Differences in mortality in Fusobacterium necrophorum and Fusobacterium nucleatum infections detected by culture and 16S rRNA gene sequencing.

Fusobacterium species are components of the normal microbiota of the oral cavity, gastrointestinal tract, and female genital tract. They are increasingly recognized as causative agents of oral, laryngeal, and tonsillar infections. Several fusobacterial species are involved in infections, with F. necrophorum and F. nucleatum being the most commonly cultured subtypes. In this study, we aimed to investigate clinical and prognostic differences in terms of mortality and association with malignancy between F. necrophorum and F. nucleatum detected by culture and 16S rRNA gene sequencing. This is a systematic, comparative, retrospective, non-interventional study. Data were extracted from the Department of Clinical Microbiology, Region Zealand, Denmark: all patients with F. necrophorum or F. nucleatum detected by culture or 16S rRNA gene sequencing from 1st of January 2010 to 30th of June 2015 were included. In total, F. necrophorum was detected in samples from 75 patients, and F. nucleatum in samples from 68 patients (total: n = 143). Thirteen patients had a current cancer diagnosis at the time of fusobacterial sampling. Multivariate analyses revealed a significant association of "current cancer" with 30-day mortality. Fusobacterial subtype was not associated with mortality neither in overall nor in subgroups with or without current cancer. Despite differences in clinical disease pattern between F. necrophorum and F. nucleatum, mortality was unaffected by fusobacterial subtype. Mortality was significantly related to comorbidity, especially a current diagnosis of cancer. Our data highlights the current debate whether fusobacterial involvement in cancer may have disease-altering properties, rather than being opportunistic pathogens secondary to cancer disease.

Controversies in endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a minimally invasive highly accurate and safe endoscopic technique for the evaluation of mediastinal lymphadenopathy and mediastinal masses including centrally located lung tumors. The combination of transbronchial and transoesophageal tissue sampling has improved lung cancer staging, reducing the need for more invasive and surgical diagnostic procedures. Despite the high level of evidence regarding EBUS use in the aforementioned situations, there are still challenges and controversial issues such as follows: Should informed consent for EBUS and flexible bronchoscopy be different? Is EBUS able to replace standard bronchoscopy in patients with suspected lung cancer? Which is the best position, screen orientation, route of intubation, and sedation/anesthesia to perform EBUS? Is it advisable to use a balloon in all procedures? How should the operator acquire skills and how should competence be ensured? This Pro-Con article aims to address these open questions.

Exomic and epigenomic analysis of pulmonary blastoma.

OBJECTIVE: Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them. METHODS: We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons. RESULTS: We identified biallelic somatic DICER1 pathogenic variants in 7 of 8 cases. The remaining case had a solitary missense pathogenic variant in the RNase IIIb domain of DICER1. Six of 8 cases carried a CTNNB1 hotspot variant and 4 of 8 had a somatic pathogenic variant in TP53. Methylation analysis showed that the pulmonary blastomas clustered with other DICER1-mutated tumors and not with other more common types of lung cancer. CONCLUSION: We conclude somatic DICER1 pathogenic variants are the major driver of pulmonary blastoma and are likely to act in conjunction with CTNNB1 hotspot variants that are often present.

ERS International Congress 2023: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2023 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.

Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study.

OBJECTIVE: The renin-angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) treatment. The aim was to determine the association between treatment with RASi and the risk of acute exacerbations and mortality in patients with severe COPD. METHODS: Active comparator analysis by propensity-score matching. Data were collected in Danish national registries, containing complete information on health data, prescriptions, hospital admissions and outpatient clinic visits. Patients with COPD (n=38 862) were matched by propensity score on known predictors of the outcome. One group was exposed to RASi treatment (cases) and the other was exposed to bendroflumethiazide as an active comparator in the primary analysis. RESULTS: The use of RASi was associated with a reduced risk of exacerbations or death in the active comparator analysis at 12 months follow-up (HR 0.86, 95% CI 0.78 to 0.95). Similar results were evident in a sensitivity analysis of the propensity-score-matched population (HR 0.89, 95% CI 0.83 to 0.94) and in an adjusted Cox proportional hazards model (HR 0.93, 95% CI 0.89 to 0.98). CONCLUSION: In the current study, we found that the use of RASi treatment was associated with a consistently lower risk of acute exacerbations and death in patients with COPD. Explanations to these findings include real effect, uncontrolled biases, and-less likely-chance findings.

Safety and feasibility of oesophageal ultrasound for the work-up of thoracic malignancy in patients with respiratory impairment.

Biopsying lung tumours with endobronchial access in patients with respiratory impairment is challenging. However, fine needle aspiration with the endobronchial ultrasound-endoscope via the oesophagus (EUS-B-FNA) makes it possible to obtain tissue samples without entering the airways. Safety of EUS-B-FNA in these patients has not earlier been investigated prospectively. Therefore, this study aimed at assessing feasibility and safety of EUS-B-FNA from centrally located tumours suspected of thoracic malignancy in patients with respiratory insufficiency. The study is a prospective observational study. Patients with indication of EUS-B-FNA of centrally located tumours and respiratory impairment defined as modified Medical Research Council (mMRC) dyspnoea scale score of ≥3, saturation ≤90% or need of continuous oxygen supply were included prospectively in three centres. Any adverse events (AEs) were recorded during procedure and 1-hour recovery. AEs were defined as hypoxemia (saturation <90% or need for increased oxygen supply) or any kind of events needing intervention. Late procedure-related events were recorded during 30-day follow-up. Between April 1, 2020 and January 30, 2021, 16 patients were included. No severe AEs (SAEs) occurred, but AEs were seen in 50% (n=8) and 13% (n=2) of the patients during procedure and recovery respectively. AEs included hypoxemia corrected with increased oxygen supply and in two cases reversal of sedation. Late procedure-related events were seen in 13% (n=2) and included prolonged need of oxygen and one infection treated with oral antibiotics. In this cohort, EUS-B-FNA of centrally located tumours was safe and feasible in patients with respiratory impairment, when examined in the bronchoscopy suite. A variety of mostly mild and manageable complications may occur, a few even up to 30 days post-procedure.

ERS International Congress 2022: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging.

Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring Streptococcus pneumoniae Infection. A Multiregional Epidemiological Study.

Background: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users. Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses. Findings: A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with S. pneumoniae during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results. Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring S. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.

A rare clinical presentation of Waldenström Macroglobulinemia mimicking lung cancer.

Waldenström macroglobulinemia rarely presents as pulmonary symptoms, and even rarer as chylothorax. We present a patient who presented with bilateral pleural effusion and a 30 mm solid lesion in the lung. Biochemical analysis of the pleural fluid revealed chylothorax. The 18-fluorodeoxygenase positron emission tomography, bronchoscopy, endobronchial ultrasound, and cytological examination of the pleural fluid, showed no apparent cause of the chylothorax. The diagnostic breakthrough was made with flow cytometry of the pleural fluid, which revealed a small group of clonal B-cells. Biopsy from the parietal pleura and bone marrow led to the diagnosis Waldenström macroglobulinemia. This demonstrates that flow cytometry should be considered when routine diagnostics do not lead to a reach a specific diagnosis.

Asymptomatic lung nodules in dental professionals: A diagnostic challenge.

Dental care workers are frequently exposed to various types of volatile organic and inorganic compounds. In addition to biological materials, these compounds include silica, heavy metals, and acrylic plastics. Such exposures may cause respiratory symptoms, but the nonspecific nature of these symptoms often means that the etiology is difficult to discern. The disease severity depends on the particle size and type of the inhaled compounds, as well as the duration and intensity of exposure, which varies markedly among dental workers. Here, we present two unique cases with the same occupational exposure. Both patients showed radiological changes in the lungs that were suspicious for lung cancer. The first patient did not undergo a biopsy due to cardiac comorbidities and risk of bleeding, and the diagnosis was based on thoracic computer tomography (CT) which confirmed multiple, bilateral, solid, smooth, partly calcified lung nodules, normal positron emission tomography (PET)-CT and the relevant occupational exposure. In the second case, a CT-guided biopsy and thoracoscopic resection was done with histopathological findings consistent with granuloma. The multi-disciplinary team decision of both cases was consistent with occupational exposure related lunge disease. This is the first case study report whereby same occupational exposure related health condition is compared with two different approaches. Respiratory clinicians should be aware of this potential diagnosis, especially for asymptomatic patients with relevant exposures. Careful attention to the occupational history may help to prevent unnecessary, invasive diagnostic procedures or surgeries.

ERS International Congress 2021: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, randomised controlled trials and qualitative research that were presented during the 2021 European Respiratory Society International Congress within the sessions from the five groups of the Assembly 1 - Respiratory clinical care and physiology. Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.

Asymptomatic pleural thickening with effusion as the only manifestation of IgG4-related disease.

Immunoglobulin G4 (IgG4)-related disease is a systemic fibroinflammatory disorder that can affect almost any tissue. Isolated IgG4 pleural disease is a rare manifestation and, when present, is usually described in patients presenting with dyspnoea. We present a case of asymptomatic isolated IgG4 pleural effusion and highlight that IgG4-related disease should be remembered as a differential diagnosis in patients with pleural effusion and pleural thickening, even if asymptomatic and without any other organ involvement.

A unique case of Fusobacterium nucleatum spondylodiscitis communicating with a pleural empyema through a fistula.

Species (spp.) belonging to the genus Fusobacterium are anaerobic commensals colonizing the upper respiratory tract, the gastrointestinal tract, and the genitals. Infections with Fusobacterium spp. have been reported at many anatomical sites, including pneumonias and pleural empyemas; however, there are very few published cases of Fusobacterium spp. causing spondylodiscitis or fistulas. Bone infections with Fusobacterium can spread directly to surrounding muscular tissue or by hematogenous transmission to any other tissue including pleurae and lungs. Similarly, pleural infections can spread Fusobacterium spp. to any other tissue including fistulas and bone. Concomitant pleural empyema and spondylodiscitis are rare; however, there are a few published cases with concomitant disease, although none caused by Fusobacterium spp. A 77-year-old female patient was assessed using computed tomography (CT) scanning of the thorax and abdomen, as well as analyses of fluid drained from the region affected by the pleural empyema. A diagnosis of Fusobacterium empyema, fistula, bacteremia, and spondylodiscitis was made, and the patient's condition improved significantly after drainage of the pleural empyema and relevant long-term antibiotic treatment. We describe the first confirmed case with concomitant infection with Fusobacterium nucleatum as spondylodiscitis and pleural empyema connected by a fistula.

Adult pulmonary blastoma in an adult with urothelial cancer: A case report.

Pulmonary blastoma is an aggressive lung cancer with incidence ranging from 0.25-0.5 of all the reported lung cancers. Although, pulmonary blastoma is seen commonly in childhood its very rare in adults. Surgical treatment is often the treatment of choice, but benefits of neoadjuvant chemotherapy are unclear. People with DICER1 syndrome commonly develop Pulmonary blastoma and do have concomitant or previous history of benign or malignant tumours in extra pulmonary site like kidney, thyroid, ovary cervix testicle and eye. As per our knowledge, this is the first case of adult pulmonary blastoma previously diagnosed with urothelial cancer and a strong familial predilection of malignancy, with negative genetic test for DICER1 mutations.

Diagnosis and staging of lung cancer with the use of one single echoendoscope in both the trachea and the esophagus: A practical guide.

Accurate staging of non-small cell lung cancer (NSCLC) is crucial for allocation to surgical, medical or multimodal treatment. EUS and endobronchial ultrasound (EBUS) have gained ground in the diagnosis and staging of lung cancer in addition to radiological imaging (e.g., computed tomography, fluoroscopy, and magnetic resonance imaging), nuclear medicine techniques (e.g. positron emission tomography, PET), combined techniques (e.g., fluorodesoxyglucosepositron emission tomography scanning), and sonographic imaging including conventional transcutaneous mediastinal and lung ultrasound. By using one single echoendoscope in both the trachea and the esophagus, surgical staging procedures (e.g. mediastinoscopy and video assisted thoracoscopy) can be avoided in a considerable proportion of patients with NSCLC.

[The use of one single echoendoscope in both the trachea and the oesophagus in diagnosing and staging of lung cancer].

The use of one single ultrasound echoendoscope in both the trachea (EBUS) and the oesophagus (EUS-B) gives a fast, safe and precise diagnosis and stage of the patient with suspected lung cancer. There is solid evidence for simulator-based training in EBUS concerning safety and diagnostic outcome, but this is currently not an option in EUS-B and needs development. In this review, we recommend evidence-based simulator training and certification in EBUS and when available also in EUS-B before practicing on patients.