The surfactant system a new approach for treating the upper respir

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2011Dustri-Verlag Dr. Karl FeistleISSN 0341-3055DOI 10.5414/ATX01743

Supplement

Supplement

The surfactant system a new approach fortreating the upper respiratory tract mucosa

A. Glowania1,2, R. Msges3, M. Bhm3, A. Knopf4and L. Klimek1

1Center for Rhinology and Allergology, Wiesbaden, 2Mannheim ENT University

Hospital, 3Institute for Medical Statistics, Informatics and Epidemiology, University

of Cologne, 4ENT Clinic, Rechts der Isar Hospital, TU Munich

Key words

surfactant phospholip-

id liposomes rhinitis

sinusitis

Schlsselwrter

Surfactant Phospholip-

id Liposomen Rhinits

Sinusitis

Symposium, 6thGerman

Allergy Congress 2011,

Wiesbaden

Background

Across the whole respiratory system, at

least 2 liters of secretory products are pro-

duced within 24 hours by the mucous mem-branes and glands located therein. As the

beginning of the airways, the nose has many

functions to fulll in addition to conditioning

the air that we breathe, with nasal secretion

in particular thereby being indispensable for

mucociliary transport and mucosal defense.

Every day, approximately 12,000 liters of

air passes through the nose of an adult. The

nasal mucous membrane is exposed to large

quantities of gases, aerosols and particles in

the process. Studies have been able to dem-

onstrate that approximately 90 95% of all

particles larger than 15 m in diameter are

deposited in the nose. Pollens, for example,

are 15 200 m in size on average [1]. The

nasal mucous membrane therefore needs to

have an effective self-cleaning and defense

system, which shall be looked at more close-

ly in the following.

Liquid lm and mucociliary

transport

Mucociliary transport constitutes one of

the most important properties of the respi-

ratory mucous membrane. This continuous

transport of secretory products is brought

about by the cilia attached to the epithelial

cells, which, through constant beating, pro-

pel the lm of liquid on the surface of the

epithelial cells in the direction of the phar-

ynx. This effect is also referred to as a self-

cleaning system.

The classical model was assumed to have

a 2-layer lm of liquid: the respiratory epi-

thelium is covered by a supercial and high-

ly viscous layer of mucus (gel phase), under-

neath which is a low-viscosity aqueous layer

of uid (sol phase), which is in direct contact

with the epithelial cells.

Per ciliated epithelial cell, approximately

2,000 cilia beat at a rate of 10 30 Hz in the

periciliary sol phase. The ciliary beat consists

of a rapid effective stroke, which straightens

the cilia, thereby bringing the outstretched

ciliary tips into contact with the mucus in the

gel phase, as well as a slow recovery stroke,

where the bent cilia return to their starting

position in the sol phase. The mucus in the

gel phase is transported in one direction by

this motion sequence [3, 4, 5].From what we know today, the classical

model needs, however, to be modied some-

what. It can be assumed that surfactant can

be found at the sol phase-gel phase interface

in the form of an osmiophilic membrane (bi-

layer), which has the task of making it easier

for the gel phase to glide on the sol phase.

At the air-liquid interface, the gel phase

is covered by a surfactant lm (surfactant:

surface active agent), which, at irregular in-

tervals, can have multiple layers (multilay-

ers), but not the same number thereof [6, 7,8].

Surfactant composition

A mixture comprising various substanc-

es, synthesized primarily in Type II pneumo-

cytes in the lungs, but also in the epithelial

cells and glandular cells of the air passages,

is referred to as surfactant.

It consists of 90% lipids, 90% of which

is, in turn, made up of various phospholipids.

Saturated and unsaturated forms of phos-

Atemwegs- und Lungenkrankheiten, Jahrgang 37, 1. Supplement 2011, S. S1S5


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Glowania, Msges, Bhm, Knopf and Klimek S2

phatidylcholine make up the majority of the

phospholipids.

The remaining 10% of surfactant is com-

posed of proteins, with 4 surfactant-specic

proteins (SP-A, SP-B, SP-C and SP-D) hav-

ing been thereby identied in addition to se-

rum proteins [7].

While the existence of surfactant and its

importance in relation to the lower respira-

tory tract, particularly in the alveoli, has long

been known, investigations of upper respira-

tory tract surfactant, especially as part of the

liquid lm in the nose and paranasal sinuses,have only been intensied in recent years [9,

10, 11, 12].

Importance of surfactant

At alveolar level, its role as a so-called

surface-active factor lies in reducing the

surface tension of the alveolar liquid lm of

the alveoli. When the alveoli become smaller

upon breathing out, the surfactant lm thick-

ens on their surface, thereby preventing al-

veolar collapse.

Several properties are attributed to the

surfactant in the air passages. It improves

mucociliary transport by accelerating ciliary

beat frequency and by conditioning the vis-

cosity of the mucus [6].

Even more important in this context, as

described in the beginning, is the fact that, by

reducing surface tension, surfactant changes

the quality of mucus, which has a consider-

able impact:

To begin with, the lm of liquid, which

moistens and protects the mucous membrane

is stabilized as a result and prevented from

rupture. In addition, especially the phospho-

lipids of the surfactant are responsible for the

forces that act on inhaled particles and draw

them into the liquid lm. When an inhaled

particle comes into contact with the liquid

lm of the air passages and thus with the sur-

factant lm, surface forces between depos-

ited particles and the surfactant lm lead to

(partial) wetting of the particle. The change

in the particle surface by surfactant compo-

nents causes the particle to be displaced into

the liquid phases and thus directed to the mu-

ciliary clearance process [6, 7].

Figure 1. Schematic representation of the motion

of a single cilium. a) Effective stroke; b) recovery

stroke.

Figure 2. Structure of the liquid lm.

Figure 3. Surfactant layer on the gel phase.


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The surfactant system a new approach for treating the upper respiratory tract mucosa S3

This natural defense and self-cleaningsystem only works when the surfactant lm

is unimpaired. Should this not be the case,

the liquid lm situated beneath the surfactant

threatens to rupture, as a result of which the

mucous membranes are rendered unprotect-

ed and exposed to direct physical forces (e.g.

heat and cold), harmful substances as well as

to viral pathogens.

On the basis of these ndings, an impor-

tant goal of treatment has to be the restora-

tion and stabilization of surfactant and, as-

sociated with this, the continuous dispersal

of the whole liquid lm, which is needed, in

turn, to keep the bodys own self-cleaning

and defense system working.

A new therapy approach in this context is

the substitution of the major surfactant com-

ponent with phospholipid-liposomes.

Liposomes are phosphatidylcholine ves-

icles, i.e. spherical encapsulated lamellar

lipid membranes. They possess an aqueous

interior, separated by a continuous aqueous

phase. The membrane consists of a double

lipid layer (bilayer) of amphiphilic lipids

(phospholipids), the hydrophilic parts (head

group) of which face the aqueous side.

In line with the new therapy concept, li-

posomes made of phosphatidylcholine are

applied in nasal spray form. The applied

phospholipids are to stabilize and comple-ment the surfactant lm, as shown schemati-

cally in Figure 7.

The effectiveness of this drug-free treat-

ment concept, which has been outlined here

in theory, has already proved successful in

practice in relation to various indications, as

demonstrated by numerous study results and

eld reports.

Within the context of this summary, the

following paragraphs are to provide a brief

overview of the treatment range for lipo-

somes. Kindly refer to the respective publi-cations for further details.

Allergic rhinitis

Mucosal barrier disturbance plays a ma-

jor role in the development of allergic con-

ditions. Various studies have already been

able to demonstrate that nasal application to

the inamed mucous membrane effectively

reduces the symptoms of seasonal allergic

rhinitisis (SAR) [13, 14, 15].

With the help of a nasal provocation test,

one pilot study was able to demonstrate that

symptomatic treatment with a liposomal na-

sal spray leads to a signicant improvement

in allergic symptoms [13].

A comparative study demonstrated that

treatment with a liposomal nasal spray leads

to a signicant reduction in symptoms as

well as to an improvement in the quality of

life of patients and does not signicantly

vary thereby from guideline antihistamineand glucocorticoid spray therapy, although

guideline combination therapy was used dur-

ing the study twice as often [14].

Given that many patients are extremely

skeptical of cortisone treatment and have a

phobia of steroids, whether justied or not,

the new therapy concept constitutes a perti-

nent non-pharmacological alternative for the

treatment of allergic rhinitis.

Figure 4. Impaired surfactant causes the liquid

lm to rupture.

Figure 5. Missing liquid lm with exposed and un-

protected mucosal epithelial cells.


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Glowania, Msges, Bhm, Knopf and Klimek S4

Rhinitis atrophicans

Atrophic rhinitis involves degeneration

and the destruction of the cell structures of

the respiratory epithelium. In addition to

symptoms such as recurrent infections as

well as cephalalgia, impaired smell and the

formation of crusts, it leads to a signicant

reduction in the quality of life of those af-

fected.

The use of a topical phosphatidyl solu-

tion led, on an individually attempted treat-

ment basis, to a signicant improvement in

ndings on the one hand and to a clear drop

in nasal obstruction and head and face pains

on the other. Further studies are needed in or-

der to conrm the ndings obtained.

Sjgrens syndrome

Sjgrens syndrome constitutes the most

common rheumatic condition involving the

head and neck region and is characterized by

marked dryness symptoms affecting the eyes

and the upper aerodigestive tract. Severe

complications in the form of troublesome

and sometimes painful swallowing, impaired

smell and taste, caries, periodontosis and in-

ammation of the salivary glands are linked

to the dryness symptoms. Subjective com-

plaints can be eased signicantly through the

use of nasal, eye and mouth sprays, which

are based on phospholipid-liposomes. The

saliva interleukin 6 concentration, as a pos-

sible surrogate parameter for autoimmune

inammation, was lowered signicantly inthe high-risk group after only two months

treatment with the phospholipid-liposome

products.

Future prospects

Chronic sinusitis

The initial results of a comparative study

investigating the treatment of patients with

chronic sinusitis show that the treatmentconcept with phospholipid-liposomes is also

effective in this commonly occurring condi-

tion [17].

Rhinitis sicca

The results of the comparative study in-

vestigating the treatment of rhinitis sicca

demonstrate the good efcacy of the lipo-

somal nasal spray compared to established

therapeutic agents [18].

Rhinitis medicamentosa

The theoretical approach would suggest

that using the liposomal nasal spray would

be of benet. Field reports are not yet avail-

able.

Figure 6. Image of a liposome with lipid bilayer

membrane.

Figure 7. Schematic representation of the treat-

ment concept.


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The surfactant system a new approach for treating the upper respiratory tract mucosa S5

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A. Glowania

Facharzt fr Hals-Nasen-Ohrenheilkunde

Zentrum fr Rhinologie und

Allergologie Wiesbaden

An den Quellen 10

D65183 Wiesbaden

e-mail: [email protected]

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