For many years it has been observed that girls with CF do not grow as well as boys and have poorer lung function. By the time they reach middle age the survival of women with the disease has been quoted to be 4 to 5 years worse than men. In one American study, which amalgamated the survival data from a large number of CF care centres, 50% of women could be expected to be alive at 25 years of age compared to men where 50% were alive at 28 years. Indeed under the age of 20 years there was a 60% greater chance of girls dying compared to boys (1). There has been much speculation as to the cause of the difference. There is some evidence to show that girls develop Pseudomonas aeruginosa infection of their lungs at an earlier age. Other evidence shows that as girls reach their teens their weight deteriorates more quickly. This has been explained partly by body image factors but not entirely.
However, one of the problems of studies looking at clinical outcomes derived from observations from a large number of centres is that they can sometimes hide individual centre differences. In addition, in an international context there may be differences in clinical practice between countries. In Denmark, for example, it has been suggested that the remarkable survival and quality of life figures for patients may be attributable to all patients being cared for in one centre and all patients infected with Pseudomonas aeruginosa receiving elective regular intravenous antibiotics every 3 months irrespective of how unwell they may be. With such a policy over 80% of patients survive into their 5th decade irrespective of sex (2).
At the Royal Brompton and Harefield NHS Trust in London, we constructed a retrospective study to examine the clinical progress of children and adolescents with CF (3). We compared our clinic population in 1993 (n=105) with the clinic population in 2002 (n=209) (the cross-sectional study). We found that patients in 2002 had better lung function compared to 1993. In terms of the percent predicted FEV1: 1993 - females 86%, males 84% and in 2002, females 93%, males 92% (Fig 1). Standardised growth scores for females and males revealed that female height and weight Z-scores were at least as good as males (Fig 2). By 2004 88% of the original 1993 population, now in their early 20s, were alive. From these 2 populations we selected 2 sub-groups of patients and tracked their lung function and growth over 5-year periods, the first starting in 1993 and the second in 1998 (the longitudinal study). We found that lung function and growth remained relative constant over the 5-year periods but the overall percent predicted FEV1 appeared to be better in females than males for both cohorts (Fig 3).
We feel that the improved figures over time and the failure to find a female disadvantage may be attributable to aggressive management strategies. It is our policy for example to treat first isolation of Pseudomonas aeruginosa with 3 months nebulised antibiotics and oral ciprofloxacin similar to the policy adopted in Copenhagen (4, 5). If the organism is grown a second time then life-long inhaled antibiotic is advised. We also employ an elective regular 3 monthly IV anti-Pseudomonas antibiotic policy for children with more advanced lung disease. It is difficult to prove any individual policy on it’s own explain our figures. In all probability it is a many different care factors that make the difference. The task of proving the significance of any single treatment schedule is difficult and controversial (6).
The overall message from our work is that there is no reason why girls with CF cannot do just as well as boys. Centres where there is still a gender difference in favour of boys should address and review their management protocols.
Figure 1: Cross Sectional analyses. FEV1 (forced expiratory volume in 1second) percentage predicted values for female and male CF patients from annual assessment records in 1993 and 2002. Horizontal lines represent the median values.
Figure 2: Cross Sectional analyses. FVC (forced vital capacity) percentage predicted values for female and male cystic fibrosis patients from annual assessment records in 1993 and 2002 Horizontal lines represent the median values
Figure 3: Longitudinal analyses. Graph showing the trend in median values in FEV1 (forced expiratory volume in 1 second) percentage predicted (PR) for male and female cystic fibrosis patients reviewed for 5 consecutive years between 1993-1997 and 1998-2002. Error bars represent upper and lower quartile values about the median values.
Roger Buchdahl MBBCh, MD FRCP FRCPCH, was awarded his MD at Cambridge in 1990 for his thesis “The Relationship between Resting Energy Expenditure, Growth, Malnutrition and Pulmonary Disease in Cystic Fibrosis.” Currently he is Consultant Paediatrician in Paediatric Respiratory Disease, Royal Brompton and at Harefield NHS Trust in London - both world renowned centres for the treatment of heart and lung disease. He is also Consultant in General Paediatrics, at Hillingdon Hospital, Middlesex. Roger is the author of numerous scientific articles in the field of paediatric respiratory disease including CF, air pollution and asthma.
Andrew Bush MB BS(Hons) MA MD FRCP FRCPCH is Professor of Paediatric Respirology, Imperial College and Honorary Consultant Paediatric Chest Physician at the Royal Brompton Hospital and Harefield NHS Trust, in London UK. He was awarded the MD degree(Cambridge) in 1987, following his research on the functional assessment of pulmonary circulation in man. He is the author of scores of research articles on CF and has been an invited speaker to many CF scientific meetings and conferences. Current research interests and publications in the field of paediatric respiratory disease, include invasive and non-invasive monitoring of airway inflammation, and severe asthma.
Nisha Verma attained a BSc degree in Respiratory Science 2005 and is currently a final year medical student at Imperial College School of Medicine in London. We have great hopes that when she graduates in June 2006, she will continue her interest and research studies in CF.
The original paper “Is there a Gender Gap in CF?” was published in Chest: The Cardiopulmonary and Critical Care Journal. To view a PDF of the full research paper, visit http://www.chestjournal.org/cgi/content/full/128/4/2824. Chest is the official publication of the American College of Chest Physicians (ACCP). Each month it features cutting edge clinical investigations in the multidisciplinary specialties of chest medicine, such as pulmonology, cardiology, thoracic surgery, transplantation, sleep and breathing, airways disease, and more. Chest also features basic science, special reports, case reports, board review questions, and more.
References & Further Reading
1. Rosenfeld M, Davis R, FitzSimmons S et al. Gender gap in Cystic Fibrosis Mortality. Am J Epidemiol 1997; 145:794-803
2. Frederiksen B, Lanng S, Koch C, Hoiby N. Improved survival in the Danish center-treated cystic fibrosis patients: results of aggressive treatment. Pediatr Pulmonol. 1996;21:153-158.
3. Verma N, Bush A, Buchdahl R Is there still a gender gap in cystic fibrosis? Chest 2005; 123: 2828-34
4. 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. 1996;23:330-335.
5. The Royal Brompton and Harefield NHS Trust: Clinical Guidelines for the Care of Children with Cystic Fibrosis 2003. www.rbh.nthames.nhs.uk/childrencf
6. Fiel SB. Early aggressive intervention in cystic fibrosis: is it time to redefine our "best practice" strategies? Chest. 2003; 123:1-3