CD4 T-cell immunephenotype in hypersenstivity pneumonitis

Hypersensitivity pneumonitis (HP) is a granulomatous lung disorder triggered by exposure to one of a multitude of organic antigens. Incidence rates of HP vary by geography, season and population studied but it is estimated to be the third most common interstitial lung disease with an estimated prevalence rate in the USA of 420-3000/100,0002. HP accounts for at least 7.5% of ILD related lung transplant. Exposure to an antigen in a susceptible host induces an inflammatory response with the subsequent formation of poorly formed granulomas that impact gas exchange which clinically manifests as shortness of breath, hypoxia and radiographic changes. HP can present acutely, subacutely or chronically depending on the duration of symptoms and radiographic changes. Radiographic manifestations of HP include ground-glass changes, centrilobular nodules, air trapping known as mosaic pattern, fibrosis, emphysema, or more frequently a combination of these. The cornerstone of management is identification and avoidance of the inciting agent which is effective if accomplished early in the disease process.

Although detection and avoidance of possible triggers can attenuate or reverse the disease, a significant number of patients continue to have active and/or progressive disease requiring chronic immunosuppressive therapy. Standard of care for IS therapy is corticosteroids and azathioprine but this is based on clinical experience and not based on randomized clinical trials(ref). The efficacy of this regimen is not known and patients develop persistent or progressive disease in spite of aggressive therapy leading to end stage lung disease necessitating lung transplantation or ending with death. To date, there are no randomized trials for immunosuppressive therapies and no reports of the use of biological agents in HP. The lack of studies is partially due to the lack of a thorough understanding of the immune response in HP especially in patient based studies that focus at the site of disease activity, the lungs.

The immunological response and pathways leading to this response have not been fully investigated especially in humans. The Th17 pathway has been implicated in disease pathogenesis and T-regulatory cell dysfunction has been described although studies in humans are limited. Recent work in sarcoidosis, a granulomatous lung disease, has shown that Th17.1 cells play a potential important role in granuloma immunopathogenesis. Through an R01 mechanism, the investigators are currently investigating the role of T-cell skewing and associated gene expression in sarcoidosis that is associated with progressive disease vs stable disease and the investigators are investigating its impact on disease course.

This gap in knowledge in HP has limited the choice and study of immunomodulatory agents in HP and especially biological agents in the treatment of persistent and progressive disease. To narrow this knowledge gap, the investigators propose conducting a study to investigate the lung CD4+ T-cell immunophenotype and CD4+ T-cell gene expression in HP to enhance the investigators' understanding of the immune response in HP and the pathways involved in the immune response which would enable the investigators to further pursue guided therapeutic trials in subacute and chronic HP.