Background Steroids remain the first-choice therapeutic in sarcoidosis; however, long-term use is associated with toxicity. Evidence defining the best second-line therapeutic is currently lacking. ...The aim of this study was to compare the effect of methotrexate and azathioprine on prednisone tapering, pulmonary function, and side effects in the second-line treatment of sarcoidosis. Methods An international retrospective cohort study was performed, reviewing all patients with sarcoidosis who started methotrexate or azathioprine until 2 years after initiation or discontinuation. A linear mixed model with FEV1 , vital capacity (VC), diffusing capacity of lung for carbon monoxide (D lco) , and prednisone dose changes over time as end points was used. Side effects were compared with χ2 tests. Results Two hundred patients were included, of whom 145 received methotrexate and 55 azathioprine. Prednisone daily dose decreased a mean of 6.32 mg/y ( P < .0001) while on therapy, with a similar steroid-sparing capacity for methotrexate and azathioprine. Of all patients completing 1 year of therapy, 70% had a reduction in daily prednisone dose of at least 10 mg. FEV1 showed a mean increase of 52 mL/y ( P = .006) and VC of 95 mL/y ( P = .001) in both treatment groups. D lco % predicted increased, with a mean of 1.23%/y ( P = .018). There were more patients with infections in the azathioprine group (34.6% vs 18.1%, P = .01), but no differences regarding other side effects. Conclusions This retrospective study comparing the effect of second-line therapy in sarcoidosis shows that both methotrexate and azathioprine have significant steroid-sparing potency, a similar positive effect on lung function, and comparable side effects, except for a higher infection rate in the azathioprine group.
Physical inactivity in patients with chronic obstructive pulmonary disease (COPD) is associated with poor health status and increased disease burden. The present study aims to test the efficacy of a ...previously developed mobile (m)Health intervention to improve or maintain physical activity in patients with COPD after pulmonary rehabilitation.A randomised controlled trial was performed in 32 physiotherapy practices in the Netherlands. COPD patients were randomised into intervention or usual care groups. The intervention consisted of a smartphone application for the patients and a monitoring website for the physiotherapists. Measurements were performed at 0, 3, 6 and 12 months. Physical activity, functional exercise capacity, lung function, health-related quality of life and body mass index were assessed.157 patients started the study and 121 completed it. There were no significant positive effects of the intervention on physical activity (at 0 months: intervention 5824±3418 steps per weekday, usual care 5717±2870 steps per weekday; at 12 months: intervention 4819±2526 steps per weekday, usual care 4950±2634 steps per weekday; p=0.811) or on the secondary end-points. There was a significant decrease over time in physical activity (p<0.001), lung function (p<0.001) and mastery (p=0.017), but not in functional exercise capacity (p=0.585).Although functional exercise capacity did not deteriorate, our mHealth intervention did not improve or maintain physical activity in patients with COPD after a period of pulmonary rehabilitation.
Telomere Length in Interstitial Lung Diseases Snetselaar, Reinier, MSc; van Moorsel, Coline H.M., PhD; Kazemier, Karin M., BSc ...
Chest,
10/2015, Letnik:
148, Številka:
4
Journal Article
Recenzirano
BACKGROUND Interstitial lung disease (ILD) is a heterogeneous group of rare diseases that primarily affect the pulmonary interstitium. Studies have implicated a role for telomere length (TL) ...maintenance in ILD, particularly in idiopathic interstitial pneumonia (IIP). Here, we measure TL in a wide spectrum of sporadic and familial cohorts of ILD and compare TL between patient cohorts and control subjects. METHODS A multiplex quantitative polymerase chain reaction method was used to measure TL in 173 healthy subjects and 359 patients with various ILDs, including familial interstitial pneumonia (FIP). The FIP cohort was divided into patients carrying TERT mutations, patients carrying SFTPA2 or SFTPC mutations, and patients without a proven mutation (FIP-no mutation). RESULTS TL in all cases of ILD was significantly shorter compared with those of control subjects (P range: .038 to < .0001). Furthermore, TL in patients with idiopathic pulmonary fibrosis (IPF) was significantly shorter than in patients with other IIPs (P = .002) and in patients with sarcoidosis (P < .0001). Within the FIP cohort, patients in the FIP-telomerase reverse transcriptase (TERT) group had the shortest telomeres (P < .0001), and those in the FIP-no mutation group had TL comparable to that of patients with IPF (P = .049). Remarkably, TL of patients with FIP-surfactant protein (SFTP) was significantly longer than in patients with IPF, but similar to that observed in patients with other sporadic IIPs. CONCLUSIONS The results show telomere shortening across all ILD diagnoses. The difference in TL between the FIP-TERT and FIP-SFTP groups indicates the distinction between acquired and innate telomere shortening. Short TL in the IPF and FIP-no mutation groups is indicative of an innate telomere-biology defect, while a stress-induced, acquired telomere shortening might be the underlying process for the other ILD diagnoses.
Objectives The aim of this study was to derivate and validate a prediction model for cardiovascular events based on quantification of coronary and aortic calcium volume in lung cancer screening chest ...computed tomography (CT). Background CT-based lung cancer screening in heavy smokers is a very timely topic. Given that the heavily smoking screening population is also at risk for cardiovascular disease, CT-based screening may provide the opportunity to additionally identify participants at high cardiovascular risk. Methods Inspiratory screening CT of the chest was obtained in 3,648 screening participants. Next, smoking characteristics, patient demographics, and physician-diagnosed cardiovascular events were collected from 10 years before the screening CT (i.e., cardiovascular history) until 3 years after the screening CT (i.e., follow-up time). Cox proportional hazards analysis was used to derivate and validate a prediction model for cardiovascular risk. Age, smoking status, smoking history, and cardiovascular history, together with automatically quantified coronary and aortic calcium volume from the screening CT, were included as independent predictors. The primary outcome measure was the discriminatory value of the model. Results Incident cardiovascular events occurred in 145 of 1,834 males (derivation cohort) and 118 of 1,725 males and 2 of 89 females (validation cohort). The model showed good discrimination in the validation cohort with a C-statistic of 0.71 (95% confidence interval: 0.67 to 0.76). When high risk was defined as a 3-year risk of 6% and higher, 589 of 1,725 males were regarded as high risk and 72 of 118 of all events were correctly predicted by the model. Conclusions Quantification of coronary and aortic calcium volumes in lung cancer screening CT images—information that is readily available—can be used to predict cardiovascular risk. Such an approach might prove useful in the reduction of cardiovascular morbidity and mortality and may enhance the cost-effectiveness of CT-based screening in heavy smokers.
Summary Aim To review the currently available literature comparing the FEV1 /FVC <LLN with a fixed value of FEV1 /FVC <0.70 in diagnosing airflow obstruction in subjects aged >40 years. Methods A ...structured MEDLINE, EMBASE and Cochrane search of English-language literature was conducted. Studies comparing prevalence rates according to the LLN and a fixed value were included. Attention was paid to the choice of the reference test or gold standard used. Results Eighteen studies met the inclusion criteria. Sixteen studies compared the rates of subjects diagnosed with airflow obstruction by either definition of airflow obstruction without using a non-independent reference standard (level 4 studies). Using a fixed value of FEV1 /FVC, an overall higher number of subjects were diagnosed with airflow obstruction that increased with age. Two studies included a follow-up phase comparing risks of either hospitalization or occurrence of respiratory symptoms and mortality (level 2b studies). Adjusted risks of hospitalization (HR 2.6) or mortality (HR 1.3) were significantly larger in subjects with an FEV1 /FVC below 0.70 but above the LLN (in-between group) compared to subjects with normal lung function. Conclusion The prevalence of spirometry-based COPD is greater when using the fixed value of FEV1 /FVC in comparison to using the LLN. Based on one longitudinal study the in-between group appears to have a higher risk of hospitalization and mortality; therefore it seems that using the LLN of FEV1 /FVC underestimates COPD. In absence of a gold standard of COPD longitudinal research will be necessary to determine which criterion is better and more clinically relevant.
We compared interexamination variability of CT lung nodule volumetry with six currently available semi-automated software packages to determine the minimum change needed to detect the growth of solid ...lung nodules. We had ethics committee approval. To simulate a follow-up examination with zero growth, we performed two low-dose unenhanced CT scans in 20 patients referred for pulmonary metastases. Between examinations, patients got off and on the table. Volumes of all pulmonary nodules were determined on both examinations using six nodule evaluation software packages. Variability (upper limit of the 95% confidence interval of the Bland-Altman plot) was calculated for nodules for which segmentation was visually rated as adequate. We evaluated 214 nodules (mean diameter 10.9 mm, range 3.3 mm–30.0 mm). Software packages provided adequate segmentation in 71% to 86% of nodules (p < 0.001). In case of adequate segmentation, variability in volumetry between scans ranged from 16.4% to 22.3% for the various software packages. Variability with five to six software packages was significantly less for nodules ≥8 mm in diameter (range 12.9%-17.1%) than for nodules <8 mm (range 18.5%-25.6%). Segmented volumes of each package were compared to each of the other packages. Systematic volume differences were detected in 11/15 comparisons. This hampers comparison of nodule volumes between software packages.
The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below ...0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.
In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.
Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.
GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.
Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional ...individuals with COPD at an early stage.
To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD.
Single-center prospective cross-sectional study within an ongoing lung cancer screening trial. Prebronchodilator pulmonary function testing with inspiratory and expiratory CT on the same day was obtained from 1140 male participants between July 2007 and September 2008. Computed tomographic emphysema was defined as percentage of voxels less than -950 Hounsfield units (HU), and CT air trapping was defined as the expiratory:inspiratory ratio of mean lung density. Chronic obstructive pulmonary disease was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV(1)/FVC) of less than 70%. Logistic regression was used to develop a diagnostic prediction model for airflow limitation.
Diagnostic accuracy of COPD diagnosis using pulmonary function tests as the reference standard.
Four hundred thirty-seven participants (38%) had COPD according to lung function testing. A diagnostic model with CT emphysema, CT air trapping, body mass index, pack-years, and smoking status corrected for overoptimism (internal validation) yielded an area under the receiver operating characteristic curve of 0.83 (95% CI, 0.81-0.86). Using the point of optimal accuracy, the model identified 274 participants with COPD with 85 false-positives, a sensitivity of 63% (95% CI, 58%-67%), specificity of 88% (95% CI, 85%-90%), positive predictive value of 76% (95% CI, 72%-81%); and negative predictive value of 79% (95% CI, 76%-82%). The diagnostic model showed an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.86-0.88) for participants with symptoms and 0.78 (95% CI, 0.76-0.80) for those without symptoms.
Among men who are current and former heavy smokers, low-dose inspiratory and expiratory CT scans obtained for lung cancer screening can identify participants with COPD, with a sensitivity of 63% and a specificity of 88%.
Abstract Arterial calcification is a well-known risk factor for coronary artery disease (CAD) and myocardial infarction (MI). We performed a genome-wide association study on coronary artery ...calcification and aortic calcification as intermediate traits for CAD/MI. We tested ∼2.5 million SNPs for association with coronary artery calcification and aortic calcification in 2620 male individuals of the NELSON trial, who underwent chest CT scans. All participants were current or former heavy smokers. No SNPs were associated with aortic calcification on a genome-wide scale. The 9p21 locus was significantly associated with coronary artery calcification (rs1537370, P = 2.3 × 10−11 ). Since this locus corresponds to the strongest SNP association for CAD/MI, we tested 24 published and validated CAD/MI risk SNPs for association with arterial calcification. Besides the CAD/MI SNP at 9p21 (rs4977574, P = 3.1 × 10−10 ), two additional loci at ADAMTS7 (rs3825807, P = 6.5 × 10−6 ) and at PHACTR1 (rs12526453, P = 1.0 × 10−3 ) show a nominally significant association with coronary artery calcification with MI/CAD risk alleles increasing the degree of arterial calcification. The 9p21 locus was also nominally associated with aortic calcification ( P = 3.2 × 10−4 ). These findings indicate that these CAD and MI risk loci are likely involved in arterial calcification.
PDF
