Paula Kauppi

A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population

The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. The current population of 100,000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneous, we hypothesized that the molecular genetic mechanisms underlying asthma might also have reduced heterogeneity and therefore be easier to dissect than in mixed populations. A recent twin family study supported a strong genetic component for asthma in Finland. We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We identified two regions of suggestive linkage and studied them further with higher-density mapping. We obtained evidence for linkage in a 20-cM region of chromosome 7p14–p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes. The strongest linkage was seen for high serum IgE (non-parametric linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide significance based on simulations. We also observed linkage between this locus and asthma or atopy in two independent data sets.

Overlap Syndrome of Asthma and COPD Predicts Low Quality of Life

Background. In clinical practice, patients whose airway disease shares features of both asthma and chronic obstructive pulmonary disease (COPD) remain poorly recognized. Material and methods. The study population consisted of 1546 patients with a diagnosis of asthma or COPD or both. Based on patient-reported outcomes and retrospective medical record data, the study population was divided into three groups: (1) asthma only, (2) COPD only, and (3) both asthma and COPD (overlap syndrome group). We evaluated patient characteristics associated with health-related quality of life (HRQoL). Results. In many respects, the overlap group fell between the asthma and COPD groups. In the overlap group, however, HRQoL was the poorest of all. In the logistic regression model, with the asthma group as the reference, both the overlap and the COPD group showed higher risk for low HRQoL [odd ratio (OR): 1.9; 95% confidence interval (CI): 1.2–3.2; and OR: 1.8, 95% CI: 1.0–3.2; respectively]. In addition, female gender, obesity, duration of disease, disability pension, and coexisting cardiovascular disease were associated with low HRQoL across the study population. Conclusions. Patients with overlapping asthma and COPD differed from those patients with asthma or COPD only. Overlap syndrome was associated with low HRQoL.

Follow-up of the Finnish Asthma Programme 2000–2010: reduction of hospital burden needs risk group rethinking

The Finnish Asthma Programme 1994–2004 focused on early intervention and disease control, thereby resulting in a significant reduction of asthma morbidity. During the follow-up period from 2000 to 2010, the number of hospital days continued to fall by 54%. Patients ≥65 years, especially women, accounted for 39% of the hospital days, and they need attention if the hospital burden is to be reduced further.

Persistent asthma, comorbid conditions and the risk of work disability: a prospective cohort study

To cite this article: Hakola R, Kauppi P, Leino T, Ojajärvi A, Pentti J, Oksanen T, Haahtela T, Kivimäki M, Vahtera J. Persistent asthma, comorbid conditions and the risk of work disability: a prospective cohort study. Allergy 2011; 66: 1598–1603.

IgE-Mediated Occupational Asthma from Epoxy Resin

Background: Epoxy resins (ERs) are used in paints and other protective coatings, including flooring materials. Bisphenol A diglycidyl ether (BADGE) ERs (BADGE ERs) account for about 75% of the ERs used world-wide. ERs can cause both immediate and delayed allergic reactions, but immediate reactions are rare. Methods: Occupational asthma (OA) was diagnosed on the basis of a specific challenge test combined with the patient’s history of occupational exposure and respiratory symptoms. Results: A 39-year-old nonsmoking construction worker experienced dyspnea when laying ER-containing floors, but not in other situations. He also presented skin symptoms. IgE-mediated allergy to BADGE ER could be verified with both serum IgE antibodies and skin prick tests. The specific bronchial challenge test with BADGE ER caused an immediate asthmatic reaction. On patch testing, a positive reaction was provoked by BADGE ER. Conclusions: This is the first study on a patient exposed to BADGE ER with IgE-mediated immediate OA, based on a positive inhalation challenge test. If work-related respiratory symptoms develop when handling ERs, the possibility of OA should be recognized.

Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms

Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Most studies with asthma have been performed in patients being otherwise healthy. However, in real life, comorbid diseases are very common in adult patients. We review here the emerging comorbid conditions to asthma such as obesity, metabolic syndrome, diabetes mellitus type 2 (DM2), and cardiac and psychiatric diseases. Their role as risk factors for incident asthma and whether they affect clinical asthma are evaluated. Obesity, independently or as a part of metabolic syndrome, DM2, and depression are risk factors for incident asthma. In contrast, the effects of comorbidities on clinical asthma are less well-known and mostly studies are lacking. Cross-sectional studies in obese asthmatics suggest that they may have less well controlled asthma and worse lung function. However, no long-term clinical follow-up studies with these comorbidities and asthma were identified. These emerging comorbidities often occur in the same multimorbid adult patient and may have in common metabolic pathways and inflammatory or other alterations such as early life exposures, systemic inflammation, inflammasome, adipokines, hyperglycemia, hyperinsulinemia, lung mechanics, mitochondrial dysfunction, disturbed nitric oxide metabolism, and leukotrienes.

The Finnish Allergy Programme 2008-2018 - scientific rationale and practical implementation.

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.

Cystic Fibrosis Gene Mutations ΔF508 and 394delTT in Patients with Chronic Sinusitis in Finland

Previous studies have shown that cystic fibrosis (CF) gene mutations are linked to several severe chronic infections. Chronic sinusitis is one condition that may well be influenced by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We studied two prevalent CF mutations (AF508 and 394delTT) in a population with a low incidence of CF. The carrier frequency of the CF mutations in the Finnish population is approximately 1 in 80. We examined DNA specimens from 127 chronic sinusitis patients and found one patient who was heterozygous for 394delTT gene mutation. None of the DNA specimens had any AF508 mutation. This study shows that in a population with a low incidence of CF there was no abnormal carrier distribution of the two most common CF gene mutations in a group of chronic sinusitis patients. Routine screening of sinusitis patients for CF mutations provides no additional information on the etiology of chronic sinusitis.Previous studies have shown that cystic fibrosis (CF) gene mutations are linked to several severe chronic infections. Chronic sinusitis is one condition that may well be influenced by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We studied two prevalent CF mutations ( j F508 and 394delTT) in a population with a low incidence of CF. The carrier frequency of the CF mutations in the Finnish population is , 1 in 80. We examined DNA specimens from 127 chronic sinusitis patients and found one patient who was heterozygous for 394delTT gene mutation. None of the DNA specimens had any j F508 mutation. This study shows that in a population with a low incidence of CF there was no abnormal carrier distribution of the two most common CF gene mutations in a group of chronic sinusitis patients. Routine screening of sinusitis patients for CF mutations provides no additional information on the etiology of chronic sinusitis.

Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper

The strongest and best‐documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross‐reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper‐based documentation.

Reduced severity and improved control of self-reported asthma in Finland during 2001-2010

Background 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. Objective 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. Methods 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. Results 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. Conclusion During ten years, self-reported asthma severity has reduced and disease control improved in Finland.