Ear disease is not a common complication in cystic fibrosis

Although upper respiratory tract involvement is a common finding in cystic fibrosis (CF), there is no agreement on whether hearing is affected in these patients. We studied 75 CF subjects and 50 healthy agematched children with the same audiological protocol. An original scoring system was used to quantify the degree of hearing involvement (normal, mild, moderate and severe) in each subject. Prevalence of ear involvement in children with CF was similar to that in agematched control subjects (25.4% and 18% respectively,P>0.05). Ear disease in CF was not related to pulmonary disease, radiological sinusitis, nasal polyposis, or use of parenteral aminoglycosides. These data showed that the risk of ear disease in CF was not increased even if patients with severe audiological involvement were described only in the CF group.     

Gastroesophageal reflux in patients with cystic fibrosis

Children with cystic fibrosis (CF) and their asymptomatic siblings were surveyed to determine the incidence of symptomatic gastroesophageal reflux. A subgroup of patients with CF with poor nutritional status were studied with esophageal manometry, 24-hour esophageal pH recording, and pulmonary function testing before and after initiation of supplemental continuous nighttime nasogastric feeds. Of 68 patients with CF greater than or equal to 5 years of age, 20.6% experienced regurgitation and 26.5% had heartburn. In the control group of 23 asymptomatic siblings greater than or equal to 5 years of age, none experienced regurgitation and 5.6% had heartburn. Among the patients there was no significant association between symptoms of gastroesophageal reflux and bronchodilator therapy. Eight patients had normal lower esophageal sphincter pressure of 24.8 +/- 8.8 mm Hg and thoracoabdominal pressure gradient of 11.4 +/- 4.6 mm Hg; peristalsis and upper esophageal sphincter pressure were normal. There was a significant increase in reflux episodes, episodes greater than 5 minutes, duration of the longest episode, and percent time esophageal pH was less than 4 in patients, compared with published control data, for the entire 24-hour period and during sleep. During sleep, continuous nasogastric feeding significantly increased episodes of reflux, but did not result in an increase in percent time esophageal pH was less than 4, and was not associated with evidence of aspiration or deterioration in pulmonary function. Our findings indicate that symptoms of gastroesophageal reflux, heartburn, and regurgitation are more frequent in patients with CF than in asymptomatic siblings and that gastroesophageal reflux is significantly more common in patients with CF than in controls. Nighttime nasogastric feedings can safely be used as a means of nutritional rehabilitation in patients with CF.     

Mechanisms of gastro-oesophageal reflux in cystic fibrosis.

Abnormal degrees of gastro-oesophageal reflux (GOR) were detected by 24 hour intraoesophageal pH measurement in 12 of 14 children (mean age 7.9 years; range 5 months-16 years) affected by cystic fibrosis and complaining of symptoms suggesting GOR. These patients underwent combined recording of distal oesophageal motility and intraluminal pH in order to investigate mechanisms of GOR. Inappropriate lower oesophageal sphincter relaxation was the most common mechanism of reflux in all patients. Other mechanisms (appropriate relaxation or lowered pressure of the lower oesophageal sphincter, increased intragastric pressure) were detected less frequently. Frequency of inappropriate lower oesophageal sphincter relaxations was significantly higher in patients with cystic fibrosis than in other study groups (symptomatic GOR, GOR disease complicated by respiratory complaints). Inappropriate lower oesophageal sphincter relaxations occurred with the same frequency in patients with cystic fibrosis and in a group of children with GOR disease complicated by oesophagitis. Abnormalities of distal oesophageal contractions such as decreased amplitude or uncoordinated waves were also recorded in cystic fibrosis patients. Seven patients with cystic fibrosis completed a therapeutic trial for eight weeks consisting of postural treatment and oral cisapride, a new prokinetic drug. The oesophageal acid exposure improved in only three patients. We conclude that pathologic GOR is commonly associated with cystic fibrosis. The predominant reflux mechanism in these patients is a transient inappropriate lower oesophageal sphincter relaxation rather than a low steady state basal lower oesophageal sphincter pressure.     

Aspects of bile acid metabolism in cystic fibrosis

Previous reports have indicated that cystic fibrosis (CF) patients with pancreatic enzyme insufficiency have a raised faecal bile acid output. In this study, 18 out of 29 CF patients and 2 out of the 4 non-CF patients with pancreatic enzyme insufficiency had raised faecal bile acid levels. In the CF patients no correlation was found between faecal bile acid and faecal fat excretion, but an inverse relation was shown between faecal bile acid values and age. Those CF patients with overt liver disease tended to have the lowest faecal bile acid values.Duodenal aspiration in 5 CF patients and in one non-CF patient with pancreatic enzyme insufficiency (Shwachman-Diamond syndrome), produced very small fluid volumes. Duodenal fluid mean total bile acid concentrations were within normal limits. Estimation of serum bile acids in these 6 patients showed that 3 patients had raised serum bile acid values.It is suggested that excessive chronic faecal bile acid loss may produce a contraction of the bile acid pool, and lead eventually to a reduction of intraduodenal bile acid concentrations. Measures which curtail faecal bile acid loss may have a particular significance in the management of CF.     

Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis

AIM: To establish the incidence of pathological gastro-oesophageal reflux (GOR) in newly diagnosed infants with cystic fibrosis and to identify clinical predictors of increased reflux. METHODS: 26 infants with cystic fibrosis less than 6 months of age (14 male, 12 female; mean (SEM) age 2.1 (0.21) months, range 0.8 to 5.6 months) underwent prolonged oesophageal pH monitoring (mean duration 27.1 (0.49) hours; range 21.3 to 30.2 hours). Reflux symptoms, anthropometric variables, pancreatic status, meconium ileus, genotype, and chest x ray findings were correlated with pH monitoring data. RESULTS: Five infants (19.2%) had an abnormal fractional reflux time of greater than 10%, seven (26.9%) of 5-10%, and 14 (53.8%) of below 5%. Infants who presented with frequent vomiting had a significantly higher fractional reflux time than infants who had infrequent or no vomiting. There was no significant association between abnormal chest x rays and pathological GOR. Sex, genotype, nutritional status, meconium ileus, and pancreatic enzyme supplementation were not significantly associated with pathological GOR. CONCLUSIONS: About one in five newly diagnosed infants with cystic fibrosis had pathological GOR. Pathologically increased reflux was present before radiological lung disease was established. Apart from frequent vomiting, no useful clinical predictors of pathological reflux were found.     

Duodenogastric reflux: clinical and therapeutic aspects

BACKGROUND—Duodenogastric reflux is believed to cause damage to gastric mucosa. Most reports on this disorder concern adult patients.
PATIENTS AND METHODS—1120 children with abdominal pain were studied; endoscopic features of duodenogastric reflux were found in 92 patients. To confirm the diagnosis of duodenogastric reflux, cholescintigraphy (Tc99-HEPIDA) was performed. Children with confirmed duodenogastric reflux by scintigraphy were given a prokinetic drug (cisapride).
RESULTS—Endoscopic features of duodenogastric reflux were found in 92 children; the diagnosis was confirmed by scintigraphy in 59patients. There was no significant difference in the severity of inflammation in gastric mucosa compared with the control group, whereas significantly fewer of these patients were infected with Helicobacter pylori. There was no correlation between regions of isotope accumulation and inflammatory lesions in the stomach. The prokinetic drug (cisapride) helped eliminate or greatly reduce duodenogastric reflux in children.
CONCLUSIONS—When endoscopic features of duodenogastric reflux are found the final diagnosis should be based on an examination that does not itself influence the motility of the gastrointestinal tract: cholescintigraphy seems to be a useful method. However, because the use of milk as a test meal affects the scintigraphic image, there was no correlation between the area of isotope accumulation and the localisation of inflammatory lesions in the stomach. Duodenogastric reflux seems to be less important as a cause of inflammatory lesions than other factors (such as genetic predisposition, stress, etc). Prokinetic drugs have a beneficial influence on treatment results in children with inflammatory lesions of gastric mucosa with duodenogastric reflux.

     

Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis

Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function. AIM: To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastroesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT). METHOD: Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days. RESULTS: The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%) p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time. CONCLUSIONS: SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.     

Duodenogastric reflux: clinical and therapeutic aspects.

BACKGROUND: Duodenogastric reflux is believed to cause damage to gastric mucosa. Most reports on this disorder concern adult patients. PATIENTS AND METHODS: 1120 children with abdominal pain were studied; endoscopic features of duodenogastric reflux were found in 92 patients. To confirm the diagnosis of duodenogastric reflux, cholescintigraphy (Tc99-HEPIDA) was performed. Children with confirmed duodenogastric reflux by scintigraphy were given a prokinetic drug (cisapride). RESULTS: Endoscopic features of duodenogastric reflux were found in 92 children; the diagnosis was confirmed by scintigraphy in 59 patients. There was no significant difference in the severity of inflammation in gastric mucosa compared with the control group, whereas significantly fewer of these patients were infected with Helicobacter pylori. There was no correlation between regions of isotope accumulation and inflammatory lesions in the stomach. The prokinetic drug (cisapride) helped eliminate or greatly reduce duodenogastric reflux in children. CONCLUSIONS: When endoscopic features of duodenogastric reflux are found the final diagnosis should be based on an examination that does not itself influence the motility of the gastrointestinal tract: cholescintigraphy seems to be a useful method. However, because the use of milk as a test meal affects the scintigraphic image, there was no correlation between the area of isotope accumulation and the localisation of inflammatory lesions in the stomach. Duodenogastric reflux seems to be less important as a cause of inflammatory lesions than other factors (such as genetic predisposition, stress, etc). Prokinetic drugs have a beneficial influence on treatment results in children with inflammatory lesions of gastric mucosa with duodenogastric reflux.     

In vivo bile acid uptake from terminal ileum in cystic fibrosis

The cause(s) of excessive fecal bile acid loss in cystic fibrosis (CF) has not yet been fully determined, but in vitro studies have suggested that a primary mucosal defect in ileal bile acid uptake may be of importance. To examine this mechanism in vivo, the terminal ileal uptakes of taurocholate and glycocholate were determined using a marker-perfusion technique in three CF infants and four controls. Normal and CF ileal conditions were stimulated by varying the taurocholate:glycocholate concentration ratio (normal 1:1, CF 1:4) and pH (normal 7.8, CF 6.0) of the perfusate. The mean bile acid uptake under normal perfusate conditions was not significantly different in CF subjects (taurocholate 0.124 mumol/min/cm ileum +/- SD 0.127, glycocholate 0.117 mumol/min/cm ileum +/- 0.114), and controls (0.142 +/- 0.164 and 0.115 +/- 0.120 respectively). Similarly, under CF conditions, bile acid uptake values in CF subjects and controls were similar. The results are not consistent with deranged ileal bile acid reabsorption being a major cause of fecal bile acid loss in CF.     

Biliary infusion therapy in the inspissated bile syndrome of cystic fibrosis

A 3.5-month-old white boy was born with meconium ileus, peritonitis, and jejunal atresia from cystic fibrosis. He subsequently developed unrelenting and severe extrahepatic biliary obstruction as demonstrated by liver biopsy showing periportal inflammation, cholestasis, and fibrosis. Surgical exploration confirmed the diagnosis of extrahepatic biliary obstruction by severely inspissated bile. A cholecystostomy tube was left in place. The cholestasis remained unresponsive to conservative medical therapy. The obstruction was relieved by hydrostatic infusion of 2% N-acetylcysteine into the biliary tree over a 6-day period. The child also received concurrently four i.v. injections of synthetic cholecystokinin. This therapeutic modality was thought to be both safe and effective.     

Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis

Accepted 8 November 1996
Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function.
AIM—To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastro-oesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT).
METHOD—Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days.
RESULTS—The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%, p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time.
CONCLUSION—SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.

     

Acylcarnitine is low in cord blood in cystic fibrosis

Carnitine metabolites (total, free, short and long chain) were analyzed in cord blood of cystic fibrosis (n = 5), non-CF siblings (n = 7), and controls (n = 8). Total acylcarnitine (short and long chain combined) was significantly lower (less than 0.001) in CF compared to both control groups. Total and free carnitine showed no significant differences between the three groups. These findings are compatible with disturbed fatty acid metabolism in utero and may be related to the increased energy expenditure characteristic of CF infants.     

Reduction of bile acid loss in cystic fibrosis by dietary means.

On a ''normal'' diet increased faecal bile acid excretion was found in 14 of 16 children with cystic fibrosis who had steatorrhoea, but excretion was normal in 2 such children without steatorrhoea. The 16 children with steatorrhoea took 3 regimens of diet and therapy: a ''normal'' diet with pancreatic enzyme supplements, a diet of reduced long-chain triglycerides with added medium-chain triglycerides, and the same diet with added pancreatic enzyme supplements. On each of these three regimens steatorrhoea and faecal bile acid loss were significantly less than on no treatment, with the lowest excretions occurring on the diet of reduced long-chain triglycerides with added medium-chain triglycerides and pancreatic enzyme supplements. Although a reduction in steatorrhoea was nearly always accompanied by a decrease in bile acid excretion, the initial bile acid loss was very variable and could not be predicted for any given degree of steatorrhoea. This suggests that at least one other factor, possibly liver disease or bile acid pool size, influences bile acid loss in the faeces.     

New insights on gastro-oesophageal reflux in cystic fibrosis by longitudinal follow up.

A higher frequency (25%) of gastrooesophageal reflux (GOR) has been previously reported in patients over 5 years old with cystic fibrosis compared with controls without cystic fibrosis. It was believed that GOR was caused by the complications of cystic fibrosis. We looked for GOR in all 26 children younger than 60 months who had cystic fibrosis diagnosed. They had a classical genetic profile and the usual scattered clinical manifestations for age. GOR was confirmed in 21 (81%): 20 by abnormal pH tracings and in one on a clinical basis. After at least one month of adjusted cystic fibrosis treatment, antireflux treatment (cisapride) was given to 16 patients and variables of GOR improved dramatically. Weight gain was significant and recurrent cough and wheeze disappeared. One year later half of the patients still suffered from GOR. GOR is a major problem in the early life of those with cystic fibrosis and is not the consequence of either respiratory or gastrointestinal complications as it improves with age whereas cystic fibrosis becomes worse with age.