Fatigue in cystic fibrosis: a novel prospective study investigating subjective and objective factors associated with fatigue.

Fatigue is a debilitating symptom in patients with cystic fibrosis (CF). Although fatigue is commonly reported in these patients, an effective treatment for this symptom has not been found. The factors associated with fatigue in CF have not been investigated. We conducted a prospective, case-control study in adult patients with CF. All the patients were chronically infected with Pseudomonas aeruginosa and were enrolled in the study during disease stability. A gender and age-matched control group was also recruited. Subjective assessment included three questionnaires: the Chalder fatigue questionnaire, St Mary's Hospital sleep questionnaire (SQ), and the scaled general health and Hillier questionnaire (GHQ). For patients with CF, spirometry, body mass index (BMI), haemoglobin level, C-reactive protein, and the burden of pulmonary exacerbations (PExs) were assessed. The control group completed all the three questionnaires, and their BMI was measured. A total of 78 participants were enrolled in the study (44 patients with CF and 34 control). Female patients with CF received antibiotics for more days than male patients with CF. The fatigue score did not differ between female and male participants in either the patients with CF or the control group; however, the fatigue score was greater for both the sexes in the patients with CF compared with the control group: p = 0.038 for female and p = 0.048 for male. The scores for the SQ and the GHQ did not differ between the two study groups. The fatigue score correlated with the total score for SQ (p < 0.0001) in patients with CF, but not in control participants. In patients with CF and the individuals in the control group, a close correlation was found between the fatigue score and the GHQ domain-specific scores and with the total score; p < 0.0001 for patients with CF and p = 0.001 for control. No correlations were found between the fatigue score and any of the objective parameters studied.

A novel respiratory symptom scoring system for CF pulmonary exacerbations.

BACKGROUND: There is currently no simple scoring system to evaluate change in symptoms during a pulmonary exacerbation (PEx) in adult cystic fibrosis (CF) patients. PATIENTS AND METHODS: We evaluated 265 episodes in 58 adult CF patients. A simple symptom score was administered at the start and the end of each PEx. The score evaluated four symptoms: cough, sputum, breathlessness and fatigue. Each symptom was scored from one (mild symptoms) to four (severe symptoms). The total symptom score was the summation of all the four symptoms. The total symptom score was compared with CF Respiratory Questionnaire (CFRQ) and with spirometry. RESULTS: There was significant internal correlation between scores for each pair of symptoms. The total symptom score correlated with the functional activity score and the respiratory score domains and with the summary score for CFRQ. The total symptom score correlated with spirometry values. Symptom score improved after 2-week treatment with intravenous (IV) antibiotics in 88.3%, remained unchanged in 7.3% and worsened in 4.4% of all episodes. Changes in symptom score after IV treatment correlated with changes of all main spirometry measurements. CONCLUSION: This new symptom score is simple and sensitive to change over a short period. It correlates with established quality-of-life questionnaires and with spirometry. The changes of symptom score over a short period correlate with changes in spirometry. This score can be used as an added tool to assess the outcome of CF PExs.

Evaluation of a novel sputum clearance technique--hydro-acoustic therapy (HAT) in adult patients with cystic fibrosis: a feasibility study.

This study was designed to investigate the efficacy, safety and patients' acceptance of a novel system for sputum clearance--Hydro Acoustic Therapy (HAT) in patients with cystic fibrosis (CF). This is a prospective crossover study where 18 patients received 6 sessions of physiotherapy over 6 separate days. These consisted of 2 sessions of either HAT, flutter valve or and sitting in the bath with sounds without vibration (placebo) for 30 minutes each. The efficacy was investigated by measuring the weight of wet and dry sputum after each session and by change in spirometry values. The preference was assessed by a questionnaire completed by patients at the end of the study about their preference of which type of physiotherapy received. The weight of both dry and wet sputum produced was similar in the 3 arms of the study. Spirometry values but not oxygen saturation were reduced after HAT and flutter therapy sessions. HAT therapy was preferred to flutter and placebo in terms of breathlessness, ease of sputum production and relaxation. Of the patients, 70% stated that they would choose HAT as their preferred physiotherapy method compared to 0% for flutter (χ(2) = 20.3, p < 0.0001). There were no procedure-related complications in any of the 3 arms of the study. HAT was found to be safe, well tolerated and favoured by the majority of CF patients. The effect of HAT, however, on sputum production was not superior to flutter or placebo.

MRI appearance of the pancreas in patients with cystic fibrosis: a comparison of pancreas volume in diabetic and non-diabetic patients.

We investigated differences in the volume of the pancreas in cystic fibrosis (CF) patients with and without diabetes using MRI to study the natural history of CF-related diabetes (CFRD). We investigated 29 pancreas-insufficient adult CF patients, 13 with CFRD and 16 without diabetes. Patients with CFRD were receiving insulin therapy at the time of study. None of the non-diabetic CF patients had evidence of impaired glucose tolerance. Pancreas volume was estimated by MRI scans using T1 weighted fat-suppression sequences and assessed by an examiner who was unaware of the patients' diabetes status. Pancreas volume of CF patients was measured and subsequently compared with that of non-CF age-matched Type 1 diabetes (T1DM) patients and healthy controls previously investigated. The two CF groups were matched for age and gender. There were no differences in spirometry values, body mass index or pancreatic exocrine function. The pancreas was visible by MRI in only 3 of 13 (23.1%) patients with CFRD and in 5 of 16 (31.3%) patients without diabetes (p-value = 0.7). In total, the pancreas was not detected by MRI as an anatomical entity in 21 of 29 (72.4%) CF patients, irrespective of their diabetes status. When comparing the four study groups, the pancreas was significantly smaller in CF patients than in T1DM patients and healthy controls.

The size of the spleen by magnetic resonance imaging in patients with cystic fibrosis; with and without diabetes--a novel observational study.

BACKGROUND: Magnetic resonance imaging (MRI) has been shown to be a useful tool to evaluate the volume of the pancreas. There is currently no information about the size of the spleen in cystic fibrosis (CF) patients. PATIENTS AND METHODS: We investigated 51 adult volunteers: 28 pancreatic insufficient CF patients [13 with CF-related diabetes (CFRD) and 15 non-diabetic] and 23 male non-CF patients [12 with type 1 diabetes mellitus (T1DM) and 11 healthy control subjects]. Patients with known liver cirrhosis or portal hypertension were excluded. The size of the spleen was measured in all subjects by an investigator unaware of patients' clinical status. For comparison of spleen size in the four study groups only male CF patients were included. For CF patients, spleen size was compared with forced expiratory volume in 1 s (FEV(1)), body mass index (BMI), total number of days of intravenous (IV) antibiotic treatment for pulmonary exacerbations in year previous to study, levels of circulating white blood cells, glycosylated haemoglobin A1c (HbA1c), and exocrine function of the pancreas, as assessed by daily requirement of oral lipase. RESULTS: Amongst the four study groups, spleen size was greatest in the male non-diabetic CF patients (P = 0.01). For CF patients, spleen size was greater in male compared to female patients (P = 0.012). For patients with CFRD, there was an inverse correlation between the spleen size and HbA1c (r = -0.59, P = 0.04) and the daily intake of supplementary lipase (r = -0.63, P = 0.02). The size of the spleen in patients with CFRD, but not in CF patients without CFRD, inversely correlated with the days of IV antibiotic treatment received in the year previous to the study (r = -0.67, P = 0.012). There was no correlation between spleen size and BMI, FEV1 and white blood cell counts in any group. CONCLUSION: On MRI, the spleen size was greatest in male non-diabetic CF patients in comparison with other groups. The size of the spleen in CFRD patients was smaller when diabetes was poorly controlled, when exocrine pancreatic function was greatly impaired and in those with greater need for IV antibiotics in the year prior to the study.

Remote daily real-time monitoring in patients with COPD --a feasibility study using a novel device.

New technologies have allowed remote real-time electronic recording of symptoms and spirometry. The feasibility of utilising this technology in COPD patients has not been investigated. This is a feasibility study. The primary objective is to determine whether the use of an electronic diary with a portable spirometer can be performed by COPD patients with a moderate to severe disease. Secondary objectives are to investigate the value of this method in early detection of acute exacerbations of COPD (AECOPD). In this 6-month study, 18 patients recorded daily their symptom score and spirometry. Data was sent on real time. AECOPD which was defined according to pre-set criteria were noted. Spirometry values and scores for health-related quality of life were compared between the start and the end of the study. Hospitalisation rate due to AECOPD was compared with a parallel period in the previous year. On average, patients were able to record 77% of their total study days. The system detected 73% of AECOPD. In further 27% of AECOPD patients sought treatment although the change in symptoms did not meet AECOPD definition. The number of COPD-related hospitalisations significantly reduced compared to the previous year. There was a significant increase in FEV(1) and FVC from the start to the end of the study. The remote monitoring device used in this study can be used in COPD patients. AECOPD was detected early in the majority of cases. Hospitalisation rate due to AECOPD was reduced and FEV(1) and FVC values increased during the study.

Risk factors for increased need for intravenous antibiotics for pulmonary exacerbations in adult patients with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations (P Exs) are important in cystic fibrosis (CF). They are very common, and are associated with poor quality of life. P Exs are regarded as an important end point in clinical trials. Risk factors associated with increase in P Exs have not been examined at a large scale. This study investigates factors associated with P Exs in a large cohort of adolescent and adult patients. PATIENTS AND METHODS: This is a cross-sectional study on data collected in the South and West Regions in England in 2002. Patients aged 16 years and over were included. Data on age, gender, FEV(1), body mass index (BMI), infection with Pseudomonas aeruginosa (Pa) and on CF-related diabetes were included in the analysis. P Ex was defined as an episode treated with IV antibiotics. Forward stepwise multiple regression analysis was performed with the number of P Exs being the independent variable. The rest of the variables were considered to be the dependent variables. RESULTS: Data from 341 patients (194 female), mean age (SD), 24.9 (8.9) years were available. In 2002, a total of 599 P Exs were reported, median 1.00 range 0-16 P Exs. Using stepwise multiple regression analysis factors associated with increased number of P Exs were: infection with Pa (t-value -5.0, P < 0.0001), FEV(1), (t-value -4.9, P < 0.0001) and diabetes mellitus, (t-value -2.1, P = 0.04). Age, gender and BMI did not influence the annual number of exacerbations. CONCLUSIONS: In this study, risk factors for P Exs were found to be as follows: growth of Pa in the sputum, reduced FEV1 and CF-related diabetes mellitus.

Glucocorticoids as an adjuvant treatment to intravenous antibiotics for cystic fibrosis pulmonary exacerbations: a UK Survey.

Oral glucocorticoids are widely used to treat exacerbations of asthma and COPD. A role for their use in treating exacerbations in Cystic Fibrosis (CF) is not proven. We describe the current practice, amongst UK adult CF physicians, of oral glucocorticoid use as an adjuvant to intravenous (IV) antibiotic treatment during CF pulmonary exacerbation (P EX). The survey also examined whether physicians thought a randomised controlled trial (RCT) was necessary and their willingness to participate patients in such a trial. Eighty one percent of physicians replied. All of them used corticosteroids with P EX. Most physicians supported the need for a RCT and would be willing to enroll consenting patients in the trial. This survey highlighted the need for a RCT which would examine the role of adjuvant corticosteroids to IV antibiotics in CF P EX.

Factors associated with reduced FEV1 in adult patients with cystic fibrosis in a relatively affluent area.

Data collected on adult cystic fibrosis (CF) patients and entered onto the CF database in the south and west regions of England were analysed for the year 2001. FEV1 was taken as a marker of lung disease severity. Data on 371 patients (158 female) mean age 24.7 years (range 16.0-48.9) were assessed. FEV1 was reduced in CF patients infected with Pseudomonas aeruginosa (Pa) (mean 62.6% predicted) compared with those without (mean FEV1 77.8%, P < 0.00001). The reduction was noted irrespective of age group. FEV1 progressively reduced with the increasing need for high-intensity treatment (P < 0.00001) and with the diagnosis of diabetes mellitus (P = 0.03). FEV1 correlated with body mass index (BMI) (r = + 0.42, P < 0.0001). Genetic profile and poverty and deprivation score did not affect the value of FEV1. Chronic infection with Pa mainly in young adults, treatment intensity, diabetes mellitus and reduced body mass index are associated with reduced FEV1 in adult patients with cystic fibrosis in the south and west regions of England. In this relatively affluent area, scores of poverty and deprivation were not associated with the decline in lung function tests.

An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. ISOLDE Study Group.

Withdrawal of inhaled corticosteroids is known to worsen disease control in bronchial asthma but similar data are lacking in chronic obstructive pulmonary disease (COPD). We hypothesized that clinical exacerbations requiring treatment would occur more often in patients whose inhaled corticosteroids were stopped than in other patients not treated with these agents. We studied 272 patients in mean age 65 (SD 0.8) years, mean FEV1 42.8 (SD 12.6)% predicted, entering the run-in phase of the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. All had been clinically stable for at least 6 weeks and there were no differences in the degree of bronchodilator reversibility, baseline lung function or pack-years of smoking between the 160 patients receiving inhaled corticosteroids and those not so treated. Inhaled corticosteroids were withdrawn in the first week of the study and during the remaining 7 weeks of the study 38% of those previously treated with these drugs had an exacerbation compared to 6% of the chronically untreated group. Patients receiving inhaled corticosteroids reported a longer duration of symptoms but neither this or any other recorded variable predicted the risk of exacerbation. These data suggest that abrupt withdrawal of inhaled corticosteroids should be monitored carefully even in patients with apparently irreversible COPD.

Respiratory muscle function in patients with asbestos-related pleural disease.

The effect of asbestos-related pleural disease (ARPD) on the generation of maximum respiratory pressure was investigated in 11 male patients with ARPD mean age 57 years, range 45-74, and mean duration of asbestos exposure of 9.9 years, range 5-16. There were three smokers, seven ex-smokers and one non-smoker. Breathlessness ranged from grade 1-3 on the MRC score. The extent of pleural disease was calculated using a score based on the ILO score for pleural disease. Full respiratory function tests, global respiratory muscle strength and diaphragmatic strength were assessed. Respiratory muscle strength, including diaphragm strength, was normal. Recoil pressure was high or at the upper limit of normal in four patients and correlated with chest radiograph score for pleural disease (r = 0.65, P < 0.02). There was no difference in either global respiratory muscle or diaphragmatic strength between patients with and without involvement of one or both costophrenic angles or between patients with mild or severe breathlessness. We conclude that respiratory muscle strength is not importantly reduced in ARPD, and it is unlikely that weakness contributes to breathlessness in these patients. By contrast reduced chest wall compliance is likely to be an important factor in breathlessness in some cases.

Asbestos-related pericardial thickening detected by magnetic resonance imaging.

Magnetic resonance imaging was performed in four male asbestos workers in whom the chest radiograph revealed pleural but not pulmonary or pericardial disease. Patients underwent thoracic multislice spin echo imaging, with measurement of left and right ventricular volumes at end-diastole and end-systole, and a study of the flow in the superior vena cava as an indirect measure to the filling of the right ventricle. Patients also underwent respiratory function tests and high-resolution computed tomography (HRCT). Magnetic resonance, but not HRCT, showed pericardial thickening in two patients. Magnetic resonance demonstrated reduced diastolic flow in the superior vena cava in one patient, reflecting impaired right ventricular filling. All other magnetic resonance measurements of cardiac function were normal. HRCT demonstrated mild asbestosis in three patients in which neither the chest radiograph nor magnetic resonance showed signs of parenchymal disease, and pericardiac calcification without thickening in one patient. It is concluded that magnetic resonance is superior to HRCT in identifying pericardial thickening, but that HRCT is superior to magnetic resonance in identifying asbestos-related pleural and pulmonary disease.

A new high resolution computed tomography scoring system for pulmonary fibrosis, pleural disease, and emphysema in patients with asbestos related disease.

The aim of this study was to describe a scoring system for high resolution computed tomographic (HRCT) scans analogous to the International Labour Office (ILO) scoring system for plain chest radiographs in patients with asbestos related disease. Interstitial fibrosis, pleural disease, and emphysema were scored, the reproducibility and the interobserver agreement using this scoring system were examined, and the extent of the various types of disease was correlated with measurements of lung function. Sixty asbestos workers (five women and 55 men) mean age 59 (range 34-78) were studied. The lungs were divided into upper, middle, and lower thirds. An HRCT score for the extent of pleural disease and pulmonary disease in each third was recorded in a way analogous to the International Labour Office (ILO) method of scoring pleural and parenchymal disease on chest radiographs. A CT score for the extent of emphysema was also recorded. Pleural disease and interstitial fibrosis on the plain chest radiographs were assessed according to the ILO scoring system. A chest radiographic score for emphysema analogous to that used for HRCT was also recorded. Two independent readers assigned HRCT scores that differed by two categories or less in 96%, 92%, and 85% compared with 90%, 78%, and 79% of cases for chest radiographs for fibrosis, emphysema, and pleural disease respectively. There was better intraobserver repeatability for the HRCT scores than for the chest radiograph scores for all disorders. Multiple regression analysis showed that scores for interstitial fibrosis, emphysema, and pleural disease on chest radiographs and HRCT correlated to a similar degree with impairment of lung function.