Natural course and comorbidities of allergic and nonallergic rhinitis in children

doi:10.1016/j.jaci.2011.09.036

Journal of Allergy and Clinical Immunology

Volume 129, Issue 2, February 2012, Pages 403-408

https://doi.org/10.1016/j.jaci.2011.09.036 Get rights and content

Background

Not much data are available from large, unselected, birth cohort studies on the natural course and comorbidities of rhinitis in children.

Objective

To study phenotypes of rhinitis in relation to the natural course and comorbidities of allergic diseases in preschool-age and early school-age children.

Methods

We analyzed data from a birth cohort of 2024 children, for whom information on IgEs against 8 common inhaled allergens was available, collected at age 4 and 8 years. The children were assigned to groups of allergic rhinitis (rhinitis with sensitization to allergens), nonallergic rhinitis (rhinitis without sensitization), allergic sensitization but no rhinitis, or neither rhinitis nor sensitization.

Results

The proportion of children with allergic rhinitis increased from 5% to 14% from age 4 to 8 years, whereas the proportion of children with nonallergic rhinitis decreased slightly over the same period of development, from 8% to 6%. Of the children with allergic rhinitis when they were 4 years old, 12% underwent remission by the time they were 8 years old; of the children with nonallergic rhinitis, 73% underwent remission during this period of development. Among 4-year-olds without rhinitis who were sensitized to allergen, 56% had allergic rhinitis when they were 8 years old. Among 4- and 8-year-olds, allergic rhinitis and nonallergic rhinitis were associated with asthma, eczema, and food hypersensitivity. Twenty-five percent of 8-year-olds with allergic rhinitis also had oral allergy syndrome.

Conclusions

Fewer preschool-age children with allergic rhinitis undergo remission than do those with nonallergic rhinitis. Sensitization to inhaled allergens at an early age (4 years) precedes the development of allergic rhinitis, whereas symptoms of rhinitis do not. Oral allergy syndrome is common among 8-year-olds with allergic rhinitis.

Section snippets

Study design

We analyzed data from the population-based birth cohort Barn/Children, Allergy/Asthma, Milieu, Stockholm, Epidemiologic (BAMSE) study of 4089 children born from 1994 to 1996 in Stockholm, Sweden. The study design, enrolment procedure, and inclusion criteria are described in Wickman et al.¹⁶ In brief, children were enrolled at a median age of 3 months, and detailed information on background exposures was obtained. When the children were 1, 2, 4, and 8 years of age, they were sent questionnaires

Results

Baseline characteristics such as sex, parental history of allergic disease, or socioeconomic status did not vary between the 2024 children included in the study and the rest of the BAMSE cohort (4089 children; data not shown).

The prevalence values for ISAAC-rhinitis, ISAAC-rhinoconjuctivitis, nasal symptoms following exposure to allergen, sensitization to any inhalant allergen, and allergic rhinitis all increased significantly among children from age 4 to 8 years (Fig 1). Furthermore, the

Discussion

There seem to be different prognoses for 4-year-olds with allergic and nonallergic rhinitis, based on outcomes at age 8 years. Children with allergic rhinitis are more likely to have a persistent disease than are children with nonallergic rhinitis, who seem to remit. Among children with allergic rhinitis, sensitization to inhaled allergens seems to precede symptoms of rhinitis rather than symptoms of rhinitis preceding sensitization. OAS is common among school-aged children with allergic

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In adults, NAR was reported in 24.4% to 67.1% of participants with rhinitis.3 In children, NAR may be more prevalent in early life, with prevalence decreasing in older children compared with AR.4 Reported prevalence of NAR in school-age children ranges from 6% to 8% in a Swedish population4 to 25% in a Singaporean cohort.5
Chronic rhinitis encompassing both allergic and nonallergic rhinitis affects a significant portion of the population worldwide, having a great impact on patient quality of life, and associated comorbid conditions, with an important societal economic burden. Allergists are often the first to evaluate and treat allergic and nonallergic rhinitis, addressing the individual triggers of the disease as well as the patient-specific responses to these triggers. This review focuses on the advances that have been made in the diagnosis, management, and treatment of nonallergic and allergic rhinitis over the past 10 years, including specific allergen immunotherapy, care pathways, and digital health.
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Deinococcus radiodurans is an extremophile, well known to be extremely resistant to external stresses due to its unique physiological system and structure of cellular components. Although the proportion of D. radiodurans has been reported to be negatively correlated with atopic dermatitis, the exact function of D. radiodurans in allergic diseases and its precise mechanisms have not been studied. In the present study, we hypothesize that D. radiodurans or its cellular constituents play a critical role in the skin to prevent allergic inflammatory responses by modulating immunity. Heat-killed D. radiodurans inhibited the production of Th2 cytokines, such as IL-4 and IL-5, induced by ovalbumin (OVA) stimulation in splenocytes from OVA-sensitized mice. Among the cellular constituents of D. radiodurans, such as cell wall (DeinoWall), cell membrane (DeinoMem), and exopolysaccharide (DeinoPol), only DeinoWall inhibited the production of Th2 cytokines and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD), a Th2-predominant allergic disease in mice. Moreover, serum IgE levels and infiltration of mast cells into skin lesions, the markers of Th2 response induced by DNCB application, were significantly inhibited by treatment with DeinoWall. Remarkably, DeinoWall induced the maturation of bone marrow-derived dendritic cells (BMDCs) that promote Th1-biased immunity, which might balance Th1/Th2 and regulate allergic inflammatory responses. Collectively, these results suggest that DeinoWall acts as a major cellular constituent in the negative regulation of allergic inflammatory responses by D. radiodurans and might be a viable candidate for the treatment of allergic diseases.
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Clinical management may result in a small to moderate reduction of symptoms of AR. We included seven studies reporting the natural course of AR [30–36]. All studies reported on remission, while two also described the combined outcome measure “fewer symptoms or remission.”
To identify challenges in the application of GRADE for diagnosis when assessing the certainty of evidence in the test-treatment strategy (diagnostic accuracy, test burden, management effectiveness, natural course, linked evidence) in an illustrative example and to propose solutions to these challenges.
A case study in applying GRADE for diagnosis that looked at the added value of IgE for diagnosing allergic rhinitis.
Evaluation of the full test-treatment strategy showed a lack of (high-quality) evidence for all elements. In our example, we found a lack of evidence for test burden, natural course, and link between the test result and clinical management. Overall, systematically reviewing the evidence for all elements of a test-treatment strategy is more time-consuming than only considering test accuracy results and management effectiveness. For increasing efficiency, the guideline panel could determine critical elements of the test-treatment strategy that need a systematic review of the evidence. For less critical elements, a guideline panel can rely on gray literature and professional expertise.
A lack of high-quality evidence and time investment if the full test-treatment strategy is assessed, creating challenges in applying GRADE for diagnosis. Discussion within guideline panels about critical elements that need to be reviewed might help.
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At 4 years of age, the vast majority of grass pollen–sensitized children were still asymptomatic, highlighting an important window of opportunity for prevention of grass pollen allergy at this time point.30 Monosensitized children had a significantly higher risk for later symptoms than did nonsensitized children, reflecting the fact that sensitization per se is a risk factor for later symptoms.12,31,32 The probability of later symptoms increased with increasing number of allergen molecules, which is in line with other inhalant allergens.16,18
Grass pollen allergy is one of the most common allergies worldwide.
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Questionnaire data and sera obtained from the study subjects at the ages of 4, 8, and 16 years from the population-based Barn/Children Allergy Milieu Stockholm Epidemiology birth cohort were used. Sera from 763 representative subjects with serum samples available at all 3 ages were analyzed for IgE reactivity to 8 Phleum pratense (Phl p) allergens (MeDALL [Mechanisms for the Development of Allergies] chip) and to timothy grass extract (ImmunoCAP). Allergic rhinitis to grass pollen (ARg) was defined as upper airway symptoms during grass pollen exposure.
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Our understanding of the relationship between the upper and lower airways has greatly increased as a consequence of epidemiologic and pharmacologic studies. A consistent body of scientific evidence supports the concept that rhinitis, rhinosinusitis and asthma may be the expression of a common inflammatory process, which manifests at different sites of the respiratory tract, at different times. This paradigm states that allergic reactions may begin at the local mucosa, but tend to propagate along the airway. Central to the allergic diathesis is the eosinophil and its interaction with the airway epithelium. The implications of the interplay between upper and lower airway are not only academic, but also important for diagnostic and therapeutic reasons. Furthermore, there is significant overlap in symptomatology and pathophysiology for childhood sleep disordered breathing (SDB) and asthma. Recent evidence supports an association between these two conditions, but causality has not been demonstrated. Regardless, it is important to recognize the overlap and evaluate for the other condition when one is present. In children with poorly controlled asthma, the presence of SDB may significantly contribute to asthma morbidity and, as such, should be actively excluded. On the other hand, clinical evaluation for asthma should be considered in children with SDB.
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: This study was funded by the Stockholm County Council and the “FrimurareBarnhuset” Stockholm Foundation.

: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

View full text

Rhinitis, sinusitis, and upper airway diseaseNatural course and comorbidities of allergic and nonallergic rhinitis in children

Background

Objective

Methods

Results

Conclusions

Section snippets

Study design

Results

Discussion

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Allergy

The natural history of allergic rhinitis in childhood

Pediatr Allergy Immunol

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

Allergy

A survey of the burden of allergic rhinitis in Europe

Allergy

Rhinitis in children: co-morbidities and phenotypes

Pediatr Allergy Immunol

Rhinitis, sinusitis, and upper airway disease
Natural course and comorbidities of allergic and nonallergic rhinitis in children