Kevin Webb

Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study

Abstract Objectives: To assess the effect on clinical outcome of managing paediatric and adult patients with cystic fibrosis at specialised cystic fibrosis centres. Design: Cross sectional study. Setting: Two adult cystic fibrosis centres in the United Kingdom. Subjects: Patients from an adult cystic fibrosis centre in Manchester were subdivided into those who had received continuous care from paediatric and adult cystic fibrosis centres (group A), and those who had received paediatric care in a centre not specialising in cystic fibrosis followed by adult care in a cystic fibrosis centre (group B). Group C were referrals to the new adult cystic fibrosis centre in Cambridge who had received neither paediatric nor adult centre care for their cystic fibrosis. Main outcome measures: Body mass index (weight (kg)/height (m2)), lung function (forced expiratory volume in one second (FEV1 percentage of predicted)), the Northern chest x ray film score, and age at colonisation with Pseudomonas aeruginosa. Results: A prominent stepwise increase in body mass index was associated with increasing amounts of care at a cystic fibrosis centre; 18.3, 20.2, and 21.3 for groups C, B, and A respectively (P<0.001). Improved nutritional status was correlated with a higher FEV1 and better (lower) chest x ray film scores; r=0.52 and −0.45 respectively (P<0.001 for both). Conclusion: These findings provide the first direct evidence that management of cystic fibrosis in paediatric and adult cystic fibrosis centres results in a better clinical outcome, and strongly supports the provision of these specialist services. Key messages Management of patients with cystic fibrosis in paediatric and adult cystic fibrosis centres results in an improved clinical outcome Improved clinical outcome occurred in cystic fibrosis centres despite earlier and more frequent colonisation with Pseudomonas aeruginosa Nutritional status is an important predictor of lung disease in cystic fibrosis

Novel immunologic classification of aspergillosis in adult cystic fibrosis

BACKGROUND Patients with cystic fibrosis (CF) demonstrate a wide range of hypersensitivity responses to Aspergillus, beyond allergic bronchopulmonary aspergillosis, which require classification. OBJECTIVE This study integrated 2 new methods of Aspergillus detection-sputum galactomannan (GM) and real-time PCR-alongside established serologic markers, to reclassify aspergillosis in CF. METHODS A total of 146 adult patients with CF had serologic tests (ImmunoCap total IgE, specific Aspergillus fumigatus IgE, and specific A fumigatus IgG), sputum real-time Aspergillus PCR, and sputum GM. Patients were classified by using latent class analysis. RESULTS Both RT-PCR and GM were more sensitive than culture in detecting Aspergillus in sputum (culture 37%, RT-PCR 74%, and GM 46%). Intraassay and interassay reproducibility of PCR and GM was excellent. Latent class analysis of triazole-naive patients identified a nondiseased group and 3 disease classes: class 1 (n = 49, 37.7%) represented patients with or without positive RT-PCR but no immunologic response to A fumigatus and negative GM (nondiseased); class 2 (n = 23, 17.7%) represented patients with positive RT-PCR, elevated total and specific A fumigatus IgE/IgG, and positive GM (serologic allergic bronchopulmonary aspergillosis); class 3 (n = 19, 14.6%) represented patients with or without positive RT-PCR, elevated A fumigatus IgE (not IgG), and negative GM (Aspergillus sensitized); and class 4 (n = 39, 30%) represented patients with positive RT-PCR, elevated A fumigatus IgG (not IgE), and positive GM (Aspergillus bronchitis). CONCLUSIONS Three distinct classes of aspergillosis in CF were identified by latent class analysis by using serologic, RT-PCR, and GM data. This novel classification will facilitate improved phenotyping, pathogenesis studies, and management evaluations.

Ways of coping with cystic fibrosis: implications for treatment adherence

Purpose: How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. Methods: The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness), 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. Results: Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than adherent or non-adherent patients (all ps 0.05). Nonadherent patients used avoidance strategies to a greater extent than those who were adherent (physiotherapy p < 0.05, enzymes p < 0.04), although interestingly, adherence with exercise was associated with avoidant coping (p < 0.004). Conclusions: The degree of adherence to treatments was influenced by a persons style of coping. The identification of effective coping strategies to aid both long-term psychological and clinical well-being should improve the management of nonadherence.PURPOSE How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. METHODS The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness). 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. RESULTS Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than adherent or non-adherent patients (all ps < 0.05). Non-adherent patients used avoidance strategies to a greater extent than those who were adherent (physiotherapy p < 0.05, enzymes p < 0.04), although interestingly, adherence with exercise was associated with avoidant coping (p < 0.004). CONCLUSIONS The degree of adherence to treatments was influenced by a persons style of coping. The identification of effective coping strategies to aid both long-term psychological and clinical well-being should improve the management of non-adherence.

Variation in hydrogen cyanide production between different strains of Pseudomonas aeruginosa

There is increasing interest in using the cyanogenic properties of Pseudomonas aeruginosa to develop a nonmicrobiological method for its detection. Prior to this, the variation in cyanide production between different P. aeruginosa strains needs to be investigated. Hydrogen cyanide (HCN) released into the gas phase by 96 genotyped P. aeruginosa samples was measured using selected ion flow tube-mass spectrometry after 24, 48, 72 and 96 h of incubation. The HCN produced by a range of non-P. aeruginosa cultures and incubated blank plates was also measured. All P. aeruginosa strains produced more HCN than the control samples, which generated extremely low levels. Analysis across all time-points demonstrated that nonmucoid samples produced more HCN than the mucoid samples (p=0.003), but this relationship varied according to strain. There were clear differences in the headspace HCN concentration for different strains. Multivariate analysis of headspace HCN for the commonest strains (Liverpool, Midlands_1 and Stoke-on-Trent, UK) revealed a significant effect of strain (p<0.001) and a borderline interaction of strain and phenotype (p=0.051). This evidence confirms that all P. aeruginosa strains produce HCN but to varying degrees and generates interest in the possible future clinical applications of the cyanogenic properties of P. aeruginosa.

Homogenisation of cystic fibrosis sputum by sonication - An essential step for Aspergillus PCR

The importance of Aspergillus as a lung pathogen in cystic fibrosis (CF) is becoming increasingly recognised. However, fungal culture of CF sputum is unreliable and there is no consensus for identifying phenotypes beyond ABPA that may benefit from antifungal therapy. There are no published studies using real-time PCR to detect Aspergillus in CF sputum. The major barrier to sensitive detection of Aspergillus using PCR is sputum homogenisation. This study aimed to optimise sputum homogenisation utilising sonication to improve Aspergillus DNA extraction. Sonication amplitude and duration that enabled sputum homogenisation but ensured preservation of DNA integrity were first determined. 160 sputum samples were collected from CF patients. 49 of the sputum samples were split, one half was used for standard culture and the other half was homogenised with NALC-NaOH before undergoing DNA extraction. The subsequent 111 samples were homogenised with dithiothreitol plus sonication prior to culture and DNA extraction. Real-time PCR targeting a portion of the 18S rDNA of Aspergillus was performed on all DNA extractions. In the 49 samples with no sonication 8 (16%) were culture positive but only 4 of these were PCR positive. However, PCR was positive in 11 culture negative samples. PCR after sonication showed a significant improvement in sensitivity: 33 (30%) were culture and PCR positive, 48 (43%) were culture negative, but PCR positive (p<0.0001) and 30 (27%) were culture and PCR negative. The combination of dithiothreitol and sonication to homogenise sputum increases PCR yield, with PCR being substantially more sensitive than culture.

Relationship Between Anxiety, Depression, and Quality of Life in Adult Patients With Cystic Fibrosis

BACKGROUND: The impact of anxiety and depression on quality of life (QOL) in adult patients with cystic fibrosis (CF) is fully unknown. We investigated the prevalence and factors associated with anxiety and depression, including QOL, in adult CF patients. METHODS: One hundred twenty-one adult CF subjects, age ≥ 18 years were recruited from our out-patient clinic. Participants self-completed the Hospital Anxiety Depression Scale and the Cystic Fibrosis Quality of Life Questionnaire (CF-QOL). Socio-demographic data and values for lung function were extracted from the medical notes. RESULTS: Mean ± SD age was 30 ± 8.8 years, and age ranged 18–70 years. Forty (33%) were identified with anxiety symptoms, 20 (17%) with depressive symptoms. Factors related with depression were impaired QOL and low lung function. Anxiety was associated with difficulty in interpersonal relationships and severity of chest symptoms. The CF-QOL sub-domains (physical functioning, social functioning, treatment issues, chest symptoms, emotional functioning, concerns for the future, interpersonal relationships, body image, future/career concerns, and total CF-QOL) were all significantly correlated with anxiety (P < .001) and with depression (P < .001), respectively. CONCLUSIONS: Anxiety and depressive symptoms are common in adult CF patients. They are associated with poorer QOL, low lung function, reduced physical functioning, and severity of chest symptoms. Therefore, routine screening for symptoms of anxiety and depression is a worthy endeavor, and those identified with elevated clinical symptoms should be referred to receive appropriate treatment.

Cross cultural differences in health related quality of life in adolescents with cystic fibrosis

Purpose : Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. Method : The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV 1 % predicted and BMI) were also recorded. Results : The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. Conclusions : The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36, rather than a consequence of their disease or its management.PURPOSE Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL-measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. METHOD The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV1% predicted and BMI) were also recorded. RESULTS The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. CONCLUSIONS The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36. rather than a consequence of their disease or its management.

Can early Burkholderia cepacia complex infection in cystic fibrosis be eradicated with antibiotic therapy

Introduction: Organisms of the Burkholderia cepacia complex (BCC) are important pathogens in cystic fibrosis (CF). The majority of those who acquire BCC develop chronic infection but it can also result in rapid decline in a significant minority. In addition, chronic infection with Burkholderia cenocepacia in particular is regarded as a contraindication to lung transplantation in many units. Whilst aggressive antibiotic therapy is employed in CF to eradicate Pseudomonas aeruginosa before infection becomes irreversibly established, no formal assessment of such strategies has been previously reported for BCC, despite the apparent widespread adoption of this practice. Methods: UK adult CF centers were surveyed about their current approach to new BCC infection. Outcomes of eradication therapy were assessed in patients attending the Manchester Adult CF Center with new BCC isolates between 1st January 2002 and 1st May 2011. Patients with previous infection with the same strain of BCC were excluded. BCC were identified at the national reference laboratories and confirmed by species-specific PCR and RecA sequencing. Results: Routine use of therapies to attempt eradication of new BCC is commonly used in the UK (12/17 centers who responded). This typically involves a combination of intravenous and nebulised antibiotics. Of 19 eligible cases of new BCC infection, the organism has been eradicated in 7 (37%). Three of these did not receive specific eradication therapy. Of 14 patients who have received eradication therapy and completed follow up, BCC were cleared in only 4 (29%). Conclusions: Attempted eradication of new BCC is a common practice in UK adult CF centers. A minority of patients clear the infection spontaneously and the effects of eradication therapies are at best modest. Early treatment may be associated with better outcomes, though there are insufficient data to support the use of any specific treatment regimen. A prospective, systematic evaluation of treatments and outcomes is required.

Varicella-zoster Infection in Adults with Cystic Fibrosis: Role of Acyclovir

Of 159 adult patients with cystic fibrosis, 5 were documented to have varicella-zoster infection that resulted in an infective pulmonary exacerbation that required intravenous acyclovir and additional antibiotic treatment. Stable serial pulmonary function values were observed over a 1-year period in 4 patients and no complications resulted from treatment. Early treatment with acyclovir in combination with appropriate antibiotics may prevent pulmonary deterioration in adult patients with cystic fibrosis who develop varicella-zoster infection.

A Comparison of Aztreonam and Ceftazidime in the Treatment of Respiratory Infections in Adults with Cystic Fibrosis

A randomised double blind 2-week trial of monotherapy with ceftazidime and aztreonam was completed in 22 adults with cystic fibrosis. 26 courses of treatment were initiated and 22 courses were completed. Within groups, both ceftazidime and aztreonam demonstrated a significant improvement in FEV1 at 2 weeks (ceftazidime p less than 0.05; aztreonam p less than 0.01) and a decline in sputum weight at 2 weeks (ceftazidime p less than 0.05; aztreonam p less than 0.05). Between groups, for spirometry and sputum weight the only change was a slower decline in FEV1 in the aztreonam group at 42 days (p less than 0.05).