Little is known about the clinical factors associated with the development of lung cancer in patients with chronic obstructive pulmonary disease (COPD), although airway obstruction and emphysema have ...been identified as possible risk factors.
To explore incidence, histologic type, and factors associated with development of lung cancer diagnosis in a cohort of outpatients with COPD attending a pulmonary clinic.
A cohort of 2,507 patients without initial clinical or radiologic evidence of lung cancer was followed a median of 60 months(30–90). At baseline, anthropometrics, smoking history, lung function,and body composition were recorded. Time to diagnosis and histologic type of lung cancer was then registered. Cox analysis was used to explore factors associated with lung cancer diagnosis.
A total of 215 of the 2,507 patients with COPD developed lung cancer (incidence density of 16.7 cases per 1,000 person-years). The most frequent type was squamous cell carcinoma (44%). Lung cancer incidence was lower in patients with worse severity of airflow obstruction. Global Initiative for Chronic Obstructive Lung Disease Stages I and II, older age, lower body mass index,and lung diffusion capacity of carbon monoxide less than 80%were associated with lung cancer diagnosis.
Incidence density of lung cancer is high in outpatients with COPD and occurs more frequently in older patients with milder airflow obstruction (Global Initiative for Chronic Obstructive Lung Disease Stages I and II) and lower body mass index. A lung diffusion capacity of carbon monoxide less than 80% is associated with cancer diagnosis. Squamous cell carcinoma is the most frequent histologic type. Knowledge of these factors may help direct efforts for early detection of lung cancer and disease management.
The true role of entanglement in two-photon virtual-state spectroscopy (Saleh et al 1998 Phys. Rev. Lett. 80 3483), a two-photon absorption spectroscopic technique that can retrieve information about ...the energy level structure of an atom or a molecule, is controversial. The consideration of closely related techniques, such as multidimensional pump-probe spectroscopy (Roslyak et al 2009 Phys. Rev. A 79, 063409), suggests that spectroscopic information might also be retrieved by using uncorrelated pairs of photons. Here we show that this is not the case. In the two-photon absorption process, the ability to obtain information about the energy level structure of a medium depends on the spectral shape of existing temporal (frequency) correlations between the absorbed photons. In fact, it is a combination of both the presence of frequency correlations (entanglement) and their specific spectral shape that makes the realization of two-photon virtual-state spectroscopy possible. This result helps in selecting the type of two-photon source that needs to be used in order to experimentally perform the two-photon virtual-state spectroscopy technique.
Aspergillus niger
is widely used as a cell factory for the industrial production of enzymes. Previously, it was shown that deletion of α-1–3 glucan synthase genes results in smaller micro-colonies in ...liquid cultures of
Aspergillus nidulans
. Also, it has been shown that small wild-type
Aspergillus niger
micro-colonies secrete more protein than large mirco-colonies. We here assessed whether deletion of the
agsC
or
agsE
α-1–3 glucan synthase genes results in smaller
A. niger
micro-colonies and whether this is accompanied by a change in protein secretion. Biomass formation was not affected in the deletion strains but pH of the culture medium had changed from 5.2 in the case of the wild-type to 4.6 and 6.4 for Δ
agsC
and Δ
agsE,
respectively. The diameter of the Δ
agsC
micro-colonies was not affected in liquid cultures. In contrast, diameter of the Δ
agsE
micro-colonies was reduced from 3304 ± 338 µm to 1229 ± 113 µm. Moreover, the Δ
agsE
secretome was affected with 54 and 36 unique proteins with a predicted signal peptide in the culture medium of MA234.1 and the Δ
agsE,
respectively. Results show that these strains have complementary cellulase activity and thus may have complementary activity on plant biomass degradation. Together, α-1–3 glucan synthesis (in)directly impacts protein secretion in
A. niger
.
To compare gender differences in the clinical expression of COPD patients attending a pulmonary clinic.
We compared 53 FEV1-matched men and women with COPD attending a pulmonary clinic. We studied ...age, smoking pack-years history, Pao2, Paco2, functional residual capacity, body mass index (BMI), dyspnea, 6-min walk distance (6MWD), health-related quality of life, presence of comorbidities, and exacerbations in the previous year.
Women were younger (57 years vs 65 years, p < 0.05), smoked less (48 pack-years vs 69 pack-years, p < 0.05), had better Pao2 (74 mm Hg vs 67 mm Hg, p < 0.05), lower Paco2 (40 mm Hg vs 45 mm Hg, p < 0.05), lower BMI (25 vs 28, p < 0.05), more exacerbations in the last year (1 vs 0, p < 0.05), and fewer comorbidities (Charlson score 2 vs score 4, p < 0.05) than men. Even though women had the same FEV1, better oxygenation, better Paco2, and fewer comorbidities, they performed poorer in walking distance (6MWD percentage of predicted, 87% vs 105%; p = 0.05), had worse quality-of-life scores (Saint George's Respiratory Questionnaire SGRQ symptoms score, 51 vs 41, p < 0.05; SGRQ activity score, 58 vs 47, p < 0.05), and had a higher degree of dyspnea (Modified Medical Research Council scale > 2, 28% vs 6%, p = 0.05).
In a population of patients with COPD attending a pulmonary clinic, there are gender-related differences in the clinical expression of COPD that need further attention.
To compare the efficacy of pre-emptive versus empirical antifungal therapy in children with cancer, fever and neutropenia.
This was a prospective, multicentre, randomized clinical trial. Children ...presenting with persistent high-risk febrile neutropenia at five hospitals in Santiago, Chile, were randomized to empirical or pre-emptive antifungal therapy. The pre-emptive group received antifungal therapy only if the persistent high-risk febrile neutropenia was accompanied by clinical, laboratory, imaging or microbiological pre-defined criteria. The primary endpoint was overall mortality at day 30 of follow-up. Secondary endpoints included invasive fungal disease (IFD)-related mortality, number of days of fever, days of hospitalization and use of antifungal drugs, percentage of children developing IFD, requiring modification of initial treatment strategy and need for ICU. The trial was registered with Registro Brasileiro de Ensaios Cl쭩cos (ReBEC) under trial number RBR-3m9d74.
A total of 149 children were randomized, 73 to empirical therapy and 76 to pre-emptive therapy. Thirty-two out of 76 (42%) children in the pre-emptive group received antifungal therapy. The median duration of antifungal therapy was 11 days in the empirical arm and 6 days in the pre-emptive arm (P < 0.001), with similar overall mortality (8% in the empirical arm and 5% in the pre-emptive arm, P = 0.47). IFD-related mortality was the same in both groups (3%, P = 0.97), as were the percentage of children with IFD (12%, P = 0.92) and the number of days of fever (9, P = 0.76). The number of days of hospitalization was 19 in the empirical arm and 17 in the pre-emptive arm (P = 0.15) and the need for ICU was 25% in the empirical arm and 20% in the pre-emptive arm (P = 0.47).
Pre-emptive antifungal therapy was as effective as empirical antifungal therapy in children with cancer, fever and neutropenia, significantly reducing the use of antifungal drugs.
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Lung Cancer (LC) screening with low dose chest computed tomography (LDCT) in smokers reduces LC mortality. Patients with Obstructive Lung Disease (OLD) are at high risk for LC. The ...potential effect of LC screening in this population is unknown.
To determine if screening with LDCT reduces LC mortality in smokers with spirometrically defined OLD.
The National Lung Screening Trial-American College of Radiology Imaging Network (NLST-ACRIN) study included 13,831 subjects (55–74 years of age with ≥30 pack-year history of smoking) that had a baseline spirometry. Randomly assigned to LDCT or Chest X-ray, all had 3 annual rounds of screening. LC mortality was compared between the LDCT and chest X-ray arms during the 1st year and at 6 years of follow up. Landmark analysis explored LC mortality differences between arms after the first year.
From the 4584 subjects with OLD (FEV1/FVC <0.7), 152 (3.3%) died from LC. Multivariable analysis showed that screening trended to decrease LC mortality at 6 years (HR, 95%CI: 0.75, 0.55–1.04, p=0.09). During the 1st year no differences were found between arms (p=0.65). However, after this year, LDCT significantly decreased LC mortality (HR, 95%CI: 0.63, 0.44–0.91, p=0.01). The number needed to screen to avoid one LC death in these subjects was 108 while in those without OLD was 218.
LC screening with LDCT in smokers with spirometrically diagnosed OLD, showed a trend to reduce lung cancer mortality but a study with a larger number of patients and with a more robust design would be needed to confirm these findings.
El cribado de cáncer de pulmón (CP) utilizando la tomografía computarizada de baja dosis (LDCT, por sus siglas en inglés) de tórax en fumadores reduce la mortalidad por CP. Los pacientes con enfermedad pulmonar obstructiva (EPO) tienen un riesgo alto de presentar CP. Se desconoce el posible efecto del cribado de CP en esta población.
Determinar si el cribado con LDCT reduce la mortalidad por CP en los fumadores con EPO diagnosticada mediante espirometría.
El estudio de cribado de pulmón National Lung Screening Trial-American College of Radiology Imaging Network (NLST-ACRIN) incluyó a 13.831 sujetos (de entre 55-74 años de edad, con historia de tabaquismo de ≥30 paquetes-años) a los que se les había realizado una espirometría basal. Se los asignó aleatoriamente a LDCT o radiografía de tórax y todos pasaron por 3 rondas anuales de cribado. La mortalidad por CP se comparó entre los brazos del LDCT y radiografía de tórax durante el primer año y a los 6 años de seguimiento. El análisis de supervivencia con punto temporal de referencia (landmark analysis) estudió las diferencias en la mortalidad por CP entre los brazos después del primer año.
De los 4.584 sujetos con EPO (FEV1/FVC < 0,7), 152 (3,3%) murieron por CP. El análisis multivariante mostró que el cribado tendía a disminuir la mortalidad por CP a los 6 años (HR: 0,75, IC del 95%; 0,55-1,04, p = 0,09). Durante el primer año no se encontraron diferencias entre los brazos (p = 0,65). Sin embargo, después del año, la LDCT disminuyó significativamente la mortalidad por CP (HR: 0,63, IC del 95%: 0,44-0,91, p = 0,01). El número necesario de cribados para evitar una muerte por CP en estos sujetos fue 108, mientras que en aquellos sin EPO fue 218.
El cribado de CP con LDCT en fumadores con EPO diagnosticada mediante espirometría mostró una tendencia a reducir la mortalidad por cáncer de pulmón, pero sería necesario un estudio con un mayor número de pacientes y con un diseño más robusto para confirmar estos hallazgos.
OBJECTIVE The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative ...for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea. METHODS We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1 , 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months. RESULTS Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥ 17 and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores ≥ 2 to predict all-cause mortality. CONCLUSIONS The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov
Abstract
Background
There has been debate on whether inhaled corticosteroids (ICS) reduce the incidence of lung cancer amongst patients with Chronic Obstructive Lung Disease (COPD). We aimed to ...perform a systematic review and dose–response meta-analysis on available observational data.
Methods
We performed both a dose response and high versus low random effects meta-analysis on observational studies measuring whether lung cancer incidence was lower in patients using ICS with COPD. We report relative risk (RR) with 95% confidence intervals (CI), as well as risk difference. We use the GRADE framework to report our results.
Results
Our dose–response suggested a reduction in the incidence of lung cancer for every 500 ug/day of fluticasone equivalent ICS (RR 0.82 95% 0.68–0.95). Using a baseline risk of 7.2%, we calculated risk difference of 14 fewer cases per 1000 (95% CI 24.7–3.8 fewer). Similarly, our results suggested that for every 1000 ug/day of fluticasone equivalent ICS, there was a larger reduction in incidence of lung cancer (RR 0.68 0.44–0.93), with a risk difference of 24.7 fewer cases per 1000 (95% CI 43.2–5.4 fewer). The certainty of the evidence was low to very low, due to risk of bias and inconsistency.
Conclusion
There may be a reduction in the incidence for lung cancer in COPD patients who use ICS. However, the quality of the evidence is low to very low, therefore, we are limited in making strong claims about the true effect of ICS on lung cancer incidence.
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