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This clinical case presents an unusual case of Lemierre's syndrome (LS) in a young woman of 38-year-old. She arrived in the Emergency Department with a high fever and pharyngology resistant to antibiotic therapy with clarithromycin, ceftriaxone, and cortisone for two weeks. At the blood sampling, there is a marked leucocytosis, and the advice of the otolaryngologist is required given the strong pain in the throat. Due to the tonsillar abscess, a neck CT with a contrast medium is necessary for the otolaryngologist's opinion. The CT shows thrombosis of the jugular vein and left subclavian, with thickening of soft perivascular tissues; these findings suggest Lemierre's syndrome: a septic thrombophlebitis of the jugular vein that occurs as a complication of a peritonsillar abscess. The diagnostic process is then completed with a chest HR-CT, which reveals lung density and excavation areas suggesting tuberculosis. Blood culture reveals the presence of Veillonella Parvula (an anaerobic gram-negative coccus), sputum culture reveals the presence of some colonies of Enterobacter cloacae complex, real-time PCR examination on sputum reveals the presence of Streptococcus Pneumoniae and the borderline presence of rhinovirus. Microbiologists, after these results and neck and chest CT with a contrast agent, agree with the diagnosis of suspected LS at an early stage: a septic dissemination fortunately limited only to the neck and lungs region. [ABSTRACT FROM AUTHOR]

Background: It has been recently recognized that pulmonary cyst may develop after pulmonary resection, causing various symptoms. Most previously reported cases were after upper lobectomy in patients with chronic obstructive lung disease (COPD). Case presentation: Case 1 was a man in his 70 s with interstitial pneumonia (IP). Right lower lobectomy was performed for metastatic lung tumor using video-assisted thoracoscopic surgery (VATS). On postoperative day (POD) 19, computed tomography (CT) revealed a large cyst at the upper interlobular surface of the middle lobe, with pneumoderma and pneumomediastinum. The cyst was incised, polyglycolic acid (PGA) sheet and fibrin glue were applied, and the cyst was sutured. The sutured line was covered again with PGA sheet and fibrin glue. Case 2 was a man in his 70 s with COPD. Right upper lobectomy for primary lung cancer was performed using VATS. On POD 17, CT revealed a large pulmonary cyst at the apex of S6 and massive air leakage was observed. The same surgical procedure as that used in case 1 was performed. Cases 3 and 4 were healthy donors for living-donor lung transplantation. Two months after the right lower lobectomy in Case 3 and 3 months after the left lower lobectomy in Case 4, the patients had respiratory symptoms such as dyspnea and hemosputum. CT revealed a large cyst on the diaphragmatic surface of the right middle lobe in Case 3 and on the posterior mediastinal surface of the left upper lobe in Case 4. Cyst incision, soft coagulation, and application of PGA sheet with fibrin glue were performed in both cases. CT performed 1 year after surgery showed no development of a pulmonary cyst or air space in these four cases. Conclusions: Pulmonary cysts newly formed after lobectomy can develop not only in COPD or IP but also in healthy lungs. Our findings suggest that incision of the cyst and application of fibrin glue and PGA sheet with or without suturing the cyst wall is effective for management. [ABSTRACT FROM AUTHOR]

The clinical impact of nucleic acid amplification (NAA) tests on reducing delayed diagnosis and misdiagnosis of pulmonary TB (PTB) has rarely been investigated. PTB patients were classified into a frontline NAA group, an add-on NAA group, and a no NAA group. The outcomes of interest were the proportion of PTB case died before anti-TB treatment, the interval between sputum examination and initiation of treatment, and misdiagnosis of PTB. A total of 2192 PTB patients were enrolled, including 282 with frontline NAA, 717 with add-on NAA, and 1193 with no NAA tests. Patients with NAA tests had a lower death rate before treatment initiation compared to those without NAA tests (1.6% vs. 4.4%, p < 0.001) in all cases. Patients with frontline NAA compared to those with add-on NAA and those without NAA, had a shorter interval between sputum examination and treatment initiation in all cases (3 days vs. 6 days (p < 0.001), vs 18 days (p < 0.001)), and less misdiagnosis in smear-positive cases (1.8% vs. 5.6% (p = 0.039), vs 6.5% (p = 0.026)). In conclusion, NAA tests help prevent death before treatment initiation. Frontline NAA tests perform better than add-on NAA and no NAA in avoiding treatment delay in all cases, and misdiagnosis of PTB in smear-positive cases. [ABSTRACT FROM AUTHOR]

Purpose: Strongyloidiasis is mainly prevalent in developing countries with poor economic and sanitary conditions. The clinical manifestations of Strongyloides stercoralis infection are complex and diverse, lacking specificity, which can easily lead to misdiagnosis and delayed treatment. Methods: An elderly male patient, repeated cough and expectoration for 4 years, with exacerbation and dyspnea for 10 days, was admitted to hospital. Sputum culture and smear were taken for examination. Nematode larvae were found under the microscope. Nematodes were also found in feces. Results: Upon confirmation, the patient was diagnosed with a pulmonary infection caused by Strongyloides stercoralis. After treatment with albendazole, the symptoms improved, and the patient was discharged. Conclusion: In this case report, combination of microscopic examination of sputum and alveolar lavage fluid and CT scan were used to quickly identify the cause of the patient, it provides a diagnostic basis and method for clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hemorrhage is a life-threatening complication of cardiovascular surgery. Bronchial artery hypertrophy, a rare pathology associated with inflammatory and ischemic respiratory diseases, increases the risk of pulmonary hemorrhage; however, its involvement in cardiovascular surgery is not well known. We present two cardiovascular surgical cases in which embolization of the hypertrophied bronchial artery was effective in controlling perioperative pulmonary hemorrhage. Case presentation: The first case was a 51-year-old man with chronic obstructive pulmonary disease who developed acute type A aortic dissection. After emergent surgery, his blood pressure suddenly dropped in the intensive care unit; computed tomography revealed a right hemothorax. Because a 4-mm dilated bronchial artery was identified on preoperative computed tomography, the hemothorax was suspected to be associated with bronchial artery hypertrophy. Selective bronchial arteriography was emergently performed and revealed a right pulmonary parenchymal blush. After subsequent coil embolization of the bronchial artery, the parenchymal blush disappeared, and his hemodynamic condition stabilized. The second case was a 66-year-old man with bronchiectasis who was referred for redo aortic valve replacement due to structural valve deterioration. A bioprosthesis was previously implanted to avoid permanent anticoagulation because the patient had repeated episodes of hemoptysis; however, he still had persistent hemosputum during admission for the redo aortic valve replacement. A dilated bronchial artery 3.7 mm in size was incidentally identified on preoperative computed tomography, and hence, the repeated hemosputum was suspected to be associated with bronchial artery hypertrophy. Bronchial arteriography revealed a right pulmonary parenchymal blush, and prophylactic embolization of the bronchial artery was performed. The hemosputum disappeared after the procedure, and redo aortic valve replacement was performed uneventfully 8 days later. Conclusion: In cardiovascular surgery, the risk of pulmonary hemorrhage associated with bronchial artery hypertrophy should be considered, especially in patients with inflammatory and ischemic respiratory diseases. [ABSTRACT FROM AUTHOR]

Background: Anaplastic lymphoma kinase (ALK)–tyrosine kinase inhibitors (TKIs) have been approved for the therapy of locally advanced non-small cell lung cancer (NSCLC) caused by ALK rearrangement. However, its treatment after failure of initial ALK–TKI therapy remains controversial. Case presentation: A 47-year-old woman with a hemosputum was diagnosed with adenocarcinoma of the left lung (cT2bN3M0, stage IIIB). Gene mutation analysis indicated positive ALK translocation. Alectinib was selected as the first-line treatment. Although the treatment effect was determined as a partial response, the main tumor regrew. Alectinib was discontinued, and salvage surgery was performed without causing morbidity. The pathological diagnosis was pleomorphic carcinoma without lymph node metastasis (yp-T2bN0). After surgery, lorlatinib was administered as the second-line treatment for 8 months until the patient could not tolerate continuation. Computed tomography scan revealed no lung cancer recurrence 14 months after discontinuation. Conclusions: Our experience with this case suggests that salvage surgery after alectinib treatment followed by lorlatinib therapy may be effective for initially unresectable ALK-positive NSCLC. [ABSTRACT FROM AUTHOR]

The cystic fibrosis (CF) community seeks to explain heterogeneous outcomes of pulmonary exacerbation (PEX) treatment. Serum and sputum inflammatory mediators may identify people with CF (PwCF) at risk for suboptimal responses. However, lack of an established association between response phenotypes and these mediators limits clinical application. In this pilot study, we prospectively characterized treatment response phenotypes by assessing health-related quality-of-life (HRQoL) during PEX. We also measured lung function and iron-related biochemical parameters in serum and sputum. We classified subjects as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) based on the absence or presence, respectively, of worsened symptom scores after initial improvement. We used linear mixed models (LMMs) to determine whether trends in lung function, hematologic, serum, and sputum indices of inflammation differed between response cohorts. In 20 PwCF, we identified 10 SRs and 10 NSRs with no significant differences in lung function at PEX onset and treatment durations. SRs had better model-predicted trends in lung function than NSRs during PEX. Non-linear trends in serum and sputum iron levels significantly differed between SRs and NSRs. In adults with cystic fibrosis, PEX treatment response phenotypes may be correlated with distinctive trends in serum and sputum iron concentrations. [ABSTRACT FROM AUTHOR]

Community-level benefits of screening for active tuberculosis (TB) disease remain uncertain. Project Axshya (meaning free of TB) conducted advocacy, communication, social mobilization, and active case finding among vulnerable/marginalized populations of India. Among 15 districts of Jharkhand state, the project was initiated in 36 subdistrict level administrative units — tuberculosis units (TUs) in a staggered manner between April 2013 and September 2014, and continued till the end of 2015. Seven TUs did not implement the project. We assessed the relative change in the quarterly TB case finding indicators (n = 4) after inclusion of a TU within the project. By fitting four multilevel models (mixed-effects maximum likelihood regression using random intercept), we adjusted for secular (over previous five quarters) and seasonal trends, baseline differences within Axshya and non-Axshya TUs, and population size and clustering within districts and within TUs. After inclusion of a TU within the project, we found a significant increase [95% confidence interval (CI)] in TU-level presumptive TB sputum examination rate, new sputum-positive TB Case Notification Rate (CNR), sputum-positive TB CNR, and all forms TB CNR by 12 (5.5, 18.5), 1.1 (0.5, 1.7), 1.3 (0.6, 2.0), and 1.2 (0.1, 2.2) per 100,000 population per quarter, respectively. Overall, the project resulted in an increase (95% CI) in sputum examination and detection of new sputum-positive TB, sputum-positive TB and all forms of TB patients by 22,410 (10,203, 34,077), 2066 (923, 3210), 2380 (1162, 3616), and 2122 (203, 4059), respectively. This provides evidence for implementing project Axshya over and above the existing passive case finding. [ABSTRACT FROM AUTHOR]

Effective treatment for tuberculosis (TB) patients on first-line treatment involves triaging those with drug-resistant (DR) TB to appropriate treatment alternatives. Patients likely to have DR TB are identified using results from repeated inexpensive sputum-smear (SS) tests and expensive but definitive drug sensitivity tests (DST). Early DST may lead to high costs and unnecessary testing; late DST may lead to poor health outcomes and disease transmission. We use a partially observable Markov decision process (POMDP) framework to determine optimal DST timing. We develop policy-relevant structural properties of the POMDP model. We apply our model to TB in India to identify the patterns of SS test results that should prompt DST if transmission costs remain at status-quo levels. Unlike previous analyses of personalized treatment policies, we take a societal perspective and consider the effects of disease transmission. The inclusion of such effects can significantly alter the optimal policy. We find that an optimal DST policy could save India approximately $1.9 billion annually. [ABSTRACT FROM AUTHOR]

Despite the global significance of tuberculosis (TB), its diagnosis continues to rely on tests that have several limitations. Accurate point-of-care test has not yet been successfully developed. The objective of the present study is to evaluate the efficacy of detecting specific immunoglobulin against 38-kDa and 16-kDa proteins in the TB diagnosis compared to smear staining, culture, and tuberculin skin test (TST) . This study was conducted on 41 patients with pulmonary tuberculosis (PTB) and 35 healthy blood donors as control group. In addition to TST, sputum stained smear and TB culture, sera from patients and control groups were tested for reactivity against anti-38-16 kDa proteins with immunochromatographic point-of-care test. The number of culture proven, smear positive patients and TST reactors were 32 (78%), 25 (61%), and 32 (78%) respectively. Only 14 (34.1%) patients had positive results with anti-38-16 kDa antibodies detection test, while all control sera were negative. The sensitivity, specificity, PPV, NPV, and accuracy of anti-38-16 kDa antibodies detection test were 31.3, 55.6, 71.4, 18.5, and 36.6%, respectively with poor agreement with culture and TST results (Kappa = −0.077). The diagnostic value of anti-38-16 kDa TB screening test for routine diagnosis of PTB is restricted and cannot replace sputum smear or culture and can only used as an adjunct test. [ABSTRACT FROM AUTHOR]

The article presents a study on impact of diabetes mellitus (DM) on tuberculosis (TB) treatment outcomes. A systematic review andmeta-analysis for evaluating association between DM and TB was conducted. The process included data selection for TB treatment outcomes, assessment of sputum culture positivity and odds ratio of the combined outcome, failure, and death.

Purpose: Bronchiolitis obliterans (BO) is an inadequately researched disease in terms of lung function as well as inflammatory profile. The short-term variation of these parameters has not been investigated. Therefore, the objective of this study was the investigation of lung function, sputum cells and cytokine profiles in BO at two visits within of four to six weeks. Methods: Twenty patients with BO (median age = 14.6, range 8.3-24.3) performed lung function tests, airway reversibility testing and induction of sputum within four to six weeks. The cell composition in the sputum was analysed and cytokine levels of IL-1ß, IL-6 and IL-8 were determined by cytometric bead array analysis. The short-term variation was then statistically quantified and compared to that of twenty-two healthy controls. Furthermore, we compared data on short-term variation of lung function and airway inflammation with a previous investigation in these patients 10-15 months earlier. Results: Patients with BO showed minimal variation of lung function (VCmax, FVC, FEV1, FEV1/VC, MEF25 and RV/TLC) and the inflammatory cell profile. The lung function data were significantly lower for FVC, FEV1, the Tiffeneau index and MEF25 compared to the control group, whereas RV/TLC was significantly increased. Analysis of the BO sputum cells showed a consistent neutrophil inflammation. The levels of inflammatory cytokines IL-1ß, IL-6 and IL-8 had a great variability. Conclusions: The short-term variability of sputum neutrophilia and lung function is low in BO patients. This finding should be considered to identify successful treatment in the individual patient and could be used as endpoints for future BO-related studies. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains as one of the deadliest diseases after HIV globally with 95% of deaths confined to low-and-middle income countries. Pakistan is fifth among the 22 high-burden TB countries with the incidence rate of 230/100,000 persons, however, studies related to prevalent Mycobacterium tuberculosis strains and their spread, drug resistance pattern and evolutionary genetics are inadequate. The present study was undertaken to highlight the circulation of M. tuberculosis strains causing drug resistant TB in our community by targeting the molecular marker IS6110 and then characterization of these strains as Beijing and Non-Beijing genotypes. Sputum samples from 102 MDR TB suspects from different cities of Punjab were collected and their record was stored in a database. Sputum samples were evaluated by Ziehl Neelson staining and cultured on Lownstein Jensen medium by Modified Petroff's method. DST was performed for first-line anti-mycobacterial drugs by indirect proportion method. Mycobacterium tuberculosis isolates were investigated for the presence of IS6110 and further identification as Beijing, Non-Beijing or mixed genotype. Percentage of male and female patients was found to be 58.8 and 41.2% respectively. DST showed resistance of 93% of isolates to isoniazid and rifampicin. All of the isolates showed positive results for IS6110 amplification. Based on PCR amplification of Beijing and non-Beijing primer sets 4.9% of the patients showed infection with pure Beijing isolates, 14.7% with both Beijing and non-Beijing isolates and 80.3% with pure non-Beijing isolates. Analysis of IS6110 and Beijing sequences showed the presence of putative transposase conserved domain while non-Beijing sequences were epitomized with RAMP_I_III superfamily domain (CRISPR-associated protein family). TB in Pakistan is predominantly caused by Non-Beijing genotypes, but Beijing strains showed incessant circulation in our community as both single and mixed (co-infecting Non-Beijing and Beijing) strains. [ABSTRACT FROM AUTHOR]

Dog feces containing 500 Paragonimus westermani eggs per gram were examined by the Medical General Laboratory (MGL), the simple sedimentation (SS), and the Army Medical School III (AMS III) methods. The number of eggs per gram of feces (EPG) obtained by the MGL method was 17.2 and was significantly lower than those obtained by the SS method (324.0) and the AMS III method (505.6). When isolated P. westermani eggs were processed by the MGL method and four layers (ether, ether-fecal, formalin layers, and sediment) of the final centrifugation product were separately examined, almost 100 % of eggs were found at the ether-fecal layer. Similarly, when fecal samples containing P. westermani, Paragonimus skrjabini miyazakii, Paragonimus ohirai, or Paragonimus harinasutai eggs were processed by the MGL method, more than 95 % of the eggs were found in the supernatant layers. The formalin-ethyl acetate (FEA) method showed a similar tendency as the MGL method and over 90 % of eggs remained in the supernatant layers. Contrary to Paragonimus eggs, 63 and 96 % of Clonorchis and Metagonimus eggs were found in the sediment in the MGL method, respectively. When surfactant (Tween 80) was added to fecal solution, most of Paragonimus eggs spun down in the sediment in the MGL and FEA methods, suggesting that Paragonimus eggs have hydrophobic components on their surface. It is suggested that surfactant addition to the fecal solution should be considered when the MGL method is used for detection of Paragonimus eggs. [ABSTRACT FROM AUTHOR]

In patients with preexisting lung disease, especially a cavity, Aspergillus can infect the surface of the cavity, causing chronic cavitary pulmonary aspergillosis (CCPA), and may form an aspergilloma, collectively called chronic pulmonary aspergillosis (CPA). In the present study, we assessed tuberculosis (TB) patients for CPA based on culture and serological methods. During a period of 1 year (from March 2013 to March 2014), we studied 124 patients with TB (94 with current TB and 30 with previous TB) at Masih Daneshvari Hospital in Tehran, Iran. Sputum specimens were analyzed by direct microscopic examination (DME) and fungal culture. The clinical and radiological features of all patients were recorded, to categorize the patients into CCPA and aspergilloma. All patients were screened for serum-specific IgG against A. fumigatus, by enzyme-linked immunosorbent assay (ELISA). Out of 124 patients with TB (66 male, age range: 10-91 years), 48 patients (38.7 %) exhibited residual cavities. Eighteen (14.5 %) patients had cavities with pleural thickening. A round-shaped mass lesion was detected in six patients (6.8 %). DME was positive in ten patients for septate fungal hyphae. A. fumigatus was grown from 14 samples. Fifty-five (44.3 %) cases were positive for serum-specific IgG against A. fumigatus. Of 124 patients with TB, 3 (2.4 %) met criteria for aspergilloma and 14 (11.3 %) for CCPA. CPA is a common clinical presentation in individuals with healed TB in Iran, as reported by previous studies from other countries. [ABSTRACT FROM AUTHOR]

Background:Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer.Methods:DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities.Results:In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set.Conclusions:Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer. [ABSTRACT FROM AUTHOR]

Patients undergoing hematopoietic SCT (HSCT) display an airway neutrophilic inflammation before transplantation that persists over the years. In this study, we have investigated the cytokine profile over a period of 1 year in the sputum supernatant of patients who underwent HSCT. We have measured sputum supernatant levels of TNF-α, TGF-β1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17 and IFN-γ in 49 HSCT patients and compared the results with those found in 40 chronic obstructive pulmonary disease (COPD) and 54 healthy subjects matched for age. Compared with healthy subjects, before transplantation, HSCT patients exhibited raised levels of IL-6 (P<0.001) and IL-8 (P<0.05) while the other cytokines were generally poorly detectable. This picture was rather similar to that seen in COPD even if cytokine levels were much greater in the latter, with IL-8 being significantly greater in COPD than in HSCT patients (P<0.0001). In the 1 year following transplantation, sputum IL-6 and IL-8 did not differ from those in healthy subjects. Overall in HSCT patients, sputum IL-8 and IL-6 correlated with sputum neutrophil counts (r=0.4, P<0.0001; r=0.42, P<0.0001, respectively). In conclusion, sputum IL-6 and IL-8 may play a role in neutrophilic airway inflammation seen in patients undergoing HSCT. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Methods: Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Results: Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. Conclusions: HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. Key Points: • HRCT can assist in the early diagnosis of the infectious active PTB • HRCT imaging is useful to predict the presence of smear-positive active PTB • Predictions from the HRCT imaging are valid even before sputum smear or culture results [ABSTRACT FROM AUTHOR]

Diagnosis of pulmonary tuberculosis (TB) remains a challenge in the pediatric population because of the lack of sputum production for laboratory analysis. Chest radiography is used in the diagnosis of pulmonary TB and the hallmark of diagnosis is the demonstration of hilar or mediastinal lymphadenopathy. Point-of-care sonography of the mediastinum is an alternative to chest radiography in detection of tuberculous lymph nodes. In the rural district health care setting US is often the most commonly available imaging modality and its mobility makes it possible to examine patients at the point of care, reducing the need for patients to travel to a regional hospital to acquire a chest radiograph. We developed and used a simplified technique for performing mediastinal sonography in a pilot study of 30 children (age 0 to 13 years) with proven or suspected TB. We can report that the procedure was successful in demonstrating the anterior mediastinal anatomy and predefined zones in all 30 children. We also recorded lymphadenopathy in 12 children. This report describes our procedural methods and initial results. [ABSTRACT FROM AUTHOR]

Pouched rats can detect Mycobacterium tuberculosis, which causes tuberculosis, in human sputum. Historically, a phosphate-buffered saline solution was added to sputum in the belief that doing so improved rats' detection of M. tuberculosis, but no relevant data were available. Experiment 1 evaluated rats' performance on samples with and without phosphate-buffered saline solution added. There was no difference in detection accuracy. Adding the solution slows sample processing and will not be done in future operational applications. Experiment 2 compared the performance of rats trained on sputum samples with low versus high concentrations of M. tuberculosis. Training on low-concentration samples improves sensitivity on that sample type. Unfortunately, it is impractical to arrange low-concentration training in the current operational setting, where the rats are used for the second-line screening of samples initially evaluated by microscopy. [ABSTRACT FROM AUTHOR]

Standard disc diffusion antimicrobial susceptibility testing (C+S) on individual Pseudomonas aeruginosa colonial morphotypes cultured from cystic fibrosis (CF) sputum has questionable clinical relevance. Direct sputum sensitivity testing (DSST) is a whole-sputum susceptibility test that removes bias associated with selecting individual colonial morphotypes. We sought to determine whether, in principle, the results from DSST support the possibility of improved clinical relevance compared with C+S. Individual (DSSTi) and combination (DSST) susceptibility to gentamicin, tobramycin, ceftazidime and meropenem were determined on 130 sputum samples referred from CF subjects with antibiotic-resistant chronic Gram-negative endobronchial infection. DSSTi and concurrent C+S were compared for categorical susceptibility, synergistic combinations were evaluated and the combination DSST efficacy index (DEI) calculated. Meropenem and tobramycin were the most active individual antibiotics by DSSTi on 89 P. aeruginosa-predominant samples, with 62 % of samples sensitive to each. C+S and DSSTi showed poor agreement (κ ranging from 0.02 to 0.6), discordance ranging from 20 % (meropenem) to 49 % (tobramycin), with DSSTi demonstrating both increased susceptibility and increased resistance. The combination that most frequently had the highest DEI was tobramycin + meropenem, occurring in 76 % of samples. DSSTi appears to be reproducible, yields different antimicrobial susceptibility results from C+S without simply identifying the most resistant isolates and DSST identifies the most effective in vitro antibiotic combinations, providing preliminary proof of concept of the potentially improved clinical relevance of whole-sputum testing. Future studies will determine whether these potential theoretical advantages translate into clinical benefits. [ABSTRACT FROM AUTHOR]

This study was aimed to rapidly identify and differentiate two main pathogens of the Mycobacterium tuberculosis complex: Mycobacterium tuberculosis subsp. tuberculosis and Mycobacterium bovis by a modified loop-mediated isothermal amplification (LAMP) assay. The reaction results could be evaluated by naked eye with two optimized closed tube detection methods as follows: adding the modified fluorescence dye in advance into the reaction mix so as to observe the color changes or putting a tinfoil in the tube and adding the SYBR Green I dye on it, then making the dye drop into the bottom of the tube by centrifuge after reaction. The results showed that the two groups of primers used jointly in this assay could successfully identify and differentiate Mycobacterium tuberculosis subsp. tuberculosis and Mycobacterium tuberculosis bovis. Sensitivity test displayed that the modified LAMP assay with the closed tube system could determine the minimal template concentration of 1 copy/μl, which was more sensitive than that of routine PCR. The advantages of this LAMP method for detection of the Mycobacterium tuberculosis complex included high specificity, high sensitivity, simplicity, and superiority in avoidance of aerosol contamination. The modified LAMP assay would provide a potential for clinical diagnosis and therapy of tuberculosis in the developing countries and the resource-limited areas. [ABSTRACT FROM AUTHOR]

Objective: To quantify neutrophil migration into the lungs of patients with chronic pulmonary obstructive disease (COPD). Methods: Neutrophil loss via airways was assessed by dedicated whole-body counting 45 min, 24 h and 2, 4, 7 and 10 days after injection of very small activities of In-labelled neutrophils in 12 healthy nonsmokers, 5 healthy smokers, 16 patients with COPD (of whom 7 were ex-smokers) and 10 patients with bronchiectasis. Lung accumulation of Tc-labelled neutrophils was assessed by sequential SPECT and Patlak analysis in six COPD patients and three healthy nonsmoking subjects. Results: Whole body In counts, expressed as percentages of 24 h counts, decreased in all subjects. Losses at 7 days (mean ± SD) were similar in healthy nonsmoking subjects (5.5 ± 1.5%), smoking subjects (6.5 ± 4.4%) and ex-smoking COPD patients (5.8 ± 1.5%). In contrast, currently smoking COPD patients showed higher losses (8.0 ± 3.0%) than healthy nonsmokers ( p = 0.03). Two bronchiectatic patients lost 25% and 26%, indicating active disease; mean loss in the remaining eight was 6.9 ± 2.5%. The rate of accumulation of Tc-neutrophils in the lungs, determined by sequential SPECT, was increased in COPD patients (0.030-0.073 min) compared with healthy nonsmokers (0-0.002 min; p = 0.02). Conclusion: In patients with COPD, sequential SPECT showed increased lung accumulation of Tc-labelled neutrophils, while whole-body counting demonstrated subsequent higher losses of In-labelled neutrophils in patients who continued to smoke. Sequential SPECT as a means of quantifying neutrophil migration deserves further evaluation. [ABSTRACT FROM AUTHOR]

Irritative effects caused by vapours and aerosols of bitumen were assessed by non-invasive methods including spirometry, nasal lavage fluid (NALF) and induced sputum (IS) in a cross-shift study comparing 320 bitumen-exposed workers with 118 road construction workers as the reference group. Lung function parameters, forced vital capacity (FVC) and forced expiratory volume in one second (FEV) were within normal ranges in both the reference and the bitumen-exposed groups pre- and post-shift with marginally lower values in smokers of both groups. During the shift, a slight decline in FEV and FVC was observed in the bitumen-exposed group independent of their smoking habits, whereas in the non-smoking reference group, the decline in FEV was not observed. No significant differences between bitumen-exposed workers and the reference group and no significant shift effect were observed on the upper airways using NALF analysis. The IS concentrations of interleukin (IL)-8, total protein and matrix metalloproteinase-9 were significantly higher in bitumen-exposed workers than in the reference group. However, the concentration of these three biomarkers in the IS samples, which are indicators of inflammatory effects on the lower airways of bitumen-exposed workers, was already higher in exposed workers before shift and did not show an increase during the shift. Therefore, the key finding of this aspect of the Human Bitumen Study is the detection of potentially (sub-) chronic irritative inflammatory effects in the lower airways of bitumen-exposed workers. [ABSTRACT FROM AUTHOR]

The overgrowth of normal flora escaping the action of sputum processing chemicals is the major problem in broth-based tuberculosis (TB) detection systems. The use of phages to control the overgrowth of normal flora in processed sputum samples has already been established. Phage lysin and its supplementation to phagebiotics for the effective control of normal flora in sputum specimens were evaluated. Crude lysin was prepared from phage host mixture using standard procedures. About 120 sputum samples processed with 4% NaOH were collected and used to evaluate the effect of lysin, phagebiotics and phagebiotics supplemented with lysin on the overgrowth of normal flora. The effect of phagebiotics and lysin on the growth and retrieval of Mycobacterium tuberculosis was studied by conventional methods and the luciferase reporter phage (LRP) assay. Lysin alone and phagebiotics supplemented with lysin arrested the growth of normal flora in a significantly greater number of samples than phagebiotics alone. Lysin and phagebiotics did not show any inhibitory activity on M. tuberculosis. The use of antibiotics can be replaced by lysin or phagebiotics supplemented with lysin to control the overgrowth of normal flora in processed sputum samples without hampering the viability of M. tuberculosis. [ABSTRACT FROM AUTHOR]

The aim of this study is to confirm the usefulness of sputum sampling from the hypopharynx through the nose to identify causative bacteria of pediatric community-acquired lower respiratory tract infection (CA-LRTI) and compare its features between the patients with and without underlying diseases. A retrospective study was performed on 244 pediatric patients hospitalized for CA-LRTI of suspected bacterial etiology. Sputum sample was obtained from these patients by aspirating airway secretion through the nose or the tracheostomy orifice, or coughing up by themselves. Sputum samples were assessed as suitable in 119 (74.4%) of 160 patients with CA-LRTI of suspected pure bacterial etiology. Ninety-six (70.1%) of 137 samples suctioned from the hypopharynx through the nose were suitable for bacterial examination. Seventy-eight (73.6%) of 106 patients identified with causative bacteria had some underlying diseases, and the other 28 patients did not have any underlying diseases. Proportions and antibiotics susceptibility profiles of the identified causative bacteria were almost similar in the patients with and without underlying diseases. Sputum sampling from the hypopharynx through the nose might be significant in pediatric CA-LRTI of suspected bacterial etiology. The initial treatment for patients without underlying diseases would be applicable to those with underlying diseases in the CA-LRTI of children. [ABSTRACT FROM AUTHOR]

We identified double and triple antibiotic combinations effective against biofilm-grown Burkholderia cepacia and Pseudomonas aeruginosa sampled from cystic fibrosis (CF) patients undergoing acute pulmonary exacerbations. Sputum bacteria from 110 CF patients were grown as biofilms. Combination antibiotic susceptibility testing was used to test 94 double and triple antibiotic combinations. Biofilm-grown bacterial isolates were less susceptible to antibiotic combinations compared to the same bacterial isolates grown planktonically ( P < 0.001). Fifty-nine percent of biofilm-grown B. cepacia isolates and 29% of P. aeruginosa isolates were resistant to all double antibiotic combinations tested. Triple antibiotic combinations were more effective than double antibiotic combinations against biofilms ( P < 0.0001). For P. aeruginosa biofilms, the addition of azithromycin or rifampin to otherwise effective antibiotic combinations was frequently associated with antagonism. Bacterial biofilms of CF organisms are highly resistant to antibiotics. This study identified potentially effective antibiotic combinations to guide the empirical treatment of CF pulmonary exacerbations. [ABSTRACT FROM AUTHOR]

Patients (305 patients with pulmonary tuberculosis) and controls (290 household genetically unrelated contacts) were tested by polymerase chain reaction (PCR) for polymorphisms in the intron 15 and the 5′ untranslated region of the gene coding for the a3 isoform of the human ATPase gene. Diagnosis of pulmonary tuberculosis was based on chest radiography and sputum smear examination and confirmed by PCR and bacteriological tests. Alleles (two at each site) segregated in the form of four haplotype pairs: 13, 14 (very rare), 23, and 24. The 13/24 (double heterozygous) patients were protected against tuberculosis (OR: 0.15; P: 10−8; CI: 0.08–0.3). The 13/13 vs 13/24 and 23/23 vs 23/24 (double homozygous) patients were susceptible to the disease (OR. 5.8; P: 6 × 10−7; CI: 2.8–11.9; OR: 4.5; P: 5 × 10−7; CI: 2.5–8.4, respectively). [ABSTRACT FROM AUTHOR]

Abstract Introduction  Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) are potentially important in Chronic Obstructive Pulmonary Disease (COPD), but little is known of the relationships between these cytokines and their antagonists in disease compared with healthy controls. It is unclear if concentrations relate to disease severity. The study aimed to investigate these relationships and to assess the potential activity of each cytokine in the context of their antagonists. Methods  Plasma cytokines, soluble receptors, and cell counts were measured in patients with stable COPD and age-matched healthy controls (n = 15 for both) daily for 5 days; these mediators were also measured in corresponding sputum samples from the COPD patients. Results  COPD patients had significantly reduced concentrations of the antagonists, IL-1sRII, and IL-1RA compared with controls. In COPD, IL-1β exceeded its antagonists and correlated significantly with BMI and FEV1, while plasma IL-1RA correlated positively with BMI but negatively with sputum IL-1β, neutrophil, and macrophage counts and smoking history. TNFα antagonists exceeded agonists in both groups and did not correlate with COPD severity. Conclusions  Endogenous IL-1β antagonists appear reduced in COPD. Furthermore, IL-1β correlated with clinical aspects of disease severity, suggesting that IL-1β may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNFα has limited activity in stable COPD. [ABSTRACT FROM AUTHOR]

In patients with cystic fibrosis (CF), there is an increasing incidence of some uncommon respiratory pathogens, such as Burkholderia cepacia complex (Bcc), Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. In order to evaluate the prevalence and the clinical impact of these pathogens, we retrospectively studied a total of 109 patients followed in our center from 1996 to 2006 and reviewed the results of 1,550 sputum samples. The isolation of Pseudomonas aeruginosa slightly decreased over the observed decade, whereas Staphylococcus aureus exhibited an irregular trend. Infection with Bcc reached a peak in 1998 and successively decreased to a stable 4%. S. maltophilia and A. xylosoxidans were the real emerging pathogens, since first isolation occurred in 2004; however, the percentage of infected patients remained low (7% and 3.2%, respectively) through the years. In conclusion, in our center for CF, the reduced prevalence of P. aeruginosa over the last decade has been associated with a concurrent reduction of infections by Bcc and, as compared to other centers in Italy, Europe, and the US, with a low incidence of emerging pathogens such as S. maltophilia and A. xylosoxidans. [ABSTRACT FROM AUTHOR]

Rapid diagnosis of influenza in hospitalised patients is important to prevent the transmission of the infection in the hospital. This prospective observational cohort study was designed to determine the relationship between the clinical diagnosis of influenza made by the physician at admission and the presence of influenza virus in patients with respiratory tract infections. This prospective observational cohort study was conducted in a large Dutch teaching hospital in a period of four weeks during the influenza season 2004/2005. All patients of 18 years and older, admitted with respiratory tract infections were included in the study. Clinical and laboratory parameters, chest radiograph (CR), blood and sputum cultures and nasopharyngeal swab for polymerase chain reaction (PCR) were obtained for each patient. In addition, the physicians opinion at admission whether this patient had influenza was recorded. A total of 78 patients were hospitalized with respiratory tract infections. In 41 (53%) of them influenza virus was detected by PCR. Among the patients that were positive for influenza virus by PCR, a clinical diagnosis of influenza was made in 18 cases (44%). Conversely, clinical diagnosis of influenza was made in 16 out of 37 patients in whom influenza virus was not detected by PCR. Neither C-reactive protein, leucocytes count nor an infiltrate on CR were helpful in determining the cause of the respiratory tract infection. The present findings failed to demonstrate a significant relationship between the clinical diagnosis of influenza and PCR detection of the virus. Also, the virus was present at least twice more often than influenza was clinically diagnosed. As a consequence, the decision to take protective measures to control spread of the virus should not rely on the clinical diagnosis. [ABSTRACT FROM AUTHOR]

Possible health hazards of fumes and aerosols of bitumen are in discussion, and data on their adverse effects on human airways under current exposure conditions are limited. To assess the irritative effects of exposure to fumes and aerosols of bitumen on the airways, a cross-sectional cross-shift study was conducted including external and internal exposure measurements, spirometry and especially non-invasive methods like nasal lavage collection and induction of sputum in order to identify and evaluate more precisely inflammatory process in the upper and lower airways. The cross-shift study comprised 74 mastic asphalt workers who were exposed to fumes and aerosols of bitumen and 49 construction workers without this exposure as reference group. Questionnaire, spirometry, ambient monitoring and urinary analysis were performed. Humoral and cellular parameters were measured in nasal lavage fluid (NALF) and induced sputum. For data analysis, a mixed linear model was performed on the different outcomes with exposure group, time of measurement (pre-, post-shift), current smoking, German nationality and age as fixed factors and subjects as random factor. Based on personal exposure measurements during shift, mastic asphalt workers were classified into a low (≤10 mg/m3; n = 46) and a high (>10 mg/m3; n = 28) exposure group. High exposure was accompanied by significant higher urinary post-shift concentrations of 1-hydroxypyrene and the sum of hydroxyphenanthrenes. Acute respiratory symptoms were reported more frequently in the high exposure group after shift. Significant cross-shift declines in lung function parameters (forced expiratory volume in 1 s [FEV1 (% predicted)] and forced vital capacity [FVC (% predicted)]) were measured in mastic asphalt workers. Pre-shift FEV1 (% predicted) and FVC (% predicted) were higher in the low exposure group. In pre- and post-shift NALF samples, interleukin (IL)-1β-, IL-8- and total protein concentrations were lower in the low exposure group compared to the reference and the high exposure group. Pre- and post-shift neutrophil percentages in both nasal and sputum samples were also lower in the low exposure group. Significantly higher pre- and post-shift sputum concentrations of IL-8, IL-6, nitrogen oxide (NO) derivatives and total protein were detected especially in highly exposed workers. Irritative effects of exposure to fumes and aerosols of bitumen on the upper and lower airways were apparent, especially in mastic asphalt workers with exposure above 10 mg/m3. [ABSTRACT FROM AUTHOR]

The article focuses on the need of diagnostic tests, to provide guidance for health-care workers, test developers, funding agencies and policymakers to prevent tuberculosis. Topics include the application of the method, Sputum smear microscopy (SSM); and that the World Health Organization (WHO) introduced the Directly observed treatment, short-course strategy as a cost-effective way to control TB and improve health.

OBJECTIVE: Our aim was to evaluate lung involvement in Crohn's disease (CRD) patients by induced sputum (IS), Extraintestinal manifestations are frequent in CRD, but lung involvement is rare. Induced sputum is a reliable noninvasive method of investigating the pathogenesis, pathophysiology, and treatment of lung disease. METHODS: Twenty-four CRD patients and nine control subjects (all nonsmokers) without respiratory symptoms were tested. Sputum was induced by 20′ inhalation of 3.5% saline using ultrasonic nebulizer. Samples were studied by differential counts of 200 cells on cytopreps stained by Giemsa, T-lymphocyte subset analyses were done by FACS using three monoclonal antibodies: CD3 = total T cells, CD4 = T helper cells, and CD8 = T suppressor-cytotoxic cells, CD4/CD8 >2.5 was considered abnormal. RESULTS: Four patients did not produce sputum. Of the remaining 20 patients, seven had active CRD and 13 were in remission. They were divided into two groups: Group A patients had abnormal CD4/CD8 ratio of 6.7 ± 2.5; Group B (seven patients) had normal CD4/CD8 ratio of 1.7 ± 0.52 (p = 0.0001). The differential counts of IS samples were similar in both groups, but lymphocyte count was significantly higher in CRD patients than in the control group (13.2 ± 11.2 vs 4.8 ± 3.6, p = 0.036). There were no differences in spirometry, treatment, extent, or activity of CRD. CONCLUSION: Using a simple noninvasive method, we found that among CRD patients without respiratory symptoms there was a high (65%) incidence of lung involvement. [ABSTRACT FROM AUTHOR]

The article discusses use of meropenem drug in association with clavulanate drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). It mentions that Marie-Christine Payen, an infectious disease specialist, had used the meropenem-clavulanate combination drug successfully in 2009 for treating a 14-year-old girl. It mentions that the study conducted by the World Health Organization (WHO) in 2013, reported that 20?30 percent of patients treated with the drug had negative sputum tests.

Abstract   Haemophilus influenzae type b meningitis has been reported predominantly among infants who have not completed the primary immunization series, whereas infection by capsular f has been reported mostly in patients with significant underlying diseases. The present study analyses H. influenzae type b & f infection among 25 unvaccinated patients with respiratory tract infections and symptoms of meningitis by PCR. 5/7 isolates from CSF sample were capsular type b; whereas capsular type f was detected in 2/10 and 5/8 isolates from throat swab and sputum samples, respectively. Rest 13 strains were negative for both the capsular types. To conclude, in India where H. influenzae type b conjugate vaccine is not included in national immunization program, individuals with respiratory tract infections and meningitis are at a greater risk of developing infection with H. influenzae type b strains along with other capsular types and non-capsular types. [ABSTRACT FROM AUTHOR]

Bronchial diseases are characterised by the weak efficiency of mucus transport through the lower airways, leading in some cases to the muco-obstruction of bronchi. It has been hypothesised that this loss of clearance results from alterations in the mucus rheology, which are reflected in sputum samples collected from patients, making sputum rheology a possible biophysical marker of these diseases and their evolution. However, previous rheological studies have focused on quasi-static viscoelastic (linear storage and loss moduli) properties only, which are not representative of the mucus mobilisation within the respiratory tract. In this paper, we extend this approach further, by analysing both quasi-static and some dynamic (flow point) properties, to assess their usability and relative performance in characterising several chronic bronchial diseases (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) and distinguishing them from healthy subjects. We demonstrate that pathologies influence substantially the linear and flow properties. Linear moduli are weakly condition-specific and even though the corresponding ranges overlap, distinct levels can be identified. This directly relates to the specific mucus structure in each case. In contrast, the flow point is found to strongly increase in muco-obstructive diseases, which may reflect the complete failure of mucociliary clearance causing episodic obstructions. These results suggest that the analysis of quasi-static and dynamic regimes in sputum rheology is in fact useful as these regimes provide complementary markers of chronic bronchial diseases. [ABSTRACT FROM AUTHOR]

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Molecular diagnostic methods are becoming increasingly available for assessment of acute lower respiratory illnesses (ALRI). However, nasopharyngeal/oropharyngeal (NP/OP) swabs may not accurately reflect etiologic agents from the lower respiratory tract where sputum specimens are considered as a more representative sample. The pathogen yields from NP/OP against sputum specimens have not been extensively explored, especially in tropical countries. We compared pathogen yields from NP/OP swabs and sputum specimens from patients ≥18 years hospitalized with ALRI in rural Western Kenya. Specimens were tested for 30 pathogens using TaqMan Array Cards (TAC) and results compared using McNemar's test. The agreement for pathogen detection between NP/OP and sputum specimens ranged between 85–100%. More viruses were detected from NP/OP specimens whereas Klebsiella pneumoniae and Mycobacterium tuberculosis were more common in sputum specimens. There was no clear advantage in using sputum over NP/OP specimens to detect pathogens of ALRI in adults using TAC in the context of this tropical setting. [ABSTRACT FROM AUTHOR]

The Cystic Fibrosis (CF) lung harbors a complex, polymicrobial ecosystem, in which Pseudomonas aeruginosa is capable of sustaining chronic infections, which are highly resistant to multiple antibiotics. Here, we investigate the phenotypic and genotypic diversity of 44 morphologically identical P. aeruginosa isolates taken from a single CF patient sputum sample. Comprehensive phenotypic analysis of isolates revealed large variances and trade-offs in growth, virulence factors and quorum sensing (QS) signals. Whole genome analysis of 22 isolates revealed high levels of intra-isolate diversity ranging from 5 to 64 SNPs and that recombination and not spontaneous mutation was the dominant driver of diversity in this population. Furthermore, phenotypic differences between isolates were not linked to mutations in known genes but were statistically associated with distinct recombination events. We also assessed antibiotic susceptibility of all isolates. Resistance to antibiotics significantly increased when multiple isolates were mixed together. Our results highlight the significant role of recombination in generating phenotypic and genetic diversification during in vivo chronic CF infection. We also discuss (i) how these findings could influence how patient-to-patient transmission studies are performed using whole genome sequencing, and (ii) the need to refine antibiotic susceptibility testing in sputum samples taken from patients with CF. [ABSTRACT FROM AUTHOR]