No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients.
A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6‑min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV1), and as single components.
Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV1 with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001).
Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.
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American Thoracic Society
Area under the curve
Bronchoalveolar lavage fluid
Body mass index
Body-mass index, airflow obstruction, dyspnea, and exercise
COPD assessment test
Complete blood cell
Cluster of differentiation
Chronic obstructive pulmonary disease
- DLCO :
Diffusing capacity of the lungs for carbon monoxide
European Respiratory Society
Tilburg fatigue assessment scale
Fraction of exhaled nitric oxide
- FEV1 :
Forced expiratory volume in 1 s
Forced vital capacity
Good clinical practice
Global Initiative for Chronic Obstructive Lung Disease
Health related quality of life
Long-acting muscarinic antagonists
Modified Medical Research Council
Negative predictive value
Peak expiratory flow
Partial pressure of carbon dioxide
Partial pressure of oxygen
Positive predictive value
Arterial oxygen saturation
6 min walking test
Transforming growth factor beta
Total lung capacity
Tumor necrosis factor alpha
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No grant, equipment or drugs were received for this study.
V. Fijačko conceived the idea for the study, together with M. Labor, S. Škrinjarić-Cincar, S. Labor, T. Bačun, A. Včev and M. Fijačko collected data. D. Plavec and S. Popović-Grle were responsible together with V. Fijačko for the design of the research and for data analysis. I. Dumbović Dubravčić contributed by literature research, writing and editing the data. All authors contributed by editing and approving the final version of the manuscript. All authors have read and approved the final version of the manuscript.
Conflict of interest
V. Fijačko has received honoraria for lectures from Novartis, Sandoz, AstraZeneca, Berlin Chemie, Pliva, and Boehringer Ingelheim. S. Škrinjarić-Cincar has received honoraria for lectures from Novartis, Sandoz, AstraZeneca, Berlin Chemie, Pliva, and Boehringer Ingelheim. S. Labor has received honoraria for lectures from Novartis, and Boehringer Ingelheim. T. Bačun has received honoraria for lectures from Novo Nordisk, Eli Lilly, Novartis, Sandoz, AstraZeneca, Berlin Chemie, Pliva, and Boehringer Ingelheim. S. Popović-Grle has received honoraria for advisory boards and/or lectures from Boehringer Ingelheim, Novartis, AstraZeneca, Pliva-Teva, Takeda, GlaxoSmithKline, Meda Pharma, Sanofi Aventis, Krka farma, Berlin Chemie Menarini Hrvatska, and Sandoz Hrvatska. D. Plavec has received research grants from GlaxoSmithKline, honoraria for advisory boards and/or lectures and/or clinical trials from GlaxoSmithKline, Menarini, Pliva, Boehringer Ingelheim, Belupo, AbbVie, MSD, and Chiesi. M. Labor, I. Dumbović Dubravčić, M. Fijačko and A. Včev declare that they have no competing interests.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee (Institutional Review Board and Medical Faculty Ethics Committee) and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in the study.
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Fijačko, V., Labor, M., Fijačko, M. et al. Predictors of short-term LAMA ineffectiveness in treatment naïve patients with moderate to severe COPD. Wien Klin Wochenschr 130, 247–258 (2018). https://doi.org/10.1007/s00508-017-1307-7
- Cholinergic antagonists
- Chronic obstructive pulmonary disease
- Treatment failure
- Outcome assessments