***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 
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    ***EXAMPLES*** 
    Input: PURPOSE Viable bacteria are often isolated from airway secretions in clinical ly stable patients with chronic bronchitis . We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation . SUBJECTS AND METHODS We performed quantitative sputum cultures in 160 stable patients [ 55 with chronic obstructive pulmonary disease ( COPD ) and normal serum alpha(1)-antitrypsin levels , 62 with COPD and severe alpha(1)-antitrypsin deficiency ( PiZ ) , and 43 with idiopathic bronchiectasis ] . The results were related to several indicators of the mechanisms and severity of airway inflammation . RESULTS Airway bacterial load correlated with sputum myeloperoxidase level , an indirect measure of neutrophil activation and number ( r = 0.50 , P<0 . 001 ) ; sputum neutrophil chemoattractants [ interleukin-8 level ( r = 0 . 68 , P<0.001 ) and leukotriene B4 level ( r = 0.53 , P<0.001 ) ] ; sputum leukocyte elastase activity ( r = 0.55 , P<0.001 ) ; and albumin leakage from serum to sputum ( r = 0.26 , P<0.01 ) . Markers of inflammation increased at bacterial loads of 10(6 ) to 10(7 ) colony-forming units per milliliter , and increased progressively with increasing bacterial load . For example , the median ( interquartile range ) sputum myeloperoxidase level was 0.3 U/mL ( 0.1 to 0.5 U/mL ) for patients who were not colonized or who had mixed normal oropharyngeal flora alone ; 0.5 U/mL ( 0.2 to 0.7 U/mL ) for patients with 10(5 ) to 10(6 ) colony-forming units per milliliter ( P = 0.07 ) ; 0.5 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(6 ) to 10(7 ) colony-forming units per milliliter ( P<0.01 ) ; 0.7 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(7 ) to 10(8 ) colony-forming units per milliliter ( P < 0.005 ) ; and 2.4 U/mL ( 0.7 to 4.8 U/mL ) for patients with 10(8 ) or greater colony-forming units per milliliter ( P<0.0001 ) . The bacterial species influenced airway inflammation ; for example , sputum myeloperoxidase activity was greater ( P<0.005 ) in patients colonized with Pseudomonas aeruginosa [ median 32 U/mL ( interquartile range , 20 to 65 U/mL ) ] than those colonized with nontypeable Hemophilus influenzae [ 4 U/mL ( 2 to 31 U/mL ) ] , which in turn was greater ( P = 0.01 ) than among those colonized with Moraxella catarrhalis [ 1.1 U/mL ( 0.6 to 1.8 U/mL ) ] . We did not find a relation between bacterial load and lung function . CONCLUSIONS The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis . Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function UNLABELLED Neutrophil elastase ( NE ) activity is increased in bronchiectasis and may play a role in this condition . We wished to determine the effect of AZD9668 , a selective oral inhibitor of NE . Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a r and omised , double-blind , placebo-controlled , parallel-group , Phase II , signal- search ing study in patients with bronchiectasis . Outcome measures included : waking and post-waking sputum neutrophil counts ; lung function tests ; 24-h sputum weight ; BronkoTest ( ® ) diary card data ; St George 's Respiratory Question naire for COPD patients ( SGRQ-C ) ; sputum NE activity ; inflammatory biomarker levels ; desmosine levels ; adverse events , safety haematology and biochemistry . AZD9668 levels in plasma and sputum were measured to confirm exposure . Thirty-eight patients were r and omised : 16 to placebo and 22 to AZD9668 . There was no change in sputum neutrophils with AZD9668 . Forced expiratory volume in 1 s improved by 100 mL in the AZD9668 group compared with placebo ( p = 0.006 ) . Significant changes ( defined a priori as p < 0.1 ) in favour of AZD9668 were also seen in slow vital capacity , plasma interleukin-8 , and post-waking sputum interleukin-6 and Regulated on Activation , Normal T-cell Expressed and Secreted levels . Non-significant changes in favour of AZD9668 were seen in other lung function tests , sputum weight and the SGRQ-C.  AZD9668 was well tolerated . In this small signal- search ing study , 4 weeks ' treatment with AZD9668  improved lung function  in patients with bronchiectasis and there were trends for reductions in sputum inflammatory biomarkers . Larger studies of longer duration would be needed to confirm the potential benefits of this agent in bronchiectasis . REGISTRATION NCT00769119 BACKGROUND 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 . METHODS 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 ) . RESULTS 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 + cell 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 gl and hypertrophy . Gl and area comprised up to 40 % of the tissue in some bronchiectasis sections while no hypertrophy was noted in control biopsy specimens ( p<0.05 ) . CONCLUSION 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 prospect i ve placebo controlled trial RATIONALE Bronchiectasis is a chronic debilitating disease with few evidence -based long-term treatments . OBJECTIVES A r and omized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis . METHODS Sixty-five patients were r and omized to either twice-daily nebulized gentamicin , 80 mg , or nebulized 0.9 % saline , for 12 months . All were review ed at three-monthly intervals during treatment and at 3 months ' follow-up . MEASUREMENTS AND MAIN RESULTS At each review the following were assessed : quantitative and qualitative sputum bacteriology ; sputum purulence and 24-hour volume ; FEV(1 ) , FVC , and forced expiratory flow , midexpiratory phase ; exercise capacity ; Leicester Cough Question naire and St. George 's Respiratory Question naire ; and exacerbation frequency .  Fifty-seven patients completed the study . At the end of 12 months ' treatment , compared with the saline group , in the gentamicin group there was reduced sputum bacterial density with 30.8 % eradication in those infected with Pseudomonas aeruginosa and 92.8 % eradication in those infected with other pathogens ; less sputum purulence ( 8.7 % vs. 38.5 % ; P < 0.0001 ) ; greater exercise capacity ( 510 [ 350 - 690 ] m vs. 415 [ 267.5 - 530 ] m ; P = 0.03 ) ; and fewer exacerbations ( 0 [ 0 - 1 ] vs. 1.5 [ 1 - 2 ] ; P < 0.0001 ) with increased time to first exacerbation ( 120 [ 87 - 161.5 ] d vs. 61.5 [ 20.7 - 122.7 ] d ; P = 0.02 ) . The gentamicin group had greater improvements in Leicester Cough Question naire ( 81.4 % vs. 20 % ; P < 0.01 ) and St. George 's Respiratory Question naire ( 87.5 % vs. 19.2 % ; P < 0.004 ) score . No differences were seen in 24-hour sputum volume , FEV(1 ) , FVC , or forced expiratory flow , midexpiratory phase . No P. aeruginosa isolates developed resistance to gentamicin . At follow-up , all outcome measures were similar to baseline . CONCLUSIONS Regular , long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy . Clinical trial registered with www . clinical trials.gov ( NCT 00749866 ) The airways of cystic fibrosis ( CF ) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield . Inhalation of α1-antitrypsin ( AAT ) may restore the protease – antiprotease balance and attenuate airway inflammation in CF airways . The aims of the present study were : 1 ) to assess the best deposition region for inhaled AAT by two different inhalation strategies ; and 2 ) to examine the effect of 4 weeks of AAT inhalation on lung function , protease – antiprotease balance and airway inflammation in CF patients . In a prospect i ve , r and omised study , 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment . The levels of elastase activity , AAT , pro-inflammatory cytokines , neutrophils , immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period . Inhalation of AAT  increased AAT levels and decreased the levels of elastase activity , neutrophils , pro-inflammatory cy 
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In this review sputum NE has proved useful as an inflammatory marker both in stable state bronchiectasis and during exacerbations and local or systemic antibiotic treatment .
NE has also been associated with risk of exacerbation , time to next exacerbation and all-cause mortality .
This study review s also the role of NE as a specific target of treatment in bronchiectasis .