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Background: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. Methods: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. Results: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases. Conclusion: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life set

Background: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. Methods: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. Results: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases. Conclusion: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life set

Background: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. Methods: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. Results: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases. Conclusion: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life set

Background: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. Methods: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. Results: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases. Conclusion: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life set

Background: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. Methods: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. Results: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases. Conclusion: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life set

Aim To determine the risk of type 2 diabetes onset associated with accumulated inhaled corticosteroids (ICS) dose during the previous year in patients with chronic obstructive pulmonary disease (COPD).Materials and methods We conducted a nationwide observational cohort study based on data from patients with COPD between 1 January 2010 and 31 December 2017 extracted from Danish health databases. Patients were followed for 7 years, until death or a type 2 diabetes event. A propensity-matched Cox model and an adjusted Cox proportional hazards model (stratified on body mass index [BMI]) were used to estimate the hazard ratio (HR) for new-onset type 2 diabetes.Results A total of 50 148 patients with COPD were included, 3566 (7.1%) of whom had a type 2 diabetes event. During the previous year before study entry, 35 368 patients (70.5%) used ICS. The propensity-matched Cox model (N = 33 466) showed an increased risk of type 2 diabetes, which progressed with increasing accumulated ICS dose (low-ICS: HR 1.076, confidence interval [CI] 1.075-1.077, P <.0001; medium-ICS: HR 1.106, CI 1.105-1.108, P <.0001; high-ICS: HR 1.150, CI 1.148-1.151, P <.0001), compared with no ICS use. Results were confirmed in the adjusted Cox analysis on the entire study population, but only for patients with BMIConclusions In patients with COPD, ICS use was associated with a moderate dose-dependent increase in the occurrence of type 2 diabetes.

Aim To determine the risk of type 2 diabetes onset associated with accumulated inhaled corticosteroids (ICS) dose during the previous year in patients with chronic obstructive pulmonary disease (COPD).Materials and methods We conducted a nationwide observational cohort study based on data from patients with COPD between 1 January 2010 and 31 December 2017 extracted from Danish health databases. Patients were followed for 7 years, until death or a type 2 diabetes event. A propensity-matched Cox model and an adjusted Cox proportional hazards model (stratified on body mass index [BMI]) were used to estimate the hazard ratio (HR) for new-onset type 2 diabetes.Results A total of 50 148 patients with COPD were included, 3566 (7.1%) of whom had a type 2 diabetes event. During the previous year before study entry, 35 368 patients (70.5%) used ICS. The propensity-matched Cox model (N = 33 466) showed an increased risk of type 2 diabetes, which progressed with increasing accumulated ICS dose (low-ICS: HR 1.076, confidence interval [CI] 1.075-1.077, P <.0001; medium-ICS: HR 1.106, CI 1.105-1.108, P <.0001; high-ICS: HR 1.150, CI 1.148-1.151, P <.0001), compared with no ICS use. Results were confirmed in the adjusted Cox analysis on the entire study population, but only for patients with BMIConclusions In patients with COPD, ICS use was associated with a moderate dose-dependent increase in the occurrence of type 2 diabetes.

Objective: To compare the effect of tiotropium bromide and glycopyrronium bromide in the treatment of chronic obstructive pulmonary disease. Methods: This was an open labeled Randomized controlled trial study. Patients diagnosed with COPD according to the Global Initiative for chronic Obstructive Lung Disease (GOLD) strategy were included in the study. The patients were divided in two groups and each group had 100 patients. Group A- COPD patients on Tiotropium bromide + Salmeterol/Fluticasone; Group B – COPD patient on Glycopyrronium bromide + Salmeterol/Fluticasone. Tiotropium bromide: 18 mcg OD, Glycopyrronium bromide: 50 mcg OD along with Salmeterol 50 mcg/Fluticasone 100mcg was given. Results: The mean age of patients of Group A and Group B was 56.28±7.78 and 57.64±8.06 years respectively. Baseline variables were comparable between the groups. There was significant (p<0.05) difference in PFT parameters between the groups at 12 and 24 weeks except for FEV1/FVC. The mean change was higher in Group B compared to Group A from 0 week to 24 weeks. There was clinical improvement among all the patients in both the groups. Conclusion: Once-daily GLY demonstrated similar effects to TIO when combined with SAL/FP in patients with moderate and severe COPD.

Objective: To compare the effect of tiotropium bromide and glycopyrronium bromide in the treatment of chronic obstructive pulmonary disease. Methods: This was an open labeled Randomized controlled trial study. Patients diagnosed with COPD according to the Global Initiative for chronic Obstructive Lung Disease (GOLD) strategy were included in the study. The patients were divided in two groups and each group had 100 patients. Group A- COPD patients on Tiotropium bromide + Salmeterol/Fluticasone; Group B – COPD patient on Glycopyrronium bromide + Salmeterol/Fluticasone. Tiotropium bromide: 18 mcg OD, Glycopyrronium bromide: 50 mcg OD along with Salmeterol 50 mcg/Fluticasone 100mcg was given. Results: The mean age of patients of Group A and Group B was 56.28±7.78 and 57.64±8.06 years respectively. Baseline variables were comparable between the groups. There was significant (p<0.05) difference in PFT parameters between the groups at 12 and 24 weeks except for FEV1/FVC. The mean change was higher in Group B compared to Group A from 0 week to 24 weeks. There was clinical improvement among all the patients in both the groups. Conclusion: Once-daily GLY demonstrated similar effects to TIO when combined with SAL/FP in patients with moderate and severe COPD.

Breast cancer metastasis is facilitated by sympathetic nervous system (SNS) activation, but the role for 2-AR, a major class of SNS receptors, has not been elucidated. The goal of this proposal is to characterize the effects of dexmedetomidine (DEX), a highly selective 2-AR agonist, on tumor metastasis in preclinical models of breast cancer. We tested the hypothesis that 2- AR-induced tumor progression is mediated by alterations in fibrillar collagen microstructure as detected by multiphoton second harmonic generation (SHG) imaging. Using 4T1, a metastatic mammary adenocarcinoma in BALB/c mice, 2-AR activation increased metastasis to the lungs in conjunction with elevated tumor SHG-emitting collagen. DEX did not alter metastasis or tumor SHG in immunodeficient BALB/c SCID mice or in MMTV-PyMT mice. In BALB/c mice treated with a 2-AR-selective agonist, increased 4T1 metastasis was also associated with elevated SHG-emitting collagen. These results suggest 1) increased collagen SHG is indicative of elevated metastatic risk; 2) DEX acts via functional T cells to alter collagen SHG; and 3) the effect of DEX may be dependent on the tumor model. At the low, non-sedative dose used here, DEX did not alter sympathetic neurotransmission, confirming that DEX acts through peripheral, post-synaptic 2-AR to modify tumor collagen. Tumor associated fibroblasts (TAF) were isolated to determine if 2 AR activation directly modulates collagen microstructure., The original document contains color images.

Objectives Combinations of inhaled corticosteroids (ICSs) and long-acting 2-agonists (LABAs) are recommended for patients with moderate and severe chronic obstructive pulmonary disease (COPD). However, it is not known whether different fixed combinations are equally effective. The aim of this study was to investigate exacerbation rates in primary care patients with COPD treated with budesonide/formoterol compared with fluticasone/salmeterol. Methods Patients with physician-diagnosed COPD and a record of postdiagnosis treatment with a fixed combination of budesonide/formoterol or fluticasone/salmeterol were included. Data from primary care medical records were linked to those from Swedish national hospital, drug and cause of death registers. Pairwise (1:1) propensity score matching was carried out at the index date (first prescription) by prescribed fixed ICS/LABA combination. Exacerbations were defined as hospitalizations, emergency visits and collection of oral steroids or antibiotics for COPD. Yearly event rates were compared using Poisson regression. Results Matching of 9893 patients (7155 budesonide/formoterol and 2738 fluticasone/salmeterol) yielded two cohorts of 2734 patients, comprising 19170 patient-years. The exacerbation rates were 0.80 and 1.09 per patient-year in the budesonide/formoterol and fluticasone/salmeterol groups, respectively (difference of 26.6%; P<0.0001); yearly rates for COPD-related hospitalizations were 0.15 and 0.21, respectively (difference of 29.1%; P<0.0001). All other healthcare outcomes were also significantly reduced with budesonide/formoterol versus fluticasone/salmeterol. Conclusions Long-term treatment with fixed combination budesonide/formoterol was associated with fewer healthcare utilization-defined exacerbations than fluticasone/salmeterol in patients with moderate and severe COPD.

Background : Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation. / Methods : Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks....

Background : Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation. / Methods : Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks....

RIVM rapport:Salmeterol, een lang werkzame Beta2-adrenoreceptor agonist, werd bestudeerd in een 28-daagse toxiciteitstest in de Wistar rat. Aandacht werd daarbij geschonken aan parameters voor immunotoxiciteit. Het doel was verder bij te dragen in de validatie van deze immunotoxiciteitstesten voor geneesmiddelen. Mannelijke ratten werden oraal behandeld met 0, 0.2, 2 of 20 mg Salmeterol/kg lichaamsgewicht per dag. Gedurende de loop van het experiment bleek dat de hoogste dosering die was gekozen te hoog was. Om deze reden werd de hoogste dosering teruggebracht tot 10 mg/kg/dag, vanaf dag 9 van de behandeling. Lichaamsgewicht en beenmergcellulariteit werden door de behandeling niet beinvloed. Ook hematologische parameters waren niet veranderd in de behandelde dieren, behalve de aantallen bloedplaatjes, die in alle doseringsgroepen significant verlaagd waren. Ook de gewichten van de levers waren in alle doseringsgroepen afgenomen. Het thymusgewicht was afgenomen in de groepen die waren behandeld met 2 en met 20/10 mg/kg/dag. Er werden geen (histo)pathologische lesies waargenomen in (niet)lymfoide organen, die te relateren waren aan de behandeling. Serum immunoglobuline G spiegels waren toegenomen in de groepen behandeld met 2 en 10/20 mg/kg/dag. Percentages B cellen in de milt waren afgenomen in alle doseringsgroepen. De gegevens van deze studie geven aan dat het panel van immunotoxiciteitstesten zoals hier gebruikt om Salmeterol te onderzoeken in staat is om geringe immunotoxische potentie zoals die uit de literatuur naar voren komt te identificeren. Verder onderzoek zal moeten aangeven wat de functionele consequenties van deze geringe immunotoxiciteit van Salmeterol zijn., Salmeterol, a long-acting Beta2-adrenoreceptor agonist, was studied in a 28-day repeated dose toxicity test in Wistar rats. Attention was paid to immunotoxicity screening parameters incorporated in the study protocol. The aim of this study was to further validate these assays for pharmaceuticals. Male rats were orally treated with 0, 0.2, 2 and 20 mg salmeterol/kg body weight/day. During the course of the study, it appeared that the highest dose level used was too high, and the animals tried to resist intubation, leading to intubation errors and intercurrent death of some of them. Therefore, the magnitude of the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body weight and bone marrow cellularity were not affected, neither were hematological parameters, except for platelet counts that were decreased at all dose levels. Also liver weights were decreased at all dose levels tested. Absolute thymic weights were decreased at the 2 and 20/10 mg/kg/day dose levels. No treatment-related (histo)pathological lesions were seen in (non)lymphoid organs. Serum immunoglobulin G at the 2 and 10/20 mg/kg/day dose level. Numbers of B cells in the spleen were decreased at all dose levels tested. The data indicate that the panel of tests used in this study to examine salmeterol is able to detect the reported low immunotoxic potential. Further research is needed to elucidate whether salmeterol interferes with immune responses in rats upon antigenic challenge.

RIVM rapport:Salmeterol, een lang werkzame Beta2-adrenoreceptor agonist, werd bestudeerd in een 28-daagse toxiciteitstest in de Wistar rat. Aandacht werd daarbij geschonken aan parameters voor immunotoxiciteit. Het doel was verder bij te dragen in de validatie van deze immunotoxiciteitstesten voor geneesmiddelen. Mannelijke ratten werden oraal behandeld met 0, 0.2, 2 of 20 mg Salmeterol/kg lichaamsgewicht per dag. Gedurende de loop van het experiment bleek dat de hoogste dosering die was gekozen te hoog was. Om deze reden werd de hoogste dosering teruggebracht tot 10 mg/kg/dag, vanaf dag 9 van de behandeling. Lichaamsgewicht en beenmergcellulariteit werden door de behandeling niet beinvloed. Ook hematologische parameters waren niet veranderd in de behandelde dieren, behalve de aantallen bloedplaatjes, die in alle doseringsgroepen significant verlaagd waren. Ook de gewichten van de levers waren in alle doseringsgroepen afgenomen. Het thymusgewicht was afgenomen in de groepen die waren behandeld met 2 en met 20/10 mg/kg/dag. Er werden geen (histo)pathologische lesies waargenomen in (niet)lymfoide organen, die te relateren waren aan de behandeling. Serum immunoglobuline G spiegels waren toegenomen in de groepen behandeld met 2 en 10/20 mg/kg/dag. Percentages B cellen in de milt waren afgenomen in alle doseringsgroepen. De gegevens van deze studie geven aan dat het panel van immunotoxiciteitstesten zoals hier gebruikt om Salmeterol te onderzoeken in staat is om geringe immunotoxische potentie zoals die uit de literatuur naar voren komt te identificeren. Verder onderzoek zal moeten aangeven wat de functionele consequenties van deze geringe immunotoxiciteit van Salmeterol zijn., Salmeterol, a long-acting Beta2-adrenoreceptor agonist, was studied in a 28-day repeated dose toxicity test in Wistar rats. Attention was paid to immunotoxicity screening parameters incorporated in the study protocol. The aim of this study was to further validate these assays for pharmaceuticals. Male rats were orally treated with 0, 0.2, 2 and 20 mg salmeterol/kg body weight/day. During the course of the study, it appeared that the highest dose level used was too high, and the animals tried to resist intubation, leading to intubation errors and intercurrent death of some of them. Therefore, the magnitude of the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body weight and bone marrow cellularity were not affected, neither were hematological parameters, except for platelet counts that were decreased at all dose levels. Also liver weights were decreased at all dose levels tested. Absolute thymic weights were decreased at the 2 and 20/10 mg/kg/day dose levels. No treatment-related (histo)pathological lesions were seen in (non)lymphoid organs. Serum immunoglobulin G at the 2 and 10/20 mg/kg/day dose level. Numbers of B cells in the spleen were decreased at all dose levels tested. The data indicate that the panel of tests used in this study to examine salmeterol is able to detect the reported low immunotoxic potential. Further research is needed to elucidate whether salmeterol interferes with immune responses in rats upon antigenic challenge.

RIVM rapport:Salmeterol, een lang werkzame Beta2-adrenoreceptor agonist, werd bestudeerd in een 28-daagse toxiciteitstest in de Wistar rat. Aandacht werd daarbij geschonken aan parameters voor immunotoxiciteit. Het doel was verder bij te dragen in de validatie van deze immunotoxiciteitstesten voor geneesmiddelen. Mannelijke ratten werden oraal behandeld met 0, 0.2, 2 of 20 mg Salmeterol/kg lichaamsgewicht per dag. Gedurende de loop van het experiment bleek dat de hoogste dosering die was gekozen te hoog was. Om deze reden werd de hoogste dosering teruggebracht tot 10 mg/kg/dag, vanaf dag 9 van de behandeling. Lichaamsgewicht en beenmergcellulariteit werden door de behandeling niet beinvloed. Ook hematologische parameters waren niet veranderd in de behandelde dieren, behalve de aantallen bloedplaatjes, die in alle doseringsgroepen significant verlaagd waren. Ook de gewichten van de levers waren in alle doseringsgroepen afgenomen. Het thymusgewicht was afgenomen in de groepen die waren behandeld met 2 en met 20/10 mg/kg/dag. Er werden geen (histo)pathologische lesies waargenomen in (niet)lymfoide organen, die te relateren waren aan de behandeling. Serum immunoglobuline G spiegels waren toegenomen in de groepen behandeld met 2 en 10/20 mg/kg/dag. Percentages B cellen in de milt waren afgenomen in alle doseringsgroepen. De gegevens van deze studie geven aan dat het panel van immunotoxiciteitstesten zoals hier gebruikt om Salmeterol te onderzoeken in staat is om geringe immunotoxische potentie zoals die uit de literatuur naar voren komt te identificeren. Verder onderzoek zal moeten aangeven wat de functionele consequenties van deze geringe immunotoxiciteit van Salmeterol zijn., Salmeterol, a long-acting Beta2-adrenoreceptor agonist, was studied in a 28-day repeated dose toxicity test in Wistar rats. Attention was paid to immunotoxicity screening parameters incorporated in the study protocol. The aim of this study was to further validate these assays for pharmaceuticals. Male rats were orally treated with 0, 0.2, 2 and 20 mg salmeterol/kg body weight/day. During the course of the study, it appeared that the highest dose level used was too high, and the animals tried to resist intubation, leading to intubation errors and intercurrent death of some of them. Therefore, the magnitude of the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body weight and bone marrow cellularity were not affected, neither were hematological parameters, except for platelet counts that were decreased at all dose levels. Also liver weights were decreased at all dose levels tested. Absolute thymic weights were decreased at the 2 and 20/10 mg/kg/day dose levels. No treatment-related (histo)pathological lesions were seen in (non)lymphoid organs. Serum immunoglobulin G at the 2 and 10/20 mg/kg/day dose level. Numbers of B cells in the spleen were decreased at all dose levels tested. The data indicate that the panel of tests used in this study to examine salmeterol is able to detect the reported low immunotoxic potential. Further research is needed to elucidate whether salmeterol interferes with immune responses in rats upon antigenic challenge.