Mucolytic Effectiveness of Tyloxapol in Chronic Obstructive Pulmonary Disease - A Double-Blind, Randomized Controlled Trial.
OBJECTIVE
Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD.


METHODS
A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol.


RESULTS
A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34-5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73-3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure.


CONCLUSIONS
Our study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects.


BACKGROUND
ClinicalTrials.gov NCT02515799.
Department for Children and Adolescents, Division for Allergology, Pneumology and Cystic Fibrosis, University Hospital Goethe University, Frankfurt am Main, Germany.
Martin
M
Koppitz
Department for Children and Adolescents, Division for Allergology, Pneumology and Cystic Fibrosis, University Hospital Goethe University, Frankfurt am Main, Germany.
Charlotte
C
Eschenburg
Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, University Hospital Goethe University, Frankfurt am Main, Germany.
Emilia
E
Salzmann
Department for Children and Adolescents, Division for Allergology, Pneumology and Cystic Fibrosis, University Hospital Goethe University, Frankfurt am Main, Germany.
Martin
M
Rosewich
Department for Children and Adolescents, Division for Allergology, Pneumology and Cystic Fibrosis, University Hospital Goethe University, Frankfurt am Main, Germany.
Ralf
R
Schubert
Department for Children and Adolescents, Division for Allergology, Pneumology and Cystic Fibrosis, University Hospital Goethe University, Frankfurt am Main, Germany.
Stefan
S
Zielen
D000280:Administration, Inhalation; D000368:Aged; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D013183:Sputum / Q000187:drug effects; D016896:Treatment Outcome
D005100:Expectorants; D011092:Polyethylene Glycols; C016811:tyloxapol