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.

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.

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.

Progression and mortality of interstitial lung disease in mixed connective tissue disease: a long-term observational nationwide cohort study.

Objectives: To assess the prevalence, extent, progression, functional impact and mortality of interstitial lung disease (ILD) in a nationwide unselected MCTD cohort. Methods: The study cohort included patients with high-resolution CT lung scans available at baseline (n = 135) and at follow-up (n = 119). The extent of disease was expressed as percentage of total lung volume (TLV). Results: ILD was present in 41% of MCTD patients at follow-up. Median (interquartile) extent (% of TLV) was 5 (8) at baseline and 7 (17) at follow-up, mean length 6.4 years later. The lung disease progressed in 19% of patients across the observation period. Predictors of ILD progression were elevated anti-RNP titre [hazard ratio (HR) 1.5, 95% CI: 1.1, 2.0; P = 0.008], presence of anti-ro52 antibodies (HR = 3.5, 95% CI: 1.2, 10.2; P = 0.023), absence of arthritis (HR = 0.2, 95% CI: 0.1, 0.6; P = 0.004) and male gender (HR = 4.0, 95% CI: 1.4, 11.5; P = 0.011) after age and baseline disease adjustments. The risk of death increased by 2.9 (95% CI: 1.1, 7.9; P = 0.038) in patients where disease involved ⩾5% of TLV. Conclusion: Lung disease extent and progression in MCTD are modest. Yet, the extension continues several years after MCTD diagnosis causing lung function decline and increasing the risk of mortality. The study identified male gender, elevated anti-RNP titre, presence of anti-ro52 antibodies and absence of arthritis as the strongest predictors of ILD progression.

Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation.

BACKGROUND: Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. MATERIAL AND METHODS: LSs treated in Norway 1987-2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012-2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV1). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. RESULTS: A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV1 was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400-775 mg/m2) and current smoking were associated with increased risk of obstructive impairment, and chest RT (>13-66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400-775 mg/m2), had the lowest adjusted mean FEV1. CONCLUSIONS: Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.

Pulmonary function and high-resolution computed tomography examinations among offshore drill floor workers.

PURPOSE: The aim of this study was to assess short-term changes in pulmonary function in drill floor workers currently exposed to airborne contaminants generated as a result of drilling offshore. We also aimed to study the prevalence of pulmonary fibrosis using high-resolution computed tomography (HRCT) scans of another group of previously exposed drill floor workers. METHODS: Pulmonary function was measured before and after a 14-day work period in a follow-up study of 65 drill floor workers and 65 referents. Additionally, 57 other drill floor workers exposed to drilling fluids during the 1980s were examined with HRCT of the lungs in a cross-sectional study. RESULTS: The drill floor workers had a statistically significant decline in forced expiratory volume in 1 s (FEV1) across the 14-day work period after adjustment for diurnal variations in pulmonary function (mean 90 mL, range 30-140 mL), while the small decline among the referents (mean 20 mL, range - 30 to 70 mL) was not of statistical significance. Larger declines in FEV1 among drill workers were associated with the fewer number of days of active drilling. There were no signs of pulmonary fibrosis related to oil mist exposure among the other previously exposed drill floor workers. CONCLUSION: After 14 days offshore, a statistically significant decline in FEV1 was observed in the drill floor workers, which may not be related to oil mist exposure. No pulmonary fibrosis related to oil mist exposure was observed.

Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood.

We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

Gender-specific survival after surgical resection for early stage non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. The incidence and mortality rate of lung cancer in women has increased. Studies have indicated that females with non-small cell lung cancer (NSCLC) have better survival than males. We aimed to examine the impact of gender on 1-, 5- and 10-year survival after surgery for stage I and II NSCLC. MATERIALS AND METHODS: During the period 2003-2013, 692 patients operated for stage I and II NSCLC were prospectively registered. Patients were stratified into four groups according to gender and age over or less than 66 years. The relationship between gender and age on overall survival was investigated. Adjustment for multiple confounders was performed using the Cox proportional hazard regression model. RESULTS: Surgical resection was performed in 368 (53.2%) males and 324 (46.8%) females. During the study period, mortality was 35.2% in younger females, 34.9% in younger males, 42.8% in older females and 51.2% in older males. Stratified by age, there were no significant gender differences with regard to survival [hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.46, p = .23]. Comparing the younger and the older patients adjusted for confounders, the mortality risk was significantly increased in elderly patients [females, adjusted HR 1.60, 95% CI 1.12-2.28]. Compared with population data, standardized mortality ratio was increased to 4.1 (95% CI 3.5-4.7) in males and to 6.5 (95% CI 5.4-7.6) in females. CONCLUSION: Overall survival did not differ significantly between males and females. Adjusted for confounding factors, we found a significantly increased mortality risk in elder patients compared to their younger counterparts. However, five-year overall survival of more than 50% for older patients with NSCLC should encourage surgical treatment also in elderly lung cancer patients.

Lung function in asphalt pavers: a longitudinal study.

PURPOSE: To study longitudinal changes in lung function in asphalt pavers and a reference group of road maintenance workers, and to detect possible signs of lung disease by high-resolution computed tomography (HRCT) scans. METHODS: Seventy-five asphalt pavers and 71 road maintenance workers were followed up with questionnaires and measurements of lung function. Not every worker was tested every year, but most of them had four or more measurement points. The 75 asphalt pavers were also invited to have HRCT scans of the lungs at the end of the follow-up period. RESULTS: Mean annual decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) of the asphalt pavers was 58 and 35 ml, respectively. Adjusted for age at baseline, packyears of smoking and BMI, the asphalt pavers had a significant excess annual decline in FVC and FEV1 compared to the references. The screedmen, the most exposed group of the asphalt pavers, showed a significantly larger decline in FVC than the other asphalt pavers (P = 0.029). Fine intralobular fibrosis without evident cysts was identified with HRCT in three subjects (4 %). CONCLUSION: We conclude that our findings may indicate an excess annual decline in FVC and FEV1 related to exposure to asphalt fumes. The screedmen, who carry out their work behind and close to the paving machine, had the largest decline in lung function. The finding of adverse pulmonary effects in asphalt pavers calls for better technological solutions to prevent exposure.

Cardiorespiratory fitness in long-term lymphoma survivors after high-dose chemotherapy with autologous stem cell transplantation.

BACKGROUND: Cardiorespiratory fitness as measured by peak oxygen consumption (VO2peak) is a strong predictor of longevity and may be compromised by anticancer therapy, inactivity, and smoking. We compared VO2peak among lymphoma survivors (LSs) with reference data from healthy sedentary subjects, after a 10.2-year (mean) follow-up post high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We further examined the association between VO2peak and treatment, physical activity, smoking, pulmonary, and cardiac function. METHODS: Lymphoma survivors treated with HDT-ASCT in Norway 1987-2008 were eligible. VO2peak was assessed by cardiopulmonary exercise testing. Pulmonary function testing and echocardiography were also conducted. Data on treatment, physical activity, and smoking were collected from hospital records and questionnaires. VO2peak was compared with age-sex predicted reference data. Linear regression was used to associate clinical factors with VO2peak cross-sectionally. RESULTS: A total of 194 LSs without heart failure were studied. Mean VO2peak was 4.5% and 7.7% below norms in females and males, respectively. Twenty-two percent had impaired (<80% predicted) VO2peak. Decreasing VO2peak was associated with impaired diffusion capacity and current smoking, while physical activity level and VO2peak were positively associated. CONCLUSION: We suggest increased attention towards physical activity counseling and smoking cessation advice to preserve cardiorespiratory fitness in LSs after HDT-ASCT. Patients with impaired diffusion capacity may benefit from subsequent monitoring to detect pulmonary vascular diseases.

Associations between anti-Ro52 antibodies and lung fibrosis in mixed connective tissue disease.

OBJECTIVE: MCTD is a chronic, immune-mediated disorder defined by the combined presence of serum anti-RNP antibodies and distinct clinical features, including progressive lung fibrosis. The aim of the study was to evaluate the potential impact of anti-SSA (i.e. Ro52 and Ro60) and anti-SSB autoantibodies as markers for disease outcomes in MCTD. METHODS: Stored serum samples from 113 patients included in the cross-sectional, nationwide Norwegian MCTD cohort were screened for the presence of anti-Ro52, anti-Ro60 and anti-SSB by a commercial line immunoassay. Correlation analyses were carried out with clinical parameters, including quantitative lung fibrosis scores by high-resolution CT. Lung fibrosis was defined by reticular pattern changes according to the Fleischner Society CT criteria for interstitial lung disease. RESULTS: Anti-Ro52 antibodies were present in 29%, anti-Ro60 in 19% and anti-SSB in 6% of the MCTD sera. High-resolution CT scoring identified lung fibrosis in 38 of 113 (34%) MCTD patients. Anti-Ro52 antibodies were detected in 50% (19 of 38) of the MCTD patients with lung fibrosis and in 19% (14 of 75) without lung fibrosis (P < 0.001). The odds ratio for the presence of anti-Ro52 antibodies in lung fibrosis was 4.4 (95% CI 1.8, 10.3). Anti-Ro52 antibodies were equally frequent in patients with mild to moderate (eight of 17; 44%) and severe fibrosis (11 of 21; 52%). Anti-Ro52 was not associated with any of the other clinical parameters assessed, nor was anti-Ro60 or anti-SSB. CONCLUSION: Our cross-sectional data suggest that anti-Ro52 antibodies may serve as a potential marker for lung fibrosis in MCTD.

Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease.

OBJECTIVE: To retrospectively evaluate the efficacy and safety of rituximab (Rtx) treatment in patients with anti-synthetase syndrome (ASS) and severe interstitial lung disease (ILD). METHODS: Patients with severe ILD and >12 months follow-up post-Rtx were identified from the Oslo University Hospital ASS cohort (n = 112). Clinical data, including pulmonary function tests (PFTs), were retrospectively collected from medical reports. Extent of ILD pre-, and post-Rtx was scored on thin-section high-resolution CT (HRCT) images and expressed as a percentage of total lung volume. Muscle strength was evaluated by manual muscle testing of eight muscle groups (MMT8). RESULTS: Altogether, 34/112 ASS patients had received Rtx; 24/34 had severe ILD and >12 months follow-up post-Rtx (median 52 months). In these 24 patients, the median percentage of predicted forced vital capacity, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO) increased by 24%, 22% and 17%, respectively, post-Rtx. Seven patients (all with disease duration <12 months and/or acute onset/exacerbation of ILD) had >30% improvement in all three PFTs. HRCT analysis showed a median 34% reduction in ILD extent post-Rtx. MMT8 score increased post-Rtx. During follow-up, 7/34 (21%) Rtx-treated ASS patients died; 6/7 deaths were related to infections. The mortality rate in the Rtx-treated group was comparable to that of the remaining ASS cohort (25/78 deceased; 32%). CONCLUSION: This study, which included 24 Rtx-treated ASS patients with severe ILD, reports improved PFTs after a median 52 months follow-up post-Rtx. The best outcome was observed in patients with a disease duration <12 months and/or acute onset/exacerbation of ILD. The study indicates that Rtx could be a treatment option for selected ASS patients, but infections should be given attention.

Short-term lung function decline in tunnel construction workers.

OBJECTIVES: Tunnel construction workers are exposed to particulate and gaseous air contaminants. Previous studies carried out in the 1990s showed that tunnel construction workers were at increased risk of both short-term and long-term lung function decline. Since then, efforts have been made to reduce exposure. The objective of the present study was to investigate if current exposure may still cause short-term lung function impairment. METHODS: Tunnel workers work 12 days consecutively, and then they are off for 9 days. Ninety tunnel workers and 51 referents were examined with spirometry and questionnaires before their work period started and again 11 days later. Personal exposure to particles and α-quartz in the thoracic aerosol subfraction, elemental carbon and organic carbon, oil mist, nitrogen dioxide and ammonia was assessed on two consecutive days between the two health examinations. RESULTS: The geometric means air concentrations for particulate matter in the thoracic mass aerosol subfraction, α-quartz, oil mist, organic carbon and elemental carbon for all workers were 561, 63, 210, 146 and 35 µg/m(3), respectively. After 11 days of work, the mean forced expiratory volume in 1 s (FEV1) in healthy participants had declined 73 mL (SD 173), p<0.001 in the tunnel workers, compared to 3 mL (SD 21), p=0.9 in the referents. Also, forced vital capacity (FVC) had declined significantly. Declines in FVC and FEV1 were significantly associated with exposure to organic carbon. CONCLUSIONS: In spite of reduced levels of exposure in modern tunnelling operations, a negative impact on lung function was still observed.