The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much controversy. Major international guidelines recommend selective use of ICS. ...Recently published meta-analyses have reported conflicting findings on the effects of inhaled steroid therapy in COPD.
To determine the efficacy and safety of inhaled corticosteroids in stable patients with COPD, in terms of objective and subjective outcomes.
A pre-defined search strategy was used to search the Cochrane Airways Group Specialised Register for relevant literature. Searches are current as of July 2011.
We included randomised trials comparing any dose of any type of inhaled steroid with a placebo control in patients with COPD. Acute bronchodilator reversibility to short-term beta(2)-agonists and bronchial hyper-responsiveness were not exclusion criteria. The a priori primary outcome was change in lung function. We also analysed data on mortality, exacerbations, quality of life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and safety.
Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.
Fifty-five primary studies with 16,154 participants met the inclusion criteria. Long-term use of ICS (more than six months) did not consistently reduce the rate of decline in forced expiratory volume in one second (FEV(1)) in COPD patients (generic inverse variance analysis: mean difference (MD) 5.80 mL/year with ICS over placebo, 95% confidence interval (CI) -0.28 to 11.88, 2333 participants; pooled means analysis: 6.88 mL/year, 95% CI 1.80 to 11.96, 4823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (odds ratio (OR) 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long-term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08, 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46, 5586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86, 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years.
Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life and possibly reduced rate of decline in FEV(1)) against the potential side effects (oropharyngeal candidiasis and hoarseness, and risk of pneumonia).
Lung cancer remains the leading cause of cancer-related mortality worldwide. Tobacco consumption remains the most important risk factor. Although the prevalence of smoking has decreased overall, it ...continues to be a significant burden for global health. It is estimated that there are still nearly 1 billion cigarette smokers worldwide. Prevention strategies have largely focused on tobacco control and prevention. However, we have witnessed a dramatic increase in the use of e-cigarettes and other vaping products. Primary chemoprevention has historically not been a successful strategy for lung cancer; however, focused approaches in specific groups of patients at high risk for development of lung cancer are underway. The majority of cases with NSCLC are diagnosed with locally advanced or metastatic disease, where the overall prognosis remains very poor. Early-stage NSCLC on the other hand has a much better prognosis and can usually be treated radically with either surgical resection or radical radiotherapy, with relatively favorable long-term outcomes. In addition to image-based screening, other methods such as breath-based and biofluid-based approaches are now being investigated for early detection of NSCLC. This review will focus on recent advancements in the field of prevention, screening, and early detection of NSCLC.
Abstract Background Lung cancer is the most common type of cancer. Detection of lung cancer at an early stage can reduce mortality rates. Pulmonary nodules may represent early cancer and can be ...identified through computed tomography (CT) scans. Malignant risk can be estimated based on attributes like size, shape, location, and density. Purpose Deep learning algorithms have achieved remarkable advancements in this domain compared to traditional machine learning methods. Nevertheless, many existing anchor‐based deep learning algorithms exhibit sensitivity to predefined anchor‐box configurations, necessitating manual adjustments to obtain optimal outcomes. Conversely, current anchor‐free deep learning‐based nodule detection methods normally adopt fixed‐size nodule models like cubes or spheres. Methods To address these technical challenges, we propose a multiscale 3D anchor‐free deep learning network (M3N) for pulmonary nodule detection, leveraging adjustable nodule modeling (ANM). Within this framework, ANM empowers the representation of target objects in an anisotropic manner, with a novel point selection strategy (PSS) devised to accelerate the learning process of anisotropic representation. We further incorporate a composite loss function that combines the conventional L2 loss and cosine similarity loss, facilitating M3N to learn nodules’ intensity distribution in three dimensions. Results Experiment results show that the M3N achieves 90.6% competitive performance metrics (CPM) with seven predefined false positives per scan on the LUNA 16 dataset. This performance appears to exceed that of other state‐of‐the‐art deep learning‐based networks reported in their respective publications. Individual test results also demonstrate that M3N excels in providing more accurate, adaptive bounding boxes surrounding the contours of target nodules. Conclusions The newly developed nodule detection system reduces reliance on prior knowledge, such as the general size of objects in the dataset, thus it should enhance overall robustness and versatility. Distinct from traditional nodule modeling techniques, the ANM approach aligns more closely with the morphological characteristics of nodules. Time consumption and detection results demonstrate promising efficiency and accuracy which should be validated in clinical settings.
Lung cancer is the most common cause of cancer-related death in the world, however lung cancer screening has not been implemented in most countries at a population level. A previous Cochrane Review ...found limited evidence for the effectiveness of lung cancer screening with chest radiography (CXR) or sputum cytology in reducing lung cancer-related mortality, however there has been increasing evidence supporting screening with low-dose computed tomography (LDCT). OBJECTIVES: To determine whether screening for lung cancer using LDCT of the chest reduces lung cancer-related mortality and to evaluate the possible harms of LDCT screening.
We performed the search in collaboration with the Information Specialist of the Cochrane Lung Cancer Group and included the Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, current issue), MEDLINE (accessed via PubMed) and Embase in our search. We also searched the clinical trial registries to identify unpublished and ongoing trials. We did not impose any restriction on language of publication. The search was performed up to 31 July 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) of lung cancer screening using LDCT and reporting mortality or harm outcomes. DATA COLLECTION AND ANALYSIS: Two review authors were involved in independently assessing trials for eligibility, extraction of trial data and characteristics, and assessing risk of bias of the included trials using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. Primary outcomes were lung cancer-related mortality and harms of screening. We performed a meta-analysis, where appropriate, for all outcomes using a random-effects model. We only included trials in the analysis of mortality outcomes if they had at least 5 years of follow-up. We reported risk ratios (RRs) and hazard ratios (HRs), with 95% confidence intervals (CIs) and used the I
statistic to investigate heterogeneity. MAIN RESULTS: We included 11 trials in this review with a total of 94,445 participants. Trials were conducted in Europe and the USA in people aged 40 years or older, with most trials having an entry requirement of ≥ 20 pack-year smoking history (e.g. 1 pack of cigarettes/day for 20 years or 2 packs/day for 10 years etc.). One trial included male participants only. Eight trials were phase three RCTs, with two feasibility RCTs and one pilot RCT. Seven of the included trials had no screening as a comparison, and four trials had CXR screening as a comparator. Screening frequency included annual, biennial and incrementing intervals. The duration of screening ranged from 1 year to 10 years. Mortality follow-up was from 5 years to approximately 12 years. None of the included trials were at low risk of bias across all domains. The certainty of evidence was moderate to low across different outcomes, as assessed by GRADE. In the meta-analysis of trials assessing lung cancer-related mortality, we included eight trials (91,122 participants), and there was a reduction in mortality of 21% with LDCT screening compared to control groups of no screening or CXR screening (RR 0.79, 95% CI 0.72 to 0.87; 8 trials, 91,122 participants; moderate-certainty evidence). There were probably no differences in subgroups for analyses by control type, sex, geographical region, and nodule management algorithm. Females appeared to have a larger lung cancer-related mortality benefit compared to males with LDCT screening. There was also a reduction in all-cause mortality (including lung cancer-related) of 5% (RR 0.95, 95% CI 0.91 to 0.99; 8 trials, 91,107 participants; moderate-certainty evidence). Invasive tests occurred more frequently in the LDCT group (RR 2.60, 95% CI 2.41 to 2.80; 3 trials, 60,003 participants; moderate-certainty evidence). However, analysis of 60-day postoperative mortality was not significant between groups (RR 0.68, 95% CI 0.24 to 1.94; 2 trials, 409 participants; moderate-certainty evidence). False-positive results and recall rates were higher with LDCT screening compared to screening with CXR, however there was low-certainty evidence in the meta-analyses due to heterogeneity and risk of bias concerns. Estimated overdiagnosis with LDCT screening was 18%, however the 95% CI was 0 to 36% (risk difference (RD) 0.18, 95% CI -0.00 to 0.36; 5 trials, 28,656 participants; low-certainty evidence). Four trials compared different aspects of health-related quality of life (HRQoL) using various measures. Anxiety was pooled from three trials, with participants in LDCT screening reporting lower anxiety scores than in the control group (standardised mean difference (SMD) -0.43, 95% CI -0.59 to -0.27; 3 trials, 8153 participants; low-certainty evidence). There were insufficient data to comment on the impact of LDCT screening on smoking behaviour. AUTHORS' CONCLUSIONS: The current evidence supports a reduction in lung cancer-related mortality with the use of LDCT for lung cancer screening in high-risk populations (those over the age of 40 with a significant smoking exposure). However, there are limited data on harms and further trials are required to determine participant selection and optimal frequency and duration of screening, with potential for significant overdiagnosis of lung cancer. Trials are ongoing for lung cancer screening in non-smokers.
ABSTRACT
Particulate matter (PM) emissions involve a complex mixture of solid and liquid particles suspended in a gas, where it is noted that PM emissions from diesel engines are a major contributor ...to the ambient air pollution problem. While epidemiological studies have shown a link between increased ambient PM emissions and respiratory morbidity and mortality, studies of this design are not able to identify the PM constituents responsible for driving adverse respiratory health effects. This review explores in detail the physico‐chemical properties of diesel PM (DPM) and identifies the constituents of this pollution source that are responsible for the development of respiratory disease. In particular, this review shows that the DPM surface area and adsorbed organic compounds play a significant role in manifesting chemical and cellular processes that if sustained can lead to the development of adverse respiratory health effects. The mechanisms of injury involved included inflammation, innate and acquired immunity, and oxidative stress. Understanding the mechanisms of lung injury from DPM will enhance efforts to protect at‐risk individuals from the harmful respiratory effects of air pollutants.
Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and ...without lung cancer. Methods: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non-smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Serum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. Results: 15 miRNAs were differentially expressed between lung cancer and healthy non-smoking participants, with the greatest single miRNA being miR-205-5p (AUC 0.850), improving to AUC 0.993 in combination with miR-199a-5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR-497-5p (AUC 0.873), improving to AUC 0.953 in combination with miR-22-5p; 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR-27a-3p (AUC 0.803), with two other miRNAs (miR-106b-3p and miR-361-5p) further improving discriminatory power (AUC 0.870). Conclusion: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.
MicroRNAs (miRNAs) are a family of small, non-coding RNA species functioning as negative regulators of multiple target genes including tumour suppressor genes and oncogenes. Many miRNA gene loci are ...located within cancer-associated genomic regions. To identify potential new amplified oncogenic and/or deleted tumour suppressing miRNAs in lung cancer, we inferred miRNA gene dosage from high dimensional arrayCGH data. From miRBase v9.0 (http://microrna.sanger.ac.uk), 474 human miRNA genes were physically mapped to regions of chromosomal loss or gain identified from a high-resolution genome-wide arrayCGH study of 132 primary non-small cell lung cancers (NSCLCs) (a training set of 60 squamous cell carcinomas and 72 adenocarcinomas). MiRNAs were selected as candidates if their immediately flanking probes or host gene were deleted or amplified in at least 25% of primary tumours using both Analysis of Copy Errors algorithm and fold change (≥ ± 1.2) analyses. Using these criteria, 97 miRNAs mapped to regions of aberrant copy number. Analysis of three independent published lung cancer arrayCGH datasets confirmed that 22 of these miRNA loci showed directionally concordant copy number variation. MiR-218, encoded on 4p15.31 and 5q35.1 within two host genes (SLIT2 and SLIT3), in a region of copy number loss, was selected as a priority candidate for follow-up as it is reported as underexpressed in lung cancer. We confirmed decreased expression of mature miR-218 and its host genes by qRT-PCR in 39 NSCLCs relative to normal lung tissue. This downregulation of miR-218 was found to be associated with a history of cigarette smoking, but not human papilloma virus. Thus, we show for the first time that putative lung cancer-associated miRNAs can be identified from genome-wide arrayCGH datasets using a bioinformatics mapping approach, and report that miR-218 is a strong candidate tumour suppressing miRNA potentially involved in lung cancer.
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