Undifferentiated Connective Tissue Dysplasia and Microelement Imbalance as Determinants of Allergic Phenotype in Children with Bronchial Asthma: A Prospective Cross-Sectional Study

Abstract

Bronchial asthma (BA) remains poorly controlled in 30–40% of children despite guideline-based therapy, and undifferentiated connective tissue dysplasia (NDCT) and zinc/magnesium (Zn/Mg) deficiency may jointly amplify airway inflammation and allergen sensitisation. This study characterised molecular sensitisation, airway function and inflammatory phenotype in children with BA and comorbid NDCT, and assessed the relation of Zn and Mg depletion to disease severity. In a prospective cross-sectional study reported per STROBE, 98 children aged 7–18 years were enrolled at the International Allergy Centre, Tashkent State Medical University: BA+NDCT (n=32), BA−NDCT (n=34) and healthy controls (n=32). NDCT was graded with the modified Kadurina scale; component-resolved diagnostics used the ALEX2 multiplex array (>300 allergen molecules); spirometry (ATS/ERS 2019), FeNO (ATS 2011) and serum Zn/Mg were measured at enrolment. Children with BA+NDCT showed greater airway obstruction (FEV₁ 61.2±11.8% vs 74.8±13.2% predicted), higher FeNO (52.3±18.7 vs 34.6±15.2 ppb) and lower serum Zn (7.96±1.35 vs 10.08±1.57 µmol/L) and Mg (0.52±0.10 vs 0.74±0.10 mmol/L; all p<0.001). Polysensitisation was found in 84.4% vs 44.1% (OR 7.0; 95% CI 2.4–20.6; p<0.001). In multivariable regression, NDCT (adjusted OR 4.82; 95% CI 1.91–12.15) and Zn depletion (aOR 1.58 per µmol/L decrease; 95% CI 1.21–2.07) were independently associated with moderate-to-severe BA, and the combined NDCT+Zn+Mg model yielded AUC 0.88 (95% CI 0.81–0.95). NDCT combined with Zn/Mg depletion was associated with a distinct paediatric BA phenotype marked by polysensitisation, eosinophilic airway inflammation and greater airflow obstruction. These cross-sectional, hypothesis-generating findings warrant prospective testing of routine NDCT phenotyping and micronutrient profiling.