Abstract
In this letter, we report that ragweed-allergic participants with nasal Staphylococcus aureus carriage (n = 7) exhibited significantly smaller reductions in Peak Nasal Inspiratory Flow from baseline at 3 h (P = 0.013) and 5 h (P = 0.008) post–nasal allergen challenge compared to non-carriers (n = 12). There was no significant difference between carriers and non-carriers in the initial response within the first three hours following the challenge (all P > 0.05). Carriers also reported significantly lower Total Nasal Symptom Scores (P = 0.015) and Total Rhinoconjunctivitis Symptom Scores (P = 0.021) at 48 h. These findings suggest that S. aureus carriage does not exacerbate allergic responses and may instead be associated with more rapid symptom resolution.
Keywords: Nasal allergen challenge, Ragweed, Staphylococcus aureus, Nasal carriage, Symptoms
Staphylococcus aureus, a Gram-positive bacterium colonizing ~ 30% of individuals, has been implicated in allergic rhinitis (AR) [1]. While some studies suggest higher carriage rates in AR patients [2–7], evidence linking S. aureus to symptom severity remains conflicting [4], and its role during controlled nasal allergen challenge (NAC) has not been established.
We previously performed the Allergic Rhinitis Microbiome Study (ARMS), whereby ragweed-allergic participants were challenged to ragweed extract using a NAC outside of the Southeastern Ontario seasonal allergy seasons [8]. Nasal swab samples were collected from all participants at the screening visit to determine methicillin-sensitive S. aureus carriage. Using a sterile Transystem™ (COPAN Diagnostics, California, USA) swab set, the anterior nares of one nostril was swabbed and placed in a transport media. Samples were processed for culture and antibiotic susceptibility testing by the Clinical Microbiology Laboratory at Kingston Health Sciences Centre - KGH Site. This study received ethical approval by the Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board.
Of 19 ragweed-allergic participants, 7 (38.9%) were S. aureus carriers. Self-reported clinical symptom outcomes of mean Total Nasal Symptom Score (TNSS), Total Rhinoconjunctivitis Symptom Score (TRSS), Total Ocular Symptom Score (TOSS), and Peak Nasal Inspiratory Flow (PNIF) were stratified based on S. aureus nasal carriage status (Fig. 1). One allergic participant was excluded due to incomplete symptom diary cards. We observed that allergic participants with the presence of S. aureus in their nasal microbiome experienced significantly reduced TNSS and TRSS at 48 h post-NAC (TNSS, P = 0.015; TRSS, P = 0.021) compared to those without. TOSS was not significantly different between these participant groups at any time-point (P > 0.05). To account for differing baseline scores between participants, mean PNIF scores were normalized as mean percent PNIF fall from baseline. Allergic participants who were carriers of nasal S. aureus experienced significantly reduced percent PNIF fall at the 3 h (P = 0.013) and 5 h (P = 0.008) time-points compared to non-carrier participants.
Fig. 1.
Clinical outcomes during nasal allergen challenge in ragweed-allergic participants with (carriers) and without (non-carriers) nasal Staphylococcus aureus. Mean Total Nasal Symptom Score (TNSS; A), Total Rhinoconjunctivitis Symptom Score (TRSS; B), Total Ocular Symptom Score (TOSS; C), and normalized percent Peak Nasal Inspiratory Flow (PNIF) fall (D) are shown. Compared to carriers, non-carriers had significantly higher TNSS (P = 0.015) and TRSS (P = 0.021) at 48 h post-challenge, as well as greater PNIF fall at 3 h (P = 0.013) and 5 h (P = 0.008). No significant differences were observed in TOSS. Statistical significance was determined using two-way ANOVA with Šídák’s multiple comparisons test. *P ≤ 0.05; †P ≤ 0.01. Error bars represent standard deviation
There is disagreement on whether S. aureus impacts the severity of symptoms of AR and other atopic conditions, but considering that 30% of individuals with AR are carriers, it is important that the effects of S. aureus are understood [9]. As the first study to use an optimized and validated model of AR in ragweed-allergic participants, we were unable to replicate the findings from the group of Shiomori et al. [4] Although S. aureus carriage did not reduce early-phase symptoms, carriers experienced faster symptom resolution, suggesting a potential modulatory role in allergic inflammation. The mean TNSS difference at 48 h between carriers and non-carriers (2.58 points) falls within the range of minimally clinically important differences (1–3.6 points), suggesting a potentially clinically meaningful effect [10, 11]. PNIF measurements showed transient differences during the late-phase response; however, given the effort-dependent nature of PNIF and the small sample size, these changes should be interpreted cautiously. Larger, longitudinal studies are needed to confirm these findings and to explore mechanisms, including the contribution of Staphylococcal toxins to AR and other atopic conditions.
Acknowledgements
The authors of this manuscript would like to thank Matthew Rawls for helping conceptualize this study; Terry Walker, Janice Menzies, and Sandra Belanger for their help in conducting study visits; Wilma Hopman for her statistical consultation; and our internal microbiology laboratory at Kingston Health Sciences Centre-KGH Site for processing the nasal swab samples.
Abbreviations
- AR
Allergic rhinitis
- ARMS
Allergic rhinitis microbiome study
- PNIF
Peak nasal inspiratory flow
- NAC
Nasal allergen challenge
- TNSS
Total nasal symptom score
- TOSS
Total ocular symptom score
- TRSS
Total rhinoconjunctivitis symptom score
Author contributions
SL contributed to the study design, study conduct, sample analysis, data management, data interpretation, and manuscript preparation. LH contributed to study conduct, sample analysis, data interpretation, and manuscript preparation. AD contributed to the sample analysis, data interpretation, and manuscript preparation. JT contributed to the study design, study conduct, and sample analysis. SG contributed to the study design, study conduct, data management. HB contributed to the study conduct and data management. LS contributed to the study design, study conduct, data management. PMS oversaw all aspects of this study. AKE oversaw all aspects of this study and critically reviewed and revised the manuscript.
Funding
Queen’s Health Sciences Spear Endowment/Start Memorial Fund. CAAIF-Miravo Healthcare Research Grant in Allergic Rhinitis or Urticaria.
Data availability
The datasets generated and/or analysed during the current study are not publicly available as they are proprietary to Kingston Allergy Research but are available from the corresponding author on reasonable request.
Declarations
Competing interests
Anne Ellis, MD, MSc, FRCPC (1,2,3): In the past, Dr. Ellis has participated in advisory boards for AstraZeneca, Agence Unik, Celltrion Pharmaceuticals, GSK, Sanofi, and Tadeka Pharmaceuticals; has been a speaker for ALK Abello, AstraZeneca, COVIS Pharma, GSK, Novartis Pharmaceuticals, Orexo, Regeneron Pharmaceuticals, and Sanofi; has received research grants (through her institution) from ALK-Abello A/S, AstraZeneca, Bayer Consumer Health, Merck Canada, Novartis Pharmaceuticals, Sanofi (and Opella Healthcare SAS), and Regeneron Pharmaceuticals; and served as an independent consultant to Bayer LLC, ARS, GSK, Orexo, and Regeneron Pharmaceuticals. The remaining authors have no conflicts of interest to report.
Footnotes
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and/or analysed during the current study are not publicly available as they are proprietary to Kingston Allergy Research but are available from the corresponding author on reasonable request.