agreement of results between visits was good (ICC > 0.60). A change in R5-20, R5-20%, and AX of 0.65, 1.08, and 0.84 z-scores, respectively, would exceed 95% confidence intervals for between-visit variability.

Conclusion: We introduce cutoff values for BDR of R5-20, R5-20%, and AX, and their repeatability indices and cutoff limits for significant between-visit changes. These IOS parameters may show greater variability than the conventional IOS indices during follow-up, but the between-visit agreement remains good, providing potentially useful endpoints for monitoring lung function in young children.
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http://dx.doi.org/10.1002/ppul.23794DOI Listing
October 2017

Vitamin D, high-sensitivity C-reactive protein, and airway hyperresponsiveness in infants with recurrent respiratory symptoms.

Ann Allergy Asthma Immunol 2017 09 28;119(3):227-231. Epub 2017 Jul 28.

Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Background: Vitamin D insufficiency might be associated with biased T-cell responses resulting in inflammatory conditions such as atopy and asthma. Little is known about the role of vitamin D in low-grade systemic inflammation and airway hyperresponsiveness (AHR) in young children.

Objective: To evaluate whether vitamin D insufficiency and increased serum high-sensitivity C-reactive protein (hs-CRP) are linked to AHR in symptomatic infants.

Methods: Seventy-nine infants with recurrent or persistent lower respiratory tract symptoms underwent comprehensive lung function testing and a bronchial methacholine challenge test. In addition, skin prick tests were performed and serum 25-hydroxyvitamin D (S-25-OHD), hs-CRP, total immunoglobulin E, and blood eosinophil levels were determined.

Results: S-25-OHD was lowest in infants with blood eosinophilia and AHR (n = 10) compared with those with eosinophilia only (n = 6) or AHR only (n = 50) or those with neither (n = 13; P = .035). Moreover, vitamin D insufficiency (S-25-OHD <50 nmol/L) was most common in infants with blood eosinophilia and AHR (P = .041). Serum hs-CRP was lower in infants with recurrent physician-diagnosed wheezing (P = .048) and in those with blood eosinophilia (P = .015) than in infants without these characteristics and was not associated with S-25-OHD or AHR. S-25-OHD levels were significantly lower (median 54 nmol/L) during the autumn-winter season than in the spring-summer season (median 63 nmol/L; P = .026).

Conclusion: Vitamin D insufficiency could underlie eosinophilia and AHR in infants with troublesome lung symptoms, whereas hs-CRP-mediated low-grade systemic inflammation is rare in early childhood wheezing.
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http://dx.doi.org/10.1016/j.anai.2017.06.014DOI Listing
September 2017

Measurement of tidal breathing flows in infants using impedance pneumography.

Eur Respir J 2017 02 15;49(2). Epub 2017 Feb 15.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Tidal breathing flow volume (TBFV) profiles have been used to characterise altered lung function. Impedance pneumography (IP) is a novel option for assessing TBFV curves noninvasively. The aim of this study was to extend the application of IP for infants and to estimate the agreement between IP and direct pneumotachograph (PNT) measurements in assessing tidal airflow and flow-derived indices.Tidal flow profiles were recorded for 1 min simultaneously with PNT and uncalibrated IP at baseline in 44 symptomatic infants, and after methacholine-induced bronchoconstriction in a subgroup (n=20).The agreement expressed as the mean deviation from linearity ranged between 3.9 and 4.3% of tidal peak inspiratory flow, but was associated with specific airway conductance (p=0.002) and maximal flow at functional residual capacity () (p=0.004) at baseline. Acute bronchoconstriction induced by methacholine did not significantly affect the agreement of IP with PNT. TBFV indices derived from IP were slightly underestimated compared to PNT, but were equally well repeatable and associated with baseline (p=0.012 and p=0.013, respectively).TBFV profiles were consistent between IP and PNT in most infants, but the agreement was affected by reduced lung function. TBFV parameters were not interchangeable between IP and PNT, but had a similar association with lung function in infants.
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http://dx.doi.org/10.1183/13993003.00926-2016DOI Listing
February 2017

Sensitivity of newly defined impulse oscillometry indices in preschool children.

Pediatr Pulmonol 2017 05 13;52(5):598-605. Epub 2016 Oct 13.

Pediatric Unit of the Department of Allergology, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: Early origins of chronic obstructive pulmonary disease have been recognized. Impulse oscillometry (IOS) is suitable for assessment of lung function also in preschool children, and some novel indices have been connected to assessment of small airway function. However, limited data exist on the sensitivity of these new indices to detect lung function deficits in young symptomatic children.

Methods: IOS measurements of 103 healthy preschool children were evaluated to establish reference equations for the difference between respiratory resistance at 5 and 20 Hz (R5-20), the relative difference of R5-20 (R5-20%), and area under the reactance curve (AX). Thereafter, IOS results of children with late-onset troublesome lung symptoms (n = 20), a history of early wheeze (n = 37), or a history of bronchopulmonary dysplasia (BPD, n = 8) were compared to healthy children.

Results: None of the patient groups differed from healthy regarding respiratory resistance at 5 Hz (R5), and only children with a history of BPD differed from healthy regarding respiratory reactance at 5 Hz (X5). In contrast, z-scores of R5-20, R5-20%, and AX were significantly higher in all patient groups than in healthy children (P < 0.001), showing improved sensitivity (20-55%) compared to R5 and X5 (5-6%).

Conclusion: R5-20, R5-20%, and AX are superior to conventional IOS parameters in distinguishing children with current or past lower respiratory tract symptoms from healthy, and may prove valuable for screening early lung function deficits. Pediatr Pulmonol. 2017;52:598-605. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23627DOI Listing
May 2017

Serum soluble TH cell activity markers and high-sensitivity C-reactive protein in multiple-trigger wheezers.

Ann Allergy Asthma Immunol 2016 08 10;117(2):196-8. Epub 2016 Jun 10.

Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.anai.2016.05.022DOI Listing
August 2016

Tidal flow variability measured by impedance pneumography relates to childhood asthma risk.

Eur Respir J 2016 06 17;47(6):1687-96. Epub 2016 Mar 17.

Dept of Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Lung function variability is a fundamental feature of asthma but has been difficult to quantify in children due to methodological limitations. We assessed the feasibility and clinical implications of overnight flow variability measurement at home using impedance pneumography in young children.44 children aged 3-7 years with recurrent or persistent lower airway symptoms were recruited. Patients were divided into high- or lower-risk groups (HR and LR groups) based on their risk of asthma (modified Asthma Predictive Index), and a third group was formed of children who had a history of wheeze and who were treated with inhaled corticosteroids (ICS group). Tidal volume and the derived flow were recorded through skin electrodes using impedance pneumography at home during sleep. Quantities describing overnight change in expiratory flow-volume minimum curve shape correlation (CSRmin) and respiratory chaoticity (minimum noise limit (NLmin)) were derived.Recordings were successful in 34 children. CSRmin differed between the HR and LR groups (p=0.002) and between the HR and ICS groups (p=0.003), indicating a stronger change in flow profile shape in the HR group. NLmin differed between the HR and LR groups (p=0.014), indicating momentarily lowered chaoticity in the HR group.Impedance pneumography was found feasible for quantifying nocturnal lung function variability and the measured variability was associated with risk of asthma in young children.
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http://dx.doi.org/10.1183/13993003.00989-2015DOI Listing
June 2016

Aberrant small airways function relates to asthma severity in young children.

Respir Med 2016 Feb 19;111:16-20. Epub 2015 Dec 19.

Department of Allergology, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.

Background: Frequency dependence of resistance (R5-20) assessed by impulse oscillometry (IOS) is suggested to be a measure of small airways. Small airways involvement during induced bronchoconstriction has been shown to reflect severity of asthma in adults.

Objective: Our aim was to evaluate if methacholine (Mch) induced changes in R5-20 are associated with the severity of exercise induced bronchoconstriction (EIB) in young children.

Methods: A total of 109 children aged 3-8 years were studied, 95 with obstructive symptoms and 14 in good health, to assess small airways function during a Mch challenge. R5-20 and other IOS resistance and reactance parameters were measured at baseline and after the Mch challenge. In a standardized exercise test, the children were grouped according to the severity of EIB expressed as the percentage increase in resistance at 5 Hz (ΔR5) after exercise, indicating either no EIB (ΔR5 < 40%, n = 84), moderate EIB (ΔR5 40-80%, n = 13) and severe EIB (ΔR5 > 80%, n = 12).

Results: The baseline R5-20 was not associated with the severity of EIB, but during Mch induced bronchoconstriction the change in R5-20 was significantly higher in children with severe EIB (2.61 fold increase) than in children with moderate EIB (1.48) or no EIB (1.74, p = 0.036). No significant associations were found in changes of other IOS parameters. The children with severe EIB also used more short-acting beta-agonists during the past two months than the other two groups (p < 0.001).

Conclusion: Frequency dependence of resistance (R5-20) measured by IOS during the Mch induced bronchoconstriction and more frequent use of beta-agonists are associated with severe EIB in young children.
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http://dx.doi.org/10.1016/j.rmed.2015.12.006DOI Listing
February 2016

Preschool oscillometry and lung function at adolescence in asthmatic children.

Pediatr Pulmonol 2015 Dec 30;50(12):1205-13. Epub 2015 Mar 30.

Pediatric Unit of the Department of Allergology, Skin and Allergy Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Introduction: Reduced lung function in early childhood is associated with persistent symptoms and low lung function later in life. Impulse oscillometry (IOS) is feasible for assessing lung function also in preschool children, and some of the parameters, such as respiratory resistance at 5 Hz (Rrs5) and the frequency dependence of resistance (dRrs/df), have been suggested to reflect small airway dysfunction. Whether changes in preschool IOS predict later lung function remains unknown.

Methods: The medical data of 154 asthmatic children with IOS performed at 2-7 years and spirometry at 12-18 years were analyzed. IOS and post-bronchodilator spirometry parameters were compared, and the association was estimated in a multivariate model.

Results: Measured at preschool age, particularly Rrs5 and dRrs/df were significantly correlated with post-bronchodilator forced expiratory volume in 1 sec (FEV1) at adolescence (Rrs5: r = -0.223, P = 0.005; dRrs/df: r = 0.234, P = 0.004). Although the number of children with decreased FEV1 was low, associations of increased Rrs5 (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.7; 20.9) and decreased dRrs/df (OR 8.2, 95% CI 1.7; 39.6) with decreased FEV1 remained significant in multivariate analyses. Similar findings were observed also with other spirometric parameters.

Conclusion: In asthmatic children, preschool IOS is associated with spirometric lung function at adolescence, but the scatter is wide. Normal preschool IOS seems to indicate favourable lung function outcome, whereas in some individuals IOS could potentially be of clinical use, at a younger age than spirometry, to screen lung function deficits and increased risk for later lung function impairment.
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http://dx.doi.org/10.1002/ppul.23188DOI Listing
December 2015

Improvement in lung function is associated with a decrease in serum soluble CD30 in atopic infants.

Ann Allergy Asthma Immunol 2015 Feb 6;114(2):156-7. Epub 2014 Dec 6.

Pediatric Unit, Department of Allergology, Helsinki University Central Hospital, Helsinki, Finland; Department of Allergy, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.anai.2014.11.011DOI Listing
February 2015

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years.

Ann Allergy Asthma Immunol 2015 Feb 25;114(2):90-6. Epub 2014 Oct 25.

Department of Allergy, Helsinki University Central Hospital, Helsinki, Finland.

Background: Associations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear.

Objective: To report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes.

Methods: Fifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children.

Results: Forty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age.

Conclusion: The lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.
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http://dx.doi.org/10.1016/j.anai.2014.09.019DOI Listing
February 2015

Assessing direct and indirect airway hyperresponsiveness in children using impulse oscillometry.

Ann Allergy Asthma Immunol 2014 Aug 2;113(2):166-72. Epub 2014 Jun 2.

Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.

Background: Airway hyperresponsiveness (AHR) is a hallmark of asthma but its assessment is usually restricted to older children who are capable of performing the maneuvers involved in spirometry. In younger children, a feasible option to perform the lung function measurement is impulse oscillometry (IOS), which requires less cooperation.

Objective: To evaluate whether assessment of AHR by IOS could differentiate children with various obstructive symptoms from one another.

Methods: One hundred twenty-one children (median age 6.0 years, range 3.7-8.1 years) were examined: 31 with probable asthma characterized by current troublesome lung symptoms, 61 with a history of early wheezing disorder (recurrent wheezing ≤24 months of age), 15 with a history of bronchopulmonary dysplasia, and 14 healthy controls. Indirect AHR was assessed by exercise and mannitol challenge tests, and direct AHR was assessed with methacholine using IOS. AHR to exercise was defined as an increase of at least 40% in respiratory resistance at 5 Hz. In the mannitol and methacholine challenges, the dose causing an increase of 40% in respiratory resistance at 5 Hz was calculated.

Results: AHR to exercise was good at differentiating children with current troublesome lung symptoms from those in the other groups (P < .001). AHR to methacholine separated children with current troublesome lung symptoms, early wheezing disorder, and bronchopulmonary dysplasia from the controls (P < .001), whereas the mannitol test did not distinguish among the study groups (P = .209).

Conclusion: The methacholine and exercise challenge tests with IOS identify children with probable asthma characterized by troublesome lung symptoms and therefore may represent a practical aid in the evaluation of AHR in young children.
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http://dx.doi.org/10.1016/j.anai.2014.04.026DOI Listing
August 2014

How mothers perceive infants with unspecific gastrointestinal symptoms suggestive of cow's milk allergy?

Acta Paediatr 2014 May;103(5):524-8

Aim: To determine whether specific infant behavioural characteristics are present in children suspected of cow's milk allergy because of gastrointestinal symptoms.

Methods: We prospectively recruited 57 children (median age 8.7 months) with a suspicion of gastrointestinally manifested cow's milk protein allergy (GI-CMPA). None had detectable cow's milk-specific IgE. Mothers were asked to complete the Parenting Stress Index (PSI) Child Domain, and those with children below 18 months of age (n = 49) also the Infant Temperament Questionnaire (ITQ). GI-CMPA was diagnosed with the double-blind, placebo-controlled food challenge. Control group (n = 22) consisted of patients (age range 4-26 months), attending the Pediatric Allergy Unit, who did not have diagnosed or suspected food allergies.

Results: The scores were significantly higher for the PSI (n = 48) Child Domain (p < 0.0001) and for the ITQ (n = 44) subscale Difficultness (p = 0.0045) compared with the control patients without suspected/diagnosed food allergy. The difference between the challenge positive (n = 18) and negative (n = 39) patients remained statistically insignificant. After 6 months, in both groups, the scores (PSI Child Domain p = 0.0004, ITQ Difficultness p = 0.0393) were lower, but the ITQ Difficultness score still remained higher than in the controls (p = 0.0453).

Conclusion: The mothers often perceive infants with unspecific symptoms suggestive of GI-CMPA as demanding and temperamentally difficult.
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http://dx.doi.org/10.1111/apa.12577DOI Listing
May 2014

Markers of gut mucosal inflammation and cow's milk specific immunoglobulins in non-IgE cow's milk allergy.

Clin Transl Allergy 2014 Mar 5;4(1). Epub 2014 Mar 5.

Children's Hospital, Division of Pediatric Gastroenterology, Helsinki University Central Hospital, PO BOX 281, FIN-00029 HUS, Helsinki, Finland.

Background: Allergy to cow's milk protein (CMP) may cause gastrointestinal (GI) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood. Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow's milk protein allergy (CMPA).

Patients And Methods: We prospectively recruited infants and young children (n = 57; median age 8.7 months) with gastrointestinal complaints suspected of CMPA. The diagnosis of CMPA was made using the double-blind, placebo-controlled food challenge. Serum and stool samples were collected during CMP-free diet and after both placebo and active challenges. We analyzed the stool samples for calprotectin, human β-defensin 2 and IgA. In serum, we analyzed the levels of β-lactoglobulin and α-casein specific IgA, and IgG antibodies (total IgG and subclasses IgG1 and IgG4). Control group included children with e.g. dermatological or pulmonary problems, consuming normal diets.

Results: Fecal calprotectin levels were higher in the challenge positive group (n = 18) than in the negative (n = 37), with respective geometric means 55 μg/g [95% confidence interval 38-81] and 29 [24-36] μg/g (p = 0.0039), during cow's milk free diet. There were no significant inter-group differences in the fecal β-defensin and IgA levels. The CMP specific IgG and IgA were not elevated in patients with CMPA, but the levels of β-lactoglobulin-IgG4 (p = 0.0118) and α-casein-IgG4 (p = 0.0044), and total α-casein-IgG (p = 0.0054) and -IgA (p = 0.0050) in all patient samples (regardless of CMPA diagnosis) were significantly lower compared to the control group using dairy products.

Conclusions: Despite cow's milk elimination in children intolerant to cow's milk there might be ongoing low-grade inflammation in the gut mucosa. CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA. The observed frequency of impaired CMP specific total IgA, IgG and IgG4 production in patients following cow's milk free diet warrants further studies.
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http://dx.doi.org/10.1186/2045-7022-4-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946153PMC
March 2014