Comparative study of bacterial flora in bronchoalveolar lavage fluid of pneumonia patients based on their pneumonia subtypes and comorbidities using 16S ribosomal RNA gene analysis.

INTRODUCTION: The culture method is the gold standard for identifying pathogenic bacteria in patients with pneumonia but often does not reflect the exact bacterial flora in pulmonary lesions of pneumonia, partly owing to easiness or difficulties in culturing certain bacterial species. We aimed to evaluate bacterial flora in bronchoalveolar lavage fluid (BALF) samples directly obtained from pneumonia lesions using 16S ribosomal RNA (rRNA) gene analysis to compare the results of the BALF culture method in each category of pneumonia. METHODS: Bacterial florae were detected by a combination of the culture method, and the clone library method using the 16S rRNA gene sequencing in BALF directly obtained from pneumonia lesions in pneumonia patients from April 2010 to March 2020 at the University of Occupational and Environmental Health, Japan, and affiliated hospitals. Clinical information of these patients was also collected, and lung microbiome was evaluated for each pneumonia category. RESULTS: Among 294 pneumonia patients (120 with community-acquired pneumonia (CAP), 101 with healthcare-associated pneumonia (HCAP), and 73 with hospital-acquired pneumonia (HAP)), significantly higher percentages of obligate anaerobes were detected in CAP than in HCAP and HAP patients by the clone library method. Corynebacterium species were significantly highly detected in HAP patients and patients with cerebrovascular diseases than in patients without, and Streptococcus pneumoniae was frequently detected in patients with diabetes mellitus. CONCLUSION: Obligate anaerobes may be underestimated in patients with CAP. Corynebacterium species should be regarded as the causative bacteria for pneumonia in patients with HAP and cerebrovascular diseases.

A human respiratory tract-associated bacterium with an extremely small genome.

Recent advances in culture-independent microbiological analyses have greatly expanded our understanding of the diversity of unculturable microbes. However, human pathogenic bacteria differing significantly from known taxa have rarely been discovered. Here, we present the complete genome sequence of an uncultured bacterium detected in human respiratory tract named IOLA, which was determined by developing a protocol to selectively amplify extremely AT-rich genomes. The IOLA genome is 303,838 bp in size with a 20.7% GC content, making it the smallest and most AT-rich genome among known human-associated bacterial genomes to our best knowledge and comparable to those of insect endosymbionts. While IOLA belongs to order Rickettsiales (mostly intracellular parasites), the gene content suggests an epicellular parasitic lifestyle. Surveillance of clinical samples provides evidence that IOLA can be predominantly detected in patients with respiratory bacterial infections and can persist for at least 15 months in the respiratory tract, suggesting that IOLA is a human respiratory tract-associated bacterium.

Clinical impact of methicillin-resistant staphylococcus aureus on bacterial pneumonia: cultivation and 16S ribosomal RNA gene analysis of bronchoalveolar lavage fluid.

BACKGROUND: Determining whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen or reflective of colonization when MRSA is cultured from the respiratory tract remains important in treating patients with pneumonia. METHODS: We evaluated the bacterial microbiota in bronchoalveolar lavage fluid (BALF) using the clone library method with a 16S ribosomal RNA (rRNA) gene analysis in 42 patients from a pneumonia registry who had MRSA cultured from their sputum or BALF samples. Patients were divided into two groups: those treated with (Group A) or without (Group B) anti-MRSA agents, and their clinical features were compared. RESULTS: Among 248 patients with pneumonia, 42 patients who had MRSA cultured from the respiratory tract were analyzed (Group A: 13 patients, Group B: 29 patients). No clones of S. aureus were detected in the BALF of 20 out of 42 patients. Twenty-eight of 29 patients in Group B showed favorable clinical outcomes, indicating that these patients had non-MRSA pneumonia. Using a microflora analysis of the BALF, the S. aureus phylotype was predominant in 5 of 28 (17.9%) patients among the detected bacterial phylotypes, but a minor population (the percentage of clones ≤ 10%) in 19 (67.9%) of 28 patients. A statistical analysis revealed no positive relationship between the percentage of clones of the S. aureus phylotype and risk factors of MRSA pneumonia. CONCLUSIONS: The molecular method using BALF specimens suggests that conventional cultivation method results may mislead true causative pathogens, especially in patients with MRSA pneumonia. Further studies are necessary to elucidate these clinically important issues.

Clinical efficacy and safety of high-dose doripenem in Japanese patients with pneumonia.

BACKGROUND: Pneumonia is now the third leading cause of death in Japan, and the number of patients with pneumonia is expected to increase with the progression of aging of the country. Higher dosage of antibiotics has recently been used, and high-dose doripenem (DRPM; 3 g daily) was approved for use in Japan in April 2011. However, there is a lack of data regarding the efficacy and safety of high-dose DRPM in Japan. This study prospectively assessed the clinical efficacy and safety of high-dose DRPM in Japanese patients with refractory pneumonia. METHODS: This study was performed at University of Occupational and Environmental Health, Japan and affiliated hospitals. The efficacy and safety of DRPM in patients with pneumonia treated with 3 g daily of DRPM, including those in whom DRPM dosage was increased from 1.5 g to 3 g daily, were evaluated. RESULTS: The safety evaluations included 56 patients, and the efficacy was evaluated in 51 patients. DRPM (3 g daily) treatment showed the response rate of 92.2% (47/51). Adverse effects of DRPM (3 g daily) were observed in 11 of 56 patients (19.7%), and all of these patients improved after DRPM cessation. Two patients had to stop DRPM administration due to elevated aminotransferase levels. The efficacy of DRPM in patients with pneumonia in whom DRPM was increased from 1.5 g daily to 3 g daily was 84.6% (11/13). CONCLUSIONS: High-dose DRPM (3 g daily) treatment is effective and relatively safe in Japanese patients with pneumonia.

Prevalence of sinusitis and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis: a pilot study.

BACKGROUND: Prevalence of sinusitis on sinus computed tomography (CT) in asthmatic patients and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis on sinus CT is unclear. METHODS: Sinus CT of asthmatic patients were evaluated using the Lund-Mackay system (LMS). Intranasal corticosteroid treatment (mometasone furoate) was newly added to symptomatic asthmatic patients with rhinosinusitis treated without intranasal corticosteroids, and the findings of the Asthma Control Test (ACT), Asthma Control Questionnaire in 5 items (ACQ5), spirometry, and sinus CT were evaluated before and 3 months after additional intranasal corticosteroid treatment. RESULTS: In a total of 160 asthmatic patients, rhinosinusitis and maxillary, ethmoidal, sphenoidal, and frontal sinusitis were observed in 75.0%, 70.0%, 53.1%, 33.1%, and 28.8%, respectively. Nasal symptoms and rhinophonia were observed in 81.9% and 72.5%, respectively, and patients with nasal symptoms and those with rhinophonia both showed significantly higher LMS scores in each sinus. Chronic rhinosinusitis (CRS) was observed in 66.9%, and these patients had significantly more severe asthma than the patients without CRS. In patients with CRS, patients with rhinophonia showed significantly higher LMS scores than those without rhinophonia. ACT, ACQ5, and the value of the forced expiratory volume in 1 second (FEV1) all significantly improved 3 months after the additive intranasal corticosteroid treatment in 24 patients, despite the fact that their LMS scores remained unchanged. CONCLUSION: Additive intranasal corticosteroid treatment may be an effective treatment option for symptomatic asthmatic patients with rhinosinusitis.

A Case of Rapid Exacerbation of Pulmonary Mycobacterium Avium Complex Infection Mimicking Pulmonary Aspergillosis.

We herein report a case of pulmonary Mycobacterium avium complex (MAC) infection with pulmonary multiple nodules and the "halo sign" on chest computed tomography (CT) in which the patient showed rapid exacerbation seven years after undergoing bone marrow transplantation (BMT). A 68-year-old Japanese female visited our hospital due to a productive cough and dyspnea. She had undergone allogeneic BMT for acute myelocytic leukemia and received both prednisolone (2 mg/day) and cyclosporine (30 mg/day). Chest CT demonstrated no abnormal findings on admission; however, multiple pulmonary nodules and the "halo sign" were detected three weeks later. Although a fungal infection was initially suspected, a bronchoscopic examination revealed pulmonary MAC infection. In the present case, pulmonary MAC infection exhibited rapid progression with unique CT findings. Physicians should consider MAC infection in the differential diagnosis in patients who receive BMT and/or immunosuppressive agents, even if the clinical and radiological findings are atypical of the disease.

Possible role of anaerobes in the pathogenesis of nontuberculous mycobacterial infection.

BACKGROUND AND OBJECTIVE: Recent advances in cultivation-independent molecular biological modalities for detecting bacterial species have indicated that several bacterial species may play a role in the pathogenesis of certain infectious diseases. The aim of this study was to evaluate the role of bacterial flora in the pathogenesis of nontuberculous mycobacteriosis (NTM) using a bacterial floral analysis of bronchoalveolar lavage fluid (BALF) with 16S rRNA gene sequencing in patients with bronchiectasis. METHODS: Fifty-eight patients with bronchiectasis evaluated using chest computed tomography were enrolled. BALF obtained from the most affected lung lesions was evaluated using culture and culture-independent methodologies. Approximately 600 bp of the bacterial 16S rRNA gene (E341F-E907R) was amplified via polymerase chain reaction using universal primers, and clone libraries were constructed. Nucleotide sequences of 96 randomly chosen clones for each specimen were determined, and the homology was searched using a basic local alignment search tool to determine the bacterial phylotypes and their proportions (bacterial floral analysis) in each specimen. RESULTS: Twenty-nine patients with bronchiectasis were diagnosed with NTM based on culture-based methods using Ogawa medium. The molecular method showed a significantly high rate of anaerobes among the patients with NTM compared with that observed in the bronchiectasis patients without NTM. In addition, findings of collapse/consolidation were significantly related to the proportion of Prevotella species in the BALF samples determined using the molecular method (P < 0.001). CONCLUSION: Given the results of the present study, anaerobes may play an important role in the pathogenesis of bronchiectasis in patients with NTM.

Bacteriological assessment of healthcare-associated pneumonia using a clone library analysis.

BACKGROUND: The causative pathogens of healthcare-associated pneumonia (HCAP) remain controversial, and the use of conventional cultivation of sputum samples is occasionally inappropriate due to the potential for oral bacterial contamination. It is also sometimes difficult to determine whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen of HCAP. METHODS: We evaluated the bacterial diversity in bronchoalveolar lavage fluid (BALF) using molecular and cultivation methods in 82 HCAP patients. BALF specimens were obtained from the lesions of pneumonia using bronchoscopy. The bacterial flora was analyzed according to the clone library method using amplified fragments of the 16S ribosomal RNA gene with universal primers. In addition, sputum cultures and the above specimens were assessed. RESULTS: Eighty (97.6%) of the 82 BALF samples obtained from the patients with HCAP showed positive polymerase chain reaction results. The predominant phylotypes detected in the BALF in this study included bacteria common in cases of community- and hospital-acquired pneumonia. In addition, the phylotypes of streptococci and anaerobes were detected in 19 (23.2%) and 8 (9.8%) cases, respectively. In particular, phylotypes of streptococci were highly detected among the patients 75 of age or older. Staphylococcus aureus was cultured in 23 (28.0%) cases using conventional cultivation methods and detected in only 6 (7.3%) cases as predominant phylotypes according to the clone library method. CONCLUSIONS: The clone library analysis of BALF in the HCAP patients detected heterogeneous bacteria and a high incidence of streptococci compared with that observed using cultivation methods. In addition, the results of our study may indicate a lower incidence of MRSA than previously expected in HCAP patients.

Efficacy and safety of meropenem (3 g daily) in Japanese patients with refractory respiratory infections.

INTRODUCTION: Pneumonia is the third leading cause of mortality in Japan. In 2011, the use of meropenem (MEPM) at 3 g daily was approved to treat refractory infections in Japan. However, little has been reported on the clinical efficacy and safety of this regimen in Japanese patients with refractory infections. OBJECTIVES: This study prospectively assessed the clinical efficacy and safety of MEPM (3 g daily) in Japanese patients with refractory pneumonia and/or intrapleural infections. METHODS: This study was performed at our university hospital and affiliated hospitals. The plasma concentrations of MEPM before and one and four hours after MEPM administration were also evaluated. RESULTS: A total of 48 patients were enrolled for the efficacy and safety evaluations. The response rate to MEPM (3 g daily) treatment was 90.9% (40/44). Adverse drug reactions were observed in 17 of the 48 patients (20.8%), and all improved after the cessation of MEPM. The plasma MEPM concentration one hour after administering 1 g of MEPM was 44.9 ± 12.0 µg/ml. A pharmacokinetic analysis revealed that the percentage of time above the MIC/24 h for an MIC of 4 µg/ml or 8 µg/ml was more than 50% in 12 of 13 (92%) and in nine of the 13 patients (69%), respectively, indicating sufficient efficacy of 3 g daily of MEPM. CONCLUSION: Treatment with MEPM (3 g daily) in Japanese patients with refractory pneumonia and/or intrapleural infections is effective, with sufficient plasma concentrations of MEPM, and the treatment has a relatively good safety profile.

Nitric oxide exerts protective effects against bleomycin-induced pulmonary fibrosis in mice.

BACKGROUND: Increased expression of nitric oxide synthase (NOS) and an increase in plasma nitrite plus nitrate (NOx) have been reported in patients with pulmonary fibrosis, suggesting that nitric oxide (NO) plays an important role in its development. However, the roles of the entire NO and NOS system in the pathogenesis of pulmonary fibrosis still remain to be fully elucidated. The aim of the present study is to clarify the roles of NO and the NOS system in pulmonary fibrosis by using the mice lacking all three NOS isoforms. METHODS: Wild-type, single NOS knockout and triple NOS knockout (n/i/eNOS-/-) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0 mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS-/- mice with BLM-induced pulmonary fibrosis. RESULTS: The histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS-/- mice. Long-term treatment with the supplemental NO donor in n/i/eNOS-/- mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs. CONCLUSIONS: These results provide the first direct evidence that a lack of all three NOS isoforms led to a deterioration of pulmonary fibrosis in a BLM-treated murine model. We speculate that the entire endogenous NO and NOS system plays an important protective role in the pathogenesis of pulmonary fibrosis.

[A case of rapidly ruptured pericostal tuberculosis from calcified pleural mass].

A 25-year-old Chinese man with no medical history of pulmonary tuberculosis visited to a hospital for an evaluation of chest X-ray abnormal findings of routine health checkup. Chest computed tomography (CT) demonstrated chest wall mass surrounded by calcified walls in the right anterior chest wall. Eighteen months later, he found subcutaneous mass lesion in the right hypochondriac lesion, and this mass became painful in 5 days. Therefore he visited our hospital, and his chest CT showed low density mass with thickened calcified walls in the right anterior thoracic space, small amount of right pleural effusion and subcutaneous localized mass. A needle aspiration of the right subcutaneous mass demonstrated that the specimen were all negative for acid-fast bacilli smear, culture and PCR for M. tuberculosis. On the contrary, right pleural effusion showed positive for PCR for M. tuberculosis, in spite of negative results of acid-fast bacilli smear and culture. Pericostal tuberculosis that was progressed by the rupture of old calcified tuberculous empyema in the chest wall was confirmed. Antituberculous chemotherapy, chest tube drainage for right subcutaneous mass and pleural decortication and empyema were successfully performed. Pericostal tuberculosis should be differentially considered when the calcified mass in the chest wall changes its shape.

[Efficacy and safety of azithromycin infusion in patients with mild or moderate community-acquired pneumonia].

Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

Real-world effects of two inhaled corticosteroid/long-acting ß2-agonist combinations in the treatment of asthma.

OBJECTIVE: There are several inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) combinations currently used to treat asthmatic patients, but the differences in the clinical effects of these ICS/LABAs are currently unknown. We herein evaluated the effects of two currently available ICS/LABA combinations in a real-world setting. METHODS: A fluticasone propionate/salmeterol combined Discus inhaler (FP/SM; 250/50 µg bid) was switched to a budesonide/formoterol Turbuhaler inhaler (BUD/FM; 160/4.5 µg two inhalations bid) and FP/SM (500/50 µg bid) was also switched to BUD/FM (160/4.5 µg four inhalations bid) in symptomatic asthmatic patients treated with FP/SM over 20 years of age. RESULTS: Sixty patients were enrolled in this study, and the scores of the asthma control test (ACT) and asthma control questionnaire-5 item version (ACQ5) were significantly improved 4 and 8 weeks after the switch to ICS/LABA treatments, and well-controlled asthma (ACQ5 score <0.75) and good control (ACT score >20) was achieved in 54 (90%) and 40 (66.7%) patients, respectively, at 8 weeks. The spirometric analysis revealed significant improvements of the values of the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) after switching from FP/SM to BUD/FM, and significantly improved small airway impairments ([Formula: see text]50 and [Formula: see text]25) were observed in patients treated with high-dose ICS/LABA. These subjective and objective improvements were also seen in patients aged over 65 years old. CONCLUSION: These data demonstrated that changing the combined ICS/LABA inhaler from FP/SM to BUD/FM can lead to more effective management of symptomatic patients with asthma, especially in patients treated with high-dose ICS/LABA.

Pneumonia and empyema caused by Streptococcus intermedius that shows the diagnostic importance of evaluating the microbiota in the lower respiratory tract.

The bacterial species in the Streptococcus anginosus group (S. constellatus, S. anginosus, S. intermedius) are important causative pathogens of bacterial pneumonia, pulmonary abscesses and empyema. However, the bacteria in this group are primarily oral resident bacteria and unable to grow significantly on ordinary aerobic culture media. We experienced a case of pneumonia and empyema caused by Streptococcus intermedius detected using a 16S rRNA gene sequencing analysis of bronchoalveolar lavage fluid and pleural effusion, but not sputum. Even when applying the molecular method, sputum samples are occasionally unsuitable for identifying the causative pathogens of lower respiratory tract infections.

Incidence and outcomes of bepridil-induced interstitial pneumonia.

BACKGROUND: The incidence of bepridil-induced pulmonary toxicity, such as interstitial pneumonia, is still unknown. The aim of the present study was to evaluate the incidence of bepridil-induced pulmonary toxicity. METHODS AND RESULTS: A total of 253 patients treated with bepridil between January 2009 and January 2011 were retrospectively evaluated. Eight out of the 222 evaluable patients (male/female: 5/3, age range: 64-97 years, average age: 80.5 years, median age: 81.0 years) showed bepridil-induced pulmonary toxicity. CONCLUSIONS: The incidence of bepridil-induced pulmonary toxicity was 3.60% in our study population.

[Efficacy and safety of moxifloxacin in patients with nursing and healthcare-associated pneumonia].

Moxifloxacin (MFLX) is a respiratory quinolone, and is effective against not only Gram-positive and negative bacteria but also anaerobes. There has been no prospective studies evaluating the efficacy and safety of MFLX in patients with nursing and healthcare-associated pneumonia (NHCAP). Therefore, we assessed the efficacy and safety of MFLX in patients with NHCAP. NHCAP patients with mild and moderate severity assessed by the A-DROP system in community-acquired pneumonia guideline proposed by Japan Respiratory Society visited our hospitals from April 2011 to March 2012. Clinical symptoms, chest X-ray films and/or computed tomography, peripheral white and red blood cell and platelet counts, serum CRP, AST, ALT, BUN, creatinine were evaluated. Forty patients were eventually evaluated, and average age was 74.1 years old, male/female were 21/19, 92.5% (37/40) of them had one or more comorbidities. Median duration of MFLX administration was 7.1 days (4-15 days). The efficacy of MFLX in all patients was 87.5% (35/40). The efficacies in each age group were 87.9% (aged over 65 years old), 85.7% (aged under 64 years old), and in each pneumonia severity group by the A-DROP system were 91.7% (mild), 85.7% (moderate). Diarrhea and swelling of the breast were observed in one patient (2.5%) after starting MFLX administration. Mild elevated transaminases were observed in three patients (7.5%), and mild renal dysfunction was observed in two patients (5.0%). All abnormally increased levels of transaminases and serum creatinine were recovered after a cessation of MFLX. MFLX is effective and safe in patients with NHCAP.

A case of Good syndrome with pulmonary lesions similar to diffuse panbronchiolitis.

We herein present a case of Good syndrome complicated by diffuse pulmonary lesions similar to diffuse panbronchiolitis (DPB). A 45-year-old Japanese man was referred to our department due to recurrent lower respiratory tract infections that had started and ameliorated nine months after thymectomy for pure red cell aplasia and myasthenia gravis. Diffuse centrilobular opacities on chest computed tomography and positivity for HLA-B54 were consistent with DPB. Additionally, hypogammaglobulinemia and a marked decrease of B-lymphocytes were observed, and therefore Good syndrome was considered. Combination therapy with azithromycin and clarithromycin alleviated the patient's respiratory symptoms and reduced the exacerbation of chronic bronchitis.

Two cases of everolimus-associated interstitial pneumonia in patients with renal cell carcinoma.

We herein report two cases of everolimus-associated interstitial pneumonia in patients with renal cell carcinoma. A 68-year-old Japanese man (case 1) was admitted to our hospital because of progressive dyspnea, left infiltration and consolidation on chest radiographs. He had started receiving everolimus (10 mg daily) three months before the admission for the treatment of recurrent renal cell carcinoma. Bronchoalveolar lavage fluid taken from his left B(4) showed a marked increase of lymphocytes (42.9%). An organizing pneumonia pattern of everolimus-associated interstitial pneumonia was strongly suspected radiologically, and treatment with high-dose corticosteroids, discontinuation of everolimus and oxygen support was started. The treatment was successful, and the patient recovered with only minor pulmonary fibrotic changes in the left lower lobe. A 57-year-old Japanese man (case 2) was referred to our department for the evaluation of interstitial pneumonia. He had started to receive everolimus (10 mg daily) four months previously. Chest CT demonstrated interstitial pneumonia predominantly in bilateral lower lobes, with small pulmonary metastatic nodules. His pulmonary complications were spontaneously resolved eight days after the discontinuation of everolimus. To the best of our knowledge, Case 1 is the first reported case of successfully treated organizing pneumonia pattern of interstitial pneumonia with acute respiratory failure induced by everolimus in Japan.