Detection of sputum by interpreting the time-frequency distribution of respiratory sound signal using image processing techniques.

Motivation: Sputum in the trachea is hard to expectorate and detect directly for the patients who are unconscious, especially those in Intensive Care Unit. Medical staff should always check the condition of sputum in the trachea. This is time-consuming and the necessary skills are difficult to acquire. Currently, there are few automatic approaches to serve as alternatives to this manual approach. Results: We develop an automatic approach to diagnose the condition of the sputum. Our approach utilizes a system involving a medical device and quantitative analytic methods. In this approach, the time-frequency distribution of respiratory sound signals, determined from the spectrum, is treated as an image. The sputum detection is performed by interpreting the patterns in the image through the procedure of preprocessing and feature extraction. In this study, 272 respiratory sound samples (145 sputum sound and 127 non-sputum sound samples) are collected from 12 patients. We apply the method of leave-one out cross-validation to the 12 patients to assess the performance of our approach. That is, out of the 12 patients, 11 are randomly selected and their sound samples are used to predict the sound samples in the remaining one patient. The results show that our automatic approach can classify the sputum condition at an accuracy rate of 83.5%. Availability and implementation: The matlab codes and examples of datasets explored in this work are available at Bioinformatics online. Contact: yesoyou@gmail.com or douglaszhang@umac.mo. Supplementary information: Supplementary data are available at Bioinformatics online.

Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort.

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40-85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755-0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.

[Bronchitis Plastica - Acute Dyspnea and Branching Airway Casts]. / Bronchitis plastica ­ Akute Luftnot und bronchiale Ausgusspräparate.

A 65 year old female presented to the emergency department with dyspnea and progressive cough with very viscous elongated secretion plugs. She suffered from multiple cardiac comorbidities and chronic heart failure. The CT scan of the thorax demonstrated extensive pulmonary infiltrates, unspecific mediastinal lymphadenopathy and enlargement of pulmonary lymph vessels. Bronchoscopy was performed and showed extensive occlusive bronchial casts. We diagnosed a case of bronchitis plastica. Therapy with inhalative heparin led to clinical improvement. CONCLUSION: bronchitis plastica is a rare disease with formation of occlusive bronchial casts. They are often found in cardiac disease or lymphatic disease.

THE CONTRIBUTION OF THE FIBEROPTIC BRONCHOSCOPY IN DIAGNOSING OF SMEAR NEGATIVE PULMONARY TUBERCULOSIS. / DOPRINOS FIBERBRONHOSKOPIJE DIJAGNOSTICI PLUCNE TUBERKULOZE U INICIJALNIM, DIREKTNO NEGATIVNIM UZORCIMA SPUTUMA.

The study has analysed the role and signifi cance of fi brobronchoscopy in the early and defi nitive diagnosis of active pulmonary tuberculosis in 102 patients treated on the Pulmonary Ward of 'Dr Ivo Pedisic' hospital in Sisak ­ location Petrinja from 1st January 2007 to 31st December 2012 and whose initial sputum specimens directly tested negative for acid resistant bacilli. What has been analysed is the diagnostic effi ciency of particular bronchoscopic procedures themselves and their combinations. An early diagnosis of active tuberculosis has been made in 31 patients (30,39%), and defi nitive diagnosis in 67 patients (65,68%). The etiological diagnosis of active pulmonary tuberculosis has been made only on the basis of specimens taken during fi brobronchoscopy in 28 patients (9,65%). A statistically signifi cant number of patients in whom diagnosis has been made by fi brobronchoscopy emphasizes the importance of this method in the etiological diagnostics of active pulmonary TB in those patients whose sputum samples are microscopically directly negative and/or in those who cannot spontaneously expectorate valid sputum.

Image processing for AFB segmentation in bacilloscopies of pulmonary tuberculosis diagnosis.

Image segmentation applied to medical image analysis is still a critical and important task. Although there exist several segmentation algorithms that have been widely studied in literature, these are subject to segmentation problems such as over- and under-segmentation as well as non-closed edges. In this paper, a simple method that combines well-known segmentation algorithms is presented. This method is applied to detect acid-fast bacilli (AFB) in bacilloscopies used to diagnose pulmonary tuberculosis (TB). This diagnosis can be performed through different tests, and the most used worldwide is smear microscopy because of its low cost and effectiveness. This diagnosis technique is based on the analysis and counting of the bacilli in the bacilloscopy observed under an optical microscope. The proposed method is used to segment the bacilli in digital images from bacilloscopies processed using Ziehl-Neelsen (ZN) staining. The proposed method is fast, has a low computational cost and good efficiency compared to other methods. The bacilli image segmentation is performed by image processing and analysis techniques, probability concepts and classifiers. In this work, a Bayesian classifier based on a Gaussian mixture model (GMM) is used. The segmentations' results are validated by using the Jaccard index, which indicates the efficiency of the classifier.

CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma.

BACKGROUND: Intraluminal contributor(s) to airflow obstruction in severe asthma are patient-specific and must be evaluated to personalize treatment. The occurrence and functional consequence of airway mucus in the presence or absence of airway eosinophils remain undetermined. OBJECTIVE: The objective of this study was to understand the functional consequence of airway mucus in the presence or absence of eosinophils and to identify biomarkers of mucus-related airflow obstruction. METHODS: Mucus plugs were quantified on CT scans, and their contribution to ventilation heterogeneity (using MRI ventilation defect percent [VDP]) was evaluated in 27 patients with severe asthma. Patients were dichotomized based on sputum eosinophilia such that the relationship between mucus, eosinophilia, and ventilation heterogeneity could be investigated. Fractional exhaled nitric oxide (Feno) and related cytokines in sputum were measured. RESULTS: Mucus plugging was present in 100% of asthma patients with sputum eosinophils and 36% of those without sputum eosinophils (P = .0006) and was correlated with MRI VDP prebronchodilator (r = 0.68; P = .0001) and postbronchodilator (r = 0.72; P < .0001). In a multivariable regression, both mucus and eosinophils contributed to the prediction of postbronchodilator MRI VDP (R2 = 0.75; P < .0001). Patients with asthma in whom the mucus score was high had raised Feno (P = .03) and IL-4 (P = .02) values. Mucus plugging correlated with Feno (r = 0.63; P = .005). CONCLUSIONS: Both airway eosinophils and mucus can contribute to ventilation heterogeneity in patients with severe asthma. Patients in whom mucus is the dominant cause of airway obstruction have evidence of an upregulated IL-4/IL-13 pathway that could be identified according to increased Feno level.

Nanoparticle-Based Biosensing of Tuberculosis, an Affordable and Practical Alternative to Current Methods.

Access to community-based point-of-care, low-cost, and sensitive tuberculosis (TB) diagnostics remains an unmet need. OBJECTIVE: The objective of this study was to combine principles in nanotechnology, TB biology, glycochemistry, and engineering, for the development of a nanoparticle-based colorimetric biosensing assay (NCBA) to quickly and inexpensively detect acid-fast bacilli (AFB) in sputum samples. METHODS: In NCBA, the isolation of AFB from sputum samples was accomplished through glycan-coated magnetic nanoparticles (GMNP) interacting with AFB and then using a simple magnet to separate the GMNP-AFB complex. Acid-fastness and cording properties of mycobacteria were utilized to provide visually observable red-stained clumps of bacteria that were surrounded by brown nanoparticles under a light microscope on prepared smears. The NCBA technique was compared against sputum smear microscopy (SSM) and Xpert MTB/RIF in 500 samples from patients that were suspected to have TB. RESULTS: Statistical analysis showed that NCBA had sensitivity and specificity performances in perfect agreement with Xpert MTB/RIF as gold standard for all 500 samples. SSM had a sensitivity of 40% for the same samples. CONCLUSION: NCBA technique yielded full agreement in terms of sensitivity and specificity with the Xpert MTB/RIF in 500 samples. The method is completed in 10⁻20 min through a simple process at an estimated cost of $0.10 per test. Implementation of NCBA in rural communities would help to increase case finding and case notification, and would support programs against drug-resistance. Its use at the first point-of-contact by patients in the healthcare system would facilitate quick treatment in a single clinical encounter, thus supporting the global "End TB Strategy" by 2035.

Evaluation of a Urine-Based Rapid Molecular Diagnostic Test with Potential to Be Used at Point-of-Care for Pulmonary Tuberculosis: Cape Town Cohort.

Tuberculosis (TB) diagnosis among sputum-scarce patients is time consuming. Thus, a nonsputum diagnostic alternative is urgently needed. The Mycobacterium tuberculosis-specific transrenal (Tr) DNA from urine is a potential target for TB diagnostics. In this study, a new urine-based Tr-DNA molecular assay was evaluated for diagnosis of pulmonary tuberculosis among 428 adults suspected of having pulmonary TB (164 HIV positive, 263 HIV negative) from Cape Town, South Africa. Tr-DNA was isolated from 4 mL of EDTA urine, and a rapid, double-stranded, primer-based PCR method was performed targeting the Mycobacterium tuberculosis-specific direct repeat region. Each Tr-DNA eluate was tested in triplicate using an automated molecular analyzer with controls included in each test. With liquid culture used as the gold standard, the Tr-DNA assay showed sensitivity of 42.9% (n = 75/175; 95% CI, 35.4%-50.5%) and specificity of 88.6% (n = 210/237; 95% CI, 83.9%-92.4%). Among HIV-infected patients with TB, sensitivity and specificity were 45.2% and 89.0%, respectively. The combination of smear microscopy and Tr-DNA increased the sensitivity to 83.8% (smear microscopy alone, 75.1%), with 96.6% specificity. This study indicates that Tr-DNA has a moderate specificity with low sensitivity for diagnosis of pulmonary TB. Despite low sensitivity, this diagnostic test may have potential in combination with smear microscopy to support TB diagnosis in HIV-endemic regions, where sputum-scarce patients are common.

Establishment of hybridized focus measure functions as a universal method for autofocusing.

Exact focusing is essential for any automatic image capturing system. Performances of focus measure functions (FMFs) used for autofocusing are sensitive to image contents and imaging systems. Therefore, identification of universal FMF assumes a lot of significance. Eight FMFs were hybridized in pairs of two and implemented simultaneously on a single stack to calculate the hybrid focus measure. In total, 28 hybrid FMFs (HFMFs) and eight FMFs were implemented on stacks of images from three different imaging modalities. Performance of FMFs was found to the best at 50% region sampling. Accuracy, focus error, and false maxima were calculated to evaluate the performance of each FMF. Nineteen HFMFs provided >90% accuracy. Image distortion (noise, contrast, saturation, illumination, etc.) was performed to evaluate robustness of HFMFs. Hybrid of tenengrad variance and steerable filter-based (VGRnSFB) FMFs was identified as the most robust and accurate function with an accuracy of ≥90% and a relatively lower focus error and false maxima rate. Sharpness of focus curve of VGRnSFB along with eight individual FMFs was also computed to determine the efficacy of HFMF for the optimization process. VGRnSFB HFMF may be implemented for automated capturing of an image for any imaging system.

Automated 3-dimensional morphologic analysis of sputum specimens for lung cancer detection: Performance characteristics support use in lung cancer screening.

BACKGROUND: The LuCED Lung Test comprises an automated 3-dimensional morphologic analysis of epithelial cells in sputum. For each cell, 594 morphology-based features are measured to drive algorithmic classifiers that quantitatively assess whether neoplastic cells are present. The current interim clinical study involves sputum samples from patients with known benign and malignant outcomes to assess the feasibility of LuCED as an adjunctive test after suspicious low-dose computed tomography (LDCT) results or as an independent screening test for lung cancer. METHODS: Sputum samples were fixed, enriched for epithelial cells, and analyzed with a 3-dimensional cell scanner called Cell-CT. Candidate abnormal cells were identified by the classifiers for manual review. The sensitivity, specificity, and negative and positive predictive values were calculated for the detection of neoplastic cases. RESULTS: A total of 91 sputum samples from patients with confirmed lung cancer (49 patients) and patients with no known malignancy (42 patients) were evaluated. After cytology review, sensitivity in the positive group was 91.8%, and specificity was 95.2%. Specificity was not 100% because there were 2 cases in which abnormal cells were identified by the Cell-CT that were confirmed as such at the time of manual cytology review. However, at the time of last follow-up, malignancy had not been detected in these 2 cases. Modeling in a population with a 1% prevalence of lung cancer, the positive and negative predictive values would be 95.4% and 99.9%, respectively. CONCLUSIONS: LuCED testing is highly sensitive and specific for the detection of lung cancer and has potential value as an adjunctive test after suspicious LDCT findings or as a primary screening test in which LuCED-positive cases would be triaged to diagnostic CT. Further prospective studies currently are underway to evaluate its full usefulness.

The Cell-CT 3-dimensional cell imaging technology platform enables the detection of lung cancer using the noninvasive LuCED sputum test.

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer has changed little over the past 40 years. Early detection through emerging lung cancer screening programs promise the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Screening Trial reported that screening using 3 consecutive low-dose x-ray computed tomography scans provides a 20% reduction in lung cancer mortality compared with chest x-ray. However, this reduction in mortality comes with an unacceptable false-positive rate that increases patient risks and the overall cost of lung cancer screening. The LuCED test for detection of early lung cancer is reviewed in the current article. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT, which images cells in 3 dimensions with submicron resolution. Algorithms are applied to the 3-dimensional cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification that could enable the cost-effective detection of lung cancer.

The effects of postural drainage and positive expiratory pressure physiotherapy on tracheobronchial clearance in cystic fibrosis.

We studied the effects of two chest physiotherapy regimens on whole lung and regional tracheobronchial clearance (TBC) in ten patients with cystic fibrosis. The regimens were given on two separate days and consisted of 20 min of (1) postural drainage and the forced expiration technique (PD + FET), and (2) positive expiratory pressure (PEP-mask) and FET (PEP + FET). A third day served as control. The study days were randomized. Each day, the clearance of lung radioactivity was measured for 3 h by gamma camera. The number of spontaneous coughs was recorded and the sputum expectorated was sampled. We found that both PD + FET and PEP + FET improved whole lung TBC at 30 minutes and 1 h four or fivefold (p less than 0.01) compared with control, whereas at 2 h and 3 h only the improvement following PEP + FET (approximately 1.4 times) was significant (p less than 0.05). There was no significant difference in whole lung or regional TBC between the PD + FET and PEP + FET treatments. The correlations between TBC and the radioactivity content in sputum expectorated (rs2 = 0.76) and between TBC and numbers of coughs (rs2 = 0.65) were better than between TBC and the weight of sputum expectorated (Rs = 0.39). We conclude that PD or PEP when combined with FET have similar effects on short-term whole lung and regional TBC in patients with cystic fibrosis. Evaluation of TBC during chest physiotherapy when only based on the weight of sputum expectorated seems inadequate.

Association between gallium-67 uptake by lung foci and sputum smear status in patients with pulmonary tuberculosis.

OBJECTIVES: Rapid determination of the inflammatory and sputum smear status in patients with pulmonary tuberculosis (PTB) is crucial for clinical decision making. The purpose of this study was to assess the relationship between gallium-67 (Ga-67) uptake by lung foci and sputum smear status in patients with PTB. We also attempted to predict the patients with acid-fast bacilli (AFB) smear-positive PTB by means of a semiquantitative measurement of Ga-67 uptake ratio using single-photon emission computed tomography images. PATIENTS AND METHODS: Ninety-five patients with PTB were enrolled in this retrospective study. A volume-of-interest method was used to quantify Ga-67 uptake in single-photon emission computed tomography images. The Ga-67 uptake ratio was defined as the maximum voxel value of the pulmonary lesion divided by the maximum voxel value of normal lung tissue. RESULTS: The Ga-67 uptake ratio was higher in patients with active PTB than in those with inactive PTB (3.11 ± 1.52 vs. 1.42 ± 0.14, P<0.01). In active PTB, the Ga-67 uptake ratio was higher in smear-positive patients than in smear-negative patients (3.41 ± 1.60 vs. 2.16 ± 0.61, P<0.01). In patients with AFB smear grades 1+, 2+, and 3+, the Ga-67 uptake ratios were 2.51 ± 0.81, 3.30 ± 1.57, and 4.23 ± 1.73, respectively. The correlation between Ga-67 uptake ratio and AFB smear grading was statistically significant (Spearman's ρ=0.60, P<0.01). In receiver operating characteristic curve analyses, the area under the curve for the Ga-67 uptake ratio was 0.95 ± 0.02 (P<0.01) for predicting active PTB and 0.87 ± 0.04 (P<0.01) for predicting smear-positive active PTB. CONCLUSION: In patients with active PTB, more-intense Ga-67 uptake was associated with more AFB load in the sputum - that is a greater potential to transmit PTB. This finding might facilitate clinical decision making for immediate isolation and treatment to reduce transmission of PTB.

Induced sputum derives from the central airways: confirmation using a radiolabeled aerosol bolus delivery technique.

Indirect evidence suggests that induced sputum derives from the surfaces of the bronchial airways. To confirm this experimentally, we employed a radiolabeled aerosol bolus delivery technique that preferentially deposits aerosol in the central airways in humans. We hypothesized that there would be significantly more radioactivity recovered in an induced sputum sample, and greater airways clearance of radiolabeled particles, immediately after a central versus peripheral airways deposition. Ten healthy volunteers underwent radiolabeled aerosol deposition ((99m)Tc sulfur colloid particles) to the central and peripheral airways on separate occasions followed immediately by induced sputum or no sputum (control), while seated in front of a gamma camera. Radioactivity was measured in the selected sputum sample, processed cell pellet, and supernatant fraction. Significantly more radioactivity was present in all portions of the sputum sample after central versus peripheral airways deposition (i.e., selected sample: 15,607 counts +/- 2,985 versus 943 counts +/- 298, p = 0.001). Clearance from the whole lung was significantly greater 40 min after central versus peripheral airways deposition (48 +/- 3% versus 5 +/- 1%, p = 0.0001). Compared with control, induced sputum greatly enhanced clearance after central deposition (48 +/- 3% versus 11 +/- 6%, p = 0.0001), but not after peripheral deposition (5 +/- 1% versus 3 +/- 0.8%). These results provide direct evidence that induced sputum derives from the central airways with little or no contribution from the peripheral airways.