***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction : Induced sputum is a non‐invasive method , and a useful tool to evaluate inflammatory cells and mediators in the airway lumen in the setting of acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . However , the inhalation of hypertonic saline solution to induce sputum may cause a bronchoconstrictive response , so it is important to evaluate the success and safety of sputum induction ( SI ) BACKGROUND Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways . It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS Seventy one patients with COPD were followed prospect ively and sample d for  plasma and sputum ET-1 levels when stable and during an exacerbation . Sputum was also examined for cytokines , human rhinovirus , and Chlamydia pneumoniae . RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD ( mean ( SD ) 0.58 ( 0.31 ) pg/ml ) ; 28 pairs of stable-exacerbation plasma sample s had a mean stable ET-1 level of 0.54 ( 0.30 ) pg/ml rising to 0.67 ( 0.35 ) pg/ml at exacerbation ( mean difference 0.13 , 95 % confidence interval ( CI ) 0.04 to 0.21 , p = 0.004 ) . Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second ( FEV1;r = –0.29 , p = 0.022 ) and forced vital capacity ( FVC ; r = –0.38 , p = 0.002 ) . The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation ( Sao 2;r = –0.41 , p = 0.036 ) . In 14 stable-exacerbation pairs of sputum sample s median stable ET-1 levels were 5.37 ( 0.97–21.95 ) pg/ml rising to 34.68 ( 13.77–51.95 ) pg/ml during an exacerbation ( mean difference 25.14 , 95 % CI 3.77 to 46.51 , p = 0.028 ) . This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels ( r = 0.917 , p = 0.001 ) and sputum interleukin (IL)-6 levels ( r = 0.718 , p = 0.013 ) . CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels . ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD STUDY OBJECTIVES The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50 % of acute exacerbations of chronic bronchitis ( AECB ) is controversial . If bacterial pathogens cause these AECB , they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations . DESIGN This hypothesis was tested by comparing levels of interleukin (IL)-8 , tumor necrosis factor (TNF)-alpha , and neutrophil elastase ( NE ) in 81 sputum sample s obtained from 45 patients with AECB . Four groups were compared . In the first three groups , nontypable Haemophilus influenzae ( n = 20 ) , Haemophilus parainfluenzae ( n = 27 ) , and Moraxella catarrhalis ( n = 14 ) were isolated as sole pathogens , respectively . In the fourth group , only normal flora was isolated ( n = 20 ) . Paired sample s , obtained from individual patients at different times , that differed in their culture results were also compared . SETTING An outpatient research clinic at a Veterans Affairs Medical Center . PATIENTS These patients were participating in a prospect i ve , longitudinal study of the dynamics of bacterial infection in chronic bronchitis , for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB . INTERVENTIONS None . MEASUREMENTS AND RESULTS H influenzae exacerbations were associated with significantly higher sputum IL-8 , TNF-alpha , and NE . M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations . H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations . Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB . CONCLUSIONS Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB Background Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future . Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes . We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease ( COPD ) and clinical ly relevant disease phenotypes . Methods Breath sample s from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry .  Subjects with COPD also underwent sputum induction . Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis : 1 . principal component analysis ; 2 . multivariate logistic regression ; 3 . receiver operating characteristic ( ROC ) analysis . Results Comparing COPD versus healthy controls , principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71 % of the variance . Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69 % . The model had 85 % sensitivity , 50 % specificity and ROC area under the curve of 0.74 . Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy . Models were constructed which classified subjects with ≥2 % sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95 . Potential biomarkers correlated to clinical variables were identified in each subgroup . Conclusion The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinical ly relevant COPD subgroups . If these findings are vali date d in prospect i ve cohorts , they may have diagnostic and management value in this disease Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease ( E COPD ) . Reduced activity of histone deacetylases ( HDAC ) contributes to enhanced inflammation in stable COPD . It was hypothesised that HDAC activity is further reduced during E COPD and that theophylline , an HDAC activator , potentiates the anti-inflammatory effect of steroids in these patients . A study was performed to investigate HDAC activity during E COPD and the effects of theophylline on the anti-inflammatory effects of steroids in a r and omised single-blind controlled study . Methods : 35 patients hospitalised with E COPD and treated according to international guidelines ( including systemic steroids ) were r and omised to receive or not to receive low-dose oral theophylline ( 100 mg twice daily ) . Before treatment and 3 months after discharge , HDAC and nuclear factor-κB ( NF-κB ) activity in sputum macrophages , the concentration of nitric oxide in exhaled air ( eNO ) and total antioxidant status ( TAS ) , tumour necrosis factor α ( TNFα ) , interleukin (IL)-6 and IL8 levels in sputum supernatants were measured . Results : Patients receiving st and ard therapy showed decreased NF-κB activity , eNO concentration and sputum levels of TNFα , IL6 and IL8 , as well as increased TAS during recovery of E COPD , but HDAC activity did not change . The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFα concentrations . Conclusions : During E COPD , low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids . Trial registration number : Although inflammatory changes are found throughout the airways of patients with chronic bronchitis , the mechanisms of the pathogenesis of chronic bronchitis are still unclear . The aim of this study was to investigate airways inflammation in patients with and without an exacerbation of bronchitis . Thirteen chronic bronchitic patients and nine normal subjects were studied . Eight of the patients were studied under baseline conditions ( B ) , and five during an exacerbation of bronchitis ( E ) . Bronchoscopy and bronchoalveolar lavage ( BAL ) with cytological analysis were performed , and the levels of granulocyte/macrophage colony-stimulating factor ( GM-CSF ) were determined in sera and in BAL supernatants by a solid phase enzyme immunoassay . Compared with patients under baseline conditions , chronic bronchitic patients with an exacerbation had increased numbers of BAL neutrophils ( 10+/-3 and 83+/-18x10(3 ) cells x mL(-1 ) , respectively ; p<0.0001 ) and of BAL eosinophils ( 1.9+/-0.5 and 6.7/-1.9x10(3 ) cells x mL(-1 ) , respectively ; p=0.014 ) . Patients with chronic bronchitis , as a whole , had significantly increased levels of BAL GM-CSF compared to control subjects ( 36+/-5 and 19+/-4 pg x mL(-1 ) , respectively ; p=0.035 ) , and similar levels of serum GM-CSF . Serum levels of GM-CSF were markedly increased in chronic bronchitic patients with an exacerbation , as compared with patients under baseline conditions ( 1.4+/-0.4 and 13+/-1 pg x mL(-1 ) , respectively ; p < 0.0001 ) . BAL levels of GM-CSF were also increased in chronic bronchitic patients with an exacerbation ( 25+/-5 and 54+/-8 pg x mL(-1 ) , respectively ; p=0.009 ) . During exacerbations of chronic bronchitis there are changes in the cell population s in bronchoalveolar lavage of patients consistent with a recruitment of polymorphonuclear leucocytes in the airway lumen . The increased levels of granulocyte/macrophage colony-stimulating factor might suggest a role for this cytokine in the inflammatory processes of chronic bronchitis The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic .  The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic .  Peak flow recovered more rapidly with antibiotic treatment than with placebo .  Side effects were uncommon and did not differ between antibiotic and placebo Background : Chronic obstructive pulmonary disease ( COPD ) is characterized by airway inflammation and is associated with acute exacerbations . Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases . Objective : The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients . Methods : We conducted a r and omized , placebo-controlled , double-blind trial of erythromycin for a period of 6 months . Thirty-six COPD patients were r and omized to treatment with oral erythromycin ( 125 mg , three times/day ) or placebo . The primary outcomes were neutrophil number in sputum and exacerbations . Results : Thirty-one patients completed the study . At the end of treatment , neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients ( p = 0.005 ) . Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group ( p = 0.021 and p = 
    Output:
    
Among the clinical ly relevant molecules , those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery , as well as for directing towards an etiological diagnosis .
In conclusion , pulmonary biomarkers have the potential to provide information on the mechanisms underlying E COPD , and several correlate with clinical variables and outcomes .