The rhinologist

1

www.therhinologist.com

N.1/2016

ISSN 2531-9299

The Official Journal of the Italian Academy of RhInology

The Rhinologist The Rhinologist 1-2016

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Table of Contents 3.The Rhinologist 4.Summary of Second Italian Rhinoforum 6.The Role of Hyluronan Acid in the sinonasal Mucosa. E. Cantone 9.Asthma Phenotypes. A. Spanevello 12.Bacteria and eosinophils: is there a link? G. Nicoletti 14.How Big, how Far: Surgical Intervention in eosinophilic rhinosinusitis. C. Pipolo 16.Antimicrobial Activities. N. Mevio 21.Rhinitis. Diangostic Proposal. IAR RSC Group 24.Special Insert: Rinite Vasomotoria. IAR RSC Group 30.Authors Guidelines

EDITORIAL BOARD Journal Editorial Chief: Matteo Castelnuovo Journal Scientific Chief: Matteo Gelardi, Paolo Castelnuovo Administrator and Segretary: PSA&CF srl Editorial Staff: Stefania Gallo, Paola Terranova,

Editor: PSA&CF srl Via Procaccini, 24

21100 Varese

www.therhinologist.com Editor in Varese

- Four-monthly Magazine

Varese, 2-12-2016

ISSN 2531-9299

The Rhinologist 1-2016

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The Rhinologist The Italian Academy of Rhinology (IAR ) was

The Rhinologist, the official Journal of the

founded with the aim to collect those Rhinolo-

Academy, represents the natural evolution of

gy’s various souls that in recent years offered

this journey to improve the research and the

not only professional training opportunities and

study of Rhinology with the scope to give the

contents, but also established themselves at in-

opportunity to share best practices and

ternational level as a valued and constantly

knowledge even with the aim to reach an im-

evolving entities

portant impact factor. Within the journal read-

According to this point the Accademy wants to

give an active, responsible and significant contribution to the development of the discipline, with the belief of the absolute need to have a unique and shared vision on the nasal field that can represent the totality of the realities which compose the rhinology, including key areas (cytological medical-surgical) and especially the field of endoscopic and reconstructive surgery also with

ers will find the most important dates of courses, conferences and meetings, as well as new job opportunities and facilities. Finally, in order to help the growth of the circulation of this magazine The Rhinologist will be provided for free with the aim to spread as much as possible the values of the publications made by young talents who want to give their contribution to the world of rhinology.

the aesthetic functional-addresses.

The objective is to promote the research, educa-

tion, training and ability to attract young talents in order to make the difference with the aim to grow up the primacy of this specialty, anticipating changes to combine all available forces to implement experiences, willingness and skills.

The Italian Academy of Rhinology encourages the ambition of its members to be present and competitive on the international scene, through an expertise and a credibility solidly built over the years. Moreover in this way the IAR wants to create conditions for attracting new vital forces that can continue this path of innovation, taken and shared by many colleagues during the years, that allow the academy to be the catalyst of a process that wants to find a new strategic roadmap to make the world better in terms of medical, technical and surgical approach.

The Rhinologist 1-2016

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Summary of the Second Italian Rhinoforum Parma 2016 Italian Academy of Rhinology

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THE ROLE OF HYALURONAN ACID IN THE SINO-NASAL MUCOSA: Hyal 1 and Hyal 3, present at endoplas-

THERAPEUTIC APPLICATIONS AND

matic network and lysosomial level, depolymerize hyaluronan once endocytosed. Hyaluronan is

LITERATURE REVIEW

diffusely distributed along all airways and mainly at

Elena Cantone, University of Naples, Federico II,

nasal mucosa level, being a potential reservoir from where signal molecules for reparation can be acquired.

Naples, Italy

All hyaluronidase system components (Hyal 1,.2, 3) can be activated by oxigen free radicals (ROS), profusely generated during the first phases of tissue repair process.

Hyaluronic acid (HA) or hyaluronan is a non-sulphated glycosaminoglycan made of repeating

glucuronic

acid

and

N-

acetylglucosamine disaccharide units, linked through alternating beta-1,4 and beta-1,3 glycosidic bonds. It is one of the main components

of many extracellular matrices, including respiratory epithelial cells and nasal and tracheobronchial mucosa. (1) Recently, mounting evidence suggests that HA serves important biological roles beyond its generally accepted function as a structural component of interstitial and connective tissues. (2) For instance, hyaluronan has been shown to promote wound healing, tumor transformation, and metastasis, as well as cell motility and migration. Many of

these biological activities are mediated by either CD44 or the receptor for hyaluronic acidmediated motility (RHAMM or CD168) (1).

Tissue hyaluronan fragmentation is operated by a hyaluronidase system (Hyal 1,2,3) displaced in many cellular compartments. Hyal2, chained to the cellular membrane through glycosylphosfatidylinositol (GPI), acts on extracellular matrix hyaluronic.

Thus several fragments of smaller weight are formed. Low weight fragments act as “danger signals” while tetrasaccharides have a great antiapoptotic activity.

While other different weight fragments, which

may act as intracellular protein syntesis inductors, are able to increase the response to shock (heat shock protein), other fragments contribute into signal molecule transduction. Pre-respiratory mucosal 3 hyaluronidases may act in a coordinate manner thanks to their activity on hyaluronan: an “up-regulation” of TNF-a and IL-1 b is established, similarly to what happens in asthmatic patients when stimulated by allergens. Hyaluronan fragments interacting with neutrophils and monocytes surfaces receptors (CD44, RHAMM, TLR4) can stimulate cytokines production and many flogosis mediators activation (like activation of the nuclear factor ihibitor: factor-κBα/nuclear-kB pathway) which are able to up-regulate the expression of interleukin-1β and TNF-α17 and the expression of many other potential flogosis mediators. From a general point of view, low-weight fragments induce activation while high-weight fragments determine suppression, The Rhinologist 1-2016

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being able to prevent extreme expression of

Furthermore, HA promotes phagocyto-

flogosis as well. Hyaluronan fragments can in-

sis of Streptococcus pyogenes in vitro and in

teract with CD44 and TLR-4 and therefore reg-

vivo by interfering with mechanisms of recog-

ulate monocytic transformation into macro-

nition. In addition, hyaluronan has been shown

phage. Furthermore, monocytes own 3 hyalu-

to reduce the number of exacerbations in pa-

ronidases which can generate a pool of HA-

tients with chronic bronchitis.(4) In spite of such a wide employment,

active fragments inside healing tissues.

In particular, from the interaction with

only few studies have assessed the effects of

TLR4 signals are generated, which are able to

HA on chronic or recurrent upper respiratory

start neutrophils degranulation and induce

tract infections. Most of them have provided

autolysis; the latter produces debris and DNA

evidence that HA is beneficial in improving clin-

creating traps (NET) which concentrate, recall

ical and laboratory outcomes in affected chil-

and block other neutrophils enhancing the ac-

dren and adults. In this regard, HA has been

tion. (3). From a clinical point of view, it’s of

shown to promote wound healing, repairing of

utmost importance the concept of high and

mucosal surfaces and cell motility. Particularly,

low molecular weight, since the low molecular

studies showed that topical application of HA

weight HA is pro-inflammatory, whereas the

significantly improves the healing process of

high molecular weight HA, that is an important

the nasal mucosa, preventing extensive crust

component of many extracellular matrices,

formation, and, eventually leading to the re-

plays a central role in the homeostasis of the

covery of smell parameters and cooling sensa-

upper and lower airways, in the regulation of

tion. A prospective randomized controlled trial

vasomotor tone, in the secretion of the mu-

suggests that a new absorbable HA hydrogel,

cous glands, and in the modulation of the in-

similarly to a nasal dressing/packing following

flammatory process

functional endoscopic sinus surgery (FESS),

acting as

an anti-

inflammatory agent.

Because of its biological properties, HA has several clinical applications, such as aesthetic surgery, dermatology, orthopedics and

promotes the postoperative reepithelization process and reduces the presence of synechia, edema, crust, and mild mucopurulent drainage (1).

Furthermore, HA in association with

ophthalmology. In particular, hyaluron has an

intranasal corticosteroid and systemic antihis-

important role in the function of mucociliary

tamine, reduces the neutrophil count shown

clearance from the epithelial surface, in the

on nasal cytology in patients with allergic and

processes involved in the repairing of the mucosal surface, and in the viscoelasticity of the

non-allergic rhinitis and improves several clinical and endoscopic parameters (1). Although evidence on the effectiveness of SH on postop-

structures responsible for speech. Indeed, HA-

erative care following FESS is currently availa-

has also been assessed for its use as an antiad-

ble (1), there remains a dearth of evidence

hesive and/or augmentative agent in vocal

evaluating its actual impact as enhancer of in-

cord surgery for the treatment of vocal fold atrophy, sulcus vocalis, and post-surgery scar-

tranasal corticosteroid on the chronic rhinosinusitis with nasal polyposis (CRSwNP) and quality of life (QoL) of affected patients.

ring.

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A recent study showed that HA supplement to standard corticosteroid appears to

References 1. Forteza R, Lieb T, Aoki T, et al. Hyaluronan serves a

play an important role in improving the severi-

novel role in airway mucosal host defense.

ty of symptoms, endoscopic appearance and

FASEB J. 2001;15:2179–2186.

discomfort associated with CRSwNP. This

2. Cantone E, Castagna G, Sicignano S, et al. Impact of

effect appears to be strongest in patients with

Intranasal Sodium Hyaluronate on the Short-term

allergic CRSwNP. (5) Another recent study pro-

QoL of Patients Undergoing FESS for Chronic Rhinosi

vided further evidence in support of the effectiveness and safety of HA administered by nasal douches in preschool children with recur-

nusitis.Int Forum Allergy Rhinol. 2014; Jun;4(6):484-7 3. Castelnuovo P, Tajana G, Terranova P, Digilio E, Bignami M, Macchi A. From modeling to remodeling Of upper airways: Centrality of hyaluronan

rent or persistent upper respiratory tract infec-

(hyaluronic acid). Int J Immunopathol Pharmacol.

tions improving clinical outcomes and QoL. (6)

2015 Apr 21

In conclusion, hyaluronan

allows to

4. Gelardi M, Guglielmi AV, De Candia N, Maffezzoni E,

maintain the correct trophism of the respirato-

Berardi P, Quaranta N.Effect of sodium hyaluronate

ry airways and in particular of the nasal muco-

On mucociliary clearance after functional endoscopic

sa, improving not only the mucociliary clear-

sinus surgery. Eur Ann Allergy Clin Immunol. 2013

ance and the mucosal remodeling after sino-

May;45(3):103-8.)

nasal surgery, but also the QoL of these patients.

5. CantoneE., Iengo M. Effect of sodium hyaluronate add ed to topical corticosteroids in chronic rhinosinusitis with nasal polyposis. AJRA in press 6. Montella S, Cantone E, Maglione M, Iengo M, San tamaria F. Sodium hyaluronate improves quality of Life and nasal endoscopy features in preschool chil dren with upper respiratory tract infections. J Biol Regul Homeost Agents. 2016 Jan-Mar;30(1):303-8.

The Rhinologist 1-2016

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ASTHMA PHENOTYPES

European Respiratory Society guidelines collect all the technical aspects in order to stand-

Antonio Spanevello Università degli Studi dell’Insubria, Varese, Dipartimen-

ardize the procedure and propose a clinical interpretation of the results obtained with

to di Medicina Clinica e Sperimentale Malattie dell’Ap-

this methodology (5).

parato Respiratorio e Fondazione Salvatore Maugeri,

Healthy subjects usually have a sputum main-

IRCCS, Tradate, Dipartimento di Medicina e Riabilitazione CardiorespiratoriaU.O.C. Pneumologia Riabilitativa.

ly composed of macrophages and neutrophils while eosinophils, lymphocytes and epithelial cells are only scarcely represented (6).

Asthmatic patients are usually characterized

Asthma is a heterogeneous disease, usually

by an eosinophilic inflammation, but also neu-

characterized by chronic airway inflammation;

trophils can accumulate in their airways, par-

bronchial hyperresponsivness and reversibil-

ticularly in corticosteroid resistant patients.

ity. Symptoms vary over time and the lack of

The amount of airway eosinophils increases

control of the disease can lead to severe asth-

with the severity of the disease (7).

ma and sometimes to death (1-2). In the last few years, many clinicians and researchers tried to group patients with common characteristics of the disease in phenotypes in order to better manage symptoms and severity and to control the disease. Moore at al., consid-

Hamid et al., demonstrated the presence of these cells also in the small airways of patients with asthma, showing that also small airways are involved in the inflammatory processes of bronchial asthma. (8).

ered three clinical variables, basal FEV1, age of

Asthmatics with eosinophilic inflammation are

disease onset and FEV1 after bronchodilation,

often atopic, but the majority of patients with

and with cluster analysis he identified 5 differ-

severe adult-onset asthma whilst non-atopic

ent phenotypes of asthmatic patients (3). The

have persistent eosinophilic airway inflamma-

identification of these clusters highlights

tion (9).

different pathophysiologic mechanisms and

Nasal inflammation is an important risk factor

could have clinical and therapeutic implica-

for the development of asthma, even in the

tions. Airway inflammation is an important

absence of atopy (10) and chronic rhinosinusi-

characteristic of the disease useful to identify

tis was positively associated with late-onset

phenotypes. It can be evaluated through in-

asthma as well (11).

duced sputum analysis, exhaled nitric oxide

(FeNO) determination or by measuring blood biomarkers, which can represent, to a lower extant, airway inflammation. Induced sputum

Neutrophilic inflammation is also present in a subgroup of asthmatic patients, mainly in severe persistent asthma (12-13).

analysis, even if not routinely applied, is the

In a retrospective study aimed to identify the

most accurate methodology to evaluate air-

inflammatory characteristics of asthmatic pa-

way inflammation among the non-invasive

tients, the dominant phenotypes are the eo-

procedures and the reproducibility of sputum

sinophilic and the paucigranulocytic ones. The

cell counts is acceptable for inflammatory

study also revealed a subgroup of subjects

cells (4).

without airway inflammation (14).

The Rhinologist 1-2016

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These subjects are the ones with better pulmo-

In conclusion, phenotyping asthma,

nary function, with a well-controlled disease or

particularly from the inflammatory point of

with intermittent asthma (15).

view, is useful considering the heterogeneity of

The inflammatory phenotypes can change or

the disease, when discordance between symp-

persist depending on the occurrence of viral or

toms and functional parameters occurs and dis-

bacterial infections, or on the response to

ease control is not reached despite appropriate

treatment.

treatment.

Only a small part of asthmatic subjects has a stable inflammatory phenotype and the presence of a persistent eosinophilic phenotype seems associated to lower FEV1 (16).

The identification of the type of airway inflam-

mation in an asthmatic patient, can be useful at diagnosis, particularly when a discordance between symptoms, hyperreactivity and lung function occurs (15,17) or during the follow-up when disease control is not reached despite treatment (18).

The presence of eosinophils in the airways is in fact a good predictor of response to inhaled corticosteroid treatment (19).

Moreover, a therapeutic strategy directed at

normalisation of the induced sputum eosinophil count reduces asthma exacerbations without the need of additional anti-inflammatory treatment (17).

Blood eosinophils can be used as surrogate of sputum eosinophil evaluation but, it is important to consider that this determination has a lower sensitivity in identifying airway eosinophilia, furthermore, other factors can determine blood eosinophil increase (nasal polyposis,etc..) (20).

However, asthmatic patients with increased

References 1. Global Initiative for Asthma (GINA), Global Strategy for Asthma Management and Prevention, Update 2016. http://www.ginasthma.org.

2016 (access March 2016).

2. Saetta M, Thiene G, Crescioli S, Fabbri LM. Fatal asthma in a young patient with severe bronchial hyperresponsiveness but stable peak flow records. Eur Respir J. 1989;2:1008-12.

3. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, CurranEverett D, Fitzpatrick AM, Gaston B, Jarjour NN,

Sorkness R, Calhoun WJ, Chung KF, Comhair SA, Dweik RA, Israel E, Peters SP, Busse WW, Erzurum SC, Bleecker ER; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program.

Am

J

Respir

Crit

Care

Med.

2010;181:315-23.

4. Spanevello A, Migliori GB, Sharara A, Ballardini L, Bridge P, Pisati P, Neri M, Ind PW. Induced

sputum to assess airway inflammation: a study of reproducibility. Clin Exp Allergy. 1997;27:1138 -44.

sputum and blood eosinophils are the ones

5. Djukanović R, Sterk PJ, Fahy JV, Hargreave FE.

with the lowest airway calibre, asthma control

Standardised methodology of sputum induction

and quality of life, and the highest bronchial

and processing.Eur Respir J Suppl. 2002;37:1s2s.

hyperresponsiveness, FeNO and exacerbation

6.Spanevello A, Confalonieri M, Sulotto F, Roma-

rate (20).

no F, Balzano G, Migliori GB, Bianchi A, Michetti The Rhinologist 1-2016

11

7. Louis R, Lau LC, Bron AO, Roldaan AC, Rader-

15. Haldar P, Pavord ID. Noneosinophilic asthma:

mecker M, Djukanović R. The relationship be-

a distinct clinical and pathologic phenotype. J Al-

tween airways inflammation and asthma severi-

lergy Clin Immunol. 2007;119:1043-52.

ty. Am J Respir Crit Care Med. 2000;16:9-16.

16. McGrath KW, Icitovic N, Boushey HA, Lazarus

8. Hamid Q1, Song Y, Kotsimbos TC, Minshall E,

SC, Sutherland ER, Chinchilli VM, Fahy JV; Asthma

Bai TR Inflammation of small airways in asthma.

Clinical Research Network of the National Heart,

J Allergy Clin Immunol. 1997;100:44-51.

Lung, and Blood Institute. A large subgroup of

9. Amelink M, de Groot JC, de Nijs SB, Lutter R,

mild-to-moderate asthma is persistently none-

Zwinderman AH, Sterk PJ, ten Brinke A, Bel EH.

osinophilic. Am J Respir Crit Care Med.

Severe adult-onset asthma: A distinct pheno-

2012;185:612-9.

type. J Allergy Clin Immunol. 2013;132:336-41.

17. Green RH, Brightling CE, McKenna S, Har-

10. Shaaban R1, Zureik M, Soussan D, Neukirch

gadon B, Parker D, Bradding P, Wardlaw AJ,

C, Heinrich J, Sunyer J, Wjst M, Cerveri I, Pin I,

Pavord ID. Asthma exacerbations and sputum eo-

Bousquet J, Jarvis D, Burney PG, Neukirch F,

sinophil counts: a randomised controlled trial.

Leynaert B. Rhinitis and onset of asthma: a lon-

Lancet. 2002;360:1715-21.

gitudinal population-based study. Lancet.

18. Romagnoli M, Vachier I, Tarodo de la Fuente

2008;372:1049-57

P, Meziane H, Chavis C, Bousquet J, Godard P,

11. Jarvis D, Newson R, Lotvall J, Hastan D, To-

Chanez P. Eosinophilic inflammation in sputum of

massen P, Keil T, Gjomarkaj M, Forsberg B,

poorly controlled asthmatics. Eur Respir J.

Gunnbjornsdottir M, Minov J, Brozek G, Dahlen

2002;20:1370-7.

SE, Toskala E, Kowalski ML, Olze H, Howarth P,

19. Meijer RJ1, Postma DS, Kauffman HF, Arends

Krämer U, Baelum J, Loureiro C, Kasper L,

LR, Koëter GH. Accuracy of eosinophils and eosin-

Bousquet PJ, Bousquet J, Bachert C, Fokkens W,

ophil cationic protein to predict steroid improve-

Burney P. Asthma in adults and its association

ment in asthma. Clin Exp Allergy. 2002;32:1096-

with chronic rhinosinusitis: the GA2LEN survey

103.

in Europe. Allergy. 2012;67:91-8.

20. Schleich FN, Chevremont A, Paulus V, Henket

12. Jatakanon A, Uasuf C, Maziak W, Lim S,

M, Manise M, Seidel L, Louis R. Importance of

Chung KF, Barnes PJ. Neutrophilic inflammation

concomitant local and systemic eosinophilia in

in severe persistent asthma. Am J Respir Crit

uncontrolled asthma. Eur Respir J. 2014;44:97-

Care Med. 1999;160:1532-9.

108.

13. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of

chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma.

Eur Respir J. 2003;22:470-7.

14. Schleich FN1, Manise M, Sele J, Henket M, Seidel L, Louis R. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm Med. 2013;13:11.

The Rhinologist 1-2016

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Bacteria and eosinophils: is there a link?

Giuseppe Nicoletti* - Annamaria Speciale Biomedical and Biotecnological Sciences Dept. – University of Catania - Italy Rhinosinusitis (RS) is a group of disorders characterized by inflammation of the mucosa of the nose and the paranasal sinuses and is traditionally classified by duration as acute (4 wk), subacute (4–12 wk), or chronic (12 wk,

with or without exacerbations). Infective etiologic include Rhinovirus, Adenovirus, S. pneumoniae, H. influenzae, M. catarrhalis as principal causes of acute and subacute rhinosinusitis; anaerobic bacteria as responsible of odontogen sinusitis; P.aeruginosa, Klebsiella spp., Serratia spp. and Aspergillus spp.in nosocomial and fungal rhinosinusitis; P. aeru-

with mast cells (NARMA), non-allergic rhinitis

with eosinophils and mast cells (NARESMA), non-allergic rhinitis with eosinophils (NARES).

This last condition is currently an area of intense debate and recently, biofilms have been proposed as a potential environmental trigger.

The biofilm is primary produced by S. epidermidis, S. aureus, S. pneumoniae, and P. aeruginosa and is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface or to each other, are embedded in a matrix of extracellular polymeric substances that they have produced and exhibit an altered phenotype with respect to growth rate and gene transcription. Biofilms create an inhospitable environment for antibiotic potency by downregulating the metabolic activity of “core” bacteria and creating a metabolic milieu conducive for antibiotic resistance.

ginosa and represent the Aspergillus spp e

Despite the relative metabolic dormancy of

most frequent infective agent in the immune

these bacteria, they remain an important

deficiency rhinosinusitis. Chronic rhinosinusi-

source of superantigens and other immunogen-

tis (CRS) is a pathology that frequently occurs

ic products that may exacerbate these diseases.

as a complication of acute or subacute RS.

Although numerous bacteria may secrete su-

CRS is believed to arise primarily from persis-

perantigens, staphylococci are particularly note-

tent inflammation of the mucosa and perhaps

worthy for the extent and diversity of their su-

the underlying bone, caused by environmen-

perantigen repertoire. This is particularly im-

tal factors (e.g. pollution, allergens, viruses,

portant because CRS, especially in its eosino-

bacteria, and molds), general host factors

philic presentations, are singularly characterized

(genetic, granulomatous disorders, immune

by staphylococci colonization that reflects the

deficiency, cystic fibrosis, and ciliary defects),

specific inhibition of innate immunity against

and local host factors (chronic localized in-

Staphylococcus aureus in these Th2-mediated

flammation, anatomic obstruction, polyps

diseases (similar to what is observed in atopic

and tumors). If for allergic rhinitis (AR) and

dermatitis). In eosinophilic CRS the T cells infil-

chronic rhinosinusitis without nasal polyposis,

trating the sinuses typically display a TH2-type

the epidemiology and immunological mecha-

microenvironment with general lack of regula-

nisms are relatively well known, few data are

tory T (Treg) cell function, IL-5 induces eosino-

available for non-allergic rhinitis (NAR), in

philia, and IL-4 and IL-13 induce local IgE pro-

particular for the forms called “cellular”,

duction exacerbating the allergic inflammatory

which include non-allergic rhinitis with neu-

processes and contributing to worsening tissue

trophils (NARNE), non-allergic rhinitis

remodeling.

The Rhinologist 1-2016

13

Additionally, components of staphylococcal biofilms alone may be sufficient to skew naïve T cells to the Th2 pathway, independent of the presence of superantigens. The activation of epithelium colonized by bacteria and fungi leads to release of proinflammatory chemokines and cytokines with increased thymic stromal lymphopoietin (TSLP) and IL-32 levels. Activated epithelial cells die, with apoptosis resulting in a compromised epithelial barrier. Furthermore, the presence of S. aureus biofilms is associated with eosinophilic inflammation, as evidenced by the elevated Eosinophilic Cationic Protein (ECP) levels in this group when compared to both non-biofilm CRS and controls. Superantigen-specific IgE– positive CRS (SAE+) is associated with significantly elevated total IgE, IL-5, and ECP when compared to both superantigen-specific IgE– negative CRS (SAE) and controls. These data leaves an open question on the interrelation between the T-helper2-biased mucosal immune response and S. aureus biofilm formation. Profiting from a pre-existing Thelper2 bias within the mucosa, S. aureus may switch to the biofilm phenotype and establish itself within the damaged mucosa. Alternatively, S. aureus biofilms may induce the T-helper2 bias, which initiates the specific mucosal changes.

The Rhinologist 1-2016

14

How big, how far: Surgical intervention

ECRS and non-ECRS (NECRS) have to be an-

in eosinophilic rhinosinusitis

swered. ECRS is characterized by a predominance

Pipolo C, Saibene AM, Felisati G

posterior part, and commonly exhibits multiple

Otolaryngology Unit, San Paolo Hospital, De-

of disease in the ethmoid sinus, especially in the and bilateral nasal polyps occluding the olfactory cleft when compared to NECRS (7). Furthermore,

partment of Health Sciences, UniversitĂ degli

most ECRS patients demonstrate sinonasal secre-

Studi di Milano, Milan, Italy

tion with high viscosity, while NCRS is common with mucopurulent discharge (7). Since ECRS is considered to occur secondarily to a systemic eo-

Chronic rhinosinusitis (CRS) is a significant

sinophilic deregulation, the benefit of surgery is

health problem that in most guidelines is de-

significantly less in these patients and a surgical

fined as an inflammation of the nose and para-

approach targeting only the osteomeatal com-

nasal sinuses ongoing for at least 12 weeks (1).

plex is not efficacious (8). However, the extent of

The term CRS however, includes a variety of

surgery required to optimize outcome has not

different entities such as CRS with nasal polyps

been established and reports suggest that in this

(CRSwNP), CRS without nasal polyps (CRSsNP),

refractory disease a more extensive procedure

eosinophilic CRS (ECRS) and so on; already

may improve resolution rates. Chan et al report-

hinting that this disease will need a complex

ed results from a group of ECRS patients (most of

medical and surgical approach due to its differ-

whom presented clinically with nasal polyps)

ent endo- and phenotypes and its multifactori-

after frontal sinusotomy (Draf IIa). A very high

al pathophysiology. Patients with ECRS repre-

patency rate of 85% was achieved for this more

sent a unique subtype, thought to occur sec-

extensive procedure (9). Likewise Costa et al re-

ondarily to systemic eosinophil deregulation

ported on a series that underwent mega-

(2). However, far form being a separated enti-

antrostomies for recalcitrant maxillary sinusitis

ty also regarding its etiology, the description of

reporting complete resolution of symptoms in

many different stimuli at its base (including

72%, while 27% reported partial symptomatic

fungal antigens, allergens, bacteria, and bacte-

improvement (10). Regarding the ethmoid sinus

ria-derived superantigens) (3), shows that

no recommendations regarding the extent of sur-

ECRS is probably the reflection of an inflamma-

gery could be found. However, if considering the

tory process encompassing a wide variety of

recurrent nature of the disease and its localiza-

etiologies (4). ECRS remains the most resistant

tion, radical ethmoidal surgery with preservation

to medical and surgical interventions in the

of the mucosal lining seems pivotal to enhance

wide array of different forms of CRS (5) and its

outcomes and facilitate postoperative healing

management especially burdensome for pa-

and management. Preservation versus resection

tients and doctors. Literature regarding surgi-

of middle turbinates has also not been discussed

cal approaches to ECRS is particularly scarce

in ECRS patients but removal for recalcitrant CRS

and the only meta-analysis present actually

has been advocated by some as being associated

excludes all studies for qualitative and quanti-

with less adhesion formation and less revision

tative analysis (6). Therefore, in order to treat

surgeries (9). All surgical approaches have to

these patients in a more defined way ques-

take into account the subversion of anatomy that

tions about disease extension differentiating

occur after multiple extensive surgeries The Rhinologist 1-2016

15

and the associated risk of for e.g. vascular and

References:

skull base lesions. Magnetic resonance and navi-

1. Bachert C, Pawankar R, Zhang L et al.: ICON:

gation on top of a computed tomography should

chronic rhinosinusitis World Allergy Organ J. 2014

therefore routinely be included in preoperative

Oct 27;7(1):25.

planning. Regarding the size of sinusal openings it has to be taken into account that ECRS patients will highly benefit from local treatment able to penetrate the sinuses. Local management may

2. Ferguson BJ. Eosinophilic mucin rhinosinusitis: a distinct clinicopathological entity. Laryngoscope.

2000;110:799–13.

include in-office lavage of the sinuses to remove

3. Borish L, Rosenwasser L, Steinke JW. Fungi in

particularly viscous mucous and administration

chronic hyperplastic eosinophilic sinusitis: reaso-

of medication through high volume irrigation

nable

(11). As mentioned before, the treatment strate-

2006;30:195–204.

gies for ECRS differ from those for NECRS and

4. Sok JC, Ferguson BJ. Differential diagnosis of

early category zation of patients may be very

eosinophilic chronic rhinosinusitis. Curr Allergy

useful to decide a treatment strategy in an out-

Asthma Rep. 2006;6:203–14.

patient setting (12). Additionally, it would be possible to make it clear to patients with sinusitis involving eosinophils that they have a high possibility of a poor postoperative prognosis that will require long-term postoperative care (13).

Undoubtedly, there is still the need for further investigations of additional advanced strategies

to treat patients with ECRS and tight relationship

doubt.

Clin

Rev

Allergy

Immunol.

5. Ferguson BJ. Categorization of eosinophilic chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2004;12:237–42.

6. Sharma R1, Lakhani R, Rimmer J, Hopkins C Surgical interventions for chronic rhinosinusitis with nasal polyps Cochrane Database Syst Rev.

2014 Nov 20;11:CD006990.

with other specialties such as the immunologist,

7. Wang ET, Zheng Y, Liu PF, Guo LJ. Eosinophilic

allergologist, pulmonologist, and infective dis-

chronic rhinosinusitis in East Asians. World J Clin

ease specialist is mandatory to target this sys-

Cases. 2014 Dec 16;2(12):873 -82.

temic refractory disease from all flanks.

8. Snidvongs K, Chin D, Sacks R, Earls P, Harvey RJ. Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion. Laryngoscope. 2013 May;123 (5):1070-4. doi: 10.1002/lary.23721.

9. Fokkens WJ1, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for

otorhinolaryngologists.

Rhinology.

2012

Mar;50(1):1-12. doi: 10.4193/Rhino50E2 The Rhinologist 1-2016

16

10. Costa ML1, Psaltis AJ, Nayak JV, Hwang PH.

“Antimicrobial Activities”

Long-term outcomes of endoscopic maxillary mega-antrostomy for refractory chronic maxil-

Niccolò Mevio, ASST Grande Ospedale Metropo-

lary sinusitis. Int Forum Allergy Rhinol. 2015

litano Niguarda Milano

Jan;5(1):60-5. doi: 10.1002/alr.21407. Epub 2014 Oct 13.

Chronic rhinosinusitis (CRS) is defined as having “sinus trouble” as nasal obstruction or rhinor-

1

11. Singhal D , Weitzel EK, Lin E, Feldt B, Kriete

rhea associated with maxillary pain or facial pres-

B, McMains KC, Thwin M, Wormald PJ Effect of

sure for at least 12 weeks per year. CRS with and

head position and surgical dissection on sinus

without nasal polyps is a commin disease that

irrigant penetration in cadavers. Laryngosco-

affects 16% of the population in the US with an

pe. 2010 Dec;120(12):2528-31. doi: 10.1002/

annual cost of 6 billion $. Conventional medical

lary.21092.

therapies are represented by antibiotics, ster-

12. Sakuma Y, Ishitoya J, Komatsu M, Shiono O,

oids, antihistaminic and decongestants, while

Hirama M, Yamashita Y, et al. New clinical dia-

endoscopic sinus surgery is the treatment of

gnostic criteria for eosinophilic chronic rhinosi-

choicein patients who did not respond to medi-

nusitis. Auris Nasus Larynx. 2011;38:583–8.

cal therapy1,2. Antibiotic resistances, steroid pho-

13.Haruna S, Otori N, Moriyama H, Nakanishi M. Olfactory dysfunction in sinusitis with infiltration of numerous activated eosinophils. Auris Nasus Larynx. 2006;33:23–30.

bia, side effects of drugs and the failure of conventional therapy in a group of patients, led to seek new alternative treatment options2. Different alternative medical therapies have been used in the literature for the treatment of CRS as ascorbic acid, bromelin, N-acetylcysteine, Quer-

cetin, undecylenic acid, urtica dioica or a lactose, wheat, corn, gluten free diet. The workshop members concluded that none of these therapies has proved comparable to standard medical therapies, while a specific diet is appropriate only in patients with demonstrated allergy. Nasal douche with saline solution has been shown to be effective in the treatment of nasal symptoms in CRS and in promoting the postoperative healing following sinus surgery. Hypertonic solution

are less tolerated than hypotonic. Patients perceive high volume low pressure douches as Sinus Rinse to be more effective than low-volume and high pressure. They are easy to use and can be associated with other drugs. They have a more effective penetration in sinus cavities after surgery3. The conclusion of the workshop is that actually high volume and lower pressure nasal douches are more effective moreover after surgery

The Rhinologist 1-2016

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Rinophototherapy (PT) is, based on the use of a

Each healthy individual houses multiple distinct

red light at narrow energy band. Different photo-

microbiomes at different body sites; though

therapies were analyzed in literature, studies

inter-individual variation exists, the composi-

showed a significant improvement of clinical

tion of the microbiome at any given site is

symptoms in allergic rhinitis or CRS with or with-

broadly similar across healthy subjects. Pertur-

out polyps with an immunosuppressive and anti-

bations to these microbial ecosystems are in-

inflammatory effect. It can induce apoptosis of

creasingly associated with a myriad of inflam-

surface epithelial cells and subepithelial cells

matory and autoimmune diseases of the ga-

such as T-cells and eosinophils in addition to low-

strointestinal tract, airways, and skin. Chronic

ering levels of IL-54,5. Photodynamic therapy

inflammatory disorders (RSC) and allergic re-

(PDT) proved to be one of the great success sto-

spiratory tract are associated with dysbiosis.

ries in dermatology and has been also used in

Recurring or chronic infections, antibiotic the-

other areas such as urology, gastroenterolgy,

rapy and mucosal stress (smoking) induce alte-

ginecology. The basis of PDT is to apply a visible

rations in the microbiome8. Probiotics are live

light-absorbing photosensitizer or its precursor

microorganisms that, when administered in

before treatment with visible light. The mecha-

adequate amounts, confer a health benefit on

nism of action is based on free radical-derived

the host. Oral administration of probiotics con-

cellular toxicity and apoptosis induction. PDT

ditions the intestinal micro-environment with

permits a photodisinfection against viruses, fun-

effects

gus, bacteria also resistant to antibiotic therapy

(gastrointestinal-respiratory axis). The supple-

(MRSA, Pseudomonas). It does not affect human

mentation with probiotics induces Th1 respon-

hair cells of the respiratory mucosa and there is

ses, reduces Th2 activity, transforms the

no induction of photoresistance, so the treate-

growth factor Beta, increases the production

ment could be repeatable6. The conclusion of the

of local IgA. Probiotics have proven effective in

workshop is that PT and PDT represent a promis-

particular to reduce the symptoms of allergic

ing new treatment option, but need more datas

rhinitis. A Cochrane review showed that pro-

to be validated. Liposomal spray is based on lipo-

biotics are effective in reducing infections of

somes, produced from phosphatidylcholine. They

the upper respiratory tract, but there is still no

stabilize the surfactant film with anti- inflamma-

evidence for the treatment of chronic rhinosi-

tory and wound-healing effect and prevent the

nusitis9. The conclusion of the workshop is

moisture film lining the airways from tearing.

that probiotic therapy is a very interesting and

A liposomal nasal spray (LN) therefore represents

promising therapy, not yet fully understood.

an entirely drug-free treatment. Authors showed

The open questions are: effectiveness in chron-

no difference in term of symptom reduction

ic rhinosinusitis, route of administration (oral,

compared with beclomethasone spray, so liposo-

topical), use of a single specie or different as-

mal spray could be a therapeutic alternative in

sociations of probiotics, timing of administra-

patients with steroid phobia7.

tion.

on

the

respiratory

system

The human microbiome is the collection of microbial species and their associated genomes that live on and in the human body.

The Rhinologist 1-2016

18

References

1 Fokkens W et al: for the European Position Paper on Rhinosinusitis and Nasali Polyps group. European Position Paper on Rhinosinusitis and Nasali Polyps 2007. Rhinol Suppl 2007 2 Albu S: Novel drug-delivery systems for patients with chronic rhinosinusitis. Drug Des Devel Ther 2012 3 Salib RJ et al: prospective randomised singleblinded clinical trial comparing the efficacy and tolerability of the nasal douching products SterimarTM

and Sinus RinseTM following functional endoscopic sinus surgery Clin Otolarymgol 2013.

4 Nemeth IB et al: Ultraviolet light and photodynamic therapy induce apoptosis in nasal polyps. Journal of Photochemistry and Photobiology B. 2012 Biology 5 Varshney R et al: New innovations in office-based rhinology . Curr Opin Otolayngol Head Neck Surg 2016 6 Biel MA, et al: The effect of antimicrobial photody-

namic therapy on human ciliated respiratory mucosa. Laryngoscope 2012 7 Eitenmuller A et al: Liposomal Nasal Spray versus Guideline-Recommended Steroid Nasal Spray in Patients with Chronic Rhinosinusitis: A Comparison of Tolerability and Quality of Life. J Allergy (Cairo) 2014 8 Cope EK et al: Novel Microbiome-Based Therapeutics for Chronic Rhinosinusitis. Curr Allergy Asthma Rep 2015 9 Kramer MF et al: Probiotics in the Treatment of Chronic Rhinoconjunctivitis and Chronic Rhinosinusitis. J Allergy 2014

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Raccomandazioni per la gestione delle rinite Vasomotoria a cura dell'Accademia Italiana di Rinologia

una tra le prime dieci cause di accesso allo studio

del Medico di Medicina Generale, e porti ad una diminuzione della qualità della vita, ad un aumento delle ore di lavoro perse e ad un maggiore ri-

Articolo In Italiano

corso alle cure sanitarie con conseguente impatto

La rinite allergica e quella vasomotoria , patologie

indagare la storia, i segni e i sintomi che nella

delle prime vie aeree vantano una diffusione nel-

maggior parte dei casi potrebbero, con relativa

la popolazione difficilmente riscontrabile in altre

facilità, indirizzare alla diagnosi. 1,2

condizioni cliniche . Se si considera la prevalenza

La rinite vasomotoria è una rinite cronica, non

della rinite non allergica rispetto alla rinite allergi-

allergica, che non ha un’origine immunologica

ca, il 71% delle riniti è di tipo allergico e il 29% è

o infettiva

di tipo non allergico. L’elevata prevalenza della

quentemente, starnuti e naso chiuso.

rinite allergica ed i suoi effetti sulla qualità della

Colpisce una parte rilevante della popolazione

vita hanno portato ad includerla tra le maggiori

italiana causando problemi con importanti risvolti

malattie croniche respiratorie. I dati disponibili

sociali. Ad esempio negli Stati Uniti colpisce quasi

forniscono una prevalenza che varia dal 10% al

17 milioni di persone, con un costo di 1.8 bilio-

40% della popolazione generale e tale prevalenza

ni di dollari annuali per visite specialistiche e per i

sta continuando a crescere, sia negli adulti che

farmaci, che rappresentano il 4% dei costi diretti

nei bambini . 14 La rinite allergica riduce in ma-

per la cura delle malattie delle vie respiratorie.

niera significativa la qualità della vita, altera il

Nell’ambito della rinite non allergica, la rinite va-

sonno, e influisce negativamente sulla vita socia-

somotoria o idiopatica rappresenta il 71% delle

le, lavorativa e scolastica. I costi socioeconomici

riniti non allergiche. La rinite vasomotoria rappre-

diretti ed indiretti della rinite sono di importanza

senta quindi la più comune forma di rinite non

non trascurabile. I costi indiretti includono la per-

allergica con una prevalenza mondiale di 320 mi-

dita di giorni lavorativi e scolastici. Come è noto i

lioni di persone. 15

pazienti affetti da queste malattie oscillano tra

La rinite vasomotoria non è causata da un'infezio-

una totale autogestione basata su tradizionali ri-

ne o un'allergia. La causa della rinite vasomoto-

medi domestici, il ricorso al farmacista che forni-

ria non è nota. Sembra che ci sia una risposta

sce consigli e farmaci da banco e il consulto del

ipersensibile agli stimoli come un ambiente

proprio medico di famiglia. Questi comportamen-

asciutto, agenti atmosferici inquinanti, cibi piccan-

ti fanno sì che il fenomeno resti ancora ampia-

ti, alcool, forti emozioni, e alcuni farmaci. Infatti

mente ignorato nella sua reale dimensione epide-

La presenza di particelle in aria, tra cui pollini, pol-

miologica, con conseguenze importanti non solo

vere, muffe, o peli di animali può creare fastidio

per il paziente ma anche per il sistema sanitario. I

alle persone con rinite vasomotoria, anche se non

motivi di questa situazione vanno ricercati nella

sono in realtà allergici a queste cose. 3

sottovalutazione del problema, nella diffusa per-

La presenza dei fattori scatenanti è in grado di in-

cezione della rinite quale semplice disturbo

nescare la reazione infiammatoria a livello della

piuttosto che malattia a tutti gli effetti. Tale atteg-

mucosa nasale, che causa della sintomatologia del

giamento non è prerogativa esclusiva dei pazien-

paziente.

ti; anche i medici, infatti, malgrado la rinite sia

Quando il naso è irritato, il paziente presenta soli-

sulla spesa sanitaria, non di rado trascurano di

caratterizzata da naso che cola fre-

tamente questi sintomi:

The Rhinologist 1-2016

25

- naso che cola con muco chiaro e acquoso,

La terapia topico permette la somministrazione

- congestione nasale (naso chiuso),

di relativamente alte dosi direttamente nell’or-

- starnuti

gano bersaglio evitando o minimizzando gli effetti dei mastociti a livello mucosale. Inoltre

Che devono essere interpretati e trattati attraver-

limitano lo switch delle plasmacellule e la conse-

so una attenta diagnosi del medico.

guente sintesi di Ig E ma anche di IL-3, Il-4, IL-5 e Il -13 La terapia topico permette la somministra-

Proposta di percorso diagnostico

zione di relativamente alte dosi direttamente

Per il paziente il medico di medicina generale è il

nell’organo bersaglio evitando o minimizzando

primo riferimento, poiché conosce il paziente, la

gli effetti collaterali sistemici. La terapia locale

sua famiglia e la sua storia clinica. Il paziente si

permette inoltre un’attività più veloce. Gli steroi-

reca dal medico spinto da quello che è di solito il

di topici sono dotati di liposolubilità, caratteristi-

sintomo più disturbante: la congestione nasale. Il

ca che permette un aumentato e più rapido as-

paziente lamenta una fastidiosa sensazione di na-

sorbimento a livello della mucosa nasale, maggi-

so chiuso che può peggiorare nelle ore notturne o

ore permanenza nel tessuto assorbente, maggio-

quando si corica, accompagnata a un senso di

re capacità di raggiungere il recettore citosolico

ottundimento che rende difficile la concentrazio-

per gli steroidi. Da un punto di vista farmaco-

ne e lo svolgimento delle proprie attività quotidia-

cinetico, oltre a una ridotta biodisponibilità è

ne. Questi sintomi sono il risultato di una conge-

importante garantire una rapida eliminazione

stione nasale dei turbinati, accompagnata da una

del farmaco dal sangue. Breve emivita ed eleva-

rinorrea , aumentandone l’ingombro delle fosse

ta clearence, caratterizzano i corticosteroidi topi-

nasali. Altre manifestazioni spesso presenti quali

ci in grado di essere più rapidamente eliminati

gli starnuti, la rinorrea e il prurito.

dall’organismo, garantendo minori effetti siste-

I principali mediatori che intervengono nelle rea-

mici

zioni alla base della rinite allergica sono l’istami-

Come procedere:

na, i leucotrieni e le prostaglandine che entrano a

Dopo l’accurata anamnesi del paziente è impor-

far parte della catena infiammatoria che si viene a

tante valutare l’obiettività locale nasale, il MMG

creare a livello della mucosa nasale. Gli steroidi

sebbene normalmente non disponga di quegli

nasali topici rappresentano la prima scelta della

strumenti utilizzati in ambiente ORL che consen-

terapia della rinite allergica riducendo in maniera

tono un’ispezione approfondita, effettui un pri-

significativa i sintomi ed in modo specifico l’ostru-

mo esame obiettivo, volto a identificare la tipo-

zione. Gli steroidi esplicano la loro azione antin-

logia/forma di rinite di cui soffre il paziente.

fiammatoria sulla mucosa nasale con diversi mec-

Ad esempio, uno speculum nasale e una buona

canismi, limitando l’uptake e la processazione

fonte luminosa consentono di ispezionare l’in-

dell’antigene da parte delle cellule di Langherans,

terno delle cavità nasali, in primis, specie nei

riducendone il numero, riducendo il numero e la

bambini, per escludere la presenza di corpi

sopravvivenza degli eosinofili nella lamina propria.

estranei ostruenti o alterazioni morfologiche in

Limitano l’afflusso dei basofili e dei mastociti a

particolare a carico del setto.

livello mucosale.

L’osservazione di una mucosa edematosa che

Inoltre limitano lo switch delle plasmacellule e la

ricopre i turbinati inferiori, pallida, di colorito

conseguente sintesi di Ig E ma anche di IL-3, Il-4,

ceruleo, la presenza di secrezione nasale

IL-5 e Il -13 The Rhinologist 1-2016

26

Acquosa o translucida (come chiara d’uovo), può

Inoltre i pazienti che vivono in aree industriali e so-

orientare verso il quadro di una rinite allergica

no ex o attualmente fumatori hanno un alto rischio

ed in alcuni pazienti far sospettare la presenza

di avere una rinite non allergica. I fumatori hanno

di poliposi nasale. Nel caso l’orientamento del

un basso rischio mentre i i soggetti che vivono

medico sia per una forma non infettiva, il succes-

nell’area mediterranea anno un alto rischio di avere

sivo passo è di comprendere se si tratti di una

una rinite allergica. 6

forma allergica o non allergica. 5

È in genere possibile a questo punto per il medico tentare un inquadramento nell’ambito della classifi-

Come distinguerle In questi casi altri elementi importanti sono la precoce insorgenza (nel 70% dei casi < 20 anni di età) e l’andamento stagionale dei sintomi, il loro

manifestarsi dopo il contatto con animali o il peggioramento in ambiente esterno, specie nei pressi di aree erbose recentemente tagliate; per con-

cazione delle rinite proposta delle linee guida ARIA. La conferma diagnostica del sospetto di una rinite allergica si ottiene attraverso l’esecuzione dei test allergologici in vivo o in vitro. Tra i test cutanei quello più utilizzato è lo skin prick test. Nonostante la loro relativa semplicità di esecuzione, nella

tro, ha significato il miglioramento in ambienti

pratica quotidiana della Medicina Generale italiana

dotati di aria condizionata e l’assenza del fumo di

questi test non sono in genere diffusamente prati-

tabacco o di altre sostanze chimiche come fattori

cati, probabilmente per questioni di ordine organiz-

scatenanti. In caso di sospetto è importante tene-

zativo. I test allergologici sono invece importanti e

re presente la modalità bimodale di presenta-

vanno sicuramente prescritti in caso di fallimento

zione della rinite allergica: in genere si ha infatti

della terapia farmacologica o in vista di sottoporre il

la prima comparsa all’epoca delle scuole elemen-

paziente a immunoterapia specifica. In alternativa

tari, la remissione nel periodo delle scuole medie

alle prove cutanee è possibile utilizzare come test il

e superiori e la ricomparsa verso i 20-30 an-

dosaggio della concentrazione sierica delle immu-

ni. Nelle riniti non allergiche invece la comparsa

noglobuline (IgE) specifiche per determinati allerge-

dei sintomi si ha in genere in età adulta (nel 70% dei casi dopo i 20 anni), non vi è storia familiare di allergia mentre esiste una rispo sta di sensibilità agli stimoli quali fumo di tabacco e sostanze chimiche; inoltre, i sintomi sono provocati anche da mutamenti di clima, ma non presentano andamento stagionale e non insorgono dopo esposi-

ni. 7

Proposta Terapeutica per la rinite allergica Alla base dei diversi quadri clinici di rinite che si conoscono esiste un processo flogistico, risultato di una serie di reazioni immunochimiche. Nel caso specifico delle riniti allergiche si tratta di una rispo-

zione alla polvere o agli animali. Un recente stu-

sta esagerata in termini di produzione di IgE nei

dio italiano ha permesso di puntalizzare che nel

confronti di sostanze verso le quali normalmente il

sesso femminile vi è un significativa presenza di

nostro sistema immunitario è indifferente. È quindi

rinite non allergiche con una percentuale dal 12%

evidente che il principale obiettivo terapeutico nei

nell’età tra i 20 e i 44 anni al 7.5% tra i 65 e gli 84

confronti di queste patologie è il controllo dell’in-

anni. Mentre negli uomini la percentuale varia

fiammazione, sia attraverso la prevenzione dei

dal 10.2 % all’ 11.1 %. La rinite allergica diminui-

momenti scatenanti sia interferendo nella catena di

sce dal 26.6% nella fascia d’età dai 20 ai 44 anni

reazioni che determinano le alterazioni biologiche e

al 15.6% nella decade dai 65 agli 84 annni, senza

tissutali.

una significativa differenza tra uomini e donne.

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27

Nel caso di una rinite allergica si può seguire lo schema proposto dalle linee guida ARIA importante iniziativa sostenuta dall’Organizzazione Mondiale della Sanità attraverso un documento scientifico pubblicato alla fine del 2001

che

ha

come

obiettivo

quello

di ottimizzare la diagnosi e il trattamento della rinite e di svelare nei pazienti rinitici l’eventuale presenzadi sintomi bronchiali– anche se lievi – allo scopo di prevenire l’insorgenza di asma. ARIA è la sigla di Allergic Rhinitis and its Impact on Asthma (La Rinite Allergica ed il

suo Impatto sull’Asma). 8

Questo schema

Proposta Terapeutica della rinite vasomotoria La rinite vasomotoria essendo una patologia cronica, a causa delle frequenti recidive degli episodi, e prevede una terapia che sarà sicuramente cronica e di lunga durata, da ripetersi ciclicamente in base alle recrudescenze del problema.

La terapia ha lo scopo di alleviare i sintomi e consiste nella somministrazione di steroidi topici in prima istanza con eventualmente associati ad un antistaminico per uso topico o per via generale.

Se il trattamento ha effetto ed è efficacie conviene proseguire con la terapia per almeno 12 settidato dalle linee guida internazionali deve essere personalizzato nella realtà del paziente e nella realtà locale. Per questo motivo viene anche proposto uno schema modificato per rendere più accessibile

mane. Alla terapia farmacologica possono essere

associati lavaggi nasali con soluzioni ipertoniche, che hanno un effetto decongestionaste e agevo-

il trattamento terapeutico al paziente. La differenza

lano la pulizia delle cavità nasali attraverso un

è soprattutto nell’uso dello steroide topico fin dai

meccanismo osmotico locale. Sempre per miglio-

primi sintomi come terapia d’attacco del problema,

rare la risposta locale si possono utilizzare pro-

tenendo presente che questi pazienti dovranno effettuare ciclicamente la terapia, la scelta suggerita è quello di ricorrere ad uno steroide topico, efficace e ben tollerato.

dotti contenenti acido ialuronico, per ripristinare la corretta integrità della mucosa nasale attraverso il processo di remodelling svolto dall’acido iaTheidrantante Rhinologist 1-2016 luronico associato alla capacità locale.

28

Si è dimostrato come l’acido ialuronico abbia un’azione protettiva della mucosa nel paziente

rappresentando un’incidenza importante nella po-

allergico e non, prevenendo i danni da agenti

polazione con risvolti di rilievo a livello lavorativo e

esterni. Nel consigliare un dispositivo medico

della qualità della vita del paziente.

contenente acido ialuronico, bisogna inoltre

L’impostazione di un percorso diagnostico e tera-

considerare il peso molecolare dello stesso,in

peutico corretto rappresenta il primo passo per un

quanto maggiore è il peso molecolare, maggio-

corretto inquadramento e trattamento della rinite.

re è l’azione terapeutica. Numerosi studi hanno

Il percorso diagnostico terapeutico proposto, rap-

dimostrato come la terapia con l’acido ialuroni-

presenta una concreta azione d’aiuto per il medico

co utile in caso di rinosinusiti, riniti allergiche e

di medicina generale nel migliorare l’approccio al

non allergiche, oltre a rappresentare un presidio

paziente con rinite allergica e non allergica. 13

innovativo che aiuta il recupero post-chirurgia

nasale. L’acido ialuronico migliora il meccanismo di clearance mucociliare utile per eliminare allergeni e altre particelle nocive e, grazie alla sua particolare capacità di legarsi alle molecole d’acqua, favorisce l’idratazione delle mucose atrofiche. 9,10 Recenti studi hanno dimostrato che l’acido ialuronico, somministrato in aggiunta a corticosteroidi e antistaminici per via intranasale, svolge un’azione efficace con significativo miglioramento dei sintomi quali starnuti, rinor-

rea e congestione nasale, oltre ad essere ben tollerato dai pazienti. Nel caso di insuccesso della terapia sono ulteriori accertamenti possono essere necessari e per questo motivo l’inviare il paziente ad un centro di rinologia può rappresentare la strada giusta.

Nell’ottica di agevolare il compito del medico di medica generale, l’Accademia Italiana di Rinologia attraverso il suo gruppo di lavoro sulle riniti, propone il seguente percorso diagnostico terapeutico, dove seguendo i vari steps diagnostici e terapeutici permette di facilitare la gestione della patologia e del paziente. In questo approccio si post pone l’effettuazione dei test allergometrici, a partire dallo skin-prick test, ad una fase successiva di accertamento. 11, 12 Conclusioni La patologia rinitica rappresenta una patologia spesso misconosciuta e mal diagnosticata in ambito delle patologie delle alte vie aeree pur The Rhinologist 1-2016

29

(FIRST CHOICE)

Bibliografia 1.Eifan AO1, Durham SR1. Pathogenesis of rhinitis Clin Exp

9.Bousquet J, van Cauwenberge P, Khaltaev N. Al-

Allergy. 2016 Sep;46(9):1139-51.

lergic rhinitis and its impact on asthma. J Allergy

2.Ciprandi G, Rossi GA.The topical treatment of allergic

Clin Immunol 2001;108(Suppl.5):147-334.

and vasomotor rhinitis: the role of beclomethasone di-

10. Gendo K, Larson EB. Evidence-based diagnostic

propionate Recenti Prog Med. 2014 Nov;105(11):420-8

strategies for evaluating suspected allergic rhinitis.

3.Gelardi M. Overlapped" rhinitis: a real trap for rhinoallergologists. Eur Ann Allergy Clin Immunol. 2014 Nov;46 (6):234-6.

4. P. Wheller et al :Vasomotor Rhinitis. American Family Physician Volume 72, Number 6, September 15, 2005 5. E. Macy :A rhinitis primer for family Medicine. FAAAAI Perm J 2012 Fall;16(4):61-66 6. Gregory C, Cifaldi M. Targeted intervention programs: creating a customized practice model to improve the treatment of allergic rhinitis in a managed care population. Am J Manag Care 1999;5:485-96.

7. Mantovani LG, Bettoncelli G, Passalacqua G, et al. Allergic rhinitis in the Italian population evaluated by the national database of General Practitioners. Allergy 2007;62:569-71.

8. Krouse J. et al. Development of a self-report screener

Ann Intern Med 2004;140:278-89.

11. Leynaert B, Neukirch F, Demoly P, Bousquet J. Epidemiologic evidence for asthma and rhinitis comorbidity. J Allergy Clin Immunol 2000;106 (Suppl.5):201-5.

12. Schenkel EJ, Skoner D P, Bronsky EA, Absence on growth etardation in children with perennial allergic rhinitis after one year treatment with

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mometasone furoate aqueous

nasal spray. Pediatrics 2000;105: 22 13. Tran NP, Vickery J et al. Management of rhinitis allergic and non allergic. Allergy Asma and Immunology 2011, Jul 3 (3) 156,158 14. Dion G.R. et Al Current Approaches to Diagnosis and Management of rhinitis tSouthern Medical Journal & Volume 106, Number 9, 2013

for congestion. Presentation XXV Congress of the Euro-

15. Settipane R Epidemiology of vasomotor rhinitis

pean Academy of Allergology and Clinical Immunology,

WAO Journal, 115, 6 2009

June 10-14, 2006 Vienna, Austria

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