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Smoking cessation has reduced the incidence of lung cancer. The authors of this review discuss recent progress in diagnostic and treatment approaches, including molecular characterization to determine the likelihood of a response to targeted agents and immunotherapies.

Chronic obstructive pulmonary disease (COPD) kills more than 3 million people worldwide every year. Despite progress in the treatment of symptoms and prevention of acute exacerbations, few advances have been made to ameliorate disease progression or affect mortality. A better understanding of the complex disease mechanisms resulting in COPD is needed. Smoking cessation programmes, increasing physical activity, and early detection and treatment of comorbidities are further key components to reduce the burden of the disease. However, without a global political and economic effort to reduce tobacco use, to regulate environmental exposure, and to find alternatives to the massive use of biomass fuel, COPD will remain a major health-care problem for decades to come.

Non-small-cell lung cancer is one of the leading causes of deaths from cancer worldwide. Therefore, improvements in diagnostics and treatments are urgently needed. In this review, we will discuss the evolution of lung cancer staging towards more non-invasive, endoscopy-based, and image-based methods, and the development of stage-adapted treatment. A special focus will be placed on the role of novel surgical approaches and modern radiotherapy strategies for early stages of disease, the effect of multimodal treatment in locally advanced disease, and ongoing developments in the treatment of patients with metastatic disease. In particular, we will include an emphasis on targeted therapies, which are based on the assumption that a treatable driver mutation or gene rearrangement is present within the tumour. Finally, the position of lung cancer treatment on the pathway to personalised therapy will be discussed.

Patients with COPD were randomly assigned to triple inhaled therapy with either a 160-μg or 320-μg dose of budesonide or to one of two dual therapies. Both triple regimens were superior to the dual regimens with respect to the rate of moderate or severe exacerbations; no difference was observed between the triple regimens.

The use of benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor, allowed patients with asthma who were dependent on oral glucocorticoids to reduce the glucocorticoid dose to a greater extent than those who received placebo. Asthma is a common chronic inflammatory disease of the airways that affects an estimated 315 million persons worldwide. 1 Approximately 5 to 10% of persons with asthma have a severe form of disease that is usually managed with high-dose inhaled glucocorticoids and bronchodilators. 2 , 3 Within this group, 32 to 45% of persons rely on frequent or maintenance use of oral glucocorticoid therapy. 4 , 5 Oral glucocorticoid therapy adversely affects health-related quality of life, 6 and effective alternative therapies without severe adverse effects are needed. Eosinophilic inflammation is a key part of asthma, and increased numbers of circulating and airway eosinophils are accompanied by . . .

Patients who used oral glucocorticoids for asthma were able to reduce the dose of treatment more successfully when dupilumab, a monoclonal antibody targeting signaling through the interleukin-4 and interleukin-13 receptor, was added to their regimen than when placebo was added.

Such chronic diseases can develop either with COPD or independently of the disorder.4-7 The most common comorbidities described in association with COPD axe skeletal muscle abnormalities, hypertension, diabetes, coronary-artery disease, heart failure, pulmonary infections, cancer, and pulmonary vascular disease.47 Chronic comorbid diseases affect health outcomes in COPD;4 in fact, patients with COPD mainly die of non-respiratory disorders such as cardiovascular diseases or cancer.8 Chronic diseases account for a large proportion of human illness and include cardiovascular disease, cancer, chronic respiratory diseases, and diabetes.9 An unprecedented increase in chronic diseases is expected in the next few decades as populations age,10 a prospect that is of great concern to health authorities.9 Chronic diseases typically develop together.4,9,11 COPD is associated with chronic heart failure in more than 20% of patients12 and with osteoporosis in up to 70% of patients-in part, independently from treatment with steroids, decreased physical activity, or both.13 Furthermore, in a small study, almost 50% of patients with COPD had one or more components of the metabolic syndrome.1* Conversely, chronic heart failure is associated, in more than 50% of patients, with arterial hypertension and coronary or peripheral artery diseases, with diabetes in 20-30%, and with anaemia in 20-30%.15 Type 2 diabetes is linked to hypertension in more than 70% of individuals and to cardiovascular diseases and obesity in more than 80%.16 Diabetes is independently associated with reduced lung function, which together with obesity could further worsen the severity of COPD.17 Almost half of all people aged 65 years or older have at least three chronic medical conditions, and a fifth have five or more, with costs rising exponentially in patients with two or more comorbid chronic diseases.11,18 The strongest predictive factors of increased cost in COPD patients are age, chronic symptoms such as chronic dyspnoea and wheezing, and comorbidities; comorbid diseases account for more than 50% of health-care resources.4 Potentially, the common mechanism by which major risk factors such as smoking, hyperlipidaemia, obesity, and hypertension lead to chronic disease is systemic inflammation.19·20 C-reactive protein is almost invariably increased in all components of the chronic systemic inflammatory syndrome,21 suggesting that this acute-phase protein could represent the sentinel biomarker to all chronic diseases.

Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease. Its effect in patients using fixed combinations of inhaled corticosteroids and longacting β2 agonists is unknown. We postulated that roflumilast would reduce exacerbations in patients with severe chronic obstructive pulmonary disease at risk for exacerbations, even in combination with inhaled corticosteroid and longacting β2 agonist treatment. For this 1-year double-blind, placebo-controlled, parallel group, multicentre, phase 3–4 trial, the Roflumilast and Exacerbations in patients receiving Appropriate Combination Therapy (REACT) study, we enrolled patients with severe chronic obstructive pulmonary disease from 203 centres (outpatient clinics, hospitals, specialised pulmonologists, and family doctors) in 21 countries. Eligible patients were 40 years of age or older with a smoking history of at least 20 pack-years and a diagnosis of chronic obstructive pulmonary disease with severe airflow limitation, symptoms of chronic bronchitis, and at least two exacerbations in the previous year. We used a computerised central randomisation system to randomly assign patients in a 1:1 ratio to the two treatment groups: roflumilast 500 μg or placebo given orally once daily together with a fixed inhaled corticosteroid and longacting β2 agonist combination. Background tiotropium treatment was allowed. All patients and investigators were masked to group assignment. The primary outcome was the rate of moderate to severe chronic obstructive pulmonary disease exacerbations per patient per year, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01329029. Between April 3, 2011, and May 27, 2014, we enrolled 1945 eligible participants and randomly assigned 973 to the roflumilast group and 972 to the placebo group. The rate of moderate-to-severe chronic obstructive pulmonary disease exacerbations was 13·2% lower in the roflumilast group than in the placebo group according to a Poisson regression analysis (roflumilast 0·805 vs placebo 0·927; rate ratio [RR] 0·868 [95% CI 0·753–1·002], p=0·0529), and 14·2% lower according to a predefined sensitivity analysis using negative binomial regression (0·823 vs 0·959; 0·858 [0·740–0·995], p=0·0424). Adverse events were reported by 648 (67%) of 968 patients receiving roflumilast and by 572 (59%) of 967 patients in the placebo group; adverse event-associated patient withdrawal from the study was also more common in the roflumilast group (104/968 [11%]) than in the placebo group (52/967 [5%]). The most frequently reported serious adverse events were chronic obstructive pulmonary disease exacerbations and pneumonia, and 17 (1·8%) deaths occurred in the roflumilast group compared with 18 (1·9%) in the placebo group. Our findings suggest that roflumilast reduces exacerbations and hospital admissions in patients with severe chronic obstructive pulmonary disease and chronic bronchitis who are at risk of frequent and severe exacerbations despite inhaled corticosteroid and longacting β2 agonist therapy, even in combination with tiotropium. Takeda.

Background The origin of collagen-producing cells in lung fibrosis is unclear. The involvement of embryonic signaling pathways has been acknowledged and trans-differentiation of epithelial cells is discussed critically. The work presented here investigates the role of TGFB in cytoskeleton remodeling and the expression of Epithelial-Mesenchymal-Transition markers by Alveolar Epithelial Cells Type II and tests the hypothesis if human alveolar epithelial cells are capable of trans-differentiation and production of pro-fibrotic collagen. Methods Primary human alveolar epithelial cells type II were extracted from donor tissues and stimulated with TGFβ and a TGFβ-inhibitor. Transcriptome and pathway analyses as well as validation of results on protein level were conducted. Results A TGFβ-responsive fingerprint was found and investigated for mutual interactions. Interaction modules exhibited enrichment of genes that favor actin cytoskeleton remodeling, differentiation processes and collagen metabolism. Cross-validation of the TGFβ-responsive fingerprint in an independent IPF dataset revealed overlap of genes and supported the direction of regulated genes and TGFβ-specificity. Conclusions Primary human alveolar epithelial cells type II seem undergo a TGFβ-dependent phenotypic change, exhibit differential expression of EMT markers in vitro and acquire the potential to produce collagen.

In four clinical trials, the use of a long-acting β 2 -agonist plus an inhaled glucocorticoid did not result in a higher frequency of serious asthma events than the use of an inhaled glucocorticoid alone but was associated with a lower frequency of exacerbations.