Table 2.

Articles investigating clinical association between allergy and upper respiratory infections

Clinical evidence linking allergy to risk of upper respiratory tract infections
Author Year (ref)	Type of article	No. of cases (mean age)	Methods	Relevant results	Association (Level of evidence)
Karevold et al. 2006 [19]	Cross-sectional survey	N = 5125 (10 years)	Assess co-morbidity and risk factors for recurrent upper and lower respiratory infections	Atopic disease was a constitutional risk factor, for upper and lower airway infections	Yes (Level IV)
Ciprandi et al. 2009 [20]	Prospective study	N = 117 (4.02 ± 1.0 years); 46 allergic	Evaluate the number and duration of RI in allergic and non-allergic children	Allergic children showed a significantly higher number (mean 1.26 ± 0.73) and longer duration of RI (8.92 days) in comparison with non-allergic group (0.94 ± 1.37 and 4.85 days)	Yes (Level II)
Kværner et al. 1996 [21]	Retrospective analysis	N = 7992 (mean age not known)	Estimate comorbidity between ear infections, tonsillitis, sinusitis and related childhood diseases	The correlation between the infectious and atopic diseases was weak	Inconclusive (Level IV)
Sütçü et al. 2016 [22]	Retrospective analysis	N = 507 children (46, range 4–190, months)	Evaluate children presenting with the complaint of recurrent infections and to determine the possible predictive factors	Atopic children had longer episodes of recurrent URTI compared to controls; however, the number of episodes per year was not significantly different	No (Level IV)
Role of anti-allergy treatment in preventing upper respiratory infections
Ciprandi 1999 [20]	Double-blind and placebo-controlled study	N = 20 children with allergy; 10 terfenadine group (8.5 ± 3 years); 10 placebo (7.9 ± 2.7 years)	Continuous terfenadine (1 mg/kg per body weight per day) vs placebo for 1 year. Outcome: Symptoms; inflammatory cells and ICAM-1 measured by nasal scraping	Terfenadine treatment reduces ICAM-1 expression on nasal epithelial cells; children treated with terfenadine had significantly fewer extra visits and school absences than the placebo group	Yes (Level I)
Fasce 1996 [14]	Double-blind, placebo controlled randomized study	N = 20 children (5–14 years old) with mite allergy	Cetirizine vs placebo for 15 days. Nasal scrapings were performed to evaluate inflammatory cell infiltration and ICAM-I expression on epithelial cells	Cetirizine-treated children showed a significant reduction (or even total absence) of ICAM-I expression on epithelial cells (p = 0.002) and a reduction trend in inflammatory cell counts compared with placebo	Yes (Level I)
Barebri 2015 [25]	Prospective case control observational study, not randomized	N = 40 HDM allergic children (9.3 years)	Patients were subdivided in 2 groups: 20 treated by symptomatic drugs and 20 by high-dose HDM-SLIT	SLIT-treated children had significantly (p = 0.01) less RI episodes (3.5) than control group (5.45)	Yes (Level II)
Barberi 2018 [24]	Retrospective analysis	N = 33 HDM allergic children (9.3 years)	Investigate whether 3 year high-dose HDM-SLIT affects respiratory infections in children with allergic rhinitis	SLIT-treated children had significantly fewer RI episodes than symptomatically treated children. In addition, they had less fever and took fewer medications, such as antibiotics and antipyretics	Yes (Level IV)

HDM, house dust mites; SLIT, sub-lingual immunotherapy; URTI, upper respiratory tract infections; RI, respiratory infections; ICAM, intercellular adhesion molecule