With a lifetime prevalence of about 5%, chronic rhinosinusitis (CRS) is one of the most frequently occurring chronic disorders worldwide [
Treatment alternatives should be pointed out to patients who have a critical view of guideline-recommended steroid-based therapy. One such alternative therapy concept is the nasal application of (phospholipid) liposomes. Several studies have already demonstrated the efficacy of this nonpharmacological mechanism of action in allergic rhinitis [
Because the incidence of allergic rhinitis (AR) in adults with CRS is 40%–80%, liposome therapy therefore represents an interesting, steroid-free treatment alternative [
The study was carried out in compliance with the requirements for noninterventional studies [
This investigation was a monocenter, prospective, controlled, open, noninterventional study (NIS). Sixty patients with CRS symptoms were treated with LN, and 30 patients received guideline-recommended therapy with a steroid nasal spray. Patients were first offered the guideline-recommended therapy. Those patients having reservations towards pharmacological therapy were alternatively offered treatment with a liposomal nasal spray. No prior wash-out period was required. Patients 18 years or older were included who due to their disorder had already been undergoing treatment at the study center.
The NIS took place from 15 March 2011 to 31 January 2013 and consisted of five visits at intervals of two to four weeks within a total treatment period of three months. Efficacy was determined on the basis of the sinusitis symptom score (SSS), which was documented daily by the patients themselves in a patient diary; furthermore, the investigator recorded the SSS at every visit. For monitoring purposes, the investigator also determined the polyp score (PS) based on the size of polyps at the first and last visits [
The liposomal nasal spray
The comparative treatment used in this study was
Other components of the product are benzalkonium chloride, polysorbate 80, D-glucose, microcrystalline cellulose, carmellose sodium, purified water, sodium hydroxide, and hydrochloric acid for pH regulation.
One milliliter of nasal spray contains 0.555 mg (approx. 0.05%) beclomethasone dipropionate as the active ingredient.
One spray application (approx. 0.09 mL) contains 0.05 mg beclomethasone dipropionate.
The recommended dose for patients aged 12 years or older is 2 sprays per nostril and application. The maximum daily dosage is 4 sprays per nostril.
On Day 1 of treatment (Visit 1), the investigator documented the detailed medical history and the SSS as well as the PS and conducted a regular rhinoscopy. Videoendoscopy and/or a smell test were optional.
Patients documented the number of sprays applied per nostril daily. They also specified when an onset of action occurred after the first-time application of the nasal spray (<5 min, 5–10 min, 10–30 min, 30–60 min, 1-2 h, 2–4 h, 4–8 h, >8 h, no onset of action).
Efficacy was recorded by means of the SSS, which was chosen based on the EPOS Paper [
In addition, polyps were measured via endoscopy at the first and last visits to monitor polyp size. The PS was calculated from these data based on a 4-point scale (0 = no polyps, 1 = small polyps, 2 = medium-sized polyps, and 3 = large polyps) [
The tolerability of the nasal spray was determined by means of the Nasal Spray Sensory Scale [
Quality of life was recorded using a validated questionnaire, the “Sino-Nasal Outcome Test German Adapted Version” (SNOT-20 GAV), which patients completed at every visit [
At Visit 5, a final evaluation was made during which the investigator assessed the medication applied in terms of effect and tolerability. Patients were also able to evaluate tolerability and efficacy of the nasal spray at the end of the treatment period with a final diary entry.
The program SPSS 21 for Windows was used to conduct the statistical analysis. To reduce any input errors, double data entry was carried out. Unreported values were treated as “missing values.”
First, all data were analyzed descriptively and tested for normal distribution using the Kolmogorov-Smirnov test. In addition, the mean values of the variables from Visits 1 and 5 were compared with the aid of the
Overall, 35 women and 25 men aged 18 to 77 years (mean age = 42 years) were included in the LN group, and 16 women and 14 men aged 22 to 74 years (mean age = 46 years) were in the comparison group. The statistical analysis and the comparison of the demographic data showed no relevant differences between the groups at the beginning of treatment (Table
Demographic data.
Female | Male | Valid | Missing | Total | ||||
---|---|---|---|---|---|---|---|---|
|
% |
|
% |
|
% |
|
| |
Liposomal nasal spray |
|
58.3 |
|
41.7 |
|
100 |
|
|
Beclomethasone |
|
53.3 |
|
46.7 |
|
100 |
|
|
Distribution of allergies.
Trees | Weeds | Grasses | Mites | Mold | ||||||
---|---|---|---|---|---|---|---|---|---|---|
|
% |
|
% |
|
% |
|
% |
|
% | |
Liposomal nasal spray | ||||||||||
Patients with allergy |
|
24.1 |
|
3.4 |
|
27.6 |
|
13.8 |
|
5.2 |
Patients without allergy |
|
75.9 |
|
96.6 |
|
72.4 |
|
86.2 |
|
94.8 |
Valid |
|
100 |
|
100 |
|
100 |
|
100 |
|
100 |
Beclomethasone | ||||||||||
Patients with allergy |
|
26.7 |
|
3.3 |
|
20 |
|
26.7 |
|
10 |
Patients without allergy |
|
73.3 |
|
96.7 |
|
80 |
|
73.3 |
|
90 |
Valid |
|
100 |
|
100 |
|
100 |
|
100 |
|
100 |
In the LN group, the onset of action on Day 1 occurred within 30 minutes in 47.8% of the patients, with 39.1% not noticing any onset of action at all.
The onset of action on Day 1 in the beclomethasone group took place within 30 minutes in 20% of the patients, with 48% noticing no onset of action whatsoever.
The liposomal nasal spray and the steroid alternative were both able to improve sinusitis symptoms significantly, with rhinoscopy findings also demonstrating distinct improvement. The sinusitis symptom score in the LN group, for instance, declined from a baseline score from 6.61 (±2.668) to 3.88 (±3.674) and in the comparison group from 6.57 (±3.012) to 4.83 (±3.601) (see Table
Sinusitis sum score (SSS), rhinoscopy sum score (RS), and SNOT-20 total score.
V1 | V2 | V3 | V4 | V5 | Improvement | |
---|---|---|---|---|---|---|
Liposomal nasal spray | ||||||
SSS | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
RS | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
1.639 |
SNOT | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
Beclomethasone | ||||||
SSS | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
RS | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
SNOT | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
Sinusitis symptom score over the course of five visits in both groups.
No relevant differences with regard to symptom reduction could be determined in the statistical analysis of the patient diaries.
Overall, the morning SSS, which consisted of the diary items “runny nose,” “itching,” “sneezing,” “postnasal drip,” “facial pain,” “headache,” and “nasal obstruction,” was 4.06 in the LN group and 4.01 in the steroid group out of 15 possible points. Over the three-month observation period, the patients’ daily documented sinusitis sum scores in both groups decreased from approximately 4 at baseline to 2.16 on Day 86. The difference between both groups was not significant.
At the final evaluation, the majority of the patients in both groups rated efficacy “good” or even “very good” (Table
In the immediate evaluation of the Nasal Spray Sensory Scale, the steroid nasal spray group achieved somewhat better results than the LN group (
Sensory evaluation immediately and two minutes after application.
Immediately after |
Two minutes after | |||
---|---|---|---|---|
V1 | V5 | V1 | V5 | |
Liposomal nasal spray | ||||
MV |
|
|
|
|
SD |
|
|
|
|
Beclomethasone | ||||
MV |
|
|
|
|
SD |
|
|
|
|
In the evaluation after two minutes, both groups showed higher values, which means that the application was perceived as more pleasant. The value for the LN group was 80.4 at Visit 1 and 78.8 at Visit 5. In the group receiving beclomethasone, the value was 85.1 at Visit 1 and 78.3 at Visit 5. No significant difference existed between both nasal sprays comparing its tolerability immediately (
In the final assessment of tolerability, the majority of evaluable patients in both groups rated both treatments “good” or even “very good” (Table
Overall, both treatment modalities were tolerated well; no significant difference between both groups was observed (
Altogether, 20 patients from the LN group and seven patients from the cortisone group dropped out of the study. In most cases, the reasons for discontinuation remained unknown; only one patient from the LN group and two patients from the cortisone group dropped out of the study because of an adverse event (AE). AEs occurred in a total of 23 patients, 10 events of which were reported in the LN group and 13 in the group receiving the steroid nasal spray.
One patient from the LN group and five patients from the beclomethasone group also experienced a second AE (Table
Adverse events.
(1) Adverse event | (2) Adverse event | |
---|---|---|
Beclomethasone | Acute sinusitis | Acute rhinitis |
Minor hemorrhoid bleeding | Acute viral rhinopharyngitis | |
Cephalgia | Acute sinobronchitis | |
Acute bacterial sinusitis | Acute bacterial sinusitis | |
Rhinitis, cough | ||
Acute viral rhinopharyngitis | ||
Viral upper respiratory tract infection | ||
Acute viral infection | ||
Acute exacerbation of CRS | ||
Gastroenteritis | Tonsillitis | |
Acute viral rhinopharyngitis with rhinosinusitis | ||
Bronchitis | ||
Dysesthesia of nasal mucosa and facial pain | ||
|
||
Liposomal nasal spray | Recurrence of chronic lymphatic leukemia | |
Acute exacerbation of chronic rhinosinusitis | ||
Acute bronchitis | ||
Cephalgia | Fatigue | |
Rhinitis | ||
Infection of paranasal sinuses | ||
Capsulitis DII right hand | ||
Arthrosis of both hip joints | ||
Acute exacerbation of chronic pansinusitis | ||
Acute sinusitis |
None of these incidents were documented by the study investigators as serious adverse events in the serious adverse event (SAE) form. An association with the study drug could not be ruled out for five AEs in the beclomethasone and eight AEs in the LN group.
The application of both preparations resulted in a significant improvement in quality of life as early as V2
In the LN group, therapy caused a drop in the total sum score of the SNOT-20 Quality of Life Scale from
SNOT-20 subscales:primary nasal symptoms, secondary rhinogenic symptoms, and general quality of life.
V1 | V2 | V3 | V4 | V5 | Improvement | |
---|---|---|---|---|---|---|
Liposomal nasal spray | ||||||
Primary nasal symptoms | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
Secondary rhinogenic symptoms | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
2.657 |
General quality of life | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
Beclomethasone | ||||||
Primary nasal symptoms | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
Secondary rhinogenic symptoms | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
General quality of life | ||||||
MV |
|
|
|
|
|
|
SD |
|
|
|
|
|
|
Patients’ final evaluation of efficacy and tolerability.
Efficacy | Tolerability | |
---|---|---|
Liposomal nasal spray | ||
Very good | 17.8% | 39.4% |
Good | 53.8% | 50% |
Satisfactory | 17.9% | 7.9% |
Poor | 10.3% | 2.6% |
Beclomethasone | ||
Very good | 17.4% | 26.1% |
Good | 47.8% | 60.9% |
Satisfactory | 13% | 4.3% |
Poor | 21.7% | 8.7% |
Course of the SNOT total score V1 to V5.
Besides the evaluation of the SNOT-20, patients recorded their subjectively perceived condition daily in a diary as a further parameter for determining quality of life.
Figure
Diary assessment of the subjective condition of patients.
Besides antibiotics, topical treatment with corticosteroids is the guideline-recommended treatment of choice for symptomatic CRS [
Since symptom scores can always be subjectively influenced [
Overall, tolerability of the liposomal nasal spray was assessed positively; 50% of the valid percentages rated tolerability “good,” 39.4% “very good,” 7.9% “satisfactory,” and only 2.6% evaluated tolerability “poor.” Some patients commented on the smell of the liposomal spray. Since it was decided to deliberately forgo the addition of artificial aromas in the product to avoid possible allergic reactions or intolerances, the natural scent of lecithin (phospholipids) is perceptible.
A study by Rudmik and Smith showed that CRS leads to a significant loss of quality of life, among other things due to symptoms such as sleeplessness, headache, and facial pain, and also emotional consequences such as sadness and a sense of shame [
All in all, both of the applied treatments led to significant improvement in the patients’ condition, with no significant differences resulting between both study medications for the most part.
The values calculated in this study show that liposomal nasal spray is an effective treatment alternative for patients with CRS. Its application resulted in significant symptom reduction and improved quality of life. Furthermore, the majority of patients assessed its tolerability very positively. Liposomal nasal spray is therefore a suitable steroid-free method for treating CRS, particularly for patients who take a somewhat critical view of guideline-recommended therapy with cortisone.
Adverse event
Allergic rhinitis
Chronic rhinosinusitis
Liposomal nasal spray
Livocab beclomethasone
Non-interventional study
Polyp score
Quality of life
Rhinoscopy score
Serious adverse event
Sinusitis symptom score.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors would like to thank Gena Kittel and Marie-Josefine Joisten for their editorial assistance. The study was funded and the medication was provided by Optima Pharmazeutische GmbH, Moosburg/Wang, Germany.