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.

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.

Low Rates of Reproductive Counseling Documentation in Women With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: Women with interstitial pneumonia with autoimmune features (IPAFs), a subset of interstitial lung disease (ILD), are at risk for pregnancy complications. Family planning discussions improve pregnancy outcomes in women with ILD. The objective of this study was to evaluate the documentation of reproductive counseling in IPAF female patients of childbearing age by pulmonary and rheumatology providers at an academic medical center. METHODS: We conducted a medical record review study of pulmonary and rheumatology encounters in reproductive-aged women with IPAF to evaluate documentation of family planning discussions and contraceptive use. We used nonparametric measures of association and logistic regression to evaluate the relationship between patient characteristics and the presence of reproductive counseling documentation by providers. RESULTS: Thirty-one women met IPAF classification and were ≤50 years at initial ILD clinic visit. Twenty-five (81%) of these women had risk factors for adverse pregnancy outcomes. Ten women (32%) had a record of reproductive counseling during any visit with their pulmonary provider. Of the 21 patients who also saw a rheumatology provider, 12 (57%) women had a record of reproductive counseling during any visit with their rheumatology provider. No baseline characteristics were associated with odds of reproductive counseling documentation. CONCLUSIONS: Neither pulmonary nor rheumatology providers consistently discussed family planning/contraceptive use with reproductive-aged women with IPAF. There was a trend for rheumatology providers to discuss reproductive issues with IPAF patients more frequently than pulmonary providers. Efforts should focus on educating providers about the need for reproductive counseling in women with IPAF of childbearing age.

Interstitial Pneumonia with Autoimmune Features: What the Rheumatologist Needs to Know.

PURPOSE OF REVIEW: This narrative review will focus on the role of the rheumatologist in evaluating patients with interstitial lung disease (ILD) without a defined rheumatic disease and will outline the current classification criteria for interstitial pneumonia with autoimmune features (IPAF) and describe what is known regarding IPAF pathobiology, natural history, prognosis, and treatment. Lastly, knowledge gaps and opportunities for future research will be discussed. RECENT FINDINGS: IPAF is a recently defined classification of ILD patients who have features suggesting an autoimmune-mediated process, but do not fulfill current rheumatic disease criteria. The goal of the IPAF criteria is to provide a uniform case definition for the study of autoimmune ILD patients who do not currently fit within standard ILD diagnostic categories, ultimately improving diagnosis and therapy. Many of these patients are referred for rheumatologic evaluation to aid the diagnostic process. The care of the IPAF patient is complex and is multidisciplinary with pulmonology, rheumatology, pathology, radiology, physical therapy, primary care, pulmonary transplant providers all serving vital roles. The rheumatologist has several roles which include classification, disease monitoring, and management.

Variables Associated With Response to Therapy in Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: We have limited knowledge regarding characteristics of patients with interstitial pneumonia with autoimmune features (IPAF) that are associated with response to immunosuppression. In this study, we used published IPAF criteria to characterize features associated with response to treatment. METHODS: We conducted a single-center medical records review study of 63 IPAF patients to evaluate for serological, clinical, and morphological characteristics that are associated with response to immunosuppression. Response was defined as % relative functional vital capacity decline of less than 10% and absence of death or lung transplant within the first year of continuous immunosuppressive therapy. Nonparametric measures of association and multivariate logistic regression were used to evaluate the relationship between baseline characteristics and immunosuppressive response. RESULTS: There was a trend of greater progression among men, ever smokers, those negative for antisynthetase antibodies, and those with usual interstitial pneumonia radiographic pattern, but no statistically significant relationship was found between baseline serological, clinical, or morphological features and response to immunosuppression. Patients on combination therapy with mycophenolate mofetil and prednisone had less disease progression (p = 0.018) than those on regimens that did not include both of these medications. CONCLUSIONS: In our cohort, baseline clinical assessment did not identify which patients with IPAF will respond to immunosuppressive therapy. Combination therapy with mycophenolate mofetil and prednisone was associated with lack of disease progression in our IPAF patients, including in IPAF-usual interstitial pneumonia. Further studies are needed to evaluate which IPAF patients would benefit from immunosuppressive therapy, antifibrotic therapy, or a combination of both.

Eosinophilic Chronic Obstructive Pulmonary Disease.

Recent therapeutic advances in the management of asthma have underscored the importance of eosinophilia and the role of pro-eosinophilic mediators such as IL-5 in asthma. Given that a subset of patients with COPD may display peripheral eosinophilia similar to what is observed in asthma, a number of recent studies have implied that eosinophilic COPD is a distinct entity. This review will seek to contrast the mechanisms of eosinophilia in asthma and COPD, the implications of eosinophilia for disease outcome, and review current data regarding the utility of peripheral blood eosinophilia in the management of COPD patients.

Utility of Bronchoalveolar Lavage and Transbronchial Biopsy in Patients with Interstitial Lung Disease.

PURPOSE: Bronchoalveolar lavage and transbronchial biopsy can be a useful tool in the evaluation of interstitial lung disease (ILD), but patient selection for this procedure remains poorly defined. Determining clinical characteristics that help with patient selection for bronchoscopy may improve confidence of ILD classification while limiting potential adverse outcomes associated with surgical lung biopsy. The purpose of this study is to identify factors that were associated with change in multidisciplinary ILD diagnosis (MDD) before and after incorporation of BAL and TBBx data. METHODS: We conducted a retrospective cohort study of ILD patients at a single center who underwent bronchoscopy in the diagnostic workup of ILD. We performed sequential MDD both pre- and post-bronchoscopy to calculate the frequency of change in diagnosis after incorporating information from BAL and TBBx and identify features associated with change in diagnosis. RESULTS: 245 patients were included in the study. Bronchoscopy led to a change in diagnosis in 58 patients (23.7%). The addition of TBBx to BAL increased diagnostic yield from 21.8 to 34.1% (p = 0.027). Identification of antigen, HRCT scan inconsistent with UIP, and absence of a pre-bronchoscopy diagnosis of CTD-ILD or IPAF were associated with a change in diagnosis after bronchoscopy. CONCLUSION: Our study suggests clinical features that may assist with patient selection for bronchoscopy. We suggest bronchoscopy in patients with identified antigen or an HRCT that is consistent with a non-IPF diagnosis. Appropriate patient selection for bronchoscopy may improve ILD diagnostic confidence and avoid potential complications from more invasive and higher risk procedures.

Utility of Bronchoalveolar Lavage and Transbronchial Biopsy in Patients with Hypersensitivity Pneumonitis.

INTRODUCTION: Making the diagnosis of HP is challenging due to a lack of consensus criteria and variability of both pathologic and radiographic findings. The purpose of this retrospective study was to determine the diagnostic utility of the combination of BAL lymphocyte count and TBBX in patients with HP. METHODS: We conducted a retrospective cohort study of all patients with a MDD diagnosis of HP at a single center. RESULTS: 155 patients were included in the study. 49% of patients who underwent BAL had a lymphocyte count > 20, 42% had a lymphocyte count > 30, and 34% had lymphocyte count > 40%. The median BAL lymphocyte count was higher in inflammatory HP compared to fibrotic HP. The addition of TBBX to BAL significantly increased the diagnostic yield regardless of the BAL lymphocyte cutoff used. The yield of bronchoscopy with TBBX and BAL when a lymphocyte count > 40% was used as a cutoff was 52%. CONCLUSIONS: Our study suggests that the combination of TBBX with BAL significantly increases the likelihood that the procedure will provide adequate additional information to allow a confident MDD diagnosis of HP and may reduce the need for SLB in the diagnostic workup of HP.

High Interleukin-13 level is associated with disease stability in interstitial Lung disease.

Purpose: Cytokines can help predict prognosis in interstitial lung disease (ILD) and to differentiate between ILD subtypes. The objectives of our study were to evaluate association of baseline cytokine levels with time to ILD progression and to compare baseline cytokine levels between ILD subtypes. Methods: We quantified 27 cytokines using a multiplex assay in peripheral blood samples from 77 patients. Cox proportional hazards regression analysis was performed to evaluate cytokine impact on the time to progression in the total cohort and within each ILD type. We evaluated for significant differences in cytokine levels between ILD types using ANOVA, Wilcoxon signed-rank test and Tukey method. Results: Higher IL-13 level was associated with longer time to progression (hazard ratio 0.52 [0.33-0.81], p-value 0.004). FGF-ß, GM-CSF, and IL-17 levels differed significantly between fibrotic and inflammatory ILD subgroups. Conclusion: IL-13 may be a useful biomarker predicting ILD stability.

Imaging Features of Idiopathic Interstitial Lung Diseases.

Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unclear etiology and are distinguished from diffuse parenchymal lung diseases of known cause, such as connective tissue disease-related interstitial lung diseases or hypersensitivity pneumonitis by history, physical exam, imaging, serologic testing, and, when necessary, histopathology. The 2013 American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines are the most widely accepted classification of IIPs and include the following diagnoses: idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, idiopathic lymphocytic interstitial pneumonia, idiopathic pleuro-parenchymal fibroelastosis, respiratory bronchiolitis-interstitial lung disease, and desquamative interstitial pneumonia. The gold standard for diagnosis of IIP involves multidisciplinary discussion among pulmonologists, radiologists, and pathologists. The focus of this review will be to discuss the imaging features of the most common IIPs and the role of multidisciplinary discussion as the gold standard for diagnosis.

Addressing Mental Health Needs Among Frontline Health Care Workers During the COVID-19 Pandemic.

Frontline workers experienced inordinate stress levels during the COVID-19 pandemic, as historically high volume and acuity in our hospitals was accompanied by concerns about our safety. We suggest that supporting frontline workers is an essential part of the pandemic response plan. We propose strategies to address the emotional and mental health (MH) needs of frontline health care workers during and after a pandemic that integrates knowledge from the disaster MH literature with the lessons learned during the COVID-19 pandemic. The disaster MH literature emphasizes distinguishing development of defined psychiatric disorders from emotional distress representing normative responses to disaster trauma and stress. Differentiating psychopathology from distress requires diagnostic assessment by a trained clinician. Where shortages of psychiatrists exist, primary care physicians may be trained to assist with disaster-related psychiatric assessment and initiation of treatment for psychopathologic features. The first component of a pandemic MH plan for critical frontline workers is to distinguish psychiatric illness from normative distress and to provide adequate treatment of psychopathologic symptoms. A second component of the comprehensive pandemic MH response is the provision of supportive care interventions and resources for normative distress. These interventions may include psychological first aid, individual or group counseling, broadening the pool of frontline workers, and buddy systems. Although these interventions were unknown or difficult to put in place at the beginning of the COVID-19 pandemic, we now have an opportunity to implement postpandemic MH response plans and to create response planning for subsequent COVID-19 surges integrating MH care into the front lines.

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.

A case of diffuse alveolar hemorrhage secondary to fat embolism after long bone fracture.

Fat embolism syndrome (FES) is a known complication of long bone fractures, frequently presenting with hypoxemia. Diffuse alveolar hemorrhage (DAH) is a rare complication of the condition. Imaging characteristics are frequently non-specific to FES, as are findings on bronchoalveolar lavage. No specific treatment exists, though steroids and albumin can be considered. We present the case of an 18 year old male who presented to the emergency room after a motorcycle collision. His CXR was initially clear, but he developed pulmonary infiltrates, a new oxygen requirement, and hemoptysis. Bronchoscopy confirmed DAH by serial lavage, and BAL was notable for abundant lipid-laden macrophages by Oil-red-O stain. He improved with methylprednisolone and albumin. This case highlights the need for a high index of suspicion both for FES, and for DAH as a complication that may develop days after trauma. We review treatment paradigm for this serious condition.

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.