Features Of Usual Interstitial Pneumonia Research Articles

The impact of nintedanib and pirfenidone on lung function and survival in patients with idiopathic pulmonary fibrosis in real-life setting

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2–5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. MethodsA real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020. Two groups (under nintedanib or pirfenidone) were analyzed at diagnosis through their clinical features and radiological patterns. Lung function was assessed at diagnosis (time 0) and after 6, 12 and 24 months of treatment. We also compared this antifibrotic cohort with an older naïve antifibrotic cohort, mainly treated with immunosuppressive drugs and/or N- acetylcysteine. Survival was analyzed and prognostic features were also studied. Statistical analysis was performed with IBM® SPSS®. ResultsA cohort of 108 patients under antifibrotics (nintedanib n = 54; pirfenidone n = 54) was assessed. Lung function analysis showed an overall stabilization in FVC and DLCO mean predicted percentages at 6, 12 and 24 months of treatment. The mean decline in FVC and DLCO, at 12 months, was −40.95 ± 438.26 mL and −0.626 ± 1.31 mL/min/mmHg, respectively. However, during this period, 34.2% of the patients died mostly due to acute exacerbation associated with a poorer lung function at diagnosis. Mean survival in the naïve antifibrotic cohort was significantly lower than in the antifibrotic cohort (39.9 months versus 58.2 months; p < 0.005). Regarding lung function evolution and survival, we found no differences between definitive or probable UIP radiological patterns, both on patients under nintedanib and pirfenidone (p = 0.656). ConclusionsIn this real-life observational study, the positive impact of antifibrotic therapy on the IPF clinical course and on survival was corroborated. Regarding efficacy, there was no difference between patients taking nintedanib or pirfenidone. The need for an early treatment was also demonstrated, since a worse outcome is clearly associated with lower lung volumes and lower diffusing capacity at diagnosis.

Interstitial lung disease related to occupational hard metal exposure: two case reports

BackgroundHard metal lung disease (HMLD) is a relatively less known occupational interstitial lung disease, and instances of HMLD resulting from para-occupational exposure are rarely reported.Case presentationThis paper presents two cases of interstitial lung disease caused by exposure to hard metal. The first case involves a 37-year-old Taiwanese man who had worked at a grinder station for hard metal materials for 12 years without respiratory protective equipment. He experienced a dry cough and exertional dyspnea, and his chest imaging and pathology findings were consistent with the features of usual interstitial pneumonia. Analysis of his lung tissue revealed the presence of tungsten and cobalt. The second case involves a 68-year-old Taiwanese woman, the mother of the first patient, who had hand-washed her son’s workwear. She experienced a dry cough and had similar imaging findings to her son. After her son left his job, they both exhibited improved symptoms and lung functions with nintedanib treatment. These findings suggest a diagnosis of HMLD and interstitial lung disease resulting from para-occupational exposure to hard metal dust.ConclusionsThe diagnosis of HMLD relies on obtaining a detailed occupational exposure history. If HMLD is diagnosed, discontinuing exposing to hard metal dusts can lead to improved lung function.

Features of transbronchial lung cryobiopsy-diagnosed fibrotic hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a common type among all the interstitial lung diseases, and transbronchial lung cryobiopsy is an alternative diagnostic technique for interstitial lung diseases. In this study, we describe the clinical and pathological features of fibrotic hypersensitivity pneumonitis diagnosed with transbronchial lung cryobiopsy (TBLC). A total of 46 diffused parenchyma lung disease (DPLD) patients received TBLC were included in this study. Medical records including medical history spirometry examinations, 6-min walk test (6MWT) results, high resolution computed tomographic (HRCT) scans, BAL, and histopathology were collected. Results of HRCT and histopathology were compared and classified, especially. Sixteen patients were diagnosed with fibrotic HP, the mean age of whomwas 56.3 ± 12.1 years, and 62.5% of them were male. Three of the 16 patients had been misdiagnosed as tuberculosis and received antituberculosis medications, five patients had been diagnosed as unclassifiable pulmonary fibrosis, and five patients had been diagnosed as idiopathic pulmonary fibrosis (IPF). Thirteen (81.3%) patients had a normal lymphocyte count in BAL. The pathological features of usual interstitial pneumonia (UIP) were detected in 11 (68.8%) of the cases, poor defined granulomatous was detected in nine (56.3%) of the cases, and bronchiolocentric fibrosis was detected in two (12.5%) of the 16 cases. Fibrotic hypersensitivity pneumonitis should be included in differential diagnosis of pulmonary fibrosis. Pathological characteristics of fibrotic hypersensitivity pneumonitis could be demonstrated from cryobiopsy lung tissue. TBLC is recommended as an alternative diagnostic technique, which may improve the specificity of hypersensitivity pneumonia detection, and UIP is the most frequent pathological finding.

Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis.

Background: Fibroblastic foci (FF) are characteristic features of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) and one cardinal feature thought to represent a key mechanism of pathogenesis. Hence, FF have a high impact on UIP/IPF diagnosis in current guidelines. However, although less frequent, these histomorphological hallmarks also occur in other fibrotic pulmonary diseases. Currently, there is therefore a gap in knowledge regarding the underlying molecular similarities and differences of FF in different disease entities. Methods: In this work, we analyzed the compartment-specific gene expression profiles of FF in IPF and sarcoidosis in order to elucidate similarities and differences as well as shared pathomechanisms. For this purpose, we used laser capture microdissection, mRNA and protein expression analysis. Biological pathway analysis was performed using two different gene expression databases. As control samples, we used healthy lung tissue that was donated but not used for lung transplantation. Results: Based on Holm Bonferroni corrected expression data, mRNA expression analysis revealed a significantly altered expression signature for 136 out of 760 genes compared to healthy controls while half of these showed a similar regulation in both groups. Immunostaining of selected markers from each group corroborated these results. However, when comparing all differentially expressed genes with the fdr-based expression data, only 2 of these genes were differentially expressed between sarcoidosis and IPF compared to controls, i.e., calcium transport protein 1 (CAT1) and SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), both in the sarcoidosis group. Direct comparison of sarcoidosis and IPF did not show any differentially regulated genes independent from the statistical methodology. Biological pathway analysis revealed a number of fibrosis-related pathways pronounced in IPF without differences in the regulatory direction. Conclusions: These results demonstrate that FF of end-stage IPF and sarcoidosis lungs, although different in initiation, are similar in gene and protein expression, encouraging further studies on the use of antifibrotic agents in sarcoidosis.

The Clinical, Radiological, and Laboratory Profile of Patients With Interstitial Pneumonitis With Autoimmune Features From India: An Observational, Cross-Sectional Study.

IntroductionInterstitial pneumonia with autoimmune features (IPAF) refers to interstitial lung disease (ILD) with co-existing features of other clinical, serologic, or pulmonary features that suggest the presence of an underlying systemic autoimmune condition that does not fulfill the current rheumatologic criteria for connective tissue disorder (CTD). It is a relatively newly described clinical syndrome with only a handful of reports describing it. This study aimed at studying the clinical, radiological, and laboratory profiles of IPAF patients from a tertiary care hospital in South India.MethodsThis was an observational cross-sectional study conducted in a tertiary care hospital in South India over a period of one year. Patients diagnosed to have IPAF as per the European Respiratory Society (ERS)/American Thoracic Society (ATS) criteria were included in the study, and their demographics, clinical features, radiological features, and laboratory markers were collected along with a descriptive analysis.ResultsA total of 14,433 patients were screened during the study period. Twenty-four patients were diagnosed to have IPAF during the study period with a prevalence of 0.17%. Out of these 24 patients, 11 (45.8%) patients were males. The mean (M) ± standard deviation (SD) age was 47.8±10.7 years. Twenty-one (87.5%) of the patients reported having a cough, 18 (75%) patients had breathlessness, and 10 (41.7%) patients had digital clubbing. On radiological imaging, five (20.8%) patients had features of usual interstitial pneumonia (UIP) and 14 (58.3%) had nonspecific interstitial pneumonia (NSIP). On pulmonary function testing, the M±SD forced expiratory volume in the first second (FEV1) was 56.4±13.9%. The M±SD forced vital capacity (FVC) was 44.2±24.1%. The M±SD FEV1/FVC ratio was 0.8±0.04. On performing diffusing capacity of the lungs for carbon monoxide (DLCO), the M±SD was 34.2±21.9%. Of the patients, 95.8% had a positive antinuclear antibody (ANA) while 25% of patients had a positive anti-AMA-M2.ConclusionsThe prevalence of IPAF in the studied population was very low. IPAF had nonspecific clinical features, pulmonary function tests, and radiological findings. Further large-scale studies are required from different parts of the world in order to understand the epidemiology of IPAF. Research is also required into developing effective management options for IPAF.

Radiological diagnosis of fibrosing interstitial lung diseases: innovations and controversies.

Following the introduction of new effective antifibrotic drugs, interest in fibrosing interstitial lung diseases (FILD) has been renewed. In this context, radiological evaluation of FILD plays a cardinal role. Radiological diagnosis is possible in about 50% of the cases, which allows the initiation of effective therapy, thereby avoiding invasive procedures such as surgical lung biopsy. Usual interstitial pneumonia (UIP) pattern may be diagnosed based on clinical, radiological, and pathological data. High-resolution computed tomography features of UIP have been widely described in literature; however, interpreting them remains challenging, even with specific expertise on the subject. Diagnostic difficulties are understandable given the continuous evolution of FILD classifications and their complexity. Both early-stage diseases and advanced or combined patterns are not easily classifiable, and many end up being labelled 'indeterminate´ or 'unclassifiable´. Especially in these cases, optimal patient management involves collaboration and communication between different specialists. Here, we discuss the most critical aspects of radiological interpretation in FILD diagnosis based on the most recent classifications. We believe that the clinicians´ awareness of radiological diagnostic issues of FILD would improve comprehension and dialogue between physicians and radiologists, leading to better clinical practice.

Usefulness and safety of transbronchial biopsy with large forceps during flexible bronchoscopy

Transbronchial lung biopsy (TBLB) using forceps is one of the most common procedures used to obtain lung tissue. The procedure’s usefulness remains limited when diagnosing interstitial lung diseases. This retrospective descriptive study analyzed the feasibility and safety of using large forceps for TBLB in all patients who underwent TBLB from 2014 to 2018 for diffuse lung disease where the diagnosis could not be made by high-resolution chest computed tomography. We excluded patients with radiographic features of usual interstitial pneumonia. Among the 35 study patients, 7 were men and 28 were women. Diagnoses included respiratory associated bronchiolitis (7), diffuse alveolar damage (4), organizing pneumonia (4), nonspecific interstitial pneumonitis (3), acute fibrinous organizing pneumonia (3), sarcoidosis (2), hypersensitivity pneumonitis (2), IgG4 interstitial lung disease (1), eosinophilic pneumonia (1), pulmonary alveolar proteinosis (1), pulmonary fibrosis (1), pneumocystis (1), plasma-rich bronchiolitis (1), and diffuse alveolar hemorrhage (1). In three cases, the biopsies were nondiagnostic. Two patients developed a pneumothorax, and one required chest tube placement. There was one episode of minor bleeding. No escalation of care or hospitalization was required. Large-forceps TBLB is a feasible and safe method for obtaining parenchymal lung biopsies.

CHILDHOOD-ONSET INTERSTITIAL LUNG DISEASE: A RARE CASE OF IDIOPATHIC, NONSPECIFIC INTERSTITIAL PNEUMONIA IN A TEENAGER

SESSION TITLE: Fellows Diffuse Lung Disease SESSION TYPE: Fellow Case Reports PRESENTED ON: October 18-21, 2020 INTRODUCTION: Childhood interstitial lung disease (chILD) is remarkably rare with a reported prevalence from 0.13 per 100,000 children under 17 years to 16.2 per 100,000 children under 15 years of age (1). Here we present a case of a teenager with idiopathic nonspecific interstitial pneumonia (NSIP). CASE PRESENTATION: A 15-year old previously healthy female presented with a three-week history of dry cough, fever, malaise and shortness of breath which progressed to dyspnea on exertion despite a course of outpatient antibiotics. She had no environmental exposures, history of smoking or vaping nor family history of pulmonary pathology. Initial vital signs were significant for hypoxemia to 80% and a chest x-ray and CT scan with bilateral consolidations and ground glass opacities. Initial laboratory tests showed elevated inflammatory markers, other tests including SARS-CoV-2 PCR were negative . Bronchoscopy, bronchoalveolar lavage, and transbronchial biopsies yielded no definitive diagnosis. Following bronchoalveolar lavage, she developed rapid clinical deterioration necessitating mechanical ventilation, paralytics, and inhaled nitric oxide. Given elevated inflammatory markers and after infection was excluded, intravenous steroids were initiated with partial improvement. After extubation, a protracted inability to wean off oxygen support, and spirometry showing ongoing, severe restrictive lung disease, lung biopsy via video-assisted thorascopic surgery was performed lending to the ultimate diagnosis NSIP. Hypersensitivity pneumonitis panel, ILD panel and genetic testing were unrevealing, as such her case was classified as idiopathic NSIP. DISCUSSION: NSIP in adolescents is very rare. A meta-analysis (2) reports the average age of patients with NSIP to be 54.8 years. In the pediatric population, NSIP can be associated with systemic disease processes such as collagen vascular disease, including systemic lupus erythematosus, juvenile rheumatoid arthritis, and dermatomyositis associated with antibodies to melanoma differentiation-associated gene 5 (anti-MDA5), as well as a complication of blood stem cell transplants and surfactant dysfunction mutations, although most cases are idiopathic (3). Given that the etiology of NSIP is broad and in most cases idiopathic, response to corticosteroids is also variable. Our patient had a partial response to corticosteroids early on in her treatment, manifested by augmented gas exchange and improved symptomatology. The relatively slow response to treatment in the first several weeks is likely consistent with her biopsy findings which showed fibroblast proliferation and fibrosis. CONCLUSIONS: ILD and particularly NSIP are rare conditions in adolescents but should be suspected in patients with hypoxemia and abnormal imaging in the absence of infectious or autoimmune etiologies. An extensive workup is recommended to determine association with systemic conditions, treatment and prognosis. Reference #1: (1) Griese M, Haug M, Brasch F, et al. Incidence and classification of pediatric diffuse parenchymal lung diseases in Germany. Orphanet J Rare Dis. 2009;4:26. Published 2009 Dec 12. doi:10.1186/1750-1172-4-26 Reference #2: (2) Ebner L, Christodoulidis S, Stathopoulou T, et al. Meta-analysis of the radiological and clinical features of Usual Interstitial Pneumonia (UIP) and Nonspecific Interstitial Pneumonia (NSIP). PLoS One. 2020;15(1):e0226084. Published 2020 Jan 13. doi:10.1371/journal.pone.0226084 Reference #3: (3) Vece TJ, Fan LL. Interstitial Lung Disease in Children Older Than 2 Years. Pediatr Allergy Immunol Pulmonol. 2010;23(1):33-41. doi:10.1089/ped.2010.0008 DISCLOSURES: No relevant relationships by Giuliana Cerro, source=Web Response No relevant relationships by Gary Goulin, source=Web Response No relevant relationships by Jack Green, source=Web Response No relevant relationships by Michael Lewis, source=Web Response No relevant relationships by Tim Shen, source=Web Response

The Association Between MUC5B Mutations and Clinical Outcome in Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Retrospective Exploratory Study in China.

BackgroundPatients with rheumatoid arthritis (RA) who develop interstitial lung disease (RA-ILD), show features of usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT). This retrospective exploratory clinical study aimed to investigate the association between mutations in the MUC5B gene and clinical outcome in patients with RA, with or without RA-ILD, using whole-exome sequencing (WES).Material/MethodsWES was performed using peripheral blood samples for mutations in the MUC5B gene in 51 patients diagnosed with RA without ILD, and 45 patients with RA-ILD. The cumulative incidence in acute exacerbations of RA-ILD and variables associated with acute exacerbations of RA-ILD were analyzed.ResultsIn patients with RA-ILD, the main genetic variants of MUC5B were identified, with an odds ratio (OR) of 3.410 (p=0.013). Nine patients with RA without ILD (17.6%) and 19 patients with RA-ILD (42.2%) expressed MUC5B variants. Patients with RA-ILD carrying MUC5B variants had a significantly increased duration of RA-ILD (p=0.03) and showed a UIP pattern on lung HRCT (p=0.01). Acute exacerbations of RA-ILD occurred in 25 patients during follow-up, including 13 patients with mutant MUC5B and 12 patients with wildtype MUC5B. Univariate analysis showed that MUC5B mutations (p=0.043), older age of onset of RA (p=0.041), increased serum anti-citrullinated protein antibodies (ACPAs) (p=0.033), and a UIP imaging pattern on HRCT (p=0.015) were significantly correlated with acute exacerbations of RA-ILD. However, these findings were not supported by multivariate analysis (p=0.065).ConclusionsThe carrier status of MUC5B variants was an indicator of reduced prognosis and increased exacerbations of RA-ILD.

Meta-analysis of the radiological and clinical features of Usual Interstitial Pneumonia (UIP) and Nonspecific Interstitial Pneumonia (NSIP).

PurposeTo conduct a meta-analysis to determine specific computed tomography (CT) patterns and clinical features that discriminate between nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP).Materials and methodsThe PubMed/Medline and Embase databases were searched for studies describing the radiological patterns of UIP and NSIP in chest CT images. Only studies involving histologically confirmed diagnoses and a consensus diagnosis by an interstitial lung disease (ILD) board were included in this analysis. The radiological patterns and patient demographics were extracted from suitable articles. We used random-effects meta-analysis by DerSimonian & Laird and calculated pooled odds ratios for binary data and pooled mean differences for continuous data.ResultsOf the 794 search results, 33 articles describing 2,318 patients met the inclusion criteria. Twelve of these studies included both NSIP (338 patients) and UIP (447 patients). NSIP-patients were significantly younger (NSIP: median age 54.8 years, UIP: 59.7 years; mean difference (MD) -4.4; p = 0.001; 95% CI: -6.97 to -1.77), less often male (NSIP: median 52.8%, UIP: 73.6%; pooled odds ratio (OR) 0.32; p<0.001; 95% CI: 0.17 to 0.60), and less often smokers (NSIP: median 55.1%, UIP: 73.9%; OR 0.42; p = 0.005; 95% CI: 0.23 to 0.77) than patients with UIP. The CT findings from patients with NSIP revealed significantly lower levels of the honeycombing pattern (NSIP: median 28.9%, UIP: 73.4%; OR 0.07; p<0.001; 95% CI: 0.02 to 0.30) with less peripheral predominance (NSIP: median 41.8%, UIP: 83.3%; OR 0.21; p<0.001; 95% CI: 0.11 to 0.38) and more subpleural sparing (NSIP: median 40.7%, UIP: 4.3%; OR 16.3; p = 0.005; 95% CI: 2.28 to 117).ConclusionHoneycombing with a peripheral predominance was significantly associated with a diagnosis of UIP. The NSIP pattern showed more subpleural sparing. The UIP pattern was predominantly observed in elderly males with a history of smoking, whereas NSIP occurred in a younger patient population.

Idiopathic pulmonary fibrosis in patients with early-stage non-small-cell lung cancer after surgical resection.

BackgroundThe outcomes of patients with both lung cancer and idiopathic pulmonary fibrosis (IPF) are unfavorable. Therapeutic interventions for lung cancer such as surgery can cause acute exacerbation of IPF (aeIPF). This study aimed to assess the frequency of IPF in a group of patients with early-stage non-small-cell lung cancer (NSCLC) and to report clinical characteristics and outcomes of this cohort of patients.Patients and methodsThis observational cohort retrospective study analyzed 641 pathological records of patients after surgical resection of early-stage non-small-cell lung cancer (NSCLC) at University Clinic Golnik from May 2010 to April 2017. Pathological records of NSCLC with coexisting IPF were reviewed. CT scans and biopsy specimens for this group of patients were analyzed by a thoracic radiologist and pathologist, independently. We searched radiological and pathological features of usual interstitial pneumonia (UIP) pattern in this group of patients. We report the clinical characteristics and outcome of this cohort of patients.ResultsOut of 641 patients with early-stage NSCLC, only 13 (2.0%) had histologically and radiologically proven coexisting UIP/IPF. Squamous cell carcinoma was the most common type of lung cancer (7/13 patients). The majority of tumors were small size (all being pT1 or pT2), stage I–II (11/13 patients), located in the lower lung lobes (11/13 patients). Almost all patients were current or ex-smokers (11/13 patients). There were two pathologically confirmed fatal cases (15.4%) due to aeIPF in the first two months after radical treatment, one after adjuvant radiotherapy and the other after surgery. Out of 13 patients, one patient had a lung cancer relapse.ConclusionsFrequency of UIP/IPF in surgically treated early stage NSCLC is rather low. Our observational study shows that radical treatment of lung cancer can cause aeIPF with dismal outcome in this group of patients. The standard of care in these mostly elderly patients still remains unresolved.

Transbronchial cryobiopsy validity in diagnosing diffuse parenchymal lung diseases in Egyptian population.

ObjectivesWe aimed to evaluate the efficacy, safety, and diagnostic utility of transbronchial cryobiopsy (TBCB) in diagnosing diffuse parenchymal lung diseases (DPLDs) in an Egyptian population and to identify common DPLD pathologies among them.MethodsThis prospective interventional study enrolled 25 Egyptian patients presenting to the Main Alexandria University Hospital who had clinical and radiological features of DPLD, but insufficient elements to achieve definite features of usual interstitial pneumonia on chest high-resolution computed tomography. Twelve patients were subjected to TBCB and 13 to forceps transbronchial lung biopsy (TBLB).ResultsThe diagnostic yield was significantly higher among the TBCB group (83.3%), and increased to 100% with clinicopathological correlation vs the TBLB group (38.5%, P=0.041). Granulomatous diseases (24%, either sarcoidosis or hypersensitivity pneumonitis) were the commonest pathology, followed by malignancy (12%) in both groups. TBCB sizes were 2.5–5 mm vs 1-3 mm in TBLB (P<0.001), with preserved tissue architecture (91.7% vs 38.5%, respectively; P=0.011). Only 8.3% were complicated by insignificant bleeding grade 2 after TBCB, but no pneumothorax was detected.ConclusionTBCB is a safe, tolerable procedure with high diagnostic yield for evaluating DPLD with indefinite usual interstitial pneumonia pattern on high-resolution computed tomography.

Overlap of interstitial pneumonia with autoimmune features with undifferentiated connective tissue disease and contribution of UIP to mortality.

Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome. Patients with prior UCTD-interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all-cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features. One hundred and one UCTD-ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud's phenomenon, positive anti-nuclear antibody (ANA) and non-specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features. Current IPAF criteria encompassed the majority of broadly defined UCTD-ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.

Series of rare lung diseases mimicking imaging patterns of common diffuse parenchymal lung diseases.

Diffuse parenchymal lung diseases (DPLDs) encompass a variety of restrictive and obstructive lung pathologies. In this article, the authors discuss a series of rare pulmonary entities and their high-resolution computed tomography imaging appearances, which can mimic more commonly encountered patterns of DPLDs. These cases highlight the importance of surgical lung biopsies in patients with imaging findings that do not show typical imaging features of usual interstitial pneumonia.

Diagnostic utility of surgical lung biopsies in elderly patients with indeterminate interstitial lung disease.

Idiopathic pulmonary fibrosis (IPF) is increasingly diagnosed by clinical and computed tomography (CT) criteria; however, surgical lung biopsy (SLB) may still be required in patients who lack definite CT features of usual interstitial pneumonia (UIP). We reviewed a cohort of elderly patients who underwent SLB, to evaluate the benefit of SLB in diagnosing idiopathic interstitial pneumonia (IIP). We searched the pathology records of Mayo Clinic for ambulatory patients at least 75 years old, who underwent SLB between 2000 and 2012 for indeterminate IIP. Histologic slides were reviewed and clinical data were extracted from the record. A total of 55 patients (35 male) were enrolled. Median (interquartile range) age was 77 (76-80) years. Forced vital capacity was 70 (61-76)% and diffusing capacity of the lungs for carbon monoxide was 48 (42-54)% of predicted. In total, 37 (67%) patients had IPF, including 61% of those with HRCT findings inconsistent with UIP. Thirty-day mortality was 10% and 90-day mortality was 15%. The high mortality rate of SLB complicates the risk-benefit analysis in elderly patients with IIP. The expected value of the SLB is probably highest when the HRCT features are inconsistent with UIP, due to the frequent (39%) retrieval of patterns other than UIP.

Effect of Nintedanib in Subgroups of Idiopathic Pulmonary Fibrosis by Diagnostic Criteria.

In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia (UIP), on high-resolution computed tomography (HRCT). Thus, the patients in these trials represented patients with definite UIP and a large subgroup of patients with possible UIP. To investigate the potential impact of diagnostic subgroups on the progression of IPF and the effect of nintedanib. We conducted a post hoc subgroup analysis of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy versus patients without either, using pooled data from the INPULSIS trials. Seven hundred twenty-three (68.1%) patients had honeycombing and/or biopsy, and 338 (31.9%) patients had no honeycombing or biopsy. In these subgroups, respectively, the adjusted annual rate of decline in FVC in patients treated with placebo was -225.7 and -221.0 ml/yr, and the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 117.0 ml/yr (95% confidence interval, 76.3-157.8) and 98.9 ml/yr (95% confidence interval, 36.4-161.5). There was no significant treatment-by-subgroup interaction (P = 0.8139). Adverse events were similar between the subgroups. Patients with IPF diagnosed in clinical practice who had possible UIP with traction bronchiectasis on HRCT and had not undergone surgical lung biopsy had disease that progressed in a similar way, and responded similarly to nintedanib, to that of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy.

Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis.

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP.

Transbronchial Lung Cryobiopsy in the Diagnosis of Fibrotic Interstitial Lung Diseases

BackgroundHistology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited.ObjectivesTo evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD.MethodProspective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features.ResultsSafety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable.ConclusionsTBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

A retrospective study of microscopic polyangiitis patients presenting with pulmonary fibrosis in China

BackgroundPulmonary involvement is a common feature of MPA. Although alveolar hemorrhage is the most common pulmonary manifestation of MPA, a few recent studies have described instances of MPA patients with pulmonary fibrosis. Pulmonary fibrosis was seen to predate, be concomitant with, or occur after the diagnosis of MPA. The goal of this study was to describe the clinical features and prognosis of microscopic polyangiitis (MPA) patients whose initial respiratory presentation was pulmonary fibrosis.MethodsWe conducted a retrospective analysis of 19 MPA patients who presented with pulmonary fibrosis at Peking Union Medical College Hospital between 1990 and 2012.ResultsOf 67 total MPA cases, 19 patients presented with pulmonary fibrosis. There were 8 males and 11 females, with a median age of 63.6 years. Common clinical manifestations included fever (89.5%), cough (84.2%), dyspnea (78.9%) and velcro rales (84.2%). Eleven patients experienced weight loss, several had kidney involvement, and most had an increased erythrocyte sedimentation rate and C-reactive protein. All were positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA), with 6 patients being positive at the time of their initial diagnosis of pulmonary fibrosis. Every patient had typical features of usual interstitial pneumonia on High-resolution CT. All were treated with corticosteroids and cyclophosphamide, which lead to an improvement in twelve cases. One of the remaining patients progressed slowly, whereas six died.ConclusionsPatients with MPA, who also presented with pulmonary fibrosis in our cohort, were more likely to be older, female, and have extrapulmonic involvement. Most patients had a delayed positive ANCA. Corticosteroids plus cyclophosphamide was the remission-induction treatment scheme for all cases. The current prognosis for MPA patients with pulmonary fibrosis appears to be poor, suggesting that they may be candidates for new therapies.

Histopathologic Features of Usual Interstitial Pneumonia and Related Patterns: What is Important for Radiologists?

In interstitial lung diseases, the diagnosis of idiopathic pulmonary fibrosis is important where pathology and radiology show usual interstitial pneumonia (UIP) pattern. Recently, revised guidelines of idiopathic pulmonary fibrosis were published in which the diagnostic algorithm requires a stricter definition for both pathology and radiology. In spite of the progress, there are issues that still need to be considered especially when facing cases where there may be a lower confidence of UIP diagnosis. As a matter of course, various etiologic backgrounds represent UIP pattern. However, their distinction is important irrespective of the etiology, because the histologic UIP pattern indicates a significantly worse prognosis than other chronic interstitial lung diseases. In this review, we describe the histologic features of UIP, effects of revised guidelines, interobserver agreement, etiologic variations of UIP pattern, and finally we include a few of our hypothetical thoughts on the "UIP bucket."