Discussion
Saline irrigation has been paramount for CRS treatment, with its role recently being
considered as a vehicle to deliver anti-inflammatory drugs into the sinus. The sinus ostium is not the sole targeted area for medical exposure, but the distribution of the drug to the sinus mucosa is also key to restoring the disease. Thus, the modification of the delivery system has been developed with a much greater focus on the distribution method of the drug into the sinus cavity. There has been a growing amount of robust evidence on the administration of corticosteroids via nasal irrigation with respect to technically distributing medication into the sinus and clinically improving symptoms; however, most studies to date have been conducted on post-surgical sinus status.(2-5)  Therefore, corticosteroid nasal irrigation as an initial treatment before the sinus surgery has not been adopted as a general practice. Clinically, Jiramongkolchai P. et al.(15)  recently conducted a randomized controlled trial that showed the comparable efficacy of corticosteroid irrigation and spray in CRSsNP patients who have not undergone sinus surgery regarding the improvement of SNOT-22 scores. In addition, Tait et al.(16)  carried out another randomized controlled trial to investigate the efficacy of large-volume, low-pressure corticosteroid irrigation compared with a placebo in CRS patients, of which 70% of patients in the study never had any sinus surgery. The authors reported that the mean change of SNOT-22 scores from baseline was greater for the treatment group in the subgroup of patients who had no prior sinus surgery; however, the results were not significantly different.
Regarding the technical concept, some publications investigated the extent of sinus
distribution among the delivery system in the unoperated sinus.(9-11, 17)  However, most studies have been done on the cadavers, and in healthy subjects, which might not sufficiently represent the actual physiology of diseased sinuses and the natural mechanisms of oropharyngeal functions during sinus irrigation. Moreover, the role of the mucociliary function that might impact the sinus penetration of the solution was one of the biases from previous studies. Wormald PJ. et al.(10)  reported the restriction of radioactivity via nuclear medicine imaging in unopened sinus cavities on healthy control subjects. Most radioactivity appeared in the maxillary sinuses from nasal douching, while there no radioactivity was detected in any sinus cavity from the spray and nebulizer techniques. Harvey RJ. et al.(9)  conducted a study on cadavers and reported a significant limitation of contrast distribution in unoperated sinuses, particularly in sphenoid and frontal sinuses, regardless of the delivery technique. Another study conducted in the pathological sinuses by Grobler A. et al.(17) found that both unoperated sinuses and sinuses with a small sinus ostium even after sinus surgery had unreliable penetration. However, the results of this study were not compared with the other delivery methods. The following research by Snidvongs K. et al.(11) utilized a comparative study between nasal irrigation and nasal spray. Nevertheless, they used low-volume nasal irrigation and found neither the nasal irrigation nor the nasal spray could enhance sinus penetration in the unopened sinus.
The present study’s advantage was the fact that it was designed to dynamically evaluate
the potential sinus distribution of different delivery methods in actual pathological sinuses. In addition, the alternative intervention that was intended to be investigated has been proven as a gold standard in terms of high-volume irrigation to deliver drugs into the opened sinus cavity.(6)  This study confirmed that the overall sinus distribution of nasal irrigation had significantly more superiority than the nasal spray with the conclusive effect size. In addition, the effect of nasal irrigation could create a greater sinus distribution in each anatomical site. However, consistent with previous studies, the maxillary and anterior ethmoid sinuses were the most significantly affected areas.(9,10) The OMU was the area that could reach the solution regardless of the delivery method. The rest of the sinuses, particularly the frontal and sphenoid sinuses, had the least significant solution distribution from both techniques. These limitations were explained by their anatomical locations, which sit at the most posterior and superior parts of the paranasal sinus system. Also, the bony septation and the sinus pathology under the unoperated sinus were critical barriers blocking the flow pathway. In the subgroup analysis, the difference in sinus distribution between the two methods was significantly greater, and remarkable in the moderate to severe sinus diseases, in which nasal irrigation had a better result. In the CRSwNP patients, nasal irrigation, regardless, provided significantly greater overall sinus distribution than nasal spray but had less significant effect than the CRSsNP subgroup.
Theoretically, saline irrigation has mechanisms as removing crust and mucous, reducing
antigen load, enhancing ciliary beat, and response for a vehicle to deliver the drugs into the sinus. This intervention brings the advantage of opportunely providing anti-inflammatory medications into the sinus using a one-step approach, resulting in more satisfactory compliance of the patients. Furthermore, sufficient therapy duration might help relieve inflammation at the OMU, maxillary and ethmoid sinuses, ultimately promoting the distribution of the drug into the most challenging parts, i.e., the frontal and sphenoid sinuses. Fortunately, as per the updated evidence, the adverse events of corticosteroid irrigation showed no serious effects, even in long-term use.(18-20)
The limitation of this study was that sinus penetration of a solution can be influenced by
multiple factors, not only the delivery technique, and such factors, i.e., the head position and the surgical status of the sinus cavity, were beyond the context of this study. In addition, finding of this study could not represent the symptomatic outcomes in clinical applications and could not entirely be used as a substitute for the standard therapy. Therefore, using corticosteroid irrigation as the initial treatment for CRS in selected phenotypes, i.e., moderate to high severity sinus diseases on CT scan or CRSsNP, might potentially benefit clinical outcomes. Further study on specific phenotypes or even endotypes might increase the extension of clinical application.