A Preliminary Study of Microbiota Diversity in Saliva and Bronchoalveolar Lavage Fluid from Patients with Primary Bronchogenic Carcinoma.

BACKGROUND The present study aimed to evaluate the difference in microbiota diversity in the oral cavity and fluid bronchoalveolar lavage (BALF) of patients with lung cancer. MATERIAL AND METHODS Buccal (saliva) and lower respiratory tract BALF samples were collected from 51 patients with primary bronchogenic carcinoma and 15 healthy controls, and bacterial genomic DNA was extracted. High-throughput 16S rDNA amplicon sequencing was performed, and microbial diversity, composition, and functions of microbiota were analyzed by bioinformatics methods. RESULTS Patients with lung cancer have lower microbial diversity than healthy controls in both saliva and BALF samples. Significant segregation was observed between the different pathological types of lung cancer groups and the control group regardless of the sampling site. Treponema and Filifactor were identified as potential bacterial biomarkers in BALF samples, while Filifactor was ideal to distinguish healthy controls from lung cancer patients. Moreover, the predictive variation analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway showed that the metabolic differences in microbiota varied by sampling site. CONCLUSIONS Lung cancer patients carry a different and less diverse microorganism community than healthy controls. Certain bacterial taxa might be associated with lung cancer, but the exact species depends on the sampling site and the pathological type. This study provides basic data on the microbiota diversity in BALF and saliva samples from lung cancer patients. Further investigation with a larger sample size should help validate the enriched species in different pathological types of lung cancers.

Fungal colonization in patients with chronic respiratory diseases from Himalayan region of India.

BACKGROUND: We screened patients with chronic respiratory diseases for microbiological and serological evidences of fungal colonisation; in order to determine its prevalence in this group of patients, examine potential clinical and radiological predictors of fungal colonisation and characterise fungal agents associated with individual diseases. METHODS: BAL samples from 60 consecutive patients were subjected to microscopy and culture for fungal agents. Serum samples were analysed for precipitin antibodies to Aspergillus antigen and Candida cytoplasmic antigen. Statistical significance in the difference of fungal recovery between patient groups was determined using the Chi-square test. RESULTS: The major diagnostic groups included patients with bronchogenic carcinoma (n = 31) and tubercular sequelae (n = 16). In all, 28 patients (46.7%) were culture-positive, with Candida and Aspergillus being recovered from 14 and 13 patients respectively. Twenty-one patients (35%) showed presence of precipitin antibodies. Patients with bronchogenic carcinoma showed increased predilection for colonisation with Aspergillus, while Candida was recovered more commonly in tubercular sequelae (p = 0.02). There was no statistically significant association between culture-positivity and specific risk factors/radiological findings. CONCLUSION: The point-prevalence of fungal colonization was almost 50%. The combination of fungal culture and serology helped improve diagnostic sensitivity. An interesting predilection was observed for Aspergillus and Candida, to preferentially infect patients with Bronchogenic carcinoma and Tubercular sequelae respectively. In absence of specific predictors, the possibility of fungal colonization needs to be explored actively in these patients.

Association between paracoccidioidomycosis and cancer.

OBJECTIVE: To analyze the association between paracoccidioidomycosis (Pcm) and cancer in a series of 25 cases and to review the literature on this topic. METHODS: A retrospective review of 25 cases diagnosed with Pcm and cancer, retrieved from a series of 808 consecutive adult patients diagnosed with Pcm based on tests conducted in the Mycology Laboratory of the Santa Casa Complexo Hospitalar, in the city of Porto Alegre, Brazil, between 1972 and 2007. The diagnosis of Pcm was confirmed by means of direct microscopic examination, histopathological examination or immunodiffusion test. All cancer cases were confirmed by histopathological or cytopathological examination. RESULTS: Respiratory symptoms were the principal complaints of the patients evaluated. Pulmonary involvement predominated, followed by skin and lymph node involvement. The most prevalent tumor was bronchial carcinoma, in 15 patients, followed by other types of carcinoma, and 1 patient had Hodgkin's lymphoma. In 16 patients (64%), the site of the Pcm was the same as that of the tumor. In most cases, Pcm treatment consisted of the isolated administration of sulfanilamide, sulfamethoxazole-trimethoprim, ketoconazole, itraconazole or amphotericin B. The most common treatment for cancer was surgery, followed by radiotherapy and chemotherapy. Of the 25 patients, 12 were cured of Pcm, and 4 died. In 9 patients, the final outcome was unknown. In the general population of the area under study, the prevalence of lung cancer was significantly higher in smokers with Pcm than in smokers without Pcm (p < 0.001). CONCLUSIONS: A diagnosis of Pcm appears to increase the risk of lung cancer.

Associação entre paracoccidioidomicose e câncer / Association between paracoccidioidomycosis and cancer

OBJETIVO: Analisar a associação entre paracoccidioidomicose (Pcm) e câncer e realizar uma revisão da literatura sobre esse tópico. MÉTODOS: Revisão retrospectiva de 25 casos diagnosticados com Pcm e câncer, extraídos de uma série de 808 casos consecutivos de pacientes adultos diagnosticados com Pcm com base nos testes realizados no Laboratório de Micologia da Santa Casa Complexo Hospitalar de Porto Alegre (RS), entre 1972 e 2007. O diagnóstico de Pcm foi confirmado através de exame microscópico direto, exame histopatológico ou imunodifusão. Todos os casos de câncer foram confirmados por exame histopatológico ou citopatológico. RESULTADOS: Sintomas respiratórios foram as principais queixas dos pacientes. O envolvimento pulmonar foi o achado mais predominante, seguido pelo tegumentar e linfático. O tipo de tumor mais prevalente foi o carcinoma brônquico, em 15 casos, seguido de outros tipos de carcinoma, e 1 paciente apresentou linfoma de Hodgkin. Em 16 pacientes (64 por cento), o sítio de Pcm era o mesmo do tumor. Na maioria dos casos, o tratamento de Pcm consistiu na administração isolada de sulfanilamida, sulfametoxazol-trimetoprim, cetoconazol, itraconazol ou anfotericina B. A cirurgia foi o tratamento mais comum para o câncer, seguida de radioterapia e quimioterapia. Dos 25 pacientes, 12 foram curados para Pcm, e 4 faleceram. Em 9, o desfecho final era desconhecido. A prevalência de câncer de pulmão na população geral na área em estudo foi significativamente maior em fumantes com Pcm que em fumantes sem Pcm (p < 0,001). CONCLUSÕES: .O diagnóstico de Pcm parece aumentar o risco de câncer de pulmão.

OBJECTIVE: To analyze the association between paracoccidioidomycosis (Pcm) and cancer in a series of 25 cases and to review the literature on this topic. METHODS: A retrospective review of 25 cases diagnosed with Pcm and cancer, retrieved from a series of 808 consecutive adult patients diagnosed with Pcm based on tests conducted in the Mycology Laboratory of the Santa Casa Complexo Hospitalar, in the city of Porto Alegre, Brazil, between 1972 and 2007. The diagnosis of Pcm was confirmed by means of direct microscopic examination, histopathological examination or immunodiffusion test. All cancer cases were confirmed by histopathological or cytopathological examination. RESULTS: Respiratory symptoms were the principal complaints of the patients evaluated. Pulmonary involvement predominated, followed by skin and lymph node involvement. The most prevalent tumor was bronchial carcinoma, in 15 patients, followed by other types of carcinoma, and 1 patient had Hodgkin's lymphoma. In 16 patients (64 percent), the site of the Pcm was the same as that of the tumor. In most cases, Pcm treatment consisted of the isolated administration of sulfanilamide, sulfamethoxazole-trimethoprim, ketoconazole, itraconazole or amphotericin B. The most common treatment for cancer was surgery, followed by radiotherapy and chemotherapy. Of the 25 patients, 12 were cured of Pcm, and 4 died. In 9 patients, the final outcome was unknown. In the general population of the area under study, the prevalence of lung cancer was significantly higher in smokers with Pcm than in smokers without Pcm (p < 0.001). CONCLUSIONS: A diagnosis of Pcm appears to increase the risk of lung cancer.

Saccharopolyspora rosea sp. nov., isolated from a patient with bronchial carcinoma.

The taxonomic status of a bacterium isolated from a patient with bronchial carcinoma was established using a polyphasic taxonomic approach. The strain had morphological and chemotaxonomic characteristics consistent with those of members of the genus Saccharopolyspora. The generic assignment was confirmed by comparative analysis of the 16S rRNA gene sequence, which showed that the strain constituted a distinct phyletic line, displaying 93.5-96.9 % sequence similarity with respect to members of the genus Saccharopolyspora. The isolate was distinguished from the type strains of recognized members of the genus Saccharopolyspora by means of various biochemical tests. The genotypic and phenotypic data obtained demonstrated that strain IMMIB L-1070(T) represents a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora rosea sp. nov. is proposed. The type strain is IMMIB L-1070(T) (=DSM 45226(T)=CCUG 56401(T)).

[Bronchoalveolar lavage in lower respiratory tract infections in patients with bronchopulmonary carcinoma. Our experience]. / Il lavaggio broncoalveolare nelle infezioni delle basse vie respiratorie nei pazienti con carcinoma broncopolmonare. Una nostra esperienza.

UNLABELLED: In order to evaluate the usefulness of the endoscopic procedures with BAL, we conducted a study on 92 patients with diagnosis of lung cancer, underwent to chemotherapy, identifying pathogenic species involved and the antibiotic sensibility and antibiotic resistance. Moreover, to evaluate possible modifications of alveolar cell population in neutropenic patients, we studied the specimens from BALs performed via fibreoptic bronchoscopy. METHODS: The cellular pattern of BALs in terms of concentration of total cells, concentrations of alveolar macrophages (AMs), of polymorphonucleates (PMNs) and lymphocytes (Ls) were compared in neutropenic and non-neutropenic patients. RESULTS: In the statistical analysis of our study we found a correlation, statistically significant, between patients with neutropenic episodes on the previous chemotherapy courses and incidence of LTRI. The mean concentrations x 100,000/ml of BAL fluid of total alveolar cells, AMs, PMNs and Ls were significantly lower, after chemotherapy, in group of neutropenic patients than in non neutropenic patients, respectively. CONCLUSIONS: In this study we found that during neutropenia the alveolar cell population was quantitatively deficient, confirming the hypothesis, proposed by other authors, of "lung aplasia" as a consequence or a concomitant event of chemotherapy-induced marrow toxicity.

Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study.

In contrast to the healthy population, distal airway bacterial colonization may occur in patients with chronic lung diseases, who often have altered pulmonary defences. However, the information dealing with this issue is insufficient and is based mainly on nonspecific samples, such as sputum cultures. Using quantitative cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples, we studied the bacterial colonization of distal airways in 16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long-term tracheostomy due to laryngeal carcinoma. All patients were without exacerbation, and free from antibiotic treatment at least 1 month before the study protocol. Thresholds for quantitative cultures to define colonization were > or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and > or = 10(3) cfu x mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs); in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%) long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic carcinoma, COPD, bronchiectasis and long-term tracheostomized patients, respectively. Pseudomonas aeruginosa colonization was infrequent in all the groups. Our results show that distal airway bacterial colonization is a frequent feature in stable patients with chronic lung diseases and also in patients with long-term tracheostomy. However, the pattern of colonization differs among groups studied. The knowledge of different colonization patterns may be important for future antibiotic prophylactic strategies and for the empirical antibiotic regimens when exacerbations occur in these patients.

[Netilmicin in single daily doses for the bacterial bronchopulmonary complications in patients with advanced bronchogenic carcinoma]. / La netilmicina in monodose giornaliera nelle complicanze batteriche broncopolmonari in pazienti con carcinoma broncogeno avanzato.

In 40 patients with bacterial bronchopulmonary complications during polychemotherapy for advanced bronchogenic carcinoma, once-daily netilmicin (4.5 mg/kg every 24 h) brought about complete resolution of the infective process in 90% of the cases and eradication of the responsible pathogen in 82%. This result must be considered good in view of the patients' precarious condition due to their advanced neoplastic disease.

Distribution of intrapleural and intravenous Corynebacterium parvum in humans; 99mTc-, and 131I-labeled bacteria.

The distribution of Corynebacterium parvum labeled with 131iodine or 99mtechnetium was studied in 17 patients with bronchogenic carcinoma. The labeled bacteria were given intravenously or intrapleurally and monitored by whole-body gamma tracking and samples of blood and urine. Even though the rate of physical decay is quite different for 131iodine and 99mtechnetium, the tracking time of labeled bacteria was limited to 24 h after injection for both radioactive isotopes. Technetium labeling was preferred because of greater imaging resolution and less radiation dose to the patient. Following intravenous administration, labeled C. parvum was found predominantly in the liver and spleen, and in a lesser amount in the lung. Radioactivity was confined to the pleural cavity after intrapleural injection. These results suggest the combined intravenous and intrapleural route of adjuvant immunosupportive agents such as C. parvum for operable lung cancer patients.

Evidence that respiratory tract is major reservoir for Epstein-Barr virus.

Exfoliated cells harvested from bronchial washings of 53 patients with suspected bronchogenic carcinoma were tested by means of DNA dot hybridisation using the cloned large internal repeat (IR) sequence of Epstein-Barr virus (EBV) genome as a probe. 25 of these patients gave positive results. Since the patients had diseases that were not related to the virus, this finding suggests that the lower respiratory tract is a major reservoir for EBV. Attempts at cellular localisation of the virus revealed only an occasional cell which harboured the viral genome or expressed viral capsid antigens. These cells could not account for the quantity of the viral DNA detected in bronchial washings. Moreover, patients had similar profiles of serum EBV antibodies whether they were positive or negative for EBV DNA by dot hybridisation. These findings are compatible with a state of viral latency in which cells harbour a low copy number of the viral genome. Viral expression rarely occurs in these cells, which seem to elicit a minimum host immune response. If it is assumed that each latently infected cell harbours a maximum of approximately 30 EBV genomes (which is the lower limit of detection by the in-situ hybridisation method used in this study), the findings suggest that a considerable proportion of the exfoliative cells from the lower respiratory tract, of the order of 0.1-16%, harbour latent EBV.

Microbial flora associated with pulmonary neoplasms.

The microbial flora associated with various tumors of the lung was studied in 19 patients. Biopsy specimens taken from the resected bronchus and from peripheral lung tissue at thoracotomy were cultured for aerobic and anaerobic microorganisms prior to administration of prophylactic antibiotics. Bacterial growth was obtained in bronchial and/or pulmonary biopsy culture in eight patients, with additional growth of fungi (Candida parapsilosis) in one of them. The microflora was of oropharyngeal origin, with streptococci and staphylococci predominating. The remaining 11 patients were culture-negative. The results of the study suggest that a prophylactic antibiotic regimen consisting of antistreptococcal and antistaphylococcal drugs is appropriate.

Tracheobronchial epithelial multinucleation, viral inclusion bodies and malignant disease.

Patients with malignant disease are known to have an increased incidence of multinucleation in their tracheobronchial ciliated epithelial cells as compared with controls matched by age, sex and smoking habit. A seasonal relationship of viral inclusion bodies in the cilated epithelium of asymptomatic subjects has also been shown and is not related to age, sex and smoking habit. We have conducted an epidemiologic study to determine the possible relationships between these factors. Smears from 4,150 patients with a wide variety of pathologic conditions were examined for the presence of viral inclusions and multinucleated, ciliated epithelial cells. High degress of multinucleation were observed least frequenctly in the summer both in patients with and without known malignancy. Cytoplasmic inclusion bodies were also seen least frequently in the summer and autumn both in patients with and without know malignancy. In the presence of cancer, multinucleated epithelial cells and inclusion bodies were seen more frequently regardless of the season. When the seasonal incidence of multinucleated cells in 155 smears containing viral inclusion bodies was analyzed, it was found that patients without cancer had the lowest levels of multinucleation in the summer, whereas cancer patients had a depressed incidence of multinucleation in the winter and spring. Respiratory viruses may have a specific effect on the ciliated epithelium of cancer patients.