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1.  Reduced severity and improved control of self-reported asthma in Finland during 2001-2010 
Asia Pacific Allergy  2015;5(1):32-39.
Asthma and allergies are common and cause substantial burden in symptoms and suffering, hospitalizations and medication costs. However, despite the high prevalence, asthma burden has already decreased in Finland in 2000s.
We carried out an asthma barometer survey in all Finnish pharmacies to study changes in asthma severity and control, and use of health care services from 2001 to 2010.
Asthma severity, comorbid allergic conditions, and use of medication and health care services were assessed in subjects who purchased asthma or allergy medication from the pharmacies all across the country during one week in 2001 and again in 2010. In 2001, 3,062 patients (mean age, 49 years), and in 2010, 1,114 patients (mean age, 51 years) participated.
In 2001 90% and in 2010 73% of the respondents reported physician-diagnosed asthma and were entitled to special reimbursement for their drug costs, i.e., they needed regular maintenance treatment. In 2001, 10% of the asthmatics regarded their disease as severe, compared with 4% in 2010, while the figures for mild asthma were 45% and 62%, respectively (p < 0.001). The proportion of patients needing emergency care during the last year decreased from 34% (2001) to 14% (2010) (p < 0.001) and the need for hospitalizations from 18% to 6% (p < 0.001). Smoking reduced from 24% to 18% among asthmatics ( p = 0.002). In 2010, risk factors for severe asthma were older age, comorbid atopic eczema, and food allergy.
During ten years, self-reported asthma severity has reduced and disease control improved in Finland.
PMCID: PMC4313758  PMID: 25653918
Allergy; Drug therapy; Emergency treatment
2.  The relation of airway obstruction to asthma, chronic rhinosinusitis and age: results from a population survey of adults 
Allergy  2014;69(9):1205-1214.
There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample.
In 17 centers in 11 European countries, case–control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function.
A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and 1916 controls who had neither asthma nor CRS). Participants with asthma had lower FEV1/FVC (−4.09% (95%CI: −5.02, −3.15, P < 0.001) and a steeper slope of FEV1/FVC against age (−0.14%/annum [95%CI: −0.19, −0.08]) equivalent to smoking 1–2 packs of cigarettes per day. Those with atopy had a slope equivalent to controls.
People with asthma have a steeper decline in postbronchodilator lung function with age, but neither CRS nor atopy alone were associated with such decline.
PMCID: PMC4233404  PMID: 24841074
asthma; atopy; pulmonary function; rhinitis
3.  Long-term smoking increases the need for acute care among asthma patients: a case control study 
BMC Pulmonary Medicine  2014;14:119.
To examine risk factors for asthma patients’ emergency room (ER) visits in a well organized asthma care setting.
A random sample of 344 asthma patients from a Pulmonary Clinic of a University Hospital were followed through medical records from 1995 to 2006. All the ER visits due to dyspnea, respiratory infections, chest pain, and discomfort were evaluated.
The mean age of the study population was 56 years (SD 13 years), 72% being women. 117 (34%) of the patients had had at least one ER visit during the follow-up (mean 0.5 emergency visits per patient year, range 0–7). Asthma exacerbation, lower and upper respiratory infections accounted for the 71% of the ER visits and 77% of the hospitalizations. The patients with ER visits were older, had suffered longer from asthma and more frequently from chronic sinusitis, were more often ex- or current smokers, and had lower lung function parameters compared to the patients without emergency visits. Previous (HR 1.9, CI 1.3-3.1) and current smoking (HR 3.6, CI 1.6-8.2), poor self-reported health related quality of life (HRQoL) (HR 2.5, CI 1.5-4), and poor lung function (FEV1 < 65%, HR 2.2, CI 1.3-3.7) remained independent risk factors for ER visits after adjustment for age and gender.
Asthma patients who are or have been long-term smokers are more likely to require ER care compared to never smokers.
PMCID: PMC4108236  PMID: 25030656
Obstructive lung disease; Emergency visits; Hospitalizations; Smoking cessation
4.  Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles" 
We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children.
This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children.
The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant.
Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.
PMCID: PMC4077962  PMID: 24991459
Allergy; IgE; IL-4; IL-13; maternal genetic effects
5.  The skin prick test – European standards 
Skin prick testing is an essential test procedure to confirm sensitization in IgE-mediated allergic disease in subjects with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and food and drug allergy. This manuscript reviews the available evidence including Medline and Embase searches, abstracts of international allergy meetings and position papers from the world allergy literature. The recommended method of prick testing includes the appropriate use of specific allergen extracts, positive and negative controls, interpretation of the tests after 15 – 20 minutes of application, with a positive result defined as a wheal ≥3 mm diameter. A standard prick test panel for Europe for inhalants is proposed and includes hazel (Corylus avellana), alder (Alnus incana), birch (Betula alba), plane (Platanus vulgaris), cypress (Cupressus sempervirens), grass mix (Poa pratensis, Dactilis glomerata, Lolium perenne, Phleum pratense, Festuca pratensis, Helictotrichon pretense), Olive (Olea europaea), mugwort (Artemisia vulgaris), ragweed (Ambrosia artemisiifolia), Alternaria alternata (tenuis), Cladosporium herbarum, Aspergillus fumigatus, Parietaria, cat, dog, Dermatophagoides pteronyssinus, Dermatophagoides farinae, and cockroach (Blatella germanica). Standardization of the skin test procedures and standard panels for different geographic locations are encouraged worldwide to permit better comparisons for diagnostic, clinical and research purposes.
PMCID: PMC3565910  PMID: 23369181
Sensitization; Inhalant allergens; Skin prick test panel; Aallergies; Type I allergy; Diagnostic test; Asthma
6.  The biodiversity hypothesis and allergic disease: world allergy organization position statement 
Biodiversity loss and climate change secondary to human activities are now being associated with various adverse health effects. However, less attention is being paid to the effects of biodiversity loss on environmental and commensal (indigenous) microbiotas. Metagenomic and other studies of healthy and diseased individuals reveal that reduced biodiversity and alterations in the composition of the gut and skin microbiota are associated with various inflammatory conditions, including asthma, allergic and inflammatory bowel diseases (IBD), type1 diabetes, and obesity. Altered indigenous microbiota and the general microbial deprivation characterizing the lifestyle of urban people in affluent countries appear to be risk factors for immune dysregulation and impaired tolerance. The risk is further enhanced by physical inactivity and a western diet poor in fresh fruit and vegetables, which may act in synergy with dysbiosis of the gut flora. Studies of immigrants moving from non-affluent to affluent regions indicate that tolerance mechanisms can rapidly become impaired in microbe-poor environments. The data on microbial deprivation and immune dysfunction as they relate to biodiversity loss are evaluated in this Statement of World Allergy Organization (WAO). We propose that biodiversity, the variability among living organisms from all sources are closely related, at both the macro- and micro-levels. Loss of the macrodiversity is associated with shrinking of the microdiversity, which is associated with alterations of the indigenous microbiota. Data on behavioural means to induce tolerance are outlined and a proposal made for a Global Allergy Plan to prevent and reduce the global allergy burden for affected individuals and the societies in which they live.
PMCID: PMC3646540  PMID: 23663440
Allergy plan; Biodiversity; Civilization disease; Epigenetics; Immune dysfunction; Microbiota; Microbiome; Urbanization
7.  Persistent asthma, co-morbid conditions and the risk of work disability: a prospective cohort study 
Allergy  2011;66(12):1598-1603.
This study examined whether asthma alone or together with chronic co-morbidity is associated with increased risk of long-term work disability.
We examined data from 2,332 asthmatic and 66,354 non-asthmatic public sector employees in Finland who responded to a survey between 1997 and 2004. Respondents were coded as persistent asthmatics based on the special reimbursement for continuous asthma medication by the Social Insurance Institution. Data on long-term work disability (sickness absences or disability pensions >90 days) were obtained from national registers. The risk of work disability was examined by Cox proportional hazard models adjusted for age, gender, socioeconomic status, type of employment contract and type of employer.
Asthma increased the risk of all-cause long-term work disability, hazard ratio (HR) 1.8 (95 % CI 1.62–2.09) compared to controls (no asthma). Asthma and one other chronic co-morbidity increased the risk for long-term all-cause work disability with HR 2.2 (95% CI 1.78–2.83). Asthma together with two or more other chronic conditions increased the risk with HR 4.5 (95% CI 2.98–6.78). Asthma and depression increased the risk with HR 3.6 and the risk was especially high for permanent work-disability (HR 6.8). Among those with asthma there were more women, obesity (BMI ≥30), ex-smokers and lower-grade non-manual workers.
Asthma is associated with increased risk of long-term all-cause work disability. The risk increases further with chronic co-morbidities, and is especially high in patients with asthma and depression.
PMCID: PMC3203316  PMID: 21958351
Asthma; co-morbidity; sickness absence; work disability
8.  Clinical Use of Probiotics in Pediatric Allergy (cuppa): A World Allergy Organization Position Paper 
Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.
A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.
A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.
Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.
Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.
PMCID: PMC3651185  PMID: 23282383
probiotics; prevention of allergy; pediatric allergy
9.  Endoscopic sinus surgery might reduce exacerbations and symptoms more than balloon sinuplasty 
Endoscopic sinus surgery (ESS) is considered after medical therapy failure of chronic rhinosinusitis (CRS). The balloon sinuplasty dilates the natural ostium without moving mucosa or bone. It still lacks evidence from randomized controlled trials. The aim of this retrospective controlled study was to compare the symptom outcomes after maxillary sinus surgery with either the ESS or the balloon sinuplasty technique. No previous or additional sinonasal operations were accepted.
Two hundred eight patients with CRS without nasal polyps underwent either balloon sinuplasty or ESS. The patients who met with the inclusion criteria (n = 45 in ESS group and n = 40 in balloon group) replied to a questionnaire of history factors, exacerbations, and a visual analog scale (VAS) scoring of the change in symptoms, on average 28 ± 6 (mean ± SD) months postoperatively.
The groups were identical in the response rate (64%), patient characteristics, and the improvement in all of the asked symptoms. Patients with CRS-related comorbidity and/or present occupational exposure had a statistically significantly better symptom reduction after ESS than after balloon sinusotomy. Moreover, the balloon sinusotomy group reported a statistically significant higher number of maxillary sinus punctures and antibiotic courses during the last 12 months.
ESS might be superior to balloon sinuplasty, especially in patients with risk factors. There is a need to perform more controlled studies on the treatment choices of CRS.
PMCID: PMC3903106  PMID: 23232189
Balloon sinuplasty; chronic sinusitis; endoscopy; occupation; sinus surgery
10.  The Finnish Allergy Programme 2008-2018 - scientific rationale and practical implementation 
Asia Pacific Allergy  2012;2(4):275-279.
There are no nationwide, comprehensive public health programmes on allergic disorders with set goals and systematic follow-up. The Finnish initiative is based on the idea that the so called allergy epidemic in modern, urban societies is caused by inadequately developed or broken tolerance. The immune system is not trained to make the difference between danger and non-danger (allergy) or the difference between self and non-self (autoimmune diseases). The immune dysfunction leads to inappropriate inflammatory responses and clinical symptoms. The 10-year implementation programme is aimed to reduce burden of allergies both at the individual and societal levels. This is done by increasing both immunological and psychological tolerance and changing attitudes to support health instead of medicalising common and mild allergy symptoms. Severe forms of allergy are in special focus, e.g. asthma attacks are prevented proactively by improving disease control with the help of guided self-management. Networking of allergy experts with primary care doctors and nurses as well with pharmacists is the key for effective implementation. Non-governmental organizations have started a campaign to increase allergy awareness and knowledge among patients and general public. It is time to act, when allergic individuals are becoming a majority of Western populations and their numbers are in rapid increase worldwide. The first results of the Finnish Programme indicate that allergy burden can be reduced with relatively simple means.
PMCID: PMC3486973  PMID: 23130334
Allergy programme; Asthma attack; Immune tolerance; Public health programme; Self-management
11.  Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA 
PLoS ONE  2012;7(9):e44008.
Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.
To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.
The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5x10−8) and three variants reported as suggestive (P<5×10−7). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever.
Main Results
We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4×10−9). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10−9), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10−8), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status.
Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
PMCID: PMC3461045  PMID: 23028483
13.  Inspiratory flows through dry powder inhaler in chronic obstructive pulmonary disease: age and gender rather than severity matters 
Dry powder inhalers (DPIs) are inspiratory flow driven and hence flow dependent. Most patients with chronic obstructive pulmonary disease (COPD) are elderly and have poor lung function. The factors affecting their inspiratory flows through inhalers are unclear.
To study peak inspiratory flows (PIFs) and their determinants through a DPI in COPD patients of varying age and severity.
Flow-volume spirometry was performed in 93 COPD patients. Maximum PIF rates were recorded through an empty Easyhaler® (PIFEH; Orion Corporation, Espoo, Finland), a DPI that provides consistent dose delivery at inhalation rates through the inhaler of 28 L/min or higher.
The mean PIFEH was 54 L/min (range 26–95 L/min) with a coefficient of variation of 7%. All but two patients were able to generate a flow of ≥28 L/min. In a general linear model, the independent determinants for PIFEH were age (P = 0.02) and gender (P = 0.01), and forced expiratory volume in 1 s (FEV1) expressed as percent predicted was not a significant factor. The regression model accounted only for 18% of the variation in PIFEH.
In patients with COPD, age and gender are more important determinants of inspiratory flow through DPIs than the degree of expiratory airway obstruction. Most COPD patients with varying age and severity are able to generate inspiratory flows through the test inhaler that is sufficient for optimal drug delivery to the lower airways.
PMCID: PMC2921694  PMID: 20714380
COPD; forced expiratory volume; peak inspiratory flow
14.  Transient Dimers of Allergens 
PLoS ONE  2010;5(2):e9037.
Allergen-mediated cross-linking of IgE antibodies bound to the FcεRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking.
Methodology/Principal Findings
An analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release.
The results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.
PMCID: PMC2816702  PMID: 20140203
15.  A 10 year asthma programme in Finland: major change for the better 
Thorax  2006;61(8):663-670.
A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society.
The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti‐inflammatory treatment from the outset. The key for implementation was an effective network of asthma‐responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini‐Programme was launched.
The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were €218 million which had fallen to €213.5 million in 2003. Costs per patient per year have decreased 36% (from €1611 to €1031).
It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.
PMCID: PMC2104683  PMID: 16877690
asthma; guidelines; medication programme; costs
16.  Persistence of oxidant and protease burden in the airways after smoking cessation 
Oxidative stress is associated with the pathogenesis of cigarette smoke related lung diseases, but longitudinal effects of smoking cessation on oxidant markers in the airways are unknown.
This study included 61 smokers; 21 with chronic bronchitis or COPD, 15 asthmatics and 25 asymptomatic smokers followed up for 3 months after smoking cessation. Fractional exhaled nitric oxide (FeNO), sputum neutrophil counts, sputum 8-isoprostane, nitrotyrosine and matrix metalloproteinase-8 (MMP-8) were investigated at baseline and 1 and 3 months after smoking cessation.
After 3 months 15 subjects had succeeded in quitting of smoking and in these subjects symptoms improved significantly. Unexpectedly, however, sputum neutrophils increased (p = 0.046) after smoking cessation in patients with chronic bronchitis/COPD. At baseline, the other markers did not differ between the three groups so these results were combined for further analysis. Sputum 8-isoprostane declined significantly during the follow-up at 3 months (p = 0.035), but levels still remained significantly higher than in non-smokers. The levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during the 3 months after smoking cessation.
Whilst symptoms improve after smoking cessation, the oxidant and protease burden in the airways continues for months.
PMCID: PMC2697135  PMID: 19473482
17.  Eight Years of Severe Allergic Reactions in Finland: A Register-Based Report 
No data have been available on severe allergic reactions in Finland.
Materials and Methods
We summarize the data accumulated from 2000 to 2007 in the national register established at the Skin and Allergy Hospital of the Helsinki University Central Hospital, where physicians voluntarily report on patients with severe allergic reactions.
During the period, the 530 reported cases of severe allergic reactions represented an annual frequency of 0.001%. Of the patients, 66% were adults and 56% were female, with a median age of 27 years. Food was the causative agent in 53% of the cases, drugs in 26%, allergen preparations in 12%, and insects in 8%. Dermatologic symptoms were reported in 85%, respiratory in 76%, cardiovascular in 50%, gastrointestinal in 33%, and eye/nose symptoms in 18%. The reaction was a life-threatening anaphylactic shock in 26% of the cases, with no deaths reported. Patients were treated with intramuscular adrenaline in 75% of the cases. Not only nuts and seeds, but also fruit and vegetables were the most important allergens for the adults. Nuts were also important allergens for children, along with milk, egg, and wheat. In addition, many "exotic" allergens were identified: patent blue, carmine dye, yeast, buckwheat, and macrogol.
Severe allergic reactions are underreported, but a register reflects the real-life situation and helps to identify new causative agents. It also contributes to improvements in first aid treatment practice.
PMCID: PMC3650993  PMID: 23282762
allergen preparation; anaphylaxis; drug; food; insect; register
18.  Should milk-specific IgE antibodies be measured in adults in primary care? 
To study the association of milk-IgE antibodies in serum to milk-related gastrointestinal symptoms in adults in primary care.
Open clinical study.
Five outpatient clinics in primary care in Southern Finland.
A total of 756 subjects who reported milk-related gastrointestinal symptoms in primary care and as controls 101 subjects with no such symptoms.
IgE values for specific food antigens were measured (Pharmacia CAP System) in a total of 857 subjects. All food screen-positive samples (>0.35 IU/l) were analysed further for IgE for untreated skimmed milk (milk-IgE) and for boiled milk. Those found positive for milk-IgE were invited for an open milk challenge test.
Some 5.4% (46/857) of all subjects had a positive IgE antibody screen for food antigens. Of those with a positive food screen, 28% (13/46) had milk-IgE antibodies comprising 1.5% of the total group screened. The prevalence of milk-IgE was not statistically different between those with milk-related symptoms and those with no such symptoms. IgE antibodies for boiled milk were rare. All specific IgE antibody levels were low. Bloating was the only observed symptom in milk challenge tests.
IgE antibodies to cow's milk were relatively rare in the adult population and were not indicative of milk protein allergy. The observed IgE levels were low and did not correlate with subjective milk-related symptoms. The measurement of milk-specific IgE in adults should be discouraged in outpatient clinics.
PMCID: PMC3406635  PMID: 18609255
Abdominal symptoms; cow's milk; food hypersensitivity; primary care
19.  Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study) 
Archives of Disease in Childhood  2007;93(8):654-659.
To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma.
Patients, design and interventions:
176 children aged 5–10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 μg twice daily for 1 month, 200 μg twice daily for months 2–6, 100 μg twice daily for months 7–18); (2) budesonide, identical treatment to group 1 during months 1–6, then budesonide for exacerbations as needed for months 7–18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1–18. Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks.
Main outcome measures:
Lung function, the number of exacerbations and growth.
Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7–18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth.
Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.
PMCID: PMC2532957  PMID: 17634183
20.  Allergic rhinitis and asthma: inflammation in a one-airway condition 
BMC Pulmonary Medicine  2006;6(Suppl 1):S5.
Allergic rhinitis and asthma are conditions of airway inflammation that often coexist.
In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened.
Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.
PMCID: PMC1698498  PMID: 17140423
21.  Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma 
Thorax  2003;58(6):494-499.
Background: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FENO), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma.
Methods: Ninety six preschool children (age 3.8–7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FENO was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS).
Results: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FENO than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FENO (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FENO provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted.
Conclusions: FENO is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.
PMCID: PMC1746693  PMID: 12775859
22.  Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment 
Thorax  2003;58(6):500-504.
Background: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks.
Methods: Twenty six asthmatic patients aged 21–59 years were selected for this randomised, double blind, parallel group study. The effect of 250 µg inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV1) by 15% (PD15FEV1) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD15FEV1 were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves.
Results: The increase in PD15FEV1 from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD15FEV1 was 1.85–2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment.
Conclusions: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 µg. The effect tapered within 2 weeks of cessation of treatment.
PMCID: PMC1746689  PMID: 12775860
24.  Cell specific markers for eosinophils and neutrophils in sputum and bronchoalveolar lavage fluid of patients with respiratory conditions and healthy subjects 
Thorax  2002;57(5):449-451.
Methods: Induced sputum and bronchoalveolar lavage fluid samples from 14 patients with respiratory conditions and four healthy individuals were studied. Antigens were detected at their intracellular sites in cells with well preserved structures using optimal techniques for fixation, permeabilisation, and immunolabelling.
Results: Anti-EPO antibodies reacted only with eosinophils, and anti-HNL antibodies only with neutrophils. Anti-ECP antibodies reacted with both eosinophils and neutrophils and anti-MPO antibodies with neutrophils and monocytes. Cells not stained by monoclonal anti-EPO and anti-HNL antibodies included lymphocytes, monocytes, macrophages, squamous epithelial cells, and ciliated epithelial cells.
Conclusions: EPO, a unique component of eosinophils, and HNL, a unique component of neutrophils, are useful markers for the identification of eosinophils and neutrophils, respectively, in sputum and bronchoalveolar lavage fluid.
PMCID: PMC1746329  PMID: 11978925
25.  Asthma programme in Finland: a community problem needs community solutions 
Thorax  2001;56(10):806-814.
PMCID: PMC1745939  PMID: 11562522

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