Scientific rationale for the Finnish Allergy Programme 2008-2018: emphasis on prevention and endorsing tolerance.

In similarity to many other western countries, the burden of allergic diseases in Finland is high. Studies worldwide have shown that an environment rich in microbes in early life reduces the subsequent risk of developing allergic diseases. Along with urbanization, such exposure has dramatically reduced, both in terms of diversity and quantity. Continuous stimulation of the immune system by environmental saprophytes via the skin, respiratory tract and gut appears to be necessary for activation of the regulatory network including regulatory T-cells and dendritic cells. Substantial evidence now shows that the balance between allergy and tolerance is dependent on regulatory T-cells. Tolerance induced by allergen-specific regulatory T-cells appears to be the normal immunological response to allergens in non atopic healthy individuals. Healthy subjects have an intact functional allergen-specific regulatory T-cell response, which in allergic subjects is impaired. Evidence on this exists with respect to atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration of impaired allergen-specific regulatory T-cell response and tolerance induction has furthermore been demonstrated during allergen-specific subcutaneous and sublingual immunotherapy and is crucial for good therapeutic outcome. However, tolerance can also be strengthened unspecifically by simple means, e.g. by consuming farm milk and spending time in nature. Results so far obtained from animal models indicate that it is possible to restore tolerance by administering the allergen in certain circumstances both locally and systemically. It has become increasingly clear that continuous exposure to microbial antigens as well as allergens in foodstuffs and the environment is decisive, and excessive antigen avoidance can be harmful and weaken or even prevent the development of regulatory mechanisms. Success in the Finnish Asthma Programme was an encouraging example of how it is possible to reduce both the costs and morbidity of asthma. The time, in the wake of the Asthma Programme, is now opportune for a national allergy programme, particularly as in the past few years, fundamentally more essential data on tolerance and its mechanisms have been published. In this review, the scientific rationale for the Finnish Allergy Programme 2008-2018 is outlined. The focus is on tolerance and how to endorse tolerance at the population level.

Finnish Allergy Programme 2008-2018--time to act and change the course.

BACKGROUND: The prevalence of allergic diseases has grown in Finland, similarly to many other western countries. Although the origin of allergy remains unresolved, increasing body of evidence indicates that the modern man living in urban built environment is deprived from environmental protective factors (e.g. soil microorganisms) that are fundamental for normal tolerance development. The current dogma of allergen avoidance has not proved effective in halting the 'epidemic', and it is the Finnish consensus that restoring and strengthening tolerance should more be in focus. AIM: The national 10-year programme is aimed to reduce burden of allergies. The main goals are to (i) prevent the development of allergic symptoms; (ii) increase tolerance against allergens; (iii) improve the diagnostics; (iv) decrease work-related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies and (vi) decrease costs caused by allergic diseases. METHODS: For each goal, specific tasks, tools and evaluation methods are defined. Nationwide implementation acts through the network of local co-ordinators (primary care physicians, nurses, pharmacists). In addition, three nongovernmental organizations (NGOs) take care of the programme implementation. The 21 central hospital districts carry out a three step educational process: (i) healthcare personnel; (ii) representatives and educators of NGOs and (iii) patients and the general population. For outcome evaluation, repeated surveys are performed and healthcare registers employed at the beginning, at 5 years, and at the end of the programme. The process will be evaluated by an independent external body. CONCLUSION: The Finnish initiative is a comprehensive plan to reduce burden of allergies. The aim is to increase immunological tolerance and change attitudes to support health instead of medicalizing common and mild allergy symptoms. It is time to act, when allergic individuals are becoming a majority of western populations and their numbers are in rapid increase worldwide. The Programme is associated with the Global Alliance of Chronic Respiratory Diseases (GARD), WHO.

Corticosteroid allergy in asthma.

BACKGROUND: Glucocorticosteroids form the basis of therapy for asthma and other allergic diseases. However, they frequently cause delayed contact allergy and occasionally immediate allergy. The purpose of this study was to investigate the occurrence of corticosteroid allergy among patients with asthma and with some complaints caused by inhaled corticosteroids. METHODS: Patch tests with corticosteroids were performed in 51 asthma patients with side-effects from inhalant corticosteroids and in 50 symptom-free asthma patients using the Finn Chamber system. The corticosteroids and their vehicles were: betamethasone-17-valerate 1% in petrolatum, hydrocortisone-17-butyrate (Hc-17-B) 1% in ethanol, tixocortol-21-pivalate 1% in petrolatum, budesonide 0.1% in petrolatum, beclomethasone dipropionate 0.1 and 0.5% in petrolatum and as inhalant powder 200 microg, and fluticasone propionate 0.1 and 0.5% in petrolatum and as inhalant powder 250 microg. The results were read twice, on D4-5 and again on D10. RESULTS: Two patients in the symptomatic group reacted to corticosteroids in patch tests, one to betamethasone-17-valerate, Hc-17-B and budesonide, and the other to budesonide and Hc-17-B. The first patient suffered from widespread eczematous dermatitis when using beclomethasone. Fluticasone caused oropharyngeal irritation, hoarseness and shortness of breath. The second patient experienced a severe rash after the fourth budesonide inhalation. She had used various topical corticosteroids for her atopic dermatitis without any side-effects. None of the symptom-free patients showed positive results. CONCLUSIONS: Delayed allergy to corticosteroids occurs occasionally in asthma, perhaps in the same frequency as in dermatitis. A positive patch test reaction usually means clinical allergy, i.e. the patient cannot use that particular steroid. Cross allergy between corticosteroids is common. However, such patients usually tolerate some other common corticosteroids.

A multicenter study of patch test reactions with dental screening series.

BACKGROUND: Dental products contain many allergens, and may cause problems both for patients undergoing dental treatment and for dental personnel because of occupational exposure. Individual patch test clinics may not study sufficient numbers of patients to collect reliable data on uncommon allergens. OBJECTIVE: To collect information on dental allergens based on a multicenter study. MATERIALS AND METHODS: The Finnish Contact Dermatitis Group tested more than 4,000 patients (for most allergens, 2,300 to 2,600 patients) with dental screening series. Conventional patch testing was performed. The total number and percentage of irritant (scored as irritant [IR] or doubtful [?]) and allergic (scored as +, ++, or +++) patch test reactions, respectively, were calculated, as well as the highest and lowest percentage of allergic patch test reactions recorded by the different patch test clinics. A reaction index (RI) was calculated, giving information on the irritancy of the patch test substances. RESULTS: The most frequent allergic patch test reactions were caused by nickel (14.6%), ammoniated mercury (13%), mercury (10.3%), gold (7.7%), benzoic acid (4.3%), palladium (4.2%) and cobalt (4.1%). 2-hydroxyethyl methacrylate (2.8%) provoked most of the reactions caused by (meth)acrylates. Menthol, peppermint oil, ammonium tetrachloroplatinate, and amalgam alloying metals provoked no (neither allergic nor irritant) patch test reactions. CONCLUSION: Patch testing with allergens in the dental screening series, including (meth)acrylates and mercury, needs to be performed to detect contact allergy to dental products.

Benefits and risks of sauna bathing.

Although sauna bathing causes various acute, transient cardiovascular and hormonal changes, it is well tolerated by most healthy adults and children. Sauna bathing does not influence fertility and is safe during the uncomplicated pregnancies of healthy women. Some studies have suggested that long-term sauna bathing may help lower blood pressure in patients with hypertension and improve the left ventricular ejection fraction in patients with chronic congestive heart failure, but additional data are needed to confirm these findings. The transient improvements in pulmonary function that occur in the sauna may provide some relief to patients with asthma and chronic bronchitis. Sauna bathing may also alleviate pain and improve joint mobility in patients with rheumatic disease. Although sauna bathing does not cause drying of the skin-and may even benefit patients with psoriasis-sweating may increase itching in patients with atopic dermatitis. Contraindications to sauna bathing include unstable angina pectoris, recent myocardial infarction, and severe aortic stenosis. Sauna bathing is safe, however, for most people with coronary heart disease with stable angina pectoris or old myocardial infarction. Very few acute myocardial infarctions and sudden deaths occur in saunas, but alcohol consumption during sauna bathing increases the risk of hypotension, arrhythmia, and sudden death, and should be avoided.

Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis.

It has been suggested that trioxsalen bath and ultraviolet (UV) A (PUVA) is associated with a very low or no risk of non-melanoma skin cancer, but the numbers of patients in individual studies have been limited. In order to attain statistically relevant information about the cancer risk associated with trioxsalen bath PUVA, two follow-up studies were combined and the joined cancer incidence was analysed among 944 Swedish and Finnish patients with psoriasis. The mean follow-up time for skin cancer was 14.7 years. Standardized incidence ratios (SIR) were calculated as a ratio of observed and expected numbers of cases. The expected numbers of cases were based on the national cancer incidence rates in the respective countries. There was no excess of squamous cell skin carcinoma [SIR 1.1, 95% confidence interval (CI) 0.2-3.2] or malignant melanoma (SIR 0.9, 95% CI 0.1-3.2) in the combined cohort. Basal cell skin carcinoma was not studied. The incidence of all non-cutaneous cancers was not increased (SIR 1.1, 95% CI 0.8-1.4). A threefold excess risk of squamous cell skin carcinoma after trioxsalen bath PUVA could therefore be excluded, which is a markedly lower risk than that associated with oral 8-methoxypsoralen PUVA. The result needs to be confirmed in a future follow-up, however, as the number of patients with high PUVA exposures was low.

The effect of the apolipoprotein E phenotype on cholesteryl ester transfer protein activity, plasma lipids and apolipoprotein A I levels in hypercholesterolaemic patients on colestipol and lovastatin treatment.

BACKGROUND: Apolipoprotein E (apo E) allele E 4 is associated with high atherogenic lipid levels and coronary heart disease. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from (high density lipoprotein) HDL to other lipoproteins. CETP gene expression is enhanced in hypercholesterolaemia and correlates with plasma apo E concentration. OBJECTIVE: The effect of the apo E phenotype on plasma CETP activity and the hypolipidaemic efficacy of colestipol and lovastatin was studied in patients with type II a or II b hypercholesterolaemia. RESULTS: The baseline mean plasma total, low density lipoprotein (LDL) and HDL cholesterol, triglyceride, apolipoprotein A I (apo A I) concentrations and CETP activity were 8.89 mmol x l(-1), 6.78 mmol x l(-1), 1.39 mmol x l(-1), 1.59 mmol x l(-1), 1.49 g x l(-1) and 114 nmol x h(-1) x ml(-1), respectively. The colestipol-induced changes were -26%, -36%, +5%, + 12%, -1% and -17%, and the lovastatin-induced changes -34%, -44%, +6%, -18%, +1% and -19%. The lipid and apo A I concentrations or the CETP activity did not differ statistically significantly according to the apo E phenotype, although the HDL cholesterol and apo A I levels were lowered in patients with apo E 4/4 but elevated in patients with the other phenotypes. The CETP activity correlated with the LDL cholesterol concentration (r = 0.52, P = 0.01) and the change in the LDL cholesterol during colestipol (r = 0.51, P = 0.02) and lovastatin (r = 0.65, P = 0.001) treatment, but only in patients without the apo E 4 allele. CONCLUSION: Colestipol and lovastatin reduced CETP activity to the same amount, regardless of the apo E phenotype. The apo E phenotype seems to modify the interaction between CETP activity and LDL cholesterol in hypercholesterolaemia and during pharmacological lowering of cholesterol.

Contact urticaria from protein hydrolysates in hair conditioners.

Protein hydrolysates (PHs) are added to hair-care products (to "repair" broken hair), soaps, bath gels, creams, etc. From one to 22 PHs used in hair-care products (collagen, keratin, elastin, milk, wheat, almond, and silk) were tested in three patient groups: A) 11 hairdressers with hand dermatitis B) 2160 consecutive adults with suspected allergic respiratory disease subjected to routine skin prick tests C) 28 adults with atopic dermatitis. In group A, all the 22 PHs were tested with scratch and patch tests. In groups B and C, one to three PHs were tested with prick tests. Positive scratch/prick test reactions were seen in 12 patients from three PHs altogether. All were women with atopic dermatitis, and all reacted to at least hydroxypropyl trimonium hydrolyzed collagen (Crotein Q). In three patients, prick and open tests with a hair conditioner containing Crotein Q were performed with positive results. One patient reported contact urticaria on her hands, and two reported acute urticaria on their head, face, and upper body from a hair conditioner containing Crotein Q. In seven of the eight studied sera, specific IgE to Crotein Q was detected. In conclusion, PHs of hair cosmetics can cause contact urticaria, especially in patients with atopic dermatitis.

Allergy to feathers.

Skin prick test reactivity to commercial and self-made feather-allergen extracts was examined in 269 consecutive adult patients with suspected allergic cutaneous or respiratory symptoms who had been referred to a university clinic. Some 177 subjects reacted to any inhalant allergen. Twenty-four (9% of the whole group and 14% of those positive to any inhalant allergen) reacted to commercial feather extracts from ALK (Hørsholm, Denmark), and 51 to any of the seven feather extracts used. Feather-mix RAST (Pharmacia, Sweden) was positive in three cases only. Skin prick test or CAP-RAST or both to house-dust mite were positive in 16 of those 24 subjects positive to the commercial feather extracts, but in only 23 of the 150 other atopic subjects (P < 0.001). A nasal challenge with a feather extract was made in 20 cases, always with negative result. In immunospot studies, concomitant allergy to feather-allergen extracts and house-dust mite could be demonstrated. Mite allergens in feather extracts were verified in RAST-inhibition studies. A clinically significant feather allergy was found in one patient only. The results suggest that true feather allergy is very rare, and most of the positive reactions seen in skin prick tests to feather extracts are probably caused by mite allergens present in feathers.

Altered transfer of cholesteryl esters and phospholipids in plasma from alcohol abusers.

The net mass transfer (NMT) of cholesteryl esters (CEs), triglycerides (TGs), and phospholipids (PLs) between lipoproteins was measured after incubation of fresh plasma for up to 2 hours from 18 male alcohol abusers and 17 male volunteer control subjects. In alcohol abusers the mean value of CE NMT was 3.7 nmol.mL-1.h-1 from apolipoprotein B-containing lipoproteins (apoB-containing lipoproteins) to HDL and in control subjects 8.7 nmol.mL-1.h-1 from HDL to apoB-containing lipoproteins. The NMT of PL was higher in alcohol abusers than in control subjects (35.0 vs 11.6 nmol.mL-1.h-1 from apoB-containing lipoproteins to HDL, respectively), and plasma PL transfer protein (TP) activity was 33% higher (P < .05) in alcohol abusers than in control subjects. The lack of correlation between the NMTs and CETP and PLTP activities suggests that the NMT could more closely reflect the role of lipoprotein properties in reverse cholesterol transport in vivo, whereas in vitro activities reflect the total capacity of transfer but not its direction. The rate of CE NMT from HDL to apoB-containing lipoproteins was dependent on the VLDL TG concentration. Moreover, at low VLDL TG levels, the increased HDL cholesterol concentration in alcohol abusers reversed the direction of CE NMT. This situation could be reconstructed in the plasma of control subjects by adding autologous HDL or VLDL to mimic the lipoprotein profiles of the alcohol abusers. Addition of VLDL enhanced the CE NMT from HDL to apoB-containing lipoproteins, whereas addition of HDL had an opposite effect, and at higher HDL levels, even reversed the direction of CE NMT. In conclusion, the NMT of CE and PL in alcohol abusers differs from that in control subjects. The concentrations of HDL and VLDL seem to be the major determinants of the direction of CE NMT in alcohol abusers.

Effect of apolipoprotein E phenotype on plasma lipids and lipoproteins in alcohol abusers.

The effect of apolipoprotein (apo) E phenotype on the concentration and chemical composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50 male controls. The apo E phenotype was confirmed by genotyping to avoid possible effects of posttranslational modifications by alcohol or its metabolites. The lipid and protein concentrations of both intermediate density lipoprotein and low density lipoprotein were lower among the alcohol abusers than among the controls, those with E4 having the highest low density lipoprotein masses in both groups. In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid and protein concentrations were higher than in the controls with respective phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL subfractions. This effect was not explained by cholesteryl ester transfer protein activity, which was lower in the alcohol abusers (25 to 34%, p < 0.01), but without significant difference between the apo E groups. In conclusion, alcohol abuse does not cause major changes in the electric charge of apo E in humans. Heavy alcohol intake seems to have a beneficial effect on plasma lipids and lipoproteins, regardless of the apo E phenotype, but the modulation of the alcohol-induced increase in HDL by apo E phenotype should be taken into consideration in future studies.

Proposal for a revised international standard series of patch tests.

Worldwide, there are 3 major standard series of patch tests, the European, North American and Japanese, together presenting 32 allergens, the differences between them being the result of regional variation in allergen distribution as well as differences in dermatological opinion. We propose a "minimal" international standard series of 20 allergens, together with an "extended" international standard series of 14 allergens.