Kristina Irander

Peripheral blood eosinophilia in infants at 3 months of age is associated with subsequent development of atopic disease in early childhood

BACKGROUND We tested the hypothesis that eosinophilia in peripheral blood and nasal mucosa of infants is an early sign of allergic disease. METHODS The appearance of eosinophilic leukocytes in peripheral blood and nasal mucosa was studied prospectively in 67 infants up to 18 months of age, with or without a family history of atopy. RESULTS Eosinophilia was associated with simultaneous presence or subsequent development of atopic disease at 3, 9, and 18 months of age, but not significantly so at 6 months. At 3 months children in whom atopic disease developed later during the observation period had significantly higher numbers of blood eosinophils than children without atopy (p < 0.01). Thus pronounced eosinophilia (> 7 x 10(8) cells/L) at that age was associated with moderate or severe allergic disease during the 18-month observation period. These children continued to have eosinophilia throughout the follow-up period. Blood eosinophilia at 3 months of age also correlated significantly to cord blood IgE levels and to skin prick test reactivity later during the follow-up period. Nasal eosinophilia was a common finding and therefore had little diagnostic or predictive value. CONCLUSIONS Elevated eosinophil counts in peripheral blood of apparently healthy infants at 3 months of age is associated with a subsequent diagnosis of atopic disease.

Middle ear diseases in relation to atopy and nasal metachromatic cells in infancy

The relation between middle ear morbidity and atopy was prospectively studied in 44 infants with and 20 without a confirmed family history of atopy. Signs of atopy were recorded at 3, 6, 9 and 18 months of age and signs of middle ear disease were recorded and controlled as needed. Twenty-seven children developed definite signs of atopy, while 12 showed probable signs and 25 remained free from allergic symptoms. The number of episodes of acute otitis media was higher and the duration of episodes of otitis media with effusion were longer in 13 infants with respiratory tract allergy, as compared with 14 allergic children with only skin manifestations and with 25 non-atopic children. Middle ear diseases were more commonly encountered in infants in whom nasal metachromatic cells were detected. Children exposed to tobacco smoke suffered more often from respiratory tract infections but not from increased middle ear morbidity in comparison with non-exposed children. In conclusion, middle ear morbidity during the first 18 months of life is more common in atopic children with asthma than in non-atopic infants and early appearance of nasal metachromatic cells is associated with middle ear infections.

Nasal lavage fluid and proteomics as means to identify the effects of the irritating epoxy chemical dimethylbenzylamine.

The aims of this study were to describe the changes in the nasal lavage fluid (NLF) protein pattern after exposure to the irritating epoxy chemical dimethylbenzylamine (DMBA) and to identify the affected proteins using a proteomic approach. The protein patterns of NLF from six healthy subjects and eight epoxy workers with airway irritation were analysed using two-dimensional gel electrophoresis (2-DE) before and after exposure to 100 μg m−3 DMBA for 2 h in an exposure chamber. NLF proteins were identified by (i) comparison with a 2-DE NLF reference database; (ii) N-terminal amino acid sequencing; and (iii) mass spectrometry. In NLF from healthy subjects, the levels of immunoglobulin A increased and the levels of Clara cell protein 16 (CC16) decreased after chamber exposure, while in NLF from epoxy workers, α2-macroglobulin and caeruloplasmin increased. Two previously unidentified proteins decreased in NLF from epoxy workers after exposure; these were identified as statherin and calgranulin B. In addition, the subjects who developed high counts of eosinophils in their nasal mucosa after chamber exposure had significantly lower levels of immunoglobulin-binding factor (IgBF) before exposure than subjects with low eosinophil infiltration. These results show that short-term exposure to DMBA causes distinct changes in NLF proteins. Moreover, three proteins that have previously not been associated with upper airway irritation were identified: statherin, calgranulin B and IgBF. Further studies are needed to investigate whether these proteins may be used as biomarkers of airway irritation and to give new insight into the ways in which occupational exposure to irritants causes inflammation of the airways.

Metachromatic cells in nasal mucosa after allergen challenge

Metachromatic cells in the nasal mucosa were studied in relation to symptoms in 16 schoolchildren and 11 adults with hay fever who were challenged with pollen outside the pollen season, using either a gentle scraping‐cytocentrifugation method for collection of mucosal specimens or biopsies. There was a temporary redistribution of metachromatic cells towards the mucosal surface appearing 5–24 h after challenge, with a correlation between the quantity of metachromatic cells and symptom scores. Thus, a single exposure to high doses of allergen may contribute to priming in susceptible individuals.

How Many Teenagers Think They Have Allergic Rhinoconjunctivitis and What They Do About It

OBJECTIVE A study was made to assess the proportion of 17-year-old students who consider themselves to have allergic rhinoconjunctivitis and to find out how they treat themselves. METHOD The study was performed outside the pollen season in 1993 and 1994 and 5,938 first-year secondary school students in eight different cities were asked to answer a questionnaire during class. RESULTS A total of 1,458 students (24%) claimed that they suffered from allergic rhinoconjunctivitis after being given a description of the disease. Sixty-five percent had had symptoms for 3 or more years and most of the sufferers, 71%, had had symptoms during the spring and/or summer. In 32% of the sufferers the causative agent was unknown. Seventy-six percent (n = 1,103) of the sufferers treated themselves with drugs. The most commonly used drugs for a systemic effect were nonsedating antihistamines and for a local effect, sodium cromoglycate. Of those who used nasal drugs (sodium cromoglycate and/or steroids, n = 545), only 14% used them daily, 51% always when having symptoms, and 35% occasionally when having symptoms. The reasons for not using nasal sprays daily were inconvenience and embarrassment. Twenty-five percent had bought the drug over the counter in 1992, the first year when allergy drugs could be purchased without a prescription. The use of over-the-counter treatment increased in the following year to 33% (P < .05). CONCLUSION We conclude that many young people perceive themselves as having allergic rhinoconjunctivitis and that the treatment can be much improved for the group as a whole.

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

BackgroundClara 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.MethodsThe 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.ResultsThe levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects.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.ConclusionsThe 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.

Nasal metachromatic cells in infants in relation to allergic disease and family history of atopy

The appearance of metachromatic cells in nasal scrapings was studied prospectively in 67 children from birth to 18 months of age. The findings were related to family history of atopy and development of allergic disease in the infants. Allergic disease was diagnosed during the 18‐month follow‐up period in 54% of the infants with heredity for atopic disease. The corresponding figure for children with no heredity was 11%. Using a gentle scraping‐cytocentrifugation method for collection of mucosal specimens, metachromatic cells were identified in the nasal scrapings in 20 of 30 children who developed definite allergic disease (67%) and in 6 of 9 with probable allergy. The cells appeared before or at the time of diagnosis in 19 of the infants with definite allergic disease. Metachromatic cells were also found in 7 of 25 healthy children who did not develop allergic disease during the follow‐up period. Six of them had definite and one possible heredity for allergic disease. No metachromatic cells were found in any of the 8 infants who lacked heredity for atopy and did not develop atopic disease. In conclusion, the appearance of metachromatic cells in the nasal mucosa during the first 18 months of life of infants was associated with atopic propensity, as defined by development of atopic disease and/or a strong family history of allergy.

Treatment of hay fever with loratadine ‐ a new non‐sedating antihistamine

The efficacy and safety of loratadine, a new orally active specific H‐receptor blocking antihistamine with poor penetration into the CNS, was evaluated in a double blind comparative study. One hundred and seven hay fever patients, sensitive to birch pollen, were randomized into three parallel groups receiving loratadine 40 mg once daily, clemastine 1 mg twice daily, or placebo during the birch pollen season. Both active treatments showed reduction of symptoms in comparison with placebo, but the results were more pronounced with loratadine treatment, which significantly reduced the overall allergic condition as well as all separate allergic rhino‐conjunctivitis symptoms except nasal stuffiness. Compared with placebo the sedation rate was significantly higher with clemastine treatment (P < 0.05) but not with loratadine, Loratadine was thus concluded to be efficacious in hay fever treatment with a sedation rate not differing from placebo.

Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life.

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.

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 mucosal 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 rhinometry. 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 < 0.01) and the SPLUNC1 levels were lower compared to non-smokers. A significant correlation was found between SPLUNC1 and Vol2(increase) (p < 0.01; 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 SPLUNC1in 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.