Resp Res
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Randomized Controlled Trial Multicenter Study
A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma.
Preclinical studies suggest that interleukin-9 may be a central mediator in the development and maintenance of airway inflammation in asthma. The aim of this study was therefore to evaluate the effects of MEDI-528, an anti-interleukin-9 monoclonal antibody, in adults with confirmed uncontrolled moderate-to-severe asthma. ⋯ The addition of MEDI-528 to existing asthma controller medications was not associated with any improvement in ACQ-6 scores, asthma exacerbation rates, or FEV1 values, nor was it associated with any major safety concerns.
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Review
Respiratory mechanics and ventilatory control in overlap syndrome and obesity hypoventilation.
The overlap syndrome of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD), in addition to obesity hypoventilation syndrome, represents growing health concerns, owing to the worldwide COPD and obesity epidemics and related co-morbidities. These disorders constitute the end points of a spectrum with distinct yet interrelated mechanisms that lead to a considerable health burden. The coexistence OSA and COPD seems to occur by chance, but the combination can contribute to worsened symptoms and oxygen desaturation at night, leading to disrupted sleep architecture and decreased sleep quality. ⋯ Although a unifying concept for the pathogenesis of both disorders is lacking, it seems that these patients are in a vicious cycle. This review outlines the major pathophysiological mechanisms believed to contribute to the development of these specific clinical entities. Knowledge of shared mechanisms in the overlap syndrome and obesity hypoventilation may help to identify these patients and guide therapy.
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Despite receiving 'weak no' recommendations in the updated guidelines on treating patients with Idiopathic Pulmonary Fibrosis (IPF), two key treatment options are pirfenidone and N-acetylcysteine (NAC), and both are used in clinical practice. The efficacy of pirfenidone is supported by a number of Phase III trials as well as a Cochrane meta-analysis. Tolerability data are also provided by clinical trials and a long-term extension phase of these studies. ⋯ A Phase III trial suggested some benefit of the NAC, prednisone and azathioprine regimen for IPF patients, but the study had many limitations. A further study to investigate this regimen, compared with a placebo alone arm, was recently stopped due to increased mortality in the triple-therapy arm. Discussion of these data and recent findings highlight the importance of a further update to the existing guidelines, so that IPF specialists can provide the most up-to-date advice and treatment to patients in clinical practice.
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Patient management in Idiopathic Pulmonary Fibrosis (IPF) is largely based on societal guidelines and recommendations. A recent update by the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS) and Latin American Thoracic Association (ALAT) provided updated guidance on the diagnosis and management of IPF, along with recommendations on pharmacologic and non-pharmacologic approaches to patient management. The treatment guidance is based on GRADE criteria, which rates the quality of evidence according to previously published methodology. ⋯ In addition we discuss the assessment and recommendations for a number of pharmacological agents that have been the focus of clinical trials over the past years. Although no single pharmacological agent was recommended by the guidelines committee, we discuss how since then, more recent data have resulted in the approval of pirfenidone in Europe, and preliminary negative findings regarding the safety of a triple therapy regimen consisting of prednisone, azathioprine and N-acetylcysteine have raised the question of whether it is no longer a treatment option. As clinicians, we must interpret the available guidance and recommendations as we consider each individual patient and as we discuss the available clinical data and the patient's own preferences in our approach to the management of this disease.
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Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear. ⋯ These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.