***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: OBJECTIVES To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis ( CF ) , rather than st and ard therapy , was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions . STUDY DESIGN Costs were assessed in a r and omized controlled trial conducted in Australia and New Zeal and on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or st and ard therapy until they reached 5 years of age . A health care funder perspective was adopted . Re source use measurement was based on st and ardized data collection forms administered for patients across all sites . Unit costs were obtained primarily from government schedules . RESULTS Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in st and ard therapy group ( mean difference AUD1902 , 95 % CI AUD-27 782 to 31 586 , P = .90 ) . Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the st and ard therapy group ( mean difference AUD-9288 ; 95 % CI AUD-35 252 to 16 676 , P = .48 ) . CONCLUSIONS BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a st and ard protocol based upon clinical features and oropharyngeal culture results alone . Following on our previous findings that BAL-directed treatment offers no clinical advantage over st and ard therapy at age 5 years , flexible bronchoscopy with BAL can not be recommended for the routine management of preschool children with CF on the basis of overall cost savings The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined . Variables including age , increased cough frequency and sputum production , new crackles and wheezing , asthma , symptomatic sinusitis , hemoptysis , decreased lung function , weight loss , and new acquisition of Pseudomonas aeruginosa were collected in a large prospect i ve multicenter data base ( Epidemiologic Study of Cystic Fibrosis ) . During a 12-month baseline period , data from 11692 patients were compared with data collected during the subsequent 6-month study period . Because pulmonary function assessment s were unavailable for patients < 6 years of age , separate analyses were done for those < 6 and > or=6 years of age . The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation . Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression . For patients < 6 years of age , the strongest independent associations with treatment for a pulmonary exacerbation were new crackles , increased cough frequency , decline in weight , and increased sputum production . For those patients > or=6 years of age , the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec , increased cough frequency , new crackles , and hemoptysis . The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation . The reproducibility of the model over time was confirmed by application to a subsequent set of data . This model has potential for use as an outcome measure in clinical trials , and to assist in treatment decisions for individual patients CONTEXT Although Pseudomonas aeruginosa is the most common virulent respiratory pathogen in cystic fibrosis ( CF ) , the longitudinal development of P aeruginosa infection and its effect on antibody responses and lung disease progression in children with CF remain unclear . OBJECTIVE To prospect ively examine the epidemiology of P aeruginosa infection and its impact on CF pulmonary morbidity . DESIGN , SETTING , AND PATIENTS We prospect ively evaluated 56 CF patients at 2 CF centers in Madison and Milwaukee , Wis , from birth up to age 16 years between April 15 , 1985 , and April 15 , 2004 , with diagnoses made through the Wisconsin CF Neonatal Screening Project . MAIN OUTCOME MEASURES Timing of nonmucoid P aeruginosa and mucoid P aeruginosa acquisition was assessed by first positive result . Longitudinal development from no P aeruginosa to nonmucoid P aeruginosa and from nonmucoid P aeruginosa to mucoid P aeruginosa was examined . Outcome measurements included antibody titers , respiratory symptoms , quantitative chest radiography , and pulmonary function tests . RESULTS Sixteen patients ( 29 % ) acquired nonmucoid P aeruginosa in the first 6 months of life . The age-specific prevalence of mucoid P aeruginosa increased markedly from age 4 to 16 years . Nonmucoid and mucoid P aeruginosa were acquired at median ages of 1.0 and 13.0 years , respectively . In contrast with the short transition time from no P aeruginosa to nonmucoid P aeruginosa , the transition time from nonmucoid to mucoid P aeruginosa was relatively long ( median , 10.9 years ) and could be slightly extended by brief/low anti-P aeruginosa antibiotic treatment . Antibody titers increased with both transitions , but the deterioration in cough scores , chest radiograph scores , and pulmonary function correlated best with transition from nonmucoid to mucoid P aeruginosa . CONCLUSIONS Early prevention and detection of nonmucoid and mucoid P aeruginosa are critical because of early acquisition and prevalence . There is a window of opportunity for suppression and possible eradication ( by aggressive anti-P aeruginosa treatment ) of initial nonmucoid P aeruginosa . Mucoid P aeruginosa plays a much greater role in CF lung disease progression than nonmucoid P aeruginosa . Antibody titers , cough scores , and chest radiographs are early signs of nonmucoid P aeruginosa and especially mucoid P aeruginosa stages Background Newborn screening allows novel treatments for cystic fibrosis ( CF ) to be trialled in early childhood before irreversible lung injury occurs . As respiratory exacerbations are a potential trial outcome variable , we determined their rate , duration and clinical features in preschool children with CF ; and whether they were associated with growth , lung structure and function at age 5 years . Methods Respiratory exacerbations were recorded prospect ively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years , when all participants underwent clinical assessment , chest CT scans and spirometry . Results 168 children ( 88 boys ) experienced 2080  exacerbations , at an average rate of 3.66 exacerbations per person-year ; 80.1 % were community managed and 19.9 % required hospital admission . There was an average increase in exacerbation rate of 9 % ( 95 % CI 4 % to 14 % ; p<0.001 ) per year of age . Exacerbation rate differed by site ( p<0.001 ) and was 26 % lower ( 95 % CI 12 % to 38 % ) in children receiving 12 months of prophylactic antibiotics . The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores . Ever having a hospital-managed exacerbation was associated with bronchiectasis ( OR 2.67 , 95 % CI 1.13 to 6.31 ) in chest CT scans , and lower weight z scores at 5 years of age ( coefficient −0.39 , 95 % CI −0.74 to −0.05 ) . Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group OBJECTIVE This study was pursued as an extension of a r and omized clinical investigation of neonatal screening for cystic fibrosis ( CF ) . The project included assessment of respiratory secretion cultures for pathogens associated with CF . The objective was to determine whether patients diagnosed through neonatal screening and treated in early infancy were more likely to become colonized with Pseudomonas aeruginosa compared with those identified by st and ard diagnostic methods . METHODOLOGY The design involved prospect i ve cultures of respiratory secretions obtained generally by oropharyngeal swabs at least every 6 months and more often if clinical ly indicated . Patients were managed with a st and ardized evaluation and treatment protocol at the two Wisconsin certified CF centers ; however , there were community and environmental variations associated with the follow-up period as described below . RESULTS Overall , there were no differences in acquisition of respiratory pathogens between the screened and the control ( st and ard diagnosis ) groups . Evaluation of the data between and within the two centers , however , revealed significant differences with earlier acquisition of P aeruginosa in the center with the following distinguishing characteristics : urban location ; following patients with the st and ard US approach in which newly diagnosed , young children were interspersed with older CF patients ; and where there were more opportunities for social interactions with other CF patients . The differences were confined to the screened group followed in the urban center in which the median pseudomonas-free survival period was 52 weeks contrasted with 289 weeks in the other center . In addition , assessment of data for the entire CF population s followed at the two centers revealed that the urban center showed a significantly higher prevalence of P aeruginosa colonization in patients between the ages of 3 and 9 years . CONCLUSIONS These results present questions and generate hypotheses on risk factors for acquisition of P aeruginosa in CF and suggest that clinic exposures and /or social interactions may predispose such patients to pseudomonas infections BACKGROUND Many patients with cystic fibrosis are malnourished at the time of diagnosis . Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known . METHODS We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by st and ard diagnostic methods .  A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots ( from April 1985 through June 1991 ) or by combining the trypsinogen test with DNA analysis ( from July 1991 through June 1994 ) . Of 325,171 infants assigned to an early-diagnosis group , cystic fibrosis was diagnosed in 74 infants , including 5 with negative screening tests . Excluding infants with meconium ileus , we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by st and ard methods  ( the control group ) . Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets , pancreatic-enzyme therapy , and fat-soluble vitamin supplements . RESULTS The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group ( mean age , 12 vs. 72 weeks ) . At the time of diagnosis , the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile ( 52nd , vs. 32nd in the control group ; P=0.003 ) . The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period , especially the children with pancreatic insufficiency and those who were homozygous for the deltaF508 mutation . CONCLUSIONS Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis Complications of flexible bronchoscopy ( FB ) were prospect ively evaluated during 1,328 diagnostic procedures in children , not in intensive care units . A total 92.8 % of the procedures were performed in conscious patients under sedation and 7.2 % under deep sedation . Supplementary oxygen was provided in ∼80 % of cases via endoscopic face mask ( n=783 ) or nasal prongs ( n=290 ) . At least one complication was recorded in 91 cases ( 6.9 % ) . Minor complications ( n=69 ; 5.2 % ) included moderate and transient episodes of desaturation ( n=15 ) , isolated excessive coughing ( n=22 ) , excessive nausea reflex with coughing ( n=20 ) , transient laryngospasm ( n=6 ) and epistaxis ( n=6 ) . Major complications ( n=22 ; 1.7 % ) included oxygen desaturation to < 90 % , either isolated ( n=10 ) or associated with laryngospasm ( n=6 ) , coughing ( n=4 ) , bronchospasm ( n=1 ) , and pneumothorax ( n=1 ) . Major complications involving oxygen desaturation were associated with age < 2 yrs ( 13 of 529 versus 8 of 778 ) and laryngotracheal abnormalities ( 7 of 85 versus 14 of 1,222 ) . The overall frequency of complications was similar in conscious ( 6.7 % ) but se date d patients and patients under deep ( 7.3 % ) sedation . However , the frequency of transient desaturation was significantly higher in children undergoing FB under deep sedation . Transient fever after bronchoalveolar lavage was observed in 52 of 277 cases ( 18.8 % ) . Flexible bronchoscopy is a safe procedure with < 2 % major complications . Careful analysis of indications and clinical status for each patient , and proper anaesthesia and monitoring during the examination ensure that the procedure 
    Output:
    
The quality of evidence for the key parameters was grade d as moderate except high-resolution computed tomography scoring and cost of care analysis , which were grade d as high quality .At five years of age , there was no clear benefit of bronchoalveolar lavage-directed therapy on lung function z scores or nutritional parameters .
Evaluation of total and component high-resolution computed tomography scores showed no significant difference in evidence of structural lung disease in the two groups .
In addition , this study did not show any difference between the number of isolates of Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage-directed therapy group compared to the st and ard therapy group .
The eradication rate following one or two courses of eradication treatment was comparable in the two groups , as were the number of pulmonary exacerbations .
However , the number of hospitalizations was significantly higher in the bronchoalveolar lavage-directed therapy group , but the mean duration of hospitalizations was significantly less compared to the st and ard therapy group .
Mild adverse events were reported in a proportion of participants , but these were generally well-tolerated .
This review , limited to a single , well design ed r and omized-controlled study , shows no clear evidence to support the routine use of bronchoalveolar lavage for the diagnosis and management of pulmonary infection in pre-school children with cystic fibrosis compared to the st and ard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms .
No evidence was available for adult and adolescent population