Assessment of antibody levels to SARS-CoV-2 in patients with idiopathic inflammatory myopathies receiving treatment with intravenous immunoglobulin.

Antibodies to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) have been reported in pooled healthy donor plasma and intravenous immunoglobulin products (IVIG). It is not known whether administration of IVIG increases circulating anti-SARS-CoV-2 antibodies (COVID ab) in IVIG recipients. COVID ab against the receptor binding domain of the spike protein were analyzed using a chemiluminescent microparticle immunoassay in patients with idiopathic inflammatory myopathies (IIM) both receiving and not receiving IVIG (IVIG and non-IVIG group, respectively). No significant differences in COVID ab levels were noted between IVIG and non-IVIG groups (417 [67-1342] AU/mL in IVIG vs 5086 [43-40,442] AU/mL in non-IVIG, p = 0.11). In linear regression models including all post-vaccination patient samples, higher number of vaccine doses was strongly associated with higher COVID ab levels (2.85 [1.21, 4.48] log AU/mL, regression coefficient [Formula: see text] [95% CI], p = 0.001), while use of RTX was associated with lower ab levels (2.73 [- 4.53, - 0.93] log AU/mL, [Formula: see text][95%CI], p = 0.004). In the IVIG group, higher total monthly doses of IVIG were associated with slightly higher COVID ab levels (0.02 [0.002-0.05] log AU/mL, p = 0.04). While patients on IVIG did not have higher COVID ab levels compared to the non-IVIG group, higher monthly doses of IVIG were associated with higher circulating levels of COVID ab in patients receiving IVIG, particularly in patients concomitantly receiving RTX. Our findings suggest that IIM patients, especially those at increased risk of COVID infection and worse COVID outcomes due to RTX therapy may have protective benefits when on concurrent IVIG treatment.

The disconnect between visual assessment of air trapping and lung physiology for assessment of small airway disease in scleroderma-related interstitial lung disease: An observation from the Scleroderma Lung Study II Cohort.

Objective: To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. Methods: Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. Results: A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. Conclusion: We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.

Altered Gut Microbiome in Patients With Dermatomyositis.

OBJECTIVE: The study objective was to compare the microbial composition of patients with dermatomyositis (DM) and healthy controls (HCs) and determine whether microbial alterations are associated with clinical manifestations of DM. METHODS: The 16S ribosomal RNA gene sequencing was performed on fecal samples from patients with DM and HCs. Microbial composition and diversity were compared between subjects with DM and HCs and in association with several DM-specific clinical variables, including myositis-specific autoantibodies (MSAs). Differentially abundant microbial taxa and genes associated with clinical characteristics were identified, and functional analysis was performed using predicted metagenomics. Dietary intake was assessed using a 24-hour dietary recall. RESULTS: The fecal microbiome of 36 patients with DM and 26 HCs were analyzed. Patients with DM trended toward lower microbial diversity compared with HCs. The higher physician global damage score was significantly correlated with the lower microbial diversity in patients with DM. Patients with interstitial lung disease (ILD)-associated MSA (antisynthetase antibody (ab), anti-melanoma differentiation-associated protein 5 ab, n = 12) had significant differences in microbial composition and lower microbial diversity compared with HCs. Differential abundance testing demonstrated a unique taxonomic signature in the ILD-MSA subgroup, and predictive metagenomics identified functional alterations in a number of metabolic pathways. A significant increase in the relative abundance of Proteobacteria was positively correlated with multiple pathways involved in lipopolysaccharide synthesis and transport in the ILD-MSA group. CONCLUSION: Patients with DM, particularly with ILD-associated MSAs, have lower microbial diversity and a distinct taxonomic composition compared with HCs. Further studies are needed to validate our findings and elucidate specific pathogenetic mechanisms that link the gut microbiome to clinical and pathological features of DM.

Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies.

OBJECTIVES: Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients. METHODS: A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes. RESULTS: The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes. CONCLUSIONS: The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

Major Lipids and Future Risk of Pneumonia: 20-Year Observation of the Atherosclerosis Risk in Communities (ARIC) Study Cohort.

BACKGROUND: Circulating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia. METHODS: A retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization. RESULTS: A total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels. CONCLUSION: Lower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.

2020 American College of Rheumatology Guideline for the Management of Gout

To provide guidance for the management of gout, including indications for and optimal use of urate- lowering therapy (ULT), treatment of gout ares, and lifestyle and other medication recommendation Fifty- seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta- analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the nal recommendations and grade their strength as strong or conditional.Results. Forty- two recommendations (including 16 strong recommendations) were generated. Strong recommen-dations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout ares; allopurinol as the preferred rst- line ULT, including for those with moderate- to- severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat- to- target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinammatory prophylaxis therapy for a duration of at least 3­6 months was strongly recommended. For management of gout ares, colchicine, nonsteroidal antiinammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.Conclusion. Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Statin use in patients with non-HMGCR idiopathic inflammatory myopathies: A retrospective study.

BACKGROUND: Statins are the most widely used lipid lowering therapies which reduce cardiovascular risk, but are associated with muscular adverse events (AEs). Idiopathic inflammatory myopathies (IIM) are autoimmune diseases of the muscle with higher risk of cardiovascular disease. More data is needed regarding statin safety in patients with intrinsic muscle disease such as IIM. HYPOTHESIS: Statins are tolerated in patients with IIM without leading to significant increase in muscular AEs. METHODS: Statin use was retrospectively examined in a longitudinal IIM cohort. Safety analysis included assessment of muscular and nonmuscular AEs by chart review. IIM patients receiving a statin during the cohort follow-up period were matched to IIM patients not receiving a statin for comparative analysis of longitudinal outcomes. RESULTS: 33/214 patients had a history of statin use. 63% started for primary prevention, while others were started for clinical ASCVD events, vascular surgery, IIM related heart failure, and cardiac transplantation. A high intensity statin was used in nine patients with non-HMGCR myositis, and tolerated in 8/9 patients. Statin related muscular AE was noted in three patients. There were no cases of rhabdomyolysis, or statin related nonmuscular AEs in a median observation period of 5 years. In patients newly started on statins during cohort follow-up (n = 7) there was no change in disease activity after statin initiation. Long term outcomes were not different between statin and nonstatin IIM control groups. CONCLUSION: Statins were well tolerated in patients with non-HMGCR positive IIM. Given the accelerated atherosclerotic risk in IIM patients, further prospective studies of statin safety in IIM patients are warranted.

2020 American College of Rheumatology Guideline for the Management of Gout.

OBJECTIVE: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. METHODS: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. RESULTS: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. CONCLUSION: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

2020 American College of Rheumatology Guideline for the Management of Gout.

OBJECTIVE: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. METHODS: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. RESULTS: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. CONCLUSION: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Oral cyclophosphamide in treatment of patients with refractory idiopathic inflammatory myopathies: a retrospective observational study.

To describe the use of oral cyclophosphamide (PO CYC) in a single center longitudinal cohort of patients with idiopathic inflammatory myopathies (IIM). Patients using PO CYC were identified through a retrospective chart review of a myositis cohort at a single academic center. PO CYC dose, duration, adverse events, and disease activity measures before and after CYC were analyzed. Disease activity measures included muscle enzymes, manual muscle testing (MMT8), 100-mm visual analog scale (VAS), and 1-4 Likert scale for physician global assessment. Fourteen patients were treated with PO CYC within the cohort between 2008 and 2017; 9 dermatomyositis (DM), 3 polymyositis (PM), and 2 with immune-mediated necrotizing myopathy (IMNM). Age was 51.1 (40-72) years and the cumulative dose of PO CYC was 41 (2-131) grams over duration of 12.4 (0.5-43) months, mean (range) for all. All patients had severe refractory IIM, 10 (72%) with ILD, 3 (21%) with cardiac involvement and 4 (29%) were dependent in most activities of daily living. Median number of prior failed therapies was 4.5 (range 3-6) including intravenous CYC in 5 patients. Disease activity measures significantly improved following CYC use and concomitant daily prednisone dose decreased. The most common adverse events during CYC therapy were infections. We report the first cohort study of PO CYC use in IIM patients with severe, treatment refractory disease. Further trials are needed to verify these results as well as to evaluate long-term safety outcomes.

Sirukumab for the treatment of rheumatoid arthritis: update on sirukumab, 2018.

INTRODUCTION: Interleukin-6 (IL-6) is well-known for its pro-inflammatory properties, has been proven to target a wide range of cells in the joint, and has been implicated in extra-articular and articular manifestations in rheumatoid arthritis (RA). Tocilizumab (TCZ) is now widely used in patients with active RA and a number of additional agents that target the IL-6 pathways are under development, including sirukumab (SRK). Areas covered: SRK is an IgG1κ human anti-IL-6 monoclonal antibody which binds to IL-6 and prevents IL-6-mediated downstream effects. Initial trial results in phase-III studies in patients with RA seemed promising, showing improved results in patients with moderate-to-severe RA. Data derive from the phase-II study and the various SIRROUND studies (phase III). Expert commentary: The available data show that SRK50 mg every 4 weeks or 100 mg every 2 weeks will be effective in treating the RA population, with clinical improvements as early as week 2 and sustained over time. The adverse-event profile seems to be similar to TCZ, except for an increased mortality post open-label studies due to infections and cardiovascular events, our knowledge of which will be deepened with post-marketing surveillance and registry data.

Cardiac Transplantation in Dermatomyositis: A case report and literature review.

BACKGROUND AND OBJECTIVES: Cardiac involvement has been well recognized in patients with dermatomyositis (DM) and polymyositis (PM) with a variable frequency between 9 and 72%. However, clinically significant heart involvement in DM/PM is relatively infrequent and there have been rare reports of cardiac transplantation in DM. Our aims were to describe a case of severe cardiac involvement in DM requiring heart transplantation and review the literature of cardiac disease in DM and PM. METHODS: A patient with dermatomyositis who was referred to our institution with severe heart failure is described. Pathology of the patient's skeletal and cardiac muscle is reviewed. A MEDLINE database search of reports of cardiac involvement in DM and PM was also conducted. RESULTS: A 36 year-old man with DM presented with severe heart failure to our institution for evaluation of heart transplantation. After a three month hospitalization he underwent successful cardiac transplantation. Pathological examination of his explant heart revealed a pattern of inflammation and damage similar to DM in skeletal muscle. The patient is currently doing well, 20 months post-transplant, and is maintained on tacrolimus, cellcept, rituximab, and low dose prednisone. To our knowledge, this is the first case report of heart transplantation in dermatomyositis in which the muscle pathology is similar in both heart and skeletal muscle. CONCLUSIONS: Severe cardiac involvement requiring transplantation is rare in dermatomyositis but does occur and appears to be related to a similar inflammatory process as noted in the skeletal muscle.

Assessment of skin involvement in systemic sclerosis.

Skin involvement in SSc is an important marker of disease activity, severity and prognosis, making the assessment of skin a key issue in SSc clinical research. We reviewed the published data assessing skin involvement in clinical trials and summarized the major conclusions important in SSc clinical research. A systematic literature review identified randomized controlled trials using skin outcomes in SSc. Analysis examined the validity of the different skin measures based on literature findings. Twenty-two randomized controlled trials were found. The average study duration was 10.2 (s.d. 4.5) months, mean (s.d.) sample size 32.4 (32.6) and 26.7 (27.8) in intervention and control arms, respectively. The 17-site modified Rodnan skin score is a fully validated primary outcome measure in diffuse cutaneous SSc. Skin histology seems to be an appropriate method for evaluation of skin thickness. These findings have important implications for clinical trial design targeting skin involvement in SSc.

Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards.

OBJECTIVE: SSc is clinically and aetiopathogenically heterogeneous. Consensus standards for more uniform trial design and selection of outcome measures are needed. The objective of this study was to develop evidence-based points to consider (PTCs) for future clinical trials in SSc. METHODS: Thirteen international SSc experts experienced in SSc clinical trial design were invited to participate. One researcher with experience in systematic literature review and three trainees were also included. A systematic review using PubMed and the Cochrane Central Register of Controlled Trials was conducted and PTCs when designing clinical trials in SSc were developed. As part of that development we conducted an Internet-based Delphi exercise regarding the main points to be made in the consensus statement. Consensus was defined as achieving a median score of ≥7 of 9. RESULTS: By consensus, the experts decided to develop PTCs for each individual organ system. The current document provides a unifying outline on PTCs regarding general trial design, inclusion/exclusion criteria and analysis. Consensus was achieved regarding all the main points of the PTCs. CONCLUSION: Using European League Against Rheumatism suggestions for PTCs, a general outline for PTCs for controlled clinical trials in SSc was developed. Specific outlines for individual organ systems are to be published separately. This general outline should lead to more uniform and higher-quality trials and clearly delineate areas where further research is needed.

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. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements. RESULTS: Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1ß inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra. CONCLUSION: NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout.

Associations between a scleroderma-specific gastrointestinal instrument and objective tests of upper gastrointestinal involvements in systemic sclerosis.

OBJECTIVES: UCLA-SCTC-GIT 2.0 is an instrument designed to evaluate gastrointestinal (GI) symptoms in systemic sclerosis (SSc). The objective of our study was to assess the associations between the upper GI (UGI) symptom scales (reflux and distention/bloating [D/B] scales) versus objective/laboratory studies. METHODS: Fifty-five patients with SSc were enrolled at 2 centres. Each patient completed the GIT 2.0 and had objective and laboratory tests. Correlations were assessed using the Spearman's test. We also assessed the average scores in patients with positive vs. negative tests and compared them using the t-test and Wilcoxon test. RESULTS: The mean (SD) age was 53.6 (11.8), 90% were women and 49% had limited SSc. The mean reflux and D/B scores were 0.82 and 1.25, respectively (moderate severity). The reflux scale had moderate correlations with upper GI objective evaluations (correlation coefficient ≥0.40) and was able to differentiate between patients with endoscopy proven esophagitis and manometric abnormalities (p=0.01 for both). D/B scores were numerically higher in patients with abnormal objective tests. The GIT 2.0 reflux and D/B scales had a high sensitivity ranging from 80% to 94% but very low specificity (range; 0-20%) based on objective gold standard GI measures. CONCLUSIONS: The GIT 2.0 reflux and D/B scales have a high sensitivity (range 80-94%) for UGI involvement. The GIT 2.0 instrument complements the objective tests for assessment of the UGI.

Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry.

BACKGROUND: Patients with normal (mean pulmonary arterial pressure (mPAP) ≤20 mm Hg) and borderline mean pulmonary pressures (21-24 mm Hg) are "at risk" of developing pulmonary hypertension (PH). The objectives of this analysis were to examine the baseline characteristics in systemic sclerosis (SSc) with normal and borderline mPAP and to explore long-term outcomes in SSc patients with borderline mPAP versus normal haemodynamics. METHODS: PHAROS is a multicentre prospective longitudinal cohort of patients with SSc "at risk" or recently diagnosed with resting PH on right heart catheterisation (RHC). Baseline clinical characteristics, pulmonary function tests, high-resolution CT, 2-dimensional echocardiogram and RHC results were analysed in normal and borderline mPAP groups. RESULTS: 206 patients underwent RHC (results showed 35 normal, 28 borderline mPAP, 143 resting PH). There were no differences in the baseline demographics. Patients in the borderline mPAP group were more likely to have restrictive lung disease (67% vs 30%), fibrosis on high-resolution CT and a higher estimated right ventricular systolic pressure on echocardiogram (46.3 vs 36.2 mm Hg; p<0.05) than patients with normal haemodynamics. RHC revealed higher pulmonary vascular resistance and more elevated mPAP on exercise (≥30; 88% vs 56%) in the borderline mPAP group (p<0.05 for both). Patients were followed for a mean of 25.7 months and 24 patients had a repeat RHC during this period. During follow-up, 55% of the borderline mPAP group and 32% of the normal group developed resting PH (p=NS). CONCLUSIONS: Patients with borderline mPAP have a greater prevalence of abnormal lung physiology, pulmonary fibrosis and the presence of exercise mPAP ≥30 mm Hg.