***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: Abstract Sixty‐four patients with chronic bronchitis with a history of recurrent respiratory tract infections were admitted to a double‐blind r and omised controlled study in which the efficacy of an oral vaccine containing killed Haemophilus influenzae in preventing acute exacerbations of chronic bronchitis was compared with placebo . Patients given vaccine developed fewer acute infective episodes . Although the numbers of patients who required antibiotic therapy in the two groups were not significantly different , the number of antibiotic prescriptions given to the vaccinated group of patients was significantly less than that required by the control group . A reduction in colonisation with Haemophilus influenzae occurred in the active group , which was maximal 14 weeks after the onset of the study . ( Aust NZ J Med 1991 ; 21 : 427–432 . Subjects prone to recurrent acute bronchitis were admitted to a six-month double-blind clinical study , in which the value of oral immunization with a preparation of killed Haemophilus influenzae was tested . Most subjects had early smoking-related chronic lung disease , unrecognized by either the patient or his/her doctor . Subjects taking the active agent had a 41 % reduction in the total number of episodes of acute bronchitis ( P = 0.16 ) , a 60 % reduction in the number of episodes of acute wheezy bronchitis ( P = 0.02 ) and a 58 % reduction in antibiotic use ( P = 0.07 ) . The power of analysis was restricted by the small study group . Parameters of episode severity favoured the test group , suggesting that individual episodes of acute bronchitis in subjects taking an oral preparation of killed H. influenzae were less severe than in those taking placebo tablets . Oral immunization with H. influenzae selectively reduced the increase in colonization of the oropharynx with H. influenzae which occurred in the group taking placebo . This is the first demonstration that the common mucosal system can be activated to modify a colonization pattern at a distant site BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease ( COPD ) .  Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases . METHODS We performed a r and omized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment , resting tachycardia , or apparent risk of prolongation of the corrected QT interval . RESULTS A total of 1577 subjects were screened ; 1142 ( 72 % ) were r and omly assigned to receive azithromycin , at a dose of 250 mg daily ( 570 participants ) , or placebo ( 572 participants ) for 1 year in addition to their usual care . The rate of 1-year follow-up was 89 % in the azithromycin group and 90 % in the placebo group . The median time to the first exacerbation was 266 days ( 95 % confidence interval [ CI ] , 227 to 313 ) among participants receiving azithromycin , as compared with 174 days ( 95 % CI , 143 to 215 ) among participants receiving placebo ( P<0.001 ) . The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group , as compared with 1.83 per patient-year in the placebo group ( P=0.01 ) , and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 ( 95 % CI , 0.63 to 0.84 ; P<0.001 ) . The scores on the St. George 's Respiratory Question naire ( on a scale of 0 to 100 , with lower scores indicating better functioning ) improved more in the azithromycin group than in the placebo group ( a mean [ ±SD ] decrease of 2.8±12.8 vs. 0.6±11.4 , P=0.004 ) ; the percentage of participants with more than the minimal clinical ly important difference of -4 units was 43 % in the azithromycin group , as compared with 36 % in the placebo group ( P=0.03 ) . Hearing decrements were more common in the azithromycin group than in the placebo group ( 25 % vs. 20 % , P=0.04 ) . CONCLUSIONS Among selected subjects with COPD  , azithromycin taken daily for 1 year , when added to usual treatment , decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects . Although this intervention could change microbial resistance patterns , the effect of this change is not known . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00325897 . ) The PARI-IS Study is a double-blind placebo-controlled r and omized clinical trial to study the effect of an immunostimulating agent to prevent acute respiratory exacerbation in patients with COPD . Three hundred eighty-one ambulatory patients ( 190 placebo and 191 immunostimulant )  were followed at home for 6 mo by experienced research nurses . The risk of having at least one episode of acute exacerbation ( primary outcome ) was similar in the two groups ( p = 0.872 ) . In contrast , the total number of days of hospitalization for a respiratory problem was 55 % less in the group treated with OM-85 BV ( 287 d ) than in the group treated with placebo ( 642 d ) . Patients treated with OM-85 BV spent an average of 1.5 d in hospital compared with 3.4 d for patients treated with placebo ( p = 0.037 ) . The risk of being hospitalized for a respiratory problem was 30 % lower in the treated group ( 16.2 % ) than in the placebo group ( 23.2 % ) ; p = 0.089 . Eight deaths were observed : two in patients treated with OM-85 BV and six in patients treated with placebo ( p = 0.153 ) . During the course of the study dyspnea improved slightly in patients treated with OM-85 BV , whereas it deteriorated slightly in patients receiving placebo ( p = 0.028 ) . These results suggest that this immunostimulating agent may be beneficial for patients with COPD by reducing the likelihood of severe respiratory events leading to hospitalization Following the administration of a st and ardized question naire , 62 adult patients with chronic bronchitis were enrolled into a double-blind controlled trial of an oral killed Haemophilus influenzae vaccine  in the highl and s of Papua New Guinea . A 3-day course of vaccine or placebo was given monthly for 3 consecutive months . Participants were monitored weekly over 12 months for acute exacerbations ; early morning sputum specimens were collected monthly and during acute exacerbations . Density of colonization by H. influenzae and H. parainfluenzae was determined by st and ard quantitative and semiquantitative techniques , and the latter method ( quadrant score ) was used to determine the density of growth of pneumococci . A total of 30 patients received vaccine and 32 placebo .  The incidence rate of acute bronchitis in the vaccine group ( 0.011 episodes/person-weeks ) was significantly lower than that in the placebo group ( 0.021 episodes/person-weeks ) , but there was no difference between the two groups in the incidence rates of more severe disease . Vaccine efficacy was maximal at times of peak incidence of disease . There was no evidence of a decline in vaccine efficacy for acute bronchitis over the 12-month follow-up period . The number of viable H. influenzae in the sputum declined in both vaccine and placebo groups over the 12-month follow-up period . The average concentration of H. influenzae in the vaccine group fell below that in the placebo group within 1 to 2 months after first immunization and remained so for 12 months , although the difference between the two groups narrowed during the follow-up period . ( ABSTRACT TRUNCATED AT 250 WORDS Oral immunotherapy with inactivated non‐typeable Haemophilus influenzae ( NTHi ) prevents exacerbations of chronic obstructive pulmonary disease , but the mechanism is unclear . The aim of this study was to determine the mechanism of protection . This was a placebo versus active prospect i ve study over 3 months in 64 smokers . The active treatment was three courses of oral NTHi given at monthly intervals , followed by measurement of bacteriological and immunological parameters . The results can be summarized : ( i ) NTHi‐specific T cells increased in the placebo treatment group over time ( P < 0·05 ) ; ( ii ) the T cell response in the oral NTHi group started earlier than that in the placebo group ( P < 0·05 ) ; and ( iii ) serum NTHi‐specific immunoglobulin (Ig)G had significantly greater variation in the placebo group ( P < 0·0001 ) . The increase in antibody in placebos over time correlated with exposure to live H. influenzae ( P < 0·05 ) determined from culture of gargles ; ( iv ) reduction in saliva lysozyme over time ( P < 0·05 ) was detected only in the oral NTHi treatment group . These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut , with oral immunotherapy augmenting this process leading to enhanced bronchus protection . The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group , contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group . Saliva lysozyme was a useful biomarker of mucosal inflammation , falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation Fifty patients with chronic obstructive lung disease were r and omly allocated to three groups , to assess whether an oral vaccine containing non-typable Haemophilus influenzae protected against  acute bronchitis .  The double-blind prospect i ve study over a three-month winter period included two placebo groups and one test group . Oral immunisation with H influenzae induced a tenfold reduction in the incidence of infection ( p less than 0.001 ) . During the subsequent winter , without further immunisation , protection by the vaccine was no longer statistically significant . There was no clear correlation between clinical protection and either carriage of H influenzae or the level of antibody to H influenzae antigen in saliva BACKGROUND Acute exacerbations of COPD reflect in part an inappropriate host response to abnormal bacterial colonization . Orally administered inactivated nontypeable Haemophilus influenzae ( NTHi ) can drive a specific T-cell response that by promoting intrabronchial phagocytosis down-regulates bronchus inflammation . METHODS Subjects with recurrent exacerbations of COPD were studied in a r and omized , multicenter , double-blind , placebo-controlled trial , to test efficacy of an NTHi oral immunotherapeutic ( HI-164OV ) . This report describes the outcome in 38 subjects with severe COPD defined as having an FEV(1 ) < or = 50 % of predicted normal . RESULTS Exacerbations defined as an increase in volume and purulence of sputum were reduced by 16 % ( not significant ) in the active group . However , moderate-to-severe exacerbations ( defined as requiring corticosteroid therapy ) were reduced by 63 % ( P = .05 ) . The proportion with any acute exacerbation was little changed with treatment , but the proportion with episodes requiring corticosteroid therapy was reduced by 56 % ( P = .07 ) . The mean duration of episodes was reduced by 37 % ( P = .01 ) and prescribed courses of antibiotics were reduced by 56 % ( P = .03 ) following therapy . Exacerbations requiring admission into hospital were reduced by 90 % ( P = .04 ) in the active group . No specific adverse effect was detected . CONCLUSIONS Treatment of severe COPD with frequent exacerbations with HI-164OV was safe and effective , especially with respect to reduction in parameters of severity . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au ; identifier : ACTRN012606000074594 
    Output:
    
Analyses demonstrate that NTHi oral vaccination of people with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations .
Evidence was mixed , and the individual trials that showed a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD