title: A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.
abstract: The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.
authors.affiliation: 1 The National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Jorid B
authors.identifier: http://orcid.org/0000-0001-5453-433X
authors.initials: JB
authors.lastname: Sørli
authors.affiliation: 1 The National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Emilie
authors.initials: E
authors.lastname: Da Silva
authors.affiliation: 2 AstraZeneca, Mölndal, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Bäckman
authors.affiliation: 1 The National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Marcus
authors.initials: M
authors.lastname: Levin
authors.affiliation: 1 The National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Birthe L
authors.initials: BL
authors.lastname: Thomsen
authors.affiliation: 1 The National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Ismo K
authors.initials: IK
authors.lastname: Koponen
authors.affiliation: 1 The National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Larsen
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000418:Albumins / Q000008:administration & dosage / Q000633:toxicity; D001688:Biological Products / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry; D000068759:Formoterol Fumarate / Q000008:administration & dosage; D007785:Lactose / Q000008:administration & dosage / Q000737:chemistry; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D010743:Phospholipids / Q000008:administration & dosage; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000008:administration & dosage; D019141:Respiratory System Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D018570:Risk Assessment; D013500:Surface Tension; D013726:Terbutaline / Q000008:administration & dosage; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000336:Aerosols; D000418:Albumins; D001688:Biological Products; D001993:Bronchodilator Agents; D005079:Excipients; D010743:Phospholipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D019141:Respiratory System Agents; D019819:Budesonide; D007785:Lactose; C068291:poractant alfa; D013726:Terbutaline; D000068759:Formoterol Fumarate
keywords: constrained drop surfactometer; in vitro toxicology; inhalation toxicology; lung surfactant