Showing papers on "Interstitial lung disease published in 2016"
TL;DR: Single-cell RNA sequencing analyses identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF, and provides a rich data source to further explore lung health and disease.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease characterized by airway remodeling, inflammation, alveolar destruction, and fibrosis. We utilized single-cell RNA sequencing (scRNA-seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of normal human lung epithelial cells defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis. In contrast, scRNA-seq of IPF cells identified 3 distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and an additional atypical transitional cell that contributes to pathological processes in IPF. Individual IPF cells frequently coexpressed alveolar type 1 (AT1), AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development. Pathway analysis predicted aberrant activation of canonical signaling via TGF-β, HIPPO/YAP, P53, WNT, and AKT/PI3K. Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells. scRNA-seq analyses identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF. The present study provides a rich data source to further explore lung health and disease.
416 citations
TL;DR: Male sex, increasing age, increasing comorbidity, open surgery, and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease-related interstitial lung disease were risk factors for increased mortality in in-hospital mortality after elective surgical lung biopsy.
Abstract: Rationale: Surgical lung biopsy can help to determine a specific diagnosis in interstitial lung disease but has associated risks Most currently available mortality data are derived from case series and may not be generalizable to broader populationsObjectives: To assess in-hospital mortality after surgical lung biopsy for interstitial lung disease in a national secondary care dataset from the United StatesMethods: Data were obtained from the 2000–2011 Nationwide Inpatient Sample Cases were identified using International Classification of Diseases codes for interstitial lung disease and surgical lung biopsies Lung resections and cases of lung cancer were excluded Weighted data were used to estimate numbers of biopsies nationwide and in-hospital mortality, and multivariable logistic regression was used to adjust for sex, age, geographic region, comorbidity, type of operation, and provisional diagnosisMeasurements and Main Results: We estimated there to be around 12,000 surgical lung biopsies performe
317 citations
TL;DR: Inter-multidisciplinary team agreement for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnoses made by individual clinicians or radiologists.
311 citations
TL;DR: BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF.
Abstract: Rationale: Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable.Objectives: To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF.Methods: In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels.Measurements and Main Results: We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 ...
277 citations
TL;DR: Cryobiopsy is safe and has lower complication and mortality rates compared to SLB, and TBLC might be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.
Abstract: Background: A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung cryobiopsy (TBLC) is adopting an important role. Objectives: The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis. Methods: We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015). Results: A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p Conclusion: Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.
268 citations
TL;DR: Data from this study suggest that in rheumatoid-arthritis associated interstitial lung disease, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but notHRCT pattern, independently predicts mortality.
Abstract: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a "definite" or "possible" usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.
246 citations
TL;DR: Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations and had a higher incidence of haematological comorbidities, but there was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.
Abstract: Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.
115 patients with mutations in telomerase reverse transcriptase ( TERT ) (n=75), telomerase RNA component ( TERC ) (n=7), regulator of telomere elongation helicase 1 ( RTEL1 ) (n=14) and poly(A)-specific ribonuclease ( PARN ) (n=19) were identified and clinical data were analysed.
Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year−1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.
Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive.
Mutations in four telomere-related genes lead to progressive pulmonary fibrosis, regardless of ILD diagnosis
240 citations
TL;DR: Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis.
Abstract: The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation (“lung dominant” CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjogren’s syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation—for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because of other manifestations of CTD and comorbidities. Clinical trials of novel therapies including immunosuppressive therapies are needed to inform best treatment strategies.
216 citations
TL;DR: This work applied IPAF criteria to patients with idiopathic interstitial pneumonia and undifferentiated CTD-ILD and characterised the clinical, serological and morphological features of the IPAF cohort, compared outcomes to other ILD cohorts and validated individual IPAF domains using survival as an endpoint.
Abstract: Patients with interstitial lung disease (ILD) may have features of connective tissue disease (CTD), but lack findings diagnostic of a specific CTD. A recent European Respiratory Society/American Thoracic Society research statement proposed criteria for patients with interstitial pneumonia with autoimmune features (IPAF).We applied IPAF criteria to patients with idiopathic interstitial pneumonia and undifferentiated CTD-ILD (UCTD). We then characterised the clinical, serological and morphological features of the IPAF cohort, compared outcomes to other ILD cohorts and validated individual IPAF domains using survival as an endpoint.Of 422 patients, 144 met IPAF criteria. Mean age was 63.2 years with a slight female predominance. IPAF cohort survival was marginally better than patients with idiopathic pulmonary fibrosis, but worse than CTD-ILD. A non-usual interstitial pneumonia pattern was associated with improved survival, as was presence of the clinical domain. A modified IPAF cohort of those meeting the clinical domain and a radiographic or histological feature within the morphological domain displayed survival similar to those with CTD-ILD.IPAF is common among patients with idiopathic interstitial pneumonia and UCTD. Specific IPAF features can identify subgroups with differential survival. Further research is needed to replicate these findings and determine whether patients meeting IPAF criteria benefit from immunosuppressive therapy.
199 citations
TL;DR: Disease-specific differences in mechanics and respiratory muscle activity did not influence the key association between dyspnea intensity and inspiratory neural drive to the diaphragm.
Abstract: Rationale: The mechanisms underlying dyspnea in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are unknown.Objectives: To examine whether the relationship between inspiratory neural drive to the diaphragm and exertional dyspnea intensity is different in ILD and COPD, given the marked differences in static respiratory mechanics between these conditions.Methods: We compared sensory–mechanical relationships in patients with ILD, patients with COPD, and healthy control subjects (n = 16 each) during incremental cycle exercise with diaphragmatic electromyography (EMGdi) and respiratory pressure measurements.Measurements and Main Results: In patients with mild to moderate ILD or COPD with similarly reduced inspiratory capacity, the peak oxygen uptake, work rate, and ventilation were lower (P < 0.05) than in healthy control subjects. EMGdi expressed as a percentage of the maximum (EMGdi/EMGdi,max), respiratory effort (esophageal pressure expressed as percentage of the maximum), a...
187 citations
TL;DR: A flow cytometry panel in human BAL and lung tissue is defined that allows identification of multiple immune cell types and delineates alveolar from interstitial-associated macrophages and has important implications for defining myeloid cells in human lung samples.
Abstract: Clear identification of specific cell populations by flow cytometry is important to understand functional roles. A well-defined flow cytometry panel for myeloid cells in human bronchoalveolar lavage (BAL) and lung tissue is currently lacking. The objective of this study was to develop a flow cytometry-based panel for human BAL and lung tissue. We obtained and performed flow cytometry/sorting on human BAL cells and lung tissue. Confocal images were obtained from lung tissue using antibodies for cluster of differentiation (CD)206, CD169, and E cadherin. We defined a multicolor flow panel for human BAL and lung tissue that identifies major leukocyte populations. These include macrophage (CD206(+)) subsets and other CD206(-) leukocytes. The CD206(-) cells include: (1) three monocyte (CD14(+)) subsets, (2) CD11c(+) dendritic cells (CD14(-), CD11c(+), HLA-DR(+)), (3) plasmacytoid dendritic cells (CD14(-), CD11c(-), HLA-DR(+), CD123(+)), and (4) other granulocytes (neutrophils, mast cells, eosinophils, and basophils). Using this panel on human lung tissue, we defined two populations of pulmonary macrophages: CD169(+) and CD169(-) macrophages. In lung tissue, CD169(-) macrophages were a prominent cell type. Using confocal microscopy, CD169(+) macrophages were located in the alveolar space/airway, defining them as alveolar macrophages. In contrast, CD169(-) macrophages were associated with airway/alveolar epithelium, consistent with interstitial-associated macrophages. We defined a flow cytometry panel in human BAL and lung tissue that allows identification of multiple immune cell types and delineates alveolar from interstitial-associated macrophages. This study has important implications for defining myeloid cells in human lung samples.
TL;DR: In this article, the association of anti-melanoma differentiation-associated gene 5 (anti-MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD).
Abstract: Objective
Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti–melanoma differentiation–associated gene 5 (anti–MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti–MDA-5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM.
TL;DR: The histopathological and multidisciplinary discussion-based diagnostic yield of transbronchial cryobiopsy appears high, but with variable frequencies of complications dominated by pneumothorax and moderate-to-severe hemorrhage.
Abstract: Rationale: The diagnostic usefulness and safety of transbronchial lung cryobiopsy for the evaluation of interstitial lung disease remain unclear.Objectives: This systematic review and metaanalysis aims to establish the diagnostic accuracy and yield of transbronchial cryobiopsy for interstitial lung diseases.Methods: We searched MedLine, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings to identify studies assessing the diagnostic accuracy (compared with surgical biopsy) or yield of transbronchial lung cryobiopsy for interstitial lung disease (from database inception to January 2016). The diagnostic accuracy and yield were quantified and stratified by the method of diagnosis determination (histologic interpretation in isolation vs. incorporation within a multidisciplinary discussion). The frequency of procedure-related complications was also assessed from these reports. For full-text studies, random-effects models were used to calculate pooled estimates of diagnostic accura...
TL;DR: It is expected that a greater awareness of the clinical features of this syndrome will allow for an earlier diagnosis and appropriate treatment to improve outcomes in patients with antisynthetase syndrome.
Abstract: Anti-synthetase syndrome is an autoimmune condition, characterized by antibodies directed against an aminoacycl transfer RNA synthetase along with clinical features that can include interstitial lung disease, myositis, Raynaud's phenomenon, and arthritis. There is a higher prevalence and increased severity of interstitial lung disease in patients with anti-synthetase syndrome, as compared to dermatomyositis and polymyositis, inflammatory myopathies with which it may overlap phenotypically. Diagnosis is made by a multidisciplinary approach, synthesizing rheumatology and pulmonary evaluations, along with serologic, radiographic, and occasionally muscle and/or lung biopsy results. Patients with anti-synthetase syndrome often require multi-modality immunosuppressive therapy in order to control the muscle and/or pulmonary manifestations of their disease. The long-term care of these patients mandates careful attention to the adverse effects and complications of chronic immunosuppressive therapy, as well as disease-related sequelae that can include progressive interstitial lung disease necessitating lung transplantation, pulmonary hypertension, malignancy and decreased survival. It is hoped that greater awareness of the clinical features of this syndrome will allow for earlier diagnosis and appropriate treatment to improve outcomes in patients with anti-synthetase syndrome.
TL;DR: All possible causes of eosinophilia, including drug, toxin, fungus related etiologies, must be thoroughly investigated andExtrathoracic manifestations should raise the suspicion of eOSinophilic granulomatosis with polyangiitis.
TL;DR: In this paper, the authors identified all pharmacologic treatments evaluated for IPF and analyzed their efficacy via Bayesian network meta-analysis and pairwise indirect treatment comparisons, finding that no treatments performed better than placebo for respiratory-specific mortality.
TL;DR: The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI.
Abstract: Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs). Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children with HAIDs: the most common pulmonary manifestation is pleuritis in familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively caused by mutations in the MEFV and TNFRSF1A genes, while interstitial lung disease can be observed in STING-associated vasculopathy with onset in infancy (SAVI), caused by mutations in the TMEM173 gene. The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI.
TL;DR: Surgical lung biopsy for ILD has a similar mortality to lobectomy for lung cancer, and clinicians and patients should understand the likely risks involved.
Abstract: Introduction: International guidelines and new targeted therapies for idiopathic pulmonary fibrosis have increased the need for accurate diagnosis of interstitial lung disease, which may lead to more surgical lung biopsies. This study aims to assess the risk of this procedure in patients from the United Kingdom.
Methods: We used Hospital Episodes Statistics data from 1997-2008 to assess the frequency of surgical lung biopsy for interstitial lung disease in England. We identified cardiothoracic surgical patients using ICD-10 codes for interstitial lung disease and OPCS-4 codes for surgical lung biopsy. We excluded those with lung resections or lung cancer. We estimated in-hospital, 30-day and 90-day mortality following the procedure, and linked to cause of death using data from the Office of National Statistics.
Results: We identified 2,820 patients with interstitial lung disease undergoing surgical lung biopsy during the 12 year period. The number of biopsies increased over the time period studied. In-hospital, 30-day and 90-day mortality were 1.7%, 2.4% and 3.9% respectively. Male sex, increasing age, increasing co-morbidity and open surgery were risk factors for mortality.
Discussion: Surgical lung biopsy for interstitial lung disease has a similar mortality to lobectomy for lung cancer, and clinicians and patients should understand the likely risks involved.
TL;DR: A deeper understanding of the mechanisms responsible for an accelerated course of the disease and the identification of biomarkers of progression would lead to a better stratification of the Disease, essential for delivering individualized therapeutic strategies.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disorder of unknown aetiology whose diagnosis involves the careful exclusion of secondary causes for pulmonary fibrosis and the presence of a pattern of usual interstitial pneumonia (UIP) at either high-resolution computed tomography (HRCT) scan or surgical lung biopsy. Despite great efforts made in establishing precise, universally acknowledged diagnostic criteria for IPF, its ascertainment remains a challenge, especially in those individuals presenting with atypical HRCT patterns. With new drugs emerging, establishing a precise diagnosis is becoming a clinically relevant issue. Although regarded as a rare disease, IPF epidemiology is controversial due to studies relying on old data and adopting mixed, incomparable methodologies for cases definition. Overall, the prevalence and incidence appear to be increasing over the last decades, suggesting that in earlier studies they might have been underestimated because of diagnostic uncertainty. IPF is invariably progressive, although its clinical course might greatly vary on an individual basis, with episodes of severe acute respiratory deterioration (acute exacerbations) being unpredictable. A deeper understanding of the mechanisms responsible for an accelerated course of the disease and the identification of biomarkers of progression would lead to a better stratification of the disease, essential for delivering individualized therapeutic strategies.
TL;DR: A biomarker index of SP-D, MMP-7, and osteopontin enhanced diagnostic accuracy in patients with IPF compared with those with non-IPF ILD and is suggested to improve diagnostic confidence in IPF.
Abstract: Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) characterized by abnormal extracellular matrix (ECM) remodeling. We hypothesized that ECM remodeling might result in a plasma profile of proteins specific for IPF that could distinguish patients with IPF from other idiopathic ILDs.Objectives: To identify biomarkers that might assist in distinguishing IPF from non-IPF ILD.Methods: We developed a panel of 35 ECM, ECM-related, and lung-specific analytes measured in plasma from 86 patients with IPF (derivation cohort) and in 63 patients with IPF (validation cohort). Comparison groups included patients with rheumatoid arthritis–associated ILD (RA-ILD; n = 33), patients with alternative idiopathic ILDs (a-ILD; n = 41), and healthy control subjects (n = 127). Univariable and multivariable logistic regression models identified biomarkers that differentiated patients with IPF from those with a-ILD. Both continuous and diagnostic threshold versions of biomarkers w...
Columbia University Medical Center1, Roy J. and Lucille A. Carver College of Medicine2, Albert Einstein College of Medicine3, University of Pennsylvania4, University of Arizona5, National Institutes of Health6, University of Washington7, University of Alabama8, Duke University9, Columbia University10, University of Vermont11
TL;DR: High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.
Abstract: Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking. We measured high attenuation areas (HAA; percentage of lung voxels between −600 and −250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis. HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3–11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8–13.0), lower forced vital capacity (FVC) (mean adjusted difference −82 mL, 95% CI −119–−44), lower 6-min walk distance (mean adjusted difference −40 m, 95% CI −1–−80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43–2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39–1.79). High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.
TL;DR: This review covers the existing evidence on the pharmacologic and nonpharmacologic management of myositis-related ILD, highlighting the lack of randomized controlled data to guide treatment.
TL;DR: In this large single-centre cohort of patients with RA-ILD, most patients were seropositive and had a history of smoking, and the GAP model may be useful in assessing mortality risk.
Abstract: Objective. To characterize a cohort of patients with RA who have interstitial lung disease (ILD) and to assess the utility of previously developed mortality staging systems [gender, age, lung physiology (GAP) and ILD-GAP].
Methods. All patients with RA and ILD seen at the Mayo Clinic from 1998 to 2014 were identified and manually screened for study inclusion. RA disease characteristics and pulmonary findings including high-resolution CT and pulmonary function testing were evaluated. Survival was estimated using Kaplan–Meier methods. GAP and ILD-GAP models were evaluated using c-statistics and standardized incidence ratios.
Results. The study included 181 patients with RA-associated ILD (96% Caucasian; 48% females; 37% never-smokers). The mean age at ILD diagnosis was 67.4 years (s.d. 9.9). The median time from RA diagnosis to ILD was 4.9 years (range −10.9–48.1). The median follow-up was 3.1 years (range 0.01–14.8). Age, RA disease duration and low initial diffusing capacity for carbon monoxide were predictive of premature mortality in multivariate modelling. Sex, smoking status, obstructive lung disease, seropositivity and erosive disease were not associated with mortality. The 5-year survival rate was 59.7% (95% CI 51.5, 69.2). Survival did not differ between usual interstitial pneumonia, non-specific interstitial pneumonia and organizing pneumonia (P = 0.42). The GAP model performed well in this cohort for both discrimination and calibration (c-statistic 0.71, standardized incidence ratio 0.97).
Conclusion. In this large single-centre cohort of patients with RA-ILD, most patients were seropositive and had a history of smoking. ILD most commonly occurred after the RA diagnosis. Mortality was high and did not differ among the types. The GAP model may be useful in assessing mortality risk.
TL;DR: All three subjects had a mutation in the previously described autoinflammatory disease called SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy, which emphasize the need to consider this possibility in children and young adults with lung fibrosis after common causes have been ruled out.
TL;DR: Dyspnea at ILD onset and a steady FVC decrease over time were related to a poorer respiratory prognosis, and anti-Jo1 ASS is a heterogeneous syndrome.
TL;DR: Cryo-transbronchial lung biopsy is a relatively safe procedure with good diagnostic yield in diseases diffusely involving the lung parenchyma and there was evidence of publication bias.
Abstract: BACKGROUND: Transbronchial lung biopsy with flexible forceps is the most commonly used technique in diagnosis of diseases diffusely involving the lung parenchyma. Recently, transbronchial lung biopsy using the flexible cryoprobe (cryo-transbronchial lung biopsy) has also been reported. Herein, we perform a systematic review and meta-analysis describing the efficacy and safety of cryo-transbronchial lung biopsy.
METHODS: The PubMed and EMBASE databases were searched for studies reporting the outcomes of cryo-transbronchial lung biopsy in subjects with diffuse parenchymal lung involvement. The quality of individual studies was assessed using the QualSyst tool. The pooled diagnostic yield of cryo-transbronchial lung biopsy was calculated using proportion meta-analysis (random effects model). Heterogeneity was evaluated using the I2 test and Cochran Q test. Publication bias was determined using both statistical and graphical methods.
RESULTS: Our search yielded 14 studies (1,183 subjects). The pooled diagnostic yield of cryo-transbronchial lung biopsy was 76.9% (95% CI 67.2–85.3) if only definitive diagnoses were considered and 85.9% (95% CI 78.2–92.2) if both definitive and probable diagnoses were considered. Four studies (321 subjects) the performance of flexible forceps biopsy and cryo-transbronchial lung biopsy. The diagnostic yield of cryo-transbronchial lung biopsy (86.3, 95% CI 80.2–90.8) was significantly higher than that of flexible forceps biopsy (56.5%, 95% CI 27.5–83.2) with an odds ratio of 6.7 (95% CI 3.6–12.4) and a number needed to treat of 4. Lung tissue was obtained in 98% of all samples with cryo-transbronchial lung biopsy and was free of compression artifacts. The size of samples obtained with cryo-transbronchial lung biopsy was significantly bigger compared with flexible forceps biopsy (20.4 vs 4.3 mm2, P = .005). The complications of cryo-transbronchial lung biopsy included pneumothorax (6.8%), severe bleeding (0.3%), and death (0.1%). Clinical and statistical heterogeneity was present, and there was evidence of publication bias.
CONCLUSIONS: Cryo-transbronchial lung biopsy is a relatively safe procedure with good diagnostic yield in diseases diffusely involving the lung parenchyma.
TL;DR: Patients with ILD receive poorer access to specialist EOL care services and experience more breathlessness than patients with lung cancer, and this study highlights the need of better E OL care in oxygen-dependent ILD.
Abstract: Rationale Advanced fibrosing interstitial lung disease (ILD) is often progressive and associated with a high burden of symptoms and poor prognosis. Little is known about the symptom prevalence and access to palliative care services at end of life (EOL). Objectives Compare prevalence of symptoms and palliative treatments between patients dying with oxygen-dependent ILD and patients dying of lung cancer. Methods Nationwide registry-based cohort study of patients with oxygen-dependent ILD and patients with lung cancer who died between 1 January 2011 and 14 October 2013. Prevalence of symptoms and treatments during the last seven days of life were compared using data in Swedish Registry of Palliative Care. Measurements and main results 285 patients with ILD and 10 822 with lung cancer were included. In ILD, death was more likely to be ‘unexpected’ (15% vs 4%), less likely to occur in a palliative care setting (17% vs 40%) and EOL discussions with the patients (41% vs 59%) were less common than in lung cancer. Patients with ILD suffered more from breathlessness (75% vs 42%) while patients with lung cancer had more pain (51% vs 73%) (p Conclusions Patients with ILD receive poorer access to specialist EOL care services and experience more breathlessness than patients with lung cancer. This study highlights the need of better EOL care in oxygen-dependent ILD.
TL;DR: Though ILD contributes substantially to morbidity and mortality in patients with CTD, there are minimal data to guide its management except in SSc-ILD, and cyclophosphamide, mycophenolate and calcineurin inhibitors in IIM-ILD show promise.
Abstract: Purpose of reviewInterstitial lung disease (ILD), though a common and often a severe manifestation of many connective tissue diseases (CTD), is challenging to manage because of its variable presentation and the relative lack of guidelines to assist the clinician. In this review, we discuss the appro
TL;DR: Rituximab is a therapeutic option in treatment-refractory CTD-associated ILD and some disease subgroups may respond better than others, however, more work is needed to define its role in managing these patients.
Abstract: Objective CTD-associated interstitial lung disease (ILD) often fails to respond to conventional immunomodulatory agents. There is now considerable interest in the use of rituximab in systemic autoimmune CTD in patients refractory to standard treatments. The aim of this study was to review the experience of North Bristol NHS Trust managing patients with CTD-associated ILD with rituximab and explore possible associations with treatment response. Methods We conducted a retrospective analysis of all patients who received rituximab under the Bristol CTD-ILD service, having failed to respond to other immunomodulatory treatments. Results were collated for pulmonary function and radiological outcomes before and after treatment. Results Twenty-four patients were treated with rituximab. Their physiological parameters had failed to improve despite other immunomodulatory agents, with a mean change in forced vital capacity (FVC) prior to therapy of - 3.3% (95% CI - 5.6, -1.1) and mean change in diffusing capacity of carbon monoxide of - 4.3% (95% CI - 7.7, -0.9). After rituximab, radiology remained stable or improved for 11 patients, while worsening was observed in 9 patients. The decline in FVC was halted following treatment, with a mean change of + 4.1% (95% CI 0.9, 7.2), while diffusing capacity of carbon monoxide was stable [mean change +2.1% (95% CI - 1.0, 5.2)]. Patients with myositis overlap or antisynthetase syndrome appeared to respond well to treatment, with four patients showing clinically significant improvement in FVC >10%. Conclusion Rituximab is a therapeutic option in treatment-refractory CTD-associated ILD. Some disease subgroups may respond better than others, however, more work is needed to define its role in managing these patients.
TL;DR: In this article, lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) expressed mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of EndoMT.
Abstract: Objective To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT). Methods Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting. Results Immunohistochemical staining revealed cells expressing the EC-specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and α-smooth muscle actin in small and medium-sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2). Conclusion Cells coexpressing EC- and mesenchymal cell-specific molecules are present in the lungs of patients with SSc-associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell- and EC-specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc-associated ILD.