Nebulized Mannitol, Particle Distribution, and Cough in Idiopathic Pulmonary Fibrosis.
BACKGROUND: Inhaled interferon, a potential treatment for idiopathic pulmonary fibrosis, must be formulated with mannitol, which can cause bronchospasm and cough. Coughing during drug inhalation can be affected by many factors, but some factors are fixed by the needs of the formulation and inflammat...
| Publicado en: | Respiratory Care Vol. 63; no. 11; pp. 1407 - 1413 |
|---|---|
| Autores principales: | , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Mary Ann Liebert, Inc.
Nov2018
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=133121603&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 133121603 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00201324 4GG jtl: Respiratory Care issn: 00201324 maglogo: N pubinfo: dt: Nov2018 vid: 63 iid: 11 pid: 1365 pub: Mary Ann Liebert, Inc. place: New Rochelle, New York artinfo: ui: 133121603 133121603 133121603 10.4187/respcare.06153 133121603 ppf: 1407 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Nebulized Mannitol, Particle Distribution, and Cough in Idiopathic Pulmonary Fibrosis. aug: au: Kanth, Pooja M. Alaienia, Caesar Smaldone, Gerald C. affil: Pulmonary, Critical Care and Sleep Division, Department of Medicine, Health Sciences Center, Stony Brook, New York sug: subj: Idiopathic Pulmonary Fibrosis Drug Therapy Mannitol Administration and Dosage Administration, Inhalation Mannitol Adverse Effects Cough Dose-Response Relationship, Drug Human Spirometry Nebulizers and Vaporizers Chemistry, Pharmaceutical Interferons Descriptive Statistics ab: BACKGROUND: Inhaled interferon, a potential treatment for idiopathic pulmonary fibrosis, must be formulated with mannitol, which can cause bronchospasm and cough. Coughing during drug inhalation can be affected by many factors, but some factors are fixed by the needs of the formulation and inflammatory disease in the airways. A component of the cough response may be related to sites of deposition, particularly upper and central airways. If deposition sites are important, then manipulating the particle distribution of the aerosol may mitigate coughing. To design a therapeutic formulation and delivery system for formulations that contain mannitol, we tested the effect of particle distribution on cough during mannitol inhalation in volunteers with idiopathic pulmonary fibrosis. METHODS: A solution of mannitol was formulated to match requirements for future interferon formulations (40 mg/mL, 220 mOsm/L). Mannitol aerosols were generated by using different nebulizers providing particle distributions that were expected to vary upper airway deposition. The nebulizer fill volume was adjusted to correct for differences in nebulizer efficiency with a target inhaled mass of 20 mg. Particle distributions were measured by cascade impaction (mass median aerodynamic diameters, 1.2 and 6.5 µm). Seven subjects with idiopathic pulmonary fibrosis participated in the study. To maximize deposition, the subjects were trained to inhale slowly and deeply (6 s inspiration). Spirometry was measured before and after inhalation. The study was carried out on separate days (day 1: 1.2 µm; day 2: 6.5 µm), and the pattern of coughing was observed. RESULTS: Coughing was often spontaneous and provoked by spirometry. When inhaling the 1.2-µm distribution, no subject coughed during inhalation. Six of the seven subjects coughed when inhaling the 6.5-µm particles. Spirometry was unaffected. CONCLUSIONS: In subjects with idiopathic pulmonary fibrosis, nebulized mannitol can cause coughing. Modifying the aerosol distribution prevents coughing during mannitol inhalation. Mannitol aerosols can be inhaled safely without bronchospasm. These data serve to inform future formulation and/or device combinations for planned interferon therapy. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|