Authored by Laurent Navarro
Mini Review
Chronic rhinosinusitis (CRS) is a common disorder characterized
by mucosal inflammation of the nose and paranasal sinuses.
Recent years have seen numbers of findings and improvements
in CRS treatment using nebulization process. Targeting delivery
of nebulized antibiotics into the maxillary sinuses, the sites of
infection, could improve clinical outcomes in patients with CRS.
Thus, nasal drug delivery by nebulization is widely used in sinus
disorders, because of its safety and convenience and due to its
advantages as a painless therapy. However, the nebulization
conditions to facilitate penetration of aerosols into the sinus
cavities are not well established. The practice of aerosol therapy to
treat CRS has not been studied thoroughly, despite few works have
shown clinical benefit. This paper demonstrates that the music
signal superimposed to aerosol provides a considerable innovative
solution for the treatment of CRS patients. It encompasses
frequency values among which the resonance frequency of the
maxillary sinuses of patients regardless the initial sinus anatomy
of the patient and the pathology stage and is thus more efficient to
deliver the aerosol into the maxillary sinuses.
“Music heals”. This adage is generally studied by
neuropsychologists and music therapists based on psychological
approaches [1]. Unfortunately, one knows that it is difficult to
prove since it is hardly measurable [2]. Moreover, in these studies,
music is used traditionally through speakers or headphones as it
was designed for. In the meantime, it is well known that music has
complex features in terms of signal properties, especially if regarded
as a random signal. In short, music belongs to the class of pseudostationarity
signals which implies some statistical randomness but
also some stationarity. In addition, music has a large frequency
spectrum which is mainly linked to the human ear’s response of
20Hz to 20kHz. Most of the musical information lies in the 40Hz-
16kHz range, and this range depends a lot on the musical style.
These characteristics can be exploited when such frequency ranges
must be used for medical treatments like nebulization process.
Instead of using ear-fatiguing signals like sinusoidal, or sum of
sinusoidal, signals. Then, music can be used for its characteristics
as a signal. Patients are more likely to accept the presence and the
hearing of a signal if it is music.
Chronic rhinosinusitis (CRS) is a disorder characterized by
mucosal inflammation of the nose and paranasal sinuses. This
common disease is marked by chronic sinonasal symptoms
persisting for greater than 12 weeks that above all diminish patients’
quality of life. It is a significant and increasing health problem
which results in a large financial burden on society. CRS reportedly
affects 5% to 13% of the general population in the United States,
Europe and China [3]. Recent years have seen numbers of findings
and improvements in CRS treatment using nebulization process
[4-5]. Targeting delivery of nebulized antibiotics into the maxillary
sinuses, the sites of infection, could improve clinical outcomes
in patients with CRS. Thus, nasal drug delivery by nebulization
is widely used in sinus disorders, because of its safety and
convenience and due to its advantages as a painless therapy. Topical
delivery of antimicrobial drugs for treatment of CRS also brings
intuitive advantages over systemic therapy. It minimizes the risk
of systemic side effects, the development of antibiotic resistance
in non-targeted areas and allows a high topical drug concentration
deposition with a minimal systemic adsorption.
However, the nebulization conditions to facilitate penetration
of aerosols into the sinus cavities are not well-established. The
practice of aerosol therapy to treat CRS has not been studied
thoroughly, despite few works have shown clinical benefit. To
enhance the penetration of nebulized particles into badly ventilated
areas (i.e. sinuses in healthy subject) or non-ventilated areas
(i.e. sinuses in patients with sinus diseases), a pressure gradient
generated by an acoustic airflow can be added to a usual nebulizer.
The effectiveness of the nebulization process is important because of
the huge incidence of CRS, and the cost of the devices used in the
process. This implies public authorities’ awareness of the problem
of efficiency and reimbursement of treatment.
Since the 1950s, acoustic airflow superimposed to nebulization
process is empirically used as a medical treatment to improve
the penetration of aerosols in nasal cavities mainly for the
treatment of chronic rhinosinusitis. For long, the principle of
sound superimposed to nebulization has been used with more or
less success, using a sound which is basically a 100Hz or 50 Hz
sinusoidal signal. Historically, this value was found accidentally
because of dust found in the sinuses of workers using electrical
rotating machines inducing this type of sinusoidal signal. But today,
this process is questioned by numerous studies and experiments.
The hypothesis to explain this phenomenon was based on the
Helmholtz resonator principle. In fact, the sinuses can be seen as
cavities opened on a small tube with a relatively constant diameter.
As seductive as it may be, the Helmholtz resonator formula
giving the fundamental frequency (Figure 1) is based on few
elementary parameters. This simple empirical equation means that
in good conditions of sphere volume (i.e. the maxillary sinus cavity
in our case), length and diameter of the tube (i.e. the maxillary
ostium in our case), one can find a resonance frequency of 100Hz.
However, any geometric variation from this fragile equilibrium
can lead to a wide range of different resonance frequencies, which
means that using a fixed frequency of 100Hz may be ideal only for
very few patients. Looking closely to Figure 1, one can see that the
inter-individual anatomical variability existing between patients
can lead to large differences in the resulting resonant frequency.
Moreover, even for a same patient with a given geometric features
of maxillary sinuses, this resonant frequency can change during the
evolution of the CRS. The inflammation and the mucus secretion
can decrease the ostium diameter which is more or less obstructed,
and the volume of the cavity can also vary due to the more or less
fluid-filled sinus (Figure 1).
In the past years, strategies have been developed to use
varying acoustic frequencies that led to better results concerning
penetration of aerosols in the sinuses [4-5]. These methods are
based on the use of a frequency sweep that allow to reach all
possible resonance frequencies within a specific range [5]. To allow
for the choice of a wide variety of signals, it has been necessary to
develop a specific device consisting of a membrane mounted on
a vibrating pot linked to a computer through a power amplifier.
This device led us to push the concept of using varying frequencies
further while considering the patient’s well-being. Considering
that music is often associated with certain levels of well-being
and enjoying the good properties of such signals, we decided to
explore their efficiency for the use in the drug delivery process by
nebulization to target the maxillary sinuses (Figure 2).
We tested two different musical pieces: “Für Elise” by
Beethoven and “Get Lucky” by Daft Punk. The first one is
categorized as classical music and is a quite smooth signal with no
big amount of low frequencies, but a more complex behavior and
few stationarities. The second one can be categorized in popular
electronic music and is opposite to the first one with higher level
of low frequencies and more stationarity due to the electronic kick
beating approximatively two times per second. Using rigorously
the same experimental procedure described in [5], the results we
achieved exceeded what we expected. The first finding was that musical
signals were clearly the best signals for aerosols deposition
in sinuses, even at relatively low levels, compared to fixed 100Hz
frequency and acoustic sweep frequencies. To do so, we measured
in a nasal replica the Sodium Fluoride (NaF) deposition in maxillary
sinuses, and we found that music and random noise of frequency
range [100-850] were way more efficient to help the aerosol
penetrate the sinuses. We measured ten times increase in the
deposition for an amplitude of the signal of 80dB.
(Figure 3) Aerosol deposition (using NaF as a chemical tracer)
in left maxillary sinus (LMS) for 5 different acoustic configurations:
Non-acoustic airflow, Fixed 100Hz sinusoidal acoustic airflow,
100-850 Hz random noise, “Für Elise” and “Get Lucky”. Control
experiments refers to nebulization of water without NaF chemical
tracer. Experimental procedures described in [5].
In the light of results obtained in this study, the music signal
superimposed to aerosol provides a considerable innovative
solution for the treatment of CRS patients as it encompasses
frequency values among which the resonance frequency of the
maxillary sinuses of patients regardless the initial sinus anatomy
of the patient and the pathology stage. Besides, the music aerosol
is also patients-driven to make the aerosol treatment more funny
and let them feel more comfortable in order to improve the patient
compliance with airborne drug treatment.
Conclusion
The relationship between fishing and deafness appears to be
widespread among sea workers. It must to promote the culture
of safety and health protection of workers in the maritime sector,
in order to detect, analyze and study the risk factors in the fishing
sector.
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