Takehiko Kobayashi

Hypereosinophilic Obliterative Bronchiolitis Clinically Mimicking Diffuse Panbronchiolitis: Four-year Follow-up

A 73-year-old man with a known history of asthma presented with dyspnea, worsening wheezing and a productive cough complicated by chronic sinusitis. Chest computed tomography showed bronchial wall thickening with centrilobular nodules and ground-glass opacity in the right lower lobe. Features meeting the diagnostic criteria for diffuse panbronchiolitis (DPB) were identified, and lobectomy confirmed the presence of lung cancer. Over the subsequent four years, the patients symptoms worsened. We reevaluated a lung lobe specimen, which showed hypereosinophilic obliterative bronchiolitis (HOB). A transbronchial lung biopsy also indicated bronchitis with eosinophilic infiltration. Our initial diagnosis of DPB was subsequently changed to HOB after four years. We herein describe this case of HOB, which was initially diagnosed as DPB primarily based on high-resolution computed tomography, with a focus on the histopathology and long-term clinical course. This is the first report to document the long-term clinical course of HOB.

Association between sequevar and antibiotic treatment outcome in patients with Mycobacterium abscessus complex infections in Japan

Purpose. Macrolide susceptibility differs between subspecies in the Mycobacterium abscessus complex, likely due to differences in erm(41) sequevars. Patients with M. abscessus complex infection generally show poor clinical outcomes in response to antibiotic treatment. Here, the association between genotype and treatment outcome was investigated. Methodology. We collected 69 isolates from 35 patients with non‐cystic fibrosis bronchiectasis: 24 had M. abscessus complex lung disease and non‐cystic fibrosis bronchiectasis, and 11 were colonized. Outcome analysis was performed in the 24 infected patients. Molecular analyses, including erm(41) and rrl sequencing, and variable‐number tandem‐repeat (VNTR) analysis of 69 isolates, from 24 infected and 11 colonized patients, were performed to elucidate the influence of genotype on antibiotic susceptibility. Results. Among the 24 patients, 18 (14 infected with M. abscessus subsp. abscessus and 4 with M. abscessus subsp. massiliense) showed unfavourable outcomes; six (three infected with M. abscessus subsp. abscessus and three with M. abscessus subsp. massiliense) exhibited favourable outcomes. Patients with unfavourable outcomes showed acquired clarithromycin resistance (33.3 vs 0 %), mixed sequevars (38.9 vs 16.7 %) and differing VNTR patterns between initial and serial isolates (33.3 vs 16.7 %). In contrast, in the 11 colonized patients, M. abscessus subsp. abscessus C28 (sequevar 02) and M. abscessus subsp. massiliense were the most prevalent subspecies. Conclusion. Patients infected with multiple sequevars and genotypes were more likely to exhibit treatment failure and/or recurrence. The precise identification of subspecies and analyses of mycobacterial characteristics may help to predict treatment outcomes in patients with M. abscessus complex lung disease.

A Case of Pulmonary Tuberculosis Complicated with Severe Thrombocytopenia with Diffuse Alveolar Hemorrhaging during Anti-tuberculosis Chemotherapy: An Autopsy Report

Tuberculosis may be accompanied by various hematological abnormalities during treatment, and occasionally thrombocytopenia is also noted. Most cases of thrombocytopenia in tuberculosis are moderate, and there are few reports about thrombocytopenia with diffuse alveolar hemorrhaging (DAH) in pulmonary tuberculosis. We describe the case of an 82-year-old man with pulmonary tuberculosis and tuberculous pleurisy. He underwent anti-tuberculosis chemotherapy; during tuberculosis treatment, he experienced DAH due to fulminant thrombocytopenia. Thrombocytopenia is a common finding in patients with pulmonary tuberculosis, but the laboratory findings should be carefully evaluated. Thrombocytopenia during anti-tuberculosis chemotherapy can cause life-threatening DAH.

Mycobacterium abscessus subsp. abscessus Lung Disease: Drug Susceptibility Testing in Sputum Culture Negative Conversion

Background: Among Mycobacterium abscessus complex infections, patients with M. abscessus subsp. abscessus (MAA) lung disease are difficult to treat and no standard therapy has been established. Few reports have investigated the drug susceptibility of these strains. We retrospectively investigated how in vitro drug susceptibility testing (DST) of MAA affects the induction of sputum conversion using pharmacotherapy. Methods: Patients with MAA lung disease diagnosed and treated between 2010 and 2014 at our hospital were enrolled and divided into Group A (sputum conversion without relapse within 1 year) and Group B (persistent positive cultured or negative conversion with relapse). MAA was identified in M. abscessus using sequence with genotyping, and DST of MAA was performed. Results: We assessed 23 patients (9 males and 14 females). There were 8 patients in Group A and 15 in Group B. Higher prevalence of susceptible isolates for clarithromycin (CAM) susceptibility on day 14 was noted in Group A than in Group B (P = 0.03) and no significant difference observed in the two groups for other drugs. Conclusions: In vitro DST of MAA, especially CAM susceptibility on day 14, affected the results of negative conversion. No other drugs were found to affect sputum culture negative conversion.

Change in lung function in never-smokers with nontuberculous mycobacterial lung disease: A retrospective study

Purpose Never-smokers account for a large proportion of subjects in general population studies on nontuberculous mycobacteria lung disease (NTM-LD). However, the influence of NTM infection on the lung function of never-smokers has not yet been evaluated. The aim of this study was to determine how NTM-LD impairs the lung function in never-smokers, and whether there are an association between successful NTM-LD treatment in radiologic outcomes and improvement in lung function of never-smokers with NTM-LD or not. Methods We performed a retrospective study of patients (1) who have never smoked during their lifetime; (2) with at least two respiratory specimens from sputum, one bronchial washing sample, or one lung tissue that were culture positive for the same NTM species; and (3) who underwent at least two pulmonary function tests. We enrolled healthy never-smokers as the control group. Results In 22 never-smokers with NTM-LD, the median forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at baseline was lower than those in 9 healthy never-smokers [1800 vs 2080 ml (p = 0.23) and 2230 vs 2620 ml (p = 0.06)], respectively. The median change in FEV1 in never-smokers with NTM-LD was lower than that in healthy never-smokers [−70 vs 20 ml per year (p = 0.07), respectively]. On univariate analysis, baseline %-predicted FEV1 in never-smokers with NTM-LD was associated with changes in FVC (p = 0.026) and FEV1 (p = 0.013). Anti-NTM treatment was administered for at least 1 year in 19 patients (86.4%). The relationship between worsening chest CT findings and rapid progressive decline in both FVC (p = 0.66) and FEV1 (p = 0.23) were not significant. Conclusion Never-smokers with NTM-LD showed lung function decline. There was no association between successful NTM-LD treatment in radiologic outcomes and improvement in lung function of never-smokers.

Discrepancies between the genotypes and phenotypes of clarithromycin-resistant Mycobacterium abscessus complex

SETTING Macrolides are a key drug class used for the treatment of Mycobacterium abscessus complex disease. OBJECTIVE To verify the relationship between phenotypic susceptibility and genotypic resistance to clarithromycin (CLM). DESIGN Subspecies of M. abscessus complex from 145 consecutive patients were identified using hsp65 and rpoB gene sequencing, and tested for CLM susceptibility, classification into the erm(41) sequevars responsible for inducible resistance and the presence of rrl mutations associated with acquired resistance. RESULTS The isolates comprised 74 M. abscessus subsp. abscessus, 69 M. abscessus subsp. massiliense and two M. abscessus subsp. bolletii. M. abscessus subsp. abscessus isolates comprised 15 sequevars, with the majority corresponding to sequevar 1 (n = 24), sequevar 6 (n = 13) and sequevar 2 (n = 8). Interestingly, seven M. abscessus subsp. abscessus isolates (9.5%) presented genetically functional, but not phenotypic, inducible resistance. Moreover, rrl was mutated in only 14.3% (1/7) of acquired resistance isolates. However, M. abscessus subsp. massiliense and M. abscessus subsp. bolletii isolates with acquired resistance at day 3 showed mutations at positions 2057-2059 (P < 0.05). CONCLUSIONS Our study indicates that genotypic inducible and acquired resistance in M. abscessus subsp. abscessus does not always coincide with phenotypic susceptibility. Rigorous phenotypic evaluation is thus important because of the considerable impact on patients.

Clinical Features of Nontuberculous Mycobacterial Pleurisy: A Review of 12 Cases

Objective The incidence of pulmonary nontuberculous mycobacterial (NTM) infections has increased in recent decades. Nevertheless, NTM pleurisy is still a rare disease. The objective of the present study was to elucidate the clinical features and outcomes of NTM pleurisy. Methods A retrospective study was undertaken of consecutive patients whose pleural effusion culture yielded NTM, from 2002 to 2016 at a respiratory hospital in Japan. The clinical features, treatment, and outcomes of these patients were analyzed. Result The 12 patients with NTM pleurisy were predominantly male, with a median age of 69 years (range, 48-93 years). They included eight patients with a history of smoking and six patients with immunosuppressive comorbidities such as malignancy, diabetes mellitus, and conditions requiring steroid administration. Fibrocavitary disease was the most common radiographic feature of these patients, and Mycobacterium avium complex was the most common pathogen. Pneumothorax was complicated in 11 patients. Surgery was performed on seven patients, in addition to thoracic drainage for the treatment of pleurisy and pneumothorax. Three patients died of respiratory failure. Conclusion Pneumothorax is a frequent complication of NTM pleurisy, often making the condition difficult to treat. Surgery at an appropriate time should therefore considered for refractory cases.

A Cryptogenic Case of Fulminant Fibrosing Organizing Pneumonia

Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. Rare cases of organizing pneumonia are rapidly progressive. Yousem et al. studied pathologic predictors of idiopathic bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis. Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74-year-old female non-smoker presented with a 2-week history of dry cough followed by dyspnea and a fever. The clinical course was fulminant, but we successfully performed bronchoscopy. After the diagnosis of FOP, we treated the patient with mechanical ventilation and high-doses of steroids/immunosuppressants, which improved the disease.