Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers.

BACKGROUND: Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP. OBJECTIVE: To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP. METHODS: Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production. RESULTS: KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P = .01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P < .001. KL-6 correlated with IgG antibody titre in those with symptoms, r = .591, P = .006. High KL-6, irrespective of symptom category, was associated with higher antibody (P = .006) and lymphocyte proliferation (P = .041), and lower CD4+ T lymphocyte proportion (P = .032). CONCLUSION AND CLINICAL RELEVANCE: Raised KL-6 is associated with acute symptoms of early-stage HP, and its correlation with antibody may support therapeutic strategies when HP is suspected. KL-6 may act as a mechanistic biomarker of early pathogenesis by linking lung pathophysiological changes with an endotype of immune hypersensitivity.

Nocardia cyriacigeorgica: a case of endocarditis with disseminated soft-tissue infection.

Nocardia cyriacigeorgica is a common environmental organism. It has been isolated from clinical samples in Europe, Asia and North America, predominantly from respiratory samples but also from samples from several other sites. We present a case report of an 85-year-old female patient in the UK who was found to have a multi-focal soft-tissue infection from which N. cyriacigeorgica was isolated. She had a background history of chronic obstructive pulmonary disease and corticosteroid use for polymyalgia rheumatica. During the course of her treatment echocardiography showed the presence of a mobile heart mass attached to a valve leaflet, a major Dukes criterion for endocarditis. We suggest that in cases of disseminated Nocardia infection, endocarditis should be tested for, particularly in cases failing to respond to treatment. We also review previous reports of both N. cyriacigeorgica infection, and of endocarditis due to Nocardia species and related genera.

Nerve growth factor in serum and lymphocyte culture in pigeon fanciers' acute hypersensitivity pneumonitis.

BACKGROUND: Nerve growth factor (NGF) is a neurotrophic cytokine with immunomodulatory activity. NGF contributes to neurogenic inflammation and has been described in asthma and idiopathic pulmonary fibrosis. OBJECTIVES: To identify and quantify NGF in serum and peripheral blood lymphocyte cultures from pigeon fanciers, and to investigate an association with the immune response to inhaled avian antigens, and with symptoms of acute hypersensitivity pneumonitis (HP). METHODS: NGF was quantified and compared with serum IgG antibody against inhaled avian antigens, with serum C-reactive protein (CRP), and with KL-6, a marker of lung interstitial inflammation. These were measured using enzyme-linked immunoassay. Levels were compared with symptom history in 55 pigeon fanciers (26 subjects with acute HP but symptom-free at the time of testing) and 15 subjects with no avian exposure. RESULTS: Pigeon fanciers had higher-than-normal serum IgG antibody, CRP, and KL-6 levels (p < 0.01 each). These measures were unrelated to HP symptom category; instead, in all pigeon fanciers, the concentrations of CRP and KL-6 correlated with each other and with the antibody titers (p < 0.01 each). Serum NGF levels were normal; however, NGF production by mitogen-activated lymphocytes was higher than normal, and correlated with IgG antibody titer (p < 0.05) and with serum CRP (p < 0.05). CONCLUSIONS: Serum NGF was normal in pigeon fanciers; however, their blood lymphocytes ex vivo synthesized increased NGF in concentrations that correlated with the titer of serum IgG antibody to inhaled avian antigens. These also correlated with CRP and KL-6 levels, suggesting that antigen exposure in seropositive subjects is associated with subclinical inflammation involving coordinated synthesis of neurotrophin and immune mediators.

Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis.

BACKGROUND: Detecting serum antibody against inhaled antigens is an important diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a quantitative fluorimetric assay testing serum from bird fanciers. METHODS: Antibody activity was assessed in bird fanciers and control subjects using various avian antigens and serological methods, and the titer was compared with symptoms of HP. RESULTS: IgG antibody against pigeon serum antigens, quantified by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L were insignificant, and increasing titers were associated with disease. The assay was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg antigens. Antigens from pigeon serum seem sufficient to recognize immune sensitivity to most common pet avian species. Decreasing antibody titers confirmed antigen avoidance. CONCLUSION: Increasing antibody titer reflected the likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying antibody was rapid and the increased sensitivity will improve the rate of false-negative reporting and obviate the need for invasive diagnostic procedures. Automated fluorimetry provides a method for the international standardization of HP serology thereby improving quality control and improving its suitability as a diagnostic adjunct.

Extrinsic allergic alveolitis.

Extrinsic allergic alveolitis (also known as hypersensitivity pneumonitis) is caused by repeated inhalation of mainly organic antigens by sensitized subjects. This induces a hypersensitivity response in the distal bronchioles and alveoli and subjects may present clinically with a variety of symptoms. The aims of this review are to describe the current concepts of the immunological response, the diverse clinical presentation of this disease, the relevant investigations and management, and areas for future studies.