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An 18 year Follow-up of Allergy Development: Findings of Nasal Markers of Allergic Inflammation
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
2008 (English)Licentiate thesis, comprehensive summary (Other academic)Alternative title
En 18 års uppföljning av allergiutveckling : fynd av markörer i näsa vid allergisk inflammation (Swedish)
Abstract [en]

Background: In addition to the family history of allergy (FH), there is a need o find objective markers of allergy development as early in life as possible in order to focus preventive measurements on high risk infants. Rhinitis problems are common causes to morbidity in adults due to allergic as well as non-allergic mechanisms. Accurate diagnoses are essential for decisions of optimal management of the patients, but in non-allergic rhinitis groups there are no objective tests to verify the diagnosis, if this is needed.

Aims: The primary aim was to evaluate the occurrence of nasal metacromatic (MC) cells during infancy as predictors for allergy development in a group of high risk subjects from birth up to 18 years of age. Additional aims were to find and evaluate nasal markers with ability to differentiate between allergic rhinitis with and without current allergen exposure from normal controls.

Subjects and methods: New-borns (n = 67) with and without family histories of allergy were included, and during the first 18 months of life occurrence of nasal MC could be evaluated in 64 infants (33 positive/31 negative MC findings). The cohort was followed up for allergy development at the ages of 18 months, 6 years and 18 years. Nasal markers as MC, nasal NO, nitrite/nitrate in nasal lavage and acoustic rhinometry at the 18-years follow-up were related to the allergic manifestations at this age.

Results: Positive nasal MC findings during infancy predicted allergy development up to 18 years of age in 31/33 subjects (94 %), as compared to 37/44 with positive FH (84 %). Negative MC findings during infancy did not exclude the risk, as 15/31 developed allergy (48 %). At the 18-years follow-up the numbers of individuals with demonstrable MC were significantly higher (p = 0.01) in the group of individuals with allergy symptoms (16/30) compared to the group of individuals with no allergy (1/12). Nasal NO levels, nitrite/nitrate concentrations in nasal lavages and acoustic rhinometry did not differentiate the allergic groups from the normal group.

Conclusions: Positive nasal MC findings during infancy predicted allergy development up to 18 years of age, and the cell findings often preceded the allergic symptoms. The marker can not be used as a single predictor of allergy development due to negative MC findings in a high proportion of allergic subjects. Positive MC findings combined with positive FH resulted in the best the risk evaluation. Differences between groups with and without current allergen exposure and healthy controls were not found by means of acoustic rhinometry, nasal MC, nasal NO or nitrites/nitrates levels. Further research to find reliable nasal markers is needed.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2008. , 40 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 89
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-15853ISBN: 978-91-7393-748-1 (print)OAI: oai:DiVA.org:liu-15853DiVA: diva2:127649
Presentation
2008-12-03, Elsa Brändströms sal, Campus US, Linköpings Universitet , Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2008-12-09 Created: 2008-12-09 Last updated: 2009-04-30Bibliographically approved
List of papers
1. Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life
Open this publication in new window or tab >>Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life
1997 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 52, no 7, 770-774 p.Article in journal (Refereed) Published
Abstract [en]

The relationship between the appearance of nasal metachromatic cells (basophils and mast cells) during the first 18 months of life and the development of respiratory and other allergic diseases up to 6 years of age was studied prospectively in 67 children. Follow-up was done at 3, 6, 9, and 18 months and 6 years. Of the 31 children who had detectable metachromatic cells in the nasal mucosa during infancy, 18 had atopic manifestations at 6 years (58%), two were probably atopic (6%), and 11 (36%) were nonatopic. The corresponding numbers for the 33 children without detectable metachromatic cells during infancy were 10 atopic (30%), two probably atopic (6%), and 21 nonatopic (64%) at 6 years (P<0.05). Children having detectable nasal metachromatic cells at every examination were more often allergic than children with no detectable cells at any time during the 6-year follow-up period (P<0.05). In contrast, nasal metachromatic cells were equally commonly demonstrated at 6 years in children with and without current atopic manifestations. We conclude that metachromatic cells appear at an earlier age in the nasal mucosa of atopic than nonatopic infants. The observation further supports the existence of a primary immunologic abnormality in atopic patients as related to allergic inflammatory responses. The diagnostic efficacy of this marker was too low, however, to be clinically useful as a predictor of allergy.

Place, publisher, year, edition, pages
Wiley InterScience, 1997
Keyword
Allergy prediction, infancy, metachromatic cells, nasal mucosa
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-15852 (URN)10.1111/j.1398-9995.1997.tb01237.x (DOI)9265995 (PubMedID)
Available from: 2008-12-10 Created: 2008-12-09 Last updated: 2011-06-13Bibliographically approved
2. An 18-year Follow-up of Allergy Development Related to Nasal Metachromatic Cell Findings During Infancy
Open this publication in new window or tab >>An 18-year Follow-up of Allergy Development Related to Nasal Metachromatic Cell Findings During Infancy
2010 (English)In: Allergology International, ISSN 1323-8930, E-ISSN 1440-1592, Vol. 59, no 2, 193-200 p.Article in journal (Refereed) Published
Abstract [en]

Background: The ability to predict the development of allergic diseases in infants is important. Predictive biomarkers are wanted to improve the risk evaluation in addition to known heredity of allergy. Biomarkers taken during infancy need to be evaluated through longitudinal studies into adulthood. The objective of this study was to analyse the occurrence of metachromatic cells in the nasal mucosa during infancy (MCinfancy) and evaluate the cells as predictive biomarkers of allergy development.

Methods: Previously, MCinfancy occurrences were analysed in 64 infants with and without allergy heredity, and related to allergy development at 18 months and 6 years of age. In this third follow-up at 18 years of age, current allergy symptoms were analysed. MCinfancy findings were related to the cumulative number of allergic subjects. The predictive values of MCinfancy and known heredity were compared.

Results: The cumulative number of subjects with allergy was 46, probable allergy 5, and no allergy 13. Detected MCinfancy predicted allergy with high accuracy (31/33), but negative MCinfancy findings did not exclude the risk (15/31). In the group of allergic subjects positive MCinfancy were found in 31/46 (67%), positive heredity in 37/46 (80%) and one/both factors positive in 43/46 (93%). Detection of MCinfancy could precede the debut of allergy symptoms by many years.

Conclusions: Detected MCinfancy predicted allergy development, but absence of MCinfancy did not exclude the risk, and therefore this biomarker was not found to be adequate. There is a further need to find biomarkers with high ability to both predict and exclude the risk.

Keyword
Metachromatic cells, nasal mucosa, infancy, allergy, asthma, allergic rhinitis, dermatitis, prediction, 18 year follow-up
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-15850 (URN)10.2332/allergolint.09-OA-0132 (DOI)20299825 (PubMedID)
Available from: 2008-12-10 Created: 2008-12-09 Last updated: 2013-07-04Bibliographically approved
3. Nasal nitric oxid and nasal nitrate and nitrite in relation to allergy and smoking habits
Open this publication in new window or tab >>Nasal nitric oxid and nasal nitrate and nitrite in relation to allergy and smoking habits
2008 (English)Article in journal (Refereed) Submitted
Abstract [en]

Background: The role of nasally exhaled nitric oxide (nNO) in diagnosis of allergic rhinitis is still unclear, in contrast to orally exhaled nitric oxide (eNO), which is well established as a marker of inflammation in the lower airways.

Objective: Levels of nNO, nitrite/nitrate in nasal lavage (NAL) and acoustic rhinometry results were analysed in order to evaluate these markers in allergic rhinitis.

Methods: Altogether 45 subjects were subgrouped according to airway into: allergy with ongoing allergen exposure (I) or in a latent phase of exposure (II) and no allergy (III). The level of nNO was calculated by subtraction of eNO after mouthwash from nasally exhaled NO. The findings were related to acoustic rhinometry and spirometry, before and after an exercise provocation of the airways. Nitrite/nitrate levels were analysed by the Greiss reaction after reduction of nitrate to nitrite.

Results: A weak correlation between nNO and nitrite/nitrate levels was found in males, but neither of these markers nor acoustic rhinometry showed differences between the subgroups. In contrast, eNO, but not spirometry, differentiated allergy with ongoing allergen exposure from allergy in a latent phase of exposure and no allergy.

Conclusions: No difference of nNO levels was found in allergic and normal subjects.

Keyword
Nitic oxide, nitrite/nitrate, nasal mucosa, allergic rhinitis, smoking habits
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-15851 (URN)
Available from: 2008-12-10 Created: 2008-12-09 Last updated: 2009-02-11Bibliographically approved

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