interleukin-8 and Bronchiectasis

Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans.. A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074).. Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 μg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups.. Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis.. Cystic Fibrosis Foundation.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Child; Child, Preschool; Cystic Fibrosis; Double-Blind Method; Humans; Infant; Infant, Newborn; Inflammation; Interleukin-8; Leukocyte Elastase

Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy.. Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test-20.. Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO.. In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification.. ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov.

Topics: Aged; Aged, 80 and over; Bronchiectasis; Cough; Cytokines; Disease Progression; Epidermal Growth Factor; Female; Humans; Humidifiers; Humidity; Hypertension, Pulmonary; Interleukin-10; Interleukin-8; Macrophages; Male; Middle Aged; Mucociliary Clearance; Mucus; Nasal Lavage Fluid; Oxygen Inhalation Therapy; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Respiratory Function Tests; Surface Tension

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% versus placebo (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 (nine versus eight), but these led to more study discontinuations with AZD5069 (four versus zero). Sputum interleukin (IL)-6 and growth-regulated oncogene (GRO)-α and serum GRO-α, IL-1ß and IL-8 levels increased with AZD5069 versus placebo (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.

Topics: Adult; Aged; Bronchiectasis; C-Reactive Protein; Cell Count; Chemokine CXCL1; Double-Blind Method; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Pyrimidines; Receptors, Interleukin-8B; Sputum; Sulfonamides; Surveys and Questionnaires; Treatment Outcome

The therapeutic benefit of inhaled corticoids in bronchiectasis not due to cystic fibrosis is still not well documented. The aim of the present study was to assess the efficacy and safety of inhaled corticoids in this disease.. This study was conducted at a tertiary university hospital in the city of Barcelona, Catalonia, (Spain).. A prospective, double-blind, parallel, placebo-masked study was conducted. Seventy-seven patients (40 women; mean age: 68 years) were randomly assigned to receive either 400 mcg budesonide twice daily or placebo and were regularly reviewed for six months.. Differences in forced vital capacity and forced expiratory volume in the first second between the beginning and end of the study were not significantly lower in the budesonide group than in the placebo group, either in absolute values [-17.4 (386.9) versus -21.4 (375.5)] or in percentages [-1.9(9.5) versus -2.8 (11.6)]. Microbiological criteria applied to evaluate changes between the beginning and end of the study showed no worsening in the budesonide group compared with the control group, whereas a non-significant improvement was obtained in 8.1 % of cases in the budesonide group compared to 3 % in the placebo group. Although significance was only achieved for sputum eosinophils (p = 0.021), a consistent tendency towards improvement was also observed in secondary end-points (symptoms, number and duration of exacerbations, quality of life, sputum cytology and interleukin-8) in the budesonide group.. Although further studies are required, inhaled corticoid treatment may be efficacious and safe in bronchiectasis not due to cystic fibrosis.

Topics: Administration, Inhalation; Aged; Bronchiectasis; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Interleukin-8; Male; Quality of Life; Sputum; Vital Capacity

The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF).. To evaluate the effects of a macrolide antibiotic [clarithromycin (CAM)] on the process of inflammation [by measuring IL-8, TNF-alpha, IL-10 levels and cell profiles in bronchoalveolar lavage (BAL) fluid], pulmonary function and sputum production in children with steady-state bronchiectasis, secondary to causes other than CF or primary immunodeficiencies.. Seventeen patients randomized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only.. Compared with the control group, the treatment group showed a significant decrease in IL-8 levels, total cell count, neutrophil ratios in BAL fluid and daily sputum production at the end of the third month. There was also a significant increase in the treatment group's BAL fluid macrophage ratios. The differences in pulmonary function test parameters were not significant.. Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs. No corresponding clinical improvement could be shown but although this is possible with long-term use, trial validation is necessary.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bronchiectasis; Bronchoalveolar Lavage Fluid; Child; Clarithromycin; Colony Count, Microbial; Female; Humans; Interleukin-10; Interleukin-8; Leukocyte Count; Male; Respiratory Function Tests; Sputum; Tumor Necrosis Factor-alpha

Although corticosteroid therapy might be clinically beneficial for bronchiectasis, very little is known of its effects on the inflammatory and infective markers in bronchiectasis. We have therefore performed a double-blind, placebo-controlled study to evaluate the effects of a 4-wk administration of inhaled fluticasone in bronchiectasis. Twenty-four patients (12 female; mean age 51 yr) were randomized into receiving either inhaled fluticasone (500 microgram twice daily) via the Accuhaler device (n = 12) or placebo. At each visit, spirometry, 24-h sputum volume, sputum leukocyte density, bacterial densities, and concentrations of interleukin (IL)-1beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4 (LTB4) were determined. There was a significant (p < 0.05) decrease in sputum leukocyte density and IL-1beta, IL-8, and LTB4 after fluticasone treatment. The fluticasone group had one and the placebo group three episodes of exacerbation. There were no significant changes in spirometry (p > 0.05) or any reported adverse reactions in either group. The results of this study show that high-dose fluticasone is effective in reducing the sputum inflammatory indices in bronchiectasis. Large-scale and long-term studies are indicated to evaluate the effects of inhaled steroid therapy on the inflammatory components in bronchiectasis.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Bronchiectasis; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Inflammation; Interleukin-1; Interleukin-8; Leukocyte Count; Leukotriene B4; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Placebos; Pseudomonas aeruginosa; Sputum; Tumor Necrosis Factor-alpha; Vital Capacity

To explore the clinical benefits of azithromycin in the treatment of Pseudomonas aeruginosa induced bronchiectasis and to evaluate its effect on MUC5AC. From April 2018 to June 2020, 160 patients with bronchiectasis due to Pseudomonas aeruginosa infection were selected. The patients were divided into a control groupand an azithromycin group. Statistics of patients' general clinical data, lung function indexes, sputum volume, oxidative stress level, Bhalla score before and after treatment; Western blot analysis of MUC5AC expression; RT-PCR analysis of TNF-α, IL-8, IL- 1β mRNA expression. The mRNA expression of TNF-α, IL-8 and IL-1β in the azithromycin group was lower than that in the control group (P<0.05). After treatment, the protein expression of MUC5AC in the azithromycin group was lower than that in the control group (P<0.05). The improvement rate in the azithromycin group was significantly higher than that in the control group (P<0.05). The azithromycin group had a lower lung infection rate than the control group (P<0.05). The azithromycin group had a lower dyspnea rate than the control group (P<0.05). Azithromycin treatment has certain clinical benefits for patients with bronchiectasis induced by Pseudomonas aeruginosa and inhibits the MUC5AC expression.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Dyspnea; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Mucin 5AC; Pseudomonas aeruginosa; Pseudomonas Infections; RNA, Messenger; Tumor Necrosis Factor-alpha

Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non-cystic fibrosis (non-CF) bronchiectasis, little is known about non-invasive techniques used for evaluating airway inflammation in obstructive airway diseases.. We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non-CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD.. We evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients.. We enrolled 40 subjects (21men, mean age 63.5yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic-eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL-8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL-13. Sputum IL-8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r=0.799), the extent of bronchiectasis in HRCT (r=0.765) and post-bronchodilator FEV. Sputum cell counts and IL-8 and IL-13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non-invasively assessing inflammation in non-cystic fibrosis bronchiectasis.

Topics: Bronchiectasis; Cell Count; Cystic Fibrosis; Demography; Female; Humans; Inflammation; Interleukin-13; Interleukin-8; Male; Middle Aged; Neutrophils; Phenotype; Pseudomonas aeruginosa; Respiratory Function Tests; Severity of Illness Index; Sputum

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is demonstrating promise as an inflammatory biomarker of acute infection in various pulmonary conditions; including community acquired pneumonia, ventilator associated pneumonia and non-tuberculous mycobacterial infection.. The expression of sTREM-1 has been poorly studied in all forms of bronchiectasis, both in the context of cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis.. Induced sputum samples were collected for sTREM-1 determination in children with HIV-associated bronchiectasis and CF-bronchiectasis. The presence or absence of an exacerbation was noted at study entry. Lung function parameters (FEV1, FVC, FEV1 /FVC, FEF(25-75)) were measured using the Viasys SpiroPro Jaeger Spirometer (Hoechberg, Germany).. A total of twenty-six children with HIV-associated bronchiectasis and seventeen with CF were included. With respect to sTREM-1, the levels were readily detected in both groups, but were significantly higher in children with HIV-associated bronchiectasis (1244.0 pg/ml (iqr 194.5; 3755.3 pg/ml) and 204.9  pg/ml (iqr 66.9; 653.6 pg/ml) P = 0.003. There was a positive correlation between sTREM-1 and IL-8 as well as sputum neutrophil elastase in the HIV-bronchiectasis group (r = 0.715 and r = 0.630), respectively both P < 0.005. sTREM-1 was not further increased in subjects presenting with an acute pulmonary exacerbation in the HIV-associated bronchiectasis and in CF participants (P = 0.971 and P = 0.481), respectively. In the CF group sTREM-1 strongly correlated with FVC% predicted and FEV1 % predicted (r = 0.950 and r = 0.954), both P < 0.005.. The pulmonary innate immune functions are over-active in HIV-associated bronchiectasis, with readily detected sTREM-1 values, which were higher than those in CF. sTREM-1 does not correlate with markers of HIV-disease activity but does correlate with markers of neutrophilic inflammation. In CF sTREM-1 has a negative correlation with pulmonary function parameters.

Topics: Adolescent; Biomarkers; Bronchiectasis; Child; Cystic Fibrosis; Female; HIV Infections; Humans; Interleukin-8; Leukocyte Elastase; Membrane Glycoproteins; Receptors, Immunologic; Sputum; Triggering Receptor Expressed on Myeloid Cells-1

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Exacerbation episodes impair lung function leading to disease progression. Levels of inflammation markers correlate with disease severity. Bacterial immunomodulators have shown a beneficial effect in COPD, improving symptoms and reducing the rate of exacerbations. This is an observational prospective study on 30 patients diagnosed with bronchiectasis and COPD, who received bacterial autogenous vaccine for 12 months. The rate of exacerbation, severity of symptoms and lung function were studied at baseline and after treatment. In addition, plasma levels CRP, IL6, IL8, and TNFα were measured. After treatment we found a reduction in mean acute respiratory infections and signs of lung disease. Acute phase proteins IL6 and CRP increased in blood and IL8 decreased. These changes may be related to the repeated injection of inactivated bacteria. Given the implication of these factors in the pathogenesis of COPD, particularly the production of IL8, the causes and consequences of cytokine modulation by bacterial vaccines should be investigated. Vaccination with autogenous vaccines for 1 year can produce a significant clinical improvement in COPD patients, reducing the frequency of exacerbations associated to changes in the profile of markers of inflammation.

Topics: Bacterial Vaccines; Biomarkers; Bronchiectasis; C-Reactive Protein; Disease Progression; Female; Humans; Immunotherapy; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha

The role of the innate immune system in the pathogenesis of asthma is unclear. Activation of innate immune receptors in response to bacterial lipopolysaccharide, viral infection and particulate matter triggers a pre-programmed inflammatory response, which involves interleukin (IL)8 and neutrophil influx. The inflammatory response in asthma is heterogeneous.. To test the hypothesis that innate immune activation may be a relevant inflammatory mechanism in neutrophilic asthma where IL8 levels are increased.. Induced sputum was obtained from non-smoking adults with asthma (n = 49), healthy controls (n = 13) and a positive reference group with bronchiectasis (n = 9). Subjects with asthma were classified into inflammatory subtypes using induced sputum cell counts. Sputum was examined for mRNA expression of the innate immune receptors toll-like receptor (TLR)2, TLR4 and CD14, and inflammatory cytokines. A separate sputum portion was dispersed and the supernatant assayed for surfactant protein A, IL8, soluble CD14 and endotoxin.. Expression of innate immune receptors was increased in subjects with bronchiectasis and neutrophilic asthma compared with other asthma subtypes and controls. Increased expression of the receptors TLR2, TLR4 and CD14, as well as the pro-inflammatory cytokines IL8 and IL1beta, was observed. Subjects with neutrophilic asthma had higher airway levels of endotoxin than the other groups studied.. There is evidence of activation of the innate immune system in asthma which results in the production of pro-inflammatory cytokines and may contribute to the pathogenesis of neutrophilic asthma.

Topics: Adult; Aged; Asthma; Bronchiectasis; Cross-Sectional Studies; Endotoxins; Eosinophils; Female; Humans; Immunity, Cellular; Interleukin-8; Male; Middle Aged; RNA, Messenger; Toll-Like Receptors

To study clinical, radiological and laboratory features of children with non-cystic fibrosis (non-CF) bronchiectasis (BE) and the association between symptom scores, spirometry, high-resolution computed tomography (HRCT) findings and inflammatory markers in induced sputum in these children. Twenty-seven children with steady-state non-CF BE were cross-sectionally evaluated by symptom scores, pulmonary function tests, anatomic extension and severity scores of BE in HRCT and tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) levels in induced sputum. There were 16 girls and 11 boys. Median (interquartile range) age of study group was 11.4 (9.5-13.6) years, follow-up duration was 3.5 (2-6.5) years and symptom scores were 4 (3-6). Pulmonary function tests revealed FEV(1) of 82%pred (72-93), FVC of 82%pred (74-92), and FEF(25-75%) of 82%pred (68-95). According to anatomic extent of BE on HRCT; 2 patients had mild, 4 had moderate and 21 had severe BE. Based on severity scores of HRCT; 10 patients had mild, 10 had moderate and 7 had severe BE. Neutrophils consisted 29.9% (14.9-53.7) of the total leucocytes in induced sputum samples. Sputum concentration of TNF-alpha was 58 pg/ml (9.2-302) while IL-8 concentration was 2.7 ng/ml (1.7-2.8). Symptom scores correlated with FEV(1) and sputum IL-8 levels (r=-0.49, r=0.67, P<0.05). There was a significant correlation between HRCT severity scores and symptoms, FEV(1), sputum IL-8 and TNF-alpha levels (r=0.64, r=-0.68, r=0.41, r=0.41, respectively, P<0.05). In children BE is associated with ongoing inflammation. This inflammation can be reliably monitored by radiological scores, spirometry, as well as sputum inflammatory markers. Follow-up of children with BE using these clinical tools may improve patient care.

Topics: Adolescent; Biomarkers; Bronchiectasis; Child; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Interleukin-8; Male; Neutrophils; Respiratory Function Tests; Severity of Illness Index; Sputum; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha

To explore the effects of Zhikuofang, a TCM prescription, and Ofloxacin on the inflammation and cytostatics of the airway model of bronchiectasis.. The airway model of bronchiectasis (AMB) was set up and infused with Ps. Aeruginosa. A comparison between the effects of Zhikuofang and Of loxacin on the AMB was made.. Zhikuofang is better than Ofloxacin in following aspects: lowering the density of inflammation cells in blood, decreasing the volume of tracheal secretion and inhibiting the cytostatics (IL-8 and TNF-alpha) of the trachea tissue, but Ofloxacin is more effective in diminishing the amount of bacteria in trachea flushing liquor. There was no marked difference between them in their histopathy effects on the trachea.. Zhikuofang probably plays antiphlogistic and bacteriostatic effects by inhibiting the IL-8 and TNF-alpha, resisting secretion, decreasing the inflammation cells and resisting inflammation of trachea.

Topics: Animals; Anti-Infective Agents; Bronchiectasis; Bronchitis; Drug Combinations; Drugs, Chinese Herbal; Female; Interleukin-8; Male; Ofloxacin; Phytotherapy; Plants, Medicinal; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases.. To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum.. The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001).. These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Topics: alpha 1-Antitrypsin; Biomarkers; Bronchiectasis; Bronchitis; Cathepsin B; Color; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Peroxidase; Proteinase Inhibitory Proteins, Secretory; Proteins; Sputum

Endothelin (ET)-1 has been suggested to promote neutrophil adhesion to endothelium, migration to inflamed areas, and release of elastase. ET-1 might therefore play a role in the pathogenesis of bronchiectasis, a chronic inflammatory and infective airway disease which is still poorly understood. Thirty five patients with stable bronchiectasis (20 females, mean age+/-SD 49.1+/-15.0 yrs) and 18 control subjects (8 females, 49.4+/-11.3 yrs) were recruited prospectively. The ET-1 levels in serum and sputum were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits. Patients with Pseudomonas aeruginosa in their sputum had a significantly higher serum level of ET-1 (median 25.8, interquartile range 13-43.9 pg x mL(-1)) than patients without P. aeruginosa (0, 0-10.5 pg x mL(-1); p=0.0004) and healthy control subjects (4.6, 0-16.3 pg x mL(-1); p=0.002). However, patients with and without P. aeruginosa infection had no significant difference in sputum ET-1 level (p=0.15). There was no correlation between serum or sputum ET-1 levels with the serum and sputum levels of the interleukin (IL)-1beta, IL-8 and tumour necrosis factor (TNF)-alpha; the number of bronchiectasis lung lobes; and spirometry. Serum ET-1 level correlated with 24 h sputum volume for the bronchiectasis patients (r=0.51, p=0.002). The results, therefore, suggest a significant pathogenic role for endothelin-1 among Pseudomonas aeruginosa-infected patients with bronchiectasis. Further studies should be performed to evaluate the clinico-pathological correlation and expression of endothelin-1 in bronchiectasis.

Topics: Bronchiectasis; Endothelin-1; Female; Humans; Interleukin-1; Interleukin-8; Leukocytes; Male; Middle Aged; Pancreatic Elastase; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sputum; Tumor Necrosis Factor-alpha

The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.

Topics: Anti-Bacterial Agents; Bronchiectasis; Bronchiolitis; Bronchoalveolar Lavage Fluid; Chemotactic Factors; Chronic Disease; Forced Expiratory Volume; Humans; In Vitro Techniques; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Macrophages, Alveolar; Middle Aged; Neutrophils; Oxygen; Respiratory Tract Infections; Roxithromycin; Vital Capacity

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Topics: Acute Disease; Anti-Bacterial Agents; Antibodies, Monoclonal; Benzoates; Bronchiectasis; Bronchitis; Cell Movement; Chemotactic Factors; Chemotaxis, Leukocyte; Chronic Disease; Disease Progression; Female; Humans; Interleukin-8; Leukotriene B4; Male; Middle Aged; Mucus; Neutrophils; Receptors, Leukotriene B4; Reproducibility of Results; Sputum; Suppuration

The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.

Topics: Acute Disease; Adolescent; Adult; Aged; Bronchiectasis; CD11 Antigens; CD18 Antigens; Cell Movement; Cell Separation; Chemotaxis, Leukocyte; Chronic Disease; Cystic Fibrosis; Female; Flow Cytometry; Gene Expression Regulation; Humans; Interleukin-8; L-Selectin; Macrophage-1 Antigen; Male; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophil Activation; Neutrophils; Pseudomonas aeruginosa; Pseudomonas Infections; Up-Regulation

Bronchiectasis is a chronic suppurative lung disease characterised by irreversible dilation of the bronchi and persistent purulent sputum. The immunopathology of the disease was studied using a quantitative immunostaining technique with particular reference to T lymphocytes, macrophages, and granulocytes.. Bronchial mucosal biopsy specimens were obtained by fibreoptic bronchoscopy from 12 patients with bronchiectasis (six receiving inhaled steroids) and 11 normal healthy controls. Immunostaining (APAAP method) was performed on frozen cryostat sections with a panel of monoclonal antibodies to total leucocytes (CD45), T lymphocyte phenotypic markers (CD3, CD4, CD8), macrophages (CD68), eosinophils (EG2), and neutrophils (elastase).. There was a mononuclear cell infiltrate in both patients with bronchiectasis and normal controls, but an overall increase in total leucocyte cell numbers (CD45+ cells) was identified in those with bronchiectasis (median values 422 cells/mm2 versus 113 cells/mm2 in control tissue, p < 0.001). Intense infiltration of CD3+ T lymphocytes was observed compared with healthy controls (292 cells/mm2 and 40 cells/mm2, respectively, p < 0.001). This comprised predominantly CD4+ T cells (118 cells/mm2) rather than CD8+ T cells (47 cells/mm2). CD3+ cells counts were reduced in those subjects on inhaled steroids compared with those not receiving inhaled steroids (197 cells/mm2 versus 369 cells/mm2, p < 0.05), as were CD4+ cell counts (82 cells/mm2 versus 190 cells/mm2, p < 0.05). Neutrophil and macrophage cell numbers were also increased in patients with bronchiectasis (114 cells/mm2 and 213 cells/mm2, respectively) compared with controls (41 neutrophils/mm2 and 40 macrophages/mm2). EG2+ (activated) eosinophil numbers were much lower than T cells, macrophages, and neutrophils in patients with bronchiectasis but were increased compared with controls (36 cells/mm2 versus 0 cells/mm2, p < 0.001). In view of the markedly increased neutrophil counts in patients with bronchiectasis, biopsy specimens were immunostained for interleukin 8 (IL-8) which was highly significantly increased compared with controls (47 cells/mm2 versus 15 cells/mm2, p < 0.01). IL-8+ cells were less prominent in steroid treated patients than in patients not receiving treatment (30 cells/mm2 versus 60 cells/mm2, p < 0.05). A further characteristic of bronchiectasis was mucous gland hypertrophy. Gland area comprised up to 40% of the tissue in some bronchiectasis sections while no hypertrophy was noted in control biopsy specimens (p < 0.05).. Airway inflammation in bronchiectasis is characterised by tissue neutrophilia, a mononuclear cell infiltrate composed mainly of CD4+ T cells and CD68+ macrophages, and increased IL-8 expression. Inhaled corticosteroid treatment in patients with bronchiectasis is associated with a less marked infiltration by T cells and IL-8+ cells within the bronchial mucosa, although this finding requires confirmation in a prospective placebo controlled trial.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bronchiectasis; Bronchoscopy; CD3 Complex; CD4-Positive T-Lymphocytes; Cell Count; Female; Humans; Immunohistochemistry; Interleukin-8; Leukocyte Count; Lung; Macrophages, Alveolar; Male; Middle Aged; Neutrophils; Statistics, Nonparametric; Steroids

We examined the activity of neutrophils isolated from sputum and blood of subjects with chronic bronchial sepsis in terms of interleukin-8 (IL-8), IL-1beta, and tumor necrosis factor-alpha (TNF alpha) production. In sputum, the numbers of neutrophils correlated with the concentrations of these cytokines. Sputum neutrophils constitutively secreted large amounts of IL-8, IL-1beta, and TNF alpha. The patterns of secretion, however, differed from those of blood neutrophils stimulated with bacterial lipopolysaccharide (LPS). Cytokine secretion was time-dependent and was inhibited by cycloheximide and dexamethasone. IL-10 inhibition of IL-8 production by sputum neutrophils was significantly less than that noted with activated neutrophils. Antibody to IL-1beta but not to TNF alpha, inhibited IL-8 secretion by sputum neutrophils, contrasting with results found using blood neutrophils. Incubation of blood neutrophils in sputum sol induced a similar cytokine secretion profile to that following exposure to LPS. The inhibitory effects on IL-8 protein production correlated with messenger RNA (mRNA) gene expression. These observations indicate that neutrophils are a significant source of IL-8 in purulent sputum, and that an autocrine loop involving IL-1beta maintains secretion within the bronchus lumen.

Topics: Blood; Bronchiectasis; Chronic Disease; Cycloheximide; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-1; Interleukin-8; Neutrophils; Polymerase Chain Reaction; Protein Synthesis Inhibitors; RNA, Messenger; Sputum; Tumor Necrosis Factor-alpha

We investigated the interleukin-8 (IL-8) levels and neutrophil numbers in the sputum of 9 elderly patients with lower respiratory tract infections, including Pseudomonas aeruginosa infection, before and after treatment with various antimicrobial agents. The IL-8 levels in sputum supernatants and the neutrophil numbers in sputum smears from 9 patients decreased significantly after the elimination of the causative respiratory pathogens. We also demonstrated that human recombinant IL-8 at a range of 6.25-25 ng/ml significantly enhanced opsonophagocytic killing of P. aeruginosa immunotype-1 strain by human neutrophils in the presence of a serotype-specific anti-lipopolysaccharide monoclonal antibody and fresh normal human serum. These data suggest that the level of IL-8 production in the airways of patients with lower respiratory tract infections is dependent on bacterial densities, and indicate the important role of IL-8 not only in neutrophil migration but also in opsonophagocytic killing of bacteria in the lower respiratory tract.

Topics: Aged; Bacterial Infections; Bronchiectasis; Bronchitis; Bronchopneumonia; Female; Humans; Interleukin-8; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Recombinant Fusion Proteins; Respiratory Tract Infections; Serum Albumin; Sputum

To study the role of T cells in diffuse panbronchiolitis (DPB), we investigated T-cell subsets in bronchoalveolar lavage fluid (BALF) or 33 patients with DPB, nine patients with bronchiectasis, and 20 healthy volunteers. BALF from DPB patients contained a higher percentage of neutrophils than that from patients with bronchiectasis or healthy volunteers, whereas the percentage of lymphocytes was similar in the three groups. DPB patients, however, had a higher number of lymphocytes and a reduced CD4/CD8 ratio compared with the other subjects. A two-color analysis of T-cell subsets in peripheral blood and BALF revealed a significant increase in the percentage and number of CD8+HLA-DR+ cells and in the number of CD4+HLA-DR+ cells in BALF of DPB patients. The expression of the adhesion molecules CD 11a and CD18 on lung CD3+ cells was enhanced over that on blood CD3+ cells in DPB patients. However, there was no significant difference in the expression of these antigens in peripheral blood or BALF among the groups. There was no significant relationship between BALF interleukin (IL)-8 and lymphocyte accumulation in the lungs of the DPB patients, whereas a significant correlation between the percentage of neutrophils and IL-8 levels in BALF of DPB patients was observed. After treatment with macrolide antibiotics, a significant reduction in the number of lymphocytes and activated CD8+ cells and an elevation in the CD4/CD8 ratio in BALF of DPB patients was observed. Our findings suggest an activation of CD8+ cells in the airway lumen of DPB patients, supporting the hypothesis that lymphocytes are important cellular components of bronchial inflammation in DPB.

Topics: Anti-Bacterial Agents; Bronchi; Bronchiectasis; Bronchiolitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; CD18 Antigens; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Female; HLA-DR Antigens; Humans; Interleukin-8; Leukocyte Count; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Function-Associated Antigen-1; Macrolides; Male; Neutrophils; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer

Topics: Adult; Anti-Bacterial Agents; Antigens, CD; Bronchi; Bronchiectasis; Cytokines; Female; Humans; Immunity, Cellular; Immunophenotyping; Interleukin-1; Interleukin-8; Leukocytes; Male; Middle Aged; Sputum; Tumor Necrosis Factor-alpha

Sputum from patients with cystic fibrosis, bronchiectasis, and chronic bronchitis contains neutrophils and neutrophil proteases, which have been implicated in the pathophysiology of mucus hypersecretion in airways. We asked whether interleukin-8 (IL-8), a potent neutrophil chemoattractant, might be involved in recruiting neutrophils into airways of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis. We found significant neutrophil chemotactic activity in sputum obtained from these patients. The IL-8 concentrations that we measured in sputum of patients with cystic fibrosis (7.1 +/- 1.0 x 10(-9) M, mean +/- SE), bronchiectasis (9.6 +/- 2.9 x 10(-9) M), and chronic bronchitis (2.8 +/- 1.0 x 10(-9) M) have been reported to cause significant chemotaxis in vitro and in airways in vivo, whereas concentrations measured in induced sputum from healthy subjects (1.1 +/- 0.3 x 10(-10) M) do not. A monoclonal antibody to IL-8 significantly inhibited the chemotactic activity in patients' sputum by 75-98%, but not in induced sputum from healthy subjects (9%). We conclude that IL-8 is an important chemotactic factor in sputum of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis, and we suggest that IL-8 accounts, at least in part, for neutrophil recruitment into airways of patients with these diseases.

Topics: Adult; Biomarkers; Bronchiectasis; Bronchitis; Chemotaxis, Leukocyte; Chronic Disease; Cystic Fibrosis; Female; Humans; Inpatients; Interleukin-8; Male; Middle Aged; Neutrophils; Outpatients; Reference Values; Sputum

1. Some bronchiectatic patients persistently expectorate purulent secretions containing many polymorphonuclear leucocytes (PMN) and bacteria, suggesting ineffective microbial clearing from the lung. We have therefore studied several aspects of PMN recruitment to the lung by chemotaxis. 2. Circulating PMN from patients with bronchiectasis show a variable chemotactic response to the synthetic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. This is similar to the response of PMN from healthy controls and suggests that failure to clear microbial organisms is not due to defective chemotaxis as measured here. 3. Purulent sputum solphase demonstrates chemotactic activity against control PMN. This activity is greater (P less than 0.001) than that found with mucoid sputum solphase, which is consistent with the neutrophil content of the secretions in vivo. 4. Successful antibiotic therapy reduces the chemotactic activity of purulent sputum solphase from a median value of 183 (range 28-201) cells/high power field to 33.5 (range 0.7-64) cells/high power field (P less than 0.0025). This indicates that the chemotactic activity is largely associated with bacterial load.

Topics: Adult; Aged; Amoxicillin; Bronchiectasis; Chemotactic Factors; Chemotaxis, Leukocyte; Female; Humans; Interleukin-8; Male; Middle Aged; Mucus; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Sputum; Suppuration