Evaluating the relationship between allergic rhinitis and sleep disordered breathing: a retrospective case series

Introduction

Allergic rhinitis is a common disease of childhood, particularly in developed nations, and its prevalence is increasing (1). Katelaris et al. (2) used the International Study of Asthma and Allergies in Childhood (ISAAC) study questionnaires to demonstrate that the prevalence of allergic rhinitis in the paediatric Australian population ranges from 12% to 20%, with the incidence reported as high as 40% in other developed countries (3).

Allergic rhinitis is a reaction at the level of the nasal mucosa to an allergen, producing an immunoglobulin E (IgE) mediated reaction (3). This inflammation of the mucosa causes oedema which results in congestion, nasal obstruction, itching, sneezing and rhinorrhoea, the common symptoms of allergic rhinitis (4).

Sleep disordered breathing (SDB), another common disease of childhood, occurs in 2–4% of the paediatric population (5) and can range from primary snoring to obstructive sleep apnoea (OSA). Common symptoms in children include snoring and apnoea as well as nocturnal diaphoresis, restless sleep, nocturnal enuresis, and poor behaviour (6). SDB is associated with significant morbidity including adverse cardiovascular, behavioural and neurocognitive issues (7). The most common cause of paediatric SDB is adenotonsillar hypertrophy (8), however a bidirectional association between allergic rhinitis and SDB has been investigated (4).

This link between paediatric SDB and allergic rhinitis has been explored in previous research with a systematic review by Lin et al. (3) supporting a correlation between SDB and allergic rhinitis in the paediatric population. It was concluded that the studies included were of low quality of evidence and further research was required, including the use of higher sample sizes and standardised testing to determine the diagnosis of allergic rhinitis (3). Understanding the relationship between allergic rhinitis and SDB can help manage both conditions to a higher standard in clinical practice, potentially reducing inadequate treatment of patient symptoms and rationalising the role of surgery.

The aim of this study was to further investigate the association between allergic rhinitis and SDB, utilising total IgE (tIgE) and specific IgE (sIgE) as objective parameters for allergic rhinitis. As patient data was acquired through a specialist allergy clinic, this study had a secondary outcome of evaluating the sensitivity and specificity of tIgE/sIgE for allergic rhinitis signs and symptoms. We present this article in accordance with the STROBE reporting checklist (available at https://www.theajo.com/article/view/10.21037/ajo-24-29/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Mater Misericordiae Ltd. Human Research Ethics Committee (project ID: 87606). Individual consent for this retrospective analysis was waived.

Patients

Paediatric patients less than 18 years of age at the time of surgery, who underwent an adenoidectomy and/or tonsillectomy/tonsillotomy and/or cautery/reduction of inferior turbinates from 1 January 2017 to 31 December 2022 and had symptoms and/or examination findings of allergic rhinitis were recruited from the a private ear, nose and throat clinic in Townsville, Australia. Patients were excluded from the study if they did not have symptoms and/or examination findings of allergic rhinitis, if they did not have allergy testing performed, and if there was no pre-operative clinical notes available.

Data collection

All electronic patient files at the surgeon’s practice were searched for Medicare billing codes for tonsil, adenoid and turbinate surgery from 1 January 2017 to 31 December 2022. The search was filtered to only include patients under the age of 18 years. The remaining files were then reviewed by a single researcher and data collected. Patients with incomplete history, examination or pathology results were included and missing data points excluded from the analysis.

Demographics and symptoms

Demographics and symptoms were collected from the patient chart using a standard form that summarised history and examination details. Data included age at time of surgery, sex, surgery performed, any significant medical history in particular asthma and eczema and any previous or planned revision surgery. Sleep symptoms such as snoring, apnoea, restless sleep, nocturnal diaphoresis, daytime somnolence, poor behaviour and nocturnal enuresis were recorded. Nasal symptoms including nasal obstruction, rhinorrhoea, sneezing and post nasal drip were also documented. Examination and operative findings including adenoid and tonsil size, and if there were examination findings of allergic rhinitis (one or more of inferior turbinate hypertrophy, significant nasal secretions, allergic shiners, etc.) was also collected.

sIgE, tIgE and SPT

An ImmunoCap assay from Sullivan Nicolaides Pathology was used to perform sIgE and tIgE testing. For both parameters, the level (kU/L) was recorded as well as if the result was positive. The cutoff value for whether the result was positive differed for each allergen and is based off the 95% positive predictive value. Patients who had seen an allergy specialist but did not have sIgE or tIgE results available, had their skin prick test (SPT) results examined and recorded as either positive (a response >3 mm than the negative control) or negative. If several individual allergens were tested for SPT, e.g., multiple grasses, multiple weeds, multiple dust mite species, this was recorded as positive to grass, weed or dust in general. SPT results were only utilised in prevalence analyses.

Statistical analysis

IBM SPSS version 27 was utilised for statistical analysis, with the significance level set at P<0.05. The SPSS power analysis function was used to calculate the minimum sample size for a Pearson correlation. For an expected correlation of 0.4 and a margin of error of 0.05, the sample size was calculated to be of 369. Patient demographics were compared using a Pearsons chi-square test (or Fisher’s exact test) for categorical variables and the independent t-test for continuous variables. Due to the large sample size, small groups for multiple hypothesis testing, and preference for reducing false negatives, the Bonferroni correction was not applied to multiple hypothesis testing. Considering the large sample size, the sensitivity and specificity were calculated for both sIgE and tIgE, as well as the prevalence of sleep-disordered breathing in the studied population.

Results

Patient demographics

A total of 1,165 patients were identified from a database of patients <18 years old, who underwent tonsillectomy/otomy (n=303), adenoidectomy (n=401) and/or cautery of inferior turbinates (n=310) between 1 January 2017 and 31 December 2022. After removing patients without allergy testing (n=734) and without allergy symptoms/signs (n=21), a total of 410 patients were included in this study (Figure 1). The age range was 1–16 years old with a mean age of 6.20 years old. The cohort was 66% male (Table 1).

Figure 1 Patient identification and recruitment.

sIgE

Of the 410 patients with allergy testing, 376 patients had sIgE testing performed with 53.3% of those positive for one or multiple allergens (Table 2). 73% of patients with a positive sIgE test were male compared to 60% in the negative sIgE group (P=0.008). There was a statistically significant correlation between age and sIgE; patients with a positive sIgE had a mean age of 6.91 years old compared to 4.97 in the negative group (P<0.001). There was also a significantly higher history of atopy in the sIgE positive group (P=0.03).

Symptom findings demonstrated a significant association between a negative sIgE and patients having sleep symptoms in general (P=0.03) (Table 2). Regarding nasal symptoms, there was also a significant association between sneezing and a positive sIgE (P<0.001). Examination findings showed patients had significantly smaller adenoids in the sIgE positive group (P=0.003) (Table 2).

As demonstrated in Figure 2, the age distribution of sIgE results showed an increase in positive results and a sharp decline in negative results at five years of age. This was thought to potentially be a confounding variable and a subgroup analysis was undertaken. Ages were divided into two groups of less than five years old and five years or older, and all results re-examined. Sneezing was found to continue to be associated with a positive sIgE in both age groups (P=0.003, n=50 and P=0.02, n=151 respectively), whereas sleep symptoms in general were found to be significantly lower in only the younger age group (P=0.03, n=50). Nasal obstruction was also found to be significantly lower in the sIgE positive older age group (P=0.002, n=151). Subgroup analysis of adenoid and tonsil size was not possible due to the small sample in each group.

Figure 2 Age distribution of sIgE results in patients undergoing upper airway surgery. sIgE, specific immunoglobulin E.

tIgE

Of the patients who had allergy testing, 311 had tIgE testing done with 61.9% positive for a significant level of tIgE as determined by a result >50 kIU/L. Patients with a positive tIgE were significantly older (7.02 vs. 4.88 years) than those with a negative result (P<0.001) (Table 3). As with sIgE, there were more males (70.3%) than females with a positive tIgE.

Regarding symptoms, tIgE negative patients had a higher incidence of snoring (P=0.02), while tIgE positive patients had a higher incidence of sneezing (P=0.001) (Table 3). For examination findings, there was no significant difference between the tIgE positive and negative groups.

Similar to sIgE testing, the age distribution of sIgE results showed an increase in positive results and a sharp decline in negative results at 5 years of age (Figure 3). As the significant difference in age between the two groups may have been a confounding variable, a subgroup analysis was undertaken. Again, two groups were used: less than 5 years and 5 years or older. Snoring and tIgE were not significantly associated in either age group (P=0.67, n=46 and P=0.25, n=148 respectively). The prevalence of diaphoresis and sneezing was significantly higher in the tIgE positive younger age group (P=0.009, n=46 and P=0.002, n=46 respectively).

Figure 3 Age distribution of tIgE results in patients undergoing upper airway surgery. tIgE, total immunoglobulin E.

Sensitivity and specificity

The sensitivity and specificity of sIgE for symptoms of allergic rhinitis was 52.5% and 34.8% respectively. In comparison, tIgE had values of 62.1% and 40.1%, respectively (Table 4). These values were largely unchanged for sIgE (54.9%, 60.5%) and tIgE (61.9%, 37.5%) when correlating examination findings of allergic rhinitis instead of symptoms. When controlling for age, there was a notable difference in sensitivity and specificity between the two groups. The younger age group had decreased sensitivity and increased specificity, while the older age group had increased sensitivity and decreased specificity, for both symptoms and examination findings of allergic rhinitis (Table 4).

Of the 410 patients with allergy testing, 75.6% had tIgE levels, 91.5% sIgE and 8.8% SPT. The prevalence of allergic rhinitis using a positive sIgE or SPT results was 57.0%. The prevalence of SDB in the entire studied population of pediatric allergic rhinitis patients was 86.1% by way of atleast habitual snoring and 38.5% by way of atleast apnoeas. Of those patients with positive allergy testing (sIgE and/or SPT), the prevalence of snoring and apnoeas was was 82.4% 33.0%, respectively. For patients with a negative sIgE or SPT, the prevalence of snoring and apnoeas were higher at 91.0% and 44.6%.

Discussion

SDB is reported to have an incidence of 2–4% in the general paediatric population (9). While this study selected for patients with signs and symptoms of SDB and allergic rhinitis, Ishman et al.’s (9) case control study found the incidence of SDB amongst children with a positive allergy test to be 29%. Similar results by Loekmanwidjaja et al. (10) demonstrated higher Children’s Sleep Habits Questionnaire (CSHQ) scores in children with allergic rhinitis compared to controls, with significant differences in daytime sleepiness and parasomnia subscales despite the use of nasal corticosteroids. This correlation between SDB and allergic rhinitis is alluded to in the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, where ‘sleep disturbance’ is listed as a marker of moderate/severe allergic rhinitis (11). Nevertheless, there have been few studies to quantitatively evaluate the relationship between the two diseases in children.

A meta-analysis and systematic review (12) of 27 observational studies up to 2019, including both adult and paediatric patients, found allergic rhinitis patients had significantly worse sleep latency, efficiency, daytime sleepiness, morning headaches, restless sleep, SDB and OSA, though the general standard of studies included was judged to be low or very low. A recent, large-scale observational study in children from the general community found an association between allergic disease and psychological distress that was mediated through sleep problems (13). In our study, however, the only SDB symptom that was significantly associated with a positive tIgE was diaphoresis, and that to only for patients less than or equal to 4 years old. In fact, sleep symptoms in general were more prevalent in the sIgE negative group, while snoring was more prevalent in the tIgE negative group. These results may confer false positives due to multiple hypothesis testing, but this is countered by the large sample size used in this study (14).

Despite the disparity between our results and the literature, the association between SDB and allergic rhinitis is not surprising. It is well recognised that nasal obstruction is a common symptom of both allergic rhinitis and SDB (15). The obstruction may be a result of enlarged turbinates or enlarged adenoids. Interestingly, this study found patients to have significantly smaller adenoids with a positive sIgE result. While a subgroup analysis could not be undertaken, this could have been of consequence as older children are likely to have smaller adenoids due to adenoid regression (11). This may also explain the lower incidence of nasal obstruction in older children with positive allergy testing compared to younger children. Non-allergic rhinitis is another common cause of nasal obstruction and rhinorrhoea in younger children (16), and may have been a confounding variable.

The mean age of children with a positive sIgE and/or tIgE test was significantly higher than those with a negative sIgE and/or tIgE. The age discrepancy between the two groups and the differences found between symptoms in the younger age group may be due to several reasons. False negative sIgE and tIgE results in the younger group may be caused by limited allergens being screened. Food allergies are more common in infants and younger children (17) and these were not tested in this study. Non-allergic rhinitis may also explain symptoms and examination findings of allergic rhinitis with negative tIgE and sIgE results (11) as the prevalence of non-allergic rhinitis is higher in children less than five (16). Thirdly, the incidence of allergic rhinitis has also been found to increase with age, rising significantly after the age of four (16,18). Lastly, IgE levels are lower in very young children and increase with age, irrespective of allergy status (19,20).

The sex discrepancy in the diagnosis of paediatric allergic rhinitis has been noted in previous studies (21) with more male than female children diagnosed in the earlier years with allergic rhinitis and subsequent positive allergy testing. Interestingly this affect has been reported to normalise in the teenage years or even reverse in other studies (15). However, this was not identified in our study.

Our results also indicate generally poor sensitivity and specificity of both tIgE and sIgE, correlating with symptom and examination findings of allergic rhinitis, particularly in the younger age group. The values ranged from 32.6% to 66.3% and 21.4% to 61.3% respectively, depending on the age group and sIgE/tIgE status. As previously stated, this may be due to the presence of non-allergic rhinitis within the study cohort. The ARIA guidelines report sensitivity and specificity of sIgE can be over 85% for diagnosing allergy (11). Furthermore, the use of tIgE as a screening or diagnostic test for allergic rhinitis has not been recommended in the ARIA guidelines due to false positives from unrelated conditions and inadequate treatment from false negatives (11). In spite of this, Wise et al. (15) suggests that there may be a role in assessing atopy status using tIgE, with Rø et al. (22) finding a positive tIgE test in early childhood to correlate with allergic disease in later life. Both argue that this information could be used provide early intervention, such as allergy avoidance and medical therapies.

sIgE has been found to correlate well with SPT results in the diagnosis of allergic rhinitis (15) and there are several benefits to this testing method. In comparison to SPT, medications do not need to be ceased prior to testing, skin conditions don’t preclude testing and there is no risk of anaphylaxis (15). Levels of sIgE may also correlate with symptoms of allergic rhinitis, and in patients with multiple allergies it may help to target the most relevant allergen for immunotherapy (15). In Australia, SPT can also be difficult to access, particularly in regional and remote areas in comparison to IgE testing, which is readily available and inexpensive.

Overall, the strengths of this study were the large sample size and use of objective measures for allergic rhinitis (tIgE and sIgE), a notable issue with prior studies (3). The extensive use of subgroup analysis allowed thorough investigation of the impact of age on SDB, allergic rhinitis and the utilisation of tIgE and sIgE testing.

There were several limitations to this study. Firstly, the poor sensitivity and specificity of IgE testing limits the ability to detect a correlation between allergic rhinitis and SDB. As SPT has been shown to be more sensitive to serum IgE testing (23-25), this would have improved the methodology. Secondly, the studied population were all children undergoing tonsil/adenoid/turbinate surgery, reducing the translatability of results to the general population. As pediatric patients without allergy symptoms are unlikely to have IgE testing, this negative control group would need to be recruited through a prospective study. Thirdly, the lack of standardised questionnaires for the clinical diagnosis of SDB and allergic rhinitis may have under or over-estimated the true prevalence of the disease processes and affected the sensitivity and specificity results of tIgE and sIgE tests. Although, the use of a single surgeon to interview and examine patents and a consistent method of reporting would have alleviating this error to some extent. Lastly, the use of polysomnography to formally diagnose SDB and its severity would have also been preferable. However, accessibility of paediatric polysomnography is limited in Australia and not routinely used to assess paediatric patients prior to surgical intervention.

Conclusions

In conclusion, there was no strong correlation between IgE-positive allergic rhinitis and SDB in this large retrospective case series. In fact, the only SDB symptom that was significantly associated with a positive tIgE was diaphoresis, and that to only for patients less than or equal to 4 years old. This contrasts to the literature, which reports allergic rhinitis to be associated with reduced sleep efficiency, daytime sleepiness, SDB and OSA. This can be explained by the relatively poor sensitivity and specificity of IgE testing for allergic rhinitis signs and symptoms, which ranged from 32.6% to 66.3% and 21.4% to 61.3% respectively, depending on the age group (<5 and ≥5 years) and whether it’s sIgE or tIgE. This is significantly lower than the reported 85% for both parameters. Future studies should aim to be prospective, include all paediatric patients with allergic rhinitis (not just limited to surgical candidates), have a control group, include food allergens with sIgE, and use standardised questionnaires for SDB and allergic rhinitis symptoms. Understanding the correlation of allergic rhinitis and SDB can help manage both conditions to a higher standard in clinical practice, potentially reducing pediatric surgery and inadequate treatment.

Acknowledgments

This work was presented at the Frank Szallasi Journal Club Queensland on 29/11/2022.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://www.theajo.com/article/view/10.21037/10.21037/ajo-24-29/rc

Study Protocol: Available at https://www.theajo.com/article/view/10.21037/ajo-24-29/sp

Data Sharing Statement: Available at https://www.theajo.com/article/view/10.21037/ajo-24-29/dss

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-24-29/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-24-29/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by Mater Misericordiae Ltd. Human Research Ethics Committee (Project ID: 87606). Individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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