Machine Learning of Plasma Proteomics Classifies Diagnosis of Interstitial Lung Disease.

RATIONALE: Distinguishing connective tissue disease associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF) can be clinically challenging. OBJECTIVES: Identify proteins that separate and classify CTD-ILD from IPF patients. METHODS: Four registries with 1247 IPF and 352 CTD-ILD patients were included in analyses. Plasma samples were subjected to high-throughput proteomics assays. Protein features were prioritized using Recursive Feature Elimination (RFE) to construct a proteomic classifier. Multiple machine learning models, including Support Vector Machine, LASSO regression, Random Forest (RF), and imbalanced-RF, were trained and tested in independent cohorts. The validated models were used to classify each case iteratively in external datasets. MEASUREMENT AND MAIN RESULTS: A classifier with 37 proteins (PC37) was enriched in biological process of bronchiole development and smooth muscle proliferation, and immune responses. Four machine learning models used PC37 with sex and age score to generate continuous classification values. Receiver-operating-characteristic curve analyses of these scores demonstrated consistent Area-Under-Curve 0.85-0.90 in test cohort, and 0.94-0.96 in the single-sample dataset. Binary classification demonstrated 78.6%-80.4% sensitivity and 76%-84.4% specificity in test cohort, 93.5%-96.1% sensitivity and 69.5%-77.6% specificity in single-sample classification dataset. Composite analysis of all machine learning models confirmed 78.2% (194/248) accuracy in test cohort and 82.9% (208/251) in single-sample classification dataset. CONCLUSIONS: Multiple machine learning models trained with large cohort proteomic datasets consistently distinguished CTD-ILD from IPF. Identified proteins involved in immune pathways. We further developed a novel approach for single sample classification, which could facilitate honing the differential diagnosis of ILD in challenging cases and improve clinical decision-making.

Association of antinuclear antibody seropositivity with inhaled environmental exposures in patients with interstitial lung disease.

BACKGROUND: Interstitial lung diseases (ILDs) are diffuse parenchymal lung disorders that cause substantial morbidity and mortality. In patients with ILD, elevated antinuclear antibody (ANA) titres may be a sign of an autoimmune process. Inhalational exposures contribute to ILD pathogenesis and affect prognosis and may trigger autoimmune disease. The association of inhalational exposures with ANA seropositivity in ILD patients is unknown. METHODS: This was a retrospective cohort study of adult ILD patients from five centres in the United States. Exposures to tobacco, inhaled organic antigens and inhaled inorganic particles were extracted from medical records. A multivariable logistic regression model was used to analyse the effects of confounders including age, ILD diagnosis, gender and exposure type on ANA seropositivity. RESULTS: Among 1265 patients with ILD, there were more ANA-seropositive (58.6%, n=741) than ANA-seronegative patients (41.4%, n=524). ANA-seropositive patients had lower total lung capacity (69% versus 75%, p<0.001) and forced vital capacity (64% versus 70%, p<0.001) than patients who were ANA-seronegative. Among patients with tobacco exposure, 61.4% (n=449) were ANA-positive compared to 54.7% (n=292) of those without tobacco exposure. In multivariable analysis, tobacco exposure remained independently associated with increased ANA seropositivity (OR 1.38, 95% CI 1.12-1.71). This significant difference was similarly demonstrated among patients with and without a history of inorganic exposures (OR 1.52, 95% CI 1.12-2.07). CONCLUSION: Patients with ILD and inhalational exposure had significantly higher prevalence of ANA-seropositivity than those without reported exposures across ILD diagnoses. Environmental and occupational exposures should be systematically reviewed in patients with ILD, particularly those with ANA-seropositivity.

Adult onset Still's disease in a patient with scleroderma: case report.

BACKGROUND: Scleroderma and adult onset Still's disease (AOSD) are both uncommon autoimmune disorders. These two disorders have rarely been documented to occur simultaneously. In fact, after a thorough literature review, we discovered only one prior case report in a pregnant individual. Here, we describe the first documented case of scleroderma and AOSD in a postmenopausal patient. CASE PRESENTATION: The patient is a 61-year-old Caucasian female with a past medical history significant for peptic ulcer disease, mitral valve prolapse, chronic idiopathic pancreatitis, and limited cutaneous scleroderma with sclerodactyly, Raynaud's, and calcinosis. She was sent to the emergency room by her primary care physician due to one-week history of intermittent spiking fevers (Tmax 101°F), sore throat, myalgias, arthralgias, and non-pruritic bilateral lower extremity rash. Diagnostic evaluation in the hospital included complete blood count, comprehensive metabolic panel, respiratory viral panel, antinuclear antibody panel, bone marrow biopsy, and imaging with computerized tomography. Our patient fulfilled Yamaguchi Criteria for AOSD and all other possible etiologies were ruled out. She was treated with a steroid taper and methotrexate was initiated on post-discharge day number fourteen. Clinical and biochemical resolution was obtained at three months. CONCLUSIONS: In this report, we describe the first ever documented case of scleroderma and AOSD in a postmenopausal patient. The clinical presentation, diagnostic work up, and management discussed herein may serve as a framework for which rheumatologists and other physicians may draw upon in similar future encounters.

CPAP Adherence, Mortality, and Progression-Free Survival in Interstitial Lung Disease and OSA.

BACKGROUND: OSA, a common comorbidity in interstitial lung disease (ILD), could contribute to a worsened course if untreated. It is unclear if adherence to CPAP therapy improves outcomes. RESEARCH QUESTION: Does adherence to CPAP therapy improve outcomes in patients with concurrent interstitial lung disease and OSA? STUDY DESIGN AND METHODS: We conducted a 10-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 (apnea-hypopnea index score < 15) or moderate/severe OSA (apnea-hypopnea index score ≥ 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. Sixty-six 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 vs 138 ± 93 months, respectively; P = .61) and crude mortality rate (2.9 per 100 person-years vs 2.9 per 100 person-years, respectively; P = .60). Adherence to CPAP was not associated with improvement in all-cause mortality risk (hazard ratio [HR], 1.1; 95% CI, 0.4-2.9; P = .79) or PFS (HR, 0.9; 95% CI, 0.5-1.5; P = .66) compared with those that were nonadherent or untreated. Among subjects requiring supplemental oxygen, those adherent to CPAP had improved PFS (HR, 0.3; 95% CI, 0.1-0.9; P = .03) compared with nonadherent or untreated subjects. INTERPRETATION: Neither OSA severity nor adherence to CPAP was associated with improved outcomes in patients with ILD except those requiring supplemental oxygen.

Portal vein thrombosis: When to treat and how?

Portal vein thrombosis is an unusual thrombotic condition not frequently seen in the general population; however, it has a higher prevalence in special circumstances such as in liver cirrhosis and hepatic or pancreatic malignancy. It also can be associated with significant morbidity and mortality. In this review, we discuss the current data available to guide therapy in the setting of different associated co-morbidities, hypercoagulable states, and associated thrombosis of the remaining splanchnic circulation. We discuss indications for anticoagulation, including the choice of anticoagulants, as well as the role of conservative 'wait and watch' and invasive therapies, such as thrombolysis, thrombectomy, and transjugular intrahepatic portosystemic shunt.

Conditions presenting with symptoms of peripheral arterial disease.

Peripheral artery disease (PAD) is estimated to affect more than 20% of people older than 65 years. The vast majority of patients with symptoms suggestive of PAD have atherosclerosis often associated with conventional vascular risk factors such as smoking, diabetes, dyslipidemia, and inflammation. A minority of people presenting with symptoms suggesting PAD have an alternative etiology. These groups of disorders are often underdiagnosed, and if diagnosed correctly the diagnosis may be delayed. Understanding these pathologies well is important, as they can be very debilitating and optimal treatment may vary significantly. Inappropriate treatment of these disorders can lead to worsening morbidity and mortality. This article discusses the underlying causes of nonatherosclerotic PAD, including the diagnosis and treatment of these disorders.