Trampoline use as physiotherapy for cystic fibrosis patients.

Physicians and physiotherapists who care for CF patients have recommended the use of trampolines as a physiotherapeutic tool for enhancing cardiopulmonary performance, encouraging sputum production, and improving general well-being. Despite some therapeutic and recreational benefits associated with trampoline use, papers in the general pediatric population mostly document an increased incidence of injuries, ranging from minor trauma to spinal cord injuries and even death. The aim of this review is to examine the accumulated published data regarding the use of trampolines, to assess their potential contributions and disadvantages for CF patients, and to define whether trampoline use should be recommended. An extensive search in the published medical literature retrieved approximately 60 articles that primarily dealt with trampolines, out of which only two dealt with CF. The preponderance of these articles are reports pertaining to injuries related to the use of trampolines, with only a few describing the medical, physiologic, and/or psychological benefits of trampolines. Based on the accumulated data, the presumed benefits of trampoline use for CF patients are not proven. Furthermore, the suggested benefits could be acquired using other types of exercise. Weighing the known risks of trampolines against the potential benefits that are not unique to this modality suggests that the use of trampolines for CF should not be recommended.

Systemic inflammatory mediators and cystic fibrosis genotype.

Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (deltaF508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4 +/- 2.1 pg/ml vs. 5 +/- 0.9 pg/ml and 157 +/- 16 pg/ml vs. 88.8 +/- 16.4 pg/ml, respectively) (P < 0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r = -0.37, P < 0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P < 0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin-8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.

Serum CA 19-9 levels as a diagnostic marker in cystic fibrosis patients with borderline sweat tests.

Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19-9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19-9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19-9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19-9 levels was significantly different between the three groups ( p<0.01); high CA 19-9 levels were found in 60% (30/50) of group Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the controls. CA 19-9 levels were inversely related to forced expiratory volume in 1 s, while no association was found with the other clinical parameters examined. Our findings suggest that the serum CA 19-9 in cystic fibrosis patients originates in the respiratory system, and has a useful ancillary role, particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic fibrosis should be considered in patients with borderline sweat tests and high CA 19-9 levels, but normal levels do not exclude cystic fibrosis.

Prediction of mortality and timing of referral for lung transplantation in cystic fibrosis patients.

Lung transplantation (Tx) is an optional treatment for cystic fibrosis (CF) patients with end-stage lung disease. The decision to place a patient on the Tx waiting list is frequently complex, difficult, and controversial. This study evaluated the current criteria for lung Tx and assessed additional parameters that may identify CF patients at high risk of death. Data were extracted from the medical records of 392 CF patients. Forty of these patients had a forced expiratory volume in 1 s (FEV(1)) less than 30% predicted, and nine of these 40 patients were transplanted. A comparison was performed between the survival of those transplanted (n = 9) and those not transplanted (n = 31), by means of Kaplan-Meier survival curves. The influence on survival of age, gender, nutritional status, sputum aspergillus, diabetes mellitus, recurrent hemoptysis, oxygen use, and the decline rate of FEV(1), were investigated by means of univariate and multivariate analyses. The rate of decline of FEV(1) was evaluated employing the linear regression model. CF patients with a FEV(1)< 30% and who did not receive a lung transplant had survived longer than CF patients who did receive a lung transplant (median survival 7.33 vs. 3.49 yr, 5-yr survival 73% vs. 29%). Two factors--rate of decline in FEV(1) values and age < 15 yr--were found to influence the mortality rate, while the other parameters examined did not. Our results indicate that the current criterion of FEV(1)< 30% predicted, alone is not sufficiently sensitive to predict the mortality rate in CF patients and time of referral for Tx, as many of these patients survive for long periods of time. Additional criteria to FEV(1)< 30%, should include rapidly declining FEV(1) values and age < 15 yr.

Soluble P-selectin and the postoperative course following cardiopulmonary bypass in children.

BACKGROUND: Cytokine-inducible leucocyte-endothelial adhesion molecules were shown to affect the postoperative inflammatory response following cardiopulmonary bypass (CPB). Soluble P-selectin (sP-selectin) is one of these molecules. We investigated the correlation between plasma sP-selectin levels and the intra- and postoperative course in children undergoing CPB. METHODS: Serial blood samples of 13 patients were collected preoperatively upon initiation of CPB and seven times postoperatively. Plasma was recovered immediately and frozen at - 70 degrees C until use. Circulating soluble selectin molecules were measured with a sandwich enzyme-linked immunoabsorbent assay technique. RESULTS: The significant post-CPB changes in sP-selectins plasma levels were associated with patient characteristics, operative variables and postoperative course. sP-selectin levels correlated significantly with surgery time, aortic cross-clamping time and inotropic support, as well as with the postoperative Pediatric Risk of Mortality score, hypotension and tachycardia. CONCLUSIONS: A relation between CPB-induced mediators and both early and late clinical effects is suggested. The up-regulation and expression of sP-selectin indicate neutrophil activation as a possible mechanism for the increase, and inhibiting it may reduce the inflammatory response associated with CPB.

Transillumination of the palm for venipuncture in infants.

AIM: To assess the efficacy of transillumination of the palm of the hand in establishing venous access in small infants. METHODS: One hundred infants aged 2 to 36 months were considered for venipuncture under transillumination following failure to find an accessible vein or a failed venipuncture attempt. RESULTS: In 40 of the 100 infants, a vein was visible with transillumination. In 22 of these children, previous attempts to achieve a venous line failed (mean number of failed venipunctures 2.11 +/- 0.6) and in 18 infants, no vein could be identified. Using transillumination, venous access was established with just one venipuncture in 39 of the 40 patients. CONCLUSIONS: Transillumination of the palm can aid in establishing venous access in infants. This can be easily carried out using a common otoscope.

Serum lipase levels as a diagnostic marker in cystic fibrosis patients with normal or borderline sweat tests.

Patients with normal or borderline sweat test present a diagnostic challenge. In spite of the availability of different methods such as genetic analysis and measurements of nasal potential difference, uncertainty in diagnosing cystic fibrosis (CF) in some patients still exists. Neonates with CF have high serum lipase levels, which decline over time in pancreatic-insufficient patients, whereas pancreatic-sufficient patients demonstrate high serum lipase levels beyond infancy. Because patients with borderline or normal sweat test are almost always pancreatic sufficient, this study was aimed to assess whether serum lipase levels may be of help in establishing the diagnosis of CF in these patients. Serum lipase levels were measured in 100 CF patients and in 17 healthy individuals. Patients were grouped according to their genotype. Group A patients (n = 70) carried two mutations previously found to be associated with a pathologic sweat test and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R). Group B (n = 30) were compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat tests and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 17 healthy controls. Serum lipase levels ranged between 2 and 104.4 U/L (mean +/- SD 16.9 +/- 14.7), 6.1-200 U/L (mean +/- SD 53.9 +/- 47.9), and 8.5-27.8 U/L (mean +/- SD 16.9 +/- 5.1) in Groups A, B, and C, respectively, with some overlapping between groups. The distribution of lipase levels was significantly different in Group B vs Groups A and C (P < 0.01). High lipase levels were found in 63.3% (19/30) of Group B patients, but in only 4.3% (3/70) and 0% (0/17) of Group A and C, respectively. Lipase levels were found to be inversely related to sweat chloride concentrations (r = -0.19, P < 0.05). Patients with borderline or normal sweat tests had high lipase levels, whereas low lipase levels were associated with pathologic sweat tests. Our findings indicate that the serum lipase level is genetically determined and that it has a useful role in the diagnosis of CF. Thus, in patients with borderline sweat tests and high lipase levels, the diagnosis of CF should be considered.

A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal are expected to produce little or no CFTR chloride channels. It has been shown in vitro, that aminoglycoside antibiotics can increase the frequency of erroneous insertion of nonsense codons hence permitting the translation of CFTR alleles carrying missense mutations to continue reading to the end of the gene. This led to the appearance of functional CFTR channels at the apical plasma membrane. The aim of this research was to determine if topical application of gentamicin to the nasal epithelium of patients with cystic fibrosis (CF) carrying stop mutations can express, in vivo, functional CFTR channels. Nine CF patients carrying stop mutations (mean age 23 +/- 11 yr, range 12 to 46 yr) received gentamicin drops (0.3%, 3 mg/ml) three times daily intranasally for a total of 14 d. Nasal potential difference (PD) was measured before and after the treatment. Before gentamicin application all the patients had abnormal nasal PD typical of CF. After gentamicin treatment, significant repolarization of the nasal epithelium representing chloride transport was increased from -1 +/- 1 mV to -10 +/- 11 mV (p < 0. 001). In conclusion, gentamicin may influence the underlying chloride transport abnormality in patients with CF carrying stop mutations.

Lundh meal: a single non-invasive challenge test for evaluation of exocrine and endocrine pancreatic function in cystic fibrosis patients.

The determination of endocrine and exocrine pancreatic function in cystic fibrosis patients is clinically important. Recently, a new non-invasive test, in which pancreatic stimulation by a Lundh meal is followed by sequential serum lipase measurements, was found to be a good indicator of exocrine pancreatic status. Since the Lundh meal also contains glucose, the present study assessed whether it also might be suitable for evaluation of the pancreatic endocrine axis. After an overnight fast, 10 healthy non-diabetic subjects and 14 cystic fibrosis patients ingested a Lundh meal. Glucose, insulin, and C peptide levels were measured at various time intervals following the meal. For purposes of comparison, the oral glucose tolerance test was also performed on the cystic fibrosis patients. All healthy subjects demonstrated an increase in glucose levels post Lundh meal, peaking at 45 min (mean 140+/-21 mg/dl) and then gradually declining and reaching the normal range at 120 min. Concordant peaks of insulin (46.3+/-20 IU/ml) and C peptide (5.8+/-1. 5 ng/ml) levels were noted at 60 min. All 14 cystic fibrosis patients had normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal oral glucose tolerance test, and their hemoglobin A(1C) levels were within the normal range. The other 6 cystic fibrosis patients demonstrated glucose levels above 200 mg/dl 30-60 min post Lundh meal, and all also had an impaired oral glucose tolerance test. Of these 6, 4 had high levels of hemoglobin A(1C). This study demonstrates that the Lundh meal challenges the endocrine pancreas as well as the oral glucose tolerance test. Thus, determination of both exocrine and endocrine pancreatic status can be achieved by a single non-invasive test.

A large deletion mutation in the CFTR gene (3120+1Kbdel8.6Kb): a founder mutation in the Palestinian Arabs. Mutation in brief no. 231. Online.

A deletion mutation of 8.6Kb in the CFTR gene, spanning the exons 17a, 17b and 18 was identified in 4 homozygous unrelated Palestinian CF patients. The patients were of various ethnic subgroups including Muslims, Christians and Druze. The deletion breakpoint occurred within an identical 4bp sequence in introns 16 and 18, and the mutation was defined as 3120+1Kbdel8.6Kb. A simple PCR based assay was designed and using this assay two compound heterozygote patients with the 3120+1Kbdel8.6Kb were identified. The 3120+1Kbdel8.6Kh hearing chromosomes had a common intragenic haplotype and variable flanking polymorphic markers, indicating that it is an ancient founder mutation.

Parental estimates of their child's weight: accurate for resuscitation drug doses.

OBJECTIVE: The aim of this study was to assess parental reliability in estimating child body weight in emergency situations, when weighing the child is often impossible. METHODS: 312 parents were asked to complete an anonymous questionnaire that included estimating their child's weight. 233 questionnaires were enrolled in the study and were assessed statistically using Students t test, and chi2 and ANOVA tests. RESULTS: 51.5% of parents estimated their child's body weight within +/-5% of the true weight, 73.4% within +/-10%, and 87.5% within +/-20%. A significant difference was found between paternal and maternal estimations, with 56% of mothers and only 40.3% of fathers estimating within a 5% range of accuracy (P < 0.05). CONCLUSIONS: Parents, especially mothers, can estimate their child's body weight within clinically acceptable limits. These estimations can reliably be used to calculate drug doses in prehospital and emergency department situations, when children's weight is not known and cannot be measured.

Clinical and genetic risk factors for cystic fibrosis-related liver disease.

OBJECTIVE: The aim of this study was to define the role of possible risk factors for the development of cystic fibrosis (CF)-related liver disease and to analyze the association between liver disease and the different genotypes present in the Israeli CF patient population. PATIENTS AND METHODS: All patients followed at the seven CF centers in Israel were included in this study. Liver disease was determined by persistently elevated serum liver enzymes and/or bilirubin, and/or significant ultrasonographic changes suggestive of chronic liver disease. The following clinical parameters were evaluated: ethnic origin, age at assessment of liver function, sex, history of meconium ileus, pancreatic function, history of distal intestinal obstruction syndrome, pulmonary function, and cystic fibrosis transmembrane conductance regulator mutation analysis. RESULTS: Of the 288 patients screened, 80 (28%) had liver disease. Of the 256 patients with pancreatic insufficiency, 80 (31%) had liver disease compared with none of the 32 patients with pancreatic sufficiency. Genotype-phenotype correlation was performed on 207 patients carrying identified mutations that were previously classified according to phenotype severity. Liver disease was found in 56 (32%) of 173 patients carrying mutations associated with a severe phenotype and in 6 (38%) of 16 patients carrying at least one mutation associated with a variable genotype (G85E and/or 5T allele). None of the 18 patients carrying the 3849+10kb C->T mutation had liver disease. Prevalence of liver disease increased with age. No correlation was found between liver disease and severity of lung disease, nutritional status, history of meconium ileus, or distal intestinal obstruction syndrome. CONCLUSION: CF patients who have pancreatic insufficiency and carry mutations associated with a severe or a variable genotype are at increased risk to develop liver disease.

Acute respiratory distress syndrome in children: a 10 year experience.

BACKGROUND: Acute respiratory distress syndrome is a well-recognized condition resulting in high permeability pulmonary edema associated with a high morbidity. OBJECTIVES: To examine a 10 year experience of predisposing factors, describe the clinical course, and assess predictors of mortality in children with this syndrome. METHODS: The medical records of all admissions to the pediatric intensive care unit over a 10 year period were evaluated to identify children with ARDS. Patients were considered to have ARDS if they met all of the following criteria: acute onset of diffuse bilateral pulmonary infiltrates of non-cardiac origin and severe hypoxemia defined by < 200 partial pressure of oxygen during > or = 6 cm H2O positive end-expiratory pressure for a minimum of 24 hours. The medical records were reviewed for demographic, clinical, and physiologic information including PaO2/forced expiratory O2, alveolar-arterial O2 difference, and ventilation index. RESULTS: We identified 39 children with the adult respiratory distress syndrome. Mean age was 7.4 years (range 50 days to 16 years) and the male:female ratio was 24:15. Predisposing insults included sepsis, pneumonias, malignancy, major trauma, shock, aspiration, near drowning, burns, and envenomation. The mortality rate was 61.5%. Predictors of death included the PaO2/FIO2, ventilation index and A-aDO2 on the second day after diagnosis. Nonsurvivors had significantly lower PaO2/FIO2 (116 +/- 12 vs. 175 +/- 8.3, P < 0.001), and higher A-aDO2 (368 +/- 28.9 vs. 228.0 +/- 15.5, P < 0.001) and ventilation index (43.3 +/- 2.9 vs. 53.1 +/- 18.0, P < 0.001) than survivors. CONCLUSIONS: Local mortality outcome for ARDS is comparable to those in tertiary referral institutions in the United States and Western Europe. The PaO2/FIO2, A-aDO2 and ventilation index are valuable for predicting outcome in ARDS by the second day of conventional therapy. The development of a local risk profile may allow early application of innovative therapies in this population.

The molecular basis of disease variability among cystic fibrosis patients carrying the 3849+10 kb C-->T mutation.

Disease severity varies among cystic fibrosis (CF) patients carrying the same CFTR genotype. Here we studied the mechanism underlying disease variability in individuals carrying a splicing CFTR mutation, 3849+10 kb C-->T. This mutation was shown to produce both correctly and aberrantly spliced CFTR transcripts containing an additional cryptic exon. Semiquantitative nondifferential RT-PCR showed considerable variability in the level (0-28%) of aberrantly spliced RNA transcribed from the 3849+10 kb C-->T mutation in nasal epithelium from 10 patients. A significant inverse correlation was found between the level of the aberrantly spliced CFTR transcripts and pulmonary function, expressed as FEV1 (r = 0.92, P < 0.0001). Patients with normal pulmonary function (FEV1 > 80% predicted) had lower levels of aberrantly spliced CFTR RNA (0 to 3%) than those with FEV1 < 80%, (9 to 28% aberrantly spliced RNA). Only aberrantly spliced CFTR RNA was detected in the lung of a patient with severe lung disease who underwent lung transplantation. Our results show that the severity of CF lung disease correlates with insufficiency of normal CFTR RNA. Thus, the regulation of alternative splice site selection may be an important mechanism underlying partial penetrance in CF. Further understanding of this regulation will contribute to potential therapy for patients carrying splicing mutations in human disease genes.

Severe acute asthma in a community hospital pediatric intensive care unit: a ten years' experience.

BACKGROUND: The clinical literature on the incidence and subsequent mortality of asthma has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of asthma in smaller, community-based intensive care units. OBJECTIVES: The purpose of this study was to explore the course and outcome of children with acute severe asthma treated within a community hospital PICU compared with those described in the literature from larger tertiary referral centers. DESIGN: A retrospective analysis of 49 asthmatic children admitted to the Pediatric Intensive Care Unit (PICU) over a 10-year period was performed. MEASUREMENTS AND RESULTS: The mean age was 5.2 years (range 2 months to 16 years), and the male:female ratio was 3:1. Duration of symptoms prior to admission to hospital was less than 24 hours in 60.4% of the patients. The majority of patients was not treated with either inhaled or oral steroids before admission. Drugs used in the PICU included nebulized beta2-agonists, theophylline, steroids, intravenous salbutamol, and intravenous isoproterenol. Although a pharmacologic approach was successful in the majority of patients, intubation and mechanical ventilation were necessary for progressive hypercapnea, exhaustion, and cardiorespiratory arrest in 11/49 of these patients. The average stay in the ICU for our patient group was 2.4 days. Intubated patients had a mean average stay of 3.5 days. Two patients had pneumothorax related to positive pressure ventilation, requiring chest tube insertion for drainage. There were no deaths among the 49 patients admitted to our PICU. CONCLUSIONS: These data show that for acute severe asthma, outcome is comparable in a community PICU to a tertiary referral institution. We conclude that early ICU admission along with close monitoring is important in reducing morbidity and mortality in children with severe asthma.

Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis.

We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.

Serum lipase levels pre and post Lundh meal: evaluation of exocrine pancreatic status in cystic fibrosis.

Determination of pancreatic function is essential in cystic fibrosis. The most-reliable method is by measuring pancreatic enzymes in the duodenum following intravenous or oral stimulation. However, this is invasive, time consuming, and expensive. Indirect tests are non-invasive but lack accuracy. This study examines a simple test which combines pancreatic stimulation by Lundh meal and sequential serum lipase measurements. The test was performed on three groups: group A, 36 cystic fibrosis patients carrying two mutations associated with severe disease and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R); group B, 8 compound heterozygote cystic fibrosis patients carrying one mutation causing mild disease with pancreatic sufficiency (3849 + 10 kb C-->T); group C, 17 healthy individuals. Basal lipase levels were 2-16.5, 16.4-73, and 8.5-27.8 U/l in groups A, B, and C, respectively, with some overlapping between groups. There were three patterns of lipase activity (1) consistently low levels (group A) suggested a severely affected insufficient pancreas; (2) normal basal levels followed by a linear rise peaking 30 min after the meal (found in 16 of 17 healthy individuals and 3 patients of group B) reflecting an unaffected sufficient pancreas; (3) elevated lipase levels not influenced by the meal (5 patients of group B). This reflects an ongoing destructive process in the pancreas which will eventually result in conversion from pancreatic sufficiency to pancreatic insufficiency. Hence serum lipase activity prior to and 30 min after Lundh meal is a good indicator of pancreatic status allowing categorization of cystic fibrosis patients as pancreatic insufficient, pancreatic sufficient, or pancreatic sufficient with late conversion to insufficiency.

The critical first six months in cystic fibrosis: a syndrome of severe bronchiolitis.

The syndrome of infantile bronchiolitis in cystic fibrosis (CF) carries a high mortality. Fifteen cases of CF encountered over the past 19 years with severe bronchiolitis with onset during the first 6 months of life are described. Treatment include steroids in high doses. All patients recovered. Further progress resembled the usual natural course of CF and showed no evidence of persisting lung damage. The mechanism of this syndrome is not clear and is probably dependent on many factors involved in early lung disease in CF. The frequency of severe bronchiolitis in cystic fibrosis may not be high, but it continues to be seen in clinical practice today.

Nephrotic syndrome and fibrillary glomerulonephritis.

A 28-year-old female with cystic fibrosis presented with nephrotic syndrome and progressive renal failure. In addition, she complained of blurred vision and there was a purpuric skin eruption localized to her legs. A renal biopsy revealed fibrillary glomerulonephritis. Skin biopsy demonstrated swelling of capillary endothelium, thickening of arteriolar walls and deposition of IgA, C3 and fibrinogen by immunofluorescence. Opthalmoscopy and fluorescein angiography disclosed cotton wool spots with intraretinal haemorrhages and ischaemia of the macula. Albumin infusions resulted in worsening of eye symptoms and signs. The presence of these three clinicopathologic entities in a patient with CF may indicate the possibility of systemic involvement related to continued exposure to chronic bacterial lower lung infection.