pulmicort and Cystic-Fibrosis

Reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review.. To assess the effectiveness of taking regular inhaled corticosteroids, compared to not taking them, in children and adults with cystic fibrosis.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.Date of most recent search of the Group's Trials Register: 15 August 2016.. Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis.. Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas.. The searches identified 34 citations, of which 26 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 506 people with cystic fibrosis aged between six and 55 years. One was a withdrawal trial in individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information. Many of the risk of bias judgements were unclear due to a lack of available information. Only two trials specified how participants were randomised and less than half of the included trials gave details on how allocation was concealed. Trials were generally judged to have a low risk of bias from blinding, except for two which were open label or did not use a placebo. There were some concerns that a number of trials had not been published in peer-reviewed journals, but the risk of bias from this was unclear. Inclusion criteria varied between trials, as did type and duration of treatment and timing of outcome assessments. Objective measures of airway function were reported in most trials but were often incomplete. Significant benefit has not been conclusively demonstrated. Four trials systematically documented adverse effects and growth was significantly affected in one study using high doses.. Evidence from these trials is insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Child; Cystic Fibrosis; Fluticasone; Glucocorticoids; Humans; Middle Aged; Randomized Controlled Trials as Topic; Young Adult

Patients with cystic fibrosis (CF) frequently experience gastrointestinal symptoms including nausea, emesis, malnutrition and indigestion; diseases such as gastroesophageal reflux disease (GERD), distal intestinal obstructive syndrome, and cholelithiasis are commonly implicated. We have recently diagnosed eosinophilic esophagitis (EoE) in three patients with CF. EoE is a TH-2 driven, allergen-mediated disease which causes esophageal eosinophilia and presents with symptoms of nausea, feeding intolerance, regurgitation, and dysphagia. EoE is diagnosed when esophageal biopsies reveal greater than 15 eosinophils per high power field in the setting of the appropriate clinical scenario and after exclusion of other causes of esophageal eosinophilia. Although described with increasing frequently in the gastrointestinal literature, there have been no prior cases documenting the co-existence of EoE and CF. We speculate that this is related to lack of familiarity with EoE symptoms by CF providers. We present three patients with CF diagnosed with EoE and review the current literature regarding diagnosis and management, focusing on management issues in patients with CF.

Topics: Adolescent; Budesonide; Child, Preschool; Cystic Fibrosis; Eosinophilic Esophagitis; Female; Glucocorticoids; Humans; Prognosis

Therapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. This article considers the issue of physico-chemical compatibility of admixtures of drug solutions/suspensions in nebulizers. A search of databases, prescribing information and primary literature was conducted to locate literature concerning the physico-chemical compatibility of inhalation solutions/suspensions. This was supplemented by telephone interviews. Admixtures of albuterol with ipratropium and/or cromolyn, of albuterol and budesonide, or tobramycin, or colistin are physico-chemically compatible. Physico-chemical compatibility has been demonstrated for admixtures of cromolyn with albuterol and/or ipratropium and for admixtures of cromolyn and budesonide. Admixtures of budesonide with ipratropium and/or fenoterol, and admixtures of budesonide and albuterol, or cromolyn are physico-chemically compatible. Both cromolyn and colistin are incompatible with benzalkonium chloride. Admixtures should be prepared from inhalation solutions/suspensions formulated without preservatives. Besides studies of the physico-chemical compatibility, the aerodynamic behaviour of physico-chemical mixtures needs to be studied before a final recommendation of simultaneous nebulization of compatible admixtures can be made.

Topics: Acetylcysteine; Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bronchodilator Agents; Budesonide; Colistin; Cromolyn Sodium; Cystic Fibrosis; Deoxyribonuclease I; Drug Therapy, Combination; Expectorants; Humans; Ipratropium; Nebulizers and Vaporizers; Respiratory Therapy; Tobramycin

A wide range of topics can be covered when considering a review of respiratory therapeutics. This review focuses on advances and controversies in the therapy of asthma, including issues regarding medications such as inhaled beta 2-agonists, inhaled corticosteroids, cromolyn sodium, and theophylline. Bronchodilator therapy for acute viral bronchiolitis remains a controversial issue and is discussed in light of recent published manuscripts. Issues regarding surfactant therapy for respiratory distress syndrome remain prominent in the neonatal respiratory therapeutics literature and recent findings in this area are reported. Advances in the treatment of cystic fibrosis, as well as a review concerning the pulmonary toxicity of various medications used in the treatment of pediatric illness are discussed.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchiolitis, Viral; Bronchodilator Agents; Budesonide; Child; Cystic Fibrosis; Hemosiderosis; Humans; Infant, Newborn; Lung Diseases; Methotrexate; Pregnenediones; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Theophylline

A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide. An adrenocorticotrophic hormone (ACTH) test (250 microg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls. Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2-10 months after itraconazole treatment had been discontinued. Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adult; Antifungal Agents; Budesonide; Child; Cystic Fibrosis; Drug Interactions; Female; Follow-Up Studies; Gonadal Disorders; Gonads; Granulomatous Disease, Chronic; Humans; Itraconazole; Male; Polypharmacy; Prospective Studies; Time Factors

The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63% of predicted. Analysis of all patients entered, irrespective of trial adherence ("intention to treat"), showed a decrease in FEV1 in the first period of -0.032 L in patients on budesonide versus -0.187 L in patients on placebo (p = 0.08). The corresponding figures for the patients adhering to the protocol during the first period were -0.017 L versus -0.198 L (p < 0.05, confidence interval of the difference: -0.035 to +0.327 L). For all patients entered, as well as for patients adhering to the trial, there was always a trend in favor of budesonide, as judged by changes in FEV1 and FVC in both 3-mo periods. None of the patients had asthma, but the patients on budesonide had a mean improvement in histamine reactivity of +1.15 dose steps over the entire 6-mo period, as opposed to +0.017 dose steps in patients on placebo (p < 0.05). There was also a significant (p = 0.01) correlation between pre-trial histamine reactivity and the change in FEV1 in the first period in patients on budesonide. We conclude that inhaled glucocorticosteroids can be of short-term benefit in patients with CF and chronic P.a. infection and that those patients most likely to benefit from this treatment are patients with hyperreactive airways. Prolonged studies in larger number of patients are necessary to determine the long-term efficacy of this treatment.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biomarkers; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchopneumonia; Budesonide; Child; Chronic Disease; Cystic Fibrosis; Double-Blind Method; Follow-Up Studies; Forced Expiratory Flow Rates; Histamine; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Treatment Outcome

Bronchial hyperresponsiveness is present in 40-60% of adult patients with cystic fibrosis (CF). Drugs which alter airway hyperresponsiveness have not yet been studied in CF. In this randomized placebo-controlled study, we investigated the effects of an inhaled corticosteroid, budesonide, on lung function and bronchial hyperresponsiveness in adult CF patients, with proven bronchial hyperresponsiveness to histamine. Twelve patients were treated with budesonide, 1600 micrograms day-1, and with placebo during two periods of 6 weeks in a randomized, double-blind, cross-over study. Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine, spirometry and clinical symptom scores. After treatment with budesonide, no significant differences in spirometry were seen, however, bronchial hyperresponsiveness to histamine significantly improved as compared to baseline. Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine. Daily symptom scores showed small, but statistically significant, improvements in dyspnoea and cough after budesonide treatment. There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF. Treatment with oral corticosteroids improved the clinical course of selected CF patients, but was associated with unacceptable adverse effects. We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small, but significant, improvement in bronchial hyperresponsiveness to histamine, and symptoms of cough and dyspnoea in adult CF patients. Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF.

Topics: Adolescent; Adult; Bronchial Hyperreactivity; Budesonide; Cystic Fibrosis; Double-Blind Method; Female; Glucocorticoids; Histamine; Humans; Male; Pregnenediones; Respiratory Function Tests

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Cystic Fibrosis; Endoscopy; Glucocorticoids; Humans; Nasal Lavage; Nasal Surgical Procedures; Nose Diseases; Paranasal Sinuses; Sublingual Immunotherapy

Small molecules that correct the folding defects and enhance surface localization of the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) comprise an important therapeutic strategy for cystic fibrosis lung disease. However, compounds that rescue the F508del mutant protein to wild type (WT) levels have not been identified. In this report, we consider obstacles to obtaining robust and therapeutically relevant levels of F508del CFTR. For example, markedly diminished steady state amounts of F508del CFTR compared to WT CFTR are present in recombinant bronchial epithelial cell lines, even when much higher levels of mutant transcript are present. In human primary airway cells, the paucity of Band B F508del is even more pronounced, although F508del and WT mRNA concentrations are comparable. Therefore, to augment levels of "repairable" F508del CFTR and identify small molecules that then correct this pool, we developed compound library screening protocols based on automated protein detection. First, cell-based imaging measurements were used to semi-quantitatively estimate distribution of F508del CFTR by high content analysis of two-dimensional images. We evaluated ~2,000 known bioactive compounds from the NIH Roadmap Molecular Libraries Small Molecule Repository in a pilot screen and identified agents that increase the F508del protein pool. Second, we analyzed ~10,000 compounds representing diverse chemical scaffolds for effects on total CFTR expression using a multi-plate fluorescence protocol and describe compounds that promote F508del maturation. Together, our findings demonstrate proof of principle that agents identified in this fashion can augment the level of endoplasmic reticulum (ER) resident "Band B" F508del CFTR suitable for pharmacologic correction. As further evidence in support of this strategy, PYR-41-a compound that inhibits the E1 ubiquitin activating enzyme-was shown to synergistically enhance F508del rescue by C18, a small molecule corrector. Our combined results indicate that increasing the levels of ER-localized CFTR available for repair provides a novel route to correct F508del CFTR.

Topics: Alleles; Benzoates; Cells, Cultured; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Endoplasmic Reticulum; Furans; Gene Deletion; HEK293 Cells; HeLa Cells; High-Throughput Screening Assays; Humans; Hydroxamic Acids; Microscopy, Fluorescence; Protein Folding; Protein Structure, Tertiary; Pyrazoles; RNA, Messenger; Small Molecule Libraries; Ubiquitination; Vorinostat

Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated.. We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide.. GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration.. These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

Topics: Anti-Inflammatory Agents; Apoptosis; Bronchi; Budesonide; Calcium; Cell Line; Cells, Cultured; Cystic Fibrosis; Dexamethasone; Epithelial Cells; Epithelium; Glucocorticoids; Humans; Interleukin-6; Interleukin-8; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Anti-Inflammatory Agents; Azathioprine; Biopsy; Budesonide; Colonoscopy; Crohn Disease; Cystic Fibrosis; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Skin Diseases; Time Factors; Treatment Outcome; Young Adult

Topics: Administration, Inhalation; Adolescent; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Child; Cystic Fibrosis; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Respiratory Therapy

A 4-year-old boy with cystic fibrosis developed hypertension, rapid weight gain and a moon face 2 weeks after starting a combined treatment of oral itraconazole and inhaled budesonide for a suspected allergic bronchopulmonary aspergillosis. Adrenal suppression was documented and found to persist 3 months after stopping this combined treatment.. To the best of our knowledge, this is the first time that an iatrogenic Cushing syndrome in a young child with cystic fibrosis after such combined treatment is reported. The inhibition of cytochrome P4503A by intraconazole and a higher glucocorticoid tissue sensitivity is suggested as the underlying mechanism.

Topics: Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Child, Preschool; Comorbidity; Cushing Syndrome; Cystic Fibrosis; Drug Therapy, Combination; Humans; Itraconazole; Male; Time Factors

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Bronchodilator Agents; Budesonide; Child; Cystic Fibrosis; Drug Therapy, Combination; Female; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Itraconazole; Male; Pituitary-Adrenal System

Two CF patients developed Cushing's syndrome during administration of inhaled budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug co-administration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchodilator Agents; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Fatal Outcome; Female; Humans; Iatrogenic Disease; Infant, Newborn; Itraconazole; Lung Diseases; Male; Mycobacterium Infections, Nontuberculous

Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo.. This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge.

Topics: Adult; Anti-Inflammatory Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Follow-Up Studies; Humans; Itraconazole; Risk Assessment

Drug delivery to patients using dry powder inhalers, such as the Turbuhaler, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m (99mTc)-labelled budesonide was performed in order to determine the effect of age on delivery. Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99mTc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler. Immediately afterwards they inhaled from a noncommercial Turbuhaler containing budesonide labelled with 99mTc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach. As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged > 6 yrs use the Turbuhaler, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics.

Topics: Adolescent; Budesonide; Child; Child, Preschool; Cystic Fibrosis; Female; Gastric Mucosa; Humans; In Vitro Techniques; Inspiratory Capacity; Lung; Male; Nebulizers and Vaporizers; Oropharynx; Particle Size; Technetium

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Breath Tests; Budesonide; Child; Child, Preschool; Cystic Fibrosis; Drug Administration Schedule; Humans; Kartagener Syndrome; Nitric Oxide; Nose; Pregnenediones

To evaluate the use of eosinophil cationic protein (ECP) in monitoring disease activity in childhood asthma, serum ECP in 175 asthmatic children was assessed. Forty five patients with cystic fibrosis, 23 with lower respiratory tract infections (LRTI), and 87 healthy children were used as controls. Serum ECP concentrations (34.3 micrograms/l v 9.8 micrograms/l) were significantly higher in children with bronchial asthma than in healthy control subjects. In symptomatic patients with asthma serum ECP concentrations were increased compared with those from asymptomatic patients (40.2 micrograms/l v 14.4 micrograms/l), irrespective of treatment modalities (that is steroids, beta 2 agonists, or sodium cromoglycate). Moreover, atopy and infection appeared to be factors enhancing eosinophil activity in bronchial asthma as measured by serum ECP (58.4 micrograms/l v 36.8 micrograms/l and 68.8 micrograms/l v 42.2 micrograms/l, respectively). In a longitudinal trial, antiasthmatic treatment modalities (that is steroids) reduced serum ECP within four weeks (42.2 micrograms/l v 19.0 micrograms/l). In conclusion, the data indicate that (1) eosinophils also play a central part in childhood asthma; (2) serum concentrations of ECP in children with bronchial asthma are related to the disease severity and may thus be used for monitoring inflammation in childhood asthma; (3) eosinophil activity appears to be enhanced by atopy and infection; and (4) longitudinal measurements of serum ECP concentrations may be useful for optimising anti-inflammatory treatment in children with bronchial asthma.

Topics: Albuterol; Asthma; Blood Proteins; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cystic Fibrosis; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Pregnenediones; Respiratory Tract Infections; Ribonucleases