Sweat chloride: quantitative patch for collection and measurement.

OBJECTIVE: To compare two quantitative pilocarpine iontophoresis tests for sweat chloride. DESIGN: Simultaneous right and left arm sweat tests were done with the Gibson/Cooke and the CF quantum technologies. SETTING: Sweat tests were performed in a quality controlled cystic fibrosis (CF) sweat test laboratory by an experienced technologist at the University of Minnesota CF Center. PATIENTS: Patients referred for sweat tests as well as volunteer CF and control subjects (50 CF and 114 'normals') were tested. INTERVENTIONS: Standard procedures were used for the Gibson/Cooke test (GCST). The manufacturer of the CF quantum test (CFQT) provided factory standardized materials. MAIN OUTCOME MEASURES: Sweat chloride concentration, test time, failed tests, sensitivity, specificity, and cost. RESULTS: Duplicate test comparing the CFQT and the GCST revealed good comparability (R2 = 0.9434). Sensitivity and specificity of the two methods are comparable at about 94% and 99% respectively. Rate of failed tests was 1% for the CFQT and 15% for the GCST. The CFQT and the GCST are comparable (R2 = 0.9434). Sensitivity (94%) and specificity (99%) are the same for both tests. CONCLUSIONS: The CFQT method is equal in accuracy and reliability to the more labor-intensive and costly GCST. Advantages of the CFQT are: the small sample size required (three to ten mg), decreased operator dependence, simpler to perform, and requires less equipment. It could be used in a clinic setting to diagnose CF in patients with suggestive symptoms.

Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline.

In patients with cystic fibrosis, CF-related diabetes mellitus (CFRD) has been associated with increased morbidity and mortality. Whether glucose intolerance is also associated with poor outcomes is unclear. To better define these relationships we prospectively followed a group of 152 patients with CF without diabetes for 4 yr. Patients were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CFRD without fasting hyperglycemia (CFRD-No FH). FEV(1), FVC, and body mass index (BMI) were measured at baseline and quarterly. At baseline 45% of the patients had NGT, 38.8% had IGT, and 15.8% had CFRD-No FH. FEV(1), FVC, and BMI at baseline were comparable among these groups (all p > 0.1). After 4 yr an overall decline in FEV(1) and FVC occurred, with no change in BMI. The rates of decline for FEV(1) and FVC correlated with the glucose tolerance groups, with the highest rates of decline occurring among the CFRD-No FH group. In addition, patients in the lowest quartile for insulin production at baseline experienced the highest rates of pulmonary function decline over time, suggesting a relationship between insulin deficiency and clinical deterioration. We conclude that the degree of glucose intolerance is a strong determinant of future lung function decline in patients with CF.

Eating disorders in patients with cystic fibrosis.

This study was designed to examine rates of eating disorders and psychopathology in patients with cystic fibrosis (CF). Fifty-eight CF patients and 43 healthy control participants were evaluated using structured psychiatric interviews and rating scales. Two control participants and no CF patients were diagnosed with an eating disorder. Additionally, 11 CF patients were diagnosed with one or more psychiatric disorders. Group means on the rating scales did not show clinically meaningful elevations in either group. These data indicate no evidence for elevated rates of eating disorders in CF patients. Similarly, rates of other psychiatric disorders in the CF group were not greater than the prevalence reported in the general population.

Risk of death in cystic fibrosis patients with severely compromised lung function.

BACKGROUND: Lung disease accounts for most of the mortality in patients with cystic fibrosis (CF). Lung transplantation is an option for patients severely impaired, being recommended when life expectancy is estimated to be <2 years. Our objectives were to evaluate in our patient population the validity of currently accepted criteria for low life expectancy and to identify other potentially useful criteria. METHODS: Data were retrieved from CF patients followed up at our center who reached and kept an FEV1 <30% predicted. A life table was created and stratified according to characteristics believed to be of importance. In addition, the rate of decline in percent predicted FEV1 was analyzed. These characteristics were evaluated as predictors of risk of death. RESULTS: The median survival was 3.9 years (95% confidence interval, 2.88 to 4.12 years), with no significant differences according to gender, nutritional status, presence of diabetes, or decade in which the patient was cared for. Only by age was there a significant difference in the median survival (p<0.05). By proportional hazards regression, only the rate of decline in percent predicted FEV1 was a significant predictor of the risk of death, with a borderline effect from younger age (p=0.06). CONCLUSION: In our patient population, a cutoff value of FEV1 of < 30% predicted is not a reliable predictor of high risk of death within 2 years. The yearly rate of decline of percent predicted FEV1 is a better parameter to identify those patients at high risk for death.

Cystic fibrosis-associated colitis and fibrosing colonopathy.

OBJECTIVE: To describe our experience with cystic fibrosis (CF)-associated colitis and fibrosing colonopathy, and to assess treatment strategies. STUDY DESIGN: We reviewed hospital charts and autopsy reports of all University of Minnesota patients with CF between 1975 and August 1994. We identified six patients with colonopathy and compared them with a cohort of 79 patients with CF in the same age range and seen during the same period. RESULTS: All patients with colonopathy had bloody diarrhea; five of the six had abdominal pain. Stool frequency and related symptoms distinguished the patients with colonopathy from the cohort population. All took a higher median dose of pancreatic enzymes than the cohort population during the 3 months preceding the onset of symptoms (p < 0.002). For all six patients, barium studies revealed loss of haustration, and shortening and diffuse narrowing of the colonic lumen with relative rectal sparing. The distal ileal mucosa was irregular in four patients. A histopathologic study reveal fibrosis of the submucosa or lamina propria, and focal acute cryptitis in all six patients. Other features included ascites (2/6) and nodular regenerative hyperplasia of the liver (1/6). One patient continues to have symptoms, three had subtotal colectomy, and the condition of two improved after a regimen including a low-fat diet, withholding of pancreatic enzymes, and supplemental parenteral nutrition was initiated. CONCLUSIONS: Fibrosing colonopathy represents a newly recognized gastrointestinal complication of cystic fibrosis. Affected persons have taken larger doses of pancreatic enzymes than similar patients with cystic fibrosis, and have bloody diarrhea. We developed a medical protocol that may avoid surgical resection of the colon in some of these patients.

Serum fatty acid profiles in cystic fibrosis patients and their parents.

Fatty acid compositions of the major serum lipid classes from 43 cystic fibrosis (CF) homozygotes (CF patients), 36 obligate heterozygotes (parents of CF patients) and 34 controls were determined by capillary gas chromatography. Fatty acid compositions of the homozygote CF patients were skewed in the direction of relative essential fatty acid deficiency in comparison with the controls. Less pronounced, but similar deviations from normal, were observed in the heterozygotes. Homozygotes with normal fatty acid compositions and heterozygotes with considerably disturbed fatty acid profiles were found.

Mucus transport mechanisms in relation to the effect of high frequency chest compression (HFCC) on mucus clearance.

High frequency chest compression (HFCC) appears promising as a form of chest physiotherapy. Studies published by several clinical centers support its efficacy, and further clinical data are expected to become available.

Contrasting clinical and statistical significance within the research setting.

When designing a clinical trial or study, the value of the following interrelated parameters should be determined prior to collecting data: clinical significance, statistical significance, power, and sample size. Too often, clinical importance and the other design issues are ignored and only statistical significance dictates the conclusions of the study. In order to evaluate the frequency that each of these design parameters is addressed in the published literature, the topic of pulmonary function tests (specifically forced vital capacity) was chosen, and all relevant articles for one year (1990) were identified using Minnesota MEDLINE. A total of 121 articles met the selection criteria and were reviewed. Of all the articles, 13.2% discussed clinical significance, 21.5% discussed sample size, and only 5.0% addressed statistical power. As expected, the majority of the articles (92.6%) discussed statistical significance (P values). None of the articles mentioned all four factors. When choosing the level of clinical significance several methods may be used. Such might be well established in certain clinical areas or available from previous publications and references or they may be attainable from pilot study data and, in the absence of any prior information, a clinician may use personal experience. To minimize subjectivity, the clinical effect-size can be based on the population distribution of the measurement of interest.

Family correlates of a 10-year pulmonary health trend in cystic fibrosis.

In this study, 33% of the variance in the 10-year trend of forced expiratory volume in 1 second (FEV1), used as an index of pulmonary health, was explained by differences in family characteristics at the start of the study. Balanced family coping, a family emphasis on personal growth, and compliance with treatment for 91 children with cystic fibrosis were assessed at the start of the study and the FEV1 was observed at every clinic visit over the next 10 years. When both parents' coping emphasized family integration, support for self, and medical consultation, the FEV1 trend was better. Compliance with daily chest physical therapy and with quarterly clinic visits was associated with a better FEV1 trend. Poorer FEV1 trend was associated with active social involvement of family members. Older patients and patients whose parents worked more hours outside the home had lower compliance. These findings support the importance of encouraging families to balance their resources between the child's health needs and family needs.

The impact of home monitoring and daily diary recording on patient status in cystic fibrosis.

An experimental home monitoring system for assessing the progress and planning changes in the care of patients with cystic fibrosis (CF) has been implemented at the University of Minnesota Cystic Fibrosis Center. One group of patients and families did daily recording of physical measurements and symptoms, and sent the diary to the data coordinating center weekly for analysis. The remaining patients were not part of the home monitoring program. Twenty-five patients were randomly selected from the home monitoring group. They were compared to an age- and sex-matched control group not doing home monitoring to ascertain if home self-measurement and daily diary recording, in the absence of any therapeutic intervention, produced any change in physical or psychological status, pulmonary function, or growth over a 4-year study period. Subjects ranged in age from 6 to 43 years. Clinical status was measured by the National Institutes of Health cystic fibrosis scoring system. Pulmonary function was assessed as percent of predicted forced vital capacity and percent of predicted forced expiratory volume in 1 sec (FEV1). Growth was analyzed as percent of predicted weight based on age-, sex-, and height-dependent equations. Psychological status was determined by self-assessment and referral for conseling. Only percent predicted FEV1 in the control group declined significantly. There were no statistically significant changes in any other measures either within or between diary and nondiary groups over the 4-year period.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term effect of high-frequency chest compression therapy on pulmonary complications of cystic fibrosis.

A high-frequency chest compression (HFCC) device for clearance of mucous secretions from airways was tested in 16 cystic fibrosis (CF) patients with significant improvement in pulmonary function for the HFCC period, which averaged 22 months per patient. The device consists of a variable air pulse delivery system and a non-stretch inflatable vest worn by the patient to cover the entire torso. The patients perform 30 minute therapy sessions divided into 5 minute periods at each of six frequencies. Individual patient therapy time per day ranged from 30 to 240 minutes. Frequencies used by each patient were determined by measuring air flow at the mouth and calculated volume expired per chest compression during tidal breathing while receiving HFCC at frequencies between 5 and 22 Hz at 1 Hz increments. The frequencies that produced the three highest flows and the three largest volumes were selected for each patient's therapy. Ninety-four percent of patients' regression line slopes for percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) became more positive during self-administered HFCC therapy as compared to slopes before HFCC therapy, when manual chest physical therapy was used. Two-sided t-test showed that the mean slopes were more positive for FVC and FEV1 during HFCC therapy than for the manual chest physical therapy period before HFCC therapy. The significance level for both FVC and FEV1 was at P less than 0.001.

Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study.

The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation.

High-frequency chest compression system to aid in clearance of mucus from the lung.

The authors developed a high-frequency chest compression (HFCC) device to aid in mucous clearance for patients with obstructive lung disease. The device, designed for self-therapy, consists of a large-volume variable-frequency air-pulse delivery system and a nonstretchable inflatable vest worn by the patient. Pressure pulses are controlled by the patient and applied during expiration. Pulse frequency is tunable from 5 to 25 Hz. Maximum vest pressure is 39 mmHg (5.2 kPa), with patient-controlled vest inflation and deflation time constants of 0.5 s. Vest pressure increases from 28 mmHg (3.7 kPa) at 5 Hz to 39 mmHg (5.2 kPa) at 25 Hz. Preliminary clinical trials have shown the HFCC device to be more effective than standard chest physical therapy. The HFCC device yielded a mean volume of cleared mucus of 3.3 cc per session, compared with 1.8 cc for a conventional therapy session.

Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone.

We evaluated patients with cystic fibrosis (CF) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement. For the first 4 days of study, all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics. During this time, the patients showed significant improvement in mean FVC, FEV1, and maximal midexpiratory flow rate (FEF25-75). In 12 of 13 trials, the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days. In these 12 trials, the patients were stratified by their initial FVC and randomized to receive either parenteral tobramycin and ticarcillin (n = 7) or placebo (n = 5), in addition to continued aerosol and chest physiotherapy. In the remaining trial, the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p less than 0.01) greater reductions in log10 colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV1, and FEF25-75 than did the placebo group. The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly (p less than 0.001) with the degree of improvement in FVC, FEV1, and FEF25-75.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of family functioning on health changes in children with cystic fibrosis.

Family stress, family and personal resources, and parental coping were operationalized from self-report questionnaires completed by mothers and fathers in 72 two-parent families who had a child with cystic fibrosis (CF). Three-month and 15-month changes in clinically recorded measures of the CF child's height and weight data and pulmonary functioning were correlated with the family functioning variables. Each of the four criterion indices of CF child health changes were regressed separately on the significant family functioning variables. Twenty-two percent of the variance in 15-month height and weight changes were explained by family stress, family resources, and parental coping. Family functioning variables also explained 17% of the variance in 3-month pulmonary functioning changes and 15% of the variance in 3-month height and weight changes. These findings suggest that the way in which the family functions has indirect effects on critical indices of a CF child's health. These data lend support to an increased focus by physicians and other medical professionals on the health of the total family system as a way to enhance outcomes for children with CF.

Quantification of chloride in sweat with the Cystic Fibrosis Indicator System.

We examined the relation between chloride concentration and the area of complexed chloride of Medtronic's Cystic Fibrosis Indicator System, using a high-resolution x-y coordinated digitizer to measure the circumference of the chloride precipitation ring. These digitized points were entered directly into an IBM PC computer, where the area of the chloride precipitation was calculated with use of a repetitive rectangular estimation program. Using these data, we determined the relationship between the area of chloride precipitation and the chloride concentration of the standard NaCl solutions. When the area of the ring of chloride precipitation in the system's patch is measured immediately after the sweat test is completed, the concentration of chloride in the sweat can be calculated with a reproducibility equal to that of the Gibson-Cooke sweat test.