Sputum Colour Research Articles

The Sputum Colour Chart as a predictor of lung inflammation, proteolysis and damage in non‐cystic fibrosis bronchiectasis: A case–control analysis

Non-cystic fibrosis bronchiectasis (NCFB) is characterized by a vicious cycle of airway infection, inflammation and structural damage with inappropriate mucus clearance. Our aim was to relate the value of proteolytic enzymes, proteolytic enzyme activity and inflammatory markers to disease severity and symptoms in patients with NCFB. Sputum induction in NCFB patients and healthy controls was performed. Sputum was analysed for total and differential cell count, markers of inflammation (CXCL8 (also known as interleukin-8) and tumour necrosis factor-α (TNF-α)) and proteolytic enzymes (neutrophil elastase (NE), gelatin zymography and total gelatinolytic activity (TGA)). Each patient was evaluated by spirometry, Leicester Cough Questionnaire (LCQ) and Sputum Colour Chart (SCC). Patient files were analysed to determine Pseudomonas aeruginosa colonization status. The computed tomography (CT) closest to the date sputum induction was scored by a radiologist. NCFB patients showed significantly higher neutrophils, CXCL8, TNF-α, NE and TGA than healthy controls. TGA subanalysis showed that the majority of the activity was NE (82 ± 6.4%). Residual activity was mainly zinc ion-dependent matrix metalloproteinase (MMP) activity (18 ± 6.4%). Subanalysis showed that patients with chronic Pseudomonas aeruginosa colonization had more activated MMP-9. Correlations were seen between proteolytic enzymes and inflammation and disease severity (spirometry and CT score), but not with the LCQ. SCC was associated with increased markers of inflammation, proteolytic enzymes and worse CT score. We show that sputum purulence assessment in daily clinical practice using the SCC is a quick and easy tool that reflects severity of inflammation, destruction and proteolytic enzymatic activity/presence.

Effects of long‐term azithromycin therapy on airway oxidative stress markers in non‐cystic fibrosis bronchiectasis

To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate (EBC) of adult patients with stable non-cystic fibrosis (CF) bronchiectasis. Open-label prospective study of 30 patients randomized to azithromycin 250 mg three times per week during 3 months (16 patients) or control (14 patients). Primary outcome were changes in nitric oxide, 8-isoprostane, pH, nitrites and nitrates in EBC. Secondary outcomes were changes in exacerbation rates, dyspnoea (Borg scale), sputum volume (cc), sputum colour (15-point scale), bacterial infection, health-related quality of life (St George's Respiratory Questionnaire), lung function and radiological extension. Azithromycin produced a significant decrease in sputum volume (8.9 (1.8) mL vs 2.1 (3.4) mL) and number of exacerbations (0.1 (0.6) vs 1.2 (0.9)). Dyspnoea (0.4 (0.1) vs 0.1 (0.2)) and health-related quality of life also improved after therapy. However, oxidative stress markers in EBC, systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy. A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients. In this subgroup, treatment was followed by a significant reduction in sputum volume, number of exacerbations, dyspnoea and St George's Respiratory Questionnaire total score. Of all airway oxidative stress markers, only nitrates in EBC were reduced after therapy. Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis, but it does not affect airway oxidative stress markers.

Extraction and Segmentation of Sputum Cells for Lung Cancer Early Diagnosis

Lung cancer has been the largest cause of cancer deaths worldwide with an overall 5-year survival rate of only 15%. Its symptoms can be found exclusively in advanced stages where the chances for patients to survive are very low, thus making the mortality rate the highest among all other types of cancer. The present work deals with the attempt to design computer-aided detection or diagnosis (CAD) systems for early detection of lung cancer based on the analysis of sputum color images. The aim is to reduce the false negative rate and to increase the true positive rate as much as possible. The early detection of lung cancer from sputum images is a challenging problem, due to both the structure of the cancer cells and the stained method which are employed in the formulation of the sputum cells. We present here a framework for the extraction and segmentation of sputum cells in sputum images using, respectively, a threshold classifier, a Bayesian classification and mean shift segmentation. Our methods are validated and compared with other competitive techniques via a series of experimentation conducted with a data set of 100 images. The extraction and segmentation results will be used as a base for a CAD system for early detection of lung cancer which will improve the chances of survival for the patient.

Automatic Sputum Color Image Segmentation for Lung Cancer Diagnosis

Lung cancer is considered to be the leading cause of cancer death worldwide. A technique commonly used consists of analyzing sputum images for detecting lung cancer cells. However, the analysis of sputum is time consuming and requires highly trained personnel to avoid errors. The manual screening of sputum samples has to be improved by using image processing techniques. In this paper we present a Computer Aided Diagnosis (CAD) system for early detection and diagnosis of lung cancer based on the analysis of the sputum color image with the aim to attain a high accuracy rate and to reduce the time consumed to analyze such sputum samples. In order to form general diagnostic rules, we present a framework for segmentation and extraction of sputum cells in sputum images using respectively, a Bayesian classification method followed by region detection and feature extraction techniques to determine the shape of the nuclei inside the sputum cells. The final results will be used for a (CAD) system for early detection of lung cancer. We analyzed the performance of a Bayesian classification with respect to the color space representation and quantification. Our methods were validated via a series of experimentation conducted with a data set of 100 images. Our evaluation criteria were based on sensitivity, specificity and accuracy.

Significance of sputum purulence to guide antibiotic therapy in exacerbations of COPD

From the authors: We thank D. Aggarwal and co-workers for their interest in our recently published paper regarding a sputum purulence-guided strategy of antibiotic treatment in patients with exacerbations of chronic obstructive pulmonary disease (COPD) requiring hospitalisation [1]. Their comments highlight important issues relating to the discrepancies reported in the literature about the relationship between sputum colour and the presence of pathogenic bacteria in the lower respiratory tract. First, the question of whether isolation of bacteria from the sputum of patients with COPD is or is not directly related to exacerbations is still a subject of controversy. Classically, the Anthonisen criteria ( i.e . increased dyspnoea, sputum production and sputum purulence) have been considered the most reliable predictors of bacterial infection as a cause of exacerbation [2]. Moreover, the most relevant advance in our ability to predict bacterial …

Sputum color guides antibiotic treatment in COPD

Sputum color guides antibiotic treatment in COPD

Lung Cancer Detection by Using Artificial Neural Network and Fuzzy Clustering Methods

The early detection of lung cancer is a challenging problem, due to the structure of the cancer cells, where most of the cells are overlapped with each other. This paper presents two segmentation methods, Hopfield Neural Network (HNN) and a Fuzzy C-Mean (FCM) clustering algorithm, for segmenting sputum color images to detect the lung cancer in its early stages. The manual analysis of the sputum samples is time consuming, inaccurate and requires intensive trained person to avoid diagnostic errors. The segmentation results will be used as a base for a Computer Aided Diagnosis (CAD) system for early detection of lung cancer which will improve the chances of survival for the patient. However, the extreme variation in the gray level and the relative contrast among the images make the segmentation results less accurate, thus we applied a thresholding technique as a pre-processing step in all images to extract the nuclei and cytoplasm regions, because most of the quantitative procedures are based on the nuclear feature. The thresholding algorithm succeeded in extracting the nuclei and cytoplasm regions. Moreover, it succeeded in determining the best range of thresholding values. The HNN and FCM methods are designed to classify the image of N pixels among M classes. In this study, we used 1000 sputum color images to test both methods, and HNN has shown a better classification result than FCM, the HNN succeeded in extracting the nuclei and cytoplasm regions.

S107 The influence of viral symptoms in infective exacerbations of non-cystic fibrosis bronchiectasis

AimThe aim of this study was to determine whether presence of viral symptoms influenced severity or outcome of exacerbations of bronchiectasis.MethodsPatients presenting to our outpatient service with exacerbations of bronchiectasis...

P210 Which symptoms prompt patients with an exacerbation of COPD to persevere, self-treat or seek care? A comparison with health professionals

Introduction and ObjectivesExacerbations of Chronic Obstructive Pulmonary Disease are a major cause of morbidity and mortality. Despite the increased healthcare utilisation involved in treatment, little is known about how patients...

Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis

We examined the correlation between sputum colour and the presence of potentially pathogenic bacteria in acute exacerbations of chronic bronchitis (AECBs). Data were pooled from six multicentre studies comparing moxifloxacin with other antimicrobials in patients with an AECB. Sputum was collected before antimicrobial therapy, and bacteria were identified by culture and Gram staining. Association between sputum colour and bacteria was determined using logistic regression. Of 4,089 sputum samples, a colour was reported in 4,003; 1,898 (46.4%) were culture-positive. Green or yellow sputum samples were most likely to yield bacteria (58.9% and 45.5% of samples, respectively), compared with 18% of clear and 39% of rust-coloured samples positive for potentially pathogenic microorganisms. Factors predicting a positive culture were sputum colour (the strongest predictor), sputum purulence, increased dyspnoea, male sex and absence of fever. Green or yellow versus white sputum colour was associated with a sensitivity of 94.7% and a specificity of 15% for the presence of bacteria. Sputum colour, particularly green and yellow, was a stronger predictor of potentially pathogenic bacteria than sputum purulence and increased dyspnoea in AECB patients. However, it does not necessarily predict the need for antibiotic treatment in all patients with AECB.

Defining pulmonary exacerbation in children with non‐cystic fibrosis bronchiectasis

Exacerbations in non-cystic fibrosis (CF) bronchiectasis are associated with worsening lung functions and quality of life. A standardized definition of exacerbation could improve clinical care and research. To formulate a clinically useful definition of pulmonary exacerbation for pediatric non-CF bronchiectasis. A cohort of 69 children with non-CF bronchiectasis was prospectively followed for 900 child-months. The changes in clinical, systemic, and lung function parameters from 81 exacerbations were statistically evaluated using conditional logistic regression, receiver operating characteristic, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) to formulate a definition of a pulmonary exacerbation. Formation of major and minor criteria was statistically based and models were developed. Wet cough and cough severity (score ≥ 2) over 72-hr were the best predictors of an exacerbation with area under the curve (AUC) of 0.85 (95% CI 0.79-0.92) and 0.84 (95% CI 0.77-0.91), respectively. Sputum color, chest pain, dyspnea, hemoptysis, and chest signs were significant though minor criteria. Inclusion of serum C-reactive protein, amyloid-A, and IL6 to the definition improved its specificity and PPV. Our final combined model consisted of one major with one investigatory criterion (PPV 91%, NPV 72%); two major criteria (PPV 79%, NPV 91%); or one major and two minor criteria (PPV 79%, NPV 94%). Pulmonary exacerbation in children with non-CF bronchiectasis can be validly predicted using a standardized assessment of clinical features, with additional systemic markers improving predictive values. This definition potentially facilitates earlier detection (leading to appropriate management) of exacerbations.

The Effect of Chronic Sputum Production on Respiratory Symptoms in Severe COPD

Background: Chronic sputum production is a significant but variable complaint in COPD; its effect on symptom burden has not been comprehensively described. We sought to characterize the daily burden of chronic sputum production in severe COPD and the phenotype of those with chronic sputum symptoms. Methods: We studied 50 outpatients with severe COPD who used an electronic diary to document peak expiratory flow (PEF) and respiratory symptoms daily for up to 2 years. A sputum index was derived based on complaints of sputum quantity, color, and consistency, and patients were divided into groups based on average daily sputum index (Low, Medium, High). The presence and severity of respiratory symptoms were scored by a novel method using daily changes in symptoms and PEF from baseline and were categorized into mild, moderate, and severe. Percent emphysema was measured using quantitative CT. Results: In the 14,500 observation days, severe symptom days were greater in the Medium and High groups (379/6089, 1609/4091, and 2624/4317 observation days in Low, Medium, and High, p < 0.0001). The same trend was found even when sputum complaints were removed from the symptom severity score. Observed/predicted PEF ratio was lower in the High group (0.56 ± 0.24, 0.55 ± 0.19, and 0.42 ± 0.12 in each group, p < 0.05 for High compared to Medium and Low). Percent emphysema inversely correlated with average sputum index and quantity (r = −0.449 and r = −0.584, respectively, p < 0.05). Conclusions: Increased sputum production in severe COPD is frequently encountered daily and is associated with more respiratory symptoms, worse airflow obstruction, and less emphysema.

Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection

We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p = 0.68) or green (coefficient -0.01; p = 0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p = 0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.

Treatment of acute cough/lower respiratory tract infection by antibiotic class and associated outcomes: a 13 European country observational study in primary care

Acute cough/lower respiratory tract infection (LRTI) is one of the commonest reasons for consulting and antibiotic prescribing. There are theoretical reasons why treatment with particular antibiotic classes may aid recovery more than others, but empirical, pragmatic evidence is lacking. We investigated whether treatment with a particular antibiotic class (amoxicillin) was more strongly associated with symptom score resolution and time to patients reporting recovery than each of eight other antibiotic classes or no antibiotic treatment for acute cough/LRTI. Clinicians recorded history, examination findings, symptom severity and antibiotic treatment for 3402 patients in a 13 country prospective observational study of adults presenting in 14 primary care research networks with acute cough/LRTI. 2714 patients completed a symptom score daily for up to 28 days and recorded the day on which they felt recovered. A three-level autoregressive moving average model (1,1) model investigated logged daily symptom scores to analyse symptom resolution. A two-level survival model analysed time to reported recovery. Clinical presentation was controlled for using clinician-recorded symptoms, sputum colour, temperature, age, co-morbidities, smoking status and duration of illness prior to consultation. Compared with amoxicillin, no antibiotic class (and no antibiotic treatment) was associated with clinically relevant improved symptom resolution (all coefficients in the range -0.02 to 0.01 and all P values greater than 0.12). No antibiotic class (and no antibiotic treatment) was associated with faster time to recovery than amoxicillin. Treatment by antibiotic class was not associated with symptom resolution or time to recovery in adults presenting to primary care with acute cough/LRTI.

Sputum colour reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of chronic obstructive pulmonary disease

Sputum colour is regarded as a good marker of bacterial involvement in acute exacerbations of chronic obstructive pulmonary disease (COPD) and guides many physicians in deciding on antibiotic treatment. Although most doctors rely on the sputum colour that is reported by patients, it can also be assessed using a validated colour chart. In this study, reported sputum colour and assessed sputum colour were compared as markers of the presence of bacteria, bacterial load, and systemic inflammation. Data on 257 exacerbations in 216 patients hospitalized with an acute exacerbation were analysed (mean age, 72 years; mean forced expiratory volume in 1 s, 44.8% ± 17.8% (± standard deviation)). Sputum colour was reported by the patients and assessed at the laboratory with a colour chart. Subsequently, quantitative sputum cultures were performed. C-reactive protein was measured as a marker of systemic inflammation. A sputum sample was obtained in 216 exacerbations (84%), of which 177 (82%) were representative. A pathogen was identified in 155 patients (60%). Assessed sputum colour was a better marker of the presence of bacteria (OR 9.8; 95% CI 4.7–20.4; p <0.001) than reported sputum colour (OR 1.7; 95% CI 1.0–3.0; p 0.041). The sensitivity and specificity were 73% and 39% for reported sputum colour, and 90% and 52% for assessed sputum colour. Assessed sputum colour was clearly related to sputum bacterial load and C-reactive protein levels, whereas reported sputum colour was not. It is concluded that sputum colour reported by patients is an unreliable marker of the presence of bacteria in acute exacerbations of COPD. Assessed sputum colour is clearly superior and is also related to bacterial load and systemic inflammation.

Colour of sputum is a marker for bacterial colonisation in chronic obstructive pulmonary disease

BackgroundBacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations. We assessed risk factors for bacterial colonisation in COPD.MethodsPatients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis. Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥102 colony-forming units (CFU)/mL on quantitative bacterial culture. Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load.ResultsA total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated. Bacterial colonisation was demonstrated in 58 (48.7%) patients. Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour. Thirty-six patients (62% of those colonised) had a high bacterial load. More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture. In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001). Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum.ConclusionsAlmost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs. Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised.

Inflammation Markers in the Exhaled Air of Patients with Bronchiectasis Unassociated with Cystic Fibrosis

Introduction The aim of the study was to analyse the relationship between the intensity of the respiratory tract inflammation, expressed by oxidative stress markers, and the severity of the disease in patients with bronchiectasis unassociated with cystic fibrosis. Patients and methods The study included 25 patients with stable bronchiectasis (15 females and 10 males). As determining factors of severity, the following parameters were collected: degree of dyspnoea, number of exacerbations/admissions in the last year, mean daily sputum volume, sputum colour (graduated colour scale), bacterial colonisation, respiratory function tests, quality of life (St. George questionnaire) and radiological extension of the lesions (Bhalla scale). Inflammation was analysed using the measurement of nitric oxide, pH and concentration of nitrites, nitrates and isoprostane in the exhaled air condensate. The C reactive protein and erythrocyte sedimentation rate were also determined in peripheral blood. Results There were no significant relationships between the markers in the exhaled air condensate and the clinical, radiological and functional involvement or the quality of life of the patients. Only bacterial colonisation (16 cases) was associated with higher values of nitrates in exhaled air (mean ± standard deviation: 18 ± 4 compared to 7 ± 2 μM; r 2 = 0.6) and a higher number of exacerbations (3.1 ± 1.9 compared to 1.7 ± 1.9; r 2 = 0.3). Conclusions In our study, the measurement of inflammation markers in exhaled air is only associated with some parameters of severity in patients with bacterial bronchiectasis.

Estudio de marcadores de inflamación en el aire exhalado de pacientes con bronquiectasias no asociadas a fibrosis quística

Introduction The aim of the study was to analyse the relationship between the intensity of the respiratory tract inflammation, expressed by oxidative stress markers, and the severity of the disease in patients with bronchiectasis unassociated with cystic fibrosis. Patients and methods The study included 25 patients with stable bronchiectasis (15 females and 10 males). As determining factors of severity, the following parameters were collected: degree of dyspnoea, number of exacerbations/admissions in the last year, mean daily sputum volume, sputum colour (graduated colour scale), bacterial colonisation, respiratory function tests, quality of life (St. George questionnaire) and radiological extension of the lesions (Bhalla scale). Inflammation was analysed using the measurement of nitric oxide, pH and concentration of nitrites, nitrates and isoprostane in the exhaled air condensate. The C reactive protein and erythrocyte sedimentation rate were also determined in peripheral blood. Results There were no significant relationships between the markers in the exhaled air condensate and the clinical, radiological and functional involvement or the quality of life of the patients. Only bacterial colonisation (16 cases) was associated with higher values of nitrates in exhaled air (mean±standard deviation: 18±4 compared to 7±2 μM; r 2=0.6) and a higher number of exacerbations (3.1±1.9 compared to 1.7±1.9; r 2=0.3). Conclusions In our study, the measurement of inflammation markers in exhaled air is only associated with some parameters of severity in patients with bacterial bronchiectasis.

Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis

This study explored the utility of sputum colour in clinically stable patients with bronchiectasis. Interpretation of sputum colour between the doctor and the patient was reliable (intraclass correlation coefficient 0.83 (95% confidence interval 0.76-0.89). Sputum colour predicted bacterial colonisation (5% in mucoid sputum; 43.5% in mucopurulent sputum; 86.4% in purulent sputum; p<0.0001). On multivariate logistic regression analysis, independent factors associated with purulent sputum were bacterial colonisation, varicose or cystic bronchiectasis, forced expiratory volume in 1 s <80% predicted and diagnosis of bronchiectasis aged <45 yrs.

Value of adding a polyvalent mechanical bacterial lysate to therapy of COPD patients under regular treatment with salmeterol/fluticasone

This study investigated the value of adding Ismigen, a polyvalent mechanical bacterial lysate, to therapy of COPD patients (FEV(1) <60% predicted) under regular treatment with salmeterol/fluticasone (SFC). 63 patients enrolled from September to December 2007 were randomly divided into two groups (A and B). All patients were treated with salmeterol/fluticasone (SFC) 50/500 microg BID. Thirty-three subjects also received Ismigen one capsule daily the first 10 days of three consecutive months (group B). This treatment was reaped three months after the end of the first course. We assessed at inclusion and at scheduled (every 2 months) or intercurrent visit: symptoms (amount and colour of sputum, severity of dyspnoea, frequency of cough, fever), diagnosis of exacerbation, concomitant medications (antibiotics and oral corticosteroids) and hospitalization. During the course of the study two patients died. At the end of the observation period (12 months), another six patients could not be visited because they had withdrawn. Compared with SFC, adding on Ismigen reduced the total number of exacerbations (23 out of 30 patients in group A and 21 out of 33 patients in group B), the number (rate) of exacerbations per patient per year (18 out of 27 patients [0.67] in group A and 15 out of 28 patients [0.54] in group B), the number of exacerbations that needed treatment with oral corticosteroids (12 out of 23 [52%] in group A and 9 out of 21 [43%] in group B) and the total number (rate) of hospitalizations (4/30 [0.13] in group A and 3/33 [0.09] in group B). There were no significant differences between treatments with respect to their effect on the symptoms of exacerbations. A decrease in the need for antibiotics was also observed in group B. Our data suggest that COPD patients benefit from the addition of Ismigen on top of the routine maintenance treatment with SFC.