Bronchial thermoplasty increases airway volume measured by functional respiratory imaging.

BACKGROUND: The purpose of this study was to use CT scanning with computational fluid dynamics to evaluate the mechanisms by which Bronchial Thermoplasty (BT) improves asthmatic symptoms. METHODS: The study was conducted in a university teaching hospital, experienced in performing BT. Imaging studies were performed before, and after, BT of the left lung, and prior to treatment of the right lung, which therefore acted as a control. On each occasion, two high-resolution CT scans were performed, one at full inspiration (TLC) and the other at Functional Residual Capacity (FRC). The study protocol was offered to 10 patients, all of whom met the definition of severe asthma, despite high dose inhaled corticosteroids and dual long acting bronchodilators. RESULTS: Significant increases in airway luminal volume were observed on the treated side, compared with control, at both full inspiration (by 27%) and at FRC (by 17%). The ratio of distal airway volume to lung volume significantly increased on the treated side. The change in airway volume with inspiration from FRC increased by 48% on the treated side compared to 5% in the control lung, suggesting treatment increased airway distensibility. No effect was observed on airway wall thickness, nor air trapping. There was a trend towards correlation between the improvement in airway volume at TLC and improvement in symptoms. CONCLUSION: This study demonstrates that BT increases the luminal airway volume on the treated side compared to the control lung. We suggest that this is an important link between the airway smooth muscle atrophy demonstrated pathologically, and the improvement in symptoms observed clinically.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

Comparison of two methods of determining lung de-recruitment, using the forced oscillation technique.

Airway closure has proved to be important in a number of respiratory diseases and may be the primary functional defect in asthma. A surrogate measure of closing volume can be identified using the forced oscillation technique (FOT), by performing a deflation maneuver and examining the resultant reactance (Xrs) lung volume relationship. This study aims to determine if a slow vital capacity maneuver can be used instead of this deflation maneuver and compare it to existing more complex techniques. Three subject groups were included in the study; healthy (n = 29), asthmatic (n = 18), and COPD (n = 10) for a total of 57 subjects. Reactance lung volume curves were generated via FOT recordings during two different breathing manoeuvres (both pre and post bronchodilator). The correlation and agreement between surrogate closing volume (Volcrit) and reactance (Xrscrit) at this volume was analysed. The changes in Volcrit and Xrscrit pre and post bronchodilator were also analysed. Across all three subject groups, the two different measures of Volcrit were shown to be statistically equivalent (p > 0.05) and demonstrated a strong fit to the data (R2 = 0.49, 0.78, 0.59, for asthmatic, COPD and healthy subject groups, respectively). A bias was evident between the two measurements of Xrscrit with statistically different means (p < 0.05). However, the two measurements of Xrscrit displayed the same trends. In conclusion, we have developed an alternative technique for measuring airway closure from FOT recordings. The technique delivers equivalent and possibly more sensitive results to previous methods while being simple and easily performed by the patient.

Breast milk polyunsaturated fatty acids: associations with adolescent allergic disease and lung function.

BACKGROUND: It has been hypothesized that n-3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long-term effects on allergic disease and lung function. The aim was to investigate associations of n-3 and n-6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. METHODS: Polyunsaturated fatty acids were measured in 194 colostrum samples and in 118 three-month expressed breast milk samples from mothers of children enrolled in the Melbourne Atopy Cohort (MACS) Study, a high-risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. RESULTS: Higher levels of n-3 but not n-6 PUFAs in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 (OR = 5.69[95% CI: 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n-3 PUFAs were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV1 (-166 ml [-332, -1]) and FEV1 /FVC ratio (-4.6%, [-8.1, -1.1]) at 12 years. CONCLUSION: Higher levels of colostrum n-3 PUFAs were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n-3 PUFA intake may not aid in allergic disease prevention.

Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria.

BACKGROUND: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). OBJECTIVES: To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. METHODS: Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). RESULTS: Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1 ) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1 . CONCLUSIONS AND CLINICAL RELEVANCE: Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.

Ruling out low- and moderate-risk probability pulmonary emboli without radiological imaging: appraisal of a clinical prediction algorithm after implementation and revision with higher D-dimer thresholds.

BACKGROUND: A study conducted at an Australian hospital between 2007 and 2009 led to the implementation of a clinical prediction algorithm for pulmonary embolism (PE) consisting of the Wells criteria and D-dimer testing. Since then, studies conducted in other countries have recommended new D-dimer cut-offs to the algorithm. AIMS: To appraise the implemented algorithm and see if its ability to stratify patient risk has been maintained and to test retrospectively new D-dimer thresholds. METHODS: Data from 300 patients with computed tomography pulmonary angiograms (CTPA) scans between February 2010 and March 2012 were included. Results were reviewed for algorithm compliance, patient risk stratification and PE prevalence. A higher D-dimer and an age-adjusted D-dimer cut-off were then retrospectively applied to the algorithm and results were re-evaluated. RESULTS: Pre-test probabilities between the current and original study remain within 1%, with slightly higher PE prevalence in the original study (12.7% vs 13.8%). Of the imaged cases, 14% (42/300) were not compliant with the algorithm. Of the low- and moderate-risk patients that underwent D-dimer testing, the retrospective application of 0.5 mg/L D-dimer cut-off resulted in a further 12.1% (95% confidence intervals 8.0-17.1%) of patients excluded from undergoing a CTPA. When combined with an age-adjusted D-dimer cut-off, 27.9% (60/215 95% confidence intervals 22.0-34.3%) were excluded from undergoing a CTPA. CONCLUSION: The implemented algorithm has maintained risk stratification and PE prevalence results. Along with evidence in other studies, we have shown that raising the D-dimer and applying age-adjusted D-dimer cut-offs might improve the efficiency of the clinical prediction algorithm in patients aged over 50.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

BACKGROUND: Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. AIMS: To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. METHODS: A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. RESULTS: Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). CONCLUSION: Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.

Seasonal recurrence of food bolus obstruction in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a newly recognised condition that is apparently increasing in prevalence, and the aetiology is poorly understood. The role of aeroallergens in EoE is controversial, given the success of dietary therapy. Massive aeroallergen exposure leading to food bolus obstruction events (FBOE) has been described, and the diagnosis of EoE by esophageal biopsy noted to be more common in the pollen season according to previous case series. AIM: To determine if a seasonal variation and a geographical variation occurred in EoE presenting as FBOE in adults, and to track the prevalence of FBOE and EoE over time. METHOD: A retrospective case-control study analysis was performed from January 2002 to January 2012 to identify all FBOE in adults presenting to five tertiary hospitals in Melbourne, Australia. Endoscopy, histopathological reports, case notes and blood tests were examined, and postcodes recorded. Records of pollen counts were obtained. Cases were defined according to esophageal biopsy and grouped based on month of diagnosis. All other causes of FBOE served as controls. RESULTS: One thousand, one hundred and thirty-two FBOE were identified. Biopsies were only performed in 278 of these cases, and 85 patients were found to have EoE after biopsy. Patients with EoE were younger (mean age 38 years, range 18-72) compared with those with alternative diagnosis (mean age 64.4 range 22-92), more likely to be male (M : F = 4:1 compared with 1.68:1 ) and had a higher eosinophil count in venous blood. Overall no seasonality was demonstrated in FBOE secondary to any diagnosis, although the six cases of recurrent FBOE secondary to EoE mainly occurred in the grass pollen season in subsequent years. FBOE cases were evenly distributed throughout metropolitan Melbourne irrespective of population density. EoE as a percentage of FBOE increased over time. CONCLUSION: Seasonal aeroallergens may be important for a subgroup of patients with EoE presenting as recurrent FBOE. Esophageal biopsies are performed in a minority of patients, representing a significant departure from ideal management and contributing to recurrent unnecessary FBOE. EoE is an increasingly important cause of FBOE.

Risk factors for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic antigen driven disease, whereby food and/or aeroallergens result in inflammation and luminal narrowing, and the clinical symptoms of dysphagia and food bolus obstruction events (FBOE). Established risk factors are male gender, Caucasian race and atopy. Increased risk amongst family members, and a single nucleotide polymorphism (SNP) in a gene coding thymic stromal lymphopoietin (TSLP) on the pseudoautosomal region of the X and Y chromosomes supports a genetic predisposition. Environmental factors including the timing and nature of food and aeroallergen exposure to the developing immune system may be important, whilst esophageal barrier function integrity and the influence of microbiota are worthy of future research.

Junior doctor training in pleural procedures: a quality survey.

Pleural effusion is a common medical condition encountered by doctors. This study was conducted to ascertain the level of junior doctor (physician-in-training) training, knowledge and supervision in the management of pleural effusion. The information was collected with the help of a proforma, from 49 junior medical doctors working in a metropolitan health service. All the doctors who participated in the survey had come across pleural effusion in their practice, but only 67% of doctors had any experience with the procedure of diagnostic thoracentesis. Sixty-seven percent of doctors conveyed that they will refer the majority of cases (75-100%) for radiological-guided thoracentesis. The main reasons for referral for radiologically guided procedure were lack of experience (65%), fear of complications (61%), lack of supervision and guidance (49%), and lack of time (38%). A significant proportion of doctors interviewed (47%) was unaware of the major indications for intercostal tube drainage of parapneumonic effusions. This survey highlights deficiencies in junior doctor knowledge and procedural skills. Junior doctor training should be tailored to increase the 'hands-on' training time and increased patient contact. Senior clinicians should be given sufficient 'protected time' for teaching and training.

Implementation of a clinical prediction tool for pulmonary embolism diagnosis in a tertiary teaching hospital reduces the number of computed tomography pulmonary angiograms performed.

AIM: To evaluate the effect of implementing the Wells score clinical prediction tool (CPT) on rationalising the use of computed tomography pulmonary angiography (CTPA) for diagnosing pulmonary embolism (PE). METHODS: Within a tertiary teaching hospital, a retrospective study was conducted applying Wells score to all CTPA ordered in the first quarter of 2007. Subsequently, an algorithm including Wells score and d-dimer assay was developed to assist clinicians in rationalising their ordering of CTPA. A prospective study was performed from February to August 2009 to assess the impact of this algorithm. CTPA results, d-dimer levels, referral sources and dates were recorded. The number of CTPA performed over a 7-month period following implementation of the algorithm was compared with the same period during the previous year. PE prevalence within each risk category was compared with the published literature. RESULTS: Three hundred and thirty-three patients were investigated with CTPA in the prospective study period. Two hundred and sixty-eight patients (80.4% of cases) had complete data. The prevalence of PE in the present study was 13.8% with 57 (21.2%) patients stratified to low risk, 169 (63.0%) to intermediate risk and 42 (15.6%) to high risk. Subgroup prevalence was 8.8%, 11.8% and 23.8% respectively. Compared with the same period in 2008, 121 (26.6%) less CTPA were performed. CONCLUSION: Institutional implementation of a clinical prediction tool into the decision-making process is feasible and significantly reduces the number of CTPA being performed, with substantial cost savings and patient benefits.

Ear-acupressure for allergic rhinitis: a systematic review.

BACKGROUND: Allergic rhinitis affects 10-40% of the population globally with a substantial health and economic impact on the community. OBJECTIVE OF REVIEW: To assess the effectiveness and safety of ear-acupuncture or ear-acupressure for the treatment of allergic rhinitis by reviewing randomised controlled trials and quasi-randomised controlled trials. TYPE OF REVIEW: This review followed the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. SEARCH STRATEGY: A total of 21 electronic English and Chinese databases were searched from their respective inceptions to April 2008. Key words used in the search included the combination of ear, auricular, acupuncture, acupressure, acupoint, allergic, allergy, rhinitis, hayfever, randomised clinical trial and their synonyms. EVALUATION METHOD: The methodological quality was assessed using Jadad's scale. The effect size analysis was performed to explore the difference between interventional groups. RESULTS: Ninety-two research papers were identified and seven of them referring to five studies met the inclusion criteria. All included studies involved ear-acupressure treatment. These studies mentioned randomisation, but no details were given. None of the five studies used blinding or intention-to-treat analysis. Ear-acupressure was more effective than herbal medicine, as effective as body acupuncture or antihistamine for short-term effect, but it was more effective than anti-histamine for long-term effect. CONCLUSIONS: The benefit of ear-acupressure for symptomatic relief of allergic rhinitis is unknown due to the poor quality of included studies.

Associations between fatty acids in colostrum and breast milk and risk of allergic disease.

BACKGROUND: Exposure to n-3 polyunsaturated fatty acids (PUFA) in early life is hypothesized to offer protection against atopic disease. However, there is controversy in this area, and we have previously observed that high levels of n-3 fatty acid (FA) in colostrum are associated with increased risk of allergic sensitization. OBJECTIVE: The aim of the study was to assess the relationship between FA profile in breast milk and risk of childhood atopic disease. METHODS: A high-risk birth cohort was recruited, and a total of 224 mothers provided a sample of colostrum (n=194) and/or 3-month expressed breast milk (n=118). FA concentrations were determined by gas chromatography. Presence of eczema, asthma and rhinitis were prospectively documented up to 7 years of age. RESULTS: High levels of n-3 22:5 FA (docosapentaenoic acid, DPA) in colostrum were associated with increased risk of infantile atopic eczema [odds ratio (OR)=1.66 per 1 standard deviation increase, 95% confidence interval (CI)=1.11-2.48], while total n-3 concentration in breast milk was associated with increased risk of non-atopic eczema (OR=1.60, 95% CI=1.03-2.50). Higher levels of total n-6 FA in colostrum were associated with increased risk of childhood rhinitis (OR=1.59, 95% CI=1.12-2.25). There was no evidence of associations between FA profile and risk of asthma. CONCLUSION: In this cohort of high-risk children, a number of modest associations were observed between FA concentrations in colostrum and breast milk and allergic disease outcomes. Further research in this area with larger sample sizes is needed.

Flow and particle deposition patterns in a realistic human double bifurcation airway model.

Velocity profiles, local deposition efficiencies (DE), and deposition patterns of aerosol particles in the first three generations (i.e., double bifurcations) of an airway model have been simulated numerically, in which the airway model was constructed from computed tomography (CT) scan data of real human tracheobronchial airways. Three steady inhalation conditions, 15, 30, and 60 L/min, were simulated and a range of micrometer particle sizes (1-20 mum diameter) were injected into the model. Results were then compared with experimental and other numerical results which had employed either similar model geometry or test conditions. The effects of inhalation conditions on velocity profiles and particle deposition were studied. The data indicated that the local deposition efficiencies in the first bifurcation increased with a rise in the Stokes number (St) within St range from 0.0004 to 0.7. Within the same St range, DE in the second bifurcations (both left and right) was dropped dramatically after St increased to 0.17. Also, the second bifurcation in the right side (B2.1, closer to first bifurcation than left side, B2.2) was found to show a much higher (almost double) DE than the left side. This may be due to the fact that the left main bronchus is longer and has greater angulation than the right main bronchus. Generally, the present simulation using a computational fluid dynamic (CFD) technique obtained concurrent results with subtle differences compared to other works. However, due to omission of larynx in the model, which is known to significantly modify airflow and hence particle deposition, the present model may only serve as the "stepping stone" to simulating and analyzing dose-response or inhalation risk assessment visually for clinical researchers.

A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis.

BACKGROUND: Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE). AIM: To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm. METHODS: Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group). RESULTS: Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission. CONCLUSIONS: Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.

Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities.

BACKGROUND: The use of allergy tests to guide dietary treatment for eosinophilic oesophagitis (EoE) is controversial and data are limited. Aeroallergen sensitisation patterns and food triggers have been defined in Northern Hemisphere cohorts only. AIMS: To determine if allergy tests that are routinely available can predict food triggers in adult patients with EoE. To define the food triggers and aeroallergen sensitisation patterns in a novel Southern Hemisphere (Australian) cohort of patients. METHODS: Consecutive patients with EoE who elected to undergo dietary therapy were prospectively assessed, demographic details and atopic characteristics recorded, and allergy tests, comprising skin-prick and skin-patch tests, serum allergen-specific IgE, basophil activation test and serum food-specific IgG, were performed. Patients underwent a six-food elimination diet with a structured algorithm that included endoscopic and histological examination of the oesophagus a minimum of 2 weeks after each challenge. Response was defined as <15 eosinophils per HPF. Foods defined as triggers were considered as gold standard and were compared with those identified by allergy testing. RESULTS: No allergy test could accurately predict actual food triggers. Concordance among skin-prick and serum allergen-specific IgE was high for aeroallergens only. Among seasonal aeroallergens, rye-grass sensitisation was predominant. Food triggers were commonly wheat, milk and egg, alone or in combination. CONCLUSIONS: None of the currently-available allergy tests predicts food triggers for EoE. Exclusion-rechallenge methodology with oesophageal histological assessment remains the only effective investigation. The same food triggers were identified in this southern hemisphere cohort as previously described.

Chronic airflow obstruction in long-term survivors of allogeneic bone marrow transplantation.

Prospective pulmonary function tests (PFTs) of 49 long-term survivors of identical sibling bone marrow transplants (BMT) were analysed. Eight (16%) developed a persistent pulmonary syndrome characterised by a late onset, cough and dyspnoea, hyperinflation or patchy infiltrates on plain radiography and episodic bacterial infections. The predominant PFT pattern was obstructive (reduced forced expiratory ratio, FER) with a variable restrictive component (reduced vital capacity, VC). When compared with the other 41 patients (controls), mean FER (53% absolute) and VC (73% predicted) were significantly lower at 12 months (P = 0.005). Graft-versus-host disease (GVHD) was the only identifiable risk factor (odds ration 7.1). Five of 7 patients compared with 4 of 31 controls tested at 3 months had an abnormal FER or maximum mid-expiratory flow rate (MMFR), but not VC, prior to the onset of symptoms (P = 0.015). Patients with mild to moderate disease (FER 50-70%) had stable pulmonary function while severe cases progressed despite immunosuppressive agents. Earlier recognition of this syndrome by a reduced FER or MMFR may allow the initiation of therapy at a potentially reversible stage.

Eicosanoids and asthma: an update.

There have been significant advances in our understanding of the role of eicosanoids as mediators in inflammation since their discovery over 50 years ago. Our more recent understanding of asthma as an inflammatory disease has led to the appreciation of eicosanoids potentially being pivotal mediators in promoting some of the changes in asthma. Of particular importance are the cysteinyl LTs in producing bronchospasm and bronchial hyperresponsivenss, and PGE2 in modulating the bronchospastic and inflammatory response. Evidence from clinical studies suggests that other eicosanoids may also contribute, but their importance is secondary and their relative contributions vary between individuals. The development of new drugs based on our partial understanding of the role that eicosanoid mediators may play in asthma promises new approaches to the treatment of this common chronic inflammatory condition.