Poor Outcome and Mortality in Patients with Lower Lung-Dominant Sarcoidosis.

Background: Pulmonary sarcoidosis predominantly affects the upper lung zones but sometimes affects the lower lung zones. We hypothesised that patients with lower lung zone-dominant sarcoidosis had lower baseline forced vital capacity, progressive restrictive lung function decline, and higher long-term mortality. Methods: We retrospectively reviewed clinical data including the pulmonary function tests of 108 consecutive patients with pulmonary sarcoidosis pathologically confirmed by lung and/or mediastinal lymph node biopsy from 2004 to 2014 from our database. Results: Eleven patients (10.2%) with lower lung zone-dominant sarcoidosis were compared with 97 patients with nonlower lung zone-dominant sarcoidosis. The median age of the patients with lower dominance was significantly older (71 vs. 56, p = 0.0005). The patient with lower dominance had a significantly lower baseline percent forced vital capacity (FVC) (96.0% vs. 103%, p = 0.022). The annual change in FVC was -112 mL in those with lower dominance vs. 0 mL in nonlower dominance (p = 0.0033). Fatal acute deterioration was observed in three patients (27%) in the lower dominant group. Overall survival in the lower dominant group was significantly worse. Conclusions: Patients with lower lung zone-dominant sarcoidosis had an older age and lower baseline FVC with disease progression and acute deterioration associated with higher long-term mortality.

Predictive factors for relapse in corticosteroid-treated patients with chronic eosinophilic pneumonia.

Background: Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterised by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lungs. Systemic corticosteroid (CS) therapy leads to marked improvement. However, relapse is common in the clinical course, and the predictive factors for relapse of CEP are not well known. This study aimed to investigate predictive factors for relapse in CS-treated cases of CEP. Methods: We identified consecutive patients with CEP at our institution between 1999 and 2019. We retrospectively reviewed 36 CS-treated patients with CEP who underwent bronchoalveolar lavage (BAL) and high-resolution computed tomography (CT) at diagnosis. We examined relapse at least 1 year after the initiation of CS treatment. Statistical analysis included univariate and multivariate Cox proportional hazard regression analyses; P<0.05 was considered statistically significant. Results: The median (interquartile range) age at diagnosis was 59.5 years (47.8-70.0 years). This study included 13 men and 23 women. Twenty-five patients (69.4%) were never smokers and 15 (41.7%) had asthma. The peripheral blood eosinophil percentage was 35.0% (15.6-55.8%), and the BAL eosinophil percentage was 40.8% (10.7-68.5%). The median serum surfactant protein-D (SP-D) level was 135 ng/mL (82.2-176.7 ng/mL). High-resolution CT revealed centrilobular opacities in 23 patients (63.9%). Relapse of CEP was observed in 20 patients (55.6%). Higher serum SP-D levels and the presence of centrilobular opacities on high-resolution CT were significant predictors of relapse in multivariate Cox proportional hazard regression analysis (P=0.017 and P=0.028, respectively). Additionally, we devised a relapse prediction model for CS-treated CEP using two categorical parameters: the presence of centrilobular opacities and serum levels of SP-D (>135/≤135 ng/mL). Based on these parameters, cases were scored 2, 1, or 0. Patients with a score of 2 experienced relapses earlier than those with scores of 1 and 0 (log-rank test; P=0.006, P=0.003, respectively). Conclusions: Centrilobular opacities on high-resolution CT and higher serum SP-D levels at diagnosis may be predictive factors for relapse in CS-treated patients with CEP.

The feasibility of rifampicin Re-administration in patients with tuberculosis and Clostridioides difficile infection.

BACKGROUND: The effects of a rifampicin (RIF) on the evolution of Clostridioides difficile infection (CDI) have not previously been investigated and there is currently no consensus on whether RIF re-administration is feasible. METHODS: This retrospective observational study included consecutive tuberculosis (TB) patients diagnosed with comorbid RIF-associated CDI (RA-CDI) using strict diagnostic criteria. We investigated the association between RA-CDI and clinical outcomes, and also examined the feasibility of re-administering RIF. RESULTS: Out of the 11,230 patients were admitted to TB ward at our hospital, 156 TB patients (1.4%) were diagnosed with CDI and the overall incidence of CDI was calculated as 2.1 cases per 10,000 patient-days. Of 156 patients with CDI, 86 were diagnosed with RA-CDI, of whom 28 (32.6%) were re-administered with RIF. In the re-administration group, time to initial sputum smear conversion was significantly shorter than for patients who were not re-administered with RIF (42 days [interquartile range, IQR: 35-65] vs. 55 days [IQR: 44-70], p = 0.041). Further, RIF re-administration significantly reduced length of hospital stay (69 days [IQR: 66-82] vs. 81 days [IQR: 72-89], p = 0.014). Ten patients (35.7%) had recurrent CDI after RIF re-administration. On the other hand, 15 patients (53.6%) were able to continue their TB treatment, including the RIF regimen. CONCLUSIONS: The present study strengthens the argument for including RIF in the list of antibiotics that can induce CDI, particularly in elderly men suffering from underlying conditions. Although careful attention must be paid to the possibility of CDI recurrence, a strategy of re-administration of RIF is feasible.

Hemosiderin-Laden Macrophages in Bronchoalveolar Lavage: Predictive Role for Acute Exacerbation of Idiopathic Interstitial Pneumonias.

Background: Hemosiderin-laden macrophages (HLMs) have been identified in the bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF). This retrospective study examined the ability of HLMs in BALF to predict the acute exacerbation (AE) of chronic idiopathic interstitial pneumonias (IIPs). Methods: Two hundred and twenty-one patients with IIP diagnosed by bronchoscopy were enrolled in the study (IPF, n = 87; IIPs other than IPF, n = 134). Giemsa stain was used to detect HLMs in BALF specimens. Prussian blue stain was used to quantify HLMs in BALF, and a hemosiderin score (HS) was given to the specimens containing HLMs. Results: Twenty-four patients had a positive HS (range: 7‒132). The receiver-operating characteristic curve analysis identified the cutoff HS value for predicting the AE of IIPs to be 61.5. Seven cases had a higher HS (≥61.5) and 214 had a lower HS. AE occurred significantly earlier in the higher HS group (4/7 cases) than in the lower HS group (41/214 cases) during a median observation period of 1239 days (log-rank test, p = 0.026). Multivariate Cox proportional hazard regression analysis showed that a higher HS was a significant predictor of AE in addition to IPF, percent predicted forced vital capacity, and modified Medical Research Council score. The C-statistics for the prediction of AE did not significantly improve by all the above parameters with HS as compared without HS. Conclusions: A higher HS was a significant predictor of AE in IIPs but did not significantly improve the predictive ability of other parameters.

Clinical characteristics of COVID-19 in Osaka, Japan: Comparison of the first-third waves with the fourth wave.

BACKGROUND: The fourth wave of COVID-19 in Osaka Prefecture, Japan, caused a medical crisis. Here, we aim to identify the risk factors for COVID-19 severity and compare patients between the first-third waves and the fourth wave. METHODS: We performed an observational retrospective study of COVID-19 cases at the National Hospital Organization Kinki-Chuo Chest Medical Center. RESULTS: We identified 404 patients (median age: 71.0 years [interquartile range: 56.0-80.0]), of whom 199 (49.1%) had mild disease, 142 (35.2%) had moderate disease, and 63 (15.6%) had severe disease. The overall mortality rate was 5.4% (22/404). Based on multivariate logistic regression analysis, cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were independent risk factors for moderate to severe disease. For every 1 mg/dL increase in C-reactive protein, 10 IU/L increase in lactate dehydrogenase, and 100 ng/mL increase in ferritin, the risk for moderate to severe disease increased by 18.3%, 12.9%, and 8.9%, respectively. Overall disease severity in the fourth wave was higher than in the first-third waves. However, there was no significant difference in mortality. Because of a shortage of beds, four of the 28 severe patients (14.3%) in the fourth wave could not be transferred to the advanced hospital. CONCLUSIONS: Cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were risk factors for moderate to severe COVID-19 in our cohort. During the fourth wave, COVID-19 severity worsened, increasing the number of patients who could not be transferred to beds for severe cases, resulting in a medical crisis in Osaka.

Drug-related pneumonitis with radiographic hypersensitivity pneumonitis pattern: Three case series.

Novel therapies have recently emerged for various diseases, and the management of drug-related pneumonitis (DRP) has become increasingly important. In particular, the hypersensitivity pneumonitis (HP) pattern of DRP has been increasingly recognized due to development of new therapeutic strategies, such as immunotherapy. However, literature describing detailed clinical cases is still lacking. Herein, we report three cases of DRP with typical HP radiographic pattern. These patients were treated with different drugs, namely nano albumin-bound (nab)-paclitaxel, everolimus, or nivolumab, but had common clinical features, including a good prognosis.

Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin.

BACKGROUND: Acute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs. METHODS: This study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse. RESULTS: Univariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality. CONCLUSIONS: A higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome. TRIAL REGISTRATION NUMBER: UMIN000014969.

Histologically Proven Dendriform Pulmonary Ossification: A Five-case Series.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by metaplastic bone formation in the lung parenchyma. It has been reported to be often associated with primary lung diseases, such as usual interstitial pneumonia (UIP) or chronic aspiration of gastric acid; however, its clinical features and pathophysiology remain unclear, especially in idiopathic cases. We herein report five DPO cases, including three with an idiopathic origin. In all cases of idiopathic DPO, the pathological and radiological examinations showed localized pulmonary lesions suggesting inflammation or hemorrhaging.

Lymphoplasmacytic lymphoma involving the mediastinum and the lung, followed by amyloidosis: A surgically and genetically proven case.

A 60-year-old man was admitted for ground glass opacity in the lower lung field and mediastinal lymphadenopathy. Blood tests revealed elevated serum IgM levels, and the urine test detected Bence-Jones protein. Surgical biopsy from the mediastinal lymph node and lung showed small lymphocytes and plasma cells between follicles, and AL kappa amyloid deposition. Genetic examination detected MYD88 L265P mutation. Our diagnosis was lymphoplasmacytic lymphoma (LPL), involving the mediastinum and the lung, followed by amyloidosis. Mutation analysis, in addition to conventional histological evaluation, was useful for a precise diagnosis.

Seroradiologic prognostic evaluation of acute exacerbation in patients with idiopathic interstitial pneumonia: a retrospective observational study.

BACKGROUND: We previously reported that high-resolution computed tomography (HRCT) patterns and certain serum marker levels can predict survival in patients with acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and in those with idiopathic interstitial pneumonias (IIPs). The utility of serum marker changes before and during AE has not been previously evaluated. This study aimed to clarify whether changes in serum marker levels could improve the prognostic significance of HRCT patterns in patients with AE-IIPs. METHODS: Seventy-seven patients (60 males, 17 females) with AE-IIP diagnosed between 2004 and 2016 and whose serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D levels were measured before and at the onset of AE were enrolled in this study. The HRCT pattern of each patient was classified as diffuse, multifocal, or peripheral. We examined the prognostic significance of the HRCT pattern, increased serum marker levels, and a combination of these parameters using Cox proportional hazard regression analysis. RESULTS: Fifty-three patients had IPF and 24 had non-IPF IIP. A serum KL-6 level that was increased compared with the level in the stable state (ΔKL-6/ST-KL-6: ≤0.211) was a significantly poor prognostic factor in patients with a multifocal pattern. Multivariate Cox analysis identified long-term oxygen therapy, a partial oxygen tension/fraction of inspired oxygen ratio ≤200 Torr, and an elevated SP-D level during a stable state to be significantly poor prognostic factors in all patients. A diffuse HRCT pattern was not a significant prognostic factor in an AE-IIP in multivariate analysis after adjustment; however, a multifocal pattern accompanying a ΔKL-6/ST-KL-6 ≤0.211 or a diffuse pattern was a significantly poor prognostic factor than a peripheral pattern or a multifocal pattern with ΔKL-6/ST-KL-6 >0.211. CONCLUSIONS: Combining the HRCT pattern and the ΔKL-6/ST-KL-6 value can improve our ability to predict the survival of AE-IIP patients.

Clinical significance of serum anti-granulocyte-macrophage colony-stimulating factor autoantibodies in patients with sarcoidosis and hypersensitivity pneumonitis.

BACKGROUND: Anti-granulocyte-macrophage colony-stimulating factor autoantibody (GMAb) has been recognized as a diagnostic biomarker for autoimmune pulmonary alveolar proteinosis (aPAP). The aims of this study were to know the incidence of increased level of serum GMAb in granulomatous lung diseases (sarcoidosis and hypersensitivity pneumonitis [HP]) and to clarify the role of GMAb. Consecutive individuals diagnosed with sarcoidosis (n = 92) and HP (n = 45) at National Hospital Organization Kinki-Chuo Chest Medical Center were retrospectively analyzed. We measured serum GMAb levels at the diagnosis. Cut-off values of GMAb discriminating aPAP (n = 110) from healthy controls (n = 31) were determined by receiver operating characteristic (ROC) curve analysis. We compared the clinical features of sarcoidosis and HP patients with GMAb levels above the cut-off value ("Elevated-GMAb") with those of patients whose GMAb levels below the cut-off value ("Low-GMAb"). Radiological and pathological findings in elevated-GMAb patients were re-evaluated to elucidate the role of GMAb in granulomatous lung diseases. RESULTS: Analysis of ROC indicated a sensitivity and specificity of 100% at GMAb level of 3.33 µg/mL for discriminating aPAP from healthy controls (area under curve = 1.000, p < 0.0001). The percentages of elevated-GMAb sarcoidosis and HP patients were 5.4% (n = 5) and 11.1% (n = 5), respectively. The number of comorbid sarcoidosis and HP patients with aPAP was two and one, respectively. Elevated-GMAb sarcoidosis patients presented with significantly higher serum levels of Krebs von den Lungen (KL)-6, surfactant protein-D (SP-D), lactate dehydrogenase, and the requirement of systemic corticosteroid therapy. Elevated-GMAb HP patients demonstrated older age, higher serum KL-6, SP-D, carcinoembryonic antigen, and cytokeratin fragment 21-1 levels, and a higher percentage of lymphocytes in bronchoalveolar lavage than low-GMAb patients. A subset of patients presented with radiological and pathological findings characteristic of aPAP. CONCLUSIONS: We demonstrated the percentage of elevated-GMAb sarcoidosis and HP patients who presented with several features suggestive of aPAP. Elevated-GMAb sarcoidosis and HP patients without definitive aPAP diagnosis may have subclinical or early-stage aPAP and may not necessarily indicate false positives. Upon diagnosis of sarcoidosis or HP, measurement of GMAb may be useful in detecting possible comorbidity of subclinical or early-onset aPAP.

Autoimmune Pulmonary Alveolar Proteinosis Complicated with Sarcoidosis: the Clinical Course and Serum Levels of Anti-granulocyte-macrophage colony-stimulating Factor Autoantibody.

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction due to anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. We experienced 2 cases of APAP complicated with sarcoidosis in a 42-year-old woman and a 51-year-old man (age at the sarcoidosis diagnosis). APAP preceded sarcoidosis in the woman, and both diseases were diagnosed simultaneously in the man. Sarcoidosis lesions were observed in the lung, skin, and eyes, and the pathological findings of APAP were not marked at the diagnosis of sarcoidosis in either case. Low-grade positive serum anti-GM-CSF autoantibody was suspected to be correlated with the occurrence of sarcoidosis and resolution of APAP.

Massive atelectasis by mucoid impaction in an asthma patient during treatment with anti-interleukin-5 receptor antibody.

Benralizumab is an interleukin-5 (IL-5) receptor α-directed cytolytic monoclonal antibody that reduces rapid and nearly complete depletion of eosinophils by enhancing antibody-dependent cell-mediated cytotoxicity. The depletion of eosinophilic inflammation is expected to reduce mucus hypersecretion and mucoid impaction. A 75-year-old non-smoking female had been treated for uncontrolled bronchial asthma with multiple drugs. Treatment with benralizumab was initiated after the asthma attack; however, four months later, she developed massive atelectasis in the left lung leading to the tracheal deviation, to the extent that nasal high-flow therapy was required. The laboratory data showed elevated neutrophil count, whereas blood eosinophils were almost completely depleted. The thick mucus was removed by bronchofiberscopy and the atelectasis was completely resolved. No exacerbation has been observed for nine months after discontinuation of benralizumab and initiation of erythromycin. This is the first documented case that developed atelectasis by mucoid impaction during treatment with anti-IL-5 receptor antibody.

Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial.

BACKGROUND: Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP. METHODS: In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP. RESULTS: We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0). CONCLUSIONS: Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.

Characteristics and prognosis of interstitial pneumonias complicated with pneumomediastinum.

BACKGROUND: The clinical characteristics and prognostic impact of complication with pneumomediastinum in patients with interstitial pneumonias (IPs) are not well studied due to the relatively limited nature of available reports. The purpose of this study was to clarify the characteristics and prognostic factors of IPs complicated with pneumomediastinum. METHODS: Consecutive patients with IPs complicated with pneumomediastinum detected by computed tomography (CT) between July 1, 2011, and April 30, 2014 were retrospectively reviewed. Clinical data including symptoms associated with pneumomediastinum, laboratory data, lung function tests, treatments, and mortality were collected from medical records. RESULTS: Forty-five patients (25 males, 20 females), including 32 with idiopathic IP (IIPs) and 13 connective tissue disease-associated interstitial lung diseases (CTD-ILDs) were identified. The median age of onset of pneumomediastinum was 72 years (interquartile range [IQR] 68-79 years). The most common symptom associated with occurrence of pneumomediastinum was appearance or worsening of dyspnoea. No specific treatment was performed for most (84%) of the cases. The median period between occurrence and improvement of pneumomediastinum was 29 days (IQR 5-69 days). Multivariate analysis revealed that IIPs and no improvement of pneumomediastinum were associated with poor prognosis. CONCLUSIONS: Patients with IIPs complicated with pneumomediastinum and those without improvement of pneumomediastinum had poor prognosis.

Severe clopidogrel-induced DRESS with eosinophilic pneumonia associated with Epstein-Barr virus reactivation.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a type of hypersensitivity drug reaction. Here, we report the case of a 78-year-old man who presented with a rash, fever, dry cough, and swollen parotid glands who had been prescribed clopidogrel for one year. Computed tomography showed consolidation and interlobular septal thickening with enlarged mediastinal lymph nodes. As oxygen therapy was ineffective, the patient was intubated and bronchoalveolar lavage cellular analysis showed an increase in eosinophils. Clopidogrel was discontinued and the parotid biopsy revealed periductal lymphocytic infiltration. High doses of corticosteroids were administered, and his symptoms improved. However, his symptoms recurred when clopidogrel was restarted. Skin biopsy showed mild lymphocytic infiltration in the upper dermis with vasculitis, and Epstein-Barr virus (EBV) DNA was detected in his blood and lymph node tissue. On the basis of the pathology and disease manifestations, the patient was diagnosed with DRESS. Once clopidogrel treatment ceased, his symptoms never recurred.

Airway-centered Fibroelastosis Accompanied by Subpleural Lesions of Unknown Cause in a Young Man Who Later Developed Pulmonary Hypertension.

A 26-year-old man with a history of bronchial asthma was found to have high-density shadows along the bronchovascular bundle and in the subpleural area on computed tomography of the chest. Surgical lung biopsy specimens from the right S5 showed fibroelastosis in the subpleural and central airway area with alveolar destruction. He was diagnosed with airway-centered fibroelastosis of unknown cause after multidisciplinary discussions. The patient developed pulmonary hypertension and died 6 years later. The patient was younger in comparison to patients in earlier reports and had more obvious subpleural fibroelastic lesions in the upper lobes than in previously described cases.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Prognosis of chronic pulmonary aspergillosis in patients with pulmonary non-tuberculous mycobacterial disease.

BACKGROUND: Pulmonary non-tuberculous mycobacterial disease (PNTM) is a known risk factor for chronic pulmonary aspergillosis (CPA). However, few studies have focused on the prognosis of PNTM-associated CPA. In the present investigation, we aimed to elucidate the clinical course and prognostic factors of CPA in patients with PNTM. METHODS: We retrospectively investigated the medical records of 62 patients with CPA and a history of PNTM who were admitted to Kinki-chuo Chest Medical Center between 2010 and 2015. Co-morbidities, causative microorganisms, radiological findings, and outcomes were evaluated. RESULTS: The patients' median age was 69.5 years, and the median follow-up period was 4.2 years. The major underlying diseases, other than PNTM and CPA, were old pulmonary tuberculosis, chronic obstructive pulmonary disease, and interstitial pneumonia. The most common causative NTM species were Mycobacterium avium complex (MAC; 37 patients; 59.7%) and Mycobacterium kansasii (20 patients; 32.3%). Survival was 83% after 1 year and 61% after 5 years. Use of systemic corticosteroids (hazard ratio: 3.32, 95% confidence interval: 1.23-9.51; P=0.00177) and C-reactive protein levels ≥ 5.0 mg/dL (hazard ratio: 8.96, 95% confidence interval: 2.15-62.9; P=0.0014) at the time of CPA diagnosis were associated with increased over-all mortality. CONCLUSIONS: CPA frequently developed in patients with MAC and M. kansasii PNTM. The treatment course of PNTM was not associated with all-cause mortality. However, systemic corticosteroid use and high CRP levels were negative prognostic factors of CPA in patients with PNTM. Since the prognosis is poor, early diagnosis and treatment of CPA are important in patients with PNTM.

Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan.

BACKGROUND: Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients. METHODS: To quantify the incidence and outcomes of colonization and disease caused by NTM and aspergillosis in recipients before and after lung transplantation, we reviewed the medical records and microbiology data from 240 consecutive cadaveric lung transplant recipients between 2000 and 2014. RESULTS: Before lung transplantation, NTM and Aspergillus species were isolated from five (2.1%) and six (2.5%) patients, respectively, out of the total 240 recipients. All patients with NTM infection received treatment, resulting in culture conversion. They had no recurrence after lung transplantation. All patients with aspergillosis received treatment, one of whom had recurrence after lung transplantation. Over a median follow-up period of 3.3 years, NTM species were isolated after transplantation from eight of 240 patients (3.3%). Five of these patients met the criteria for NTM disease, and four of them received treatment. Four patients survived without a worsening of NTM disease. Over the same median follow-up period, Aspergillus species were isolated from seven of 240 patients (2.9%), six of whom received treatment. CONCLUSIONS: Isolation of NTM or Aspergillus species from lung transplant recipients is uncommon. Adequate pre-transplant control and post-transplant management of NTM and Aspergillus infections allows for safe lung transplantation.