Development of Sensitization to Multiple Allergen Molecules from Preschool to School Age Is Related to Asthma

Abstract

Introduction: Allergic sensitization in early life has been identified as a strong risk factor for subsequent asthma in childhood. It is still unclear why only a part of sensitized children develop asthma, and the role of specific allergen molecules in asthma pathogenesis is ambiguous [Pharmacol Ther. 2009 Feb;121(2):174-84]. We assessed the sensitization to multiple allergen molecules longitudinally and explored its relation to persistent asthma at 7 years.

Methods: Seventy-two children included during an acute wheezing episode (cases) were followed prospectively from early preschool age (EPA) to age 7, and compared to 43 healthy controls at EPA. Allergen molecules were analyzed at EPA and age 7 using ImmunoCAP Solid-phase Allergen Chip (ISAC). Asthma diagnosis at 7 years was based on symptoms, medication, and spirometry.

Results: At EPA, cases compared to controls showed a tendency toward having a higher prevalence of allergic sensitization (23.6% vs. 9.3%, p = 0.055). The prevalence of sensitization increased in cases from EPA to 7 years (23.6% vs. 38.9%; p = 0.048) as well as the median number (range) of immunoglobulin E (IgE)-reactive molecules 3 (3-14) versus 6.5 (1-21); p = 0.024. Sensitization to each additional molecule from EPA to the age of 7 was significantly related to asthma at 7 (OR = 1.25, 95% confidence interval [1.01, 1.54]).

Conclusion: Polysensitization, assessed by allergen molecules, had a significant impact on persistent asthma at school age. The extent of sensitization, illustrated by molecular spreading from preschool to school age, was related to asthma diagnosis at 7 years in children with a history of wheezing at early life.

Keywords: Allergen molecules; Allergic sensitization; Asthma; Longitudinal; Polysensitization; Preschool wheeze.

Fig. 1

Flowchart GEWAC population included in the current study; the number of the cases and controls included in the different timepoints. ^#The group of cases with available sera at the first revisit and at 7 years (n = 65) was merged with 7 cases that provided sera at the emergency visit and at 7 years. Accordingly, the first timepoint of the longitudinal assessment of the cases is referred as the EPA. *Nasopharyngeal samples, **Complete Blood Counts.

Fig. 2

Trajectory of allergic sensitization in cases from EPA to the age of 7. The prevalence of allergic sensitization, sensitization to airborne molecules*, food molecules ** and to each of the highest ranked molecules at EPA and at 7 years in all included cases (N = 72) (a), in cases without asthma diagnosis at 7 years (N = 23) (b), and in cases with asthma diagnosis at 7 years (N = 49) (c). *Sensitized to at least one of the airborne molecules; Phl p 1, Phl p 2, Phl p 4, Phl p 5, Phl p 6, Phl p 11, Phl p 12, Aln g 1, Bet v 1, Cor a 1.01, Cry j 1sens, Cup a 1, Ole e 7, Ole e 9, Pla a 1, Pla a 2, Pla a 3, Art v 1, Art v 3, Mer a 1, Can f 1, Can f 2, Can f 3, Can f 5, Equ c 1, Fel d 1, Fel d 2, Fel d 4sens, Mus m 1, Alt a 6, Asp f 3, Asp f 6, Der f 1, Der f 2, Der p 1, Der p 2, Der p 10, Bla g 2, and Bla g 7. **Sensitized to at least one of the food molecules; Gal d 1, Gal d 2, Gal d 3, Gal d 5, Bos d 4, Bos d 5, Bos d 6, Bos d 8, Bos d L, Pen m 1, Pen m 2, Ana o 2, Ber e 1, Cor a 1.04, Cor a 8, Cor a 9, Jug r 1, Jug r 3, Jug r 2, Jug r 3, Ses i 1, Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, Ara h 9, Gly m 4, Gly m 5, Gly m 6, Act d 1, Act d 2, Act d 8, Api g 1, Mal d 1, Pru p 1, and Pru p 3.

Fig. 3

Box plots for the number of molecules with IgE reactivity per individual at EPA and at 7 years among all of the sensitized cases (a), and the sensitized cases without and with asthma at 7 years (b).

Fig. 4

a The difference in the number of allergen molecules with IgE reactivity per individual between EPA and the age of 7 and probability for asthma at 7 years. OR 1.248, 95% CI (1.011–1.540), p = 0.039; calculated by logistic regression in cases (N = 72). b The number of allergen molecules with IgE reactivity per individual at 7 years and probability for asthma at 7 years. OR 1.195, 95% CI (1.006–1.419), p = 0.043; calculated by logistic regression in cases (N = 72).