Interstitial lung disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases.

Population-based, longitudinal studies spanning decades linking risk factors in childhood, adolescence and early adulthood to incident clinical interstitial lung disease (ILD) events in late adulthood have not been performed. In addition, no observational or randomized clinical trials have been conducted; therefore, there is presently no evidence to support the notion that reduction of risk factor levels in early life prevents ILD events in adult life. Primary prevention strategies are host-directed interventions designed to modify adverse risk factors (i.

Cellular mechanisms of tissue fibrosis. 8. Current and future drug targets in fibrosis: focus on Rho GTPase-regulated gene transcription.

Tissue fibrosis occurs with excessive extracellular matrix deposition from myofibroblasts, resulting in tissue scarring and inflammation. It is driven by multiple mediators, such as the G protein-coupled receptor ligands lysophosphatidic acid and endothelin, as well as signaling by transforming growth factor-β, connective tissue growth factor, and integrins. Fibrosis contributes to 45% of deaths in the developed world.

Improved transplant-free survival in patients with systemic sclerosis-associated pulmonary hypertension and interstitial lung disease.

Objective: Survival in patients with systemic sclerosis (SSc)-associated pulmonary hypertension (PH) and interstitial lung disease (ILD) is poor. Evidence supporting the efficacy of aggressive pulmonary arterial hypertension (PAH)-targeted therapy in this population is limited. The aim of this study was to investigate transplant-free survival in patients with isolated SSc-related PAH or SSc-related PH-ILD who were treated with aggressive PAH-targeted therapy.

Multicriteria decision analysis methods with 1000Minds for developing systemic sclerosis classification criteria.

Objectives: Classification criteria for systemic sclerosis (SSc) are being developed. The objectives were to develop an instrument for collating case data and evaluate its sensibility; use forced-choice methods to reduce and weight criteria; and explore agreement among experts on the probability that cases were classified as SSc.

Study Design And Setting: A standardized instrument was tested for sensibility.

Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study.

Objectives: PHAROS registry is a prospective longitudinal cohort study to understand the natural history of pulmonary hypertension (PH) in systemic sclerosis (SSc).

Methods: "At-risk" pulmonary arterial hypertension (PAH) is defined by these entry criteria: echocardiogram (echo) systolic pulmonary arterial pressure (sPAP) >40 mmHg, diffusion lung capacity of carbon monoxide (DLco) <55% predicted, or ratio of percentage forced vital capacity (FVC)/percentage DLco >1.6, as measured by pulmonary function testing (PFT).

Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury.

Systemic sclerosis (SSc), or scleroderma, similar to many fibrotic disorders, lacks effective therapies. Current trials focus on anti-inflammatory drugs or targeted approaches aimed at one of the many receptor mechanisms initiating fibrosis. In light of evidence that a myocardin-related transcription factor (MRTF)-and serum response factor (SRF)-regulated gene transcriptional program induced by Rho GTPases is essential for myofibroblast activation, we explored the hypothesis that inhibitors of this pathway may represent novel antifibrotics.

Correlates and responsiveness to change of measures of skin and musculoskeletal disease in early diffuse systemic sclerosis.

Objective: Skin and musculoskeletal involvement are frequently present early in diffuse cutaneous systemic sclerosis (dcSSc). The current study examined the correlates for skin and musculoskeletal measures in a 1-year longitudinal observational study.

Methods: Patients with dcSSc were recruited at 4 US centers and enrolled in a 1-year study.

Construct validity of the Patient-Reported Outcomes Measurement Information System gastrointestinal symptom scales in systemic sclerosis.

Objective: Gastrointestinal (GI) involvement is common in patients with systemic sclerosis (SSc; scleroderma). The Patient-Reported Outcomes Measurement Information System (PROMIS) GI symptom item bank captures upper and lower GI symptoms (reflux, disrupted swallowing, nausea/vomiting, belly pain, gas/bloating/flatulence, diarrhea, constipation, and fecal incontinence). The objective of this study was to evaluate the construct validity of the PROMIS GI bank in SSc.

Achieving serum urate goal: a comparative effectiveness study between allopurinol and febuxostat.

Background: Febuxostat is recommended as 1 of 2 first-line urate-lowering therapies (ULT) for treating gout in the 2012 American College of Rheumatology Guidelines. Several efficacy trials have compared febuxostat with allopurinol treatment, but real-world comparative data are limited.

Methods: We compared effectiveness of the 2 agents in reaching serum urate (sUA) level goal (< 6 mg/dL) within 6 months (main endpoint), factors impacting the likelihood of reaching goal, and outcomes in allopurinol patients who were switched to febuxostat therapy after failing to reach sUA level goal.

Treatment of acute gout: a systematic review.

Objective: Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis.

Methods: A systematic search was performed using PubMed and Cochrane database through May 2013.

Connective tissue disease-associated interstitial pneumonia and idiopathic interstitial pneumonia: similarity and difference.

Interstitial lung diseases (ILDs) are increasingly recognized in patients with systemic diseases. Patients with early ILD changes may be asymptomatic. Features of ILD overlap among systemic diseases and with idiopathic variety.

Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis.

Background: Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype.

Methods: Open-label, prospective analysis of patients with PF-PH referred for lung transplantation (LT).

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region.

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

Rationale: Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.

Methods: The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients.

Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and is associated with serum proteins: a cross-sectional, controlled study of carotid ultrasound.

Objectives: SSc is associated with an increased prevalence of atherosclerosis (ATS). This study assessed the prevalence of subclinical ATS as measured by carotid US and explored serum proteins to identify potential biomarkers of SSc-ATS.

Methods: Forty-six SSc female patients and 46 age- and ethnicity-matched controls underwent carotid US to assess the presence of plaque and carotid intima media thickness (CIMT).

Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis.

The objectives of this study were to develop a standard classification of digital ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic studies and to assess the reliability of these definitions as well as of the measurement of ulcer area. Ten North American rheumatologists with expertise in SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and came to a consensus on the definitions for digital, active, healed, and indeterminate ulcers. These ten raters then examined the right hand of ten SSc subjects twice and the left hand once to classify ulcers and to measure ulcer area.

Definitions and diagnosis of pulmonary hypertension.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥ 25 mm Hg at rest, measured during right heart catheterization. There is still insufficient evidence to add an exercise criterion to this definition. The term pulmonary arterial hypertension (PAH) describes a subpopulation of patients with PH characterized hemodynamically by the presence of pre-capillary PH including an end-expiratory pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg and a pulmonary vascular resistance >3 Wood units.

Development of an online library of patient-reported outcome measures in gastroenterology: the GI-PRO database.

Objectives: Because gastrointestinal (GI) illnesses can cause physical, emotional, and social distress, patient-reported outcomes (PROs) are used to guide clinical decision making, conduct research, and seek drug approval. It is important to develop a mechanism for identifying, categorizing, and evaluating the over 100 GI PROs that exist. Here we describe a new, National Institutes of Health (NIH)-supported, online PRO clearinghouse-the GI-PRO database.

Outcome measures in acute gout: a systematic literature review.

Objective: Five core domains have been endorsed by Outcome Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. We evaluated instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination.

Methods: A systematic search strategy for instruments used to measure the acute gout core domains was formulated.

OMERACT endorsement of measures of outcome for studies of acute gout.

Objective: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed.

Methods: Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session.

Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative.

Objectives: The aim of this study was to utilise the Quality Enhancement Research Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc).

Methods: Rheumatologists enrolled patients with SSc (aged ≥ 18 years) and provided data on a panel of diagnostic tests over 3 years. Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal pro-brain natriuretic peptide assays, high-resolution computed tomography of the lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when appropriate) were emphasised.

Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study.

Objective: To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE).

Methods: We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE.