Diagnosis of cystic fibrosis in the Republic of Ireland: epidemiology and costs.

There were four objectives in this study: (1) determine the incidence of cystic fibrosis (CF) in Ireland; (2) estimate the cost of diagnosing CF; (3) clarify the characteristics and outcomes of the nationwide diagnostic efforts and (4) identify disparities. Surveys were conducted to determine the number, methods, costs and outcomes for sweat tests in Ireland from 2001 through 2003. The results allowed us to determine that Ireland's CF incidence is the world's highest at 1:1353. The average cost for diagnosis was Euro 2663 per patient. Analyses of data in The Cystic Fibrosis Registry of Ireland revealed longer delays when diagnosis followed respiratory symptoms, rather than gastrointestinal signs, and also in girls compared to boys, particularly those presenting with respiratory symptoms. Although expenditures for diagnosing of CF in Ireland are relatively modest, the high incidence and age of diagnosis, as well as gender-related disparities, are sufficient to warrant investment in national newborn screening.

Respiratory function and cosmesis at maturity in infantile-onset scoliosis.

STUDY DESIGN: Retrospective review of patient records, clinical and radiographic, and patient recall for full pulmonary function studies and surface topography. OBJECTIVES: Assessment of outcome of treatment policy after age 15 during the previous 30 years to establish the efficacy of management protocols in a group that is too small and too varied for more formal assessment. BACKGROUND DATA: Spinal deformity presenting during infancy or early childhood poses a clinical problem caused by small numbers, long growth period, variable presentation and treatment methods, and, finally, the length of time that must pass before meaningful outcome results can be assessed. The aims of treatment are to preserve respiratory function and cosmetic appearance. MATERIALS AND METHODS: The records of patients with infantile onset, nonsyndromic, and noncongenital scoliosis were reviewed. Thirty two were at least age 15 years at the time of review and 21 of these agreed to attend for full pulmonary function testing (spirometry, lung volumes, gas diffusion) and surface topography, whereas two more had recent spirometry results available in their record. Treatment had been serial casting with Risser jacket, bracing, or surgery. RESULTS: Those whose scoliosis resolved or was stabilized by nonoperative means (N = 6) at an acceptable Cobb angle had normal cosmesis and pulmonary function (mean FEV1 = 98.7%, mean FVC = 96.6%). Those who were managed by casting or bracing and underwent surgery after age 10 (N = 6, mean age at surgery 12.9 y) had variable cosmesis and acceptable pulmonary function (mean FEV1 = 79%, mean FVC = 68.3%). Those whose deformity necessitated early surgery (N = 11, mean age at surgery 4.1 y) had recurrence of deformity and diminished respiratory function (mean FEV1= 41%, range 14%-72%, mean FVC = 40.8%, range 12%-67%). CONCLUSIONS: Although these are small numbers and treatment methods have changed since the beginning of the series, the results indicate that this condition is not simple to treat and for some children still has the risk for serious deformity and respiratory compromise. There is, as yet, no evidence that early surgical intervention in this group of patients with infantile scoliosis has altered their prognosis in any meaningful way.

A randomized controlled trial of a 3-year home exercise program in cystic fibrosis.

OBJECTIVES: To evaluate the effects of a 3-year home exercise program on pulmonary function and exercise tolerance in mildly to moderately impaired patients with cystic fibrosis (CF) and to assess whether regular aerobic exercise is a realistic treatment option. STUDY DESIGN: Seventy-two patients with CF (7-19 years) were randomly assigned to an exercise group (a minimum of 20 minutes of aerobic exercise, at a heart rate of approximately 150 beats/min, 3 times weekly) or a control group (usual physical activity participation). Pulmonary function, exercise tolerance, clinical status, hospitalizations, and compliance with therapy were monitored during scheduled visits to the hospital's CF clinic. RESULTS: Sixty-five patients were included in the analyses. The control group demonstrated a greater annual decline in percent of predicted forced vital capacity compared with the exercise group (mean slope +/- SD, -2.42 +/- 4.15 vs -0.25 +/- 2.81; P =.02), with a similar trend for forced expiratory volume in 1 second (-3.47 +/- 4.93 vs -1.46 +/- 3. 55; P =.07). Patients remained compliant with the exercise program over the study period. An improved sense of well-being was reported with exercise. CONCLUSIONS: Pulmonary function declined more slowly in the exercise group than in the control group, suggesting a benefit for patients with CF participating in regular aerobic exercise. Consistent compliance with the home exercise program and a self-reported positive attitude toward exercise provide further evidence of the feasibility and value of including an aerobic exercise program in the conventional treatment regimen of patients with CF.

Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.

OBJECTIVE: In children with mild acute asthma, to compare treatment with a single dose of albuterol delivered by a metered dose inhaler (MDI) with a spacer in either a weight-adjusted high dose or a standard low-dose regimen with delivery by a nebulizer. STUDY DESIGN: In this randomized double-blind trial set in an emergency department, 90 children between 5 and 17 years of age with a baseline forced expiratory volume in 1 second (FEV1 ) between 50% and 79% of predicted value were treated with a single dose of albuterol, either 6 to 10 puffs (n = 30) or 2 puffs (n = 30) with an MDI with spacer or 0.15 mg/kg with a nebulizer (n = 30). RESULTS: No significant differences were seen between treatment groups in the degree of improvement in percent predicted FEV1 (P =.12), clinical score, respiratory rate, or O2 saturation. However, the nebulizer group had a significantly greater change in heart rate (P =.0001). Our study had 93% power to detect a mean difference in percent predicted FEV1 of 8 between the treatment groups. CONCLUSION: In children with mild acute asthma, treatment with 2 puffs of albuterol by an MDI with spacer is just as clinically beneficial as treatment with higher doses delivered by an MDI or by a nebulizer.

Does ketotifen have a steroid-sparing effect in childhood asthma?

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.

The role of corticosteroids in respiratory diseases of children.

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.

Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: a short-term, double-blind study followed by six months open-label treatment.

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (FVC) of > 40% predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severly ill CF patients (FVC < 40% predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC < 40% predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase.

Comparison of airway reactivity induced by cold air and metacholine challenges in asthmatic children.

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 FEV1 from baseline at 4 min. after the challenge (delta % FEV1 CAH), and the response to methacholine as the provocative concentration required to reduce the FEV1 by 20% from baseline (PC20MCH). Both tests were sensitive (94%) for detecting airway hyperreactivity. There was no statistically significant relationship between delta % FEV1 CAH and the log PC20MCH (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.

Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma.

The aim of this study was to compare the response to inhaled albuterol after administration by nebulizer with the response after administration by a metered-dose inhaler and spacer device (MDI-spacer) to children with acute asthma. In a double-blind fashion, 33 children (6 to 14 years of age) with forced expiratory volume in 1 second (FEV1) between 20% and 70% of predicted values, and who were seen in the emergency department with acute asthma, were studied. They were treated with aerosolized albuterol or placebo by MDI-spacer, followed immediately by albuterol or placebo administered by nebulizer with oxygen. The dose ratio for albuterol by MDI-spacer versus nebulizer was 1:5. Outcome measures included a clinical score, respiratory rate, arterial oxygen saturation, and FEV1, measured before and 10, 20, and 40 minutes after treatment. With the exception of heart rate (which increased in the nebulizer group and decreased in the MDI-spacer group (p < 0.05), no difference in the rate of improvement of clinical score, respiratory rate, arterial oxygen saturation, or FEV1 was noted during the 40-minute study period between children who received albuterol by nebulizer and those who received it by MDI-spacer. We conclude that spacers and nebulizers are equally effective means of delivering beta 2-agonists to children with acute asthma.

Meconium ileus in the absence of cystic fibrosis.

Although meconium ileus in the absence of cystic fibrosis is considered a rare event, it was found that eight of 37 (21.6%) newborn infants with meconium ileus had no laboratory or clinical evidence of cystic fibrosis.

Prediction of mortality in patients with cystic fibrosis.

BACKGROUND: The majority of patients with cystic fibrosis die in early adulthood of lung disease. Lung transplantation is a treatment option for patients with advanced pulmonary disease, although the waiting period for organs may be as long as two years. Our purpose was to determine whether the risk of death due to respiratory failure could be predicted one or two years in advance on the basis of pulmonary function, blood gas levels, and nutritional status. METHODS: The study cohort consisted of 673 patients followed between 1977 and 1989. In each patient, pulmonary function, blood gas levels, nutritional status, and vital status were assessed between 1977 and 1987. Cox proportional-hazards regression analysis was used to compute the relative risk of death within one or two years after particular measurements. The effects of age and sex on mortality were also included in the analysis. RESULTS: One hundred ninety patients (28 percent) died during the study period. Overall, patients with a forced expiratory volume in one second (FEV1) less than 30 percent of the predicted value, a partial pressure of arterial oxygen below 55 mm Hg, or a partial pressure of arterial carbon dioxide above 50 mm Hg had two-year mortality rates above 50 percent. Among the laboratory measurements, the FEV1 was the most significant predictor of mortality, but age and sex were also significant in predicting risk. After adjustment for age and sex, the relative risk of death within two years was 2.0 (95 percent confidence interval, 1.9 to 2.2) for each decrement in the FEV1 of 10 percent below the predicted value. Among patients with the same FEV1, the relative risk of death was 2.0 (95 percent confidence interval, 1.5 to 2.6) in patients 10 years younger than other patients, and 2.2 (1.6 to 3.1) in female patients as compared with male patients. CONCLUSIONS: Patients with cystic fibrosis should be considered candidates for lung transplantation when the FEV1 falls below 30 percent of the predicted value. Female patients and younger patients may need to be considered for transplantation at an earlier stage.

Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma.

To determine the response to nebulized beta 2 agonist, 28 children younger than 2 years of age who visited the emergency department during an episode of acute asthma were studied. Each subject had a previous history of recurrent wheezing episodes. They were randomly assigned to receive two administrations of either nebulized albuterol (0.15 mg/kg per dose) or placebo (normal saline) with oxygen, 1 hour apart. After two nebulizations, the albuterol-treated patients had a greater improvement in clinical status (respiratory rate, degree of wheezing and accessory muscle use, total clinical score, and arterial oxygen saturation) than the placebo group. None of the patients in the albuterol group experienced a decrease of arterial oxygen saturation of greater than or equal to 2%. It is concluded that a trial of nebulized beta 2 agonists is warranted in the treatment of acute asthma in infants and young children.

Diffuse pulmonary angiomatosis.

A six year old girl with diffuse pulmonary angiomatosis presented with haemoptysis and diffuse interstitial changes with bilateral pleural effusions on the chest radiograph. The lung lesion as seen on biopsy specimens (and confirmed at necropsy) consisted of bloodless, thin walled, endothelium lined channels, affecting the interstitial septae, pleura, bronchi, and adventitia of large vessels. There was no response to oral corticosteroids or a trial of cyclosphamide. This lesion may be an example of an angiogenic disease.

Pregnancy and cystic fibrosis.

Despite reduced fertility, pregnancy is likely to occur with increasing frequency in cystic fibrosis in proportion to the number of patients reaching childbearing age. Thirty-eight pregnancies in 25 patients with cystic fibrosis are presented. Twelve of the 25 mothers were pancreatic-sufficient. Despite previous reports of the hazards of pregnancy in cystic fibrosis, we found that pregnancy was well tolerated by the vast majority of our patients and had little effect on their pulmonary and nutritional status. Therapeutic abortion for medical indications was required in two pregnancies. The incidence of prematurity and the neonatal mortality rate were low, and no congenital abnormalities occurred. We conclude that pregnancy can be tolerated by the majority of cystic fibrosis patients, particularly those who are pancreatic-sufficient.

Appendicitis in cystic fibrosis.

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.