Therapeutic options of post-COVID-19 related olfactory dysfunction: a systematic review and meta-analysis.

BACKGROUND: Olfactory dysfunction is a typical post-COVID-19 presentation, affecting patients' quality of life. There are currently multiple treatment options in this group of patients such as oral and intranasal corticosteroids, olfactory training, oral vitamin-mineral supplementation, amongst others. This meta-analysis aims to consolidate existing evidence for current therapies in patients with persistent olfactory dysfunction related to COVID-19 infection and evaluate the possible role of corticosteroid add-on therapy in olfactory training. METHODOLOGY: A systematic review and meta-analysis to study current treatments/interventions for olfactory dysfunction in post-COVID-19 infection were conducted. Data were pooled for the meta-analysis. The outcomes include subjective or objective olfactory assessment major and minor adverse reactions. RESULTS: Eleven studies (1414 participants) were included in this review, with six studies (916 participants) then assessed for the meta-analysis. Combined treatment of intranasal corticosteroid (INCS) with olfactory training (OT) has no benefit over OT monotherapy from both a VAS score improvement and identification component of Sniffin' Sticks test standpoint. In addition, there were no differences in improvement of TDI score between combined oral corticosteroid (OCS) with OT therapy compared to OT alone. Olfactory function was, however, significantly improved after OT. CONCLUSION: There were no significant differences in the improvement of olfactory scores in combination INCS+OT or OCS+OT therapies compared to OT monotherapy. However, there is improvement in olfactory function after OT.

As-needed intranasal corticosteroid spray for allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: As-needed intranasal corticosteroid spray (INCS) is commonly used by patients with allergic rhinitis (AR) who have suboptimal symptom control. This systematic review aimed to assess the effectiveness of as-needed INCS for treating AR. METHODOLOGY: Systematic searches for randomized controlled trials studying the effects of as-needed INCS compared to regular INCS, as-needed antihistamine, or placebo were performed. Primary outcomes were total nasal symptom score (TNSS) and disease-specific quality of life (DSQoL). RESULTS: Eight studies (882 participants) met the criteria. Regular use of INCS showed greater improvements than as-needed INCS in TNSS, DSQoL, nasal peak inspiratory flow, sneezing, and nasal congestion scores with small effect sizes. There were no differences between regular and as-needed INCS usage for ocular symptoms, symptom-free days, nasal itching, and rhinorrhea scores. As-needed INCS was superior to as-needed antihistamine and placebo with medium effect sizes. There were no differences in risk of adverse events between the groups in all three comparisons. CONCLUSIONS: Regular use of INCS improved total nasal symptoms score and DSQoL better than as-needed INCS. However, as-needed INCS improved TNSS better than as-needed antihistamine and placebo. The effects of as-needed INCS were closer to regular INCS usage than to placebo or as-needed AH usage.

Allergen-specific immunotherapy for local allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of chronic rhinitis exhibiting a local Th2-driven inflammation without positive clinical markers of atopy. Immunomodulatory effects of allergen-specific immunotherapy (AIT) induce allergen-specific tolerance. However, AIT is not well-recognized as a treatment for LAR. METHODOLOGY: Systematic search on six electronic databases and registries was performed. Experimental and observational studies of AIT for LAR patients were retrieved. The primary outcomes were symptom score, medication score, combined symptom medication score, and disease-specific quality of life. Secondary outcomes were serum specific(s) IgG4, sIgE, and adverse events. RESULTS: Four double-blind randomized controlled trials (156 patients) from two research units assessed the effects of subcutaneous immunotherapy (SCIT). Compared with placebo, SCIT showed significant reductions in symptom score, medication score, combined symptom medication score, disease-specific quality of life, and an increase in serum sIgG4. There was no significant change in serum sIgE. Likewise, two observational studies (one using SCIT and one using sublingual immunotherapy) improved post-therapeutic symptom score. No studies assessed the effects after discontinuation of treatment. AIT was safe without serious adverse events. CONCLUSION: AIT has beneficial effects and safe for LAR. Its effects are restricted to studies with short-term follow-up. AIT may be considered in LAR patients.

Prolonged breastfeeding and protective effects against the development of allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: There is insufficient evidence to confirm the protective effects of prolonged breastfeeding against the development of allergic rhinitis (AR). METHODOLOGY: A systematic review and meta-analysis was performed to assess the associations between prolonged breastfeeding and AR symptoms later in life. Comparisons were conducted between breastfeeding durations less than 6 months and 6 months or more and between less than 12 months and 12 months or more. Exclusive breastfeeding and nonexclusive breastfeeding were analysed separately. Outcomes were risks of AR development later in life. RESULTS: Twenty-three observational studies (161,611 children, age 2-18 years, 51.50% male) were included. Two studies (9%) were with high quality. Both exclusive and nonexclusive prolonged breastfeeding (6 months or more) decreased the risk of AR. The long-term (12 months or more) nonexclusive breastfeeding lowered the likelihood of AR compared to the 12 months or fewer. The long-term exclusive breastfeeding did not show the same protective effect; however, this result was restricted to only one study. CONCLUSIONS: Exclusive breastfeeding and nonexclusive breastfeeding for 6 months or more may have protective effects against the development of AR up to 18 years of age. The findings should be interpreted with caution given the limitation of low-quality observational studies.

Predictive factors for identifying macrolide responder in treating chronic rhinosinusitis.

BACKGROUND: Low-dose macrolides (LDM) are anti-inflammatory agents with antineutrophilic activity, but patient selection for LDM therapy in treating chronic rhinosinusitis (CRS) is controversial. This study aimed to assess factors which predict LDM responders. METHODOLOGY: A prospective cohort study was performed. Patients with CRS received roxithromycin (150 mg) once daily for 12 weeks. Nasal secretions and serology were collected. Nine predictors for LDM response were assessed: nasal secretion IgE, nasal secretion IL-5, serum IgE, serum eosinophils, serum neutrophils, nasal polyps, asthma, allergy, and aspirin hypersensitivity, using receiver-operating curve analysis and multivariable logistic regression. Macrolide responders were those with sino-nasal outcome test-22 improvement, symptoms visual analogue scale decreased to ≤ ≤ ≤5, and no rescue medication. RESULTS: One hundred CRS patients (mean age 47.4 +- 14.1 years, 45% male) were enrolled. Univariable logistic regression showed local total IgE less than 5.21; and serum eosinophils less than 2.2% associated with macrolide response. Multivariate models showed local total IgE maintained an independent association with macrolide response, with an ability to discriminate between responders and non-responders of 63%. Serum total IgE, nasal secretion IL-5, serum neutrophil, nasal polyp, asthma, allergy, and aspirin hypersensitivity showed no association with LDM response. CONCLUSIONS: Low total IgE level in the nasal secretion but not in the serum, predict LDM response.

Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis.

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a new route of allergen-specific immunotherapy. Data confirming its effect is restricted to a small number of studies. METHODOLOGY: A systematic review with meta-analysis was conducted. The short-term (less than 24 weeks), medium-term (24-52 weeks), and long-term (more than 52 weeks) effects of ILIT in patients with allergic rhinoconjunctivitis (ARC) were assessed. The outcomes were combined symptom and medication scores (CSMS), symptoms visual analog scale (VAS), disease-specific quality of life (QOL), specific IgG4 level, specific IgE level, and adverse events. RESULTS: Eleven randomized controlled trials and 2 cohorts (483 participants) were included. Compared with placebo, short term benefits of ILIT for seasonal ARC improved CSMS, improved VAS and increased specific IgG4 level but did not change QOL or specific IgE level. Medium-term effect improved VAS. Data on the long-term benefit of ILIT remain unavailable and require longer term follow-up studies. There were no clinical benefits of ILIT for perennial ARC. ILIT was safe and well-tolerated. CONCLUSION: ILIT showed short-term benefits for seasonal ARC. The sustained effects of ILIT were inconclusive. It was well tolerated.

Leukotriene receptor antagonist addition to intranasal steroid: systematic review and meta-analysis.

BACKGROUND: Intranasal corticosteroids (INCS) and leukotriene receptor antagonist (LTRA) have different mechanisms of action. The combination of INCS and LTRA (INCS+LTRA) are utilized to control the allergic rhinitis (AR) symptoms. The effects of this com- bination have not been made evident yet. METHODOLOGY: Randomized controlled trials studying the effects of INCS+LTRA vs INCS in monotherapy on rhinoconjunctivitis symptoms in patients with AR were included. Data were pooled for meta-analysis. The outcomes were nasal symptoms, ocular symptoms, disease-specific quality of life (QOL), and adverse events. RESULTS: Six studies (358 participants) met the inclusion criteria. There were no differences between INCS+LTRA and INCS mono- therapy on composite nasal symptom score, total daytime symptom score, total night time symptom score, disease-specific QOL and adverse events. The results favoured the effects of INCS-LTRA on ocular symptoms. CONCLUSIONS: The effects of the INCS+LTRA combination are not different from INCS in monotherapy in the improvement of both nasal symptoms and patient's QOL. The combination may, however, be better on improving ocular symptoms.

The use of steroids to reduce complications after tonsillectomy: a systematic review and meta-analysis of randomized controlled studies.

OBJECTIVES: To systemically review and compare the efficacy of intravenous, local, and oral steroids in decreasing post-tonsillectomy pain, nausea, and vomiting, and its risk of causing hemorrhage. METHODS: We searched electronic databases (PubMed, Scopus, Cochrane Library) and additional sources. The date of the most recent search was June 20th, 2018. We selected RCTs of steroids in all routes of administration, in all age groups who underwent tonsillectomy or adenotonsillectomy and studied the results of nausea/vomiting, pain, and hemorrhage. Data analysis was done using Review Manager 5.3.5 software. RESULTS: We included 64 studies (6,327 participants) with variety quality assessed by the Cochrane Handbook for Systematic Reviews of Interventions. IV steroids statistically and clinically significant decrease post-tonsillectomy nausea/vomiting in children and adult, with superior effect to local steroids (Children: OR 0.21; 95% CI 0.15-0.30; P < 0.001, I2 = 67%, Adult: OR 0.32; 95% CI 0.16-0.67; P = 0.002, I2 = 40%). In the analysis of local steroids studies, there was only evidence in children that local steroids decrease post-tonsillectomy nausea/vomiting (OR 0.54; 95% CI 0.33-0.88; P = 0.01, I2 = 32%). IV and local steroids statistically significant decrease immediate post-operative pain severity. Local steroids had extended effect in reducing pain scores on the first day after tonsillectomy. However, the clinical significance of pain relief had to be concerned due to decreasing VAS only about 1 out of 10. Adding oral steroids to IV steroids gave no difference in effect from IV steroids alone. There are very few local steroids studies in adults and oral steroids studies to show the significant effects. Steroids have no statistically significant effect in reducing pain severity after a 1-day period. Steroids in all routes had no statistically significant effects on post-operative hemorrhage (primary hemorrhage: OR 0.96; 95% CI 0.55-1.67; P = 0.88, I2 = 0%; secondary hemorrhage: OR 1.05; 95% CI 0.74-1.51; P = 0.79, I2 = 0%). CONCLUSION: Intravenous steroids statistically significantly decrease post-tonsillectomy nausea/vomiting, and immediate pain scores (< 24 h) in children and adults. There is evidence in only children that local steroids statistically significantly decreases post-tonsillectomy nausea/vomiting, and pain scores during the 0-h to 1-day period.

EPOS2012 has better specificity compared to IDSA2012 for diagnosing acute bacterial rhinosinusitis.

BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a subtype of acute rhinosinusitis (ARS). To prevent excessive antibiotic prescribing, clinical criteria for diagnosing ABRS are presented in two major international guidelines from European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2012) and the Infectious Diseases Society of America (IDSA2012). This study aims to assess accuracy of these criteria. METHODOLOGY: Patients with ARS were recruited. Clinical features were collected including discolored nasal discharge, facial pain, fever, double sickening, symptoms persisting longer than 10 days, and elevated serum C reactive protein (CRP) and erythrocyte sedimentation rate (ERS). Using middle meatal bacterial culture as a reference, accuracy of EPOS2012 and IDSA2012 criteria were analyzed. RESULTS: Eighty-eight patients (age 43.2+/-14.5 years, 67% female) with ARS were recruited. Using the two criteria for diagnosing ABRS, EPOS2012 and IDSA2012 have sensitivity of 50% (95%CI: 38%-62%) versus 69% (95%CI: 57%-79%), specificity of 63% (95%CI: 43%-79%) versus 46% (95%CI: 28%-65%), and accuracy of 53% versus 63%, respectively. CONCLUSION: Both EPOS2012 and IDSA2012 had modest accuracy. EPOS2012 had less sensitivity but a better specificity compared to IDSA2012. This suggests that IDSA2012 diagnostic criteria may contribute to inappropriate use of antibiotics due to poorer specificity.

Antihistamines for treating rhinosinusitis: systematic review and meta-analysis of randomised controlled studies.

BACKGROUND: Without the release of histamines, patients with rhinosinusitis may not benefit from antihistamines. Additionally, anticholinergic effects may do more harm than good. This study aimed to investigate the effectiveness of antihistamines in treating rhinosinusitis. METHODS: An electronic search was performed. Randomised controlled trials comparing antihistamines with either placebo or other treatments for patients with rhinosinusitis were selected. RESULTS: Two studies (184 patients) met the inclusion criteria. Loratadine decreased nasal obstruction in allergic rhinitis patients with acute rhinosinusitis (mean difference = -0.58; confidence interval = -0.85 to -0.31, p < 0.01), but had no benefit on total symptom score (mean difference = -1.25; confidence interval = -2.77 to 0.27, p = 0.11), or rhinorrhoea symptoms (mean difference = -0.06; confidence interval = -0.37 to 0.25, p = 0.71). CONCLUSION: There is limited evidence to support the use of antihistamines in treating rhinosinusitis. The number of included studies in this systematic review is limited. Antihistamines may relieve nasal obstruction in allergic rhinitis patients with acute rhinosinusitis.