nintedanib and Gastroesophageal-Reflux

Idiopathic pulmonary fibrosis (IPF) is characterized by relentlessly progressive lung function impairment that is consistently fatal in the absence of lung transplantation, as no curative pharmacological treatment exists. The pace of progression varies across patients, and acute life-threatening exacerbations occur unpredictably, causing further sharp drops in lung function. Recently introduced antifibrotic agents slow the pace of disease progression and may improve survival but fail to stop the fibrotic process. Moreover, the magnitude and kinetics of the response to these drugs cannot be predicted in the individual patient. These characteristics require that lung transplantation be considered early in the course of the disease. However, given the shortage of donor lungs, lung transplantation must be carefully targeted to those patients most likely to benefit. Current guidelines for lung transplantation listing may need reappraisal in the light of recent treatment advances. Patients with IPF often have multiple comorbidities such as coronary heart disease, frailty, and gastro-oesophageal reflux disease (GERD). Consequently, extensive screening for and effective treatment of concomitant conditions is crucial to appropriate candidate selection and outcome optimisation. A multidisciplinary approach is mandatory. Pulmonologists with expertise in IPF must work closely with lung transplant teams. Careful consideration must be given to preoperative optimisation, surgical technique, and pulmonary rehabilitation to produce the best post-transplantation outcomes.

Topics: Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Comorbidity; Disease Progression; Frailty; Gastroesophageal Reflux; Humans; Hypertension, Pulmonary; Idiopathic Interstitial Pneumonias; Idiopathic Pulmonary Fibrosis; Indoles; Lung Neoplasms; Lung Transplantation; Prognosis; Pyridones; Telomere Shortening

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with poor survival. Recent studies have improved understanding of IPF and new discoveries have led to novel treatment options, which now have become available for patients. In face of the newly available therapies we present an update on the pathophysiology and epidemiology of IPF. We discuss the typical clinical findings and elaborate diagnostic procedures according to current guidelines and our daily practice approach. The role of biomarkers will briefly be outlined. Finally, we discuss novel antifibrotic treatment options for IPF (pirfenidone, nintedanib) and the management of patients regarding to comorbidities and complications. Both pirfenidone and nintedanib were shown to reduce the progression of IPF and therefore represent novel therapeutic strategies in this so far untreatable chronic lung disease.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Disease Progression; Enzyme Inhibitors; Gastroesophageal Reflux; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Indoles; Practice Guidelines as Topic; Pyridones

Idiopathic pulmonary fibrosis (IPF) is a devastating progressive disease of unknown etiology that carries a grim prognosis. Over the last few decades there have been significant advances in our understanding of the mechanisms that drive the fibrotic process. In this review, we discuss the natural history of IPF, recent discoveries of the genetic factors, and environmental and infectious exposures that influence the development and progression of the disease, and highlight some of the novel discoveries in our understanding of the mechanisms that govern lung fibrosis. Finally, we discuss the new and exciting therapies that are now available to manage this illness.

Topics: Clinical Trials as Topic; Disease Progression; Environmental Exposure; Fibroblasts; Gastroesophageal Reflux; Genetic Predisposition to Disease; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung; Mutation; Myofibroblasts; Polymorphism, Genetic; Prognosis; Pyridones; Treatment Outcome

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan. A less clear but still negative recommendation (B, 1-b) was attributed to the treatment of IPF with the phosphodiesterase-5-inhibitor sildenafil and acetyl-cysteine monotherapy. In contrast to the international guideline antacid therapy as a general treatment for IPF was rated negative, based on conflicting results of recent analyses (recommendation C; evidence 4). An unanimous positive recommendation was granted for the antifibrotic drugs nintedanib and pirfenidone for the treatment of IPF (A, 1-a). For some open questions in the management of IPF patients for which firm evidence is lacking the guideline also offers recommendations based on expert consensus.. Die idiopathische Lungenfibrose (idiopathische pulmonale Fibrose, IPF) ist eine schwerwiegende Lungenerkrankung, die häufig innerhalb von zwei bis vier Jahren nach Diagnosestellung zum Tod führt. Seit Veröffentlichung der deutschen IPF-Leitlinie im Jahr 2013 liegen neue Therapiestudien vor, die eine Neubewertung der Behandlungsstrategien erfordern. Abweichend von der Vorgängerleitlinie wurde in der aktuellen Überarbeitung nicht mehr das GRADE-System sondern die Oxford Evidenzsystematik mit drei Empfehlungsgraden (A, B, C) verwendet, weil dieses System eine differenziertere Betrachtung erlaubt. Folgende Medikamente wurden mit dem Empfehlungsgrad A und dem Evidenzgrad 1-b als nicht geeignet für die Behandlung der IPF klassifiziert: Triple-Therapie aus Prednisolon, Azathioprin und Acetylcystein; Antikoagulation mit Vitamin-K-Antagonisten; Imatinib; Ambrisentan; Bosentan; Macitentan. Weniger eindeutig ist die negative Bewertung des Phosphodiesterase-5-Inhibitors Sildenafil und der Acetylcystein-Monotherapie (Empfehlungsgrad B, Evidenzgrad 2-b). Eindeutig positiv fiel die Empfehlung für Nintedanib und Pirfenidon zur Behandlung von IPF-Patienten aus (Empfehlungsgrad A, Evidenzgrad 1-a). Mit Empfehlungsgrad C und Evidenzgrad 4 wurde der generelle Einsatz von Antazida zur Behandlung der IPF als nicht zu empfehlen bewertet, da die Datenlage widersprüchlich ist; hier weicht die deutsche Leitlinie auch am deutlichsten von der internationalen Leitlinie ab. Am Ende der Leitlinie wird aus Expertensicht zu offenen Fragen in der Therapie der IPF Stellung genommen, für die bisher keine ausreichende Evidenzbasis existiert.

Topics: Acetylcysteine; Adult; Aged; Aged, 80 and over; Antacids; Bosentan; Clinical Trials as Topic; Evidence-Based Medicine; Female; Gastroesophageal Reflux; Guideline Adherence; Humans; Idiopathic Pulmonary Fibrosis; Imatinib Mesylate; Indoles; Male; Middle Aged; Phenylpropionates; Pyridazines; Pyridones; Pyrimidines; Sildenafil Citrate; Sulfonamides

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines.

Topics: Adrenal Cortex Hormones; Disease Progression; Disease-Free Survival; Evidence-Based Medicine; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Indoles; Meta-Analysis as Topic; Pulmonary Emphysema; Pyridones; Randomized Controlled Trials as Topic; Societies, Medical; Spain

Idiopathic pulmonary fibrosis is defined as a chronic fibrosing interstitial pneumonia limited to the lung, of unknown cause, with poor prognosis and few treatment options. In recent years there has been an increase in their prevalence, probably due to the optimization of diagnostic methods and increased life expectancy. The ATS/ERS Consensus (2000) established the diagnostic criteria and recommendations for the assessment of the disease course and treatment. Later studies have helped to redefine diagnostic criteria and treatment options. In 2011, an international consensus was published, establishing diagnostic criteria and new treatment strategies. These guidelines have been updated with the newest aspects of diagnosis and treatment of idiopathic pulmonary fibrosis. A level of evidence has been identified for the most relevant questions, particularly with regard to treatment options.

Topics: Acetylcysteine; Biopsy; Bronchoalveolar Lavage Fluid; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Contraindications; Diagnostic Imaging; Disease Progression; Evidence-Based Medicine; Gastroesophageal Reflux; Genetic Therapy; Glucocorticoids; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Immunologic Factors; Incidence; Indoles; Lung; Lung Transplantation; Oxygen Inhalation Therapy; Palliative Care; Prevalence; Prognosis; Pulmonary Emphysema; Pyridones; Risk Factors; Spain