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1.
Genes (Basel) ; 15(5)2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38790257

RESUMO

BACKGROUND: Sjögren's disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. METHODS: RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). RESULTS: RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. CONCLUSIONS: We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies.


Assuntos
Linfócitos B , Perfilação da Expressão Gênica , Síndrome de Sjogren , Transcriptoma , Humanos , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Feminino , Linfócitos B/imunologia , Linfócitos B/metabolismo , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos , Interferons/genética , Interferons/metabolismo , Adulto , Autoanticorpos/imunologia , Autoanticorpos/sangue , Autoanticorpos/genética , Idoso
2.
Thorax ; 78(11): 1097-1104, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37028940

RESUMO

BACKGROUND: Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients. METHODS: We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety. RESULTS: After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference -0.76%, 95% CI -6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events. CONCLUSIONS: The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP. TRIAL REGISTRATION MUMBER: NCT02958917.


Assuntos
Alveolite Alérgica Extrínseca , COVID-19 , Fibrose Pulmonar Idiopática , Adulto , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Resultado do Tratamento , Pandemias , Capacidade Vital , Piridonas/efeitos adversos , Método Duplo-Cego , Progressão da Doença , Alveolite Alérgica Extrínseca/tratamento farmacológico
3.
Chest ; 162(3): 614-629, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35738345

RESUMO

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.


Assuntos
Alveolite Alérgica Extrínseca , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologia , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Tomografia Computadorizada por Raios X
4.
Thorax ; 77(5): 508-510, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34996848

RESUMO

A subset of patients with hypersensitivity pneumonitis (HP) develop lung fibrosis that is clinically similar to idiopathic pulmonary fibrosis (IPF). To address the aetiological determinants of fibrotic HP, we investigated whether the common IPF genetic risk variants were also relevant in study subjects with fibrotic HP. Our findings indicate that common genetic variants in TERC, DSP, MUC5B and IVD were significantly associated with fibrotic HP. These findings provide support for a shared etiology and pathogenesis between fibrotic HP and IPF.


Assuntos
Alveolite Alérgica Extrínseca , Fibrose Pulmonar Idiopática , Alveolite Alérgica Extrínseca/genética , Fibrose , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Fatores de Risco
5.
Am J Surg Pathol ; 46(4): e71-e93, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753865

RESUMO

Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the pathologic features as outlined in the CHEST guidelines. The histologic criteria are divided into 4 diagnostic categories: (1) Typical nonfibrotic HP or fibrotic HP; (2) Compatible with nonfibrotic HP or fibrotic HP; (3) Indeterminate for nonfibrotic or fibrotic HP; and (4) Alternative Diagnosis. It is important to emphasize that patterns 1 to 3 do not represent discrete histologic entities or pathologic diagnoses. Rather, these categories are meant to serve as a practical guide for organizing a complex set of overlapping histologic patterns into an integrated diagnostic framework for facilitating multidisciplinary discussion. High-resolution computed tomography features are also summarized, emphasizing how the correlation of lung biopsies with computed tomography findings can help to favor the diagnosis, particularly in cases where biopsies are not typical for HP. This review highlights details of the histologic spectrum of HP as well as the utility of different types of biopsies and bronchoalveolar lavage. We also emphasize the importance of multidisciplinary discussion and the complex differential diagnosis.


Assuntos
Alveolite Alérgica Extrínseca , Doenças Pulmonares Intersticiais , Médicos , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologia , Biópsia , Diagnóstico Diferencial , Fibrose , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia
6.
Chest ; 160(2): 595-615, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33865835

RESUMO

BACKGROUND: The purpose of this summary is to provide a synopsis of evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability. STUDY DESIGN AND METHODS: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, and Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. RESULTS: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations, and 2 ungraded consensus-based statements. All evidence was of very low quality. INTERPRETATION: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Tomada de Decisão Clínica , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos
7.
Chest ; 160(2): e97-e156, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33861992

RESUMO

BACKGROUND: The purpose of this analysis is to provide evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability. STUDY DESIGN AND METHODS: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. A diagnostic algorithm is provided, using supporting data from the recommendations where possible, along with expert consensus to help physicians gauge the probability of HP. RESULTS: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations and 2 ungraded consensus-based statements. All evidence was of very low quality. INTERPRETATION: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Criteria are presented to facilitate diagnosis of HP. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Medicina Baseada em Evidências , Humanos
8.
BMC Pulm Med ; 20(1): 289, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160338

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating condition characterized by progressive lung function decline and early mortality. While early accurate diagnosis is essential for IPF treatment, data evaluating the impact of hospital academic status on IPF-related mortality remains limited. Here we examined in-hospital mortality trends for patients with IPF from 2013 to 2017. We hypothesized that in-hospital IPF mortality would be influenced by hospital academic setting. METHODS: Hospitalization data was extracted from the National Inpatient Sample (NIS) for subjects with an international classification of disease code for IPF. In-hospital mortality stratified by hospital setting (academic versus non-academic) was the primary outcome of interest, with secondary analyses performed for subgroups with and without respiratory failure and requiring mechanical ventilation. Predictors of mortality were then assessed. RESULTS: Among 93,680 patients with IPF requiring hospitalization, 58,450 (62.4%) were admitted to academic institutions. In-hospital mortality decreased significantly in those admitted to an academic hospital (p < 0.001) but remained unchanged in patients admitted to a non-academic hospital. A plateau in-hospital mortality was observed among all hospitalized patients (p = 0.12), with a significant decrease observed for patients with admitted respiratory failure (p < 0.001) and those placed on mechanic ventilation (p < 0.001). CONCLUSION: In-hospital mortality decreased significantly for patients with IPF admitted to an academic hospital, suggesting that management strategies may differ by hospital setting. Mortality among those with respiratory failure and those requiring mechanical ventilation has dropped significantly. Our findings may underscore the importance of promoting early referral to an academic institution and adherence to international treatment guidelines.


Assuntos
Centros Médicos Acadêmicos , Mortalidade Hospitalar/tendências , Hospitalização/tendências , Fibrose Pulmonar Idiopática/mortalidade , Insuficiência Respiratória/mortalidade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Fidelidade a Diretrizes , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Respiração Artificial , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Am J Respir Crit Care Med ; 202(7): 1013-1023, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32501729

RESUMO

Rationale: A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients.Objectives: To measure ABC-like cell percentages in patients with lung granulomatous diseases.Methods: Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet.Measurements and Main Results: ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood.Conclusions: Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.


Assuntos
Alveolite Alérgica Extrínseca/sangue , Subpopulações de Linfócitos B/metabolismo , Beriliose/sangue , Líquido da Lavagem Broncoalveolar/citologia , Sarcoidose Pulmonar/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alveolite Alérgica Extrínseca/imunologia , Subpopulações de Linfócitos B/imunologia , Beriliose/imunologia , Antígeno CD11c/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Receptores de Superfície Celular/metabolismo , Receptores de Complemento 3d/metabolismo , Receptores Fc/metabolismo , Receptores Imunológicos/metabolismo , Sarcoidose Pulmonar/imunologia , Proteínas com Domínio T/metabolismo , Adulto Jovem
10.
Chest ; 157(6): 1513-1521, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31877269

RESUMO

BACKGROUND: The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because it shares genetic, histopathologic, and radiographic features with the fibrosing interstitial lung disease seen in rheumatoid arthritis (RA), the goal of this study was to investigate RA-related autoantibodies in IPF. METHODS: The study included patients with IPF from two separate cohorts at National Jewish Health and Brigham Women's Hospital (n = 181), general population control subjects (n = 160), and control subjects with disease (n = 86 [40 with RA-usual interstitial pneumonia and 46 with hypersensitivity pneumonitis]). Serum was tested for RA-associated antibodies (including IgG and IgA) to citrullinated protein antigens (ACPA). Lung tissue in 11 patients with IPF was examined for ectopic lymphoid aggregates. RESULTS: An increased prevalence of ACPA positivity was found in two separate IPF cohorts. In particular, positivity for IgA-ACPA was increased in these two IPF cohorts compared with general population control subjects (21.3% and 24.8% vs 5.6%; P < .01). Patients with IPF were more likely to be IgA-ACPA-positive than IgG-ACPA-positive (23.2% vs 8.3%; P < .01), whereas patients with RA were more likely to be IgG-ACPA-positive than IgA-ACPA-positive (72.5% vs 52.5%; P = .04). There was a strong correlation between IgA-ACPA level and the number of ectopic lymphoid aggregates on lung histologic examination in IPF (r = 0.72; P = .01). CONCLUSIONS: In this study, IgA-ACPA was elevated in patients with IPF and correlated with lymphoid aggregates in the lung, supporting the theory that IgA-ACPA may play a role in lung disease pathogenesis in a subset of individuals with IPF. Future studies are needed to determine whether this subset of ACPA-positive patients with IPF is distinct from patients with IPF but without antibodies.


Assuntos
Autoanticorpos/sangue , Fibrose Pulmonar Idiopática/imunologia , Imunoglobulina A/sangue , Idoso , Autoanticorpos/imunologia , Biomarcadores/sangue , Feminino , Humanos , Fibrose Pulmonar Idiopática/sangue , Imunoglobulina A/imunologia , Masculino , Pessoa de Meia-Idade
11.
Lancet Respir Med ; 8(1): 25-33, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575509

RESUMO

BACKGROUND: Connective tissue growth factor (CTGF) is a secreted glycoprotein that has a central role in the process of fibrosis. This study was designed to assess the safety, tolerability, and efficacy of pamrevlumab (FG-3019), a fully recombinant human monoclonal antibody against CTGF, in idiopathic pulmonary fibrosis. The aim was to establish whether pamrevlumab could slow, stop, or reverse progression of idiopathic pulmonary fibrosis. METHODS: The phase 2, randomised, double-blind, placebo-controlled PRAISE trial was done at 39 medical centres in seven countries (Australia, Bulgaria, Canada, India, New Zealand, South Africa, and the USA). Patients with idiopathic pulmonary fibrosis and percentage of predicted forced vital capacity (FVC) of 55% or greater were enrolled and randomly assigned (1:1) by use of interactive responsive technology to intravenous infusion of pamrevlumab 30 mg/kg or placebo every 3 weeks over 48 weeks (16 infusions). The primary efficacy outcome was change from baseline in percentage of predicted FVC at week 48. Disease progression (defined as a decline from baseline in percentage of predicted FVC of ≥10%, or death) at week 48 was a key secondary efficacy outcome. All patients in the pamrevlumab group received at least one dose of the study drug and were analysed for safety. Two patients in the placebo group were excluded from the intention-to-treat population for the efficacy analyses because of enrolment error. This trial is registered with ClinicalTrials.gov, NCT01890265. FINDINGS: Between Aug 17, 2013, and July 21, 2017, 103 patients were randomly assigned (50 to pamrevlumab and 53 to placebo). Pamrevlumab reduced the decline in percentage of predicted FVC by 60·3% at week 48 (mean change from baseline -2·9% with pamrevlumab vs -7·2% with placebo; between-group difference 4·3% [95% CI 0·4-8·3]; p=0·033). The proportion of patients with disease progression was lower in the pamrevlumab group than in the placebo group at week 48 (10·0% vs 31·4%; p=0·013). Pamrevlumab was well tolerated, with a safety profile similar to that of placebo. Treatment-emergent serious adverse events were observed in 12 (24%) patients in the pamrevlumab group and eight (15%) in the placebo group, with three patients on pamrevlumab and seven on placebo discontinuing treatment. Of the three (6%) deaths in the pamrevlumab group and six (11%) in the placebo group, none was considered treatment related. INTERPRETATION: Pamrevlumab attenuated progression of idiopathic pulmonary fibrosis and was well tolerated. Now in phase 3 development, pamrevlumab shows promise as a novel, safe, and effective treatment for idiopathic pulmonary fibrosis. FUNDING: FibroGen.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Fator de Crescimento do Tecido Conjuntivo/administração & dosagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Fator de Crescimento do Tecido Conjuntivo/efeitos adversos , Fator de Crescimento do Tecido Conjuntivo/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacos
12.
Eur Respir Rev ; 27(150)2018 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-30578336

RESUMO

The availability of epidemiological data relating to interstitial lung diseases (ILDs) has increased over recent years, but information on the prevalence and incidence of ILDs of different aetiologies remains limited. Despite global distribution, the proportion of patients who develop a progressive phenotype across different ILDs is not well known. Disease behaviour is well documented in idiopathic pulmonary fibrosis but idiosyncratic in other ILDs that may present a progressive fibrosing phenotype. Possible reasons may include the heterogeneous nature of the aetiology, the complexity of diagnosis (and subsequent documentation of cases) and the methods employed to retrospectively analyse patient databases. This review presents a broad overview of the epidemiological data available for ILDs that may present a progressive-fibrosing phenotype, collectively and stratified according to clinical classification. We also note where further data are needed in comparison to the well-studied IPF indication.


Assuntos
Fibrose Pulmonar Idiopática/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Pulmão , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Meio Ambiente , Feminino , Predisposição Genética para Doença , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/fisiopatologia , Incidência , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Prognóstico , Fatores de Risco
14.
Ann Am Thorac Soc ; 14(10): 1533-1538, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28513215

RESUMO

RATIONALE: Significant heterogeneity of computed tomography (CT) presentation exists within chronic hypersensitivity pneumonitis (HP). There are limited data aimed at delineating the prognostic value of specific CT features, distribution, and patterns in chronic HP. OBJECTIVES: To examine whether the presence of CT mosaic attenuation (MA) and air trapping (AT), and the distribution or patterns of fibrosis impact survival in subjects with chronic HP. METHODS: We retrospectively identified 110 consecutively enrolled, well-characterized, biopsy-proven adult subjects with chronic HP between 1982 and 2015 from the National Jewish Health interstitial lung disease research database. The first available CT scan of diagnostic quality from each subject was formally evaluated for specific CT findings associated with chronic HP and for overall CT pattern. A Cox proportional hazards model was used to identify independent predictors in time-to-death analysis, and bootstrap analysis was performed for internal model validation. RESULTS: Fibrotic HP (65%; 72/110) was most often peripheral in the axial plane and lower lung preponderant. The distribution of lung disease in those without fibrosis was most often axially and zonally diffuse. There was no association between survival and CT distribution or CT pattern in the whole cohort or within the fibrotic subset of subjects. After multivariate adjustment, AT/MA was independently associated with survival in the whole cohort (HR = 0.26; 95% confidence interval = 0.07-0.97). Results were similar after restricting the analyses to fibrotic HP cases. CONCLUSIONS: Among subjects with chronic HP, the presence of CT AT/MA may identify subjects with better prognosis.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/mortalidade , Alveolite Alérgica Extrínseca/patologia , Pulmão/patologia , Idoso , Doença Crônica , Colorado/epidemiologia , Diagnóstico Diferencial , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X
15.
Respir Med ; 126: 100-104, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28427540

RESUMO

PURPOSE: Interstitial lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA-ILD) and is associated with significant morbidity and mortality. However, limited data exist regarding predictors of mortality. We sought to examine the prognostic value of the high-resolution computed tomography (HRCT) patterns in patients with RA-ILD. MATERIALS AND METHODS: RA-ILD patients with HRCT patterns of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) were identified among a longitudinal cohort of individuals evaluated at National Jewish Health. A total of 158 subjects were included in the study. For each subject, the earliest available HRCT was reviewed independently by two expert thoracic radiologists blinded to clinical data. HRCT patterns were classified as demonstrating definite UIP, possible UIP, or NSIP. Kaplan-Meier curves were generated and survival was compared among the three patterns using a log rank test for trend. RESULTS: One hundred subjects (63%) had HRCT findings classified as definite UIP, 23 (15%) as possible UIP and 35 (22%) as NSIP. No difference in survival was seen between subjects with definite UIP versus those with possible UIP. The combined group of subjects with either definite- or possible UIP had significantly worse survival than those with NSIP (log-rank p = 0.03). CONCLUSIONS: In patients with RA-ILD, patients with either definite UIP or possible UIP have equally poor survival when compared to those with an NSIP pattern.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Artrite Reumatoide/complicações , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/complicações , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Capacidade de Difusão Pulmonar , Fator Reumatoide , Fumar/epidemiologia , Análise de Sobrevida , Capacidade Vital
16.
Semin Respir Crit Care Med ; 37(3): 441-56, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27231866

RESUMO

Eosinophils play a key role in orchestrating the complex clinicopathological pulmonary and extrapulmonary disease features in patients with eosinophilic syndromes. Eosinophilic pulmonary syndromes consist of a heterogeneous group of disorders characterized by the presence of peripheral blood eosinophilia and/or eosinophilic-related pulmonary impairment. These disorders can present with varying degrees of organ involvement, and while their presentation may be similar, it is important to define the disease state, as management and prognosis differ. In this article, we discuss acute and chronic eosinophilic pneumonias, eosinophilic granulomatosis with polyangiitis, and the hypereosinophilic syndromes. The mainstay of therapy for these disorders has been corticosteroids; however, recent and ongoing studies have provided strong grounds for optimism for specific targeted treatment approaches.


Assuntos
Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/terapia , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/terapia , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/terapia , Humanos
17.
Ann Am Thorac Soc ; 13(7): 1042-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27064856

RESUMO

RATIONALE: Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. OBJECTIVES: To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. METHODS: Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. MEASUREMENTS AND MAIN RESULTS: The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5-179.1), polyarthritis (OR, 19; 95% CI, 2.3-206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87-0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. CONCLUSIONS: Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.


Assuntos
Imunodeficiência de Variável Comum/complicações , Granuloma/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Adulto , Artrite/complicações , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Hiperesplenismo/complicações , Leucopenia/complicações , Modelos Logísticos , Pulmão/patologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Radiografia , Fatores de Risco , Estados Unidos
18.
Eur Respir J ; 47(2): 588-96, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26585429

RESUMO

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.


Assuntos
Artrite Reumatoide/complicações , Fibrose Pulmonar Idiopática/mortalidade , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/fisiopatologia , Estimativa de Kaplan-Meier , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Capacidade Vital
19.
Chest ; 146(3): 775-785, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24700149

RESUMO

BACKGROUND: The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS: We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco %), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS: There were no significant differences between groups in longitudinal changes in FVC % or Dlco % up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco % per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS: Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF--an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF.


Assuntos
Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiopatologia , Idoso , Biópsia , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Capacidade de Difusão Pulmonar/fisiologia , Testes de Função Respiratória , Taxa de Sobrevida , Capacidade Vital/fisiologia
20.
Chest ; 144(5): 1644-1651, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23828161

RESUMO

BACKGROUND: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. METHODS: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis. RESULTS: Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047). CONCLUSIONS: Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival.


Assuntos
Alveolite Alérgica Extrínseca/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Alberta/epidemiologia , Alveolite Alérgica Extrínseca/mortalidade , Doença Crônica , Feminino , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo
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