Diagnoses and prescription patterns among users of medications for obstructive airway diseases in Finland.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common diseases mostly treated in primary care. However, the usage patterns of drugs for obstructive airway diseases (R03 drugs) at the national level are not known. OBJECTIVE: The aims of this study were to describe (1) for which diagnoses each class of R03 drugs were used, (2) the usage pattern of different drug classes for asthma and COPD, and (3) how often these medications were used without a diagnosis of asthma or COPD in Finland. METHODS: We sent questionnaires that included questions on physician-diagnosed asthma and COPD to a random sample of 2000 Finnish subjects who had been dispensed R03 medications in the previous year. Details of R03 medications dispensed were retrieved from national registries. RESULTS: Altogether, 803 subjects (40.6%) responded. Of these, 61.6% had asthma, 5.7% had both asthma and COPD, 5.1% had COPD, and 27.5% had neither asthma nor COPD. Among subjects with asthma or asthma and COPD, inhaled corticosteroids (ICS) were the most frequently dispensed class of drugs (93.7% and 97.8%, respectively). Even among subjects with COPD, ICS were dispensed as frequently (68.3%) as long-acting bronchodilators (70.7%). Antileukotrienes were dispensed mainly to asthmatic individuals only (18.4%) but far less frequently than ICS. The use of theophylline and roflumilast was rare. CONCLUSIONS: R03 medications are dispensed far more frequently for asthma than for COPD and often also for subjects without asthma or COPD. In line with guidelines, asthma is treated mainly with ICS, but there seems to be overuse of ICS for COPD.

Association of temperature and absolute humidity with incidence of exercise-induced bronchoconstriction in children.

AIM: Exercise test outdoors is widely used to diagnose asthma in children, but it is unclear how much outdoor air factors affect the results. METHODS: We analysed 321 outdoor exercise challenge tests with spirometry in children 6-16 years conducted due to suspicion of asthma or for assessing the effect of medication on asthma. We studied the association of FEV1 decrease and incidence of exercise-induced bronchoconstriction (EIB) with temperature, relative humidity (RH) and absolute humidity (AH). RESULTS: Asthma was diagnosed in 57% of the subjects. AH ≥5 g/m3, but not RH or temperature, was associated with the EIB incidence (p = 0.035). In multivariable logistic regression, AH ≥5 g/m3 was negatively associated (OR = 0.51, 95% CI [0.28─0.92], p = 0.026) while obstruction before exercise (OR = 2.11, 95% CI [1.16─3.86], p = 0.015) and IgE-mediated sensitisation were positively associated with EIB (OR = 2.24, 95% CI [1.11─4.51], p = 0.025). AH (r = -0.12, p = 0.028) and temperature (r = -0.13, p = 0.023) correlated with decrease in FEV1. In multivariable linear regression, only AH was associated with FEV1 decrease (coefficient = -0.044, 95% CI [-0.085 to -0.004], p = 0.033). CONCLUSION: AH of outdoor air associates with occurrence and severity of EIB in outdoor exercise tests in children. Care should be taken when interpreting negative outdoor exercise test results if AH of air is high.

Paediatric asthma hospitalisations continue to decrease in Finland and Sweden between 2015 and 2020.

We previously reported a decreasing incidence of paediatric asthma hospitalisations in Finland, but a rather stable trend in Sweden, between 2005 and 2014. We now aimed to investigate the incidence of paediatric asthma hospitalisations in these countries between 2015 and 2020, using Finland's National Hospital Discharge Register and Sweden's National Patient Register, which cover all hospitalisations in the respective countries. From 2015 to 2019, the incidence of paediatric asthma hospitalisations decreased by 36.7% in Finland and by 39.9% in Sweden and are increasingly approaching parity. In 2020, despite differences in COVID-19-related restrictions, asthma hospitalisations decreased by over 40%, thus warranting future research on the subject.

Higher prevalence but later age at onset of asthma in cross-country skiers compared with general population.

Cross-country skiing causes strain in the airways because skiers train and compete in cold air. The aim of this survey was to investigate the prevalence and age at onset of asthma, asthma control, and use of asthma medication in Finnish competitive cross-country skiers. All cross-country skiers who were enrolled in the largest national competitions in winter 2019 (n = 1282) were invited to the study via the Finnish Ski Association. A control group (n = 1733) was matched for the responding skiers by age, gender, and region. The response rate was 27.4% (n = 351) for skiers and 19.5% (n = 338) for the controls. The prevalence of asthma was 25.9% in skiers and 9.2% in the controls (p < 0.001). Median (IQR) age at first asthma-related symptoms was higher in skiers than in the controls (13.0 (8.25-16.0) vs. 8.0 (2.25-11.75) years, p < 0.001), and the difference in asthma prevalence was evident only after the start of skiing career. Median (IQR) Asthma Control Test (ACT) score in skiers and controls with asthma was 22.0 (21-24) vs. 22.0 (19-24) (p = 0.611), and 89.0% of skiers and 77.4% of controls had well-controlled asthma (ACT score ≥20). In skiers with asthma, 82.4% used regular inhaled corticosteroids (ICS), and 80.2% used bronchodilators. A fixed combination of ICS +long-acting ß2-agonist was regularly used by 47.3% of the skiers and 22.6% of the controls with asthma (p = 0.016). In conclusion, asthma prevalence is about 2.5 times higher, and age at onset of asthma is later in skiers compared with the controls. Asthma in cross-country skiers is mostly well controlled and on regular maintenance treatment.

Risk factors for severe adult-onset asthma: a multi-factor approach.

BACKGROUND: The aim was to identify risk factors for severe adult-onset asthma. METHODS: We used data from a population-based sample (Adult Asthma in Finland) of 1350 patients with adult-onset asthma (age range 31-93 years) from Finnish national registers. Severe asthma was defined as self-reported severe asthma and asthma symptoms causing much harm and regular impairment and ≥ 1 oral corticosteroid course/year or regular oral corticosteroids or waking up in the night due to asthma symptoms/wheezing ≥ a few times/month. Sixteen covariates covering several domains (personal characteristics, education, lifestyle, early-life factors, asthma characteristics and multiple morbidities) were selected based on the literature and were studied in association with severe asthma using logistic regressions. RESULTS: The study population included 100 (7.4%) individuals with severe asthma. In a univariate analysis, severe asthma was associated with male sex, age, a low education level, no professional training, ever smoking, ≥ 2 siblings, ≥ 1 chronic comorbidity and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) (p < 0.05), and trends for association (p < 0.2) were observed for severe childhood infection, the presence of chronic rhinosinusitis with nasal polyps, and being the 1st child. The 10 variables (being a 1st child was removed due to multicollinearity) were thus entered in a multivariate regression model, and severe asthma was significantly associated with male sex (OR [95% CI] = 1.96 [1.16-3.30]), ever smoking (1.98 [1.11-3.52]), chronic comorbidities (2.68 [1.35-5.31]), NERD (3.29 [1.75-6.19]), and ≥ 2 siblings (2.51 [1.17-5.41]). There was a dose-response effect of the total sum of these five factors on severe asthma (OR [95% CI] = 2.30 [1.81-2.93] for each one-unit increase in the score). CONCLUSIONS: Male sex, smoking, NERD, comorbidities, and ≥ 2 siblings were independent risk factors for self-reported severe asthma. The effects of these factors seem to be cumulative; each additional risk factor gradually increases the risk of severe asthma.

Reduced expiratory variability index (EVI) is associated with controller medication withdrawal and symptoms in wheezy children aged 1-5 years.

BACKGROUND: Lung function testing is an essential part of diagnostic workup and monitoring of asthma, but young children are lacking easy, routine testing methods. However, recent discoveries show reduced tidal breathing variability measured using impedance pneumography (IP) at home during sleep as a sign of airway obstruction. In this study, we assessed (a) the discriminative capacity of expiratory variability index (EVI) between healthy controls and young children with recurrent wheeze on-and-off controller medication, (b) association between EVI and parentally perceived obstructive symptoms (need for bronchodilator) and (c) measurement success rate. METHODS: We included 68 patients (aged 1.0-5.6) and 40 healthy controls (aged 1.0-5.9 years). The patients were prescribed a three-month inhaled corticosteroid (ICS) treatment due to recurrent obstructive bronchitis. We measured EVI using IP at home at the end of the treatment (0W) and 2 (2W) and 4 (4W) weeks after ICS withdrawal. RESULTS: EVI was higher in controls than in patients, and significant within-patient reduction occurred at 4W as compared to 2W or 0W. Area under curve of the ROC curve (controls vs all patients) at 4W was 0.78 (95% CI 0.70-0.85). Children who were administered bronchodilator by parental decision had lower EVI than those without bronchodilator need at 4W, but not at 0W or 2W. Patients with parent-reported airway infection, but no bronchodilator need, had normal EVI. Measurement success rate was 94%. CONCLUSION: EVI was lower in patients than in controls and it reduced further after controller medication withdrawal, especially in the presence of parentally perceived wheeze symptoms. This technique shows a significant potential for routine lung function testing of wheezy young children.

The use of short-acting beta-2 adrenergic receptor agonists for asthma increased among Finnish and Swedish children from 2006 to 2017.

AIM: Paediatric asthma hospitalisation has decreased in Finland, but has remained stable in Sweden. The reasons for these intercountry differences are unclear. The aim of this study was to explore the trend of dispensed asthma medication, including inhaled corticosteroids (ICS), among paediatric populations in the two countries. METHODS: We explored trends in dispensed asthma medication among paediatric populations aged 0-19 in Finland and Sweden from 2006 to 2017. The Finnish Statistics on Reimbursements for Prescription Medicines and The Swedish Prescribed Drug Register provided data on all dispensed asthma prescriptions. RESULTS: During the study period, the prevalence of dispensed ICS in paediatric populations was fairly stable in Finland and Sweden. Among children aged 0-4, ICS were 1.5 times more commonly dispensed in Sweden than in Finland. The prevalence of children dispensed short-acting beta-2 adrenergic receptor agonists (SABA) increased in both countries, but rose more in Finland (51%) than in Sweden (27%). CONCLUSION: Inhaled corticosteroids were more commonly dispensed for children aged 0-4 in Sweden than in Finland during the study period. This study showed an increasing prevalence of children dispensed SABA in Finland and Sweden, particularly in Finland. Differences and trends in asthma medication may effect asthma hospitalisation and asthma deaths.

Risk of adult-onset asthma increases with the number of allergic multimorbidities and decreases with age.

BACKGROUND: The aim was to study the association between allergic multimorbidity and adult-onset asthma considering the number of allergic diseases and the age effect. METHODS: We used population-based data from Finnish national registers including 1205 adults over 30 years of age with recently diagnosed asthma (age range: 30-93), matched for gender, age, and living region with one or two controls (n = 2050). Allergic rhinitis (AR), allergic conjunctivitis (AC), and allergic dermatitis (AD) were defined from self-completed questionnaire. Conditional logistic regression adjusted on potential confounders (smoking, growing in countryside, childhood hospitalized infection/pneumonia, parental asthma/allergy, parental smoking, education level, professional training, number of siblings, and birth order) was applied to estimate the asthma risk associated with allergic multimorbidity. RESULTS: A total of 1118 cases with asthma and 1772 matched controls were included [mean (SD, min-max) 53 (11, 31-71) years, 37% men)]. AR, AC, and AD were reported by 50.2%, 39.6%, and 33.8%, respectively, among subjects with asthma and 26.1%, 20.0%, and 23.5%, respectively, among controls. Compared to nonatopics, adult-onset asthma increased with the number of allergic diseases; adjusted OR for asthma [95% CI] associated with 1, 2, and 3 allergic diseases was 1.95 [1.52-2.49], 2.87 [2.19-3.77], and 4.26 [3.07-5.90], respectively. The association between adult-onset asthma and ≥ 1 allergic multimorbidity decreased with increasing age (3.52 [2.51-4.94], 2.44 [1.74-3.42], and 1.68 [1.04-2.71]) in subjects < 50 years, 50-62 years, and > 62 years, respectively (p for age*≥1 allergic multimorbidity interaction, 0.002). CONCLUSIONS: Adult-onset asthma was positively associated with the number of allergic diseases, and this association decreases with age.

Trends in paediatric asthma hospitalisations - differences between neighbouring countries.

Paediatric asthma hospitalisation trends in Finland and Sweden over the past 10 years are unclear. We investigated the incidence of paediatric asthma hospitalisations in both countries from 2005 to 2014, using Finland's National Hospital Discharge Register and Sweden's National Patient Register which cover all hospitalisations in the respective countries. During the study period, the incidence of paediatric asthma hospitalisations decreased by 51% in Finland, but remained stable in Sweden. In both countries, asthma hospitalisations decreased over time among children aged 0-4 years, with unclear trends for older ages. The reasons for these intercountry differences are unclear, thus warranting future research.

The Finnish experience to save asthma costs by improving care in 1987-2013.

The Finnish National Asthma Program 1994-2004 markedly improved asthma care in the 1990s. We evaluated the changes in costs during 26 years from 1987 to 2013. Direct and indirect costs were calculated by using data from national registries. Costs from both the societal and patient perspectives were included. The costs were based on patients with persistent, physician-diagnosed asthma verified by lung function measurements. We constructed minimum and maximum scenarios to assess the effect of improved asthma care on total costs. The number of patients with persistent asthma in the national drug reimbursement register increased from 83,000 to 247,583. Improved asthma control reduced health care use and disability, resulting in major cost savings. Despite a 3-fold increase in patients, the total costs decreased by 14%, from €222 million to €191 million. Costs for medication and primary care visits increased, but overall annual costs per patient decreased by 72%, from €2656 to €749. The theoretical total cost savings for 2013, comparing actual with predicted costs, were between €120 and €475 million, depending on the scenario used. The Finnish Asthma Program resulted in significant cost savings at both the societal and patient levels during a 26-year period.

Self-Reported Allergic Rhinitis and/or Allergic Conjunctivitis Associate with IL13 rs20541 Polymorphism in Finnish Adult Asthma Patients.

BACKGROUND: Our aim was to observe factors associated with IL13 rs20541 polymorphism and other factors with or without allergic comorbidities such as subject-reported allergic rhinitis (AR) and/or allergic conjunctivitis (AC) symptoms in adult asthmatics. METHODS: A population-based sample of Finnish adult asthma patients (n = 1,156) and matched controls (n = 1,792) filled in a questionnaire. Asthma was diagnosed based on a typical history of asthma symptoms and lung function tests. Skin prick tests with 17 aeroallergens and blood tests including analysis of interleukin 13 (IL13) rs20541 (G/A) genotypes were performed for a subsample (n = 193). RESULTS: The proportion of asthmatics reporting AR was 61.9% and reporting AC was 40.7%. After adjustments, the presence of the IL13 rs20541A- allele (OR 3.06, 95% CI 1.42-6.58, p = 0.004) or multisensitization (adjusted OR 4.59, 95% CI 1.48-14.26, p = 0.008) was associated with AR/AC asthma. Nasal polyps and acetylsalicylic acid-exacerbated respiratory disease was also associated with AR/AC asthma. CONCLUSIONS: Adult AR/AC asthma could putatively be a phenotype, characterized by the presence of atopic and/or eosinophilic factors and a high prevalence of the IL13 rs20541A- allele. Studies on the mechanisms behind this and in other populations are needed.

[Work aggravated asthma]. / Tyon pahentama astma.

One out of five working persons with asthma has work-related respiratory symptoms. When exploring the symptoms of a working-age patient it is essential to survey the job description and working conditions. Early intervention in the factors aggravating the respiratory symptoms will decrease morbidity, maintain working capacity and improve the quality of life. Occupational health service and the employer play a central role in identifying and decreasing the exposure factors in the working environment as well as in patient guidance for asthma therapy and protecting from the stimuli. The working capacity of an asthmatic person can be improved by applying vocational rehabilitation.

[Irritant-induced asthma]. / Ärsytyksen aiheuttama astma.

Irritant-induced asthma is a rare disease, usually being caused by an accidental or other exceptionally strong exposure to substances irritating the respiratory passages. High-dose inhaled corticosteroid medication is immediately started at the emergency call service. If severe exposure is suspected, it is important to monitor the patient at least for a couple of days in hospital. Immediately after the acute stage diagnostic investigations are carried out, including a metacholine or histamine challenge test, since demonstration of airway hyperreactivity is of diagnostic and prognostic significance. The asthma may remain permanent.

Relation of changes in PEF and FEV1 in exercise challenge in children.

Decrease in forced expiratory volume in one second (FEV1 ) of 10% or 15% in exercise challenge test is considered diagnostic for asthma, but a decrease of 15% in peak expiratory flow (PEF) is recommended as an alternative. Our aim was to assess the accuracy of different PEF cut-off points in comparison to FEV1 . We retrospectively studied 326 free running exercise challenge tests with spirometry in children 6-16 years old. FEV1 and PEF were measured before and 2, 5, 10 and 15 min after exercise. Receiver operating characteristics (ROC) analysis, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and Ï°-coefficient were used to analyse how decrease in PEF predicts decrease of 10% or 15% in FEV1 . In the ROC analysis, areas under the curve were 0.851 (p < 0.001) and 0.921 (p < 0.001) for PEF decrease to predict a 10% and 15% decrease in FEV1 , respectively. The agreement between changes in PEF and FEV1 varied from slight to substantial (Ï° values of 0.199-0.680) depending on the cut-points. Lower cut-off for decrease in PEF had higher sensitivity and NPV, while higher cut-off values had better specificity and PPV. Decrease of 20% and 25% in PEF seemed to be the best cut-offs for detecting 10% and 15% decrease in FEV1 , respectively. Still, a fifth of the positive findings based on PEF were false. Change in PEF is not a precise predictor of change in FEV1 in exercise test. The currently recommended cut-point of 15% decrease in PEF seems to be too low and leads to high false positive rate.

Relation of changes in peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) during bronchoconstriction.

Diagnosis of asthma can be confirmed based on variability in peak expiratory flow (PEF) or changes in forced expiratory volume in 1 s (FEV1) measured with spirometry. Our aim was to use methacholine challenge as a model of induced airway obstruction to assess how well relative changes in PEF reflect airway obstruction in comparison to relative changes in FEV1. We retrospectively studied 878 patients who completed a methacholine challenge test. To assess congruency along with differences between relative changes in FEV1 and PEF during airway obstruction, a regression analysis was performed, and a Bland & Altman plot was constructed. ROC analysis, sensitivity, specificity, positive and negative predictive values and κ-coefficient were used to analyze how decrease in PEF predicts decrease of 10% or 15% in FEV1. The relative change in PEF was on average less than the relative change in FEV1. In the ROC analysis areas under the curve were 0.844 and 0.893 for PEF decrease to predict a 10% and 15% decrease in FEV1, respectively. The agreement between changes in PEF and FEV1 varied from fair to moderate. Airway obstruction detected by change in PEF was false in about 40% of cases when compared to change in FEV1. Change in PEF is not a very accurate measure of airway obstruction when compared to change in FEV1. Replacing peak flow metre with a handheld spirometer might improve diagnostic accuracy of home monitoring in asthma.

Comorbidities associated with adult asthma: a population-based matched cohort study in Finland.

BACKGROUND: Asthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%-10% of the adult population. Adult asthma is associated with higher all-cause mortality compared to individuals without asthma. In this study, we investigate the comorbidities that may affect the management of asthma. METHODS: Total of 1648 adults with asthma and 3310 individuals without asthma aged 30-93 were matched with age, gender and area of residency, and followed from 1 January 1997 to 31 December 2013. Baseline information was collected with questionnaires 1997 and follow-up register data from the national discharge registry Finnish Institute for Health and Welfare. Data included diagnoses from outpatient care and day surgery of specialised health care, and data from inpatient care of specialised and primary health care. We included all main diagnoses that had at minimum 200 events and number of diagnoses based on their common appearance with adult asthma. RESULTS: The mean follow-up time varied between 14.2 and 15.1 years, and age at the time of enrolment was 53.9 years for subjects without asthma and 54.4 years for patients with asthma. Chronic obstructive pulmonary disease was 10 times more common among asthmatics. Risk of acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis and vocal cord dysfunction was fourfold and risk of pneumonia, and chronic rhinosinusitis was 2.5 times more common among asthmatics. Sleep apnoea, gastro-oesophageal reflux disease, diabetes, allergic rhinitis and dysfunctional breathing were twofold and cataract nearly twofold higher in the asthmatic group. Adult asthma was also significantly associated with musculoskeletal diseases, incontinence and bronchiectasis. CONCLUSIONS: The most common and most severe comorbidity of adult asthma in this study was chronic obstructive pulmonary disease. Other common comorbidities of adult asthma include acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, allergic rhinitis, dysfunctional breathing, diabetes, pneumonia, sleep apnoea and gastro-oesophageal reflux disease.

Salbutamol Easyhaler provides non-inferior relief of methacholine induced bronchoconstriction in comparison to Ventoline Evohaler with spacer: A randomized trial.

BACKGROUND: Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event. OBJECTIVE: We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed. METHODS: This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV1) were randomized to receive Salbutamol Easyhaler (2 × 200 µg), Ventoline Evohaler with spacer (4 × 100 µg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 µg) as a reliever. The treatment was repeated if FEV1 did not recover to at least -10 % of baseline. RESULTS: 180 participants (69 % females, mean age 46 yrs [range 18-80], FEV1%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV1 difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV1 between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose. CONCLUSION: The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.