Graft-Versus-Host-Disease and Health-Related Quality of Life in Young Long-term Survivors of Cancer and Allogeneic Hematopoietic Stem Cell Transplantation.

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment predominantly for malignancies. Chronic graft-versus-host disease (cGVHD) is the leading long-term complication after allo-HSCT, but knowledge on cGVHD and health-related quality of life (HRQOL) in long-term survivors of allo-HSCT performed in childhood, adolescence, and young adulthood (CAYA) is scarce. Therefore, we aimed to (1) assess prevalence and risk factors of active cGVHD using the 2014 National Institutes of Health-Consensus criteria, (2) investigate associations between cGVHD severity, patient-reported symptom burden, and HRQOL, and (3) compare HRQOL of survivors to population norms. Methods: We conducted a nationwide cross-sectional study in long-term survivors of CAYA allo-HSCT combining clinical examinations and patient-reported outcome measures. Results: We included 103 survivors, 55 (53%) females, median age of 19.6 years [range 0.3-29.9] at HSCT, 16.8 years [6.0-32.0] from HSCT, and 77 (75%) with underlying malignancy. Overall, 32 (31%) survivors were diagnosed with active cGVHD. The risk of active cGVHD was increased with prior acute GVHD and reduced with in vivo T cell depletion. cGVHD severity was associated with increased symptom burden, but not with adverse HRQOL. Compared to Norwegian population norms, allo-HSCT survivors reported significantly lower HRQOL. Conclusion: These results indicate a high prevalence of cGVHD in long-term survivors of CAYA allo-HSCT. Although we did not find an association between cGVHD severity and HRQOL, survivors reported significantly poorer HRQOL compared to population norms. Knowledge on the long-term consequences of cGVHD will be important for optimizing treatment and long-term follow-up care after CAYA allo-HSCT.

Associations between cardiac and pulmonary involvement in patients with juvenile dermatomyositis-a cross-sectional study.

This study aimed at exploring the association between detectable cardiac and pulmonary involvement in long-term juvenile dermatomyositis (JDM) and to assess if patients with cardiac and pulmonary involvement differ with regard to clinical characteristics. 57 JDM patients were examined mean 17.3 (10.5) years after disease onset; this included clinical examination, myositis specific/associated autoantibodies (immunoblot), echocardiography, pulmonary function tests and high-resolution computed tomography. Cardiac involvement was defined as diastolic and/or systolic left ventricular dysfunction and pulmonary involvement as low diffusing capacity for carbon monoxide, low total lung capacity and/or high-resolution computed tomography abnormalities. Patients were stratified into the following four groups: (i) no organ involvement, (ii) pulmonary only, (iii) cardiac only, and (iv) co-existing pulmonary and cardiac involvement. Mean age was 25.7 (12.4) years and 37% were males. One patient had coronary artery disease, seven had a history of pericarditis, seven had hypertension and three had known interstitial lung disease prior to follow-up. There was no association between cardiac (10/57;18%) and pulmonary (41/57;72%) involvement (p = 0.83). After stratifying by organ involvement, 21% of patients had no organ involvement; 61% had pulmonary involvement only; 7% had cardiac involvement only and 11% had co-existing pulmonary or cardiac involvement. Patients with co-existing pulmonary or cardiac involvement had higher disease burden than the remaining patients. Patients with either cardiac or pulmonary involvement only, differed in clinical and autoantibody characteristics. We found no increased risk of developing concomitant cardiac/pulmonary involvement in JDM. Our results shed light upon possible different underlying mechanisms behind pulmonary and cardiac involvement in JDM.

Coping Patterns and Emotional Distress in Patients With Chronic Obstructive Lung Disease Who Are Undergoing Lung Transplant Evaluation.

OBJECTIVES: Living with severe lung disease like chronic obstructive pulmonary disease (COPD) is a very stressful situation. The way patients cope may impact their symptoms of anxiety and depression and physical function as well. We studied how ways of coping are associated with levels of emotional distress and lung function in patients with COPD being evaluated for lung transplantation. METHODS: Sixty-five (mean age 57 years, 46% females) patients completed the General Health Questionnaire-30 (GHQ-30) assessing emotional distress and the Ways of Coping Questionnaire. Measurements of lung function and 6-minute walk test were included. RESULTS: Seventeen (26%) patients had elevated emotional distress. Logistic regression of chronic GHQ score with gender, age, body mass index, lung function, and coping scales as covariates showed that escape avoidance and self-controlling coping and forced vital lung capacity were significantly associated with high emotional distress. Odds ratio of emotional distress increased with 5.2 per tertile (P = .011) in escape avoidance coping score. Moreover, we revealed that emotionally distressed patients cope with their current situation by refusing to believe the current situation and taking their distress out on other people. CONCLUSION: Among patients with COPD, a high level of emotional distress was uniquely associated with escape-avoidance coping and lung function. Future work should ascertain whether coping style predicts distress or whether distress increases the use of escape-avoidance coping. Nevertheless, our findings indicate that if either element is present, health care professionals should be attentive to the need for interventions to improve patients' well-being.

ILD-specific health-related quality of life in systemic sclerosis-associated ILD compared with IPF.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) are fibrotic ILDs with divergent disease populations. Little is known about health-related quality of life (HRQL) in SSc-ILD relative to IPF. METHODS: We used the Kings Brief Interstitial Lung Disease Questionnaire (K-BILD) to compare HRQL in a cross-sectional study of 57 patients with IPF and 29 patients with SSc-ILD. Analysis of covariance was used to adjust for age, gender and lung function. RESULTS: The unadjusted mean K-BILD score was 63.1 (95% CI 57.1 to 69.1) among patients with SSc-ILD, as compared with 54.7 (51.8-57.5) among those with IPF (p=0.005). However, this difference in HRQL was attenuated after adjustment for age, gender and lung function. In a multivariable model, only forced vital capacity was associated with K-BILD scores. K-BILD scores were correlated with both forced vital capacity and with other relevant HRQL measures, regardless of ILD diagnosis. DISCUSSION: Patients with SSc-ILD may have better ILD-specific quality of life than patients with IPF, but this difference appears to be driven primarily by better lung function. These results underscore the impact of lung function on HRQL in fibrotic ILD and the utility of K-BILD to assess HRQL in SSc-ILD.

Pulmonary function and high-resolution computed tomography in outdoor rock drillers exposed to crystalline silica.

OBJECTIVES: Chronic obstructive pulmonary disease and silicosis are associated with exposure to crystalline silica. We determined the exposure to respirable crystalline silica and estimated exposure-response relationships between cumulative exposure and pulmonary function in outdoor rock drillers. METHODS: 136 rock drillers and 48 referents were recruited from three heavy construction companies. 98 air samples were collected by personal sampling for determination of respirable particulate matter and crystalline silica. Information about individual job tasks, type of drilling equipment and years of exposure in different job categories was obtained by interview. Cumulative exposure to crystalline silica was calculated for all workers. Pulmonary function was assessed by spirometry. A subgroup of 39 subjects with high cumulative exposure to crystalline silica underwent high-resolution computed tomography (HRCT). RESULTS: Cumulative exposure (mean (min-max)) to crystalline silica was 0.69 mgÙ years m-3 (0.01-5.89) in the exposed group. Mean time of exposure among rock drillers was 10.7 years (1-42). Compared with referents, the rock drillers had a lower forced expiratory volume in one second/forced vital capacity ratio (79.4 vs 81.4, p<0.05) and maximal mid-expiratory flow% (85.6 vs 93.9, p<0.05). Further, by stratifying the exposed workers into three equally large groups, a dose-response relationship was demonstrated in the highest exposed group, also in never smokers, at a mean cumulative exposure of 21.7 years at 0.08 mgÙ m-3/years. Silicosis was not detected in HRCT, but other patterns of fibrosis and emphysema were seen. CONCLUSIONS: Outdoor rock drillers exposed to crystalline silica had significantly lower pulmonary function than referents, and signs of airflow obstruction. Silicosis was not detected.

Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.

OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc. METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing. RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo. CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.

Cardiorespiratory Fitness and Physical Activity following Lung Transplantation: A National Cohort Study.

BACKGROUND: Low cardiorespiratory fitness and inactivity are common after lung transplantation (LTx). The causes of exercise intolerance are incompletely understood. OBJECTIVES: The aim of this study was to objectively assess cardiorespiratory fitness and physical activity, evaluate causes of exercise intolerance, and explore clinical factors associated with cardiorespiratory fitness after bilateral LTx (BLTx). MATERIALS AND METHODS: Peak oxygen uptake (V∙O2peak) and exercise-limiting factors were evaluated by a treadmill cardiopulmonary exercise test (CPET) 6-60 months after BLTx. Physical activity was measured with accelerometers, and results were compared with Norwegian normative data and the World Health Organization's (WHO) recommendations for physical activity. RESULTS: In 54 included BLTx recipients (mean age 50 ± 15 years, 50% females), V∙O2peak (mL × kg-1 × min-1) was 21.8 ± 7.7 for men and 22.4 ± 6.2 for women, corresponding to 57 ± 17 and 70 ± 12% of predicted, respectively. Three patients (6%) met criteria for normal V∙O2peak. Deconditioning limited V∙O2peak in 22 patients (41%), while ventilatory limitation and abnormal gas exchange were observed in 14 (26%) and 20 (37%) patients, respectively (some had more than 1 finding). Forty-three patients (86%) did not meet the WHO physical activity recommendations. There was a moderate correlation between V∙O2peak and physical activity (r = 0.642, p < 0.01). Body mass index, physical activity, forced expiratory volume after 1 second, sex, and hemoglobin together accounted for 73% of the variability in V∙O2peak. CONCLUSIONS: Low cardiorespiratory fitness was observed in the majority of BLTx recipients. Both deconditioning and cardiopulmonary limitations were common findings. Nearly 90% were classified as being inactive according to physical activity recommendations. CPET appears to identify a deconditioned subgroup of BLTx recipients for whom exercise training may be especially beneficial.

Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort.

Rationale: Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities for screening and management strategies.Objectives: Evaluate impact of ILD in a unique, nationwide, population-based SSc cohort.Methods: ILD was assessed prospectively in the Norwegian SSc (Nor-SSc) cohort, including all 815 patients with SSc resident in the country from 2000 to 2012. Lung high-resolution computed tomography (HRCT) scans were available for fibrosis quantification at baseline (n = 650, 80%) and follow-up. Pulmonary function tests were assessed at baseline (n = 703, 86%) and follow-up. Vital status and standardized mortality ratios (SMRs) were estimated at study end (2018) in the 630 incident Nor-SSc cases and 15 individually matched control subjects. Cumulative survival rates were computed.Measurements and Main Results: At baseline, 50% of the subjects with SSc (n = 324) had ILD by HRCT and 46% displayed pulmonary function declines consistent with ILD progression. Mortality correlated with extent of lung fibrosis as SMR increased from 2.2 with no fibrosis to 8.0 with greater than 25% fibrosis. SMR was inversely related to baseline FVC% and increased at all FVC levels below 100%. In patients with normal-range baseline FVC (80-100%), the 5- and 10-year survival rates correlated with presence or absence of lung fibrosis, being 83% and 80%, respectively, with no fibrosis and 69% and 56%, respectively, with lung fibrosis (P = 0.03).Conclusions: The mere presence of ILD at baseline appears to affect outcome in SSc, suggesting that all patients with SSc should undergo a baseline pulmonary function test and lung HRCT screening to diagnose ILD early and tailor further management.

Pulmonary Manifestations and Progression of Lung Disease in Juvenile-onset Mixed Connective Tissue Disease.

OBJECTIVE: To assess the occurrence and extent of interstitial lung disease (ILD) in patients with juvenile mixed connective tissue disease (JMCTD), compare pulmonary function in patients and matched controls, study associations between ILD and disease-related variables, and examine progression of pulmonary manifestations over time. METHODS: A cohort of 52 patients with JMCTD were examined in a cross-sectional study after a mean 16.2 (SD 10.3) years of disease duration with high-resolution computed tomography (HRCT) and pulmonary function tests (PFT) comprising spirometry, DLCO, and total lung capacity (TLC). Matched controls were examined with PFT. Previous HRCT and PFT were available in 37 and 38 patients (mean 8.8 and 10.3 yrs before study inclusion), respectively. RESULTS: Compared to controls, patients with JMCTD had lower forced vital capacity (FVC), DLCO, and TLC (p < 0.01). The most frequent abnormal PFT was DLCO in 67% of patients versus 17% of controls (p < 0.001). Fourteen patients (27%) had ILD on HRCT. Most had ILD in < 10% of their lungs. ILD was associated with low values for FVC and TLC, but not with DLCO. HRCT findings did not progress significantly over time, but FVC declined (p < 0.01). CONCLUSION: Compared to controls, patients with JMCTD had impaired pulmonary function. ILD was present in 27% of patients after a mean 16 years of disease duration, mostly as mild disease, and did not progress. ILD seems to be less common in juvenile-onset than in adult-onset MCTD, and ILD in JMCTD seems mostly mild and stable over time.

Augmented concentrations of CX3CL1 are associated with interstitial lung disease in systemic sclerosis.

BACKGROUND: Dysregulation of Fractalkine (CX3CL1) and its receptor CX3CR1 has been linked to the pathobiology of chronic inflammatory conditions. We explored CX3CL1 in systemic sclerosis (SSc) related progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in two different but complementary sources of biomaterial. METHODS: We collected lung tissue at the time of lung transplantation at UCLA from SSc-ILD patients (n = 12) and healthy donors (n = 12); and serum samples from the prospective Oslo University Hospital SSc cohort (n = 292) and healthy donors (n = 100). CX3CL1 was measured by ELISA. Cellular sources of CX3CL1/CX3CR1 in lung tissues were determined by immunohistochemistry and immunofluorescence. ILD progression and new onset PH endpoints were analysed. RESULTS: CX3CL1 concentrations were increased in SSc in lung tissue as well as in sera. In the UCLA cohort, CX3CL1 was highly correlated with DLCO. In the SSc-ILD lungs, CX3CL1 was identified in reactive type II pneumocytes and airway epithelial cells. CX3CR1 stained infiltrating interstitial mononuclear cells, especially plasma cells. In the Oslo cohort, CX3CL1 correlated with anti-Topoisomerase-I-antibody and lung fibrosis. CX3CL1 was associated with ILD progression in multivariable regression analysis but not PH. CONCLUSION: CX3CL1 is associated with progressive SSc-ILD but not SSc-PH. The CX3CR1/CX3CL1-biological axis may be involved in recruiting antibody secreting plasma cells to SSc lungs, thereby contributing to the immune-mediated pathobiology of SSc-ILD.