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Alterations in Serum-Free Amino Acid Profiles in Childhood Asthma

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Alterations in Serum-Free Amino Acid Profiles in Childhood Asthma International Journal of Environmental Research and Public Health Article Alterations in Serum-Free Amino Acid Profiles in Article Childhood Asthma AlterationsJoanna Matysiak in Serum1,* , Agnieszka-Free Klupczynska Amino 2Acid, Kacper Profiles Packi 2, in ChildhoodAnna Mackowiak-Jakubowska Asthma 2, Anna Br˛eborowicz 3, Olga Pawlicka 2, Katarzyna Olejniczak 3, Zenon J. Kokot 1 and Jan Matysiak 2 Joanna Matysiak1 Faculty 1,*, Agnieszka of Health Sciences, Klupczynska The President 2, Kacper Stanisław Packi 2, Anna Wojciechowski Mackowiak State-Jakubowska University 2 of, Applied Sciences Anna Bręborowiczin Kalisz, 3, Olga 62-800 Pawlicka Kalisz, 2 Poland;, Katarzyna [email protected] Olejniczak 3, Zenon J. Kokot 1 and Jan Matysiak 2 2 Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 1 Faculty of Health60 -780 Sciences, Poznan, The Poland; President [email protected] Stanisław Wojciechowski State (A.K.); University [email protected] of Applied Sciences (K.P.); in Kalisz, [email protected] 62-800, Poland; [email protected] (A.M.-J.); [email protected] (O.P.); [email protected] (J.M.) 3 2 DepartmentDepartment of Inorganic ofand Pulmonology, Analytical Chemistry, Pediatric Poznan Allergy University and Clinical of Medical Immunology, Sciences; Poznan 60 - 780, PolandPoznan; [email protected] University of Medical (A.K.); Sciences, [email protected] 60-572 Poznan, (K.P.); Poland; [email protected] [email protected] (A.B.); (A.M.-J.); [email protected]@gmail.com (O.P.); (K.O.) [email protected] (J.M.) 3 Department* Correspondence: of Pulmonology, Pediatric [email protected] Allergy and Clinical Immunology, Poznan University of Medical Sciences; Poznan 60-572, Poland; [email protected] (A.B.); [email protected] (K.O.) * Correspondence:Received: [email protected] 17 June 2020; Accepted: 28 June 2020; Published: 2 July 2020 Received: 17 June 2020; Accepted: 28 June 2020; Published: date Abstract: Asthma often begins in childhood, although making an early diagnosis is difficult. AbstractClinical: Asthma manifestations,often begins in childhood, the exclusion although of other making causes an early of bronchialdiagnosis is obstruction, difficult. Clinical and responsiveness to manifestations,anti-inflammatory the exclusion therapyof other causes are the of main bronchial tool obstruction, of diagnosis. and However, responsiveness novel, to precise, anti- and functional inflammatorybiochemical therapy markers are the aremain needed tool of in diagnosis. the differentiation However, ofnovel, asthma precise, phenotypes, and functional endotypes, and creating biochemicalpersonalized markers are therapy. needed The in aimthe ofdifferentiation the study was of asthma to search phenotypes, for metabolomic-based endotypes, and asthma biomarkers creating amongpersonalized free amino therapy. acids The (AAs).aim of the A wide study panel was to of search serum-free for metabolomic AAs in asthmatic-based asthma children, covering both biomarkers among free amino acids (AAs). A wide panel of serum-free AAs in asthmatic children, proteinogenic and non-proteinogenic AAs, were analyzed. The examination included two groups covering both proteinogenic and non-proteinogenic AAs, were analyzed. The examination included two groupsof individuals of individuals between between 3 3 and and 1818 yearsyears old old:: asthma asthmatictic children children and and the thecontrol control group group consisted of consistedchildren of children with with neither neither asthma asthma nor a allergies.llergies. High High-performance-performance liquid liquid chromatography chromatography combined combinedwith with tandem tandem massmass spectrometry spectrometry (LC (LC-MS-MS/MS/MS technique) technique) was used was for used AA for measurements. AA measurements. The data The datawere were analyzedanalyzed by by applying applying uni uni-- and and multivariate multivariate statistical statistical tests. tests.The obtained The obtained results results indicate indicate thethe decreaseddecreased serum serum concentration concentration of taurine, of taurine, L-valine, L-valine, DL-β DL--aminoisobutyricβ-aminoisobutyric acid, and acid, and increased increasedlevels levels ofof ƴ -amino-n-butyric -amino-n-butyric acid acid and and L-arginineL-arginine in in asthmatic asthmatic children children when when compared compared to controls. to controls.The The altered altered concentration concentration ofof these AAs AAs can can testify testify to their to their role rolein th ine pathogenesis the pathogenesis of of childhood childhoodasthma. asthma. The The authors’ authors’ results results should should contribute contribute to to the the future future introduction introduction of of new new diagnostic markers diagnostic markers into clinical practice. into clinical practice. Keywords: metabolomics; metabolites; amino acids; biomarkers; asthma; diagnosis; children Keywords: metabolomics; metabolites; amino acids; biomarkers; asthma; diagnosis; children 1. Introduction 1. Introduction Asthma is a serious problem in contemporary medicine. It is a chronic illness, caused by both genetic and environmentalAsthma is a seriousfactors and problem characterized in contemporary by the inflammation medicine. of It isthe a lower chronic airways. illness, caused by both Inflammationgenetic leads and to environmentaloedema and the infiltration factors and of the characterized bronchial mucosa, by the bronchospasm, inflammation and of an the lower airways. excessiveInflammation mucus secretion leads, resulting to oedema in reversible and the airway infiltration obstruction of the. bronchialHowever, mucosa,in a significant bronchospasm, and an percentage of patients, chronic inflammation leads to the remodeling of the bronchial walls and fixed excessive mucus secretion, resulting in reversible airway obstruction. However, in a significant airflow limitation. The highest incidence rates of asthma are recorded in developed countries [1]. The recent globalpercentage epidemiological of patients, report chronic has shown inflammation that nowadays leads tothis the ailment remodeling is affecting of the more bronchial than walls and fixed 300 millionairflow people limitation. all over the The world. highest In many incidence patients, rates asthma of asthmabegins in are childhoo recordedd [2]. inRecurrent developed countries [1]. wheezingThe episodes recent triggered global epidemiological by viral infection report are the has most shown common that nowadays manifestation this ailmentof asthma is in aff ecting more than 300 million people all over the world. In many patients, asthma begins in childhood [2]. Recurrent Int. J. Environ. Res. Public Health 2020, 17, x; doi: www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2020, 17, 4758; doi:10.3390/ijerph17134758 www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2020, 17, 4758 2 of 17 wheezing episodes triggered by viral infection are the most common manifestation of asthma in infancy and preschool children. However, the nonspecific symptoms, such as wheezing, cough, and chest tightness, make it difficult to distinguish asthma from other diseases [3,4]. An atopic background predisposes to asthma development but is not an essential condition. Objective tests supporting preschool asthma diagnoses are not commonly available and clinical criteria remain a major diagnostic tool in clinical practice. There are significant differences between childhood and adulthood asthma, concerning immunology, histopathology, and clinical manifestations. Many researchers have tried to identify specific biological markers of childhood asthma that would aid in the diagnosis of this disorder. Finding such compounds is extremely important because accurate diagnosis and optimal treatment play a crucial role in the proper functioning of asthmatic children and can greatly improve their quality of life. One of the disciplines being used to discover new biomarkers of various diseases and to identify biochemical pathways involved in their pathogenesis is metabolomics. This latest of the so-called omic techniques is focused on low-molecular-weight intermediates and the products of metabolism, such as amino acids, fatty acids, carbohydrates, or nucleotides. The composition of the metabolome is determined by the current condition of the organism, which is affected by external and internal factors, including pathology, applied therapy, or diet [5,6]. It was found that changes in the human metabolome precede clinical symptoms’ occurrence [7]. Therefore, the metabolomic approach offers a powerful tool in the development of new diagnostic tests, including respiratory tract diseases. In metabolomic research, two strategies are used: targeted and non-targeted analysis. A targeted approach is used for the precise quantitative analysis of a limited number of metabolites with known biochemical properties. By using highly sensitive and selective analytical techniques, a certain group of metabolites can be detected and quantified, even if they are present in very low concentrations. A non-targeted analysis, also called metabolite fingerprinting, enables the classification of the tested biological material on the basis of the complete metabolic profile, rather than individual substances. The non-targeted strategy aims to structurally detect diverse compounds present in the metabolome, however, without quantitative data [5,6,8,9]. Metabolomics has provided potential biomarkers
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