Novel Features of Eukaryotic Photosystem II Revealed by Its Crystal Structure Analysis from a Red Alga.

Photosystem II (PSII) catalyzes light-induced water splitting, leading to the evolution of molecular oxygen indispensible for life on the earth. The crystal structure of PSII from cyanobacteria has been solved at an atomic level, but the structure of eukaryotic PSII has not been analyzed. Because eukaryotic PSII possesses additional subunits not found in cyanobacterial PSII, it is important to solve the structure of eukaryotic PSII to elucidate their detailed functions, as well as evolutionary relationships. Here we report the structure of PSII from a red alga Cyanidium caldarium at 2.76 Å resolution, which revealed the structure and interaction sites of PsbQ', a unique, fourth extrinsic protein required for stabilizing the oxygen-evolving complex in the lumenal surface of PSII. The PsbQ' subunit was found to be located underneath CP43 in the vicinity of PsbV, and its structure is characterized by a bundle of four up-down helices arranged in a similar way to those of cyanobacterial and higher plant PsbQ, although helices I and II of PsbQ' were kinked relative to its higher plant counterpart because of its interactions with CP43. Furthermore, two novel transmembrane helices were found in the red algal PSII that are not present in cyanobacterial PSII; one of these helices may correspond to PsbW found only in eukaryotic PSII. The present results represent the first crystal structure of PSII from eukaryotic oxygenic organisms, which were discussed in comparison with the structure of cyanobacterial PSII.

The risk factors for developing of chronic pulmonary aspergillosis in nontuberculous mycobacteria patients and clinical characteristics and outcomes in chronic pulmonary aspergillosis patients coinfected with nontuberculous mycobacteria.

Patients with chronic pulmonary aspergillosis (CPA) have a poor prognosis and CPA occurs in patients with various underlying diseases. Recently, the number of patients with CPA complicated by nontuberculous mycobacteria (NTM) has increased. Additionally, complications of both diseases have several problems like drug interactions. Since the impact of NTM on the outcome of CPA is not well understood, we investigated the risk factors for developing CPA and the clinical characteristics of CPA patients with or without NTM. We retrospectively investigated the medical records of NTM and CPA patients who were admitted to Nagasaki University Hospital between April 2008 and September 2013. Comorbid diseases, causative microorganisms, radiological findings, and outcomes were evaluated. During the study period, 82 and 41 patients were diagnosed as having NTM and CPA, respectively. Nine patients were coinfected with NTM and CPA, and cavitary type NTM and steroid usage were independent risk factors of development of CPA. Mortality rates in the coinfection group were significantly higher than those of the NTM without CPA group (P = .003, log-rank test). The rate of treatment initiation in the co-infection group (33.3%) was significantly lower than in the CPA without NTM group (84.4%) (P = .006). However, there were no significant differences in cumulative survival rate between both groups (P = .760, log-rank test). Cavity formation and steroid usage were the independent risk factors for NTM patients to develop CPA within long observation period, and development of CPA made outcomes poor. It is important to diagnose the development of CPA early and initiate treatment for CPA.

A mortality prediction rule for non-elderly patients with community-acquired pneumonia.

BACKGROUND: No mortality prediction rule is suited for non-elderly patients with community-acquired pneumonia. Therefore, we tried to create a mortality prediction rule that is simple and suitable for non-elderly patients with community-acquired pneumonia. METHODS: Because of low mortality at young age, we used information from an administrative database that included A-DROP data. We analysed the rate and risk factors for in-hospital community-acquired pneumonia-associated death among non-elderly patients and created a mortality prediction rule based on those risk factors. RESULTS: We examined 49,370 hospitalisations for patients aged 18-64 years with community-acquired pneumonia. The 30-day fatality rate was 1.5%. Using regression analysis, five risk factors were selected: patient requires help for feeding, the existence of malignancy, confusion, low blood pressure, and age 40-64 years. Each risk factor of our proposed mortality risk scoring system received one point. A total point score for each patient was obtained by summing the points. The negative likelihood ratio for the score 0 group was 0.01, and the positive likelihood ratio for the score ≥4 group was 19.9. The area under the curve of the risk score for non-elderly (0.86, 95% confidence interval: 0.84-0.87) was higher than that of the A-DROP score (0.72, 95% confidence interval: 0.70-0.74) (P < 0.0001). CONCLUSIONS: Our newly proposed mortality risk scoring system may be appropriate for predicting mortality in non-elderly patients with community-acquired pneumonia. It showed a possibility of a better prediction value than the A-DROP and is easy to use in various clinical settings.

Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan.

OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population. METHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined. RESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications. CONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.

Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis.

Invasive pulmonary mucormycosis is a life-threatening fungal infection encountered in immunocompromised patients. An intravenous high-dose lipid formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not been evaluated. We evaluated the efficacy of inhaled aerosolized L-AMB in murine invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with cortisone acetate and cyclophosphamide and challenged on day 0 with 1 × 106 conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were assigned to one of the following 3 treatment groups: (i) control, (ii) treatment only (aerosolized L-AMB from day 1-5 after challenge), and (iii) prophylaxis followed by treatment (aerosolized L-AMB from day -2 to 5 before and after challenge). Survival was monitored until 12 days after challenge. For fungal-burden and histopathological examination, mice were sacrificed 4 h after treatment on day 3. Numbers of colony-forming units per lung were calculated. To study the distribution of AMB after inhalation of L-AMB, immunohistochemical studies using AMB antibody were performed. Aerosolized L-AMB significantly improved survival rate and decreased fungal burden compared with control group, and histopathology findings were superior to those of control group. However, no significant differences were detected between the treatment-only and prophylaxis followed by treatment groups. Immunohistochemical analysis showed that L-AMB was promptly distributed in lung tissue after inhalation therapy. Aerosolized L-AMB showed modest efficacy against R. oryzae infection in mice treated after fungal challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal model.

Pathogenesis and clinical features of chronic pulmonary aspergillosis - is it possible to distinguish CNPA and CCPA clinically?

BACKGROUND: The pathogenesis of chronic pulmonary aspergillosis (CPA) including chronic necrotizing pulmonary aspergillosis (CNPA), chronic cavitary pulmonary aspergillosis (CCPA), and simple aspergilloma (SA) has been poorly investigated. We examined all types of CPA cases with histopathological evidence to clarify the differences in pathogenesis and clinical features. METHOD: We searched for cases diagnosed as pulmonary aspergillosis by histopathological examination in Nagasaki University Hospital between 1964 and September 2010. All available clinical information including radiological findings were collected and analyzed. RESULT: We found 7, 5, 8, and 7 cases of proven CNPA, probable CNPA, CCPA, and SA, respectively. The radiograph of proven and probable CNPA was initially infiltrates or nodules that progress to form cavities with or without aspergilloma, whereas the radiograph of CCPA showed pre-existed cavities and peri-cavitary infiltrates with or without aspergilloma. The patients with proven and probable CNPA exhibited not only respiratory symptoms but also systemic symptoms and malnutrition. Aspergillus fumigatus was the most frequently isolated Aspergillus species (n = 14), however, Aspergillus niger was the predominant isolated species in proven CNPA cases (n = 4). CONCLUSION: Our data indicate that the cases with chronic infiltration, progressive cavitation, and subsequent aspergilloma formation should be diagnosed as CNPA, and the cases with pre-existed cavities showing peri-cavitary infiltrates with or without aspergilloma would mean CCPA. However, it may be difficult to distinguish the two subtypes if a series of adequate radiography films are not available. We propose the term "chronic progressive pulmonary aspergillosis (CPPA)" for the clinical syndrome including both CNPA and CCPA.

[Two cases of emphysematous urinary tract infections successfully treated with conservative management].

Emphysematous urinary tract infection is a rare, fulminant complication that is characterized by the presence of gas in the pelvicaliceal system, renal parenchyma, perinephric tissues and retroperitoneum. Surgical resection is usually regarded as the treatment of choice, however several studies have shown the safety and efficacy of conservative management under the correct diagnosis and appropriate antibiotic administration. We herein report on two cases of emphysematous urinary tract infection, pyelonephritis and cystitis infected with ESBL-producing Eschrerichia coli, complicated with diabetic mellitus which were successfully treated with conservative treatment.

[A case of influenza pneumonia following pneumococcal infection in an adult patient with concurrent encephalopathy with a lesion in the splenium of the corpus callosum].

A 35-year-old male patient had a fever, cough, and other symptoms since the end of December 2010. The patient then developed a high fever and decreased SpO2, suggesting possible pneumonia. The patient was admitted to our hospital on the 6th day of illness. Chest computed tomography revealed multiple infiltrative shadows and ground-glass opacities distributed in a patchy pattern in the bilateral lungs. An atypical pneumonia was suspected, and we initiated antibiotic treatment with minocycline. However, the patient developed consciousness disturbance in the afternoon of the 7th day of illness. The high fever persisted, suggesting the patient's poor response to minocycline treatment, which was then replaced with ciprofloxacin and imipenem/cilastatin on the 8th day of illness. Streptococcus pneumoniae was detected in the blood culture bottles submitted at the time of admission. A head magnetic resonance imaging performed on that day showed a high intensity area in the splenium of the corpus callosum, leading to a diagnosis of encephalopathy. Methylprednisolone pulse therapy and gamma globulin treatment were initiated. The patient then recovered consciousness gradually with improvement of inflammatory responses and imaging findings. Subsequently, an influenza virus (H1N1) antibody level was found to have increased from less than 10 times to 640 times. Thus, it was determined that the patient's pneumonia and encephalopathy were attributable to the influenza A (H1N1) pdm09 virus during the flu season and Streptcoccal infection. Combination therapy, such as steroid pulse treatment, appropriate antibiotics and gamma globulin preparation was effective for both the flu-induced mixed pneumonia and encephalopathy in this patient.

Antifungal susceptibilities of Aspergillus fumigatus clinical isolates obtained in Nagasaki, Japan.

We investigated the triazole, amphotericin B, and micafungin susceptibilities of 196 A. fumigatus clinical isolates in Nagasaki, Japan. The percentages of non-wild-type (non-WT) isolates for which MICs of itraconazole, posaconazole, and voriconazole were above the ECV were 7.1%, 2.6%, and 4.1%, respectively. A G54 mutation in cyp51A was detected in 64.2% (9/14 isolates) and 100% (5/5 isolates) of non-WT isolates for itraconazole and posaconazole, respectively. Amphotericin B MICs of ≥2 µg/ml and micafungin minimum effective concentrations (MECs) of ≥16 µg/ml were recorded for two and one isolates, respectively.

Correlation between triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus.

This is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154 Aspergillus fumigatus clinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r = 0.5700, P < 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 µg/ml (0.5 µg/ml versus 2 µg/ml, P = 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r = 0.5237, P < 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 µg/ml (0.25 µg/ml versus 0.5 µg/ml, P = 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r = -0.2627, P = 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistant A. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in the cyp51A gene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistant A. fumigatus if itraconazole is used for extended periods.

Pravastatin inhibits farnesol production in Candida albicans and improves survival in a mouse model of systemic candidiasis.

Candidemia remains a major cause of morbidity and mortality, especially in immunocompromised patients. A strategy of reducing virulence and virulence factors of Candida spp. is an attractive approach for the treatment of serious infections caused by these yeasts. Recently, farnesol has been reported to be a quorum-sensing autoinducer, as well as a virulence factor of C. albicans. In the present study, we examined the effects of pravastatin, a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor on the in vitro production of farnesol. In addition, the synergistic effects of pravastatin with fluconazole (FLC) were examined in a mouse model of systemic infections. In vitro experiments demonstrated that pravastatin had synergistic activity with FLC as judged by fractional inhibitory concentration index (FICI) and suppression of farnesol production at sub-minimum inhibitory concentrations. Furthermore, significant improvement of survival in systemic infection models was shown with pravastatin supplementation. The survival benefits of pravastatin were correlated with reductions of fungal burden. These data suggest the potential of pravastatin as a supportive therapy against C. albicans infections. Synergistic antifungal activity and suppression of HMG-CoA reductase-associated Candida virulence factors, including farnesol, may explain, at least in part, the in vivo efficacy of pravastatin.

Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis.

Diagnosing chronic pulmonary aspergillosis (CPA) is complicated, and there are limited data available regarding the identification of galactomannan (GM) in clinical specimens to assist the detection of this infection. The purpose of this study was to evaluate the detection of GM in bronchoalveolar lavage fluid (BALF) and serum and to assess its utility for diagnosing CPA. We retrospectively reviewed the diagnostic and clinical characteristics of 144 patients, with and without CPA, in Nagasaki University Hospital, Japan, whose BAL and serum specimens were examined for the presence of GM. The Platelia Aspergillus enzyme immunoassay (PA EIA) was performed according to the manufacturer's instructions. The mean values of BALF GM antigen were 4.535 (range, 0.062-14.120) and 0.430 (range, 0.062-9.285) in CPA (18) and non-CPA (126) patients, respectively. The mean values of serum GM antigen were 1.557 (range, 0.232-5.397) and 0.864 (range, 0.028-8.956) in CPA and non-CPA patients, respectively. PA EIA of BALF is superior to the test with serum, with the optimal cut-off values for BALF and serum of 0.4 and 0.7, respectively. The sensitivity and specificity of PA EIA in BALF at a cut-off of 0.4 were 77.2% and 77.0%, respectively, whereas with serum at a cut-off of 0.7, they were 66.7% and 63.5%, respectively. GM testing using BALF showed reasonable sensitivity and specificity as compared to that using serum. Thus, assessing GM levels in BALF may enhance the accuracy of diagnosing CPA.

[An adult case of influenza-associated encephalitis successfully treated with high dose intravenous immunoglobulins].

A 73-year-old man was admitted to our hospital with a high fever and left paresis. A rapid diagnosis test was positive for influenza A was positive by rapid diagnosis test and diffusion-weighted MRI imaging of the brain showed a high intensity lesion of the right cerebral peduncle. The patient was therefore diagnosed as having influenza A virus infection complicated with lacunar infarction. In spite of initial treatment with oseltamivir and anticoagulant therapy, he lost consciousness eight hours after admission. The high intensity lesion of the cerebral peduncle enlarged and new lesions in the thalamus, hippocampus and calcarine cortex were detected with brain MRI. Additionally, an electroencephalographic study showed an entire slow wave and as the other causative pathogens of central nerve system infection were not detected, the likely diagnosis was influenza-associated encephalitis. We administered a high dose of intravenous immunoglobulin since the low-grade fever and mild unconscious state had continued in spite of the treatment with methylprednisolone pulse therapy. His consciousness was restored and body temperature became normal immediately. We could confirm the efficacy of our treatment by measurement of IL-6 levels in the serum and cerebrospinal fluid during the entire clinical course. In conclusion, a high dose of intravenous immunoglobulin therapy might be one of the effective treatments for influenza-associated encephalitis.

Diagnostic significance of Aspergillus species isolated from respiratory samples in an adult pneumology ward.

Although the diagnostic significance of isolating Aspergillus spp. from respiratory cultures has been studied in immunocompromised hosts with invasive pulmonary aspergillosis (IPA), little is known of such infections in immunocompetent patients with other forms of aspergillosis. In this study of adult pneumology ward patients, we examined the association between Aspergillus spp. and disease prevalence. Laboratory records from April 1998 to March 2009 were reviewed to identify patients with Aspergillus spp. in respiratory samples. Correlations between the isolated species and clinical characteristics of patients were evaluated. During the study period, 165 Aspergillus spp. isolates were detected in the respiratory cultures of 139 patients. Of these patients, 62 (45%) were colonized with Aspergillus spp. and displayed no clinical symptoms of aspergillosis, while 77 (55%) had a form of pulmonary aspergillosis, characterized as either chronic necrotizing pulmonary aspergillosis (CNPA) (48%), aspergilloma (29%), IPA (13%), or allergic bronchopulmonary aspergillosis (ABPA) (10%). The dominant species were Aspergillus fumigatus (41%), A. niger (32%), and A. versicolor (12%). A. fumigatus was most commonly isolated in patients with IPA, aspergilloma, and CNPA, whereas A. niger was the dominant species in colonized patients and those with ABPA. Isolation of an Aspergillus spp. from respiratory samples does not confirm it as the etiologic pathogen because airway colonization by Aspergillus spp. is a common feature in several chronic lung diseases. Repeated isolation of the identical Aspergillus species and detection of anti-Aspergillus antibodies and/or Aspergillus antigens in sera are needed to determine the isolate represents the etiologic agent of disease.

Characteristics and disease severity of healthcare-associated pneumonia among patients in a hospital in Kitakyushu, Japan.

Healthcare-associated pneumonia (HCAP) is a newly identified condition, and epidemiologic studies in Japan are still limited. We retrospectively observed patients with HCAP and community-acquired pneumonia (CAP) who were hospitalized between December 2004 and March 2005, and compared their disease characteristics. A total of 34 patients (14 with HCAP and 20 with CAP) were evaluated. Of the patients with HCAP, seven (50%) were hospitalized for at least 2 days in the preceding 90 days and five (35.7%) resided in a nursing home or extended care facility. Compared with patients with CAP, patients with HCAP were older, had more complications, including central nerve diseases, had greater disease severity, but lower serum albumin level. More methicillin-resistant Staphylococcus aureus, Pseudomonas spp., and anaerobes were isolated from patients with HCAP than from those with CAP. Conversely, more Streptococcus pneumoniae was detected and more penicillin was used in patients with CAP. This study provides additional evidence that HCAP should be distinguished from CAP and suggests the pathogenesis and therapeutic strategy for HCAP may be similar to those for hospital-acquired pneumonia.

[Chronic fungal infection, up-to-date].

Deep-seated mycosis usually occurred in severe immunocompromised patients and is sometimes fatal. Hence, chronic fungal infection occurred in the patients with mild to moderate immunocompromised status and persists for longer period. Biofilm formation is one of the factors related to persisting infection of Candida spp. Biofilm formation resists to the antifungals in catheter-related Candida infection and selection of appropriate antifungals will be an important key to achieve good outcome. Although azoles possessed excellent antifungal activity against planktonic Candida spp., they show lower activity against biofilm-formed Candida spp. Overexpression of efflux pump of Candida spp. is reported to be involved in lowered activity of azoles. Amphotericin B, liposomal amphotericin B, and micafungin however, are expected to have high antifungal activity against biofilm-formed Candida spp. Recently, Aspergillus is also reported to possess potential of forming biofilm. Biofilm formation of Aspergillus is considered to be related to pathogenesis of chronic pulmonary aspergillosis. General antifungals are not highly active to biofilm-formed Aspergillus as same as Candida, and only amphotericin B and its liposomal formulation are expected to be effective in vitro.

Expression and DNA microarray analysis of a platelet activating factor-related molecule in severe pneumonia in mice due to influenza virus and bacterial co-infection.

Platelet-activating factor (PAF) is a critical mediator of severe inflammatory diseases such as pneumonia, and the PAF-receptor (PAFR) is known to be an anchor for Streptococcus pneumoniae attachment to lung epithelial cells. We conducted a DNA microarray analysis to detect critical factors that mediate fulminant pneumonia due to influenza virus and S. pneumoniae co-infection in mice. Among the factors detected, levels of PAF-acetyl hydrolase (PAF-AH), which functions as inactivated PAF, were significantly increased, and PAFR was expressed in co-infected mouse lungs, as compared to the respective levels in mice infected with either S. pneumoniae or virus alone. Significantly elevated PAF-AH enzymatic activity was observed in the co-infected mouse lung, suggesting that co-infection activated PAF-related factors. These findings suggest that PAF and related molecules play important roles in fulminant pneumonia due to influenza virus infection, especially when severe bacterial pneumonia is complicated by co-infection with influenza virus.

Efficacy of SPK-843, a novel polyene antifungal, in a murine model of systemic cryptococcosis.

SPK-843, a new polyene antifungal, possessed efficacy in a murine model of systemic infection caused by Cryptococcus neoformans. The administration of 4.0 mg/kg SPK-843 led to better survival prolongation and fungal reduction than those observed with the administration of 0.7 mg/kg amphotericin B and 80 mg/kg fluconazole (P < 0.001), without histopathological renal changes.

Efficacy of SPK-843, a novel polyene antifungal, in comparison with amphotericin B, liposomal amphotericin B, and micafungin against murine pulmonary aspergillosis.

SPK-843, a new polyene antifungal, exhibited dose-dependent efficacy on murine pulmonary aspergillosis models. SPK-843 doses of higher than 1.0 mg/kg of body weight exhibited no renal toxicities and a tendency toward better survival prolongation than the estimated maximum tolerated doses of amphotericin B (Fungizone) (1.0 mg/kg) and liposomal amphotericin B (AmBisome) (8.0 mg/kg).

Lung fibrosis 10 years after cessation of bleomycin therapy.

Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several types of malignancy, including germ cell tumors, lymphoma, and certain types of squamous-cell carcinoma. The common adverse effect of BLM is interstitial pneumonitis, followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in up to 46% of patients treated with BLM-containing chemotherapy and lung toxicity usually appears during treatment. Here we describe a patient with lung fibrosis, who presented with slow progressive breathlessness and pneumothorax more than 10 years after cessation of BLM therapy. A 15 year-old girl presented with abnormal shadows on chest X-ray. The patient had a yolk sac carcinoma in the sacral region at 1 year of age and obtained complete remission after being treated with tumor resection, radiation, and several anti-cancer drugs including BLM. There were no abnormal findings in chest X-ray until she reached 3 years of age, when she had developed respiratory distress that worsened with age. The patient had experienced an episode of pneumothorax at 13 years of age. Chest CT at the time revealed interstitial reticular opacities. Radiological findings and pathological examination of the lung tissue obtained during bullectomy with video-assisted thoracic surgery were compatible with BLM-induced pneumonitis. The present study suggests that lung fibrosis may surface more than 10 years after cessation of BLM therapy at the age of 1 year, with no chest radiographic findings 1 year after completion of chemotherapy. The use of BLM in infants requires strict supervision and observation and careful long-term follow up.