Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease.

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse event of anticancer drugs. In recent years, the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents. Due to the diverse clinical manifestations and the lack of specific diagnostic criteria, DILD is difficult to diagnose and may even become fatal if not treated properly. Herein, a multidisciplinary group of experts from oncology, respiratory, imaging, pharmacology, pathology, and radiology departments in China has reached the "expert consensus on the diagnosis and treatment of anticancer DILD" after several rounds of a comprehensive investigation. This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening, diagnosis, and treatment of anticancer DILD. This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Safety and accuracy of transbronchial lung cryobiopsy in diagnosing desquamative interstitial pneumonia.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a new technique to obtain specimens for diagnosis of interstitial lung disease (ILD) in recent years. The objective of this study is to evaluate the safety and the diagnostic accuracy of TBLC in patients of desquamative interstitial pneumonia (DIP). METHODS: In this study twelve patients confirmed with DIP were selected from January 2019 to December 2020 at the department of pulmonary and critical care medicine in China-Japan Friendship Hospital. All cases underwent TBLC in a hybrid cone beam CT (CBCT) operation room with a single general anesthesia. The definitive diagnosis was made by a multidisciplinary team that involved clinicians, radiologists and pathologists. This study analyzed the biopsy sample surface areas, main complications and the consistency between TBLC pathology and multidisciplinary discussion (MDD) diagnosis for DIP. RESULTS: An average of 3.1 ± 1.1 specimens were obtained per patient. The mean surface area of the specimen was 23.7 ± 6.1 mm2 . None of the cases had pneumothorax or massive hemorrhage. Ten cases (83.3%) had no or mild bleeding and two cases (16.7%) had moderate bleeding. All cases had the typical pathologic characteristics of DIP, which was highly consistent with the diagnosis of MDD. CONCLUSION: TBLC can obtain sufficient samples for the pathological diagnosis of DIP, which has high security and accuracy in experienced specialist centers.

Water-Soluble C60 Protects Against Bleomycin-Induced Pulmonary Fibrosis in Mice.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia. And, oxidation/antioxidant imbalance plays an important role in the progress of IPF. Fullerene is considered to be a novel "structural" antioxidant. This study aimed to explore if water-soluble C60 (C60(OH)22) can exhibit antifibrotic activity in its antioxidant role. METHODS: Healthy C57BL/6J mice were randomly grouped and induced pulmonary fibrosis by intratracheal injection of bleomycin. RESULTS: The survival rate of mice was observed and found that 10mg/kg was the optimal dose of water-soluble C60 for pulmonary fibrosis. We observed that water-soluble C60 can alleviate the severity of pulmonary fibrosis by observing the chest computed tomography, pulmonary pathology, and content of collagen, alpha smooth muscle actin and fibronectin in lung. Compared with bleomycin group, ROS, the content of TNF-α in BALF, and the number of fibroblasts was significantly decreased and the number of type Ⅱ alveolar epithelial cells was increased after treatment with C60. CONCLUSION: Therefore, thanks to its powerful antioxidant action, water-soluble C60 can reduce the severity of pulmonary fibrosis induced by bleomycin in mice.

Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway.

Background: Follistatin-like 1 (FSTL1) is a novel profibrogenic factor that induces pulmonary fibrosis (PF) through the transforming growth factor-beta 1 (TGF-ß1)/Smad signaling. Little is known about its effects on PF through the non-Smad signaling, like the mitogen-activated protein kinase (MAPK) pathway. Therefore, this study aimed to investigate the role of FSTL1 in PF through the MAPK signaling pathway and its mechanisms in lung fibrogenesis. Methods: PF was induced in Fstl1+/-and wild-type (WT) C57BL/6 mice with bleomycin. After 14 days, the mice were sacrificed, and lung tissues were stained with hematoxylin and eosin; the hydroxyproline content was measured to confirm PF. The mRNA and protein level of FSTL1 and the change of MAPK phosphorylation were measured by quantitative polymerase chain reaction and Western blotting. The effect of Fstl1 deficiency on fibroblasts differentiation was measured by Western blotting and cell immunofluorescence. MAPK signaling activation was measured by Western blotting in Fstl1+/- and WT fibroblasts treated with recombinant human FSTL1 protein. We pretreated mouse lung fibroblast cells with inhibitors of the extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) signaling and analyzed their differentiation, proliferation, migration, and invasion by Western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, and transwell assays. The Student's t-test was used to compare the differences between two groups. Results: Fstl1 deficiency attenuated phosphorylation of the ERK, p38, and JNK signaling in bleomycin-induced fibrotic lung tissue 14 days after injury (0.67 ± 0.05 vs. 1.22 ± 0.03, t = 14.92, P = 0.0001; 0.41 ± 0.01 vs. 1.15 ± 0.07; t = 11.19; P = 0.0004; and 0.41 ± 0.01 vs. 1.07 ± 0.07, t = 8.92, P = 0.0009; respectively), compared with WT lungs at the same time and in primary lung fibroblasts (0.82 ± 0.01 vs. 1.01 ± 0.04, t = 4.06, P = 0.0150; 1.04 ± 0.03 vs. 1.24 ± 0.03, t = 4.44, P = 0.0100; and 0.76 ± 0.05 vs. 0.99 ± 0.05, t = 4.48, P = 0.0100; respectively), compared with TGF-ß1-stimulated WT group. Recombinant human FSTL1 protein in lung fibroblasts enhanced TGF-ß1-mediated phosphorylation of the ERK (1.19 ± 0.08 vs. 0.55 ± 0.04, t = 6.99, P = 0.0020), p38 (1.18 ± 0.04 vs. 0.66 ± 0.03, t = 11.20, P = 0.0020), and JNK (1.11 ± 0.01 vs. 0.84 ± 0.04, t = 6.53, P = 0.0030), compared with the TGF-ß1-stimulated WT group. Fstl1-deficient fibroblasts showed reduced alpha-smooth muscle actin (α-SMA) expression (0.70 ± 0.06 vs. 1.28 ± 0.11, t = 4.65, P = 0.0035, compared with the untreated WT group; 1.40 ± 0.05 vs. 1.76 ± 0.02, t = 6.31, P = 0.0007; compared with the TGF-ß1-treated WT group). Compared with the corresponding condition in the control group, the TGF-ß1/FSTL1-mediated α-SMA expression was significantly suppressed by pretreatment with an inhibitor of p38 (0.73 ± 0.01 vs. 1.13 ± 0.10, t = 3.92, P = 0.0078) and JNK (0.78 ± 0.03 vs. 1.08 ± 0.06, t = 4.40, P = 0.0046) signaling. The proliferation of mouse lung fibroblast cells (MLgs) significantly decreased after treatment of an inhibitor of p38 (0.30 ± 0.01 vs. 0.46 ± 0.03, t = 4.64, P = 0.0009), JNK (0.30 ± 0.01 vs. 0.49 ± 0.01, t = 12.84, P = 0.0001), and Smad2/3 (0.18 ± 0.02 vs. 0.46 ± 0.02, t = 12.69, P = 0.0001) signaling compared with the dimethylsulfoxide group. The migration and invasion cells of MLgs significantly decreased in medium pretreated with an inhibitor of p38 (70.17 ± 3.28 vs. 116.30 ± 7.11, t = 5.89, P = 0.0042 for the migratory cells; 19.87 ± 0.84 vs. 32.70 ± 0.95, t = 10.14, P = 0.0005 for the invasive cells), JNK (72.30 ± 3.85 vs. 116.30 ± 7.11, t = 5.44, P = 0.0056 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 11.00, P = 0.0004 for the invasive cells), and Smad2/3 (64.76 ± 1.41 vs. 116.30 ± 7.11, t = 7.11, P = 0.0021 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 13.29, P = 0.0002 for the invasive cells) signaling compared with the corresponding condition in the dimethylsulfoxide group. Conclusion: FSTL1 affects lung fibroblast differentiation, proliferation, migration, and invasion through p38 and JNK signaling, and in this way, it might influence the development of PF.

[Research on Life Quality Scale for Patients with Idiopathic Pulmonary Fibrosis].

OBJECTIVE: To develop a life quality scale suitable for idiopathic pulmonary fibrosis (IPF) patients, objectively reflecting its changes. METHODS: Authors first put forward a theoretical structure model of a scale according to patient-reported outcome (PRO) scale formulation principle by combining basic theories of Chinese medicine (CM). Then authors developed an initial scale on the basis of various life quality scales for respiratory disease patients by using structural decision making. Totally 34 patients with confirmed diagnosis of IPF were tested by questionnaire. Items were screened using expert importance scoring method, factor analysis, correlation coefficient method, Cronbach's alpha coefficient method. IPF patient reported outcomes (IPF PRO, IP) were finally defined. RESULTS: A new IP scale was developed covering three areas and 38 items. Pearson correlation coefficient for correlation analysis of clinical symptom scores in ST-George Respiratory Questionnaire and IP scale was 0.828 (P < 0.01). Pearson correlation coefficient for correlation analysis of activity ability scores was 0.929 (P < 0.01). Pearson correlation coefficient for correlation analysis of total scores was 0.862 (P < 0.01). By reliability of IP scale itself (reliability) analysis, Cronbach's alpha coefficient was 0.713. By using factor analysis method for data analysis, KMO statistics was 0.902. CONCLUSION: IP scale fully reflected the connotation of IPF patients' quality of life, so it could be used as CM clinical therapeutic effect evaluation tool.

Double-Blind Randomized Trial of Pirfenidone in Chinese Idiopathic Pulmonary Fibrosis Patients.

Idiopathic pulmonary fibrosis (IPF) lacks effective treatment. Pirfenidone has been used to treat IPF patients. N-acetylcysteine (NAC) exerts antioxidant and antifibrotic effects on IPF cases.This study is a double-blind, modified placebo-controlled, randomized phase II trial of pirfenidone in Chinese IPF patients. We randomly assigned the enrolled Chinese IPF patients with mild to moderate impairment of pulmonary function to receive either oral pirfenidone (1800 mg per day) and NAC (1800 mg per day) or placebo and NAC (1800 mg per day) for 48 weeks. The primary endpoints were the changes in forced vital capacity (FVC) and walking distance and the lowest SPO2 during the 6-minute walk test (6MWT) at week 48. The key secondary endpoint was the progression-free survival time. This study is registered in ClinicalTrials.gov as number NCT01504334.Eighty-six patients were screened, and 76 cases were enrolled (pirfenidone + NAC: 38; placebo + NAC: 38). The effect of pirfenidone treatment was significant at the 24th week, but this effect did not persist to the 48th week. At the 24th week, the mean decline in both FVC and ΔSPO2 (%) during the 6MWT in the pirfenidone group was lower than that in the control group (-0.08 ± 0.20 L vs -0.22 ± 0.29 L, P = 0.02 and -3.44% ± 4.51% vs -6.29% ± 6.06%, P = 0.03, respectively). However, there was no significant difference between these 2 groups at the 48th week (-0.15 ± 0.25 L vs -0.25 ± 0.28 L, P = 0.11 and -4.25% ± 7.27% vs -5.31% ± 5.49%, P = 0.51, respectively). The pirfenidone treatment group did not achieve the maximal distance difference on the 6MWT at either the 24th or the 48th week. But pirfenidone treatment prolonged the progression-free survival time in the IPF patients (hazard ratio = 1.88, 95% confidence interval: 1.092-3.242, P = 0.02). In the pirfenidone group, the adverse event (AE) rate (52.63%) was higher than that in the control group (26.3%, P = 0.03). Rash was more common in the pirfenidone group (39.5% vs 13.2%, P = 0.02).Compared with placebo combined with high-dose NAC, pirfenidone combined with high-dose NAC prolonged the progression-free survival of Chinese IPF patients with mild to moderate impairment of pulmonary function. (ClinicalTrials.gov number, NCT01504334).

Incidence and clinical characteristics of pulmonary hypertension in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH) frequently complicates the course of idiopathic pulmonary fibrosis (IPF) patients and is associated with significantly worse outcomes. The aim of the present study was to investigate the incidence of PH in IPF patients and evaluate the correlation between clinical parameters and systolic pulmonary artery pressure (sPAP). METHODS: Hospitalized patients with IPF, who were evaluated for sPAP by Doppler echocardiography from January 2004 to December 2011, were enrolled in our study. Patients were defined as PH by an estimated sPAP > 50 mmHg and graded as PH likely, PH possible and PH unlikely, based on the 2009 European Society of Cardiology/European Respiratory Society PH Guidelines. The correlations between clinical parameters and sPAP were analyzed by multiple linear regression. RESULTS: Totally, 119 IPF patients were enrolled in our study and 28 (23.5%), 20 (16.8%) and 71 (59.7%) patients were PH likely, PH possible and PH unlikely, respectively. Borg dyspnea score was positively correlated with sPAP, r = 0.467, P < 0.001. Oxygen saturation was negatively correlated with sPAP, r = -0.416, P < 0.001. Diffusing capacity of the lung for carbon monoxide percentage predicted was negatively correlated with sPAP, r = -0.424, P = 0.003. N-terminal fragment of pro-brain natriuretic peptide and pulmonary artery width was positively correlated with sPAP, r = 0.452, P = 0.011 and r = 0.513, P < 0.001, respectively. CONCLUSIONS: The incidence of PH in IPF patients was 23.5% in a single center of China. PH may worsen the dyspnea, right heart dysfunction and decrease the life quality of the patients with IPF.

[Clinicopathological characteristics and prognosis of malignant pleural mesothelioma].

OBJECTIVE: To investigate the clinicopathological characteristics and prognosis of malignant pleural mesothelioma. METHODS: Thirty patients with malignant pleural mesothelioma diagnosed between January 2006 and June 2012 in our hospital were studied retrospectively. Clinical manifestations, radiological characteristics, endoscopic features, histopathology, and survival status were analyzed. RESULTS: There were 15 males and 15 females, with a median age of 58 years. The commonest clinical symptoms were dyspnea on exertion (26 cases), followed by chest pain (15 cases). The main radiological manifestations were small to large amount of pleural effusions (28 cases), often accompanied by pleural thickening and/or pleural nodules.Of the 30 cases, 25 were diagnosed through medical thoracoscopy and 1 through surgical thoracoscopy. Thoracic lesions manifested as nodules of diffuse distribution on the diaphragmatic pleura and parietal pleura.Some pleural surface was covered with lesions like white tiles.Histopathological examination showed epithelial type in 24 cases, sarcomatoid type in 5 and biphasic type in 1 case.Immonohistological examination showed that the positive rates of calretinin, MC, D2∼40 were 27, 25 and 19 cases respectively.Fifteen patients received chemotherapy, 2 underwent pleurectomy, and 8 were treated with best supportive care. Twenty-four patients were followed for 1 month to 6 years, and 6 patients were lost.Overall survival time was 1-54 months. Those who survived longer than 24 months received chemotherapy with pemetrexed and cisplatin/carboplatin or pleurectomy. CONCLUSIONS: Clinical manifestations of malignant pleural mesotheliome were nonspecific, medical thoracoscopy can make early diagnosis. The pathological diagnosis of malignant pleural mesothelioma was based on immunohistochemical examination, calretinin, MC and D2-40 had positive diagnostic value. Malignant pleural mesothelioma had poor prognosis, chemotherapy with pemetrexed and cisplatin/carboplatin could prolong the survival time of the patients.

Clinical features and imaging findings in pulmonary capillary hemangiomatosis: report of two cases and a pooled analysis.

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a rare disease and no Chinese case has been reported yet. The disease is often misdiagnosed and its clinical characteristics are incompletely described. The aim of this study was to describe two Chinese cases and to clarify the clinical and radiographic parameters of patients with PCH. METHODS: Two PCH cases were presented and other cases were searched from the English literature. All available clinical and radiographic data were collected from 62 literature reported PCH cases. A pooled analysis of total 64 cases was made. RESULTS: Dyspnea and hemoptysis were the most common clinical symptoms of PCH. Pulmonary hypertension (PH) was found in 78% of the reported cases. PCH typically showed characteristic diffuse or patchy ground-glass opacities (GGOs) and/or multiple ill-defined centrilobular nodules in the computed tomography. CONCLUSIONS: The diagnosis of PCH requires a high clinical suspicion. However, both clinical presentations and radiographic studies often provide clues to the diagnosis, which may prompt early lung biopsy for a definite diagnosis.

[Pulmonary capillary hemangiomatosis: a clinicopathologic analysis of 2 cases with review of literature].

OBJECTIVE: To investigate the clinicopathologic features of pulmonary capillary hemangiomatosis (PCH). METHODS: The clinical and pathologic profiles of 2 PCH cases were evaluated. Immunohistochemical study (EnVision method) was performed on fixed tissues. The biologic behavior was analyzed with follow-up data. RESULTS: The main presenting symptom was dyspnea. Chest radiography of the two cases depicted diffuse, ground-glass nodules, accompanied by enlarged central pulmonary arteries. Microscopically, the most distinctive feature was proliferation of capillary channels within pulmonary interstitium and alveolar walls, accompanied by muscularization of arterioles. Immunohistochemical study showed an abundance of mast cells in the lesion, and staining for platelet-derived growth factor receptor-beta (PDGFR-ß) localized to vascular smooth muscles surrounding the proliferating capillaries and the mast cells. The index of Ki-67 was less than 1 percent and the p53 was negative. CONCLUSIONS: PCH is a rare vascular proliferative disease of yang patients. Increased number of mast cell and the up-regulation of PDGFR-ß may suggest mechanism for PCH. The clinical and radiologic diagnosis of PCH can be very difficult, and the histological examination is regarded as the most reliable means to establish the diagnosis. Pathologists should improve their knowledge on PCH.

Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-ß1 and plasminogen activator inhibitor 1.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrotic lung disease of unknown etiology. Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-ß1 (TGF-ß1, a potent profibrotic cytokine) and plasminogen activator inhibitor 1 (PAI-1) play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-ß1 869 T > C and PAI-1 4G/5G and the susceptibility to IPF in Han ethnicity. METHODS: Polymerase chain reaction (PCR) and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-ß1 in 869T > C and PAI-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status. RESULTS: There was a significant difference in 869T > C genotype distribution of TGF-ß1 between IPF cases and controls, a significant negative association between TC genotype and the development of IPF (OR = 0.508, 95%CI: 0.275 - 0.941) and a positive association between CC genotype and the development of IPF (OR = 1.967, 95%CI: 1.063 - 3.641). There was a significant positive association between PAI-1 5G/5G genotype and the development of IPF (OR = 0.418, 95%CI: 0.193 - 0.904). CONCLUSIONS: Gene polymorphisms of TGF-ß1 in 869T > C and PAI-1 4G/5G may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population.

[Pathologic diagnosis and clinical analysis of chronic extrinsic allergic alveolitis].

OBJECTIVE: To study the clinicopathologic features and diagnostic approach of chronic extrinsic allergic alveolitis (EAA). METHODS: Seven cases of chronic EAA diagnosed by open lung biopsy or lung transplant were enrolled into the study. The clinical and pathologic features were analyzed and the literature was reviewed. RESULTS: There were altogether 4 men and 3 women. The age of the patients ranged from 30 to 65 years (mean = 48 years). All cases represented chronic form and five cases diagnosed by open lung biopsy also showed features of recent aggravation, leading to hospitalization. Four cases had known history of exposure to inciting gases, pollens and pets, and only 2 cases were positive for allergens. High-resolution CT scan showed ground-glass attenuation and reticular pattern that often had a patchy distribution and central predominance. Bronchoalveolar lavage analysis showed marked lymphocytosis, with CD4(+)/CD8(+) ratio less than 1. Lung function test demonstrated a restrictive ventilatory defect, with decreased compliance, reduced diffusion capacity and high airway obstruction. Five cases had open lung biopsy performed and two cases had undergone lung transplantation. Pathologic examination showed bronchiolocentric cellular interstitial pneumonia, interstitial fibrosis, non-caseating epithelioid granulomas, epithelioid histiocytic infiltrate in the respiratory bronchioles and intraluminal budding fibrosis. The five cases with open lung biopsy performed also showed neutrophilic infiltrate in the alveoli. The two lung transplant cases were complicated by severe fibrotic changes. CONCLUSIONS: Chronic EAA demonstrates characteristic pathologic features. Definitive diagnosis requires correlation with clinical and radiologic findings due to possible morphologic mimicry of other diffuse parenchymal lung diseases.

Prevalence of deep venous thrombosis in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is always associated with a high incidence and mortality. Because of the presence of some concomitant risk factors such as immobilization, bronchial superinfection, patients who are admitted for acute exacerbations of COPD are generally considered to be at moderate risk for the development of venous thromboembolism. In this study, we investigated the prevalence and the clinical manifestations of deep venous thrombosis (DVT) in patients with acute exacerbation of COPD. METHODS: From March 2007 to March 2009, 520 consecutive patients were included in this study. On admission, color Doppler ultrasound of lower extremities in all cases was performed for diagnosing DVT. Patients with DVT were compared with those without DVT from such aspects as demographics, symptoms, physical signs and risk factors. RESULTS: Among the 520 patients, DVT was found in 46 cases (9.7%). In patients with DVT, the duration of hospitalization was longer (P = 0.01), and the mechanical ventilation requirement increased (P < 0.001). Other indicators for patients with more possibility of DVT were immobility exceeding 3 days (P < 0.001); pneumonia as concomitance (P = 0.01); respiratory failure type II (P = 0.013); current smoking (P = 0.001). Lower extremity pain was more common in DVT cases in comparison to those without DVT (34.8% vs. 15.2%, P = 0.01). CONCLUSIONS: The acute exacerbation of COPD patients, who were immobilized for over 3 days, complicated by pneumonia and had respiratory failure type II, had a higher risk of DVT. In addition, DVT detection awareness should be increased in cases that had a lower extremity pain.

[The relationship between gastroesophageal reflux disease and idiopathic pulmonary interstitial fibrosis].

OBJECTIVE: To determine the prevalence of gastroesophageal reflux disease (GERD) in patients with idiopathic pulmonary interstitial fibrosis (IPIF). METHODS: From December 2006 to January 2008, 24 consecutive patients with IPIF admitted to Beijing Chaoyang Hospital underwent 24-hour esophageal pH monitoring and esophageal manometry. Meanwhile, 23 patients with diffuse parenchymal lung disease (DPLD) (excluding IPIF) admitted to the hospital in the same period served as a control group. Comparison of the prevalence of pathologic esophageal acid exposure GERD symptoms, and ineffective esophageal motility (IEM) between the two groups was made. In this study, nocturnal acid exposure is defined as acid reflux episodes occurring from 10pm to 6am. RESULTS: (1) 16 out of the 24 (66.7%) patients with IPIF were demonstrated to have pathologic esophageal acid exposure; the prevalence of GERD in IPIF patients was significantly higher than that in other DPLD patients, whose prevalence was 26.1% (P < 0.05) ; (2) 87.5% patients with IPIF and GERD (GERD-IPIF) had nocturnal acid exposure episodes; (3) only 37.5% of the GERD-IPIF patients was found to have typical GERD symptoms such as heartburn and regurgitation; (4) The prevalence of IEM was similar in IPIF and other DPLD patients, being 42.9% and 39.1% respectively (P > 0.05). CONCLUSIONS: IPIF patients have higher prevalence of GERD and most of them usually do not show typical reflux symptoms. It is hereby suggested that IPIF patients should be screened with pH monitoring for GERD.