xRead - Nonallergic Rhinitis (September 2025)

15314995, 2023, 12, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/lary.30706 by University Of Chicago, Wiley Online Library on [15/07/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

Data Extraction The same reviewing authors reviewed the included arti cles for the study type, INIB dosage, frequency of administra tion, duration of treatment, number of patients in each arm, mean age, and measured outcome. The nasal symptom scores, the rhinorrhea severity scores, and the quality of life assess ments were evaluated. Adverse events (AE) were also exam ined. The main outcome was an assessment of the severity and duration of rhinorrhea following INIB use compared with pla cebo. The secondary outcomes were the improvement of other reported nasal symptoms and the assessment of quality of life with INIB. Extracted data from included articles was summa rized in the included table (Table I). This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. able information from studies that are dated and have limited data. To accomplish this, we digitized the published graphs and plots and extracted the approximate values using WebPlotDigitizer. 10 In four out of fi ve studies, the effect of IB or the vehicle was assessed over at least four dates, and an average was plotted. Therefore, we calculated the mean and SD (as standard errors) of the averages to approximate the population ’ s mean and SD, ignoring the in fl uence of different dates and assuming the therapeutic effect to be uniform. Fur thermore, speci fi c approximation methods for replacing missing covariance, variance, and SD were also used. 11 – 13 All meta-analyses were conducted utilizing R language, 14 speci fi cally the meta package. 15 Two methods were employed to calculate pooled estimates: a fi xed-effects analysis and a random effects analysis that considered any potential heterogeneity. To determine the heterogeneity of the data across studies, statistical assessments were performed using the Q-test statistic and I-square ( I 2 ). Moderate-to-high heterogeneity was de fi ned as p <0.10 and I 2 >50%. The impact of either treatment was analyzed for rhinorrhea severity, duration, and the proportion of patients judging the treatments “ good-to-excellent. ” The severity was scored differ ently between studies, so standardization of the scores and then transformation to a 0 – 1 was necessary. Subgrouping was done to compare the decrease in severity between vehicle and IB, with a moderator for dose exploring the sources of variation. Side effects, particularly epistaxis, nasal congestion, and nasal dry ness, were analyzed using a binary method for overall risk of development. Lastly, a meta-analysis of severity percent-change was conducted to fi t all fi ve studies. Risk of Bias Studies were subjected to a risk of bias assessment using the Cochrane risk of bias tool. The following types of biases were assessed: the randomization process, deviation from intended interventions, missing outcome data, measurement of the out come, selection of the reported result, and overall bias. The risk was then graded for each study as low, high, or unclear. A “ low risk of bias ” was determined if the low-risk bias method for each domain was clearly described. A “ high risk of bias ” was judged if a high risk was indicated in the description. A “ some concerns ” were indicated when there was inadequate information or uncer tainty over the potential for bias. Due to the limited number of studies (<10), a funnel plot could not be created to determine whether publication bias affected the data used in the meta-analysis. Statistical Analysis Our objective was to conduct a meta-analysis of the avail

The effectiveness of IB in NAR has not been the sub ject of a systematic review. Hence, a systematic review and meta-analysis were conducted to determine whether intranasal IB (INIB) is more effective than placebo in reducing nasal symptoms, particularly rhinorrhea, and improving quality of life in NAR patients.

MATERIALS AND METHODS Protocol Registration

No registered review protocol similar to ours was identi fi ed prior to the beginning of this review. The protocol of this system atic review has been validated and registered in the Interna tional Prospective Register of Systematic Reviews (PROSPERO) of the National Institute for Health Research (NIHR). Registra tion number: CRD42020162401. Eligibility Criteria Randomized controlled trials (RCTs) and non-randomized comparative parallel group trials (non-RCTs) comparing INIB with placebo were included. Patients suffering from NAR were targeted. INIB treatment is compared with placebo with the pri mary goal of determining nasal symptom control and quality of life. The inclusion criteria were the diagnosis of NAR as con fi rmed by negative allergic, infectious, and mechanical sino-nasal diseases. Data on IB dosage and frequency, and duration of use, were collected. Exclusion criteria encompassed articles not written in English and studies that included patients with other types of rhinitis or other treatment modalities. The outcome measures were not used as inclusion or exclusion criteria. Information Sources and Search Strategy A comprehensive review of the literature was conducted on Medline, Embase, and the Cochrane Central Register of Con trolled Trials, for articles from 1990 to December 2021. The search terms used were: (vasomotor rhinitis) AND (therapy OR treatment) OR (NAR) AND (therapy OR treatment). The reference lists of included articles were examined for addi tional articles meeting inclusion criteria. Study Selection The selection of the included articles was independently per formed by two reviewing authors (P. K and M. K). At fi rst, records were screened and chosen by relevancy of the titles and abstracts. The full texts of the selected articles were then reviewed. The above-cited eligibility criteria guided the choice of trials to be fi nally included in the study. In case of insuf fi cient data, the corresponding authors were contacted by electronic mail. Disagreements in study selection were solved by the senior author (N. K). Patient/Population, Intervention, Comparison, and Outcomes (PICO) Criteria The PICO criteria for the present review were as follows: P: Patients with NAR. I: INIB treatment. C: Comparison with a placebo (saline vehicle adjusted to the pH of the nasal mucosa). O: Nasal symptoms control and quality of life.

Laryngoscope 133: December 2023

El Khoury et al.: Ipratropium Bromide in Non-Allergic Rhinitis

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