Resp Res
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Review
Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme.
The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases. This review describes how the nintedanib clinical programme has helped to address some of these challenges. ⋯ The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and other progressive fibrosing interstitial lung diseases, are described. Further developments in these areas should continue to improve patient outcomes.
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Randomized Controlled Trial
The impact of palliative care on quality of life, anxiety, and depression in idiopathic pulmonary fibrosis: a randomized controlled pilot study.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease that results in poor quality of life due to progressive respiratory symptoms, anxiety, and depression. Palliative care improves quality of life and survival in other progressive diseases. No randomized controlled trials have investigated the impact of palliative care on quality of life, anxiety, or depression in IPF. ⋯ This pilot study demonstrated that a randomized controlled trial of palliative care in idiopathic pulmonary fibrosis patients is feasible. Receiving palliative care did not lead to improved quality of life, anxiety, or depression compared to usual care after 6 months. Patients in the UC + PC group trended towards worsening symptoms and a small but statistically significant transient worsening in depression. These findings should be interpreted with caution, and need to be evaluated in adequately powered clinical trials. NCT03981406, June 10, 2019, retrospectively registered.
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Ventilator-induced diaphragmatic dysfunction is a serious complication associated with higher ICU mortality, prolonged mechanical ventilation, and unsuccessful withdrawal from mechanical ventilation. Although neurally adjusted ventilatory assist (NAVA) could be associated with lower patient-ventilator asynchrony compared with conventional ventilation, its effects on diaphragmatic dysfunction have not yet been well elucidated. ⋯ Preservation of spontaneous breathing using either PSV or NAVA can preserve the cross sectional area of the diaphragm to prevent atrophy. However, NAVA may be superior to PSV in preventing sarcomere injury and apoptosis of myofibrotic cells of the diaphragm, and this effect may be mediated by patient-ventilator asynchrony.
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β2 receptor agonists induce airway smooth muscle relaxation by increasing intracellular cAMP production. PKA is the traditional downstream signaling pathway of cAMP. Exchange protein directly activated by cAMP (Epac) was identified as another important signaling molecule of cAMP recently. The role of Epac in asthmatic airway inflammation and airway remodeling is unclear. ⋯ Our results suggest that Epac has a protecting effect on asthmatic airway inflammation and airway remodeling, and Epac reduces ASMCs proliferation by inhibiting SOCE in part.
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Meta Analysis
Inhaled corticosteroids and FEV1 decline in chronic obstructive pulmonary disease: a systematic review.
Rate of FEV1 decline in COPD is heterogeneous and the extent to which inhaled corticosteroids (ICS) influence the rate of decline is unclear. The majority of previous reviews have investigated specific ICS and non-ICS inhalers and have consisted of randomised control trials (RCTs), which have specific inclusion and exclusion criteria and short follow up times. We aimed to investigate the association between change in FEV1 and ICS-containing medications in COPD patients over longer follow up times. ⋯ Longer follow-up studies (greater than 1 year) were more likely to report a decline in FEV1 from baseline in patients on ICS and in patients on non-ICS containing medications but rates of FEV1 decline were similar. Further studies are needed to better understand changes in FEV1 when ICS-containing medications are prescribed and to determine whether ICS-containing medications influence rate of decline in FEV1 in the long term. Results from inclusive trials and observational patient cohorts may provide information more generalisable to a population of COPD patients.