Impact of antigen identification on transplant free survival in interstitial lung disease.

INTRODUCTION: Antigen identification impacts diagnosis as well as prognosis in patients with hypersensitivity pneumonitis. An antigen may also be present in other etiologies of interstitial lung disease, however it is unknown whether identification impacts survival. METHODS: We evaluated a retrospective cohort in order to determine if antigen identification affects transplant free survival in patients with hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, connective tissue disease interstitial lung disease, and interstitial pneumonia with autoimmune features. Only patients with definite or high probability of hypersensitivity pneumonitis by American Thoracic Society guidelines were included in the analysis. RESULTS: Transplant free survival was improved with antigen identification in patients with hypersensitivity pneumonitis but not in patients with idiopathic pulmonary fibrosis, connective tissue disease interstitial lung disease, and interstitial pneumonia with autoimmune features. CONCLUSION: Our study suggests that removal of identified antigen in interstitial lung diseases other than hypersensitivity pneumonitis may not be impactful. Additionally, it further suggests that definitive diagnosis of hypersensitivity pneumonitis with bronchoalveolar lavage and transbronchial biopsy may be beneficial prior to recommending antigen removal.

Impact of radiographic honeycombing on transplant free survival and efficacy of immunosuppression in fibrotic hypersensitivity pneumonitis.

BACKGROUND: The distinction between hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF) was thought to be important due to the difference in mortality between the conditions as well as the response to treatment. However, recent work suggests that the clinical diagnosis may matter less than certain radiographic features, namely usual interstitial pneumonia (UIP) pattern. The purpose of this study is to evaluate whether radiographic honeycombing is more predictive of transplant-free survival (TFS) than other clinical, radiographic, or histologic findings that distinguish HP from IPF in the current guidelines and to evaluate the impact of radiographic honeycombing on the efficacy of immunosuppression in fibrotic HP. METHODS: We retrospectively identified IPF and fibrotic HP patients evaluated between 2003 and 2019. Univariable and multivariable logistic regression was performed for patients with fibrotic HP and IPF to evaluate TFS. To assess the impact of treatment with immunosuppression on TFS in fibrotic HP, a cox proportional hazard model adjusted for known predictors of survival in HP including age, gender, and baseline pulmonary function testing results was constructed, and p-interaction for the presence of honeycombing on high resolution computed tomography and use of immunosuppression was calculated. RESULTS: Our cohort included 178 with IPF and 198 with fibrotic HP. In a multivariable analysis, the presence of honeycombing had a greater impact on the TFS than the diagnosis of HP vs. IPF. Among the criteria used in the HP diagnostic guidelines, only typical HP scan impacted survival in a multivariable model, while identification of antigen and surgical lung biopsy findings had no impact on survival. We identified a trend toward worse survival on immunosuppression in those with HP with radiographic honeycombing. CONCLUSION: Our data suggests that honeycombing and baseline pulmonary function testing have a greater impact on TFS than the clinical diagnosis of IPF vs. fibrotic HP and that radiographic honeycombing is a predictor of poor TFS in fibrotic HP. We suggest that invasive diagnostic testing including surgical lung biopsy may not be useful in predicting mortality in HP patients with honeycombing and may potentially increase risk of immunosuppression.

Characteristics of a diagnostic bronchoscopy in hypersensitivity pneumonitis.

BACKGROUND: Bronchoalveolar lavage and transbronchial biopsy can increase diagnostic confidence in the diagnosis of hypersensitivity pneumonitis (HP). Improving the yield of bronchoscopy may help to improve diagnostic confidence while decreasing the risk of potential adverse outcomes associated with more invasive procedures such as surgical lung biopsy. The purpose of this study is to identify factors that were associated with a diagnostic BAL or TBBx in HP. METHODS: We conducted a retrospective cohort study of HP patients at a single center who underwent bronchoscopy during the diagnostic evaluation. Imaging characteristics, clinical characteristics including use of immunosuppressive medications and presence of active antigen exposure at the time of bronchoscopy, and procedural characteristics were collected. Univariable and multivariable analysis was performed. RESULTS: 88 patients were included in the study. 75 patients underwent BAL and 79 patients underwent TBBx. Patients who had an active fibrogenic exposure at the time of bronchoscopy had a higher BAL yield than those who were out of exposure at the time of bronchoscopy. TBBx yield was higher when more than 1 lobe was biopsied, with a trend toward higher yield of TBBx when nonfibrotic lung was biopsied compared to fibrotic lung. DISCUSSION: Our study suggests characteristics that may improve yield of BAL and TBBx in patients with HP. We suggest that bronchoscopy be performed when patients are in the antigen exposure and that TBBx samples are taken from more than 1 lobe in order to improve diagnostic yield of the procedure.

Rhabdomyolysis and Resultant Acute Renal Failure due to Legionella Pneumonia in a Patient with Human Immunodeficiency Virus.

Legionnaires' disease is a severe pneumonia caused by Legionella that results in laboratory abnormalities including hyponatremia and elevated liver enzymes. Rarely skeletal muscle and renal abnormalities occur. This case report describes a case of Legionella pneumonia complicated by rhabdomyolysis and acute renal failure in a patient with the human immunodeficiency virus.

Impact of number and type of identified antigen on transplant-free survival in hypersensitivity pneumonitis.

BACKGROUND: Identification of inciting antigen can affect diagnostic confidence, quality of life, and prognosis in patients with HP. It is unknown whether the number and type of antigen affect results of diagnostic testing or prognosis, whether antigen identified by clinical history alone affects prognosis, and whether feather exposure is associated with outcomes similar to those of other antigens. METHODS: To evaluate whether the number or type of antigen identified by clinical history alone affects clinical outcomes, we evaluated a retrospective cohort of patients with a high or definite probability of HP based on recent guidelines. RESULTS: In our retrospective cohort, 136 patients met high or definite probability of HP and were included in the analysis. Median transplant-free survival was better in patients with antigen identified on clinical history alone than patients without identified antigen. Feather exposure was associated with improved TFS compared to patients without antigen identified; there was no difference in TFS between patients with feather exposure and either mold or live bird exposure. Mold antigen was associated with increased risk of fibrotic HP compared to avian antigen. Among patients with identified antigen, the number and type of antigen did not affect TFS. DISCUSSION: Our study suggests that clinical history is adequate for providing prognostic information to patients with HP and classifying the diagnostic probability of HP according to recent guidelines. Feather exposure should be considered an inciting antigen in patients with ILD.

Addition of antifibrotic therapy to immunosuppression in hypersensitivity pneumonitis: A case series.

Hypersensitivity pneumonitis has historically been treated with immunosuppression, but recently nintedanib was approved for the treatment of progressive fibrotic HP. One limitation of INBUILD is that the only immunosuppression (IS) permitted at the time of enrollment was glucocorticoids at a dose of less than 20mg per day, so the additive effect of antifibrotic (AF) therapy to IS in HP remains unclear. We present 5 cases of patients with HP for whom AF therapy was added to IS. Trends observed in the cohort include reduced decline in FVC, oxygen requirement, and symptoms in the year after adding AF to IS in 4 of the 5 patients. All 5 patients (100%) in our series demonstrated progression in the year prior to initiation of antifibrotic based on criteria outlined in the INBUILD trial, but only 1 of 5 (20%) progressed in the year after AF. There was a significant decrease in the rate of relative decline in % predicted FVC in the 12 months after initiation of antifibrotic compared to the 12 months prior to antifibrotic (0.4% ±7.6 vs -17.5% ±7.6, p = 0.0495). Compared to the 12 months prior to antifibrotic therapy, fewer patients met criteria for progression in the 12 months after initiating antifibrotic therapy (p = 0.048). Similarly, fewer patients met criteria for progression in the 6 months after initiating antifibrotic therapy compared to the 6 months prior (p = 0.048). A larger study with control groups on IS alone and AF alone is needed to confirm the role of AF therapy in combination with IS in patients with HP.