Effects of Heated Humidification and Topical Steroids on Compliance, Nasal Symptoms, and Quality of Life in Patients with Obstructive Sleep Apnea Syndrome Using Nasal Continuous Positive Airway Pressure

Abstract

Background:

Nasal side effects are common in patients with obstructive sleep apnea syndrome (OSAS) starting on nasal continuous positive airway pressure (CPAP) therapy. We tested the hypothesis that heated humidification or nasal topical steroids improve compliance, nasal side effects and quality of life in this patient group.

Methods:

125 patients with the established diagnosis of OSAS (apnea/hypopnea index ≥ 10/h), who tolerated CPAP via a nasal mask, and who had a successful CPAP titration were randomized to 4 weeks of dry CPAP, humidified CPAP or CPAP with additional topical nasal steroid application (fluticasone, GlaxoWellcome). Groups were similar in all demographic variables and in frequency of nasal symptoms at baseline. Outcome measures were objective compliance, quality of life (short form 36), subjective sleepiness (Epworth Sleepiness Scale score) and nasal symptoms such as runny, dry or blocked nose, sneezing and headaches; all variables assessed using a validated questionnaire and by direct interview.

Results:

There was no difference in compliance between groups after 4 weeks (dry: 5.21 ± 1.66 h/night, fluticasone: 5.66 ± 1.68, humidifier: 5.21 ± 1.84; p = 0.444). Quality of life and subjective sleepiness improved in all groups, but there were no differences in the extent of improvement. Nasal Symptoms were less frequently reported in the humidifier group (28%) than in the remaining groups (dry: 70%, fluticasone: 53%, p = 0.002). However, the addition of fluticasone resulted in increased frequency of sneezing.

Conclusion:

The addition of a humidifier, but not nasal steroids decreases the frequency of nasal symptoms in unselected OSAS patients initiating CPAP therapy; however compliance and quality of life remain unaltered.

Citation:

Ryan S; Doherty LS; Nolan GM; McNicholas WT. Effects of heated humidification and topical steroids on compliance, nasal symptoms, and quality of life in patients with obstructive sleep apnea syndrome using nasal continuous positive airway pressure. J Clin Sleep Med 2009;5(5):422-427.

Obstructive sleep apnea syndrome (OSAS) is a common and potentially serious disorder, affecting around 4% of adults.¹ It is characterized by repeated episodes of apnea during sleep, up to several hundred times per night, which lead to hypoxia, sleep fragmentation, and excessive daytime sleepiness. OSAS is associated with serious sequelae such as road traffic accidents and significant cardiovascular morbidity and mortality.^2–4

Nasal continuous positive airway pressure (CPAP) is the current therapy of choice, particularly in moderate and severe cases. It has been shown to improve quality of life, to reduce the risk of driving and occupational accidents, and to decrease cardiovascular morbidity and mortality.^5–8 However, the device is cumbersome and compliance rates are only moderately satisfactory.^9,10 Nasal congestion, rhinorrhea, and sneezing are among the most frequent side effects of nasal CPAP therapy for OSAS directly affecting patient adherence to treatment.^10,11 Therefore, interventions to improve these side effects could potentially lead to improved compliance and furthermore to a better quality of life. Heated humidification and topical nasal steroid sprays are frequently prescribed to treat nasal complaints. Whether heated humidification improves patient compliance and quality of life is still under debate. In a cohort study of 82 patients with OSAS, heated humidification was associated with improved CPAP compliance.¹² In two further studies using a short-term crossover design, the addition of heated humidification led to a significantly better compliance and decrease in nasal side effects.^13,14 However, in a recent parallel study comparing humidification and standard therapy, no difference in compliance and quality of life were observed, despite improvement in nasal side effects.¹⁵ No randomized study so far has assessed the benefit of topical nasal steroid medication on patient compliance and quality of life.

We performed a prospective randomized study to test the hypothesis that heated humidification or nasal topical steroids improve compliance, nasal side effects, and quality of life in OSAS patients initiating CPAP therapy.

METHODS

Subjects

Patients were recruited consecutively from the Respiratory Sleep Disorders Unit at St. Vincent's University Hospital, Dublin, Ireland. Patients were eligible to participate if they had a confirmed diagnosis of OSAS with an apnea/hypopnea index (AHI) of ≥ 10/h, never treated with CPAP, had a successful nasal CPAP titration study, and if they had adequate nasal breathing. Exclusion criteria were requirement for bilevel positive airway pressure therapy or supplemental oxygen; malignant disease; psychiatric disease; and regular use of narcotics, sedatives, or psychoactive medications. The study protocol was approved by the St. Vincent's University Hospital Ethics Committee. Each subject gave written informed consent.

Study Design

All subjects were assigned a CPAP machine (PV10, Breas Medical, Moelnlycke, Sweden) and had a nasal mask fitted by an experienced sleep specialist nurse. Patients were randomly assigned to standard CPAP therapy (dry CPAP), heated humidified CPAP (humidifier HA 50, Breas Medical) or CPAP with additional nasal steroid spray (fluticasone propionate, Glaxo Wellcome, Burgos, Spain, 50 mcg [1 metered dose] twice daily). Patients assigned to humidification received detailed instruction in the use of the device. Subjects on fluticasone were instructed in the application of the drug and were asked to keep a record of usage. All participants were asked to contact our sleep laboratory in the event of problems developing during the trial.

After 4 weeks patients were evaluated by an experienced physician and specifically interviewed about side effects and nasal symptoms. Time-coded compliance data from the CPAP device were downloaded at the time of this visit.

Questionnaires

All participants were asked to complete a set of questionnaires at baseline and after 4 weeks of treatment. Quality of life was assessed using the Short Form 36 Health Survey (SF-36).¹⁶ Subjective sleepiness was evaluated with the Epworth Sleepiness Scale (ESS).¹⁷ Nasal side effects were assessed by using the validated Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ).¹⁸ Briefly, MiniRQLQ contains of 14 items in 5 domains (activity limitations, practical problems, nose symptoms, eye symptoms, and other problems including tiredness, thirst, and feeling irritable). The questionnaire is in self-administered form, and patients are asked to consider how they have been during the last 4 weeks and to respond to each question on a 7-point scale (0 = no impairment, 6 = severely impaired).

Statistical Analysis

Data are expressed as mean ± standard deviation. Baseline characteristics and changes in outcome variables were compared by one-way analysis of variance (ANOVA) followed by post hoc comparisons (Student-Newman-Keuls and Duncan). Categorical values were compared using a χ² test. Changes in outcome measures over time in the whole study population were compared by paired t-test. All analyses were undertaken using the intention-to-treat principle.

The expected difference in the primary outcome variable (compliance) which might be clinically important and the pooled standard deviation were specified on the basis of the previous published studies and on an in-house pilot trial. The required sample size to detect a difference of 1.0 h with 80% power at the 5% significance level, based on a pooled standard deviation of 1.7 h, was 38 subjects in each group.

RESULTS

Subjects

One hundred twenty-five consecutive patients who met inclusion criteria were recruited. No subject refused participation. Two patients were dropped from the study because of inadequate nasal CPAP titration. Patient characteristics of the study population are described in Table 1. The 3 groups were similar with regards to age, gender, body mass index, smoking status, and severity of OSAS. There was no significant difference in the prevalence of chronic nasal symptoms prior to CPAP initiation.

Table 1.

Baseline Characteristics of Study Population

	Dry	Fluticasone	Humidifier
No	39	42	42
Male	36 (92%)	40 (95%)	40 (95%)
Age (years)	48 ± 8	48 ± 12	50 ± 12
BMI* (kg/m2)	35.1 ± 6.4	33.0 ± 5.3	35.3 ± 6.1
Current smokers	8 (21%)	13 (31%)	13 (31%)
History of sinusitis	12 (29%)	16 (38%)	15 (36%)
ESS†	12 ± 5	13 ± 6	13 ± 6
AHI‡	36 ± 22	35 ± 21	36 ± 20
CPAP pressure (cm H2O)	10 ± 2	10 ± 2	10 ± 2

^*body mass index;

^†Epworth Sleepiness Scale;

^‡apnea/hypopnea index

Of the 123 patients participating in the study, 112 subjects (91%) completed the trial. One patient was dropped following admission with acute myocardial infarction 10 days after enrollment, and 10 subjects did not wish to continue nasal CPAP therapy because of intolerance to the treatment (n = 5) or unknown reasons (n = 5). Of the 10 patients wishing to discontinue CPAP, 5 were randomized to dry treatment, 2 were commenced on additional nasal steroid, and 3 were started on additional humidification [p = 0.207]).

Nasal Symptoms

Nasal symptoms prior to CPAP therapy and at time of follow-up were assessed by a validated nasal questionnaire and by direct questioning of the patients. Analyzing the MiniRQLQ, there was no difference between baseline and follow-up or between groups in the domains activities, practical problems, and eye symptoms (Table 2). There was an overall significant improvement between baseline and follow-up in the mean scores for the domains tiredness (3.44 ± 1.83 vs. 1.84 ± 1.63, p < 0.001), thirst (2.00 ± 1.77 vs. 1.15 ± 1.54, p < 0.001) and feeling irritable (2.23 ± 1.86 vs. 1.21 ± 1.42, p < 0.001); however, there was no difference in the extent of improvement between groups (Table 2). Nose symptoms increased between baseline and follow-up (overall: 1.21 ± 1.16 vs. 1.68 ± 1.35, p < 0.001; sneezing: 1.17 ± 1.36 vs. 1.64 ± 1.71, p = 0.006; blocked nose: 1.44 ± 1.44 vs. 2.06 ± 1.65, p = 0.001; runny nose: 1.01 ± 1.41 vs. 1.35 ± 1.69, p = 0.025). While there was no difference between nose symptoms between groups at baseline, at time of follow-up there was an overall difference (p = 0.009 by ANOVA) with highest scores in the fluticasone group (p = 0.008 vs. humidifier), scores for sneezing and runny nose were also highest in the fluticasone group. Score for blocked nose was significantly lower in the humidifier group than in the other 2 groups (Table 2).

Table 2.

MiniRQLQ scores at baseline (BL) and after 1 month (1 mo) of CPAP therapy

	Dry		Fluticasone		Humidifier
	BL	1 mo	BL	1 mo	BL	1 mo
Activity limitations	1.57 ± 1.39	1.35 ± 1.10	1.68 ± 1.55	1.59 ± 1.51	1.69 ± 1.39	1.24 ± 1.05
Regular activities at home	1.36 ± 1.62	1.03 ± 1.24	1.21 ± 1.53	1.25 ± 1.50	1.34 ± 1.48	0.95 ± 1.31
Recreational activities	1.15 ± 1.42	1.18 ± 1.36	1.44 ± 1.80	1.40 ± 1.72	1.29 ± 1.39	0.97 ± 1.07
Sleep	2.18 ± 1.83	1.85 ± 1.50	2.38 ± 2.20	2.13 ± 1.90	2.45 ± 2.09	1.81 ± 1.60
Practical problems	1.23 ± 1.08	1.50 ± 1.42	2.00 ± 1.59	2.08 ± 1.64	1.37 ± 1.62	1.54 ± 1.55
Need to rub nose/eyes	1.39 ± 1.30	1.36 ± 1.39	1.87 ± 1.81	2.00 ± 1.83	1.34 ± 1.76	1.54 ± 1.56
Need to blow nose repeatedly	1.36 ± 1.30	1.58 ± 1.73	1.83 ± 1.89	2.15 ± 1.82	1.39 ± 1.70	1.54 ± 1.84
Nose symptoms	0.89 ± 0.87	1.56 ± 1.22	1.40 ± 1.24	2.16 ± 1.48	1.28 ± 1.25	1.27 ± 1.15^
Sneezing	0.98 ± 1.08	1.15 ± 1.44^	1.23 ± 1.26	2.15 ± 1.85	1.26 ± 1.64	1.44 ± 1.65
Stuffy/blocked nose	1.26 ± 1.17	2.52 ± 1.72	1.62 ± 1.62	2.38 ± 1.82	1.58 ± 1.45	1.38 ± 1.14^#
Runny nose	0.93 ± 1.15	1.00 ± 1.39^	1.16 ± 1.52	1.95 ± 1.92	1.00 ± 1.49	0.97 ± 1.45
Eye Symptoms	0.92 ± 1.10	0.57 ± 0.71	1.36 ± 1.39	1.18 ± 1.38	0.88 ± 1.26	0.97 ± 1.08
Itchy eyesa	1.19 ± 1.11	0.61 ± 0.86	1.44 ± 1.68	1.23 ± 1.44	0.82 ± 1.31	0.92 ± 1.21
Sore eyes	0.76 ± 1.20	0.48 ± 0.83	1.41 ± 1.71	0.98 ± 1.56	0.82 ± 1.37	0.84 ± 1.19
Watery eyes	0.91 ± 1.23	0.61 ± 1.09	1.23 ± 1.61	1.35 ± 1.72	1.00 ± 1.80	1.16 ± 1.44
Other symptoms	2.36 ± 1.30	1.27 ± 1.13	3.03 ± 1.71	1.50 ± 1.56	2.17 ± 1.25	1.36 ± 1.32
Tiredness/fatigue	3.24 ± 1.56	1.82 ± 1.51	3.85 ± 2.00	1.80 ± 1.74	3.16 ± 1.79	1.84 ± 1.64
Thirst	1.82 ± 1.61	0.94 ± 1.22	2.51 ± 2.01	1.28 ± 1.74	1.55 ± 1.50	1.19 ± 1.58
Feeling irritable	2.03 ± 1.65	1.06 ± 1.22	2.72 ± 2.06	1.42 ± 1.62	1.79 ± 1.76	1.05 ± 1.33

^{^}p-value < 0.05 vs. fluticasone,

^#p-value < 0.05 vs. dry treatment

On direct questioning, nasal symptoms were more commonly reported in the dry group (dry: 70%, fluticasone: 53%, humidifier: 28%; ANOVA: p = 0.002) (Figure 1). Nasal congestion was more frequent in the dry group than the other 2 groups. Sneezing was most frequently reported in the fluticasone group.

Figure 1.

Frequency of nasal side effects in patients on dry treatment (black bars), additional fluticasone (white bars), and with heated humidification (grey bars) (A = analysis as per intention-to-treat, B = analysis excluding patients switching treatment). P-values: *p < 0.05 versus humidifier; #p < 0.05 versus fluticasone.

In 3 patients of the group assigned to dry treatment, nasal symptoms were a moderate to severe problem, which required the addition of fluticasone in 2 patients and a humidifier in one patient during the trial. Of the fluticasone group, 4 patients were crossed over to dry treatment because of intolerance to the spray, and one patient required the addition of a humidifier because of increasing nasal symptoms. Eight patients of the humidifier group crossed over to dry treatment because of intolerance to heated humidification. After exclusion of all subjects who did not finish the trial with their randomized treatment form, frequencies of nasal symptoms did not change significantly (Figure 1B). Overall, there was no significant difference in the frequency of crossovers between groups.

Compliance

Compliance with nasal CPAP of the 3 groups is given in Table 3. There was no difference in objective compliance between groups in the analysis as per intention-to-treat and also after the exclusion of patients who were crossed over to a different treatment during trial, although a small trend towards improved compliance in the group on fluticasone therapy was noted.

Table 3.

CPAP Compliance

	Dry	Fluticasone	Humidifier
A
% of nights used	76 ± 25	82 ± 22	77 ± 26
Average duration (h)	5.21 ± 1.66	5.66 ± 1.68	5.21 ± 1.84
B
% of nights used	77 ± 25	84 ± 19	76 ± 28
Average duration (h)	5.39 ± 1.48	5.90 ± 1.57	5.22 ± 1.94

A = analysis as per intention-to-treat, B = analysis excluding patients switching treatment

Quality of Life and Sleepiness

Analysis of the SF-36 quality of life questionnaire showed a significant improvement at follow-up from baseline in the overall score and in all domains except for role limitation due to emotional problems (p = 0.092). However, there were no significant differences between the three groups. Subjective sleepiness was evaluated by the ESS. Overall, ESS was reduced by CPAP therapy from a pre-treatment baseline of 14 ± 5 to 8 ± 5 (p < 0.001), but there was no significant change in the extent of improvement between groups (dry: 9 ± 5, fluticasone: 9 ± 5, humidifier: 8 ± 6; ANOVA: p = 0.694).

Treatment Following Trial

At the end of the study, patients were assessed to determine if current treatment form was appropriate to continue, or if a change was indicated. Twenty-three (70%) patients on dry treatment remained on this form; a humidifier was added for 3 patients, and fluticasone nasal spray was added for persistent nasal symptoms in 4 patients. Of the fluticasone group, only 14 (35%) continued with the nasal steroid; a humidifier was added for 9 patients, and 12 subjects continued on dry CPAP. Eighteen (46%) subjects in the humidifier group continued with the same treatment, 9 switched to dry treatment, and 4 switched to fluticasone.

DISCUSSION

The present report demonstrates that the addition of heated humidification but not nasal steroid medication decreases the incidence of nasal side effects in OSAS patients initiating nasal CPAP therapy. However, compliance rates and quality of life remain unaltered by these interventions.

The overall incidence of nasal side effects, particularly nasal congestion, rhinorrhea, and sneezing in our cohort was high (49%), in keeping with previous reports in the literature.^11,12,19 These symptoms might be caused by inflammation as a result of reduced relative humidity in the inspired gas, resulting in increased airway resistance.²⁰ Therefore, humidification of the delivered gas may improve these symptoms, and it has been demonstrated that heated but not cold humidification during CPAP therapy increases the relative humidity of the inspired air and reduces the water loss during respiration.²¹ Given this background, it is not surprising that nasal side effects improved with the addition of a heated humidifier. However, this did not result in improvements in compliance, quality of life, or sleepiness when compared to dry treatment. These findings are in keeping with another parallel trial comparing humidification to dry treatment.¹⁵ However, 2 short-term crossover trials detected an improvement in compliance, but again not in quality of life or sleepiness with the addition of a heated humidifier.^13,14 However, the improvement in compliance was relatively small ranging from 0.2 to 0.5 hours. Our study was not powered to detect such a small difference, which may contribute to the different conclusions. We chose 1 hour in compliance difference as the outcome variable, because in the early period of CPAP treatment, as in our study, it is necessary to establish adherence to CPAP therapy; various studies suggest that determination of long-term adherence is predicted by larger difference in compliance.^22–24

Topical nasal steroids are frequently prescribed as an alternative approach to treat nasal complaints associated with CPAP therapy. Various studies have demonstrated an association of OSAS with allergic rhinitis,^25,26 and a recent randomized placebo-controlled study from our unit showed a significant improvement in nasal obstruction and AHI in patients with OSAS following one month's therapy with intranasal fluticasone.²⁷ However, the present study is the first to assess the efficacy of intranasal steroids in consecutive patients with OSAS initiating CPAP therapy. While the frequency of nasal congestion was significantly less in the fluticasone group than in the group receiving dry treatment, this benefit was outweighed by the increased frequency of sneezing and rhinorrhea. As a result, only 35% subjects of the fluticasone group were happy to continue with the topical steroids after the trial. Sneezing with the usage of fluticasone is likely caused by a local irritation caused by the aqueous spray and listed as a mild side effect by the producing company. All of our patients reported a cessation of this side effect within a few minutes of application.

Overall, our results support previous findings indicating that nasal side effects, although commonly reported, do not usually result in reduced adherence to CPAP therapy or discontinuation of the treatment.^28,29 Patient perception of symptoms and improvement in sleepiness and daily functioning seem to be most important in determining compliance,²⁸ and emerging data suggest that various behavioral interventions such as adequate education, instruction, and support play an important role.³⁰ We chose a cohort of consecutive patients without specific focus on pre-existing rhinitis/sinusitis for our study in order to draw conclusions relevant to the general OSAS population initiating CPAP therapy. However, there may be a significantly greater benefit of humidification or fluticasone in patients complaining of chronic nasal symptoms prior to initiating CPAP.

Our results have further clinical implications. Nearly half the patients in our study population did not remain on the treatment form on which they were originally started after finishing the trial; this affected all 3 groups equally. Reasons for the switches were numerous and included improvement in nasal side effects and intolerance and/or lack of benefit of the assigned treatment. These findings emphasize the importance of assessing patients on an individual basis and do not support the routine addition of humidification at initiation of CPAP therapy.

A potential limitation of our study relates to the fact that compliance with the assigned treatment form of humidification or intranasal corticosteroid could not be objectively measured. The humidifier used in our study is a separate device, ensuring that all other patients could not use it. Inspection of the water chamber in the humidifier group indicated usage, but it was impossible to quantify the extent. Patients on fluticasone were asked to keep a diary about the application and were interviewed specifically for this point at their follow-up visit, but similarly, there was no objective way of measuring compliance. However, this limitation applies to all previous studies addressing this issue.

We chose a parallel trial design for our study, as early experience with CPAP therapy may influence long-term acceptance and compliance,³¹ and therefore early intervention might be most beneficial. We assessed compliance only at the 4-week time point and therefore, it remains speculative how our results relate to long-term effects. The investigator administering the questionnaires and downloading the CPAP devices was blinded to the treatment arm. However, patients were not blinded, since blinding would be difficult to achieve and requiring the use of placebo humidification, which has also been a limitation of previous studies.^13–15 However, there was no difference in compliance as the main outcome variable, so that we feel this point is unlikely to be of great significance. Our data apply to a general OSAS population; subjects with preexisting allergic rhinitis might have experienced greater benefit with the addition of humidification or fluticasone, as previously described.²⁶

About 10% of our study population was unable to remain in their randomization group during the trial. The analysis as per study design was by intention-to-treat. However, statistical analysis of the results after excluding subjects who switched therapy during the trial was very similar, and thus we believe did not affect the study conclusions.

In summary, the addition of heated humidification but not topical steroid led to a decrease in nasal side effects in OSAS patients initiating CPAP therapy but compliance, quality of life, and sleepiness remained unaffected by these measurements. Thus, we recommend that patients be evaluated on an individual basis for the addition of a heated humidifier or topical steroids when initiating CPAP therapy.

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest.