The emerging association between bronchiectasis and systemic sclerosis: assessing prevalence and potential causality.

BACKGROUND: Bronchiectasis has been observed in association with systemic sclerosis (SSc). Theorised aetiology includes aspiration related to oesophageal dysmotility, immunosuppressant medication use and the direct effect of collagen deposition on airway calibre. AIMS: To detail bronchiectasis prevalence in an SSc population who have had a high-resolution computed tomography (HRCT) of the thorax. We assessed whether oesophageal dysmotility, demographic variables, SSc duration or subclass were associated with bronchiectasis. METHODS: Participants in the Australian Scleroderma Cohort Study (ASCS) with a HRCT were included. The ASCS provided demographic and clinical data. HRCT studies were reviewed for bronchiectasis, oesophageal dilatation and interstitial lung disease (ILD). Traction bronchiectasis associated with ILD was recorded as a separate entity to bronchiectasis. Oesophageal dysmotility was defined by symptoms and/or oesophageal dilatation. RESULTS: Of the 256 participants, 16.4% (n = 42) had bronchiectasis. Logistic regression analysis revealed no significant association between bronchiectasis and oesophageal dysmotility (observed in 95.7%), any demographic variable, SSc duration or subclass. A negative association between bronchiectasis and ILD was observed (P = 0.009; odds ratio 0.322; 95% confidence intervals 0.137-0.756). CONCLUSION: Those with SSc appear to have an increased risk for bronchiectasis. Since bronchiectasis was not more frequent in participants with a longer duration of SSc, we hypothesise that its development is not related to immunosuppression alone. Oesophageal dysmotility was almost universal in our population such that its effect on bronchiectasis development could not be concluded. A negative association between bronchiectasis and ILD reflects that bronchiectasis occurring alongside ILD was recorded as a separate entity.

The impact of the 2022 Ukraine/Russian conflict on cancer clinical trials.

Since the invasion of Ukraine in February 2022, clinical trial conduct has become extremely challenging due to damage to the healthcare infrastructure and patient displacement. This current study aimed to estimate the number of cancer clinical trials at risk of impact from the conflict. A descriptive analysis and narrative review were completed using data from cancer clinical trials with sites in Russia or Ukraine using the 'clinical trials.gov' online database between February 2022 and May 2022. There were 508 clinical trials involving sites in Ukraine or Russia. Most were multinational studies (470 of 508; 93%). The majority of studies were phase 3 (344 of 508; 68%) and these also had the largest sample sizes (median 624, range 12-5637). The most common tumour types were lung (128 of 508; 25%), urogenital (94 of 508; 19%) and breast (78 of 508; 15%). A meaningful number of trials had curative intent (129 of 508; 25%). The most common intervention was immunotherapy-related (218 of 508; 43%), followed by other targeted therapy (185 of 508; 36%). Ukraine and Russia are both large centres for global clinical trial activity. The invasion of Ukraine may result in underpowering of international clinical trial results with loss of future recruitment sites for both countries.

Transfer learning artificial intelligence for automated detection of atrial fibrillation in patients undergoing evaluation for suspected obstructive sleep apnoea: a feasibility study.

BACKGROUND: Individuals with obstructive sleep apnoea (OSA) experience a higher burden of atrial fibrillation (AF) than the general population, and many cases of AF remain undetected. We tested the feasibility of an artificial intelligence (AI) approach to opportunistic detection of AF from single-lead electrocardiograms (ECGs) which are routinely recorded during in-laboratory polysomnographic sleep studies. METHODS: Using transfer learning, an existing ECG AI model was applied to 1839 single-lead ECG traces recorded during in-laboratory sleep studies without any training of the algorithm. Manual review of all traces was performed by two trained clinicians who were blinded to each other's review. Discrepancies between the two investigators were resolved by two cardiologists who were also unaware of each other's scoring. The diagnostic accuracy of the AI algorithm was calculated against the results of the manual ECG review which were considered gold standard. RESULTS: Manual review identified AF in 144 of the 1839 single-lead ECGs (7.8%). The AI detected all cases of manually confirmed AF (sensitivity = 100%, 95% CI: 97.5-100.0). The AI model misclassified many ECGs with artefacts as AF, resulting in a specificity of 76.0 (95% CI: 73.9-78.0), and an overall diagnostic accuracy of 77.9% (95% CI: 75.9%-97.8%). CONCLUSION: Transfer learning AI, without additional training, can be successfully applied to disparate ECG signals, with excellent negative predictive values, and can exclude AF among patients undergoing evaluation for suspected OSA. Further signal-specific training is likely to improve the AI's specificity and decrease the need for manual verification.

Patterns of immunotherapy-induced pneumonitis in patients with non-small-cell lung cancer: a case series.

BACKGROUND: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. CASE PRESENTATIONS: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian man with squamous cell lung cancer who developed early-onset pneumonitis with rebound on steroid taper. CONCLUSIONS: This case series has provided further insight into the presentation and risk factors for pneumonitis in patients with non-small-cell lung cancer. Each of the cases of immunotherapy-induced pneumonitis illustrates the different potential patterns that may arise when immunotherapy-induced pneumonitis develops. This case series provides key learning points that may assist physicians managing non-small-cell lung cancer with immunotherapy.

Case report of osteolytic lesions in a patient with multisystem granulomatous disease.

We present a case of a 70-year-old Caucasian woman with multisystem granulomatous disease involving her lungs, bones and lymph nodes. The patient initially presented with cervical lymphadenopathy and subsequently developed progressive breathlessness. Imaging revealed extensive mediastinal, hilar and intra-abdominal lymphadenopathy as well as bilateral pulmonary parenchymal infiltrates. Lymph node and lung biopsy confirmed non-necrotising granulomatous inflammation while a BAL showed scanty growth of Cryptococcus neoformans and moderate growth of Staphylococcus aureus The patient received intravenous ceftriaxone and had a good response to treatment. She also completed 3 months of oral fluconazole. Although a diagnosis of sarcoidosis was considered most likely, the patient was not initially started on systemic corticosteroids due to concern around possible infection and initial response to antimicrobials. However, her exercise tolerance gradually deteriorated. A craniofacial CT revealed multiple lytic lesions involving the skull and visualised cervical spine. Biopsy of a clivus lesion revealed non-necrotising granulomatous inflammation while fungal cultures and histopathological stains were negative. The patient was diagnosed with widespread sarcoidosis and she was initiated on prednisolone and methotrexate which led to marked clinical and radiological improvement.

Dilemmas in anticoagulation and use of inferior vena cava filters in venous thromboembolism; a survey of Respiratory Physicians, Haematologists and Medical Oncologists and a review of the literature.

Twenty percent of patients with Cancer Associated Thrombosis receive an inferior vena cava filter annually. Insertion is guided by practice guidelines, which do not specify or discuss the use of inferior vena cava filters in malignancy. Adherence to these guidelines is known to be variable. We aimed to see if there was consistent management of venous thromboembolism among Medical Oncologists/Haematologists and Respiratory Physicians, with respect to inferior vena cava filter use in the setting of suspected and confirmed malignancy. Medical Oncologists, Haematologists and Respiratory Physicians were surveyed with four theoretical cases. Case 1 concerns a patient who develops a pulmonary embolism following spinal surgery. Cases 2 and 4 explore the use of inferior vena cava filters in the setting of malignancy. Case 3 covers the role of inferior vena cava filters in recurrent thrombosis despite systemic anticoagulation. There were 56 responses, 32 (57%) Respiratory Physicians and 24 (43%) Haematologists/Oncologists. Respiratory Physicians were significantly more likely to insert an inferior vena cava filter in case 1 (p = 0.04) whilst Haematologists/Medical Oncologists were more likely to insert an inferior vena cava filter in case 3 (p = 0.03). No significant differences were found in cases 2 and 4. There were significant disparities in terms of type and timing of anticoagulation. Consistency of recommendations with guidelines was variable likely in part because guidelines are themselves inconsistent. The heterogeneity in responses highlights the variations in venous thromboembolism management, especially in Cancer Associated Thrombosis. International Societies should consider addressing inferior vena cava filter use specifically in the setting of Cancer Associated Thrombosis. Collaboration between interested specialities would assist in developing consistent, evidence-based guidelines for the use of inferior vena cava filters in the management of venous thromboembolism.

Doctors' understanding of consent law.

BACKGROUND: Obtaining informed consent is an important responsibility of all doctors and is a major component of their day-to-day practice. However, little is known regarding practising doctors' understanding of consent in relation to medical law. AIMS: To gain insights into current doctors' understanding of the legal requisites that underpin the consent of patients to medical procedures in Australia. METHODS: A cross-sectional survey of Western Australian medical practitioners was conducted. A 15-question online questionnaire (SurveyMonkey, USA) was developed and distributed to Western Australia medical practitioners via social media, hospital-based Junior doctor society pages and through the email accounts of practitioners registered with MDA National - a large medical defence organisation. Doctors were questioned on their understanding of medicolegal responsibilities, informed consent practice and knowledge of a historically significant Australian medicolegal case (Rogers v Whitaker, 1992). RESULTS: A total of 172 responses was received during the survey period. The respondents came from various levels of seniority and from a variety of subspecialist areas. The survey demonstrated that among the respondents, the understanding of their medicolegal responsibilities around the issues of informed consent was deficient. Only 31% of respondents were aware that it is a court of law that defines the reasonable standard of care in relation to obtaining informed consent. Less than half of the respondents (48%) were aware of the High Court of Australia's definition by which the standard of reasonable care is defined. CONCLUSION: The results from our survey suggest that there is a requirement to enhance the education of medical practitioners to meet the medicolegal requirements and optimise consent.

Management of neutropenic fever in a private hospital oncology unit.

BACKGROUND: Neutropenic fever is a medical emergency, which poses a significant morbidity and mortality risk to cancer patients receiving chemotherapy. National guidelines recommend that patients presenting with suspected neutropenic fever receive appropriate intravenous antibiotics within 60 min of admission. AIM: We aimed to investigate the management of neutropenic fever in a large private oncology centre. METHODS: A retrospective audit of all patients who presented to St John of God Hospital, Subiaco, in the 2017 calendar year, with a known solid organ malignancy and a recorded diagnosis of neutropenic fever was conducted. Patients were identified through the hospitals Patient Administration System and ICD-10 codes. Information was collected from the hospital medical records using a standardised data collection tool. RESULTS: There were 98 admissions relating to 88 patients with neutropenic fever during the study period. The median age was 64 years (range: 23-85 years) with 57 (65%) females. Antibiotic selections consistent with the Australian guidelines were made in 88 (89%) admissions. The mean time to antibiotic administration was 279 min, with a median of 135 min (range: 15-5160 min). Antibiotics were administered within the recommended time frame in only eight (11%) admissions. CONCLUSION: Clinicians prescribed antibiotics in accordance with national guidelines; however, there were systemic inefficiencies which resulted in delayed antibiotic initiation. This has resulted in implementation of strategies to minimise delay.

Threshold of Pulmonary Hypertension Associated With Increased Mortality.

BACKGROUND: There is increasing evidence that current thresholds for diagnosing pulmonary hypertension (PHT) underestimate the prognostic impact of PHT. OBJECTIVES: The aim of this study was to determine the prognostic impact of increasing pulmonary pressures within the National Echocardiography Database of Australia cohort (n = 313,492). METHODS: The distribution of estimated right ventricular systolic pressure (eRVSP) was examined in 157,842 men and women. All had data linkage to long-term survival during median follow-up of 4.2 years (interquartile range: 2.2 to 7.5 years). RESULTS: The cohort comprised 74,405 men and 83,437 women 65.6 ± 17.7 years of age. Overall, 17,955 (11.4%), 7,016 (4.4%), and 4,515 (2.9%) subjects had eRVSP levels indicative of mild (40 to 49 mm Hg), moderate (50 to 59 mm Hg), or severe (≥60 mm Hg) PHT, respectively, assuming a right atrial pressure of 5 mm Hg. These subjects were more likely to die during long-term follow up (for severe PHT, adjusted hazard ratio: 9.73; 95% confidence interval: 8.60 to 11.0; p < 0.001). After adjustment for age, sex, and evidence of left heart disease, those subjects with eRVSP levels within the third (28.05 to 32.0 mm Hg; hazard ratio: 1.410; 95% confidence interval: 1.310 to 1.517) and fourth (32.05 to 38.83 mm Hg; hazard ratio: 1.979; 95% confidence interval: 1.853 to 2.114) quintiles had significantly higher mortality (p < 0.001) than those in the lowest quintile. Accordingly, a clear and consistent threshold of increased mortality (including 1- and 5-year actuarial mortality) around an eRVSP of 30.0 mm Hg was evident. CONCLUSIONS: In this large and unique cohort, the prognostic impact of clinically accepted levels of PHT was confirmed. Moreover, a distinctly lower threshold for increased risk for mortality (eRVSP >30.0 mm Hg) indicative of PHT was identified. (A Longitudinal Cohort Study of Echocardiograms From Public and Private Echocardiography Laboratories From Around Australia, Linked With the National Deaths Index; ACTRN12617001387314).

Pulmonary arterial hypertension outcomes upon endothelin-1 receptor antagonist switch to macitentan.

OBJECTIVES: To assess whether switching patients with suboptimally controlled pulmonary arterial hypertension from bosentan or ambrisentan to macitentan would improve six-minute walk test (6MWT) distance and World Health Organization functional class. METHODS: This was a retrospective cohort analysis of 37 patients from a single center. Patients were separated into three heterogeneous treatment groups and followed for 18 months: switch group (n = 14): patients switched to macitentan from bosentan/ambrisentan; added group (n = 11): patients who began macitentan as de novo therapy (n = 5) or who added macitentan to an existing sildenafil regimen (n = 6); and control group (n = 12): patients for whom sildenafil and/or bosentan/ambrisentan therapy was unchanged. RESULTS: Mortality was observed in two patients (one each, switch and added groups). Patients in the control group had one hospital admission and 100% survival. There was significant improvement in functional class for the switch and added groups. Statistically significant improvement was observed in 6MWT distance in the added group alone. Overall, 92% of patients continued macitentan throughout the study. CONCLUSION: Macitentan was well tolerated. For bosentan/ambrisentan-treated patients with suboptimally controlled pulmonary arterial hypertension, switching to macitentan may facilitate an improvement in functional class.

Advances in screening for undiagnosed atrial fibrillation for stroke prevention and implications for patients with obstructive sleep apnoea: a literature review and research agenda.

Atrial fibrillation (AF) is the most common type of sustained cardiac arrhythmia encountered in clinical practice, and its burden is expected to increase in most developed countries over the next few decades. Because AF can be silent, it is often not diagnosed until an AF-related complication occurs, such as stroke. AF is also associated with increased risk of heart failure, lower quality of life, and death. Anticoagulation has been shown to dramatically decrease embolic risk in the setting of atrial fibrillation, resulting in growing interest in early detection of previously undiagnosed AF. Newly developed monitoring devices have improved the detection of AF and have been recommended in guidelines for screening of AF in individuals aged 65 years and over. While screening is currently targeted to these older individuals, younger patients with obstructive sleep apnoea (OSA) are at higher risk of AF and stroke than the general population, indicating a need for targeted early detection of AF in this group. Compared to individuals without OSA, those with OSA are four times more likely to develop AF, and the risk of AF is strongly associated with OSA severity. The overall prevalence of AF among individuals with OSA remains unknown because of limitations related to study design and to the conventional methods previously used for AF detection. Recent and emerging technological advances may improve the detection of undiagnosed AF in high-risk population groups, such as those with OSA. In this clinical review, we discuss the methods of screening for AF and the applications of newer technologies for AF detection in patients with OSA. We conclude the review with a brief description of our research agenda in this area.

Polyarticular arthropathy and encephalopathy in a 70-year-old woman.

A 70-year-old woman with a background of portopulmonary hypertension, managed with sildenafil and oral diuretics, and cirrhosis, presented with acute on chronic haemorrhoidal bleeding, iron deficiency anaemia and worsening right heart failure. She presented in a normal conscious and cognitive state. Management involved intravenous diuresis with frusemide and blood transfusion. She quickly begun to develop fever, severe polyarticular arthropathy and progressive encephalopathy. Analgesia was started and antibiotics administered for potential septic sources. Extensive investigations, including full septic screen and neurological imaging, revealed no explainable aetiology for her precipitous decline. She continued to have febrile episodes, worsening polyarticular arthropathy and progressive encephalopathy eventually becoming unresponsive. Given the severe polyarticular arthropathy knee aspiration was performed. Urate crystals were identified and intravenous hydrocortisone and colchicine were started. Within 2 days she achieved full resolution of her systemic, musculoskeletal and neurological symptoms. We propose this as a rare case of gout-induced encephalopathy.

The National Echocardiography Database Australia (NEDA): Rationale and methodology.

The National Echocardiography Database Australia (NEDA) is a new echocardiography database collecting digital measurements on both a retrospective and prospective basis. To date, echocardiographic data from 435,133 individuals (aged 61.6 ±â€¯17.9 years) with linkage to 59,725 all-cause deaths during a median of 40 months follow-up have been collected. These data will inform a number of initial analyses focusing on pulmonary hypertension, aortic stenosis and the role of artificial intelligence to facilitate accurate diagnoses of cardiac abnormalities.

Lung transplant: the Western Australian experience.

BACKGROUND: The Western Australian lung transplant programme commenced in 2004 to serve the growing demand of patients with end-stage lung disease. AIM: This report summarises our 11-year experience in lung transplantation. METHODS: Data on 115 consecutive patients and their respective donors transplanted between 2004 and 2015 were collected. The Kaplan-Meier method was used to estimate survival. Cox regression was used to analyse the impact of donor and recipient characteristics on survival. RESULTS: A total of 88 bilateral, 22 single-lung and 5 heart-lung transplants were performed in Western Australia during the first 11 years of the lung transplant programme. The most common indications for transplantation were interstitial lung disease (30.4%), cystic fibrosis (27.8%) and chronic obstructive pulmonary disease (excluding alpha-1 antitrypsin deficiency) (22.6%). Median recipient age was 50 years. Overall survival rates were 96% at 3 months, 93% at 1 year, 84% at 3 years and 70% at 5 years. Older age and higher BMI negatively impacted survival. Chronic lung allograft dysfunction was the leading cause of late mortality. CONCLUSION: Lung transplantation is a treatment option in end-stage lung disease, with annual transplant rates in Western Australia continuing to rise. Our patients enjoy survival rates that compare favourably against international standards.

Inferior vena cava filters (IVCFs): a review of uses and application to international guidelines at a single Australian center; implications of venous thromboembolism associated with malignancy.

Venous thromboembolism (VTE) is a potentially lethal event. Anticoagulation is the cornerstone of treatment. Inferior vena cava filters (IVCFs) may be used in circumstances when anticoagulation is contraindicated or as an adjunct to anticoagulation. IVCF use is not without controversy due to concerns over their safety profile, differences in guidelines from international societies, and a limited randomized control trial evidence. We retrospectively undertook a review of IVCF use over a three-year period (2014-2016) at our center, which has a large oncology service but no trauma unit. There were 44 patients with successful IVCF insertion and one patient with an unsuccessful attempt. Indications for insertion included: a contraindication to anticoagulation (n = 28); recurrent VTE on anticoagulation (n = 10); and extensive VTE (n = 7). There were 13 retrieval attempts, of which ten were successful. There were five documented IVCF complications (tilting: n = 2, IVC thrombus: n = 3) with one episode of IVCF failure and two episodes of deep vein thrombosis during the follow-up period. Of the patients, 71% had an active malignancy (of whom 71% had metastatic disease). Seventeen patients died due to progressive malignancy during the study period. There were no life-threatening VTEs or IVCF-associated mortalities. Adherence with published international guidelines was variable. Patients with malignancy were less likely to undergo IVCF retrieval and had a reduced rate of retrieval success. None of the international guidelines comment on the use of IVCFs in patients with malignancy despite being commonly used. IVCF use may be an underappreciated tool in this group.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

INTRODUCTION: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. METHODS AND ANALYSIS: This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. ETHICS AND DISSEMINATION: Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. TRIAL REGISTRATION NUMBER: ACTRN12614000418673, Pre-results.

The role of asymmetric dimethylarginine alone and in combination with N-terminal pro-B-type natriuretic peptide as a screening biomarker for systemic sclerosis-related pulmonary arterial hypertension: a case control study.

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this proof of concept study, we sought to evaluate the role of ADMA as a screening biomarker for incident systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). METHODS: ADMA levels were measured using high performance liquid chromatography in 15 consecutive treatment-naive patients with newly-diagnosed SSc-PAH and compared with 30 SSc-controls without PAH. Logistic regression models were used to evaluate the independent association of ADMA with PAH. The optimal cut-point of ADMA for SSc-PAH screening was determined. NT-proBNP levels were previously measured in the same patients and the optimal cut-point of NT-proBNP of ≥210ng/mL was coupled with the optimal cut-point of ADMA to create a screening model that combined the two biomarkers. RESULTS: The PAH group had significantly higher mean ADMA levels than the control group (0.76±0.14 µM versus 0.59±0.07 µM; p<0.0001). ADMA levels remained significantly associated with PAH after the adjustment for specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications (all p<0.01). An ADMA level ≥0.7 µM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. A screening model that combined an NT-proBNP ≥210ng/mL and/ or ADMA ≥0.7 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH. CONCLUSIONS: In this small study, use of ADMA in combination with NT-proBNP produced excellent sensitivity and specificity for the non-invasive identification of SSc-PAH. The role of ADMA as a screening biomarker for SSc-PAH merits further evaluation.

Quantifying change in pulmonary function as a prognostic marker in systemic sclerosis-related interstitial lung disease.

OBJECTIVES: Clinically meaningful change in systemic sclerosis (SSc) related interstitial lung (SSc-ILD) disease is unknown. The aim of this study was to quantify change in pulmonary function as a predictor of outcome in SSc-ILD. METHODS: All patients had SSc-ILD defined by HRCT chest. All PFTs during follow-up, including FVC (L), DLCO (ml/min/mmHg) and KCO (DLCO/alveolar volume ratio; DLCO/VA) (ml/min/mmHg/L) were retrieved. The rate of change over the first four years, and percentage change in the first year of follow-up were used in ROC curve analysis to determine the best cut-off points to predict adverse outcome (home oxygen, lung transplantation, or death). RESULTS: Among 264 patients, there were 49 events (38 deaths, 10 supplemental oxygen, one lung transplant) over a mean (±SD) follow-up of 3.0 (±1.7) years. The rates of decline over time and percentage change over one year in each of FVC, DLCO and KCO were predictive of adverse outcome. Stable PFTs over four years gave the optimal negative predictive values (NPVs) of 88-96%. The best sensitivity-specificity trade-off was a decline in FVC of 10% and in DLCO and KCO of 15% with NPVs of 92-93%. CONCLUSIONS: The course that SSc-ILD takes is evident within the first 1-4 years of follow up. Patients who have no decline in PFTs over 4 years have better outcomes. A decline within one year in DLCO or KCO of 15% or more is a poor prognostic factor, and identifies patients who should be monitored more closely and considered for therapy.