Effectiveness of Amikacin liposome inhalation suspension for refractory Mycobacterium avium complex pulmonary disease at 6 months post initiation.

BACKGROUND: Amikacin  liposome inhalation suspension (ALIS) improved sputum culture conversion rate at 6 months for patients with refractory Mycobacterium avium complex pulmonary disease (MAC-PD) in an international phase 3 trial. Patient characteristics and chest high-resolution CT (HRCT) findings associated with ALIS effectiveness are poorly documented. OBJECTIVE: We aimed to clarify ALIS effectiveness for refractory MAC-PD at 6 months, elucidating associated patient characteristics and chest CT findings. METHODS: We reviewed medical records of 12 patients with refractory MAC-PD for whom ALIS treatment was initiated at Toho University Omori Medical Center from November 2021 through September 2022. All patients demonstrated treatment persistence for at least 3 months. They were divided into culture conversion and non-conversion groups using sputum culture conversion status after 6-month ALIS treatment initiation. Clinical and radiological characteristics were compared. RESULTS: Seven of the 12 patients (58.3%) achieved sputum culture conversion within 6 months. The culture conversion group had shorter pre-ALIS initiation treatment duration [21 months (16-25) vs. 62 months (32-69); p = 0.045]; lower cavitary lesion incidence on HRCT (28.6% vs. 100%; p = 0.028); and fewer clarithromycin (CLA)-resistant strains [0/7 (0%) vs. 3/5 (60%); p = 0.045]. Chest HRCT findings improved in 4 of 7 (57.1%) and 1 of 5 (20%) patients in the culture conversion and non-conversion groups, respectively. CONCLUSION: ALIS facilitated sputum culture conversion within 6 months in 58.3% of patients with refractory MAC-PD. Sputum culture conversion was significantly more frequent for CLA-susceptible strains and patients with fewer cavitary lesions. Improved CT findings after ALIS did not always correspond to sputum culture conversion.

BRCA2-positive lung adenocarcinoma treated with olaparib: A case report.

A 66-year-old woman was found to have abnormal shadows on a chest radiograph at a previous hospital 4 years ago, which led to a diagnosis of lung adenocarcinoma, cT2aN1M1b stage IVA. First-line treatment included carboplatin and paclitaxel plus thoracic radiotherapy and stereotactic radiation therapy for brain metastases. The patient later underwent second-line pemetrexed treatment, followed by third-line nivolumab, fourth-line docetaxel and bevacizumab, fifth-line tegafur-gimeracil-oteracil, and sixth-line gemcitabine. Two years ago, after observing an increase in the primary lesion and carcinoembryonic antigen levels (104.0 ng/mL), a computed tomography-guided biopsy was performed from the primary site of lung cancer. A cancer genomic profiling test (FoundationOne® CDx cancer genome profile) revealed a breast cancer susceptibility (BRCA) 2 gene mutation. Therefore, she started taking olaparib. The treatment led to stable disease for approximately 2 years.

The First Case of Mycobacterium interjectum Pulmonary Disease in Japan.

We herein report a case of Mycobacterium interjectum pulmonary disease (M. interjectum-PD) that improved considerably after azithromycin (AZM), rifampicin (RFP), and ethambutol (EB) therapy. A 69-year-old woman, managed locally for suspected NTM-PD based on chest computed tomography (CT) findings was referred to our hospital for worsening productive cough six years after the initial diagnosis. High-resolution chest CT showed right middle and left lower lobe bronchiectasis with middle and centrilobular nodules. Bronchial washing and sputum culture yielded M. interjectum. Treatment with AZM, RFP, and EB resulted in sputum culture conversion, and the chest CT findings subsequently improved. This is the first reported case of M. interjectum-PD in Japan.

Intrinsic clarithromycin heteroresistance in Mycobacterium avium.

BACKGROUND: Mycobacterium avium is associated with pulmonary disease in otherwise healthy adults. Several clarithromycin-refractory cases have been reported, including some cases caused by clarithromycin-susceptible strains. OBJECTIVES: To characterize the reason for the discrepancy between clinical response and antibiotic susceptibility results. METHODS: We conducted population analysis of clarithromycin-tolerant and heteroresistant subpopulations of M. avium cultured in vitro and in homogenates of infected lungs of mice. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for 28 M. avium and two M. kansasii strains. Mice were intranasally infected with M. avium and treated with or without clarithromycin (100 mg/kg) thrice weekly. They were sacrificed on day 35 and the bacteria in lung homogenates were tested for clarithromycin resistance. Population analysis assays were performed based on colony growth on plates containing two-fold dilutions of clarithromycin. RESULTS: The MBC/MIC ratios were ≥8 in all 28 strains of M. avium tested. In the population analysis assay, several colonies were observed on the plates containing clarithromycin concentrations above the MIC (2-64 mg/L). No growth of M. kansasii colonies was observed on the plates containing clarithromycin concentrations ≥2 mg/L. M. avium in the homogenates of infected lungs showed clearer clarithromycin-resistant subpopulations than in vitro, regardless of clarithromycin exposure. CONCLUSION: M. avium shows intrinsic heterogeneous resistance (heteroresistance) to clarithromycin. This may explain the observed discrepancies between clarithromycin susceptibility testing results and clinical response to clarithromycin treatment. Further studies are needed to confirm a link between heteroresistance and clinical outcomes.

Outcomes and prognosis of progressive pulmonary fibrosis in patients with antineutrophil cytoplasmic antibody-positive interstitial lung disease.

Approximately one-third of fibrosing interstitial lung diseases exhibit progressive pulmonary fibrosis (PPF), a clinicopathological condition distinct yet resembling idiopathic pulmonary fibrosis (IPF). PPF in ANCA-positive ILD (ANCA-ILD) is poorly documented. To clarify incidence, predictors of PPF in ANCA-ILD, and their prognostic impact, 56 patients with ANCA-ILD were followed for ≥ 1 year (April 2004 to April 2021). PPF was defined per ATS/ERS/JRS/ALAT PPF 2022 guideline. We compared PPF and non-PPF in 38 patients with pulmonary function tests and ≥ 1 year follow up. ANCA-ILD (19 male, 19 female; mean age 72 years) comprised 21 patients with microscopic polyangiitis ILD (MPA-ILD) and 17 with ANCA-positive IP without systemic vasculitis (ANCA-IP). PPF occurred in 15/38 (39.5%) overall, and 27% of patients with MPA-ILD and 53% with ANCA-IP. Patient characteristics did not differ between PPF and non-PPF, however, the survival was significantly worse in patients with PPF than those with non-PPF. On multivariate regression analysis, higher age, higher serum SP-D level, and lower baseline %FVC were associated with PPF. In ANCA-ILD, 39.5% of patients demonstrated PPF, which is associated with increased mortality. Predictors of PPF were older age, higher SP-D, and lower baseline %FVC.

ATS/JRS/ALAT Hypersensitivity Pneumonitis Guidelines for Diagnosis of humidifier lung and summer-type hypersensitivity pneumonitis.

BACKGROUND: The ATS/JRS/ALAT Guidelines for the Diagnosis of Hypersensitivity Pneumonitis (GL for HP) were published in 2020. Humidifier lung and summer-type HP are forms of HP, but it is unclear whether they can be diagnosed using GL for HP. This study examined the level of confidence where humidifier lung and summer-type HP can be diagnosed with GL for HP. METHODS: Data from 23 patients with humidifier lung and 20 patients with summer-type HP (mean age, 67.3 and 57.4 years, respectively) diagnosed between October 2012 and January 2022 were retrospectively reviewed. We evaluated high resolution computed tomography (HRCT) patterns, bronchoalveolar lavage fluid (BALF) findings, exposures, and histopathological findings to determine the level of confidence where a diagnosis of HP could be made using the GL for HP. RESULTS: HRCT pattern was classified as typical HP in 5 (22%) and compatible with HP in 18 (78%) patients with humidifier lung and considered as typical HP in 17 (85%) and compatible with HP in 3 (15%) patients with summer-type. The confidence level for diagnosis of HP was definite in 2 (8.7%), moderate in 14 (60.9%), and low in 7 (30.4%) patients with humidifier lung. It was definite in 12 (60%), high in 3 (15%), and moderate in 5 (25%) patients with summer-type HP. CONCLUSIONS: GL for HP showed utility in diagnosing humidifier lung in many patients with a moderate to low confidence. However, there was a definite to high confidence for patients with summer-type HP.

Upregulation of long non­coding RNA LINC00460 in EGFR­mutant lung cancer indicates a poor prognosis in patients treated with osimertinib.

The long non-coding RNA (lncRNA) LINC00460 is involved in tumor growth, metastasis and drug resistance. The present study investigated the clinical significance of LINC00460 expression in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer treated with osimertinib. Osimertinib-resistant cells we derived from EGFR-mutant non-small-cell lung cancer (NSCLC) cell lines, after which, small interfering RNA (siRNA)-mediated silencing and in vitro-transcribed (IVT), synthetic LINC00460 RNA transfection were used to investigate the effects of LINC00460 expression on acquired resistance to osimertinib. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate LINC00460 expression in 54 samples (RNA extracted from the tumor tissues of 30 cases and cell-free RNA from 24 cases) obtained from patients with EGFR mutation-positive lung cancer who had received osimertinib as the initial treatment. The acquisition of osimertinib resistance increased the expression of LINC00460 in the EGFR-mutant NSCLC cell lines. By contrast, knockdown of LINC00460 in osimertinib-resistant cell lines increased their sensitivity to osimertinib, whereas treatment of NSCLC cells with IVT LINC00460 RNA decreased their sensitivity to osimertinib. The present study examined LINC00460 expression at the primary tumor site and demonstrated that compared with in the low-expression group (n=24), the high-expression group (n=6) had a significantly lower best overall response rate to osimertinib (16.6% vs. 60.0%; P=0.044), significantly shorter median progression-free survival (PFS; 224 days vs. 669 days; P=0.001) and significantly shorter median overall survival (724 days vs. not reached; P=0.011). Moreover, following osimertinib therapy, PFS was significantly shorter for patients with high LINC00460 expression in plasma cell-free RNA (n=12) than for those with low LINC00460 expression (n=12) (median PFS: 655 days vs. 210 days; P=0.020). In conclusion, the upregulation of LINC00460, the expression of which is implicated in osimertinib resistance, in the primary site and plasma of patients with EGFR mutation-positive lung cancer may be associated with a poor prognosis in those treated with osimertinib.

Efficacy of three sputum specimens for the diagnosis of Mycobacterium avium complex pulmonary disease.

BACKGROUND: In Mycobacterium avium complex pulmonary disease (MAC-PD), diagnosis requires a positive culture from at least two separate expectorated sputum specimens. The optimal number of sputum examinations remains unclear. OBJECTIVE: This study sought to elucidate the diagnostic yield of acid-fast bacilli in MAC-PD using 3 sputum specimens and to clarify the clinical characteristics of patients with MAC-PD diagnosed using 3 sputum specimens. Furthermore, we investigated the correlation between increased number of sputum specimens and diagnostic yield. METHODS: We reviewed the medical records of 139 patients with MAC-PD diagnosed at Toho University Omori Medical Center for whom at least three sputum specimens were examined before treatment from November 2014 through June 2021. Patients were classified into the 3-sputum diagnosed and the non-3 sputum diagnosed groups based on diagnostic procedure; clinical and radiological characteristics were compared. We also assessed diagnostic yield with the increased number of sputum specimens. RESULTS: Diagnostic yield with 3 sputum specimens was 16.5% (23/139). The 3-sputum diagnosed group had a lower body mass index [18.6(17-19.5) vs. 19.5(18-21.5); p = 0.014], and higher chest CT score [9(6.5-13) vs. 6(4-9); p = 0.011] including cavitary lesions (39.1% vs. 19%; p = 0.037) compared with the non-3 sputum diagnosed group. When the number of sputum specimens was increased to 6, the diagnostic yield increased to 23.7% (33/139). CONCLUSION: Diagnostic yield with 3 sputum specimens was 16.5%. Patients diagnosed using 3 sputum specimens had more severe chest CT findings including cavitary lesions. Increasing the number of sputum specimens to 6 improved diagnostic yield by 7.2%.

Apoptosis Inhibitor of Macrophages Contributes to the Chronicity of Mycobacterium avium Infection by Promoting Foamy Macrophage Formation.

In Mycobacterium avium infections, macrophages play a critical role in the host defense response. Apoptosis inhibitor of macrophage (AIM), also known as CD5L, may represent a novel supportive therapy against various diseases, including metabolic syndrome and infectious diseases. The mechanisms of AIM include modulating lipid metabolism in macrophages and other host cells. We investigated the role of AIM in M. avium infections in vitro and in vivo. In a mouse model of M. avium pneumonia, foamy macrophages were induced 6 wk after infection. The bacteria localized in these macrophages. Flow cytometric analysis also confirmed that the percentage of CD11chighMHCclassIIhigh interstitial and alveolar macrophages, a cell surface marker defined as foamy macrophages, increased significantly after infection. AIM in alveolar lavage fluid and serum gradually increased after infection. Administration of recombinant AIM significantly increased the number of bacteria in the lungs of mice, accompanied by the induction of inflammatory cytokine and iNOS expression. In mouse bone marrow-derived macrophages, the mRNA expression of AIM after M. avium infection and the amount of AIM in the supernatant increased prior to the increase in intracellular bacteria. Infected cells treated with anti-AIM Abs had fewer bacteria and a higher percentage of apoptosis-positive cells than infected cells treated with isotype control Abs. Finally, AIM in the sera of patients with M. avium-pulmonary disease was measured and was significantly higher than in healthy volunteers. This suggests that AIM production is enhanced in M. avium-infected macrophages, increasing macrophage resistance to apoptosis and providing a possible site for bacterial growth.

A 52-Year-Old Obese Man With Persistent Cough.

CASE PRESENTATION: A 52-year-old man was referred to our hospital with an abnormal chest radiography infiltrate. He presented with cough that persisted for 1 month without fever, chills, dyspnea, or sputum. He has been treated with clarithromycin 400 mg/d for 1 week with no improvement. He had a history of hypertension, hyperuricemia, and gastroesophageal reflux disease. He had no family history of respiratory disease. He smoked 10 cigarettes daily for 10 years, which he had quit 15 years ago. He denied a history of alcohol or illicit drug use, occupational exposure, recent travel, and exposure to TB. He reported being sexually active with one current partner.

Co-infection with Nocardia spp. in a patient with Mycobacterium avium complex pulmonary disease: A case report.

Mycobacterium avium complex pulmonary disease (MAC-PD) is sometimes accompanied by co-infection with other pathogenic microorganisms such as Pseudomonas aeruginosa and Haemophilus influenzae. However, co-infection with Nocardia spp. has been rarely reported. We report on a patient diagnosed as having co-infection with Nocardia after treatment for MAC-PD, which was successfully treated using trimethoprim-sulfamethoxazole (TMP-SMX). A 74-year-old woman with MAC-PD was admitted to our hospital to undergo re-examination for pathogenic microorganisms because chest computed tomography (CT) findings did not improve after treatment for MAC-PD. She underwent bronchoscopy and Nocardia spp. was detected from bronchoalveolar lavage fluid culture. Chest CT findings improved after 6 months of treatment using TMP-SMX. Co-infection with other pathogenic microorganisms should be considered when chest CT findings worsen after adequate treatment of MAC-PD. Chest CT findings of Nocardia pulmonary disease in immunocompetent patients can mimic those of MAC-PD and should therefore be differentiated one from the other.

Multifocal locules including the anterior mediastinum side as a surgical indicator in pleural infection.

Background: The indication for and the timing of surgery in patients with pleural infection remains unclear. Determining the need for surgery in patients with pleural infection may help in the early consultation of surgeons. Methods: Data of 167 consecutive patients with pleural infection were retrospectively reviewed. To detect a surgical indicator, the variables of patients who required surgery were compared with those of patients who were cured by non-surgical therapy (n=94) and patients resistant to the non-surgical therapy (n=73; 62 underwent surgery, and 11 showed recurrence or disease-related death after non-surgical treatment). Prognosis and timing of surgery were analyzed by comparing three groups: patients who underwent surgery within 7 days of admission (n=33), patients who underwent surgery after 7 days of admission (n=29), and patients who underwent non-surgical therapy (n=105). Results: The presence of multifocal locules, including a locule on the anterior mediastinum side (LAMS) was a significant indicator of resistance to initial non-surgical therapy, as compared to the absence of locules (P<0.0001), a single locule (P<0.0001), or multifocal locules without a LAMS (P=0.0041). Recurrence and mortality were not observed in the patients who underwent surgery within 7 days of admission, and the hospitalization period (P=0.0071) and duration of C-reactive protein (CRP) improvement (P<0.0001) were significantly shorter in these patients compared with those who that underwent surgery after 7 days. Conclusions: In patients with pleural infection, the presence of multifocal locules, including a LAMS, was associated with resistance to non-surgical therapy. Early surgery should be considered for these patients to shorten the hospitalization period and improve the prognosis.

Impact of chronic co-infection in pulmonary Mycobacterium avium complex disease after treatment initiation.

BACKGROUND: The impact of co-infection with other pathogenic microorganisms after initiation of treatment for Mycobacterium avium complex pulmonary disease (MAC-PD) has not been clearly described. This study sought to clarify the clinical outcomes of co-infection with MAC after antimycobacterial therapy for MAC. METHODS: Co-infection status was defined as the detection of pathogenic microorganisms other than MAC in at least two consecutive sputum cultures 6-24 months after initiation of treatment. Chest computed tomography (CT) findings and culture results were compared between co-infection and MAC alone groups. RESULTS: The co-infection and MAC alone groups comprised 12 and 36 patients, respectively. The proportion of patients with sputum culture positive for MAC after 24 months of therapy did not differ significantly between the two groups [25% (3/12) vs. 16.7% (6/36); p = 0.671]. The proportion of patients with improved chest CT score after 24 months of starting treatment compared to baseline was significantly lower for the co-infection group than for the MAC alone group [16.7% (2/12) vs. 79.4% (27/34); p < 0.001]. In the co-infection group, median CT score values at 12 and 24 months did not differ from baseline. However, the MAC alone group showed significant improvement at 12 and 24 months compared with baseline. CONCLUSIONS: In the patient group with co-infection of other pathogenic microorganisms after treatment initiation for MAC there was no impact on therapeutic efficacy compared to the MAC alone group. However, therapeutic intervention interfered with improvement in chest CT findings such as nodule formation, bronchiectasis, infiltration, and cavitary lesions.

Exophiala dermatitidis pneumonia with bronchiectasis required prolonged voriconazole treatment.

Exophiala dermatitidis is a black fungus that rarely causes respiratory infection. We report a case of E. dermatitidis pneumonia with bronchiectasis that relapsed after 11 months of voriconazole (VRCZ) treatment in a rheumatoid arthritis (RA) patient with bronchiectasis. A 65-year-old woman with RA and abnormal findings on chest radiography was referred for assessment of chronic cough and increased sputum production. She underwent bronchoscopy, and E. dermatitidis was identified from bronchoalveolar lavage fluid (BALF). Exophiala dermatitidis chronic lower respiratory tract infection and pneumonia were diagnosed. Although her condition improved after 11 months of VRCZ treatment, chest computed tomography (CT) images showed worsening at five months after the cessation of VRCZ treatment and E. dermatitidis was again detected in BALF. Re-administration of VRCZ for two years improved symptoms and chest CT images, and her condition is currently stable. In patients with bronchiectasis, E. dermatitidis pneumonia might require prolonged antifungal treatment.

Bronchial Brushing and Diagnosis of Pulmonary Nontuberculous Mycobacteria Infection.

BACKGROUND: The optimal bronchoscopy procedure for diagnosis of pulmonary nontuberculous mycobacteria (NTM) infection is unclear. OBJECTIVE: This study investigated the usefulness of bronchial brushing in bronchoscopy for diagnosis of pulmonary NTM infection in patients with suspected NTM lung disease and nodular bronchiectasis on chest computed tomography (CT) images. METHODS: Bronchoscopy was prospectively performed for 69 patients with clinically suspected pulmonary NTM infection on chest CT from December 2017 through December 2019. Before and after bronchial brushing, bronchial washing was performed with 20 or 40 mL of normal sterile saline at the same segmental or subsegmental bronchi. Before and after bronchial brushing, samples of the washing fluid (pre- and postbrushing samples) and brush deposits (brush samples) were obtained and cultured separately. RESULTS: NTM was detected in 37 of the 69 (53.6%) patients (Mycobacterium avium in 27, Mycobacterium intracellulare in 7, M. abscessus in 2, and M. kansasii in 2). NTM was detected in 34 (49.3%) prebrushing samples, in 27 (39.1%) postbrushing samples, and in 20 (29.0%) brush samples from the 69 patients. In 2 (2.9%) patients, NTM was detected only in postbrushing samples; in 1 (1.4%) patient, NTM was detected only in a brush sample. As compared with bronchial washing only, additional bronchial brushing increased the NTM culture-positive rate by 4.3% (3/69). Bronchial brushing caused bleeding, requiring hemostasis in 5 (7.2%) patients. CONCLUSION: Additional bronchial brushing increased the NTM culture-positive rate by only 4.3% (3/69), as compared with bronchial washing alone. Thus, the usefulness of brushing appears to be limited.

Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer.

BACKGROUND: The response rate for osimertinib is high among patients with untreated epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, there exist no biomarkers to predict the efficacy of the same. This study investigated whether BIM-γ mRNA expression in circulating tumor cells (CTCs) predicts poor outcomes for osimertinib treatment in patients with EGFR mutation-positive NSCLC. METHODS: Patients with advanced EGFR-tyrosine kinase inhibitor-untreated NSCLC or post-operative recurrence with EGFR-sensitive mutations (exon 19 deletion or L858R mutation) were included. Informed consent was obtained from all participants. The candidate biomarker BIM-γ was measured in CTCs after blood collection (10 mL of whole blood) at baseline. CTCs were collected with the ClearCell FX system, and quantitative real-time PCR was performed. Relative expression of BIM-γ mRNA from CTCs, as normalized to the reference gene (GAPDH mRNA), was calculated using the KCL22 cell line for calibration. RESULTS: We enrolled 30 EGFR mutation-positive NSCLC patients treated with osimertinib during the period from April 2018 through December 2019. All the patients had an EGFR mutation at the primary site: exon 19 deletion in 15 cases and L858R in 15 cases. Median CTC count at baseline was 12 (range 3-127)/7.5 mL, and median BIM-γ mRNA expression was 0.073 (range 0-1.37). Furthermore, the response rate to osimertinib was worse in patients with high than in those with low BIM-γ mRNA expression (n = 15 each) (26.6% vs. 73.3%, respectively; p = 0.011). Progression-free survival did not significantly differ between groups (p = 0.13). CONCLUSIONS: BIM-γ mRNA overexpression in CTCs from EGFR mutation-positive NSCLC patients is a potential a biomarker for poor response to osimertinib. CLINICAL TRIAL REGISTRATION NUMBER: UMIN:00032055.

Clinical and radiological characteristics of ultrasonic humidifier lung and summer-type hypersensitivity pneumonitis.

BACKGROUND: Ultrasonic humidifier lung is a rare form of hypersensitivity pneumonitis (HP), and its clinical and radiological features are unclear. This study examined the clinical and radiological characteristics of humidifier lung. METHODS: Data from 18 patients with humidifier lung (mean age, 67.3 years) diagnosed during October 2012 through April 2018 were retrospectively reviewed. We compared clinical, laboratory, and CT findings and bronchoalveolar lavage fluid (BALF) characteristics of these patients with those of 19 patients with summer-type HP (mean age, 57.4 years). RESULTS: Cough and dyspnea were the most common symptoms. White blood cell count and serum C-reactive protein titers were higher for humidifier lung than for summer-type HP. Serum levels of Krebs von den Lungen-6 and surfactant protein D were significantly lower for humidifier lung than for summer-type HP. The most common chest CT findings in humidifier lung were ground-glass opacities (88.9%) and mosaic attenuation (50.0%). Centrilobular ground glass nodules were less common in humidifier lung than in summer-type HP (27.8% vs 63.1%; P = 0.043). Peribronchovascular or subpleural nonsegmental consolidation was more frequent in humidifier lung than in summer-type HP (44.4% vs 5.3%; P = 0.013). Lymphocyte fractions in BALF specimens were significantly lower for humidifier lung than for summer-type HP (37.3% vs 69.0%; P < 0.001). Neutrophil fractions were higher for humidifier lung, but the difference was not significant (22.1% vs 8.1%; P = 0.153). The CD4/8 ratio was higher for humidifier lung than for summer-type HP (1.7 vs 0.8; P = 0.003). CONCLUSIONS: The clinical and radiological characteristics of humidifier lung differ from those of summer-type HP.

Serial change in serum biomarkers during treatment of Non-HIV Pneumocystis pneumonia.

BACKGROUND: For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. OBJECTIVE: This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. METHODS: We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (ß-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. RESULTS: There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated ß-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03). CONCLUSION: Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.

Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium complex infection.

BACKGROUND: We occasionally treat patients with clinically suspected pulmonary Mycobacterium avium complex (MAC) infection and negative MAC culture on bronchoscopy. OBJECTIVE: This study aimed to investigate the usefulness of bronchoscopy in patients with suspected MAC lung disease with nodular bronchiectasis on chest computed tomography (CT) and to clarify the clinical characteristics of these patients. METHODS: We reviewed the records of 71 patients with clinically suspected pulmonary MAC infection on chest CT who underwent bronchoscopy. The patients were classified on the basis of MAC culture result, and their clinical characteristics were compared. RESULTS: MAC was detected in 33 of the 71 (46.5%) patients (positive group), and 35 (49.3%) were culture-negative for nontuberculous mycobacteria (NTM) (negative group). NTM other than MAC were detected in 3 of 71 (4.2%) patients. MAC was not detected in 14 of 38 (36.8%) patients positive for GPL core IgA antibody. Patients in the positive group had a higher body mass index (20.1 ± 3.4 vs 18.5 ± 2.9 kg/m2; p = 0.047) and positive rate for GPL core IgA antibody (72.7% vs 40%; p = 0.006) and a lower chronic obstructive pulmonary disease assessment test score (6.6 ± 6.6 vs 11.7 ± 8.5; p = 0.016) and rate of positive culture for Pseudomonas aeruginosa or Haemophilus influenzae (12.1% vs 45.7%; p = 0.003), as compared with the negative group. CONCLUSION: Bronchoscopy is useful for diagnosis of MAC in patients who cannot be diagnosed by sputum examination. In addition, patients with pulmonary MAC disease had less severe subjective symptoms and weight loss than did those with a negative MAC culture on bronchoscopy.

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and ß-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis.

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a ß-d-glucan (ßDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and ßDG testing of BALF, respectively. The sensitivity and specificity of the GM test, ßDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and ßDG tests had the highest diagnostic odds ratio. The combination of the GM and ßDG tests on BALF was more useful than any single test for diagnosing CPA.