Connect
MJA
MJA

Clinical outcomes of Queensland children with cystic fibrosis: a comparison between tertiary centre and outreach services

Clare L Thomas, Peter K O’Rourke and Claire E Wainwright
Med J Aust 2008; 188 (3): 135-139. || doi: 10.5694/j.1326-5377.2008.tb01554.x
Published online: 4 February 2008

In 2001, there were 2311 people in Australia with cystic fibrosis (CF); two-thirds of these were children and adolescents.1 Long-term survival for children with CF has improved markedly, with a predicted mean life expectancy of about 40 years.2 The reasons for improved survival include earlier diagnosis with neonatal screening, improved nutrition and management of respiratory infections, and management in a tertiary cystic fibrosis centre (CFC).3-6 It is recommended that children with CF have at least quarterly visits to a multidisciplinary team at a CFC.4,7-9

People living in rural and remote Australia have poorer health than those living in metropolitan zones, with higher mortality and lower life expectancy.10 Specialist outreach clinics have evolved across almost all clinical disciplines in many different countries as a means of providing specialist care for patients in remote areas. The CF clinic at the Royal Children’s Hospital, Brisbane, provides cystic fibrosis outreach services (CFOS) at seven sites in Queensland: Cairns, Townsville, Mackay, Rockhampton, Hervey Bay, Toowoomba, and the Gold Coast, with the greatest distance being 1700 km from the tertiary centre. The teams attending CFOS usually include a respiratory physician, physiotherapist, dietitian and nurse. Local health workers are invited to attend the clinics. Children attending outreach clinics are also managed by their local paediatrician or general practitioner. Outreach clinics occur twice a year, except at one site, which has one clinic and two telehealth clinics per year. Some form of CF education or post-clinic multidisciplinary meeting has been provided for local health care teams at least once a year at most sites.

Most studies comparing patients treated at CFCs with those treated in non-CFC settings have found better outcomes in CFC-treated patients.3,8,11 Our hypothesis was that children attending the CFOS would have worse clinical outcomes than children attending the CFC, and our aim was to determine the differences in clinical outcomes between children with CF treated primarily at a CFC and those treated at regional centres by local health care professionals and the CFOS.

Methods

Children included in the study were born between 19 October 1982 and 19 February 2002, had a proven diagnosis of CF (either positive sweat testing or the carriage of two CF gene mutations), and had clinical data available between 1 January 2000 and 31 December 2002. Available data on patients who died (6), transferred to adult care (11), or were lost to follow-up (2) during this period were included.

Patients were divided according to the level of care (LOC) they received (Box 1). The criteria for determining the LOC categories were drawn from the Clinical practice guidelines for cystic fibrosis,7 and reflected frequency of review by the CFOS and whether the CFOS was multidisciplinary. The degree of remoteness was calculated for all patients using the Accessibility/Remoteness Index of Australia (ARIA).12

Patients were categorised into four groups by birth cohort: 0–4 years old, 5–9 years old, males aged 10 years and older, and females aged 10 years and older. Genotypes were grouped as homozygous delta F508 mutation (ΔF508/ΔF508), heterozygous delta F508 mutation (ΔF508/other), no delta F508 mutation (other/other), or not available.

The study was approved by the Royal Children’s Hospital and Health Service District Ethics Committee.

Clinical outcomes
Pulmonary function tests

Pulmonary function data were collected from database records for patients aged 8 years and older. Forced expiratory volume in 1 second (FEV1) was measured at CFCs (Vitalograph Compact II, Fisher & Paykel, Melbourne, VIC) and at CFOS (Microlab 3300, Micro Medical Ltd, Rochester, UK) according to American Thoracic Society guidelines.13 The best of three maximal forced expiratory manoeuvres was recorded, and expressed as a percentage of predicted normal reference values based on the patient’s height, age and sex.14 Pulmonary function rate of change from 1 January 2000 to 31 December 2002 was calculated by simple linear regression using two methods: using all FEV1 % predicted measurements available for each child against time (slope FEV1 %), and using only the first and last FEV1 % predicted measurements available for each child against time (first to last FEV1 %).

Lung function severity was categorised according to the maximum FEV1 % predicted as normal lung function (≥ 90% predicted FEV1), mild impairment (70%–89% predicted FEV1), moderate impairment (40%–69% predicted FEV1) and severe impairment (< 40% predicted FEV1).

Nutritional status

Anthropometric variables were obtained with each clinic visit, and heights and weights were expressed as z scores.15 To allow for comparisons with the Australasian CF Data Registry 2001,1 mean height and weight z scores were distributed from <  3 to > 3.

Results

There were 273 patients with CF aged between 0 and 20 years, with median age 9 years (interquartile range [IQR], 5–13 years), including 131 (48%) from the CFC. Over the 3-year period of data collection, no patient changed LOC category. Patient characteristics for age, sex and genotype were similar across the LOC domains (Box 2) and the ARIA domains. Six patients (2.2%) died during the 3-year period (two from LOC 1, three from LOC 2, and one from LOC 4).

Clinical outcomes
P. aeruginosa status

Sputum analysis was available for 243 (89%) of the 273 patients. There was no difference in sputum culture availability between the LOC categories (P = 0.47) (Box 2). P. aeruginosa status was not significantly different across LOC groups (P = 0.39). The proportion of children with chronic P. aeruginosa infection increased with age (P < 0.01) from 16% for 0–4-year-olds, to 32% for 5–9-year-olds and 81% for children aged 10 years and older.

Nutritional status

There were no significant differences in mean height z scores (P = 0.65) or mean weight z scores (P = 0.56) by LOC (Box 4). The z scores for height and weight declined with increasing age, but this was only significant for weight (P = 0.01). Mean z scores for height ( 0.47; 95% CI, 0.59 to 0.36) and weight ( 0.34; 95% CI, 0.46 to 0.23) were significantly lower than the normal population mean z score of 0 (P < 0.01). The distribution of height and weight z scores was similar to child and adolescent height and weight z scores published in the Australasian CF Data Registry 2001 (P = 0.63).1

Mean weight z scores were significantly affected by P. aeruginosa infection (P = 0.003) (Box 4). To correct for the effect of age, the mean weight z scores were stratified for age and sex. The relationship between P. aeruginosa infection and weight was mostly explained by the 0–4-year-old group, where those with P. aeruginosa infection had a significantly lower (P = 0.026) weight z score ( 0.58; 95% CI, 1.04 to 0.13) for intermittent infection and ( 0.63; 95% CI, 1.35 to 0.09) for chronic infection, compared with (0.09; 95% CI, 0.26 to 0.43) for children not infected with P. aeruginosa. For children aged 5 years and older, we found no significant relationship between mean weight z scores and P. aeruginosa status.

Admission rates for CF-related illnesses

Children in LOC 1 and LOC 2 were more likely to have multiple admissions than children in LOC 3 and LOC 4 (P < 0.001) (Box 2). For LOC 2, 49% of admissions were to the CFC. Children aged 5–9 years were less likely to be admitted (38%) than children aged 10 years and older (62%), who were more likely to have multiple admissions (P = 0.04). Multiple admissions were more likely with chronic P. aeruginosa infection (89/141; 63%), compared with no (27/141; 19%) or intermittent (25/141; 18%) P. aeruginosa infection (P < 0.01).

Discussion

To our knowledge, this is the first reported study to compare clinical outcomes between children with CF receiving treatment at a specialist CFC with children having care in regional centres with specialist outreach services. We did not find poorer clinical outcomes in the CFOS-managed patients.

There were a number of weaknesses in our study. Despite relatively large study numbers, limitations apply to analysis of small subgroups. The LOC 4 group had less data available for analysis, particularly for analysis of pulmonary function rate of change, so these data should be interpreted with caution. In addition, patients in LOC 1 had pulmonary function measured at every visit, including when they presented with pulmonary exacerbations, whereas children seen in the regional areas by CFOS would only have pulmonary exacerbations recorded by chance if they coincided with the outreach visit. Only the maximum measurement has been reported here, although all data were included to estimate slope. A high proportion of patients had normal lung function, and this may have limited our ability to detect differences between groups. There can be considerable discrepancy between lung function and structure, and advanced structural damage can be present in lungs of patients with normal lung function.16 More sensitive methods, such as high-resolution computed tomography, may be better at detecting differences between patient groups in which there is a high percentage of normal pulmonary function. The levels of service provision in different regional centres were also quite heterogeneous, with some centres having fewer resources. This may explain why some patients in LOC 2 were seen at both the CFC and the CFOS although, as the admission rates were highest in LOC 2, it may have been due to patients in this group being sicker despite having no difference in other clinical outcomes.

Patients seen at the CFOS were reviewed twice a year by the CF specialist team whereas patients attending the CFC were likely to be seen more frequently. Although the clinical outcomes were similar in both groups, the study was not designed to examine frequency of review by a CF specialist team. In addition, the quality of review, involvement of local teams, and the educational component may be important determinants of outcome.

Variability in sputum analysis between laboratories prevented differentiation between mucoid and non-mucoid strains of P. aeruginosa, which has also been reported in another study,17 and microbial sensitivity patterns could not be examined because of variability of testing methods between laboratories.

Children receiving CFOS care had the same prevalence of intermittent and chronic P. aeruginosa infection as those attending the CFC. Our study also supports the existing evidence that P. aeruginosa infection increases with age17 and is associated with poorer pulmonary function18-21 and higher rates of admissions.18

A significant association was found between early infection with P. aeruginosa and reduced weight in the 0–4 years age group. This is in contrast to another study that found no significant difference in weight or height, which was attributed to aggressive therapeutic and nutritional interventions.22 However, unlike in our study, patients were not diagnosed through neonatal screening, with most diagnoses due to poor growth, and symptoms of malabsorption. This suggests that the subjects in the earlier study were already likely to be undernourished, perhaps making it more difficult to detect the effect of early P. aeruginosa acquisition.

Studies, including a Cochrane review of 73 studies, of specialist outreach clinics in primary care and rural hospital settings in 14 countries across five continents have shown that simple consultation-based outreach services improve patient access but have no effect on health care outcomes. However, more complex multifaceted outreach clinics that involve collaboration with primary care, education and other services are associated with improved health care outcomes and more efficient and guideline-consistent care.23,24 There is an active education program by the CFOS, and an annual CF education course has been available in Brisbane for health care professionals, which may have contributed to the good outcomes in patients managed in outreach in this study.

In conclusion, our study demonstrates adequate clinical outcomes in rural CF patients receiving an outreach model of care, when compared with the CFC-treated population. Additional support of the CFOS model of care comes from a recent report of equivalent health-related quality of life in children with CF living in regional Queensland compared with those attending the CFC.25 Differences between CFC and CFOS care may not be apparent until more sensitive outcome measures are used or until longitudinal observational studies over a longer period (ie, 10 years) are undertaken. Additional research addressing the influence of other services, such as telemedicine, workshops, outpatient intravenous treatments and alternative outcome measures, such as survival rates and patient–carer treatment preferences are required, as well as studies of the cost-effectiveness of the CFOS model of service delivery.

2 Clinical characteristics and demographics of children attending a cystic fibrosis centre and/or a cystic fibrosis outreach service

CFC


CFOS


P

LOC 1

LOC 2

LOC 3

LOC 4

Total


Number

131

35

72

35

273

ARIA category

Highly accessible

113 (86%)

14 (40%)

38 (53%)

23 (66%)

188 (69%)

< 0.001

Accessible

10 (8%)

16 (46%)

20 (28%)

5 (14%)

51 (19%)

Moderately accessible

8 (6%)

2 (6%)

9 (12%)

4 (11%)

23 (8%)

Remote

0

1 (3%)

2 (3%)

3 (9%)

6 (2%)

Very remote

0

2 (6%)

3 (4%)

0

5 (2%)

Sex and age group

Boys and girls 0–4 years

28 (21%)

9 (26%)

21 (29%)

6 (17%)

64 (23%)

0.59

Boys and girls 5–9 years

38 (29%)

8 (23%)

23 (32%)

7 (20%)

76 (28%)

Males ≥ 10 years

35 (27%)

8 (23%)

15 (21%)

13 (38%)

71 (26%)

Females ≥ 10 years

30 (23%)

10 (29%)

13 (18%)

9 (26%)

62 (23%)

FEV1 % predicted*

No data

57 (44%)

14 (40%)

35 (49%)

17 (49%)

123 (45%)

0.79

≥ 90%

40 (54%)

10 (48%)

17 (46%)

8 (44%)

75 (50%)

0.84

70%–89%

23 (31%)

7 (33%)

15 (41%)

6 (33%)

51 (34%)

40%–69%

8 (11%)

3 (14%)

5 (13%)

4 (22%)

20 (13%)

< 40%

3 (4%)

1 (5%)

0

0

4 (3%)

Genotype

ΔF508/ΔF508

72 (55%)

12 (34%)

33 (46%)

16 (46%)

133 (49%)

0.45

ΔF508/other

48 (37%)

16 (46%)

27 (37%)

12 (34%)

103 (38%)

Other/other

4 (3%)

2 (6%)

4 (6%)

2 (6%)

12 (4%)

Not available

7 (5%)

5 (14%)

8 (11%)

5 (14%)

25 (9%)

Pseudomonas status*

No data

14 (11%)

3 (9%)

7 (10%)

6 (17%)

30 (11%)

0.47

No infection

35 (30%)

6 (19%)

21 (32%)

5 (17%)

67 (28%)

0.39

Intermittent infection

16 (14%)

8 (25%)

13 (20%)

7 (24%)

44 (18%)

Chronic infection

66 (56%)

18 (56%)

31 (48%)

17 (59%)

132 (54%)

Admission rates

No admissions

28 (21%)

1 (3%)

27 (37%)

17 (49%)

73 (27%)

< 0.001

1 admission

31 (24%)

8 (23%)

12 (17%)

5 (14%)

56 (20%)

≥ 2 admissions

72 (55%)

26 (74%)

33 (46%)

13 (37%)

144 (53%)


ARIA = Accessibility/Remoteness Index of Australia. CFC = cystic fibrosis centre. CFOS = cystic fibrosis outreach service. FEV1 = forced expiratory volume in 1 second. LOC = level of care. * Percentages for FEV1 and Pseudomonas aeruginosa status are of the total for whom data were available.

Received 20 May 2007, accepted 5 September 2007

  • Clare L Thomas1
  • Peter K O’Rourke2
  • Claire E Wainwright3

  • 1 Paediatric Department, Nambour General Hospital, Nambour, QLD.
  • 2 Cancer and Population Studies, Queensland Institute of Medical Research, Brisbane, QLD.
  • 3 Department of Respiratory Medicine, Royal Children’s Hospital, Brisbane, QLD.



Acknowledgements: 

For their assistance with data collection, we wish to acknowledge and thank Penny Mitchell and Drs J Prebble, M Williams, W Frishman, D Price, R Messer and J Van der Westhuyzen.

Competing interests:

None identified.

  • 1. Cystic Fibrosis Australia. Cystic Fibrosis in Australia and New Zealand 2001. Annual report from the Australasian Cystic Fibrosis Data Registry. Sydney: CFA, 2003.
  • 2. Elborn JS, Shale DJ, Britton JR. Cystic fibrosis: current survival and population estimates to the year 2000. Thorax 1991; 46: 881-885.
  • 3. Merelle M, Schouten J, Gerritsen J, Dakert-Roelse J. Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients. Eur Respir J 2001; 18: 306-315.
  • 4. Walters S, Britton J, Hodson ME. Hospital care for adults with cystic fibrosis: an overview and comparison between special cystic fibrosis clinics and general clinics using a patient questionnaire. Thorax 1994; 49: 300-306.
  • 5. Collins C, MacDonald-Wicks L, Rowe S, et al. Normal growth in cystic fibrosis associated with a specialised centre. Arch Dis Child 1999; 81: 241-246.
  • 6. Hill D, Martin J, Davidson G, Smith G. Survival of cystic fibrosis patients in South Australia. Med J Aust 1985; 143: 230-232.
  • 7. Cystic Fibrosis Foundation. Clinical practice guidelines for cystic fibrosis. Bethesda, Md: Cystic Fibrosis Foundation, 1997.
  • 8. Mahadeva R, Webb K, Westerbeek R, et al. Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study. BMJ 1998; 316: 1771-1775.
  • 9. Frederiksen B, Koch C, Hoiby N. Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974–1995). Pediatr Pulmonol 1999; 28: 159-166.
  • 10. Strong K, Trickett P, Titulaer I, Bhatia K. Health in rural and remote Australia. Canberra: AIHW, 1998. (AIHW Cat. No. PHE 6.)
  • 11. Dankert-Roelse J, te Meerman G. Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre. Thorax 1995; 50: 712-718.
  • 12. Commonwealth Department of Health and Aged Care. Measuring remoteness: Accessibility/Remoteness Index of Australia (ARIA). Revised edition. Canberra: Department of Health and Aged Care, 2001. (Occasional Papers: New Series No. 4.)
  • 13. American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995; 152: 1107-1136.
  • 14. Hibbert M, Lannigan A, Landau L, Phelan P. Lung function values from a longitudinal study of healthy children and adolescents. Pediatr Pulmonol 1989; 7: 101-109.
  • 15. Welkowitz J, Ewen R, Cohen J. Introductory statistics for the behavioral sciences. New York: Academic Press, 1971.
  • 16. Tiddens H. Detecting early structural lung damage in cystic fibrosis. Pediatr Pulmonol 2002; 34: 228-331.
  • 17. Fitzsimmons S. The changing epidemiology of cystic fibrosis. J Pediatr 1993; 122: 1-9.
  • 18. Emerson J, Rosenfeld M, McNamara S, et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol 2002; 34: 91-100.
  • 19. Nixon G, Armstrong D, Carzino R, et al. Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. J Pediatr 2001; 138: 699-704.
  • 20. Frederiksen B, Koch C, Hoiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997; 23: 330-335.
  • 21. Kerem E, Corey M, Gold R, Levison H. Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonisation with Pseudomonas aeruginosa. J Pediatr 1990; 116: 714-719.
  • 22. Rosenfeld M, Gibson R, McNamara S, et al. Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol 2001; 32: 356-366.
  • 23. Gruen RL, Baillie RS, Wang Z, et al. Specialist outreach to isolated and disadvantaged communities: a population-based study. Lancet 2006; 368: 130-138.
  • 24. Gruen RL, Weeramanthri TS, Knight SE, Bailie RS. Specialist outreach clinics in primary care and rural hospital settings (Cochrane review). Chichester, UK: John Wiley & Sons, 2004.
  • 25. Thomas CL, Mitchell P, O’Rourke P, Wainwright C. Quality-of-life in children and adolescents with cystic fibrosis managed in both regional outreach and cystic fibrosis center settings in Queensland. J Pediatr 2006; 148: 508-516.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.