Iva Mrkić Kobal

Background: T2 low asthma in children is an emerging yet underexplored endotype that challenges traditional views of type 2 inflammation. Recent data suggest that it is more prevalent than previously thought and is defined by low type 2 biomarkers, non-allergic clinical profiles, and strong associations with modifiable comorbidities such as obesity, passive smoke exposure, and recurrent respiratory infections. This phenotype often shows a poor response to standard inhaled corticosteroid therapy and T2-targeted biologics, underscoring the urgent need for improved diagnostic and therapeutic approaches. Methods: This narrative review conducted a literature search from PubMed and WoS databases (2020–2025), focusing on T2-low asthma defined by low blood eosinophils (<150–300/µL), FeNO (<20–25 ppb), and absent atopy in children under 18. Results: This review highlights the heterogeneity of T2-low asthma, including subtypes from neutrophilic/Th 17-high to paucigranulocytic airway remodeling and metabolic driven forms, as well as diagnostic challenges from biomarker supresssion by high-dose therapies. Pragmatic phenotyping algorithms using routine tests enable identification, directing comorbidity management over ineffective biologics. Conclusions: Systematic T2-low phenotyping in pediatric practice, alongside prospective studies and non-T2 therapy trials, promises precision medicine to enhance outcomes for these children, moving beyond eosinophil-centric care.

Type -2 (T2) low asthma in children represents a clinically important yet still insufficiently recognized endotype. Current data suggest that it is more prevalent than previously thought and is defined by low type 2 biomarkers, non-allergic clinical profiles, and a high burden of comorbidities such as obesity and passive smoke exposure, while remaining largely understudied phenotype in terms of validated biomarkers and specific targeted therapies. This review aims to highlight and clarify T2-low asthma in children by summarizing emerging evidence on risk factors, pathophysiological mechanisms, bi-omarkers, and treatment strategies, with the goal of informing and improving future care for affected children.

Food allergies are becoming more common globally. The strict elimination diet, as the main approach so far, has a negative impact on different areas of the lives of children suffering from food allergies, as well as on their caregivers. Oral immunotherapy (OIT), which consists of ingesting small, gradually increasing amounts of food allergens, is a promising approach. Although efficient, this approach is accompanied by frequent adverse reactions (AR), some of which are as severe as anaphylaxis. It seems that, generally, slow dose escalation, as well as low maintenance doses with longer durations, make OIT safer, especially in children with severe food allergies. Furthermore, less allergenic forms of allergens, such as baked milk or egg, also contribute to OIT safety. Adjuvant therapy in combination with OIT has the potential to improve OIT efficiency and safety. Treatment with monoclonal antibodies such as omalizumab and dupilumab in combination with OIT is promising. While both could improve efficiency, omalizumab seems to have a better effect on safety. Interferon γ shows promising results. In contrast, the effect of probiotics and vitamin D supplementation in combination with OIT is still controversial, and new trials about their synergistic effect are needed.

Asthma is a chronic lung disease characterized by reversible bronchoconstriction and inflammation of the bronchi. Its increasing prevalence in childhood as well as different triggers make asthma a challenging disease in several ways: defining its phenotype/endotype, the diagnostic approach (especially in younger children), therapeutic options, and systematic follow-up. Considering these problems, this review approaches the current status and limitations of guidelines used for asthma management in children. It also emphasizes the key points which could lead to a better understanding and the direction to take in future studies.

Tijekom posljednjeg desetljeća napredak u razumijevanju patogenetskih mehanizama alergijskih bolesti doveo je do razvoja molekularno specifičnih lijekova, tzv. bioloških lijekova koji su se pokazali učinkovitima u liječenju na dosadašnju terapiju ref...

The atopic march encompasses a sequence of allergic conditions, including atopic dermatitis, food allergy, allergic rhinitis, and asthma, that frequently develop in a sequential pattern within the same individual. It was introduced as a conceptual framework aimed at elucidating the developmental trajectory of allergic conditions during childhood. Following the introduction of this concept, it was initially believed that the atopic march represented the sole and definitive trajectory of the development of allergic diseases. However, this perspective evolved with the emergence of new longitudinal studies, which revealed that the evolution of allergic diseases is far more intricate. It involves numerous immunological pathological mechanisms and may not align entirely with the traditional concept of the atopic march. The objective of our review is to portray the atopic march alongside other patterns in the development of childhood allergic diseases, with a specific emphasis on the potential for a personalized approach to the prevention, diagnosis, and treatment of atopic conditions.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase (NOS) enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nNO measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD, and CF based on the latest literature. nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD, and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis and acute and chronic rhinosinusitis.

Aim: The authors conducted two cross-sectional studies 8 years apart with the aim of assessing temporal trends in the prevalence of asthma and atopic diseases in Međimurje County, Northwestern Croatia.Methods: Studies were conducted in children aged 12 years 0 months to 14 years 11 months in 2005 and in 2013; additionally, in adolescents aged 18 years in 2013 according to the international study on asthma and allergies protocol.Results: In the age group 12–14 years, a significant increase in the prevalence of asthma (5.1% vs 8.31%), allergic rhinitis (10.86% vs 16.24%), allergic rhinoconjunctivitis (7.14% vs 10.95%) and atopic dermatitis (5.34% vs 8.12%) was observed. When the age group 12–14 years in 2005 was compared with the age group 18 years in 2013, a significant increase in symptoms of asthma (5.1% vs 11.5%), allergic rhinitis (10.86% vs 19.59%), allergic rhinoconjunctivitis (7.14% vs 14.25%), and atopic dermatitis (5.34% vs 7.69%) was observed.Conclusion: This study shows an increasing trend in Međimurje County in the prevalence of all symptoms associated with atopic diseases: Asthma, allergic rhinitis, allergic rhinoconjunctivitis, and atopic dermatitis.

Our aim was to assess the differences in intraregional prevalence of asthma in adolescents in Split-Dalmatia County to determine asthma risk factors in our population and estimate the specificity and sensitivity of the questionnaire used. We conducted the study using the European Community Respiratory Health Survey II short questionnaire supplemented by some questions from the International Study of Asthma in Childhood questionnaire. The participants suspected to have asthma were invited for examination by an asthma specialist who established the final diagnosis of asthma according to the medical history, physical examination, skin-prick tests, and peak flow measurements. A total of 4027 students (51.2% male) participated in the study. According to the prevalence of wheezing during the last 12 months, asthma prevalence was estimated at 9.7%. The total prevalence of asthma confirmed by an asthma specialist in the selected population was 5.60% (95% CI, 4.93–6.36%); 6.18% in Split (95% CI, 5.37–7.09), 5.63% in Imotski (95% CI, 3.48–8.58), and 2.90% in Sinj (95% CI, 1.67–4.68) (P=0.0028). We found sensitization to aeroallergens and peanuts, and active smoking to be independent risk factors for asthma. Split-Dalmatia County has moderate asthma prevalence, with a significant intraregional difference. Asthma prevalence estimated by a questionnaire (9.7%) overestimates the prevalence of asthma confirmed by an asthma specialist (5.6%) in adolescents in Croatia. Our data confirmed the need of a more complex questionnaire to evaluate the accurate prevalence of current asthma or the need for subsequent clinical evaluation of the questionnaire obtained data. Allergic sensitization to aeroallergens and active smoking were important risk factors for asthma.