Usual Interstitial Pneumonia Patients Research Articles

Clinical and Serological Characteristics of a Monocentric Cohort of Patients Affected by Interstitial Pneumonia with Autoimmune Features (IPAF).

Interstitial lung diseases (ILDs) are diseases characterised by excessive deposition of collagen matrices in the pulmonary interstitium. Some of them are considered idiopathic (idiopathic pulmonary fibrosis - IPF), others are related to known pathologies such as connective tissue diseases (CTDs-ILD). Patient affected by ILD and features referable to CTD, not satisfying CTD criteria, are called Interstitial pneumonia with autoimmune features (IPAF) patients. The aim of this report was to investigate clinical and serologic features of a monocentric cohort of patients with IPAF. Another objective was to describe the autoantibody profile, clinical features, High Resolution Computerised Tomography (HRCT) and Nailfold Video Capillaroscopy (NVC) patterns. 36 IPAF patients were consecutively enrolled. Clinical, serological, and morphological features were collected. 36 consecutive IPAF patients were enrolled from January 2021 to January 2022. Raynaud's phenomenon was the most frequent symptom identified. We also described other signs and symptoms not included in IPAF criteria. 36,1% of patients demonstrated a Usual Interstitial Pneumonia (UIP) pattern by HRCT. Pulmonary arterial pressure estimation (PAPs) resulted elevated (≥ 25 mmHg) in 6 patients. Antinuclear antibodies (ANA) ≥ 1/80 was the most frequent autoantibody, followed by anti-Ro, in patients with UIP pattern and Non-Specific Interstitial Pneumonia (NSIP) pattern at HRCT. NVC highlighted non-specific microangiopathy as the most common pattern especially in UIP patients. This paper may contribute to stimulate the interest in better characterisation of clinical, serologic, and instrumental features for IPAF patients by redefining IPAF classification criteria in order to treat them as best as possible.

Clinical and Prognostic Significance of p-ANCA Positivity in Idiopathic Pulmonary Fibrosis: A Retrospective Observational Study.

Perinuclear Anti Neutrophil Cytoplasmic Antibody (p-ANCA) is a serological marker of Microscopic Polyangiitis (MPA), a vasculitis associated with lung involvement potentially mimicking Idiopathic Pulmonary Fibrosis (IPF). In this study, we evaluated the role of p-ANCA in predicting clinical evolution and prognosis in a cohort of IPF patients. In this observational, retrospective, case-control study, we compared 18 patients with an IPF diagnosis and p-ANCA positivity with 36 patients with seronegative IPF, matched for age and sex. IPF patients with and without p-ANCA showed similar lung function decline during the follow-up, but IPF p-ANCA+ showed better survival. Half of IPF p-ANCA+ patients were classified as MPA for the development of renal involvement (55%) or skin signs (45%). The progression towards MPA was associated with high levels of Rheumatoid Factor (RF) at baseline. In conclusion, p-ANCA, mainly when associated with RF, could predict the evolution of Usual Interstitial Pneumonia (UIP) towards a definite vasculitis in patients, with a better prognosis compared with IPF. In this view, ANCA testing should be included in the diagnostic workup of UIP patients.

Lung cancer resection in patients with underlying usual interstitial pneumonia: a meta-analysis

ObjectivePatients with lung cancer with underlying idiopathic pulmonary fibrosis and usual interstitial pneumonia (UIP) pattern on CT represent a very high-risk group in terms of postoperative UIP acute exacerbations (AEs)...

[Clinical features and survival analysis of microscopic polyangiitis-associated interstitial lung disease:a retrospective study of 28 patients].

Objective: To explore the clinical features, laboratory examination and imaging features of microscopic polyangiitis (MPA)-associated interstitial lung disease (ILD), and to perform survival analysis. Methods: The records of 28 patients with MPA-ILD who were treated at the Affiliated Hospital of Medical School of Ningbo University were reviewed retrospectively from August 2014 to November 2021. The patients' clinical features, laboratory parameters, pulmonary function test, echocardiography, chest CT scan findings and therapeutic regimen were analyzed, and the relevant data were statistically analyzed. Results: There were 18 males and 10 females, with an average age of (70.1±9.3) years. Among them, 13 patients had a history of smoking. The main clinical manifestations were cough (14/28), fever (12/28), chest tightness, shortness of breath (12/28) and hemoptysis (3/28). Sixteen patients had renal involvement, and 78.57% (22/28) and 89.28% (25/28) of the patients had elevated C-reactive protein (CRP) and ESR respectively. Sixteen (16/28) patients had increased rheumatoid factor (RF), and the positive rate of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) was 82.12% (23/28). 96.43% (27/28) of ILDs were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly usual interstitial pneumonia (UIP) or UIP-like (15/28), followed by nonspecific interstitial pneumonia (NSIP) (8/28). Compared with non-UIP-like patients, UIP or UIP-like patients were older (P=0.018), and had higher serum LDH level (P=0.041), but serum creatinine level was significantly lower (P=0.041). Univariate and multivariate survival analysis showed that inappropriate treatment (HR=9.81, 95%CI: 1.68-57.29, P=0.011) and elevated serum LDH (HR=4.11, 95%CI: 0.99-17.00, P=0.051) were independent risk factors for shortened survival of MPA-ILD, while elevated RF (HR=0.22, 95%CI: 0.06-0.91, P=0.037) was a protective factor for prolonged survival. Conclusions: MPA-ILD patients had fewer systemic vasculitis symptoms. Most of the ILD patients were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly UIP or UIP-like, followed by NSIP. Early use of glucocorticoids combined with immunosuppressant or rituximab could improve the survival rate of MPA-ILD. The elevated serum LDH was an independent risk factor for shortened survival of MPA-ILD, while elevated RF was a protective factor for prolonged survival.

CT-based lung motion differences in patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.

We applied quantitative CT image matching to assess the degree of motion in the idiopathic ILD such as usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Twenty-one normal subjects and 42 idiopathic ILD (31 UIP and 11 NSIP) patients were retrospectively included. Inspiratory and expiratory CT images, reviewed by two experienced radiologists, were used to compute displacement vectors at local lung regions matched by image registration. Normalized three-dimensional and two-dimensional (dorsal-basal) displacements were computed at a sub-acinar scale. Displacements, volume changes, and tissue fractions in the whole lung and the lobes were compared between normal, UIP, and NSIP subjects. The dorsal-basal displacement in lower lobes was smaller in UIP patients than in NSIP or normal subjects (p = 0.03, p = 0.04). UIP and NSIP were not differentiated by volume changes in the whole lung or upper and lower lobes (p = 0.53, p = 0.12, p = 0.97), whereas the lower lobe air volume change was smaller in both UIP and NSIP than normal subjects (p = 0.02, p = 0.001). Regional expiratory tissue fractions and displacements showed positive correlations in normal and UIP subjects but not in NSIP subjects. In summary, lung motionography quantified by image registration-based lower lobe dorsal-basal displacement may be used to assess the degree of motion, reflecting limited motion due to fibrosis in the ILD such as UIP and NSIP.

POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

SESSION TITLE: Late Breaking Diffuse Lung Disease PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: Progressive deterioration is the clinical hallmark of Usual Interstitial Pneumonia (UIP). While this entity is an essential criterion for ascertaining a diagnosis of Idiopathic Pulmonary Fibrosis (IPF), it is nonspecific, and it is associated with poor prognosis in patients with Progressive Pulmonary Fibrosis (PPF) beyond IPF. An accurate UIP diagnosis in both groups guides treatment choices. The Envisia Genomic Classifier (EGC) is a clinically validated molecular diagnostic test that identifies a genomic UIP pattern in transbronchial biopsies. Given that a UIP genomic signature reflects the molecular biology of the underlying interstitial lung disease (ILD), we hypothesized that an EGC (+) result is a biomarker of disease progression in patients with fibrotic interstitial ling diseases (ILD).METHODS: We identified 135 patients enrolled in the BRAVE study who underwent pathological evaluation for an undiagnosed ILD, had an EGC result, and had longitudinal forced vital capacity (FVC) measurements. Patients were required to have an FVC performed within six months of BRAVE enrollment and additional measurements at least six months after the baseline FVC. Retrospective analyses of EGC result, change in FVC, and treatment for ILD were performed.RESULTS: Of the 135 patients evaluated, 73 (54%) patients had an EGC UIP (+) result. Overall, patients with an EGC UIP (+) result had a baseline FVC of 66.9% predicted with an absolute 1-year decline in FVC of 3.7% compared to 62 (46%) patients with an EGC UIP negative (-) result who had a baseline FVC of 73.4% with an absolute 1-year decrease in FVC of 0.1% (p=0.06). The 1-year decline in FVC in the Envisia UIP (+) group was observed irrespective of findings on pathology. In pathology UIP (+) patients, 1-yr decline in FVC was 2.4%, compared to a decline of 1.8% in patient in whom pathology was diagnostic but negative for UIP and 1.4% in patients in whom pathology was nondiagnostic (p=0.9).CONCLUSIONS: An Envisia Genomic Classifier UIP (+) result identified patients who demonstrated disease progression as measured by a decline in FVC in the subsequent 6 + months. FVC decline was observed even in ECG UIP (+) patients in whom pathology was negative for UIP and those in whom pathology was considered nondiagnostic.CLINICAL IMPLICATIONS: It has been established previously that an EGC UIP (+) result has clinical utility in multidisciplinary discussions for making a confident diagnosis of ILD including IPF in the appropriate clinical setting. These results suggest the additional clinical utility of an EGC UIP (+) result as a biomarker for predicting PPF and may prompt consideration of early antifibrotic therapy with the potential for improved outcomes in patients with ILD. Further studies are warranted to determine utility and validate results from this study.DISCLOSURES:Employee relationship with Veracyte Please note: 2/1/2021-present by William Bulman, value=SalaryEmployee relationship with Veracyte Inc. Please note: 05/19/2019 - present Added 06/06/2022 by Jeremy Burbanks-Ivey, value=SalaryEmployee relationship with Veracyte Please note: >$100000 by Jing Huang, value=SalaryEmployee relationship with Veracyte Please note: >$100000 by Marla Johnson, value=SalaryEmployee relationship with Veracyte, Inc. Please note: 2008-present by Giulia Kennedy, value=SalarySpeaker/Speaker's Bureau relationship with Genentech Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=HonorariaSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=HonorariaResearch relationship with Celgene Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Novartis Please note: pending Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Bellerophon Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Galactic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Respivant Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportMy spouse/partner as a Employee relationship with Medtronic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=SalaryConsultant relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with Bellerophon Please note: active Added 03/28/2022 by Lisa Lancaster, value=HonorariaConsultant relationship with BMS Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeGrant/Research support relationship with fibrogen Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportGrant/Research support relationship with Pliant Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportConsultant relationship with Astrazeneca Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with nashville biosciences Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with DevProBiopharma Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeResearch Grant relationship with Roche Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportConsultant relationship with Daewoong Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with United Therapeutics Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeEmployee relationship with Veracyte Please note: 4.5 years Added 03/31/2022 by Lori Lofaro, value=SalaryRemoved 06/08/2022 by Lori LofaroEmployee relationship with Veracyte Please note: 5 years Added 06/08/2022 by Lori Lofaro, value=SalaryEmployee relationship with Veracyte, Inc. Please note: 07/2018 - Present Added 03/31/2022 by Eric Morrie, value=SalaryScientific Medical Advisor relationship with Veracyte Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting feeResearch grant reviewer relationship with Boerhinger Ingelheim Please note: 2020-2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting feeScientific Medical Advisor relationship with United therapeutics Please note: 2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting feeScientific Medical Advisor relationship with BMS Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting feeScientific Medical Advisor relationship with roche -genentech Please note: 2020++ Added 06/11/2022 by Ganesh Raghu, value=nonesceintific medical advisor relationship with Fibrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneRemoved 06/11/2022 by Ganesh RaghuScientific Medical Advisor relationship with FIbrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneScientific Medical Advisor relationship with ROCHE -GENENTECH Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneScientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONRRemoved 06/11/2022 by Ganesh RaghuScientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONEScientific Medical Advisor relationship with BELLEROPHAN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONEDATA SAFETY MONITORIN BOARD relationship with AVALYN Please note: 2019 - Added 06/11/2022 by Ganesh Raghu, value=noneRemoved 06/11/2022 by Ganesh RaghuScientific Medical Advisor relationship with AVALYN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneGrant relationship with Boehringer Ingelheim Please note: 2014 to present by Christopher Ryerson, value=Grant/ResearchConsultant relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=Consulting feeSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=RoyaltyConsultant relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=Consulting feeSpeaker/Speaker's Bureau relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=RoyaltySpeaker/Speaker's Bureau relationship with Cipla Ltd. Please note: 2020 by Christopher Ryerson, value=RoyaltyAdvisory Committee Member relationship with Veracyte Please note: 2021 by Christopher Ryerson, value=Consulting feeAdvisory Committee Member relationship with Astra Zeneca Please note: 2021 by Christopher Ryerson, value=Consulting feeConsultant relationship with Pliant Therapeutics Please note: ongoing Added 06/06/2022 by Christopher Ryerson, value=Consulting feeAdvisory Committee Member relationship with veracyte Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting feeAdvisory Committee Member relationship with genentech Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting feeAdvisory Committee Member relationship with united therapeutics Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting feeSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=HonorariaAdvisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeAdvisory Committee Member relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeSpeaker/Speaker's Bureau relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeAdvisory Committee Member relationship with Veracyte Please note: May 2022 Added 06/21/2022 by Athol Wells, value=Consulting fee SESSION TITLE: Late Breaking Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Progressive deterioration is the clinical hallmark of Usual Interstitial Pneumonia (UIP). While this entity is an essential criterion for ascertaining a diagnosis of Idiopathic Pulmonary Fibrosis (IPF), it is nonspecific, and it is associated with poor prognosis in patients with Progressive Pulmonary Fibrosis (PPF) beyond IPF. An accurate UIP diagnosis in both groups guides treatment choices. The Envisia Genomic Classifier (EGC) is a clinically validated molecular diagnostic test that identifies a genomic UIP pattern in transbronchial biopsies. Given that a UIP genomic signature reflects the molecular biology of the underlying interstitial lung disease (ILD), we hypothesized that an EGC (+) result is a biomarker of disease progression in patients with fibrotic interstitial ling diseases (ILD). METHODS: We identified 135 patients enrolled in the BRAVE study who underwent pathological evaluation for an undiagnosed ILD, had an EGC result, and had longitudinal forced vital capacity (FVC) measurements. Patients were required to have an FVC performed within six months of BRAVE enrollment and additional measurements at least six months after the baseline FVC. Retrospective analyses of EGC result, change in FVC, and treatment for ILD were performed. RESULTS: Of the 135 patients evaluated, 73 (54%) patients had an EGC UIP (+) result. Overall, patients with an EGC UIP (+) result had a baseline FVC of 66.9% predicted with an absolute 1-year decline in FVC of 3.7% compared to 62 (46%) patients with an EGC UIP negative (-) result who had a baseline FVC of 73.4% with an absolute 1-year decrease in FVC of 0.1% (p=0.06). The 1-year decline in FVC in the Envisia UIP (+) group was observed irrespective of findings on pathology. In pathology UIP (+) patients, 1-yr decline in FVC was 2.4%, compared to a decline of 1.8% in patient in whom pathology was diagnostic but negative for UIP and 1.4% in patients in whom pathology was nondiagnostic (p=0.9). CONCLUSIONS: An Envisia Genomic Classifier UIP (+) result identified patients who demonstrated disease progression as measured by a decline in FVC in the subsequent 6 + months. FVC decline was observed even in ECG UIP (+) patients in whom pathology was negative for UIP and those in whom pathology was considered nondiagnostic. CLINICAL IMPLICATIONS: It has been established previously that an EGC UIP (+) result has clinical utility in multidisciplinary discussions for making a confident diagnosis of ILD including IPF in the appropriate clinical setting. These results suggest the additional clinical utility of an EGC UIP (+) result as a biomarker for predicting PPF and may prompt consideration of early antifibrotic therapy with the potential for improved outcomes in patients with ILD. Further studies are warranted to determine utility and validate results from this study. DISCLOSURES: Employee relationship with Veracyte Please note: 2/1/2021-present by William Bulman, value=Salary Employee relationship with Veracyte Inc. Please note: 05/19/2019 - present Added 06/06/2022 by Jeremy Burbanks-Ivey, value=Salary Employee relationship with Veracyte Please note: >$100000 by Jing Huang, value=Salary Employee relationship with Veracyte Please note: >$100000 by Marla Johnson, value=Salary Employee relationship with Veracyte, Inc. Please note: 2008-present by Giulia Kennedy, value=Salary Speaker/Speaker's Bureau relationship with Genentech Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Honoraria Research relationship with Celgene Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Novartis Please note: pending Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Bellerophon Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Galactic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Respivant Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support My spouse/partner as a Employee relationship with Medtronic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Salary Consultant relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with Bellerophon Please note: active Added 03/28/2022 by Lisa Lancaster, value=Honoraria Consultant relationship with BMS Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Grant/Research support relationship with fibrogen Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Grant/Research support relationship with Pliant Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Consultant relationship with Astrazeneca Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with nashville biosciences Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with DevProBiopharma Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Research Grant relationship with Roche Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Consultant relationship with Daewoong Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with United Therapeutics Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Employee relationship with Veracyte Please note: 4.5 years Added 03/31/2022 by Lori Lofaro, value=Salary Removed 06/08/2022 by Lori Lofaro Employee relationship with Veracyte Please note: 5 years Added 06/08/2022 by Lori Lofaro, value=Salary Employee relationship with Veracyte, Inc. Please note: 07/2018 - Present Added 03/31/2022 by Eric Morrie, value=Salary Scientific Medical Advisor relationship with Veracyte Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Research grant reviewer relationship with Boerhinger Ingelheim Please note: 2020-2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Scientific Medical Advisor relationship with United therapeutics Please note: 2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Scientific Medical Advisor relationship with BMS Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Scientific Medical Advisor relationship with roche -genentech Please note: 2020++ Added 06/11/2022 by Ganesh Raghu, value=none sceintific medical advisor relationship with Fibrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Removed 06/11/2022 by Ganesh Raghu Scientific Medical Advisor relationship with FIbrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Scientific Medical Advisor relationship with ROCHE -GENENTECH Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Scientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONR Removed 06/11/2022 by Ganesh Raghu Scientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONE Scientific Medical Advisor relationship with BELLEROPHAN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONE DATA SAFETY MONITORIN BOARD relationship with AVALYN Please note: 2019 - Added 06/11/2022 by Ganesh Raghu, value=none Removed 06/11/2022 by Ganesh Raghu Scientific Medical Advisor relationship with AVALYN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Grant relationship with Boehringer Ingelheim Please note: 2014 to present by Christopher Ryerson, value=Grant/Research Consultant relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=Royalty Consultant relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=Consulting fee Speaker/Speaker's Bureau relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=Royalty Speaker/Speaker's Bureau relationship with Cipla Ltd. Please note: 2020 by Christopher Ryerson, value=Royalty Advisory Committee Member relationship with Veracyte Please note: 2021 by Christopher Ryerson, value=Consulting fee Advisory Committee Member relationship with Astra Zeneca Please note: 2021 by Christopher Ryerson, value=Consulting fee Consultant relationship with Pliant Therapeutics Please note: ongoing Added 06/06/2022 by Christopher Ryerson, value=Consulting fee Advisory Committee Member relationship with veracyte Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting fee Advisory Committee Member relationship with genentech Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting fee Advisory Committee Member relationship with united therapeutics Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Advisory Committee Member relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Advisory Committee Member relationship with Veracyte Please note: May 2022 Added 06/21/2022 by Athol Wells, value=Consulting fee

Mortality risk prediction with ILD-GAP index in a fibrotic hypersensitivity pneumonitis cohort.

Fibrotic hypersensitivity pneumonitis (fHP) is associated with significant morbidity and mortality. Interstitial lung disease-gender-age-physiology (ILD-GAP) performance in fHP outside the initial cohort was never performed. To assess the ILD-GAP index's ability to predict mortality in a Portuguese cohort of patients with fHP and analyse whether other clinical variables add value. Retrospective analysis of fHP cohort in two Portuguese ILD centres. The baseline ILD-GAP index was calculated. Survival was analysed in months; mortality was the primary outcome. Univariate and multivariate analyses to identify mortality risk factors were performed. A total of 141 patients were included. Fifty-three patients (37.6%) died during the follow-up. The usual interstitial pneumonia (UIP) pattern was found in 49.6%, and their survival was inferior to non-UIP [32 months (interquartile range, IQR = 19, 60) versus 52 months (IQR = 28, 98), p = 0.048]. Patients with an ILD-GAP index higher than three double their risk of mortality [hazard ratio (HR) = 6.48, 95% confidence interval (CI) = (3.03-13.96)] when compared with the patients with an index between 2 and 3 [HR = 3.04, 95% CI = (1.62-5.71)] adjusting for acute exacerbation history. Even though UIP patients had worse survival, it did not reach statistical significance when UIP pattern was added to this model. Acute exacerbation history was an independent risk factor for mortality; however, ILD-GAP still predicted mortality after adjusting for this factor. PaO2 and 6-minute walk test desaturation were not significant risk factors. ILD-GAP index is a good predictor for mortality in fHP, even after adjusting for other mortality risk factors.

Usual Interstitial Pneumonia is the Most Common Finding in Surgical Lung Biopsies from Patients with Persistent Interstitial Lung Disease Following Infection with SARS-CoV-2.

BackgroundThere is increasing interest in persistent interstitial lung disease (ILD) following resolution of acute COVID-19. No studies have yet reported findings in surgical lung biopsies (SLB) from this patient population.MethodsOur Michigan Medicine pathology database was queried for SLB reviewed between January 2020 and April 2021 from patients with persistent ILD following recovery from acute COVID-19. Slides for our retrospective observational study were independently reviewed by two thoracic pathologists, who were blinded to patient clinical data, radiographic findings, and previous pathologic diagnosis.FindingsEighteen cases met inclusion criteria. Of these, nine had usual interstitial pneumonia (UIP). These included two patients with superimposed acute lung injury (ALI). Five cases showed a spectrum of ALI that ranged from persistent diffuse alveolar damage to organizing pneumonia. Four patients had desquamative interstitial pneumonia (1), acute and organizing bronchopneumonia (1), or no diagnostic abnormality (2). Compared to patients without UIP, those with UIP tended to be older and have pre-existing lung disease prior to COVID-19. In patients with UIP, pre-SLB chest computed tomography changes included groundglass with interstitial thickening or peripheral reticulations with bronchiectasis; no UIP patients had groundglass only. The most common radiographic finding in patients without UIP was groundglass opacities only.InterpretationUIP was the most common pathologic finding in patients undergoing evaluation for post-COVID-19 ILD. Our preliminary data suggests that CT changes described as interstitial thickening, peripheral reticulations, and/or bronchiectasis may be helpful in identifying patients with underlying fibrotic chronic interstitial pneumonia for which UIP is the chief concern.FundingNo intramural or extramural funding sources supported this work.

"Usual" interstitial pneumonia with autoimmune features: a prospective study on a cohort of idiopathic pulmonary fibrosis patients.

The classification interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease (ILD) associated with autoimmune characteristics insufficient to reach classification criteria for a specific autoimmune disease (SAD). These criteria are divided into three domains: clinical, serological and morphological. The latter domain does not include the usual interstitial pneumonia (UIP) pattern, which is deemed not to be significantly associated with SAD. Therefore, the enrolment of these patients is more difficult, requiring at least one item from both of the other domains. The objective of this study is to evaluate the rate of progression towards SAD of a cohort of UIP patients satisfying only one IPAF domain (we called this group "UIPAF") compared with classic idiopathic pulmonary fibrosis (IPF). We prospectively enrolled IPF patients with radiologic and/or histologic UIP pattern, followed jointly by rheumatologists and pulmonologists from January 2017 to January 2021, with a minimum follow-up of 12 months. We enrolled 190 IPF patients, 38 (20%) of whom were classified as UIPAF. IPF and UIPAF patients were similar for general characteristics, severity and prognosis, at presentation and at annual check-up. However, 28.9% of UIPAF patients progressed towards SAD, compared with 2% of IPF patients (χ2=30.4, p≤0.0001). The association between a single clinical or serological domain of IPAF and UIP pattern is predictive for the development of a SAD if compared with isolated UIP. ILD can be the first manifestation of SAD, even with a UIP pattern, therefore, the morphological domain of IPAF criteria could be removed.

Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a genetically mediated, age-associated, progressive form of pulmonary fibrosis characterised pathologically by a usual interstitial pneumonia (UIP) pattern of fibrosis. The UIP pattern is also found in pulmonary fibrosis attributable to clinical diagnoses other than IPF (non-IPF UIP), whose clinical course is similarly poor, suggesting common molecular drivers. This study investigates whether IPF and non-IPF UIP lungs similarly express markers of telomere dysfunction and senescence. To test whether patients with IPF and non-IPF UIP share molecular drivers, lung tissues from 169 IPF patients and 57 non-IPF UIP patients were histopathologically and molecularly compared. Histopathological changes in both IPF and non-IPF UIP patients included temporal heterogeneity, microscopic honeycombing, fibroblast foci, and dense collagen fibrosis. Non-IPF UIP lungs were more likely to have lymphocytic infiltration, non-caseating granulomas, airway-centred inflammation, or small airways disease. Telomeres were shorter in alveolar type II (AECII) cells of both IPF and non-IPF UIP lungs than in those of age-similar, unused donor, controls. Levels of molecular markers of senescence (p16 and p21) were elevated in lysates of IPF and non-IPF UIP lungs. Immunostaining localised expression of these proteins to AECII cells. The mucin 5B (MUC5B) gene promoter variant minor allele frequency was similar between IPF and non-IPF UIP patients, and MUC5B expression was similar in IPF and non-IPF UIP lungs. Molecular markers of telomere dysfunction and senescence are pathologically expressed in both IPF and non-IPF UIP lungs. These findings suggest that common molecular drivers may contribute to the pathogenesis of UIP-associated pulmonary fibrosis, regardless of the clinical diagnosis.

Non-invasive IGFBP1, IGFBP2 biomarkers as predictors and outcomes of usual interstitial pneumonia (UIP) therapeutic response

BackgroundUsual interstitial pneumonia (UIP) is a fatal disease that is associated with poor prognosis and survival. Several growth factors such as IGFs (insulin-like growth factors) and IGFBPs (insulin-like growth factor binding proteins) seem to take part to this pathogenesis.Pirfenidone is an immunosuppressant drug that is thought to have anti-inflammatory and anti-fibrotic effects both in vitro and in vivo.ObjectiveTo assess IGFBP1 and IGFBP2 as non-invasive biomarkers for prediction and outcomes of UIP clinical activity and therapeutic response to the anti-fibrotic pirfenidone.ResultsSerum levels of IGFBP1 and IGFBP2 were significantly higher in the UIP group than in the healthy subjects (p ≤ 0.005). After 6 months therapy, UIP patients were divided into 2 groups according to improvement in MRC dyspnea grading into clinically improved and non-improved groups. 6MWT and SPaO2 were significantly improved in the clinically improved group compared to the non-improved one with no differences as regards other parameters (p < 0.0001). Both IGFBP1 and IGFBP2 were significantly decreased in serum while only IGFBP2 was decreased in BAL of all UIP after completing 12 months therapy.ConclusionIGFBP1 and IGFBP2 were increased in active UIP patients and reduced after 12 months anti-fibrosing therapy. IGFBPs may be promising biomarkers and predictors of response to therapy in UIP.

Clinical significance of minor salivary gland biopsy in patients with idiopathic interstitial pneumonia

BackgroundSignificant overlap may occur between idiopathic interstitial pneumonia (IIP) and connective tissue diseases (CTDs) that do not meet the established classification criteria for any known CTDs (i.e., occult CTD). Performing minor salivary gland biopsy (MSGB) to detect occult primary Sjogren's syndrome (pSS) in IIP patients is not well studied. MethodsConsecutive IIP patients underwent MSGB to determine the prevalence of positive MSGB findings. Furthermore, we characterised the clinical, physiological and serological profiles of the MSGB-positive patients. Cox regression models were used to identify independent predictors of survival. ResultsThe data of 155 patients with IIP were available for analysis. Sixty patients (38.7%) had positive MSGB findings. Of them, the mean age was 63.3 years, 51.6% were women, usual interstitial pneumonia (UIP) was the predominant pattern (63.3%), and seronegative antibodies (61.6%) were likely. Patients with positive MSGB findings had significantly greater survival than those with negative MSGB findings (p = 0.041). After stratifying the MSGB cohort based on the presence of a UIP pattern, no significant difference in survival was noted between those with positive MSGB-UIP pattern and those with a negative MSGB-UIP pattern (p = 0.231). Multivariate analysis on all UIP patients showed that higher forced vital capacity (p = 0.010) and smoking status (p = 0.035) were independently associated with survival. ConclusionsA substantial number of IIP patients had underlying occult CTD, highlighting the importance of performing MSGB to identify the salivary component of pSS when evaluating patients with interstitial lung disease of undetermined aetiology.

New York Heart Association class associated with imaging is a prognostic mortality risk predictor in interstitial lung diseases.

Mortality risk factors as forced vital capacity, diffuse lung capacity for carbon monoxide, and 6-minutes' walk test were studied in clinical trials monitoring patients affected by interstitial lung diseases (ILD). However, these parameters showed scarce accuracy. Our aim was to identify New York Heart Association (NHYA) class, in association with high resolution computed tomography (HRCT) and somatostatin receptor scintigraphy (Octreoscan), as a prognostic mortality risk factor in ILD patients. Study population comprised 128 ILD patients (78 Males and 50 Females). Histological diagnosis was usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP) and granulomatous lung disease in 59, 19 and 50 patients, respectively. Patients were monitored by NYHA class, HRCT and Octreoscan at baseline and every 3 years up to a 10-year follow up. Overall survival was calculated from the date of diagnosis until death or last follow-up update. Statistical analysis was performed using Kaplan-Meier, log-rank test (LRT), multivariate analysis with Cox proportional hazard regression model, and log-likelihood ratio test. Overall median survival was 89.3 months (7.4 years) with the poorer survival rate observed in UIP patients. NYHA class came out as a reliable prognostic mortality risk factor in each group of patients and prognosis was progressively worse with NYHA class increase (LRT p<0.001). A strong correlation was found between NYHA class and age, CT-score, and Octreoscan in UIP patients (p<0.001). The determination of NYHA class can therefore be recommended as an additional prognostic mortality risk factor in ILD patients.

Idiopathic pulmonary fibrosis: Significance of the usual interstitial pneumonia (UIP) CT-scan patterns defined in new international guidelines

IntroductionThe new 2018 international guidelines for diagnosing usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) by CT scan split the old pattern possible UIP (2011 IPF guidelines) into two new patterns: probable UIP and indeterminate for UIP. However, the proportions and prognoses of these new CT-scan patterns are not clear. MethodsWe used a monocentric retrospective cohort of 322 patients suspected of having IPF (University Hospital of Rennes; Competence Center for Rare Lung Diseases; 1 January 2012-31 December 2017). All patients initially diagnosed by CT scan as possible UIP were included. The chest CT-scans were then reclassified according to the new 2018 international guidelines by 3 observers. These data were then subjected to survival analysis with multivariate Cox regression using a composite endpoint of death, lung transplantation, a decline of≥10% in forced vital capacity (FVC), or hospitalization. ResultsOf the 89 possible UIP patients included, 74 (83%) were reclassified as probable UIP and 15 (17%) as indeterminate for UIP. Probable UIP patients were more likely to meet the composite endpoint (56/74 [75.7%] vs. 5/15 [33%] patients; HR [IC 95%] =3.12 [1.24; 7.83], P=0.015). Multivariate analysis indicated that the probable UIP pattern was associated with significantly increased risk of reaching the composite endpoint (HR [95% CI]=2.85[1.00; 8.10], P=0.049). ConclusionThe majority of possible UIP diagnoses corresponded to probable UIP, which was associated with a significantly worse prognosis than indeterminate for UIP. This distinction between these two CT patterns emphasizes the relevance of the new international guidelines for the diagnosis of IPF.

Lung Segmentation on HRCT and Volumetric CT for Diffuse Interstitial Lung Disease Using Deep Convolutional Neural Networks.

A robust lung segmentation method using a deep convolutional neural network (CNN) was developed and evaluated on high-resolution computed tomography (HRCT) and volumetric CT of various types of diffuse interstitial lung disease (DILD). Chest CT images of 617 patients with various types of DILD, including cryptogenic organizing pneumonia (COP), usual interstitial pneumonia (UIP), and nonspecific interstitial pneumonia (NSIP), were scanned using HRCT (1-2-mm slices, 5-10-mm intervals) and volumetric CT (sub-millimeter thickness without intervals). Each scan was segmented using a conventional image processing method and then manually corrected by an expert thoracic radiologist to create gold standards. The lung regions in the HRCT images were then segmented using a two-dimensional U-Net architecture with the deep CNN, using separate training, validation, and test sets. In addition, 30 independent volumetric CT images of UIP patients were used to further evaluate the model. The segmentation results for both conventional and deep-learning methods were compared quantitatively with the gold standards using four accuracy metrics: the Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), mean surface distance (MSD), and Hausdorff surface distance (HSD). The mean and standard deviation values of those metrics for the HRCT images were 98.84 ± 0.55%, 97.79 ± 1.07%, 0.27 ± 0.18mm, and 25.47 ± 13.63mm, respectively. Our deep-learning method showed significantly better segmentation performance (p < 0.001), and its segmentation accuracies for volumetric CT were similar to those for HRCT. We have developed an accurate and robust U-Net-based DILD lung segmentation method that can be used for patients scanned with different clinical protocols, including HRCT and volumetric CT.

Comparison of Treatment Methods and Responsiveness Between Patients With Usual Interstitial Pneumonia and Possible Usual Interstitial Pneumonia Radiographic Patterns

SESSION TITLE: Diffuse Lung Disease 1 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: The usual interstitial pneumonia (UIP) pattern of radiographic and histologic findings is commonly associated with idiopathic pulmonary fibrosis (IPF), although it can be associated with secondary interstitial lung diseases (ILD). Based on the radiographic findings, ILD can be classified as “UIP, “possible UIP”, or “inconsistent with UIP.” The purpose of this study is to analyze and compare treatment patterns and responsiveness between UIP and possible UIP radiographic patterns. METHODS: 220 patients seen and evaluated at Rush University Medical Center and/or Rush Oak Park Hospital for newly diagnosed interstitial lung disease were identified. Patients with previous workup, incomplete workup, or with an “inconsistent with UIP” pattern on radiography were excluded (180 patients). Patients were then split into the categories “UIP” or “possible UIP” based on the radiologist’s read of high-resolution CT. The rates of use of immunosuppressants and other medications (including anti-fibrotic agents, such as pirfenidone and nintedanib) were compared between the two groups. Response to treatment was also analyzed based on PFT data, using a cutoff of a 10% change in VC, TLC, or DLCO. Fisher’s exact tests compared frequencies between groups. RESULTS: 40 patients met inclusion criteria. There were 11 total pulmonologists who evaluated these patients. 13 patients had the UIP pattern and 27 patients had possible UIP, based on the radiologist’s read of a high-resolution CT scan. 8 UIP patients were treated with immunosuppressants, compared to 11 possible UIP patients (p = 0.3140); 2 UIP patients were treated with other medications, compared to 7 possible UIP patients (p = 0.6904). In UIP patients, 2 had improved VC, 5 had stable VC, and 3 had a worsened VC, compared to 1 improved, 12 stable, and 9 worsened VCs in possible UIP patients (p = 0.406). 1 UIP patient demonstrated improvement in TLC, 5 showed stable TLC, and 2 had a worsened TLC, compared to 2 improved, 13 stable, and 7 worsened TLCs in possible UIP patients (p = 0.999). Finally, for UIP, 1 patient had improved DLCO, 3 had stable DLCOs, and 4 had worsened DLCO, compared to 4 improved, 7 stable, and 11 worsened DLCOs in possible UIP (p = 0 .999). There were no statistically significant changes in PFTs when comparing UIP patients treated with immunosuppressants or other medications to those not treated; similarly, there were no statistically significant changes in PFT data comparing treated possible UIP pattern patients to those not treated. 3 out of the 13 typical UIP patients had a biopsy, compared to 8 of the 27 possible UIP patients (p = 1.000). CONCLUSIONS: Patients with both UIP and possible UIP patterns on radiographic imaging are more commonly treated with immunosuppressants. Despite this, there is no statistically significant improvement or prevention of decline in treated or untreated patients. CLINICAL IMPLICATIONS: Possible UIP and typical UIP patients tend to have similarly poor response to treatment with antifibrotic agent and immunosuppresants. When treating ILD with a UIP pattern, providers should carefully weigh subjective benefits against the risks of immunosuppressant or antifibrotic therapies. DISCLOSURE: The following authors have nothing to disclose: Krishnan Warrior, Mark Yoder No Product/Research Disclosure Information

Development of a Computer-Aided Differential Diagnosis System to Distinguish Between Usual Interstitial Pneumonia and Non-specific Interstitial Pneumonia Using Texture- and Shape-Based Hierarchical Classifiers on HRCT Images.

A computer-aided differential diagnosis (CADD) system that distinguishes between usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) using high-resolution computed tomography (HRCT) images was developed, and its results compared against the decision of a radiologist. Six local interstitial lung disease patterns in the images were determined, and 900 typical regions of interest were marked by an experienced radiologist. A support vector machine classifier was used to train and label the regions of interest of the lung parenchyma based on the texture and shape characteristics. Based on the regional classifications of the entire lung using HRCT, the distributions and extents of the six regional patterns were characterized through their CADD features. The disease division index of every area fraction combination and the asymmetric index between the left and right lungs were also evaluated. A second SVM classifier was employed to classify the UIP and NSIP, and features were selected through sequential-forward floating feature selection. For the evaluation, 54 HRCT images of UIP (n=26) and NSIP (n=28) patients clinically diagnosed by a pulmonologist were included and evaluated. The classification accuracy was measured based on a fivefold cross-validation with 20 repetitions using random shuffling. For comparison, thoracic radiologists assessed each case using HRCT images without clinical information or diagnosis. The accuracies of the radiologists' decisions were 75 and 87%. The accuracies of the CADD system using different features ranged from 70 to 81%. Finally, the accuracy of the proposed CADD system after sequential-forward feature selection was 91%.

Sex steroid receptor expression in idiopathic pulmonary fibrosis

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF.

Non-specific and Usual Interstitial Pneumonia, Short-Term Survival After Surgical Biopsy

To the Editors, Idiopathic interstitial pneumonia (IIP) is a diagnostic challenge. The diagnostic work-up in general includes medical history, physical examination, lung function tests, chest X-ray, high-resolution computed tomography and bronchoalveolar lavage. If no clinical diagnosis can be established on the basis of these data, a surgical lung biopsy might be indicated. In this setting, possible therapeutic and prognostic implications should be weighed against the risk of postoperative complications such as infections, prolonged air leakage, respiratory failure, acute exacerbation of underlying disease and even mortality. Review of literature shows that postoperative mortality after surgical lung biopsy in IIP was found to be 4.8 % after 30 days and 6 % after 90 days [1]. Reported risk factors for mortality were low diffusing capacity for carbon monoxide (DLCO) and low forced vital capacity (FVC) [2, 3]. There are reports suggesting that surgical lung biopsy itself increases the risk of acute exacerbation of underlying disease [2, 3]. The aim of this study was to evaluate the 30- and 90-day mortality rate after surgical lung biopsy in two histological distinct groups of patients: one with a histological pattern of usual interstitial pneumonia (UIP) and one with a pattern of non-specific pneumonia (NSIP). In this retrospective study, we included all patients with a histological UIP or NSIP who underwent surgical lung biopsy between 1993 and 2011 in our centre. Baseline characteristics are presented in Table 1. Data on mortality rate at 30 and 90 days, length of postoperative hospital stay, duration of air leakage, time to drain removal after surgery and infectious complications were collected. Table 1 Baseline characteristics Data of 69 patients were analysed (Table 1). There were 23 patients with histological NSIP and 46 with UIP. Baseline characteristics showed significant differences between both groups: mean forced expiratory volume in 1 s (FEV1) and diffusion capacity (DLCO) were lower in the NSIP group compared with the UIP group. Patients with a UIP pattern in this study were more often male and were older. No significant differences were found in FVC, total lung capacity, Body Mass Index (BMI) and smoking status. Overall, the 90-day mortality rate after surgical lung biopsy in all patients was 11.6 % (8 out of 69). In the UIP group, all patients who died underwent an open lung biopsy, the 30-day mortality rate was 8.7 % (4 out of 46) and the 90-day mortality rate was 15.2 % (7 out of 46). The median pre-operative FVC was 86 % and DLCO 46 % of the seven patients who passed away. Two patients died of pneumonia with radiologic evidence of progression of fibrosis. Post-mortem examination revealed diffuse alveolar damage in one case. Three patients died in the second and third month due to progression of fibrosis, and in two cases, this was proven by post-mortem examination and in one case radiologically. One cause of death was unknown due to loss to follow-up. Among seven patients with UIP who died, five were ultimately diagnosed to have idiopathic pulmonary fibrosis (IPF) and two to nonclassifiable interstitial pneumonia. In the NSIP group, only one patient died due to pneumonia in the first month after surgery. The 30- and 90-day mortality rates were both 4.3 % in the NSIP group. No significant differences were found in postoperative hospital stay (p = 0.906), duration of air leakage (p = 0.721), time to drain removal after surgery (p = 0.65) and infectious complications (p = 0.977) between the NSIP and UIP group. There was no correlation between year of surgery and mortality. Although the difference in mortality rate between the UIP and NSIP group was not statistically significant, we observed a trend towards a higher mortality rate in patients with UIP pattern, which is in agreement with reports in the literature [2, 3]. Interestingly, all deceased UIP patients with a known cause of death showed progression of fibrosis, while no progression of fibrosis was observed in the patient who died in the NSIP group. This observation suggests that the UIP non-survivors, who had relatively good pre-operative lung functions compared to the all NSIP patients, experienced rapid progression of their disease which cannot be excluded to be related to the surgical procedure. We hypothesize that this rapid progression of fibrosis might be induced by the surgical procedure itself causing increased damage of the highly vulnerable alveolar epithelium. Increased vulnerability of the alveolar wall appears to be a fundamental problem in IPF. In conclusion, mortality after surgical lung biopsy is relatively high, especially in patients with a histological pattern of UIP. We think that these results should be taken into account when considering open lung biopsy in patients with suspected IIP.

Clinical findings and outcomes in patients with possible usual interstitial pneumonia

Patients with possible usual interstitial pneumonia (UIP) constitute a substantial group, and their clinical characteristics and outcomes are not well defined. We compared the clinical characteristics and survival between patients with possible UIP and the UIP pattern. We evaluated 62 patients with possible UIP and 544 patients with the UIP pattern. Both groups were diagnosed by clinical characteristics and high-resolution computed tomography (HRCT) findings. Two radiologists performed radiological evaluation based on the new idiopathic pulmonary fibrosis (IPF) guidelines. Two risk-stratification methods were used to compare UIP pattern and possible UIP patients. The groups had similar demographic and clinical characteristics. Pulmonary function tests revealed no significant differences in lung volumes between the 2 groups. However, DLCO was significantly lower with the UIP pattern than with possible UIP (p=0.004). Multivariate analysis showed age, sex, and carbon monoxide diffusing capacity (DLCO) as important independent variables for survival. The UIP HRCT pattern did not affect survival (hazard ratio, 0.83; 95% confidence interval, 0.51-1.24; p=0.32). Possible UIP was not associated with prognosis when independent predictors for survival rate and propensity score were considered. In the case-control study, the 3-year survival rate was 44.6% in the UIP pattern group and 56.8% in the possible UIP group (p=0.16). Clinical characteristics and outcomes were similar in possible UIP and UIP patients, except for differences in DLCO. The UIP pattern itself did not affect survival.