nintedanib and Chronic-Disease

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive-fibrosing interstitial lung disease of unknown origin that affects 3 million people worldwide and imparts substantial burdens to patients, their families, and the healthcare system. The IPF disease course is highly variable and presents several diagnostic and management-related challenges. Two therapies, nintedanib and pirfenidone, are FDA approved and are recommended by clinical practice guidelines for the treatment of IPF. Although neither of these treatments is curative, both slow disease progression and impact survival of patients with IPF. To ensure optimal management, this supplement will provide an overview of the epidemiology, pathophysiology, and diagnosis of IPF, along with management-based considerations including evidence-based guideline recommendations, in-depth reviews of nintedanib and pirfenidone, and outcomes from other completed clinical trials.

Topics: Age Distribution; Aging; Antineoplastic Agents; Chronic Disease; Comorbidity; Disease Progression; Health Expenditures; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Patient Education as Topic; Practice Guidelines as Topic; Pyridones; Sex Distribution

This is a time of substantial progress in the evaluation and care of patients with idiopathic pulmonary fibrosis (IPF). In addition to the approval and widespread availability of the first IPF-specific therapies, there have been improvements in imaging interpretation and lung biopsy methods to enable more expeditious and more accurate diagnosis. Recent advances in identifying genetic factors that underlie susceptibility to IPF and affect prognosis have raised the possibility of personalized therapeutic approaches in the future. Further, evolving work is elucidating novel mechanisms influencing epithelial, mesenchymal, and inflammatory cell responses during the injury-repair process, thus advancing understanding of disease pathogenesis. As analytic approaches mature, the field is now poised to harness the power of rapidly advancing "omics" technologies to further accelerate progress.

Topics: Aged; Biopsy, Needle; Chronic Disease; Comprehension; Disease Management; Disease Progression; Female; Humans; Idiopathic Pulmonary Fibrosis; Immunohistochemistry; Indoles; Lung Transplantation; Male; Middle Aged; Precision Medicine; Prognosis; Pyridones; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Treatment Outcome

Idiopathic Pulmonary Fibrosis (IPF) is a most common progressive interstitial lung disease (ILD) of unknown etiology, although majority of patients are elderly male smokers. The main pathogenesis is aberrant recovery of epithelial injury and collagen deposition. Fibrotic nonspecific interstitial pneumonia, connective tissue disease (CTD) especially rheumatoid arthritis (RA) associated ILD, and chronic hypersensitivity pneumonia(CHP) are important differential diagnosis. Main symptoms are non-productive cough and progressive exertional dyspnea. Crucial physical findings are scalene muscle hypertrophy, bibasilar fine crackles, and finger clubbing. The serum markers such as lactate dehydrogenase (LDH) and Krebs von den Lungen-6 (KL-6) are sensitive for ILD detection and activity. Both pulmonary function test (PFT) and the 6-minute walk test (6MWT) are useful tool for evaluation of disease progression of IPF. Serial changes of forced vital capacity (FVC) and 6MWT distance predict mortality in IPF effectively. Recently published international IPF guidelines highlight the importance of chest high resolution computed tomography (HRCT) findings such as honeycombing, traction bronchiectasis (TBE), and sub-pleural reticular opacity. IPF is chronic and progressive; therefore, tracking disease behavior is crucial. Unifying clinical, physiological, and imaging information over time is useful. With regard to its management, two anti-fibrotic drugs such as pirfenidone and nintedanib have been available. These drugs can slow the decline of FVC and prevent acute exacerbation (AE). In this review, I outline the clinical characteristics of IPF, physiological, imaging, pathological findings and review diagnosis process and management.

Topics: Biomarkers; Chronic Disease; Cough; Diagnosis, Differential; Disease Progression; Dyspnea; Humans; Idiopathic Pulmonary Fibrosis; Indoles; L-Lactate Dehydrogenase; Mucin-1; Pyridones; Respiratory Function Tests; Tomography, X-Ray Computed; Vital Capacity

Pulmonary hypertension (PH) due to chronic lung disease is associated with a poor prognosis, regardless of the underlying respiratory condition. Updated PH guidelines recommend optimal treatment of the underlying lung disease, including long-term oxygen therapy, in patients with chronic hypoxemia despite the lack of randomized controlled clinical trials supporting this statement. So far, randomized controlled trials of drugs approved for pulmonary arterial hypertension have yielded discouraging results in both interstitial lung diseases and COPD with PH. In some cases, the trials were terminated because of an increase in death and other major adverse events in the active treatment arm vs placebo. In cases of PH due to idiopathic pulmonary fibrosis, new therapies under investigation use a combination of novel antifibrotic treatments and other treatments approved for pulmonary arterial hypertension. The choice of robust end points as well as a target group of patients with specific hemodynamic criteria may help in the selection of innovative therapeutic strategies. The aim of this review is to discuss recent studies and clinical trials for the treatment of PH due to the main chronic respiratory diseases and to discuss possible future scenarios for the evaluation of new therapeutic strategies.

Topics: Antihypertensive Agents; Chronic Disease; Clinical Trials as Topic; Endothelin Receptor Antagonists; Endpoint Determination; Epoprostenol; Forecasting; Guanylate Cyclase; Humans; Hypertension, Pulmonary; Indoles; Lung Diseases, Interstitial; Phosphodiesterase 5 Inhibitors; Pilot Projects; Protein-Tyrosine Kinases; Pulmonary Disease, Chronic Obstructive; Pyridones

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is complicated by diagnostic challenges, multiple comorbidities, and a poor prognosis. Although considered a relatively rare disease, healthcare costs are substantial and disproportionate to the incidence and prevalence of the disease. The comorbidities associated with IPF not only complicate treatment strategies but also increase the burden for patients via higher costs and undesirable health outcomes. Historically, pharmacologic treatment options for IPF have been limited and are often associated with low efficacy. Two drugs approved for IPF, nintedanib and pirfenidone, offer promise for improving health outcomes and survival during the course of the disease. Considerations of cost and adverse events are important when planning treatment options. Optimizing care through patient-centered care management programs can improve outcomes and health-related quality of life for patients. Such programs emphasize communication between healthcare professionals and patients in order to educate patients on their condition, so they can make informed healthcare decisions. Disease registries can be important tools for optimizing data collection and analysis for a disease with limited incidence and prevalence.

Topics: Antineoplastic Agents; Chronic Disease; Comorbidity; Cost of Illness; Health Expenditures; Health Resources; Health Services; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Medication Adherence; Patient Care Management; Patient Education as Topic; Practice Guidelines as Topic; Pyridones; Quality of Life; Registries

Topics: Acute Disease; Adrenal Cortex Hormones; Alveolitis, Extrinsic Allergic; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Bronchoalveolar Lavage Fluid; Chronic Disease; Disease Progression; Enzyme Inhibitors; Humans; Immunoglobulin G; Immunologic Factors; Immunosuppressive Agents; Indoles; Lung; Lung Transplantation; Pyridones; Tomography, X-Ray Computed

Topics: Allografts; Bronchiolitis Obliterans; Chronic Disease; Enzyme Inhibitors; Female; Humans; Indoles; Lung Transplantation; Middle Aged; Primary Graft Dysfunction; Tomography, X-Ray Computed