Effect of high-dose ibuprofen in patients with cystic fibrosis. High-dose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial. Ibuprofen in children with cystic fibrosis: pharmacokinetics and adverse effects. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis. [The effect of ipratropium bromide on lung function in patients with cystic fibrosis]. Long-term daily high and low doses of azithromycin in children with cystic fibrosis: a randomized controlled trial. The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease.
Since the inflammatory response to chronic infection contributes to lung destruction in patients with cystic fibrosis, we hypothesized that anti-inflammatory therapy might slow the progression of lung disease.
                In a double-blind trial, 85 patients, 5 to 39 years of age, with mild lung disease (forced expiratory volume in one second [FEV1], > or = 60 percent of the predicted value) were randomly assigned to receive ibuprofen or placebo orally twice daily for four years. Doses were adjusted individually to achieve peak plasma concentrations of 50 to 100 micrograms per milliliter. Changes in pulmonary function, the percentage of ideal body weight, the chest-radiograph score, and the frequency of hospitalization were assessed.
                Patients randomly assigned to ibuprofen had a slower annual rate of change in FEV1 than the patients assigned to placebo (mean [+/- SE] slope, -2.17 +/- 0.57 percent vs. -3.60 +/- 0.55 percent in the placebo group; P = 0.02), and weight (as a percentage of ideal body weight) was better maintained in the former group (P = 0.02). Among the patients who took ibuprofen for four years and had at least a 70 percent rate of compliance, the annual rate of change in FEV1 was even slower (-1.48 +/- 0.69 percent vs. -3.57 +/- 0.65 percent in the placebo group, P = 0.03), and this group of patients also had a significantly slower rate of decline in forced vital capacity, the percentage of ideal body weight, and the chest-radiograph score. There was no significant difference between the ibuprofen and placebo groups in the frequency of hospitalization. One patient was withdrawn from the study because of conjunctivitis, and one because of epistaxis related to ibuprofen.
                In patients with cystic fibrosis and mild lung disease, high-dose ibuprofen, taken consistently for four years, significantly slows the progression of the lung disease without serious adverse effects. To assess the effectiveness and safety of high-dose ibuprofen when used as part of routine therapy in patients with cystic fibrosis (CF).
                In this multicenter, double-blinded, placebo-controlled trial, a total of 142 patients age 6 to 18 years with mild lung disease (forced expiratory volume in 1 minute [FEV1] > 60 predicted) were randomized to receive either high-dose ibuprofen (70 subjects, 20 to 30 mg/kg/twice daily, adjusted to a peak serum concentration of 50 to 100 mug/mL) or placebo (72 subjects) for a 2-year period. The primary outcome was the annualized rate of change in FEV1% predicted.
                The patients in the high-dose ibuprofen group exhibited a significant reduction in the rate of decline of forced vital capacity percent predicted (0.07 +/- 0.51 vs -1.62 +/- 0.52; P = .03), but not FEV1%. The ibuprofen group also spent fewer days in hospital after adjusting for age (1.8 vs 4.1 days per year; P = .07). A total of 11 patients (4 in the ibuprofen group and 7 in the placebo group) withdrew due to adverse events.
                High-dose ibuprofen has a significant effect on slowing the progression of lung disease in CF and generally is well tolerated. Antiinflammatory therapy with ibuprofen has been proposed to retard the progression of lund disease in cystic fibrosis (CF). The pharmacokinetics and toxicity of ibuprofen were investigated in a randomized, double-blind, placebo-controlled, 3-month dose-escalation study in 19 children with CF, 6 to 12 years of age. The subjects received orally and twice daily 300 mg of drug during the first month, 400 mg in the second month, and 600 mg in the third month. Ibuprofen pharmacokinetics and evaluation for adverse effects were performed at the beginning and end of each month. The dose of ibuprofen was increased if peak plasma concentration (Cmax) was less than 50 micrograms/ml. To preserve the blind nature of the study, the dose in matched subjects taking placebo was also increased. The subjects randomly assigned to receive ibuprofen (n = 13) completed 26 months of treatment; placebo subjects (n = 5) completed 12 months. With dose escalation, Cmax and the area under the concentration-time curve from zero to infinity significantly increased (p less than 0.01). The pharmacokinetics of ibuprofen in 13 children with CF who received 13.4 +/- 4.1 mg/kg (mean +/- SD) were compared with those in four healthy children who received a similar dose. Peak plasma concentration (48 +/- 17 micrograms/ml) was decreased by 27% (p = 0.06), the area under the concentration-time curve (6.1 +/- 1.7 mg.min/ml) was decreased by 46% (p less than 0.001), apparent total clearance (2.3 +/- 0.6 ml/min.kg-1) was increased by 77% (p less than 0.01), and apparent volume of distribution during terminal phase (291 +/- 91 ml/kg) was increased by 84% (p = 0.01) in the children with CF. Time to Cmax (66 +/- 20 minutes) and elimination half-life (92 +/- 27 minutes) were not significantly different. No subjects were withdrawn from the study because of side effects. No adverse effects could be attributed to ibuprofen. Thus ibuprofen administration has no significant toxic effects, but Cmax will need to be monitored for effective dosing in patients with CF. Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF.
                To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit.
                Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035).
                AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit. A randomised, double-blind, placebo-controlled study examined the effects of alternate-day prednisone therapy on morbidity and progression of lung disease in cystic fibrosis (CF). At baseline the patients (aged 1-12 years) had mild to moderate lung disease, and the prednisone group did not differ significantly from the placebo group for any values measured. After 4 years, the prednisone-treated group had significant advantages over the placebo group for height, weight, vital capacity, forced expiratory volume in 1 s, peak flow rate, erythrocyte sedimentation rate, and serum IgG. The prednisone-treated group required 9 admissions to hospital for CF-related pulmonary disease compared with 35 for the placebo group. There were no steroid-induced side-effects. To rule out bias in case selection, 69 CF clinic patients comparable in age and clinical status but not included in the study were compared with the placebo group at 4 years; no significant differences between the groups were found. The main manifestation of cystic fibrosis (CF) of the lungs is an obstructive ventilation disturbance. The fact that the administration of atropine improves pulmonary function in patients with CF suggests a vagal mechanism for the development of bronchal obstruction. In a single-blind, placebo-controlled study, we investigated the effect of 250 micrograms of an inhalation solution of the anticholinergic substance ipatropium bromide (IB) on the pulmonary function of 11 patients with CF (age range: 8 to 29 years). The mean figures for the changes in FEV1.0, FEF25-75%, RV and TLC after inhalation of IB and placebo did not differ significantly. However, FEV1.0 and FEF25-75% after administration of IB increased in 4 out of 11 patients, and decreased in one. The lung volumes changed significantly in only a single case. This variable effect of inhaled IB in CF patients is in agreement with findings that have been observed for other substances with a "bronchodilatory" effect in patients with CF. Long-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration are not very well studied in children with CF.
                A randomized controlled trial was conducted to compare the effect of two doses of azithromycin (5mg/kg/day and 15mg/kg/day) on FEV(1) and pulmonary exacerbations in children with cystic fibrosis. Enrolled children were randomly allocated to receive daily azithromycin (5mg/kg/day or 15mg/kg/day) for 6months. Clinical assessment and FEV(1) measurement were performed monthly.
                56 children (28 in high dose group and 28 in low dose group) were enrolled. 47 (24 and 23 children in low and high dose groups) completed 12months of follow up. There was no difference in clinical scores, FEV(1), pulmonary exacerbation rates between two groups at baseline, 6months and at 12months. Per protocol analysis revealed that pulmonary exacerbation increased after discontinuing AZM and there was significantly more increase after 12months of enrolment in children getting high dose azithromycin. There was no improvement in FEV(1) in either group at the end of treatment period. Children tolerated daily low as well as high dose AZM well for 6months. There was no significant side effect of azithromycin.
                In this randomized controlled trial, we did not find differences in the effect of 2 doses (5mg/kg/day or 15mg/kg/day) of AZM on change in percentage predicted FEV(1), clinical scores, Pseudomonas colonization rates, pulmonary exacerbations and need for antibiotics. There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6months after discontinuing azithromycin. 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. Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimer's disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD.
                This was a 12-month multicenter, randomized, double-blind, placebo-controlled, parallel group trial. Participants with mild-moderate AD (Mini-Mental State Examination score >15, <26; Clinical Dementia Rating= 0.5-1), 65 years or older, with reliable caregivers, were recruited between April 2003 and September 2004. Seven AD Outpatient Treatment Centers screened 530 patients, 132 of whom were enrolled. Intervention consisted of 400 mg ibuprofen twice a day or placebo, together with 20 mg once a day of esomeprazol, or placebo. The primary measure was any one-year change in the Alzheimer Disease Assessment Scale- Cognitive (ADAS-Cog) subscale score. Secondary measures included changes in MMSE, CDR, Basic and Instrumental Activities of Daily Living scales, and Neuropsychiatric Inventory (NPI).
                Fifty-one patients (77%) in the ibuprofen vs 46 (70%) in the placebo group completed the protocol (p>0.20). In intention-to- treat analysis, ADAS-Cog score worsening was similar in the two groups (p=0.951, treatment difference= 0.1, CI -2.7; 2.9). No differences were found for any secondary outcomes. In a subsample of genotyped patients, ApoE epsilon4 carriers treated with ibuprofen (n=27) were the only group without significant cognitive decline.
                Ibuprofen, if used for relatively short periods of time and although well tolerated thanks to gastroprotection, does not seem to be effective in tertiary prevention of mild-moderate AD. Our results suggest the need to examine whether differences in the response to NSAIDs exist, based on ApoE epsilon4 carrier status.
High-dose ibuprofen can slow the progression of lung disease in people with CF, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with CF.