Assessment of hyperinflation in children with cystic fibrosis.

BACKGROUND--Radiological estimates of hyperinflation are used in several clinical and radiographic scoring systems for cystic fibrosis, but it is not known if these estimates of hyperinflation are related to measured total lung capacity. METHODS--Comparison was made of independent clinical estimates of hyperinflation from chest radiographs with objective plethysmographic and radiographic measurements of total lung capacity in 25 children with cystic fibrosis. RESULTS--There was good agreement between plethysmographic and radiographic measurements. Clinical estimation correctly predicted the extremes of hyperinflation, but grading was no more than 50% accurate in all other groups. CONCLUSION--The degree of hyperinflation cannot be estimated by inspecting chest radiographs in many children with cystic fibrosis. This does not invalidate the scoring systems, but suggests that a better term than "hyperinflation" should be sought.     

Towards an individualized protocol for workload increments in cardiopulmonary exercise testing in children and adolescents with cystic fibrosis

BackgroundThere is no single optimal exercise testing protocol for children and adolescents with cystic fibrosis (CF) that differs widely in age and disease status. The aim of this study was to develop a CF-specific, individualized approach to determine workload increments for a cycle ergometry testing protocol.MethodsA total of 409 assessments consisting of maximal exercise data, anthropometric parameters, and lung function measures from 160 children and adolescents with CF were examined. 90% of the database was analyzed with backward linear regression with peak workload (W_peak) as the dependent variable. Afterwards, we [1] used the remaining 10% of the database (model validation group) to validate the model's capacity to predict W_peak and [2] validated the protocol's ability to provide a maximal effort within a 10 ± 2 minute time frame in 14 adolescents with CF who were tested using this new protocol (protocol validation group).ResultsNo significant differences were seen in W_peak and predicted W_peak in the model validation group or in the protocol validation group. Eight of 14 adolescents with CF in the protocol validation group performed a maximal effort, and seven of them terminated the test within the 10 ± 2 minute time frame. Backward linear regression analysis resulted in the following equation: W_peak (W) = − 142.865 + 2.998 × Age (years) − 19.206 × Sex (0 = male; 1 = female) + 1.328 × Height (cm) + 23.362 × FEV₁ (L) (R = .89; R² = .79; SEE = 21). Bland–Altman analysis showed no systematic bias between the actual and predicted W_peak.ConclusionWe developed a CF-specific linear regression model to predict peak workload based on standard measures of anthropometry and FEV₁, which could be used to calculate individualized workload increments for a cycle ergometry testing protocol.     

Adherence of adult cystic fibrosis patients with airway clearance and exercise regimens.

BACKGROUND: Regular airway clearance and exercise form an important part of the physiotherapy management of patients with cystic fibrosis (CF). Previous research has found that adherence of these patients with physiotherapy regimens is variable and influenced by factors such as sex and disease severity. To date, the adherence of Australian patients with CF has not been investigated. The aim of this study was to measure the adherence of a sample of Australian adult patients with CF and to ascertain factors that improved or decreased their adherence with physiotherapy. METHODS: Patients attending an Australian CF Unit were surveyed by an independent physiotherapist using a questionnaire based on the Manchester Cystic Fibrosis Compliance Questionnaire. RESULTS: Fifty seven of the 84 patients registered with the Unit (67.9% response rate) completed the survey. Over the previous six months, 96.5% of patients reported doing some form of airway clearance, with 70.2% doing this daily or only occasionally missing one or two days. Regular exercise was performed by 91.2% of patients when well, with 77.8% also exercising regularly when unwell. The most common reasons for non-adherence with airway clearance regimens were being too busy and not being bothered. Being too busy and too tired were the most frequent reasons for decreased adherence with exercise. Frequency of performing airway clearance regimens significantly improved when patients felt unwell. Adherence with exercise regimens was significantly higher in those who worked or studied full time. CONCLUSION: Overall, the levels of adherence with physiotherapy regimens found in this study were considered to be satisfactory and higher than those previously reported in the literature, with time related factors being the most commonly reported reasons for decreasing adherence.     

Patterns of dynamic hyperinflation during exercise and recovery in patients with severe chronic obstructive pulmonary disease

BACKGROUND: Not all patients with severe chronic obstructive pulmonary disease (COPD) progressively hyperinflate during symptom limited exercise. The pattern of change in chest wall volumes (Vcw) was investigated in patients with severe COPD who progressively hyperinflate during exercise and those who do not. METHODS: Twenty patients with forced expiratory volume in 1 second (FEV(1)) 35 (2)% predicted were studied during a ramp incremental cycling test to the limit of tolerance (Wpeak). Changes in Vcw at the end of expiration (EEVcw), end of inspiration (EIVcw), and at total lung capacity (TLCVcw) were computed by optoelectronic plethysmography (OEP) during exercise and recovery. RESULTS: Two significantly different patterns of change in EEVcw were observed during exercise. Twelve patients had a progressive significant increase in EEVcw during exercise (early hyperinflators, EH) amounting to 750 (90) ml at Wpeak. In contrast, in all eight remaining patients EEVcw remained unchanged up to 66% Wpeak but increased significantly by 210 (80) ml at Wpeak (late hyperinflators, LH). Although at the limit of tolerance the increase in EEVcw was significantly greater in EH, both groups reached similar Wpeak and breathed with a tidal EIVcw that closely approached TLCVcw (EIVcw/TLCVcw 93 (1)% and 93 (3)%, respectively). EEVcw was increased by 254 (130) ml above baseline 3 minutes after exercise only in EH. CONCLUSIONS: Patients with severe COPD exhibit two patterns during exercise: early and late hyperinflation. In those who hyperinflate early, it may take several minutes before the hyperinflation is fully reversed after termination of exercise.     

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.


     

Risks associated with exercise testing and sports participation in cystic fibrosis

BackgroundSevere adverse reactions (SARs) associated with physical exercise have not been systematically studied in cystic fibrosis (CF).MethodsTwo surveys were conducted to assess the incidence of exercise-related SARs: a caregiver survey asking for complications associated with exercise testing and in-hospital training therapy and a web-based patient survey asking for problems with exercise.Results78 of 107 CF facilities caring for 4208 patients responded to the caregiver survey, 256 patients answered the web-based survey. No SARs were reported for 713 exercise tests. With in-hospital training, the yearly incidence of exercise-related SARs such as pneumothorax, cardiac arrhythmia, injury or hypoglycaemia was < 1% each, the respective lifetime incidences reported by the patients were 0.8–6.3%. 67% of the patients reported no SARs with exercise.ConclusionsExercise testing is safe in patients with CF. Despite the limitations in quality of data, the incidence of exercise-related SARs appears low in this population.     

Predictors of desaturation during formal hypoxic challenge in adult patients with cystic fibrosis

Assessment of the potential risk of in flight hypoxaemia in patients with cystic fibrosis is often based on a hypoxic challenge where individuals have saturations and/or blood gases taken before and after inspiring 15% normobaric oxygen. The aim of this study was to see if routine clinical measurements could predict the outcome of this test. This was a prospective study comparing the modified 6-min walking test, lung function, body mass index, Northern (N) and Shwachman-Kulczycki (SK) scores with a hypoxic challenge (flight test) in 69 adults attending the Leeds regional CF Unit. Although, there was a significant correlation between post flight test PaO(2) and N score (P=0.003), SK score (P=0.002), FVC % predicted (P=0.01), FEV(1) % predicted (P=0.002), resting saturations (P<0.001), 6 min saturation on walking test (P<0.001) and baseline PaO(2) (P<0.001), no single parameter could accurately predict all patients who desaturated during the flight test. No individual clinical parameter appears to fully predict the need for in flight oxygen but patients most at risk appear to have either a low FEV(1) (<60%), high N score (>13) or low baseline PaO(2) (<10.5 kPa).     

Blood flow regulation and oxidative stress during submaximal cycling exercise in patients with cystic fibrosis

Background

The impact of blood flow regulation and oxidative stress during exercise in cystic fibrosis (CF) has yet to be investigated.

A survey of exercise testing and training in UK cystic fibrosis clinics

BackgroundExercise testing is a valuable prognostic tool and exercise training has many health benefits in cystic fibrosis (CF). The objective of this study was to survey the provision of exercise testing and training in UK CF clinics.MethodsA three-page questionnaire was used to determine the extent of, scope and importance assigned to exercise testing and training.ResultsData from returned questionnaires showed that 38.9% of paediatric and 27.8% of adult patients had performed an exercise test in the preceding 12 months, most as part of an annual review process. Pulmonary rehabilitation programmes were accessible in only 31.3% of clinics, and only 26.0% provide exercise training programmes. When assigning importance for exercise testing on a scale from 1 ‘not important’ to 5 ‘very important’, the mean and median respondent scores were 3.5 and 4.0, respectively, and for the importance of training were 4.0 and 4.0, respectively.ConclusionsDespite the level of importance given to exercise testing and training by healthcare providers, exercise is underused as either an assessment tool or therapeutic intervention in the healthcare of patients with CF in the UK.     

Reduced fat oxidation rates during submaximal exercise in boys with cystic fibrosis

BackgroundExercise is a viable form of therapy for children with cystic fibrosis (CF). Understanding the energy sources used during exercise would aid CF patients in obtaining proper nutrition in order to sustain an active lifestyle.MethodsSix boys with CF (mean age ± SD: 14.8 ± 2.3 yrs, FEV1: 99 ± 18% predicted) and six matched controls (14.0 ± 2.2 yrs) completed a session of two 30 min bouts of cycling at an intensity set at 50% peak mechanical power. Rates of total fat and carbohydrate (CHO) oxidation were calculated from expired gases. Plasma insulin, glucose and free fatty acid (FFA) were determined before, during and at the end of the exercise.ResultsRates of fat oxidation (expressed in mean mg × kg body weight^− 1 × min^− 1 ± SD) were significantly lower in children with CF (5.7 ± 1.6) compared to controls (8.6 ± 1.8, p < 0.05). Children with CF also had lower values than controls in amount of fat oxidized (CF: 17.3 ± 5.0 g, controls: 26.1 ± 5.9 g, p < 0.05) and percent of total energy expenditure from fat (CF: 32 ± 6%, controls: 43 ± 7%, p < .0.05), but a higher contribution from CHO (CF: 68 ± 6%, controls: 57 ± 7% p < .0.05). Plasma FFA was significantly lower in children with CF compared to controls during (CF: 252.5 ± 117.9 μM, controls: 602.2 ± 295.6) and at the end of exercise (CF: 430.9 ± 180.6, controls: 1147.5 ± 473.5). There were no differences in the rates of CHO oxidation, insulin or glucose between groups.ConclusionFat metabolism during exercise is impaired in boys with CF and may be attributed to an inability to mobilize FFA.     

Hypertriglyceridemia is associated with insulin levels in adult cystic fibrosis patients

BackgroundRecent studies have identified hypertriglyceridemic cystic fibrosis patients (CF-TG). However, whether hypertriglyceridemia is associated with an altered metabolic profile remains unknown.ObjectiveTo characterize CF-TG and determine whether triglycerides (TG) levels are associated with metabolic alterations.Methods210 adult CF subjects from the Montreal Cystic Fibrosis Cohort without known diabetes were included in the analysis. All subjects underwent an OGTT to assess glucose tolerance, insulin secretion (insulin AUC) and insulin sensitivity (Stumvoll index). Fasting lipid profiles, pulmonary function (%FEV₁) and BMI were determined. Hypertriglyceridemia (TG > 1.7 mmol/L) was observed in 20 CF patients. These subjects were matched for age, sex and glucose tolerance category with 20 CF patients (CF-normal-TG) and 20 healthy controls that had TG levels below 1.7 mmol/L. Pearson correlations were performed in the complete study sample (n = 210) to examine the associations between TG levels and other parameters.ResultsThe prevalence of hypertriglyceridemia was 9.5%. Compared to CF-normal-TG, CF-TG subjects displayed significantly higher %FEV_1, insulin AUC (AUC_0–120, AUC_0–30, AUC_30–120), cholesterol levels and a higher ratio of total cholesterol to HDL-cholesterol. Pearson analysis demonstrated that TG levels were associated with BMI, %FEV₁, fasting insulin, insulin AUC_0–120 and AUC_30–120, Stumvoll index, cholesterol levels and the ratio of total cholesterol to HDL-cholesterol. All these correlations remained significant after correction for BMI except %FEV₁.ConclusionTG levels are associated with a mild alteration of the metabolic profile. Whether these changes will increase the long-term risk of CF patients in developing cardiometabolic complications remains to be investigated.     

Plasma ghrelin and leptin in adult cystic fibrosis patients

BackgroundWeight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data on leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin.MethodsPlasma ghrelin, leptin, TNF-α, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n = 19), moderate (n = 30) and severe (n = 25).ResultsSevere CF patients (% predicted FEV1 27 ± 7; median BMI 21 kg/m²) had significantly elevated ghrelin and decreased leptin compared to controls and other CF subjects. Ghrelin correlated (r value, p value) with BMI (− 0.35,< 0.001), FFM (− 0.22,< 0.05), FM (− 0.41,< 0.0001), FEV1 (− 0.62,< 0.001), TNF-α (0.51,< 0.0001), IL-1 (0.56,< 0.0001), and IL-6 (0.33,< 0.01). Leptin correlated (r value, p value) with BMI (0.40,< 0.0001), FM (0.56,< 0.0001), FEV1 (0.34,< 0.05), IL-1 (− 0.51,< 0.05) and TNF-α (− 0.43,< 0.0001). BMI and FEV1 were independent predictors of ghrelin (− 0.35,< 0.05;−0.59,< 0.001). FM was a predictor of leptin (0.56,< 0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-α (3.4 ± 0.6 vs. 1.2 ± 0.4), IL-1 (3.5 ± 1 vs. 0.2 ± 0.1), IL-6 (17.4 ± 4 vs. 2.4 ± 2).ConclusionsElevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF.     

Subclinical anaemia of chronic disease in adult patients with cystic fibrosis.

Patients with chronic hypoxaemia develop secondary polycythaemia that improves oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in the presence of chronic arterial hypoxaemia in cystic fibrosis constitute 'relative anaemia'. We sought to determine the cause of this relative anaemia in patients with cystic fibrosis. We studied haematological indices and oxygen saturation in healthy volunteers (n=17) and in adult patients with cystic fibrosis (n=15). Patients with cystic fibrosis had lower resting arterial oxygen saturation when compared with normal volunteers (P<0.0001), and exercise led to a greater reduction in arterial oxygen saturation (P<0.0001). However, haemoglobin and haematocrit values in patients with cystic fibrosis did not significantly differ from normal volunteers. Serum iron (P=0.002), transferrin (P=0.02), and total iron-binding capacity (P=0.01) were lower in patients with cystic fibrosis. There were no significant differences in serum ferritin, percentage iron saturation, serum erythropoietin or red cell volume between the groups. The data presented demonstrate a characteristic picture of anaemia of chronic disease in adult patients with cystic fibrosis, except for normal haemoglobin and haematocrit values. Normal haemoglobin and haematocrit values in patients with cystic fibrosis appear to represent a combination of the effects of arterial hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation promoting anaemia of chronic disease.     

Knowledge of adult patients with cystic fibrosis about their illness.

BACKGROUND: Adult patients need to understand their illness if the locus of control is to move from doctor to patient. Previous studies have shown important misconceptions and gaps in patients' knowledge about cystic fibrosis. METHODS: Patients were invited to complete a multiple choice questionnaire covering all major aspects of cystic fibrosis. The questionnaire score was compared with a predicted score derived from the consultant, cystic fibrosis fellow, nurse, and physiotherapist ratings of patient knowledge. Data were obtained to provide a comprehensive patient profile and disease severity score. Both scores were tested for any associations with patient characteristics. RESULTS: Although patients had good general knowledge about the aspects of cystic fibrosis that impacted most on their daily lives--that is, respiratory and gastrointestinal problems--important gaps and misconceptions in these areas were still present. Knowledge and understanding of genetic and reproductive issues and the less common complications of cystic fibrosis were only moderate. Older more severely affected patients, and those who had more contact with the hospital caring team, had better multiple choice questionnaire knowledge scores. Professional carers were poor judges of the knowledge of individual patients. CONCLUSIONS: Important gaps persist into adult life in the knowledge patients with cystic fibrosis have about their illness. Objective assessment of these deficits is required so that each patient can be counselled according to his or her needs.