Increased risk of cancer among gout patients: a nationwide population study

ObjectiveFew studies have investigated the association between gout and cancer. The present study examined the relative risk of cancer in a nationwide cohort.MethodsThe primary data source was the National Health Insurance database of Taiwan. Data recorded between 2000 and 2008 for subjects ≥ 20 years and with no history of malignancy were included for the analysis. A gout case definition was defined by records of gout diagnosis and anti-gout treatment (urate-lowering drugs, including allopurinol, benzbromazone, probenacid and sulfinpyrazone, and colchicine). Cox proportional hazards models were used to examine the association between gout and cancer.ResultsA total of 694,361 patients (355,278 men, 339,083 women) were included; among them, 25,943 had a history of gout. Mean age (± standard deviation) was 42.3 ± 16.3 years. During 5,471,272 patient-years of follow-up, cancer was detected in 24,088 patients (1745 with gout and 22,343 controls). The most cancers were liver, lung, and colonic cancers. The overall incidence of cancer was significantly higher among gout patients than controls (8.7 vs. 4.2 cases per 1000 patient-years, P < 0.001). After adjustment for age and sex, gout was found to be associated with a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.10–1.21; P < 0.001) for cancer. Gout was most closely associated with prostate cancer, with an age- and sex-adjusted HR of 1.71 (1.45–2.02). On the other hand, gout tended to have an inverse, albeit insignificant, association with breast cancer (adjusted HR, 0.81; 95% CI, 0.63–1.04).ConclusionGout was associated with increased risk of cancer, particularly that of prostate cancer in males.     

Hypermethylation of Anti-oncogenic MicroRNA 7 is Increased in Emphysema Patients

IntroductionMicroRNA-7 (miR-7) has a suppressive role in lung cancer and alterations in its DNA methylation may contribute to tumorigenesis. As COPD patients with emphysema have a higher risk of lung cancer than other COPD phenotypes, we compared the miR-7 methylation status among smoker subjects and patients with various COPD phenotypes to identify its main determinants.Methods30 smoker subjects without airflow limitation and 136 COPD patients without evidence of cancer were recruited in a prospective study. Clinical and functional characteristics were assessed and patients were classified into: frequent exacerbator, emphysema, chronic bronchitis and asthma COPD overlap (ACO). DNA collected from buccal epithelial samples was isolated and bisulfite modified. miR-7 methylation status was evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).ResultsmiR-7 Methylated levels were higher in COPD patients than in smokers without airflow limitation (23.7 ± 12.4 vs. 18.5 ± 8.8%, p = 0.018). Among COPD patients, those with emphysema had higher values of methylated miR-7 (27.1 ± 10.2%) than those with exacerbator (19.4 ± 9.9%, p = 0.004), chronic bronchitis (17.3 ± 9.0%, p = 0.002) or ACO phenotypes (16.0 ± 7.2%, p = 0.010). After adjusting for clinical parameters, differences between emphysematous patients and those with other phenotypes were retained. In COPD patients, advanced age, mild-moderate airflow limitation, reduced diffusing capacity and increased functional residual capacity were identified as independent predictors of methylated miR-7 levels.ConclusionThe increase of miR-7 methylation levels experienced by COPD patients occurs mainly at the expense of the emphysema phenotype, which might contribute to explain the higher incidence of lung cancer in these patients.     

El papel de la metaloproteinasa de la matriz MMP-9 y del inhibidor tisular de metaloproteinasa TIMP-2 como marcadores séricos de cáncer vesical

IntroductionThe diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer.Material and methodQuantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves.ResultsThere is a correlation between the determinations of MMP-2 and TIMP-2 (R = .699; P > .0001) and MMP-9 and TIMP-2 (R = .305; P = .049). Patients with bladder cancer have higher levels of MMP-9 (p < 0.0001) and TIMP-2 (P = .047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P < .001). Differences were not detected between cancer and controls regarding age (P = .64) or gender (P = .64). Differences were also not detected regarding MMP-2 (P = .35) or MMP-2/TIMP-2 rate (P = .45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P = .022 and P = .038, respectively) and those of the TIMP-2 according to M category (P = .036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively.ConclusionsThe results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of bladder cancer, and a potential utility as clinical markers of the disease. Multicenter, prospective studies that confirm their preliminary results are necessary.     

Perioperative risks of narcolepsy in patients undergoing general anesthesia: A case-control study

Study objectiveTo compare the perioperative outcomes between patients with narcolepsy and matched controls undergoing anesthetic management.DesignRetrospective 2:1 matched study design.SettingLarge tertiary medical center.PatientsNarcoleptic patients who underwent general anesthesia from January 1, 2011, through September 30, 2015, were matched with controls by age, sex, and type and year of surgery.MeasurementsMedical records were reviewed for episodes of respiratory depression during phase I recovery and for other meaningful perioperative outcomes.Main resultsThe perioperative courses of 76 narcoleptic patients and their controls were examined. Compared to controls, narcoleptic patients were more often prescribed central nervous system stimulants (73.7% vs 4.0%, P < 0.001) and antidepressants (46.1% vs 27.6%, P = 0.007) and more often had obstructive sleep apnea (40.8% vs 19.1%, P < 0.001). The intraoperative course was similar. The number of episodes of respiratory depression was not different between patients and controls (5 [6.6%] vs 12 [7.9%], respectively; P = 0.80). Narcoleptic patients had a higher frequency of emergency response team activations (5 of 76 [6.6%]; 95% CI, 2.2%–14.7%) compared to controls (2 of 152 [1.3%]; 95% CI, 0.2%–4.7%) (P = 0.04). Hemodynamic instability was the indication for all emergency response team activations except 1, which was for a narcoleptic patient who had excessive postoperative sedation and respiratory depression.ConclusionsNarcoleptic patients had similar intraoperative courses as the matched controls, including phase I anesthetic recovery. However, they had a higher rate of emergency response team activations than the controls, which suggests that patients with narcolepsy may be at increased perioperative risk.     

Molecular analysis of changes in Pseudomonas aeruginosa load during treatment of a pulmonary exacerbation in cystic fibrosis

BackgroundIntravenous antibiotics for pulmonary exacerbations (PEs) of cystic fibrosis (CF) usually target Pseudomonas aeruginosa. Insights into the CF lung microbiome have questioned this approach. We used RT-qPCR to determine whether intravenous antibiotics reduced P. aeruginosa numbers and whether this correlated with improved lung function. We also investigated antibiotic effects on other common respiratory pathogens in CF.MethodsSputa were collected from patients when stable and again during a PE. Sputa were expectorated into a RNA preservation buffer for RNA extraction and preparation of cDNA. qPCR was used to enumerate viable P. aeruginosa as well as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Burkholderia cepacia complex and Aspergillus fumigatus.ResultsFifteen CF patients were followed through 21 PEs. A complete set of serial sputum samples was unavailable for two patients (three separate PEs). P. aeruginosa numbers did not increase immediately prior to a PE, but numbers during intravenous antibiotic treatment were reduced ≥ 4-log in 6/18 and ≥ 1-log in 4/18 PEs. In 7/18 PEs, P. aeruginosa numbers changed very little with intravenous antibiotics and one patient demonstrated a ≥ 2-log increase in P. aeruginosa load. H. influenzae and S. pneumoniae were detected in ten and five PEs respectively, but with antibiotic treatment these bacteria rapidly became undetectable in 6/10 and 4/5 PEs, respectively. There was a negative correlation between P. aeruginosa numbers and FEV₁ during stable phase (r_s = 0.75, p < 0.05), and reductions in P. aeruginosa load with intravenous antibiotic treatment correlated with improved FEV₁ (r_s = 0.52, p < 0.05).ConclusionsExacerbations are not due to increased P. aeruginosa numbers in CF adults. However, lung function improvements correlate with reduced P. aeruginosa burden suggesting that current antibiotic treatment strategies remain appropriate in most patients. Improved understanding of PE characterised by unchanged P. aeruginosa numbers and minimal lung function improvement following treatment may allow better targeted therapies.     

Detection and molecular staging of bladder cancer using real-time RT-PCR for gelatinases (MMP-2, MMP-9) and TIMP-2 in peripheral blood

IntroductionMolecular staging of bladder cancer based on the detection of mRNA of urothelial specific genes in circulating cancer cells has been inconclusive. We analyze whether real-time RT-PCR evaluation of gelatinases (MMP-9, MMP-2) and TIMP-2 in peripheral blood to diagnose and characterize patients with bladder neoplasm.Material and methodTotal RNA is extracted from circulating blood cells in 42 individuals (11 healthy controls, 31 patients with bladder cancer of different stages) and real-time RT-PCR performed using specific primers for MMP-9, MMP-2, TIMP-2 and ribosomal 18S. The quantification values of mRNA are described as relative to 18S mRNA (ΔΔCt method) and the results are blindly compared with data obtained from histological diagnosis and clinical staging.ResultsNormalized levels of MMP-9 and MMP-2 mRNA are higher in patients with cancer than controls (1.82 ± 0.6-fold and 2.7 ± 0.6-fold, respectively; P < .05). Patients with metastatic disease also have increased MMP-9, MMP-2 and TIMP-2 mRNA levels (9.6 ± 0,20-fold, 5.22 ± 0.26-fold and 1,97 ± 0,22-fold, respectively; P < .05). MMP-9 and MMP-2 are also associated with advanced clinical stage and grade (P < .05). A ratio between variables that increases the ability to segregate patients with Ta, T1, T2-4M0 and T2-4M1 tumours is proposed.ConclusionsBoth non-invasive bladder tumor recognition and molecular staging of the disease is possible using real-time RT-PCR-based detection of gelatinases and TIMP-2 in peripheral blood. The ability to distinguish metastatic disease is higher for MMP-9 but MMP-2 discriminates better levels of tumour invasion. Further investigation in this field could yield promising results regarding molecular evaluation of bladder neoplasia.     

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors.MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed.Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n = 9), bladder tumor (n = 7), testis tumors (n = 4), and prostate cancer (n = 2). There was no intraoperative complication. Postoperative complications were seen in 2 patients.ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.     

HLA association with the susceptibility to anti-synthetase syndrome

ObjectiveTo investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD).MethodsWe conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing.ResultsA statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed.ConclusionsOur results support the association of the HLA complex with the susceptibility to ASSD.     

Terapia de privación de andrógenos y obesidad mórbida: ¿tienen en común el riesgo cardiovascular por síndrome metabólico?

BackgroundAlthough the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal.ObjectivesEvaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men.MethodsThis is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese.ResultsPatients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97 ± 12.53% vs. 26.09 ± 14.80%; p = 0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p = 0.054).ConclusionThis study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.     

Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients

BackgroundThe clinical course of cystic fibrosis (CF) lung disease varies between patients bearing identical CFTR mutations. This suggests that additional genetic modifiers may contribute to the pulmonary phenotype. The highly conserved ancestral haplotype 8.1 (8.1AH), carried by up to one quarter of Caucasians, comprises linked gene polymorphisms on chromosome 6 that play a key role in the inflammatory response: LTA + 252A/G; TNF −308G/A, HSP70-2 + 1267A/G and RAGE −429T/C. As inflammation is a key component inducing CF lung damage, we investigated whether the 8.1AH represents a lung function modifier in CF.MethodsWe analyzed the lung function of 404 European CF patients from France (n = 230), Germany (n = 95) and UK (n = 79). FEV₁ differences between 8.1AH carriers and non-carriers were calculated in each country and pooled using a random effects model.ResultsThe frequency of 8.1AH carriers was similar between French (22%), German (29%) and UK (27%) patients. We found that 8.1AH carriers had significantly lower FEV₁, adjusted for age classes and countries (P < 0.04, mean FEV₁ difference − 6.4% CI95% [− 12.4%, − 0.5%]). No difference was observed with respect to BMI Z-scores and chronic colonization with P. aeruginosa.ConclusionsThese findings support the concept that 8.1AH is an important genetic modifier of lung disease in CF. To conclude, multiple linked genes outside the CF locus might explain some of the variability in lung phenotype.     

Lung transplantation in cystic fibrosis normalizes essential fatty acid profiles

BackgroundCystic fibrosis (CF) can be a devastating disease. Disorders in essential fatty acid state are increasingly reported and various supplementation trials have been performed in an attempt to improve outcomes. However, the mechanisms leading to these disturbances remain elusive.We wanted to investigate the role of the diseased CF lung on fatty acid profiles.MethodsWe compared fatty acid profiles in patients with CF after lung transplantation (n = 11) to age-matched healthy controls and homozygous F508del patients (n = 22 each).ResultsCompared to healthy controls, in patients with CF, there are decreased levels of docosahexaenoic, linoleic and arachidonic acid and increased levels of mead acid. In patients that underwent a lung transplantation, levels of docosahexaenoic, linoleic and arachidonic acid were normal. Mead acid did not decrease significantly.ConclusionsThe diseased CFTR deficient lung is a major determinant in the disturbed fatty acid profile in CF.     

Management of bone fragility in patients with rheumatoid arthritis in France: An analysis of a national health insurance claims database

ObjectivesRheumatoid arthritis (RA) is considered a major risk factor for fragility fractures. We examined the quality of management of bone fragility in RA patients in a real-life setting.MethodsWe performed a longitudinal case-control retrospective study in a 1/97th random sample of French health care claims database from 2014 to 2016 to determine the extent of bone fragility management in patients with RA compared with non-RA matched controls.ResultsCompared to their non-RA controls (n = 4652), RA patients (n = 1008; mean age: 61.1 years; methotrexate: 69.7%; other conventional disease-modifying antirheumatic drugs (cDMARDs): 26.8%; biologic: 26.0%; corticosteroids: 36.9%) had more reimbursements for bone mineral density (BMD) measurements (21.6 vs. 9.2%; OR = 2.7 [2.3; 3.3]; P < 0.01) and for bisphosphonates (7.1 vs. 3.6%, OR = 2.0 [1.5; 2.7]; P < 0.05). In patients exposed to corticosteroids, RA patients underwent more BMD assessments than non-RA controls (28.0 vs. 18.8%; OR = 1.7 [1.3; 2.2]; P < 0.05). RA patients exposed to corticosteroids were more likely to sustain fracture than non-exposed RA patients (5.7 vs. 2.4%, P < 0.01). In addition, only when comparing patients exposed to corticosteroids, was there statistical evidence of an association between RA and an increased fracture rate (6.2 vs. 3.5%, P < 0.05).ConclusionPatients with RA exposed to corticosteroids are at high risk of fracture. Patients with RA had more bone fragility management than controls.     

Colonisation and infection of the paranasal sinuses in cystic fibrosis patients is accompanied by a reduced PMN response

BackgroundWe studied whether the sinuses might be foci for Pseudomonas aeruginosa lung infection.MethodsEndoscopic Sinus Surgery was performed in 78 CF patients; PFGE was used for bacterial genotyping. Material from sinuses and lungs were Gram-stained to detect biofilms. Immunoglobulins were measured in serum and saliva.ResultsWhen P. aeruginosa was cultured simultaneously from the sinuses and the lungs they were genetically identical in 38 of the 40 patients (95%). In the sinuses, P. aeruginosa formed biofilms with minimal cellular inflammation, probably because of a significantly higher local production of secretory IgA compared with IgG (p < 0.001).ConclusionsWe have shown that P. aeruginosa form biofilm in the sinuses, which constitute an important bacterial reservoir for subsequent lung infection. The high amount of IgA in the upper airways probably protects P. aeruginosa from the inflammatory immune system, and they can proceed unnoticed into a permanent infectious focus that cannot be eradicated with antibiotics.     

Plasma mitochondrial DNA levels were independently associated with lung injury in elderly hip fracture patients

IntroductionHip fracture in the elderly can induce systemic inflammatory response (SIRS) and lung injury which increases the risk of lung infection and death. Mitochondrial DNA (mtDNA) plays a role in SIRS and lung injury in patients with multi-trauma, and also in patients with hip fractures. This study evaluated the potential value of plasma mtDNA in the early prognosis of lung injury in elderly fracture patients.MethodsThis study enrolled 156 elderly patients with intertrochanteric fracture. Plasma mtDNA, IL-6, IL-10, prostaglandin E2 (PGE2) levels were measured at admission. Sixty-one and 31 patients were diagnosed with systemic inflammatory response syndrome (SIRS) and lung injury, respectively.ResultsPlasma mtDNA levels were higher in hip fracture patients compared to healthy controls (P < 0.001) and significantly higher in the lung injury subgroup compared to the lung injury absent subgroup (P < 0.001). MtDNA levels were correlated with the SIRS score (r = 0.446, P < 0.001), IL-6 (r = 0.506, P < 0.001), IL-10 (r = 0.523, P < 0.001), and PGE2 (r = 0.360, P < 0.001). Logistic regression analysis revealed that plasma mtDNA, IL-6, PGE2 and SIRS score were independent predictors of the risk of lung injury.ConclusionPlasma mtDNA release induced by hip fracture in elderly patients, might be an early predictor of lung injury in these patients.     

Nutritional decline in cystic fibrosis related diabetes: The effect of intensive nutritional intervention

BackgroundReports indicate that nutritional and respiratory decline occur up to four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim was to establish whether intensive nutritional intervention prevents pre-diabetic nutritional decline in an adult population with CFRD.Methods48 adult patients with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen status. Nutritional and other clinical indices were recorded at annual intervals from six years before until two years after diagnosis. Data were also analysed to examine the impact of early and late acquisition of CFRD.ResultsNo important differences in weight, height, body mass index (BMI), lung function or intravenous treatment were found between groups in the six years prior to diagnosis, nor any significant deviation over time. In those who developed diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF Controls), OR 4.0, CI 1.3 to 16.4, p = 0.01]. Age at onset of CFRD played a significant role in determining the pre-diabetic clinical course. Younger diabetics with continued growth at study onset (n = 17) had a lower BMI from 2 years prior to diagnosis compared to controls [BMI 18.9 kg/m² (CFRD) v 20.8 kg/m² (CF Controls), diff = 1.9, CI − 0.1 to 3.7 p = 0.04]. The BMI of older diabetics (completed growth at study onset) was equal to that of controls throughout.ConclusionPre-diabetic nutritional decline is not inevitable in adults with CFRD, but is influenced by age of onset. In the group overall, those with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite intensive nutritional intervention, patients who continue to grow throughout the pre-diabetic years, show a level of nutritional decline absent in older adults.     

Psoas Muscle Density Evaluated by Chest CT and Long-Term Mortality in COPD Patients

RationalePoor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality.MethodsAt baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65 ± 8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48–119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality.ResultsPsD was lower in COPD patients than in controls (40.5 vs 42.5, p = 0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV₁%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02–1.12, p = 0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94–0.99, p = 0.023) were the variables independently associated with all-cause mortality.ConclusionsIn COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.     

Pulmonary outcome differences in U.S. and French cystic fibrosis cohorts diagnosed through newborn screening

BackgroundA comparison of the longitudinal progression of lung disease in cystic fibrosis patients identified through newborn screening (NBS) in cohorts located in two different countries has never been performed and was the primary objective of this study.MethodsThe study included 56 patients in Brittany diagnosed through NBS between 1989 and 1994 and 69 similar patients in Wisconsin between 1985 and 1994. The onset and progression of lung disease was radiographically quantified using the Wisconsin Chest X-ray (WCXR) scoring system. A single pediatric pulmonologist blinded to all identifiers scored the films.ResultsGeneralized estimating equation analyses adjusted for age, genotype, sex, pancreatic insufficiency, and meconium ileus showed worse WCXR scores in Brittany patients compared to Wisconsin patients (average score difference = 4.48; p < 0.001). Percent predicted FEV1 was also worse among Brittany patients (p < 0.001).ConclusionsThe finding of milder radiographically-quantified lung disease using the WCXR scoring system, as well as better FEV1 values, may be explained by variations in nutrition, environmental exposures, or healthcare delivery.     

Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on respiratory microbiota composition

Background

G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised.