title: Pilot Randomized Controlled Trial Evaluating the Effect of Hypertonic Saline With and Without Hyaluronic Acid in Reducing Inflammation in Cystic Fibrosis.
abstract: Hypertonic saline (HS) has been established as a therapy aimed at restoring the surface liquid of airways liquid and enhancing mucociliary clearance in patients with cystic fibrosis (CF). A formula containing 7% HS and 0.1% hyaluronic acid (HA) is also available, basing its use on the protective effects of HA against elastin injury and on its greater ease of administration (i.e., the perceived acceptability of inhalation). This study explores the effect of HA+HS in reducing the inflammation of airways, by measuring cytokine levels in sputum, its safety profile, and the prevalence of commonly reported symptoms like cough, throat irritation, and saltiness.
  
  
  
  In a pilot, double-blind, randomized controlled, parallel-group, 1:1 trial, clinically stable CF patients older than 6 years of age and with a FEV1pred. >40% were randomized to one of the treatment arms, HS or HS+HA, to be administered twice a day at home. Clinical data, inflammatory markers (IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF) in sputum, and judgments on the tolerability and pleasantness were collected at the beginning and after 28 days.
  
  
  
  HA+HS had no significant effect on inflammatory markers versus HS alone, as shown by broad confidence intervals. In the HS+HA group, the highest decrement from baseline values was observed for IL-1β (-58.8%) followed by VEGF (-49.9%), whereas in the HS group a significant increment of IL-10 levels (+83.0%; p = 0.011) was the only significant finding. Prevalence of unfavorable scores was 36.8% in HA+HS versus 55% in HS group (p = 0.207); no significant differences were detected in the prevalence of moderate/severe symptoms of cough, saltiness, and throat irritation in pulmonary functions tests after 28 days.
  
  
  
  HS+HA administration in CF patients does not show any significant effects on lung inflammation and function as compared to HS alone.
authors.affiliation: 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan, Italy .
authors.forename: Anna
authors.initials: A
authors.lastname: Brivio
authors.affiliation: 2 Department of Medical and Surgical Sciences, Centro di Ricerche Biomediche "E. Altomare", Laboratory of Experimental and Regenerative Medicine, University of Foggia , Foggia, Italy .
authors.forename: Massimo
authors.initials: M
authors.lastname: Conese
authors.affiliation: 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan, Italy .
authors.forename: Simone
authors.initials: S
authors.lastname: Gambazza
authors.affiliation: 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan, Italy .
authors.forename: Arianna
authors.initials: A
authors.lastname: Biffi
authors.affiliation: 3 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Laboratory of Clinical Pathology and CF Microbiology , Milan, Italy .
authors.forename: Amedea Silvia
authors.initials: AS
authors.lastname: Tirelli
authors.affiliation: 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan, Italy .
authors.forename: Maria
authors.initials: M
authors.lastname: Russo
authors.affiliation: 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan, Italy .
authors.forename: Michaela
authors.initials: M
authors.lastname: Foà
authors.affiliation: 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan, Italy .|4 University of Milan , Italy .
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007558:Italy; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009330:Nebulizers and Vaporizers; D057240:Patient Preference; D010865:Pilot Projects; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000009:adverse effects; D013183:Sputum / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004338:Drug Combinations; D018836:Inflammation Mediators; D012462:Saline Solution, Hypertonic; D006820:Hyaluronic Acid
keywords: clinical trial; cystic fibrosis; cytokines; hyaluronic acid; hypertonic saline; lung function