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Objective monitoring of nasal airway inflammation in rhinitis - 18/08/11

Doi : 10.1016/j.jaci.2004.12.1134 
Peter H. Howarth, BSc (Hons), DM, FRCP a, , Carl G.A. Persson, PhD b, Eli O. Meltzer, MD c, Mikila R. Jacobson, PhD d, Stephen R. Durham, MD d, Philip E. Silkoff, MBBS, MRCP, FCCP e
a From Southampton General Hospital 
b Departments of Clinical Pharmacology, Physiological Sciences, and Otorhinolaryngology, University Hospital of Lund 
c Allergy and Asthma Medical Group and Research Centre, San Diego 
d Upper Respiratory Medicine, Imperial College School of Medicine, National Heart and Lung Institute, London 
e AstraZeneca, Wilmington 

Reprint requests: Peter H. Howarth, BSc (Hons), DM, FRCP, IIR Research Division, Mail Point 810, Southampton General Hospital, Tremona Road, Southampton, Hampshire, SO16 6YD, United Kingdom.

Southampton and London, United Kingdom, Lund, Sweden, San Diego, Calif, and Wilmington, Del

Abstract

Allergic rhinitis is an inflammatory nasal disorder in which a range of different cells participates. A variety of approaches has been used to monitor nasal inflammation objectively to investigate disease processes and to evaluate the effect of therapeutic intervention. These approaches include nasal lavage, nasal cytology, and nasal biopsy, together with the more recently established measurement of nasal nitric oxide (NO) concentration. Although all provide information about nasal mucosal inflammation, the extent of information that can be obtained by each approach, the ease of sampling, and the complexity of sample handling differ. Such considerations influence the choice of approach when measurement of nasal inflammation is to be an objective outcome parameter in a clinical trial. In addition, the choice of approach is also determined by the questions or hypotheses that are to be addressed.

Nasal lavage is simple and rapid to perform, is well tolerated, and provides a sample that can provide information about luminal cell recruitment, cell activation, and plasma protein extravasation. Nasal cytology involves sampling and recovering mucosal surface cells. It is also easy to perform and is well tolerated in general, although some find that the procedure causes a transient unpleasant sensation. A differential cell count from the sample provides information about relative cell populations. Both nasal lavage and nasal cytology are readily applicable to clinical trials. Nasal cytology sample handling is easier, but nasal lavage offers the advantage of providing considerably greater information from the sample.

Nasal biopsy is a considerably more invasive procedure and requires expertise not only in tissue sampling but also in biopsy processing. Therefore, it is applicable only in specialist centers. However, nasal biopsy is the only sampling technique that directly informs about tissue cellular events, although these may be implied, in part from the other sampling approaches. Tissue specimens can be used to evaluate both protein and gene expression.

Measurement of nasal NO involves expensive equipment but provides an instantaneous result, unlike the other approaches, all of which require sample processing and analysis. Recommendations for standardization of measurement have been made, and measures are considered in part to reflect allergic inflammation within the nasal mucosa. The limitations of nasal NO are that it reflects only a certain aspect of allergic mucosal inflammation, and that because a proportion of nasally measured NO is derived from the sinuses under normal circumstances, nasal NO is not specific for nasal disease. The high contribution from the sinus mucosa limits the discriminatory ability of nasal NO to reflect nasal tissue–specific alterations.

The incorporation of measures of nasal inflammation in clinical trials has distinguished anti-inflammatory therapy from symptomatic therapy and has the potential to provide information about the efficacy of novel therapies for allergic rhinitis.

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Key words : Rhinitis, allergic inflammation, lavage, cytology, biopsy, exhaled nitric oxide, immunohistochemistry, in situ hybridization, mast cells, eosinophils, epithelial cells, T-cells, plasma protein exudation

Abbreviations used : ATS, ECP, EPX, GMA, GM-CSF, H, HPF, ICAM-1, IL, iNOS, ISH, LT, MIP, NARES, NO, PAR, PG, RANTES, SAR, TAME


Plan


 Disclosure of potential conflict of interest: P. H. Howarth has been an advisory board member for AstraZeneca, GlaxoSmithKline, Sanofi-Aventis, and Altana. C. G. A. Persson—none disclosed. E. O. Meltzer has consultant arrangements with Alcon, Altana, AstraZeneca, Sanofi Aventis, Dey, Genentech, GSK, Merck, Pfizer, Rigel, Schering, and Wyeth; is employed with the Allergy and Asthma Medical Group and Research Center, San Diego, Calif; and is a member of the Speakers' Bureau for Sanofi Aventis, Genentech, GSK, Merck, Pfizer, Schering, and UCB. M. R. Jacobson—none disclosed. S. R. Durham has consultant arrangements with AstraZeneca, GSK, Aventis, UCB, and ALK-Abelló; receives grants or research support from GSK and ALK-Abelló; and is a member of the Speakers' Bureau for GSK, UCB, Schering Plough, and ALK-Abelló. P. E. Silkoff is a full time employee of AstraZeneca.
Guest Editor:
Peter H. Howarth, BSc (Hons), DM, FRCP
Attribution of Sections:
Nasal lavage: Peter H. Howarth, BSc (Hons), DM, FRCP, and Carl G. A. Persson, PhD
Nasal cytology: Eli O. Meltzer, MD
Nasal biopsy: Mikila R. Jacobson, PhD, and Stephen R. Durham, MD
Nasal nitric oxide: Philip E. Silkoff, MD


© 2005  American Academy of Allergy, Asthma and Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 115 - N° 3S

P. S414-S441 - mars 2005 Retour au numéro
Article précédent Article précédent
  • Clinical outcomes and adverse effect monitoring in allergic rhinitis
  • Elizabeth F. Juniper, Elisabeth Ståhl, Richard L. Doty, F. Estelle R. Simons, David B. Allen, Peter H. Howarth
| Article suivant Article suivant
  • Objective monitoring of nasal patency and nasal physiology in rhinitis
  • Robert A. Nathan, Ron Eccles, Peter H. Howarth, Sverre K. Steinsvåg, Alkis Togias

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