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Pulmonary perfusion by iodine subtraction maps CT angiography in acute pulmonary embolism: comparison with pulmonary perfusion SPECT (PASEP trial).
Dissaux, B, Le Floch, PY, Robin, P, Bourhis, D, Couturaud, F, Salaun, PY, Nonent, M, Le Roux, PY
European radiology. 2020;(9):4857-4864
Abstract
OBJECTIVE To assess the diagnostic accuracy of iodine map computed tomography pulmonary angiography (CTPA), for segment-based evaluation of lung perfusion in patients with acute pulmonary embolism (PE), using perfusion single-photon emission CT (SPECT) imaging as a reference standard. METHODS Thirty participants who have been diagnosed with acute pulmonary embolism on CTPA underwent perfusion SPECT/CT within 24 h. Perfusion SPECT and iodine map were independently interpreted by 2 nuclear medicine physicians and 2 radiologists. For both modalities, each segment was classified as normoperfused or hypoperfused, as defined by a perfusion defect of more than 25% of a segment. The primary end point was the diagnostic accuracy (sensitivity and specificity) of iodine map for segment-based evaluation of lung perfusion, using perfusion SPECT imaging as a reference standard. Following blinded interpretation, a retrospective explanatory analysis was performed to determine potential causes of misinterpretation. RESULTS The median time between CTPA with iodine maps and perfusion SPECT was 14 h (range 2-23 h). A total of 597 segments were analyzed. Sensitivity and specificity of iodine maps with CTPA for the detection of segmental perfusion defects were 231/284 = 81.3% (95% CI 76.4 to 85.4%) and 247/313 = 78.9% (95% CI 74.1 to 83.1%), respectively. In retrospect, false results were explained in 48.7%. CONCLUSION Iodine map CTPA showed promising results for the assessment of pulmonary perfusion in patients with acute PE, with sensitivity of 81.3% and specificity of 78.9%, respectively. Recognition of typical pitfalls such as atelectasis, fissures, or beam-hardening artifacts may further improve the accuracy of the test. KEY POINTS • Sensitivity and specificity of iodine subtraction maps for the detection of segmental perfusion defects were 81.3% (95% CI 76.4 to 85.4%) and 78.9% (95% CI 74.1 to 83.1%), respectively. • Recognition of typical pitfalls such as atelectasis, fissures, or beam-hardening artifacts may further improve the diagnostic accuracy of the test.
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Associations of α- and γ-tocopherol during early life with lung function in childhood.
Kumar, R, Ferrie, RP, Balmert, LC, Kienzl, M, Rifas-Shiman, SL, Gold, DR, Sordillo, JE, Kleinman, K, Camargo, CA, Litonjua, AA, et al
The Journal of allergy and clinical immunology. 2020;(6):1349-1357.e3
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Abstract
BACKGROUND Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE Our aim was to determine the extent to which plasma α-tocopherol (α-T) or γ-tocopherol (γ-T) isoform levels in early childhood or in utero are associated with childhood lung function. METHODS We included 622 participants in the Project Viva cohort who had lung function at a mid-childhood visit (age 6-10 years). Maternal and child tocopherol isoform levels were measured by HPLC at the second trimester and 3 years of age, respectively. Multivariable linear regression models (adjusted for mid-childhood body mass index z scores, maternal education, smoking in pregnancy, and prenatal particulate matter with diameter of <2.5 micrometers (PM2.5) particulate exposure) stratified by tertiles of child γ-T level were used to assess the association of α-T levels with FEV1 and forced vital capacity (FVC) percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. RESULTS The median maternal second trimester α-T level was 63 μM (interquartile range = 47-82). The median early-childhood level was 25 μM (interquartile range = 20-33 μM). In the lowest tertile of early-childhood γ-T, children with a higher α-T level (per 10 μM) had a higher mid-childhood FEV1 percent predicted (β = 3.09; 95% CI = 0.58-5.59 and a higher FVC percent predicted (β = 2.77; 95% CI = 0.47-5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC. CONCLUSION When γ-T levels were in the lowest tertile, a higher early-childhood α-T level was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than in the adult nonpregnant female population.
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Effect of antiretroviral therapy on longitudinal lung function trends in older children and adolescents with HIV-infection.
Rylance, S, Rylance, J, McHugh, G, Majonga, E, Bandason, T, Mujuru, H, Nathoo, K, Rowland-Jones, S, Henrion, MYR, Simms, V, et al
PloS one. 2019;(3):e0213556
Abstract
INTRODUCTION Chronic respiratory disease is a common cause of morbidity in children with HIV infection. We investigated longitudinal lung function trends among HIV-infected children, to describe the evolution of lung disease and assess the effect of anti-retroviral therapy (ART). METHODS Prospective follow-up of two cohorts of HIV-infected children, aged 6 to 16 years, in Harare, Zimbabwe; one group were ART-naïve at enrolment, the other established on ART for a median of 4.7-years. Standardised spirometric assessments were repeated over a 2-year follow-up period. Forced expiratory volume (FEV1) and forced vital capacity (FVC) were expressed as Global Lung Initiative defined z-scores (FEV1z and FVCz). Linear mixed-effects regression modelling of lung function was performed, with co-variate parameters evaluated by likelihood ratio comparison. RESULTS We included 271 ART-naïve and 197 ART-established children (median age 11 years in both groups) incorporating 1144 spirometric assessments. Changes in FEV1 and FVC were associated with age at ART initiation and body mass index for both cohorts. Our models estimate that ART initiation earlier in life could prevent a deterioration of 0.04 FVCz/year. In the ART-naïve cohort, likelihood ratio comparison suggested an improvement in 0.09 FVCz/year during the two years following treatment initiation, but no evidence for this among participants established on ART. CONCLUSION Early ART initiation and improved nutrition are positively associated with lung function and are important modifiable factors. An initial improvement in lung growth was seen in the first 2-years following ART initiation, although this did not appear to be sustained beyond this timeframe.
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Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function.
Duvallet, C, Larson, K, Snapper, S, Iosim, S, Lee, A, Freer, K, May, K, Alm, E, Rosen, R
PloS one. 2019;(5):e0216453
Abstract
BACKGROUND Children with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration. METHODS We conducted a prospective cohort study of 220 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected from all recruited patients and 16S sequencing was performed. A subset of 104 patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. To ensure the validity of the results, we compared the microbiome of these aerodigestive patients to the microbiome of pediatric patients recruited to a longitudinal cohort study of children with suspected GERD; patients recruited to this study had oropharyngeal, gastric and/or stool samples available. The relationships between microbial communities across the aerodigestive tract were described by analyzing within- and between-patient beta diversities and identifying taxa which are exchanged between aerodigestive sites within patients. These relationships were then compared in patients with and without aspiration to evaluate the effect of aspiration on the aerodigestive microbiome. RESULTS Within all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.56 for both; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 4x10-5, respectively). CONCLUSIONS The gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swallow function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes.
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Impairment of lung diffusion capacity-a new consequence in the long-term childhood leukaemia survivors.
Wasilewska, E, Kuziemski, K, Niedoszytko, M, Kaczorowska-Hać, B, Niedzwiecki, M, Małgorzewicz, S, Jassem, E
Annals of hematology. 2019;(9):2103-2110
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Abstract
Childhood leukaemia survivors (CLS) are known to have developed long-term impairment of lung function. The reasons for that complication are only partially known. The aims of this study were to assess pulmonary function in CLS and identify (1) risk factors and (2) clinical manifestations for the impairment of airflow and lung diffusion. The study group included 74 CLS: 46 treated with chemotherapy alone (HSCT-), 28 with chemotherapy and haematopoietic stem cell transplantation (HSCT+), and 84 healthy subjects (control group (CG)). Spirometry and diffusion limit of carbon monoxide (DLCO) tests were performed in all subjects. Ten (14%) survivors had restrictive, five (7%) had obstructive pattern, and 47 (66%) had reduced DLCO. The age at diagnosis, type of transplant, and type of conditioning regimen did not significantly affect the pulmonary function tests. The DLCO%pv were lower in CLS than in CG (p < 0.03) and in the HSCT+ than in the HSCT- survivors (p < 0.05). The pulmonary infection increased the risk of diffusion impairment (OR 5.1, CI 1.16-22.9, p = 0.019). DLCO was reduced in survivors who experienced CMV lung infection (p < 0.001). The main symptom of impaired lung diffusion was poor tolerance of exercise (p < 0.005). The lower lung diffusion capacity is the most frequent abnormality in CLS. HSCT and pulmonary infection, in particular with CMV infection, are strong risk factors for impairment of lung diffusion capacity in CLS. Clinical manifestation of DLCO impairment is poor exercise tolerance. A screening for respiratory abnormalities in CLS seems to be of significant importance.
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Tolerability of inhaled N-chlorotaurine in humans: a double-blind randomized phase I clinical study.
Arnitz, R, Stein, M, Bauer, P, Lanthaler, B, Jamnig, H, Scholl-Bürgi, S, Stempfl-Al-Jazrawi, K, Ulmer, H, Baumgartner, B, Embacher, S, et al
Therapeutic advances in respiratory disease. 2018;:1753466618778955
Abstract
BACKGROUND N-chlorotaurine (NCT), a long-lived oxidant produced by human leukocytes, can be synthesized chemically and used topically as a well-tolerated antiseptic to different body regions including sensitive ones. The aim of this study was to test the tolerability of inhaled 1% NCT in aqueous solution upon repeated application. METHODS The study was performed double-blind and randomized with a parallel test group (1% NCT) and control group (0.9% NaCl as placebo). There were two Austrian centres involved, the hospitals, Natters and Vöcklabruck. Healthy, full age volunteers were included, 12 in each centre. A total of 12 patients were treated with NCT, and 12 with placebo, exactly half of each group from each centre. The single dose was 1.2 ml inhaled over a period of 10 min using an AKITA JET nebulizer. One inhalation was done every day for five consecutive days. The primary criterion of evaluation was the forced expiratory volume in 1 second (FEV1). Secondary criteria were subjective sensations, further lung function parameters such as airway resistance, physical examination, and blood analyses (gases, electrolytes, organ function values, pharmacokinetic parameters taurine and methionine, immune parameters). RESULTS All included 15 females and 9 males completed the treatment and the control examinations according to the study protocol. FEV1 (100.83% ± 8.04% for NCT and 92.92% ± 11.35% for controls) remained unchanged and constant during the treatment and in control examinations 1 week and 3 months after the treatment (98.75% ± 7.37% for NCT and 91.17% ± 9.46% for controls, p > 0.082 between time points within each group). The same was true for all other objective parameters. Subjective mild sensations with a higher frequency in the test group were chlorine taste ( p < 0.01) and occasional tickle in the throat ( p = 0.057). Taurine and methionine plasma concentrations did not change within 60 min after inhalation or later on. CONCLUSIONS Inhaled NCT is well tolerated as in other applications of different body regions. Side effects are mild, topical and transitory. The study was registered prospectively in the European Clinical Trials Database of the European Medicines Agency. The EudraCT number is 2012-003700-12.
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Higher Lipoprotein (a) Levels Are Associated with Better Pulmonary Function in Community-Dwelling Older People - Data from the Berlin Aging Study II.
Buchmann, N, Kassner, U, Norman, K, Goldeck, D, Eckardt, R, Pawelec, G, Steinhagen-Thiessen, E, Demuth, I
PloS one. 2015;(9):e0139040
Abstract
Reduced pulmonary function and elevated serum cholesterol levels are recognized risk factors for cardiovascular disease. Currently, there is some controversy concerning relationships between cholesterol, LDL-cholesterol, HDL-cholesterol, serum triglycerides and lung function. However, most previous studies compared patients suffering from chronic obstructive pulmonary disease (COPD) with healthy controls, and only a small number examined this relationship in population-based cohorts. Moreover, lipoprotein a [Lp(a)], another lipid parameter independently associated with cardiovascular diseases, appears not to have been addressed at all in studies of lung function at the population level. Here, we determined relationships between lung function and several lipid parameters including Lp(a) in 606 older community-dwelling participants (55.1% women, 68±4 years old) from the Berlin Aging Study II (BASE-II). We found a significantly lower forced expiration volume in 1 second (FEV1) in men with low Lp(a) concentrations (t-test). This finding was further substantiated by linear regression models adjusting for known covariates, showing that these associations are statistically significant in both men and women. According to the highest adjusted model, men and women with Lp(a) levels below the 20th percentile had 217.3ml and 124.2ml less FEV1 and 239.0ml and 135.2ml less FVC, respectively, compared to participants with higher Lp(a) levels. The adjusted models also suggest that the known strong correlation between pro-inflammatory parameters and lung function has only a marginal impact on the Lp(a)-pulmonary function association. Our results do not support the hypothesis that higher Lp(a) levels are responsible for the increased CVD risk in people with reduced lung function, at least not in the group of community-dwelling older people studied here.
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18F-FDG PET/CT lung 'focalities' without coregistered CT findings: an interpretative clinical dilemma.
Chondrogiannis, S, Marzola, MC, Grassetto, G, Zorzi, A, Milan, E, Rampin, L, Rubello, D, Colletti, PM
Nuclear medicine communications. 2015;(4):334-9
Abstract
AIM: The aim of the study was to assess the prevalence of focal fluorine-18 fluorodeoxyglucose (18F-FDG) activity in the lungs using 18F-FDG PET/computed tomography (CT) without matching CT findings. MATERIALS AND METHODS A total of 10,500 consecutive 18F-FDG PET/CT records over 4 years were reviewed for focal incongruence between PET and CT, potentially indicating an artifact 18F-FDG (2.2 MBq/kg) was injected through a butterfly needle, followed by a 10 ml saline flush. Non-contrast-enhanced low-dose CT (140 kV and 40-80 mA) was coregistrated with PET. RESULTS Sixteen patients (12 men and four women; mean age 63 years, range 44-83) had focal pulmonary areas of high 18F-FDG activity [mean maximum standardized uptake value (SUV max) 15.8; range 3.5-81.0], typically peripheral, with a mean maximum diameter of 1.3 cm (range 0.5-2.2 cm) on PET. 18F-FDG focality was singular in 14 patients, whereas two patients had two foci each. None had corresponding CT abnormalities. Identification of these 'focalities' during the acquisition phase led to late respiratory gated thoracic PET acquisitions in eight patients at 2 h with no significant changes in the location or size of the 'focalities'. Five PET/CTs repeated at 48 h did not confirm the 'focalities'. Five had negative follow-up contrast-enhanced CT. 18F-FDG-positive 'focalities' at PET/CT without anatomical correlation findings were considered as 'artefactual accumulation' of the tracer. CONCLUSION In the absence of morphological abnormality, focal pulmonary 18F-FDG activity is very rare (1.5 cases/1000 PET scans) but potentially very 'dangerous'. Artefact identification during acquisition can lead to late respiratory gated images for more confident interpretation, avoiding erroneous reports or further imaging procedures.
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The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas.
Kennedy, GT, Okusanya, OT, Keating, JJ, Heitjan, DF, Deshpande, C, Litzky, LA, Albelda, SM, Drebin, JA, Nie, S, Low, PS, et al
Annals of surgery. 2015;(4):602-9
Abstract
BACKGROUND With increasing use of chest computed tomography scans, indeterminate pulmonary nodules are frequently detected as an incidental finding and present a diagnostic challenge. Tissue biopsy followed by histological review and immunohistochemistry is the gold standard to obtain a diagnosis and the most common malignant finding is a primary lung adenocarcinoma. Our objective was to determine whether an intraoperative optical biopsy (molecular imaging) may provide an alternative approach for determining if a pulmonary nodule is a primary lung adenocarcinoma. METHODS Before surgery, 30 patients with an indeterminate pulmonary nodule were intravenously administered a folate receptor-targeted fluorescent contrast agent specific for primary lung adenocarcinomas. During surgery, the nodule was removed and the presence of fluorescence (optical biopsy) was assessed in the operating room to determine if the nodule was a primary pulmonary adenocarcinoma. Standard-of-care frozen section and immunohistochemical staining on permanent sections were then performed as the gold standard to validate the results of the optical biopsy. RESULTS Optical biopsies identified 19 of 19 (100%) primary pulmonary adenocarcinomas. There were no false positive or false negative diagnoses. An optical biopsy required 2.4 minutes compared to 26.5 minutes for frozen section (P < 0.001) and it proved more accurate than frozen section in diagnosing lung adenocarcinomas. CONCLUSIONS An optical biopsy has excellent positive predictive value for intraoperative diagnosis of primary lung adenocarcinomas. With refinement, this technology may prove to be an important supplement to standard pathology for examining close surgical margins, identifying lymph node involvement, and determining whether suspicious nodules are malignant.
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[Nebulized colistin versus tobramycin in the treatment of chronic Pseudomonas colonization in cystic fibrosis patients].
Quintana-Gallego, E, Lopez-Campos, JL, Calero, C, Dapena, FJ
Medicina clinica. 2014;(2):59-63
Abstract
BACKGROUND AND OBJECTIVE To compare the efficacy, safety and treatment satisfaction with inhaled colistin versus tobramycin in the cure of chronic Pseudomonas colonization in cystic fibrosis patients. PATIENTS AND METHOD A quasi-experimental open paired data trial in which patients with cystic fibrosis and chronic colonization by Pseudomonas aeruginosa were included. Patients performed 2 periods of 6 consecutive months of nebulized antibiotics: inhaled tobramycin at a dose of 300 mg/12 h (Pari LC Plus(®)) and colistimethate (I-neb(®)) at a dose of 1 MIU twice a day. Visits were made monthly and at the beginning and the end of each period; we evaluated the body mass index, lung function, number of exacerbations and sputum microbiology. Patient satisfaction was assessed with 2 questionnaires of satisfaction on the treatment and the inhalation devices. RESULTS A group of 25 patients (8 men and 6 under 14 years) with a mean age of 21.4 (7.2) years and 59.8 (21.1) % of forced expiratory volume in one second (FEV1) were included. During the second period, clinical benefits were obtained in terms of lung function with an FEV1 gain of 5% at 6 months of treatment and reducing the number of exacerbations (1.84 [1.2] vs 0.8 [0.8]; P=.001). The questionnaire score was higher in period 2. CONCLUSIONS Colistimethate sodium administered through the misting system I-neb(®) provides clinical benefits in terms of exacerbations and improvement of lung function and patient satisfaction for the nebulized antibiotic treatment.