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1.
Chest ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32450237

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA), a common co-morbidity in ILD, could contribute to a worsened course if untreated. It is unclear if adherence to CPAP therapy improves outcomes. METHODS: We conducted a ten-year retrospective observational multicenter cohort study, assessing adult patients with ILD who had undergone polysomnography. Subjects were categorized based on OSA severity into 'no/mild OSA' (AHI <15) or 'moderate/severe OSA' (AHI ≥15). All subjects prescribed and adherent to CPAP were deemed to have 'treated OSA'. Cox regression models were used to examine the association of OSA severity and CPAP adherence with all-cause mortality risk and progression-free survival (PFS). RESULTS: Of 160 subjects that met inclusion criteria, 131 had OSA and were prescribed CPAP. 66 patients (41%) had no/mild untreated OSA, 51 (32%) had moderate/severe untreated OSA, and 43 (27%) had treated OSA. Subjects with no/mild untreated OSA did not differ from those with moderate/severe untreated OSA in mean survival time (127±56 months vs 138±93 months; P=0.61) and crude mortality rate (2.9/100 person-years vs 2.9/100 person-years; P=0.60). Adherence to CPAP was not associated with improvement in all-cause mortality risk (HR, 1.1; 95% CI=0.4-2.9; P=0.79), or PFS (HR, 0.9; 95% CI=0.5-1.5; P=0.66) compared to those that were non-adherent or untreated. Among subjects requiring supplemental oxygen, those adherent to CPAP had improved PFS (HR, 0.3; 95% CI, 0.1-0.9; P=0.03) compared to non-adherent or untreated subjects. CONCLUSIONS: Neither OSA severity nor adherence to CPAP was associated with improved outcomes in ILD patients except those requiring supplemental oxygen.

2.
Chest ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32450241

RESUMO

BACKGROUND: A number of circulating plasma biomarkers have been shown to predict survival in patients with idiopathic pulmonary fibrosis (IPF), but most were identified prior to the use of anti-fibrotic therapy (AF) in this population. Because pirfenidone and nintedanib have been shown to slow IPF progression and may prolong survival, the role of such biomarkers in AF treated patients is unclear. RESEARCH QUESTION: To determine whether plasma concentration of CA-125, CXCL13, MMP7, SP-D, YKL-40, VCAM-1 and OPN is associated with differential transplant-free survival (TFS) in AF exposed and non-exposed patients with IPF. STUDY DESIGN AND METHODS: A pooled, multi-center, propensity-matched analysis of IPF patients with and without AF exposure was performed. Optimal thresholds for biomarker dichotomization were identified in each group using iterative Cox regression. Longitudinal biomarker change was assessed in a subset of patients using linear mixed regression modeling. A clinical-molecular signature of IPF TFS was then derived and validated in an independent IPF cohort. RESULTS: Three hundred and twenty-five patients were assessed, of which 68 AF exposed and 172 non-exposed patients were included after propensity matching. CA-125, CXCL13, MMP7, YKL-40 and OPN predicted differential TFS in AF exposed patients but at higher thresholds than in AF non-exposed individuals. Plasma biomarker level generally increased over time in non-exposed patients but remained unchanged in AF exposed patients. A clinical-molecular signature predicted decreased TFS in AF exposed patients (HR 5.91; 95% CI 2.25-15.5; p<0.001) and maintained this association in an independent AF exposed cohort (HR 3.97; 95% CI 1.62-9.72; p=0.003). INTERPRETATION: A majority of plasma biomarkers assessed predicted differential TFS in AF exposed patients with IPF, but at higher thresholds than in non-exposed patients. A clinical-molecular signature of IPF TFS may provide a reliable predictor of outcome risk in AF treated patients but requires additional research for optimization and validation.

4.
Am J Respir Crit Care Med ; 201(5): 564-574, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710517

RESUMO

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion.Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations.Methods: We conducted genome-wide analyses across three independent studies and meta-analyzed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression, and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF.Measurements and Main Results: We identified and replicated three new genome-wide significant (P < 5 × 10-8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1, and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as yet unreported IPF susceptibility variants contribute to IPF susceptibility.Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF supports recent studies demonstrating the importance of mTOR signaling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.

6.
Respir Res ; 20(1): 253, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718645

RESUMO

BACKGROUND: Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP). METHODS: A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT. RESULTS: One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03-4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles. CONCLUSIONS: Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.

7.
Am J Respir Crit Care Med ; 200(9): 1154-1163, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268371

RESUMO

Rationale: Rare genetic variants in telomere-related genes have been identified in familial, idiopathic, and rheumatoid arthritis-associated pulmonary fibrosis. Short peripheral blood leukocyte (PBL) telomere length predicts poor outcomes in chronic hypersensitivity pneumonitis (CHP).Objectives: Determine the prevalence and clinical relevance of rare protein-altering variants in telomere-related genes in patients with CHP.Methods: Next-generation sequences from two CHP cohorts were analyzed to identify variants in TERT (telomerase reverse transcriptase), TERC (telomerase RNA component), DKC1 (dyskerin pseudouridine synthase 1), RTEL1 (regulator of telomere elongation helicase 1), PARN (poly[A]-specific RNase), and TINF2 (TERF1-interacting nuclear factor 2). To qualify, variants were required to have a minor allele frequency less than 0.005 and be predicted to be damaging to protein function. Variant status (binary variable) was used in statistical association tests, including Cox proportional hazard models for transplant-free survival. PBL telomere length was measured using quantitative PCR.Measurements and Main Results: Qualifying variants were identified in 16 of 144 patients (11.1%; 95% confidence interval [CI], 6.5-17.4) in the discovery cohort and 17 of 209 patients (8.1%; 95% CI, 4.8-12.7) in the replication cohort. Age- and ancestry-adjusted PBL telomere length was significantly shorter in the presence of a variant in both cohorts (discovery: -561 bp; 95% CI, -933 to -190; P = 0.003; replication: -612 bp; 95% CI, -870 to -354; P = 5.30 × 10-6). Variant status was significantly associated with transplant-free survival in both cohorts (discovery: age-, sex-, and ancestry-adjusted hazard ratio, 3.73; 95% CI, 1.92-7.28; P = 0.0001; replication: hazard ratio, 2.72; 95% CI, 1.26-5.88; P = 0.011).Conclusions: A substantial proportion of patients diagnosed with CHP have rare, protein-altering variants in telomere-related genes, which are associated with short peripheral blood telomere length and significantly reduced transplant-free survival.

8.
Chest ; 156(4): 715-723, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31181198

RESUMO

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) have been reported to occur in 7% to 10% of patients with idiopathic pulmonary fibrosis (IPF), but their clinical relevance remains unclear. The aim of this study was to estimate the prevalence of ANCAs in a North American population with IPF and evaluate their clinical significance. METHODS: This was a retrospective study of two independent cohorts of patients diagnosed with IPF at the University of California San Francisco (discovery cohort) and the University of Chicago (replication cohort). Myeloperoxidase (MPO) and proteinase 3 (PR3) ANCAs were measured in all patients. Prevalence and associations of ANCAs with clinical characteristics and transplant-free survival were evaluated. RESULTS: A total of 14 of 353 (4.0%; 95% CI, 2.2-6.5) and 20 of 392 (5.1%; 95% CI, 3.1-7.8) patients with IPF were positive for ANCAs at the time of diagnosis in the discovery and replication cohorts, respectively. Among those positive for MPO antibodies, two of six (33%) in the discovery cohort and three of 12 (25%) in the replication cohort developed vasculitis. None of the patients who were PR3-positive developed vasculitis. Patients who were ANCA-positive were more likely to be women than patients who were ANCA-negative, and were more likely to have some ground-glass opacities on CT scan. In the combined cohort of 745 patients, median transplant-free survival was not significantly different in patients who were ANCA-positive vs ANCA-negative (P = .57). CONCLUSIONS: ANCA positivity is uncommon in North American patients with IPF and not associated with baseline disease severity or transplant-free survival; however, a significant proportion of patients who are MPO-positive with IPF develop clinical vasculitis.

10.
Chest ; 155(5): 1026-1040, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30660786

RESUMO

Fibrotic interstitial lung diseases (ILDs) have a high mortality rate with an unpredictable disease course and clinical features that frequently overlap. Recent data indicate important roles for genomics in the mechanisms underlying susceptibility and progression of pulmonary fibrosis. The impact of these genomic markers on pharmacotherapy and their contribution to outcomes is increasingly recognized. Interstitial lung abnormalities, frequently considered representative of early ILD, have been consistently associated with the MUC5B promoter polymorphism, a common gene variant. Other rare gene variant mutations, including TERT, TERC, SFTPC, and DKC1, may be present in patients with familial interstitial pneumonia and are frequently associated with a usual interstitial pneumonia pattern of fibrosis. The minor allele of the MUC5B rs35705950 genotype is prevalent in several sporadic forms of ILD, including idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Gene mutations that characterize familial pulmonary fibrosis may be present in patients with connective tissue disease-related ILD, such as rheumatoid arthritis-ILD. Additionally, shorter telomere lengths and mutations in telomere biology-related genes have been demonstrated in both familial and sporadic ILD, with significant implications for disease progression, lung function, and survival. An improved understanding of the impact of genetic and genomic risk factors on disease progression would better guide personalized therapeutic choices in persons with fibrotic ILD.


Assuntos
Predisposição Genética para Doença/epidemiologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/genética , Mucina-5B/genética , Polimorfismo Genético , Causas de Morte , Progressão da Doença , Feminino , Genótipo , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Terapia de Alvo Molecular/métodos , Mucina-5B/efeitos dos fármacos , Mutação/genética , Prognóstico , Regiões Promotoras Genéticas/genética , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/fisiopatologia , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
11.
Eur Respir J ; 53(4)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30635297

RESUMO

Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF).In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator.The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of -0.05±0.29 and -0.04±0.25, respectively) is longer than that of IPF patients (-0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (-6.43% per year versus -0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (-0.14±0.27 versus -0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4-46.3 versus 14.1, 95% CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.

12.
Respir Med ; 146: 23-27, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30665514

RESUMO

INTRODUCTION: Idiopathic interstitial pneumonias (IIP) are diffuse lung diseases whose cause is unknown and often present with features of autoimmunity despite not meeting criteria for a connective tissue disease (CTD). Recent studies suggest that anti-RNA binding protein (anti-RBP) antibodies, which include anti-SSA, anti-SSB, anti-Sm, and anti-RNP, play a role in the loss of immune tolerance and severity of pulmonary hypertension (PH) in CTDs. We hypothesized that anti-RBP positive (RBP+) subjects would have worse measures of lung function, radiographic findings, PH, and survival than anti-RBP negative (RBP-) subjects. METHODS: Subjects with both IIP and serologies for review were identified retrospectively and stratified based on anti-RBP antibody seropositivity. Baseline cohort characteristics, pulmonary function tests (PFT), ambulatory oxygen requirement, radiographic characteristics, markers of PH, and transplant-free survival were compared between anti-RBP positive and negative groups. RESULTS: Five hundred twenty patients with IIP were identified, of which ten percent (n = 53) were anti-RBP positive. RBP+ as compared to RBP- subjects had significantly worse PFTs as indicated by FEV1 (59.6 vs. 64.9, p = 0.046) and FVC (71.6 vs. 78.8, p = 0.018). There was a higher prevalence of radiographic honeycombing (49.1% vs. 38.3%, p = 0.006) and emphysema (22.6% vs. 5.1%, p < 0.001) in the RBP+ group despite no difference in smoking history. The Pulmonary Artery-Aorta ratio was also larger in the RBP+ group (0.93 vs. 0.88, p = 0.040). There was no difference in transplant-free survival between groups (log rank = 0.912). CONCLUSION: Anti-RBP+ IIP patients may have worse lung function, increased chest radiographic abnormalities, and PH compared with those without these antibodies.

14.
Ann Am Thorac Soc ; 16(5): 580-588, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30653927

RESUMO

Rationale: Honeycombing on chest computed tomography (CT) has been described in diverse forms of interstitial lung disease (ILD); however, its prevalence and association with mortality across the spectrum of ILD remains unclear. Objective: To determine the prevalence and prognostic value of CT honeycombing and characterize associated mortality patterns across diverse ILD subtypes in a multicenter cohort. Methods: This was an observational cohort study of adult participants with multidisciplinary or adjudicated ILD diagnosis and documentation of chest CT imaging at index diagnosis across five U.S. hospitals (one tertiary and four nontertiary medical centers). Participants were stratified based on presence or absence of CT honeycombing. Vital status was determined from review of medical records and social security death index. Transplant-free survival was analyzed using univariate and multivariable Cox regression. Results: The sample comprised 1,330 participants (mean age, 66.8 yr; 50% men) with 4,831 person-years of follow-up. The prevalences of CT honeycombing were 42.0%, 41.9%, 37.6%, and 28.6% in chronic hypersensitivity pneumonitis, connective tissue disease-related ILD (CTD-ILD), idiopathic pulmonary fibrosis (IPF), and unclassifiable/other ILDs, respectively. Among those with CT honeycombing, cumulative mortality hazards were similar across ILD subtypes, except for CTD-ILD, which had a lower mortality hazard. Overall, the mean survival time was shorter among those with CT honeycombing (107 mo; 95% confidence interval [CI], 92-122 mo) than those without CT honeycombing (161 mo; 95% CI, 147-174 mo). CT honeycombing was associated with an increased mortality rate (hazard ratio, 1.72; 95% CI, 1.38-2.14) even after adjustment for center, sex, age, forced vital capacity, diffusing capacity, ILD subtype, and use of immunosuppressive therapy (hazard ratio, 1.62; 95% CI, 1.29-2.02). CT honeycombing was associated with an increased mortality rate within non-IPF ILD subgroups (chronic hypersensitivity pneumonitis, CTD-ILD, and unclassifiable/other ILD). In IPF, however, mortality rates were similar between those with and without CT honeycombing. Conclusions: CT honeycombing is prevalent in diverse forms of ILD and uniquely identifies a progressive fibrotic ILD phenotype with a high mortality rate similar to IPF. CT honeycombing did not confer additional risk in IPF, which is already known to be a progressive fibrotic ILD phenotype regardless of the presence of CT honeycombing.

15.
Am J Respir Crit Care Med ; 199(6): 747-759, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30216085

RESUMO

RATIONALE: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. OBJECTIVES: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. METHODS: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity-related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. MEASUREMENTS AND MAIN RESULTS: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12-2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17-1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15-2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21-14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. CONCLUSIONS: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.


Assuntos
Doenças Pulmonares Intersticiais/mortalidade , Linfonodos/diagnóstico por imagem , Mediastino/diagnóstico por imagem , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Eur Respir J ; 51(6)2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29724923

RESUMO

We studied whether African-American race is associated with younger age and decreased survival time at diagnosis of interstitial lung disease (ILD).We performed a multicentre, propensity score-matched analysis of patients with an ILD diagnosis followed at five US hospitals between 2006 and 2016. African-Americans were matched with patients of other races based on a time-dependent propensity score calculated from multiple patient, physiological, diagnostic and hospital characteristics. Multivariable logistic regression models were used. All-cause mortality and hospitalisations were compared between race-stratified patient cohorts with ILD, and sensitivity analyses were performed.The study included 1640 patients with ILD, 13% of whom were African-American, followed over 5041 person-years. When compared with patients of other races, African-Americans with ILD were younger at diagnosis (56 years versus 67 years), but in the propensity-matched analyses had greater survival (hazard ratio 0.46, 95% CI 0.28-0.77; p=0.003) despite similar risk of respiratory hospitalisations (relative risk 1.04, 95% CI 0.83-1.31; p=0.709), and similar GAP-ILD (gender-age-physiology-ILD) scores at study entry. Sensitivity analyses in a separate cohort of 9503 patients with code-based ILD diagnosis demonstrated a similar association of baseline demographic characteristics with all-cause mortality.We conclude that African-Americans demonstrate a unique phenotype associated with younger age at ILD diagnosis and perhaps longer survival time.


Assuntos
Afro-Americanos , Hospitalização/estatística & dados numéricos , Doenças Pulmonares Intersticiais/mortalidade , Adulto , Idoso , Causas de Morte , Feminino , Humanos , Modelos Logísticos , Doenças Pulmonares Intersticiais/etnologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Estudos Retrospectivos , Estados Unidos
18.
AJR Am J Roentgenol ; 210(5): 1034-1041, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29547052

RESUMO

OBJECTIVE: The purpose of this study was to assess the diagnostic significance of CT patterns that cannot be classified according to current idiopathic pulmonary fibrosis (IPF) guidelines and of specific findings of the inconsistent with usual interstitial pneumonitis (UIP) pattern. MATERIALS AND METHODS: Subjects with a multidisciplinary diagnosis of interstitial lung disease who had undergone surgical lung biopsy and chest CT within 1 year of each other were included in the study. The predominant distribution and pattern of disease were scored. Cases were classified as UIP, possible UIP, or inconsistent with UIP at chest CT according to 2011 IPF guidelines. Cases that could not be confidently categorized with current guidelines were annotated as indeterminate. RESULTS: UIP, possible UIP, and inconsistent with UIP CT patterns were associated with pathologic UIP in 89.6%, 81.6%, and 60.0% of subjects. An indeterminate CT pattern (7.7% [20/259]) was associated with a UIP pathologic diagnosis in 55.0% of cases. This finding was not statistically different from the findings in the group with the inconsistent with UIP CT pattern (p = 0.677) but was different from the findings in the UIP (p < 0.001) and possible UIP (p = 0.031) groups. In regard to specific findings of the inconsistent with UIP CT category, ground-glass opacity, air-trapping, consolidation, and axial distribution were associated with a non-UIP pathologic diagnosis; however, there was no significant association with zonal distribution. CONCLUSION: A substantial minority of cases cannot be confidently categorized according to current guidelines for IPF and differ diagnostically from the possible UIP and UIP CT categories. The term "inconsistent with UIP" is misleading and should be renamed.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X/métodos , Idoso , Biópsia , Feminino , Humanos , Fibrose Pulmonar Idiopática/cirurgia , Masculino , Pessoa de Meia-Idade
19.
BMC Pulm Med ; 18(1): 30, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422061

RESUMO

BACKGROUND: Mortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients. METHODS: A single center, retrospective cohort analysis was performed. Patients with UIP due to IPF and IPAF were stratified according to ANA status to and NAC exposure. Transplant-free survival (TFS) was assessed using the Kaplan-Meier estimator and multivariable Cox regression adjusted for diagnosis, gender/age/physiology score, immunosuppressant exposure and anti-fibrotic exposure. RESULTS: Of 293 individuals with UIP due to IPF (74%) or IPAF (26%), NAC exposure was documented in 58 (19.8%). Among NAC exposed individuals, 33 (56.9%) were ANA seropositive and 25 (43.1%) were seronegative. NAC exposure was associated with improved TFS survival among ANA seropositive individuals in unadjusted analysis (plogrank = 0.02) and after multi-variable adjustment (HR 0.51, 95% CI 0.30-0.87; p = 0.01). There was no association between NAC exposure and TFS in ANA seronegative individuals (HR 1.26, 95% CI 0.69-2.32; p = 0.45). Formal interaction testing confirmed NAC*ANA interaction (p = 0.04) and sensitivity analysis demonstrated an increasing effect size associated with NAC therapy as ANA titer increased. Among patients with available genetic data, a marginally higher proportion of ANA positive patients (p = 0.08) carried the rs3750920 (TOLLIP) genotype previously shown to predict favorable outcome in NAC exposed patients. CONCLUSION: NAC exposure is associated with improved transplant-free survival ANA positive patients with UIP. These findings support the prospective collection of ANA data in in future NAC clinical trials performed in patients with UIP.


Assuntos
Acetilcisteína/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Idoso , Anticorpos Antinucleares/imunologia , Estudos de Coortes , Feminino , Humanos , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/mortalidade , Estimativa de Kaplan-Meier , Transplante de Pulmão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
20.
AJR Am J Roentgenol ; 210(2): 307-313, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29140119

RESUMO

OBJECTIVE: A substantial proportion of cases of usual interstitial pneumonia (UIP) are due to connective tissue disease (CTD)-associated interstitial lung disease (ILD). The purpose of this study was to determine whether specific CT findings can help differentiate a UIP pattern of CTD-ILD from a UIP pattern of idiopathic pulmonary fibrosis (IPF) and whether these signs are associated with survival. MATERIALS AND METHODS: Adults visiting an ILD clinic from 2006 to 2015 enrolled in a research registry with a multidisciplinary diagnosis of CTD-ILD or IPF and a UIP pattern at high-resolution CT were included in the study. In these subjects with CT findings of UIP due to either IPF or CTD-ILD, three CT findings anecdotally associated with CTD-ILD were assessed for diagnostic accuracy: the "straight-edge" sign, the "exuberant honeycombing" sign, and the "anterior upper lobe" sign. Survival assessments were performed with univariate and multivariable techniques. RESULTS: The subjects included 63 patients who had CTD-ILD and 133 patients who had IPF with a UIP pattern at CT. All three CT signs were significantly more common in subjects with CTD-ILD than those with IPF (prevalence, 22.2-25.4% for CTD-ILD, 6.0-12.8% for IPF; p = 0.028 to < 0.001). The highest specificity (94.0%) and sensitivity (25.4%) were seen for the straight-edge sign. No CT sign was associated with survival in multivariable analysis. CONCLUSION: Although UIP is usually associated with IPF, the index of suspicion for CTD-ILD should be raised in the care of patients with any of the three CT signs. A thorough workup for CTD-ILD should be pursued, including referral to the rheumatology department.


Assuntos
Doenças do Tecido Conjuntivo/diagnóstico por imagem , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Sensibilidade e Especificidade
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