Immune Response in Hypersensitivity Pneumonitis
| Status: | Recruiting |
|---|---|
| Conditions: | Pneumonia, Neurology |
| Therapuetic Areas: | Neurology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 3/15/2019 |
| Start Date: | November 29, 2018 |
| End Date: | June 30, 2021 |
CD4 T-cell Immunephenotype in Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that is caused by exposure
of susceptible individuals to organic materials in the environment. It is also known by
various names depending on the exposure and some of these names include farmer's lung, pigeon
breeder's lung, hot tub lung to name a few. HP can cause lung scarring that impairs breathing
and oxygenation. Early detection and avoidance of triggers can stop and reverse the disease
but a significant number of patients continue to have active disease requiring treatment in
spite of avoiding the trigger. The current choice of therapies is based on clinical
experience and not on rigorous clinical trials. Not fully understanding the type of
inflammation that is seen in HP and the cells involved in this inflammatory response limits
health care providers' ability to choose drugs to study in HP that can stop the inflammation
and limit scar formation. The goal of the investigators' study is to better understand the
type of cells that are involved in the inflammatory response in the lungs of HP patients and
what drives these cells to be active. By better understanding the type of cells and what
drives them, health care providers can begin to choose and study drugs that can limit the
inflammation and subsequent scarring. The investigators' will recruit HP patients and with
their consent perform a scope of the lungs (bronchoscopy) with a limited lung wash to get the
inflamed cells out of the lungs to further study them in the lab. The investigators' study
will provide us with preliminary results to guide us in performing a more detailed study in
the future to better understand the disease.
of susceptible individuals to organic materials in the environment. It is also known by
various names depending on the exposure and some of these names include farmer's lung, pigeon
breeder's lung, hot tub lung to name a few. HP can cause lung scarring that impairs breathing
and oxygenation. Early detection and avoidance of triggers can stop and reverse the disease
but a significant number of patients continue to have active disease requiring treatment in
spite of avoiding the trigger. The current choice of therapies is based on clinical
experience and not on rigorous clinical trials. Not fully understanding the type of
inflammation that is seen in HP and the cells involved in this inflammatory response limits
health care providers' ability to choose drugs to study in HP that can stop the inflammation
and limit scar formation. The goal of the investigators' study is to better understand the
type of cells that are involved in the inflammatory response in the lungs of HP patients and
what drives these cells to be active. By better understanding the type of cells and what
drives them, health care providers can begin to choose and study drugs that can limit the
inflammation and subsequent scarring. The investigators' will recruit HP patients and with
their consent perform a scope of the lungs (bronchoscopy) with a limited lung wash to get the
inflamed cells out of the lungs to further study them in the lab. The investigators' study
will provide us with preliminary results to guide us in performing a more detailed study in
the future to better understand the disease.
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.
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.
Inclusion:
1. Adult between the ages of 18 and 80 years old.
2. Non-smoker or previous smoker quit >6months ago.
3. Radiological findings compatible with sub-acute or chronic HP4.
4. Histopathological findings compatible with sub-acute or chronic HP4.
5. Able to understand the consent process and procedures involved in the study.
Exclusion:
1. Unable to understand the consent process or procedures involved in the study.
2. End-stage lung disease defined as predominantly honeycombing on chest CT and/or
FVC<60% and/or DLCO <30%.
3. Requiring high oxygen needs >4L.
4. Pregnancy.
5. Treated with a biological agent within the past 6 months.
6. Suspicion of current infection or within the past 3 months.
7. Bleeding disorder or on anti-coagulants other than aspirin.
8. Any co-morbid condition that increases risk of bronchoscopy including but not limited
to cardiac disease, uncontrolled hypertension, uncontrolled diabetes and/or morbid
obesity.
9. Systemic immunosuppressive therapy within the past 6 months.
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