Conjoint Professor Peter Wark

Pseudomonas aeruginosa is an important cause of pulmonary infection in cystic fibrosis (CF). Its correct identification ensures effective patient management and infection control strategies. However, little is known about how often CF sputum isolates are falsely identified as P. aeruginosa. We used P. aeruginosa-specific duplex real-time PCR assays to determine if 2,267 P. aeruginosa sputum isolates from 561 CF patients were correctly identified by 17 Australian clinical microbiology laboratories. Misidentified isolates underwent further phenotypic tests, amplified rRNA gene restriction analysis, and partial 16S rRNA gene sequence analysis. Participating laboratories were surveyed on how they identified P. aeruginosa from CF sputum. Overall, 2,214 (97.7%) isolates from 531 (94.7%) CF patients were correctly identified as P. aeruginosa. Further testing with the API 20NE kit correctly identified only 34 (59%) of the misidentified isolates. Twelve (40%) patients had previously grown the misidentified species in their sputum. Achromobacter xylosoxidans (n = 21), Stenotrophomonas maltophilia (n = 15), and Inquilinus limosus (n = 4) were the species most commonly misidentified as P. aeruginosa. Overall, there were very low rates of P. aeruginosa misidentification among isolates from a broad cross section of Australian CF patients. Additional improvements are possible by undertaking a culture history review, noting colonial morphology, and performing stringent oxidase, DNase, and colistin susceptibility testing for all presumptive P. aeruginosa isolates. Isolates exhibiting atypical phenotypic features should be evaluated further by additional phenotypic or genotypic identification techniques. Copyright © 2009, American Society for Microbiology. All Rights Reserved.

INTRODUCTION: Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens. The role of smoking or of environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear. A third of people may have longer-term symptoms or recurrence.METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute bronchitis in people without chronic respiratory disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).RESULTS: We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin [with or without clavulanic acid], cephalosporins, or macrolides), antihistamines, antitussives, beta(2) agonists (inhaled or oral), cephalosporins, expectorants, and analgesics.

BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWERS' CONCLUSIONS: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.

The aim of this article is to review therapeutic agents that are currently being developed for chronic obstructive pulmonary disease (COPD) and examine them in the context of how they may influence disease progression. Developing disease-modifying agents for COPD has been identified as a priority by the World Health Organization, and the migration of inflammatory cells, the inflammatory response, antiproteases and mucociliary clearance have all been identified as viable targets for treating the disease. © Current Drugs.

BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline (HS) has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of treatment with nebulised hypertonic saline on people with CF compared to placebo and or other treatments that enhance mucociliary clearance. SEARCH STRATEGY: 'We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's register: October 2001. SELECTION CRITERIA: All controlled trials (any language) assessing the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with cystic fibrosis of any age or severity. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was assessed along with allocation concealment. MAIN RESULTS: Fourteen controlled trials were identified. Nine trials met the inclusion criteria; these involved 235 participants with an age range of 6 to 46 years. Two short-term trials of immediate effect on mucociliary clearance demonstrated that HS increased isotope clearance compared to control. Lung function as measured by improvement in Forced Expiratory Volume at one second (FEV1 l/min) was observed in four trials. When 3% to 7% saline was used in a volume of 10mls twice a day, in comparison to placebo, HS led to a significant increase in FEV1, WMD 12.20 (95%CI 4.30 to 20.10). In comparison to deoxyribonuclease (DNase) two trials used a similar concentration and volume of HS. Over a three week period the groups showed a similar increase in FEV1, WMD -1.60 (95%CI -11.16 to 7.96). However after 12 weeks treatment in participants with moderate to severe lung disease compared to DNase, HS 5mls twice a day showed less benefit to FEV1, WMD -13.00 (95%CI -22.46 to -3.54). No serious adverse events were noted. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance in short term clinical trials and appears to increase lung function compared to control. In comparison to DNase it may be less effective at improving lung function, after three months. At this stage there is insufficient evidence to support the use of hypertonic saline as routine treatment for people with cystic fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWER'S CONCLUSIONS: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.

Dyax (formerly Protein Engineering Corp) and Debiopharm are developing DX-890, an inhibitor of human ncutrophil elastase (HNE),for the potential treatment of pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). In December 1999, Debiopharm initiated phase I trials with an aerosol formulation of DX-890; studies were completed by October 2000. By August 2000, DX-890 was in phase II evaluation for the potential treatment of CF, and in May 2002, Dyax planned to initiate a further study, in children with CF, within the year. By June 2002, phase II trials in CF were ongoing in France and Spain, with results expected soon after this date. In September 2000, JP Morgan predicted a 2005 launch for this drug, with estimated sales in that year of US $23 million rising to US $63 million in 2007. © PharmaPress Ltd.

Rationale: The role of neutrophils in airway inflammation in acute asthma is unclear. Lactate dehydrogenase (LDH) is a marker of cell necrosis. The aim of this study was to determine if levels of LDH were elevated in acute asthma and to determine how this related to airway inflammation and the clinical severity of acute asthma. Methods: Subjects with acute asthma had spirometry and sputum induction. Infection was determined using sputum PCR for common respiratory viruses. Sputum supernatant LDH activity was measured using the enzymatic rate method with isoenzyme pattern determined by gel electrophoresis. Results: We recruited 37 subjects with acute severe asthma: 12 had infection with respiratory syncytial virus (RSV), 9 with influenza, 6 picornaviruses, 10 non-infective exacerbations. There were 8 healthy controls. Sputum LDH was highest in those with RSV (653.1 lU/mL), influenza infection (549.5 lU/raL) and picornaviruses (501.2 lU/mL) compared to those with no infection (182 lU/mL), while all those with acute asthma were higher than the controls (25 lU/mL, p 0.01). LDH-5 was the main isoenzyme present suggesting neutrophil lysis with elevated LDH-5. Sputum LDH was associated with elevated sputum neutrophils (r = 0.8), a lower FEV| (r = -0.5), more severe acute symptoms (r = 0.6) and a longer length of hospital stay (r = 0.4). Conclusion: Sputum LDH is elevated in acute asthma with viral infection. Cell necrosis in acute asthma may potentiate neutrophilic airway inflammation and more severe clinical disease.

BACKGROUND: Allergic Broncho-pulmonary Aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for ABPA remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of Allergic Broncho-pulmonary Aspergillosis. SEARCH STRATEGY: The Cochrane Airways Group Asthma register was searched using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for ABPA were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 month. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p<0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p<0.03). Meta analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Odds Ratio 3.3; 95% confidence intervals 1.3, 8.2). REVIEWER'S CONCLUSIONS: Itraconazole modifies the immunologic activation associated with ABPA and improves clinical outcome in ABPA at least over the period of 16 weeks.

BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance, recurrent bronchial infection and airway inflammation. Hypertonic saline has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To determine if nebulised hypertonic saline treatment improved lung function, exercise tolerance, quality of life and decreased the incidence of exacerbations of respiratory infections in patients with cystic fibrosis. SEARCH STRATEGY: Studies were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register. Titles and abstracts were reviewed to identify all controlled trials. Review articles and bibliographies identified from this process were surveyed for additional citations & RCTs. Identification of unpublished work was obtained from abstract books from the three major Cystic Fibrosis conferences (International Cystic Fibrosis Conference, The European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference). Trial authors were contacted for additional information when only abstracts were available to review. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All controlled trials that assessed the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in subjects with cystic fibrosis of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve controlled trials of hypertonic saline were identified. Seven trials met the inclusion criteria; these involved 143 subjects with an age range of 6 to 46 years. Of these, six were published studies and one in abstract form. The durations of the trials were limited to immediate effects on mucociliary clearance to a maximum of three weeks. In two studies, involving thirty five subjects, a score for the feeling of cleared chest was made using visual analogue scales. This analysis showed a weighted mean difference of -0.98 (95% confidence Interval -1.6, -0.34), favouring hypertonic saline over isotonic saline. In two trials with 22 subjects hypertonic saline improved mucociliary clearance as measured by isotope clearance from the lungs in 90 minutes demonstrating a weighted mean difference of -11.3 (95% confidence Interval -18.6, -4.0), and as area under the clearance time curve; weighted mean difference of -212 (95%CI -272, -152), also favouring hypertonic saline over isotonic saline. Lung function as measured by improvement in FEV1 was observed in one study of 27 subjects. The percentage increase in FEV1 at two weeks increased by a mean 15.0% with hypertonic saline and 2.8% with isotonic saline (p=0.004). Adverse events were adequately described in only one trial and none were serious. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance immediately after administration which may have a longer term beneficial effect in cystic fibrosis. The maximum time data were recorded for was only three weeks. Most of the patients had mild to moderate lung disease and the effect on severe lung disease remains unclear. Further studies of hypertonic saline should be carried out to determine the effect on pulmonary function tests, quality of life, frequency of exacerbations of respiratory disease and efficacy comparisons with nebulised deoxyribonuclease, with larger numbers and for longer duration. At this stage there is insufficient evidence to support the use of hypertonic saline in routine treatment for patients with cystic fibrosis.

BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance, recurrent bronchial infection and airway inflammation. Hypertonic saline has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To determine if nebulised hypertonic saline treatment improved lung function, exercise tolerance, quality of life and decreased the incidence of exacerbations of respiratory infections in patients with cystic fibrosis. SEARCH STRATEGY: Studies were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register. Titles and abstracts were reviewed to identify all controlled trials. Review articles and bibliographies identified from this process were surveyed for additional citations & RCTs. Identification of unpublished work was obtained from abstract books from the three major Cystic Fibrosis conferences (International Cystic Fibrosis Conference, The European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference). Trial authors were contacted for additional information when only abstracts were available to review. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All controlled trials that assessed the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in subjects with cystic fibrosis of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve controlled trials of hypertonic saline were identified. Seven trials met the inclusion criteria; these involved 143 subjects with an age range of 6 to 46 years. Of these, six were published studies and one in abstract form. The durations of the trials were limited to immediate effects on mucociliary clearance to a maximum of three weeks. In two studies, involving thirty five subjects, a score for the feeling of cleared chest was made using visual analogue scales. This analysis showed a weighted mean difference of -0.98 (95% confidence Interval -1.6, -0.34), favouring hypertonic saline over isotonic saline. In two trials with 22 subjects hypertonic saline improved mucociliary clearance as measured by isotope clearance from the lungs in 90 minutes demonstrating a weighted mean difference of -11.3 (95% confidence Interval -18.6, -4.0), and as area under the clearance time curve; weighted mean difference of -212 (95%CI -272, -152), also favouring hypertonic saline over isotonic saline. Lung function as measured by improvement in FEV1 was observed in one study of 27 subjects. The percentage increase in FEV1 at two weeks increased by a mean 15.0% with hypertonic saline and 2.8% with isotonic saline (p=0.004). Adverse events were adequately described in only one trial and none were serious. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance immediately after administration which may have a longer term beneficial effect in cystic fibrosis. The maximum time data were recorded for was only three weeks. Most of the patients had mild to moderate lung disease and the effect on severe lung disease remains unclear. Further studies of hypertonic saline should be carried out to determine the effect on pulmonary function tests, quality of life, frequency of exacerbations of respiratory disease and efficacy comparisons with nebulised deoxyribonuclease, with larger numbers and for longer duration. At this stage there is insufficient evidence to support the use of hypertonic saline in routine treatment for patients with cystic fibrosis.

BACKGROUND: Allergic Broncho-pulmonary Aspergillosis (ABPA) is hypersensitivity to the fungus Aspergillus Fumigatus that complicates patients with asthma and cystic fibrosis. The condition usually results in an increase in symptoms, a greater reliance on corticosteroids to control the disease process and may lead to a progressive decline in lung function. The mainstay of treatment for ABPA remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review is to determine the efficacy of azoles in the treatment of ABPA SEARCH STRATEGY: An initial search was carried out using the Cochrane Airways Group Asthma RCT register. The register was searched using the following terms: (asthma or wheeze) and (allergic bronchopulmonary aspergillosis or aspergillosis or allergic pulmonary aspergillosis or allergic fungal and disease or allergic mycotic and disease) and (azole or triazole or itraconazole or ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard, for any duration or dose regimen in subjects with ABPA of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: A total of 11 trials were identified concerning the use of azoles in ABPA. Only two prospective controlled trials were identified. The first trial examined the use of Ketoconazole 400 mg daily for 12 months and demonstrated a reduction in immunological markers of disease activity and symptom scores, there was no significant improvement in lung function. The other trial examined the use of itraconazole for 16 weeks. This demonstrated a reduction in corticosteroid usage, an improvement in immunological markers, an improvement in pulmonary function and exercise tolerance. This study was only available as an abstract and limited details were available. REVIEWER'S CONCLUSIONS: There is insufficient information available to recommend the use of azole anti-fungal agents in the routine treatment of patients with ABPA.

Allergic bronchopulmonary aspergillosis (ABPA) is a serious complication of asthma. In uncomplicated asthma airway inflammation(ai) is characterised by sputum eosinophilia without an increase in the total cell count (TCC). In bronchiectasis the intensity of ai increased and there is a neutrophil infiltrate. Airway inflammation in ABPA is not well defined. This study tested the hypothesis that ai in ABPA would be of increased intensity with a mixed eosinophil/neutrophil pattern. Methods: In subjects with asthma, ABPA was assessed by 5 criteria; 1. positive allergy skin test to Aspergillus Fumigatus (Af); 2. raised specific serum IgE to Af; 3. positive precipitating antibodies to Af; 4. total IgE > 10001U/ml and 5. bronchiectasis (CT scan). Subjects were classified as definite ABPA (n=13) with criteria 1, 2, 3 and either 4 or 5; or as probable ABPA (n=18) with 1 and 2 and either 3, 4 or 5 (n=13). These groups were combined for analysis. Af sensitised subjects (n=19 with positive skin testing alone), were compared to a matched group with asthma (negative to Af on skin test) (n=15) and healthy controls (n=8). Spirometry, saline challenge and sputum induction were performed, with results reported as medians and interquartile ranges. Results: Patients with ABPA had an increased TCC (4.6, 0.9-29.6) compared to: Af sensitised (3.6, 1.4-7.4), asthma (1.5, 0.8-3.2), and controls (1.35, 1.3-1.4) (p<0.05). Those with ABPA had increased sputum eosinophils (3.8, 0.3-16.3), compared to: Af sensitised (1.4, 0.1-6), asthma (1.6, 0.01-3), and controls (0.3, 0.3-0.31 ) (p=0.001). Those with ABPA had increased levels of eosinophil cationic protein(ng/ml) (5471, 311-42485) compared to: Af sensitised (1432, 338-6902), asthma (244, 78-857), and controls (110, 99-121 ) (p<0.001). Neutrophil counts were similar in all groups. Myeloperoxidase was similar in ABPA (232, 66-454) and asthma (177, 57-318) (p=0.3) but greater than in healthy controls (76, 76-89) Conclusion: Airway inflammation in ABPA is of increased intensity compared to that of chronic asthma. Unlike bronchiectasis, the cellular infiltrate is predominantly eosinophilic. The eosinophils demonstrate increased activation.

Thick tenacious secretions that are difficult to expectorate and recurrent infection that leads to progressive end stage fibrotic disease typify lung disease in cystic fibrosis (CF). Mucolytic treatment can improve expectoration of sputum and lung function in CF. Our aim was to examine the efficacy of hypertonic saline (HS) in CF as an alternative or supplementary treatment. Methods: A meta-analysis of controlled trials was done. A search was carried out via the Cochrane Cystic Fibrosis Group specialist trials register. The titles and abstracts were reviewed to identify all potential controlled trials, articles were surveyed for additional citations. Identification of unpublished work was obtained from abstract books from (The International CF Conference, The European CF Conference and the North American CF Conference). All controlled trials that assessed the efficacy of Hypertonic Saline in subjects with cystic fibrosis were reviewed. The reviewers independently reviewed all trials. Data was analysed and compared using Revman. Results: A total of ten controlled trials were identified. Adequate data was available for analysis from seven of the studies, n = 166, age range (7-36years). Two studies showed that hypertonic saline (HS) improved lung function at two weeks by increasing the percentage change in FEV1. This showed a weighted mean difference (WMD) of +12.2 (95%CI +13.860, +10.540), favouring HS over isotonic saline (IS). An immediate effect on mucociliary clearance as measured by radioisotope was assessed in two trials. Analysis of isotope clearance at 90 mins found a WMD of +11.28 (95%CI +18.562, +3.998), favouring HS over IS. Measuring clearance as area under the curve showed a WMD of +212.059 (95%CI +271.641, +152.477), favouring HS over IS. Nebulised hypertonic saline appears to have a beneficial effect in cystic fibrosis, improving muco-ciliary clearance immediately after administration and lung function after two weeks of administration in combination with chest physiotherapy. Comparative data was not available to assess outcomes such as improvement in objective exercise testing, effect on symptom scores, quality of life measures or long term efficacy.

ABPA is an important complication of chronic asthma resulting from hypersensitivity to the fungus Aspergillus Fumigatus ( AF}. ABPA is characterised by an intense immune response with increased use of oral steroids and potentially progressive lung disease. The aim of this study was to determine if treatment of subjects with ABPA with the antifungal agent Itraconazole (Itz) reduced airway and systemic inflammation. Methods: A randomised double blind placebo controlled trial was performed in stable subjects with ABPA (n=29). Subjects with cystic fibrosis ere excluded. The diagnosis of ABPA was based upon; the presence of asthma, IgE sensitisation to Af. a total serum IgE of lOOOIl'/mL or greater and serum IgG to Af or central bronchiectasis on CT scan. Subjects received Itz 400mg per day (n=15) or placebo (n=14) for 16 weeks. All subjects were reviewed monthly with history, spirometry. sputum induction to measure airway inflammation, serum total IgE and IgG to Af and blood eosinophils. Results: Subjects receiving Itz had a greater reduction in sputum eosinophils from baseline (median fall of 94.5%) compared to placebo (45.4%. p<0.01 ). Those on Itz had a fall in sputum total cell count from baseline (43.9%) compared to a rise in those on placebo (rise 10%. p=0.049). Subjects that received Itz also had a reduction in systemic immune activation; there was a fall in serum IgE (3IOIU/mL) compared to placebo (rise ISIU-'mL, p<0.01) and a fall in IgG to Af(15.4IU/mL) compared to placebo (rise 3.7IU-mL, p=0.03). Conclusion: Treatment of subjects with stable ABPA with Itz 400mg daily reduces eosinophilic airway inflammation along with measures of systemic immune activation. These results imply that Itz is a potential adjunctive treatment for ABPA and this should be further investigated with larger studies of lone term clinical efficacv.