title: The Influence of Nebulized Drugs on Nasal Ciliary Activity.
abstract: Nebulized drugs are used in the treatment of cystic fibrosis (CF) lung disease, asthma, and COPD, and increasingly also in other chronic lung diseases. Their use in CF is reasonably evidence based, but this is not so for use in other orphan diseases. Potential side effects often have not been studied. Therefore, we evaluated the influence of nebulized drugs on ciliary activity in an in vitro model.
  
  
  
  We constructed an in vitro nebulization model to examine the effect of drugs on ciliary activity. The model was validated by testing solutions with known neutral, positive, or negative effect on ciliary beat frequency (CBF). Next, the influence on CBF of other inhaled drugs was tested.
  
  
  
  Nebulization of NaCl 0.9% had no influence on CBF, and was used as paired neutral control in further experiments. Salbutamol (Ventolin(®)) had a ciliostimulatory effect (CBF +18%, CBF at t0-t10-t60 7.1-8.5-8.6 Hz, p = 0.002), while hypertonic saline (CBF - 11%, CBF at t0-t10-t60 6.5-5.1-5.9 Hz, p = 0.018) and dry air (CBF -10%, CBF at t0-t10-t60 6.8-5.8-6.1 Hz, p = 0.008) had a cilioinhibitory effect. Nebulization of tobramycin inhaled solution (TOBI(®)) (p = 0.662), colistimethate (Colistineb(®)) (p = 0.369), rhDNAse (Pulmozyme(®)) (p = 0.069), ceftazidim (Glazidim(®)) (p = 0.875), and aztreonam (Cayston(®)) (p = 0.435) did not affect CBF. Obracin(®), a tobramycin containing solution manufactured for intravenous use, had a negative effect on CBF (CBF - 21%, CBF at t0-t10-t60 6.9-5.2-4.5 Hz, p = 0.004).
  
  
  
  Inhaled drugs that are used off-label might have an influence on ciliary activity. This must be taken into account when prescribing these drugs for non-CF indications.
authors.affiliation: 1 Department of Pediatrics, Pediatric Pulmonology, University Hospital Gasthuisberg , Leuven, Belgium .
authors.forename: Mieke
authors.initials: M
authors.lastname: Boon
authors.affiliation: 2 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Gasthuisberg , Leuven, Belgium .
authors.forename: Mark
authors.initials: M
authors.lastname: Jorissen
authors.affiliation: 2 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Gasthuisberg , Leuven, Belgium .
authors.forename: Martine
authors.initials: M
authors.lastname: Jaspers
authors.affiliation: 3 Drug Delivery and Disposition, KU Leuven , Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium .
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: 1 Department of Pediatrics, Pediatric Pulmonology, University Hospital Gasthuisberg , Leuven, Belgium .
authors.forename: François L
authors.initials: FL
authors.lastname: Vermeulen
authors.affiliation: 1 Department of Pediatrics, Pediatric Pulmonology, University Hospital Gasthuisberg , Leuven, Belgium .
authors.forename: Marijke
authors.initials: M
authors.lastname: Proesmans
authors.affiliation: 1 Department of Pediatrics, Pediatric Pulmonology, University Hospital Gasthuisberg , Leuven, Belgium .
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
mesh_terms: D000280:Administration, Inhalation; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D009330:Nebulizers and Vaporizers; D015203:Reproducibility of Results; D019141:Respiratory System Agents / Q000008:administration & dosage* / Q000633:toxicity; D013997:Time Factors
chemical_list: D019141:Respiratory System Agents
keywords: CBF; cilia; cystic fibrosis; in vitro; nebulized drugs; non-CF bronchiectasis