J Hedman’s research while affiliated with South Karelia Central Hospital and other places

Background An investigator‐driven, real‐life follow‐up study of adult‐onset steroid‐naïve, newly diagnosed asthma (162 patients) to investigate the treatment results over the 25‐year course of the disease and whether the first treatment year's forced expiratory volume in one second (FEV1) predicts the long‐term prognosis. Methods Eighty‐three per cent of the 133 living patients participated in the 25‐year examinations. At this visit, basic asthma examinations including lung function, as well as questionnaires for health‐related quality of life (HRQoL), GINA and the Asthma Control Test, were used for evaluation. The use of medication and remission was verified. Results There was no statistically significant change in mean FEV1% predicted (FEV1%) from baseline to the 25‐year control. The changes in FEV1% during the first year predicted the results at the end of follow‐up. Normal FEV1% at the end of the first year predicted normal FEV1, and below‐normal FEV1% at 1 year predicted below‐normal FEV1% at 25 years. Twenty‐nine patients (26.4%) had discontinued their medication, and six (5.5%) used ICS periodically. Clinical remission was reached by 16.4% of the patients, and 7.6% reached functional remission. The general HRQoL remained unchanged. Conclusion In adult‐onset asthma, the level of FEV1 reached during the first treatment year seems to predict the later lung function level. One quarter of the patients discontinued the asthma treatment, but their HRQoL was better than that of those continuing to use ICS. Clinical remission was reached by 16% of the patients, which is in concordance with other studies.

We have shown that salt chamber treatment reduces airway hyper-responsiveness as an add-on therapy in adult asthmatics on inhaled corticosteroids. We assessed whether this effect is due to the suppression of eosinophilic airway inflammation. Thirty-nine adult asthmatics on inhaled corticosteroids were randomized to receive active salt chamber treatment with low-salt treatment 6.6 mg/m3 (n = 14), high-salt treatment 10.8 mg/m3 (n = 15) or placebo 0.3 mg/m3 (n = 10) 10 times in a 2 weeks' period in a double-blind manner. The level of induced sputum eosinophilic cationic protein μg/l, was 3070 before and 4651 after the low-salt treatment period, on average. In the high-salt treatment group, it was 12 192 μg/l vs 11 803 and in the placebo group 3942 vs 4144, respectively. Salt chamber treatment had no effect on sputum eosinophil or neutrophil cell numbers. The reduction in hyper-responsiveness observed in the previous study is probably not due to the effect on eosinophilic inflammation.

Sarcoidosis is a multiorgan immune-mediated disease of unknown etiology with varying clinical pictures. We studied 3 genes in the major histocompatibility complex region (HLA-DRB1 and complement C4A and C4B) in patients with resolved disease after a 2-year follow-up (n = 90) and in patients whose disease was still active at that time point (n = 98) and compared them with controls (n = 150). Our primary aim was to detect genetic differences between the patient groups. We observed that the susceptibility allele for sarcoidosis was HLA-DRB1*15:01 (p = 0.011; odds ratio [OR] = 1.67) and the protective allele was HLA-DRB1*01:01 (p = 0.001; OR = 0.43). HLA-DRB1*03:01 was associated with resolving disease when compared with the persistent group (p = 0.011; OR = 2.22). The probability of having resolving disease was even greater if the patient had HLA-DRB1*03:01 and did not have extrapulmonary lesions (p = 0.001; OR = 3.39). By evaluating amino acid variants of the HLA-DRB1 gene, we determined that specific amino acids in pockets 4, 7, and 9 were associated with the prognosis of sarcoidosis. Our results support the importance of HLA-DRB1 as a predisposing gene for sarcoidosis. Particularly, HLA-DRB1*03:01 and polymorphisms of DRB1 pocket residues were associated with a favorable prognosis. Thus, accurate categorization of disease phenotype and HLA-DRB1 sequencing offer a basis for disease course estimation of sarcoidosis.

We assessed the 10-year effectiveness of self-management guidance in a prospective follow-up study of patients with asthma when inhaled corticosteroids were used from the beginning in the treatment. Consecutive newly diagnosed asthmatics (n = 162) were randomized: 80 to an intervention group (IG) and 82 to a control group (CG). Lung function (LF), airway hyperresponsiveness (AHR), and health-related quality of life (HRQoL) were examined at 10 years. The advantages of intensive education with regards to LF measured by forced expiratory volume in 1 second and forced vital capacity were seen only after the first year. Later, there were no statistically significant differences in any parameters between the groups. However, during 10-year follow-up, peak expiratory flow, AHR, and HRQoL improved significantly in both groups (no differences as regards gender, smoking, or atopy). At 10 years, 68% of the IG and 75% of the CG patients still showed AHR after histamine challenge. Generic HRQoL scores in both groups equaled that of the age-standardized group a general population but only 50% in the IG and 55% in the CG had normal disease-specific HRQoL scores. According to Global Initiative for Asthma (GINA) criteria 23% of patients in the IG and 25% in the CG had asthma under control. The effectiveness of intensive self-management education could be shown only in the short term. The groups did not differ significantly in any of the parameters investigated, and showed nearly normal LF and HRQoL. AHR improved only partly and only a minority of the patients had asthma under good control according to GINA criteria. This study showed that evaluation of asthma using LF alone does not show the whole truth about asthma treatment results. HRQoL should be used in conjunction with GINA criteria, to assess asthma treatment outcomes. The value and importance of AHR for the evaluation of treatment remains obscure.

The effects of salt chamber treatment on asthmatics

The repeatability of a rapid dosimetric method for methacholine challenge was evaluated with 11 asthmatic patients. A Spira Elektro 2 dosimeter was used for methacholine delivery and a pocket turbine spirometer (Micro Spirometer©) for FEVj measurements. Methacholine was delivered in four successive, increasing doses ranging from 80 μg up to a cumulative dose of 6900 μg. The single determination standard deviation was low (12.5%), corresponding to a 95% confidence interval of ±0.925 doubling doses. The mean difference (±SE) between measurements of log PD20 FEV1 was -0.015 (0.056), and the absolute value of the difference in log PD20 FEV1 was not significantly related to the average log PD20 FEV1 (r = -0.155, P = 0.65). The rapid dosimetric methacholine challenge test, performed with a pocket turbine spirometer, proved to be as reproducible as previous methods. Furthermore, this methacholine challenge is clearly less time consuming than conventional provocations, including bronchodilator aerosol (given to resolve post-challenge bronchoconstriction); the whole test can be performed in 20 min. This is especially valuable in epidemiologic studies, as well as in clinical practice.

Salt chamber treatment in relation to inflammatory markers in asthma patients

Randomized controlled trials are needed to evaluate the effects of complementary treatments in asthma. This study assessed the effect of salt chamber treatment as an add-on therapy to low to moderate inhaled steroid therapy in asthma patients with bronchial hyperresponsiveness (BHR). After a 2-week baseline period, 32 asthma patients who exhibited BHR in the histamine inhalation challenge were randomized: 17 to 2-week active treatment, during which salt was fed to the room by a salt generator, and 15 to placebo. The salt chamber treatment lasted 40 min and was administered five times a week. Median provocative dose causing a decrease of 15% in Fev(1) (PD(15)FEV(1)) [corrected] increased significantly in the active group (P = 0.047) but not in the placebo group. The difference in changes between the active and placebo groups was significant (P = 0.02). Nine patients (56%) in the active group and two patients (17%) in the placebo group exhibited at least one doubling dose decrease in BHR (P = 0.040). Six patients (38%) in the active group and none in the placebo group became non-hyperresponsive (P = 0.017). Neither the peak expiratory flow (PEF) values measured just before and after the treatment, nor FEV(1) values measured before the histamine challenges, changed. The reduction in BHR was not caused by changes in the baseline lung function. Salt chamber treatment reduced bronchial hyperresponsiveness as an add-on therapy in asthmatics with a low to moderate dose of inhaled steroids. The possibility that salt chamber treatment could serve as a complementary therapy to conventional medication cannot be excluded.

Objective: The aim of this study was to compare the bronchodilating effect, tolerability and acceptability of a single 100μg dose of salbutamol inhaled via Easyhaler® multidose dry powder inhaler with a single 250μg dose of terbutaline inhaled via Turbuhaler®, also a multidose dry powder inhaler. Design, Setting and Patients: The study was conducted according to a single-dose, crossover, randomised, double-blind with double-dummy design in four centres in Finland. A total of 29 adult patients with stable asthma without previous experience with the tested devices completed the study, which comprised 2 study days with 4-hour follow-up periods including spirometric measurements. The acceptability of the devices to the patients in the study was also evaluated. Results: The mean (SD) maximum value of forced expiratory volume in 1 second (FEV1max) after salbutamol Easyhaler® was 3.14L (1.26L), and after terbutaline Turbuhaler® was 3.07L(1.11L). The mean (SD) percentage change from baseline of forced expiratory volume in 1 second (FEV1) to FEV1max was 12.7% (12.4%) after Easyhaler® and 13.1% (10.8%) after Turbuhaler®. The observed differences in the increase in FEV1 and in the area under the curve (AUC) of FEV1 between the treatments were not statistically significant. Four patients reported mild adverse events after inhaling salbutamol via Easyhaler®, compared with five patients who reported adverse events after inhaling terbutaline via Turbuhaler®. Based on the VAS assessment of the acceptability, Easyhaler® was found to be better accepted than Turbuhaler® in terms of ease of administration, ease of inhaling, and the strength of sensation on receiving a dose. Overall, 62% of the patients would have chosen Easyhaler®. Conclusions: Easyhaler® containing salbutamol (100μg/dose) is comparable in efficacy and as well tolerated as Turbuhaler® containing terbutaline (250μg/dose), and Easyhaler® was well accepted by patients.

An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 microgram of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. It was concluded that the devices tested were equivalent in terms of efficacy and safety.