title: Acute high-altitude exposure reduces lung diffusion: data from the HIGHCARE Alps project.
abstract: The causes and development of lung fluid, as well as the integrity of the alveolar-capillary membrane at high altitude, are undefined. This study was conceived to see whether fluid accumulates within the lung with acute high altitude exposure, and whether this is associated with alveolar capillary membrane damage. We studied lung carbon monoxide diffusion (DLCO), its components - membrane diffusion (DM) and capillary volume (VC) and alveolar volume (VA) measured in 43 healthy subjects in Milan (122 m) and after 1 and 3 days at Capanna Regina Margherita (4559 m). DLCO measurement was adjusted for hemoglobin and inspired oxygen. We also measured plasma surfactant derived protein B (SPB) and Receptor of Advanced Glycation End-products (RAGE) as markers of alveolar-capillary membrane damage, and ultrasound lung comets as a marker of extravascular lung water. 21 subjects received acetazolamide and 22 placebo. DLCO was lower at Capanna Regina Margherita (day 1: 24.3 ± 4.7 and day 3: 23.6 ± 5.4 mL/mmHg/min), than in Milan (25.8 ± 5.5; p<0.001 vs. day 1 and 3) due to DM reduction (Milan: 50.5 ± 14.6 mL/mmHg/min, Capanna Regina Margherita day 1: 45.1 ± 11.5 mL/mmHg/min, day 3: 43.2 ± 13.9 mL/mmHg/min; p<0.05 Milan vs. day 3) with a partially compensatory VC increase (Milan: 96 ± 37 mL, Capanna Regina Margherita day 1: 152 ± 66 mL, day 3: 153 ± 59 mL; p<0.001 Milan vs. day 1 and day 3). Acetazolamide did not prevent the fall in DLCO albeit, between day 1 and 3, such a trend was observed. Regardless of treatment lung comets increased from 0 to 7.2 ± 3.6 (p<0.0001). SPB and RAGE were unchanged. Lung fluid increased at high altitude without evidence from plasma measurements, supporting alveolar-capillary damage.
authors.affiliation: Centro Cardiologico Monzino, IRCCS, via Parea 4, 20138 Milan, Italy. piergiuseppe.agostoni@unimi.it
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
authors.forename: Erik R
authors.initials: ER
authors.lastname: Swenson
authors.forename: Roberto
authors.initials: R
authors.lastname: Fumagalli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.forename: Gaia
authors.initials: G
authors.lastname: Cattadori
authors.forename: Stefania
authors.initials: S
authors.lastname: Farina
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bussotti
authors.forename: Margherita
authors.initials: M
authors.lastname: Tamplenizza
authors.forename: Carolina
authors.initials: C
authors.lastname: Lombardi
authors.forename: Daniele
authors.initials: D
authors.lastname: Bonacina
authors.forename: Maura
authors.initials: M
authors.lastname: Brioschi
authors.forename: Sergio
authors.initials: S
authors.lastname: Caravita
authors.forename: Pietro
authors.initials: P
authors.lastname: Modesti
authors.forename: Miriam
authors.initials: M
authors.lastname: Revera
authors.forename: Andrea
authors.initials: A
authors.lastname: Giuliano
authors.forename: Paolo
authors.initials: P
authors.lastname: Meriggi
authors.forename: Andrea
authors.initials: A
authors.lastname: Faini
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bilo
authors.forename: Cristina
authors.initials: C
authors.lastname: Banfi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Parati
mesh_terms: D000328:Adult; D000531:Altitude; D001794:Blood Pressure / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008168:Lung / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000502:physiology; D011653:Pulmonary Diffusing Capacity / Q000502:physiology*; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric
chemical_list: D002248:Carbon Monoxide
keywords: Gas exchange; Hypoxia; Pulmonary edema; Surfactant derived proteins