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Internal Medicine (Tokyo, Japan) 2017The patient was a 69-year-old man with idiopathic pulmonary fibrosis who was taking pirfenidone. After 7 weeks of treatment, he suffered from left-sided eosinophilic...
The patient was a 69-year-old man with idiopathic pulmonary fibrosis who was taking pirfenidone. After 7 weeks of treatment, he suffered from left-sided eosinophilic pleurisy. Medical thoracoscopy was performed and the histopathological examination of the parietal pleura revealed the massive infiltration of eosinophils and lymphoid follicles. After stopping pirfenidone therapy, the patient's pleural effusion disappeared without additional treatment, and never recurred. This is the first case report of pirfenidone-induced pleurisy.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Eosinophils; Humans; Male; Pleurisy; Pulmonary Fibrosis; Pyridones; Thoracoscopy
PubMed: 28717083
DOI: 10.2169/internalmedicine.56.7738 -
BMC Pulmonary Medicine Feb 2023Idiopathic pulmonary fibrosis (IPF) is frequently accompanied by comorbidities, with the management of these comorbidities crucial for clinical outcomes. This study...
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is frequently accompanied by comorbidities, with the management of these comorbidities crucial for clinical outcomes. This study investigated the prevalence, incidence, changes over time, and clinical impact of comorbidities in IPF patients, based on nationwide claims data in South Korea.
METHODS
This retrospective cohort study utilised nationwide health claim data in South Korea between 2011 and 2019. Patients with IPF were defined as those with ICD-10 code J84.1 and Rare Intractable Disease code V236 who made at least one claim per year. Patients were classified by sex, age, pirfenidone use and burden of comorbidities, and differences among groups were determined.
RESULTS
The yearly prevalence rate of IPF increased from 7.50 to 23.20 per 100,000 people, and the yearly incidence rate increased from 3.56 to 7.91 per 100,000 person-years over time. The most common respiratory comorbidity was chronic obstructive pulmonary disease (37.34%), followed by lung cancer (3.34%), whereas the most common non-respiratory comorbidities were gastro-oesophageal reflux disease (70.83%), dyslipidaemia (62.93%) and hypertension (59.04%). The proportion of some comorbidities differed by sex, age and use of pirfenidone. The proportion of lung cancer was higher in patients treated with pirfenidone, whereas the proportion of anxiety and depression were lower in patients not treated with pirfenidone. Charlson comorbidity index ≥ 4 was associated with increases in hospitalisations and total medical costs.
CONCLUSIONS
The yearly prevalence and incidence of IPF and comorbidities in Korea increased over time. These comorbidities affected the use of pirfenidone and medical resources.
Topics: Humans; Cohort Studies; Retrospective Studies; Comorbidity; Idiopathic Pulmonary Fibrosis; Lung Neoplasms; Pyridones
PubMed: 36739401
DOI: 10.1186/s12890-023-02340-8 -
Annals of the American Thoracic Society Oct 2016Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet... (Review)
Review
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. In Puerto Rico, patients with HPS are often identified shortly after birth by their albinism, although the degree of hypopigmentation is highly variable. Ten subtypes have been described. Patients with HPS-1, HPS-2, and HPS-4 tend to develop pulmonary fibrosis in Puerto Rico; 100% of patients with HPS-1 develop HPS-PF. HPS-PF and idiopathic pulmonary fibrosis are considered similar entities (albeit with distinct causes) because both can show similar histological disease patterns. However, in contrast to idiopathic pulmonary fibrosis, HPS-PF manifests much earlier, often at 30-40 years of age. The progression of HPS-PF is characterized by the development of dyspnea and increasingly debilitating hypoxemia. No therapeutic interventions are currently approved by the U.S. Food and Drug Administration for the treatment of HPS and HPS-PF. However, the approval of two new antifibrotic drugs, pirfenidone and nintedanib, has prompted new interest in identifying drugs capable of reversing or halting the progression of HPS-PF. Thus, lung transplantation remains the only potentially life-prolonging treatment. At present, two clinical trials are recruiting patients with HPS-PF to identify biomarkers for disease progression. Advances in the diagnosis and management of these patients will require the establishment of multidisciplinary centers of excellence staffed by experts in this disease.
Topics: Animals; Biomarkers; Disease Progression; Hermanski-Pudlak Syndrome; Hispanic or Latino; Humans; Indoles; Lung Transplantation; Membrane Proteins; Mice; Mutation; Puerto Rico; Pulmonary Fibrosis; Pyridones; Randomized Controlled Trials as Topic; Tomography, X-Ray Computed
PubMed: 27529121
DOI: 10.1513/AnnalsATS.201603-186FR -
Annals of Medicine Feb 2015Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of idiopathic interstitial pneumonia. The disease, which occurs primarily in middle-aged and older... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of idiopathic interstitial pneumonia. The disease, which occurs primarily in middle-aged and older adults, is thought to arise following an aberrant reparative response to alveolar epithelial cell injury characterized by secretion of excessive amounts of extracellular matrix components, resulting in scarring of the lung, architectural distortion, and irreversible loss of function. A complex interplay between environmental and host factors is thought to contribute to the development of the disease, although the cause of IPF remains elusive and its pathogenesis incompletely understood. Over the last decade, disease definition and diagnostic criteria have evolved significantly, and this has facilitated the design of a number of high-quality clinical trials evaluating novel therapeutic agents for IPF. This massive effort of the medical and industry community has led to the identification of two compounds (pirfenidone and nintedanib) able to reduce functional decline and disease progression. These promising results notwithstanding, IPF remains a major cause of morbidity and mortality and a largely unmet medical need. A real cure for this devastating disease has yet to emerge and will likely consist of a combination of drugs targeting the plethora of pathways potentially involved in disease pathogenesis.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Health Services Needs and Demand; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Middle Aged; Pyridones; Risk Factors
PubMed: 25613170
DOI: 10.3109/07853890.2014.982165 -
International Journal of Molecular... Aug 2018Renal fibrosis is the final common pathway of numerous progressive kidney diseases, and transforming growth factor-β (TGF-β) has an important role in tissue fibrosis... (Review)
Review
Renal fibrosis is the final common pathway of numerous progressive kidney diseases, and transforming growth factor-β (TGF-β) has an important role in tissue fibrosis by up-regulating matrix protein synthesis, inhibiting matrix degradation, and altering cell-cell interaction. Many strategies targeting TGF-β, including inhibition of production, activation, binding to the receptor, and intracellular signaling, have been developed. Some of them were examined in clinical studies against kidney fibrosis, and some are applied to other fibrotic diseases or cancer. Here, I review the approaches targeting TGF-β signaling in kidney fibrosis.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Fibrosis; Humans; Kidney; Kidney Diseases; Molecular Targeted Therapy; Pyridones; Signal Transduction; Transforming Growth Factor beta
PubMed: 30150520
DOI: 10.3390/ijms19092532 -
Archives of Pathology & Laboratory... Sep 2018- Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease that up to now has been associated with a poor outcome. Some advances have been made in... (Review)
Review
CONTEXT
- Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease that up to now has been associated with a poor outcome. Some advances have been made in understanding the multiple interrelated pathogenic pathways underlying IPF. The disease is now believed to result from complex interactions among genetic, epigenetic, transcriptional, posttranscriptional, metabolic, and environmental factors. The discovery and validation of theranostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve the prediction of future disease behavior. Two drugs recently approved by the US Food and Drug Administration, pirfenidone and nintedanib, have shown the ability to reduce the progression of the disease, although survival benefits are only minimal and neither drug prevents or reverses the disease.
OBJECTIVE
- To provide a critical overview of the main experimental studies carried out for testing the principal effects of pirfenidone and nintedanib on IPF.
DATA SOURCES
- Experimental (animal and in vitro) studies concerning both drugs were used.
CONCLUSIONS
- Pirfenidone has a longer history of preclinical experimental studies than nintedanib. Many studies have been reported more recently (after 2014) and some of them evaluated the association of both drugs, thus suggesting their combination in future therapeutic approaches. Future investigations focusing on targets at molecular, cellular, and tissue levels are necessary to have a better in-depth knowledge of the properties of these drugs and to explore the potential efficacy of both or other drug combinations.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Fibroblasts; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones
PubMed: 30141997
DOI: 10.5858/arpa.2018-0080-RA -
European Journal of Pharmacology Jun 2024Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery...
Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery remodeling. Serum and parenchyma levels of Interleukin 11 (IL-11) are elevated in IPF-PH patients and contributes to pulmonary artery remodeling and PH. However, the effect of current approved therapies against IPF in pulmonary artery remodeling induced by IL-11 is unknown. The aim of this study is to analyze the effects of nintedanib and pirfenidone on pulmonary artery endothelial and smooth muscle cell remodeling induced by IL-11 in vitro. Our results show that nintedanib (NTD) and pirfenidone (PFD) ameliorates endothelial to mesenchymal transition (EnMT), pulmonary artery smooth muscle cell to myofibroblast-like transformation and pulmonary remodeling in precision lung cut slices. This study provided also evidence of the inhibitory effect of PFD and NTD on IL-11-induced endothelial and muscle cells proliferation and senescence. The inhibitory effect of these drugs on monocyte arrest and angiogenesis was also studied. Finally, we observed that IL-11 induced canonical signal transducer and activator of transcription 3 (STAT3) and non-canonical mitogen-activated protein kinase 1/2 (ERK1/2) phosphorylation, but, PFD and NTD only inhibited ERK1/2 phosphorylation. Therefore, this study provided evidence of the inhibitory effect of NTD and PFD on markers of pulmonary artery remodeling induced by IL-11.
Topics: Pulmonary Artery; Interleukin-11; Indoles; Animals; Myocytes, Smooth Muscle; STAT3 Transcription Factor; Endothelial Cells; Pyridones; Cell Proliferation; Rats; Humans; Male; Cellular Senescence; MAP Kinase Signaling System; Idiopathic Pulmonary Fibrosis; Monocytes; Vascular Remodeling
PubMed: 38561103
DOI: 10.1016/j.ejphar.2024.176547 -
Swiss Medical Weekly 2015Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with poor survival. Recent studies have improved understanding of IPF and new discoveries have... (Review)
Review
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
PubMed: 26024356
DOI: 10.4414/smw.2015.14139 -
European Respiratory Review : An... Sep 2017Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients.
Topics: Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung; Lung Transplantation; Palliative Care; Pyridones; Respiratory Function Tests; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 28954763
DOI: 10.1183/16000617.0047-2017 -
Eye (London, England) Sep 2017PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of...
PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect.ResultsClinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, αSMA, and TGFβ in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged.ConclusionThis animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of pirfenidone.
Topics: Actins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Collagen Type I; Cytokines; Disease Models, Animal; Electroretinography; Eye Injuries, Penetrating; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation; Intravitreal Injections; Pyridones; Rabbits; Real-Time Polymerase Chain Reaction; Retina; Vitreoretinopathy, Proliferative; Vitreous Body
PubMed: 28304388
DOI: 10.1038/eye.2017.21