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Background: Influenza is an acute respiratory infection caused by influenza viruses, with influenza A virus (IAV) being the most common and most likely to progress to critically ill cases leading to death. Pneumocystis jiroveci is an opportunistic lung-causing fungus that occurs most often in immunocompromised individuals and can cause Pneumocystis jiroveci pneumonia (PJP). It is rare for both diseases to occur in the same patient., Methods: Appropriate laboratory tests, chest computed tomography (CT), bronchoalveolar lavage fluid, second-generation macro gene sequencing, and pathogenetic tests to clarify the diagnosis., Results: G test and LDH were high, and chest CT showed rapidly progressive interstitial pneumonia, which was confirmed by bronchoalveolar lavage fluid and macrogenomic second-generation sequencing (mNGS) to be a mixed infection of H. influenzae type A virus and Pneumocystis jiroveci., Conclusions: In rapidly progressive interstitial pneumonia, bronchoalveolar lavage and mNGS should be done early to clarify the presence of infection with specific pathogenic organisms.

Background: Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD., Methods: We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission., Results: Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA., Conclusions: mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients., (© 2024. The Author(s).)

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research., (© 2024 Wiley Periodicals LLC.)

Connective tissue disease-related interstitial lung disease (CTD-ILD) is a frequent and serious complication of CTD, leading to high morbidity and mortality. Unfortunately, its pathogenesis remains poorly understood; however, one intriguing contributing factor may be the microbiome of the mouth and lungs. The oral microbiome, which is a major source of the lung microbiome through recurrent microaspiration, is altered in ILD patients. Moreover, in recent years, several lines of evidence suggest that changes in the oral and lung microbiota modulate the pulmonary immune response and thus may play a role in the pathogenesis of ILDs, including CTD-ILD. Here, we review the existing data demonstrating oral and lung microbiota dysbiosis and possible contributions to the development of CTD-ILD in rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus. We identify several areas of opportunity for future investigations into the role of the oral and lung microbiota in CTD-ILD., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis., Methods: We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures)., Results: This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors., Conclusions: In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.

Interstitial Lung Disease (ILD) involves lung disorders marked by chronic inflammation and fibrosis. ILDs include pathologies like idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), hypersensitivity pneumonitis (HP) or sarcoidosis. Existing data covers pathogenesis, diagnosis (especially using high-resolution computed tomography), and treatments like antifibrotic agents. Despite progress, ILD diagnosis and management remains challenging with significant morbidity and mortality. Recent focus is on Progressive Fibrosing ILD (PF-ILD), characterized by worsening symptoms and fibrosis on HRCT. Prevalence is around 30%, excluding IPF, with a poor prognosis. Early diagnosis is crucial for optimizing outcomes in PF-ILD individuals. The lung microbiome comprises all the microorganisms that are in the respiratory tract. Relatively recent research try to evaluate its role in respiratory disease. Healthy lungs have a diverse microbial community. An imbalance in bacterial composition, changes in bacterial metabolic activities, or changes in bacterial distribution within the lung termed dysbiosis is linked to conditions like COPD, asthma and ILDs. We conducted a systematic review of three important scientific data base using a focused search strategy to see how the lung microbiome is involved in the progression of ILDs. Results showed that some differences in the composition and quality of the lung microbiome exist in ILDs that show progressive fibrosing phenotype. The results seem to suggest that the lung microbiota could be involved in ILD progression, but more studies showing its exact pathophysiological mechanisms are needed.

Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host-microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.

Objective: To investigate the role of bronchoalveolar lavage (BAL) in DM-associated interstitial lung disease (ILD)., Methods: We retrospectively reviewed the medical records of patients with DM-ILD who underwent bronchoscopy between October 2015 and September 2019. We then collated clinical features, laboratory data and bronchoscopy findings. The follow-up study was terminated on the 1 May 2020., Results: A total of 113 DM-ILD patients were included in this study, including 27 patients with acute/subacute interstitial pneumonia (A/SIP) and 86 patients with chronic interstitial pneumonia (CIP). The A/SIP group had significantly lower proportions of lymphocytes and eosinophils in the bronchoalveolar lavage fluid (BALF) than the CIP group, but had a significantly higher proportion of neutrophils. Pathogens were discovered in BALF from 28 (24.8%) patients. Twenty-five (22.1%) patients commenced or changed antibiotic therapy on the basis of their bronchoscopy results. Lymphopenia and intensive care unit care were significantly associated with pathogen-positive BALF findings. Complications of bronchoscopy occurred in nine (8.0%) patients; fever (5.3%) was the most common complication. Twenty-five deaths (25/106, 23.6%) were observed during a mean follow-up of 22 months. Age, A/SIP and anti-MDA5 antibody were identified as independent predictors of a poor outcome, while mechanic's hands was an independent protective factor. However, cellular and pathogen findings in BALF had no significant influence on 30-day or overall mortality., Conclusion: Bronchoscopy is a relatively useful instrument to evaluate ILD in patients with DM, and BAL can improve the diagnosis of infection. However, cellular and pathogen findings from BALF had no significant influence on prognosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pulmonary involvement is common in children with scrub typhus. Our paper outlines the clinical characteristics of pulmonary involvement and analyses the predictors of its severity. All scrub typhus serology-positive (optical density >0.5) children with pulmonary symptoms were included. Of 506 serology-positive scrub typhus cases, 256 (50.5%) had pulmonary symptoms, of whom 50 (9.8%) were severe. These severe cases were compared with non-severe cases. Interstitial pneumonitis was the commonest chest radiographic finding. Logistic regression analysis identified 'fever clearance time' >48 h, facial puffiness, maculopapular rash and anaemia to be significantly associated with severe pulmonary involvement.

Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102-0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992-0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059-8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

Studying respiratory illness-specific microbial signatures and their interaction with other micro-residents could provide a better understanding of lung microbial ecology. Each respiratory illness has a specific disease etiology, however, so far no study has revealed disease-specific microbial markers. The present study was designed to determine disease-specific microbial features and their interactions with other residents in chronic obstructive pulmonary diseases (stable and exacerbated), sarcoidosis, and interstitial lung diseases. Broncho-alveolar lavage samples (n = 43) were analyzed by SSU rRNA gene sequencing to study the alveolar microbiome in these diseases. A predominance of Proteobacteria followed by Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria was observed in all the disease subsets. Shannon diversity was significantly higher in stable COPD when compared to exacerbated chronic obstructive pulmonary disease (ECOPD) (p = 0.0061), and ILD patient samples (p = 0.037). The lung microbiome of the patients with stable COPD was more diverse in comparison to ECOPD and ILD patients (p < 0.001). Lefse analysis identified 40 disease-differentiating microbial features (LDA score (log10) > 4). Species network analysis indicated a significant correlation (p < 0.05) of diseases specific microbial signature with other lung microbiome members. The current study strengthens the proposed hypothesis that each respiratory illness has unique microbial signatures. These microbial signatures could be used as diagnostic markers to differentiate among various respiratory illnesses.

Competing Interests: Declaration of Competing Interest The authors report no declarations of interest.

Background: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy., Case Presentation: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident., Conclusions: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

Background: The presence of the human lung microbiota has been demonstrated in patients with different lung diseases, mainly in sputum samples. However, for study of the alveolar microbiota, a bronchoalveolar lavage (BAL) sample represents the lower respiratory tract (LRT) environment. It is currently unknown whether there is a specific alveolar microbiota profile in human lung diseases, such as pulmonary tuberculosis (TB) and interstitial pneumonia (IP)., Methods: BAL samples from six active TB patients, six IP patients and ten healthy volunteers were used for DNA extraction followed by amplification of the complete bacterial 16S ribosomal RNA gene (16S rDNA). The 16S rDNA was sequenced with a MiSeq Desktop Sequencer, and the data were analysed by QIIME software for taxonomic assignment., Results: The alveolar microbiota in TB and IP patients and healthy volunteers was characterized by six dominant phyla, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Fusobacteria and Cyanobacteria. A significant reduction in the abundance of Firmicutes was observed in IP patients. In TB and IP patients, the diversity of the alveolar microbiota was diminished, characterized by a significant reduction in the abundance of the Streptococcus genus and associated with increased Mycobacterium abundance in TB patients and diminished Acinetobacter abundance in IP patients with respect to their abundances in healthy volunteers. However, an important difference was observed between TB and IP patients: the Fusobacterium abundance was significantly reduced in TB patients. Exclusive genera that were less abundant in patients than in healthy volunteers were characterized for each study group., Conclusions: This study shows that the alveolar microbiota profile in BAL samples from TB and IP patients, representing infectious and non-infectious lung diseases, respectively, is characterized by decreased diversity., Competing Interests: Declaration of competing interest None of the authors have any competing interests., (Published by Elsevier Ltd.)

We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grew Cryptococcus neoformans on fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Treatment of chronic lung infection becomes a great challenge due to the drug resistant bacteria. In this scenario, evolving a new drug based on lipid metal conjugation loaded with potential antibiotic provides better drug delivery. In this study, ciprofloxacin loaded selenium-lipid nanoparticle (CxLSENPs) is produced in a novel route and its antimicrobial properties were tested against clinically important Gram-negative P. aeruginosa. The synthesized CxLSENPs was characterized by biophysical techniques (UV, Fluorescence spectroscopy, Raman spectroscopy, FTIR, FESEM, HRTEM and Zeta potential). Raman spectra coupled with FTIR spectra confirmed the possible interaction of lipid components in the NPs. HRTEM analysis confirmed the spherical shape of NPs. CxLSENPs recorded greater antibacterial effects on P. aeruginosa. A drastic reduction in the count of P. aeruginosa was observed after treatment with CxLSENPs. In order to further confirm the antibacterial efficiency, the live/dead cell assay was carried out. Live/dead analysis helps us to investigate the viability of bacterial cells. The number of dead bacterial cells was significantly higher in CxLSENPs treated groups when compare to the control. Furthermore, CxLSENPs increased the antioxidant enzyme activities (SOD, GPx, CAT and LPO) in mouse and protected the liver damage from bacterial infection. This study concludes that the developed CxLSENPs might be employed as strong antimicrobial and antioxidant agents for treating lung infection or interstitial lung diseases., (Copyright © 2019. Published by Elsevier B.V.)

Background: Sarcoidosis is a systemic disease of unknown etiology. The disease mechanisms are largely speculative and may include the role microbial patterns that initiate and drive an underlying immune process. The aim of this study was to characterize the microbiota of the lung of patients with sarcoidosis and compare its composition and diversity with the results from patients with other interstitial lung disease (ILD) and historic healthy controls., Methods: Patients (sarcoidosis, n = 31; interstitial lung disease, n = 19) were recruited within the PULMOHOM study, a prospective cohort study to characterize inflammatory processes in pulmonary diseases. Bronchoscopy of the middle lobe or the lingula was performed and the recovered fluid was immediately sent for analysis of the pulmonary microbiota by 16sRNA gene sequencing. Subsequent bioinformatic analysis was performed to compare the groups., Results: There were no significant differences between patients with sarcoidosis or other ILDs with regard to microbiome composition and diversity. In addition, the abundance of the genera Atopobium, Fusobacterium, Mycobacterium or Propionibacterium were not different between the two groups. There were no gross differences to historical healthy controls., Conclusion: The analysis of the pulmonary microbiota based on 16sRNA gene sequencing did not show a significant dysbiosis in patients with sarcoidosis as compared to other ILD patients. These data do not exclude a microbiological component in the pathogenesis of sarcoidosis.

Background: RGM medium is an agar-based, selective culture medium designed for the isolation of nontuberculous mycobacteria (NTM) from the sputum of patients with cystic fibrosis (CF). We evaluated RGM medium for the detection of NTM in patients with CF (405 samples), bronchiectasis (323 samples) and other lung diseases necessitating lung transplantation (274 samples)., Methods: In total, 1002 respiratory samples from 676 patients were included in the study. Direct culture on RGM medium, with incubation at two temperatures (30 °C and 37 °C), was compared with conventional culture of decontaminated samples for acid-fast bacilli (AFB) using both a solid medium (Löwenstein-Jensen medium) and a liquid medium (the Mycobacterial Growth Indicator Tube; MGIT)., Results: For all three patient groups, significantly more isolates of NTM were recovered using RGM medium incubated at 30 °C than by any other method (sensitivity: 94.6% vs. 22.4% for conventional AFB culture; P < 0.0001). Significantly more isolates of Mycobacterium abscessus complex were isolated on RGM at 30 °C than by AFB culture (sensitivity: 96.1% vs. 58.8%; P < 0.0001). The recovery of Mycobacterium avium complex was also greater using RGM medium at 30 °C compared to AFB culture (sensitivity: 83% vs. 70.2%), although this difference was not statistically significant and a combination of methods was necessary for optimal recovery (P = 0.21)., Conclusions: In the largest study of RGM medium to date, we reaffirm its utility for isolation of NTM from patients with CF. Furthermore; we show that it also provides an effective tool for culture of respiratory samples from patients with bronchiectasis and other lung diseases.

We report 7 patients with interstitial lung disease seen at computed tomographic scan review. Coxiella burnetii infection was diagnosed in situ in 1 lung biopsy specimen. Q fever may be a cofactor of interstitial lung disease, especially in endemic areas.

Three Florida pumas ( Puma concolor coryi) that had spent time in captivity prior to being released in the wild were found exhibiting respiratory signs and reluctance to move. All 3 pumas died shortly after immobilization, despite supportive veterinary care. Significant autopsy findings included necrotizing interstitial pneumonia, with pulmonary edema and hyaline membranes, and suppurative myocarditis. Organisms morphologically consistent with Bartonella henselae were identified in intravascular histiocytes in the lung of one of the pumas on histopathology and confirmed via transmission electron microscopy. B. henselae was detected in fresh lung tissue and confirmed by PCR and sequence analysis (16S-23S spacer region, pap31, and rpoB genes) from one of the affected pumas. In all affected pumas, B. henselae was detected by PCR in formalin-fixed, paraffin-embedded lung tissue, and positively staining organisms were identified in sections of lung by immunohistochemistry for B. henselae. In situ hybridization detected B. henselae DNA in lung tissue from 2 of 3 affected pumas. Our case series suggests that B. henselae can be associated with a fatal disease syndrome in Florida pumas. The cause of susceptibility to fatal disease associated with B. henselae infection in these pumas remains unknown.

Introduction: Syphilis is a sexually transmitted disease that can affect numerous organs in its secondary or tertiary stages. We describe a case of secondary syphilis with pulmonary involvement and we present a literature review., Patients and Methods: A 69-year-old male patient was admitted to hospital for dyspnoea and extended papular exanthema with palmoplantar involvement. The serological test for syphilis was positive. Ocular examination showed bilateral papillitis and retinal haemorrhage. Chest radiography revealed an interstitial alveolar infiltrate predominantly in the upper lobes, mild pleural effusion and hilar adenopathy. These infiltrates were slightly hypermetabolic on PET scan suggesting inflammatory or infectious origin. Treatment with intravenous penicillin G was effective on cutaneous, ocular and pulmonary manifestations., Discussion: Lung involvement in secondary syphilis is poorly known and rarely described. We found 27 cases of pulmonary syphilis reported in English and the main European languages since 1967. Mean age at diagnosis was 46 years with clear male predominance (89%). HIV co-infection was declared in 5 cases. Treponema pallidum was found in 6 patients using PCR on bronchoalveolar lavage (BAL) (3 patients) or on a lung biopsy (1 patient), immunohistochemistry (IHC) on BAL (1 patient) and Giemsa staining on a pleural fluid sample (1 patient). Chest X-rays may show unilateral or bilateral infiltrates or nodules with or without pleural effusion or hilar adenopathy. Sub-pleural involvement is frequent and penicillin is the treatment of choice., Conclusion: Pulmonary syphilitic involvement should be suspected where pulmonary symptoms or radiological changes occur in secondary syphilis. IHC, special staining or PCR on BAL, pleural fluid or lung tissue are useful for the identification of spirochetes., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

To investigate the frequency, severity and predictors of interstitial lung disease (ILD) in a cohort of South Africans with systemic sclerosis (SSc). Retrospective record review of SSc patients attending a tertiary Connective Tissue Diseases Clinic. Patients with ILD, defined by a combination of clinical findings, imaging, and lung function tests were compared to patients without ILD in terms of demographics, clinical features and autoantibodies. The majority (86.8%) of the 151 patients included were of Black ethnicity, 40% had ILD, of whom 39% had moderate-severe lung disease. Univariate predictors of ILD included: disease duration (OR 1.08, 95% CI 1.01-1.15); cough (OR 2.93, 95% CI 1.37-6.29); dyspnoea (OR 2.44, 95% CI 1.23-4.87); bibasal crackles (OR 7.58, 95% CI 3.31-17.37); diffuse cutaneous SSc (dcSSc) (OR 4.55, 95% CI 2.10-9.86) and a speckled anti-nuclear antibody (ANA) pattern (OR 2.47, 95% CI 1.25-4.90). Conversely, limited cutaneous disease (OR 0.22, 95% CI 0.09-0.50) and anti-centromere antibody (ACA) (OR 0.12, 95% CI 0.02-0.97) were protective. Independent predictors of ILD on multivariate analysis were bibasal crackles (OR 9.43, 95% CI 3.25-27.39), disease duration (OR 1.19, 95% CI 1.09-1.30) and speckled ANA (OR 2.95, 95% CI 1.22-7.15). Almost all (86.4%) patients received immunosuppressive treatment and the leading cause of death was related to ILD itself (44.4%). In this cohort of predominantly Black South Africans, SSc ILD was common and carried a poor prognosis. ILD occurred mainly, but not exclusively, in patients with dcSSc, especially those with a speckled ANA pattern. Conversely, the presence of ACA was protective against ILD.

This review focuses on the role of the lung microbiome in idiopathic pulmonary fibrosis. Although historically considered sterile, bacterial communities have now been well documented in lungs both in healthy and pathological conditions. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. Existing published data suggesting that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. Taken altogether, published literature suggests that the lung microbiome might serve in the future as a prognostic biomarker, a therapeutic target, and/or provide an explanation for disease pathogenesis in IPF., Competing Interests: The authors declare no conflict of interest.

In the present review we provide currently available evidence for the use of macrolides in the treatment of diffuse interstitial lung diseases (ILDs). Up to now, research on macrolides has mainly focused on three areas. First, macrolides have shown some promising results in cellular models and case reports as antifibrotic agents, by promoting autophagy and clearance of intracellular protein aggregates and acting as regulators of surfactant homeostasis. Secondly, macrolides have an immunomodulatory effect, which has been applied in some organising pneumonia cases. In particular, macrolides have been tested in association with systemic corticosteroids as steroid-sparing agents and alone as either first-line agents in mild cases or second-line agents where steroids were poorly tolerated or had failed. Thirdly, a recent area of research concerns the possible role of macrolides as modulators of lung microbiota and the host-microbiota interaction. This function has been particularly studied in idiopathic pulmonary fibrosis patients, in whom changes in microbiota have been proved to be associated with disease progression. However, the lack of high-quality studies makes the application of macrolide therapy in ILDs a field in which research should be conducted on a large scale., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Purpose of Review: This review summarizes current knowledge of the role of the lung microbiome in interstitial lung disease and poses considerations of the microbiome as a therapeutic target., Recent Findings: Although historically considered sterile, bacterial communities have now been well documented in lungs in health and disease. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. In support of this, studies of interstitial lung diseases other than IPF suggest that it may be the host immune response, which shapes the microbiome in these diseases. Some clinical and mouse model data also suggest that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux., Summary: Evidence suggests that the lung microbiome may serve as a prognostic biomarker, a therapeutic target, or provide an explanation for disease pathogenesis in IPF.

Aims: Co-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalaemia to be associated with co-trimoxazole, which may stem from an amiloride-like potassium-sparing effect. The current study investigated changes in serum potassium in patients without acute infections, and the influence of concomitant antikaliuretic drugs on this effect., Methods: A post hoc analysis was carried out of a randomized controlled trial in patients with interstitial lung disease who were assigned to placebo or 960 mg co-trimoxazole twice daily. Serum potassium and creatinine were measured at baseline, 6 weeks, and 6, 9 and 12 months. The primary outcome was the difference in mean serum potassium concentrations between co-trimoxazole and placebo at 6 weeks., Results: Mean serum potassium levels were similar at baseline: 4.24 (± 0.44) mmol l -1 in the 87 co-trimoxazole group participants and 4.25 (± 0.39) mmol l -1 in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium levels at 6 weeks, with a difference between means compared with placebo of 0.21 mmol l -1 [95% confidence interval (CI) 0.09, 0.34; P = 0.001). This significant increase in serum potassium was detectable even after exclusion of patients on antikaliuretic drugs, with a difference between means for co-trimoxazole compared with placebo of 0.23 mmol l -1 (95% CI 0.09, 0.38; P = 0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium concentrations reached ≥5.5 mmol l -1 during the study period., Conclusions: Co-trimoxazole significantly increases serum potassium concentration, even in participants not using antikaliuretic drugs. While the magnitude of increase was often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance., (© 2017 The British Pharmacological Society.)

Vemurafenib improves survival of melanoma patients. However, cutaneous side-effects commonly occur in them. Nivolumab and ipilimumab are monoclonal antibodies against programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4, both of which regulate excessive T-cell activation. Although these agents induce antitumor immunity against melanoma, the modified immune condition may result in an unexpected adverse reaction which has not been observed previously. Herein, we report a case who manifested severe erythema multiforme-like eruption with mucosal involvement associated with vemurafenib following nivolumab. The patient also subsequently suffered from ipilimumab-induced interstitial pneumonia with refractory course. Such a case has never been reported. This case suggested that dermatologists should pay special attention to unexpected adverse events of these drugs, and carefully observe cutaneous and respiratory status of patients during the treatment of melanoma., (© 2017 Japanese Dermatological Association.)

Infections with Pneumocystis jirovecii can result in asymptomatic colonization or induce life threatening clinical symptoms. However, there appears to be a 'gray area' between colonization and severe pneumonia that remains underestimated so far. We describe a case with chronic interstitial lung disease and chronic cough that was attributed to P. jirovecii. The patient's history of chronic cough, although very likely being fostered by the underlying Waldenström's macroglobulinemia and interstitial lung disease, was most likely caused by P. jirovecii infection. This gives raise to the hypothesis that P. jirovecii infections do not necessarily induce life threatening pneumonia. Consequently, serial testing is required in eligible patients with positive PCR results in order to discriminate between colonization, 'gray zone' infection, and beginning pneumonia.

Background: Mycoplasma pneumoniae is a bacterium responsible for 15 to 40 % of acute community-acquired pneumonia in children and 20 % of adult cases. Several extrapulmonary manifestations have been reported. We report a rare case of an adult patient suffering from pneumonia associated with an acute pancreatitis in the setting of Mycoplasma pneumoniae infection., Case Presentation: A 28-year-old Caucasian woman was referred for anorexia lasting for 1 week. Her past medical history was notable for congenital hydrocephalus with consecutive ventriculo-peritoneal shunt, epilepsia and paraparesis. The patient rapidly deteriorated, presenting with dyspnea, tachypnea, productive cough, abdominal pain, and onset of fever. C-reactive protein was at 270 mg/L, with a rise in serum lipase (670 UI/L, N: 13-60). A computed-tomography scan showed an acute interstitial edematous pancreatitis without necrosis, consistent with grade C on the Balthazar score. Thoracic sections revealed diffuse parenchymal consolidations combined with ground glass opacities. Calcium and triglyceride levels were normal. There was no history of recent trauma, alcoholic intake or drug intoxication. Mycoplasma pneumoniae serological assay showed an elevated IgM titer (22 UA/mL), compatible with recent infection, and cold agglutinins were present. A diagnosis of acute pancreatitis and diffuse interstitial pneumonia caused by an infection with Mycoplasma pneumoniae was considered. Respiratory and abdominal evolution was quickly favorable after initiation of clarithromycin 500 mg bid., Conclusions: The relationship between Mycoplasma pneumoniae infection and acute pancreatitis has been debated in the literature for many years. This observation, supported by clinical, biological and radiological features, is an additional argument in favor of a non-fortuitous association.

In this retrospective, single-center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log-rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease., (Published by Elsevier B.V.)

Background: Acute exacerbation and bacterial pneumonia are major life-threatening conditions in patients with interstitial lung disease (ILD). The rapid recognition of these 2 different conditions is important for their proper treatment. An elevated procalcitonin (PCT) level is commonly detected in patients with bacterial infections. This study assessed the usefulness of the serum PCT level as a biomarker for the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD., Materials and Methods: In this prospective observational study, we enrolled patients with ILD who had experienced recently progressive dyspnea and exhibited new infiltrations on chest radiographs. We classified these patients into an acute exacerbation group and a bacterial pneumonia group and compared their baseline characteristics and laboratory parameters, including the PCT level., Results: Of 21 patients with ILD, 9 patients had bacterial pneumonia. Both the groups showed similar baseline characteristics. The bacterial pneumonia group demonstrated a high PCT level. The PCT level in the acute exacerbation group was significantly lower than that in the bacterial pneumonia group (0.05 versus 0.91ng/mL, respectively; P < 0.001). Other parameters, such as the C-reactive protein level, leukocyte count and body temperature, were also lower in the acute exacerbation group. At a cutoff value of 0.1ng/mL, the sensitivity, specificity and negative predictive values of the serum PCT level were 88.9%, 100.0% and 92.3%, respectively., Conclusions: These findings suggest that the serum PCT level is useful in the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Acute interstitial pneumonia (AIP) of feedlot cattle is a sporadically occurring respiratory condition that is often fatal. Affected cattle have a sudden onset of labored breathing. There is no confirmed effective treatment of feedlot AIP; however, administration of antibiotics effective against common bacterial respiratory pathogens and nonsteroidal anti-inflammatory drugs, especially aspirin, has been recommended. Protective strategies are not well defined, but efforts to limit dust exposure and heat stress; to ensure consistent formulation, mixing, and delivery of feed; and to identify and treat infectious respiratory disease in a timely manner may decrease rates of feedlot AIP., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Good's syndrome is a rare primary immunodeficiency associated with adult thymoma. Complications are mainly autoimmune manifestations and recurrent infections with encapsulated bacteria. Only one possible case of combined granulomatous-lymphocytic interstitial lung disease (GL-ILD) and Good's syndrome have been described earlier, but the patient died at the time of diagnosis. This is the first case of GL-ILD in Good's syndrome with a successful outcome. We present a case of a 43-year-old man with GL-ILD, who suffered from recurrent infections of Haemophilus influenzae and Pneumocystis jirovecii, with 8-year follow-up. After a thymectomy, he was diagnosed with Good's syndrome and GL-ILD. He was treated with prophylactic pivampicillin, quinolones and cephalosporins for his recurrent P. jirovecii and H. influenzae infections, an approach that proved unsuccessful due to resistance, with relapse after cessation. He was stabilised with oral diaminodiphenyl-sulfone for P. jirovecii and colistimethate-sodium inhalations for H. influenzae, which is a new approach to prophylactic treatment., (2015 BMJ Publishing Group Ltd.)

A case of fungemia with interstitial lung compromise caused by Malassezia sympodialis is reported in an obese pediatric patient on long-term treatment with inhaled corticosteroids for asthma. The patient was hospitalized due to a post-surgical complication of appendicitis. The patient was treated with amphotericin B for 3 weeks, with good clinical evolution and subsequent negative cultures., (Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Interstitial lung disease (ILD) is a clinical disorder associated with changes of lung structure. Concurrent infection is a serious complication and one of the major factors that exacerbates ILD. Pathogen screening is a critical step in early diagnosis and proper treatment of ILD with secondary infection. Here we analyzed distribution and drug susceptibility of pathogens isolated from hospitalized ILD patients from January, 2007 to December, 2008 and compared them to bacterial drug resistance data in CHINET during the same period. The main specimens were from sputum culture, lavage fluid culture, lung biopsy tissue culture, and pleural effusion culture and bacterial or fungal cultures were performed on these specimens accordingly. Drug susceptibility was tested for positive bacterial cultures using disk diffusion (Kirby-Bauer method) and E Test strips in which results were determined based on the criteria of CLSI (2007). A total of 371 pathogen strains from ILD patients, including 306 bacterial strains and 65 fungal strains were isolated and cultured. Five main bacterial strains and their distribution were as follows: Klebsiella pneumoniae (31.7%), Pseudomonas aeruginosa (20.6%), Acinetobacter (12.7%), Enterobacter cloacae (8.2%), and Staphylococcus aureus (7.8%). The results showed that ILD patients who had anti-infection treatment tended to have Gram-negative bacteria, whether they acquired an infection in the hospital or elsewhere. Drug resistance screening indicated that aminoglycosides and carbapenems had lower antibiotic resistance rates. In addition, we found that the usage of immunosuppressants was associated with the increased infection rate and number of pathogens that were isolated. In conclusion, aminoglycosides and carbapenems may be selected as a priority for secondary infection to control ILD progression. Meanwhile, the use of anti-MRSA/MRCNS drugs may be considered for Staphylococcus infection., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Is necessary to develop models for the study of leptospirosis., Objective: To genotype a Colombian strain of Leptospira isolated from a human with Weil´s syndrome and to evaluate its infection dynamics in the hamster experimental model., Materials and Methods: Genotyping was performed by amplification and sequence analysis of the rrs 16S and lipL32 genes. The median lethal dose was determined in intraperitoneally inoculated hamsters. The patterns of clinical chemistry, the duration of leptospiremia, leptospiruria and pathological findings were studied and compared in the same animal model infected with L. interrogans (Fiocruz L1-130)., Results: Molecular typing revealed that the isolate corresponded to the pathogenic species L. santarosai, which was recovered from hamsters´ kidneys and lungs and detected by lipL32 PCR from day 3 post-infection in these organs. There was a marked increase of C-reactive protein in animals at day 5 post-infection (3.25 mg/dl; normal value: 0.3 mg/dl) with decreases by day 18 (2.60 mg/dl: normal value: 0.8 mg/dl). Biomarkers of urea showed changes consistent with possible renal acute failure (day 5 post-infection: 49.01 mg/dl and day 18 post-infection: 53.71 mg/dl). Histopathological changes included interstitial pneumonia with varying degrees of hemorrhage and interstitial nephritis., Conclusion: The pathogenic species L. santarosai was identified in Colombia. Its pathogenicity as determined by tropism to lung and kidney was comparable to that of L. interrogans Fiocruz L1-130, well known for its virulence and pulmonar tropism. The biological aspects studied here had never before been evaluated in an autochthonous isolate.

Rationale: HIV-1-induced interstitial pneumonitis (IP) is a serious complication of HIV-1 infection, characterized by inflammation and cellular infiltration in lungs, often leading to respiratory failure and death. The barrier function of the pulmonary endothelium is caused in part by tight junction (TJ) proteins, such as claudin-5. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in lung tissues and regulates inflammation. We hypothesize that HIV-1 induces vascular lung injury, and HIV-1-mediated damage of the pulmonary endothelium and IP is associated with dysregulation of PPAR-γ., Objectives: Investigate the effects of HIV-1 infection on the pulmonary microvasculature and the modulatory effects of the PPAR-γ ligands., Methods: Using human lung tissues, we demonstrated down-regulation of claudin-5 (marker of pulmonary barrier integrity), down-regulation of PPAR-γ transcription, and expression in lung tissues of HIV-1-infected humans with IP., Measurements and Main Results: Human lung microvascular endothelial cells expressed the TJ proteins claudin-5, ZO-1, and ZO-2; HIV-1 decreased TJ proteins expression and induced nuclear factor-κB promoter activity, which was reversed by PPAR-γ agonist. Using two murine HIV/AIDS models, we demonstrated decreased claudin-5 expression and increased macrophage infiltration in the lungs of HIV-1-infected animals. Activation of PPAR-γ prevented HIV-1-induced claudin-5 down-regulation and significantly reduced viremia and pulmonary macrophage infiltration., Conclusions: HIV-induced IP is associated with injury to the lung vascular endothelium, with decreased TJ and PPAR-γ expression, and increased pulmonary macrophage infiltration. PPAR-γ ligands abrogated these effects. Thus, regulation of PPAR-γ can be a therapeutic approach against HIV-1-induced vascular damage and IP in infected humans. Removal of Expression of Concern: Issues leading to the previous expression of concern for this article have been resolved after further revisions and editorial review. No further concerns exist.

Pneumocystis carinii f. sp. suis is a fungus multiplying in the respiratory tract of pigs which occasionally is associated with interstitial pneumonia. Identification of Pneumocystis in tissue samples is considered difficult and there are only scarce data on its occurrence in European pigs. This investigation presents an in situ hybridization (ISH) procedure for identification of Pneumocystis spp. in paraffin wax embedded tissue samples and its application for labeling the agent in lung samples of pigs with interstitial pneumonia. Thirty-two out of 100 lung samples from pigs on Austrian farms were identified as positive, five of them with multiple, 12 with moderate and 15 with few organisms but Grocott’s methenamine silver staining demonstrated that only 20 cases were unequivocally positive for Pneumocystis carinii. In addition to interstitial pneumonia Pneumocystis-positive pigs were more frequently affected with granulomatous pneumonia than Pneumocystis-negative pigs. Frequently concurrent infections with different viral or bacterial lung pathogens were noted but there was no positive correlation between Pneumocystis- and PCV-2-infections. With other infections, no clear-cut differences between Pneumocystis-positive and Pneumocystis-negative animals were found. This study shows that Pneumocystis infections occur frequently in Austrian pigs with interstitial pneumonia. It remains to be shown which are the factors triggering severe multiplication and whether infection with Pneumocystis alone is able to induce lung disease in pigs.

Objective: We retrospectively investigated the clinical features of pulmonary aspergillosis associated with interstitial pneumonia., Methods: We reviewed the medical records of all patients treated for interstitial pneumonia with or without pulmonary aspergillosis at our institution between April 2006 and August 2012 and evaluated the clinical features as well as risk and prognostic factors for pulmonary aspergillosis associated with interstitial pneumonia., Results: Among 539 patients with interstitial pneumonia, 15 who suffered from pulmonary aspergillosis were identified. The median age was 69.2±7.0 years, and fourteen patients were men. The subtypes of pulmonary aspergillosis were chronic pulmonary aspergillosis (n=14) and invasive pulmonary aspergillosis (n=1). The forms of interstitial pneumonia included idiopathic pulmonary fibrosis (n=9), rheumatoid arthritis-related interstitial pneumonia (n=4) and pleuroparenchymal fibroelastosis (n=2). The underlying conditions were emphysema (n=9) and a history of oral corticosteroid and/or immunosuppressive use (n=4). Home oxygen therapy (HOT) was administered in 11 patients. Following the diagnosis of pulmonary aspergillosis, all patients were treated with antifungal drugs. Ten patients (66.6%) died. A comparison of the interstitial pneumonia patients with and without pulmonary aspergillosis showed that the presence of emphysema, use of HOT and death were significantly associated with pulmonary aspergillosis., Conclusion: Pulmonary aspergillosis is one of the major complications of interstitial pneumonia and its prognosis is poor. Therefore, providing careful monitoring and proper treatment is extremely important.

A 71-year-old man with interstitial pneumonia was hospitalized due to a pulmonary infection. He had been living in Thailand and had returned to Japan three months earlier. Antibiotic therapy initially cleared the infection; however, the patient's condition relapsed. Pseudomonas aeruginosa and Penicillium sp. were both detected in sputum and bronchial lavage fluid cultures and Penicillium sp. was identified to be P. marneffei. The infiltration observed on chest radiographs improved following treatment with itraconazole and tazobactam/piperacillin, and no relapse occurred. We herein report the first case of a non-HIV patient with P. marneffei infection in Japan.

Although intestinal microbiota are essential for the development of T cell-mediated colitis, it remains undetermined whether they enhance or suppress the chronic extraintestinal inflammation that often complicates inflammatory bowel diseases. In this study, we investigate the role of intestinal microbiota in the development of colitis and extraintestinal manifestations in a mouse model in which colitis was induced in SCID mice by adoptive transfer of CD4(+)CD45RB(high) T cells. Under specific pathogen-free conditions, these mice developed both colitis and extraintestinal interstitial pneumonia, whereas mice given a mixture of antibiotics did not develop colitis, but, surprisingly, developed Th1/Th17-mediated IP. Irrespective of antibiotic treatment, cotransfer of CD4(+)CD25(+) regulatory T cells suppressed the development of pneumonitis and colitis, with all local CD4(+)CD45RB(high) T cell-derived cells converted to CD44(high)CD62L(-)IL-7Rα(high) effector-memory T cells. Retransfer of CD4(+) effector-memory T cells from the lungs of antibiotic-treated mice with IP not only induced IP in both antibiotic-treated and -untreated recipients but also induced colitis in the untreated recipients. In summary, we have established a unique model of Th1/Th17-mediated IP in microbiota-free and antibiotic-treated mice. This model may be valuable in investigating the immunological mechanisms underlying extraintestinal disorders in patients with inflammatory bowel disease.