Published papers

BACKGROUND: Pulmonary nocardiosis frequently occurs in immunocompromised hosts and in some immunocompetent hosts with chronic lung disease; however, few reports have described pulmonary nocardiosis with nontuberculous mycobacterial lung infection. Here we report for the first time two cases of pulmonary nocardiosis caused by Nocardia cyriacigeorgica associated with Mycobacterium avium complex (MAC) lung disease caused by M. avium. CASE PRESENTATION: Case 1 is that of a 72-year-old Japanese man with untreated MAC lung disease, who was diagnosed with rheumatoid arthritis and initiated on methotrexate. After 3 years of methotrexate therapy, the patient remained smear-negative and culture-positive for MAC, but also became smear-positive for Nocardia species. He received trimethoprim/sulfamethoxazole, and his symptoms and lung infiltrates improved. Case 2 is that of an immunocompetent 53-year-old Japanese woman with MAC lung disease, who was treated with a combined therapy of clarithromycin, rifampicin, ethambutol, and levofloxacin. MAC sputum culture was negative after 1 year of combined treatment, which was maintained for 2 years. After four treatment-free years, Nocardia species were occasionally isolated from her sputum, although MAC was rarely isolated from sputum cultures over the same period. In both cases, the Nocardia species were identified as the recently defined N. cyriacigeorgica by 16S ribosomal RNA gene sequencing. CONCLUSION: We report two cases of pulmonary nocardiosis caused by N. cyriacigeorgica associated with MAC lung disease caused by M. avium and suggest that N. cyriacigeorgica may be a major infective agent associated with MAC lung disease.

BACKGROUND AND OBJECTIVE: No reports exist regarding skeletal muscle involvement in patients with Mycobacterium avium complex lung disease (MAC-LD). The cross-sectional area of the erector spinae muscles (ESMCSA) reflects physical activity and can be assessed by computed tomography (CT). We investigated the relationship between ESMCSA and physiological parameters and prognosis in MAC-LD patients. MATERIAL AND METHODS: In this prospective observational study, the ESMCSA was measured on single-slice axial CT images. MAC-LD patients and sex- and age-matched controls (non-MAC-LD participants) were evaluated. We evaluated the relationship between the ESMCSA and physiological parameters and prognosis. RESULTS: A total of 260 patients (209 female; median age, 69 years; 190 with nodular/bronchiectatic disease; 74 with cavitary lesions) were enrolled. The ESMCSA was not different between MAC-LD patients and controls. In MAC-LD patients, the ESMCSA was significantly associated with age, body mass index (BMI), pulmonary function, CT severity, and health-related quality of life (HRQL). Multivariate Cox proportional hazards analyses revealed that an ESMCSA < -1 standard derivation (hazards ratio [HR], 2.76; P = 0.047) was significantly associated with all-cause mortality, along with BMI < 18.5 kg/m2 (HR, 3.67; P = 0.02) and presence of cavitary lesions (HR, 5.84; P = 0.001). However, the ESMCSA was not significantly associated with all-cause mortality when current treatment status, % predicted functional vital capacity, and forced expiratory volume in 1 s were added to the analyses. CONCLUSIONS: Although the prognostic impact was limited, ESMCSA was significantly associated with HRQL and prognostic physiological parameters, such as BMI and pulmonary function.

A 77-year-old Japanese man with disseminated Mycobacterium avium complex (MAC) disease due to anti-interferon-gamma autoantibodies received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy because of non-Hodgkin lymphoma complication. The hepatobiliary nodules due to MAC resolved with R-CHOP and multidrug antimycobacterial treatment. R-CHOP could serve as an alternative adjunctive therapy for patients with anti-interferon-gamma autoantibodies.

We report a case of recurrent disseminated Mycobacterium avium complex (DMAC) disease with anti-gamma interferon autoantibodies. To our knowledge, this is the first reported case caused by reinfection with a separate isolate of M. avium. DMAC disease activity was monitored using serum IgG antibody titers against lipid antigens extracted from a MAC strain.

A 56-year-old woman with pulmonary Mycobacterium avium complex disease was started on inhalation liposomal amikacin. One month later, she developed hoarseness and was diagnosed with laryngitis. The laryngitis healed immediately after treatment discontinuation, and no recurrence occurred even after resuming intermittent inhalation.

Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis.

Background: Pulmonary resection along with multiple antimicrobial therapy has produced favorable outcomes at a few centers. However, little is known regarding the risk factors for long-term survival and microbiological recurrence after pulmonary resection for nontuberculous mycobacterial pulmonary disease (NTMPD). We evaluated the long-term outcomes of pulmonary resection, including microbiological recurrence and survival. Methods: This retrospective cohort study included 125 patients (median age, 60 years) with NTMPD treated by pulmonary resection at two referral centers between January 1994 and August 2015. Results: Postoperative complications occurred in 27 patients (22%). The complication rate after pneumonectomy was significantly higher than those after other types of pulmonary resection (odds ratio, 4.1; 95% confidence interval [CI], 1.6-10.3; P = .005). The median follow-up period was 7.1 years. While 19 patients experienced microbiological recurrence, 26 died. Multivariate analysis revealed pneumonectomy (adjusted hazard ratio [aHR], 0.12; 95% CI, .007-.66; P = .0098) and cavitary lesions after surgery (aHR, 6.73; 95% CI, 1.68-22.7; P = .0095) to be predictors of microbiological recurrence and old age (aHR, 1.06; 95% CI, 1.01-1.13; P = .016), low body mass index (BMI; aHR for every 1-kg/m2 increase, 0.72; 95% CI, .60-.85; P < .0001), pneumonectomy (aHR, 4.38; 95% CI, 1.78-11.3; P = .014), and remnant cavitary lesions (aHR, 3.53; 95% CI, 1.35-9.57; P = .011) to be predictors of poor prognosis. Conclusions: Patients who could benefit from pulmonary resection should be carefully selected considering age, BMI, remnant lesions after surgery, and type of pulmonary resection.

BACKGROUND: Although previous cross-sectional studies showed the feasibility and clinical association of the St. George's Respiratory Questionnaire (SGRQ) in Mycobacterium avium complex pulmonary disease (MAC-PD), its longitudinal validity is poorly understood. We aimed to determine the longitudinal validity and prognostic significance of SGRQ. METHODS: In this prospective observational study conducted between May 2012 and August 2018, we evaluated 269 enrolled patients with MAC-PD and examined associations between baseline SGRQ total scores and mortality or clinical variables (anchors), including serum C-reactive protein levels and pulmonary function test results. RESULTS: Age- and sex-matched SGRQ scores indicated significantly greater impairment in patients with MAC-PD than in the general population (P < 0.001). On multivariable Cox proportional hazards regression analysis, the SGRQ total score ≥25 was an independent risk factor for mortality (adjusted hazard ratio, 5.90; 95% confidence interval, 1.65-37.7) as well as age, body mass index, and forced vital capacity (FVC). Mixed-effect model results showed a significant association between SGRQ symptom/total scores and forced expiratory volume in 1 s (FEV1), FVC, and diffusing carbon monoxide capacity. Older age, a positive smear, non-nodular/bronchiectatic form, and cavity regions were associated with SGRQ total score deterioration. Patients with a greater decline from baseline FEV1 (% predicted) exhibited significantly worse impairment in the SGRQ total score (mean ± SE, 4.69 ± 10.9 points, P = 0.001). CONCLUSIONS: SGRQ showed longitudinal validity in assessing disease severity and was sensitive to changes in patients with MAC-PD, especially changes in %FEV1. The SGRQ total score may be an important prognostic factor.