Hyaluronic Acid (Hyaluronan) in BAL Fluid Distinguishes Farmers with Allergic Alveolitis from Farmers with Asymptomatic Alveolitis

doi:10.1378/chest.101.1.109

Chest

Volume 101, Issue 1, January 1992, Pages 109-114

https://doi.org/10.1378/chest.101.1.109 Get rights and content

Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers with no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic formers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in formers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.

Section snippets

Subjects

Farmers with Symptoms of Alveolitis (A Group). Twelve nonsmoking farmers (six women) with a mean age of 49 years (range, 33 to 64 years) who were admitted to the hospital due to symptoms of allergic alveolitis constituted the alveolitis group (A group). Eleven had experienced attacks of fever or shivering, and all had dyspnea, which had progressed during the weeks or months prior to admittance to the hospital. At the time of admittance, all farmers had chest roentgenographic changes indicating

Pulmonary Function

Pulmonary function data are shown in Table 1. Farmers with symptoms of allergic alveolitis (A group) had significant pulmonary function impairment with regard to VC, FEV₁, and Dsb. The asymptomatic farmers (C group) had normal pulmonary function (Table 1). The FEV₁/VC was normal in both groups. In the six farmers of the A group in whom pulmonary function was measured again after one year, pulmonary function had improved; VC increased from 74 percent to 93 percent, FEV₁ from 78 percent to 96

DISCUSSION

The randomly selected farmers without respiratory symptoms had normal pulmonary function; TLC was above 85 percent (mean, 99 percent) of the predicted value, and the Dsb was normal in all subjects. These results are in agreement with earlier findings showing normal gas exchange at rest and during heavy exercise in farmers.⁸ The present results show that asymptomatic farmers have normal pulmonary function despite marked alterations in the BAL fluid composition of cells and soluble products.

ACKNOWLEDGMENTS

We thank Roine Hernbrand, Britt-Marie Sundblad, Catrine Åkesson, and the Department of Cytology, University Hospital, Umeå, Sweden, for expert technical assistance.

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Hyaluronate did not influence the pulmonary function test or the physiological parameters recorded during exercise. There was a decrease in the percentage of BAL neutrophils after the treatment, suggesting a possible anti-inflammatory effect at the pulmonary level. As well, the concentration of isoprostanes in the pulmonary epithelium lining fluid was significantly lower after the treatment, which might be either a consequence of the decrease of the BAL neutrophils, or related to a possible antioxidant effect of the treatment. Lastly, the exercise-induced increase in plasma uric acid was significantly less marked after the treatment, which could be due to a systemic antioxidant effect of the hyaluronate.
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Biochemical changes in sarcoidosis
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Sarcoidosis: A model of granulomatous inflammation of unknown etiology associated with a hyperactive immune system
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Sarcoidosis is a systemic granulomatous disorder of unknown etiology, characterized by hyperactive cellular and humoral immune function. We review pertinent history, pathology, and biochemistry of sarcoidosis and reconcile the common finding of cutaneous anergy with the presence of a hyperactive immune system. A hypothetical model of antigen-driven granuloma formation is discussed, citing relevant studies from blood, bronchoalveolar lavage, andin vitro-cultured intact sarcoidal skin granulomas. The etiology of sarcoidosis is considered, and we focus on the Kveim–Siltzbach skin test as anin vivomodel for elucidation of the immune mechanisms of sarcoid granuloma formation, as well as a model for study of the sarcoid granulomagenic factor. We have adapted this skin test model to study the granulomagenicity of sarcoid autologous bronchoalveolar lavage and peripheral blood cells and demonstrate that early after onset of disease symptoms, bronchoalveolar lavage macrophages and peripheral blood monocytes are granulomagenic. This method extends our understanding of the source of the sarcoid granulomagenic factor and offers a model for tracking the agent as its identity is unraveled.
Kinetic retrieval of eosinophil cationic protein, hyaluronan, secretory IgA, albumin, and urea during BAL in healthy subjects
1995, Chest
Determination of absolute concentrations of various soluble components of the epithelial lining fluid (ELF) may be valuable to estimate inflammatory activities within the underlying lung tissue. Internal standards may then be used as markers of dilution of bronchoalveolar lavage (BAL). The aim of this study was to determine whether different dwell times would affect the relationship between the concentrations of any of the three potential internal standards (secretory IgA [SIgA], albumin, and urea), and the concentrations of two potential markers of inflammation (eosinophil cationic protein [ECP] and hyaluronan [HA]) in BAL. A series of aliquots of BAL fluid were aspirated every 60 s up to 8 min after a bolus instillation of saline solution in 20 healthy subjects (10 smokers). The BAL concentrations of albumin and urea increased with time, consistent with continuous diffusion from the body water pool, absorption of the BAL fluid, or both. The rate constant of diffusion was 1,000 times higher for urea than for albumin (3.38×10⁻¹ and 3.64×10⁻⁴, respectively), reflecting the difference in molecular weights, and in agreement with the notion that albumin and urea appeared in BAL fluid by a rate-limited procedure related to osmotic transfer. Biexponential increases of SIgA were recorded, suggesting a two-compartmental origin of this compound, normally located to mucosal membranes and presumed to be dissolved in ELF. Time-dependent increases in BAL fluid of HA also were recorded, but on the other hand, the ECP concentrations tended to level off after an initial increase, suggesting that the bulk of ECP appeared in BAL by a nonosmotic mechanism. We conclude that the kinetics of these three internal standards in BAL fluid differs greatly from each other and from the kinetics of the two selected markers of inflammation. Consequently, internal standards for determination of absolute concentrations of markers of inflammation in ELF should be carefully selected because of the requirement of matched kinetics of the markers.

View all citing articles on Scopus

: Supported by grants from the Swedish Heart and Lung Foundation and the National Work Environment Fund 85-0508 and 86-1229.

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Chest

Clinical InvestigationsHyaluronic Acid (Hyaluronan) in BAL Fluid Distinguishes Farmers with Allergic Alveolitis from Farmers with Asymptomatic Alveolitis

Section snippets

Subjects

Pulmonary Function

DISCUSSION

ACKNOWLEDGMENTS

Chest

Am J Med

Anal Biochem

Respir Med

Life Sci

Chest

Clin Chim Acta

Abnormal bronchoalveolar lavage in asymptomatic dairy farmers: study of lymphocytes

Am Rev Respir Dis

Persistent bronchoalveolar lymphocytosis in asymptomatic farmers

Am Rev Respir Dis

Exposure to microorganisms, airway inflammatory changes and immune reactions in asymptomatic dairy farmers: bronchoalveolar lavage evidence of macrophage activation and permeability changes in the airways

Int Arch Allergy Appl Immunol

The fluctuant nature of precipitating antibodies in dairy farmers

Thorax

Bronchoalveolar mastocytosis in farmer's lung is related to the disease activity

Arch Intern Med

Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis

J Clin Invest

Relationship among antigen contact, alveolitis, and clinical status in farmer's lung disease

Arch Intern Med

Exposure to microorganisms, febrile and airway-obstructive symptoms, immune status and lung function of Swedish farmers

Scand J Work Environ Health

Hyaluronate and type III procollagen peptide concentrations in bronchoalveolar lavage fluid as markers of disease activity in farmer's lung

Br Med J

Influence of corticosteroid treatment on the course of farmer's lung

Eur J Respir Dis

An electron-microscopic study of the airways in patients with farmer's lung

Eur J Respir Dis

Non-specific bronchial reactivity and ultrastructure of the airway epithelium in patients with sarcoidosis and allergic alveolitis

Eur J Respir Dis (suppl)

Bronchial hyperreactivity to inhaled histamine in patients with farmer's lung

Lung

Importance of airway inflammation for hyperresponsiveness induced by ozone

Am Rev Respir Dis

Clinical Investigations
Hyaluronic Acid (Hyaluronan) in BAL Fluid Distinguishes Farmers with Allergic Alveolitis from Farmers with Asymptomatic Alveolitis