Accumulation of Hyaluronan (Hyaluronic Acid) in the Lung in Adult Respiratory Distress Syndrome

Abstract

The concentrations of hyaluronan (HA) were measured in bronchoalveolar lavage (BAL) fluid and serum from 12 patients with adult respiratory distress syndrome (ARDS). The median BAL fluid HA concentration was 353 micrograms/L, about six times higher than that seen in control patients (p less than 0.001). The median serum HA value was 619 micrograms/L, which was a 30-fold increase compared with that in the control patients (p less than 0.001). Another connective tissue component, type III procollagen peptide, was not recovered in significant amounts during lavage in patients with ARDS, but it appeared in the bloodstream in increased concentrations (p less than 0.001). Obtained recovery of HA during lavage of patients with ARDS cannot be explained by an enhanced passive leakage from the bloodstream because of increased alveolar-capillary permeability, but rather could reflect a mobilization of HA from lung interstitial tissue because of hydrostatic mechanisms. Alternatively, the appearance of HA in the alveolar space in ARDS might reflect an enhanced lung synthesis of HA. An increased HA production can possibly be mediated, directly or indirectly, by activated complement components, since a significant relationship was seen between increased plasma concentrations of C3a des Arg and BAL fluid HA (r = 0.61; p less than 0.05). The observed accumulation of HA in the small airways in ARDS may be expected to immobilize water and thereby contribute to the interstitial and alveolar edema. The inverse correlation (r = 0.71; p less than 0.01) seen between BAL fluid HA and pulmonary oxygenation index (PaO2/inspired oxygen fraction) supports such a hypothesis.

Simultaneous measurement of collagen type-VI-related antigen and procollagen type-III-N-propeptide levels in bronchoalveolar lavage

“…Our measurements of PIIINP agree with previous studies indicating elevated PIIINP levels in BAL of patients with diffuse lung diseases, such as IPF, adult respiratory distress syndrome (ARDS), sarcoidosis and farmer's lung [5][6][7][8][10][11][12][13][14][15].…”

“…Thus, biochemical measurements of the balance between collagen synthesis and degradation would be helpful in monitoring the progress of fibrotic lung disease. In recent years, an assay for the procollagen type-III Nterminal propeptide (PIIINP) [3,4] has been used to assess collagen turnover both in serum and bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis [5,6], sarcoidosis [7,8], adult respiratory distress syndrome [9,10], and farmer's lung [11][12][13]. Most of these studies have investigated PIIINP levels either in serum or BALF: In a few studies both PIIINP levels were investigated [10,14,15].…”

Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation

“…Experimental studies have also demonstrated a link between the alveolar and interstitial accumulation of HYA and the intraalveolar oedema and oedema of the fragile alveolar structure [25]. The hypothesis that interstitial water trapped by HYA may result in impaired lung function is further supported by the clinical observations of a close relationship between high amounts of HYA recovered by BAL and reduced gas diffusion of the lung in patients with acute farmer's lung [20] or adult respiratory distress syndrome [26].…”

Hyaluronan turnover in relation to infection and sepsis

“…The adult respiratory distress syndrome (ARDS), one of many possible components of MODS, is still a disease incompletely understood where a causal therapy is lacking. In human ARDS increased concentrations of hyaluronan in bronchoalveolar lavage fluid (BAL) has been found [27], and in a porcine model of sepsis-induced lung injury resembling ARDS, accumulation of interstitial hyaluronan has been seen [19]. This is in analogy to the increased amounts of hyaluronan found both interstitially and in BAL fluid in other interstitial inflammatory pulmonary diseases such as sarcoidosis and allergic alveolitis [28,29,30].…”