ZLN005 improves the protective effect of mitochondrial function on alveolar epithelial cell aging by upregulating PGC-1α.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal pulmonary interstitial disease that usually occurs in the elderly. The senescence of alveolar epithelial cells (AECs) is an important mechanism of IPF. The AECs of patients with IPF have lower expression of peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which has been shown to play an important role in maintaining mitochondrial morphology and energy metabolism. This study sought to explore the mechanism by which ZLN005 improves mitochondrial function by upregulating PGC-1α to protect AECs from aging. Methods: Western blot was used to detect the expression of PGC-1α, mitochondrial synthesis protein nuclear respiratory factor-1 (NRF-1), and p21WAF1 in the lung tissue of the IPF patients and the mice with bleomycin (BLM)-induced pulmonary fibrosis. A549 cells and mice AEC2 cells were treated with hydrogen peroxide (H2O2) to construct cell senescence models. Cell senescence was detected by senescence-associated beta-galactosidase staining. The mitochondrial respiratory function was measured, including the adenosine triphosphate (ATP) generation, reactive oxygen species (ROS) level, changes in cell membrane potential, and energy metabolism. Using lentivirus as a vector and using gene editing technology to over express (upPGC-1α) and knockdown PGC-1α (shPGC-1α) in the A549 cells. The PGC-1α agonist ZLN005 was used to pretreat the A549 and shPGC-1α A549 cells, and cell aging and mitochondrial respiratory function were observed. Results: The Western blot and immunofluorescence assays showed that the expression of PGC-1α and NRF-1 was decreased in the lung tissues of the IPF patients and BLM-induced mice pulmonary fibrosis model, while the expression of p21WAF1 was increased. The results of the immunofluorescence and mitochondrial function experiments also indicated that the expression of PGC-1α and mitochondrial synthesis protein NRF-1 were decreased in the senescent cells. Further, the mitochondrial morphology was abnormal and the mitochondrial function was impaired. PGC-1α was involved in the AEC senescence by regulating mitochondrial morphology and function. Treatment with the agonist of PGC-1α (i.e., ZLN005) blocked the H2O2-induced cell senescence by enhancing the expression of PGC-1α. Conclusions: These results provide preliminary insights into the potential clinical application of ZLN005 as a novel therapeutic agent for the treatment of IPF.

A Case of Paraneoplastic Neurological Syndrome Leading to the Diagnosis of Large Cell Neuroendocrine Carcinoma From Opsoclonus-Myoclonus Syndrome.

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder characterized by myoclonus, ataxia, and tremors. It can be classified as neoplastic or idiopathic, with small cell lung cancer being commonly associated. Herein, we present a rare case of refractory paraneoplastic neurological syndrome (PNS) caused by large cell neuroendocrine carcinoma (LCNEC), a rare form of non-small cell lung cancer (NSCLC). A 60-year-old otherwise healthy man presented with acute-onset dysarthria, gait instability, and numbness on the right side of his body. According to the clinical symptoms and neurological examination, we initially suspected cerebellar infarction; however, brain imaging revealed no abnormal findings. After a few days, the patient developed worsening horizontal nystagmus, irregular ocular rhythms, and generalized involuntary movements, indicative of OMS. A systemic evaluation revealed a solitary nodule in the lower lobe of the right lung, leading to a clinical diagnosis of PNS. The patient underwent segmentectomy to treat an early-stage LCNEC nodule after one month from onset. Despite all therapeutic interventions, OMS was refractory, and after consulting with the person himself and the family, palliative care was selected. However, the patient showed a clinical response belatedly five months after surgery. This case highlights the importance of considering PNS, and that it may be associated with a rare malignancy when cerebellar symptoms are observed, and the challenges in managing refractory PNS associated with rare forms of NSCLC.

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib.

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy.

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study.

BACKGROUND: Skeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. METHODS: We performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. RESULTS: Of the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00-2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98-2.60]; model 2, 1.55 [0.95-2.56], and model 3, 1.67 [1.00-2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88-2.20). CONCLUSIONS: Low ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

Early corticosteroid dose tapering in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. METHODS: In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. RESULTS: The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22-0.76] and 0.65 [0.36-1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14-0.99] and 0.27 [0.094-0.83] in the multi-center and administrative cohorts, respectively). CONCLUSION: Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Prognostic implication of IgG4 and IgG1-positive cell infiltration in the lung in patients with idiopathic interstitial pneumonia.

Immunoglobulin (Ig) G4-positive cells are rarely observed in the lungs of patients with idiopathic interstitial pneumonias (IIPs). IgG1 may be more pathogenic than IgG4, with IgG4 having both pathogenic and protective roles in IgG4-related disease (IgG4-RD). However, the role of both IgG1 and IgG4 in IIPs remains unclear. We hypothesized that patients with IgG4-positive interstitial pneumonia manifest different clinical characteristics than patients with IgG4-RD. Herein, we identified the correlation of the degree of infiltration of IgG1- and IgG4-positive cells with IIP prognosis, using a Japanese nationwide cloud-based database. We included eighty-eight patients diagnosed with IIPs after multidisciplinary discussion, from April 2009 to March 2014. IgG4-positive cell infiltration was identified in 12/88 patients with IIPs and 8/41 patients with idiopathic pulmonary fibrosis (IPF). Additionally, 31/88 patients with IIPs and 19/41 patients with IPF were diagnosed as having IgG1-positive cell infiltration. IgG4-positive IIPs tended to have a better prognosis. Conversely, overall survival in cases with IgG1-positive IPF was significantly worse. IIPs were prevalent with IgG1- or IgG4-positive cell infiltration. IgG1-positive cell infiltration in IPF significantly correlated with a worse prognosis. Overall, evaluating the degree of IgG1-positive cell infiltration may be prognostically useful in cases of IPF.

Paradoxical worsening of nontuberculous mycobacterial disease after the discontinuation of antitumor necrosis factor therapy: A case report.

Antitumor necrosis factor-associated nontuberculous mycobacteria-immune reconstitution inflammatory syndrome (IRIS) has rarely been reported. An 84-year-old woman with a history of rheumatoid arthritis treated with etanercept was diagnosed with Mycobacterium avium complex (MAC) pulmonary disease six years before admission. Etanercept was discontinued two years ago because of MAC pulmonary disease progression and restarted nine months before admission because of worsening arthritis, again resulting in MAC pulmonary disease progression. Etanercept was discontinued again; however, the pulmonary disease progressed more rapidly. The condition was considered paradoxical worsening caused by IRIS due to etanercept discontinuation. The disease resolved quickly with chemotherapy for MAC.

Systemic lupus erythematosus presenting with lymphoid interstitial pneumonia as an initial manifestation.

A 25-year-old woman with an extensive travel history developed chronic cough and multiple lung nodules. The lung biopsy revealed lymphoid interstitial pneumonia. The patient later developed cervical lymphadenopathy, arthritis and livedo reticularis, then systemic lupus erythematosus was diagnosed with positive double-stranded DNA and low complement. The patient's symptoms responded to prednisolone and azathioprine.

Radiological and Physiological Predictors of IPF Mortality.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) has a variable clinical course, which ranges from being asymptomatic to progressive respiratory failure. The purpose of this study was to evaluate the novel clinical parameters of IPF patients who receive an anti-fibrotic agent. Materials and Methods: From January 2011 to January 2021, we identified 39 IPF patients at Okinawa Chubu Hospital. Clinical information was obtained, such as laboratory data, pulmonary function test (PFT) results, and chest images, including of soft tissue thickness and the high-resolution computed tomography (HRCT) pattern at diagnosis. Results: The mean age was 72.9 ± 7.0 (53-85); 27 patients were men and 12 were women. The mean body mass index was 25.1 ± 3.9 (17.3-35). Twenty-four were active smokers and the median number of packs per year was 20. Regarding laboratory findings, mean white blood cell (WBC), lactate dehydrogenase (LDH), and Krebs Von den Lungen-6 (KL-6) values were 7816 ± 1859, 248 ± 47, and 1615 ± 1503, respectively. In PFT, the mean percent predicted FVC, percent predicted total lung capacity, percent predicted functional residual capacity (FRC), and percent predicted diffusion capacity of the lung for carbon monoxide (DLco) were 66.8 ± 14.9%, 71.8 ± 13.7%, 65 ± 39.6%, and 64.6 ± 27.9%, respectively. In chest radiological findings, soft tissue thickness at the right 9th rib was 26.4 ± 8.8 mm. Regarding chest HRCT patterns, 15 showed the definite usual interstitial pneumonia (UIP) pattern, 16 showed the probable UIP pattern, and eight showed the indeterminate for UIP pattern. In the treatment, 24 patients received pirfenidone and 15 patients took nintedanib. The mean observation period was 38.6 ± 30.6 months and 24 patients died. The median survival time was 32.4 months (0.9-142.5). Multivariate analysis adjusted for age showed that both soft tissue thickness [Hazard ratio (HR): 0.912, 95% confidence interval (CI): 0.859-0.979, p-value: 0.009] and percent FRC [HR: 0.980, 95% CI: 0.967-0.992, p-value: 0.002] were robust predictors of IPF mortality. Conclusions: In IPF patients treated with anti-fibrotic agents, both soft tissue thickness at the right 9th rib shown on the chest radiograph and %FRC can be novel predictors of IPF mortality.

Decision-Making Strategy for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD).

Rheumatoid arthritis (RA) is a common type of autoimmune arthritis. Patient clinical outcomes might be influenced by numerous respiratory diseases, but interstitial lung disease (ILD) is the most important comorbidity. RA-associated ILD (RA-ILD) is divided into acute/subacute and chronic forms. In the acute/subacute course, if the disease is severe as indicated by a diffuse alveolar damage pattern, high-dose corticosteroids combined with antimicrobial agents should be promptly initiated while considering the differential diagnoses, primarily acute exacerbation (AE) of RA-ILD, drug-induced pneumonitis, and Pneumocystis pneumonia. As initial therapeutic management in the chronic course, the RA itself should be stabilized without delay; thereafter, the activity of ILD itself can be stabilized, considering the safety of each anti-rheumatic drug. The formation of the usual interstitial pneumonia (UIP) pattern is the most important determinant because lung function can worsen more quickly with this pattern. However, because clinicians can fail to identify specific radiological patterns, it is important to determine whether each patient with RA-ILD has UIP-like lesions such as subpleural reticulation, traction bronchiectasis, and honeycombing especially progressively enlarged cysts. In patients with progressive RA-ILD and high risk for infection or AE of ILD in whom fibrosis is dominant, clinicians should consider starting an anti-fibrotic agent.

Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial.

BACKGROUND: A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown. METHODS: This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (D LCO) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability. RESULTS: 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in D LCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups. CONCLUSIONS: Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.

Potential Predictors of Poor Prognosis among Critical COVID-19 Pneumonia Patients Requiring Tracheal Intubation.

Coronavirus disease 2019 (COVID-19) is a global public health concern that can be classified as mild, moderate, severe, or critical, based on disease severity. Since the identification of critical patients is crucial for developing effective management strategies, we evaluated clinical characteristics, laboratory data, treatment provided, and oxygenation to identify potential predictors of mortality among critical COVID-19 pneumonia patients. We retrospectively utilized data from seven critical patients who were admitted to our hospital during April 2020 and required mechanical ventilation. The primary endpoint was to clarify potential predictor of mortality. All patients were older than 70 years, five were men, six had hypertension, and three ultimately died. Compared with survivors, non-survivors tended to be never smokers (0 pack-years vs. 30 pack-years, p = 0.08), to have higher body mass index (31.3 kg/m2 vs. 25.3 kg/m2, p = 0.06), to require earlier tracheal intubation after symptom onset (2.7 days vs. 5.5 days, p = 0.07), and had fewer lymphocytes on admission (339 /µL vs. 518 /µL, p = 0.05). During the first week after tracheal intubation, non-survivors displayed lower values for minimum ratio of the partial pressure of oxygen to fractional inspiratory oxygen concentration (P/F ratio) (44 mmHg vs. 122 mmHg, p < 0.01) and poor response to intensive therapy compared with survivors. In summary, we show that obesity and lymphopenia could predict the severity of COVID-19 pneumonia and that the trend of lower P/F ratio during the first week of mechanical ventilation could provide useful prognostic information.

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses. METHODS: We investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion. This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan-Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis. RESULTS: In this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DLCO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DLCO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test). CONCLUSIONS: FF and %DLCO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.

Pulmonary interstitial emphysema is a risk factor for poor prognosis and a cause of air leaks.

BACKGROUND: Pulmonary interstitial emphysema is a rare, abnormal condition in which air pressure from the alveolar airspace tears the adjacent interstitial tissues of the lung and causes the formation of cystic spaces. Pulmonary interstitial emphysema is a known indication for mechanical ventilation in premature infants with neonatal respiratory distress syndrome, and it can be observed in various types of interstitial lung disease. Nevertheless, its pathogenesis and clinical impact remain unknown. METHODS: We reviewed data from 433 cases of interstitial lung disease from an external consultation archive. Multidisciplinary diagnosis along with clinical and follow-up data, including events of air leaks such as pneumothorax and mediastinal emphysema, were obtained and compared to those of 150 control cases of interstitial lung disease without pulmonary interstitial emphysema. RESULTS: We found 22 (5.1%) cases of interstitial lung disease with pulmonary interstitial emphysema. The diagnoses included idiopathic pulmonary fibrosis (5/22 [22.7%]), pleuroparenchymal fibroelastosis (4/22 [18.2%]), chronic hypersensitivity pneumonia (4/22 [18.2%]), and others (9/22 [40.9%]). Cases involving pulmonary interstitial emphysema demonstrated a significantly higher frequency of air leaks than did those without pulmonary interstitial emphysema (12/22 [54.5%] versus 23/150 [15.3%]; P < 0.001; odds ratio, 6.63) and were associated with worse prognosis (P = 0.009 [log-rank]) and a lower median percent forced vital capacity (73.2% versus 84.0%; P < 0.001). CONCLUSIONS: We found that pulmonary interstitial emphysema is an independent factor for poor prognosis, which also shows a trend to cause air leaks, including pneumothorax and mediastinal emphysema.

Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study.

Thoracic diseases in patients with systemic lupus erythematosus (SLE), especially interstitial pneumonia (SLE-IP), are rare and have been poorly studied. The aims of this multicentre study were to evaluate SLE-IP and elucidate its clinical characteristics and prognosis. Fifty-five patients with SLE-IP who had attended the respiratory departments of participating hospitals were retrospectively evaluated in this multicentre study. Clinical information, high-resolution computed tomography (HRCT), and surgical lung biopsy/autopsy specimens were analysed by respiratory physicians, pulmonary radiologists, and pulmonary pathologists. IP patterns on HRCT and lung specimens were classified based on the international classification statement/guideline for idiopathic interstitial pneumonias. The most frequent form of SLE-IP at diagnosis was chronic IP (63.6%), followed by subacute (20.0%), and acute IP (12.7%). Radiologically, the most common HRCT pattern was "Unclassifiable" (54%). Histologically, "Unclassifiable" was the most frequently found (41.7%) among 12 patients with histologically proven IP. Interestingly, accompanying airway diseases were present in nine of these patients (75%). In multivariate analysis, current smoking (hazard ratio [HR] 6.105, p = 0.027), thrombocytopenia (HR 7.676, p = 0.010), anti-double-strand DNA titre (HR 0.956, p = 0.027), and nonspecific interstitial pneumonia (NSIP) + organizing pneumonia (OP) pattern on HRCT (vs. NSIP, HR 0.089, p = 0.023) were significant prognostic factors. In conclusion, chronic IP was the most frequent form of IP in patients with SLE-IP, and "Unclassifiable" was the commonest pattern radiologically and histologically.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. Idiopathic pulmonary fibrosis is often seen in elderly men who smoke. A diagnosis of IPF is based on a combination of a detailed clinical history, specific physical examination, laboratory findings, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, and histopathology. Idiopathic pulmonary fibrosis has a heterogeneous clinical course, from an asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). Acute exacerbation of IPF has several important differential diagnoses, such as heart failure and volume overload. The International Working Group project proposed new criteria for defining AE of IPF in 2016, which divides it into triggered and idiopathic AE. On the basis of these criteria, physicians can detect AE of IPF more easily. The recent international IPF guidelines emphasized the utility of chest HRCT. In addition, two antifibrotic agents have become available. We should focus on both the management and prevention of AE. The diagnostic process, laboratory findings, typical chest imaging, management, and prognosis of AE are comprehensively reviewed in this article.