Comorbidity and mortality in systemic sclerosis and matched controls: Impact of interstitial lung disease. A population based cohort study based on health registry data.

OBJECTIVE: This population-based, matched cohort study evaluates the impact of comorbidities on mortality among systemic sclerosis (SSc) patients with and without interstitial lung disease (ILD). METHOD: Patients with a first-time SSc diagnosis between 2002 and 2015 were identified in the Danish National Patient Registry, separated into two cohorts - with ILD (SSc-ILD) and without ILD (non-ILD SSc), and matched 1:4 with controls from the general population on age, sex, residency and marital status. Comorbidity and mortality data were obtained from national registries. The Deyo-Charlson comorbidity score (DCcs) was used for assessment of the burden of comorbidities. RESULTS: 1732 patients with SSc and 6919 controls were included; 258 (14.9%) patients had SSc-ILD. The hazard ratio (HR) for death was 2.8 (95% CI 2.4-3.3) in SSc, and especially increased in SSc-ILD (HR 4.2 (95% CI 3.2-5.4)), males (HR 3.1 95% CI 2.4-4.1) and younger adults (aged 18-40 (HR 6.9, 95% CI 3.4-14.2) and 41-50 (HR 7.7, 95% CI 3.8-15.6)). In non-ILD SSc, mortality increased with increasing DCcs. Cancer was the most frequent cause of death in SSc (24.9% of deaths) and in controls (33.5%), in SSc followed by musculoskeletal and connective tissue diseases (22.7%); the cause of only 0.8% of deaths among controls. CONCLUSION: The high prevalence of comorbidities in SSc had extensive impact on mortality. Mortality was increased in males, in young adults and in SSc-ILD, underlining the excess mortality associated with ILD. These findings emphasise the importance of timely diagnosis and optimal management of organ involvement and comorbidities in SSc.

Decision support to general practice in choice of chest imaging for patients with pulmonary symptoms.

INTRODUCTION: The choice of chest imaging for patients with respiratory problems is based on risk profile and symptoms. In 2018-2020, GPs in the catchment area of Silkeborg Regional Hospital, Denmark, were offered direct referral for either X-ray or low-dose computed tomography (LDCT) of the chest for patients with respiratory symptoms who did not meet the criteria for a contrast-enhanced CT (CECT) of the chest and upper abdomen as part of the lung cancer referral pathway. The aim of this study was 1) to estimate the percentage of patients referred for LDCT or chest X-ray who met CECT criteria based on the clinical information in the referral letters, and 2) to assess the GPs' response to standard questions regarding the active feedback provided. METHODS: The study was conducted from April to October 2019. Radiographers initially assessed all referrals for X-ray or LDCT, and contacted the GPs if they assessed that symptoms and clinical characteristics justified CECT. RESULTS: In the study period, 1,112 referrals for chest imaging from GPs were received; in 97 cases (9%), the referral information warranted CECT as part of a lung cancer referral package. In 71% (69/97) of these cases, the GP accepted the conversion to CECT; 55 of 73 LDCTs and 14 of 24 X-rays. In 15 cases, the GP adhered to the requested imaging owing to clinical assessment or their agreement with the patient, and in the remaining 13 cases no specific reason was given. CONCLUSION: The feedback provided was well received by GPs and the approach adopted may be a step towards structured decision support to facilitate the choice of chest imaging. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Effect of telemonitoring on quality of life for patients with chronic obstructive pulmonary disease-A randomized controlled trial.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) often experience severe physical limitations and psychological distress, which can lead to a deterioration in quality of life (QoL). Telemonitoring (TM) may improve QoL and reduce the number of hospitalizations and readmissions, but results from previous studies have been conflicting. The aim of this study was to assess the effect of TM on QoL in patients with moderate to severe COPD recruited during hospitalization for acute exacerbation (AECOPD). METHODS: We conducted a randomized controlled trial at Silkeborg and Viborg Regional Hospitals in Denmark. Participants were recruited during hospitalization for AECOPD and randomized to a six-month telemonitoring service in addition to standard COPD care or standard COPD care alone. Patients were followed for 24 months. QoL was measured by the Hospital Anxiety and Depression Scale (HADS), and St Georges Respiratory Questionnaire (SGRQ) at 3-, 6-, 12-, and 24-months follow-up. The main outcome was QoL at 6 months. RESULTS: In total, 101 patients were randomized to the TM intervention and 97 to standard care. The between-group difference in SGRQ at 6 months was -2.0 (-8.5; 4.5), in HADS-Anxiety -0.3 (-2.0; 1.4) and in HADS-depression 0.2 (-1.0; 1.4) corresponding to no significant difference in health-related QoL for patients receiving TM compared to standard care. No difference was seen at 12-24 months follow-up either. DISCUSSION: TM in addition to standard care did not improve QoL in patients with moderate to severe COPD. Other means of improving management and QoL in severe COPD are urgently needed.

Twelve-month follow-up after hospitalization for SARS-COV-2: Physiology improves, symptoms remain.

OBJECTIVES: Persistent symptoms on short-term follow-up after infection with COVID-19 are common, but long-term consequences have been insufficiently studied. The aim of this study was to characterize pulmonary function and ongoing symptoms 12 months after hospitalization with COVID-19. METHODS: This prospective multicenter study included 222 patients hospitalized with PCR-confirmed COVID-19 in the Central Denmark Region. Disease severity was stratified using WHO Clinical Progression Scale. Clinical characteristics, pulmonary function test (PFT), 6-minute walk test (6MWT), and patient-reported outcome measures were collected at follow-up 3 and 12 months after discharge. Outcome measures from follow-up 3 months after discharge have previously been published. RESULTS: A total of 179 (81%) patients completed the 12-month follow-up. Median age was 60 years (IQR 51, 69) and 58% were male patients. At 12-month follow-up 49.7% had a normal diffusion capacity for carbon monoxide (DLCO), while 39.4% had DLCO < 80%. The 6MWT distance increased significantly (29 m 95% CI 19, 40; p < 0.01). An mMRC score of 0 was reported by 51% and an mMRC ≥ 2 by 20%. The frequency and severity of fatigue, depression, and anxiety did not improve over time. CONCLUSIONS: The study found that impaired DLCO percentage is common 12 months after hospitalization with SARS-CoV-2 and reduction in DLCO percentage is associated to dyspnea.

Effect of telemonitoring on readmissions for acute exacerbation of chronic obstructive pulmonary disease: A randomized clinical trial.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease are associated with high morbidity and mortality. Telemonitoring may reduce the frequency of hospitalization. The aim of this study was to investigate the effect of telemonitoring on hospitalization rates for acute exacerbations of chronic obstructive pulmonary disease. METHODS: Patients were recruited during hospitalization and equally randomized to telemonitoring or usual care. Telemonitoring participants recorded symptoms and monitored oxygen saturation, heart rate, peak expiratory flow, and body weight. Alerts were generated if readings breached thresholds. Acute exacerbations of chronic obstructive pulmonary disease hospitalizations during the 6 months intervention were compared using logistic regression, and time to first hospitalization was assessed using Cox proportional hazard modeling. The incidence rates for acute exacerbations of chronic obstructive pulmonary disease hospitalization were compared using a negative binomial regression model with between-group comparisons expressed as incidence rate ratios. The telemonitoring group was used as reference. RESULTS: A total of 222 patients were randomized. 37/112 (33%) in the control group and 31/110 (28%) in the telemonitoring group experienced acute exacerbations of chronic obstructive pulmonary disease hospitalization during the intervention period, odds ratio of 1.26, confidence interval 0.71-2.23, p = 0.4. No difference was seen in time to first hospitalization, hazard ratio 1.23, CI 0.77-1.99, p = 0.4. The number of hospitalizations in the intervention period was 66 in the control group and 42 in the telemonitoring group, with incidence rate ratio 1.42, confidence interval 1.04-1.95, p = 0.03. Adjustment for dyspnea score, smoking, and cohabitation status did not change the results, incidence rate ratio 1.44, confidence interval 1.05-1.99, p = 0.02. DISCUSSION: Patients who received telemonitoring experienced significantly fewer acute exacerbations of chronic obstructive pulmonary disease hospitalizations, although the overall risk of having at least one hospitalization and the time to first hospitalization was similar between the two groups.

Immunomodulatory treatment in unclassifiable interstitial lung disease: A retrospective study of treatment response.

BACKGROUND AND OBJECTIVE: The optimal management of unclassifiable Interstitial lung disease (ILD) remains a challenge. The aim of this study was to describe pulmonary function trajectories for patients treated with immunomodulatory therapy and for untreated patients. METHODS: Clinical information and treatment data were obtained retrospectively at two ILD centres. Pulmonary function data were analysed using (1) mixed effects linear regression models with and without clinical covariates and (2) propensity score matching using gender, age, physiology (GAP) stage, smoking and presence of ground glass opacities. RESULTS: Sixty-five percent of the 249 patients included received corticosteroids and/or other immunomodulators. Treated patients had lower forced vital capacity (FVC) (72% vs. 83% predicted) and diffusing capacity for carbon monoxide (DLco) (44% vs. 60% predicted). In mixed effects linear regression, the adjusted change in FVC was -0.22%, [-0.34; -0.11], and -0.15% [-0.28;-0.012] for DLco. The difference in pulmonary function decline between treated and untreated patients was insignificant, -0.082% per month, [-0.28; 0.11], p = 0.10 for FVC and -0.14% per month, [-0.36; 0.079], p = 0.15, for DLco. In propensity score matched analysis, the difference in change in FVC was 0.039% per month, p = 0.12, and for DLco, 0.0085% per month, p = 0.7. CONCLUSION: The pulmonary function trajectories for treated and untreated patients were parallel, despite treated patients having more severe disease at baseline. The persisting differences between the groups suggest no overall effect, although improvement or stabilization may be seen in some patients. Prospective studies are needed to define subsets of patients with unclassifiable interstitial lung disease and their optimal management.

[Pulmonary manifestations in rheumatoid arthritis].

Rheumatoid arthritis (RA) affects more than 30,000 Danes. In this review, we discuss RA in connection with chronic obstructive pulmonary disease (COPD), bronchiectasis and interstitial lung disease (ILD) which are among the most common lung manifestations and are associated with increased mortality. Early suspicion based upon respiratory symptoms should prompt imaging and pulmonary function test. Smoking cessation, vaccination, and rehabilitation are important. COPD and bronchiectasis are treated according to guidelines. Multidisciplinary collaboration in RA-ILD is important and treatment decisions are based on clinical experience and imaging suggesting an inflammatory or fibrotic phenotype.

Incidence, prevalence and regional distribution of systemic sclerosis and related interstitial lung Disease: A nationwide retrospective cohort study.

OBJECTIVE: To investigate incidence and prevalence of Systemic Sclerosis (SSc) and association with interstitial lung disease (SSc-ILD) in a nationwide population-based study. METHODS: Patients with an incident diagnosis of SSc in 2000-2016 were identified in the Danish National Patient Registry and categorised based on diagnosis of ILD. Incidence- and prevalence proportions were calculated based on the annual population estimates. A cox proportional hazards model was used to evaluate the association between age, sex, region and marital status and presence of ILD. RESULTS: In total, 1869 patients with SSc were identified; 275 patients (14.7%) had SSc-ILD. The majority of patients were females (75.5%). The percentage of males was higher in SSc-ILD than in SSc alone (30.9% and 23.4%, p = 0.008). Median time from SSc to ILD diagnosis was 1.4 years (range 0-14.2). ILD was diagnosed from ≤4 years before to ≥7 years after SSc. Development of ILD was associated with male gender (HR 1.75, 95% CI 1.15-2.66), age 41-50 (HR 1.81, 95% CI 1.07-3.05) and residency in the North Denmark Region (HR 1.95, 9 5% CI 1.12-3.40). Mean annual incidence proportion of SSc was 2.9/100,000 and mean annual prevalence proportion was 16.8/100,000. The incidence remained stable, but prevalence proportion increased from 14.1 - 16.5/100,000 in 2000-2008 to 17.9-19.2/100,000 in 2009-2016. CONCLUSION: The prevalence of SSc increased during the study period, while the incidence remained stable. The prevalence of SSc-ILD was 14.7% and thus less frequent than expected. Male sex and age between 41 and 50 years were associated with ILD.

Intravenous immunoglobulin treatment stabilizing a patient with Anti-PL7 antisynthetase syndrome with interstitial lung disease and eosinophilic inflammation.

Antisynthetase syndrome (AS) is a rare autoimmune disease characterized by autoantibodies against aminoacyl-transfer RNA synthetase and clinical features which can include interstitial lung disease (ILD). Current available evidence of treatment is based on expert opinions and case reports. Here, we present a patient with an initial diagnosis of eosinophilic pneumonia, who was later diagnosed with anti-PL7 antisynthetase syndrome with ILD and eosinophilic inflammation. The patient was non-responsive to classic immunosuppressants but responded remarkably well to intravenous immunoglobulin.

Fatigue Is a Major Symptom at COVID-19 Hospitalization Follow-Up.

Persistent symptoms after hospitalization with COVID-19 are common, but the frequency and severity of these symptoms are insufficiently understood. We aimed to describe symptoms and pulmonary function after hospitalization with COVID-19. Patients hospitalized with COVID-19 in Central Denmark Region were invited for follow-up 3 months after discharge. Clinical characteristics, patient reported outcomes (Fatigue Assessment Scale (FAS), anxiety and depression (HADS)), symptoms, pulmonary function test and 6-min walk test were collected. We included 218 patients (mean age 59.9 (95% CI: 58.2, 61.7), 59% males). Fatigue, dyspnea and impaired concentration were the most prevalent symptoms at follow-up. Using FAS, 47% reported mild-to-moderate fatigue and 18% severe fatigue. Mean HADS was 7.9 (95% CI: 6.9, 8.9). FAS was correlated to HADS (ß = 0.52 (95% CI: 0.44, 0.59, p < 0.001)). Mean DLCO was 80.4% (95% CI: 77.8, 83.0) and 45% had DLCO ˂ 80%. Mean DLCO was significantly reduced in patients treated in the ICU (70.46% (95% CI 65.13, 75.79)). The highest FAS and HADS were seen in patients with the shortest period of hospitalization (2.1 days (95% CI: 1.4, 2.7)) with no need for oxygen. In conclusion, fatigue is a common symptom after hospitalization for COVID-19 and ICU treatment is associated to decreased diffusion capacity.

Increased use of diagnostic CT imaging increases the detection of stage IA lung cancer: pathways and patient characteristics.

BACKGROUND: At Silkeborg Regional Hospital, Denmark, the number of stage IA lung cancer increased after implementation of increased use of CT investigations and a corresponding reduction in chest X-ray. The aim of the present study was to understand the changes in referral pathways, patient characteristics and imaging procedures behind the observed increase in early-stage lung cancer. METHODS: The referral and imaging pathways for all patients diagnosed with lung cancer in 2013-2018 were described based on manually curated information from the electronic health care systems and staging information from the Danish Lung Cancer Registry. We compared the clinical characteristics of patients diagnosed in 2013-2015 and in 2016-2018 after implementation of a change in the use of low dose CT scan (LDCT). For patients diagnosed in 2016-2018, stage IA lung cancer were compared to higher stages using univariable logistic regression analysis. RESULTS: Five hundred and forty-seven patients were diagnosed with lung cancer in 2013-2018. Stage IA constituted 13.8% (34/247) in 2013-2015, and 28.3% (85/300) in 2016-2018. Stage IA patients in 2016-2018 were characterised by more comorbidity, fewer packyears and tended to be older than patients with higher stages. In 2016-2018, the largest proportion of stage IA patients (55%) came from within-hospital referrals. The majority of these lung cancers were detected due to imaging procedures with other indications than suspicion of lung cancer. The proportion of stage IA increased from 12% (12/99) to 36% (47/129) (p < 0.001) for hospital referrals and from 17% (22/129) to 23% (38/165) for GP referrals (p = 0.21). The imaging procedures contributing to the increase in stage IA was contrast enhanced CT (22%¸11/51), LDCT (35%; 18/51) and X-ray followed by LDCT (25%; 13/51). CONCLUSION: The increased access to LDCT for patients referred from general practice and the increased hospital requested CT activity resulted in an increase in the number of stage IA lung cancers. Incidental findings on imaging performed for diagnostic purposes unrelated to suspicion of lung cancer contributed a large proportion of the increase.

Comorbidities in unclassifiable interstitial lung disease.

BACKGROUND: Comorbidities are common in interstitial lung diseases (ILD) and have an important association with survival, but the frequency and prognostic impact of comorbidities in unclassifiable interstitial lung disease (uILD) remains elusive. We aimed to describe the prevalence of comorbidities and assess the impact on survival in patients with uILD. Furthermore, we aimed to identify and characterize potential phenotypes based on clusters of comorbidities and examine their association with disease progression and survival. METHODS: Incident patients diagnosed with uILD were identified at two ILD referral centers in Denmark and Germany from 2003 to 2018. The diagnosis uILD was based on multidisciplinary team meetings. Clinical characteristics and comorbidities were extracted from ILD registries and patient case files. Survival analyses were performed using Cox regression analyses, disease progression was analyzed by linear mixed effects models, and clusters of comorbidities were analyzed using self-organizing maps. RESULTS: A total of 249 patients with uILD were identified. The cohort was dominated by males (60%), former (49%) or current (15%) smokers, median age was 70 years, mean FVC was 75.9% predicted, and mean DLCO was 49.9% predicted. One-year survival was 89% and three-year survival was 73%. Eighty-five percent of the patients had ≥ 1 comorbidities, 33% had ≥ 3 comorbidities and 9% had ≥ 5 comorbidities. The only comorbidity associated with excess mortality was dyslipidemia. No association between survival and number of comorbidities or the Charlson comorbidity index was observed. Three clusters with different comorbidities profiles and clinical characteristics were identified. A significant annual decline in FVC and DLCO % predicted was observed in cluster 1 and 2, but not in cluster 3. No difference in mortality was observed between the clusters. CONCLUSIONS: The comorbidity burden in uILD is lower than reported in other types of ILD and the impact of comorbidities on mortality needs further clarification. Three clusters with distinct comorbidity profiles were identified and could represent specific phenotypes. No difference in mortality was observed between clusters, but slower disease progression was observed in cluster 3. Better understanding of disease behavior and mortality will require further studies of subgroups of uILD with longer observation time.

Interstitial Lung Disease in Connective Tissue Diseases: Survival Patterns in a Population-Based Cohort.

OBJECTIVES: Interstitial lung disease (ILD) is associated with impaired survival among patients with connective tissue diseases (CTDs), but population-based data on the frequency of ILD and pulmonary hypertension (PH) in different CTD subtypes and the impact on survival are sparse. METHODS: We included patients with a first-time ICD-10 diagnosis of systemic sclerosis (SSc), mixed connective tissue disease (MCTD), myositis, systemic lupus erythematosus (SLE), or Sjögren's disease registered in the Danish National Patient Registry between 2000 and 2015. Among these, we identified patients with ILD and PH. Using Kaplan-Meier analysis, we assessed survival for the five subtypes of CTD ± ILD and compared survival among CTD patients overall ± ILD with survival in the general population ± ILD. RESULTS: We identified 11,731 patients with a diagnosis of CTD; 637 (5.4%) had a diagnosis of ILD. The proportion of patients with ILD was higher in SSc (13.4%) and MCTD (9.1%) than in myositis (6.0%), SLE (4.1%), and Sjögren (2.8%). Fifty-one percent were diagnosed with ILD in their fifties and sixties. PH was more frequent in SSc (7.5%) and MCTD (4.1%). Five-year survival was 73.3% (66.7-80.6) in SSc-ILD, 81.0% (69.0-95.1) in MCTD-ILD, 84.7% (77.3-92.9) in myositis-ILD, 83.5% (76.2-91.5) in SLE-ILD, and 84.7 (78.4-91.6) in Sjögren-associated ILD. Survival in CTD-ILD overall was impaired for all age groups compared with CTD alone. Age-stratified survival was comparable between CTD-ILD and ILD in the general population. The survival gap between ILD and non-ILD increased with age. CONCLUSION: Survival was comparable between different CTD-ILD subtypes and comparable to survival in non-CTD-ILD.

Outcomes of patients with advanced idiopathic pulmonary fibrosis treated with nintedanib or pirfenidone in a real-world multicentre cohort.

BACKGROUND AND OBJECTIVE: Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with idiopathic pulmonary fibrosis (IPF). However, patients with advanced IPF, as defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have not been included in randomized trials, and the outcomes of such patients who initiate treatment are not well understood. We determined lung function, disease progression and mortality outcomes following initiation of antifibrotic therapy in patients with advanced IPF at the time of treatment initiation compared to those with mild-moderate IPF. METHODS: We included 502 patients enrolled in IPF registries from four Nordic countries. Linear mixed models were used to assess change in FVC and DLCO over time. Cox proportional hazards models were used to assess transplant-free survival and progression- and transplant-free survival. RESULTS: Of 502 patients, 66 (13%) had advanced IPF. Annual change in FVC was -125 ml (95% CI -163, -87) among patients with mild-moderate IPF, and +28 ml (95% CI -96, +152) among those with advanced IPF. Advanced IPF at treatment initiation was associated with poorer transplant-free survival (hazard ratio [HR] 2.39 [95% CI 1.66, 3.43]) and progression- and transplant-free survival (HR 1.60 [95% CI 1.15, 2.23]). CONCLUSION: In a broadly representative IPF population, patients with advanced IPF at the initiation of antifibrotic therapy did not have greater lung function decline over time compared with those with mild-moderate IPF, but had substantially higher mortality. Prospective studies are needed to determine the effect of antifibrotic therapy in patients with advanced IPF.

An E-Learning Program Improves Patients' Knowledge After Lung Transplantation.

Background: Adherence to immunosuppressive medicine in lung transplant recipients is associated with improved long-term survival. Patient education and support from health care providers are key components. We investigated e-learning as a tool to improve lung transplant recipients' knowledge of post-transplant care such as hygiene, self-monitoring, travel precautions, vaccinations, and the importance of adherence to medication. Objective: To compare the effect of e-learning and conventional patient education with respect to level of knowledge and drug adherence. A single-center open randomized controlled trial design was used. Methods: Lung transplant recipients were randomized to an e-learning program or standard care. One month before a scheduled follow-up visit, the intervention group received a link by e-mail to a 15-min e-learning program. At the follow-up visit, all lung transplant recipients completed two drug adherence questionnaires (Basel Assessment of Adherence with Immunosuppressive medication Scales [BAASIS] and Transplant Adherence Questionnaire [TAQ]) and a questionnaire testing their knowledge of post-transplant care. Results: Fifty lung transplant recipients were randomized with 24 recipients in each group completing the study. Recipient adherence measured by BAASIS showed a tendency toward improved drug adherence in the intervention group compared with the control group (71% vs. 55%, p = 0.23). TAQ showed no difference between the two groups (p = 1.0). Recipients in the intervention group had a significantly higher number of correct answers to questions about transplant-friendly lifestyle (median 11 vs. 10, p = 0.02). Conclusion: A 15-min e-learning program is a simple and effective tool to improve lung transplant recipients' knowledge of post-transplant care.

Changes in management of idiopathic pulmonary fibrosis: impact on disease severity and mortality.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease (ILD) with a median survival of 3-5 years. The aim of the present study was to evaluate disease severity and survival in patients diagnosed with IPF in the era of antifibrotic therapies compared with an earlier IPF cohort. METHODS: We identified all patients with fibrotic ILD in the hospital electronic case record system between 2011 and 2016, and reviewed each case in order to identify incident patients with IPF. We used the GAP-index to compare disease severity and mortality to previous findings in patients with IPF diagnosed at our center between 2003 and 2009. RESULTS: 260 patients were diagnosed with IPF between 2011 and 2016. Mean age was 72.6 years, 79% were male, mean forced vital capacity (FVC) was 80%, and mean diffusing capacity for carbon monoxide (DLco) was 44%. Age, FVC and DLco were significant predictors of mortality, but the presence of a typical usual interstitial pneumonia pattern on HRCT was not. Eighty percent of patients in GAP stage I received antifibrotic therapy, 73% in GAP stage II, and 29% in GAP stage III.The median survival was four years in the 2011-2016 cohort compared with three years in the 2003-2009 cohort. The distribution of patients between GAP stages was unchanged in 2011-2016 compared with 2003-2009, (stage I 34% vs. 32%, stage II 49% vs. 48% and stage III 20% vs. 16%). One-year mortality was 13% in 2011-2016 and 26% in 2003-2009. In severe disease (GAP stage III), one-year mortality was 26% and 54%, respectively, (p=0.019). CONCLUSION: Short-term mortality was significantly lower in the 2011-2016 cohort compared with 2003-2009. This improvement may be linked to changes in treatment strategies towards limited use of corticosteroids. Although early diagnosis of IPF still needs increased focus, the improvement is encouraging.

Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians.

Interstitial lung disease (ILD) is a serious complication of rheumatoid arthritis (RA) contributing to significantly increased morbidity and mortality. Other respiratory complications, such as chronic obstructive pulmonary disease and bronchiectasis, are frequent in RA. Infections and drug toxicity are important differential diagnoses and should be considered in the diagnostic work-up of patients with RA presenting with respiratory symptoms. This review provides an overview of the epidemiology and pathogenesis of RA-ILD, the radiological and histopathological characteristics of the disease as well as the current and future treatment options. Currently, there is no available evidence-based therapy for RA-ILD, and immunosuppressants are the mainstay of therapy. Ongoing studies are exploring the role of antifibrotic therapy in patients with progressive fibrotic ILD, which may lead to a new treatment approach for subgroups of patients with RA-ILD.

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Clinical Characteristics and Predictors of Mortality.

INTRODUCTION: Interstitial lung disease (ILD) is a serious extraarticular manifestation of rheumatoid arthritis (RA), but no evidence-based therapy exists. Ongoing studies investigate the role of antifibrotic therapies for progressive fibrosing ILD (PF-ILD), including RA-ILD. The aim of the present study was to investigate the frequency of PF-ILD and the clinical characteristics of RA-ILD in a well-characterised, population-based cohort. METHODS: We identified patients with RA-ILD diagnosed and followed at the ILD referral centre in Aarhus, Denmark, from 2004 to 2016. Adjusted hazard rate ratios for death were estimated using Cox regression models. The presence of PF-ILD was assessed using recently proposed definitions of relative forced vital capacity (FVC) decline ≥10%, relative diffusion capacity of the lung for carbon monoxide (DLco) decline ≥15% or worsening symptoms or a worsening radiological appearance accompanied by a ≥5 to <10% FVC decline. RESULTS: We identified 102 patients with RA-ILD, and 52% had PF-ILD. Mean follow-up was 3.8 years and median survival was 7.1 years. Thirty-eight patients died during follow-up, and most deaths were from respiratory causes. Predictors of mortality in a multivariate model were DLco and high titres of IgM rheumatoid factor. CONCLUSION: PF RA-ILD was common and the associated mortality was high.

Clinical characteristics and outcome in patients with antisynthetase syndrome associated interstitial lung disease: a retrospective cohort study.

Background and objective: To describe the clinical characteristics including the bronchoalveolar lavage fluid (BALF) characteristics of patients with antisynthetase syndrome (AS) associated interstitial lung disease (ILD) in a tertiary ILD outpatient clinic, their medical therapy and outcome. Methods: Retrospective cohort study of patients with AS-ILD. All available data of clinical characteristics, pulmonary function tests, laboratory parameters, BALF analysis, histology, high-resolution computed tomography (HRCT) and treatment were collected from the patient files. Results and conclusions: Twelve patients with AS-ILD were identified. Mean age at diagnosis was 55 years (range 45-69), 67% were female. Mean follow-up time was 7 years. The anti-aminoacyl tRNA-synthetase antibodies presented were anti-Jo1 (n = 6), anti-PL7 (n = 3), anti-PL12 (n = 2) and anti-EJ (n = 1). HRCT patterns were mainly non-specific interstitial pneumonia (75%). Four patients had BALF-eosinophilia (two of four anti-Jo1 patients) and two anti-PL12 positive patients had BALF-neutrophilia. Two AS-ILD patients improved on rituximab (RTX) as induction treatment and three out of four patients were stabilised on RTX as maintenance treatment. Two patient obtained remission by cyclophosphamide. Four patients were stabilised on azathioprine alone or in combination with oral corticosteroids. Our cohort of AS-ILD patients showed clinical characteristics in accordance with previous reports at baseline and was comparable to other cohorts. Most patients can be stabilised with immunosuppressive treatment.