Does a Type of Inciting Antigen Correlate with the Presence of Lung Fibrosis in Patients with Hypersensitivity Pneumonitis?

Introduction: Hypersensitivity pneumonitis (HP) is an interstitial inflammatory lung disease that develops as a result of exposition to various, mostly organic antigens. In some patients, fibrotic HP is diagnosed. Factors predisposing to the development of fibrotic lung disease in HP patients are not well documented in the literature. The genetic susceptibility of the patient, type of inciting antigen, and type of exposure, as well as various demographic and clinical variables, may influence the fibrotic process. Aim: The aim of the present study was to investigate whether the type of inciting antigen increases the risk of fibrotic lung disease in HP patients. Methods: Clinical data of consecutive patients with HP diagnosed between 2019 and 2023 were retrospectively reviewed. The exposition to the inciting antigens was investigated by the standardized questionnaire. Recent HP classification into fibrotic (fHP) and non-fibrotic (non-fHP) types was applied. Results: Sixty-six patients diagnosed with HP were analyzed. All patients filled out the exposure questionnaire, and 62 (94%) reported at least one possible exposure. The most prevalent exposures reported were avian, water systems, feather duvets, and hay/straw. Exposure to avian antigens as well as to coal/biomass heating were significantly more prevalent among patients with fHP compared to those with non-fHP (70% vs. 40%, p = 0.03 and 27% vs. 5%, p = 0.04, respectively). Nevertheless, in the multivariate analysis, older age at diagnosis was the only factor influencing the development of fHP (OR 1.064, 95% CI 1.004 to 1.138, p = 0.04). Reported avian antigen exposure correlated well with positive precipitins to avian antigens, whereas no correlation was found between hay/straw exposure and positive antibodies to termophilic actinomycetes. Conclusions: Exposure to birds and coal heating was the most frequently present factor in subjects with fHP, but only older age at diagnosis remained a significant fHP predictor in the multifactor analysis.

Dopamine D2 and Serotonin 5-HT1A Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain.

Targeted therapy uses multiple ways of ensuring that the drug will be delivered to the desired site. One of these ways is an encapsulation of the drug and functionalization of the surface. Among the many molecules that can perform such a task, the present work focused on the antibodies of single-chain variable fragments (scFvs format). We studied scFv, which specifically recognizes the dopamine D2 and serotonin 5-HT1A receptor heteromers. The scFvD2-5-HT1A protein was analyzed biochemically and biologically, and the obtained results indicated that the antibody is properly folded and non-toxic and can be described as low-immunogenic. It is not only able to bind to the D2-5-HT1A receptor heteromer, but it also influences the cAMP signaling pathway and-when surfaced on nanogold particles-it can cross the blood-brain barrier in in vitro models. When administered to mice, it decreased locomotor activity, matching the effect induced by clozapine. Thus, we are strongly convinced that scFvD2-5-HT1A, which was a subject of the present investigation, is a promising targeting ligand with the potential for the functionalization of nanocarriers targeting selected areas of the brain.

Chronic hypersensitivity pneumonitis is associated with an increased risk of venous thromboembolism: a retrospective cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis share commonalities in pathogenesis shifting haemostasis balance towards the procoagulant and antifibrinolytic activity. Several studies have suggested an increased risk of venous thromboembolism in IPF. The association between venous thromboembolism and chronic hypersensitivity pneumonitis has not been studied yet. METHODS: A retrospective cohort study of IPF and chronic hypersensitivity pneumonitis patients diagnosed in single tertiary referral center between 2005 and 2018 was conducted. The incidence of symptomatic venous thromboembolism was evaluated. Risk factors for venous thromboembolism and survival among those with and without venous thromboembolism were assessed. RESULTS: A total of 411 (259 IPF and 152 chronic hypersensitivity) patients were included (mean age 66.7 ± 8.4 vs 51.0 ± 13.3 years, respectively). There were 12 (4.6%) incident cases of venous thromboembolism in IPF and 5 (3.3%) in chronic hypersensitivity pneumonitis cohort. The relative risk (RR) of venous thromboembolism in chronic hypersensitivity pneumonitis was not significantly different to that found in patients with IPF (7.1 vs 11.8/1000 person-years, RR 1.661 95% CI 0.545-6.019, respectively). The treatment with systemic steroids (OR 5.38; 95% CI 1.65-18.8, p = 0.006) and GAP stage 3 (OR 7.85; 95% CI 1.49-34.9; p = 0.037) were significant risk factors for venous thromboembolism in IPF. Arterial hypertension and pulmonary hypertension significantly increased risk of venous thromboembolism in chronic hypersensitivity pneumonitis. There were no significant differences in survival between patients with and without venous thromboembolism. CONCLUSIONS: The patients with chronic hypersensitivity pneumonitis have a marked increase in the risk of venous thromboembolism, similar to the patients with IPF. Venous thromboembolism does not affect the survival of patients with IPF and chronic hypersensitivity pneumonitis.