C. Etherington

Development of a disease specific health related quality of life measure for adults and adolescents with cystic fibrosis

BACKGROUND Health related quality of life (HRQoL) measurement is important in determining the impact of disease on daily functioning and subsequently informing interventions. In cystic fibrosis (CF) generic HRQoL measures have been employed but these may not be sufficiently specific. The aim of the current work was to develop and validate a disease specific HRQoL measure for adults and adolescents with cystic fibrosis. METHODS Areas of concern to adults and adolescents with CF were identified by unstructured interviews, self-administered questionnaires, consultation with multidisciplinary specialist staff, a review of the relevant literature, and examination of other HRQoL measures. Items for the questionnaire were generated on the basis of this process. Continued evaluation and development of the Cystic Fibrosis Quality of Life (CFQoL) questionnaire was undertaken by a process of statistical analysis and continued feedback from patients. The full testing and validation of the CFQoL questionnaire took place over four phases: (1) initial item generation and testing of a preliminary questionnaire, (2) testing and validation of the second version of the questionnaire, (3) test-retest reliability of a third and final version of the questionnaire, and (4) sensitivity testing of the final version of the questionnaire. RESULTS Nine domains of functioning were identified using principal components analysis with varimax rotation. Internal reliability of the identified domains was demonstrated using Cronbach alpha coefficients (range 0.72–0.92) and item to total domain score correlations. Concurrent validity (ranger = 0.64–0.74), discriminatory ability between different levels of disease severity, sensitivity across transient changes in health (effect size range, moderate d = 0.56 to large d = 1.95), and test-retest reliability (r = 0.74–0.96) were also found to be robust. CONCLUSIONS The CFQoL questionnaire is a fully validated disease specific measure consisting of 52 items across nine domains of functioning which have been identified by, and are of importance to, adolescents and adults with cystic fibrosis. This measure will be useful in clinical trials and longitudinal studies.

Validation of the SF-36 for the assessment of quality of life in adolescents and adults with cystic fibrosis

BACKGROUND Generic health-related quality of life measures are often applied to disease groups without assessment of their psychometric properties. The current work assesses the properties of the Short Form 36-item (SF-36) questionnaire in a British sample of adolescents and adults with cystic fibrosis (CF). METHODS Two hundred and twenty-three adolescents and adults with CF completed the SF-36 with a further 185 approached and not responding by non-completion of the questionnaire. The structure and internal reliability of the instrument was assessed by principal components analysis, Cronbach alpha coefficients and item to domain correlations. Differences between disease severity groups were assessed by analysis of variance. RESULTS Factor analysis of the SF-36 scores broadly confirmed domain structures for the SF-36. Cronbach alpha coefficients were high (range 0.82-0.91) and item-to-same domain correlations were stronger than item-to-unrelated domain correlations. Examination of differences between mild, moderate and severe disease states revealed four significant main effects for: physical functioning, role limitation due to physical functioning, general health perceptions and energy and vitality. The analysis also revealed the presence of numerous ceiling effects across domains. CONCLUSIONS The domain structure of the SF-36 was demonstrated to be robust. However, the discriminatory ability of the measure was disappointing. The presence of ceiling effects and the low frequency of differences between intermediate disease severity groups indicated that the SF-36 was not discriminatory with respect to mild disease states or progression of illness.

Safety and Tolerability of Bolus Intravenous Colistin in Acute Respiratory Exacerbations in Adults with Cystic Fibrosis

OBJECTIVE: To assess the safety and tolerability of bolus intravenous doses of colistin during acute respiratory exacerbations in adults with cystic fibrosis and chronic Pseudomonas aeruginosainfection. METHODS: Twelve patients with acute exacerbations of cystic fibrosis were enrolled in a Phase I open-label study. On day 1, patients received three doses of colistin 2 mega-units (160 mg), reconstituted in 50 mL of NaCl 0.9%, by infusion over 30 minutes three × daily. On days 2, 3, and 4, the same dose of colistin was administered by bolus injection three × a day over five minutes after reconstitution in 20, 15, and 10 mL of NaCl 0.9%, respectively. The injection was given by a nurse or physician using a hand-held syringe. If the latter dose was tolerated, it was continued for the remaining eight days of the study. If any dose was not tolerated, treatment reverted to the previously tolerated concentration, which was continued throughout the remainder of the study. RESULTS: No serious adverse events occurred during the course of the trial. Patients without total indwelling venous access systems experienced mild to moderate injection pain. There were no clinically significant changes in renal function. CONCLUSIONS: This study indicates that the administration of bolus intravenous colistin as 2 mega-units (160 mg) in 10 mL of NaCl 0.9% three × a day is safe. It is well-tolerated by patients with total indwelling venous access systems.

Perceived Body Image and Eating Behavior in Young Adults with Cystic Fibrosis and Their Healthy Peers

Treatment aimed at achieving an ideal nutritional status is an integral part of the management of patients with cystic fibrosis (CF). Emphasis is continually placed upon dietary intake and weight. The effects of this on eating behavior and self-perceptions are unclear. This work compared male and female CF adults with a healthy male and female control population with regard to (a) clinical variables, (b) actual, perceived, and desired body shape/body mass index (BMI), and (c) body satisfaction, eating behaviors and attitudes, and self-esteem. Clinical data were recorded for 221 adults with CF and 148 healthy controls. All subjects completed BMI Charts (perception of body weight/BMI), the Eating Attitudes Test, and scales of body satisfaction and self-esteem. CF patients had poorer lung function and nutritional status than controls. Control males accurately perceived their body shape/BMI and were content with it, whereas CF males viewed their BMI as greater than it actually was and desired to be much heavier. Control females viewed their body shape/BMI as less than it actually was and desired to be even slimmer, in comparison with CF females, who perceived their BMI as less than it actually was but were happy with their perceived shape/weight. Control subjects, especially females, dieted to a greater extent and were more preoccupied with food (with binge eating and intended vomiting) than CF patients. Conversely, those with CF reported greater pressure from others to eat than did controls. More problems with food/eating behavior were associated with less body satisfaction and reduced self-esteem. In comparison with a healthy control population, the perceptions and behaviors of CF adults relating to eating, weight, and body image are not abnormal. Indeed, females with CF have fewer problems than their healthy peers.

Nutritional decline in cystic fibrosis related diabetes: The effect of intensive nutritional intervention

BACKGROUND Reports indicate that nutritional and respiratory decline occur up to four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim was to establish whether intensive nutritional intervention prevents pre-diabetic nutritional decline in an adult population with CFRD. METHODS 48 adult patients with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen status. Nutritional and other clinical indices were recorded at annual intervals from six years before until two years after diagnosis. Data were also analysed to examine the impact of early and late acquisition of CFRD. RESULTS No important differences in weight, height, body mass index (BMI), lung function or intravenous treatment were found between groups in the six years prior to diagnosis, nor any significant deviation over time. In those who developed diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF Controls), OR 4.0, CI 1.3 to 16.4, p=0.01]. Age at onset of CFRD played a significant role in determining the pre-diabetic clinical course. Younger diabetics with continued growth at study onset (n=17) had a lower BMI from 2 years prior to diagnosis compared to controls [BMI 18.9 kg/m(2) (CFRD) v 20.8 kg/m(2) (CF Controls), diff=1.9, CI -0.1 to 3.7 p=0.04]. The BMI of older diabetics (completed growth at study onset) was equal to that of controls throughout. CONCLUSION Pre-diabetic nutritional decline is not inevitable in adults with CFRD, but is influenced by age of onset. In the group overall, those with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite intensive nutritional intervention, patients who continue to grow throughout the pre-diabetic years, show a level of nutritional decline absent in older adults.

The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation

BACKGROUND Respiratory viruses have become increasingly recognised as important agents in pulmonary exacerbations in infants and children with CF. The aim of this study was to determine the prevalence of respiratory viruses during acute pulmonary exacerbations in adults and compare the severity of these exacerbations with non-viral associated exacerbations. METHODS This was a retrospective case control study. Viral throat swabs were taken from all patients presenting with an acute pulmonary exacerbation requiring intravenous antibiotic treatment over a 12 month period. RESULTS There were 432 pulmonary exacerbations in 180 adults. A positive viral PCR in 42 exacerbations indicated a prevalence of 9.7%. The commonest virus isolated was rhinovirus (n = 29, 69%) with influenza A/H1N1 in seven patients (16.7%). Exacerbations associated with a positive viral PCR had a greater fall in lung function at presentation with higher levels of inflammatory markers. They received more days of intravenous antibiotics, showed less response to treatment and had a shorter time to next pulmonary exacerbation compared to matched controls. CONCLUSION Viral associated pulmonary exacerbations in adults with CF are associated with more severe pulmonary involvement and respond less well to standard treatment.

Rapid desensitization for non-immediate reactions in patients with cystic fibrosis

Non-immediate hypersensitivity reactions to antibiotics in patients with CF represent a real-life challenge for clinicians. Desensitization is often performed in patients who have exhausted all therapeutic options. Whilst desensitization is an established procedure for immediate reactions we assessed the outcomes and safety of desensitization for non-immediate reactions. We retrospectively reviewed 275 desensitization procedures in 42 patients with a range of non-immediate reactions to six commonly used antibiotics. Desensitization was performed using a 7-step rapid intravenous protocol on a normal medical ward. 250 (91%) of overall desensitization procedures were successful; however, this figure incorporates certain individuals having multiple successful procedures. Individual patient success ranged from 55% with tazocin through to 88% with tobramycin. In the 25 patients who failed desensitization the reactions were mild and the majority occurred within 48 h of starting treatment. Prophylactic anti-histamines and steroids did not reduce the risk of reaction. Whilst the mechanisms remain uncertain we can confirm that rapid desensitization is a safe and effective way of re-introducing an antibiotic to a patient with a non-immediate reaction.

Ocular signs and symptoms and vitamin A status in patients with cystic fibrosis treated with daily vitamin A supplements

BACKGROUND/AIMS Patients with cystic fibrosis (CF) may have low plasma vitamin A levels from malabsorption, zinc deficiency, liver disease, or poor compliance with prescribed supplements. In view of the increasing number of adults with CF, many of whom drive cars, it is important to assess vitamin A status. In our centre an attempt has been made to achieve normal levels of fat soluble vitamins by annual estimation of plasma levels and appropriate oral supplementation. This study aimed to determine if this approach prevents vitamin A deficiency and the consequent problems with dark adaptation. METHODS The study was conducted at the regional adult and paediatric cystic fibrosis unit and the patients were recruited from there. Dark adaptation studies were conducted at the department of ophthalmology, St James’s University Hospital. All patients are regularly seen in the outpatient department by a CF specialist dietitian and have a comprehensive annual dietary assessment. 28 patients had the following investigations: serum retinol, plasma zinc, serum retinol binding protein, liver function tests, dark adaptation, contrast sensitivity, and anterior ocular surface status. 25 age and sex matched controls without CF or ocular pathology were also recruited for the dark adaptation study. RESULTS None of the patients had vitamin A deficiency, the median value of serum retinol being 48 μg/dl, range 31–80 μg/dl (normal range 30–80 μg/dl). Dark adaptation was normal in all cases compared with the control group where the mean value was 3.4 log units of threshold luminance (95% confidence interval 2.4–4.0). None of the test group had a value of threshold luminance 2 SD above the mean value for the control group. Eight patients had reduced contrast sensitivity. The median value for serum zinc was 14.2 μmol/ l, range 13–81 μmol/l (normal range 8–23 μmol/l) and the median value for retinol binding protein was 36 mg/l, range 13–81 mg/l (normal range 35–58 mg/l). There was no correlation between dark adaptation and serum retinol, zinc, or retinol binding protein. Two patients had clinical evidence of dry eye. CONCLUSION Regular estimates of plasma vitamin A together with appropriate supplementation and expert dietetic review can maintain normal dark adaptation in patients with cystic fibrosis. The occurrence of reduced contrast sensitivity function is well documented but remains an unexplained phenomenon and deserves further study.

Ten years of viral and non-bacterial serology in adults with cystic fibrosis

Viral infections are associated with pulmonary exacerbations in children with cystic fibrosis (CF), but few studies have addressed the frequency in adults. This paper investigates the frequency and impact of viral infections in adults with CF receiving intravenous antibiotics. Pre- and post-treatment spirometry, inflammatory markers and antibody titres against influenza A, influenza B, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetti were analysed over a 10-year period. Non-bacterial infections were identified in 5.1% of 3156 courses of treatment. The annual incidence of admissions per patient associated with viral infection was 4.9%. The presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term. Adults with CF have a lower incidence of respiratory viral infections associated with pulmonary exacerbations requiring intravenous antibiotics compared to children and infants with CF.

A pilot study of zafirlukast as an anti-inflammatory agent in the treatment of adults with cystic fibrosis

BACKGROUND Persistent endobronchial inflammation is in part responsible for the attrition of lung function seen in cystic fibrosis. Leukotrienes act as pro-inflammatory mediators. The aim of this study was to assess the efficacy of the leukotriene receptor antagonist zafirlukast as a potential anti-inflammatory agent in the treatment of adult patients with cystic fibrosis. METHODS Clinically stable patients were enrolled in the study if they had no history or clinical evidence of asthma, bronchial hyper-reactivity, or aspergillosis. They were randomised to receive zafirlukast 20 mg twice daily with all routine treatment for four months or routine treatment alone in an open cross-over design. Primary endpoints were changes in respiratory function tests and a modified NIH clinical score. RESULTS Thirty patients were enrolled and 25 completed. There was a significant improvement in the modified NIH clinical score but no significant increase in respiratory function with zafirlukast. CONCLUSIONS Patients receiving a leukotriene receptor antagonist in addition to routine treatments showed significant improvement in a clinical score which is a composite of clinical wellbeing, chest radiograph appearance, and physical examination. Respiratory function showed a non-significant trend towards improvement with treatment. Zafirlukast may benefit patients with CF. An adequately powered study is justified on the basis of these results.