Clinical outcomes of dose modification during pirfenidone treatment for IPF: A nationwide post-marketing surveillance study

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone’s reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up—1800 mg, 1,200 mg, and <1,200 mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11 months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy. Copyright © 2023 Kang, Chung, Park, Oh, Lee, Kim, Park, Uh, Kim, Jegal and Song.ope

Medical Complications of Lung Transplantation

Lung transplantation (LT) is now considered as an effective treatment option for end-stage lung diseases that improves the short and long-term survival rates and quality of life. As increasingly many LT procedures are being performed, the medical complications of LT are also increasing in frequency and emerging as a very important issue for transplant clinicians. Although chronic lung allograft dysfunction and infection are major causes of death after LT, many medical complications, several of which result from immunosuppressive treatment, contribute to increased mortality and morbidity. This article reviews the most frequent and important medical complications of LT, accompanied by a review of the literature and studies from South Korea, including lung allograft rejection, infection, and non-allograft organ systemic complications.ope

Diffuse Alveolar Hemorrhage

Diffuse alveolar hemorrhage (DAH) is a life-threatening and medical emergency that can be caused by numerous disorders and presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is usually required to confirm the diagnosis and rule out infection. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, anti-glomerular basement membrane disease, and systemic lupus erythematosus, but DAH may also result from coagulation disorders, drugs, inhaled toxins, or transplantation. The diagnosis of DAH relies on clinical suspicion combined with laboratory, radiologic, and pathologic findings. Early recognition is crucial, because prompt diagnosis and treatment is necessary for survival. Corticosteroids and immunosuppressive agents remain the gold standard. In patients with DAH, biopsy of involved sites can help to identify the cause and to direct therapy. This article aims to provide a general review of the causes and clinical presentation of DAH and to recommend a diagnostic approach and a management plan for the most common causes.ope

Mycobacterial pulmonary infections in patients with idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.ope

The effect of socioeconomic status, insurance status, and insurance coverage benefits on mortality in critically ill patients admitted to the intensive care unit

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Recent Advances in Predicting Mortality and Progression of Systemic Sclerosis-Associated Interstitial Lung Disease

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A Soft Voting Ensemble-Based Model for the Early Prediction of Idiopathic Pulmonary Fibrosis (IPF) Disease Severity in Lungs Disease Patients

Idiopathic pulmonary fibrosis, which is one of the lung diseases, is quite rare but fatal in nature. The disease is progressive, and detection of severity takes a long time as well as being quite tedious. With the advent of intelligent machine learning techniques, and also the effectiveness of these techniques, it was possible to detect many lung diseases. So, in this paper, we have proposed a model that could be able to detect the severity of IPF at the early stage so that fatal situations can be controlled. For the development of this model, we used the IPF dataset of the Korean interstitial lung disease cohort data. First, we preprocessed the data while applying different preprocessing techniques and selected 26 highly relevant features from a total of 502 features for 2424 subjects. Second, we split the data into 80% training and 20% testing sets and applied oversampling on the training dataset. Third, we trained three state-of-the-art machine learning models and combined the results to develop a new soft voting ensemble-based model for the prediction of severity of IPF disease in patients with this chronic lung disease. Hyperparameter tuning was also performed to get the optimal performance of the model. Fourth, the performance of the proposed model was evaluated by calculating the accuracy, AUC, confusion matrix, precision, recall, and F1-score. Lastly, our proposed soft voting ensemble-based model achieved the accuracy of 0.7100, precision 0.6400, recall 0.7100, and F1-scores 0.6600. This proposed model will help the doctors, IPF patients, and physicians to diagnose the severity of the IPF disease in its early stages and assist them to take proactive measures to overcome this disease by enabling the doctors to take necessary decisions pertaining to the treatment of IPF disease.ope

Diagnosis and Treatment of Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is an immunologically mediated granulomatous, inflammatory disease of the lungs caused by repeated inhalation of various antigens. HP may occur in acute, subacute, or chronic forms. Chronic HP may be progressive, irreversible, and evolve to fibrotic interstitial lung disease. The diagnosis of HP can be made from a combination of clinical, laboratory, radiologic, and pathologic findings. A careful environmental and occupational history and establishment of exposure to a known inciting antigen are key factors in making the diagnosis of HP. Serum precipitating antibodies, bronchoalveolar lavage, and lung biopsy may be helpful in making the diagnosis. The pathology of HP is characterized by interstitial lymphocytic infiltration, poorlyformed noncaseating granulomas, cellular bronchiolitis, and fibrosis. In the pathogenesis of HP, recent studies showed that both type III and type IV hypersensitivity reactions are involved and are mediated by immune complexes and Th1 T cells, respectively. IFN-γ is essential for the development of HP, and IL-10 appears to modulate the severity of the disease. TNF-αand TGF- βhave been implicated in development of the pulmonary fibrosis that is seen in chronic HP. Avoidance of organic antigen exposure is the most important factor for the management of HP. There is often an apparent beneficial response to corticosteroids in the cases of severe acute and subacute HP, and for chronic HP that is severe or progressiveope

Clinical features of bronchogenic large cell carcinoma confirmed by surgical resection

Background : To define the final outcome of large cell carcinoma (LCC) after surgical treatment, we reviewed the histopathology, clinical features and follow-up results of 28 cases. Methods : We retrospectively reviewed 28 patients with LCC who underwent surgical resection during the last 15 years from 1986 to 2001 in Severance Hospital. We evaluated clinical data, radiologic findings, pathologic findings, treatment modalities, and survival. Results : The prevalence of LCC was 2.9% (29 cases) among the surgically resected cases in primary lung cancer (1003 cases) during 15 years. The mean age was 59 years old and twenty five cases were male. There were 23 smokers and the average pack year was 33. The cough was the most frequent symptom. Fifteen cases were located in the peripheral part of the lung. Twenty cases consisted of lobulated mass. In chest CT scan, twenty six cases had necrotic portions which appeared to be lower density. Postoperative stage was IA in 1 case (3.6%), IB in 11 cases (39.3%), IIB in 8 cases (28.5%), IIIA in 7 cases (25%), and IV in 1 case (3.6%). Preoperative and postoperative stage concordance rate was 43%. Median survival time was 54.5 months and 5 year-survival rate was 45%. Conclusion : Our results suggest that LCC in the lung is predominant in male and is equally located in the central and peripheral parts of the surgically resected cases. To define the treatment outcome and risk factors of LCC of the lung, further multicenter studies are needed.ope

Mitogen-activated protein kinase phosphatase-1 modulates regional effects of injurious mechanical ventilation in rodent lungs

RATIONALE: Mechanical ventilation induces heterogeneous lung injury by mitogen-activated protein kinase (MAPK) and nuclear factor-κB. Mechanisms regulating regional injury and protective effects of prone positioning are unclear. OBJECTIVES: To determine the key regulators of the lung regional protective effects of prone positioning in rodent lungs exposed to injurious ventilation. METHODS: Adult rats were ventilated with high (18 ml/kg, positive end-expiratory pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H(2)O; 3 h) in supine or prone position. Dorsal-caudal lung mRNA was analyzed by microarray and MAPK phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1(-/-) or wild-type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6-7 ml/kg; PEEP 3 cm H(2)O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate-buffered saline was administered preventilation. Injury was assessed by lung mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury scoring. Immunoblotting for MKP-1, and IκBα and cytokine ELISAs were performed on lung lysates. MEASUREMENTS AND MAIN RESULTS: Prone positioning was protective against injurious ventilation in rats. Expression profiling demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1(-/-) mice experienced amplified injury. PG490-88 improved static lung compliance and injury scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and induced MKP-1 and IκBα. CONCLUSIONS: Injurious ventilation induces MAPK in an MKP-1-dependent fashion. Prone positioning is protective and induces MKP-1. PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor-κB-dependent manner. MKP-1 is a potential target for modulating regional effects of injurious ventilation.ope