Tiotropium improves lung function in patients with severe uncontrolled asthma: A randomized controlled trial  Huib A.M. Kerstjens, MD, PhD, Bernd Disse,

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Tiotropium improves lung function in patients with severe uncontrolled asthma: A randomized controlled trial  Huib A.M. Kerstjens, MD, PhD, Bernd Disse, MD, PhD, Winfried Schröder-Babo, MD, Theo A. Bantje, MD, Martina Gahlemann, MD, Ralf Sigmund, Dipl-Math oec, Michael Engel, MD, Jan A. van Noord, MD  Journal of Allergy and Clinical Immunology  Volume 128, Issue 2, Pages 308-314 (August 2011) DOI: 10.1016/j.jaci.2011.04.039 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Screening, randomization, and study completion. Journal of Allergy and Clinical Immunology 2011 128, 308-314DOI: (10.1016/j.jaci.2011.04.039) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 FEV1 (A) and FVC (B) responses relative to baseline values within 3 hours after dosing after 8 weeks of treatment. The difference in level at 0:00 h is the trough effect of tiotropium administered 24 hours earlier. The measurement obtained at baseline (visit 2 before any maintenance or study medication) is defined as the baseline value. At the on-treatment visits, this was immediately followed by the usual medication (including ICS plus LABA), and this in turn was followed by the study medication. Error bars represent SEMs. Arrows indicate the timing of the maintenance medication: ICS plus LABA. Tiotropium R5, 5 μg of tiotropium; Tiotropium R10, 10 μg of tiotropium. Journal of Allergy and Clinical Immunology 2011 128, 308-314DOI: (10.1016/j.jaci.2011.04.039) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Twenty-four-hour FEV1 (A) and FVC (B) responses as shown in Fig 2 in the subgroup of patients with 24-hour assessments (n = 67). The baseline value was defined on visit 2 before any maintenance or study medication. At the on-treatment visits, this was immediately followed by the usual medication (including ICS plus LABA), which was followed in turn by the study medication. The afternoon dosing of ICS plus LABA treatment was also taken. Error bars represent SEMs. Arrows indicate the timing of the maintenance medication: ICS plus LABA. Tio R5, 5 μg of tiotropium; Tio R10, 10 μg of tiotropium. Journal of Allergy and Clinical Immunology 2011 128, 308-314DOI: (10.1016/j.jaci.2011.04.039) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Mean weekly morning PEF measured before dosing in the last 5 weeks of the 8–week treatment period. Note: the first 3 weeks of the treatment period were prespecified as probably reflecting a carryover effect of the previous treatment because there was no washout period between treatments. Error bars represent SEMs. Journal of Allergy and Clinical Immunology 2011 128, 308-314DOI: (10.1016/j.jaci.2011.04.039) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions