Non-expectorating Children Research Articles

Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis.

Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients.This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection.300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection.The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF.

Diagnosis of pulmonary tuberculosis from gastric aspirate samples in nonexpectorating pediatric patients in a tertiary care hospital.

The aim of this study was to assess the utility of Xpert assay, Ziehl-Neelsen (ZN) staining, and Mycobacteria Growth Indicator Tube (MGIT™) culture for diagnosis of pediatric pulmonary tuberculosis from gastric aspirate (GA) samples and to compare Xpert assay and ZN staining with MGIT rapid liquid culture. GA samples from 210 nonexpectorating children, aged between 6 months to 12 years, presenting to the pediatric out-patient department (OPD) with clinical suspicion of tuberculosis (TB) were collected. The samples were tested by GeneXpert, ZN staining, and MGIT liquid culture. GeneXpert is a more sensitive method for rapid and early diagnosis of pediatric TB when compared with microscopy.

A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials

BackgroundDefinition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas. MethodsAn exhaustive literature search was performed. The clinimetric properties of different definitions of Pa microbiological status were evaluated. ResultsHistorical studies have mostly used culture-based definitions, although some have also involved complementary anti-Pa antibodies. Clinimetric analysis showed great variability in the definitions used, leading to differences in reliability, validity, responsiveness to treatment and correlation with outcome measures.Use of serology for initial Pa infection and successful Pa eradication introduced a greater level of complexity as antibody tests are not standardised. Moreover, the chronology of the immune response to Pa antigenic determinants was not completely clear.Chronic Pa infection was characterized by high levels of antibodies and good concordance between culture results and serology. ConclusionsMicrobiological monitoring, regular sampling from the airways and standardization of culture methods remain essential requisites for microbiological definitions. Despite limitations, serology should be incorporated in the definitions of initial infection and eradication used in clinical trials to better classify patients at enrolment, mainly in non-expectorating children. This requires standardization of serological testing.

P172 Simultaneous collection of cough plate and cough swab samples increases the detection of respiratory pathogens in non-expectorating children with cystic fibrosis

P172 Simultaneous collection of cough plate and cough swab samples increases the detection of respiratory pathogens in non-expectorating children with cystic fibrosis

Early detection of non-tuberculous mycobacteria in children with cystic fibrosis using induced sputum at annual review.

Non-tuberculous mycobacteria (NTM) have emerged as an important pathogen in cystic fibrosis (CF). Early detection and treatment of NTM can preserve lung function and maintain good lung health. Many children with CF are not regular sputum producers and cough swabs cannot routinely be used to diagnose NTM. We aimed to test the hypothesis that performing sputum induction at routine annual review results in earlier identification of NTM in non-sputum producing children with CF. We conducted a 5-year prospective observational cohort study involving children with CF aged 5-17 years who had sputum induction with hypertonic saline for microbiological surveillance including NTM at their annual review. Forty-two children (19 males, mean age 11.4 years ± 3.6, mean FEV1 % predicted 94.7 ± 20.6) participated in the study. Forty-one induced sputum samples from 29 children yielded bacterial pathogens. Six samples from six children (14% of the cohort) yielded NTM never previously isolated from the patient. We also detected three isolates of Pseudomonas aeruginosa and one isolate each of Burkholderia cepacia complex and Meticillin resistant Staphylococcus aureus (MRSA), all of which were first time isolates. We conclude that annual induced sputum for microbiological surveillance is useful for early detection of NTM and other important respiratory pathogens, particularly in non-expectorating children. This may lead to earlier identification and help inform initiation of eradication treatment in children with NTM. Children can also be cohorted earlier, before they potentially infect other children in the clinic.

P138 Sampling methods used in non-expectorating children ≤3 years of age with cystic fibrosis in a London CF centre

P138 Sampling methods used in non-expectorating children ≤3 years of age with cystic fibrosis in a London CF centre

151 Bronchoalveolar lavage is more sensitive than standard cultures at identifying failed Pseudomonas aeruginosa eradication in non-expectorating children

151 Bronchoalveolar lavage is more sensitive than standard cultures at identifying failed Pseudomonas aeruginosa eradication in non-expectorating children

Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods.

Oropharyngeal (OP) swabs and induced sputum (IS) are used for airway bacteria surveillance in nonexpectorating children with cystic fibrosis (CF). Molecular analyses of these airway samples detect complex microbial communities. However, the optimal noninvasive sampling approach for microbiota analyses and the clinical relevance of microbiota, particularly its relationship to airway inflammation, is not well characterized. The goals of this study were to compare molecular analyses of concurrently collected saliva, OP swabs, IS, and expectorated sputum (ES) from children with CF and to determine the association between microbiota, lung function, and airway inflammation. Saliva, OP swabs, IS, and ES were collected from 16 children with CF. Spirometry was performed. Respiratory and saliva samples (n = 61) were sequenced for bacterial microbial communities, and total and CF-specific bacterial quantitative PCR assays were performed. Airway samples underwent conventional culture for CF-specific pathogens. Neutrophil elastase, IL-1β, IL-1ra, IL-6, Il-8, TNF-α, and vascular endothelial growth factor were measured in ES and IS. Sequencing results from individual subjects were similar across samples, with greater between-subject than within-subject variation. However, Pseudomonas and Staphylococcus were detected in higher relative abundance from lower airways (ES and IS) compared with paired upper airway samples (OP and saliva). Pseudomonas, Staphylococcus, and Enterobacteriaceae correlated with increased airway inflammation. Divergence between microbiota in upper airway compared with lower airway samples, indicating greater differences between communities, was associated with increased sputum neutrophil elastase. Bacteria detected in IS samples resemble ES samples, whereas OP samples may underrepresent bacteria associated with airway inflammation. Divergence of lower airway communities from upper airway was associated with airway inflammation and may portend disease progression.

Pseudomonas aeruginosa genotypes acquired by children with cystic fibrosis by age 5-years

BackgroundWe describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. MethodsOf 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. ResultsEighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. ConclusionsCF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children.

The findings of a clinical surveillance bronchoalveolar lavage programme in pre-school patients with cystic fibrosis.

Evidence suggests infection is present in the lower airways of young children with cystic fibrosis (CF), even when clinically stable. Oropharyngeal samples (OPS) are typically used for airway surveillance in these children but have been shown to have low positive predictive values and low sensitivity in detecting lower airway infection when compared with the reference standard, bronchoalveolar lavage (BAL). The aim of this study was to determine the prevalence of pathogens in lower airway samples detected as part of a pilot clinical BAL surveillance programme, in young children aged from one to six years old, and to ascertain if their detection resulted in a change in treatment. During the study 78 bronchoscopies were performed on 38 patients. The average age at the time of bronchoscopy was 2.7 years (range 0.3-7.0 year). A significant organism was detected in 58 (74.5%) BALs. Haemophilus influenzae was detected in 27 (34.6%) samples, 16 (20.5%) samples had Staphylococcus aureus, and nine (11.5%) had Pseudomonas aeruginosa. Change in treatment occurred after 46 (58.9%) BALs. This study suggests that, in young non-expectorating children with CF, routine surveillance bronchoscopy allows the detection of significant lower airway pathogens and provides the opportunity for targeted treatment of sub-clinical infection.

The use of bronchoscopy in the diagnosis of pulmonary exacerbations in non-expectorating children with cystic fibrosis

The use of bronchoscopy in the diagnosis of pulmonary exacerbations in non-expectorating children with cystic fibrosis

Induced Sputum in the Very Young: A New Key to Infection and Inflammation

<h3>Background</h3> Chronic inflammation and infection in patients with cystic fibrosis (CF) and other lung diseases begin early, making noninvasive diagnostic techniques vital. As induced sputum (IS) testing is useful in older patients, we investigated its adaptation to young nonexpectorating children. <h3>Methods</h3> Following the inhalation of a 4.5% saline solution, sputum was collected by nasopharyngeal or oropharyngeal suction for culture and testing for inflammatory markers, with paired preceding oropharyngeal cough swabs (OCSs) in a subgroup. Specimens from 48 IS procedures (46 successful) in 20 CF children (median age, 3 years) were compared with 8 specimens from 8 non-CF pulmonary patients (median age, 4.5 years). <h3>Results</h3> The procedure was safe, with arterial oxygen saturation remaining at ≥ 96%. Cultures from 14 of 46 CF patients (30%) grew <i>Pseudomonas aeruginosa</i>, whereas cultures from 19 of 46 CF patients (41%) had no growth. Cultures from seven of eight non-CF subjects grew bacteria, but none were <i>P aeruginosa</i>. Comparing 29 paired IS and OCS samples, 11 and 5 samples, respectively, cultured <i>P aeruginosa</i> (not significant), whereas 12 and 21 samples, respectively, had no growth (p = 0.02). A correlation was found between the independent inflammatory markers NE and both interleukin (IL)-8 (<i>r</i> = 0.85; p < 0.001) and the percentage of neutrophils (<i>r</i> = 0.35; p < 0.05), confirming the validity of IS samples in evaluating early airway disease. IL-8 levels also increased with age (<i>r</i> = 0.41; p < 0.05). Inflammation was similar in CF and non-CF subjects. <h3>Conclusions</h3> IS testing in the young is feasible, safe, and clinically useful, and could serve as an outcome measure for new therapies.

Variability of markers of inflammation and infection in induced sputum in children with cystic fibrosis

To determine reproducibility of inflammatory marker concentrations in induced sputum from subjects with cystic fibrosis (CF), 15 nonexpectorating children, 6 to 13 years of age with mild CF lung disease, underwent 3 weekly sputum inductions with 3% saline. Neutrophil elastase concentration and bacterial cultures were reproducible. This study provides useful information for investigators designing trials of anti-inflammatory therapies in CF involving sputum induction.