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Physiological Research Mar 2020Asthma is a complex disease with a variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not... (Review)
Review
Asthma is a complex disease with a variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. Biomarker research has expanded greatly with the advancement of molecular research techniques. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient - exhaled breath analysis, blood cells and serum biomarkers, sputum cells and mediators and urine metabolites could be potential biomarkers of asthma bronchiale. Unfortunately, at the moment, an ideal biomarker doesn't exist and the overlap between the biomarkers is a reality. Using panels of biomarkers could improve probably the identification of asthma endotypes in the era of precision medicine.
Topics: Animals; Asthma; Biomarkers; Humans; Precision Medicine; Predictive Value of Tests; Sputum
PubMed: 32228009
DOI: 10.33549/physiolres.934398 -
Thorax Dec 1975Bronchorrohea has been defined as a condition in which more than 100 ml of sputum is produced within 24 hours, an amount in excess of that seen in chronic lung diseases....
Bronchorrohea has been defined as a condition in which more than 100 ml of sputum is produced within 24 hours, an amount in excess of that seen in chronic lung diseases. The rheological and chemical characteristics of the sputum are here described. Levels of viscosity, dry weight, N-acetyl neuraminic acid (NANA), fucose, and sulphate fall between those in saliva and mucoid sputum from chronic lung diseases. These levels were always higher in bronchorrhoea sputum than in saliva and therefore may be used in the differential diagnosis of bronchorrhoea and hypersalivation. Bronchorrhoea sputum has the constituents of a bronchial secretion but is low in acid glycoprotein. Certain other features are commonly found - a large amount of froth, increase in viscosity with time, and separation into two phases. Some cases respond to steroids, particularly when the levels of NANA in the sputum are low.
Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Bronchial Diseases; Bronchiectasis; Bronchitis; Circadian Rhythm; Elasticity; Female; Fucose; Humans; Lung Neoplasms; Male; Middle Aged; Neuraminic Acids; Sputum; Sulfates; Viscosity
PubMed: 176747
DOI: 10.1136/thx.30.6.624 -
Oxidative Medicine and Cellular... 2016Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In... (Review)
Review
Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases.
Topics: Antioxidants; Biomarkers; DNA Damage; Humans; Oxidative Stress; RNA; Sputum
PubMed: 26885248
DOI: 10.1155/2016/2930434 -
The European Respiratory Journal Aug 2000Over the past few years cellular and biochemical sputum examinations have become important instruments to assess airway inflammation. The aim of this review is to... (Review)
Review
Over the past few years cellular and biochemical sputum examinations have become important instruments to assess airway inflammation. The aim of this review is to summarize new methodological developments and aspects, which are currently under investigation. The use of isotonic saline has increased safety of inductions in patients with severe asthma and in children. The origin of sputum is better understood, as is the need to standardize the volume and duration of induction. It also needs to be borne in mind that the induction procedure itself is able to cause changes in sputum composition. However, the basic induction and processing procedures have not changed much over the last few years, and therefore the method is still time consuming. The analysis of ECP in lysed sputum cells as a marker for the number of eosinophils has been suggested to overcome this problem, but needs further validation. Furthermore, storage of sputum has been studied, as well as early fixation or freezing of sputum cells to elongate the time between induction and processing. Differential cell counts by flow cytometry are still difficult, but the method has increased knowledge concerning lymphocyte subsets and the activation status of sputum cells. The use of induced sputum to noninvasively measure airway inflammation in clinical trials will offer additional information, but the proper use and interpretation of sputum outcome parameters will need further investigation.
Topics: Administration, Inhalation; Clinical Trials as Topic; Humans; Methods; Safety; Saline Solution, Hypertonic; Sputum; Time Factors
PubMed: 10968514
DOI: 10.1034/j.1399-3003.2000.16b26.x -
BMC Pulmonary Medicine Nov 2022Currently, the microbial etiology of community-acquired pneumonia in children remains challenging. While Gram stain and sputum culture are commonly used to detect...
Value of sputum Gram stain, sputum culture, and bronchoalveolar lavage fluid Gram stain in predicting single bacterial pathogen among children with community-acquired pneumonia.
BACKGROUND
Currently, the microbial etiology of community-acquired pneumonia in children remains challenging. While Gram stain and sputum culture are commonly used to detect bacterial pathogens, it is unclear whether these approaches can predict single pathogen from bronchoalveolar lavage fluid (BALF) culture.
METHODS
A retrospective study involving 287 children hospitalized for pneumonia was conducted. Sputum specimens were collected on admission; and BALF specimens were collected within 24 h after admission. Taking BALF culture as the reference standard, the sensitivity and specificity of Sputum Gram stain (SGS), sputum culture, and BALF Gram stain (BGS) were calculated. The agreement between these approaches and BALF culture was compared using kappa statistics.
RESULTS
For SGS, the specificity was 23%. The overall sensitivity was 70%, including 87% for Gram-positive (G+) cocci, 56% for Gram-negative (G-) cocci, and 50% for G-bacilli. For sputum culture, the specificity was 70%. The overall sensitivity was 64%, including 71% for Streptococcus pneumoniae, 71% for Moraxella catarrhalis, and 64% for Haemophilus influenzae. For BGS, the specificity was 71%. The overall sensitivity was 60%, including 77% for G+cocci, 38% for G-cocci, and 44% for G-bacilli. While SGS had poor agreement with BALF culture, both sputum culture and BGS had moderate agreement with BALF culture.
CONCLUSIONS
Both sputum culture and BGS are helpful in predicting single bacterial pathogen from BALF culture among children with community-acquired pneumonia. Sputum cultures and BGS can provide early clues for BALF pathogen when BALF culture results are pending or bronchoscopy is not performed.
Topics: Humans; Child; Bronchoalveolar Lavage Fluid; Sputum; Retrospective Studies; Community-Acquired Infections; Pneumonia; Bacteria
PubMed: 36402959
DOI: 10.1186/s12890-022-02234-1 -
Journal of Visualized Experiments : JoVE Dec 2017The technique of sputum induction and processing is a recognized non-invasive method allowing the collection and analysis of cells from the airways, which is interesting...
The technique of sputum induction and processing is a recognized non-invasive method allowing the collection and analysis of cells from the airways, which is interesting in various respiratory diseases like asthma, chronic obstructive pulmonary disease (COPD), chronic cough, or idiopathic pulmonary fibrosis. This technique is well tolerated, safe and non-invasive, but is currently limited to research services and specialized centers in clinical practice because it is technically demanding, time-consuming, and requires trained staff. The success rate of sputum induction and analysis is about 80%. Here, we describe the induction and laboratory processing of sputum samples. Sputum is induced by inhalation of hypertonic or isotonic saline with salbutamol. For the processing, we use the whole sputum technique. Dithiothreitol (DTT) is used to allow mucolysis of sputum samples. The primary aim of sputum processing is to obtain a differential cell count to study the cell types present in the airway lumen. Additional analyses may also be performed on sputum supernatant and sputum cells, which may allow further investigation into inflammatory processes and immune mechanisms. Examples include studying mediators in sputum supernatant and performing a large spectrum of analysis on sputum cells such as flow cytometry, genomics, or proteomics. Finally, representative results of sputum analysis in healthy controls, asthmatics, and COPD patients are presented.
Topics: Humans; Laboratories; Sputum
PubMed: 29286433
DOI: 10.3791/56612 -
Lab on a Chip Aug 2015We demonstrate the first microfluidic-based on-chip liquefaction device for human sputum samples. Our device is based on an acoustofluidic micromixer using oscillating...
We demonstrate the first microfluidic-based on-chip liquefaction device for human sputum samples. Our device is based on an acoustofluidic micromixer using oscillating sharp edges. This acoustofluidic sputum liquefier can effectively and uniformly liquefy sputum samples at a throughput of 30 μL min(-1). Cell viability and integrity are maintained during the sputum liquefaction process. Our acoustofluidic sputum liquefier can be conveniently integrated with other microfluidic units to enable automated on-chip sputum processing and analysis.
Topics: Cell Survival; Eosinophils; Equipment Design; Flow Cytometry; Humans; Microfluidic Analytical Techniques; Neutrophils; Sonication; Specimen Handling; Sputum
PubMed: 26082346
DOI: 10.1039/c5lc00539f -
Respiratory Medicine 2022Proteomics can reveal molecular pathways of disease and provide translational perspectives to inform clinical decision making. Although several studies have previously... (Observational Study)
Observational Study
BACKGROUND
Proteomics can reveal molecular pathways of disease and provide translational perspectives to inform clinical decision making. Although several studies have previously reported the cystic fibrosis airway proteome, the relationship with severity of lung disease has not been characterised. The objectives of this observational study were to investigate differences in the CF sputum proteome associated with disease severity and identify potential markers of disease with translational potential.
METHODS
Sputum samples from healthy volunteers and cystic fibrosis subjects (some prescribed modulator therapies) were analysed using liquid-chromatography tandem mass spectrometry. Severity of lung disease was based on baseline spirometry (percentage predicted forced expiratory volume in 1 s, FEV1%).
RESULTS
Multiple sputum proteins (108 increased; 202 decreased) were differentially expressed in CF (n = 38) and healthy volunteers (n = 32). Using principal component analysis and hierarchical clustering, differences in sputum proteome were observed associated with progressive lung function impairment. In CF subjects, baseline FEV1% correlated with 87 proteins (positive correlation n = 20, negative n = 67); most were either neutrophil derived, or opposed neutrophil-driven oxidant and protease activity.
CONCLUSION
Predictable and quantifiable changes in the CF sputum proteome occurred associated with progressive lung function impairment, some of which might have value as markers of disease severity in CF sputum. Further work validating these markers in other patient cohorts and exploring their clinical utility is needed.
Topics: Humans; Sputum; Cystic Fibrosis; Proteome; Lung; Severity of Illness Index; Biomarkers
PubMed: 36274446
DOI: 10.1016/j.rmed.2022.107002 -
BMC Infectious Diseases Apr 2022Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent...
BACKGROUND
Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent medical need. Development efforts continue to be hampered by the reliance on culture-based methods, which often take weeks to obtain due to the slow growth rate of Mtb. The availability of a "real-time" measure of treatment efficacy could accelerate TB drug development. Sputum lipoarabinomannan (LAM; an Mtb cell wall glycolipid) has promise as a pharmacodynamic biomarker of mycobacterial sputum load.
METHODS
The present analysis evaluates LAM as a surrogate for Mtb burden in the sputum samples from 4 cohorts of a total of 776 participants. These include those from 2 cohorts of 558 non-TB and TB participants prior to the initiation of treatment (558 sputum samples), 1 cohort of 178 TB patients under a 14-day bactericidal activity trial with various mono- or multi-TB drug therapies, and 1 cohort of 40 TB patients with data from the first 56-day treatment of a standard 4-drug regimen.
RESULTS
Regression analysis demonstrated that LAM was a predictor of colony-forming unit (CFU)/mL values obtained from the 14-day treatment cohort, with well-estimated model parameters (relative standard error ≤ 22.2%). Moreover, no changes in the relationship between LAM and CFU/mL were observed across the different treatments, suggesting that sputum LAM can be used to reasonably estimate the CFU/mL in the presence of treatment. The integrated analysis showed that sputum LAM also appears to be as good a predictor of time to Mycobacteria Growth Incubator Tube (MGIT) positivity as CFU/mL. As a binary readout, sputum LAM positivity is a strong predictor of solid media or MGIT culture positivity with an area-under-the-curve value of 0.979 and 0.976, respectively, from receiver-operator curve analysis.
CONCLUSIONS
Our results indicate that sputum LAM performs as a pharmacodynamic biomarker for rapid measurement of Mtb burden in sputum, and thereby may enable more efficient early phase clinical trial designs (e.g., adaptive designs) to compare candidate anti-TB regimens and streamline dose selection for use in pivotal trials. Trial registration NexGen EBA study (NCT02371681).
Topics: Biomarkers; Humans; Lipopolysaccharides; Mycobacterium tuberculosis; Sputum
PubMed: 35366820
DOI: 10.1186/s12879-022-07308-3 -
Biomolecules Oct 2022Frequent acute exacerbations are the leading cause of high rates of hospitalization and mortality in chronic obstructive pulmonary disease (COPD). Despite the enormous...
Frequent acute exacerbations are the leading cause of high rates of hospitalization and mortality in chronic obstructive pulmonary disease (COPD). Despite the enormous worldwide medical burden, reliable molecular markers for effective early diagnosis and prognosis of acute exacerbations are still lacking. Both the host genetics and airway microbiome are known to play potential roles in the pathogenesis of frequent exacerbations. Here, we performed whole exome sequencing (WES) and 16S rRNA gene sequencing to explore the interaction between these two factors and their implications in the pathogenesis of frequent exacerbations. We collected peripheral blood (n = 82), sputum samples (n = 59) and clinical data from 50 frequent-exacerbation phenotype (FE) COPD patients and 32 infrequent-exacerbation phenotype (IE) as controls. Based on filtering the deleterious sites, candidate mutated genes shared only in FE patients and did not occur in the IE group were identified. Microbiota analysis revealed significant differences in bacterial diversity and composition between FE and IE groups. We report the underlying pathogenic gene including, , genes, etc., and explore their possible genotypic-phenotypic correlations with microbiota dysbiosis. Importantly, we observed that gene mutations were significantly negatively correlated with microbial richness and diversity. Our study indicated several deleterious mutations in candidate genes that might be associated with microbial dysbiosis and the increased risk of frequent acute exacerbations in COPD patients. These results provide novel evidence that exomes and related microbiomes may potentially serve as biomarkers for predicting frequent acute exacerbations in COPD patients.
Topics: Humans; Sputum; RNA, Ribosomal, 16S; Dysbiosis; Exome; Exome Sequencing; Pulmonary Disease, Chronic Obstructive; Microbiota; Biomarkers; Disease Progression; Repressor Proteins; Apoptosis Regulatory Proteins
PubMed: 36291689
DOI: 10.3390/biom12101481