Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

Association between antinuclear antibody seropositivity and telomere length: a nationwide population-based study.

OBJECTIVES: Telomere shortening is a well-established marker of biological aging. Whether telomere erosion coincides with age-related increases in antinuclear antibody (ANA) seropositivity remains unknown. Our study aimed to determine the association between ANA seropositivity and shortened telomeres among 1999-2002 National Health and Nutrition Examination Survey (NHANES) subjects. METHODS: We performed a cross-sectional analysis of 2,188 NHANES study participants with available ANA and telomere length data. ANA testing was performed using indirect immunofluorescence. Telomere lengths were measured via quantitative polymerase chain reaction methods. Applying appropriate sample weighting techniques, we used univariate and multivariate logistic regression methods to assess the association between shortened telomeres (i.e. lowest decile of the cohort) and ANA seropositivity. RESULTS: ANAs were positive in 322 out of 2,188 (14.7%, 95% CI 13.3-16.3%) individuals. Subjects with shortened telomeres were more likely to be older (p<0.001), male (p=0.005), and have a cancer history (p<0.001). A higher proportion of non-Hispanic white participants (61.6% vs. 49.3%) and a lower proportion of non-Hispanic black participants (7.8% vs. 17.9%) had shortened telomeres (p<0.001). Shortened telomeres were not independently associated with ANA seropositivity (OR 1.48, 95% CI 0.87-2.52, p=0.14). However, female sex (OR 1.91, 95% CI 1.23-2.96, p=0.006), age ≥80 years (OR 2.06, 95% CI 1.08-3.92, p=0.03), and African American race (OR 1.58, 95% CI 1.00-2.51, p=0.05) were independent risk factors for ANA seropositivity. Neither sex nor race modified the relationship between ANA seropositivity and telomere length. CONCLUSIONS: Telomere erosion does not appear to be responsible for age-related increases in the prevalence of ANA seropositivity.

A CT Algorithm Can Elevate the Differential Diagnosis of Interstitial Lung Disease by Non-specialists to Equal That of Specialist Thoracic Radiologists.

BACKGROUND: Diagnosis of diffuse parenchymal lung diseases (DPLD) on high resolution CT (HRCT) is difficult for non-expert radiologists due to varied presentation for any single disease and overlap in presentation between diseases. RATIONALE AND OBJECTIVES: To evaluate whether a pattern-based training algorithm can improve the ability of non-experts to diagnosis of DPLD. MATERIALS AND METHODS: Five experts (cardiothoracic-trained radiologists), and 25 non-experts (non-cardiothoracic-trained radiologists, radiology residents, and pulmonologists) were each assigned a semi-random subset of cases from a compiled database of DPLD HRCTs. Each reader was asked to create a top three differential for each case. The non-experts were then given a pattern-based training algorithm for identifying DPLDs. Following training, the non-experts were again asked to create a top three differential for each case that they had previously evaluated. Accuracy between groups was compared using Chi-Square analysis. RESULTS: A total of 400 and 1450 studies were read by experts and non-experts, respectively. Experts correctly placed the diagnosis as the first item on the differential versus having the correct diagnosis as one of their top three diagnoses at an overall rate of 48 and 64.3%, respectively. Pre-training, non-experts achieved a correct diagnosis/top three of 32.5 and 49.7%, respectively. Post-training, non-experts demonstrated a correct diagnosis/top three of 41.2 and 65%, a statistically significant increase (p < 0.0001). In addition, post training, there was no difference between non-experts and experts in placing the correct diagnosis within their top three differential. CONCLUSION: The diagnosis of DPLDs by HRCT imaging alone is relatively poor. However, use of a pattern-based teaching algorithm can improve non-expert interpretation and enable non-experts to include the correct diagnosis within their differential diagnoses at a rate comparable to expert cardiothoracic trained radiologists.

Autoantibody Seropositivity and Risk for Interstitial Lung Disease in a Prospective Male-Predominant Rheumatoid Arthritis Cohort of U.S. Veterans.

Rationale: Prior studies investigating associations of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) seropositivity with risk for rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) have mostly used cross-sectional or case-control designs.Objectives: To determine whether combined autoantibody seropositivity and higher individual autoantibody concentrations were associated with increased risk for RA-ILD in a prospective RA cohort.Methods: Within the Veterans Affairs Rheumatoid Arthritis prospective registry, we performed a cross-sectional study of prevalent ILD and a retrospective cohort study of incident ILD (diagnosed after at least 12 mo of longitudinal follow-up). We used logistic and Cox regression methods to determine whether combined RF/ACPA seropositivity and higher autoantibody concentrations were independently associated with greater risk for prevalent and incident ILD, respectively.Results: Among 2,328 participants (median age 64 yr, 89.3% male), 100 (4.3%) subjects had prevalent ILD at enrollment. During 14,281 patient-years of follow-up, 83 (3.7%) of the remaining 2,228 were subsequently diagnosed with incident ILD (5.8 cases per 1,000 person-years). Patients with combined RF/ACPA seropositivity had a higher probability of prevalent ILD compared with seronegative subjects (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.24-6.78). RF titers demonstrated a monotonic association with prevalent ILD (OR, 2.69; 95% CI, 1.11-6.51 for low-positive [15-45 IU/ml] titers; OR, 3.40; 95% CI, 1.61-7.18 for high-positive [>45 IU/ml] titers; P for trend 0.01). Patients with high-positive (>15 U/ml) ACPA titers were also at higher risk for prevalent ILD (OR, 1.91; 95% CI, 1.04-3.49) compared with ACPA-negative subjects. Combined RF/ACPA seropositivity was not associated with increased risk for incident ILD, nor were high- or low-positive RF or ACPA titers. In a piecewise linear spline model, however, RF titers greater than 90 IU/ml independently correlated with increased risk for incident ILD (hazard ratio, 1.68, 95% CI, 1.02-2.77).Conclusions: Combined RF/ACPA seropositivity and individual autoantibody concentrations were strongly associated with prevalent but not incident RA-ILD. Only patients with RF concentrations >90 IU/ml were observed to be at higher risk of incident RA-ILD.