Expert review of respiratory medicine
-
Expert Rev Respir Med · Jun 2015
ReviewOxygen therapy in acute exacerbations of chronic obstructive pulmonary disease.
During the last decade, there have been major advances in knowledge of the effects of oxygen therapy in patients with acute exacerbations of chronic obstructive pulmonary disease. This includes a randomised controlled trial of oxygen therapy in the pre-hospital setting, which showed that high concentration oxygen therapy leads to a 2.4-fold increased risk of mortality compared with titrated oxygen therapy to maintain oxygen saturations (SpO2) within a target range of 88-92%. ⋯ The aim of this review is to provide an overview of the evidence base that underpins these recommendations. We suggest that their implementation will require important changes to current clinical practice in which there is an entrenched culture of the use of high concentration oxygen therapy.
-
Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized surfactant is affected. Hereditary PAP is caused by mutations involving the GM-CSF signaling, particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations. ⋯ Myeloid cells' immunity deteriorates, increasing the risk of infections. Treatment of PAP is based on its etiology. In aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under general anesthesia to the inhalation of GM-CSF 'as needed'.
-
Expert Rev Respir Med · Jun 2015
Alectinib: a selective, next-generation ALK inhibitor for treatment of ALK-rearranged non-small-cell lung cancer.
Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC). Despite initial responses, acquired resistance to crizotinib inevitably develops, with the brain being a common site of relapse. Alectinib is a highly selective, next-generation ALK inhibitor with potent inhibitory activity also against ALK mutations conferring resistance to crizotinib, including the gatekeeper L1196M substitution. ⋯ Alectinib also demonstrated promising antitumor activity in crizotinib-resistant patients, including those with CNS metastases. Based on these data, the drug received Breakthrough Therapy Designation by the US FDA and has been recently approved in Japan for the treatment of ALK-positive, advanced NSCLC patients. However, patients may eventually develop resistance to alectinib, highlighting the need for novel therapeutic strategies to further improve the management of ALK-rearranged NSCLC.
-
Expert Rev Respir Med · Jun 2015
ReviewDefining exacerbations in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease is a very common disease often punctuated by intermittent episodes of exacerbation. These exacerbations affect the natural history of the disease, accelerating a decline in lung function. They affect the individual in many ways and affect the health service caring for these patients. ⋯ The definitions used most are either symptom based, for example, breathlessness, sputum production and sputum purulence, or event driven, for example, an event causing a patient to seek healthcare input or change to medications. In this article, we discuss the importance of exacerbations, the clinical definitions, clinical trial definitions, physiological and biomarker evidence of exacerbations and the challenges associated with each of these. Application of a practical definition would aid in our clinical management of patients with chronic obstructive pulmonary disease and facilitate developments in future therapeutic advances through clinical trials.