Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact. Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations. The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events. Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy. GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol. Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present. Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components. This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease.
Currently available data on tiotropium plus salmeterol are conflicting. Initial investigations indicated the benefits of tiotropium plus salmeterol versus either monotherapy alone, while suggesting co-administration of once-daily salmeterol plus tiotropium was inadvisable, due to the shorter duration of bronchodilation provided by salmeterol [76]. The Canadian Optimal Therapy of COPD trial investigated the impact of tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus salmeterol/fluticasone on clinical outcomes in 449 patients with moderate to severe COPD [48]. Tiotropium plus salmeterol/fluticasone (but not tiotropium plus salmeterol) statistically improved lung function and quality of life, and, while no improvement in overall exacerbation rate was seen, reduced the number of hospitalizations for exacerbations compared to tiotropium plus placebo [48] (Table 3). A more recent study, however, demonstrated significant improvements in FEV1 with salmeterol once or twice daily plus tiotropium [59], and the combination was also associated with clinically significant improvements in TDI (Table 3). These inconclusive data suggest that further research is necessary to determine any advantage of salmeterol plus tiotropium. Initial investigation of other free combinations has also been reported (Table 3); tiotropium plus indacaterol has been demonstrated to improve lung function and inspiratory capacity, as well as providing a further reduction in use of rescue medication [50]. The LAMA GSK233705 twice daily plus salmeterol has also demonstrated significantly improved trough FEV1 from baseline compared to monotherapy [61]. Overall, these data broadly confirm that combination therapy has the potential to improve outcomes versus monotherapy and justify further research in this area.
Lung Pathology Mcqs Pdf Free
High-resolution computed tomography (HRCT) of the chest is more sensitive than chest radiography in identifying lung abnormalities in bleomycin-exposed patients. HRCT patterns usually reflect the underlying histopathology [21]. Diffuse alveolar damage is associated with airspace consolidation and ground-glass opacities. Findings suggestive of end-stage fibrosis include extensive reticular markings, traction bronchiectasis, and honeycombing. Organizing pneumonia manifests as ground-glass opacities in a bilateral but asymmetric pattern or by airspace consolidation with a subpleural or peribronchial distribution. Organizing pneumonia may occasionally present as one or more nodular densities that may mimic tumor metastases [25].
Abstract: The incidence of pulmonary ground-glass opacity (GGO) lesions is increasing as a result of the widespread use of multislice spiral computed tomography (CT) and the low-dose CT screening for lung cancer detection. Besides benign lesions, GGOs can be a specific type of lung adenocarcinomas or their preinvasive lesions. Evaluation of pulmonary GGO and investigation of the correlation between CT imaging features and lung adenocarcinoma subtypes or driver genes can be helpful in confirming the diagnosis and in guiding the clinical management. Our review focuses on the pathologic characteristics of GGO detected at CT, involving histopathology and molecular pathology.
Lung adenocarcinoma is the most common histologic subtype of lung cancer and shows high heterogeneity at histology and cellular level (8,9). In 2011, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) have proposed a new classification for lung adenocarcinoma, refining its classification, which emerged into a better standard of clinical treatments (10). This new classification is of stage-independent prognostic and also of high predictive value for adjuvant treatment (11,12) and was most recently incorporated into the new 2015 WHO classification (13). Furthermore, lung cancer and especially lung adenocarcinoma, with specific mutations or rearrangements in genes such as EGFR, KRAS, and ALK, may show different tumor sensitivities to targeted therapeutic agents. Therefore, it is desirable to be aware of the correlations between GGO pattern and pathology subtypes and/or expression of driver genes.
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