Publications by authors named "Tuomas Jartti"

134 Publications

Impulse oscillometry and free-running tests for diagnosing asthma and monitoring lung function in young children.

Ann Allergy Asthma Immunol 2021 Apr 2. Epub 2021 Apr 2.

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

Background: Separating viral-induced wheezers from asthmatics is challenging, and there are no guidelines for children under 6 years of age. Impulse oscillometry is feasible beginning 4-year old children.

Objective: To explore the use of impulse oscillometry in diagnosing and monitoring asthma in young children and evaluating treatment response to inhaled corticosteroid.

Methods: Forty-two children (median age 5.3 years, range 4.0-7.9 years) with doctor diagnosed asthma and lability in oscillometry were followed for 6 months after initiation of inhaled corticosteroid treatment. All children performed the 6-minute free-running test and impulse oscillometry at three time points. After the baseline, they attended a second visit when they had achieved good asthma control, and a third visit about 60 days after the second visit. A positive ICS-response was defined as having greater than 19 points in ACT and no hyperreactivity on the third visit.

Results: In total, 38/42 children responded to ICS treatment. Exercise-induced increases of resistance at 5 Hz decreased after ICS-treatment (61% vs. 18% vs. 13.5%, p< .001), and running distance during the 6-minute test was lengthened (800m vs. 850m vs. 850m, p= .001). Significant improvements in childhood asthma control (C-ACT) scores occurred between the baseline and subsequent visits (21 vs. 24 vs. 24, p < .001) and acute doctors' visits for respiratory symptoms [(1, (0-6)vs. 0, (0-2), p = .001]. Similar profiles were observed in children without aeroallergen sensitization and among those under 5 years of age.

Conclusion: Impulse oscillometry is a useful tool in diagnosing asthma and monitoring lung function in young children.
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http://dx.doi.org/10.1016/j.anai.2021.03.030DOI Listing
April 2021

Which Wheezing Preschoolers Should be Treated for Asthma?

J Allergy Clin Immunol Pract 2021 Mar 4. Epub 2021 Mar 4.

National Heart & Lung Institute, Imperial College London, London, United Kingdom.

Wheezing disorders in children younger than 5 years are common, but lack of clarity remains about which children should be treated to prevent symptoms and acute episodes. The aim of this review was to discuss a practical approach to deciding which children younger than 5 years with asthma should be treated, and if so, with which strategy. The importance of having a clear definition of "asthma" for this age group, determined by a collection of presenting respiratory symptoms, without assumptions about underlying mechanisms is addressed. Subsequent consideration should be given to timing, severity, and frequency of symptoms, together with assessment of objective biomarkers, including aeroallergen sensitization and blood eosinophils, to inform whether or not a preschooler with recurrent wheezing requires treatment. Numerous unanswered questions remain about the optimal management of nonallergic preschool wheezing and asthma, and areas of specific unmet need and future directions for research are highlighted.
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http://dx.doi.org/10.1016/j.jaip.2021.02.045DOI Listing
March 2021

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multinational cohort.

Allergy 2021 Feb 20. Epub 2021 Feb 20.

Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes.

Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control.

Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged.

Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.
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http://dx.doi.org/10.1111/all.14787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013557PMC
February 2021

The role of interferons in preschool wheeze.

Lancet Respir Med 2021 01;9(1):9-11

Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.

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http://dx.doi.org/10.1016/S2213-2600(20)30569-5DOI Listing
January 2021

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection.

Am J Respir Crit Care Med 2021 04;203(7):822-830

University of Wisconsin-Madison, Madison, Wisconsin.

Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits ( < 0.001, χ) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5-27%) at the age of 2 years, but by the age of 16 years, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A;  < 0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age ( < 0.0001), genotype ( < 0.05), and wheezing illnesses ( < 0.05). Furthermore, certain RV types (e.g., C2, C11, A78, and A12) were consistently more virulent and prevalent over time. Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.
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http://dx.doi.org/10.1164/rccm.202010-3753OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017585PMC
April 2021

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 Oct 28;10(1):45. Epub 2020 Oct 28.

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

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
October 2020

Lung function testing and inflammation markers for wheezing preschool children: A systematic review for the EAACI Clinical Practice Recommendations on Diagnostics of Preschool Wheeze.

Pediatr Allergy Immunol 2021 Apr 27;32(3):501-513. Epub 2020 Dec 27.

Department of Pediatrics, University of Oulu and Oulu University Hospital, Oulu, Finland.

Background: Preschool wheeze is highly prevalent; 30%-50% of children have wheezed at least once before age six. Wheezing is not a disorder; it is a symptom of obstruction in the airways, and it is essential to identify the correct diagnosis behind this symptom. An increasing number of studies provide evidence for novel diagnostic tools for monitoring and predicting asthma in the pediatric population. Several techniques are available to measure airway obstruction and airway inflammation, including spirometry, impulse oscillometry, whole-body plethysmography, bronchial hyperresponsiveness test, multiple breath washout test, measurements of exhaled NO, and analyses of various other biomarkers.

Methods: We systematically reviewed all the existing techniques available for measuring lung function and airway inflammation in preschool children to assess their potential and clinical value in the routine diagnostics and monitoring of airway obstruction.

Results: If applicable, measuring FEV1 using spirometry is considered useful. For those unable to perform spirometry, whole-body plethysmography and IOS may be useful. Bronchial reversibility to beta2-agonist and hyperresponsiveness test with running exercise challenge may improve the sensitivity of these tests.

Conclusions: The difficulty of measuring lung function and the lack of large randomized controlled trials makes it difficult to establish guidelines for monitoring asthma in preschool children.
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http://dx.doi.org/10.1111/pai.13418DOI Listing
April 2021

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 28;10:45. Epub 2020 Oct 28.

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

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592594PMC
October 2020

Eucapnic voluntary hyperventilation test decreases exhaled nitric oxide level in children.

Clin Physiol Funct Imaging 2021 Jan 11;41(1):1-3. Epub 2020 Nov 11.

Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Background: Exhaled nitric oxide (FeNO) measurements and eucapnic voluntary hyperventilation (EVH) tests have been used as diagnostic tools for asthma. Data on the impact of hyperventilation on the level of FeNO are limited.

Aim: We aimed to evaluate whether EVH tests affect the level of FeNO in children aged 10-16 years.

Methods: A total of 234 children aged 10-16 years had a 6-min EVH test performed. In total, FeNO values for 153 of 234 children were measured before the test and within 15 min after the test. According to a baseline FeNO level of 20 ppb, children were divided into two groups: those with low values (FeNO < 20 ppb) and those with high values (FeNO ≥ 20 ppb).

Results: The median age of the children was 13.4 years (interquartile range 12.3-15.3 years); 58% were boys and 42% were girls. Of these children, 51% were sensitized to aeroallergens. In 101 of 153 children (66%), the FeNO values decreased after the EVH test. In children with low and high baseline levels, the median level of FeNO decreased after the EVH test: 10.5 ppb before versus 9.5 ppb after (p < .011), and 31.0 ppb before versus 28.0 ppb after (p < .011), respectively. The decrease in FeNO after EVH test was not associated with induced bronchoconstriction expressed as a change in FEV1 (R  = .19).

Conclusions: The EVH test decreases FeNO levels. Therefore, FeNO should be measured before an EVH test is performed.
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http://dx.doi.org/10.1111/cpf.12673DOI Listing
January 2021

Reply to: Medical algorithm: Diagnosis and treatment of preschool asthma.

Allergy 2020 10;75(10):2716-2717

Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland.

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http://dx.doi.org/10.1111/all.14285DOI Listing
October 2020

Preschool wheezing and asthma in children: A systematic review of guidelines and quality appraisal with the AGREE II instrument.

Pediatr Allergy Immunol 2021 Jan 5;32(1):92-105. Epub 2020 Oct 5.

Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland.

Background: Asthma-like symptoms in preschool children, such as wheezing and dyspnea, are common time- and resource-consuming diagnostic and management challenges. Quality of wheezing and asthma recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma.

Methods: The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.

Results: We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%.

Conclusion: Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non-asthmatic preschool wheeze.
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http://dx.doi.org/10.1111/pai.13334DOI Listing
January 2021

Clinical correlates of rhinovirus infection in preschool asthma.

Allergy 2021 01 21;76(1):247-254. Epub 2020 Jul 21.

Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.

Background: Investigation of preschool asthma is important since not all children outgrow their illness during this age. Data are scarce on the role of rhinovirus (RV) infections in this patient group.

Objectives: To investigate the role of RV infections in preschool asthma: (i) susceptibility factors, (ii) clinical course, and (iii) medium-term outcome.

Methods: A total of 130 asthmatic children aged 4-6 years from the multinational PreDicta cohort were prospectively followed for a 12-month period. Allergy tests and a standard health questionnaire were carried out at study entry. Respiratory virus presence in nasopharyngeal washes was studied at illness visits and at 3 scheduled visits.

Results: At study entry, mean age of the children was 5.3 years. Of 571 visits, 54% were positive for any virus and 39% for RV. Patient characteristics were only assessed with RV infection due to low number of other viruses. The use of supplementary vitamin D was inversely associated with RV infection (P < .05). RV infection was associated with more severe course of acute illness in terms of more severe nighttime coughing, more sleep disturbances, and more days with runny nose (all P < .05). RV infection was also associated with more severe disease course during the 12-month follow-up in terms of more nights with awakenings and more days of exercise-related symptoms (both P < .05).

Conclusions: Vitamin D supplementation may have an anti-rhinovirus effect. Both short- and medium-term outcomes suggest RV infection to be an important clinical marker of instable preschool asthma.
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http://dx.doi.org/10.1111/all.14479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818397PMC
January 2021

Intratonsillar detection of 27 distinct viruses: A cross-sectional study.

J Med Virol 2020 Jun 30. Epub 2020 Jun 30.

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Palatine tonsils have been observed to harbor several distinct respiratory and herpesviruses in separate studies. In this study, the presence of these viruses in palatine tonsils was comprehensively studied in both children and adults. A cross-sectional analysis of 181 patients (median age 22 years; range, 2.6-66) operated for a benign tonsillar disease was conducted. Real-time polymerase chain reaction was performed to detect 27 distinct viruses in all: eight human herpesviruses, 16 respiratory viruses, parvo B19, and polyoma BK/JC viruses. Clinical characteristics of the patients and underlying conditions were evaluated. In total, 92% of patients had virus detected in tonsils (Epstein-Barr virus 72%, human herpesvirus 7, and 6B 54% and 16%, respectively, enterovirus 18%, parvovirus B19 7% and the rest <4%). No herpes simplex virus 2, varicella zoster virus, polyoma JC virus, parainfluenza-, metapneumo-, or coronaviruses were found. Enterovirus was more common in children and was frequently observed in the presence of HHV6B. None of the viruses showed a positive association to the tonsillar disease. Respiratory symptoms were not associated with the prevalence of viruses. This study comprehensively reports a cross-sectional view of intratonsillar virus infections in elective tonsillectomy patients in a wide age range cohort. Tonsils are a major virus reservoir for distinct herpes and respiratory viruses without a positive association with tonsillar disease or respiratory symptoms.
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http://dx.doi.org/10.1002/jmv.26245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689766PMC
June 2020

Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden.

J Allergy Clin Immunol Pract 2020 09 17;8(8):2592-2599.e3. Epub 2020 Jun 17.

Department of Pediatrics & Child Health, MRC Unit on Child & Adolescent Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.

Background: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic.

Objective: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients.

Methods: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma.

Results: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts.

Conclusions: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.
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http://dx.doi.org/10.1016/j.jaip.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297686PMC
September 2020

Increased antiviral response in circulating lymphocytes from hypogammaglobulinemia patients.

Allergy 2020 12 16;75(12):3147-3158. Epub 2020 Jul 16.

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Background: B cells play a crucial role during rhinovirus (RV) infections by production of virus-neutralizing antibodies. A main feature of common variable immunodeficiency (CVID) is hypogammaglobulinemia (HG). HG patients have severely reduced levels of antibody-producing B cells and suffer from prolonged virus infections. Here, we addressed whether antiviral response of peripheral blood lymphocytes differs between HG patients and healthy individuals during natural RV infection.

Methods: Using fluorescence-activated cell sorting, B-cell subsets were analyzed. Simultaneously, CD19 + B cells, CD14 + monocytes, and CD3 + T cells were sorted from frozen peripheral blood mononuclear cells from 11 RV-infected hypogammaglobulinemia patients, 7 RV-infected control subjects, and 14 noninfected control subjects. Real-time PCR was used to study expression of antiviral genes. A pan-RV PCR was used to detect RV genome in all samples.

Results: In HG patients, total B-cell numbers, as well as IgA + and IgG + switched memory B cells, were reduced while naïve B cells and T cells were increased. STAT1 expression was increased in HG patients compared to controls in all lymphocyte subsets analyzed. The expression of antiviral genes IFITM1 and MX1 correlated with STAT1 expression in B cells and monocytes. RV RNA was found in 88.9% of monocytes from infected HG patients, 85.7% of monocytes from infected controls, and 7.1% of monocytes from uninfected controls.

Conclusions: We demonstrate an increased antiviral response in B cells and monocytes in HG patients and their correlation with STAT1 expression. Monocytes of infected HG patients and infected non-HG controls carry RV RNA.
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http://dx.doi.org/10.1111/all.14445DOI Listing
December 2020

Cut-off values to evaluate exercise-induced asthma in eucapnic voluntary hyperventilation test for children.

Clin Physiol Funct Imaging 2020 Sep 26;40(5):343-350. Epub 2020 Jun 26.

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Background And Aim: The eucapnic voluntary hyperventilation (EVH) testing is a diagnostic tool for diagnostics of exercise-induced bronchoconstriction; while the testing has become more common among children, data on the test's feasibility among children remain limited. Our aim was to investigate EVH testing feasibility among children, diagnostic testing cut-off values, and which factors affect testing outcomes.

Methods: We recruited 134 patients aged 10-16 years with a history of exercise-induced dyspnoea and 100 healthy control children to undergo 6-min EVH testing. Testing feasibility was assessed by the children's ability to achieve ≥70% of the target minute ventilation of 30 times forced expiratory volume in 1 s (FEV1). Bronchoconstriction was assessed as a minimum of 8%, 10%, 12%, 15% or 20% fall in FEV1. Patient characteristics were correlated with EVH outcomes.

Results: Overall, 98% of the children reached ≥70%, 88% reached ≥80%, 79% reached ≥90% and 62% reached ≥100% of target ventilation in EVH testing; of children with a history of exercise-induced dyspnoea, the decline percentages were as follows: 24% (≥8% fall), 17% (≥10% fall), 10% (≥12% fall), 6% (≥15% fall) and 5% (≥20% fall) in FEV1, compared to 11%, 4%, 3%, 1% and 0% among the healthy controls, respectively. Healthy controls and boys performed testing at higher ventilation rates (p < .05).

Conclusion: Eucapnic voluntary hyperventilation testing is feasible among children aged 10-16 years and has diagnostic value in evaluating exercise-induced dyspnoea among children. A minimum 10% fall in FEV1 is a good diagnostic cut-off value. Disease status appears to be important covariates.
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http://dx.doi.org/10.1111/cpf.12647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496314PMC
September 2020

Tonsillar microbial diversity, abundance, and interrelations in atopic and non-atopic individuals.

Allergy 2020 08 19;75(8):2133-2135. Epub 2020 Apr 19.

Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

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http://dx.doi.org/10.1111/all.14306DOI Listing
August 2020

Research Priorities in Pediatric Asthma: Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank.

J Allergy Clin Immunol Pract 2020 06 4;8(6):1953-1960.e9. Epub 2020 Mar 4.

Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom; Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: Pediatric asthma remains a public health challenge with enormous impact worldwide.

Objective: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities.

Methods: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared.

Results: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations.

Conclusions: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.
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http://dx.doi.org/10.1016/j.jaip.2020.01.059DOI Listing
June 2020

Role of viruses in asthma.

Semin Immunopathol 2020 02 27;42(1):61-74. Epub 2020 Jan 27.

Department of Pediatric Pneumonology and Allergy, The Medical University of Warsaw, Warsaw, Poland.

Respiratory viral infections are the most important triggers of asthma exacerbations. Rhinovirus (RV), the common cold virus, is clearly the most prevalent pathogen constantly circulating in the community. This virus also stands out from other viral factors due to its large diversity (about 170 genotypes), very effective replication, a tendency to create Th2-biased inflammatory environment and association with specific risk genes in people predisposed to asthma development (CDHR3). Decreased interferon responses, disrupted airway epithelial barrier, environmental exposures (including biased airway microbiome), and nutritional deficiencies (low in vitamin D and fish oil) increase risk to RV and other virus infections. It is intensively debated whether viral illnesses actually cause asthma. Respiratory syncytial virus (RSV) is the leading causative agent of bronchiolitis, whereas RV starts to dominate after 1 year of age. Breathing difficulty induced by either of these viruses is associated with later asthma, but the risk is higher for those who suffer from severe RV-induced wheezing. The asthma development associated with these viruses has unique mechanisms, but in general, RV is a risk factor for later atopic asthma, whereas RSV is more likely associated with later non-atopic asthma. Treatments that inhibit inflammation (corticosteroids, omalizumab) effectively decrease RV-induced wheezing and asthma exacerbations. The anti-RSV monoclonal antibody, palivizumab, decreases the risk of severe RSV illness and subsequent recurrent wheeze. A better understanding of personal and environmental risk factors and inflammatory mechanisms leading to asthma is crucial in developing new strategies for the prevention and treatment of asthma.
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http://dx.doi.org/10.1007/s00281-020-00781-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066101PMC
February 2020

Evolution of Airway Inflammation in Preschoolers with Asthma-Results of a Two-Year Longitudinal Study.

J Clin Med 2020 Jan 9;9(1). Epub 2020 Jan 9.

Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4-6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0-8.6; 6.0, CI: 2.8-12.0; 8.0, CI: 4.0-14.0; 8.5, CI: 4.4-14.5 ppb, respectively) increased with age (correlation ≤ 0.001) and atopy ( = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence ( = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study ( < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma.
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http://dx.doi.org/10.3390/jcm9010187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020050PMC
January 2020

Rhinovirus C Is Associated With Severe Wheezing and Febrile Respiratory Illness in Young Children.

Pediatr Infect Dis J 2020 04;39(4):283-286

From the Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Background: Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity.

Methods: This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3-23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008.

Results: Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing.

Conclusions: Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.
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http://dx.doi.org/10.1097/INF.0000000000002570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749725PMC
April 2020

Rhinovirus species and tonsillar immune responses.

Clin Transl Allergy 2019 2;9:63. Epub 2019 Dec 2.

5Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Background: Rhinovirus A and C infections are important contributors to asthma induction and exacerbations. No data exist on the interaction of local immune responses in rhinovirus infection. Therefore, we aimed to determine the tonsillar immune responses according to rhinovirus A, B and C infections.

Methods: We collected tonsillar samples, nasopharyngeal aspirates and peripheral blood from 42 rhinovirus positive tonsillectomy patients. Fifteen respiratory viruses or their types were investigated from nasopharynx and tonsil tissue, and rhinovirus species were typed. The expression of 10 cytokines and 4 transcription factors (IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet) were studied from tonsil tissue by quantitative PCR. A standard questionnaire of respiratory symptoms and health was filled by the patient or his/her guardian. The patients were divided into three groups by the determination of rhinovirus species.

Results: Overall, 16 patients had rhinovirus A, 12 rhinovirus B and 14 rhinovirus C infection. In rhinovirus B positive group there were significantly less men ( = 0.0072), less operated in spring ( = 0.0096) and more operated in fall ( = 0.030) than in rhinovirus A or C groups. Rhinovirus A positive patients had more respiratory symptoms ( = 0.0074) and particularly rhinitis ( = 0.036) on the operation day. There were no significant differences between the groups in virus codetection. In adjusted analysis, rhinovirus C infections were associated with increased IFN-α ( = 0.045) and decreased RORC2 expression ( = 0.025).

Conclusions: Rhinovirus species associated differently with clinical characteristics and tonsillar cytokine responses.
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http://dx.doi.org/10.1186/s13601-019-0302-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886181PMC
December 2019

Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma.

J Allergy Clin Immunol Pract 2020 02 11;8(2):588-595.e4. Epub 2019 Sep 11.

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland. Electronic address:

Background: Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types.

Objective: To study whether RSV or RV types are differentially associated with the future use of asthma control medication.

Methods: Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication.

Results: A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03).

Conclusions: Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.
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http://dx.doi.org/10.1016/j.jaip.2019.08.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012669PMC
February 2020

No Correlation Between Nasopharyngeal Human Bocavirus 1 Genome Load and mRNA Detection or Serology in Adeno-/Tonsillectomy Patients.

J Infect Dis 2019 07;220(4):589-593

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Finland.

Human bocavirus 1 (HBoV1) can persist in nasopharynx and tonsils. Using HBoV1 serology, reverse-transcription polymerase chain reaction (PCR) for detecting messenger RNA (mRNA) and quantitative PCR for HBoV1 genome load count, we studied to what extent the HBoV1 DNA loads in nasopharynx correlate with acute infection markers. Tonsillar tissue, nasopharyngeal aspirate, and serum were obtained from 188 elective adeno-/tonsillectomy patients. Relatively high loads of HBoV1 DNA were detected in the nasopharynx of 14 (7%) primarily asymptomatic subjects with negative mRNA and/or serodiagnostic results. Quantitative HBoV1 DNA PCR may have lower specificity than HBoV1 mRNA detection for diagnosing symptomatic infection.
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http://dx.doi.org/10.1093/infdis/jiz166DOI Listing
July 2019

Respiratory tract virus infections in the elderly with pneumonia.

BMC Geriatr 2019 04 16;19(1):111. Epub 2019 Apr 16.

Department of Pediatrics and Adolescent Medicine, University of Turku and Turku University Hospital, PO Box 52, 20520, Turku, Finland.

Background: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia.

Methods: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints.

Results: Median age of the patients was 83 years (range 76-90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 10/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes.

Conclusion: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons.
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http://dx.doi.org/10.1186/s12877-019-1125-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469155PMC
April 2019

Human bocaviruses and paediatric infections.

Lancet Child Adolesc Health 2019 06 1;3(6):418-426. Epub 2019 Apr 1.

Department of Paediatrics, Turku University Hospital and University of Turku, Turku, Finland.

Human bocavirus 1 (HBoV1), belonging to the Parvoviridae family, was discovered in 2005, in nasopharyngeal samples from children with respiratory tract infections. Three additional bocaviruses, HBoV2-4, were discovered in 2009-10. These viruses have mainly been found in faecal samples and their role in human diseases is still uncertain. HBoV1 causes a wide spectrum of respiratory diseases in children, including common cold, acute otitis media, pneumonia, bronchiolitis, and asthma exacerbations. HBoV1 DNA can persist in airway secretions for months after an acute infection. Consequently, acute HBoV1 infection cannot be diagnosed with standard DNA PCR; quantitative PCR and serology are better diagnostic approaches. Because of their high clinical specificity, diagnostic developments such as HBoV1 mRNA and antigen detection have shown promising results. This Review summarises the knowledge on human bocaviruses, with a special focus on HBoV1.
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http://dx.doi.org/10.1016/S2352-4642(19)30057-4DOI Listing
June 2019

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments.

Allergy 2019 01 25;74(1):40-52. Epub 2018 Nov 25.

Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland.

Current data indicate that the "bronchiolitis" diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)-induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV-specific monoclonal antibody is available; (b) rhinovirus-induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2-year-old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.
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http://dx.doi.org/10.1111/all.13624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587559PMC
January 2019

Pulmonary function and bronchial reactivity 4 years after the first virus-induced wheezing.

Allergy 2019 03 8;74(3):518-526. Epub 2018 Oct 8.

Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Background: Wheezing illnesses among young children are common and are a risk factor for asthma. However, determinants of childhood bronchial reactivity, a key feature of asthma, are largely unknown. The aim of this study was to determine how patient characteristics during the first severe virus-induced wheezing episode are associated with pulmonary function at preschool age.

Methods: Study consisted of 76 children presenting with their first wheezing episode at the ages of 3 to 23 months. At study entry, viral etiology, rhinovirus genome load, atopic and clinical characteristics, and standardized questionnaire were analyzed. At 4-year follow-up visit, impulse oscillometry with exercise challenge was performed.

Results: At study entry, the mean age of the children was 12 months (SD 6.0), 57 (75%) were rhinovirus positive, and 22 (30%) were sensitized. At follow-up visit four years later, the mean age of the children was 60 months (SD 7.9) and 37 (49%) were using asthma medication regularly (discontinued before testing in 25 [68%] children). Bronchial reactivity (≥35% change in mean crude values of resistance) after exercise challenge or bronchodilation was present in nine (12%) children. Children with atopic sensitization at the time of the first wheezing episode were more often likely to develop bronchial reactivity (odds ratio 8.8, P = 0.03) than the children without sensitization. No other significant associations were found.

Conclusions: Atopic sensitization at the time of the first severe wheezing episode is an important early risk factor for increased bronchial reactivity at preschool age.
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http://dx.doi.org/10.1111/all.13593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387855PMC
March 2019