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Astma je najčešća kronična bolest djece. U liječenju astme važno je prepoznati pridružene bolesti/stanja koja mogu utjecati na kontrolu astme, posebice ako se radi o teško lječivoj ili teškoj astmi. Anksioznost je jedno od takvih pridruženih stanja koja utječu na uspješnost liječenja astme, smanjenje tjelesne aktivnosti, kvalitetu života i posljedično na razvitak pretilosti. Također ima utjecaj na tijek i težinu astme preko endogenih mehanizama poput mijenjanja citokinskog profila, parasimpatičke aktivnosti i utjecaja na osovinu hipotalamus – hipofiza – nadbubrežna žlijezda. Kod djece s astmom posebnu pozornost treba usmjeriti i na anksioznost roditelja koja također značajno utječe na kontrolu dječje astme i razinu tjelesne aktivnosti. Anksioznost majki prenatalno i u ranom djetinjstvu može utjecati na razvoj astme djece putem epigenetskih mehanizama., Asthma is the most common chronic disease of children. In asthma treatment it is important to recognize associated treatible traits that can affect asthma control, especially if it is difficult to treat or severe asthma. Anxiety is associated condition that affects the success of asthma treatment, the reduction of physical activity, the quality of life and, consequently, the development of obesity. It also has an influence on the course and severity of asthma through endogenous mechanisms like changening of the cytokine profile, parasympathetic activity and the influence on the axis of the hypothalamus-pituitary-adrenal gland. In children with asthma, special attention should be paid to parents’ anxiety, which also significantly affects the control of children’s asthma and the level of physical activity. Maternal anxiety prenatally and in early childhood can influence the development of asthma in children through epigenetic mechanism.

Astma je kronična upalna bolest koja se klinički očituje reverzibilnom bronhalnom opstrukcijom. Kašalj i piskanje (engl. wheezing) su učestali simptomi u dječjoj dobi, ali ne označavaju uvijek tešku bolest. Iako je astma najčešći uzrok kašlja, teškog disanja i dispneje u djece i odraslih, dijagnoza astme se često neprimjereno pripisuje simptomima drugih bolesti. Pažljivo uzeta anamneza, prisutnost zvučnih fenomena, spirometrija i mjerenje acidobaznog statusa pružaju nam korisne podatke za rješavanje različitih uzroka i izbjegavanje neprikladnog liječenja kliničkih manifestacija bolesti koje nalikuju na astmu., Bronchial asthma is defined as a chronic inflammatory disease resulting in a reversible and variable bronchial obstruction. Cough and wheeze are common symptoms in childhood, but mostly do not signify a serious illness. Although asthma is the most common cause of cough, wheeze, and dyspnea in children and adults, asthma is often attributed inappropriately to symptoms from other causes. A careful history, attention to the nature of the respiratory sounds that are present, spirometry, exercise testing, and blood-gas measurement provide useful data to sort out the various causes and avoid inappropriate treatment of these pseudo-asthma clinical manifestations.

Teška astma je složena i heterogena bolest obilježena neprimjerenom kontrolom unatoč visokom stupnju liječenja. Procjenjuje se kako je prisutna u 2 - 5% djece s astmom, češće u djece starije od 10 godina i u dječaka. Iako je teška astma rijetka, ova skupina djece ima povećani rizik nuspojava liječenja, kao i teških i po život opasnih egzacerbacija. Povećani su izravni i neizravni troškovi u vidu potrošnje lijekova, češćih redovitih i hitnih posjeta liječniku, hospitalizacija, izostanaka s nastave i roditeljskih odsustava s posla. Definicije teške astme nisu ujednačene, ali im je svima zajednička potreba za kombinacijskim liječenjem inhalacijskim kortikosteroi- dima i bronhodilatatorima dugog djelovanja u visokim dozama neophodnima za kontrolu simptoma, ili, čak nedostatnima za punu kontrolu bolesti. Nekontrolirana astma zahtijeva iscrpno preispitivanje koje uključuje diferencijalno dijagnostičku reevaluaciju i nedvojbenu potvrdu dijagnoze astme, otkrivanje otegotnih čimbenika poput neredovitog uzimanja i/ili loše tehnike primjene inha- lacijskih lijekova, utjecaja okoliša (izloženost alergenima i iritansima) te komorbiditeta (bolesti gornjeg dišnog puta, gastroezofagu- sni refluks, pretilost i anksioznost). Ukoliko je dijagnoza astme potvrđena, a otegotni čimbenici ispravljeni, te je postignuta kontrola bolesti, radi se o teško lječivoj astmi (engl. difficult-to-treat asthma). Ako se ovim mjerama ne postigne kontrola, radi se o teškoj rezi- stentnoj astmi (engl. severe, therapy-resistant asthma). U pristupu djetetu s teško lječivom astmom slijedimo sistematičnu evaluaciju kojom u približno dvije trećine bolesnika djelovanjem na modificirajuće čimbenike ispunjavamo dugoročne ciljeve liječenja kroz postizanje kontrole simptoma te smanjenje rizika za po- goršanja i nepovratna oštećenja bronha/komplikacija liječenja. U preostale djece, u koje primjena ovih mjera ne dovodi do usposta- ve kontrole, radi se o teškoj, na terapiju rezistentnoj astmi. U njih slijedi, kroz odr, Severe asthma is considered a complex and heterogeneous disease, which includes different phenotypes, defined in terms of both clinical and molecular characteristics and underlining endotypes. It is estimated that severe asthma affects 2-5% of all children with asthma. It occurs more frequently in children older than ten years of age, with a slight prevalence among the male sex. Although severe asthma is uncommon, this group of children has an increased risk of drug side effects and life-threatening exacerbations that impair quality of life. Also, the financial burden from medication, scheduled and unscheduled doctor visits, hospitalizations and absence from school and work by parents have to be considered. There is no uniform definition of severe asthma, but the common characteristic is the need for maximal maintenance therapy, including high-dose inhaled steroids, long-acting beta-agonists, and/ or leukotriene receptor antagonists/theophylline. Despite the highest doses of maintenance therapy, patients with severe asthma fail to control the disease. Uncontrolled asthma has to be re-evaluated by confirming the diagnosis and modifying factors contribut- ing to symptoms and exacerbations like poor adherence, environmental risks (persistent allergen and pollutant exposure) and co- morbidities (upper airway disease, gastroesophageal reflux, obesity, anxiety). Children with poor asthma control due to misdiagnosed asthma, poor adherence or environmental risks have difficult-to-treat asthma, whereas children who still have poor control despite re-education to improve adherence and modification of environmen- tal risks have severe, therapy-resistant asthma. The approach to children with difficult-to-treat-asthma, which includes systematic evaluation and acting on modifying factors, enables achieving the long-term goals of asthma treatment in approximately two-thirds of patients. The remaining children, whose asthma is still uncontrolled despite optimized therapy, have seve

Teška astma je složena i heterogena bolest koja kliničara stavlja pred težak zadatak razlikovanja bolesnika prema rizičnim manife- stacijama bolesti (fenotipovi) i specifičnim patofiziološkim mehanizmima u podlozi bolesti (endotipovi), a sve u cilju odabira što učinkovitijeg liječenja prilagođenog potrebama pojedinog bolesnika. Dosadašnja istraživanja i pokušaji fenotipiziranja bolesnika s astmom, pa tako i teškom astmom, kod djece nisu dovela do jedno- značnog zaključka, osim već otprije poznatih činjenica da najveći dio djece ima atopiju s višestrukim preosjetljivostima (nerijetko kombinacija nutritivnih i aeroalergena, uloga plijesni), reverzibilnu bronhoopstrukciju i rane znakove remodelacije bronha. Samo mali broj djece ima trajnu bronhoopstrukciju (FEV1< 80%). Endotipovi teške astme ne razlikuju se od onih opisanih u astmi općenito: tip 2 (visoki Th2; eozinofili u serumu i sputumu, visoki IgE, FeNO; ključni citokini IL-4, IL-5, IL-13) i ne-tip 2 (niski Th2, neutrofilna, pau- cigranulocitna ili miješana upala; ključni citokini IL-8, IL-17, IL-22). Tip 2 je češći endotip kod djece i za njega postoji dostupna i odo- brena biološka terapija (anti-IgE i anti-IL-5). Ne-tip 2 je rjeđi endotip, obilježen općenito ograničenim terapijskim opcijama, među kojima se razmatra primjena azitromicina. Teška astma, iako kod djece rijetko zastupljena, predstavlja rizični fenotip koji ozbiljno narušava kvalitetu života. Pažljivo praćenje bolesnika i određivanje temeljnog endotipa omogućuje izbor i primjenu ciljanog i personaliziranog liječenja., Severe asthma is considered a complex and heterogeneous disease, which includes different phenotypes, defined in terms of both clinical and molecular characteristics and different underlining endotypes. According to different studies, there are several clinical phenotypes of severe asthma in children. Most children are allergic to multiple aeroallergen sensitization (house dust mites, pollen, molds) and have high levels of total and specific IgE, reversible airflow obstruc- tion and early signs of remodelation. A small subgroup of children has persistent airflow limitation (FEV1 <80% predicted). There are two major underlining functional or pathophysiologic mechanisms for different phenotypes of asthma and severe asthma accord- ing to the immune mechanism: Type 2 asthma (Th2-high asthma, eosinophils in serum and sputum, high IgE levels, high FeNO; key cytokines IL-4, IL-5, IL-13) and non-Type 2 asthma (Th2-low asthma, neutrophilic, paucigranulocytic and mixed granulocytic inflam- mation; key cytokines IL-8, IL-17, IL-22). The type 2 asthma endotype is more common in children, while biomarkers involved in the pathogenesis, such as IgE and IL-5 have become targets for biological therapy. The non-type 2 asthma endotype, less frequent in children with severe asthma, has fewer therapeutic options. The effect of azithromycin is still under investigation. Severe asthma, although uncommon, is a complex and high-risk phenotype of childhood asthma. Close monitoring of the patient and precise definition of underlying endotype during evaluation enables identification and use of personalized, endotype-targeted treatment.