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.

Comparative proteomics of nasal fluid in seasonal allergic rhinitis.

A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects (controls, n = 5). NLF samples were taken both before allergy (pollen) season and during season, and proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected and quantified. During allergy season, the levels of six sialylated isoforms of PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP), including a previously undescribed form with N-linked glycosylation, and of cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are two endogenous proteinase inhibitors. By contrast, the levels of an acidic form of alpha-1-antitrypsin were higher in SAR patients than controls. One previously unidentified NLF protein was found in all samples from the SAR patients during allergy season but not in any sample before allergy season: this protein was identified as eosinophil lysophospholipase (Charcot-Leyden crystal protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed removal of Met and acetylation of Ser. Altogether, these findings illustrate the potential use of proteomics for identifying protein changes associated with allergic rhinitis and for revealing post-translational modifications of such new potential markers of allergic inflammation.

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.

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.

Metachromatic cells and eosinophils in the nasal mucosa and N,N-dimethylbenzylamine exposure.

Six healthy non-atopic male volunteers participated in a dose-response study of N,N-dimethylbenzylamine (DMBA), which is a reactive chemical used in epoxy systems. The effects on the nasal mucosa after inhalation of 0, 20, 45, 80 and 120 microg/m3 were studied by means of symptom recordings, acoustic rhinometry, nasal lavages and nasal cytology processed for light microscopy of metachromatic cells (MC) and eosinophils (EOS). Although only minor symptoms were provoked, the numbers of MC and Eos tended to increase in a dose-response fashion after inhalation of the chemical. No signs of degranulation of the cells were found, as the levels of tryptase and eosinophil cationic protein in the nasal lavages remained low at all DMBA exposure levels. We therefore conclude that a reactive chemical such as DMBA can influence MC and Eos in the nasal mucosa even at low dose levels without causing significant clinical symptoms.

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.

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.

Langerhans cells and subsets of lymphocytes in the nasal mucosa.

Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal mucosal specimens. Intraepithelial CD1-positive dendritic cells were found in all specimens. However, there was no difference between the number of these Langerhans cells found in the study group and the number found in the controls. In every specimen the intraepithelial lymphocyte population was dominated by T lymphocytes, and there were relatively few B cells. Similarly the ratio between CD4- and CD8-positive lymphocytes in the study group and the controls was the same. In all specimens there was a dominance of T suppressor/cytotoxic cells compared with T helper/inducer cells. The study confirms that Langerhans cells are present in normal nasal surface epithelium, and suggests that there is no basic difference in the number of Langerhans cells between healthy persons, persons with nasal complaints, and persons with nasal allergy. The dominance of T lymphocytes in the epithelium may indicate the existence of a local cell-mediated immunity other than that associated with the regulation of IgE.

A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis.

This multicentre, double-blind, randomized parallel-group study compared 3 weeks' treatment with either loratadine (Clarityn) 10 mg once daily, or clemastine (Tavegyl) 1 mg twice daily, and placebo in outpatients with active perennial allergic rhinitis. 155 patients were evaluated for efficacy and safety. Grading of four nasal and three non-nasal symptoms, rhinoscopy signs, and therapeutic response was performed on treatment days 6, 13, and 20. Patients recorded daily symptoms and possible adverse experiences in a diary, also indicating when symptoms of active rhinitis were relieved. Loratadine and clemastine were statistically significantly superior to placebo throughout the study (P less than 0.05), based on assessment of patients' nasal and eye symptoms, patients' diary scores, rhinoscopy signs of symptoms, and onset of relief. The loratadine group showed a statistically significantly (P less than 0.05) faster onset of relief of symptoms compared with the group treated with clemastine. Concerning nasal stuffiness, loratadine was significantly (P less than 0.05) superior to clemastine after 1 week's treatment. Reports of adverse reactions showed that significantly (P less than 0.05) more patients complained of sedation in the clemastine than in the loratadine group. Regarding other adverse experiences and laboratory tests, the three treatment groups were statistically comparable (P less than 0.05). The study showed that compared with placebo both loratadine and clemastine were effective in relieving nasal and eye symptoms in patients with perennial allergic rhinitis. Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis.

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.

Treatment of hay fever with loratadine--a new non-sedating antihistamine.

The efficacy and safety of loratadine, a new orally active specific H1-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 less than 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.

Acrivastine in seasonal allergic rhinitis: two randomized crossover studies to evaluate efficacy and safety.

In two randomized crossover studies, the antihistamine, acrivastine, was evaluated for the treatment of seasonal allergic rhinitis. One study on 31 patients found both 4 and 8 mg acrivastine given three times daily to be significantly better than placebo for alleviating hay fever. There were no significant differences in symptom scores between the two doses, although more patients (63%) favoured 8 mg acrivastine over the 4 mg dose (46%) or placebo (35%). The other study found the higher dosage regimen to be similar in efficacy to 1 mg clemastine given three times daily. Both dosages were significantly better than placebo for reducing symptom scores in all 18 evaluable patients. The incidence of adverse experiences was low in both studies; there being no dose-related effects of acrivastine. In the second study, drowsiness, probably or possibly treatment related, occurred on seven occasions during clemastine treatment and once with acrivastine. These studies indicate that 8 mg acrivastine given three times daily is both well tolerated and of equal efficacy to clemastine for the treatment of seasonal allergic rhinitis.

A single blind clinical comparison between 2 preparations of budesonide in the treatment of seasonal allergic rhinitis.

A comparative study was carried out in 118 patients suffering from seasonal allergic rhinitis in order to evaluate possible differences between two different preparations of budesonide with regard to effect and adverse reactions. The glucocorticoid was supplied either as a freon propellant device (Rhinocort) or as a water solution in a mechanical pump spray. The freon aerosol was administered in a daily dosage of 400 micrograms. The water solution was administered in daily dosages of 400 micrograms or 200 micrograms. The patients scored their nasal and ocular symptoms daily for 1 month, and pollen counts were registered over the same period. The drugs employed in the study provided good control of the nasal symptoms. The daily dosage of 400 micrograms in both preparations proved more efficacious than the daily 200 micrograms dose in the nasal pump spray. No difference was found between the delivery systems when the same daily dosage was used. The number of adverse reactions was low and insignificant in all 3 treatment groups.

Nasal symptoms and histopathology in a group of spray-painters.

Industrial workers more and more frequently seek medical advice for nasal and sinus symptoms that they attribute to occupational exposure. The present study comprised 10 paint-sprayers exposed to solvents (primarily toluene and isobutylacetate) and dust. The working environment was checked by an industrial hygienist and a careful clinical examination including biopsies from the nasal mucosa was carried out. The results revealed prominent nasal symptoms in 3 patients and 4 suffered from cough. The histological examination showed in no case a normal nasal mucosa. The histological grading showed a significantly higher score in the exposed group compared to a matched control group. However, no conclusive connection between the duration of exposure and the clinical symptoms and morphological changes was possible to make, which will necessitate an extended study to evaluate the exact importance of the duration of exposure. The study indicates the possibilities of an early presymptomatic detection of nasal mucosal disturbances and arises the question whether the existing TLVs are adequate in preventing damage to the nasal mucosa and adherent clinical symptoms.

Upper airway problems in industrial workers exposed to oil mist.

Exposure to oil mist used in metal work sometimes gives symptoms from skin and airways. This study was performed to evaluate histological and functional respiratory tract disorders. Six male lathe workers aged 31-64 years exposed to oil mist for 4-29 years were examined and compared with matched controls. The investigation included case history, ENT examination, nasal mucociliary function, routine blood tests, IgE, RAST, X-ray of sinus and lungs and biopsy of the nasal mucosa. The mucociliary test showed no difference between the groups. However, all 6 exposed workers had pathological histology findings in the nasal mucosa including lack of cilia, basal cell hyperplasia, goblet cell hyperplasia, squamous metaplasia and subepithelial hyalinization. The biopsies from the controls were mainly normal. The remainder of the investigations revealed no pathology. The study shows that exposure to oil mist--even below the permitted threshold limit--may cause airway symptoms and histological signs comparable to a premature ageing.

Hyposensitization in allergic seasonal rhinitis as evaluated by rhinomanometry.

Hyposensitization with Allpyral extracts was performed in 38 patients suffering from seasonal allergic rhinitis. An objective evaluation of the clinical course was obtained by rhinomanometry. After one year of hyposensitization therapy, 55% of the patients (21 out of 38) showed an improvement, and after the 3-year follow-up this figure had increased to 76% (19 out of 25 patients continuing with the treatment for this period). For the patients' subjective appraisal of the therapy the respective figures were 76 and 92%.

Hyposensitization in allergic rhinitis--a comparison of aqueous extracts and Allpyral by means of rhinomanometry.

Fifty-six patients with seasonal allergic rhinitis were hyposensitized with aqueous extracts (23 patients) and Allpyral extracts (33 patients). The clinical course was appraised objectively on the basis of rhinomanometry findings at examinations performed before hyposensitization and one year later. There was no essential difference between the two groups of patients as regards the relief of symptoms. A reduction of nasal congestion was recorded in 54 and 58% of the patients, respectively. Complications were less severe and less frequent in the Allpyral group.