Rosemary Carzino

Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis

The nature and timing of lower respiratory infections in infants with cystic fibrosis is largely unknown1 because infants do not produce sputum and throat cultures may not predict lower respiratory pathogens.2 We performed a prospective cross sectional study of an unselected cohort of infants with cystic fibrosis in which bronchoalveolar lavage was used to determine lower respiratory infection and inflammation during the first three months of life. The state of Victoria, Australia (66000 births per year) has a cystic fibrosis screening programme, all patients being managed by one centre. Between February 1992 and September 1994 we recruited 45 (27 boys) of the 52 infants with newly diagnosed disease; 32 were identified by screening, 12 from meconium ileus, and one by failure to thrive, and all cases were confirmed by sweat testing. Sixteen infants had respiratory symptoms, and seven of them were receiving oral antibiotics when bronchoalveolar lavage was performed at a mean age of 2.6 (SD 1.6) months. Nine otherwise healthy infants (five boys) aged …

Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis

As collections of lower respiratory tract specimens from young children with cystic fibrosis (CF) are difficult, we determined whether oropharyngeal cultures predicted lower airway pathogens. During 1992–1994, 75 of 90 (83%) infants with CF diagnosed by neonatal screening had 150 simultaneous bronchoalveolar lavage (BAL) and oropharyngeal specimens collected for quantitative bacterial culture at a mean age of 17 months (range, 1–52). Ten children undergoing bronchoscopy for stridor served as controls. Total and differential cell counts and interleukin‐8 concentrations were measured in BAL fluid. A subset of bacterial pathogens were typed by pulsed field gel electrophoresis. A non‐linear relationship with inflammatory markers supported a diagnosis of lower airway infection when ≥105 colony‐forming units/ml were detected. This criterion was met in 47 (31%) BAL cultures from 37 (49%) children. Staphylococcus aureus (19%), Pseudomonas aeruginosa (11%), and Hemophilus influenzae (8%) were the major lower airway pathogens. In oropharyngeal cultures, S. aureus (47%), Escherichia coli (23%), H. influenzae (15%), and P. aeruginosa (13%) predominated. The sensitivity, specificity, and positive and negative predictive values of oropharyngeal cultures for pathogens causing lower respiratory infections were 82%, 83%, 41%, and 97%, respectively. When there was agreement between paired oropharyngeal and BAL cultures, genetic fingerprinting showed some strains of the same organism were unrelated. We conclude that oropharyngeal cultures do not reliably predict the presence of bacterial pathogens in the lower airways of young CF children. Pediatr Pulmonol. 1996; 21:267–275.

Severe viral respiratory infections in infants with cystic fibrosis

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991–1996 were recruited into a prospective, multiple‐birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL‐8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls.

Early airway infection, inflammation, and lung function in cystic fibrosis

Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV0.5 195 ml and 236 ml respectively). Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients.

Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x mL(-1) were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers. This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.

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

BACKGROUND We 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. METHODS Of 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. RESULTS Eighty-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. CONCLUSIONS CF 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.

Cystic fibrosis patients and families support cross-infection measures

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Childrens Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged <5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients ≥12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person–person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Childrens Hospital, Melbourne, Australia.

Induced sputum compared to bronchoalveolar lavage in young, non-expectorating cystic fibrosis children.

BACKGROUND Induced sputum (IS) is feasible and safe in young CF children and is a readily accessible, non-invasive technique. However, it has not been compared to bronchoalveolar lavage (BAL), the gold standard for diagnosing lower airway infection. METHODS We compared bacterial yield from IS and BAL in 11 non-expectorating CF children, aged 3 to 7.4 years. IS samples were obtained in 10/11 cases. RESULTS Eight out of ten had the same predominant bacteria cultured from IS and BAL: Pseudomonas aeruginosa and Stenotrophomonas maltophilia[1], Staphylococcus aureus[3], and upper respiratory tract flora [4]. In one, Serratia marcescens and Haemophilus parainfluenzae were cultured from IS alone, whereas in one, non-group B Haemophilus influenzae was cultured from BAL alone. CONCLUSIONS As proof of principle, IS samples showed good bacteriologic correlation with BAL. Larger studies are recommended to confirm IS as a clinically valuable tool and measure for early intervention studies in young CF children.

Vitamin A and E deficiency and lung disease in infants with cystic fibrosis

Objectives: Vitamin A and E deficiency is common in cystic fibrosis (CF). These vitamins have immunomodulating properties and we determined whether decreased serum vitamin A and E levels in young infants are associated with early CF lung disease and lower airway inflammation.

Geographical Differences in First Acquisition of Pseudomonas aeruginosa in Cystic Fibrosis

RATIONALE Risk of infection with Pseudomonas aeruginosa in cystic fibrosis (CF) may be associated with environmental factors. OBJECTIVES To determine whether residential location is associated with risk of first acquisition of P. aeruginosa. METHODS We performed bronchoalveolar lavage and upper airway cultures in children newly diagnosed with CF to identify infection with P. aeruginosa during infancy and early childhood. Children were assessed according to their residence in a regional or metropolitan area. Multilocus sequence typing was used to determine P. aeruginosa genotype. An environmental questionnaire was also administered. MEASUREMENTS AND MAIN RESULTS A total of 105 of 120 (87.5%) infants diagnosed with CF were included in this study. Diagnosis in 65 infants (61.9%) followed newborn screening at mean age of 4.6 weeks. Sixty subjects (57.1%) were homozygous ΔF508, and 47 (44.8%) were female. Fifty-five (52.3%) infants were regional, of whom 26 (47.3%), compared with 9 of 50 (18.0%) metropolitan children, acquired infection with P. aeruginosa (odds ratio, 4.084; 95% confidence interval, 1.55-11.30). Age at acquisition was similar (regional: median, 2.31 yr; range, 0.27-5.96 yr; metropolitan: median, 3.10 yr, range, 0.89-3.70 yr). Strain typing identified P. aeruginosa genotypes often encountered in different ecological settings and little evidence of cross-infection. Ninety questionnaires (85.7%) were completed. Those who acquired P. aeruginosa were more likely to be living in a household that used water sprinkler systems (P = 0.032), but no differences were identified to explain increased risk of acquisition of P. aeruginosa in regional children. CONCLUSIONS Geographical difference in residence of children with CF was associated with increased risk of first acquisition of P. aeruginosa, usually with strains associated with the environment rather than with cross-infection.