Beyond Symptoms: Radiologic identification of asymptomatic Mycobacterium avium complex pulmonary infections.

BACKGROUND: Although international nontuberculous mycobacterial pulmonary disease (NTM-PD) guidelines highlight symptom presence at diagnosis, the clinical characteristics of asymptomatic Mycobacterium avium complex pulmonary infection (MAC-PI) patients remain understudied. We clarified the clinical characteristics and course of asymptomatic MAC-PI patients. METHODS: We retrospectively analyzed 200 consecutive patients with MAC-PIs and adequate available data who newly met the microbiological and radiological criteria for NTM-PD at Fukujuji Hospital from January 2018 to June 2020. We compared the clinical characteristics and course of asymptomatic patients with symptomatic patients and evaluated factors influencing treatment initiation through multivariate analysis. RESULTS: 111 patients were symptomatic and 89 were asymptomatic at diagnosis. While the proportion was significantly lower than that in the symptomatic group (28.8 %), 15.7 % of asymptomatic group patients had cavitary lesions (P = 0.042). In the asymptomatic group, treatments were initiated in 38 (42.7 %) patients, and cavitary lesions, a positive acid-fast bacilli smear, and younger age were independent risk factors for treatment initiation. Among 22 (57.9 %) patients who experienced disease progression necessitating treatment during follow-up, 13 (34.2 %) displayed radiological progression without any worsening of symptoms. Agents used for treatment were consistent across the groups, with no significant differences in culture conversion, microbiological recurrence rates, or spontaneous culture conversion rates. CONCLUSION: Routine health checkups and radiological examinations can detect clinically important MAC-PIs even in the absence of symptoms. Considering that the clinical course of asymptomatic MAC-PI patients is largely similar to that of symptomatic patients, timely and appropriate management and intervention are essential for all MAC-PI patients.

Activities of Daily Living, Hypoxemia, and Lymphocytes Score for Predicting Mortality Risk in Patients With Pulmonary TB.

BACKGROUND: A clinically applicable mortality risk prediction system for pulmonary TB may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. The aim of this study was to construct a simple and objective disease severity score for patients with pulmonary TB. RESEARCH QUESTION: Does a clinical score consisting of simple objective factors predict the mortality risk of patients with pulmonary TB? STUDY DESIGN AND METHODS: The data set from our previous prospective study that recruited patients newly diagnosed with pulmonary TB was used for the development cohort. Patients for the validation cohort were prospectively recruited between March 2021 and September 2022. The primary end point was all-cause in-hospital mortality. Using Cox proportional hazards regression, a mortality risk prediction model was optimized in the development cohort. The disease severity score was developed by assigning integral points to each variate. RESULTS: The data from 252 patients in the development cohort and 165 patients in the validation cohort were analyzed, of whom 39 (15.5%) and 17 (10.3%), respectively, died in the hospital. The disease severity score (named the AHL score) included three clinical parameters: activities of daily living (semi-dependent, 1 point; totally dependent, 2 points); hypoxemia (1 point), and lymphocytes (< 720/µL, 1 point). This score showed good discrimination with a C statistic of 0.902 in the development cohort and 0.842 in the validation cohort. We stratified the score into three groups (scores of 0, 1-2, and 3-4), which clearly corresponded to low (0% and 1.3%), intermediate (13.5% and 8.9%), and high (55.8% and 39.3%) mortality risk in the development and validation cohorts. INTERPRETATION: The easy-to-calculate AHL disease severity score for patients with pulmonary TB was able to categorize patients into three mortality risk groups with great accuracy. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center; No. UMIN000012727 and No. UMIN000043849; URL: www.umin.ac.jp.

Multiple bacterial culture positivity reflects the severity and prognosis as bronchiectasis in Mycobacterium avium complex pulmonary disease.

BACKGROUND: Bacterial coinfections are observed in 19-66% of patients with Mycobacterium avium complex pulmonary disease (MAC-PD) during the entire duration of the disease. The impact of bacterial coinfection at diagnosis on the clinical course of MAC-PD has not been reported. METHODS: Among 558 patients diagnosed with MAC-PD between January 2016 and December 2020, 218 patients who underwent sputum culture tests twice or more within one year before and after diagnosis were included. We compared the patient characteristics and disease courses between the patients who had the same bacterial species detected twice or more (bacterial culture positive group: BCP group) and those who never had bacteria cultured (bacterial culture negative group: BCN group). RESULTS: We included 70 patients in the BCP group and 74 in the BCN group. The radiological findings showed that BCP at diagnosis correlated with a high modified Reiff score. During the median follow-up period of 42 months, the patients in the BCP group were more likely to accomplish spontaneous sputum conversion of MAC. The treatment initiation rate for MAC-PD in the BCP group was lower than that in the BCN group (41.4% vs. 67.6%, P = 0.003). In contrast, the time to the first bronchiectasis exacerbation in the BCP group was shorter than that in the BCN group, and the frequency of bronchiectasis exacerbations was higher in the BCP group. CONCLUSIONS: Patients with BCP at diagnosis are less likely to initiate treatment for MAC-PD and more likely to develop bronchiectasis exacerbation.

In Vitro Synergistic Effects of Omadacycline with Other Antimicrobial Agents against Mycobacterium abscessus.

The clinical importance of Mycobacterium abscessus species (MABS) infections has been increasing. However, the standard treatment regimens recommended in the current guidelines often result in unfavorable outcomes. Therefore, we investigated the in vitro activity of omadacycline (OMC), a novel tetracycline, against MABS to explore its potential as a novel therapeutic option. The drug susceptibilities of 40 Mycobacterium abscessus subsp. abscessus (Mab) clinical strains obtained from the sputum of 40 patients from January 2005 to May 2014 were investigated. The MIC results for OMC, amikacin (AMK), clarithromycin (CLR), clofazimine (CLO), imipenem (IPM), rifabutin (RFB), and tedizolid (TZD) alone and their combined effects (with OMC) were examined using the checkerboard method. Additionally, we studied the differences in the effectiveness of the antibiotic combinations based on the colony morphotype of Mab. The MIC50 and MIC90 of OMC alone were 2 and 4 µg/mL, respectively. The combinations of OMC with AMK, CLR, CLO, IPM, RFB, and TZD showed synergy against 17.5%, 75.8%, 25.0%, 21.1%, 76.9%, and 34.4% of the strains, respectively. Additionally, OMC combined with CLO (47.1% versus 9.5%, P = 0.023) or TZD (60.0% versus 12.5%, P = 0.009) showed significantly higher synergy against strains with rough morphotypes than those with smooth morphotypes. In conclusion, the checkerboard analyses revealed that the synergistic effects of OMC were observed most frequently with RFB, followed by CLR, TZD, CLO, IPM, and AMK. Furthermore, OMC tended to be more effective against rough-morphotype Mab strains.

Usefulness of gastric aspirates for diagnosing nontuberculous mycobacteriosis.

Distinguishing between nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis (TB) is difficult. We aimed to evaluate the usefulness of gastric aspirate examination for NTM-PD diagnosis and for differentiating NTM-PD from other diseases, including pulmonary TB. We retrospectively collected data for 491 patients with negative sputum smears or a lack of sputum production at Fukujuji Hospital. We compared 31 patients with NTM-PD to 218 patients with other diseases (excluding 203 with pulmonary TB). Additionally, we compared 81 patients with NTM cultured from at least one sputum or bronchoscopy sample to the other 410 patients. Gastric aspirate examination for NTM-PD diagnosis showed 74.2% sensitivity and 99.0% specificity for culture positivity. There was no significant difference between the nodular bronchiectatic disease and cavitary disease types for culture positivity (p = 0.515). The significance of NTM isolation from gastric aspirate showed 64.2% sensitivity and 99.8% specificity for culture positivity. Gastric aspirate examination revealed NTM in one TB patient, allowing TB to be ruled out in 98.1% of patients with NTM cultured from gastric aspirates. Gastric aspirate examination is helpful for early-stage NTM diagnosis and ruling out pulmonary TB. This could lead to more accurate and timely treatment.

Causative antigens of humidifier lung in vapor from a humidifier: A case report.

A 68-year-old man exhibited fever and cough three weeks prior to hospital admission after three months of ultrasonic humidifier usage. Chest computed tomography showed bilateral ground-glass opacities, lymphocyte levels in the bronchoalveolar lavage fluid were elevated (60.8%), and the histological examination of a transbronchial lung biopsy showed lymphocytic alveolitis. He gradually improved without medication after he stopped using the humidifier. Accordingly, humidifier lung was the diagnosis. Humidifier water and vapor collected from the patient's humidifier were investigated. Humidifier vapor was obtained by collecting the condensed moisture. Laboratory examinations exhibited gram-negative rods and a high concentration of endotoxin and (1 â†’ 3)-ß-D-glucan in both vapor and water. The serum-precipitating antibodies showed a stronger reaction against humidifier vapor than against humidifier water. 16S rRNA metagenomic analysis revealed a high percentage of sequences of Spirosoma lacussanchae and Sphingomonas spp. in both the humidifier vapor and water. The percentages of sequence reads were lower in humidifier vapor than in water; conversely, sequences of Pseudomonas spp. and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium were more concentrated in the humidifier vapor than in humidifier water. Although the reason for the different bacterial ratios between humidifier vapor and water is uncertain, the bacteria that were more concentrated in humidifier vapor than in humidifier water might have been the causative antigen underlying the humidifier lung diagnosis. This is the first report to indicate the presence of causative antigens in humidifier vapor.

Epidemiological characteristics of nontuberculous mycobacteriosis and bronchiectasis: comparative study using national mortality statistics from 1970 to 2015 in Japan.

Background: This study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases. Methods: We analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system. Results: The total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis. Conclusions: The trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.

Pharmacokinetics and Adverse Effects of Clofazimine in the Treatment of Pulmonary Non-Tuberculous Mycobacterial Infection.

Clofazimine (CFZ) is used to treat pulmonary non-tuberculous mycobacterial (NTM) infection; however, its pharmacokinetics remain unexplored in patients with pulmonary NTM, and the relationship between CFZ serum concentration and adverse effects has not been investigated. The objectives of this study were to characterize the pharmacokinetics of CFZ in pulmonary NTM disease treatment and to investigate the relationship between the steady-state CFZ serum concentration and adverse effects. A prospective observational study was conducted on 45 patients with pulmonary NTM treated with CFZ (UMIN000041053). A maximum of five serum samples per patient were taken at the CFZ trough, and serum concentration was measured using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetics of CFZ were analyzed using a nonlinear mixed effect model. The relationships among steady-state CFZ serum concentration and adverse effects, pigmentation, and heart rate-corrected QT (QTc) interval were investigated. Twenty-six patients had M. avium or M. intracellulare infection and nineteen had M. abscessus infection. The primary CFZ dosage was 50 mg/day. The estimated apparent CFZ clearance, apparent volume of distribution, and half-life were 2.4 L/h, 2,960 L, and 36 days, respectively. The combined use of rifampicin and CFZ significantly reduced CFZ exposure by 22%. Although there was no relationship between CFZ serum concentration and pigmentation intensity, the QTc interval was significantly correlated with CFZ serum concentration. The estimation of accurate pharmacokinetics for CFZ required approximately 5 months of monitoring. The relationship between the serum concentration and specific adverse effects of CFZ confirmed that CFZ serum concentration was not associated with pigmentation but did affect the QTc interval.

Potential Cross-Transmission of Mycobacterium abscessus among Non-Cystic Fibrosis Patients at a Tertiary Hospital in Japan.

Mycobacterium abscessus (M. abscessus) is a highly antimicrobial-resistant pathogen that causes refractory pulmonary disease. Recently, the possibility of M. abscessus cross-transmission among cystic fibrosis (CF) patients has been reported. CF is rare in Asia, but M. abscessus pulmonary disease is common. Therefore, we investigated the possibility of M. abscessus cross-transmission in a Japanese hospital setting. Of 104 M. abscessus isolates, 25 isolates from 24 patients were classified into four clusters based on their variable number of tandem repeat profiles and were subjected to whole-genome sequencing (WGS). The epidemiological linkages among our patients were investigated by integrating the WGS data of previously reported nosocomial outbreak-related M. abscessus clinical isolates in the United Kingdom and the United States. Eight transmissible clusters (TCs) were identified. The United Kingdom and United States isolates were assigned to four clusters (TC1, TC2, TC5, and TC8) and one cluster (TC3), respectively. A total of 12 isolates from our hospital belonged to 4 clusters (TC4, TC5, TC6, and TC7). Epidemiological linkage analysis inferred direct or indirect transmission between patients in our hospital in TC4 and TC5 but not in TC6 and TC7. In TC5, the single nucleotide polymorphism distance between isolates from Japanese and United Kingdom patients was less than 21; however, there was no contact. This study revealed that genetically closely related isolates exist, even in non-CF patients. However, the transmission route remains unclear, and further research is warranted to clarify whether cross-transmission is involved. IMPORTANCE Although the possibility of Mycobacterium abscessus (M. abscessus) cross-transmission in cystic fibrosis (CF) patients has often been reported, it is not clear whether similar events have occurred in Asian non-CF patients. Whole-genome sequencing analysis of M. abscessus isolates from Fukujuji Hospital in Japan indicated that genetically closely related M. abscessus isolates exist. In addition, according to epidemiological linkage analysis, some clusters were suspected of direct or indirect transmission between patients within our hospital. However, the transmission route of M. abscessus remains unclear, because interestingly, one cluster showed a single nucleotide polymorphism distance of less than 21 from the United Kingdom isolates, but no epidemiological linkage was identified.

Analysis of risk factors for pulmonary tuberculosis with persistent severe inflammation: An observational study.

INTRODUCTION: Patients with pulmonary tuberculosis (TB) sometimes show persistent severe inflammation for more than 1 month, even if TB treatment is effective. Although this inflammation can be improved through continuous antituberculous therapy, the risk factors for persistent inflammation remain unclear. Therefore, we sought to study the characteristics of patients with persistent severe inflammation. MATERIALS AND METHODS: We retrospectively analyzed 147 hospitalized adult patients with C-reactive protein (CRP) levels of 5 mg/dL or more on admission to Fukujuji Hospital from April 2019 to March 2021. The patients were divided into 2 groups: 40 patients (27.2%) had CRP levels of 5 mg/dL or more at 4 weeks after admission (persistent inflammation group), and 107 patients (72.8%) had CRP levels that fell below 5 mg/dL within 4 weeks of admission (improved inflammation group). RESULTS: The median CRP level on admission in the persistent inflammation group was 10.8 mg/dL (interquartile range 9.1-14.5), which was higher than that in the improved inflammation group (median 8.2 mg/dL [6.5-12.1], P = .002). Patients in the persistent inflammation group had a higher prevalence of large cavities, defined as cavities ≥4 cm in diameter, on chest computed tomography (CT) (n = 20 [50.0%] vs n = 12 [11.2%], P < .001). DISCUSSION AND CONCLUSIONS: This study showed that 27.2% of patients who had high or moderate inflammation on admission did not achieve low CRP levels within 4 weeks after admission. Risk factors for persistent severe inflammation in patients with TB were presence of a large cavity (cavity diameter ≥4 cm) on chest CT and a high CRP level on admission. Therefore, in a patient with a large cavity on chest CT and/or CRP ≥9.0 mg/dL on admission, long-term inflammation may occur despite antituberculous therapy if other diseases are ruled out.

Usefulness of gastric aspirate for the diagnosis of smear-negative pulmonary tuberculosis.

INTRODUCTION: Gastric aspirate can be useful for the diagnosis of pulmonary tuberculosis (TB) in patients with smear-negative pulmonary TB or without sputum production. The gastric aspirate smear technique has low sensitivity, and a previous report demonstrated that no patient was diagnosed by only gastric aspirate analysis. However, some patients with TB have been negative on sputum examination but positive on gastric aspirate examination, and the incidence of such cases is uncertain. Therefore, this study investigated the usefulness of gastric aspirate in the diagnosis of pulmonary TB. METHODS: To analyze the diagnostic accuracy of gastric aspirate examination, the data of 513 patients with negative sputum smears or a lack of sputum production, including 203 patients with pulmonary TB (39.6%) and 93 patients with nontuberculous mycobacteriosis who underwent gastric aspiration at Fukujuji Hospital from January 2016 to March 2021, were collected retrospectively. RESULTS: The accuracy rates of gastric aspirate examination for the diagnosis of pulmonary TB were as follows: 21.2% sensitivity and 91.9% specificity for smear positivity, 55.8% sensitivity and 99.6% specificity for nucleic acid amplification test positivity, and 71.4% sensitivity and 100% specificity for culture positivity. Twenty-three patients (11.2%) were diagnosed by gastric aspirate examination alone. Among the 356 patients who underwent three repeated sputum examinations in addition to gastric aspirate examination, the cumulative diagnostic rate for the 3 mycobacterial examinations plus gastric aspirate examination was higher than that for only three sputum examinations. CONCLUSIONS: Gastric aspirate is useful for the diagnosis of TB in patients with smear-negative pulmonary TB or without sputum production.

Molecular Epidemiological Characteristics of Mycobacterium abscessus Complex Derived from Non-Cystic Fibrosis Patients in Japan and Taiwan.

Mycobacterium abscessus complex (MABC) is a group of emerging, highly antimicrobial-resistant non-tuberculous mycobacteria. Specific MABC clones are spreading globally in patients with cystic fibrosis (CF); however, associated genomic epidemiology is lacking in East Asia, with very few patients with CF. Here, we investigated MABC populations derived from non-CF patients in Japan and Taiwan. Analysis of whole-genome sequencing data of 220 MABC isolates revealed that 112, 105, and 3 were M. abscessus subsp. abscessus (ABS), M. abscessus subsp. massiliense (MAS), and M. abscessus subsp. bolletii (BOL), respectively. Moreover, >50% of ABS and >70% of MAS were related to four predominant clones in the region. Known mutations conferring macrolide resistance were rare (1.4%) and were not enriched in the predominant clones. Conversely, the macrolide-susceptible erm(41) T28C mutation was significantly enriched in one predominant ABS clone. The most predominant ABS clone was genetically related to the previously described dominant circulating clone (DCC)1 in patients with CF, whereas no isolates were related to DCC2; isolates related to DCC3 were not necessarily predominant in our sample set. We found that the erm(41) T28C mutants spread globally, and some of them reacquired the functional erm(41) gene through both point mutation and recombination. This study revealed predominant MABC clones in Japan and Taiwan and their relationship with the globally superadding clones in the patient community with CF. Our study provides insights into the genetic characteristics of globally dominant and area-specific strains isolated from patients with or without CF and differences between globally spread and regionally specific strains. IMPORTANCE Members of Mycobacterium abscessus complex (MABC) are frequently isolated from patients. Studies have reported that predominant clones of MABC (known as dominant circulating clones; DCCs) are distributed worldwide and transmitted from humans to humans in patients with cystic fibrosis (CF). However, associated genomic epidemiology has not yet been conducted in East Asia, including Japan and Taiwan, where there are only a few patients with CF. Using whole-genome sequencing data derived from non-CF patients in Japan and Taiwan, we revealed prevalent clones and the incidence of macrolide resistance-associated mutations in the MABC population in this region. We also clarified the associations between these predominant clones and DCCs in the global CF patient community. Our results would assist further studies in elucidating the genetic characteristics of strains isolated from patients with or without CF, the differences between globally spread and regionally specific strains, and the adaptive evolution of MABC within the host.

Decreased incremental shuttle walk test distance characterized by fibrocavitary lesions in non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: Patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) have impaired exercise capacity, but the underlying factors are unknown. We investigated the characteristics of patients with NTM-PD and impaired exercise capacity. METHODS: In total, 149 patients with NTM-PD participated in this study. Patients completed the incremental shuttle walk test (ISWT) to assess exercise capacity. Peripheral muscle strength and pulmonary function were also assessed. Radiological findings were classified into three phenotypes: non-cavitary nodular bronchiectatic (NC-NB) form, cavitary nodular bronchiectatic form, and fibrocavitary (FC) form. RESULTS: The median ISWT distance (ISWD) and %ISWD were 450 meters and 88%. Participants were classified into three groups according to %ISWD, with %ISWD <60% as the severely decreased group, 60%-80% as the moderately decreased group, and >80% as the normal or mildly decreased group. In a comparison of %ISWD among phenotypes, FC form had significantly lower %ISWD than those with NC-NB form. In the severely decreased group, peripheral muscle strength and pulmonary function were significantly lower than the other two groups. From a radiological standpoint, significantly more patients had FC form in the group with severely decreased %ISWD. CONCLUSIONS: Decreased ISWD is characterized by a deterioration in physical function and the presence of FC lesions in NTM-PD.

Low-dosage ethambutol, less than 12.5 mg/kg/day, does not worsen the clinical outcomes of pulmonary Mycobacterium avium and Mycobacterium intracellulare disease: a retrospective cohort study.

OBJECTIVES: Multidrug chemotherapy is recommended for treating pulmonary Mycobacterium avium and Mycobacterium intracellulare disease. Although ethambutol has been demonstrated to inhibit macrolide resistance, the ethambutol dosage is sometimes decreased due to concerns about optic neuropathy. We aimed to assess whether lower ethambutol doses impact treatment outcomes. METHODS: Patients treated over 12 months between 2016 and 2020 were collected retrospectively. Clinical outcomes, including negative culture conversion, microbiological cure, adverse events, resistance to macrolides, and recurrence, were compared according to daily ethambutol dosage. RESULTS: Among 146 patients, 42 were treated with ethambutol dosages over 12.5 mg/kg/day, and 104 were treated with lower dosages. Negative culture conversion was achieved for 125 patients, and 90 patients achieved microbiological cure. Recurrence was identified in 16 patients who achieved microbiological cure. No macrolide resistance was observed, and no significant difference was observed in the percentage of negative culture conversion (P = 1.00) or microbiological cure (P = 0.67) between the high- and low-dosage ethambutol groups. Sputum smear positivity was associated with a lower adjusted odds ratio (aOR) of negative culture conversion (aOR: 0.48, 95% CI: 0.29-0.80). A lower aOR of microbiological cure was independently associated with sputum smear positivity (aOR: 0.52, 95% CI: 0.37-0.74) and with the use of an intermittent regimen (aOR: 0.60, 95% CI: 0.41-0.87). Daily ethambutol dosage was not identified as a prognostic factor for any of the outcomes. Optic neuropathy was observed in 7.1% of the high-dose ethambutol group and 1.0% of the low-dosage ethambutol group (P = 0.07). CONCLUSION: An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Influence of chronic sputum symptoms on quality of life in patients with nontuberculous mycobacterial pulmonary disease: A cross-sectional study.

BACKGROUND: The effect of chronic sputum (CS) symptoms on health-related quality of life (HRQOL) in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been studied. The aim of this study was to clarify the differences in the clinical characteristics of NTM-PD patients with and without CS and to investigate the effect of CS on HRQOL. METHODS: This cross-sectional study included patients with NTM-PD who were prescribed pulmonary rehabilitation at the Fukujuji Hospital from March 2016 to June 2019. HRQOL was evaluated using the MOS 36-Item Short-Form Health Survey (SF-36). RESULTS: Of the 99 subjects studied, 71 had CS (CS+) (71.7%), and 28 (28.3%) did not have CS (CS-). Patients in the CS + group had a lower body mass index, forced vital capacity percent predicted, and forced expiratory volume in 1 s percent predicted. Regarding the radiological evaluation, the proportion of patients with the fibrocavitary form and the radiological score were significantly higher in the CS + group. The mental component summary (MCS) score of the SF-36 were significantly lower in the CS + group. Multiple regression analysis showed that the presence of CS was independently associated with a lower MCS score of the SF-36. CONCLUSIONS: NTM-PD patients with CS had more severe disease, with reduced pulmonary function and severe radiological findings. CS was shown to independently affect HRQOL, especially mental status.

Minimum Inhibitory Concentrations before and after Antibacterial Treatment in Patients with Mycobacterium abscessus Pulmonary Disease.

The clinical importance of Mycobacterium abscessus (MABS) pulmonary disease has been increasing. However, there is still a lack of information about MIC distribution patterns and changes in clinical practice settings. The MIC results of rapidly growing mycobacteria isolated from 92 patients with nontuberculous mycobacterial pulmonary disease diagnosed from May 2019 to March 2021 were retrospectively analyzed. Most of the patients (86 patients; 93.5%) were infected with MABS; 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma). Significant differences in susceptibility to clarithromycin (15.2% versus 80.0%, P < 0.001) and azithromycin (8.7% versus 62.5%, P < 0.001) were observed between Mab and Mma. Most isolates were susceptible to amikacin (80; 93.0%), and over half were susceptible to linezolid (48; 55.8%). Only one-quarter of isolates (22, 25.6%) were susceptible to imipenem, while more than half (56; 65.1%) had intermediate susceptibility. Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, which were significantly higher than isolates for moxifloxacin (5; 5.8%), especially in Mab. Sixty-five (75.6%) isolates had MICs of less than 0.5 µg/mL to clofazimine. Two patients showed obvious MIC result changes: from susceptible to resistant to clarithromycin and from resistant to susceptible to amikacin and imipenem. In conclusion, MABS isolates were relatively susceptible to amikacin and linezolid, and clarithromycin and azithromycin were especially effective against Mma. In addition, sitafloxacin and clofazimine had low MICs and might be effective treatment agents. IMPORTANCE The MICs of isolates from 86 patients with Mycobacterium abscessus (MABS); 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma) were retrospectively analyzed. The main findings are as follows: (i) Mma were significantly more susceptible to clarithromycin and azithromycin than Mab, and both subspecies tended to be more susceptible to clarithromycin than azithromycin. (ii) Most isolates were susceptible to amikacin (93.0%), and over half to linezolid (55.8%). (iii) Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, and 65 (75.6%) had less than 0.5 µg/mL for clofazimine, which seems worth clinical investigating. (iv) Among nine cases analyzed chronological changes, only two patients showed obvious MIC result changes even after the long-term multidrug treatment. The present study revealed MICs of MABS clinical isolates before and after treatment in clinical settings, which could help develop future MABS treatments strategies.

In-hospital pulmonary rehabilitation after completion of primary respiratory disease treatment improves physical activity and ADL performance: A prospective intervention study.

INTRODUCTION: Pulmonary rehabilitation improves the physical condition of patients with chronic respiratory disease; however, there are patients who cannot leave the hospital because of their low activities of daily living (ADLs), despite the completion of primary respiratory disease treatment and rehabilitation during treatment. Therefore, this study demonstrated that those patients recovered their ADLs through in-hospital pulmonary rehabilitation after treatment completion. METHODS: We prospectively studied 24 hospitalized patients who had some remaining symptoms and showed low ADL scores of 9 points or less on the short physical performance battery after undergoing treatment for respiratory disease in Fukujuji Hospital from October 2018 to October 2019, excluding 2 patients who had re-exacerbation and 1 patient who could not be examined using the incremental shuttle walk test (ISWT). After completion of the primary respiratory disease treatment, patients moved to the regional comprehensive care ward, and they received pulmonary rehabilitation for 2 weeks. In the ward, patients who could not yet leave the hospital could undergo pulmonary rehabilitation for up to 60 days. Data were evaluated three times: upon treatment completion (baseline), postrehabilitation, and 3 months after baseline. The main outcome was an improvement in the incremental shuttle walk test (ISWT) postrehabilitation. RESULTS: The median age of the patients was 80 (interquartile range (IQR): 74.8-84.5), and 14 patients (58.3%) were male. The ISWT distance significantly increased postrehabilitation (median [IQR]: 60 m [18-133] vs 120 m [68-203], P < .001). The Barthel Index (BI) (P < .001), the modified Medical Research Council (P < .001), and other scale scores were also improved. Among patients with acute respiratory diseases such as pneumonia, chronic obstructive pulmonary disease, and interstitial pneumonia, ISWT and other data showed improvement at the postrehabilitation timepoint. Ten patients who could perform examinations at 3 months after baseline were evaluated 3 months after taking baseline data prior to starting rehabilitation. The ISWT showed significant improvement 3 months after baseline compared to baseline (P = .024), and the ISWT distance was maintained after rehabilitation. DISCUSSION AND CONCLUSIONS: Physical activity, symptoms, mental health, and ADL status in patients who had not recovered after primary treatment completion for respiratory diseases could improve through in-hospital pulmonary rehabilitation.

Effects of pain on depression, sleep, exercise tolerance, and quality of life in patients with nontuberculous mycobacterial pulmonary disease.

ABSTRACT: The experience and causes of pain in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) have not been clarified.This study aimed to determine the prevalence and severity of bodily pain (BP) in patients with NTM-PD. We also investigated the clinical indicators that contribute to pain.We used a retrospective cross-sectional study design. The participants were 114 NTM-PD patients (109 women) with a mean age of 65 years. The prevalence and severity of pain were measured using 2 items from the 36-Item Short Form Survey version 2 (SF-36), and the BP score was calculated. Functional limitation due to dyspnea was quantified using the Modified Medical Research Council Dyspnea Scale (mMRC), depression was assessed using the Center for Epidemiological Studies Depression Scale (CES-D), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); health-related quality of life was assessed using the Leicester Cough Questionnaire (LCQ), and exercise tolerance was measured using the Incremental Shuttle Walk Test (ISWT).Pain was reported by 70.2% of the patients (n = 80), and of these, 35.7% (n = 25) reported moderate to very severe pain. NTM-PD patients with high levels of pain had significantly higher scores on the mMRC, CES-D, and PSQI scores, and significantly lower performance on the ISWT and LCQ. Multiple regression analysis identified ISWT, CES-D, and PSQI as independent factors that affected BP scores.Our findings suggest that pain significantly impacts daily life associated with reduced exercise tolerance, the presence of depressive symptoms, and poor sleep quality in patients with NTM-PD.

Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis: A Multicenter Retrospective Study.

Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the clinical features and prognosis of NTM pleuritis. Methods: This retrospective observational study included patients with NTM pleuritis from January 2001 to June 2018 across eight hospitals in Japan. NTM pleuritis was defined by a positive NTM culture of pleural effusion samples. We matched patients with Mycobacterium avium complex (MAC) lung disease (MAC-LD) without pleuritis by sex and age to obtain comparative data and investigated the association between clinical parameters and the prognosis. Results: We identified 64 patients with NTM pleuritis (median age, 73 yr; 37 female patients). The median follow-up duration was 11 months, and 27 patients died. Patients with MAC pleuritis had a significantly lower survival rate than matched patients with MAC-LD without pleuritis. Multivariate analysis revealed that pleuritis (adjusted hazard ratio, 6.99; 95% confidence interval [CI], 2.58-19.00) and underlying pulmonary diseases (adjusted hazard ratio, 3.01; 95% CI, 1.44-6.28) were independently associated with all-cause mortality in patients with MAC-LD. Conclusions: The prognosis of MAC pleuritis is poorer than that of MAC-LD without pleuritis. Pleuritis is an independent prognostic factor in patients with MAC-LD.

Waterproofing spray-associated pneumonitis review: Comparison with acute eosinophilic pneumonia and hypersensitivity pneumonitis.

ABSTRACT: Waterproofing spray-associated pneumonitis (WAP) proceeds to acute respiratory failure and is characterized by diffuse bilateral ground-glass opacities on computed tomography; however, the detailed characteristics of WAP are unknown. Therefore, this study identified the characteristics of WAP from comparisons with those of acute eosinophilic pneumonia (AEP) and hypersensitivity pneumonitis (HP), which show similar features to WAP.Adult patients with WAP, AEP, and HP treated in Fukujuji Hospital from 1990 to 2018 were retrospectively enrolled. Furthermore, data from patients with WAP were collected from publications in PubMed and the Japan Medical Abstracts Society and combined with data from our patients.Thirty-three patients with WAP, eleven patients with AEP, and thirty patients with HP were reviewed. Regarding age, sex, smoking habit, and laboratory findings (white blood cell count, C-reactive protein level, and serum Krebs von den Lungen-6 level), WAP and AEP were not significantly different, while WAP and HP were significantly different. The duration from symptom appearance to hospital visit was shorter in patients with WAP (median 1 day) than in patients with AEP (median 3 days, P = .006) or HP (median 30 days, P < .001). The dominant cells in the bronchoalveolar lavage fluid of patients with WAP, AEP, and HP were different (macrophages, eosinophils, and lymphocytes, respectively).The characteristic features of WAP were rapid disease progression and macrophage dominance in the bronchoalveolar lavage fluid, and these characteristics can be used to distinguish among WAP, AEP, and HP.