Portuguese Version

Year:  2004  Vol. 70   Ed. 2 - (1º)

Artigo Original

Pages: 150 to 155

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Analysis of nasal mucociliary clearance and side-effects in use of nasal cpap in pacients with sosa

Author(s): Ricardo Gimenes Ferri 1,
Adriane Zonato 2,
Arnaldo Guilherme 3,
Luis Carlos Gregório 4

Keywords: apnea, nasal clearance, saccharin test, cpap, side effects

Abstract:
Since 1981 the use of positive airway pressure through the nasal CPAP has been considered the main clinical treatment of the SAOS- sleep obstructive apnea syndrome, despite its low adhesion on a long- term. Some authors report that the nasal complaints from the continuous positive airway pressure in the nasal cavity are the main causes for the therapy discontinuance. This would probably occur because the treatment would lead to epithelium alterations and changes in the mucociliarytransport and hence, a greater number of upper respiratory infections. Aim: To evaluate the nasal mucociliary clearance in patients with SAHOS under nasal CPAP use through saccharin test, and correlate the adverse effects of this therapy with the treatment endurance and the pressure level used in it. Study design: Clinical study case-control. Material and Method: Twenty five patients, carriers of SAHOS - between their 18 and 70 - submitted to nasal CPAP use for one month, were followed-up at the Instituto do Sono (UNIFESP-EPM) and subjected to the saccharin test. The results were compared to a group of 25 normal individuals. Results: There was no statistical difference among the groups regarding the saccharin test. The adverse effects were present in 84% of the sample, being 60% for nasal dryness and 36% for nasal obstruction. Conclusions: The mucociliary transport stays normal in the SAHOS group submitted to nasal CPAP use and the nasal obstruction and nasal dryness do not present correlation with the treatment time and pressure level used by the device.

INTRODUCTION

The obstructive sleep apnea syndrome (SOAS) is an extremely common condition in adult population with prevalence of 2% in women and 4% in men1. It presents recurrent occlusion events of the structures of upper airway tract resulting in partial or total obstruction of the airflow during sleep time. This syndrome is commonly diagnosed with clinical evaluation and polysomnography (PSG), which detects transient (hypo-apnea) or total apnea of the airflow during sleep time. It is classified as mild, moderate and severe according to the indexes of apnea and hypoapnea (AHI) during sleep time. Mild apnea occurs if the patient has 5 to 15 AHI/hour. Moderate apnea is present if AHI is 15 to 30 per hour, and severe apnea has an AHI higher than 30 events per hour2.

Sullivan introduced the primary treatment of SOAS in 1981 and it included the use of positive airway pressure applied to the Upper Airways through a nasal mask (continuous positive airway pressure - CPAP), preventing the occlusion of the pharynx. Currently the CPAP is the therapy of choice to treat moderate or severe SOAS3. The major problem of this therapy, however, is its improper use, since patient's compliance with the treatment is partial in the long run4-7. Scientific data in the literature report indexes of treatment compliance to CPAP therapy that range from 80 to less than 50% after 18 months5. Studies that used an hour meter to objectively analyze the use of CPAP reported even lower compliance levels4. Some authors believe that side effects in nasal mucosa such as dryness, nasal occlusion and discomfort caused by the mask could be the reason for CPAP therapy discontinuation.

Constantinis et al. (2000) studied a group of 126 patients under nasal CPAP as an attempt to check the presence of structural abnormalities in the nasal mucosa. The histological analysis of the mucosa of those patients was performed and nasal mucociliary clearance was evaluated (NMC) through saccharin test applied in ten individuals of this group. Results of all patients studied showed the presence of pathophysiological abnormalities compatible with nasal mucosa inflammation and extension of the nasal mucociliary transport8.

Nasal mucociliary clearance (NMC) is the most important respiratory tract defense system, corresponding to the perfect interaction between ciliary epithelium and properties of the mucus. There are several methods described in the literature to measure clearance, but the ideal method has not been found yet. Theoretically all methods measure the time a particle takes to travel all nasal cavities until it reaches the pharynx, either by using particles that the observer can easily see in the oropharynx or by using radioactive marked particles or radiopaque particles 9,10.

The saccharin test described by Andersen et al. in 1974 also follows the same principle, but the indicator used to show that saccharin reached the pharynx is the sweet taste in the throat informed by the patient 11. According to the author, the saccharin test is related to other tests that visualize particles in the oropharynx, but it depends on subjective answers9. Scientific data are quite controversial regarding this subject: some authors did not find any correlation between saccharin test and use of radioisotopes12, whereas others reported a positive correlation13. All in all, currently saccharin test is the method used in most of the trials involving the study of NMC, being considered by some authors as the best method to analyze nasal mucociliary transport, since it is easy to perform, does not cause complications and provide reliable results9-11,13-15.

The objective of this trial is to study the impact of nasal mucosa CPAP. Thus, this study was designed to evaluate nasal mucociliary clearance with saccharin test applied in patients with sleep apnea treated with nasal CPAP, as well as to relate the side effects of the therapy to the duration of CPAP therapy and pressure levels used.

MATERIAL AND METHOD

Patients were selected in the Outpatient Sleep Service of Hospital Sao Paulo, Federal University of Sao Paulo - Escola Paulista de Medicina. Fifty patients aged 18 to 70 years were selected and divided into two groups as follows:

1- Control group: Included 25 patients with no nasal complaints selected by ENT screening after interview and ENT examination excluding patients with any nasosinusal disease or using nasal topical drugs.

2- Case group: Included 25 patients with SOAS under CPAP for more than 30 days and that met the inclusion and exclusion criteria described below.

All patients were informed about the study and spontaneously agreed to take part in it. They filled out and signed the informed consent term approved by the Medical Ethics Committee of the institution (Annex 1).

Inclusion criteria:

 Adults aged 18 to 70 years, female or male, with SOAS diagnosed through PSG and under treatment for more than 30 days in a continuous basis (daily), according to the interview carried out by the researcher.
Exclusion criteria:

 Inflammatory and/or infectious nasal process up to 30 days before the evaluation.

 Chronic inflammatory and/or infectious nasal process.

 Nasal polyps, nasosinusal tumors and obstructive septum deformities.

 Former nasal, palate, pharyngeal or tonsil surgeries.

 Smoking.

 Use of nasal topical drugs.

Patients were examined by the same physician in the Outpatient Service of Otorhinolaryngology of Hospital Sao Paulo, UNIFESP-EPM, from March 2001 through April 2002. Clinical evaluation included a specific clinical chart focusing on inclusion and exclusion criteria, the date nasal CPAP began, nasal symptoms related to the use of the device, duration of use, compliance with the treatment, and pressure of the device (Annex 2). The nasal symptoms investigated included: nasal obstruction, dryness, nasal discharge, epistaxis, posterior rhinorrhea.

Nasal Mucociliary Clearance evaluation was carried out through saccharin test.

Saccharin test was applied twice by the same investigator, on different days and with no severe nasal inflammatory and/or infectious process for at least 30 days. The saccharin used had particles with 1mm diameter applied at 1cm of the cephalic portion of the medial aspect of the inferior turbinate of the most pervious nasal fossa. Patients were instructed to keep their heads horizontally, sustaining natural nasal breathing, trying to avoid blowing the nose, sneezing or making any maneuvers to accelerate normal transit of nasal mucus. Patients were also instructed to swallow at every 60 seconds and mention the moment they feel the sweet taste in the throat. The test was interrupted and repeated another day if the patient was sneezing. If the time measured exceeded 60 seconds, saccharin was placed directly in the tongue to test patient's ability of identifying sweet taste, if the patient could not identify it he/she was excluded from the sample.

Statistical evaluation was carried out through paired t-test to check the differences between the values of saccharin test in the two groups studied; the descriptive level was calculated (p), being p< 0.05 considered significant at 5% and p > indicated that this value was not significant. Linear regression was also applied to study the correlation of independent variables (obstruction and dryness), CPAP pressure, and treatment duration.

RESULTS

Graph 1 is a comparison between saccharin test of the two groups included in the study and t Student's test. We did not find statistically significant differences between the two groups.

Graph 2 displays the comparison of the studied group with and without nasal obstruction in relation to pressure applied by the device, and in Graph 3 we have the same group related to treatment.

Graph 4 displays the comparison between patients under CPAP, with and without complaints of dryness related to CPAP pressure, and Graph 5 is a comparison of the same group related to the time using the device.

Graph 6 describes the incidence of nasal complaints of patients using nasal CPAP.

Table 1 displays the values of descriptive level after applying t Student's test for the investigated variables.

DISCUSSION

Since Sullivan (1981) introduced nasal CPAP to treat SOAS, it became the primary clinical treatment of moderate to severe apnea, even though long-term compliance with the treatment is below the desirable level 5,16-18. Patients have mentioned two factors which investigators considered as major factors to discontinue the treatment, mask discomfort on the face and side effects on nasal mucosa5,7. The main reported side effects, but not limited to, were complaints of dryness, nasal obstruction, headache, epistaxis and rhinorrhea.

In the group of patients using CPAP the most common nasal complaints occurred in 76% of patients. Sixty percent (60%)out of those patients reported dryness, 36% nasal obstruction; 16% nasal discharge; 12% epistaxis, and other less common complaints (Graph 6).

These results were compatible with those reported in the literature. Sanders (1986) studied a group of 19 patients that used CPAP and found 17 patients with mask-related complaints, 13 (68%) with dryness and morning congestion. Pepin et al. (1995) studied 193 patients in two sleep centers in France and reported that 65% of the patients under CPAP therapy had morning nasal or mouth dryness, 35% had nasal discharge and sneezes, 25% nasal congestion, 8% recurrent sinusitis and 4% epistaxis.

Dryness was not related to time of CPAP use or to the pressure applied by the device (Graphs 4 and 5), similarly to reports available in the literature. Nino-Murcia et al. (1989) evaluated 144 patients for 25 months and considered nose and mouth dryness as most common side effects which were not related to time of use nor to the pressure applied by the device6.

The group of patients using CPAP with nasal obstruction compared to those without nasal obstruction presented some relation to the pressure applied by the device without reaching statistically significant values (p=0.052), but with a significant trend (Graph 2). Correlation between complaint of nasal obstruction and time of CPAP use was not reached (Graph 3). According to Pepin et al., side effects were not related to the levels of pressure applied and suggested that the speed of airflow through nasal cavities may be responsible for it19.

We believe that the symptoms occur due to dehydration of nasal mucosa and edema of sub mucosa caused by the flow of cold and dry air from the device. Martins de Araújo et al. (2000) conducted a study with a group of patients that used CPAP without humidifier with the purpose of measuring and comparing relative humidity of the inhaled air using a CPAP without humidifier and another one attached to the humidifier. The results showed that CPAP without humidifier had a relative air humidity of 60±14%, against 81±14% of the CPAP with humidifier20. Hayes et al. (1995) evaluated the impact of CPAP with or without humidifier in blood flow of nasal mucosa with the mouth opened and closed in a group of eight patients. The results of their study showed that patients using CPAP without humidifier and with the mouth opened had 65% increase in mucosa blood flow, and in the same group with humidifier the increase was only 8% 21. According to these studies one may infer that CPAP without humidifier is actually related to drop in air humidity of inhaled air and increase of blood flow in mucosa, and this may correspond to inflammatory activity and, consequently, to complaints of nasal dryness and obstruction.

Few reports were found regarding nasal mucociliary transport in patients using CPAP in the literature. Constantinis et al. (2000) evaluated 10 patients with SOAS using saccharin test and nasal biopsy before starting the CPAP therapy, three and ten months after the beginning of treatment. The results showed that all patients had an extension of mucociliary transport as of the third month sustained until the tenth month. Intense changes were also found in the structure of nasal mucosa resembling chronic inflammatory process with cilia decrease and disorientation of hair cells. These authors discussed histological changes resultant from an inflammatory process caused by high airflow applied to the nasal mucosa.

This study used the same method to measure NMC following the same evaluation criteria published by Andersen in 1974. The results did not report statistically significant differences between groups studied, and the values of saccharin test were within the normal range found in the literature (Graph 1 and Table 1).

There are scientific studies measuring NMC in healthy individuals exposed to low relative air humidity environments that presented prolonged NMC and other individuals in which nasal mucociliary clearance did not change. Andersen et al. (1972) evaluated 58 healthy individuals exposed to environmental conditions with different air relative humidity as follows: 70, 50, 30 and 10% and all individuals had similar values 22. Salah et al. (1988) analyzed 11 normal individuals exposed to environmental conditions with air relative humidity that were different among themselves (40-43% and 0.1%) and with saccharin test they found that NMC was longer in all patients within dryer environment (0.1%) and it was statistically significant 23.

The fact that NMC was similar in the two groups investigated in this study made us believe that nasal mucus properties and cilia activity were preserved and, therefore CPAP-induced dryness was not enough to change it. However, we could not assume that cilia abnormalities resulting from ongoing use of CPAP did not occur, since histological evaluation of nasal mucosa was not performed in those patients. Additionally, some previously described studies were controversial regarding alterations of NMC caused by dryness of inhaled air during the use of CPAP.

Scientific reports about this aspect remained inconclusive. This subject is quite controversial and this study raised more questions than clarifications. We believe that the perpetuation of this line of study through nasal histological analysis and electron microscopy to assess cilia abnormalities might help us to clarify such controversies. Another aspect for further consideration would be the inclusion of patients that are actually continuously using CPAP with pressure hour meter monitoring.

Still we believe that the understanding of nasal mucosa alterations resulting from CPAP use could help us identify the factors that impact the irregular use of CPAP and treatment discontinuation.

CONCLUSION

The analysis of results obtained in this study showed the following:

 In the group of investigated patients, nasal obstruction was not related to the time of CPAP use, however, it was related to the level of pressure applied by CPAP but without statistical significance.

 Nasal mucociliary clearance in patients with SOAS using nasal CPAP in the saccharin test was similar to the values of the control group.

 In the group of investigated patients, the complaints of nasal dryness were not related to the time of CPAP use or to the level of pressure applied by the device.

Graph 1. Average distribution of saccharin (min), per each group.



Graph 2. Distribution of pressure used by CPAP in the group, related to event of nasal obstruction.



Graph 3. Distribution of CPAP use duration (in months) in the studied group related to complaint of nasal obstruction.



Graph 4. Distribution of pressure used by CPAP in the studied group related to complaint of nasal dryness.



Graph 5. Distribution of CPAP use duration (in months) in the studied group related to complaint of nasal dryness.



Graph 6. Distribution of nasal complaints in nasal CPAP use.


Table 1. Inferred results of variables studied.

* Due to values of kurtosis found in the descriptive analysis, the comparison was made based on the natural logarithm of saccharin.

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1 Master Degree in Otorhinolaryngology and Head and Neck Surgery, Federal University of Sao Paulo - Escola Paulista de Medicina.
2 PhD in Otorhinolaryngology, University of Sao Paulo.
3 Joint Professor, Department of Head and Neck Surgery and Otorhinolaryngology, Federal University of Sao Paulo - Escola Paulista de Medicina.
4 Faculty Member, Department of Head and Neck Surgery and Otorhinolaryngology, Federal University of Sao Paulo - Escola Paulista de Medicina.
Affiliation: Department of Otorhinolaryngology and Human Communication Disorders, Federal University of Sao Paulo - Escola Paulista de Medicina.
Address correspondence to: Ricardo Gimenes Ferri - Av. T15 n° 1419 ap.1204 Setor Bueno Goiânia GO 74230-010. E-mail: r.gimenes@uol.com.br.

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