4. Discussion
In the current nationwide observational study, we found an increase in the prevalence of CRSwNP from 2012 to 2019. Further, about a quarter of the patients with CRSwNP suffered from comorbid asthma. Asthma, and especially more severe asthma, was associated with higher need for systemic corticosteroids and more frequent sinus surgeries.
In the last two decades, the prevalence of CRSwNP has risen (Hedman 1999, Johansson 2003), and our study showed a continued increase during the study period, from about 6.0% in 2012 to 8.6% in 2019. The increase was particularly pronounced in the subjects between 50 and 70 years of age. There was a slight decrease in incidence of CRSwNP during the study period, however, the higher incidence at the beginning of the study period may be due to the lesser availability of data in the Avohilmo register initially, which was initiated in 2011. Thus, as the incidence remained similar throughout the study period, the slight rise in prevalence is likely related to the ageing population.
The mean annual incidence peaked in patients aged 60-69 years (103.2/100 000). In general, the average age of onset of CRSwNP was 52 years, and the typical age at diagnosis ranged from 50 to 60 years, which is in line with previously reported findings 4,25. In our study, males had a higher mean annual incidence of CRSwNP than females, albeit this is inconclusive, as there is no consensus with regards to gender in the literature 26,27. Further, our study found that 27% of CRSwNP patients had asthma as a comorbidity, which is an estimate based on real-world data. In examples from literature, estimates suggest that up to 67% (range, 40%-67%) of CRSwNP patients are having comorbid asthma. The reason for the difference between the findings in our study compared with previous literature may be that in real-world, many patients with CRSwNP still have undiagnosed asthma28,29.
In Finland, CRSwNP management is initiated rapidly after the diagnosis. About two thirds (62.7%) of the patients with CRSwNP were treated with SCSs and about half of them had ESS. In our study, more than 40% of the CRSwNP patients had ESS within the first-year post diagnosis, 38.9% had only one ESS, whereas 7.8% needed ESS at least twice. Apart from a small study reporting a 7% revision rate in CRSwNP patients30, several studies report rates of 14-25%31–33. The short time between diagnosis of CRSwNP and ESS is because the official diagnosis for CRSwNP is usually given after nasal endoscopy, which is performed at the hospital, where the patient with uncontrolled CRS has been referred for consideration of ESS32.
Comorbid asthma and especially severe asthma increase the probability of being treated both with SCSs and surgical treatment. In line with previous studies, our study showed that asthma status and especially the severity of asthma was associated with the likelihood of having an earlier ESS 27,29,34). In addition, asthma comorbidity increased the likelihood of repeated ESS. For patients with more severe asthma, it has been shown that CRSwNP is more difficult to manage, and that the condition increased the probability of a recurring ESS27. However, ESS in CRSwNP patients is associated with a high rate of recurrence which is likely to contribute to the burden of the disease, further exacerbated by comorbidities such as asthma32,35.
The management of patients with CRSwNP and severe uncontrolled asthma remains a challenge 35. There is an unmet need in improving the management of CRSwNP to achieve greater patient satisfaction and disease prevention. Targeted therapies are needed that can decrease the type-2 inflammation common in CRSwNP and asthma, preferably as a single therapy treating both the upper and lower airway disease 36. In recent years, the introduction of biological therapies targeting type 2 inflammation has increased the treatment options for CRSwNP. These new biologics include dupilumab, an anti-IL-4Ra monoclonal antibody, that has demonstrated broad efficacy across upper and lower airway disease 37,38. Further, other emerging biologics have also shown effects in reducing CRSwNP symptoms, including the anti-IgE monoclonal antibody omalizumab39 and anti-IL-5 antibody mepolizumab40. Presumably, targeted biologicals may demonstrate greater beneficial effects in patients with both asthma and CRSwNP41.
Our results suggest that type-2 high conditions (comorbid CRSwNP and asthma) increase probability of revision ESS. Although these findings require validation in other populations, in terms of patient counseling use, our results emphasize the importance of diagnostics and management of both CRSwNP and asthma to prevent uncontrolled disease, suffering and costs. Further, depending on the national reimbursement policies of biological medications, some patients with comorbid asthma and CRSwNP may find it easier to access these new treatments based on the severity of asthma rather than CRSwNP.
There are certain limitations typically associated with retrospective database analyses. These include the risk that some information may not have been consistently recorded for all patients, potentially impacting the population size and other outcomes. Further, the asthma severity and the level of control were based on dispensed medication and health care visits without knowledge of asthma symptoms. Nevertheless, the major strength of this study is that it includes an unselected population-based cohort of Finnish CRSwNP patients, which limit the risk of selection bias. Furthermore, it includes real-world data from mandatory national health-care registries with high quality and coverage from both primary and secondary care, providing a solid and unique set of data.
In conclusion, CRSwNP is a prevalent and increasing health problem with frequent need for treatments with potentially severe side effects. As concurrent asthma and especially severe asthma is associated with need for even more intense treatment, these subjects need special attention. New treatment modalities, such as monoclonal antibodies, are needed to tackle airway inflammation and decrease the need for systemic corticosteroids and surgical procedures to improve burden of disease in subjects with CRSwNP.