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The specialty of clinical physiology was established in Finland about 20 years later than in Sweden. In the early 1960s, six physicians working mainly in preclinical departments of physiology were certified as specialists in clinical physiology. Many of the first specialists working in hospitals received specialist training in Sweden. The first hospital laboratories of clinical physiology were established in Tampere Central Hospital and Turku University Hospital in 1968. Thereafter, laboratories of clinical physiology were also established in Helsinki University Hospital and in Kuopio University Hospital and later also in most central hospitals. After clinical physiology laboratories were set up in hospitals and the number of specialists increased, the specialty gradually had more impact in clinical work. In the 1999 reform, nuclear medicine, which had previously been a subspecialty, was combined with clinical physiology. Arto Uusitalo was nominated the first professor of clinical physiology in Tampere University in 1984. The first professor in Helsinki University was Anssi Sovijärvi (1994), in Kuopio University Esko Länsimies (1998), and in Turku University Jaakko Hartiala (2003). Today, at four universities professors of clinical physiology and nuclear medicine lead research and medical education in this specialty. The hospital laboratories have modern equipment, which promotes multidisciplinary research with clinicians in fruitful collaboration. The Finnish Society of Clinical Physiology was founded in 1975. Today, it has about 160 members, about half of whom are specialists in the field. On its 40th anniversary, the Society decided to publish the history of clinical physiology in Finland.

Objectives Our objective was to study mortality related to different obstructive lung diseases, occupational exposure, and their potential joint effect in a large, randomized population-based cohort. Methods We divided the participants based on the answers to asthma and chronic obstructive pulmonary disease (COPD) diagnoses and occupational exposure and used a combined effects model and compared the results to no asthma or COPD with no occupational exposure. Results High exposure had a hazards ratio (HR) of 1.34 (1.11-1.62) and asthma and COPD coexistence of 1.58 (1.10-2.27). The combined effects of intermediate exposure and coexistence had an HR of 2.20 (1.18-4.09), high exposure with coexistence of 1.94 (1.10-3.42) for overall mortality, and sub-HR for respiratory-related mortality of 3.21 (1.87-5.50). Conclusions High occupational exposure increased overall but not respiratory-related mortality hazards, while coexisting asthma and COPD overall and respiratory-related hazards of mortality. publishedVersion

Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijarvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijarvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijarvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijarvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.

Background: Chronic nonrespiratory diseases are seemingly more prevalent in subjects with than without asthma, and asthma seems to differentiate by age of onset. However, studies with comparison of nonrespiratory diseases in subjects with and without asthma, considering asthma age of onset, are scarce. Objective: To compare the quantity and type of chronic nonrespiratory diseases in adults with and without asthma considering age at asthma diagnosis. Methods: In 2016, a FinEsS questionnaire was sent to 16,000 20- to 69-year-old adults randomly selected in Helsinki and Western Finland populations. Physician-diagnosed asthma was categorized to early (0-11), intermediate (12-39), and late-diagnosed (40-69 years). Results: A total of 8199 (51.5%) responded, and 842 (10.3%) reported asthma and age at diagnosis. In age and sex-adjusted binary logistic regression model, the most represented nonrespiratory disease was treated gastroesophageal reflux disease in early-diagnosed (odds ratio, 1.93; 95% CI, 1.17-3.19; P =.011) and osteoporosis in both intermediate-diagnosed (odds ratio, 3.45; 95% CI, 2.01-5.91; P

Background: Although asthma may begin at any age, knowledge about relationship between asthma age of onset and the prevalence and character of different symptoms is scarce. Objectives: The aim of this study was to investigate if adult-diagnosed asthma is associated with more symptoms and different symptom profiles than child-diagnosed asthma. Methods: A FinEsS postal survey was conducted in a random sample of 16 000 20-69-year-old Finnish adults in 2016. Those reporting physician-diagnosed asthma and age at asthma diagnosis were included. Age 18 years was chosen to delineate child- and adult-diagnosed asthma. Results: Of responders (N = 8199, 51.5%), 842 (10.3%) reported asthma diagnosis. Adult-diagnosed asthma was reported by 499 (59.3%) and child-diagnosed by 343 (40.7%). Of responders with adult-diagnosed and child-diagnosed asthma, 81.8% versus 60.6% used asthma medication (p < 0.001), respectively. Current asthma was also more prevalent in adult-diagnosed asthma (89.2% versus 72.0%, p < 0.001). Risk factors of attacks of breathlessness during the last 12 months were adult-diagnosis (OR = 2.41, 95% CI 1.64–3.54, p < 0.001), female gender (OR = 1.49, 1.07–2.08, p = 0.018), family history of asthma (OR = 1.48, 1.07–2.04, p = 0.018) and allergic rhinitis (OR = 1.49, 1.07–2.09, p = 0.019). All the analysed asthma symptoms, except dyspnea in exercise, were more prevalent in adult-diagnosed asthma in age- and gender-adjusted analyses (p = 0.032

Background Smoking and occupational airborne exposures are known to increase asthma symptoms, but less is known about their influence by the age of asthma diagnosis. Objective To evaluate the effect of exposures to VGDF (vapors, gases, dusts and fumes), tobacco smoke and their combination for asthma symptoms comparing subjects with asthma diagnosed in childhood and adulthood. Methods A random sample of 16 000 adults aged 20–69 years were invited to a postal survey on obstructive pulmonary diseases in Finland in 2016. Those reporting physician-diagnosed asthma and age at diagnosis were included in the analysis and their reported VGDF-exposure and smoking habits were analyzed. Age 18 years was chosen to delineate child- and adult-diagnosed asthma. Results 8199 (51.5%) responded. Of the responders, 831 reported physician-diagnosed asthma. 41% of asthmatics reported child-diagnosed and 59% adult-diagnosed asthma. Current smoking was reported by 25.2% and 20.2% and VGDF exposure by 31.3% and 44.7% in child -diagnosed and adult-diagnosed asthma, respectively. Combined VGDF-exposure and current smoking was reported by 9.7% and 10.6%, respectively. Compared to the unexposed, those with asthma diagnosed in childhood and with combined current smoking and VGDF exposure, had higher prevalence of wheeze (69.7% vs 39.5%, p=0.009), sputum production (39.4% vs 11.4%, p=0.001) and morning dyspnea (42.4% vs 21.9%, p=0.002). Corresponding pattern was seen in those with asthma diagnosed in adulthood; for wheeze (78.8% vs 53.6%, p=0.007), sputum production (40.4% vs 25.0%, p=0.014) and morning dyspnea (65.4% vs 42.0%, p=0.008). Child-diagnosed asthmatics both without exposure history (46.5% vs 69.6%, p=0.001) and with combined exposure to smoking and VGDF (66.7% vs 94.2%, p=0.003) reported less often ≥3 symptoms compared to adult-diagnosed asthmatics, even though they reported less frequently use of asthma medication (60.7% vs 82.0%, p>0.001). Smoking asthmatics with adult-diagnosis and exposure to VGDF had the highest prevalence estimates of having multiple symptoms (94.2%) in our study. Conclusion Although asthmatics diagnosed in child- and adulthood reported symptoms related to exposure to smoking and VGDF, symptoms were reported more often by those with adult diagnosis. The results indicate the importance of targeted asthma treatment and follow-up by patient’s exposure history and asthma diagnosis age.

In clinical practice, assessment of expiratory nitric oxide (F-ENO) may reveal eosinophilic airway inflammation in asthmatic and other pulmonary diseases. Currently, measuring of F-ENO is standardized to exhaled flow level of 50 ml s(-1), since the expiratory flow rate affects the F-ENO results. To enable the comparison of F-ENO measured with different expiratory flows, we firstly aimed to establish a conversion model to estimate F-ENO at the standard flow level, and secondly, validate it in five external populations. F-ENO measurements were obtained from 30 volunteers (mixed adult population) at the following multiple expiratory flow rates: 50, 30, 100 and 300 ml s(-1), after different mouthwash settings, and a conversion model was developed. We tested the conversion model in five populations: healthy adults, healthy children, and patients with COPD, asthma and alveolitis. F-ENO conversions in the mixed adult population, in healthy adults and in children, showed the lowest deviation between estimated FENO from 100 ml s(-1) and measured F-ENO at 50 mL s(-1): -0 center dot 28 ppb, -0 center dot 44 ppb and 0 center dot 27 ppb, respectively. In patients with COPD, asthma and alveolitis, the deviation was -1 center dot 16 ppb, -1 center dot 68 ppb and 1 center dot 47 ppb, respectively. We proposed a valid model to convert F-ENO in healthy or mixed populations, as well as in subjects with obstructive pulmonary diseases and found it suitable for converting F-ENO measured with different expiratory flows to the standard flow in large epidemiological data, but not on individual level. In conclusion, a model to convert F-ENO from different flows to the standard flow was established and validated.

Background: Difference in dyspnea mMRC >= 2 between Finnish speaking and Swedish-speaking populations in Finland has not been previously studied. Methods: In February 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland with a response rate of 52.3%. The registered native language of each subject determined whether questionnaire in Finnish or Swedish was applied. Multiple logistic regression was performed to calculate Odds Ratios (OR) with 95% CI for the simultaneous effects of independent variables on dyspnea mMRC >= 2. Results: Of all participants, 2780 (71.9%) were Finnish speakers and 1084 (28.1%) were Swedish speakers. Finnish speakers had a higher prevalence of dyspnea mMRC >= 2 (11.1% vs 6.5% p < 0.001) when compared to Swedish speakers. Finnish speakers smoked more often, had higher BMI, spent less time moving during the day, had more often occupational exposure to vapours, gases, dusts or fumes (VGDF), and had lower socioeconomic status based on occupation. Significant risk factors for dyspnea mMRC >= 2 were COPD (OR = 10.94), BMI >35 (OR = 9.74), asthma (OR = 4.78), female gender (OR = 2.38), older age (OR = 2.20), current smoking (OR = 1.59), and occupational exposure to VGDF (OR = 1.47). Conclusions: Swedish speakers had less dyspnea mMRC >= 2 which is explained by a healthier lifestyle. Smoking, obesity, and occupational exposures should be in focus to improve respiratory health.

BACKGROUND: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seem-ingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. OBJECTIVE: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. METHODS: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was catego-rized by age at diagnosis to early-(0-11 years), intermediate-(12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. RESULTS: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, signifi-cant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.373.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. CONCLUSION: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission. (C) 2020 American Academy of Allergy, Asthma & Immunology

Objective: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. Results: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7–8.2% versus 6.3–6.7%) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7 and 2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex. Accepted author version posted online: 30 May 2020Published online: 13 Jun 2020

Multimorbidity is an emerging public health priority. This study aims to assess the role of lifestyle and socioeconomic status in the prevalence of multimorbidity and chronic diseases by using two language groups that are part of the same genetic subgroup but differ by daily habits. We conducted a cross-sectional survey in 2016 with randomly selected population sample with 4173 responders (52.3%) aged 20–69 years in Western Finland. We included 3864 Finnish participants with Swedish (28.1%) or Finnish (71.9%) as a native language. We used a questionnaire to assess participants' chronic diseases and lifestyle. We determined multimorbidity as a disease count ≥ 2. Finnish speakers were more likely to have a diagnosis of COPD, heart failure, diabetes, reflux disease, chronic kidney failure, and painful conditions than Swedish speakers. The prevalence of multimorbidity was higher for Finnish speakers in the age group of 60–69 years (41.0% vs. 32.0%, p = 0.018) than Swedish speakers. A higher proportion of Finnish speakers smoked, were obese, inactive, and had lower socioeconomic status compared to Swedish speakers. All these factors, in addition to age and female sex, were significant risk factors for multimorbidity. Prevalence of multimorbidity was different in two language groups living in the same area and was associated with differences in lifestyle factors such as smoking, physical inactivity and obesity. publishedVersion

Background: Child-onset asthma is known to remit with high probability but remission in adult-onset asthma seems to be less common. Reports of association between remission and asthma onset age in adulthood are scarce. Objectives: To study if age at asthma diagnosis and gender are associated to remission rate in adult asthma population. Methods: In 2016, a random sample of 16 000 subjects aged 20-69 years from Helsinki and Western Finland were sent a FinEsS-questionnaire. Asthma was categorized by reported age when diagnosed with asthma by a physician: child (0-11 years) adolescent-young-adult (12-39 years) and late-adult-diagnosed (40-69 years). Remission was defined as a physician diagnosed asthma but not having had asthma symptoms, wheezing or use of asthma medication in the past 12 months. Results: 8199 subjects (51.5%) responded to the postal questionnaire. Remission was most common in child-diagnosed (30.2%), followed by adolescent-young-adult-diagnosed (17.9%) and least common in late-adult-diagnosed asthma (5.0%) (p Conclusion: Remission was rare (5%) in adults diagnosed with asthma after age 40 years in both sexes. Causes of poor prognosis in adult-onset asthma need to be further elucidated.

Fractional exhaled nitric oxide (F-ENO) assesses eosinophilic inflammation of the airways, but F-ENO values are also influenced by oral nitric oxide (NO). The aim of this pilot study was to measure F-ENO and compare the effect of two different mouthwashes on F-ENO and analyse the duration of the effect. F-ENO was measured in 12 randomized volunteers (healthy or asthmatic subjects) with a NIOX VERO (R) analyser at an expiratory flow rate of 50mL/s. After a baseline measurement, a mouthwash was performed either with tap water or carbonated water and was measured during 20min in 2min intervals. The procedure was repeated with the other mouthwash. We found that both mouthwashes reduced F-ENO immediately at the beginning compared to the baseline (p

Objective The aim of the study was to compare the effects of different hormone therapies on cardiac repolarization in recently postmenopausal women with and without hot flashes. Methods We recruited 150 healthy women: 72 with and 78 without hot flashes. They were randomized and treated for 6 months with transdermal estradiol (1 mg/day), oral estradiol (OE) alone (2 mg/day) or combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo. Cardiac repolarization was assessed by measuring QT intervals, rate-dependence of QT-end interval, and T waves from 24-hour electrocardiographic recording before and during hormone therapy, comprising a total of over 20 million QT-interval measurements. Results Hot flashes were accompanied with shortened median T-peak - T-end interval (at RR interval of 700, 800, and 900 ms; P = 0.040, 0.020, and 0.032; η = 0.35, 0.39, and 0.37; respectively) during the use of OE but not transdermal estradiol. In contrast, the addition of MPA to OE lengthened the maximal QT-end (at RR interval of 500 ms, P = 0.016, η = 0.27) and the maximal T-peak - T-end interval (at RR interval of 500 and 600 ms; P = 0.016 and 0.032; η = 0.25 and 0.22, respectively). These effects were not seen in women without hot flashes. Conclusions Hot flashes predict beneficial shortening in cardiac repolarization during OE, but not if MPA is combined with OE. These data may provide one explanation for MPA-related cardiac hazards in epidemiological studies.

Background Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. Methods Questionnaires were sent to 8000 randomly selected recipients aged 20–69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. Results The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0–9, 10–19, 20–29, 30–39, 40–49, 50–59 and 60–69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50–59 years old). Conclusions The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.

Background Mulibrey nanism (MUL) is a rare growth restriction disorder with multiple organ manifestations caused by genetic defects affecting the TRIM37 protein. A perimyocardial heart disease is the most serious manifestation. Many MUL children appear to suffer from airway obstruction related to infection or exercise, prompting use of inhaled therapies. Asthma medication is continued up to adolescence or even to adulthood due to persisting of symptoms. The pulmonary pathophysiology has previously not been evaluated in any MUL cohort. Methods Thirty three finnish MUL patients (median age 20 years) were investigated with several lung function tests: spirometry with bronchodilatation test, single-breath diffusing capacity for carbon monoxide, single-breath lung volume measurements with helium dilution, and thoracic gas volume, airway resistance and specific conductance measurements with a body plethysmograph. As MUL typically affects body proportions, all variables were compared with reference values and with predicted values calculated from sitting height. Results Total lung capacity and forced vital capacity were markedly reduced (total lung capacity [TLC] and forced vital capacity [FVC], P = 12% and >= 200 mL) was found only in one patient. Conclusion MUL patients typically have volume restriction of the lungs, but function of the pulmonary tissue remains intact. Evidence of asthma in lung function testing at adult age is rare.

Background: Eventual differences of expiratory nitric oxide (FENO) levels in general populations of Nordic countries may reflect differences in eosinophilic inflammation at population level.Aim: To ...

Difference in Dyspnea between Swedish and Finnish Speaking Persons in Western Finland : Association with Lifestyle

Background Mortality and hospitalization due to asthma have decreased in many European countries, but asthma symptoms still cause a lot of morbidity and costs. Objectives We evaluated prevalence trends of asthma, asthma symptoms and allergic rhinoconjunctivitis in adults aged 20–69 years during a 20-year period from 1996 to 2016 in the city of Helsinki, the capital of Finland. Methods Three cross-sectional postal surveys were conducted in random population samples 10 years apart. In 1996, 2006 and 2016, a total of 6062 (response rate 75.9%), 2449 (61.9%) and 4026 subjects (50.3%) took part, respectively. Results In all responders, the prevalence of physician-diagnosed asthma was 6.6% in 1996, 10% in 2006 and 10.9% in 2016. The prevalence increased from 1996 to 2006, but stabilized from 2006 to 2016, both in men and women and in smokers and non-smokers. The prevalence of current asthma (8.5% in 2006 and 8.8% in 2016) and of asthma with rhinoconjunctivitis (7.6% in 2006 and 7.5% in 2016) remained also at the same level. Allergic rhinoconjunctivitis decreased significantly from 2006 (42.7%) to 2016 (39.0%, p = 0.004). Those with physician diagnosed asthma reported significantly less symptoms in 2016 compared to 2006 and 1996, although there was no change in smoking habits or medication use. Young asthmatics (20–29 years) without rhinoconjunctivitis reported least symptoms. Conclusion Previously observed increase of physician-diagnosed asthma prevalence in adults seems to be levelling off in Helsinki, and patients have fewer symptoms than 20 years ago. In addition, allergic rhinoconjunctivitis is less frequent than 10 years earlier. (247 words).

The prevalence of asthma is higher in Sweden and Finland than in neighbouring eastern countries including Estonia. Corresponding difference in bronchial eosinophilic inflammation could be studied by FENO measurements. We aimed to compare FENO in adult general populations of Sweden, Finland, and Estonia, to test the plausibility of the west-east disparity hypothesis of allergic diseases. We conducted clinical interviews (N = 2658) with participants randomly selected from the general populations in Sweden (Stockholm and Örebro), Finland (Helsinki), and Estonia (Narva and Saaremaa), and performed FENO (n = 1498) and skin prick tests (SPT) in 1997–2003. The median (interquartile range) of FENO (ppb) was 15.5 (9.3) in Sweden, 15.4 (13.6) in Finland and 12.5 (9.6) in Estonia. We found the lowest median FENO values in the Estonian centres Saaremaa 13.1 (9.5) and Narva 11.8 (8.6). In the pooled population, asthma was associated with FENO ≥25 ppb, odds ratio (OR) 3.91 (95% confidence intervals: 2.29–6.32) after adjusting for SPT result, smoking, gender and study centre. A positive SPT test increased the likelihood of asthma OR 3.19 (2.02–5.11). Compared to Saaremaa, the likelihood of having asthma was higher in Helsinki OR 2.40 (1.04–6.02), Narva OR 2.45 (1.05–6.19), Örebro OR 3.38 (1.59–8.09), and Stockholm OR 5.54 (2.18–14.79). There was a higher prevalence of asthma and allergic airway inflammation in adult general populations of Sweden and Finland compared to those of Estonia. Atopy and elevated FENO level were independently associated with an increased risk of asthma. In conclusion, the findings support the earlier west-east disparity hypothesis of allergic diseases.

Background: Asthma is currently divided into different phenotypes, with age at onset as a relevant differentiating factor. In addition, asthma with onset in adulthood seems to have a poorer prognosis, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objective: To evaluate incidence of asthma diagnosis at different ages and differences between child- and adult-diagnosed asthma in a large population-based study, with gender-specific analyzes included. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Incidence rate of asthma was retrospectively estimated based on the reported age of asthma onset. Adult-diagnosed asthma was defined as a physician-diagnosis of asthma made at >= 18 years of age. Results: Among those with physician-diagnosed asthma, altogether, 63.7% of subjects, 58.4% of men and 67.8% of women, reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) and the average incidence rate during the examined period between 1946 and 2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among those with physician-diagnosed asthma by age of 50 years and 38 years in men and women, respectively. Conclusions: Asthma is mainly diagnosed during adulthood and the incidence of asthma diagnosis peaks in middle-aged women. Asthma diagnosed in adulthood should be considered more in clinical practice and management guidelines.

Fractional exhaled nitric oxide (F-ENO) is used to assess eosinophilic inflammation of the airways. F-ENO values are influenced by the expiratory flow rate and orally produced NO. We measured F-ENO at four different expiratory flow levels after two different mouthwashes: tap water and carbonated water. Further, we compared the alveolar NO concentration (C-ANO), maximum airway NO flux (J(awNO)) and airway NO diffusion (D-awNO) after these two mouthwashes. F-ENO was measured in 30 volunteers (healthy or asthmatic) with a chemiluminescence NO-analyser at flow rates of 30, 50, 100 and 300mL/s. A mouthwash was performed before the measurement at every flow rate. The carbonated water mouthwash significantly reduced F-ENO compared to the tap water mouthwash at all expiratory flows: 50mL/s (p

Background: Asthma phenotypes can be differentiated by age of disease onset, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objectives: To evaluate incidence of asthma diagnosis at different ages and dominance between child- and adult-diagnosed asthma in a population-based study, by gender. Methods: In February 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Adult-diagnosed asthma was defined as physician-diagnosis of asthma made at ≥ 18 years of age. Results: Prevalence of physician-diagnosed asthma was 11.2%. Among those with asthma, altogether, 63.7% (95% CI 59.0-68.1%) of subjects, 58.4% (51.2-65.2%) of men and 67.8% (61.6-73.3%) of women (p=0.046), reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) (Figure 1). The average incidence rate during the examined period 1946-2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among asthmatics by age of 50 years and 38 years in men and women, respectively. Conclusion: Asthma is mainly diagnosed in adulthood and the incidence of asthma diagnosis peaks in middle-aged women.

Background: Onset of allergic asthma has a strong association with childhood. Much less is known about adult onset asthma and its association with allergy.Objectives: To assess the proportion of al ...

Inspiratory spirometry is used in evaluation of upper airway disorders e.g. fixed or variable obstruction. There are, however, very few published data on normal values for inspiratory spirometry. The main aim of this study was to produce reference values for inspiratory spirometry for healthy Finnish adults.Inspiratory spirometry was preplanned to a sample of the Finnish spirometry reference values sample. Data was successfully retrieved from 368 healthy nonsmoking adults (132 males) between 19 and 83years of age. Reference equations were produced for forced inspiratory vital capacity (FIVC), forced inspiratory volume in one second (FIV1), FIV1/FIVC, peak inspiratory flow (PIF) and the ratios of FIV1/forced expiratory volume in one second and PIF/peak expiratory flow. The present values were compared to PIF values from previously used Finnish study of Viljanen etal. (1982) reference values and Norwegian values for FIV1, FIVC and FIV1/FIVC presented by Gulsvik etal. (2001). The predicted values from the Gulsvik etal. (2001), provided a good fit for FIVC, but smaller values for FIV1 with mean 108.3 and 109.1% of predicted values for males and females, respectively. PIF values were 87.4 and 91.2% of Viljanen etal. (1982) predicted values in males and females, respectively. Differences in measurement methods and selection of results may contribute to the observed differences. Inspiratory spirometry is technically more demanding and needs repeatability criteria to improve validity. New reference values are suggested to clinical use in Finland when assessing inspiratory spirometry. Utility of inspiratory to expiratory values indices in assessment of airway collapse need further study.

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R2 = 0.71; p

The objective of this study was to evaluate associations between the breathing sound spectra and glottal dimensions in exercise-induced vocal cord dysfunction (EIVCD) during a bicycle ergometry test. Nineteen subjects (mean age 21.8 years and range 13–39 years) with suspected EIVCD were studied. Vocal folds were continuously imaged with videolaryngoscopy and breathing sounds were recorded during the bicycle exercise test. Twelve subjects showed paradoxical movement of the vocal folds during inspiration by the end of the exercise. In seven subjects, no abnormal reactions in vocal folds were found; they served as control subjects. The glottal quotient (interarytenoid distance divided by the anteroposterior glottal distance) was calculated. From the same time period, the tracheal–vocal tract resonance peaks of the breathing sound spectra were analyzed, and stridor sounds were detected and measured. Subjects with EIVCD showed significantly higher resonance peaks during the inspiratory phase compared to the expiratory phase (p

K-edge subtraction computed tomography (KES-CT) allows simultaneous imaging of both structural features and regional distribution of contrast elements inside an organ. Using this technique, regional lung ventilation and blood volume distributions can be measured experimentallyin vivo. In order for this imaging technology to be applicable in humans, it is crucial to minimize exposure to ionizing radiation with little compromise in image quality. The goal of this study was to assess the changes in signal-to-noise ratio (SNR) of KES-CT lung images as a function of radiation dose. The experiments were performed in anesthetized and ventilated rabbits using inhaled xenon gas in O2at two concentrations: 20% and 70%. Radiation dose, defined as air kerma (Ka), was measured free-in-air and in a 16 cm polymethyl methacrylate phantom with a cylindrical ionization chamber. The dose free-in-air was varied from 2.7 mGy to 8.0 Gy. SNR in the images of xenon in air spaces was above the Rose criterion (SNR > 5) whenKawas over 400 mGy with 20% xenon, and over 40 mGy with 70% xenon. Although in human thorax attenuation is higher, based on these findings it is estimated that, by optimizing the imaging sequence and reconstruction algorithms, the radiation dose could be further reduced to clinically acceptable levels.

Background: Ventilator-induced lung injury occurs due to exaggerated local stresses, repeated collapse, and opening of terminal air spaces in poorly aerated dependent lung, and increased stretch in nondependent lung. The aim of this study was to quantify the functional behavior of peripheral lung units in whole-lung lavage-induced surfactant depletion, and to assess the effect of positive end-expiratory pressure. Methods: The authors used synchrotron imaging to measure lung aeration and regional specific ventilation at positive end-expiratory pressure of 3 and 9 cm H2O, before and after whole-lung lavage in rabbits. Respiratory mechanical parameters were measured, and helium-washout was used to assess end-expiratory lung volume. Results: Atelectatic, poorly, normally aerated, hyperinflated, and trapped regions could be identified using the imaging technique used in this study. Surfactant depletion significantly increased atelectasis (6.3 ± 3.3 [mean ± SEM]% total lung area; P = 0.04 vs. control) and poor aeration in dependent lung. Regional ventilation was distributed to poorly aerated regions with high (16.4 ± 4.4%; P < 0.001), normal (20.7 ± 5.9%; P < 0.001 vs. control), and low (5.7 ± 1.2%; P < 0.05 vs. control) specific ventilation. Significant redistribution of ventilation to normally aerated nondependent lung regions occurred (41.0 ± 9.6%; P = 0.03 vs. control). Increasing positive end-expiratory pressure level to 9 cm H2O significantly reduced poor aeration and recruited atelectasis, but ventilation redistribution persisted (39.2 ± 9.5%; P < 0.001 vs. control). Conclusions: Ventilation of poorly aerated dependent lung regions, which can promote the local concentration of mechanical stresses, was the predominant functional behavior in surfactant-depleted lung. Potential tidal recruitment of atelectatic lung regions involved a smaller fraction of the imaged lung. Significant ventilation redistribution to aerated lung regions places these at risk of increased stretch injury.

Objective To compare in controlled cardiovascular autonomic function tests the effects of hormone therapy (HT) on heart rate variability (HRV) responses in postmenopausal women with and without pretreatment hot flushes. Design A randomized placebo-controlled trial. Setting Finland, Helsinki University Central Hospital. Population A total of 150 recently postmenopausal and healthy women with prospectively evaluated hot flushes. Methods Women (72 with and 78 without hot flushes) were randomized to receive estradiol alone or in combination with medroxyprogesterone acetate or placebo for 6 months. Time and frequency domain measures of HRV were assessed at baseline and after HT with short-term recordings during paced quiet and deep breathing and with active orthostatic tests, both under carefully controlled laboratory conditions to avoid confounding factors present in long-term ambulatory HRV measurements. Main outcome measures Responses of time and frequency domain measures of HRV to HT. Results At baseline HRV was similar in women with and without hot flushes. Pretreatment hot flushes did not associate with changes in time domain parameters of HRV during controlled quiet or deep breathing or active orthostatic tests after different types of HT. However, HT reduced HRV in very low frequency power in women with pretreatment hot flushes (from 371 ± 40 to 258 ± 28 ms2, p = 0.018). HT did not have an effect on other frequency domain measures during quiet breathing or active orthostatic tests. Conclusions Hormone therapy did not significantly modify the HRV responses in women with or without hot flushes under controlled short-term measurements of the cardiovascular autonomic nervous system.

Our aim was to study the association of smoking habits and environmental tobacco smoke (ETS) exposure with bronchial hyperresponsiveness (BHR). A random sample of 292 adults was examined using a structured interview, spirometry, skin prick tests, exhaled nitric oxide fraction (FeNO) and bronchial histamine challenge. A large majority of subjects with BHR were smokers or ex-smokers. Starting to smoke before 20 years of age was significantly associated with BHR, as was current smoking, quantity of smoking and ETS exposure. The severity of BHR increased significantly with increasing pack-years of exposure (p

The continuing rise in asthma prevalence has been questioned, with recent reports suggesting a plateau. To assess a 10-year trend in the age-adjusted prevalence of physician-diagnosed asthma, respiratory and allergic symptoms, and use of asthma medication in the adult population of Helsinki during the Finnish Asthma Programme from 1994 to 2004. Two cross-sectional postal surveys were conducted among random Finnish National Population Registry samples 10 years apart using the same protocol. A total of 6,062 subjects (75.9%) and 2,449 subjects (61.9%) participated in 1996 and 2006, respectively. The prevalence of physician-diagnosed asthma increased from 6.5% in 1996 to 10.0% in 2006 (p

Introduction: Bronchial hyperresponsiveness (BHR) elevates the risk for development of respiratory symptoms and accelerates the decline in forced expiratory volume in the first second (FEV1). We thus aimed to assess the prevalence, determinants and quantity of BHR in Helsinki. Objectives: This study involved 292 randomly selected subjects age 26–66 years, women comprising 58%. Methods: Following a structured interview, a spirometry, a bronchodilation test, and a skin-prick test, we assessed a bronchial challenge test with inhaled histamine using a dosimetric tidal breathing method. Results included the provocative dose inducing a decrease in FEV1 by 15% (PD15FEV1) and the dose-response slope. For statistical risk factor-analyses, the severity of BHR was considered; PD15 values ≤1.6 mg (BHR) and ≤0.4 mg [moderate or severe BHR (BHRms)] served as cut-off levels. Results: BHR presented in 21.2% and BHRms in 6.2% of the subjects. FEV1

Background : New Finnish (Kainu2015) and international Global Lung Function Initiative (GLI2012) reference values for spirometry were recently published. The aim of this study is to compare the interpretative consequences of adopting these new reference values with older, currently used Finnish reference values (Viljanen1982) in the general population of native Finns. Methods : Two Finnish general population samples including 1,328 adults (45% males) aged 21–74 years were evaluated. Airway obstruction was defined as a reduced ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), possible restrictive pattern as reduced FVC, and decreased ventilatory capacity as reduced FEV1 below their respective 2.5th percentiles. The severity gradings of reduced lung function were also compared. Results : Using the Kainu2015 reference values, the prevalence of airway obstruction in the population was 5.6%; using GLI2012 it was 4.0% and with Viljanen1982 it was 13.0%. Possible restrictive pattern was found in 4.2% using the Kainu2015 values, in 2.0% with GLI2012, and 7.9% with the Viljanen1982 values. The prevalence of decreased ventilatory capacity was 6.8, 4.0, and 13.3% with the Kainu2015, GLI2012 and Viljanen1982 values, respectively. Conclusions : The application of the GLI2012 reference values underestimates the prevalence of abnormal spirometric findings in native Finns. The adoption of the Kainu2015 reference values reduces the prevalences of airways obstruction, decreased ventilatory capacity, and restrictive impairment by approximately 50%. Changing from the 2.5th percentile, the previously used lower limit of normal, to the 5th percentile recommended by the American Thoracic Society/European Respiratory Society will not increase the prevalence of abnormal findings in the implementation of spirometry reference values. Keywords: spirometry; reference values; GLI2012; obstruction; restriction; severity grading (Published: 6 September 2016) Citation: European Clinical Respiratory Journal 2016, 3: 30658 - http://dx.doi.org/10.3402/ecrj.v3.30658

Background Diagnostic assessment of lung function necessitates up-to-date reference values. The aim of this study was to estimate reference values for spirometry for the Finnish population between 18 and 80 years and to compare them with the existing Finnish, European and the recently published global GLI2012 reference values. Methods Spirometry was performed for 1380 adults in the population-based FinEsS studies and for 662 healthy non-smoking volunteer adults. Detailed predefined questionnaire screening of diseases and symptoms, and quality control of spirometry yielded a sample of 1000 native Finns (387 men) healthy non-smokers aged 18–83 years. Sex-specific reference values, which are estimated using the GAMLSS method and adjusted for age and height, are provided. Results The predicted values for lung volumes are larger than those obtained by GLI2012 prediction for the Caucasian subgroup for forced vital capacity (FVC) by an average 6·2% and 5·1% and forced expiratory volume in 1 s (FEV1) by an average 4·2% and 3·0% in men and women, respectively. GLI2012 slightly overestimated the ratio FEV1/FVC with an age-dependent trend. Most reference equations from other European countries, with the exception of the Swiss SAPALDIA study, showed an underestimation of FVC and FEV1 to varying degrees, and a slight overestimation of FEV1/FVC. Conclusion This study offers up-to-date reference values of spirometry for native Finns with a wide age range. The GLI2012 predictions seem not to be suitable for clinical use for native Finns due to underestimation of lung volumes., published version, peerReviewed

Although fractional exhaled nitric oxide (FENO) measurement is a widely used method to assess eosinophilic bronchial inflammation, knowledge on extrabronchial factors affecting measurement results is still limited. Our aim was to study the eventual modifying effect of mouth wash on FENO values and their variability.A total of 16 healthy Caucasian women performed FENO measurements with a chemiluminescence analyzer according to ATS guidelines (2005), with an exhalation flow rate of 50 ml/s against a flow resistor. On the first day three successive FENO measurements were performed: first after mouth wash with water containing sodium and potassium bicarbonates, and thereafter twice without mouth wash. On the second day, the FENO measurement was first performed without mouth wash, then with preceding mouth wash twice, and finally without preceding mouth wash. Each FENO measurement consisted of three measurements with the average reported and the time interval between the FENO measurements was 10 minutes on both days.The FENO level increased significantly in the subsequent measurements performed without mouth wash (p0.01), when the baseline measurement was performed with mouth wash. On the second day, the FENO level decreased significantly in measurements performed with preceding mouth wash, compared with the first measurement without preceding mouth wash (p0.01).The results indicate a slight but statistically significant decreasing effect of mouth wash on the FENO. The findings suggest that mouth wash prior to FENO measurement could standardize the measurement procedure, by decreasing the effect of NO produced in the mouth on the measurement result.

Objective: To assess the effects of positive end-expiratory pressure on regional ventilation distribution in normal lung and after histamine-induced bronchoconstriction. Design: Experimental study. Setting: International research laboratory. Subjects: Six healthy New Zealand rabbits weighing 2.5 ± 0.1 kg. Interventions: Rabbits were anesthetized, tracheostomized, paralyzed, and mechanically ventilated. Synchrotron radiation computed tomography images of tissue density and specific ventilation were acquired using K-edge subtraction imaging with inhaled stable xenon gas in middle and caudal thoracic levels on 0 and 5 cm H2O positive end-expiratory pressure at baseline and twice after histamine inhalation. Measurements and Main Results: At baseline, a positive end-expiratory pressure of 5 cm H2O significantly increased lung volume. Histamine inhalation caused patchy areas of decreased specific ventilation, including some areas with no ventilation. After histamine, positive end-expiratory pressure significantly increased the area of well-ventilated lung regions and decreased the heterogeneity of specific ventilation. This improvement went together with a significant but limited increase in the area of hyperinflated lung zones. Conclusions: The findings of this study suggest that in mechanically ventilated rabbit with severely heterogeneous bronchoconstriction, a positive end-expiratory pressure of 5 cm H2O significantly improves regional ventilation homogeneity through dilation of flow-limited airways and recruitment of closed airways.

A current problem after single lung transplantation is the evaluation of graft function during various pathologic conditions of the transplanted lung. In 10 single lung recipients, of which six had a parenchymal lung disease, and four pulmonary hypertension, relative perfusion of the transplanted lung $$(\dot Q_{tx} )$$ was determined with multidetector 133-Xe radiospirometry. The determinations were performed seven times during acute rejection, nine times during infection, and four times during simultaneous rejection and infection. In the patients with a follow-up period over 5 months, the effect of bronchiolitis obliterans syndrome on perfusion was assessed as well. Statistically significant decrease in the $$\dot Q_{tx} $$ was observed during acute rejection, whereas the perfusion change during infection was not significant. The $$\dot Q_{tx} $$ tended to decrease during long-term follow-up, and the decrease was more prominent in the patients who developed bronchiolitis obliterans syndrome. The assessment of the $$\dot Q_{tx} $$ with radiospirometry distinguishes acute rejection from infection and can be used for differential diagnostic aid after single lung transplantation.