Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by dyspnea and loss of lung function.

Methods: Using pooled data from the replicate, randomized, 52-week, placebo-controlled INPULSIS(®) trials, we characterized the safety and tolerability of nintedanib 150 mg twice daily in patients with IPF and described how adverse events were managed during these trials.

Results: One thousand and sixty- one patients were treated (nintedanib 638; placebo 423).

Newer modes of treating interstitial lung disease.

Purpose Of Review: This review critically discusses recent advances in the treatment of idiopathic pulmonary fibrosis (IPF). Moreover, it also focuses on the practical approach of a patient diagnosed with IPF and uncovers challenges for the future.

Recent Findings: Treatment can be divided into three major parts.

Clinical use of biomarkers of survival in pulmonary fibrosis.

Background: Biologic predictors or biomarkers of survival in pulmonary fibrosis with a worse prognosis, more specifically in idiopathic pulmonary fibrosis would help the clinician in deciding whether or not to treat since treatment carries a potential risk for adverse events. These decisions are made easier if accurate and objective measurements of the patients' clinical status can predict the risk of progression to death.

Method: A literature review is given on different biomarkers of survival in interstitial lung disease, mainly in IPF, since this disease has the worst prognosis.

Hypogonadism in male outpatients with sarcoidosis.

Hypogonadism is assumed to be present in sarcoidosis. Nevertheless, a comparison of circulating sex hormone concentrations of male sarcoidosis patients with those of healthy men has never been done. Moreover, it remains unknown if hypogonadism may contribute to a reduced muscle function, exercise intolerance, diminished vitality and depressed mood in male sarcoidosis patients.

Endobronchial ultrasonography in bronchoscopic occult pulmonary lesions.

Introduction: The diagnostic yield of flexible bronchoscopy for peripheral pulmonary lesions is variable and often limited. Endobronchial ultrasonography (EBUS) has been reported to help localize a bronchoscopic occult pulmonary lesion and thereby improve the diagnostic yield of transbronchial biopsy (TBB).

Methods: We evaluated the yield of EBUS-guided TBB in 50 consecutive patients with a bronchoscopic occult pulmonary lesion.

Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB.

Background: It has recently become clear that interleukin (IL)-8 plays a role in chronic neutrophilic inflammatory disorders, such as chronic rejection after lung transplantation. We have shown that IL-17--stimulated human airway smooth muscle cells (HASMC) are able to produce IL-8. The aim of this study was to determine whether p38 mitogen-activated protein kinase (MAPK), c-Jun amino-terminal kinase (JNK), p42/p44 extracellular signal-related kinase (ERK) and nuclear factor-kappaB (NF-kappaB) are involved in IL-17--induced IL-8 production in HASMC in vitro.

N-acetylcysteine inhibits interleukin-17-induced interleukin-8 production from human airway smooth muscle cells: a possible role for anti-oxidative treatment in chronic lung rejection?

Background: Long-term survival of lung transplantation is threatened by obliterative bronchiolitis, or its clinical equivalent, bronchiolitis obliterans syndrome. With a prevalence of >50% at 5 years after transplantation, it has emerged as the most significant long-term complication. Neutrophilic inflammation and increased interleukin (IL)-8 production seem to be part of the basic pathophysiologic mechanism of chronic rejection.

Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-kappaB in IL-1beta-induced chemokine release in human airway smooth muscle cells.

Asthma is an inflammatory disease, in which eotaxin, MCP-1 and MCP-3 play a crucial role. These chemokines have been shown to be expressed and produced by IL-1beta-stimulated human airway smooth muscle cells (HASMC) in culture. In the present study we were interested to unravel the IL-1beta-induced signal transduction leading to chemokine production.

Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma.

Study Objective: Exhaled nitric oxide (NO) levels are significantly elevated in patients with inflammatory airways disorders such as asthma, and the measurement of exhaled NO has been proposed as a noninvasive marker of airways inflammation. The aim of this study was to assess the accuracy of exhaled NO levels for the diagnosis of asthma.

Methods: Two hundred forty consecutive, nonsmoking, steroid-naive patients, who were referred to our outpatient clinic with symptoms suggestive of obstructive airways disease, were investigated.

Activation of the hexose monophosphate shunt in rat type II pneumocytes as an early marker of oxidative stress caused by cobalt particles.

Cobalt metal (mCo) and hard metal, a mixture of cobalt and tungsten carbide (CoWC), are cytotoxic for alveolar macrophages and alveolar type II cells (AT-II). Although the exact mechanisms of toxicity are not entirely elucidated, evidence exists for an oxidant-mediated toxicity. In this study, we exposed primary cultures of rat AT-II, in vitro, to different forms of cobalt (mCo particles, CoWC particles, CoCl(2)) and assessed changes in the activity of the hexose monophosphate shunt (HMS).