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Wirkmechanismen nasaler Glukokortikosteroide in der Therapie der allergischen Rhinitis

Teil 2: Praxisorientierte Aspekte der Anwendung

Mechanism of action of nasal glucocorticosteroids in the treatment of allergic rhinitis

Part 2: Practical aspects of application

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Zusammenfassung

Glukokortikosteroide (GCS) werden bei allergischer Rhinitis (AR) in der Regel topisch eingesetzt. Der Vorteil gegenüber anderen Substanzklassen ist u. a. die hohe Wirksamkeit auf die nasale Inflammation/Obstruktion. Die Patienten müssen darauf hingewiesen werden, dass eine Beschwerdebesserung nicht sofort zu erwarten ist, sondern bei intermittierender Rhinitis nach etwa 2–4 Tagen, bei persistierender Rhinitis nach etwa 2–3 Wochen. Sprays mit nasalen GCS (nGCS) müssen regelmäßig angewandt werden. Eine Anwendung „bei Bedarf“ ist weder wirkungs- noch sinnvoll. Eine Indikation für GCS sind hyperplastische Verlaufsformen perennialer Rhinitiden, oft als Begleittherapie zur operativen Sanierung der Nasenmuscheln und/oder Nasennebenhöhlen. Neue Erkenntnisse deuten darauf hin, dass intranasal applizierte GCS sich nicht nur positiv auf die nasale Symptomatik auswirken, sondern zudem auch okulare Beschwerden lindern können. Zudem wurde gezeigt, dass nGCS auch in der prophylaktischen Therapie einer saisonalen AR von Nutzen sein können. Diese Theorie wird durch Kenntnisse über die molekularen Mechanismen der antiinflammatorischen Wirkung von nGCS gestützt. Demnach sollten nasale Glukokortikosteroide als wesentliche medikamentöse Therapieoption bei AR in Betracht gezogen werden.

Abstract

Allergic rhinitis (AR) is the single most common allergic disease and one of the most common chronic diseases. It affects approximately 25–30% of the population, and can substantially worsen patients’ medical conditions, reduce quality of life, and contribute to absenteeism from work or school. It is also responsible for substantial direct and indirect economic burdens on the health care system.

The medical management of allergic rhinitis includes several available pharmacotherapies, such as α-sympathomimetics, anticholinergic drugs, natural saline or other nasal rinses, mast cell-stabilizing agents, topical and systemic antihistamines, topical and systemic glucocorticosteroids, leukotriene-receptor antagonists and the new monoclonal antibodies following a stepwise approach. Allergen-specific immunotherapy is the only treatment option that interferes with the natural course of the disease and, besides allergen elimination, is thought to be the only causative treatment option.

Nasal glucocorticosteroids (nGCS) are thought to be the most effective treatment choice for controlling the symptoms of AR. Double-blind, randomized clinical trials have demonstrated greater efficacy of nGCSs versus placebo, antihistamines or montelukast for relief of all nasal symptoms, especially congestion. Therefore, especially in the management of AR-related nasal inflammation and congestion, nGCSs are considered the most appropriate treatment. Patients should be informed that symptom improvement can be expected after 2–4 days for intermittent rhinitis and after up to 2–3 weeks for persistent rhinitis. The medication has to be taken regularly and not as “on-demand” treatment. Adherence to treatment also affects outcomes, and this may be influenced by patient preferences for the sensory attributes of an individual drug and the awareness of possible side effects.

More recently, safety studies have shown that the newer nGCS agents have improved safety profiles compared with older nGCS agents. The newer nGCS drugs have been found to have minimal adverse effects on growth and hypothalamic-pituitary-adrenal-axis function in children. This review will discuss the pathophysiology of allergic inflammation in the nasal mucosa and the mechanism of action of nGCSs; also the efficacy and safety of nGCSs will be discussed by focusing on clinical evidence.

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Abbreviations

APZ:

antigenpräsentierende Zellen

AP-1:

“activator protein-1”

AR:

allergische Rhinitis

BALF:

bronchoalveoläre Lavageflüssigkeit

bFGF:

“basic fibroblast growth factor“

cysLT:

Cysteinyl-Leukotriene

CD:

“cluster of differentiation”

cDNA:

“complementary“ Desoxyribonukleinsäure

DC:

dendritische Zelle

ECP:

eosinophiles kationisches Protein

EIA:

Enzymimmunoassay

FcεRI:

hochaffine IgE-Rezeptoren

Foxp3:

Forkhead Box P3

GILZ:

“glucosteroid-induced-leucine zipper”

GM-CSF:

“granulocyte macrophage colony-stimulating factor”

GR:

Glukokortikoidrezeptor

H1-Rezeptor:

Histaminrezeptor vom Typ 1

ICAM-1:

interzelluläres Adhäsionsmolekül 1

IFN:

Interferon

IgE:

Immunglobulin E

IL:

Interleukin

LT:

Leukotriene

MHC:

“major histocompatibility complex”

mRNA:

Messenger-Ribonukleinsäure

NFκB:

“nuclear factor kappa B”

nGCS:

nasale Glukokortikosteroide

NGF:

“nerval growth factor”

NO:

Stickstoffmonoxid

PAF:

plättchenaktivierender Faktor

PG:

Prostaglandin

TARC:

“thymus and activation regulated chemokine”

TGF:

“transforming growth factor”

TH1 :

T-Helferzellen vom Typ 1

TH2 :

T-Helferzellen vom Typ 2

TLR-Rezeptor:

Toll-like-Rezeptor

TNF-α:

Tumornekrosefaktor-α

TOVAs:

“test of variables of attention”

TXA2:

Thromboxan A2

Treg-Zellen:

T-regulatorische Zellen (Lymphozyten)

VCAM:

“vascular cell adhesion molecule”

VEGF:

“vascular endothelial growth factor”

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Der korrespondierende Autor erhielt Unterstützung für wissenschaftliche Forschungsprojekte/Vortragshonorare/Beratung von folgenden Firmen: ALK-Abello, Dänemark; Allergopharma, Deutschland; Artu Biologicals, Niederlande; Bencard, Großbritannien; Bionorica, Deutschland; Boehringer Ingelheim, Deutschland; Curalogic, Dänemark; Cytos, Schweiz; GSK, Großbritannien; HAL, Niederlande; Hartington, Spanien; Leti, Spanien; Lofarma, Italien; MSD, USA; Novartis, Schweiz; Optima, Deutschland; Phadia/Thermofisher, Schweden; Roxall, Deutschland.

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Authors and Affiliations

  1. Zentrum für Rhinologie und Allergologie, An den Quellen 10, 65183, Wiesbaden, Deutschland

    L. von Bernus, O. Pfaar &  L. Klimek

  2. Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität, Würzburg, Deutschland

    P. Högger

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  1. L. von Bernus
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  2. P. Högger
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  4. L. Klimek
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Correspondence to L. Klimek.

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von Bernus, L., Högger, P., Pfaar, O. et al. Wirkmechanismen nasaler Glukokortikosteroide in der Therapie der allergischen Rhinitis. HNO 60, 700–706 (2012). https://doi.org/10.1007/s00106-012-2484-3

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