Differences in men and women suffering from CRSwNP and AERD in quality of life

Sex- and gender-related factors are present in a variety of diseases affecting the clinical presentation and treatment of these medical conditions, as well as the impact on patients’ quality of life (QoL) [1]. Among others, sex-related aspects have not only been identified regarding genetics and hormones, but interestingly also when analysing epigenetics, immune function, aging including neurocognitive decline, vascular status as well as response to therapeutics and interaction with the health care system [2].

Chronic rhinosinusitis (CRS) is a common, yet diverse disease affecting 4–16% of the general population [3‐5]. According to the recently published current version of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020), the condition should be classified into primary and secondary CRS. While the former is associated with generalized inflammation, the latter is caused by other underlying triggers including tumours, odontogenic reasons, or fungal growth. Primary CRS can be further sub-grouped as localized (unilateral) or diffuse (bilateral) disease and phenotypically grouped according to the absence or presence of nasal polyps. Phenotypes are determined by underlying type 2 (CRS with nasal polyps, CRSwNP) or non-type 2 inflammation (CRS without nasal polyps, CRSsNP) [6]. CRSwNP affects between 2.7 and 4.4% of the population and approximately 10% of these patients with nasal polyps suffer from aspirin-exacerbated respiratory disease (AERD) syndrome, which is characterized by the clinical triad of nasal polyps, bronchial asthma, and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) [6‐8]. CRSwNP and AERD generate not only nasal symptoms but also impair quality of sleep, mood, cognition, and productivity [9].

Patient-reported outcome measures (PROMs) are important instruments to evaluate the subjective burden of disease. Sino-nasal outcome test-22 (SNOT-22) and the sino-nasal outcome test-20 German adapted version (SNOT-20 GAV) are valid, reliable, and widely used tools to specifically address CRS symptoms [10, 11]. In this study, we focused on the comparison of patients suffering from CRS presenting with nasal polyps (CRSwNP) alone and those diagnosed with AERD.

Studies evaluating sex and gender specific impact on QoL of patients with CRSwNP and AERD are discordant. Furthermore, differences in men and women could also exist in specific phenotypes of CRS. Recently, a cluster analysis of SNOT-22 and VAS values regarding CRSwNP and CRSsNP patients according to gender was performed. Three clusters were identified: the first cluster comprised 37 female patients with CRS without nasal polyps (CRSsNP), the second cluster comprised 30 patients with CRS and NP (CRSwNP; 15 males and 15 females); and the third cluster had 30 male patients with CRS without NP (CRSsNP), indicating similarities in men and women diagnosed with CRSwNP but not CRSsNP patients [12]. With regards to sex as a factor influencing PROMs, higher SNOT-22 scores in patients suffering from CRS (with and without polyps) presenting for sinus surgery have been reported in women [13]. Elaborating on sex-specific differences in CRS, a higher prevalence of facial pain and headache was observed in female patients, whereas nasal obstruction was described more frequently in men [14]. In another study examining QoL of patients with CRS, worse QoL results were found among women in spite of similarities in objective disease measures, which were attributed to the increased prevalence of depression and AERD. When patients with depression or aspirin sensitivity were removed from the analysis, no statistically significant gender differences could be found [15].

Modern therapeutic strategies aim at personalized management of the individual patient. Therefore, knowledge of sex and sex-specific influences might be relevant to improve care for patients suffering from CRSwNP and AERD. Thus, the aim of this study was to clarify the impact of CRSwNP and AERD on patients’ QoL in women and men in order to possibly adapt future therapies accordingly.

In this study, we examined the association of sex and QoL in patients suffering from CRSwNP and AERD. So far, aspects of gender and sex differences in these entities have been poorly investigated. We conducted this study with a large cohort of AERD (n = 46) and CRSwNP patients (n = 59). In summary, we found no significant difference in TPS and total SNOT-20 GAV scores between male or female patients with CRSwNP or AERD.

With the aim of achieving precision medicine, aspects of biological sex and the psychosocial aspects of a patient’s gender identity are receiving growing attention in various disease states [21‐23]. A wide range of factors including genetics, epigenetics, hormones, immune function, and behaviour might be influenced by patients’ sex and gender identity [2]. CRS is a highly prevalent disease and especially phenotypes with nasal polyps and AERD can significantly impair patients’ QoL [9]. Although the impact of sex in CRSwNP and AERD is not yet fully elucidated, studies evaluating e.g. the nasal microbiome in patients with CRS suggest differences in microbial colonization in women and men [24]. Furthermore, sex and gender specific differences might differ in CRS phenotypes like CRsNP, CRSwNP patients and patients suffering from AERD. A recently published cluster analysis evaluating QoL of CRS patients displayed three groups with similar symptoms. One cluster comprised women with CRSsNP, another cluster grouped men with CRSwNP and the third cluster represented women and men diagnosed with CRSwNP [12].

The QoL and impairment of olfactory function in AERD patients has been confirmed by previous research [25, 26], but interestingly, AERD and especially severe cases are more prevalent amongst women [27]. It has been reported that women and men can perceive and report symptoms and burden of disease differently [28]. It was considered that women are more likely to report their symptoms and give a worse assessment of their health. However, the extent of the sex differences in health also vary according to the particular symptom or condition and to the phase of life [29]. It could, therefore, be hypothesized that studies in CRS, which assess the subjective complaints by the participants, would show a lower QoL among female patients.

Interestingly, we did not observe any significant differences in QoL between male and female patients diagnosed with CRSwNP and AERD. Similarly, Mendolia-Loffredo et al. also found no difference in disease-specific health-related QoL between sexes of patients with CRS [15, 30]. In this study analysis of the whole cohort revealed that females seemed to score worse than males on QoL scores. However, when further analysing the data, the authors noted that the poorer outcome was caused by the higher prevalence of acetylsalicylic acid intolerance and depression among women. Consequently, differences in QoL according to sex were eliminated after exclusion of patients with these comorbidities [15]. These results are in line with our observation where we could not find any major differences in QoL scores between male and females regardless whether they suffered from CRSwNP or AERD. It is, therefore, conceivable that the influence of sex is restricted primarily to the general QoL and that symptoms such as migraine headache, which are more common among women, and factors such as difference in anatomic size and hormone increases the prevalence of CRS in women compared to men as suggested by Ference et al. [30].

In the analysis of SNOT-20 GAV single items, we found the highest scores and significant differences in the symptom parameters “thick nasal discharge”, “post-nasal discharge”, and “difficulty to smell or taste” between the groups with CRSwNP and AERD in male patients only. In line with these results, Schneider et al. also observed higher SNOT-20 GAV scores in AERD patients as compared to CRSwNP especially in the category nasal symptoms [9]. The fact that they only observed significant differences between those two groups with regard to the single item “difficulty to smell or taste” but not in the other two above-mentioned items may be due to the fact that no stratification according to gender was performed.

Here, we specifically analysed patients suffering from CRSwNP or AERD in a retrospective evaluation of questionnaires. However, with regard to CRS (comprising both CRSsNP and CRSwNP), Baumann et al. showed in a prospective study that women preoperatively performed worse with regard to QoL score as compared to men [31, 32]. Interestingly, postoperatively no difference between the two gender groups was observed. Similar results were shown by Lal et al. who investigated gender-specific differences in CRS patients electing endoscopic sinus surgery in a retrospective review and reported more problems with postnasal drainage, embarrassment, and facial pain in women preoperatively. In their postoperative analysis, men and women showed similar symptom scores [13]. Since our study was a retrospective evaluation of the questionnaires and independent of the time or number of surgeries, this could be a reason for the non-significant differences in symptoms between the groups. Another limitation of our study is the relatively small sample size of patients with CRSwNP in comparison to other studies. However, it needs to be mentioned that other studies did not split the subgroups of chronic sinusitis with nasal polyps and thus failed to investigate sex-specific differences depending on the presence of polyps and subtypes. By being the first to differentiate the subgroups, this study contributed to understanding differences according to sex in patients suffering from various forms of nasal polyposis.

Future studies should aim at prospectively investigating the differences in sex-specific complaints of patients with CRSwNP and AERD before and after surgical intervention. In light of current developments it would also be interesting to assess patients’ QoL before and after therapy with monoclonal antibodies targeting IgE, interleukins and interleukin receptors, which have shown promising effects in patients suffering from CRSwNP [33].

This is the first study assessing the differences in QoL between CRSwNP and a large cohort of AERD patients in relation to sex. The aim of this study was to clarify the impact of these diseases on patients’ QoL in men and women to possibly highlight important differences to be taken into account for therapeutic treatment. We did not observe significant differences in TPS or QoL between the study groups.