Ho-Il Yoon

Severe pulmonary adverse effects in lymphoma patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen plus rituximab.

Background/Aims The aim of our study was to determine the incidence and clinical features of severe pulmonary complications in patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) as the initial treatment for lymphoma. Methods A retrospective analysis of pulmonary infection and drug-induced interstitial pneumonitis (DIIP) was performed using lymphoma registry data. R-CHOP was administered in 71 patients and CHOP in 29 patients. Results The severe pulmonary adverse events tended to occur more frequently with R-CHOP (18.3%) than CHOP alone (13.8%), although the difference was not significant (p = 0.771). DIIP occurred in five patients in the R-CHOP arm (7%) and in one in the CHOP arm (3%). The continuous use of steroids for conditions other than lymphoma significantly increased the risk of pulmonary infection including Pneumocystis jiroveci pneumonia (p = 0.036) in the multivariate analysis. International prognostic index, tumor stage, smoking, previous tuberculosis, chronic obstructive pulmonary disease, and lymphoma involvement of lung parenchyma were not related to pulmonary adverse events. Patients who experienced severe pulmonary events showed shorter survival when compared to those without complications (p = 0.002). Conclusions Our experiences with serial cases with DIIP during chemotherapy and the correlation of continuous steroid use with pulmonary infection suggest that the incidence of pulmonary complications might be high during lymphoma treatment, and careful monitoring should be performed.

Determinants of recurrence after successful treatment of Mycobacterium avium complex lung disease.

BACKGROUND The long-term treatment outcomes of Mycobacterium avium complex (MAC) lung disease (LD) have not been adequately evaluated. OBJECTIVE We evaluated the determinants of microbiological recurrence after successful treatment for MAC LD. DESIGN The medical records of 295 MAC LD patients treated with combination chemotherapy from 2004 to 2013 were reviewed. The clinical data, microbiological study results and chest computerised tomography findings were collected for each patient. RESULTS Ninety-one patients who maintained negative sputum conversion during treatment and had a minimum 10-month follow-up period after treatment were included. The median duration of follow-up was 25 months. Seventy-one (78.0%) patients remained microbiologically disease-free, while 20 (22.0%) had microbiological recurrence after successful treatment. Age, sex and body mass index were not associated with microbiological recurrence. Longer intervals between initial diagnosis and administration of medication (P = 0.024), increased number of involved lobes (P = 0.033) and failure of sputum conversion within 6 months of initiating treatment (P = 0.017) were significantly associated with microbiological recurrence. CONCLUSION Microbiological recurrence after successful anti-MAC chemotherapy was associated with the time interval between initial diagnosis and administration of medication, number of lobes involved and time to sputum conversion during treatment.

Combination therapy of conditionally replicating adenovirus and histone deacetylase inhibitors.

Combination therapy of adenoviral gene therapy and a histone deacetylase (HDAC) inhibitor is important due to the enhancing effect of HDAC inhibitors on adenoviral transduction and transcription. However, contradictory results have been reported on the effect of combination of CRAd (conditionally replicating adenovirus) and HDAC inhibitors. This study was designed to investigate the interaction of CRAd and HDAC inhibitors and determine the ideal way to combine the two agents. Combination of HDAC inhibitors (SK7041, SBHA and vorinostat) at pre- and post-transductional periods with CRAd enhanced the transduction of CRAd and expression of luciferase expression from Δ24-luc in vitro. However, suppression of luciferase expression from Δ24-luc injected tumor mass was observed by in vivo tumor bioluminescence imaging and drug interaction analysis also showed an antagonistic interaction that was probably related with the inhibitory effect of the HDAC inhibitor on adenoviral replication. Suppression of p21 induction by p21 siRNA reversed the suppressive effect of vorinostat on the replication of CRAd, but still failed to reverse the antagonistic interaction. Addition of vorinostat at the pre-transductional period revealed an improvement in the transduction efficiency of CRAd and also induced a synergistic interaction between CRAd and vorinostat, which was possibly related with prevention of the suppressive effect of vorinostat on adenoviral replication. In conclusion, the addition of HDAC inhibitor before CRAd injection showed synergistic antitumor effects, which warrants further investigation on the sequence of HDAC inhibitor and CRAd treatment in an animal tumor model.

Risk factors for deterioration of nodular bronchiectatic Mycobacterium avium complex lung disease.

UNLABELLED SETTING The long-term natural course of Mycobacterium avium complex (MAC) disease with nodular bronchiectasis, the most common pulmonary non-tuberculous mycobacterial disease, is not well described. OBJECTIVE To identify risk factors for the deterioration of nodular bronchiectatic MAC lung disease over a 5-year follow-up period. DESIGN Clinical and laboratory data of 67 patients with nodular bronchiectatic MAC lung disease were collected. Chest computerised tomographic images were used to count the number of lung segments involved at diagnosis and measure subcutaneous fat thickness during follow-up. RESULTS The 34 patients who showed deterioration had significantly lower body mass index (BMI) (P = 0.004) and % predicted forced vital capacity (P = 0.032), higher numbers of lung segments involved (P < 0.001) and MAC-positive sputum cultures (P = 0.028), and thinner chest subcutaneous fat during follow-up (P < 0.001) than patients without deterioration. In particular, patients with both BMI <21.0 kg/m(2) and more than four lung segments involved had a 240-fold increased risk of deterioration (P < 0.001). CONCLUSION Patients with poor nutritional status and extensive lung involvement tend to experience deterioration of nodular bronchiectatic MAC lung disease.

The impact of previous tuberculosis history on T-SPOT.TB® interferon-gamma release assay results.

SETTING Seoul National University Bundang Hospital, a tertiary referral hospital in Korea. OBJECTIVE To evaluate whether previous tuberculosis (TB) history has a long-term effect on T-SPOT.TB® results after anti-tuberculosis treatment. DESIGN We retrospectively reviewed 489 adults (age ≥18 years) who underwent T-SPOT.TB as part of their evaluation between January 2008 and July 2009. RESULTS Among 489 subjects analysed, 369 were finally included. Active TB was diagnosed in 121/369 (32.8%). T-SPOT.TB was positive in 110 (90.9%) active TB patients. Of the 248 subjects without active TB, T-SPOT.TB positivity was significantly different between the 51 patients with a previous TB history and the 197 without (84.3% vs. 26.9%, P < 0.001). The difference in T-SPOT.TB positivity between the 51 non-active TB patients with a TB history and the 121 active TB patients was not statistically significant (84.3% vs. 90.9%, P = 0.208). Among the 51 non-active TB individuals with a TB history, the mean time since anti-tuberculosis treatment was 22.7 years (range 1-59); this had no correlation with total region of difference 1 (RD1) spot-forming cells (r = -0.076, P = 0.597). CONCLUSION T-SPOT.TB has a limited role in the diagnosis of TB infection in individuals with a previous history of TB.

Influence of previous tuberculosis treatment history on acid-fast bacilli smear and culture conversion.

SETTING A teaching hospital in the Republic of Korea, 2003-2009. OBJECTIVE To evaluate the effect of previous tuberculosis (TB) treatment history on sputum smear and culture conversion. DESIGN Data, including sputum acid-fast bacilli (AFB) results at baseline and at weeks 2, 4, 8, 12, 16, 20 and 24, were collected from patients with AFB sputum smear-positive and culture-confirmed pulmonary TB. Patients with multidrug-resistant TB or those with poor adherence were excluded. AFB conversion was compared between patients with a previous history of anti-tuberculosis treatment and those without. RESULTS The median age of the 208 patients was 49.0 years; 58.3% were male, while 43 (20.7%) had a history of previous anti-tuberculosis treatment. Patients with a history of previous treatment had significantly lower sputum smear-negative conversion at 2 weeks of treatment compared with patients without (70.0% vs. 44.8%, P = 0.005). However, the two groups did not differ in culture conversion and in smear conversion at 4, 8, 12, 16, 20 and 24 weeks of anti-tuberculosis treatment. CONCLUSION Patients with a history of previous anti-tuberculosis treatment are more likely to have positive sputum AFB smear at 2 weeks of treatment. However, sputum culture conversion is not affected by previous treatment history.

Chest Computed Tomography (CT) Immediately after CT-Guided Transthoracic Needle Aspiration Biopsy as a Predictor of Overt Pneumothorax

Background/Aims This study examined the correlation between pneumothorax detected by immediate post-transthoracic needle aspiration-biopsy (TTNB) chest computed tomography (CT) and overt pneumothorax detected by chest PA, and investigated factors that might influence the correlation. Methods Adult patients who had undergone CT-guided TTNB for lung lesions from May 2003 to June 2007 at Seoul National University Bundang Hospital were included. Immediate post-TTNB CT and chest PA follow-up at 4 and 16 hours after CT-guided TTNB were performed in 934 patients. Results Pneumothorax detected by immediate chest CT (CT-pneumothorax) was found in 237 (25%) and overt pneumothorax was detected by chest PA follow-up in 92 (38.8%) of the 237 patients. However, overt pneumothorax was found in 18 (2.6%) of the 697 patients without CT-pneumothorax. The width and depth of CT-pneumothorax were predictive risk factors for overt pneumothorax. Conclusions CT-pneumothorax is very sensitive for predicting overt pneumothorax, and the width and depth on CT-pneumothorax are reliable risk factors for predicting overt pneumothorax.

Effect of inhalers on the development of haemoptysis in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND The association of inhaler use with haemoptysis has rarely been reported in patients with non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE To elucidate the effect of inhaler use on the development of haemoptysis in patients with non-CF bronchiectasis. METHODS In a case-crossover study of 192 non-CF bronchiectasis patients with a history of haemoptysis and inhaler use, the risk of haemoptysis associated with the use of inhalers was elucidated. Two inhaled corticosteroids/long-acting β₂-agonists (ICS/LABA), one long-acting muscarinic antagonist and one short-acting β₂-agonist (SABA) were evaluated. The case and control periods were defined respectively as 030 and 180210 days before haemoptysis. RESULTS The risk of haemoptysis during the case period was 3.51 times higher than during the control period with any use of inhalers (95%CI 1.966.28). The results of clinically significant haemoptysis showed good agreement with those of total events. These associations were consistent with the sensitivity analyses. In the sub-analysis according to inhaler type, ICS/LABA and SABA were significantly associated with an increased risk of haemoptysis (aOR 2.62, 95%CI 1.255.45; aOR 2.51, 95%CI 2.235.15). CONCLUSIONS In patients with non-CF bronchiectasis, the use of inhalers, especially including 2-agonist, was associated with an increased risk of haemoptysis.

Genetic blockade of insulin-like growth factor-1 receptor via recombinant adenovirus in lung cancer can be enhanced by the histone deacetylase inhibitor, vorinostat

Many approaches have been suggested as anti‐tumor therapy for targeting insulin‐like growth factor 1 receptor (IGF‐1R), such as monoclonal antibodies and tyrosine kinase inhibitor. We introduced recombinant adenoviruses expressing antisense, dominant negative or short hairpin RNA to IGF‐1R. Moreover, we demonstrated that histone deacetylase inhibitor (vorinostat) can increase the transduction efficiency of adenoviruses by increasing CAR‐induced transduction and by enhancing the transcription of the adenoviral transgene. In the present study, we showed that the combination of ad‐sh (short hairpin) IGF‐1R with vorinostat leads to a synergistic enhancement of IGF‐1R blockade.