Microbial contamination of non-invasive ventilation devices used by adults with cystic fibrosis.

BACKGROUND: There is currently little evidence regarding potential risks of bacterial contamination of non-invasive ventilation (NIV) devices used by cystic fibrosis (CF) patients. AIM: The aim of this study was to determine the extent of bacterial contamination of NIV devices in our regional adult CF centre. METHODS: Seven NIV devices recently used by CF patients chronically infected with Pseudomonas aeruginosa or Burkholderia cepacia complex (BCC) were swabbed in seven areas, both external and internal. Two devices had undergone ethylene oxide (EtO) sterilization between patient use and swabbing, and five devices had not undergone EtO sterilization. FINDINGS: Swabs from five devices had insignificant growth of environmental organisms and two devices had significant growth of environmental organisms. No CF pathogens were isolated from any machine. CONCLUSIONS: No evidence was found of pathogenic microbial contamination of NIV devices used by CF patients in this small study. We suggest that further studies examine for evidence of bacterial contamination of NIV devices and that this issue should be included in future CF infection control guidelines.

Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status.

Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men.

OBJECTIVES: A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. METHODS: Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. RESULTS: Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). CONCLUSIONS: Iclaprim concentrations in ELF and AM exceeded the MIC(90) for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia.

Factors associated with infection by Pseudomonas aeruginosa in adult cystic fibrosis.

Cross-infection with Pseudomonas aeruginosa is an emerging issue in the care of patients with cystic fibrosis (CF). This study sought to determine the extent of, and patient factors associated with, cross-infection in a tertiary referral adult CF centre. P. aeruginosa isolates were genotyped into two groups between November 2001 and February 2003, using pulsed-field gel electrophoresis after DNA digestion by the SpeI endonuclease, and identified as clustered if there was >80% homology in the macrorestriction profiles. Patient factors and measures of disease severity were identified a priori. In total, 157 out of 227 patients had a P. aeruginosa isolate genotyped. Of these, 94 patients (60%) were infected with clustered genotypes and 47 (30%) were infected with the newly described "Midlands 1" (Md1) genotype. A further 18 patients were infected with the previously identified "Liverpool" genotype and two with the "Manchester" genotype. Logistic regression analysis revealed that the predominant predictor of infection with Md1 was age at the time of referral to the centre, suggesting that infection may have occurred prior to referral in some patients. Md1 demonstrated a relatively benign anti-biogram and did not appear to be associated with more severe disease. In conclusion, the present study provides further evidence of the emerging importance of Pseudomonas aeruginosa cross-infection in cystic fibrosis.

The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation, poor health status and recurrent infective exacerbations. Macrolide antibiotics have been shown to improve symptoms and exacerbation rate in chronic lung disease, particularly cystic fibrosis (CF) and diffuse pan-bronchiolitis. The effect of long-term oral clarithromycin on health status, sputum bacterial numbers and exacerbation rate in subjects with clinically stable COPD is undetermined. METHODS: Subjects with moderate-to-severe COPD were recruited into a prospective, double-blind, randomised-controlled trial of 3-months oral clarithromycin (Klaricid XL) or placebo once-daily. The effect of clarithromycin on health status (St. George respiratory and Short Form-36 questionnaires), sputum quantitative bacterial numbers and exacerbation rate were investigated. RESULTS: Sixty-seven subjects (46 males) were recruited; 31 and 36 subjects received clarithromycin and placebo, respectively. There were 7(10%) withdrawals. Compared to placebo, clarithromycin did not significantly improve health status, sputum bacterial numbers, or exacerbation rate. CONCLUSIONS: Three months of oral clarithromycin given to subjects with stable COPD does not improve health status, sputum bacterial numbers or exacerbation rate. Treatment of COPD with clarithromycin during the clinical stable state yields no clinical advantages and therefore cannot be recommended as means of eliminating sputum bacteria or preventing infective exacerbations.

Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD.

Chronic obstructive pulmonary disease (COPD) is characterised by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. The aim of this study was to determine the impact of sputum potentially pathogenic microorganisms (PPMs) on bronchial airway inflammation, health status and plasma fibrinogen levels in subjects with moderate-to-severe COPD during the clinical stable state. Sputum total cell and neutrophil counts, supernatant interleukin-8, leukotriene B4, tumour necrosis factor-alpha and neutrophil elastase levels, neutrophil chemotaxis and plasma fibrinogen levels were estimated. Health status was determined using the St George's Respiratory Questionnaire and the 36-item Short-Form Health Survey questionnaire. Twenty-seven (40%) subjects had PPMs and 40 (60%) non-PPMs in their sputum. Both groups were of similar age, body mass index, smoking history and lung function. The PPMs group showed significantly higher levels of interleukin-8, leukotriene B4, tumour necrosis factor-a, neutrophil elastase and increased neutrophil chemotaxis. They also exhibited worse health status and raised plasma fibrinogen levels compared to the non-PPMs group. In conclusion, subjects with clinically stable moderate-to-severe chronic obstructive pulmonary disease who had potentially pathogenic microorganisms in their sputum demonstrated an exaggerated airway inflammatory response, poorer health status and increased plasma fibrinogen levels than those who had nonpotentially pathogenic microorganisms.

Exhaled nitric oxide in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Exhaled nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO in CF patients at high risk of developing ABPA and patients at low risk. We studied nine patients at high risk of developing ABPA and 36 at low risk. The two groups were similar in age and spirometry. All patients in the high-risk group were taking oral or inhaled glucocorticoids, compared to 56% in the low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6 to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids, the exhaled NO levels were significantly lower in patients with a high risk of developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number of patients who were on inhaled, but not oral glucocorticoids was too small to analyse usefully. Exhaled NO levels were lower in CF patients with a high risk of developing ABPA and on glucocorticoids. This may be because oral glucocorticoids exert a greater effect on exhaled NO than inhaled glucocorticoids. Alternatively, inducible nitric oxide synthase may be down-regulated by Aspergillus toxin.

Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Community-acquired pneumonia in ambulatory patients: relative importance of atypical pathogens.

The presence of atypical pathogens in community-acquired pneumonia is difficult to diagnose; culture is time-consuming and requires considerable expertise and serological identification may be inaccurate. Nevertheless, the increasing importance of atypical organisms has been recognised in recent years. Variations in aetiology have been detected in different geographical regions and different patient populations. The season of the year may also influence aetiology, and some infections follow a cyclical pattern. When an atypical pathogen is suspected, a macrolide antibiotic is an appropriate choice as, in addition to activity against these organisms, they are usually effective against the Gram-positive and Gram-negative respiratory pathogens implicated in community-acquired pneumonia.

Lung concentrations of telithromycin after oral dosing.

Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Concentrations of gatifloxacin in plasma and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of gatifloxacin achieved after a single 400 mg oral dose were measured in plasma, epithelial lining fluid (ELF), alveolar macrophages (AMs) and bronchial mucosa (BM) using a microbiological assay. Fourteen patients undergoing fibre-optic bronchoscopy were studied. Mean plasma, ELF, AMs and BM concentrations, respectively, at 2, 4 and 12 h were as follows: 2 h: 3.96 mg/L, 6.00 mg/L, 69.10 mg/L, 6.24 mg/kg; 4 h: 3.22 mg/L, 6.16 mg/L, 77.32 mg/L, 5.32 mg/kg; 12 h: 1.74 mg/L, 2.98 mg/L, 61.95 mg/L, 3.00 mg/kg. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.5 mg/L), Haemophilus influenzae (0.013 mg/L), Moraxella catarrhalis (0.05 mg/L), Chlamydia pneumoniae (0.125 mg/L) and Mycoplasma pneumoniae (0.06 mg/L).

Extrapleural bronchial artery ligation for life-threatening hemoptysis in cystic fibrosis--a case report.

Hemoptyses are common in cystic fibrosis (CF) patients. They range from massive life-threatening (> 240 mL/24 hours) to recurrent minor streaking. Limited pulmonary reserve, potential concurrent chest infection, and the progressive nature of CF pose a high risk to this subgroup. Conservative management and selective bronchial artery embolization (BAE) control most acute episodes, but the recurrence rate is high. The possible need for lung transplantation in future makes an extrapleural approach for bronchial artery ligation desirable. The aim of this study was to assess the role of extrapleural bronchial artery ligation in the treatment of recurrent hemoptysis in CF patients. This is a retrospective analysis of four patients between 1986 and 1999 treated by extrapleural thoracotomy and ligation of bronchial arteries. Indications, surgical experience, and outcome are presented. Three patients underwent unilateral, and one patient bilateral extrapleural thoracotomy (in two separate sessions) for bronchial artery ligation. There were three men and one woman, with a mean age of 26.6 years (range 19-32 years). Indications were failure to stabilize the bronchial arterial catheter for BAE (three cases), recurrence after BAE previously controlled bleeding (one case), and communication with the right costocervical trunk signifying risk to the spinal circulation (one case). The mean follow-up was 68 months (range 3-144 months). There was one death in this series, a patient who was asphyxiated with hemoptysis, requiring ventilation preoperatively. He underwent successful extrapleural thoracotomy for bronchial artery ligation, with no further bleeding but succumbed to severe chest infection and multiorgan failure a few days later. Two patients had recurrent bleeding 12 and 36 months after surgery. Selective bronchial angiography proved the contralateral bronchial arteries to be the culprit. Extrapleural bronchial artery ligation is an effective method of controlling hemoptysis in CF, when BAE has failed. This approach minimizes pleural adhesions and is, therefore, desirable in the future consideration for lung transplantation. In this experience, muscle-sparing thoracotomy and postoperative epidural analgesia significantly improved the postoperative recovery.

A study to investigate the ability of subjects with chronic lung diseases to provide evidential breath samples using the Lion Intoxilyzer 6000 UK breath alcohol testing device.

The Lion Intoximeter 3000 has been used for evidential breath testing in the U.K. for some years. Some individuals with lung diseases have difficulty in providing evidential breath samples using the device. This study describes an investigation that we have carried out on a newer instrument--the Lion Intoxilyzer 6000UK--which is now in use in the U.K. The study was designed to investigate the ability of subjects with a variety of lung diseases to provide evidential breath samples using this device. The 40 adult subjects investigated comprized 10 normal controls, 10 with asthma, 10 with chronic obstructive pulmonary disease (COPD) and 10 with restrictive lung disease. After baseline spirometry, subjects were given alcohol to drink, the quantity based upon body weight. After a gap of at least 20 min, subjects were asked to provide evidential breath samples in accordance with.the test procedure built into the Lion Intoxilyzer 6000UK. The results showed that two asthmatic subjects, four with COPD and three with restrictive lung disease failed to provide evidential breath samples even after four attempts. Despite the device requiring a minimum sample volume of 1.2 l, eight of the nine subjects who failed had a forced vital capacity (FVC) of more than 1.5 l. Seven of these nine subjects had a forced expiratory volume in 1 sec (FEV1) of less than 1.0 l. In conclusion, this study has shown that some subjects with lung diseases may have difficulty in providing evidential breath samples using the Lion Intoxilyzer 6000 UK.

Asthma education and quality of life in the community: a randomised controlled study to evaluate the impact on white European and Indian subcontinent ethnic groups from socioeconomically deprived areas in Birmingham, UK.

BACKGROUND: Whether asthma morbidity in minority groups can be reduced by preventative health care measures delivered in the relevant ethnic dialects requires further evaluation. This study reports clinical outcomes and quality of life from a community based project investigating white European (W/E) and Indian subcontinent (ISC) ethnic groups with asthma living in deprived inner city areas of Birmingham, UK. METHODS: Six hundred and eighty nine asthmatic subjects (345 W/E, 344 ISC) of mean (SD) age 34.5 (15) years (range 11-59) and mean forced expiratory volume in one second (FEV(1)) of 80% predicted were interviewed in English, Punjabi, Hindi, or Urdu. Subjects randomised to the active limb of a prospective, open, randomised, controlled, parallel group, 12 month follow up study underwent individually based asthma education and optimisation of drug therapy with four monthly follow up (active intervention). Control groups were seen only at the beginning and end of the study. Urgent or emergency interactions with primary and secondary health care (clinical outcomes) and both cross sectional and longitudinal data from an Asthma Quality of Life Questionnaire (AQLQ) were analysed. RESULTS: Clinical outcomes were available for 593 subjects. Fewer of the active intervention group consulted their GP (41.8% versus 57.8%, odds ratio (OR) 0.52 (95% CI 0.37 to 0.74)) or were prescribed antibiotics (34.9% versus 51.2%, OR 0.51 (95% CI 0.36 to 0.72)), but by ethnicity statistically significant changes occurred only in the W/E group with fewer also attending A&E departments and requiring urgent home visits. Active intervention reduced the number of hospital admissions (10 versus 30), GP consultations (341 versus 476), prescriptions of rescue oral steroids (92 versus 177), and antibiotics (220 versus 340), but again significant improvements by ethnicity only occurred in the active W/E group. AQLQ scores were negatively skewed to the higher values; regression analysis showed that lower values were associated with ISC ethnicity. Longitudinal changes (for 522 subjects) in the mean AQLQ scores were small but statistically significant for both ethnic groups, with scores improving in the active and worsening in the control groups. CONCLUSIONS: Active intervention only improved clinical outcomes in the W/E group. AQLQ scores, although lower in the ISC group, were improved by active intervention in both ethnic groups.

A study to investigate the ability of subjects with chronic lung diseases to activate the roadside Lion Alcolmeter SL-400.

The Lion Alcolmeter SL-2 is widely used for road-side breath-testing by police in the UK. However, some individuals with lung diseases have difficulty in activating the device. This study describes an investigation that we have carried out on a new device called the Lion Alcolmeter SL-400 which has recently been introduced into use by police forces in the UK. The manufacturers state that the machine requires a minimum continuous expiratory flow rate of 25 litres per minute and a minimum expired volume of 1.5 litres, after which a breath sample is automatically taken and analysed. Our study was designed to investigate the ability of subjects with a variety of lung diseases to activate this device. The 40 adult subjects investigated consisted of 10 normal controls, 10 with asthma, 10 with chronic obstructive pulmonary disease and 10 with restrictive lung disease. After baseline lung function tests were performed, the subjects were then given alcohol to drink, the amount of which was based upon their body weight. After a gap of at least 20 minutes, the subjects were then asked to attempt up to three blows into the Alcolmeter. Our results showed that three asthmatic subjects, four with chronic obstructive pulmonary disease and two with restrictive lung disease, failed to successfully activate the device even after three attempts. All of the subjects who failed to activate the device had an expired breath volume of more than 1.5 litres, but seven out of these nine subjects had a Forced Expiratory Volume (FEV1) of less than 1.1 litres. In conclusion, this study has shown that some subjects with lung diseases may have difficulty in activating the SL-400 roadside alcolmeter device.

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.