En 18 års uppföljning av allergiutveckling : fynd av markörer i näsa vid allergisk inflammation

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

Verifiering av simuleringsdata : FE-beräkningar och mätmetoder för analys av ortogonal skärande bearbetning

Validerat; 20101217 (root

An 18-year Follow-up of Allergy Development Related to Nasal Metachromatic Cell Findings During Infancy

ABSTRACTBackgroundThe 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.MethodsPreviously, 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.ResultsThe 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.ConclusionsDetected 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

The effects of physical exercise and smoking habits on the expression of SPLUNC1 in nasal lavage fluids from allergic rhinitis subjects

Objective: Palate lung nasal epithelial clone (PLUNC) is a family of proteins, which are proposed to participate in the innate immune defense against infections in the upper aero-digestive tract. The aim of this study was to investigate the expression of SPLUNC1 in allergic rhinitis subjects with considerations taken to the mucosa( function and smoking habits. Methods: The participants, recruited from a cohort followed from infancy, were re-examined at the age of 18 years regarding allergy development. Based on medical histories and skin prick tests the participants were classified into groups with persistent allergic rhinitis (n = 18), intermittent allergic rhinitis (n = 8) and healthy controls (n = 13). Seven subjects (3, 2 and 2 in each group, respectively) reported smoking habits. The SPLUNC1 levels in nasal lavage fluids were analyzed by Western blot. Changes in the volume of the proper nasal cavity before and after physical exercise (Vol2(increase)) were analyzed by acoustic rhinometiy. Results: Compared to the control group the SPLUNC1 level was significantly lower in the persistent allergy group (3.8 +/- 3.4 OD vs. 1.3 +/- 1.5 OD; p = 0.02), but not in the intermittent allergy group without current exposure to allergens (3.6 +/- 4.7 OD). No differences were found in Vol2(increase) between any of the allergy groups and controls. In smokers Vol2(increase) was significantly reduced (p less than 0.01) and the SPLUNC1 levels were lower compared to non-smokers. A significant correlation was found between SPLUNC1 and vol2(increase) (pless than0.01; r = 0.53) in non-smokers. Conclusions: Current allergen exposure has an impact on SPLUNC1 expression in nasal lavage fluid, why allergy ought to be considered in study populations where analyses of SPLUNC1 levels are included in the reports. The normal nasal decongestion after exercise was not affected by allergy in contrast to smoking habits. The correlation between SPLUNC1 levels and Vol2(increase) in non-smokers may indicate involvement of SPLUNC1 in the regulation of the normal function of the nasal mucosa. Complementary studies are needed to confirm the smoke-related reduction of SPLUNC1 expression and to analyze the possible participation of SPLUNC1 in the nasal mucosa regulation

Clara cell protein in nasal lavage fluid and nasal nitric oxide - biomarkers with anti-inflammatory properties in allergic rhinitis

<p>Abstract</p> <p>Background</p> <p>Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis.</p> <p>Methods</p> <p>The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX^®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing.</p> <p>Results</p> <p>The levels of CC16 correlated with nNO levels (r²= 0.37; p = 0.02) in allergic subjects.</p> <p>The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups.</p> <p>Conclusions</p> <p>The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels and the occurrences of MC in allergic inflammation, may indicate that both biomarkers have anti-inflammatory effects by suppression of cell recruitment. The mechanisms behind these observations warrant further analyses.</p

Basophil allergen threshold sensitivity: a useful approach to anti-IgE treatment efficacy evaluation

Background: Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment. Methods: Basophils from timothy grass pollen allergic patients were, by flow cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring CD63 up-regulation on CD203c-identified basophils. The results were compared with maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick test end-point allergen titration, (SPT-sens), nasal provocation titration tests (nasal provocation titre) and serum IgE and IgE antibody concentrations. Results: There was a significant correlation (r = 0.50, P = 0.01) between CD-sens and SPT-sens, CD-sens and the IgE antibody concentration in percentage of 'total IgE' (relative IgE antibody concentration) (r = 0.72, P < 0.001) as well as between CD-sens and nasal provocation titre (r = 0.54, P < 0.05) but, in contrast, CD-max did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal provocation titre, absolute and relative IgE antibody concentration or CD-sens. CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD-max, four of seven symptom-free patients on omalizumab would have been classified as having ongoing allergy. Conclusions: CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information