In its usual form, disodium cromoglycate (DSG) contains lactose as a carrier (DSGL +). It has been suggested that lactose may effect irritant receptor sites, thus causing a degree of bronchoconstriction or less blocking of exercise-induced bronchospasm (EIB). This study was designed to assess and compare the ability of three different forms of DSG to block EIB. Eighteen asthmatic children and adolescents were given either DSGL+ by Spinhaler, DSG without lactose (DSGL-) by Spinhaler, nebulized (and also lactose-free) DSG solution (DSGN), or placebo in a randomized double-blind fashion on four occasions within a 10-day period. Pulmonary function tests were performed before and after medication and again after a standardized treadmill exercise test. After the exercise that followed treatment with each form of DSG the decreases in peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1) were significantly less than that seen after treatment with placebo. There was no significant difference between any of the three preparations of DSG. A complete block of EIB (decreases in PEFR and FEV1 of less than 12.5% and 10%, respectively) was seen in ony 11% of studies using all forms of DSG however, DSG was considered to be 'clinically effective' in 59% of studies.

The clinical course and changes in pulmonary function in 7 patients now known to have immotile cilia syndrome were followed for periods of 4 to 14 yr. Despite the high morbidity with chronic produc...

Appendicitis is said to be uncommon and difficult to diagnose in cystic fibrosis. The clinical and radiological features in nine patients with cystic fibrosis who had appendicitis were studied. All but one of the patients had an appendiceal abscess at surgery. Four patients had a delay in diagnosis of greater than three days before the correct diagnosis was made. This delay may have been due to a more indolent presentation or because these patients were initially considered to have distal intestinal obstruction syndrome. Appendicitis should be considered in the differential diagnosis if a contrast enema demonstrates extrinsic compression of the caecum. Ultrasound, computed tomography, and gallium scans were found to be of limited help in our series. Divisions of Pulmonary Medicine and Gastroenterology, Department of Paediatrics, The Hospital for Sick Children, Toronto Michael D Shields Henry Levison Joseph J Reisman Peter R Durie Gerard J Canny Correspondence to: Dr G Canny, Chest Division, The Hospital for Sick Children, 555 University Avenue, Toronto M5G IX8. Accepted 2 November 1990 Abdominal pain is a common symptom in patients with cystic fibrosis, and is most frequently due to the distal ileal obstruction syndrome (DIOS).' Other conditions, such as ^intussusception, volvulus, pancreatitis, and faecaliths are also recognised causes of lower abdominal pain in the population with cystic fibrosis and may be difficult to differentiate from DIOS.2 In contrast, the incidence of acute appendicitis is thought to be low among patients with cystic fibrosis, so that when it does occur the diagnosis may be overlooked until appendiceal perforation and abscess formation have occurred.3Indeed, these complications may only be recognised as 'incidental' findings at laparotomy or even necropsy.7-9 Previous reports advocate the use of contrast enemas in differentiating an appendix abscess from DIOS, and modern diagnostic methods, such as ultrasound, radionuclide (gallium) scanning, and computed tomography of the abdomen are recommended for diagnosing intra-abdominal abscesses. 1'13 We describe our experience with appendicitis and its complications in a group of patients with cystic fibrosis and the diagnostic value of radiographic procedures in these patients. Patients and results During the 10 year period, 1979-89, six of 803 patients with cystic fibrosis being followed up at the Hospital for Sick Children, Toronto, were identified from the hospital's medical record's computer as having undergone appendicectomy. Three other patients with cystic fibrosis had appendicectomies carried out at other hospitals. The clinical presentation and the laboratory and radiological data of these nine patients (five males) were reviewed retrospectively. CLINICAL PRESENTATION The patients' characteristics are summarised in the table. All of the patients had pancreatic insufficiency and were taking enzymes; four had meconium ileus at birth, three of whom required surgical resection. Eight of the nine patients were on long term prophylactic antibiotics: cloxacillin (n=4), cephalexin (n=2), or clindamycin (n=2). The mean (SD) forced expiratory volume in one second (FEVy) of the seven patients old enough to perform pulmonary function testing was 69 (23)% predicted. The respiratory tract in all of the patients was colonised by Pseudomonas aeruginosa and in addition, three were colonised by Pseudomonas cepacia. Five of the nine patients underwent appendicectomy within three days of the onset of symptoms. Although two of these patients were diagnosed as having DIOS on admission to hospital, they rapidly developed the classical features of acute appendicitis. In only one of these five patients was there a recent history of recurrent DIOS with a mass in the right iliac fossa. However, this patient was clinically diagnosed as having appendicitis while in the emergency room. In the remaining four patients considerable diagnostic difficulties were encountered with 5, 25, 45, and 56 days intervening respectively from the onset of symptoms and the time of surgery. Three of these patients had recently been treated for DIOS, and had been noted previously to have masses in the right iliac fossa. All three were diagnosed initially as having recurrent DIOS, and the possibility of an alternative diagnosis was considered only when they failed to respond to medical treatment for DIOS. The fourth patient with delayed diagnosis was initially thought to have a primary psoas abscess. During an emergency admission for bleeding oesophageal varices, he complained of pain in the right hip, and was noted to hold this hip flexed and abducted. He was treated with intravenous antibiotics, to which he only had a partial response. LABORATORY AND RADIOGRAPHIC DATA The average white cell count on admission was 13 9x 109/l (range 7 5-21-0), with a mean polymorphonuclear cell count of 9-9x 109/l (range 3-5-15-5). 307 group.bmj.com on June 25, 2017 Published by http://adc.bmj.com/ Downloaded from

Discordance exists between apparently reduced systemic right ventricular function and the reported asymptomatic state of mnany patients after atrial repair for transposition of the great arteries. To evaluate this clinical observation, cardiopulmonary response to exercise in 17 asymptomatic patients with no significant postoperative hemodynamic abnormalities was assessed by upright bicycle ergometry according to a modified Jomes protocol 11.5 + 1.5 years after Mustard atrial repair. Seventeen ageand sex-matched normal adolescents constituted the control group. Incremental exercise was perforrned to determine maximum work capacity, heart rate, blood pressure, oxygen saturation, and minute ventilation. Cardiac output was computed at rest and during steady-state exercise by a carbon dioxide rebreathing method at 50% of the maximum workload achieved during incremental exercise. Height and weight were similar in patients and controls (p > .05). Resting pulmonary function variables were normal in all subjects. At peak exercise, respiratory quotient was greater than 1 in both patients and controls (1.12 + 0.09 and 1.09 + 0.08 respectively, p > .05). Patients achieved a lower peak heart rate (172 t 14 vs 185 + 11 beats/min, p < .01), lower maximum work capacity (2.3 + 0.6 vs 3.3 ± 0.7 W/kg, p < .01). The ratio of minute ventilation at peak exercise to maximum resting voluntary ventilation was normal (< 80%) in both groups. The ventilatory equivalent for oxygen was similar at rest, but significantly higher in patients than in control subjects at peak exercise (42 ± 7 vs 36 ± 5, p < .006). Cardiac output was in the normal range for age at rest, and increased appropriately during steady-state exercise, with peak values remaining in the normal range, in all but one patient. Ten years or more after atrial repair for transposition of the great arteries, asyniptomatic patients have reduced maximum aerobic capacity; cardiac output and stroke volume responses to submaximal exercise are, however, normal when compared with those of normal peers, in part explaining the lack of symptoms with daily activity in these patients. Circulation 77, No. 5, 1055-1061, 1988. ABNORMAL right ventricular function both at restl-5 and during exercise69 has been documented in the majority of patients with transposition of the great arteries after atrial repair. Despite this, and the reported high incidence of other postoperative sequelae,5 7,10,11 some children are asymptomatic and report normal exercise tolerance during regular daily activities. When objectively measured by graded exercise testing, however, most patients show decreased endurance compared with normal From the Department of Pediatrics, Divisions of Cardiology, Chest Diseases, and Cardiovascular Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada. Address for correspondence: Lee N. Benson, M.D., Division of Cardiology, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8. Received Sept. 29, 1987; revision accepted Jan. 14, 1988. Vol. 77, No. 5, May 1988 subjects.7 9 12 The interpretation of these exercise tests has been complicated by the prevalence of multiple confounding variables such as arrhythmias, cyanosis, and systemic or pulmonary venous obstruction, each ofwhich may contribute to a variable extent to the decreased exercise tolerance. Additionally, it is unclear in the asymptomatic patient how the decreased right ventricular ejection fraction frequently found in these exercise studies relates to clinical status and long-term prognosis. The cardiopulmonary responses to exercise, in the absence of significant postoperative sequelae other than right ventricular dysfunction, have not been detailed late after the atrial repair. In an attempt to better understand postoperative cardiopulmonary adaptation to exercise, we studied maximum aerobic capacity during 1055 by gest on July 6, 2017 http://ciajournals.org/ D ow nladed from

Discordance exists between apparently reduced systemic right ventricular function and the reported asymptomatic state of mnany patients after atrial repair for transposition of the great arteries. To evaluate this clinical observation, cardiopulmonary response to exercise in 17 asymptomatic patients with no significant postoperative hemodynamic abnormalities was assessed by upright bicycle ergometry according to a modified Jomes protocol 11.5 + 1.5 years after Mustard atrial repair. Seventeen ageand sex-matched normal adolescents constituted the control group. Incremental exercise was perforrned to determine maximum work capacity, heart rate, blood pressure, oxygen saturation, and minute ventilation. Cardiac output was computed at rest and during steady-state exercise by a carbon dioxide rebreathing method at 50% of the maximum workload achieved during incremental exercise. Height and weight were similar in patients and controls (p > .05). Resting pulmonary function variables were normal in all subjects. At peak exercise, respiratory quotient was greater than 1 in both patients and controls (1.12 + 0.09 and 1.09 + 0.08 respectively, p > .05). Patients achieved a lower peak heart rate (172 t 14 vs 185 + 11 beats/min, p < .01), lower maximum work capacity (2.3 + 0.6 vs 3.3 ± 0.7 W/kg, p < .01). The ratio of minute ventilation at peak exercise to maximum resting voluntary ventilation was normal (< 80%) in both groups. The ventilatory equivalent for oxygen was similar at rest, but significantly higher in patients than in control subjects at peak exercise (42 ± 7 vs 36 ± 5, p < .006). Cardiac output was in the normal range for age at rest, and increased appropriately during steady-state exercise, with peak values remaining in the normal range, in all but one patient. Ten years or more after atrial repair for transposition of the great arteries, asyniptomatic patients have reduced maximum aerobic capacity; cardiac output and stroke volume responses to submaximal exercise are, however, normal when compared with those of normal peers, in part explaining the lack of symptoms with daily activity in these patients. Circulation 77, No. 5, 1055-1061, 1988. ABNORMAL right ventricular function both at restl-5 and during exercise69 has been documented in the majority of patients with transposition of the great arteries after atrial repair. Despite this, and the reported high incidence of other postoperative sequelae,5 7,10,11 some children are asymptomatic and report normal exercise tolerance during regular daily activities. When objectively measured by graded exercise testing, however, most patients show decreased endurance compared with normal From the Department of Pediatrics, Divisions of Cardiology, Chest Diseases, and Cardiovascular Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada. Address for correspondence: Lee N. Benson, M.D., Division of Cardiology, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8. Received Sept. 29, 1987; revision accepted Jan. 14, 1988. Vol. 77, No. 5, May 1988 subjects.7 9 12 The interpretation of these exercise tests has been complicated by the prevalence of multiple confounding variables such as arrhythmias, cyanosis, and systemic or pulmonary venous obstruction, each ofwhich may contribute to a variable extent to the decreased exercise tolerance. Additionally, it is unclear in the asymptomatic patient how the decreased right ventricular ejection fraction frequently found in these exercise studies relates to clinical status and long-term prognosis. The cardiopulmonary responses to exercise, in the absence of significant postoperative sequelae other than right ventricular dysfunction, have not been detailed late after the atrial repair. In an attempt to better understand postoperative cardiopulmonary adaptation to exercise, we studied maximum aerobic capacity during 1055 by gest on A ril 0, 2017 http://ciajournals.org/ D ow nladed from

Differences in the course of pulmonary disease in cystic fibrosis (CF) may be altered by different treatment strategies in different CF centers. The Copenhagen clinic uses scheduled, regular and very aggressive treatment of lung infection. The Toronto clinic treats pulmonary infection with oral, inhaled, or intravenous antibiotics, and has emphasized aggressive nutritional therapy. This study compared the clinical status of CF patients treated in the two centers (Toronto, Canada, n=302, and Copenhagen, Denmark, n=214) using a cross-sectional design in terms of Pseudomonas aeruginosa (PA) and Burkholderia cepacia (BC) lung infections, pulmonary function, and levels of PA and BC precipitating antibodies (precipitins). Median ages were similar, but the age distribution was significantly different, with a higher proportion of patients under 10 and > or = 25 years in Toronto, and higher proportion of patients 11-24 years of age in Copenhagen. A higher number of female patients was observed in Copenhagen than in Toronto. Seventy-nine percent of Copenhagen patients, and 52% of Toronto patients were deltaF508 homozygous. Of all the patients, 20.1% of Copenhagen patients and 38% of Toronto patients were deltaF508 heterozygous. Ten percent of Toronto patients had two uncommon mutations. Pulmonary function and nutritional status in both groups were similar despite varying treatment strategies. The prevalence of PA was lower in Danish children and higher in Danish adults than in Canada. These differences are probably due to cohort isolation, which was introduced in Copenhagen in 1981. The prevalence of BC was higher in Toronto than in Copenhagen patients at all ages. In both centers, the number of PA and BC precipitins increased with age in patients chronically infected with PA and BC, respectively, and the number of both PA and BC precipitins rose with declining lung function. This study suggests that the clinic populations had similar pulmonary and nutritional statuses despite differing clinic antibiotic treatment strategies. Microbial colonization seemed to differ, at least in part, because of differences in cohort isolation strategies. Early, aggressive anti-pseudomonal chemotherapy may have reduced pseudomonal colonization among younger patients in Copenhagen. Future studies will be required to assess the impact of this on this cohort's outcome.

In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of < or = 1 mg.day-1, were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief. During the baseline period, the mean daily ICS dosage was 432 micrograms in the ketotifen group versus 408 micrograms in the placebo group (NS). Among the-patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled. In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.

Background: Chronic progressive lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but severity of lung disease and rate of lung function decline are widely variable. Accurate estimates of decline have been difficult to define and compare because the timing of measurements and duration of follow-up differ in various patient groups.Patients: Three hundred sixty-six patients with CE born from 1960 to 1974, were selected from a CF database birth cohort if they had two or more measurements of pulmonary function, at least one of which was performed before the age of 10 years.Methods: Mixed model regression analysis provided estimates of the average rate of decline of spirometry measurements in subgroups on the basis of survival age, sex, pancreatic status, and genotype.Results: Patients who died before the age of 15 years had significantly poorer pulmonary function when first tested and a more rapid decline in pulmonary function thereafter than patients who survived beyond the age of 15 years. In the latter, functional levels at the age of 5 years were normal, but average rates of decline were significantly related to survival age. Female patients had significantly steeper decline than male patients, and those with pancreatic insufficiency had much steeper decline than those with pancreatic sufficiency. In the subset of 197 who survived to 1990 and were subsequently genotyped, rate of decline was greater in those homozygous for the Delta F508 mutation, compared with those who were heterozygous for Delta F508 or those who had two other mutations.Discussion: All but the most severely affected patients, who died before age 15, appear to have had normal pulmonary function when first tested in early childhood. Pancreatic sufficiency, male gender, and some non-Delta F508 mutations are associated with a slower rate of pulmonary function decline. Mixed model analysis is a valuable tool for describing and comparing pulmonary function decline in groups of patients with CF.

Glucocorticosteroids are potent anti-inflammatory agents and have an important role in a variety of respiratory diseases. Although their exact mode of action is unknown, it is thought that they exert their effects by binding to cytoplasmic glucocorticoid receptors. In certain conditions, such as asthma, the value of steroids cannot be questioned, and inhaled steroids have revolutionized management. In other situations, such as interstitial lung disease, the true role of steroids is still to be defined. In the management of diseases such as tuberculosis, the use of steroids is solely based on anecdotal experience.

Caloric intakes of preadolescent and adolescent girls and boys with cystic fibrosis (CF) were compared in order to evaluate the possibility that poor caloric intake contributes to poor nutritional status and high mortality among girls with CF. Fifty-six CF patients (26 girls and 30 boys), 10-15 years old, completed a 3-day food record, answered a short questionnaire, and underwent anthropometric and pulmonary function assessment. The mean ages of the girls and boys were similar, but the height and weight percentiles of the girls were lower than those of the boys (p = 0.02). Mean caloric intakes were no different (116% and 112% of the recommended nutrient intake in the girls and boys, respectively). Nutritional status, as determined by weight as a percentage of ideal weight for height, mean triceps skinfold thickness, and midarm muscle circumference, was normal and similar in both sexes. Most girls and boys with CF in this study had an appropriate perception of their body weight. Pulmonary function tests suggested mild lung disease with no significant difference between girls and boys (forced expiratory volume in 1 s of 82.2% and 79.8% of predicted values, respectively). The similar nutritional and pulmonary status of the girls and boys with CF in this age group is in contrast to previous reports. This finding may be the result of our policy, introduced >15 years ago, of expecting normal growth, by paying close attention to enzyme therapy and encouraging high energy intake from the time of diagnosis. It remains to be seen whether boys and girls continue to maintain similar nutritional and pulmonary status at a later age and whether both sexes experience a similar mortality rate as they age.

Bronchial responsiveness to isocapnic hyperventilation with cold air (CAH) and to inhaled methacholine (MCH) was compared in 17 children with bronchial asthma. The response to cold air was expressed as the percent drop in FEV 1 from baseline at 4 min. after the challenge (Δ% FEV 1 CAH), and the response to methacholine as the provocative concentration required to reduce the FEV 1 by 20% from baseline (PC 20 MCH). Both tests were sensitive (94%) for detecting airway hyperreactivity. There was no statistically significant relationship between A% FEV, CAH and the log PC 20 MCH ( r = 0.39; P = 0.12). In clinical practice, methacholine test is easier to perform, but in the research field cold air challenge may be preferable because it avoids potential drug effects. © 1995 Wiley‐Liss, Inc.

Objective: The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma. Methods: One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in 1 second [FEV1], <50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 μg/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes. Results: The groups were comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differences between groups were larger in those children with a baseline FEV1 ≤30% of the predicted value: FEV1 increased from 24.5% to 50.9% in group 1, from 25.0% to 39.8% in group 2, and from 25.9% to 36.5% in group 3 (p = 0.0001). In group 1, 38% of the patients were hospitalized after the study, 44% in group 2, and 46% in group 3 (p value not significant). However, in patients with FEV1 ≤30%, the hospitalization rates were 27% in group 1, 56% in group 2, and 83% in group 3 (p = 0.027). There were no toxic effects attributable to ipratropium. Conclusion: The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone; its use in patients with very severe asthma may reduce hospitalizations. (J PEDIATR 1995;126:639-45)

OBJECTIVE:To compare differences in epithelial chloride conductance according to class of mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS:We evaluated the relationship between the functional classes of CFTR mutations and chloride conductance using the first diagnostic sweat chloride concentration in a large cystic fibrosis (CF) population. RESULTS:There was no difference in sweat chloride value value between classes of CFTR mutations that produce no protein (class I), fail to reach the apical membrane because of defective processing (class II), or produce protein that fails to respond to cyclic adenosine monophosphate (class III). Those mutations that produce a cyclic adenosine monophosphate-responsive channel with reduced conductance (class IV) were associated with a significantly lower, intermediate sweat chloride value. However, patients with the mutations that cause reduced synthesis or partially defective processing of normal CFTR (class V) had sweat chloride concentrations similar to those in classes I to III. CONCLUSION:Studies of differences in chloride conductance between functional classes of CFTR mutations provide insight into phenotypic expression of the disease.

Partial forced expiratory flow-volume curves obtained by the rapid chest compression technique are being widely used to assess pulmonary function in infants and young children. The aim of this study is to assess whether in this age group flow limitation is achieved with the partial forced expiratory flow-volume curve with rapid chest compression. In eight infants and young children sedated with chloral hydrate, flow-volume curves were obtained by regular rapid chest compression technique, end-inspiratory airway occlusion prior to rapid chest compression, and expiratory clamping prior to rapid chest compression. In each technique, beginning with a cuff pressure of 20 cmH2O, the cuff pressure was increased by 10 cmH2O increments until the compression pressure reached 90 cmH2O. Maximal flow-volume curves were generated by each technique. End-inspiratory occlusion prior to rapid chest compression caused higher flows over the entire phase of expiration than the regular rapid chest compression. This increase could be observed over the entire phase of expiration. Forced expiratory flow at 50% and at 75% of vital capacity (V50 and V75) with regular rapid chest compression were 207 +/- 44 ml.s-1 (mean +/- SD) and 138 +/- 59 ml.sec-1, respectively. When end-inspiratory occlusion preceded rapid chest compression, V50 and V75 increased to 283 +/- 114 and 206 +/- 61 ml.sec-1 respectively, with a mean increase in V50 of 34% and in V75 of 31%. When expiratory clamping preceded the compression, even higher expiratory flows resulted.(ABSTRACT TRUNCATED AT 250 WORDS)