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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chest radiography in patients with cystic fibrosis (CF) frequently shows more severe changes in the upper lobes. We performed bronchoalveolar lavage (BAL) on 12 clinically stable, young adult patients with CF to determine whether inflammation varies significantly among geographically distinct areas of the lung. We found that absolute numbers of neutrophils were generally greater in BAL fluid from the upper lobe (25.7 +/- 7.9 x 10(5) neutrophils/ml [mean +/- SEM]) of the right lung than that obtained from the right lower lobe (6.8 +/- 2.8 x 10(5) neutrophils/ml; p < 0.01). The mean value of unopposed neutrophil elastase activity in upper-lobe BAL fluid (227 +/- 91 nmol peptide hydrolyzed/ml/min) was also significantly greater than that in lower-lobe BAL fluid (84 +/- 43 nmol/peptide hydrolyzed/ml/ min; p < 0.01), and similar differences were found for myeloperoxidase activity and DNA content. Neutrophil influx and unopposed neutrophil elastase for a given region correlated inversely with lung function or percentage of ideal body weight, and upper-versus lower-lobe differences were more pronounced in subjects with better preservation of lung function. Our findings suggest that regional variation in inflammation must be considered when utilizing BAL to study lower respiratory tract inflammation in CF or to monitor responses to therapeutic interventions that can potentially diminish lung inflammation. Our findings may also have implications for the study of the natural history of lung inflammation and infection in neonates, infants, and young children with CF.
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PMID:Regional variability of lung inflammation in cystic fibrosis. 937 72

Cystic fibrosis (CF) is characterized by chronic lung inflammation leading to airways obstruction. Bronchodilators, particularly short-acting beta2-agonists, are, therefore, often used by CF patients. The aim of this study was to evaluate, prospectively, the effects of the long-acting beta2-agonist salmeterol in adult CF patients. Twenty six patients with CF (10 males and 16 females; mean age (+/-SEM) 28+/-2 yrs) with mild-to-moderate airways obstruction (baseline forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 56+/-2%) were monitored in an open, cross-over trial for 4 weeks by means of peak expiratory flow rates (PEFR), self-recorded symptom scores and body plethysmography. During a 2 week run-in period, all patients continued their treatment, including regular short-acting beta2-agonists. In weeks 3 and 4, short-acting beta2-agonists were replaced by the long-acting beta2-agonist, salmeterol (50 microg b.i.d.). Salmeterol produced a significant increase in PEFR compared to the run-in period (morning 375+/-23 vs 332+/-23 L x min(-1), deltaPEFR +15.1+/-3.1%, p<0.003; evening 384+/-24 vs 349+/-24 L x min(-1), deltaPEFR +11.7+/-2.4%, p<0.04). Similarly, patients reported lower symptom scores, e.g. less dyspnoea during the day, fewer nocturnal awakenings, less intense cough, and fewer unscheduled puffs of short-acting beta2-agonists. Thus, the long-acting beta2-agonist salmeterol provided clinical benefit to a majority of adult cystic fibrosis patients with airways obstruction. These short-term results are promising enough to set up long-term controlled studies.
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PMID:Short-term effects of regular salmeterol treatment on adult cystic fibrosis patients. 938 58

Cystic fibrosis (CF) is an inherited disorder associated with severe inflammation and repeated bacterial infection and colonization in the lung. Airway epithelium is involved in defence against bacteria, but this system may be defective in CF. Pro-inflammatory cytokines can stimulate the expression of inducible nitric oxide synthase (iNOS), an enzyme generating nitric oxide, which functions as an important mediator in host defence mechanisms. To understand better the poor resistance to infections in the CF lung, the expression of the iNOS gene was investigated in explanted lungs from patients with cystic fibrosis (n = 13), bronchiectasis (n = 3), emphysema (n = 14), and in normal lungs (n = 8). In addition, bronchial epithelial cell lines were examined to study iNOS gene expression in vitro. Strong immunoreactivity for iNOS was seen in inflammatory cells and bronchial epithelium in all the diseased lungs, except for bronchial epithelium in CF. Quantitative analysis showed a significant reduction in the area of epithelium immunostained in CF [CF 6.8 +/- 1.6 (% +/- SEM); emphysema 18.2 +/- 2.8; normal 9.6 +/- 0.8, P < 0.01], regardless of steroid treatment. These results were supported by in situ hybridization of iNOS mRNA, which showed a pattern of gene expression in CF, emphysema, and normal lung which paralleled that of protein immunoreactivity. Stimulation with cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) increased the expression of iNOS mRNA detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cultures of normal (16HBE14o-), but not CF (CFBE41o-, with delta F508 CFTR mutation) epithelial cells. Expression of iNOS in inflammatory cells suggests that the gene is normal in CF. Absence of iNOS from bronchial epithelium may be due to low expression of the gene resulting from abnormalities in the signalling system that normally causes induction, such as cytokine receptors, second messengers or transcription factors. The resulting deficiency of the nitric oxide defence system may be relevant to the susceptibility of CF patients to pulmonary bacterial colonization.
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PMID:Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. 961 86

The raised nasal transepithelial potential difference (PD) in cystic fibrosis (CF) reflects accelerated active transport of Na+, and is inhibited by topical administration of the Na+ channel blocker, amiloride. The aim of this study was to investigate the dose-effect and time course of topically administered Na+ conductance inhibitors to inhibit nasal PD, including benzamil, an analog of amiloride. We measured the magnitude of drug inhibition of Na+ transport [percent inhibition of baseline PD (DeltaPD%)] and duration of inhibition of PD, defined as the time when drug inhibition of PD had recovered by 50% (effective time = ET50). Amiloride [10(-)3 M (n = 16), 3 x 10(-)3 M (n = 9), 6 x 10(-)3 M (n = 7), 10(-)2 M (n = 3)] or benzamil [1.7 x 10(-)3 M (n = 7), and 7 x 10(-)3 M (n = 5)] were administered to the nasal surface via an aerosol generated by a jet nebulizer and a nasal mask. The concentration-dependent magnitude (DeltaPD%) of inhibition was similar for amiloride and benzamil ( approximately 67- 77%), whereas the duration of inhibition (ET50) was about two-and-a-half times longer after benzamil administration as compared with equivalent concentrations of amiloride [1.6 +/- 0. 06 versus 4.5 +/- 0.6 h (ET50 +/- SEM), at 6-7 x 10(-)3 M]. In vitro studies of cultured normal nasal epithelia demonstrated directly that benzamil induced an approximately 2-fold more prolonged inhibition of active Na+ transport than amiloride. These data suggest aerosolized benzamil is a candidate long-duration Na+ channel blocker for CF.
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PMID:Effects of topically delivered benzamil and amiloride on nasal potential difference in cystic fibrosis. 962 Sep 16

Osteoporosis and fractures are increasingly recognized in children and adults with cystic fibrosis. To investigate the prevalence and pathogenesis of osteoporosis and low bone mass in adults with advanced pulmonary disease due to cystic fibrosis, we examined the relationships between bone mineral density (BMD), anthropomorphic variables, pulmonary status, glucocorticoid therapy, and vitamin D concentrations. BMD of the lumbar spine, hip, and proximal radius was measured by dual energy X-ray absorptiometry in 30 white adults (16 women), age 30 +/- 2 yr (mean +/- SEM). Compared with a normal control population, the patients had significantly reduced BMD at the lumbar spine (17 +/- 3%), total hip and femoral neck (24 +/- 3% and 20 +/- 4%, respectively). The radius was significantly less demineralized (4 +/- 2%; p <= 0.003) than the other sites. Moreover, only 21% of patients with cystic fibrosis had normal BMD (T score > -1.0) at the lumbar spine, 23% at the hip sites, and 39% at the radius. Age, weight, and body mass index (BMI) were most strongly correlated with bone mass, whereas glucocorticoid therapy and pulmonary function were not predictive. Despite oral vitamin D (400 to 800 IU daily), the mean serum 25-hydroxyvitamin D (25-OHD) concentration was at the low end of the normal range (16 +/- 2 ng/ml; normal 10 to 52 ng/ml); 8 of 20 patients (40%) had frankly low (<= 10 ng/ml) levels. BMD was significantly lower in patients with low 25-OHD concentrations at the lumbar spine (0.774 +/- 0.02 versus 0.913 +/- 0.04 g/cm2; p = 0.01) and total hip (0.648 +/- 0.04 versus 0.811 +/- 0.04 g/cm2; p = 0.01). Vertebral fractures were present in 19% of subjects and 41% had a confirmed history of previous fracture. In summary, osteoporosis, low bone mass, and fractures are common in adults with advanced cystic fibrosis lung disease. Despite oral supplements, vitamin D deficiency is also common and is associated with more severe demineralization at the lumbar spine and hip. We conclude that the widespread practice of oral supplementation with 400 to 800 units of vitamin D is ineffective in maintaining normal vitamin D stores in many patients with cystic fibrosis. To ensure adequacy of vitamin D stores, measurement of serum 25-OHD should be included in the routine management of patients with cystic fibrosis.
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PMID:Bone mass and vitamin D deficiency in adults with advanced cystic fibrosis lung disease. 962 Sep 24

The case records of 11 patients with cystic fibrosis (CF) who had 13 completed pregnancies between 1975 and 1995 were retrospectively reviewed to assess: (1) the changes in spirometry and body mass index (BMI) during pregnancy; and (2) maternal and neonatal complications and outcomes. Prepregnancy the mean age of the group was 24 (range 17-27) years. Two patients were exsmokers, 7 had pancreatic insufficiency and 7 had chest X-ray evidence of bronchiectasis. None of the patients had diabetes mellitus but 3 developed gestational diabetes. The mean +/- SEM (% predicted) forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) prepregnancy were 2.3 +/- 1.0 (83%) litres and 3.0 +/- 0.9 (85%) litres respectively. Five patients had normal spirometry (FEV1 and FVC >80% predicted) prior to 6 pregnancies. The mean body mass index (kg/height(m)2) for the group was 20.5 +/- 2.0. There was a significant decline in spirometry during pregnancy (FEV1 15.5 +/- 6.6% p<0.01; FVC 14.0 +/- 8.3% p<0.5). However, FVC but not FEV1 recovered to prepregnancy values by 12 months postpartum. There was a significant increase in both weight (7.1 kg) and BMI (2.6 kg/height(m)2) at the time of delivery compared with prepregnancy (p=0.0004). However, postpregnancy both weight and BMI had returned to their prepregnancy values (p<0.2). Mothers with an FEV1>80% had less decline in FEV1 related to pregnancy, better outcomes, fewer operative and instrumental deliveries, fewer preterm infants and fewer neonatal complications. Suggestions for the planning and management of pregnancy in women with CF are discussed.
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PMID:Cystic fibrosis and pregnancy. 965 56

Mucolytic treatment with rhDNase is part of the current therapy for cystic fibrosis (CF) lung disease. The Flutter valve, a device for enhancing airway mucus clearance, has recently been approved for use in CF patients. Exhalation through the Flutter valve leads to oscillations of expiratory airflow, improving mucus viscoelasticity and stimulating clearance. The goal of our in vitro study was to evaluate the individual and combined effects of Flutter valve oscillations and rhDNase treatment on the viscoelastic (rheological) properties of CF sputum. Sputum specimens were collected from 19 CF patients and subjected to the following protocols: 1) baseline sample with no treatment applied; 2) application of oscillations generated by airflow through the Flutter valve; 3) incubation at 37 degrees C for 30 min with 10% vol/wt rhDNase (Pulmozyme) to achieve a final concentration of 2.5 microg/mL (approximately 100 nM); 4) combination of Flutter valve oscillations and 10% vol/wt normal saline (0.9% NaCl); 5) combination of Flutter valve oscillations and 10% vol/wt rhDNase at 2.5 microg/mL final concentration. For each protocol, the mucus rigidity index (log G* at 1 rad/s) was measured at baseline and at 30 min. Values are presented as mean+/-SEM. The cough clearability index (CCI) was computed from measurements of mucus viscoelasticity, based on relationships established in model studies. Flutter valve treatment alone did not result in a significant reduction in the rigidity of CF sputum (2.24+/-0.13 vs. 2.11+/-0.13, P=0.19), nor did rhDNase (2.5 microg/mL) alone, although we have previously shown (Pediatr. Pulmonol. 1995; 20:78) that both of these treatments reduce sputum spinnability, which is more sensitive to molecular weight reduction. In comparison to individual treatments, combined treatment with Flutter valve oscillations and rhDNase significantly reduced the mucus rigidity to 1.85+/-0.19 from 2.24+/-0.13 (P< 0.001), consequently increasing the predicted clearability of the sputum (from 1.09+/-0.26 to 1.83+/-0.48, P=0.012). These in vitro results suggest that a combination of biochemical treatment (e.g., DNase) and mechanical oscillation may have a better therapeutic potential for mucus clearance in CF lung disease.
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PMID:Effects of sputum oscillations and rhDNase in vitro: a combined approach to treat cystic fibrosis lung disease. 981 Oct 74

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.
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PMID:Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa. 1046 34

Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.
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PMID:Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function. 1058 85

Ethane is produced from lipid peroxidation and can be measured in the exhaled air. Cystic fibrosis (CF) is characterized by recurrent respiratory infections, release of reactive oxygen species by inflammatory cells, and increased oxidative stress. We measured exhaled ethane in 23 CF subjects (mean age +/- SEM, 21 +/- 4 yr; 10 male, FEV(1) 62 +/- 4%) and compared it with two other noninvasive markers of oxidative stress and inflammation, carbon monoxide (CO) and nitric oxide (NO). Exhaled ethane was collected during a flow and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air. A sample (2 ml) of the expired air was analyzed by chromatography. Ethane levels were elevated in patients not on steroids (n = 13, 1.99 +/- 0.20 ppb) compared with steroid-treated patients (n = 10, 0.67 +/- 0.09 ppb, p < 0.01) and with 14 nonsmoking control (8 men, age 33 +/- 2.8 yr) subjects (0.82 +/- 0.40 ppb, p < 0.05). In patients not on steroid treatment ethane was correlated to airway obstruction as assessed by the ratio of residual volume to total lung capacity (RV/ TLC) (r = 0. 66, p < 0.05) and exhaled CO (r = 0.65, p < 0.05). CO concentrations were also higher in patients not on steroid treatment (3.4 +/- 0.2 ppm) than in steroid-treated patients (2.6 +/- 0.1 ppm, p < 0.05), whereas NO concentrations were not influenced by steroid treatment (3.0 +/- 0.4 ppm and 2.9 +/- 0.2 ppm, p > 0.05) and were lower than in a control group (7.0 +/- 0.4 ppb, p < 0.05). Exhaled ethane is elevated in CF, reduced in steroid-treated patients and correlates with CO and RV/TLC; therefore, it may be a useful noninvasive marker of oxidative stress.
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PMID:Exhaled ethane is elevated in cystic fibrosis and correlates with carbon monoxide levels and airway obstruction. 1076 19


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