Current Respiratory Medicine Reviews - Volume 12, Issue 3, 2016

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, irreversible form of fibrotic interstitial lung disease, with an estimated median survival of 3-5 years. Its prevalence has been estimated to be 0.7-63.0 per 100,000 with an incidence of 0.6-17.4 per 100,000 per year. Recent research has begun to clarify the pathophysiology of IPF. While chronic inflammation was originally thought to be the underlying cause of this disease, it is now taken as evidence that IPF is the result of aberrant wound healing and a fibroproliferative cascade. Therefore, in the last decade, the development of novel therapeutic targets for IPF has shifted in this new direction. Till recently, the development of IPF therapies is mostly disappointing. However, the recent approval of two new therapies, pirfenidone and nintedanib, has markedly changed the landscape of IPF management, regardless, there is a long way to go in treating IPF. For example, most patients continue to progress despite treatment. Novel therapies that can modify the long-term course of IPF and, prognostic markers that predict survival, disease progression, and response to antifibrotic drugs are required. This review highlights the molecular and cellular mechanisms of IPF which explain the development of new therapies and provide an overview of existing therapies and novel therapeutics currently under investigation or in early clinical trials.

Malignant mesothelioma is an aggressive form of cancer affecting the pleura and the serous membranes. Asbestos exposure has been shown to be the most important factor contributing to the development of malignant mesothelioma. The current guidelines suggest that investigations and management of patients with mesothelioma require multidisciplinary teamwork, which allows for imple-mentation of structured diagnostic algorithms resulting in more efficient and timely diagnosis and implementation of therapeutic strategies. Majority of patients with malignant mesothelioma present with pleural effusion. Therefore imaging including thoracic ultrasound, computed tomography and Positron Emission Tomography form an important part of investigations. However, in the context of malignant mesothelioma each of these imaging modalities has its limitations. For this reason, invasive procedures such as thoracocentesis, medical or surgical thoracoscopy remain important tools for obtaining histological diagnosis of malignant mesothelioma. In this review, we will discuss investigational approaches applied in diagnosing malignant mesothelioma.

Human rhinoviruses (HRVs) are responsible for most cases of the common cold. In healthy people, the consequences of HRV infections are usually minor. However, this innocuous virus can have serious consequences in certain individuals, with HRV infections linked to the onset of asthma in young children, and to potentially life threatening exacerbations in those with established asthma. Understanding the pathogenesis of HRV infections in asthma is thus a subject of much interest. This article reviews recent advances in our understanding of HRV-induced inflammatory pathways and immune responses, focussing on publications from the last 4 years. We outline new insights into the different types of HRVs, the cellular receptors they engage, and the transcriptional pathways that are engaged as a prelude to interferon synthesis. The importance of cross-talk between the innate immune response to HRV infections and cytokines produced during allergic inflammation is emphasised, with researchers continuing to document both altered anti-viral interferon production and immune dysregulation in asthma. Better definition of the mechanisms by which HRV infections induces lower airway inflammation is an important foundation on which to develop novel therapies that target HRV and/or the immunopathology that it induces.

Several pulmonary conditions were proven to be fatal in athletes. One of these conditions is pulmonary edema in athletes which requires differential diagnosis and often management in the ICU. Pulmonary edema in athletes can develop due to different sport activities including swimming, diving, running, cycling, mountain biking and the etiology and pathophysiology of these conditions may be different. This underlines the importance of pulmonary medicine specialist in the management of acute disease in athletes. The review focuses on pulmonary edema in athletes who participate in aquatic activities, running, cycling and mountain biking.

There has been an increase in understanding molecular biology of malignant pleural mesothelioma. This resulted in more clinical trials of novel therapeutic approaches. The more conventional systemic treatments for malignant mesothelioma are based on the use of Cisplatin and Pemetrexed. The newer agents such as vorinostat an Histone deacetylase inhibitor, focal adhesion kinase inhibitor Defactinib, mTOR inhibitor Everolimus, Bevacizumab a monoclonal antibody directed against Vascular Endothelial Growth Factor, immune check-point inhibitors, mesothelin targeted antibodies, Amatuximab have been investigated for their potential role in treatment of malignant mesothelioma. The role of radiation therapy in the curative treatment of malignant pleural mesothelioma has not been conclusively determined. In this review we will discuss the application of both radical and palliative radiotherapy in the context of managing of malignant mesothelioma.

Malignant melanoma is an aggressive, therapy-resistant malignancy of melanocytes. Although there is an increase in the worldwide incidences of melanoma, the recent data indicates that rates are declining among those younger than 50 years of age. We present the case of a 50-year-old Hispanic gentleman with metastatic malignant pleural melanoma, with tumor cells strongly positive for Melan-A, HMB-45, and S-100. Pleural metastatic melanoma represents a rare event that has been described in a small number of patients and they are found to be associated with reduced median overall survival. Massive pleural effusion is also an unusual presentation and has been associated to impaired lymphatic drainage due to infiltrated mediastinal lymph nodes. Melanoma can emerge in sun-shielded areas. Besides ultraviolet radiation, xenobiotics such as drugs and carcinogenic environmental toxins filtered and bound to melanin, along with viruses are etiological candidates. Only a small number of pleural metastatic melanoma cases have been reported and they are found to be associated with reduced median overall survival.