2.1.1 Evidence from the lab linking allergic inflammation to increased risk of chronic rhinosinusitis in children.
All studies included in a qualitative analysis support a specific link between CRS and AR in children (Table III). Chawes(45)studied nasal eosinophilia and nasal airway patency (assessed by acoustic rhinometry) in children with AR, non-allergic rhinitis and healthy controls. Nasal eosinophilia and irreversible nasal airway obstruction were significantly associated with AR, whilst there was no such association with non-allergic rhinitis. The authors suggested that chronic inflammation and structural remodeling of the sino-nasal mucosa may occur in allergic children even at 6 years of age.
Some authors suggested that allergic sino-nasal inflammation may support bacterial infection. Blair et al.(46) in an animal model showed that allergic inflammatory reaction may obstruct sinus drainage encouraging bacterial infection into the maxillary sinus. Shin et al.(47) demonstrated that total IgE, total eosinophil count, and serum eosinophil cationic protein levels were significantly higher in CRS children whose symptoms and radiologic abnormalities did not resolve after 12 weeks despite appropriate antibiotic therapy (non-responder) compared with responders and healthy controls. Moreover, AR in children may affect the efficiency of mucociliary clearance, which is one of the most important protective functions of the respiratory epithelium. Deterioration of muco-ciliary system appears to be related to more severe rhinitis with a higher intensity of local nasal inflammation, reflected in nasal smear eosinophilia(48).
Brożek-Mądry and co-workers(49) evaluated the relation between bacterial strains and cytological examination of nasal mucosa in children with CRS; they found that the most common strains of bacteria observed in CRS (Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus) were associated with a higher prevalence of atopy and percentage of eosinophils in cytology. It must be noted that S. aureus enterotoxins are able to induce increased severity of the disease, amplifying eosinophilic inflammation in atopic patients(50).
Clinical evidence linking allergic inflammation to increased risk of chronic rhinosinusitis.
The association between allergy and CRS in adults has been discussed for years and a strong association has been observed with particular subtypes of CRS with nasal polyps (wNP), such as central compartment atopic disease and allergic fungal rhinosinusitis(51,52). Manuscripts on pediatric CRS are less common predominantly because of ethical issues regarding administration of X-rays in the pediatric population. The publications included in the qualitative analyses are summarized in Table IV. Conclusions of the studies included in the qualitative analyses were not unanimously linking allergy to chronic rhinosinusitis.
Several manuscripts seem to support a positive clinical association between AR and CRS, describing a prevalence varying between 27% and 59% of patients(53,54,55). Brietzke et al.(56) in an expert panel consensus, suggested that there is a clinically-relevant association between AR and pediatric CRS, particularly in older children. Sedaghat et al.(57), analyzing a large series of 4044 pediatric cases, observed that AR is one of the most prevalent comorbidity observed in children with CRS (26.9%) even though a comparison with control group was not provided. Choi et al.(34) showed that age, atopy, AR, and asthma may be predisposing factors for pediatric CRS and recurrent RS. The authors proposed that specific evaluation for allergic diseases should be considered when managing chronic or recurrent RS. More recently, Anamika et al.(58) demonstrated a positive skin prick-test in 53% of the cases in a cohort of 110 children with CRS; moreover, those with atopy had higher mean Lund-Mackay endoscopic score and Sinus and Nasal Quality of Life Survey score than non-atopic patients.
Huang et al.(59) attempted discrimination among different allergies and reported that mold allergy represents a significant risk factor for development of sinusitis, compared to non-mold allergy, in a case series of 413 children followed for 5 years. These data suggest that perennial allergy may be a stronger risk factor for CRS compared to seasonal allergy.
On the other hand, some studies suggested a lack of correlation between allergic disease and pediatric CRS. Leo et al.(60), in a report on 351 children affected by CRS, demonstrated that the prevalence of sensitization to aeroallergens was comparable to that of the general pediatric population. No clinical evidence could account for a higher rate of nasal congestion, nor a harsher clinical course, in allergic children(61). Sedaghat et al.(53, 62) observed that pediatric patients with AR and CRS seem to have the same aeroallergen sensitivity profile compared to the general pediatric population with AR. Furthermore, the authors did not find a positive association between the number of aeroallergen sensitivities or the presence of atopic comorbidities with the subsequent development of CRS, suggesting that the severity of atopy alone may not be positively predictive of CRS development. These articles were not included in the qualitative analyses due to the type of article.