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Wise et al.

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can include local irritation, ear pain, nosebleeds, headache, nasal burning, nasal drainage, and bottle contamination. 1417 • Aggregate Grade of Evidence: A (Level 1a: 1 study; Level 1b: 11 studies; Table IX.B.8-1 and IX.B.8-2). Lower-level studies were not considered in this review. • Benefit: Reduced nasal symptom scores, improved QOL, improved mucociliary clearance; well tolerated with excellent safety profile. • Harm: Intranasal irritation, headaches, ear pain. • Cost: Minimal. • Benefits-Harm Assessment: Preponderance of benefit over harm. • Value Judgments: Nasal saline should be used as an adjunct to other pharmacologic treatments for AR. Isotonic solutions may be more beneficial in adults, while hypertonic may be more effective in children. • Policy Level: Strong recommendation. • Intervention: Nasal saline is strongly recommended as part of the treatment strategy for AR. IX.B.9. Probiotics— The relationship between microbiome and development of atopy is complex and incompletely understood. (See section IV.G. Pathophysiology and mechanisms of allergic rhinitis - Microbiome for additional information on this topic.) Preliminary data from observational studies suggest that microbial exposure, especially in infancy, shapes the gut and airway microbiome and affects subsequent Th2 or Th1 immunologic bias. Given the link between gut flora and atopy, manipulation of the microbiome via probiotic administration could theoretically lead to clinical improvement of allergic disease. Probiotics have been posited to elicit immunomodulatory effects on atopic disease via gut-associated lymphoid tissue. Stimulation of dendritic cells induces Th1 responses via IL-12 and IFN- γ , upregulation of Treg cells via IL-10 and TGF- β , and suppression of Th2 pathways through downregulation of IL-4, sIgE, IgG1, and IgA. 1418 The optimal timing of probiotic administration for the treatment of atopy is unknown. A meta-analysis of 17 double-blind RCTs demonstrated that probiotics in pregnancy and early infancy were associated with decreased incidence of eczema but not asthma or rhinosinusitis in early childhood. 1419 Many double-blind RCTs and randomized crossover studies have investigated the effects of probiotics on AR in older children and adults (Table IX.B.9). Meta-analyses of these studies have been published in 2015 by Zajac et al. 1420 and 2016 by Guvenc et al. 1421 with positive results. Adverse events due to probiotics were rare and minor, including diarrhea, abdominal pain, and flatulence. Guvenc et al. 1421 performed a systematic review and meta-analysis of 22 double-blind RCTs comprising 2242 patients aged 2 to 65 years with SAR or PAR. Patients received daily probiotic or placebo for 4 weeks to 12 months as an adjuvant to standard allergy therapies; primary outcomes included Total Nasal/Ocular Symptom Scores and QOL. Secondary outcomes included specific nasal symptom scores and immunologic parameters. Seventeen

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.