Introduction
Mucociliary clearance (MCC) is an important respiratory system defense mechanism,
since the human airway surfaces are constantly exposed to various particles and microorganisms
present in the ambient air.[1]
[2]
[3]
[4] Its effectiveness depends on the quantity and on the quality of the mucus, on the
structure, the synchrony and frequency of ciliary beating, and on the interaction
between these components.[5]
[6]
[7]
Mucus is a barrier that entraps inhaled microorganisms in its mobile layer, and the
cilia are the propellants, which act through coordinated beating. The interaction
of these components is responsible for the removal of microorganisms from the upper
and lower airways toward the oropharynx, where they are swallowed or expectorated,
which avoids them from entering into direct contact with epithelial cells or reaching
the alveoli.[8]
[9]
[10]
[11]
[12]
Since MCC is fundamental in lung defense, several methods have been described to evaluate
it: some analyze separately the mechanical condition of the cilia (video microscopy,
photometric method)[3]
[13] or of the mucus (contact angle measurements, displacement of mucus by simulated
cough and frog palate),[14]
[15]
[16] and others evaluate the interaction between the mucus and the cilia (clearance of
inhaled radiolabeled particles, saccharin transit time [STT] test).[17]
[18]
Methods involving radiolabeled particles are used as the reference option to measure
MCC.[19] However, the feasibility of this methodology is limited due to equipment and cost
requirements, besides presenting some risks inherent to the exposure to radiation.
The STT test was compared with the radioactively tagged particles method in the study
of Puchelle et al.[19] The authors found a good correlation between the methods for absolute results obtained
in one measurement day and for changes between two measurement days. The STT is a
useful method for scientific research, widely used in nasal MCC studies, as it is
a reproducible,[18]
[20]
[21] simple to perform, and noninvasive technique, besides being low-cost, making it
an interesting alternative to other methods that require relatively complex, invasive,
and expensive equipment, and demand greater technical aptitude from the examiners.[12]
[22]
[23]
[24]
[25]
[26]
Given the importance of MCC in lung defense, its evaluation is necessary as a contribution
to the clinical and functional screening of the individual. Thus, as the STT test
is a practical and effective evaluation method, the present literature review aims
to provide basic information related to the STT test and to present the findings of
previous studies that used this method, discussing variations in its execution, possible
influences on the obtained results, and limitations of the method, besides relating
our experience with the use of STT tests in research.
Review of a Particular Subject
The Method
The STT test was first described in 1974 by Andersen et al.[26] It consisted of the insertion of a sodium saccharin particle on the upper surface
of the inferior nasal turbinate of the subject. Next, the subjects were asked to swallow
once every minute and to notify the examiner when they noticed a sweet taste. The
distance from the start of the mucociliary membrane to the far wall of the pharynx
was measured with a probe, and from this measurement the mean velocity was determined.
This method was modified by Rutland et al,[27] who, prior to the evaluation, kept the subjects for at least an hour in an environmental
temperature between 21 and 24°C, with relative humidity between 30 and 50%, and requested
that the subjects blow their nose gently to remove any excess secretion. The saccharin
particle was 0.5 mm in diameter and was placed in the inferior turbinate of one nasal
cavity at least 7 mm behind the anterior end of the turbinate to avoid the area of
mucosa where the cilia beat in an anterior direction. Another difference in this study
lies in the fact that the subjects were not instructed to swallow regularly and that
the distance between the particle placement and the nasopharynx was not measured.
Therefore, only the time was obtained, but not the velocity of clearance.
Since then, the STT technique has been used in several studies involving MCC,[12]
[22]
[24]
[25]
[28] either to characterize different populations[11]
[21]
[22]
[29]
[30] or to evaluate the effect of interventions such as the use of anesthetics,[31]
[32] continuous positive airway pressure (CPAP),[5]
[33] and smoking cessation.[34]
However, differences are found in the execution of the technique among the published
studies, related to the position of the subject, to the manner of introduction of
the saccharin particle, to its size, and guidance to the subject being examined ([Table 1]).
Table 1
Methodological variations in saccharin transit time test in the literature
|
Variations in STT execution
|
|
Positioning of the volunteer
|
Seated, with the neck extended,[28]
[35] flexed,[29]
[36] or maintained in the horizontal plane[5]
[12]
[37]
Supine position[38]
|
|
Nostril choice
|
Non-obstructed nostril[2]
[21]
[39]
Standardization of a specific side[28]
[34]
|
|
Instrument for the placement of saccharin
|
Plastic straw[28]
Cotton[40]
[41]
[42]
Surgical pincers[11]
[32]
[43]
|
|
Location of saccharin placement
|
Inferior nasal turbinate[11]
[30]
[32]
1 cm behind the inferior nasal turbinate[5]
[20]
[24]
[29]
[40]
Below the middle nasal turbinate[12]
2 cm inside the nostril[2]
[28]
[34]
[39]
|
|
Utilized amount of saccharin
|
1 particle of 0.5 mm,[12] 1mm[25]
[30]
[32]
[44]
[45] or 1.5mm[24] in diameter
5 mg,[2]
[46] 25 mg,[22] or 250 micrograms (µg)[34]
|
|
Guidance during the test
|
Not to cough, sneeze, blow, or scratch the nose[2]
[43]
[47]
[48]
[49]
[50]
Breathe normally[22]
[51] or through the mouth[2]
[39]
Swallow normally,[12]
[21]
[22] every 30 seconds,[40]
[52]
[53] every 60 seconds,[5]
[26] or regularly[37]
|
Abbreviations: STT, saccharine transit time.
The pretest guidance found in the literature includes not ingesting alcoholic or caffeine-based
substances, such as coffee, tea, soda, and energy drinks; drugs such as anesthetics,
analgesics, barbiturates, tranquilizers, and antidepressants; not smoking for at least
12 hours; and not performing vigorous physical activities during the 12 hours preceding
the test.[22]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
This guidance is given due to the fact that MCC changes in different conditions, such
as age, level of physical activity in daily life, smoking, and use of drugs and other
substances, such as caffeine and alcohol. Therefore, it is essential to consider these
aspects and control them, when possible, before evaluating this lung defense mechanism.
The normality values for STT have been published for the Spanish population. Plaza
Valía et al[21] found a median of 16 minutes, and 50% of their results ranged from 12 to 20 minutes
(interquartile interval). While these values can shed light on what can be expected
as a result of this test, they might not be representative of other populations, with
different ethnicities and living in different environmental conditions. To the best
of our knowledge, there are no studies presenting reference values for other populations.
Factors that Influence MCC
Age
The respiratory system undergoes changes with advancing age, such as loss of lung
elasticity, decrease in diaphragm strength, lung function decline, and an increase
in the susceptibility to infections.[22] Studies indicate that age also interferes with MCC.[11]
[22] A correlation analysis has shown that MCC becomes progressively slower with advancing
age, beginning at the early twenties,[21]
[55] probably due to an increasing incidence of defects in the structure of the cilia.[11]
Septal Deviations
Kamani et al[56] have shown that young adults with septal deviations presented impaired MCC in both
nostrils when compared with matched controls. When looking only at the study group,
the concave (opposite side) presented even more impaired MCC than the convex side
of the deviation. Therefore, this anatomical alteration might be considered an exclusion
criterion for cross-sectional studies comparing different cohorts. In the case of
longitudinal/interventional studies, it should be considered, a priori, whether this
alteration could implicate possible bias in the findings.
Smoking
Smoking is an accelerator of lung function decline.[57] Besides interfering in the respiratory tract, it causes inflammation and mutagenic
effects, which can result in the development of malignant neoplasias.[58]
[59]
[60] Stanley et al[29] evaluated the MCC of 29 smokers and of 27 nonsmokers and observed higher values
of STT in the first group (20.8 ± 9.3 minutes) compared with the second (11.1 ± 3.8
minutes). More recently, Proença et al[23] also observed a higher STT in smokers after 8 hours of abstinence (16 ± 6 minutes)
compared with nonsmokers (10 ± 4 minutes). However, immediately after smoking, smokers
presented a similar STT to nonsmokers (11 ± 6 minutes). Most likely, this represents
an immediate defense response. Cigarette smoke leads to an increase in the ciliary
beat frequency, probably as a consequence of the stimulation of sensory receptors
from the epithelium or by the action of inflammatory mediators. Therefore, in addition
to the chronic condition of smoking, the influence exerted by acute exposure to cigarette
smoke should also be considered before evaluating MCC.
Physical Activity in Daily Life
Exercise is, in general, classified as a stressful stimulus,[61] which can generate acute responses and chronic adaptations.[62] The first is associated with increased levels of adrenergic mediators,[63] and these stimulate ciliary beat frequency and, therefore, the MCC.[64] Proença et al[28] evaluated the interference of physical activity in daily life in MCC and found that
both nonsmokers and even light smokers with a high level of physical activity in daily
life presented faster STTs than individuals with a less active or inactive lifestyle.
Ingested Substances
Some ingested substances also influence the functioning of MCC. It is known that a
brief exposure to alcohol can quickly stimulate the cilia, through the production
of nitric oxide and the activation of the kinase dependent protein, whereas prolonged
exposure blocks the β-agonist stimulation of kinase protein activity and ciliary beating.[6]
[65]
Caffeine consumption is related to autonomic modulation alteration resulting in an
increased respiratory rate and bronchodilatation.[66]
[67] It is known that MCC is also, at least in part, influenced by the autonomic system.[54] It has been shown in humans that anticholinergic agents slow clearance,[68] while cholinergic stimulation[69] and sympathomimetic agents speed clearance through changes in the ciliary beat frequency.[68]
[70]
Drugs
Some drugs are employed for the purpose of changing MCC. Begrow et al[71] observed that the use of standard Myrtol improved MCC in rats. Boek et al[72] found that MCC improved under the action of salbutamol, while it reduced under sodium
chloride, and xylometazoline caused no significant change. Bercin et al[52] found that the topical nasal medications xylometazoline hydrochloride, fluticasone
propionate, and seawater, which are often used without medical prescription, may worsen
the MCC of individuals with nasal air flow lower than 500 ml and concluded that these
drugs should be used carefully and selectively in patients with nasal complaints.
Other medications, which are not employed to act on MCC, can also cause alterations
as a side effect. Houtmeyers et al[73] conducted a review on the effects of routine clinical use of medications on MCC
and concluded that anticholinergics (tertiary ammonium compounds), aspirin, anesthetics,
and benzodiazepines (tranquilizers and anxiolytics) depress the MCC, probably by decreasing
the ciliary beat frequency and mucus secretion. On the other hand, cholinergic agents,
methylxanthines (theophylline, aminophylline, and bamifylline), sodium cromoglycate
(anti asthmatic), antibiotics (those orally administered for chronic rhinosinusitis,
such as penicillin, cephalosporin and sulfonamide), surfactant, hypertonic saline
solution, and water aerosol improve the MCC, apparently by increasing the ciliary
beat frequency and mucus secretion, and stimulating fluid secretion in the airway
surface.
Circadian Cycle
The circadian cycle refers to rhythmic biological phenomena that occur in all forms
of life and are influenced by the solar cycle (dark/light cycle) and by the environment.
In humans, it is related to internal regulators of the central nervous system and
interferes with the organization and sequencing of metabolic and physiological events,
such as body temperature, blood hormone levels, urinary volume, cognitive and motor
performance, sleep-wake cycle, and the breathing control system.[74]
[75]
[76]
[77] The upper and lower airways undergo normal cyclic changes; the size of the tracheobronchial
tree decreases at night and increases during the day, and the venous erectile tissue
of the nasal mucosa demonstrates normal cycles of congestion and constriction that
cause alternations in the air flow from one nostril to the other over a period of
several hours.
Environmental Conditions
Temperature, relative humidity, and altitude also interfere with MCC, as the nose,
besides filtering the inhaled air, also participates in heating and humidification
processes, ceding heat and water from its mucosa.[78]
[79]
Experimental and clinical studies have shown decreased MCC under environmental temperature
changes[80]
[81] due to increased mucus secretion by the nasal epithelium in order to facilitate
heat exchange,[79] and altered ciliary beat frequency, which is slower at lower temperatures.[82]
[83]
Prolonged exposure to low humidity also results in greater dehydration of the nasal
mucosa, which causes a change in the rheological properties of the mucus and impairs
ciliary movements.[39]
[84]
At high altitudes, both conditions, low humidity and temperature, are added together,
submitting the respiratory system to a more hostile condition, in which MCC is also
impaired.[84]
Studies of the Last Decade
[Table 2] presents the studies published over the past 10 years in journals indexed in the
PubMed and BIREME databases, written in English and Portuguese, found through the
keywords mucociliary clearance and saccharin.
Table 2
Studies published in the last decade that employed the saccharin transit time test
to evaluate mucociliary clearance
|
Category
|
Author; publication year; journal and its impact factor
|
Sample
|
Obtained results
|
|
Reference values
|
Plaza Valía et al[21]; 2008
Arch Bronconeumol: 1.372
|
249 healthy nonsmokers.
|
The STT mean was 17.17 ± 8.43 minutes, and the median was 16 (12–20) minutes.
There was no difference between the STTs of men and women, but they were positively
correlated with age.
|
|
Special physical conditions
|
Deniz et al[86]; 2014
Am J Rhinol Allergy: 2.302
|
122 patients with mild, moderate and severe obstructive sleep apnea syndrome (OSAS),
and 49 healthy subjects as control group
|
Mild and moderate OSAS had SST similar to that of the control group. Severe OSAS had
a slower STT. In all groups, smokers had a slower STT than nonsmokers.
|
|
Baby et al[87]; 2014
Lung India
|
30 adult smokers and 30 adult nonsmokers. Volunteers were healthy and aged between
21 and 40 years old.
|
STT was prolonged in smokers in comparison to nonsmokers. STT was also increased in
subjects smokers for a longer time.
|
|
Janic et al[88]; 2013
Oral Surg Oral Med Oral Pathol Oral Radiol: 1.457
|
144 patients who sustained zygomaticomaxillary-orbitalis fracture
|
STT was impaired on the affected side compared with the control side. However, it
did not vary regardless of age, gender, degree of injury, method of treatment, time
since fracture, and duration of surgery
|
|
Xavier et al[49]; 2013
Respiration: 2.615
|
24 adult nonsmokers and 75 smokers, divided into mild (n = 15), moderate (n = 34), and heavy (n = 27) smokers.
|
Heavy and moderate smokers had a greater STT than mild and nonsmokers.
STT correlated with the concentration of exCO and cigarettes/day.
|
|
Special physical conditions
|
Altuntas et al[50]; 2013
J Craniofac Surg: 0.686
|
20 children infected with Crimean Congo hemorrhagic fever and 20 healthy children.
|
There was no difference between the STTs of infected and healthy children.
|
|
Proença et al[23]; 2011
Rev Port Pneumol: 0.562
|
19 active smokers and 19 nonsmokers (control).
|
Immediately after smoking, the STT of the smokers was similar to that of the control
group.
After 8 hours of smoking abstinence, the STT of the smokers was slower than that of
the control group.
|
|
Naiboglu et al[25]; 2010
J Laryngol Otol: 0.681
|
18 adult patients with unilateral or bilateral epiphora and 20 healthy adults.
|
The STT of the patients was higher than that of healthy individuals.
The STT was also higher in the affected nostril compared with the contralateral.
|
|
Kirtsreesakul et al[89]; 2009
Laryngoscope: 1.979
|
73 patients with mild intermittent allergic rhinitis (MIAR), moderate-severe intermittent
allergic rhinitis (MSIAR), mild persistent allergic rhinitis (MPAR), or moderate-severe
persistent allergic rhinitis (MSPAR).
|
MSPAR had the worst STT, followed by the MSIAR, MPAR, and MIAR groups.
The STT correlated with the symptoms.
|
|
Delehaye et al[37]; 2009
Auris, Nasus, Larynx: 0.948
|
50 gastroesophageal reflux patients.
|
74% of the patients, who had only typical gastroesophageal symptoms, had a higher
STT than the other individuals, who also reported extraesophageal symptoms.
|
|
Yoruk et al[53]; 2008
Rhinology: 1.72
|
83 young men with silicosis and 84 apparently healthy individuals (control).
|
The STT of the patients was higher than that of the control subjects.
|
|
Boatsman et al[48]; 2006
Otolaryngol Head Neck Surg: 1.625
|
83 young men with silicosis and 84 apparently healthy individuals (control).
|
The STT of the patients was higher than that of the control subjects.
|
|
Kamani et al[56]; 2006
Laryngoscope: 1.979
|
20 patients with nasal septal deviation and 30 patients without septal deviation (control).
|
In patients with septal deviation, the STT was higher in the opposite nostril to the
deviation, and both nostrils of these patients resulted in a higher STT than that
of the control group.
|
|
Special physical conditions
|
Nakagawa et al[2]; 2005
Chest: 5.85
|
16 ICU patients who did not receive mechanical ventilation and had no nasogastric
or enteral intubation, and 16 healthy individuals (control).
|
The STT improved in the recovery period after discharge from the ICU compared with
at the time of admission.
In healthy subjects, the STT was not changed.
|
|
Rosen et al[43]; 2005
Laryngoscope: 1.979
|
25 patients with HIV infection and 29 healthy controls. The patients received either
placebo or guaifenesin for 3 weeks.
|
The STT of the patients was higher than that of the control group. There was no difference
between the STT of patients receiving guaifenesin and of those receiving placebo.
|
|
Alho et al[90]; 2004
Am J Rhinol: 1.36
|
9 allergic patients, 16 with sinusitis, and 20 healthy subjects were evaluated from
the 2nd to the 4th day of flu and after 3 weeks.
|
The STT was higher during the flu than in convalescence. The allergic subjects tended
to present the worst STT.
|
|
Philpott et al[91]; 2004
Clin. Otolaryngol Allied Sci: 1.869
|
18 pregnant women, followed-up from the 1st trimester of pregnancy until the postpartum period.
|
Accelerated STT was observed in the 3rd gestational trimester compared with the1st,
and also in the postpartum period compared with the 3rd trimester.
|
|
Effects of environmental pollution
|
Priscilla et al[36]; 2011
Lung India
|
30 adult women who used biomass fuel and 30 adult women who used clean fuel (control).
|
STT was higher in women who used biomass fuel than in the control group.
|
|
Ferreira Ceccato et al[92]; 2011
Respir Med: 2.585
|
45 young sugarcane cutters, of whom 33 were nonsmokers and 12 were light smokers.
|
The STT was similar between smokers and nonsmokers and decreased at the end of the
first day of harvest in both groups.
|
|
Cinar et al[93]; 2004
Otolaryngol Head Neck Surg: 1.625
|
39 coal mine workers exposed to dust, and 38 control subjects.
|
The STT in workers exposed to coal was higher than in control subjects.
|
|
Effects of drug interventions
|
Oysu et al[94]; 2014
Auris Nasus Larynx: 0.948
|
42 geriatric patients with nasal symptoms received either 2 weeks of isotonic sodium
chloride solution (ISCS) followed by 2 weeks of N. sativa oil (NG oil), or the same
treatment in the inverse order
|
There was no change in mucociliary clearance during any of the treatment periods.
|
|
Gelardi et al[95]; 2013
Eur Ann Allergy Clin Immunol
|
36 patients with nasal polyposis received intranasal sodium hyaluronate 9 mg twice
daily or saline solution for 30 days after endoscopic sinus surgery
|
Patients receiving sodium hyaluronate had faster STTs at 1 month compared with controls.
|
|
Riechelmann et al[96]; 2003
J Occup Environ Med: 1.845
|
32 healthy volunteers exposed to 0 (control), 500, 1,000, and 5,000 μg/m3 of calcium
carbonate powder for 3 hours.
|
There was a dose-dependent acceleration in the STT after exposure to dust concentrations
and a slowing in the control situation.
|
|
Bencova et al[97]; 2012
J Phisiol Pharmacol: 2.476
|
43 healthy young men made use of inhaled hypertonic saline solution.
|
The STT decreased 30 minutes after inhalation of the solution.
There was no correlation between STT and nasal nitric oxide.
|
|
Bilgi et al[31]; 2011
Eur J Anaesthesiol: 2.792
|
50 adult patients were divided into two groups; one received low flow inhalational
anesthesia, and the other, high flow.
|
The STT in the immediate postoperative period in both groups was higher than before
the intervention.
The increase in STT of the high flow group was higher than in the low flow group.
|
|
Isaacs et al[42]; 2011
Am J Rhinol Allergy: 2.302
|
27 healthy adults who received nasal irrigation with 50 ml of 1% baby shampoo.
|
The STT was higher 15 minutes after the administration of the solution when compared
with preadministration.
|
|
Effects of drug interventions
|
Cingi et al[98]; 2010
Ther Adv Respir Dis.
|
100 adult patients with allergic rhinitis, who used sea water and saline solution
spray.
|
The STT decreased by 12% with the use of sea water and by 4% with saline solution.
|
|
Gorpelioglu et al[40]; 2010
Int J Dermatol: 1.342
|
40 young patients with acne vulgaris received oral isotretinoin for at least 3 months.
|
After 3 months of treatment, the STT of the patients increased. The STT correlated
with the dosage of the medication.
|
|
Fooanant et al[99]; 2008
J Med Assoc Thai.
|
110 patients with rhinosinusitis undergoing endoscopic sinus surgery, half of which
received dexpanthenol in sea water spray, and the other half, saline solution spray.
|
The STT improved in both groups after 12 weeks of surgery, but there was a greater
magnitude in the group using dexpanthenol.
|
|
Kesimci et al[32]; 2008
Minerva anestesiol: 2.818
|
60 patients undergoing neck or ear surgery, of which 20 received the anesthetic sevoflurane,
20 isoflurane, and 20 desflurane.
|
There was no difference in STTs before and after the use of each type of anesthesia,
or among the three anesthetics.
|
|
Unsal et al[100]; 2008
Am J Otolaryngol: 1.228
|
54 patients with persistent allergic rhinitis who underwent chemosurgery with trichloroacetic
acid.
|
The STT decreased 1 month and 1 year after surgery, when compared with presurgery.
|
|
Zhang et al[38]; 2008
An Otol, Rhinol Laryngol: 1.05
|
29 healthy subjects received application of oxymetazoline spray.
|
The STT of the evaluated subjects increased after 30 minutes of the application of
2 sprays of oxymetazoline.
|
|
Kim et al[101]; 2006
Ann Otol Rhinol Laryngol: 1.05
|
20 patients with chronic sinusitis underwent endoscopic sinus surgery, and an antibiotic
was administered in one nostril, and in the other, saline solution.
|
The STT decreased in all evaluations (1, 3, and 6 months) compared with the time immediately
after surgery, with no difference between the nostrils.
|
|
Effects of drug interventions
|
Saieed et al[102]; 2006
J Clin Pharmacol: 2.841
|
24 subjects received a single dose of montelukast (5 mg), and 24 subjects received
placebo.
|
There was a decrease in STT after the administration of montelukast compared with
placebo.
|
|
Cmejrek et al[47]; 2005
Otolaryngol Head Neck Surg: 1.625
|
42 allergic patients treated with immunotherapy for 1 year. Of them, 23 repeated the
assessment at the end of the treatment.
|
The STT of the allergic patients was higher than that of controls described in the
literature. After 1 year of immunotherapy, there was improvement in the STT in the
evaluated patients.
|
|
Riechelmann et al[103]; 2004
Am J Rhinol: 1.36
|
16 healthy individuals subjected to the use of benzalkonium chloride for 8 days.
|
There was no change in the STT of the evaluated individuals.
|
|
Effects of surgical interventions
|
Yazici et al[104]; 2014
Int J Pediatr Otorhinolaryngol: 1.350
|
33 children with adenoid hypertrophy (AH) and 31 with AH and otitis media with effusion
(AHOME) undergoing surgical procedure
|
The STT improved in all patients after surgery. Patients with AHOME had slower pre-
and postoperative STTs.
Exposure to cigarette smoke and adenoid size had a negative correlation with STT.
|
|
Ozkul et al[105]; 2014
J Craniofac Surg: 1.252
|
23 patients with symptomatic nasoseptal perforations, treated using the mucosal regeneration
technique.
|
STT improved at 3 and 6 postoperative months in comparison with the preoperative evaluation
|
|
Parida et al[106]; 2013
Indian J Otolaryngol Head Neck Surg: 0.054
|
45 patients with symptomatic inferior turbinate hypertrophy undergoing diode laser
turbinate reduction
|
There was prolongation of STT after the intervention. However, it returned to preoperative
values after 6 months.
|
|
Effects of surgical interventions
|
Alobid et al[35]; 2013
Neurosurgery: 2.532
|
36 patients with pituitary adenoma who underwent the transnasal trans-sphenoidal endoscopic
approach, and 14 patients with other benign tumors undergoing the expanded endonasal
approach.
|
Both groups showed a higher STT after surgery compared with baseline. In addition,
patients submitted to the expanded endonasal approach showed a slower STT than the
other group.
|
|
Arnaoutakis et al[24]; 2011
Int J Pediatr Otorhinolaryngol: 1.350
|
10 children with adenoid hypertrophy, chronic adenoiditis, and/or chronic rhinosinusitis
undergoing adenoidectomy.
|
After 1 month of surgery, STT decreased compared with at the preoperative time.
|
|
Miwa et al[107]; 2011
Ear Nose Throat J: 0.66
|
25 patients with chronic sinusitis, 10 of whom underwent maxillary sinus counteropening
via extranasal approaches; 8 underwent enlargement of the maxillary sinus natural
by intranasal endoscopic surgery; 4 received an indwelling maxillary sinus tube, and
3 received a Yamik catheter.
|
STT was similar between groups prior to the intervention. The STT decreased in all
patients who underwent deobstruction and enlargement. In the group receiving the indwelling
tube, the STT increased, and there was a decrease in STT in the catheter group.
|
|
Yigit et al[108]; 2011
Ear Nose Throat J: 0.66
|
50 adult patients undergoing endoscopic dacryocystorhinostomy.
|
Prior to surgery, the STT of both nostrils were similar. One and 3 months after surgery,
the operated nostril showed a higher STT when compared with the contralateral nostril.
|
|
Okuyuku et al[44]; 2009
Otolaryngol Head Neck Surg: 1.625
|
22 patients who underwent unilateral endoscopic dacryocystorhinostomy and 22 who underwent
an external approach.
|
The procedures resulted in STT increase in the nostril subjected to intervention compared
with the contralateral, and there was no difference between the protocols.
|
|
Effects of surgical interventions
|
Chen et al[109]; 2008
Laryngoscope: 1.979
|
160 patients with allergic rhinitis, of whom 80 underwent submucosal resection of
the inferior turbinate, and 80 who underwent assisted inferior turbinoplasty. The
control group comprised 10 individuals without respiratory complaints.
|
Prior to the interventions, the rhinitis groups had worse STTs than the control group.
One year after the surgery, there was a decrease in STT, which was maintained for
up to 3 years in both groups.
|
|
Hu et al[110]; 2008
J Otolaryngol Head Neck Surg: 1.625
|
21 patients with nasopharyngeal carcinoma undergoing endoscopic surgery and 5 control
subjects.
|
Control subjects showed lower STTs than the pre- and postoperative values in the case
group. However, 1 year after the surgery, there was improvement in the STTs of the
patients.
|
|
Sakthikumar et al[111]; 2008
Indian J Otolarygol Head Neck Surg: 0.054
|
20 patients with chronic sinusitis underwent functional endoscopic sinus surgery.
|
There was a decrease in STT 6 weeks after the surgery, when compared with the presurgery
evaluation.
|
|
Chen et al[112]; 2007
Int J Pediatr Otorhinolaryngol: 1.350
|
120 children with chronic nasal obstruction. 60 underwent submucosal resection (SR),
and 60 underwent microdebrider-assisted inferior turbinoplasty (MAIT), and, for control,
10 children without respiratory discomfort.
|
Before surgery, the STT of the children with nasal obstruction was higher than that
of the control group.
One week after the SR, there was an increase in STT, followed by a decrease 1 month
after the surgery. The MAIT group presented no changes in STT at any of the evaluated
moments.
|
|
Clayman et al[113]; 2006
Otolaryngol Head Neck Surg: 1.625
|
5 patients with allergic rhinitis undergoing inferior turbinectomy.
|
The STT mean, performed after 22.6 years of intervention, was 11.8 minutes.
|
|
Effects of surgical interventions
|
Deniz et al[41]; 2006
Eur Arch Otorhinolaryngol: 1.458
|
39 patients underwent total laryngectomy, divided by time since the operation (more
or less than 2 years) and also with associated conditions such as diabetes mellitus
and smoking. The control group consisted of 36 healthy individuals.
|
The STT of individuals who had < 2 years since the surgery was lower than that of
the control group. However, patients with > 2 years since the laryngectomy had higher
STTs.
Diabetic subjects, as well as smokers, presented higher STTs than healthy subjects,
both in the surgery and control groups.
|
|
Huang et al[114]; 2006
Int J Pediatr Otorhinolaryngol: 1.350
|
25 children with edematous and polypoid sinusitis undergoing endoscopic surgery, and
5 controls without sinusitis, undergoing adenoidectomy.
|
There was improvement in the STT after surgery in children with both types of sinusitis,
and the group of edematous sinusitis became similar to the control group.
|
|
Unal et al[46]; 2004
Clin Otolaryngol Allied Sci: 1.869
|
17 patients undergoing dacryocystorhinostomy.
|
Three months after the surgery, the operated nostril showed a worse STT compared with
the side that had no obstruction.
|
|
Other interventions
|
Bhardwaj et al[115]; 2013
AYU
|
40 patients with rhinosinusitis practiced alternate nostril breathing exercise for
40 days, 30 minutes daily, for 2 months
|
There was a reduction in the STT at the end of the intervention period.
|
|
Develioglu et al[51]; 2013
Eur Arch Otorhinolaryngol: 1.458
|
40 adults underwent Ramadan (fasting on average 15 hours per day for 29 days), and
26 adults underwent Nineveh (60 uninterrupted hours of fasting).
|
Individuals who underwent Nineveh had slower STTs at the end of fasting than after
4 weeks of normal diet. There was no difference in the STT of the Ramadan group, or
between groups.
|
|
Other interventions
|
Oozawa et al[12]; 2012
Auris Nasus Larynx: 0.948
|
14 healthy men were exposed to low relative humidity (RH) for 4 hours with prehydration
with water, carbohydrate-electrolyte beverage (CE), and without prehydration (control).
|
The STT increased less in the CE group after 2 hours compared with the low RH exposure
group. Control and hydrated with water groups were not different. After 4 hours of
low RH, the 3 groups presented similar increases in STT.
|
|
Parida et al[116]; 2011
Indian J Med Sci: 1.67
|
50 patients with allergic rhinitis and permanent nasal obstruction undergoing tissue
volume reduction by radiofrequency.
|
The STT did not change significantly between preintervention and 1, 3, and 6 months
postintervention, except 1 week after the intervention.
|
|
Ramos et al[34]; 2011
Respirology: 2.781
|
33 smokers enrolled in a smoking cessation program, and 33 nonsmokers (control).
|
Before quitting smoking, smokers showed higher STTs than controls. After 15 days of
smoking abstinence, the STT decreased to normal levels and remained at these levels
after 30, 60, 90, 120, and 180 days of abstinence.
|
|
Gupta et al[117]; 2006
Indian J Otolaryngol Head Neck Surg: 0.054
|
50 patients with head and neck cancer treated with radiotherapy, and 20 healthy subjects
who received no irradiation.
|
Before starting the radiation therapy, the STTs of the patients were similar to those
of the control subjects. However, 6 months after the end of the treatment, the STT
of the case group was impaired.
|
|
de Oliveira et al[33]; 2006
Respir Med: 2.585
|
11 healthy subjects underwent 20 minutes of CPAP, and 5 controls, evaluated after
20 minutes of rest.
|
The STT decreased immediately after the use of CPAP and did not change in the control
group.
|
|
Kamel et al[118]; 2004
Acta Otolaryngol: 1.106
|
32 patients with nasopharyngeal carcinoma undergoing radiotherapy.
|
There was an increase in STT after radiotherapy.
|
Abbreviations: µg/m3, micrograms per cubic meter; CPAP, continuous positive airway pressure; ex CO, exhaled
carbon monoxide; HIV, human immunodeficiency virus; ICU, intensive care unit; min,
minutes; STT, saccharin transit time.
Experience Report
Considering the aspects that interfere in MCC mentioned in the literature, along with
the experience acquired after years of use of STT in developed researches, our research
group has standardized STT execution as follows:
Previous orientations: Request the patients to abstain from alcoholic substances,
foods and beverages containing caffeine, cigarettes, and drugs for at least 12 hours
prior to the evaluation and ask them not to perform strenuous physical activity the
day before, as these are associated with increased levels of adrenergic mediators
that stimulate the ciliary beat frequency, and thus the clearance.[6]
[54]
[63]
[64]
[65]
[66]
[67] If it is necessary to temporarily cease using any medication to perform the STT,
the doctor should be consulted.
Evaluation scheduling: Ensure the subjects present clinic stability. If they are apparently
healthy, consider a week free from fever, cough, and/or increased mucous production,
since these are common symptoms of respiratory tract infections and it is known that
this impairs MCC.[85] For patients with lung disease, consider 30 days free from exacerbation.
It is essential that the same period of the day is chosen for the evaluations. It
is preferable to schedule them in the morning, since the previous night, in most cases,
the subjects sleep, and in these sleeping hours they do not make use of the substances
previously described, making it easier to complete the required 12 hours of abstinence.
In addition, in the first hours of the morning, subjects are normally exposed to environmental
pollution for less time until the time of evaluation.
Preparation of the evaluation environment: The environment should be quiet, free from people flow and previously prepared to
a maintained temperature of 25° C and to a relative humidity between 50 and 60%, since
variations in these parameters interfere in the MCC.[80]
Required materials: For the preparation of the environment, an air conditioner unit
and a humidifier are needed to ensure the required temperature and relative humidity.
For the placement of sodium saccharin, a plastic straw, trimmed to facilitate the
deposition of particles inside the nostril, ([Fig. 1A]) should be used.
Fig. 1 Saccharin transit time test materials and execution.
The amount of introduced saccharin is standardized as 2.5 micrograms, which corresponds
to ∼ 5 particles of the substance.
Execution of the STT test: Subjects are in a sitting position, with the head supported
in a slight extension (∼ 10° neck extension) ([Fig. 1B]).
The placement of saccharin is performed under visual control, 2 cm into the inferior
turbinates of the right nostril of the subjects. The right nostril is chosen as a
way of standardizing and facilitating the reproduction of the method.
Subjects are asked to maintain their natural breathing and swallowing and not to get
up, talk, cough, sneeze, or manipulate their nose. If this happens, the test is cancelled
and rescheduled for another day. These guidelines are to prevent the change in airflow
or mechanical touches from modifying the movement of the particles and interfering
with the test results.
The expected flavor and nature of the substance should not be disclosed to prevent
false positives.
Limitations of the Method
Despite subjects being instructed on how to breathe and swallow, these aspects are
not objectively controlled by the evaluators and can vary among volunteers.
The test does not present visible results for evaluators, who take the report of the
subjects as true. One way to avoid a false positive is not revealing the real flavor
of the substance to be perceived by the subject, so the result is more reliable.
Even though saccharin presents a strong taste, its perception is subjective and may
vary among subjects, and it is possible that some of them present altered taste, which
would interfere in the results, not due to MCC conditions, but to individual taste
perception.
The placement of saccharin, although not invasive, requires great attention and some
manual skill training from the evaluator, since anatomical differences may hinder
the insertion of the particle and even interfere with the exact location of deposition.
Cleaning the nostrils before the evaluation may be helpful to avoid possible additional
mechanical barriers to the passage of the particle. However, the act of blowing the
nose of the subject can interfere with the MCC due to the change in airflow.
