Provent Therapy for Obstructive Sleep Apnea: Impact of Nasal Obstruction

Transcription

1 The Laryngoscope VC 2015 The American Laryngological, Rhinological and Otological Society, Inc. Provent Therapy for Obstructive Sleep Apnea: Impact of Nasal Obstruction Michael Friedman, MD; Michelle S Hwang, BS; Sreeya Yalamanchali, MD; Thomas Pott, MD; Mandeep Sidhu, BS; Ninos J. Joseph, BS Objectives/Hypothesis: Determine the impact of nasal obstruction on efficacy, success, and adherence of Provent therapy in patients with obstructive sleep apnea (OSA). Study Design: Prospective, two-arm, clinical pilot study at a single clinical site. Methods: Patients with OSA who failed continuous positive airway pressure therapy were divided into two treatment arms: arm 1 were patients with no complaints of nasal obstruction and <50% nasal obstruction on exam, and arm 2 were patients with occasional complaints of nasal obstruction and 50% to 80% nasal obstruction on exam. Sleep testing at home was performed prior to the trial and on day 10 of the study with the use of Provent. Results: Apnea-hypopnea index (AHI) decreased significantly from to (P <.001) in our total patient population. Patients in arm 1 had statistically significant improvement in their AHI ( to , P <.001), oxygen desaturation index (ODI) ( to , P <.001), and minimum oxygen saturation (81.3% 6 6.7% to 86.9% 6 5.6%, P ) from baseline sleep study to sleep study 2. Patients in arm 2 had improvements in their AHI ( to ), ODI ( to ) and minimum 0 2 %. However, none of these reached statistical significance. Conclusions: In this study, Provent therapy had a high failure rate. Patients without nasal obstruction showed greater improvements using Provent than patients with obstruction. Correction of nasal obstruction may be a useful prerequisite for treatment with Provent. Key Words: Obstructive sleep apnea, Provent sleep apnea therapy. Level of Evidence: 2B. Laryngoscope, 126: , 2016 INTRODUCTION The idea of expiratory positive airway pressure (EPAP) was described almost 30 years ago by Mahadevia et al. as a treatment for the reduction of apneic events during sleep. 1 Recently, an EPAP nasal device (Provent; Theravent Medical Inc., Belmont, CA) has been developed to provide a new therapeutic option for those with obstructive sleep apnea (OSA). Provent sleep apnea therapy creates EPAP using the patient s own breathing. It is a one-time use, disposable device worn nightly and consists of a small valve held in place just inside each nostril by a hypoallergenic adhesive. During inhalation, the device allows nearly unrestricted airflow through the nose. During exhalation, air is directed through From the Section of Sleep Surgery (M.F.), Rush University Medical Center, Chicago, Illinois; and the Advanced Center for Specialty Care (M.F., M.S.H., S.Y., T.P., M.S., N.J.J.), Advocate Illinois Masonic Medical Center, Chicago, Illinois, U.S.A. Editor s Note: This Manuscript was accepted for publication March 16, Michael Friedman, MD, is the recipient of a grant from Imthera Medical to conduct a clinical research trial on hypoglossal nerve stimulation. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Michael Friedman, MD, Medical Director, Chicago ENT an Advanced Center for Specialty Care, 30 North Michigan Ave, Suite 1107, Chicago, IL mfriedmanmd@gmail.com DOI: /lary smaller channels increasing resistance to airflow, thus increasing the upper airway pressure. Similar to continuous positive airway pressure (CPAP), the EPAP created helps to maintain an open airway during sleep (Fig. 1). Provent sleep apnea therapy has been shown to achieve therapeutically acceptable improvements in apnea-hypopnea index (AHI) in multiple prior studies. 2 7 A prospective, randomized, sham-controlled trial noted a 42.7% reduction in the AHI (vs. 10.1% in the sham control) over a period of 3 months. 2 Furthermore, studies also noted a significant reduction in the number of snoring events as well as improvements in the Epworth Sleepiness Scale score after continued use of Provent. 2,5,6 However, prior studies had stringent exclusion criteria and excluded patients with upper airway surgery, patients who had tried CPAP, and patients with nasal obstruction. Prior studies focused on the efficacy and tolerability of Provent, and baseline predictors of treatment success were not identified. Studies also show that correction of nasal obstruction leads to a significant decrease in CPAP titration levels and improved CPAP use On the basis of the previous CPAP studies, we hypothesized that the tolerability and efficacy of Provent sleep apnea therapy might be similarly linked to nasal patency. Thus, the objective of this study was to assess tolerability, efficacy, and compliance with Provent sleep apnea therapy with respect to preexisting nasal airway patency in patients

2 Fig. 1. The Provent device is attached via an adhesive sticker. The valve placed just inside the nostrils creates expiratory positive airway pressure that increases the airway caliber. [Color figure can be viewed in the online issue, which is available at with OSA-hypopnea syndrome (OSAHS). From this study, we will be able to define a subgroup of patients for whom nasal EPAP therapy is most beneficial. MATERIALS AND METHODS Patient Recruitment and Study Initiation This prospective study received approval from Western Institutional Review Board. Informed consent was obtained from each patient enrolled in the study. Participants were recruited among adult patients (18 years of age) from the study site s patient population between September 2012 and September Patient s had an existing diagnosis of OSA based upon a formal sleep study within the preceding 12 months and had a history of previously failed CPAP therapy. They were given the option of a trial with Provent as an alternative to an oral appliance or surgical correction of the upper airway. Patients seeking Provent treatment were divided into three clinical groups based on patient-reported symptoms and physical examination. A complete history of daytime and nocturnal nasal symptoms was obtained. Speculum examination included assessment of the nasal valve area with the Cottle maneuver. Examination of the nasal airway was performed with and without decongestant spray. Endoscopy was performed to rule out any unusual findings in the posterior nares or posterior nasopharynx. Patients with evidence of soft tissue congestion were treated with a standardized combination of topical steroids and antihistamines. Acoustic rhinometry was performed on all patients, but used primarily to show a pre- and postoperative change in the cross-sectional area at the nasal valve. Patients in arm 1 did not have any complaints of nasal obstruction, neither in the upright or supine positions, and physical exam supports <50% mechanical obstruction of the nasal airway. Patients in arm 2 did not have significant complaints of nasal obstruction, but admitted to having occasional symptoms of nasal obstruction and or mouth breathing at times during the day or night. Physical exam confirmed the presence of nasal obstruction, but neither side had >80% obstruction. Patients in arm 3 had frequent day or night nasal symptoms in addition to physical exam findings of a minimum of >80% mechanical obstruction on one side of the nasal passageway or both. In our treatment algorithm for patients with OSA, all patients in arms 1, 2, or 3 were candidates for CPAP therapy in combination with medical treatment for any turbinate congestion. If patients were seeking surgical correction of their upper airway, group 2 and group 3 patients were referred for corrective procedures of their nasal airway prior to surgery on their hypopharynx or pharynx. Sites of nasal surgical correction can include the nasal valve, septum, turbinates, or removal of polyps. Based on these guidelines and the algorithm for general treatment of OSA, the purpose of this study was to assess whether patients in arm 2 would do better with correction of their nasal airway prior to Provent therapy. Therefore, the study was designed to compare untreated patients in arm 2 against a control of patients in arm 1. Provent Patients were provided with 30 nights worth of standard resistance, nightly use disposable Provent sleep apnea therapy devices and were instructed to continue nightly use of the device. The device consists of a single-use valve inserted into each nostril and held in place by a hypoallergenic adhesive. A leak-free seal is formed between the valve and the nose by applying the adhesive to the outer edges of the nares. Treatment Evaluations During the 30-day period, patients were asked to complete a 30-night diary sheet to be filled in each morning with respect to the previous night of sleep. Approximate numbers of hours of sleep and approximate numbers of hours of Provent used were tracked. Patients also completed the Epworth Sleepiness Scale (ESS), Sleep Apnea Quality of Life Index (SAQLI), and Snoring Intensity Visual Analogue Scale (VAS) on the first day before the use of Provent sleep apnea therapy and after 30 days of use. The ESS is a validated method of assessing daytime somnolence in patients with OSAHS. 11 The SAQLI is a validated questionnaire for measuring the effect of OSAHS on a subject s quality of life. 12 The VAS is a scale by which the subject s bed partner is asked to rank the severity of his/her snoring from 0 (no snoring) to 10 (very loud/severe snoring). 13 Polysomnography The ResMed ApneaLink Plus (ResMed Corp., San Diego, CA)system was used for unattended sleep testing at home. This system has been validated against formal polysomnography to be used in patients with a high pretest probability of moderate 255

3 to severe OSA. 14 Patients were given a ResMed ApneaLink Plus system to be used on day zero prior to starting use of Provent sleep apnea therapy (baseline home sleep study). After an adjustment period of 7 to 10 days of using Provent, patients once again underwent a subsequent home sleep test with the Provent device in place (home sleep study 2). A specifically designed Provent compatible nasal cannula was used that attached securely to the nasal EPAP device. AHI, oxygen desaturation Index (ODI), minimum oxygen saturation (min SpO 2 ), number of snoring events, and sleep duration were all recorded by the ResMed Apnea Link Plus system. Apnea was defined as 90% decrease in airflow amplitude relative to baseline value lasting for 10 seconds. Hypopnea was defined as 50% decrease in the airflow amplitude relative to baseline value lasting for 10 seconds, with the presence of arousal or oxygen desaturation of at least 4%. The ODI was calculated as the total number of 4% or greater decreases in the oxygen saturation per hour of sleep. Snoring events were captured through the vibrations of the airway passages. The ResMed Apnea Link Plus device derives the snoring signal from the sensing device and filters the signal to allow a 0 to 60 Hz waveform to be analyzed for snoring events. The minimum amplitude threshold necessary for the event to be classified as snoring is 6%. A snoring event was counted if it lasted anywhere from a minimum of 0.3 seconds to a maximum of 3.5 seconds. Noise that lasted longer than 3.5 seconds was classified as an interference noise. Analysis All analyses were performed by SPSS 19.0 (SPSS Inc., Chicago, IL), and P <.05 was accepted as statistically significant. Objective measurements of sleep apnea between the baseline home sleep study and the second home sleep study and quality-oflife questionnaires from baseline to the end of the study were compared using paired t tests. Adherence was analyzed by dividing the total number of hours of Provent use to the total number of hours of sleep (hours of Provent use/hours of sleep). Cure was defined as an AHI 5 on polysomnography 2. Success was defined as a decrease in baseline AHI by 50% and an AHI between 5 and 20. Everyone else was considered a treatment failure. RESULTS Baseline Characteristics A total of 59 patients were recruited into our study and divided into two treatment arms based on patient reported symptoms of nasal obstruction and the degree of nasal obstruction (Fig. 2). Thirty-eight patients completed the full 30 days of Provent treatment. Arm 1 consisted of 21 patients with <50% nasal obstruction, whereas arm 2 consisted of 17 patients with 50% to 80% nasal obstruction. As Table I shows, there were no significant demographic differences between arm 1 and arm 2. Out of the 21 patients who dropped out of the study, seven patients explicitly stated that they were unable to tolerate Provent within the first 7 days prior to the second home study, whereas 14 patients were lost to follow-up and did not complete the study. There were no statistically significant differences in the percentage of dropouts between treatment arm 1 (47.6%) and treatment arm 2 (64.7%) (P 5.771). Thus, there was no association between nasal obstruction and the dropout rate. Sleep-Disordered Breathing Parameters Tables II and III summarize the mean 6 standard deviation results of objective and subjective parameters. Multivariate analysis of the change in AHI using age, body mass index, gender, and Friedman tongue position did not show any significant correlations. Overall, AHI decreased significantly from to (P <.001) in our total patient population. Patients in arm 1 had significant improvements in their AHI ( to , P <.001), ODI ( to , P <.001), and min SpO 2 (81.3% 6 6.7% to 86.9% 6 5.6%, P 5.008) from baseline home sleep study to home sleep study 2 with the use of Provent. Patients in arm 2 had slight improvements in their AHI ( to ), ODI ( to ) and min SpO 2 percent. However, none of these improvements reached statistical significance. Importantly, patients in both treatment arms had significant reductions in the number of snoring events from to (P 5.001) in arm 1 and from to in arm 2 (P 5.001). ESS, SAQLI, VAS At baseline, patients in arm 1 had a mean ESS of , which improved to after 30 days of Provent use. However, this was not a statistically significant improvement. On the other hand, patients in arm 2 had a mean baseline ESS of , which improved significantly to (P 5.046). Patients in arm 1 had a baseline SAQLI of , which improved slightly to after 30 days of Provent use. However, this improvement was not significant (P 5.805). Patients in arm 2 had a baseline SAQLI of , which after 30 days of Provent use did not change ( , P 5.833). However, patients in both treatment arms noted a significant reduction in the severity of snoring as measured by the VAS. Patients in arm 1 had a baseline VAS of , which improved significantly to (P 5.009). Patients in arm 2 had a baseline VAS of , which improved significantly to (P <.001). Adherence The overall reported mean adherence rate in all patients was 86.3% of total sleep time. Patients in arm 1 reported wearing the device for 84.2% of their total sleep time, and patients in arm 2 reported wearing the device for 89.1% of their total sleep time. There was no statistically significant difference between the adherence rate of arm 1 and arm 2. Cure, Success, and Failure Rates (Intent to Treat Analysis) For patients in treatment arm 1, 14 out of 31 patients (45.2%) were cured of disease, whereas three out of 31 patients (9.7%) achieved successful treatment (Table IV). However, Provent therapy failed to achieve successful treatment or cure in 43.3% of patients in treatment arm

4 Fig. 2. Flowchart of recruitment. TABLE I. Demographics of All Subjects. Arm 1: No Nasal Symptoms 1 <50% Nasal Obstruction Arm 2: Occasional Nasal Symptoms 1 50% 80% Nasal Obstruction P Value Sample size Age, yr Gender, male 52.4% 76.5% BMI Mean baseline AHI Mean baseline ODI Dropouts *.771 Analysis of variance showed no statistically significant difference in demographics between arm 1 and arm 2. *v 2 test showed no statistically significant difference in dropout rates between arm 1 and arm 2. AHI 5 apnea-hypopnea index; BMI 5 body mass index; ODI 5 oxygen desaturation index. For patients in treatment arm 2, seven out of 28 patients (25.0%) were cured of disease, whereas three out of 28 patients (10.7%) achieved successful treatment. Similarly, Provent therapy failed to achieve successful treatment or cure in 64.3% of patients in treatment arm 2. There were no significant differences between the cure rates, success rates, or failure rates between the two treatment arms (P 5.251). DISCUSSION Previous studies on nasal EPAP have validated the efficacy and tolerability of nasal EPAP therapy in only a subset of patients due to the application of stringent exclusion criteria. 15,16 A study by Patel et al. attempted to identify a patient population for whom nasal EPAP therapy may be appropriate. However, this pilot study was unable to find any consistent demographics or polysomnography-related predictors to establish predictors of success. 7 Correction of nasal obstruction alone has not been shown to effectively correct respiratory parameters and cure OSAHS. In 2011, Li et al. conducted a metaanalysis of 13 studies, and found that nasal surgery had a pooled surgical success rate of 16.7% in treating OSAHS, despite significant subjective symptom improvements. 17 However, nasal obstruction has been shown to play a role in the efficacy of treatment. Several studies 257

5 TABLE II. Objective and Subjective Changes in Treatment Arm 1 With the Use of Provent (N 5 21). Baseline Post-Provent Treatment P Value AHI <.001* ODI <.001* Minimum 81.3% 6 6.7% 86.9% 6 5.6%.008* O 2 % Snoring * events ESS SAQLI * VAS * *Statistically significant improvement with the use of Provent AHI 5 apnea-hypopnea index; ESS 5 Epworth Sleepiness Scale; ODI 5 oxygen desaturation index; SAQLI 5 Sleep Apnea Quality of Life Index; VAS 5 visual analogue scale. have demonstrated that increased nasal resistance prior to CPAP treatment had a remarkable impact on the clinical efficacy and initial acceptance of CPAP Sugiura et al. noted that high nasal resistance was a significant risk factor for acceptance of CPAP, and that nasal resistance could be a predictive parameter for the acceptance of CPAP. 8 Friedman et al. noted that nasal airway reconstruction may contribute to a decrease in CPAP level and improvement in oxygen saturation. 9 On the basis of these results, we hypothesized that the efficacy and tolerability of Provent nasal EPAP might similarly be linked to nasal patency and might be a predictor of success. Although there were no significant differences between the dropout rates and adherence rates in treatment arm 1 versus treatment arm 2, patients in arm 1 had a greater reduction in their AHI than patients in arm 2. In concordance with prior studies, our results also show an effective reduction in AHI with the use of a nasal EPAP device in our overall group. However, analysis of our two treatment arms show that patients with no reported symptoms of nasal obstruction and <50% TABLE III. Objective and Subjective Changes in Treatment Arm 2 With the Use of Provent (N 5 17). Baseline Post-Provent Treatment P Value AHI ODI Minimum 76.8% % 79.2% %.335 O 2 % Snoring * events ESS * SAQLI VAS * *Statistically significant improvement with the use of Provent. AHI 5 apnea-hypopnea index; ESS 5 Epworth Sleepiness Scale; ODI 5 oxygen desaturation index; SAQLI 5 Sleep Apnea Quality of Life Index; VAS 5 visual analogue scale. TABLE IV. Cure Rate, Success Rate, and Failure Rate With the Use of Provent in Both Treatment Arms. Treatment Arm 1 Treatment Arm 2 Cure rate (%) 45.2% 25% Success rate (%) 9.7% 10.7% Failure rate (%) 43.3% 64.3% No statistically significant differences in cure rates, success rates, and failure rates between the two treatment arms. nasal obstruction had a greater and statistically significant reduction in AHI and ODI and greater improvements in their min SpO 2 percent with the use of Provent. Patients with occasionally reported symptoms of nasal obstruction who had >50% nasal obstruction, however, did not have significant improvements in AHI, ODI, and min SpO 2 percent. Therefore, increased nasal obstruction did have a significant impact on the clinical efficacy of nasal EPAP but did not have an impact on acceptance or tolerability. It is possible that patients with increased nasal obstruction are more likely to open their mouths during treatment with nasal EPAP, which would decrease therapeutic efficacy. As such, correction of nasal obstruction might thus be a valuable prerequisite for nasal EPAP devices such as Provent sleep apnea therapy to improve their clinical efficacy. Patients reported mixed results in quality-of-life improvements from the use of Provent. Yet consistently, patients in both treatment arms noted a significant decrease in the intensity of their snoring as recorded on the VAS, and were also noted to have a significant decrease in the number of snoring events as measured by the ResMed system. Nasal EPAP devices might thus be an effective adjuvant therapy for patients with significant complaints of snoring. Adherence rates for the 38 patients who completed the 30 study days was high. However, these adherence rates reflect only short-term adherence and cannot be extrapolated as long-term adherence rates. Certainly, future studies should address a larger population group over a longer duration. Another limitation to this study includes loss to follow-up and an overall study failure rate of 52.5%. However, given the objective decrease in snoring events and improvement in sleep study findings, nasal EPAP can potentially have a significant role in treatment of OSA, and would benefit from further studies with long-term follow-up. CONCLUSION This study was unable to demonstrate the efficacy of Provent therapy due to high levels of nonadherence and loss to follow-up. In select patients who were able to tolerate the device and complete the study, patients without symptoms of nasal obstruction and <50% nasal obstruction had statistically significant improvements in AHI, ODI, and min SpO 2 percent, whereas patients with occasional symptoms of nasal obstruction and 50% to 80% nasal obstruction did not. However, no significant 258

6 difference in cure rates was identified. Given the low cost and minimally invasive nature of Provent therapy, further studies are warranted to see whether correction of nasal obstruction improves the efficacy of Provent. BIBLIOGRAPHY 1. Mahadevia AK, Onal E, Lopata M. Effects of expiratory positive airway pressure on sleep-induced respiratory abnormalities in patients with hypersomnia-sleep apnea syndrome. Am Rev Respir Dis 1983;128: Berry RB, Kryger MH, Massie CA. A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. Sleep 2011;34: Colrain IM, Brooks S, Black J. A pilot evaluation of a nasal expiratory resistance device for the treatment of obstructive sleep apnea. J Clin Sleep Med 2008;4: Rosenthal L, Massie CA, Dolan DC, et al. A multicenter, prospective study of a novel nasal EPAP device in the treatment of obstructive sleep apnea: efficacy and 30-day adherence. J Clin Sleep Med 2009;5: Walsh JK, Griffin KS, Forst EH, et al. A convenient expiratory positive airway pressure nasal device for the treatment of sleep apnea in patients non-adherent with continuous positive airway pressure. Sleep Med 2011;12: Kryger MH, Berry RB, Massie CA. Long-term use of a nasal expiratory positive airway pressure (EPAP) device as a treatment for obstructive sleep apnea (OSA). J Clin Sleep Med 2011;7: Patel AV, Hwang D, Masdeu M, et al. Predictors of response to a nasal expiratory resistor device and its potential mechanisms of action for treatment of obstructive sleep apnea. J Clin Sleep Med 2011;7: Sugiura T, Noda A, Nakata S, et al. Influence of nasal resistance on initial acceptance of continuous positive airway pressure in treatment of obstructive sleep apnea syndrome. Respiration 2007;74: Friedman M, Tanyeri H, Lim JW, et al. Effect of improved nasal breathing on obstructive sleep apnea. Otolaryngol Head Neck Surg 2000;122: Powell NB, Zonato AI, Weaver EM, et al. Radiofrequency treatment of turbinate hypertrophy in subjects using continuous positive airway pressure: a randomized, double-blind, placebo-controlled clinical pilot trial. Laryngoscope 2001;111: Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14: Flemons WW, Reimer MA. Measurement properties of the calgary sleep apnea quality of life index. Am J Respir Crit Care Med 2002;165: Flemons WW, Reimer MA. Development of a Disease-specific healthrelated quality of life questionnaire for sleep apnea. Am J Respir Crit Care Med 1998;158: Erman MK, Stewart D, Einhorn D, et al. Validation of the ApneaLink for the screening of sleep apnea: a novel and simple single-channel recording device. J Clin Sleep Med 2007;3: Kushida CA, Littner MR, Hirschkowitz M, et al. Practice parameter for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006; 29: Weaver TE, Grunstein RR. Adherences to continuous positive airway pressure therapy: the challenge to effective treatment. Prov Am Thorac Soc 2008;15: Li HY, Wang PC, Chen YP, Lee LA, Fang TJ, Lin HC. Critical appraisal and meta-analysis of nasal surgery for obstructive sleep apnea. Am J Rhinol Allergy 2011;25: