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

BMJ 1995; 310 doi: https://doi.org/10.1136/bmj.310.6994.1571 (Published 17 June 1995) Cite this as: BMJ 1995;310:1571
  1. David S Armstrong, fellow in thoracic medicinea,
  2. Keith Grimwood, senior lecturer in paediatricsa,
  3. Rosemary Carzino, research assistanta,
  4. John B Carlin, senior research fellowa,
  5. Anthony Olinsky, director of thoracic medicinea,
  6. Peter D Phelan, professor of paediatricsa
  1. a Departments of Thoracic Medicine and Paediatrics, and Clinical Epidemiology and Biostatistics Unit, Royal Children's Hospital, University of Melbourne, Parkville 3052, Victoria, Australia
  1. Correspondence to: Dr Grimwood.
  • Accepted 21 March 1995

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.

Patients, methods, and results

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 2-33 (median 8) months who were undergoing bronchoscopy for stridor served as controls.

Lavage fluid was tested by immunofluorescence, cultured for respiratory viruses, and plated on to selective media for quantitative bacteriology. Total and differential cell counts were performed in a counting chamber and after cytocentrifugation respectively. Interleukin 8 was assayed by enzyme immunoadsorbent assay (Medgenix Diagnostics, Belgium). At bronchoscopy samples from the oropharynx were also cultured for bacteria. Serum antibodies to Pseudomonas aeruginosa lipopolysaccharide and exotoxin A were measured by an enzyme immunoadsorbent assay. To adjust for upper respiratory contamination, lower respiratory infection was defined as bacterial counts >/=108 colony forming units/l or the presence of respiratory viruses in lavage fluid.3 Comparisons were by χ2 or Fisher's exact test and the two sample t test. The study was approved by the human ethics committee.

Fifteen bacterial and three viral infections were identified in 17 infants (38%; 95% confidence interval 24% to 54%). Staphylococcus aureus was present in 14, including three with mixed S aureus and Haemophilus influenzae infections; Moraxella catarrhalis was detected in another. Respiratory syncytial virus and parainfluenza virus type 3 were present in three infants, including one with S aureus infection. Four of the seven infants receiving antibiotics had S aureus infection and one had parainfluenza virus type 3 in lavage fluid. Throat cultures from 27 infants grew S aureus; H influenzae was detected in three cases and Gram negative bacilli in six others (Escherichia coli (three), Klebsiella pneumoniae (two), and P aeruginosa (one)). No controls had bacterial counts >/=108 colony forming units/l, although S aureus and H influenzae were grown from throat cultures in three controls. Serum P aeruginosa antibodies were absent in cases and controls.

Infection was not predicted by sex or cystic fibrosis genotype. Infected infants had lower mean Brasfield chest x ray scores (20.1 v 21.9; P=0.07). Although throat swabs were sensitive for lower respiratory infection (15/15), poor specificity (14/30) meant a positive culture had a predictive accuracy of 48% (30% to 67%). Eleven of the 17 infected infants (65%) had symptoms compared with five of the 28 (18%) without infection (P=0.004). Two of these five were taking antibiotics and another had evidence of pulmonary aspiration. The table shows significant differences for total cell count, macrophage and neutrophil counts, and interleukin 8 concentrations between 14 infected infants and 20 non-infected infants, and nine controls.

Inflammatory geometric cells and interleukin 8 concentrations in bronchoalveolar lavage fluid. Figures are means (95% confidence intervals)

View this table:

Comment

Within the first 3 months of life lower respiratory infection, primarily by S aureus, was present in almost 40% of infants (17/45) with cystic fibrosis. More than one third were symptom free. Infection was overestimated by throat cultures, suggesting that for many subjects bacterial pathogens remain confined to the upper airways. Although no newly diagnosed case showed P aeruginosa infection, follow up cultures in this cohort have shown that the organism may infect the lower respiratory tract as early as 4 months of age.

We found respiratory pathogens to be important causes of inflammation. Although neutrophils within the lower respiratory tract were associated with respiratory symptoms, not all infected subjects had inflammatory cells or symptoms. In addition, not all respiratory symptoms or inflammation were due to infection: in two cases there was evidence that aspiration lung disease was the most likely cause. By comparison, adults with chronic cystic fibrosis and minimal lung disease consistently showed respiratory inflammation.4 Although infants with newly diagnosed disease probably have normal lung structure, repeated episodes of infection or aspiration in young children may result in chronic respiratory inflammation and lung injury.5

This work was supported by a grant from the Royal Children's Hospital Research Foundation. DSA was supported by the Smorgon Research Fellowship. We thank Dr Colin Robertson for advice and encouragement; Dr Ethna Phelan for performing the Brasfield scores; and Dr J Que of the Swiss Serum and Vaccine Institute in Berne for giving the enzyme immunoadsorbent assay to measure antibodies to P aeruginosa and exotoxin A.

References

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