Risk factors for acute exacerbation of idiopathic pulmonary fibrosis--Extended analysis of pirfenidone trial in Japan.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a lifethreatening event and one of the important endpoints in clinical trials involving IPF. Despite this, there has been little evaluation of the potential risk factors for AE-IPF in clinical trials. We evaluated the risk factors for AE-IPF in a phase III clinical trial of pirfenidone in Japanese IPF patients. METHODS: The study population comprised 267 patients. The effects of various baseline characteristics as possible risk factors for AE-IPF during the study, as well as those of a ≥10% decline in percent vital capacity (%VC) within 6 months, were evaluated using Cox׳s proportional hazard model. The ≥10% decline in %VC was calculated in two ways: (1) an absolute decline (e.g. from 60% predicted to 50%); and (2) a relative decline (e.g. from 60% predicted to 54%). RESULTS: Over 52 weeks, 14 patients experienced AE-IPF. Univariate analysis using Cox׳s proportional hazards model showed that both relative and absolute ≥10% decline in %VC within 6 months were significant risk factors for AE-IPF. Stepwise multivariate analysis demonstrated that absolute or relative decline in both %VC and alveolar to arterial oxygen pressure difference (AaDO2) were significant risk factors for AE. The model using absolute decline [Hazard Ration (HR)=7.405, p=0.0007] and baseline AaDO2 (HR=1.063, p=0.0266) had a better fit than the model using relative decline and baseline AaDO2. CONCLUSIONS: Rapid %VC decline (≥10% within 6 months), and high baseline AaDO2, may be risk factors for AE-IPF.

Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.

BACKGROUND: A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population. METHODS: Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations. RESULTS: Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF. CONCLUSION: This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results.

Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder for which there are currently no specific or effective medical treatments. A multicentre, prospective, randomized, controlled clinical trial was conducted to assess the efficacy of inhaled N-acetylcysteine (NAC) monotherapy in Japanese patients with early stage IPF. METHODS: Eligible patients had well-defined IPF of mild-to-moderate severity, with no desaturation on exercise. Of 100 patients screened, 76 were randomly assigned to an NAC treatment group (group A; n = 38) that received 352.4 mg of NAC by inhalation twice daily or to a control group (group B; n = 38) that received no therapy. The primary endpoint was the change from baseline in forced vital capacity (FVC) at 48 weeks. RESULTS: There were no significant overall differences in the change in FVC between groups A and B. Post hoc exploratory analyses showed that NAC therapy was associated with stability of FVC in (i) a subset of patients with initial FVC <95% of predicted (n = 49; difference in FVC decline 0.12 L; P = 0.02) and (ii) in patients with initial diffusing capacity of carbon monoxide <55% of predicted (n = 21; difference in FVC decline 0.17 L; P = 0.009). CONCLUSIONS: These findings indicate that NAC monotherapy may have some beneficial effect in patients with early stage IPF. Further trials in more select IPF populations with progressive disease are required to prove the efficacy of inhaled NAC.

Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment.

BACKGROUND: A phase III trial in Japan showed that pirfenidone is effective for idiopathic pulmonary fibrosis (IPF). To find out which patients specifically benefit from pirfenidone, we analyzed in an exploratory manner the data from the phase III trial. METHODS: The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC), arterial oxygen partial pressure (PaO(2)), and the lowest oxygen saturation by pulse oximetry (SpO(2)) during the 6-minute steady-state exercise test (6MET). In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale) were evaluated in patients treated with high-dose (1800 mg/day) pirfenidone, low-dose (1200 mg/day) pirfenidone, and placebo at week 52. RESULTS: Significant efficacy of pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO(2) < 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, pirfenidone significantly suppressed cough and dyspnea. CONCLUSIONS: IPF patients having %VC ≥ 70% and SpO(2) < 90% at baseline will most likely benefit from pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from pirfenidone treatment. TRIAL REGISTRATION: This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (REGISTRATION NUMBER: JAPICCTI-050121).

The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial.

BACKGROUND: Our phase III clinical trial of pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) revealed the efficacy in reducing the decline of vital capacity (VC) and increasing the progression-free survival (PFS) time by pirfenidone. Recently, marginal decline in forced VC (FVC) has been reported to be associated with poor outcome in IPF. We sought to evaluate the efficacy of pirfenidone from the aspects of 5% change in VC. METHODS: Improvement ratings based on 5% change in absolute VC, i.e., "improved (VC ≥ 5% increase)", "stable (VC < 5% change)", and "worsened (VC ≥ 5% decrease)" at month 3, 6, 9 and 12 were compared between high-dose pirfenidone (1800 mg/day; n = 108) and placebo (n = 104) groups, and (high-dose and low-dose (1200 mg/day; n = 55)) pirfenidone (n = 163) and placebo groups. PFS times with defining the disease progression as death or a ≥ 5% decline in VC were also compared between high-dose pirfenidone and placebo groups, and low-dose pirfenidone and placebo groups. Furthermore, considering "worsened" and "non-worsened (improved and stable)" of the ratings at months 3 and 12 as "positive" and "negative", respectively, and the positive and negative predictive values of the ratings were calculated in each group. RESULTS: In the comparison of the improvement ratings, the statistically significant differences were clearly revealed at months 3, 6, 9, and 12 between pirfenidone and placebo groups. Risk reductions by pirfenidone to placebo were approximately 35% over the study period. In the comparison of the PFS times, statistically significant difference was also observed between pirfenidone and placebo groups. The positive/negative predictive values in placebo and pirfenidone groups were 86.1%/50.8% and 87.1%/71.7%, respectively. Further, the baseline characteristics of patients worsened at month 3 had generally severe impairment, and their clinical outcomes including mortality were also significantly worsened after 1 year. CONCLUSIONS: The efficacy of pirfenidone in Japanese phase III trial was supported by the rating of 5% decline in VC, and the VC changes at month 3 may be used as a prognostic factor of IPF. TRIAL REGISTRATION: This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (REGISTRATION NUMBER: JAPICCTI-050121).

Proteomic biomarkers for acute interstitial lung disease in gefitinib-treated Japanese lung cancer patients.

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10(-25)), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control.

Interstitial lung disease in gefitinib-treated Japanese patients with non-small-cell lung cancer: genome-wide analysis of genetic data.

AIM: To investigate potential relationships between SNPs and acute interstitial lung disease (ILD) events in Japanese non-small-cell lung cancer patients receiving gefitinib. MATERIALS & METHODS: Japanese non-small-cell lung cancer patients treated with gefitinib from a prospective pharmacoepidemiological cohort with a nested case-control study component ('CCS'; 52 ILD cases, 139 controls) and a retrospective study (28 ILD cases, 55 controls) were genotyped for nearly 500,000 SNPs. Associations between genotype and ILD were evaluated using Fisher's exact test and logistic regression modeling, and false discovery rate analysis was used to adjust for the large number of statistical tests. RESULTS: The CCS data provided some false discovery rate evidence that the significance of top-ranking SNPs exceeded levels expected by chance, suggesting some genuine associations. However, replication analyses using retrospective study data were not supportive and there was little evidence of strong genetic associations from a combined analysis. Adjustment of CCS analyses for clinical variables provided little additional convincing evidence. Significant gene-gene interactions between SNP pairs using CCS data were not confirmed in retrospective study replication analyses. CONCLUSION: Although it is not possible to exclude genetic influences in ILD etiology, common sequence variation is unlikely to explain a major component of ILD risk. Our top results may provide a useful hypothesis-generating starting point for further research.

Recurrence of inflammatory pseudotumor of the lung after eleven years of remission.

The standard treatment of inflammatory pseudotumor of the lung is surgical excision. However, little data is available on steroid therapy in patients with the unresectable disease. Here, we report a patient with recurrent inflammatory pseudotumor of the lung with pleural involvement who had been successfully treated with corticosteroid eleven years previously. Like the previous treatment, retreatment with corticosteroid proved to be effective for the recurred lesion. In addition, the patient had developed extramammary Paget's disease and bladder cancer after the initial onset of inflammatory pseudotumor. Steroid therapy could be an optional modality in treating unresectable inflammatory pseudotumor, although long-term follow-up is definitely necessary.

Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis.

RATIONALE: Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space. OBJECTIVES: To identify the responsible gene that causes pulmonary alveolar microlithiasis. METHODS: By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis. MEASUREMENTS AND MAIN RESULTS: We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function. CONCLUSION: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.

[A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions].

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.

[Case of lung edema occurring as a result of inhalation of fumes from a Teflon-coated flying pan overheated for 4 hours].

The patient was a 59-year-old man who had been treated with continuous positive airway pressure for a diagnosis of obstructive sleep apnea syndrome. While cooking buckwheat noodles, the patient fell asleep with a frying pan on the fire. After four hours, he was awakened by the smell of burning as well as pharyngalgia, and visited this hospital. He was found to have hypoxia, and diagnostic imaging showed diffuse concentration increase with peripheral clear zones in bilateral lung fields, a typical finding of pulmonary edema. In view of the peculiar temporal course of his disease and inhalation of Teflon fumes immediately before its occurrence, he was considered to have polymer fume fever with non-cardiogenic pulmonary edema. After admission, he was treated with oxygen inhalation and diuretics, and experienced a rapid improvement of his general condition and findings on diagnostic imaging. In European countries and the United States, cases with a history of inhalation of Teflon fumes have been given a diagnosis of polymer fume fever. This case is of interest as it is apparently the first such disease reported in Japan.

[A case of pulmonary abscess in which Haemophilus parainfluenzae and Streptococcus intermedius were isolated by percutaneous needle aspiration].

Some microbes, including the Bacteroides species, Staphylococcus aureus and Streptococcus milleri groups, can cause pulmonary abscess. Haemophilus parainfluenzae is usually categorized as one of the normal flora which colonizes in the ears and the nasopharynx, and it has been long considered that H. parainfluenzae has little pathogenicity in the lower respiratory tract and lung parenchymal. In this report, we present a case of pulmonary abscess caused by both H. parainfluenzae and Streptococcus intermedius. The patient was a 75-year-old man who had had total esophageo-gastrectomy because of esophageal cancer. He presented with purulent sputum, and chest X-ray film showed a dense consolidation in the right upper lung field. CT-guided transcutaneous fine needle aspiration was performed as a diagnostic procedure. Since both H. parainfluenzae and S. intermedius had been isolated from the lesion, pulmonary abscess caused by these two pathogens was diagnosed. The patient was treated with panipenem/betamipron, and his symptoms and pulmonary infiltrates on the chest X-ray film improved thereafter. So far, very few cases have been reported in which H. parainfluenzae caused lower respiratory tract infection. Although S. intermedius is known as one of the pathogens of pulmonary abscess, it is possible that H. parainfluenzae could also be pathogenic in infectious diseases of the lung.

[An autopsy case of obliterative bronchiolitis associated with Stevens-Johnson syndrome].

We reviewed an autopsied 27-year-old female with obliterative bronchiolitis associated with Stevens-Johnson syndrome. She had a history of Stevens-Johnson syndrome at age 10 years old and was treated with corticosteroids. Two months after the onset of dermatitis, the patient complained of dyspnea on exertion. The chest radiograph showed hyperinflation, and pulmonary function tests revealed obstructive impairment. The respiratory failure progressed due to respiratory tract infection and pneumothorax. She underwent thoracoscopic cyst surgery for right pneumothorax. Although the patient was clinically diagnosed as having obliterative bronchiolitis and received corticosteroids therapy and mechanical ventilation, she died of progressive respiratory failure 17 years after the onset of Stevens-Johnson syndrome. On autopsy, the macroscopic appearance of both lungs showed multiple white nodules in the centrilobular lesion corresponding to the obliteration of the small bronchioli. The microscopic appearance revealed constrictive bronchiolitis in the membranous bronchioli of both lungs associated with secondary bronchiectasis caused by superimposed infection.

Semi-quantitative analysis of Streptococcus pneumoniae urinary antigen: kinetics of antigen titers and severity of diseases.

Detection of urinary antigen by a rapid immunochromatographic membrane test (Binax NOW) was widely accepted as a powerful tool for diagnosis of Streptococcus pneumoniae pneumonia. This is a qualitative kit, so the value of quantitative analysis of urinary antigen, especially correlation of antigen titers and severity of diseases, remained to be determined. We examined semi-quantitative antigen titer in urines collected from urinary antigen-proven S. pneumoniae pneumonia on admission, and analyzed the kinetics of antigen titer and its relation to severity of diseases. After serial 2-fold dilution of urine, the highest dilution for positive results was determined, and this was designated as maximum dilution factor (MDF). MDFs varied from 1 to 4096 in 29 patients examined (mean MDF, 317.8). Importantly, severe cases of S. pneumoniae pneumonia were higher values of MDFs (mean MDF: 760.5) than those of non-severe cases (mean MDF: 5.4). The patients with high MDFs (> or = 64) demonstrated higher values of LDH, CRP and lower values of WBC and PaO2 compared to those of low MDFs group (< or = 32). There was no clear correlation between CRP values and antigen titers, and conversely the majority of severe cases showed relatively weak CRP responses, despite high levels of bacterial antigen. Kinetic analysis of urinary and serum antigen titers in 4 cases of S. pneumoniae pneumonia exhibited consistently higher values of antigen titers in urine than those in serum. The half lives of urinary and serum antigen titers were calculated to be 1.0-3.4 and 1.1-2.3 weeks, respectively. These data suggest that quantitative analysis of urinary antigen may be a useful indicator for severity of disease and course of S. pneumoniae pneumonia. Our results demonstrate an application for S. pneumoniae antigen titer determination in urine and serum, which may be crucial not only for diagnostic measures, but also may provide a better understanding of the pathogenesis of S. pneumoniae infection.

[A case of cryptogenic organizing pneumonia after postoperative irradiation for breast cancer].

The patient was a 69-year-old woman who had undergone breast-conserving surgery of the right breast, followed by tangential irradiation of 50 Gy to the remaining breast. Her subsequent progress was monitored by endocrine therapy with toremifene. Symptoms consisting of cough and slight fever developed 5 months after completion of radiation therapy. A chest X-ray image revealed an infiltrating shadow in the right middle and lower pulmonary fields, and the patient visited our hospital. BOOP was diagnosed by thoracoscopic biopsy. Spontaneous remission was observed during monitoring of the patient's progress. A shadow subsequently reappeared, for which a steroid was administered. Improvement was rapid. This case suggests that when tangential irradiation with or without endocrine therapy is provided, subsequent to breast-conserving treatment, patients should be monitored for the occurrence of BOOP.

Surgically curable peripheral lung carcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival.

STUDY OBJECTIVES: To define characteristics of surgically curable, early cancers of the lung, we retrospectively studied relationships between thin-section CT (TS-CT) scans, pathologic features, and outcome data in 287 patients with resected small-diameter (< 20 mm) peripheral lung carcinoma. Cases included 260 adenocarcinomas, 16 squamous cell carcinomas, 6 small cell carcinomas, 3 large cell carcinomas, and 2 others. MEASUREMENTS AND RESULTS: All tumors were classified by tumor shadow disappearance rate (TDR) on TS-CT as having either an "air-containing" or "solid-density" pattern. Adenocarcinomas are typically classified into these patterns. Air-containing patterns (n = 136) showed 1% pleural involvement and 2% vascular invasion, with no lymphatic permeation by pathology. Solid-density patterns (n = 124) showed 34% pleural involvement, 42% vascular invasion, and 29% lymphatic permeation. No cases of relapse or death were observed in cases with the air-containing pattern, in contrast to the high relapse and death rate in solid-density cases (p < 0.0001). All non-adenocarcinoma cases (n = 25) had a solid-density pattern, with 4% pleural involvement, 52% vascular invasion, and 44% lymphatic permeation. The overall 5-year survival rate for non-adenocarcinoma was 60%, similar to that for solid-density adenocarcinoma. CONCLUSIONS: When peripheral lung cancers < 20 mm in diameter show air-containing patterns on TS-CT images, surgical outcomes may be favorable with curable disease.

Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a chronic inflammatory airway disease predominantly affecting Asian populations. DPB is considered to be a complex genetic disease. Considering the mucous hypersecretion of the disease, we hypothesized that the transcriptional activity of mucin genes may be altered in DPB. We analyzed nucleotide sequences of regulatory region of six mucin genes--MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7--and detected their promoter polymorphisms. Among them, the insertion/deletion polymorphism identified in the MUC5B gene was significantly associated with the disease (p = 0.0001). Transcriptional activity observed in the three major promoter haplotypes corresponded to the strength of the disease association in which these haplotypes are involved. Immunohistochemistry of the lung tissues of DPB revealed that MUC5B was abundantly expressed not only in bronchial glands but also in increased numbers of goblet cells on the bronchial surface, where MUC5AC is predominant and MUC5B expression is generally scarce in the normal lung. Marked mucous hypersecretion observed in DPB may be partly explained by increased and aberrant expression of MUC5B. The possible involvement of MUC5B gene in DPB was demonstrated. A further role of the MUC5B polymorphism in its pathogenesis should be studied in the future.

Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.

[Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial pneumonia initially in the right lung after surgery lobectomy for left lung cancer].

A tumor was found in the left S10 in a chest CT scan of a 72-year-old male patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and mediastinal lymph nodes under video-assisted thoracoscopic surgery. The histopathological evaluation disclosed a well-differentiated squamous cell carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day, a severe hypoxemia (PaO2 48 mmHg) developed, and the chest CT showed diffuse ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started. However, despite this therapy, the diffuse GGO extended to both lung fields, and the patient died of respiratory failure 82 days later. The histopathology at autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of IPF/UIP could have been triggered by a high concentration of oxygen or mechanical lung injury during the patient's surgery.