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A K Webb

Publications and source records attributed to A K Webb.

At least 73 records · Page 4Linked to original sources
PubMed1998

Alpha1-antitrypsin deficiency alleles and the Taq-I G-->A allele in cystic fibrosis lung disease.

Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven patients were recruited from two UK CF centres. The serum concentrations of alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were determined and patients were screened for the common S and Z deficiency alleles of alpha1-antitrypsin and the G-->A mutation in the 3' noncoding region of the alpha1-antitrypsin gene (Taq-I G-->A allele). Alpha1-antitrypsin deficiency phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested CF patients and were, surprisingly, associated with significantly better lung function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The Taq-I G-->A allele was found in 21 out of 150 unrelated patients and had no significant effect on CF lung disease or on levels of alpha1-antitrypsin during the inflammatory response. We show here that, contrary to current thinking, common mutations of alpha1-antitrypsin that are associated with mild to moderate deficiency of the protein predict a subgroup of cystic fibrosis patients with less severe pulmonary disease. Moreover, the Taq-I G-->A allele has no effect on serum levels of alpha1-antitrypsin in the inflammatory response, which suggests that the previously reported association of the Taq-I G-->A allele with chronic obstructive pulmonary disease is not mediated by its effect on the serum level of alpha1-antitrypsin.

Adult↗
PubMed1997

Long-term change in exercise capacity, body mass, and pulmonary function in adults with cystic fibrosis.

STUDY OBJECTIVES: Cross-sectional studies in patients with cystic fibrosis (CF) have shown that exercise capacity is correlated with pulmonary function and body mass. We have examined whether the same relationships are seen longitudinally in adults with CF. DESIGN: Subjects who first performed progressive maximal cycle ergometry between 1986 and 1989 were retested using an identical protocol a mean of 6.3 years later. PARTICIPANTS AND SETTING: Adults with CF attending a regional center. MEASUREMENTS AND RESULTS: The principal exercise measures were peak oxygen uptake (VO2peak), ventilation (VEpeak), oxygen saturation, and heart rate. Spirometry, weight, and height were also recorded at each time point. At baseline, subjects had a mean age of 19.8 years, body mass index (BMI) of 19.0, FEV1 of 69% predicted, VO2peak of 1.56 L/min, and VEpeak of 48.9 L/min. At repeated testing after a mean interval of 6.3 years, the FEV1 had fallen significantly to 54% predicted (p < 0.001) and the BMI had risen significantly to a mean of 20.9 (p < 0.001). There were no significant differences in VO2peak or VEpeak, although VEpeak was a significantly higher proportion (72% vs 61%) of predicted maximal voluntary ventilation. CONCLUSIONS: Adults with mild to moderate pulmonary dysfunction were able to increase body mass and maintain VO2peak despite a declining FEV1. VO2peak was not reduced by the decrease in FEV1 because VEpeak was unaffected. Improved nutrition may have contributed to maintaining fitness.

Adolescent↗
PubMed1997

A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis.

Cystic fibrosis (CF) is a common, serious, inherited disease. The major cause of mortality in CF is lung disease, due to the failure of airway epithelial cells to express a functional product of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A potential treatment for CF lung disease is the expression of CFTR in the airways following gene transfer. We have undertaken a double-blinded, placebo-controlled, clinical study of the transfer of the CFTR cDNA to the nasal epithelium of 12 CF patients. Cationic liposomes complexed with plasmid containing the human CFTR cDNA were administered to eight patients, whilst four patients received placebo. Biopsies of the nasal epithelium taken 7 days after dosing were normal. No significant changes in clinical parameters were observed. Functional expression of CFTR assessed by in vivo nasal potential difference measurements showed transient correction of the CF chloride transport abnormality in two patients (15 days after dosing in one patient). Fluorescence microscopy demonstrated CFTR function ex vivo. In cells from nasal brushings. In total, evidence of functional CFTR gene transfer was obtained in six out of the eight treated patients. These results provide proof of concept for liposome-mediated CF gene transfer.

Adolescent↗
PubMed1997

Exercise testing and prognosis in adult cystic fibrosis.

BACKGROUND: The assessment of prognosis is an important issue in cystic fibrosis. The prognostic value of exercise testing in comparison with other predictors of mortality was examined. METHODS: Ninety two adult patients with cystic fibrosis performed progressive maximal exercise tests and outcome was assessed at five years. The results of exercise testing were examined along with spirometric values, age, sex, body mass index (BMI), and sputum culture. RESULTS: Twenty two subjects died during the five year follow up period and 67 survived. Five subjects received a lung transplant and were excluded from the analysis. There were significant differences between those who survived and those who died: mean (SE) forced expiratory volume in one second (FEV1) 68.9 (2.7) versus 39.7 (3.5)% predicted, BMI 19.0 (0.3) versus 17.1 (0.4) kg/m2, peak oxygen uptake (VO2 peak) 66.6 (2.2) versus (53.7) (3.7)% predicted, peak work rate (Wpeak) 89.4 (3.8) versus 71.2 (5.5)% predicted, peak minute ventilation (VEpeak) 51.3 (2.0) versus 43.3 (3.1) 1/min, and ventilatory equivalent for oxygen (VE/VO2) 32.4 (0.6) versus 38.7 (1.7). Age, sex, oxygen saturation and Burkholderia cepacia colonisation were not found to be significant predictors of mortality. When significant independent factors were entered into a multivariate logistic regression model only FEV1 was found to be a significant correlate of mortality. A cutoff for FEV1 of 55% predicted gave the best combination of specificity and sensitivity with 54% of those below this value dying within five years and 96% of those above it surviving. CONCLUSIONS: The results of maximal exercise testing are correlated with survival but they are not better than the FEV1 as prognostic indicators.

Adolescent↗
PubMed1997

Effect of tonicity of nebulised colistin on chest tightness and pulmonary function in adults with cystic fibrosis.

BACKGROUND: Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment. This study examines the relationship of chest tightness and change in lung function in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients' preference. METHODS: Twenty seven adult patients with cystic fibrosis and a mean forced expiratory volume in one second (FEV1) of 54% predicted (range 24-98) were studied. They inhaled a nebulised solution of hypertonic, isotonic, and hypotonic colistin over three consecutive days in random order in a double blind fashion. Measurements of chest tightness, using a visual analogue scale (VAS), and FEV1 were recorded before and 0, 15, 30, 60, and 90 minutes following inhalation. The solution preferred by each patient was determined at the end of the three days. RESULTS: All tonicities caused a significant fall in FEV1 % predicted and an increase in chest tightness, with no differences between the solutions. However, the mean (SE) time to the maximum fall in FEV1 % predicted was significantly different between the solutions (hypertonic 7.8 (2.1) min, isotonic 19.2 (5.5) min, and hypotonic 34.2 (5.9) min) with a mean difference (95% CI) between hypotonic and hypertonic solutions of 28.04 (14.6 to 41.5) min, between isotonic and hypertonic solutions of 12.0 (-0.1 to 24.1) min, and between hypotonic and isotonic solutions of 15.6 (1.8 to 29.4) min. Positive correlations existed for the maximum fall in FEV1 % predicted between the hypertonic and isotonic solutions (r = 0.62, p < 0.001) and between the hypotonic and isotonic solutions (r = 0.64, p < 0.001). There was no correlation between the objective and subjective measurements for any solution. The patients' preference varied. CONCLUSIONS: All tonicities of colistin caused equal symptoms of chest tightness and reduction in pulmonary function. It is recommended that the patient is challenged with nebulised colistin before prescription of the drug and that the challenge is preceded by an inhaled bronchodilator. Most of the patients preferred the isotonic or hypotonic solutions. The isotonic solution reflects a fall in FEV1 representative of all the solutions. The fall in FEV1 to the hypotonic solution occurred over a longer period and may be better tolerated by some patients.

Administration, Inhalation↗
PubMed1996

Health perceptions and treatment adherence in adults with cystic fibrosis.

BACKGROUND: Clinical and demographic variables are poor predictors of treatment adherence. This study therefore examined the relationships between the patients' perception of their cystic fibrosis and their reported adherence to physiotherapy, exercise, pancreatic enzyme and vitamin therapies. METHODS: Sixty adults with cystic fibrosis completed the Health Perception Scale, Health Locus of Control Scale, and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. RESULTS: Reported adherence to physiotherapy, exercise, pancreatic enzyme and vitamin therapies was not influenced by patients' perceptions of their past, current and future disease severity, or their perceived susceptibility to recurrent infections. The greater their level of worry regarding their disease, the more likely they were to adhere to their physiotherapy (p < 0.002), pancreatic enzyme (p < 0.001) and vitamin (p < 0.001) regimens. No difference between the exercise adherent and non-adherent groups emerged regarding their level of worry. Compared with patients who believed that they were in control of their health, those who believed that their cystic fibrosis was controlled by others (family and health professionals) reported greater levels of adherence to their physiotherapy (p < 0.001), pancreatic enzyme (p < 0.001) and vitamin (p < 0.001) therapies. In contrast, patients who adhered to their exercise regimen believed that they were in control of their disease to a greater extent than those who did not (p < 0.003). CONCLUSIONS: Worrying about cystic fibrosis and the perception of having little personal control over the disease facilitated treatment adherence. It is clear that patients perceive exercise therapy differently from other forms of treatment.

Adolescent↗
PubMed1996

Allergic bronchopulmonary aspergillosis in lung allograft recipients.

Following lung transplantation for end-stage cystic fibrosis, two male patients presented with shortness of breath, peripheral blood eosinophilia and segmental lung collapse. At bronchoscopy, each had bronchial mucous plugging containing Aspergillus fumigatus. This finding was associated with a systemic eosinophilia and skin test positivity to Aspergillus. Augmented steroid therapy resulted in the successful resolution of the symptoms. We believe that these are the first reported cases of allergic bronchopulmonary aspergillosis in lung allograft recipients.

Adult↗
PubMed1995

Clinical evaluation of meropenem versus ceftazidime for the treatment of Pseudomonas spp. infections in cystic fibrosis patients.

Cystic fibrosis patients (children and young adults) with Pseudomonas spp. chest infections were treated with meropenem or ceftazidime. This study was the first to investigate the use of meropenem in cystic fibrosis. Meropenem was well tolerated with only transient elevations of serum transaminases. No patient experienced nausea and vomiting, even when meropenem was administered as a bolus injection. This allowed home therapy to be used. Meropenem appeared to be at least as active as ceftazidime even at the low doses used. Patients showed a greater improvement in respiratory function on meropenem than ceftazidime. Only one patient (out of 60 courses) failed to respond to meropenem (98% success rate) compared with two failures out of 21 episodes with ceftazidime (90% success rate). There was little emergence of resistance to meropenem even though some patients were treated up to eight times over a 2 year period.

Adolescent↗
PubMed1995

Communicating with young adults with cystic fibrosis.

The care of the young adult with cystic fibrosis is complex, requiring a multidisciplinary input from different carers. Communication with and education of patients covers many areas; topics may include medical and personal problems, transplantation, survival, current scientific breakthroughs and the future. Communicating in these areas with knowledgeable young adults requires skill, tact and self-education upon the part of the cystic fibrosis team.

Adolescent↗
PubMed1995

District nebuliser compressor service: reliability and costs.

BACKGROUND: There is little information on the costs of maintaining a district nebuliser compressor service. This retrospective study examines the issue, reliability, and maintenance costs of electrical compressors to assist the prediction of future costs, taking into account recent safety legislation. METHODS: Records of issue, repair, and replacement for the period 1982-91 were reviewed. The current policy of repairing and replacing as necessary, and three other theoretical costings, were considered. RESULTS: The number of compressors being issued is increasing. Repaired compressors are less reliable and frequency of repair is a function of compressor age. The current policy is the most cost effective. CONCLUSIONS: To repair and replace nebuliser compressors as necessary is the most economical policy under the present terms offered by the manufacturers, but changes in safety legislation will affect the provision of such services.

Electric Power Supplies↗
PubMed1995

Outcome of pregnancy in women with cystic fibrosis.

BACKGROUND: As women with cystic fibrosis are living longer, pregnancy is becoming increasingly common. The combined experience of pregnancies in women with cystic fibrosis from adult centres in the Midlands and North of England has been examined. METHODS: A retrospective study of the case notes of 22 pregnancies in 20 patients with cystic fibrosis examined changes in lung function, body weight, and microbiological status during the course of pregnancy. Duration of pregnancy, birth weight, and maternal survival were amongst other variables studied. The relation between values before pregnancy and important outcome measures were examined. RESULTS: Eighteen of 22 pregnancies were completed producing healthy, non-cystic fibrosis infants (12 female). Mothers lost 13% of FEV1 and 11% of FVC during pregnancy, most of which was regained. Body weight changes were variable, but most mothers gained weight (mean weight gain 5.7 kg). Microbiological status remained unchanged. Six infants were preterm and two were light for dates. Four mothers died up to 3.2 years following delivery. Of the prepregnancy parameters examined, %FEV1 showed the best correlation with maternal weight gain, gestation, birth weight, and maternal survival. CONCLUSIONS: Pregnancy was well tolerated by most mothers with cystic fibrosis although those with moderate to severe lung disease (%FEV1 < 60%) before pregnancy fared worse, producing preterm infants and suffering increased loss of lung function and mortality compared with mildly affected mothers. Prepregnancy %FEV1 appears to be the most useful predictor of important outcome measures in pregnancies in women with cystic fibrosis.

Adolescent↗
PubMed1995

Different perceptions of disease severity and self care between patients with cystic fibrosis, their close companions, and physician.

BACKGROUND: An investigation was carried out to determine whether patients with cystic fibrosis, their close companions, and physician perceived the severity of the disease and the level of patient self care similarly. METHODS: Sixty adults with cystic fibrosis (16-44 years), their close companion, and physician independently completed scales measuring their perceptions of disease severity and patient self care on three occasions over a two year period. Percentage predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), Shwachman score, and weight for height were recorded following each assessment. RESULTS: Patients and close companions considered the disease to be less severe than their physician. Fifty patients (83%) rated their health as "above/well above average", and 49 (82%) close companions rated the patient's health in the same way, but only 21 (35%) patients were considered by their physician to have mild disease. Differences also emerged in the estimation of patient self care; 48 close companions (80%) rated patients as "very good" or "excellent" in their self care, compared with 26 (44%) of the patients themselves. Only nine patients (15%) were considered to achieve this level of self care by their physician. Over the two year period the physician's ratings of severity increased in accordance with the decline in lung function. Patients' perceptions remained unchanged. CONCLUSIONS: From the physician's view-point, patients and close companions underestimate the severity of cystic fibrosis and overestimate patient self care. Patients' perceptions remain constant over time even when their health is clinically deteriorating.

Adolescent↗