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The "worth" of routine spirometry in a cystic fibrosis clinic.

In our cystic fibrosis clinic, all patients older than 6 years perform spirometry at each visit just before being seen by the health care team. Upon review, we determined that our perceived rationale for this practice was that the medical history fails to detect deterioration in a sizable minority of patients whose pulmonary decline can be detected by spirometry. Furthermore, the literature and our own experience indicates that physical examination frequently will not detect changes in pulmonary status until the changes are advanced. As part of an ongoing quality/cost assessment, we decided to challenge our rationale for performing routine spirometry. Using standard methodology, we developed a six-item Likert style questionnaire, the purpose of which was to assess perceived changes in pulmonary symptoms since the last clinic visit. The questionnaire had an acceptable degree of internal consistency (Cronbach's alpha = 0.92), although the question about sputum production showed the least correlation with responses to other items. We administered the questionnaire to 103 consecutive different patients and examined the association between reported changes in symptoms and actual changes in spirometric outcomes. Overall, there was a statistically significant, but clinically weak association between symptom scores and change in FEV1, r2 = 0.16, P < 0.001. Twenty-three patients had a decline in FEV1 of > or = 10% from one clinic visit to the next. Depending on the method used to place symptom scores into categories indicating that pulmonary symptoms were "worse," "same," or "better" than at the last clinic visit, 40-60% of these 23 patients indicated they felt the "same" or "better." We conclude that spirometry is a justifiable part of all clinic visits for patients with cystic fibrosis, assuming that one would want to detect and treat declines in pulmonary status before they become advanced.

Cystic Fibrosis↗

Effect of supplementing medium chain triglycerides with linoleic acid-rich monoglycerides on severely disturbed serum lipid fatty acid patterns in patients with cystic fibrosis.

7 patients with cystic fibrosis, having serum lipids with fatty acid compositions (FACs) skewed in the direction of essential fatty acid deficiency, were given a mixture of medium chain triglycerides (MCTs) with linoleic acid-rich monoglycerides (LAMs) as food fat (about 1-1.25 g/kg body weight/day). Blood was sampled before and after a short period (4-11 days) of experimental fat feeding. The FACs of the serum triglycerides (TGs), cholesterol esters (CEs) and phospholipids (PLs) were determined before and after dietary treatment. Dietary treatment resulted in a significant increase of the previously reduced fraction of linoleic acid in all lipid classes. In TGs, the increase in the fraction of linoleic acid was accompanied by a reduction of the previously increased fraction of palmitoleic acid to normal values, by a reduction in the fraction of oleic acid to subnormal values and by an increase in the fraction of stearic acid which, however, remained normal. In PLs, the increase in the fraction of linoleic acid was accompanied by an increase in the fraction of dihomogammalinoleic acid which remained normal, however. In CEs, concomitant with the increase of the previously reduced linoleic acid fraction, there was a reduction of previously elevated palmitoleic and oleic fractions, the latter to a normal value. Thus, supplementing a MCT-containing diet with LAMs in cystic fibrosis patients results in a considerable amelioration of the previously disturbed FACs of the major serum lipid classes.

Adolescent↗

Behavioral assessment and management of food refusal in children with cystic fibrosis.

Four children with cystic fibrosis, ranging in age from 10 to 40 months, were admitted to a specialized pediatric unit for evaluation and treatment of malnutrition. All were below the fifth percentile for weight despite appropriate pancreatic enzyme replacement and outpatient nutritional counseling. Dietary evaluation revealed oral intake of 48% to 62% of that required for growth. Standardized nursing and psychological assessments of feeding behaviors during meals indicated a low acceptance rate of foods and a high rate of maladaptive feeding behaviors. Treatment consisted of behavioral management using positive reinforcement of food acceptance, extinction of negative behaviors, and parent training. Mean percentage of caloric intake increased from 54% to 92% for the four patients. At long-term follow-up, the patients who continued the program demonstrated substantial and persistent catch-up growth. Behavioral feeding disorders may contribute to failure to thrive in patients with cystic fibrosis and must be considered when growth failure occurs despite correct medical management and apparently mild pulmonary and gastrointestinal involvement.

Behavior Therapy↗

A multicenter comparison of related pharmacologic features of cephalexin and dicloxacillin given for two months to young children with cystic fibrosis.

Twenty-one cystic fibrosis patients under 3 years of age were enrolled in an open multicenter study to assess the feasibility of the study design and to compare selected pharmacologic features of cephalexin or dicloxacillin administered orally for 2 months. Patient tolerance and compliance were significantly less for dicloxacillin (p less than .01 and p less than .001, respectively). Superficial Candida infections were more common in the cephalexin group (p = 0.02), however increased stool frequency and nonspecific diaper rashes were more prevalent in patients receiving dicloxacillin (p less than .05). Staphylococcus aureus was isolated from respiratory secretions after 2 months from two dicloxacillin and no cephalexin patients. Areas under the curve and peak serum concentrations were higher for cephalexin (p less than .05 and p = .02), but antistaphylococcal activity in serum was higher for dicloxacillin (p less than .05) due to a lower mean MIC compared to cephalexin. Deep pharyngeal plus routine throat culture yielded more pathogens than either method alone. Express mail and central processing of respiratory specimens was efficient for most organisms, however there was some loss of Streptococcus pneumoniae and Haemophilus influenzae. Cephalexin was associated with better patient acceptance and compliance despite higher rates of superficial fungal infections as compared to dicloxacillin. Cephalexin, routine bacteriologic throat swabs processed locally or centrally, mail-in urine compliance assessment and a multicenter design are feasible components for a long-term prospective evaluation of antibiotic prophylaxis in patients with cystic fibrosis.

Administration, Oral↗

Oxidative stress during acute respiratory exacerbations in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis experience chronic systemic oxidative stress. This is coupled with chronic inflammation of the lung involving bronchial polymorphonuclear neutrophil accumulation and activation. We hypothesised that, during periods of acute respiratory exacerbation, free radical activity and consequent damage would be most marked and that intensive treatment of the infection would result in improvement towards values found during stable periods. METHODS: Plasma and red blood cells were collected from 12 healthy normal volunteers and from 12 patients with cystic fibrosis with an acute respiratory exacerbation (increased respiratory symptoms, reduction in forced expiratory volume in one second (FEV1) of more than 10%, and a decision to treat with intravenous antibiotics). Further samples were collected from patients following two weeks of treatment. Samples were analysed for inflammatory markers, markers of free radical damage, and aqueous and lipid phase scavengers. RESULTS: During respiratory exacerbations FEV1 and forced vital capacity (FVC) were lower than in controls (mean differences -2.82 (95% CI -2.12 to -3.52) and -3. 79 (-3.03 to -4.55) l, respectively) but improved following treatment (mean change 0.29 (95% CI 0.18 to 0.40) and 0.33 (0.23 to 0.43) l, respectively). Inflammatory markers during exacerbations were significantly higher in patients than in controls with the following mean (95% CI) differences: C reactive protein (CRP), 46 (17 to 75) g/l; neutrophil elastase alpha1-antiprotease complexes (NEAPC), 4.4 (1.77 to 7.07) mg/l; white cell count (WCC), 5.3 (4.7 to 5.9) x 10(9)/l. These markers decreased significantly following treatment with the following mean (95% CI) changes: CRP -26 (-10 to -42) g/l; NEAPC -3.1 (-1.3 to -4.9) mg/l; WCC -1.5 (-1.3 to -1.7) x 10(9)/l. Malondialdehyde (MDA) as a marker of free radical activity was significantly higher in patients during exacerbations than in controls with a mean (95% CI) difference of 193 (107 to 279) which improved with treatment (mean change -56 (95% CI -28 to -84) nmol/mmol cholesterol). Red blood cell polyunsaturated fatty acids were significantly lower in patients than in controls with a mean difference of -4.4(95% CI -2.6 to -6.2) moles percent, but did not improve significantly after treatment. Protein carbonyls during exacerbations were not different from controls but did increase with treatment compared with levels during the exacerbation (mean change 0.39 (95% CI 0.11 to 0.67) micromol/g protein). Aqueous and lipid phase scavengers in patients during exacerbations were significantly lower than in controls with the following mean (95% CI) differences: ascorbate, -19.0 (-2.7 to -35.3) micromol/l; sulphydryls, -122 (-77 to -167) micromol/l; retinol, -237 (-47 to -427) nmol/mmol cholesterol; beta-carotene, -52.8 (-11.8 to -93.8) nmol/mmol cholesterol; luteine, -50.4 (-10.4 to -90.4) nmol/mmol cholesterol; lycopene, -90.1 (-30.1 to -150.1) nmol/mmol cholesterol. Treatment resulted in improvement with the following mean (95% CI) changes: sulphydryls, 50 (32 to 68) micromol/l; retinol, 152 (47 to 257) nmol/mmol cholesterol; alpha- and beta-carotene, 0.6 (0.0 to 1.2) and 7.6 (0.0 to 15.2) nmol/mmol cholesterol, respectively; alpha-tocopherol, 839 (283 to 1405) nmol/mmol cholesterol; and lycopene, 8.2 (0.0 to 16.2) nmol/mmol cholesterol. CONCLUSIONS: Abnormalities of markers of inflammation, free radical activity, and radical scavengers were significantly more extreme during acute respiratory exacerbations and showed improvement with treatment. The need to provide protection from inflammation and free radical damage should therefore be dynamic and related to the inflammatory and oxidative processes.

Acute Disease↗

Outcome of patients with cystic fibrosis awaiting lung transplantation.

Cystic fibrosis is a common indication for lung transplantation. Under the current organ allocation system, donor lungs are distributed to patients based solely on their accrued waiting time, and the death rate on the waiting list has been high. Physiologic parameters have been used to guide the referral, but risk factors for death while awaiting transplantation have not been well defined. This study aimed to identify factors at the time of evaluation that were associated with death on the waiting list. A consecutive cohort of 146 patients with cystic fibrosis who were listed for lung transplantation was retrospectively reviewed. Characteristics of patients who died awaiting transplantation were compared with those of patients who survived until transplantation or the end of the study. Thirty-seven patients died while waiting, 76 underwent transplantation, and 33 were alive and still waiting. Actuarial survival rates for the entire cohort were 81% at 1 yr, 67% at 2 yr, and 59% at 3 yr. Although a multivariate Cox proportional hazards model (chi(2) = 29.6; p < 0.001) identified shorter six-minute walk distance (50 m increments; RR, 0.69; 95% CI, 0.57 to 0.84), higher systolic pulmonary artery pressure (5 mm Hg increments; RR, 1.41; 95% CI, 1.11 to 1.80), and diabetes mellitus (RR, 1.57; 95% CI, 1.06 to 2.32) as significant risk factors for death on the waiting list, these factors and other features overlapped considerably between the group of patients who died waiting and the group who lived until transplantation or the end of the study. The transplant evaluation selects a rather homogeneous cohort of patients for the waiting list. Unless outcome on the waiting list can be reliably predicted, establishing criteria to allocate donor lungs according to medical urgency may not be feasible.

Adult↗

[Comparisons of pulmonary and sinonasal lesions in patients with cystic fibrosis. Evaluation using computerized tomography].

INTRODUCTION: Cystic fibrosis is a recessive genetic systemic exocrinopathy caused by a variety of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease is characterized by alterations of the secretions, which become thickened and viscous. Both the paranasal sinuses and the lung parenchyma are involved in all cases. The aim of this study was to assess a correlation between the rhinosinusal and lung parenchyma changes in cystic fibrosis patients. MATERIAL AND METHODS: Eighteen patients (11 men and 7 women, age range: 8 to 22 years) were examined with chest HRCT and sinonasal low dose CT. Lung symptoms were found in all patients; 13 of them, also affected with rhinosinusal symptoms, had been examined with ENT and nasal endoscopy. The other 5 patients, without rhinosinusal symptoms and previously examined with ENT, were evaluated as control group. Chest CT was performed with the high-resolution technique, 2 mm slice thickness and 10 mm table feed. Rhinosinusal CT was performed with the low dose technique, acquiring contiguous 2-4 mm thickness coronal sections. The CT patterns were analyzed by two radiologists and scored as slight, medium and diffuse involvement of both districts. RESULTS: No statistically significant correlation between lung and sinonasal damage was found in our study. Parenchymal lung involvement appeared more severe than sinonasal involvement in 14/18 patients. The retention of secretions in the paranasal sinuses, even if limited, was demonstrated in all symptomatic and asymptomatic patients. CONCLUSIONS: The absence of correlation between pulmonary and sinonasal damage and more generally, the different severity of cystic fibrosis can be caused by different allele mutations of the cystic fibrosis transmembrane conductance regulator gene, the most frequent of which is Delta F-508.

Adolescent↗

Secretory activity of hamster tracheal explants and isolated tracheal epithelial cells and the effects of cystic fibrosis serum.

Serum from cystic fibrosis patients has been shown by scanning electron microscopy to cause release of large quantities of mucus from the cultured tracheal rings of 3-4-month-old male Golden Syrian hamsters. In order to study this phenomenon on single cells, an epithelial (HTE) cell culture has been established from the hamster tracheal rings using the cell rescue method of Goldman and Baseman (1980a, In Vitro, 16:313). The cells were demonstrated to be epithelial by histochemical staining and immunofluorescent detection of laminin. Proteins secreted by HTE cells were partially characterized and shown to consist, at least in part, of acidic glycoproteins. The proteins were precipitated by addition of buffered alcian blue (AB) to the cell-free medium under conditions in which all of a polyanionic protein [3H]-labeled mucin, was precipitated without carrier. [14C] galactosamine-labeled AB precipitate was beta-eliminated and, after neutralization and centrifugation, the material in the supernatant was sized by chromatography on a calibrated Bio-Gel P2 column. The label eluted with a molecular weight close to a disaccharide. HTE cells pulse-labeled for 1.0 hr with [3H] leucine or [14C] galactosamine secreted increasing amounts of labeled glycoprotein during the chase. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and fluorography of labeled AB precipitates revealed three major bands, two with molecular weights greater than 100 kd. Secretion was stimulated by retinoate (50% increase), but not by retinol. Exposure of HTE cells to whole sera from cystic fibrosis patients resulted in heightened secretion rates as compared to results obtained with normal sera. Heterozygote sera produced secretion rates intermediate between the two extremes.

Adolescent↗

A mouse model for the cystic fibrosis delta F508 mutation.

Most cystic fibrosis (CF) patients produce a mutant form (delta F508) of the cystic fibrosis transmembrane conductance regulator (CFTR), which is not properly processed in normal cells but is active as a chloride channel in several experimental systems. We used a double homologous recombination ('Hit and Run') procedure to generate a mouse model for the delta F508 mutation. Targeted embryonic stem (ES) cells (Hit clones) were found; of these either 80 or 20% of the clones had lost the delta F508 mutation, depending on the distance between the linearization site in the targeting construct and the delta F508 mutation. Correctly targeted clones underwent a second selection step resulting in ES cell clones (Run clones) heterozygous for the delta F508 mutation with an efficiency of 2-7%. Chimeric mice were generated and offspring homozygous for the delta F508 mutation showed electrophysiological abnormalities in nasal epithelium, gallbladder and in the intestine, and histological abnormalities in the intestine, typical of CF. Our data suggest that the delta F508 mice have residual delta F508 CFTR activity which would explain the mild pathology of the delta F508 mice. The delta F508 mouse may provide a useful model for the study of the processing defect of delta F508 CFTR and for the development of novel therapeutic approaches based on circumvention of the processing block.

Animals↗

Nebulization of a bovine surfactant in cystic fibrosis: a pilot study.

Cystic fibrosis (CF) is a lethal disorder which results in excessive airway secretions and in chronic inflammation of the airways. In vitro and in vivo studies have shown that a lack of surfactant results in the closure of the small airways. In this pilot study, we aimed to determine whether surfactant administered by aerosol might improve lung function on a short-term basis in patients with CF. In a randomized, crossover double-blind pilot study, 120 mg of a lipid-extracted bovine surfactant (Alveofact) or placebo was aerosolized to five young adult patients with CF over a period of 30 min for five consecutive days. The sample size had the power of 90% to detect an increase in forced expiratory volume in one second (FEV1) of 15% (p < 0.05). Jet nebulization of surfactant produced particles of which more than 75% were the respirable range (< 5 microns). The inhalations were well tolerated. No changes in serum antibody titres against the surfactant proteins-B and -C (SP-B/SP-C) were observed. No differences in FEV1 and forced vital capacity were found before, and 30 or 90 min after, the inhalation. This pilot study shows no acute or short-term benefits of surfactant inhalation in young adults with cystic fibrosis. However, a beneficial effect of exogenous surfactant cannot be excluded before other reasons for a lack of effect, such as insufficient quantity delivered, inhomogeneous distribution or inhibition of the surfactant in the lungs, have been completely ruled out.

Administration, Inhalation↗

[CFTR and transepithelial ionic transport abnormalities in cystic fibrosis].

The genetic disease cystic fibrosis (CF) is caused by mutations of the CF gene and generates defective Cl- transport across the affected epithelium. Recent progress have been made to understand CFTR activity and regulation in epithelia and its role in the muco-ciliary clearance of airway. This revue-overviews the mechanisms of transepithelial ion transport, the role of CFTR in that process and the consequences for CF of CFTR mutations.

Cystic Fibrosis↗

Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients.

UNLABELLED: Twenty cystic fibrosis patients aged 1.8-22 years (mean +/- SD: 9.6 +/- 4.8 years) with Pseudomonas aeruginosa pulmonary exacerbations were treated with amikacin (AM) (35 mg/kg/day in one daily 30 min infusion) associated with either ceftazidime (200 mg/kg/day in 3 i.v. injections) (n = 19) or imipenem (n = 1) at the same dose. Glomerular and tubular functions (creatinine clearance, 24-h proteinuria, beta 2 microglobulinuria, lysozymuria) and audiometry remained within normal ranges from day 0 to day 14. A peak concentration of AM of 83 +/- 19 mg/l and a trough concentration of 0.8 +/- 0.5 mg/l were observed in blood while AM levels in sputum were above the minimal inhibitory concentration 50 from 30 min to 16 h. No serum accumulation of AM was observed during the treatment. From day 0 to day 14, the following changes were observed: weight/height ratio: 96%-100% (P < 0.001); daily energy intake: 111%-128% of RDA (P < 0.001); prealbumin: 195-290 mg/l (P < 0.001); forced vital capacity (FVC): 66%-81% (P < 0.01); forced expiratory volume in 1 s: 60%-75% (P < 0.01); forced expiratory flow between 25% and 75% of FVC: 42%-56% (P < 0.01); nocturnal SaO2 also improved significantly; cardiac rate decreased from 89 +/- 18/min to 76 +/- 16/min (P < 0.001); respiratory rate decreased from 31 +/- 15/min to 26 +/- 10/min (P < 0.05); inflammatory parameters (white blood cells, polymorphonuclear cells, erythrocyte sedimentation rate) also improved. CONCLUSION: Once daily amikacin administration associated with ceftazidime is well tolerated for the treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients. Serum peak levels and diffusion in sputum are higher than with a conventional schedule.

Adolescent↗

Cystic fibrosis in Malaysian children.

Cystic fibrosis (CF) is an autosomal recessive disease commonly found among the Caucasian population. The availability of sweat test and with increasing experience have made it possible to diagnose more cases of CF. Our first case of CF was diagnosed 16 years ago and to date we have managed sixteen cases of CF. Sixteen children were diagnosed with CF in our units at the Paediatric Institute and University Malaya Medical Centre (UMMC). They were referred with either one or all of the following symptoms: i) recurrent pneumonia, ii) bronchiectasis, iii) failure to thrive, iii) malabsorption or iv) history of meconium ileus obstruction during the neonatal period. When the clinical features suggested strongly of CF, sweat tests will be performed in duplicates and considered positive when the sweat chloride or sweat sodium was more than 60 mmol/l for both results. Seventy- two hours fecal fat excretion or stool for fat globule was performed to document malabsorption. From the year 1987 to 2003, 16 patients were confirmed to have cystic fibrosis in Malaysia by positive sweat tests. Thirteen patients were diagnosed in Paediatric Institute while the remaining three were diagnosed in UMMC. On follow-up two patients died due to severe bronchopneumonia at the age of two years old. Although once considered rare, CF should now be considered in any children with clinical presentations of recurrent chest infections, bronchiectasis, in the presence or absence of malabsoption stmptoms and in neonates with meconium ileus obstruction.

Child↗

Antibacterial precipitins and autoantibodies in serum of patients with cystic fibrosis.

Sera from 84 patients with cystic fibrosis, 31 patients with other respiratory diseases and 21 control persons have been investigated for the occurrence of antibacterial precipitins and autoantibodies. Preciptins were studied by means of crossed immunoelectrophoresis, antinuclear factors by an indirect immunofluorescence technique and rheumatoid factors by the latex fixation slide test. A very heterogeneous antibacterial immune response was found in patients with cystic fibrosis, notably as regards Ps. aeruginosa. None of the other patients or controls had precipitins against this bacterium. The occurrence of precipitins against St. aureus and D. pneumoniae were more frequent in cystic fibrosis patients as compared with controls, but not as compared with other respiratory disease patients. No significant differences were found as regards precipitins against H. influenzae or the occurrence of rheumatoid factors. Antinuclear factors were more frequent in cystic fibrosis patients than in the other two groups investigated. A pronounced and heterogeneous humoral immune response against Ps. aeruginosa in cystic fibrosis patients chronically infected with mucoid strains of this bacterium was found to be correlated with poor prognosis and the reason for this is discussed.

Adolescent↗

Study of 12 mutations in Turkish cystic fibrosis patients.

67 unrelated cystic fibrosis (CF) patients were screened for some of the most common mutations of the CFTR gene. This analysis resulted in the identification of 34.6% of all CF alleles. The most common mutation is delta F508 (28.4%). Two other mutations account for a further 6.7% of the alleles (R347H: 3.0%; N1303K: 3.7%). 1677delTA, G542X, G551D, S549N/I, R553X, L558S, R334W, and R297Q were not detected.

Adolescent↗

Survival effect of lung transplantation among patients with cystic fibrosis.

CONTEXT: Patients with cystic fibrosis (CF) are the second largest group of lung transplant recipients in the United States. The survival effect of transplantation on a general CF population has not previously been measured. OBJECTIVE: To determine the impact of bilateral lung transplantation on survival in patients with CF. DESIGN, SETTING, AND PATIENTS: Retrospective observational cohort study of 11 630 CF patients who did not undergo lung transplantation (controls) and 468 transplant recipients with CF from 115 CF centers in the United States, 1992-1998. Patients were stratified into 5 groups based on a 5-year survival prediction model (survival group 1: <30%; survival group 2: 30 to <50%; survival groups 3-5: 50 to <100%.) MAIN OUTCOME MEASURE: Five-year survival from date of transplantation in 1992-1997 in the transplant group and from January 1, 1993, in the control group. RESULTS: Lung transplantation increased 5-year survival of CF patients in survival group 1. Survival group 2 had equivocal survival effects, and groups 3-5 had negative survival effects from transplantation. From 1994-1997, there was a mean annual prevalence of 238 patients in survival group 1 and mean annual incidence of 154 patients entering the group, approximately 1.5 times the number of lung transplantations performed each year in CF patients (mean, 104). Use of the criterion of forced expiratory volume in 1 second of less than 30% resulted in an equivocal survival benefit and identified 1458 potential candidates for transplantation in 1993. CONCLUSIONS: Cystic fibrosis patients in group 1 have improved 5-year survival after lung transplantation. The majority of patients with CF have equivocal or negative survival effects from the procedure. Selection of patients with CF for transplantation based on group 1 survival predictions maximizes survival benefits to individuals and may reduce the demand for scarce donor organs.

Adult↗

Pancreatic exocrine function in patients with cystic fibrosis.

Pancreatic insufficiency in cystic fibrosis (CF) is associated with more severe disease and requires replacement therapy. Outcome measures such as growth and number of stools, frequency of abdominal pain, and flatulence have often been used to identify pancreatic-insufficient patients and to adjust the dose of replacement enzymes. Unfortunately, some patients with CF are misclassified, and approximately 9% do not receive therapy appropriate for their pancreatic exocrine functional status. Growth, number of stools, frequency of abdominal pain, and flatulence cannot be used to adjust enzyme doses.

Cystic Fibrosis↗

Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis.

To investigate respiratory epithelial function in cystic fibrosis, we measured the transepithelial electrical potential difference across the upper and lower respiratory mucosa in patients with cystic fibrosis and control subjects. The nasal potential difference in the 24 patients with cystic fibrosis exceeded by more than 3 standard deviations the mean voltage in healthy controls, subjects with other diseases, and subjects heterozygous for cystic fibrosis. Potential differences in lower airways were measured in four patients and were significantly greater than in controls (P less than 0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential difference in patients than in controls. We conclude that the increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis. The greater reduction in potential difference in response to amiloride suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cystic fibrosis.

Adolescent↗