Polyp Mũi Và CPAP
Polyp Mũi Và CPAP
Polyp Mũi Và CPAP
Original Research
1 ENT Research Laboratory, Department of Otolaryngology and Head Address for correspondence Rogerio Pezato, MD, PhD,
and Neck Surgery, Universidade Federal de São Paulo, SP, Brazil Departamento de Otolaringologia e Cirurgia da Cabeça e Pescoço,
Universidade Federal de São Paulo, Rua Pedro de Toledo 847, Sao
Int Arch Otorhinolaryngol Paulo, SP, 04025011, Brazil (e-mail: pezatobau@gmail.com).
Abstract Introduction It has been hypothesized that increasing the interstitial hydrostatic
pressure within the sinonasal mucosa of patients with nasal polyposis (NP) might
decrease the size of nasal polyps.
Objective To evaluate the effects of positive airway pressure, delivered by a continuous
positive airway pressure (CPAP) device, in patients with NP and in control subjects.
Methods Twelve patients with NP and 27 healthy subjects were exposed to CPAP
(20 cm H2O) for 2 hours. Visual analog scale (VAS), Nasal Obstruction Symptom
Evaluation (NOSE) scale, acoustic rhinometry (AR), peak nasal inspiratory flow (PNIF)
and nasal endoscopy (NE—Meltzer polyp grading system) were performed before and
after the intervention, for all patients.
Results The control group showed a significant worsening in nasal obstruction
symptoms, as measured by VAS and NOSE (p < 0.01), and a significant decrease in
nasal patency, as measured by the PNIF and AR (p < 0.01). For the NP group, VAS,
Keywords NOSE, and AR did not differ significantly (p ¼ 0.72, p ¼ 0.73, and p ¼ 0.17, respec-
► chronic rhinosinusitis tively), but PNIF values worsened (p ¼ 0.04) after exposure to CPAP. There was a
► endoscopy statistically significant reduction in the nasal polyps’ size (p ¼ 0.04).
► extracellular matrix Conclusions Positive pressure worsened the nasal obstruction symptoms and decreased
► nasal airflow objective parameters of nasal patency in control subjects. In patients with NP, exposure to
dynamics CPAP reduced the nasal polyps’ size, and the nasal patency, as measured by PNIF. However,
► rhinosinusitis it had no significant effects in AR and in nasal obstruction symptoms.
Fig. 1 Illustration showing an increase in capillary permeability due to inflammation, with protein loss and increasing tissue oncotic pressure (B and C), and,
consequently, extravasation of water to the interstitial space and edema. (B) compensatory increase in interstitial hydrostatic pressure in response to
increasing oncotic pressure, thus limiting edema. (C) less marked increase in interstitial hydrostatic pressure in response to increasing oncotic pressure,
facilitating the greater loss of water from the capillary lumen into the tissues and, consequently, increased edema.
The objective of this study was to evaluate the effects of For the control group, those who had a present or recent
positive pressure, delivered by a continuous positive airway past (< 4 weeks) history of sinonasal infections and/or
pressure (CPAP) device, on patients with NP and in control inflammation were also excluded.
subjects, with special interest in nasal obstruction symptoms, After application of inclusion and exclusion criteria, 13
objective nasal patency parameters, and nasal polyps’ size. and 27 subjects were included in the NP and control groups,
respectively. Of these, 12 and 27 subjects were considered
for the final analysis, respectively, because 1 patient from
Methods
the NP group did not tolerate the intervention (CPAP). In the
Design, Setting, and Study Population NP group, 5 (41.6%) participants were women and 7 (58.4%)
An analytic, observational, and cross-sectional study was were men, with ages ranging from 34 to 65 years. Of the 27
conducted at a tertiary otorhinolaryngology referral center, individuals in the control group, 10 (37.0%) were women
from January 2016 to August 2016. Participants were divided and 17 (63.0%) were men, with ages ranging from 18 to
in two groups. The NP group included only those individuals 43 years.
with a recent diagnosis of NP, according to the European This study conforms to recognized ethical standards and
Position Paper on Rhinosinusitis and Nasal Polyps 2012 to the Declaration of Helsinki, and it was approved by the
(EPOS 2012) guidelines,5 and with polyps graded 1 accord- local institutional review board (n. 897.279, 12/2015). Writ-
ing to the Meltzer polyp grading system.6 The control group ten informed consent was obtained from every participant
included only healthy individuals. For both groups, partici- included in the study.
pants should be older than 18 years-old and younger than 65
years-old, and the following were excluded: Exposure to Positive Pressure—CPAP
All subjects were exposed to CPAP, delivered by a mechanical
• Those using or who had recently used (< 4 weeks) device (F&P Icon, Fisher & Paykel Healthcare Ltd., Auckland,
antihistaminic or antihypertensive drugs, topical vaso- New Zealand) attached to a nasal mask (Meridian Nasal
constrictors, systemic vasodilators, or systemic/topic Mask, ResMed Ltd., Bella Vista, Australia) for 2 hours, at a
corticosteroids; pressure of 20 cm H2O. All patients were in a comfortable
• Those with severe septal deviation precluding nasal endo- sitting position during the whole procedure, and air leak
scopy or the use of nasal cannulas for acoustic rhinometry; through the mask was ruled out for all cases. No topical
• Those with a present or past history of tumors, prior medications were used before or after the intervention.
sinonasal surgery, known diagnosis of obstructive sleep
apnea, and/or use of CPAP; Analyzed Variables
• Those with a present or past history of smoking or illicit The following parameters were measured for all participants,
drug use. immediately before and after exposure to the CPAP:
• Visual analog scale (VAS) for nasal obstruction symptoms; was used to prevent air leak; all participants were instructed
• Nasal Obstruction Symptom Evaluation (NOSE) scale; to control their breathing.
• Nasal endoscopy (NE); At least three curves were obtained for each nostril—after
• Acoustic rhinometry (AR); each measurement, the nosepiece was removed, reconnected,
• Peak nasal inspiratory flow (PNIF). and a new measurement was then obtained; the results were
considered adequate if the coefficient of variability was lower
Visual Analog Scale (VAS) and Nasal Obstruction than 10%; the recorded curves were used to obtain a mean
Symptom Evaluation (NOSE) Scale curve for each nostril; the values of these mean curves were
For the evaluation of nasal obstruction symptoms, all parti- then analyzed. All examinations were performed by the same
cipants were asked to score their nasal obstruction severity investigator, experienced in AR. The cross-sectional area
in a 10-cm VAS, ranging from “0” to “10,” with “0” meaning between the distances of 0 and 5 cm, expressed in cm2, was
“complete absence of nasal obstruction,” and “10” meaning used for objective comparison of findings.
“complete nasal obstruction.” The measurement of PNIF was performed with an In-
The NOSE scale, previously adapted to Brazilian Portu- Check Nasal Inspiratory Flow Meter portable device (Clem-
guese,7 was also administered and calculated for all partici- ent Clarke International Ltd., Essex, UK) equipped with an air-
pants, with scores ranging from 0 to 12. Because of the cushioned facemask. The PNIF was measured with the par-
characteristics of this study, the assessment of nasal obstruc- ticipant in the standing position, at three consecutive times
tion during sleep and exercise was not considered. with a 1-minute interval between measurements. The
results were obtained immediately, and the average of the
Nasal Endoscopy (NE) measures was considered for the final analysis.
Nasal endoscopy was performed in all patients. An 18-cm, 4-
mm, 0-degree rigid endoscope (Hopkins II, Karl Storz Ltd., Statistical Analysis
Tuttlingen, Germany) attached to a video camera system (IK- Data was plotted and analyzed in the Statistical Package for the
M51H / IK-CU51 Imaging System, Toshiba America Inc., Social Sciences (SPSS) v. 22 (IBM Corp., Armonk, NY, USA) and
Irvine-CA, USA), monitor (OEV 141, Olympus Optical Ltd., Prism v.7 (GraphPad Software Inc., La Jolla, CA, USA) software
Barlett-TN, USA), and an Innova Light & Image FX 300R light environments. The Wilcoxon, Mann-Whitney U, and Fisher
source (Innova Technik, Cajamar, SP, Brazil) were used. exact tests were used to assess differences within and between
Images were digitally recorded with an HD PVR Rocket video groups. The binomial sign test was used for estimation of
capture device (Hauppauge Inc., Hauppauge, NY, USA). statistical significance for the Meltzer score before and after
Two blinded evaluators, both of whom were experienced exposure to CPAP for the NP group. In all cases, p values < 0.05
rhinologists, watched every NE recorded, and, together, were considered statistically significant.
classified the severity of NP for every nasal cavity, according
to the Meltzer polyp grading system6 (►Table 1).
Results
Acoustic Rhinometry and PNIF There was no statistically significant difference in gender
For the objective evaluation of nasal patency, all patients distribution between groups (p ¼ 1.00). The participants in
underwent AR and PNIF, before and after exposition to CPAP. the control group were significantly younger than patients in
The AR was performed without administration of vasocon- the NP group (p < 0.01) (►Table 2).
strictors, with a calibrated acoustic rhinometer and the A1
Acoustic Rhinometer software (GM Instruments Ltd., Kilwin- Effects of Positive Pressure on Symptoms of Nasal
ning, UK). The test was conducted as standardized by the Obstruction (VAS and NOSE)
International Standardization Committee on Objective For the control group, there was a significant deterioration in
Assessment of the Nasal Airway.8 Each participant remained nasal obstructive symptoms, as measured by the VAS and
for 30 minutes in an air-conditioned room (temperature set to NOSE, after exposure to CPAP (p < 0.01). In the NP group, VAS
21°C before measurement, and ambient humidity kept in the and NOSE did not differ significantly after exposure to CPAP
50–60% range); the head of each participant was stabilized to (p ¼ 0.72 and p ¼ 0.73, respectively).
ensure proper positioning of the pulse tube; petroleum jelly
Table 2 Demographic characteristics for the control group and
Table 1 Meltzer polyp grading system the NP group
Multiple polyps occupying the middle meatus 2 Age Age 24.03 4.17 48.17 10.94 < 0.01
average
Polyps extending beyond the middle meatus 3 (SD)
Polyps completely obstructing the nasal cavity 4
Abbreviations: NP, nasal polyposis; SD, standard deviation.
Effects of Positive Pressure on Nasal Patency (AR and Strengths and Limitations of this Study
PNIF) This study presents some limitations, with its small sample
Anterior nasal cavity volume and PNIF decreased significantly in size being, arguably, the most important one. For instance,
the control group after CPAP use (p < 0.01). For the NP group, increasing the number of participants could yield statisti-
the values of PNIF worsened (p ¼ 0.04), but there was no cally significant results for nasal patency parameters in the
significant alteration in the AR after the intervention (p ¼ 0.17). NP group. It could be also questioned whether the exposure
to CPAP for longer periods of time, set at different pressures,
Effects of Positive Pressure on NE or with the patients in different positions, could yield
There was a statistically significant reduction in nasal polyps’ different results. Indeed, patients with obstructive sleep
size for the NP group, as measured by NE and the Meltzer apnea syndrome (OSA) use CPAP for 8 sleeping-hours and
score (p ¼ 0.04) (►Video 1). Results for both groups are in the horizontal position. These factors affect the lymphatic
summarized in ►Table 3. and venous drainage of the nasal mucosa and could also have
influenced the results of this study.9
Moreover, the long-term effects of CPAP on NP were not
Video 1 evaluated. Considering that oncotic pressure does not change
with time, but hydrostatic pressure decreases after CPAP expo-
sure is ended, the polyps could have returned to their preexpo-
Nasal endoscopic evaluation of the right nasal cavity of a sure size after a few hours/days. A secondary evaluation would
patient with nasal polyposis that underwent exposition be ideal to assess what are the real permanent effects of CPAP on
to continuous positive airway pressure (CPAP) for the interstitial hydrostatic pressure and the polyps’ volume.
2 hours. Note the reduction in the polyps’ size after Nonetheless, this study has the great advantage of experi-
intervention. Online content including video sequences mentally determining the effects of positive pressure on NP,
viewable at: which, to the best of our knowledge, had never been done
before. It was also possible to compare these effects in
healthy individuals. The results presented are worthy to be
taken into consideration in the understanding of the NP
pathophysiology.
Table 3 Effects of continuous positive airway pressure in patients with nasal polyposis and in control subjects
Abbreviations: CPAP, continuous positive airway pressure; NOSE, nasal obstruction symptoms evaluation; NP, nasal polyposis; PNIF, peak nasal
inspiratory flow; SD, standard deviation; VAS, visual analog scale.
p-values for comparisons within-group; † Meltzer score for both nasal cavities. ‡ Binomial sign test.
Recently, these biomechanical differences were experi- patency in control subjects. In patients with NP, exposure to
mentally demonstrated in the sinonasal mucosa of patients CPAP reduced the nasal polyps’ size, and the nasal patency, as
with NP.1–3 The biomechanical dysfunction found in NP is measured by PNIF. However, it had no significant effects on AR
characterized by a deficiency in the ability to properly raise and on nasal obstruction symptoms.
interstitial hydrostatic pressure in response to fluid extra-
vasation during the inflammatory process, a mechanism that References
is crucial to limit the development of edema, and is closely 1 Pezato R, Voegels RL, Pinto Bezerra TF, Perez-Novo C, Stamm AC,
related to the extracellular matrix composition.1–3 Gregorio LC. Mechanical disfunction in the mucosal oedema forma-
In this context, it has been shown that synechial tissues tion of patients with nasal polyps. Rhinology 2014;52(02):162–166
2 Pezato R, Voegels RL, Stamm AC, Gregório LC. Why we should
exhibit biomechanical properties similar to those of the
avoid using inferior turbinate tissue as control to Nasal Polyposis
healthy nasal mucosa. Thus, fibrosis could be a possible studies. Acta Otolaryngol 2016;136(09):973–975
remodeling mechanism that would enhance the interstitial 3 Pezato R, Voegels RL. Why do we not find polyps in the lungs?
hydrostatic pressure in NP.4 In the present study, the inter- Bronchial mucosa as a model in the treatment of polyposis. Med
stitial hydrostatic pressure in NP was indirectly increased Hypotheses 2012;78(04):468–470
through the acute and transient delivery of CPAP to the nasal 4 Gregório L, Pezato R, Felici RS, Kosugi EM. Fibrotic Tissue and
Middle Turbinate Exhibit Similar Mechanical Properties. Is Fibro-
cavity. A significant reduction in the nasal polyps’ size in
sis a Solution in Nasal Polyposis? Int Arch Otorhinolaryngol 2017;
patients with NP was observed after exposure to CPAP. This 21(02):122–125
suggests that, in fact, increasing interstitial hydrostatic 5 Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position
pressure in nasal polyps, even if indirectly, acutely and paper on rhinosinusitis and nasal polyps 2012. A summary for
transiently, can possibly affect the pathophysiology of NP. otorhinolaryngologists. Rhinology 2012;50(01):1–12
6 Meltzer EO, Hamilos DL, Hadley JA, et al; Rhinosinusitis Initiative.
In patients with OSA, the use of CPAP (especially at high
Rhinosinusitis: developing guidance for clinical trials. J Allergy
titers, such as 20 cm2), causes nasal obstruction and local
Clin Immunol 2006;118(5, Suppl):S17–S61
irritation symptoms, ultimately leading to treatment intol- 7 Bezerra TFP, Padua FGM, Pilan RRM, Stewart MG, Voegels RL.
erance and nonadherence. In this study, the control group Cross-cultural adaptation and validation of a quality of life
showed marked nasal obstruction worsening both in sub- questionnaire: the Nasal Obstruction Symptom Evaluation ques-
jective (VAS, NOSE) and objective measurements (AR and tionnaire. Rhinology 2011;49(02):227–231
8 Clement P a. R, Gordts F, Standardisation Committee on Objective
PNIF), which is in line with previous studies.19
Assessment of the Nasal Airway, IRS, and ERS. Consensus report on
In the NP group, although PNIF values worsened after acoustic rhinometry and rhinomanometry. Rhinology 2005 Sep; 43
exposure to CPAP, there was no significant worsening of nasal (03):169–179
obstruction symptoms or in AR measurements. Continuous 9 Suman JD. Current understanding of nasal morphology and physiol-
positive airway pressure also determined a decrease in the ogy as a drug delivery target. Drug Deliv Transl Res 2013;3(01):4–15
nasal polyps’ size in the NP group. The reason for these obser- 10 Liu Z, Gao Q, Zhang S, You X, Cui Y. Expression of tenascin and
fibronectin in nasal polyps. J Huazhong Univ Sci Technolog Med
vations is still unclear and admits at least two interpretations:
Sci 2002;22(04):371–374
1) The reduction in the nasal polyps’ size prevented 11 Van Bruaene N, Derycke L, Perez-Novo CA, et al. TGF-beta signal-
ing and collagen deposition in chronic rhinosinusitis. J Allergy
significant worsening of nasal patency parameters and
Clin Immunol 2009;124(02):253–259, 259.e1–259.e2
nasal obstruction symptoms in patients with NP, in spite 12 Li X, Meng J, Qiao X, et al. Expression of TGF, matrix metallopro-
of the worsening PNIF; teinases, and tissue inhibitors in Chinese chronic rhinosinusitis.
2) Or, although CPAP determined a decrease in the nasal J Allergy Clin Immunol 2010;125(05):1061–1068
polyps’ size, no improvement in nasal obstruction symp- 13 Balsalobre L, Pezato R, Perez-Novo C, et al. Epithelium and stroma
from nasal polyp mucosa exhibits inverse expression of TGF-β1 as
toms and nasal patency parameters were observed. This
compared with healthy nasal mucosa. J Otolaryngol Head Neck
could be explained by the fact that patients with NP
Surg 2013;42:29
already have significantly decreased nasal patency and 14 Figueiredo CR, Santos RP, Silva IDCG, Weckx LLM. Microarray
obstructive nasal symptoms at baseline, and this would cDNA to identify inflammatory genes in nasal polyposis. Am J
prevent further deterioration in obstructive parameters Rhinol 2007;21(02):231–235
after exposure to CPAP. 15 Pezato R, de Almeida DC, Bezerra TF, et al. Immunoregulatory effects
of bone marrow-derived mesenchymal stem cells in the nasal polyp
microenvironment. Mediators Inflamm 2014;2014:583409
Clinical Applicability 16 Pezato R, Pérez-Novo CA, Holtappels G, et al. The expression of
dendritic cell subsets in severe chronic rhinosinusitis with nasal
Although it was not the primary objective of this study, we
polyps is altered. Immunobiology 2014;219(09):729–736
conclude that CPAP could be used as a therapeutic option, 17 Perez-Novo C, Pezato R. Dendritic cell subset expression in severe
especially in patients with OSA and NP, prior or not to chronic rhinosinusitis with nasal polyps. Curr Opin Allergy Clin
endoscopic endonasal surgery. Future studies could address Immunol 2017;17(01):1–4
such possibilities. 18 de Oliveira PWB, Pezato R, Agudelo JSH, et al. Nasal Polyp-Derived
Mesenchymal Stromal Cells Exhibit Lack of Immune-Associated
Molecules and High Levels of Stem/Progenitor Cells Markers.
Conclusion Front Immunol 2017;8:39
19 Zozula R, Rosen R. Compliance with continuous positive airway
Positive pressure significantly worsened the nasal obstruction pressure therapy: assessing and improving treatment outcomes.
symptoms and decreased the objective parameters of nasal Curr Opin Pulm Med 2001;7(06):391–398