Journal articles: 'Zinc levels in sputum'

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Wagnew, Fasil, Kefyalew Addis Alene, Setegn Eshetie, Tom Wingfield, Matthew Kelly, and Darren Gray. "Effects of zinc and vitamin A supplementation on prognostic markers and treatment outcomes of adults with pulmonary tuberculosis: a systematic review and meta-analysis." BMJ Global Health 7, no. 9 (September 2022): e008625. http://dx.doi.org/10.1136/bmjgh-2022-008625.

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IntroductionUndernutrition is a major risk factor for tuberculosis (TB), which is estimated to be responsible for 1.9 million TB cases per year globally. The effectiveness of micronutrient supplementation on TB treatment outcomes and its prognostic markers (sputum conversion, serum zinc, retinol and haemoglobin levels) has been poorly understood. This study aimed to determine the effect of zinc and vitamin A supplementation on prognostic markers and TB treatment outcomes among adults with sputum-positive pulmonary TB.MethodsA systematic literature search for randomised controlled trials (RCTs) was performed in PubMed, Embase and Scopus databases. Meta-analysis with a random effect model was performed to estimate risk ratio (RR) and mean difference (MD), with a 95% CI, for dichotomous and continuous outcomes, respectively.ResultsOur search identified 2195 records. Of these, nine RCTs consisting of 1375 participants were included in the final analyses. Among adults with pulmonary TB, zinc (RR: 0.94, 95% CI: 0.86 to 1.03), vitamin A (RR: 0.90, 95% CI: 0.80 to 1.01) and combined zinc and vitamin A (RR: 0.98, 95% CI: 0.89 to 1.08) supplementation were not significantly associated with TB treatment success. Combined zinc and vitamin A supplementation was significantly associated with increased sputum smear conversion at 2 months (RR: 1.16, 95% CI: 1.03 to 1.32), serum zinc levels at 2 months (MD: 0.86 μmol/L, 95% CI: 0.14 to 1.57), serum retinol levels at 2 months (MD: 0.06 μmol/L, 95% CI: 0.04 to 0.08) and 6 months (MD: 0.12 μmol/L, 95% CI: 0.10 to 0.14) and serum haemoglobin level at 6 months (MD: 0.29 μg/dL, 95% CI: 0.08 to 0.51), among adults with pulmonary TB.ConclusionsProviding zinc and vitamin A supplementation to adults with sputum-positive pulmonary TB during treatment may increase early sputum smear conversion, serum zinc, retinol and haemoglobin levels. However, the use of zinc, vitamin A or both was not associated with TB treatment success.PROSPERO registration numberCRD42021248548.

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Rockwood, Neesha, Rachel P. J. Lai, Ronnett Seldon, Douglas B. Young, and Robert J. Wilkinson. "Variation in pre-therapy levels of selected Mycobacterium tuberculosis transcripts in sputum and their relationship with 2-month culture conversion." Wellcome Open Research 4 (July 5, 2019): 106. http://dx.doi.org/10.12688/wellcomeopenres.15332.1.

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Background:The abundance of transcripts arising fromMycobacterium tuberculosis(MTB) in sputum pre-chemotherapy may enhance our understanding of factors influencing treatment response. We hypothesized that differences in the prevalence of pre-existing slowly metabolizing MTB in sputum may be partially responsible for differences in the rate of sputum clearance during treatment.Methods:Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to characterize a selected limited transcription profile of MTB in sputum pre-chemotherapy and assess inter-individual variation. The difference in cycle threshold (Ct) per gene, normalized to 16S, between exponential/stationary phase culture and sputum was calculated and stratified by 2-month culture converter status.Results:HIV-1 uninfected patients with rifampicin-susceptible tuberculosis provided sputum pre-chemotherapy; 11 patients were negative for MTB culture after two months of therapy and 8 remained culture-positive.Increasedicl1andprpDandrpsN2:rpsN1in sputum relative to culture suggested cholesterol utilization and a low-zinc environment respectively. IncreasedhspXand decreasedatpAandnuoGrelative to exponential culture suggested a slowly metabolizing subpopulation of MTB. While the thehspXhiatpAlonuoGlosignal varied, we did not observe statistically significant enrichment of this phenotype in the non-converter population nor an association with MTB-lineage.Conclusion:Differential abundance of selected informative transcripts suggested a metabolically less-active subpopulation with a prevalence that varied between individual untreated patients.

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Moraes, Milena Lima de, Daniela Maria de Paula Ramalho, Karina Neves Delogo, Pryscila Fernandes Campino Miranda, Eliene Denites Duarte Mesquita, Hedi Marinho de Melo Guedes de Oliveira, Antônio Ruffino Netto, Marcelino José dos Anjos, Afrânio Lineu Kritski, and Martha Maria de Oliveira. "Association of Serum Levels of Iron, Copper, and Zinc, and Inflammatory Markers with Bacteriological Sputum Conversion During Tuberculosis Treatment." Biological Trace Element Research 160, no. 2 (June 24, 2014): 176–84. http://dx.doi.org/10.1007/s12011-014-0046-0.

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Gutierrez, Kristine Marie. "A randomized, double-blind, placebo controlled trial on the effect of zinc supplementation on bronchial asthma as measured by sputum eosinophil levels and asthma control test (ACT) in children ages 12-18 y/o." World Allergy Organization Journal &NA; (November 2007): S148. http://dx.doi.org/10.1097/01.wox.0000301731.45276.05.

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Ebden, P., P. Neill, and P. R. Farrow. "Sputum levels of fluconazole in humans." Antimicrobial Agents and Chemotherapy 33, no. 6 (June 1, 1989): 963–64. http://dx.doi.org/10.1128/aac.33.6.963.

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JAYARAM, LATA, SANJEEV CHUNILAL, SANDY PICKERING, RICHARD E. RUFFIN, and PETER D. ZALEWSKI. "Sputum zinc concentration and clinical outcome in older asthmatics." Respirology 16, no. 3 (March 30, 2011): 459–66. http://dx.doi.org/10.1111/j.1440-1843.2011.01932.x.

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Ribeiro-Rodrigues, Rodrigo, Tatiana Resende Co, John L. Johnson, Fabiola Ribeiro, Moises Palaci, Ricardo T. Sá, Ethel L. Maciel, et al. "Sputum Cytokine Levels in Patients with Pulmonary Tuberculosis as Early Markers of Mycobacterial Clearance." Clinical and Vaccine Immunology 9, no. 4 (July 2002): 818–23. http://dx.doi.org/10.1128/cdli.9.4.818-823.2002.

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ABSTRACT Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-γ) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-γ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-γ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-γ immunoreactivities in serum followed kinetics in sputum. TNF-α, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-γ, however, TNF-α and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.

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Gao, J., S. Ohlmeier, P. Nieminen, T. Toljamo, S. Tiitinen, T. Kanerva, L. Bingle, et al. "Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study." American Journal of Physiology-Lung Cellular and Molecular Physiology 309, no. 1 (July 1, 2015): L17—L26. http://dx.doi.org/10.1152/ajplung.00082.2015.

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A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing fold-containing protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers ( n = 31), smokers ( n = 169), and patients with COPD ( n = 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smoking-related lung diseases.

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Durry, Fara Disa, Bambang Wirjatmadi, and Merryana Adriani. "The Role Of Zinc Sulphate and Omega 3 On The Improvement Of Weight and Speed Conversion Conversion on Tuberculosis Parent Patients at Surabaya Park Hospital, 2015." Jurnal Ilmiah Kedokteran Wijaya Kusuma 7, no. 1 (March 30, 2018): 62. http://dx.doi.org/10.30742/jikw.v7i1.313.

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Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, can affect almost all organs of the body with the most locations in the lungs. Immunity and high nutrients such as vitamin C, zinc and other antioxidants have shown good effects for infections, including tuberculosis. One effort to help accelerate sputum conversion of people with pulmonary tuberculosis is by supplementation of Zinc Sulphate and Omega 3.Objective: Analyze the role of Zinc Sulphate and Omega 3 on sputum conversion acceleration in patients with pulmonary tuberculosis at Surabaya Paru Hospital 2015.Method: This research use Randomized Pre Post Test Post Control Group Design design. In patients with pulmonary tuberculosis with Zinc Sulphate and Omega 3 in the treatment and placebo group in the control group. A sample of 20 patients consisting of 10 treatment patients and 10 control patients. Statistical test using paired T-Test, Friedman test and Mann whitney.Results: Friedman test showed that in the treatment group showed significant difference in the number of BTA between before and after supplementation (p=0,001), while in the control group significance of 0.141. Mann-Whitney test showed no significant difference in the amount of reduction of BTA between the treatment group and the control group (p = 0.080). This means that statistically does not show any significant difference.Conclusions: Zinc Sulphate and Omega 3 play a role in accelerating sputum smear conversion of respondents. The results of smear test in pulmonary TB patients with Zinc Sulphate and Omega 3 supplementation showed positive results

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Mineev, V. N., T. M. Lalaeva, T. S. Vasiljeva, and A. A. Kuzmina. "Sputum as a source of adipokines in bronchial asthma." Scientific Notes of the I. P. Pavlov St. Petersburg State Medical University 21, no. 3 (September 30, 2014): 34–40. http://dx.doi.org/10.24884/1607-4181-2014-21-3-34-40.

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Forty-four patients with allergic (ABA) and non-allergic (NABA) variants of bronchial asthma (BA) were examined to evaluate levels of key adipokines (leptin, resistin, adiponectin) in sputum in different variants of BA. Adipokines in sputum and blood plasma were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The indices that reflect the percentage of adipokines in sputum regarding adipokines in plasma of the same patients were worked out to evaluate the ratio of levels of corresponding adipokines in plasma and sputum in patients with BA. Two regularities are clearly seen in the study: the first - levels of proinflammatory adipokines (leptin, resistin) in sputum in ABA correlate directly with indicators of respiratory function but levels of anti-inflammatory adipokines (adiponectin) in sputum correlate inversely with indicators of respiratory function; the second -correlation of levels of the studied adipokines with indicators of respiratory function are almost not revealed in NABA. The first regularity reflects the important fact that the content of adipokines in bronchial secretion is to a certain extent one of regulating local mechanisms in target organ controlled system levels of corresponding adipokines in exacerbation of BA.

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Higham, Andrew, Paul Cadden, Thomas Southworth, Matthew Rossall, Umme Kolsum, Simon Lea, Richard Knowles, and Dave Singh. "Leukotriene B4 levels in sputum from asthma patients." ERJ Open Research 2, no. 4 (October 2016): 00088–2015. http://dx.doi.org/10.1183/23120541.00088-2015.

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Poor asthma control is associated with increased airway neutrophils. Leukotriene B4 (LTB4) is a potent neutrophil chemoattractant. We examined the levels of LTB4 levels in the sputum of asthma patients and the relationship with disease severity.47 asthma patients (categorised according to Global Initiative for Asthma treatment stage) and 12 healthy controls provided sputum samples that were processed first with PBS to obtain supernatants and secondly with dithiothreitol (DTT) to obtain supernatants. LTB4 levels were determined by ELISA.LTB4 levels were significantly higher in step 1 (steroid naïve) and step 3 (inhaled corticosteroid (ICS) plus long acting β-agonist) patients than step 2 patients (ICS alone) (p=0.02 and p=0.01, respectively). There was very good correlation when comparing PBS processed to DTT processed supernatants.High LTB4 levels were found in the sputum of asthmatics at step 3 despite ICS use.

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Nandan, Devki, Prachi Kansal, Neha Patharia, and Parul Goyal. "Induced Sputum Nitrite Levels Correlate with Clinical Asthma Parameters in Children Aged 7–18 Years with Mild to Moderate Persistent Asthma." Journal of Laboratory Physicians 8, no. 02 (July 2016): 090–95. http://dx.doi.org/10.4103/0974-2727.180788.

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ABSTRACT Purpose: The objective of this study is to measure levels of nitrites in induced sputum in children with asthma and correlate it with clinical asthma parameters. Method: This prospective observational study was done in PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi, on 91 children aged 7-18 years with mild and moderate persistent asthma. Patients were specifically evaluated for five clinical parameters of asthma (i.e. Days of acute exacerbations, use of salbutamol as rescue medication, emergency visits, nights with cough, days of school absence) and induced sputum nitrite levels was done at the time of enrollment and 3 months after treatment with inhaled budesonide. Results: The mean age of subjects was 10.79 ± 2.563yrs. Six (6.59%) patients were not able to perform induced sputum, eighty five (93.41%) patients were suitable for data analysis. There was significant reduction in sputum nitrite levels from 33.42 ± 22.04nmol/ml at enrollment to 11.72 ± 5.61 nmol/ml (P < 0.0005) after 3 months of inhaled budesonide therapy. Significant positive correlation was found between reduction in sputum nitrite level and control of asthma symptoms: Days of acute exacerbations(r value = 0.548, P value = 0.0001), Days of salbutamol use as rescue medication (r value = 0.431, P value =< 0.0001), Number of emergency visits(r value = 0.414, P value = 0.0001), Nights with cough (r value = 0.259, P value = 0.0169), Days of school absence(r value = 0.411, P value = 0.0001). Sputum nitrite levels were significantly higher in moderate persistent asthmatics as compared to mild at the time of enrollment (P < 0.0005), which shows that induced sputum nitrite levels correlate with asthma severity. Conclusions: This study confirms that nitrites in induced sputum correlate well with clinical asthma parameters and asthma severity in children and is a simple, non invasive, and cheap method which can be used as a parameter for monitoring of asthma.

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Gauvreau, Gail M., Mark D. Inman, Margaret Kelly, Richard M. Watson, Sandra C. Dorman, and Paul M. O’Byrne. "Increased Levels of Airway Neutrophils Reduces the Inhibitory Effects of Inhaled Glucocorticosteroids on Allergen-Induced Airway Eosinophils." Canadian Respiratory Journal 9, no. 1 (2002): 26–32. http://dx.doi.org/10.1155/2002/161969.

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BACKGROUND: Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation.OBJECTIVE: Studies in which glucocorticosteroid treatment was used before allergen challenges were re-examined to determine whether the efficacy of steroid treatment could be predicted by baseline levels of sputum inflammatory cells.PATIENTS AND METHODS: Twenty-eight nonsmoking subjects with atopic asthma controlled by beta2-agonists participated in only one of three studies, each carried out with a double-blind, placebo controlled, randomized, crossover design. Subjects were treated with glucocorticosteroids or placebo for six to eight days and then underwent allergen inhalation challenge. Spirometry was measured for 7 h after allergen challenge, and then sputum inflammatory cells were measured. Sputum inflammatory cells were also measured before and after treatment, and 24 h after allergen challenge. The per cent inhibition of the allergen-induced airway responses by glucocorticosteroids was calculated.RESULTS: Inhaled gluticocorticosteroids significantly attenuated the early and late asthmatic responses, and the number of allergen-induced sputum eosinophils (P<0.05). There was a significant negative relationship between the number of sputum neutrophils at baseline, and the per cent inhibition of allergen-induced sputum eosinophils measured at 7 h (r=-0.61, P<0.001) and 24 h (r=-0.73, P<0.0001) after challenge, suggesting that glucocorticosteroids are less effective in attenuating allergen-induced airway inflammation in subjects with high levels of neutrophils. There was no correlation between the number of sputum eosinophils at baseline and the per cent inhibition of allergen-induced responses.CONCLUSIONS: Baseline airway neutrophils, not eosinophils, can be used to predict the efficacy of inhaled steroids on allergen-induced sputum eosinophils.

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Sol, I. S., Y. H. Kim, Y. A. Park, K. E. Lee, J. Y. Hong, M. N. Kim, Y. S. Kim, et al. "Relationship between sputum clusterin levels and childhood asthma." Clinical & Experimental Allergy 46, no. 5 (April 26, 2016): 688–95. http://dx.doi.org/10.1111/cea.12686.

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Kim, Soo Yeon, Jong Deok Kim, In Suk Sol, Min Jung Kim, Mi Seon Oh, Yun Seon Kim, Mina Kim, et al. "Relationship Between Sputum TWEAK Levels and Childhood Asthma." Journal of Allergy and Clinical Immunology 139, no. 2 (February 2017): AB196. http://dx.doi.org/10.1016/j.jaci.2016.12.635.

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Zeng, Mian, Yue Li, Yujie Jiang, Guifang Lu, Xiaomei Huang, and Kaipan Guan. "Local and Systemic Oxidative Stress and Glucocorticoid Receptor Levels in Chronic Obstructive Pulmonary Disease Patients." Canadian Respiratory Journal 20, no. 1 (2013): 35–41. http://dx.doi.org/10.1155/2013/985382.

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BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).OBJECTIVES: To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress.METHODS: Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]).RESULTS: MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]).CONCLUSIONS: Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients.

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Saputra, Nico Dana. "Relationship Between Serum Vitamin D Levels and Bacterial Load Sputum in Tuberculosis Patients in Simalungun, North Sumatra, Indonesia." International Journal for Research in Applied Science and Engineering Technology 10, no. 8 (August 31, 2022): 1812–17. http://dx.doi.org/10.22214/ijraset.2022.46517.

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Abstract: Vitamin D is involved in innate and adaptive immune function and its deficiency is a risk factor for tuberculosis (TB) infection. The aim of this study was to describe the prevalence of vitamin D deficiency in newly diagnosed tuberculosis patients and to examine the relationship between vitamin D levels and sputum swab positivity, which reflects bacterial load. This is a cross-sectional study conducted from June 2022 to August 2022 at multiple primary health care facilities at Buntu Turunan Public Health Center and Perdagangan Regional General Hospital, Simalungun Regency. Up to 101 adult tuberculosis patients who were sputum smear-positive, untreated, on treatment, or had a treatment duration of 1 week or less to her were recruited. Sputum examination was scored using the International Union for Tuberculosis and Lung Disease (IUATLD) rating scale. Serum 25(OH) vitamin D level was estimated using enzyme-linked immunosorbent assay (ELISA) and interpreted as deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), or optimum (30-100 ng/mL). The association between vitamin D levels and positive levels of AFB sputum was analyzed using Spearman's correlation test. The prevalence of vitamin D deficiency in new pulmonary tuberculosis patients with positive sputum smear was 20.79%. There was a weak relationship between vitamin D levels and AFB sputum positive levels (p=0.017), with a correlation coefficient of (-0.278). Despite Indonesia being an equatorial region and having plenty of sunshine throughout the year, many of the newly diagnosed tuberculosis patients were vitamin D deficient. This study shows that vitamin D does influence bacterial load and that low levels of 25(OH)-vitamin D are associated with higher bacterial load.

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Puspitasari, Yessy, and Jusak Nugraha. "CORRELATION BETWEEN IFN-ɤ LEVELS, CHEST RADIOGRAPHY AND THE POSITIVITY OF SMEAR SPUTUM IN NEW TB CASES AT THE DR.SOETOMO HOSPITAL." INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 24, no. 2 (September 30, 2018): 155. http://dx.doi.org/10.24293/ijcpml.v24i2.1316.

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Tuberculosis is an infectious disease attacking lungs, triggering damage, and pulmonary dysfunction. Host cytokine responses will influence tuberculosis manifestations. The main host immune response is cellular immunity, and Delayed-Type Hypersensitivity (DTH). IFN-γ produced by Th-1, is a major cytokine acting to eliminate TB bacteria through macrophage activation. Chest radiography has an important value for the diagnosis of TB, especially in negative sputum smears. Radiological manifestations depend on several factors including host prior to TB exposure, age, and immune status. Sputum smear is also important in diagnosing, and assessing response to treatment of adult pulmonary TB. A cross-sectional study, comprising a total of 36 new pulmonary TB cases at the Dr.Soetomo Hospital who met the inclusion, and exclusion criteria, were establish. Plasma IFN-γ was examined by ELISA. Chest radiography was divided into three categories based on the National Tuberculosis Association of USA. Sputum smear data were taken from medical records. There were significant correlations between IFN-γ plasma levels with chest radiography (r= 0.365; ρ=0.029), IFN-γ with positive sputum smear (r= 0.447; ρ=0.006), positive sputum smear with chest radiography (r=0.674; ρ=0.001) IFN-γ plasma levels could reflect lesion area on chest radiography, and sputum smear positivity. IFN-γ plasma levels, chest radigraphy, and sputum positivity may reflect a Th-1immune response, so the more severe level of diseases, an immune response Th-1 become more activated.

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Przysucha, Natalia, Katarzyna Górska, Marta Maskey-Warzęchowska, Małgorzata Proboszcz, Patrycja Nejman-Gryz, Magdalena Paplińska-Goryca, Barbara Dymek, Agnieszka Zagozdzon, and Rafał Krenke. "The Role of Chitinases in Chronic Airway Inflammation Associated with Tobacco Smoke Exposure." Cells 11, no. 23 (November 25, 2022): 3765. http://dx.doi.org/10.3390/cells11233765.

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Chitinases and chitinase-like proteins are thought to play a role in innate inflammatory responses. Our study aimed to assess whether chitinase concentration and activity in induced sputum (IS) of patients exposed to tobacco smoke are related to the level of airway inflammation including the level and activity of chitinases and chitinase-like proteins. The study included 22 patients with chronic obstructive pulmonary disease (COPD), 12 non-COPD smokers, and nine nonsmoking subjects. Sputum CHIT1 and YKL-40 levels and chitinolytic activity were compared with sputum IL-6, IL-8, IL-18, and MMP-9 levels. A hierarchical cluster analysis was also performed. Sputum YKL-40 was higher in COPD patients than in the control groups. Sputum CHIT1 and YKL-40 levels correlated with IS inflammatory cell count as well as with MMP-9 and IL-8 levels. Two main clusters were revealed: Cluster 1 had lower chitinase levels and activity, lower IS macrophage and neutrophil count, and lower IS IL-8, IL-18, and MMP-9 than Cluster 2. Comparison of COPD patients from both clusters revealed significant differences in the IS inflammatory profile despite comparable clinical and functional data. Our findings seem to confirm the involvement of chitinases in smoking-associated chronic airway inflammation and show that airway chitinases may be a potential novel marker in COPD phenotyping.

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Van der Vliet, Albert, Mai N. Nguyen, Mark K. Shigenaga, Jason P. Eiserich, Gregory P. Marelich, and Carroll E. Cross. "Myeloperoxidase and protein oxidation in cystic fibrosis." American Journal of Physiology-Lung Cellular and Molecular Physiology 279, no. 3 (September 1, 2000): L537—L546. http://dx.doi.org/10.1152/ajplung.2000.279.3.l537.

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Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3′-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO2−) and nitrate (NO3−), indicating local production of nitric oxide (NO·), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO2−. CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.

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De Soyza, Anthony, Ian Pavord, J. Stuart Elborn, David Smith, Heather Wray, Margareta Puu, Bengt Larsson, and Robert Stockley. "A randomised, placebo-controlled study of the CXCR2 antagonist AZD5069 in bronchiectasis." European Respiratory Journal 46, no. 4 (September 4, 2015): 1021–32. http://dx.doi.org/10.1183/13993003.00148-2015.

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This randomised double-blind placebo-controlled parallel-group multicentre phase IIa study evaluated the effect of the CXCR2 antagonist AZD5069 on sputum neutrophil counts in adults with bronchiectasis.Patients were randomised 1:1 to receive AZD5069 80 mg or placebo orally twice daily for 28 days. Assessments included blood cell counts, inflammatory markers in blood, morning spontaneous sputum, lung function, safety and tolerability and patients completed daily BronkoTest diary cards. The primary outcome measure was the change in absolute sputum neutrophil count.Of 52 randomised patients, 45 completed treatment, 20 (76.9%) out of 26 receiving AZD5069 and 25 (96.2%) out of 26 receiving placebo. AZD5069 reduced the absolute neutrophil cell count in morning sputum by 69%versusplacebo (p=0.004); percentage sputum neutrophil count was reduced by 36% (p=0.008). The number of infections/exacerbations was similar with AZD5069 and placebo (nineversuseight), but these led to more study discontinuations with AZD5069 (fourversuszero). Sputum interleukin (IL)-6 and growth-regulated oncogene (GRO)-α and serum GRO-α, IL-1ß and IL-8 levels increased with AZD5069versusplacebo (all p<0.001), while serum high-sensitivity C-reactive protein levels did not change. AZD5069 was well tolerated.AZD5069 markedly reduced absolute sputum neutrophil counts in bronchiectasis patients, although this was not associated with improvements in clinical outcomes in this exploratory study.

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Chaudhuri, R., A. D. McMahon, C. P. McSharry, K. J. MacLeod, I. Fraser, E. Livingston, and N. C. Thomson. "Serum and sputum neurotrophin levels in chronic persistent cough." Clinical Experimental Allergy 35, no. 7 (July 2005): 949–53. http://dx.doi.org/10.1111/j.1365-2222.2005.02286.x.

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Virchow, J. Christian, Uwe Hölscher, and Christian Virchow. "Sputum ECP Levels Correlate with Parameters of Airflow Obstruction." American Review of Respiratory Disease 146, no. 3 (September 1992): 604–6. http://dx.doi.org/10.1164/ajrccm/146.3.604.

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Palmer, Kelli L., Stacie A. Brown, and Marvin Whiteley. "Membrane-Bound Nitrate Reductase Is Required for Anaerobic Growth in Cystic Fibrosis Sputum." Journal of Bacteriology 189, no. 12 (March 30, 2007): 4449–55. http://dx.doi.org/10.1128/jb.00162-07.

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ABSTRACT The autosomal recessive disorder cystic fibrosis (CF) affects approximately 70,000 people worldwide and is characterized by chronic bacterial lung infections with the opportunistic pathogen Pseudomonas aeruginosa. To form a chronic CF lung infection, P. aeruginosa must grow and proliferate within the CF lung, and the highly viscous sputum within the CF lung provides a likely growth substrate. Recent evidence indicates that anaerobic microenvironments may be present in the CF lung sputum layer. Since anaerobic growth significantly enhances P. aeruginosa biofilm formation and antibiotic resistance, it is important to examine P. aeruginosa physiology and metabolism in anaerobic environments. Measurement of nitrate levels revealed that CF sputum contains sufficient nitrate to support significant P. aeruginosa growth anaerobically, and mutational analysis revealed that the membrane-bound nitrate reductase is essential for P. aeruginosa anaerobic growth in an in vitro CF sputum medium. In addition, expression of genes coding for the membrane-bound nitrate reductase complex is responsive to CF sputum nitrate levels. These findings suggest that the membrane-bound nitrate reductase is critical for P. aeruginosa anaerobic growth with nitrate in the CF lung.

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Allali, Slimane, Mariane de Montalembert, Rachel Rignault-Bricard, Melissa Taylor, Joséphine Brice, Valentine Brousse, Jean-Marc Talbot, et al. "IL-6 levels are dramatically high in the sputum from children with sickle cell disease during acute chest syndrome." Blood Advances 4, no. 24 (December 11, 2020): 6130–34. http://dx.doi.org/10.1182/bloodadvances.2020003519.

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Key Points Sputum interleukin-6 (IL-6) level is high during acute chest syndrome (ACS) in pediatric sickle cell disease, supporting anti–IL-6 trials. Sputum IL-8, CCL2, and CCL3 levels are also high during ACS, possibly contributing to recruitment of inflammatory cells in the lungs.

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Sibila, Oriol, Lídia Perea, Elisabet Cantó, Amelia Shoemark, Diane Cassidy, Alexandria Holly Smith, Guillermo Suarez-Cuartin, et al. "Antimicrobial peptides, disease severity and exacerbations in bronchiectasis." Thorax 74, no. 9 (July 5, 2019): 835–42. http://dx.doi.org/10.1136/thoraxjnl-2018-212895.

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RationaleRecently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.ObjectivesTo determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.MethodsA total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.Measurements and main resultsAMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.ConclusionsPatients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

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Baumann, Ulrich, Malcolm King, Ernst M. App, Shusheng Tai, Armin König, Julia J. Fischer, Torsten Zimmermann, Wolfgang Sextro, and Horst von der Hardt. "Long-Term Azithromycin Therapy in Cystic Fibrosis Patients: A Study on Drug Levels and Sputum Properties." Canadian Respiratory Journal 11, no. 2 (2004): 151–55. http://dx.doi.org/10.1155/2004/747841.

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BACKGROUND:Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro.OBJECTIVES:Drug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo.METHODS:In an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology.RESULTS:AZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 µg/mL (0.6 to 79.3 µg/mL, interquartiles 1.4 to 33.4 µg/mL) and 0.5 µg/mL (range less than 0.1 [below detection level] to 5.2 µg/mL, interquartiles 0.2 to 1.4 µg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one.CONCLUSIONS:The findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.

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Sarfati, Sacha, Julien Wils, Timothée Lambert, Céline Mory, Laurent Imbert, Gilles Gargala, Hélène Morisse-Pradier, and Fabien Lamoureux. "Therapeutic Drug Monitoring of Sputum Voriconazole in Pulmonary Aspergillosis." Pharmaceutics 14, no. 8 (July 30, 2022): 1598. http://dx.doi.org/10.3390/pharmaceutics14081598.

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Voriconazole is one of the most used antifungal azoles against pulmonary aspergillosis. Therapeutic drug monitoring (TDM) of the voriconazole concentration in plasma is recommended in clinical practice guidelines to prevent treatment failure and toxicity. The aim of this study was to evaluate the feasibility and utility of TDM of the voriconazole concentration in the sputum of patients treated for pulmonary aspergillosis. Fifty sputum and 31 plasma samples were analysed with high-performance tandem mass spectrometry (HPLC-MS/MS) in 24 patients included in the study. The voriconazole concentration was simultaneously assessed in the plasma and sputum in 22 samples. The correlation between the sputum and plasma levels was estimated with a univariate linear regression model, and the observed R2 was 0.86. We determined the following equation, Csputum = 0.45 (Cplasma) + 0.21, which could predict the voriconazole concentration in plasma from sputum. TDM of the voriconazole concentration in sputum is an easy, non-invasive and accurate method with which to evaluate voriconazole exposure in patients with pulmonary aspergillosis.

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George, S. S., S. Swaminathan, and L. Seshadri. "Zinc levels in pregnancy." International Journal of Gynecology & Obstetrics 55, no. 2 (November 1996): 175–76. http://dx.doi.org/10.1016/s0020-7292(96)02751-8.

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Margulies, J. Y., M. Statter, M. Nyska, I. Leichter, Z. Schumert, and J. Menczel. "Zinc levels in osteoporosis." Bone 7, no. 5 (January 1986): 410. http://dx.doi.org/10.1016/8756-3282(86)90338-8.

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Marguerettaz, Mélanie, Guennaëlle Dieppois, Yok Ai Que, Véréna Ducret, Sandrine Zuchuat, and Karl Perron. "Sputum containing zinc enhances carbapenem resistance, biofilm formation and virulence of Pseudomonas aeruginosa." Microbial Pathogenesis 77 (December 2014): 36–41. http://dx.doi.org/10.1016/j.micpath.2014.10.011.

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Yormaz, Burcu, Esma Menevse, Nihal Cetin, Zeliha Esin Celik, Hasan Bakir, Baykal Tulek, Muslu Kazım Korez, and Mecit Suerdem. "Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study." Allergy and Asthma Proceedings 42, no. 1 (January 23, 2021): e30-e39. http://dx.doi.org/10.2500/aap.2021.42.200102.

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Background: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilic asthma. Objective: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to compare the superiority of one over the other, especially in asthma with an eosinophilic phenotype. Methods: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants, and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E values were examined. Results: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups (p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group (p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis. The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. The present study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore, when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostin in serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Conclusion: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

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Issa, Hamdia Yousif, Ali A. Ramadhan, Abdulazeez S. Safo, and Omar A. M. Al Habib. "Relationship between pulmonary function tests, sputum eosinophilia and total serum IgE levels among asthmatic patients in Duhok, Iraq." International Journal of Research in Medical Sciences 8, no. 6 (May 26, 2020): 2033. http://dx.doi.org/10.18203/2320-6012.ijrms20202239.

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Background: Bronchial asthma is a disease characterized by reversible airway obstruction, airway inflammation; and hyper-responsiveness. The prevalence of asthma is high, and both its prevalence and burden have increased over the last several decades. The study of inflammatory markers has implications for the appropriate management of this disease. Inflammatory markers has implications for the appropriate management of this disease. Objective of the study is to determine the correlation between asthma severity using pulmonary function tests with sputum eosinophilia and total serum IgE levels.Methods: This case-control study was conducted from March 2017 to September 2018 in the respiratory unit of Azadi general teaching hospital. It included 42 asthmatic patients and 18 healthy subjects. They underwent pulmonary function tests and measurement of total serum IgE levels. Induced sputum was done for asthmatic patients.Results: The age of asthmatic patients ranged from 16-70 years (mean 42±19 years). The asthmatic patient’s female: male ratio was 1.8. Mild asthma was the most common severity group (N=18, 43%) followed by moderate asthma (N=14, 33%) then severe asthma (N=10, 24%). Abnormal sputum eosinophilia (≥3%) was detected in 90% of severe asthma (N=9) compared to 36% in moderate asthma (N=5) and 5.6% in mild asthma (N=1). There was significant statistical association between asthma severity and sputum eosinophilia (p=0.00004). The association between asthma severity and total serum IgE levels was highly significant (p<0.0000) with levels of total serum IgE increasing as the severity of asthma increases.Conclusions: Severe asthma is the least common severity group in this study. Both abnormal sputum eosinophilia and total serum IgE levels are associated with the severity of asthma.

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Jerkic, S. P., F. Michel, H. Donath, E. Herrmann, R. Schubert, M. Rosewich, and S. Zielen. "Calprotectin as a New Sensitive Marker of Neutrophilic Inflammation in Patients with Bronchiolitis Obliterans." Mediators of Inflammation 2020 (May 1, 2020): 1–7. http://dx.doi.org/10.1155/2020/4641585.

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Introduction. Bronchiolitis obliterans (BO) is a chronic disease in which persistent inflammation leads to obstruction and obliteration of the small airways. The aim of this study was to evaluate the value of calprotectin as an inflammatory marker in induced sputum. Methods. Twenty-eight patients suffering from BO and 18 healthy controls were examined. Lung function was measured by spirometry, body plethysmography, and lung clearance index (LCI). The induced sputum was obtained, cell counts were performed, and cytokines were measured using cytometric bead array (CBA). Calprotectin was quantified in the sputum and serum samples using commercially available sandwich ELISA. Results. Spirometry parameters including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and maximum expiratory flow rate at 25% vital capacity (MEF25) were significantly lower in BO patients than in healthy controls, whereas the reserve volume (RV), RV to total lung capacity ratio (RV/TLC), and LCI were significantly increased. In sputum, calprotectin levels, neutrophils, and IL-8 were significantly elevated. Calprotectin levels correlated strongly with IL-8 and other biomarkers, neutrophils FEV1 and MEF25. In serum, calprotectin was significantly diminished in BO patients compared to controls. Conclusion. Lung function is severely impaired in BO patients. Calprotectin is significantly elevated in the sputum of BO patients and reflects ongoing neutrophilic inflammation.

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Safitri, Elok Ariyani, Parluhutan Siagian, Bintang Yinke Magdalena Sinaga, and Putri Chairani Eyanoer. "Vitamin C Supplementation Improves Pulmonary Tuberculosis Patients' Sputum Conversion During Intensive Phase Category I Treatment in Medan." Respiratory Science 2, no. 2 (February 28, 2022): 72–77. http://dx.doi.org/10.36497/respirsci.v2i2.30.

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Background: Many factors influence the success of the acceleration of Acid-Fast Bacilli (AFB) sputum conversion in the treatment of the intensive phase of pulmonary tuberculosis (TB). One of these factors is the nutritional status or nutrition of pulmonary TB patients. Through a fenton reaction, Vitamin C is known to be able to sterilize Mycobacterium tuberculosis. This study aims to determine the effect of giving vitamin C on the conversion of AFB sputum in the intensive phase of pulmonary TB treatment. Method: This study was an inferential, quasi-experimental evaluation of the acceleration of AFB sputum conversion following vitamin C supplementation in patients with category I pulmonary TB. The study group was separated into two groups: 40 TB patients getting Anti Tuberculosis Treatment (ATT) with vitamin C, and 40 TB patients receiving ATT with placebo. Every two weeks, AFB sputum was examined, and vitamin C levels were measured before and after two months of therapy. Results: Conversion of AFB occurred sooner in the vitamin C group of pulmonary TB patients, with as many as 29 patients (72.5%) experiencing conversion of AFB sputum at the end of the second week of therapy, whereas there was no conversion in the placebo group. At the end of the fourth week, all patients (100%) given vitamin C showed AFB sputum conversion, whereas only eight patients (20%) in the placebo group had conversion at the end of the fourth week of treatment. Vitamin C levels increased significantly in the group of pulmonary tuberculosis patients who received vitamin C supplementation. Conclusion: Vitamin C supplementation in the treatment of pulmonary TB can accelerate the conversion of AFB sputum, which is statistically significant.

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Murphy, Ryan C., Ying Lai, James D. Nolin, Robier A. Aguillon Prada, Arindam Chakrabarti, Michael V. Novotny, Michael C. Seeds, et al. "Exercise-induced alterations in phospholipid hydrolysis, airway surfactant, and eicosanoids and their role in airway hyperresponsiveness in asthma." American Journal of Physiology-Lung Cellular and Molecular Physiology 320, no. 5 (May 1, 2021): L705—L714. http://dx.doi.org/10.1152/ajplung.00546.2020.

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The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum ( n = 18) and bronchoalveolar lavage (BAL) fluid ( n = 11) were obtained before and after exercise challenge in asthmatic subjects. Samples were analyzed for phospholipid structure, surfactant function, and levels of eicosanoids and secreted phospholipase A2 group 10 (sPLA2-X). A primary epithelial cell culture model was used to model effects of osmotic stress on sPLA2-X. Exercise challenge resulted in increased surfactant degradation, phospholipase activity, and eicosanoid production in sputum samples of all patients. Subjects with EIB had higher levels of surfactant degradation and phospholipase activity in BAL fluid. Higher basal sputum levels of cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) were associated with direct AHR, and both the postexercise and absolute change in CysLTs and PGD2 levels were associated with EIB severity. Surfactant function either was abnormal at baseline or became abnormal after exercise challenge. Baseline levels of sPLA2-X in sputum and the absolute change in amount of sPLA2-X with exercise were positively correlated with EIB severity. Osmotic stress ex vivo resulted in movement of water and release of sPLA2-X to the apical surface. In summary, exercise challenge promotes changes in phospholipid structure and eicosanoid release in asthma, providing two mechanisms that promote bronchoconstriction, particularly in individuals with EIB who have higher basal levels of phospholipid turnover.

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Keir, Holly R., Christopher J. Fong, Megan L. Crichton, Philip Barth, Eric Chevalier, Gill Brady, Gwen Kennedy, et al. "Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition." ERJ Open Research 5, no. 1 (February 2019): 00252–2018. http://dx.doi.org/10.1183/23120541.00252-2018.

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BackgroundNeutrophil elastase (NE) has been linked to lung neutrophil dysfunction in bronchiectasis and cystic fibrosis (CF), making NE inhibition a potential therapeutic target. NE inhibitor trials have given mixed result perhaps because not all patients have elevated airway NE activity.MethodsWe tested whether a single baseline sputum NE measurement or a combination of clinical parameters could enrich patient populations with elevated NE activity for “personalised medicine”. Intra- and interindividual variations of total and active NE levels in induced sputum from patients with CF or bronchiectasis were monitored over 14 days. Patients with established CF and bronchiectasis (n=5 per group) were recruited. NE was measured using three different methods: one total and two active NE assays. Subsequently, we analysed the association between clinical parameters and NE from a large bronchiectasis cohort study (n=381).ResultsAll three assays showed a high degree of day-to-day variability (0–233% over 14 days). There were strong correlations found between all assays (p<0.0001). Despite high day-to-day variability, patients could be stratified into “high” or “low” groups based on moderate cut-off levels. In the bronchiectasis cohort study, factors most associated with high sputum NE levels were: Pseudomonas aeruginosa infection (β-estimate 11.5, 95% CI −6.0–29.0), sputum colour (β-estimate 10.4, 95% CI 4.3–16.6), Medical Research Council dyspnoea score (β-estimate 6.4, 95% CI 1.4–11.4) and exacerbation history (β-estimate 3.4, 95% CI 1.4–5.3). Collectively, P. aeruginosa infection, sputum colour and exacerbation frequency provided the greatest specificity for “high” NE (98.7%, 95% CI 7.0–99.6%).ConclusionThese results show that patients with bronchiectasis and CF can be effectively divided into “high” or “low” groups, based on sputum NE assays or clinical inclusion criteria.

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Liu, Zhiqiang, Shuang Qie, Lili Li, Bingshui Xiu, Xiqin Yang, Zhenhua Dai, Xuhui Zhang, et al. "Identification of Novel RD1 Antigens and Their Combinations for Diagnosis of Sputum Smear−/Culture+ TB Patients." BioMed Research International 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/7486425.

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Rapid and accurate diagnosis of pulmonary tuberculosis (PTB) is an unresolved problem worldwide, especially for sputum smear− (S−) cases. In this study, five antigen genes including Rv3871, Rv3874, Rv3875, Rv3876, and Rv3879 were cloned fromMycobacterium tuberculosis(Mtb) RD1 and overexpressed to generate antigen fragments. These antigens and their combinations were investigated for PTB serodiagnosis. 298 serum samples were collected from active PTB patients, including 117 sputum smear+ (S+) and sputum culture+ (C+) cases, 101 S−/C+ cases, and 80 S−/C− cases. The serum IgG levels of the five antigens were measured by ELISA. Based on IgG levels, the sensitivity/specificity of Rv3871, Rv3874, Rv3875, Rv3876, and Rv3879 for PTB detection was 81.21%/74.74%, 63.09%/94.78%, 32.21%/87.37%, 62.42%/85.26%, and 83.56%/83.16%, respectively. Furthermore, the optimal result for PTB diagnosis was achieved by combining antigens Rv3871, Rv3876, and Rv3879. In addition, the IgG levels of Rv3871, Rv3876, and Rv3879 were found to be higher in S−/C+ PTB patients than in other PTB populations. More importantly, combination of the three antigens demonstrated superior diagnostic performance for both S−/C+ and S−/C− PTB. In conclusion, the combination of Rv3871, Rv3876, and Rv3879 induced higher IgG response in sputum S−/C+ PTB patients and represents a promising biomarker combination for diagnosing of PTB.

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Mulvanny, Alex, Caroline Pattwell, Augusta Beech, Thomas Southworth, and Dave Singh. "Validation of Sputum Biomarker Immunoassays and Cytokine Expression Profiles in COPD." Biomedicines 10, no. 8 (August 11, 2022): 1949. http://dx.doi.org/10.3390/biomedicines10081949.

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Immunoassays are commonly used to assess airway inflammation in sputum samples from chronic obstructive pulmonary disease (COPD) patients. However, assay performance and validation in this complex matrix is inconsistently reported. The aim of this study was to assess the suitability of various immunoassays for use with sputum samples, followed by use of validated immunoassays to evaluate biomarker levels in COPD patients. Assays were assessed for recombinant reference standard suitability, optimal sample dilution, standard recovery in the biological matrix and reproducibility. Validated assays were used to assess sputum supernatants in Cohort A (n = 30 COPD, n = 10 smokers, n = 10 healthy) and Cohort B (n = 81 COPD, n = 15 smokers, n = 26 healthy). Paired baseline and exacerbation samples from 14 COPD patients were assessed in cohort A, and associations with sputum cell counts and bacterial colonisation investigated in cohort B. 25/32 assays passed validation; the primary reason for validation failure was recombinant reference standard suitability and sample dilution effects. Interleukin (IL-)6 and IL-8 were significantly increased in COPD patients compared to healthy subjects and smokers for both cohorts. Tumour necrosis factor (TNF)α and IL-1β were higher in COPD compared to smokers using one immunoassay but not another, partly explained by different absolute recovery rates. IL-1β, IL-2, IL-4, IL-8, IL-17A, Granulocyte colony stimulating factor (G-CSF), Interferon (IFN-)γ, Interferon gamma induced protein (IP-)10, Macrophage inflammatory protein (MIP)-1α, MIP-1β and TNF-α levels correlated with sputum neutrophil percentage in COPD patients. IL-1β, IL-4, IL-8, G-CSF and IFN-γ levels were associated with Haemophilus influenzae colonisation in COPD patients. Current smokers had lower levels of IL-1β, IL-4, IL-8, G-CSF, IFN-γ, IP-10, Monocyte chemoattractant protein (MCP)-1, MIP-1α, MIP-1β and TNF-α. Validated immunoassays applied to sputum supernatants demonstrated differences between COPD patients and controls, the effects of current smoking and associations between Haemophilus influenzae colonisation and higher levels of selected cytokines. Immunoassay validation enabled inflammatory mediators associated with different COPD characteristics to be determined.

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Regan, Elizabeth A., Witold Mazur, Eleonora Meoni, Tuula Toljamo, Julie Millar, Katri Vuopala, Russell P. Bowler, et al. "Smoking and COPD increase sputum levels of extracellular superoxide dismutase." Free Radical Biology and Medicine 51, no. 3 (August 2011): 726–32. http://dx.doi.org/10.1016/j.freeradbiomed.2011.05.008.

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Hillas, Georgios, Stelios Loukides, Konstantinos Kostikas, Davina Simoes, Vasiliki Petta, Elissavet Konstantellou, Philip Emmanouil, Spyros Papiris, Nikolaos Koulouris, and Petros Bakakos. "Increased levels of osteopontin in sputum supernatant of smoking asthmatics." Cytokine 61, no. 1 (January 2013): 251–55. http://dx.doi.org/10.1016/j.cyto.2012.10.002.

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Leung, Donald Y. M., Harold S. Nelson, Stanley J. Szefler, and William W. Busse. "Sputum mediator levels resistant to inhaled corticosteroids in chronic cough." Journal of Allergy and Clinical Immunology 113, no. 6 (June 2004): 1012. http://dx.doi.org/10.1016/j.jaci.2004.04.023.

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Jaimni, Vijay, Barkur Ananthakrishna Shasty, Sharath P. Madhyastha, Ganesh V. Shetty, Raviraja V. Acharya, Ragini Bekur, and Akhila Doddamani. "Association of Vitamin D Deficiency and Newly Diagnosed Pulmonary Tuberculosis." Pulmonary Medicine 2021 (January 15, 2021): 1–6. http://dx.doi.org/10.1155/2021/5285841.

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Introduction. Vitamin D has a significant role in host immune defense against Mycobacterium tuberculosis. It has been suggested that pulmonary tuberculosis may be associated with lower levels of vitamin D. Present study was therefore undertaken to identify the association between vitamin D deficiency and pulmonary tuberculosis. Methods. A case-control study was conducted in a tertiary care hospital from 2014 to 2016, including 50 adult newly diagnosed sputum positive pulmonary tuberculosis patients as cases and 50 age and sex-matched healthy participants as control groups. All participants in the study group had undergone detailed clinical examination and routine laboratory investigations, including vitamin D, calcium, and sputum for AFB. The clinical characteristics, X-ray findings, sputum AFB, and vitamin D levels were analyzed and compared with data obtained from healthy controls. Results. In both groups, the majority were men (88%). BMI was significantly (<0.0001 ∗ ) lower in the tuberculosis group (19.40 (17.20, 22.0) vs. 24.00 (22.50, 25.47)). Serum vitamin D levels were significantly lower ( P = 0.012 ) in the tuberculosis group (19 (7.75, 27.25) ng/dl) as compared to the control group (25 (19.75, 32.00) ng/dl). Out of 50 TB patients, 27 (54%) had vitamin D deficiency, while among healthy controls, only 13 (26%) had vitamin D deficiency. Among vitamin D deficient PTB patients, 44% had 3+/hpf AFB in sputum smear examination. Conclusion. The prevalence of vitamin D deficiency in pulmonary tuberculosis cases is very high. Hypovitaminosis D was associated with more severe clinical symptoms, higher sputum smear positivity, and extensive lesions in chest radiograph among pulmonary tuberculosis patients.

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Patel, Kalpesh, Varun Patel, and Payal Gogdani. "Association of induced sputum eosinophil, absolute eosinophil count and serum immunoglobulin E level in assessment of the clinical severity in bronchial asthma." IP Indian Journal of Immunology and Respiratory Medicine 7, no. 2 (July 15, 2022): 65–68. http://dx.doi.org/10.18231/j.ijirm.2022.016.

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The study was done with the aim to determine the relationship between the severity of asthma in patient and the level of serum immunoglobulin E, peripheral eosinophil count and nature of sputum.Current research was conducted at the Department of Respiratory Medicine, GAIMS, Bhuj, India over one year. All subjects of Bronchial asthma distinct by Genetic Information Nondiscrimination Act (GINA) guidelines of age 17-61 year were registered. Severity of asthma was assessed by clinical features and by Forced expiratory volume in the first second (FEV1 in spirometry. Following evaluating the sternness of bronchial asthma all subjects undergo sputum examination for sputum eosinophil counts, blood sampling for absolute eosinophil counts and serum IgE levels. Elevated sputum eosinophil count (>3) was significantly elevated in additional subjects with severe persistent asthma even though extra than half of them had normal sputum eosinophil. An important association amid peripheral eosinophil count, sputum eosinophil count, and serum IgE with severe persistent asthma. Mean sputum eosinophil% augments considerably according to severity, demonstrates though affirmative association which was statistically important.The use of inexpensive and easy method with evaluation of AEC, sputum eosinophil count and evaluation of serum IgE level showed a straight measurement of inflammation of airway and allergic etiology of illness.

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Terranova, Leonardo, Martina Oriano, Antonio Teri, Luca Ruggiero, Camilla Tafuro, Paola Marchisio, Andrea Gramegna, et al. "How to Process Sputum Samples and Extract Bacterial DNA for Microbiota Analysis." International Journal of Molecular Sciences 19, no. 10 (October 20, 2018): 3256. http://dx.doi.org/10.3390/ijms19103256.

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Different steps and conditions for DNA extraction for microbiota analysis in sputum have been reported in the literature. We aimed at testing both dithiothreitol (DTT) and enzymatic treatments of sputum samples and identifying the most suitable DNA extraction technique for the microbiota analysis of sputum. Sputum treatments with and without DTT were compared in terms of their median levels and the coefficient of variation between replicates of both DNA extraction yield and real-time PCR for the 16S rRNA gene. Treatments with and without lysozyme and lysostaphin were compared in terms of their median levels of real-time PCR for S. aureus. Two enzyme-based and three beads-based techniques for DNA extraction were compared in terms of their DNA extraction yield, real-time PCR for the 16S rRNA gene and microbiota analysis. DTT treatment decreased the coefficient of variation between replicates of both DNA extraction yield and real-time PCR. Lysostaphin (either 0.18 or 0.36 mg/mL) and lysozyme treatments increased S. aureus detection. One enzyme-based kit offered the highest DNA yield and 16S rRNA gene real-time PCR with no significant differences in terms of alpha-diversity indexes. A condition using both DTT and lysostaphin/lysozyme treatments along with an enzymatic kit seems to be preferred for the microbiota analysis of sputum samples.

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Sakae, Thiago Mamôru, Rosemeri Maurici, Daisson José Trevisol, Marcia Margaret Menezes Pizzichini, and Emílio Pizzichini. "Effects of prednisone on eosinophilic bronchitis in asthma: a systematic review and meta-analysis,." Jornal Brasileiro de Pneumologia 40, no. 5 (October 2014): 552–63. http://dx.doi.org/10.1590/s1806-37132014000500012.

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OBJECTIVE: To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis. METHODS: We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV1-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV1. RESULTS: The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (↓8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (↓83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (↓267.60 µg/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV1 (↑8.09%; 95% CI: 5.35-10.83; p < 0.001). CONCLUSIONS: In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV1.

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Dauletbaev, Nurlan, Jens Rickmann, Klaus Viel, Holger Diegel, Christian von Mallinckrodt, Jürgen Stein, Thomas O. F. Wagner, and Joachim Bargon. "Antioxidant properties of cystic fibrosis sputum." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 5 (May 2005): L903—L909. http://dx.doi.org/10.1152/ajplung.00349.2004.

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Oxidative stress is a likely contributor to the pathogenesis of cystic fibrosis (CF) lung disease. However, hydrogen peroxide (H2O2), a physiological oxidant, is not elevated in CF exhalates. H2O2may be neutralized by antioxidants in CF airway secretions. The H2O2-detoxifying capacity of CF airway secretions, obtained via sputum induction, was studied in an in vitro H2O2cytotoxicity model. 16HBE14o- cells were exposed to H2O2in culture medium containing either 0 or 10% fetal bovine serum (FBS) or 10% CF sputum supernatant (extracted without use of dithiothreitol). The efficiency of H2O2neutralization was estimated by measuring intracellular oxidant levels (dihydrorhodamine 123) after 2 h and cell viability (propidium iodide) after 24 h of H2O2exposure. Furthermore, the presence of reduced thiols (DTNB assay) and reduced glutathione (recycling assay) in CF sputum samples was evaluated. CF sputum extracts completely prevented intracellular oxidant accumulation seen in cells incubated with H2O2in both control media (i.e., 0 or 10% FBS). Furthermore, CF sputum abolished cell death in 16HBE14o- cells exposed to up to 1 mM H2O2. In contrast, there was 100% cytotoxicity in cells exposed to 600 μM H2O2in both control media. The H2O2-detoxifying potential of CF sputum was sustained after catalase and heme peroxidases were inactivated by sodium azide, which does not affect glutathione peroxidase. In addition, reduced protein thiols were found in abundance in CF sputum. In conclusion, CF sputum is capable to neutralize H2O2and abundant reduced thiols and/or glutathione peroxidase are fully sufficient to detoxify H2O2.

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Antus, Balazs. "Oxidative Stress Markers in Sputum." Oxidative Medicine and Cellular Longevity 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/2930434.

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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.

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Niessen, Natalie M., Peter G. Gibson, Jodie L. Simpson, Hayley A. Scott, Katherine J. Baines, and Michael Fricker. "Airway monocyte modulation relates to tumour necrosis factor dysregulation in neutrophilic asthma." ERJ Open Research 7, no. 3 (June 11, 2021): 00131–2021. http://dx.doi.org/10.1183/23120541.00131-2021.

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BackgroundDysregulation of tumour necrosis factor-α (TNF-α) signalling is implicated in neutrophilic asthma. TNF-α signalling involves membrane-bound and soluble ligand (TNF-α) and receptors (TNFRs); however, little is known about how these proteins are altered in asthma. We hypothesised that intercompartment-, immune cell- and/or asthma inflammatory phenotype-dependent regulation could relate to TNF dysregulation in neutrophilic asthma.MethodsMeasurements were made in 45 adults with asthma (36 non-neutrophilic, 9 neutrophilic) and 8 non-asthma controls. Soluble TNF-α, TNF receptor 1 (TNFR1) and TNFR2 were quantified in plasma and sputum supernatant by ELISA, and membrane-bound TNF-α/TNFR1/TNFR2 measured on eosinophils, neutrophils, monocytes, and macrophages in blood and sputum by flow cytometry. Marker expression was compared between inflammatory phenotypes and compartments, and relationship of membrane-bound and soluble TNF markers and immune cell numbers tested by correlation.ResultsSoluble sputum TNFR1 and TNFR2 were increased in neutrophilic versus non-neutrophilic asthma (p=0.010 and p=0.029). Membrane-bound TNF-α expression was upregulated on sputum versus blood monocytes, while TNFR1 and TNFR2 levels were reduced on airway versus blood monocytes and neutrophils. Soluble TNFR1 and TNFR2 in sputum significantly correlated with the number of airway monocytes (p=0.016, r=0.358 and p=0.029, r=0.327).ConclusionOur results imply that increased sputum soluble TNF receptor levels observed in neutrophilic asthma relate to the increased recruitment of monocytes and neutrophils into the airways and their subsequent receptor shedding. Monocytes also increase TNF-α ligand expression in the airways. These results suggest an important contribution of airway monocytes to the altered inflammatory milieu in neutrophilic asthma.

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Grebski, E., C. Graf, G. Hinz, B. Wuthrich, and TC Medici. "Eosinophil cationic protein in sputum is dependent on temperature and time." European Respiratory Journal 11, no. 3 (March 1, 1998): 734–37. http://dx.doi.org/10.1183/09031936.98.11030734.

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Eosinophil cationic protein (ECP) in sputum may be used to estimate the severity of bronchial inflammation and obstruction in asthmatics as well as to monitor asthma drug therapy. For this purpose, standardized processing of sputum is important. The aim of our study was to determine whether time and temperature influence the ECP concentration in the sputum of asthmatics. The samples of induced sputum obtained from 12 patients with stable asthma were homogenized using ultrasonification, and centrifuged. Supernatants were evenly divided and stored for 1, 6, 24 or 72 h at either 4 or 25 degrees C, then frozen at -80 degrees C. The ECP concentrations were determined using fluoroimmunoassay and compared with the immediately frozen samples. After storing at 4 degrees C, the ECP levels at the four time points were 101.2, 96.0, 98.2 and 90.6% of the initial concentration, respectively. When sputum specimens were stored at 25 degrees C, ECP levels decreased to 96.1, 94.4, 90.7 and 87.7%, respectively. The influence of time on ECP concentrations in sputa was statistically significant (p=0.02). A significant temperature effect was found when comparing the specimens stored at 4 degrees C with those at 25 degrees C (p=0.03). Looking at individual time points, a significant decrease in ECP concentration was only seen at 25 degrees C after 24 and 72 h. We conclude that eosinophilic cationic protein in the sputum of asthmatics decreases in a time- and temperature-dependent process. If sputa cannot be processed after obtaining the specimens, they should be stored in a refrigerator at 4 degrees C, until eosinophilic cationic protein is measured.

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