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Intensified Therapy with Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial.
Am J Respir Crit Care Med. 2018 05 01; 197(9):1136-1146.AJ

Abstract

RATIONALE

The efficacy of intensified combination therapy with inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) at the onset of upper respiratory tract infection (URTI) symptoms in chronic obstructive pulmonary disease (COPD) is unknown.

OBJECTIVES

To evaluate whether intensified combination therapy with ICS/LABA, at the onset of URTI symptoms, decreases the incidence of COPD exacerbation occurring within 21 days of the URTI.

METHODS

A total of 450 patients with stable, moderate to very severe COPD, were included in this investigator-initiated and -driven, double-blind, randomized, placebo-controlled study. At inclusion, patients were assigned to open-labeled low-maintenance dose ICS/LABA. Each patient was randomized either to intensified-dose ICS/LABA or placebo and instructed to start using this medication only in case of a URTI, at the onset of symptoms, twice daily, for 10 days.

MEASUREMENTS AND MAIN RESULTS

The incidence of any exacerbation following a URTI was not significantly decreased in the ICS/LABA group, as compared with placebo (14.6% vs. 16.2%; hazard ratio, 0.77; 95% confidence interval, 0.46-1.33; P = 0.321) but the risk of severe exacerbation was decreased by 72% (hazard ratio, 0.28; 95% confidence interval, 0.11-0.74%; P = 0.010). In the stratified analysis, effect size was modified by disease severity, fractional exhaled nitric oxide, and the body mass index-airflow obstruction-dyspnea, and exercise score. Compared with the stable period, evidence of at least one virus was significantly more common at URTI, 10 days after URTI, and at exacerbation.

CONCLUSIONS

Intensified combination therapy with ICS/LABA for 10 days at URTI onset did not decrease the incidence of any COPD exacerbation but prevented severe exacerbation. Patients with more severe disease had a significant risk reduction for any exacerbation. Clinical trial registered with www.isrctn.com (ISRCTN45572998).

Authors+Show Affiliations

1 Clinic of Respiratory Medicine and Pulmonary Cell Research, and. 2 Department of Biomedicine, University of Basel, Basel, Switzerland. 3 University of Basel, Basel, Switzerland.5 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland. 2 Department of Biomedicine, University of Basel, Basel, Switzerland. 3 University of Basel, Basel, Switzerland. 4 Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.6 Lindenhof Hospital, Bern, Switzerland.7 Pneumology Department, GIGA I3 research group, University of Liege, CHU Liege, Belgium; and.1 Clinic of Respiratory Medicine and Pulmonary Cell Research, and. 2 Department of Biomedicine, University of Basel, Basel, Switzerland. 3 University of Basel, Basel, Switzerland.1 Clinic of Respiratory Medicine and Pulmonary Cell Research, and. 2 Department of Biomedicine, University of Basel, Basel, Switzerland. 3 University of Basel, Basel, Switzerland.1 Clinic of Respiratory Medicine and Pulmonary Cell Research, and. 2 Department of Biomedicine, University of Basel, Basel, Switzerland. 3 University of Basel, Basel, Switzerland.3 University of Basel, Basel, Switzerland. 8 Swiss Tropical and Public Health Institute, Basel, Switzerland.3 University of Basel, Basel, Switzerland. 8 Swiss Tropical and Public Health Institute, Basel, Switzerland.1 Clinic of Respiratory Medicine and Pulmonary Cell Research, and. 2 Department of Biomedicine, University of Basel, Basel, Switzerland. 3 University of Basel, Basel, Switzerland.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

29266965

Citation

Stolz, Daiana, et al. "Intensified Therapy With Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. a Multicenter, Randomized, Double-Blind, Placebo-controlled Trial." American Journal of Respiratory and Critical Care Medicine, vol. 197, no. 9, 2018, pp. 1136-1146.
Stolz D, Hirsch HH, Schilter D, et al. Intensified Therapy with Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018;197(9):1136-1146.
Stolz, D., Hirsch, H. H., Schilter, D., Louis, R., Rakic, J., Boeck, L., Papakonstantinou, E., Schindler, C., Grize, L., & Tamm, M. (2018). Intensified Therapy with Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial. American Journal of Respiratory and Critical Care Medicine, 197(9), 1136-1146. https://doi.org/10.1164/rccm.201709-1807OC
Stolz D, et al. Intensified Therapy With Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. a Multicenter, Randomized, Double-Blind, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018 05 1;197(9):1136-1146. PubMed PMID: 29266965.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intensified Therapy with Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial. AU - Stolz,Daiana, AU - Hirsch,Hans H, AU - Schilter,Daniel, AU - Louis,Renaud, AU - Rakic,Janko, AU - Boeck,Lucas, AU - Papakonstantinou,Eleni, AU - Schindler,Christian, AU - Grize,Leticia, AU - Tamm,Michael, PY - 2017/12/22/pubmed PY - 2019/8/20/medline PY - 2017/12/22/entrez KW - ICS KW - LABA KW - treatment for COPD exacerbations SP - 1136 EP - 1146 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 197 IS - 9 N2 - RATIONALE: The efficacy of intensified combination therapy with inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) at the onset of upper respiratory tract infection (URTI) symptoms in chronic obstructive pulmonary disease (COPD) is unknown. OBJECTIVES: To evaluate whether intensified combination therapy with ICS/LABA, at the onset of URTI symptoms, decreases the incidence of COPD exacerbation occurring within 21 days of the URTI. METHODS: A total of 450 patients with stable, moderate to very severe COPD, were included in this investigator-initiated and -driven, double-blind, randomized, placebo-controlled study. At inclusion, patients were assigned to open-labeled low-maintenance dose ICS/LABA. Each patient was randomized either to intensified-dose ICS/LABA or placebo and instructed to start using this medication only in case of a URTI, at the onset of symptoms, twice daily, for 10 days. MEASUREMENTS AND MAIN RESULTS: The incidence of any exacerbation following a URTI was not significantly decreased in the ICS/LABA group, as compared with placebo (14.6% vs. 16.2%; hazard ratio, 0.77; 95% confidence interval, 0.46-1.33; P = 0.321) but the risk of severe exacerbation was decreased by 72% (hazard ratio, 0.28; 95% confidence interval, 0.11-0.74%; P = 0.010). In the stratified analysis, effect size was modified by disease severity, fractional exhaled nitric oxide, and the body mass index-airflow obstruction-dyspnea, and exercise score. Compared with the stable period, evidence of at least one virus was significantly more common at URTI, 10 days after URTI, and at exacerbation. CONCLUSIONS: Intensified combination therapy with ICS/LABA for 10 days at URTI onset did not decrease the incidence of any COPD exacerbation but prevented severe exacerbation. Patients with more severe disease had a significant risk reduction for any exacerbation. Clinical trial registered with www.isrctn.com (ISRCTN45572998). SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/29266965/Intensified_Therapy_with_Inhaled_Corticosteroids_and_Long_Acting_β2_Agonists_at_the_Onset_of_Upper_Respiratory_Tract_Infection_to_Prevent_Chronic_Obstructive_Pulmonary_Disease_Exacerbations__A_Multicenter_Randomized_Double_Blind_Placebo_controlled_Trial_ DB - PRIME DP - Unbound Medicine ER -