Eur Resp Research Articles

PULMONARY FIBROSIS AND FOOT DROP: A CASE OF MICROSCOPIC POLYANGIITIS FOLLOWING IDIOPATHIC PULMONARY FIBROSIS (IPF) DIAGNOSIS

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Pulmonary fibrosis (PF) associated with antineutrophil cytoplasmic antibody (ANCA) is a rare but described diagnosis, with some patients meeting criteria for microscopic polyangiits (MPA). Conversion to ANCA-MPO positivity and MPA with vasculitic findings can lag behind the initial diagnosis of PF. CASE PRESENTATION: We present a case of a 75 year old man with a history of a bladder tumor and PF who presented to clinic with 6 months of worsening cough, fatigue, weight loss and neuropathy. His PF was initially diagnosed 1 year prior and considered idiopathic. At that time he had an abnormal CT chest, significantly decreased DLCO, positive ANA, and normal inflammatory markers. Approximately one year later he complained of progressive cough, fatigue and weight loss, and was hospitalized for anemia and leukocytosis with an unrevealing workup. He was prescribed antibiotics for Aeromonas pneumonia. He then presented to clinic where his physical exam was notable for mild tachypnea, left foot drop and right hand numbness. PFTs revealed a significant decline in vital capacity and DLCO. He was admitted and workup revealed CT chest with new infiltrates, an elevated ANA, elevated ESR/CRP and elevated ferritin. ANCA- MPO was positive. He underwent sural nerve and skeletal muscle biopsy which showed necrotizing vasculitis with fibrinoid necrosis, and he was started on high dose steroids. He improved and was discharged to home to start rituximab infusion as outpatient. DISCUSSION: Pulmonary fibrosis associated with ANCA vasculitis is rare and typically associated with MPA. Case studies have placed prevalence of ANCA positive PF from 2-14% of PF patients initially considered idiopathic. Of those patients, about half had seroconversion/develop MPA after initial PF diagnosis. CT imaging for ANCA-MPO patients may be indistinguishable IPF on imaging with a UIP pattern of fibrosis. The pathogenesis of ANCA-MPO associated fibrosis is unclear, but possibly related to recurrent alveolar hemorrhage, direct damage from neutrophils or ANCA induced by a pulmonary inflammatory process. ANCA positive PF patients are more likely to be treated with steroids and immunosuppression including cyclophosphamide or ritxumab. These treatments may be useful in early disease, but likely have limited efficacy in late stage/fibrotic disease. Patients with MPA and PF have a clinical progression similar to patients with IPF, with worse survival compared to MPA patients without PF. Not all PF patients with ANCA-MPO positivity develop systemic vasculitis, however, clinicians should be on alert for signs and symptoms of systemic disease as early intervention could prevent progression. CONCLUSIONS: It is important to consider ANCA vasculitis both at the time of diagnosis of pulmonary fibrosis and later in a patient’s clinical course. Reference #1: Casares MF, Gonzales MF, Caputo F, Bottinelli Y, Zamboni M. Microscopic polyangiitis associated with pulmonary fibrosis. Clin Rheumatol 2015 34:1273-1277. Reference #2: Kagiyama N, Takayanagi N, Kanauchi T, et al. Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis.BMJ Open Respiratory Research 2015;2:e000058. Reference #3: Tzelepis GE, Kokosi M, Tzioufas A, et al. Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis. Eur Resp J 2010; 36:116-121 DISCLOSURES: No relevant relationships by Samantha Parker, source=Web Response

ATYPICAL ATYPICALS: TWO CASES OF MACROLIDE-RESISTANT MYCOPLASMA PNEUMONIAE INFECTIONS

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Mycoplasma pneumoniae pneumonia is self-limiting in most cases, and is usually treated with macrolide antibiotics. However, macrolide resistance is increasingly recorded especially in South East Asia, where prevalence has been reported to be as high as 90%. The following cases describe two patients at a U.S. hospital who had severe community-acquired M. pneumoniae pneumonia (CAP) that did not respond to macrolide therapy. CASE PRESENTATION: Patient 1: A 45-year-old female was admitted to the hospital with acute hypoxemic respiratory failure and a left lower lobe pneumonia on imaging. She reported a week of respiratory symptoms, which had been treated with amoxicillin-clavulanate without improvement. The serum Mycoplasma IgM antibody titer was elevated (4.89, threshold 0.91) on admission. Patient 2: A 74-year-old female was re-admitted to the hospital with worsening hypoxemic respiratory failure. She had been admitted a week prior with similar symptoms. During that hospitalization her Mycoplasma IgM antibody titer was below diagnostic threshold (0.09). On re-admission, the Mycoplasma IgM titer had significantly increased (3.59), and she had a right middle lobe predominant pneumonia.. In each case, Mycoplasma PCR was positive, and azithromycin was started. However the patients remained profoundly hypoxemic requiring oxygen via high flow nasal cannula and the antibiotic regimen was expanded to include vancomycin and piperacllin-tazobactam without much clinical change. Azithromycin was switched to levofloxacin around hospital day 3 in each case, considering the possibility of macrolide resistance. The patients' hypoxemia and radiographic abnormalities began to improve significantly with fluoroquinolone therapy. DISCUSSION: M. pneumoniae lacks a cell wall and is thus intrinsically resistant to antibiotics that target the cell wall. The mainstays of therapy include macrolides, ketolides, tetracyclines and fluroquinolones. Resistance to antibiotic therapy occurs through acquired mutations affecting the ribosomal targets of macrolide antibiotics, most commonly the A2058G mutation in the 23S rRNA. The prevalence of macrolide resistance is extremely high in Asia, with rates up to 100% being reported in countries like China. In North America, macrolide resistance rates are 3-13% across various studies. Europe, in contrast, has lower rates of resistance (0-10%) with the exception of Italy (26%). While most studies have reported similar clinical severity amongst M. pneumoniae infections regardless of susceptibility, the patients in our series had significant hypoxemia and were at risk of poor outcomes without the change in antibiotic regimen based on recognition of potential macrolide resistance. CONCLUSIONS: Macrolide-resistant M. pneumoniae infections represent a clinical entity that should be recognized early to initiate prompt antibiotic changes and initiate effective treatment. Reference #1: Pereyre S, Goret J, Bébéar C. Mycoplasma pneumoniae: Current Knowledge on Macrolide Resistance and Treatment. Front Microbiol. 2016;7:974. Reference #2: To KKW, Chan KH, Fung YF, Yuen KF, Ho PL. Azithromycin treatment failure in macrolide-resistant Mycoplasma pneumoniae pneumonia. Eur Resp Journal 2010 36: 969-971. Reference #3: Cao B, Zhao CJ, Yin YD, et. al. High prevalence of macrolide resistance in Mycoplasma pneumoniae isolates from adult and adolescent patients with respiratory tract infection in China. Clin Infect Dis. 2010 Jul 15;51(2):189-94. DISCLOSURES: No relevant relationships by Alok Bhatt, source=Web Response No relevant relationships by John Munger, source=Web Response

WS18.3 Accuracy of modelling future trends in cystic fibrosis demography using the French Cystic Fibrosis Registry

Background We have previously modelled future trends in CF demography by calculating flows of patients entering and exiting CF cohorts (Burgel et al. Eur Resp J 2015). These forecasts, which were based on the assumption that major demographic trends remained stable over time, suggested a major increase in the number of CF adults in western European countries by 2025. Objectives To examine the effects of large variations in CF mortality or incidence on estimated numbers of CF patients. Methods Using the flow method on data from the French CF Registry from 2003 to 2012, we estimated numbers of CF children and adults by 2025 (main analysis). Because this analysis assumed that flows remained stable, we examined the impact large variations in CF incidence or mortality on future numbers of CF patients. Results In 2012, there were 6145 CF patients (3099 children; 3046 adults) in the French CF Registry. Applying average flows to these data, the number of CF patients will increase to 8344 patients (3534 children; 4810 adults) by 2025. Assuming a 50% decrease in pediatric and adult mortality, the number of CF patients in 2025 will increase to 8911 patients (+567 patients; +7%) including 3601 children (+67 children; +2%) and 5310 adults (+500 adults; +10%) as compared with the main analysis. Assuming a decrease in CF incidence by 30%, the estimated number of CF patients in 2025 will be 7969 patients (–375 patients; –4%) including 3159 children (–442 children; –12%) and 4810 adults (unchanged). Conclusion Large variations in CF mortality or incidence would have only minimal impact on the major increase in the number of CF adults that is expected in France by 2025.

32 Influence of Sleep Apnoea on Biventricular Pacing, Heart Rate Trend and Tachyarrhythmia’s in Heart Failure Patients who have undergone Cardiac Resynchronisation Therapy

Introduction Sleep apnoea syndrome (SAS) has been reported in 40–60% of people with heart failure (HF) 1 with varying reports as to whether this is predominantly central or obstructive. Undiagnosed intermittent hypoxia during sleep increases sympathetic activation and endothelial dysfunction so may worsen cardiac outcomes. SAS also prevents the normal drop in heart rate that accompanies the onset of sleep and coupled with reflex increases in central sympathetic outflow could lead to the development of recurrent nocturnal ischaemia and arrhythmias. 2 We compared average heart rate, percentage of Biventricular pacing and logged tachyarrhythmia’s in those with and without recently diagnosed SAS in a specific cohort of HF patients who underwent cardiac resynchronisation therapy (CRT). Method Prospective, cross-sectional study. 37 Consecutive HF patients, 30 males, mean (SD) age= 69.8 (8.4) yrs, BMI 29.3 (8.7) kg/m 2 , and mean LVEF 25 (7)% – who were referred to a UK tertiary cardiac centre for CRT according to National Guidelines. They underwent baseline limited channel sleep studies (Apnea Link TM ResMed, Abingdon, UK) immediately prior to CRT. All patients were deemed on optimal medication at the discretion of a cardiologist. None had known SAS. An apnoea hyopnea index (AHI) >15 events per hour was deemed a positive result for treatable SAS according to UK guidelines. Average heart rate, percentage of biventricular pacing and logged tachyarrhythmias were obtained from six weeks post CRT follow up. Results 20 from 37 (54%) had an AHI >15 events per hour. All 20 patients had predominantly obstructive sleep apnoea, 5 of these 17 patients had some central sleep apnoea, but this was still less than their obstructive episodes. None had predominantly central sleep apnoea. Conclusion There is a high prevalence (54%) of significant SAS in the group of heart failure patients referred for CRT. Unlike other studies we found a relatively low prevalence of central sleep apnoea. There was no difference in average heart rate and percent of biventricular pacing in those with and without SAS. However there is increased incidence of tachyarrhythmias in those with SAS and this might be explained by recurrent hypoxia and increased sympathetic activity in sleep apnoea patients. References Eur Resp J. 2007;29(6):1201-5 Circulation 2003;107:1671-8

P228 Efficacy And Safety Of Fluticasone Propionate/formoterol In Paediatric Patients With Asthma

Background Fluticasone propionate (FP) and formoterol (FORM) have been combined in a single inhaler (FP/FORM; flutiform ®) for the treatment of adolescents and adults with asthma. This study assessed the efficacy and safety of FP/FORM in paediatric asthma patients. Methods A total of 512 patients aged 5 to <12yrs were randomised 1:1:1 to 12 weeks of treatment with either FP/FORM (100/10 µg BID), FP (100 µg BID) or fluticasone propionate/salmeterol (FP/SAL) (100/50 µg BID) in a double-blind, parallel group, multicentre study. The objectives were to demonstrate superiority of FP/FORM to FP and non-inferiority to FP/SAL. The primary endpoint was the change from predose FEV1 at baseline to 2-hour postdose FEV1 over the 12 weeks. The two key secondary endpoints were FEV1 AUC0–4h at Week 12 and change from pre-dose FEV1 over the 12 weeks. Results FP/FORM was superior to FP for change from predose FEV1 at baseline to 2-hour postdose FEV1 (treatment difference = 0.07 L; 95% CI: 0.03, 0.11; p < 0.001) and FEV1 AUC0–4h at Week 12 (treatment difference = 0.09 L; 95% CI: 0.04, 0.13; p < 0.001). FP/FORM was non-inferior to FP/SAL for change from predose FEV1 at baseline to 2-hour postdose FEV1 (treatment difference = -0.00 L; 95% CI: -0.04, 0.04; p < 0.001), AUC0–4h at Week 12 (treatment difference = 0.01 L; 95% CI: -0.03, 0.06; p < 0.001) and change from predose FEV1 (treatment difference = -0.02 L; 95% CI: -0.06, 0.02; p < 0.001). The safety and tolerability profiles of all treatments were similar. Conclusion In children 5 to <12yrs with asthma, FP/FORM was superior to FP, and non-inferior to FP/SAL for improvements in lung function, with a similar tolerability profile to both FP and FP/SAL. Disclaimer Acknowledgement: Reproduced with permission of the European Respiratory Society: Eur Resp J September 2014; 44, Suppl. 58: In Press

P238 The Effect Of Inhalation Duration On Lung Deposition With A Pressurised Metered-dose Inhaler (pmdi)

Rationale Although the guidance for using a pMDI is to inhale ‘slow and deeply’, many patients inhale fast over a short duration. The ERS/ISAM Task Force suggested ‘slowly’ equates to inhaling over 4–5 seconds (s) for adults1, a much clearer instruction. This study therefore examined the influence of inhalation time on total lung deposition (TLD) using Functional Respiratory Imaging (FRI). Methods Three-dimensional airway models of 6 asthma patients (mean FEV1 83%), treated with an ICS/LABA combination, were included. The lung deposition characteristics of an HFA-based pMDI (MMAD ~3.0μm; fine particle fraction (FPF) ~40%) were assessed using FRI. Simulations were performed on 3 different inhalation profiles matched for the same inspiratory volume (3 L) with durations of 1s, 3s and 5s and actuation at start of inhalation. Results For the 1s, 3s and 5s profiles, the TLD values were 22.81 ± 3.71%, 36.13 ± 2.51% and 41.61 ± 3.11% of nominal dose respectively, and were predicted using a concave down quadratic model (R2 = 0.87, p Conclusions A 5 s inhalation led to highest TLD with greatest peripheral deposition. Increased deposition with longer times mainly reflected increased peripheral deposition, central deposition was less affected by flow rate. These data support ERS/ISAM guidance for inhaling over 4–5 sec to optimise deposition, although similar TLD were achieved with 3s. These data also suggest that high FPF pMDIs can achieve reasonable deposition even with short, fast inhalations. References Laube BL, et al . ERJ 2011;37(6):1308–417 Disclaimer acknowledgement: Reproduced with permission of the European Respiratory Society: Eur Resp J September 2014; 44, Suppl. 58: In Press

P168 Reduced Gas Transfer (tlco) Predicts Poor Outcome In Patients With Pulmonary Hypertension And Heart Failure With Preserved Ejection Fraction

<h3>Rationale</h3> There is limited data on predictors of survival in patients with Pulmonary Hypertension (PH) in the context of Heart Failure and Preserved Ejection Fraction (HF-pEF). Simple non-invasive tests to aid the physician in prognostication would be valuable. The aim of this study was to examine demographic and non-invasive predictors of outcome in PH-HF-pEF in a large well phenotyped PH registry. <h3>Method</h3> In the ASPIRE Registry (Hurdman J <i>et al</i> Eur Resp J, 2012), 1737 consecutive, incident, treatment-naıve patients with suspected PH underwent diagnostic evaluation between February 2001 and 2010. Patients were diagnosed as PH-HF-pEF if no other causes of PH could be identified and they fulfilled the following criteria: signs and symptoms of heart failure; mean pulmonary artery pressure ≥25 mmHg at rest and pulmonary arterial wedge pressure &gt;15 mmHg by RHC; preserved left ventricular systolic function (ejection fraction ≥50%) by echocardiography or CMR. Predictors of survival were assessed using forward stepwise Cox regression analysis. Variables with a p-value <h3>Results</h3> 98 patients who fulfilled the diagnostic criteria for PH-HF-pEF were identified. Maximum duration of follow-up was 10 years with a mean follow up 4.9 ± 2.3 years, during which 33 (34%) patients died. After multivariate analysis, only ISWT distance HR 0.99 CI (0.99–1.00) and TLCO HR 0.96 CI(0.94–0.98) at baseline, were predictors of outcome (p &lt; 0.01). Median predicted TLCO in the PH-HF-pEF population was 65%. The 5-year survival in those with a TLCO &lt;65% predicted was 60%, compared with 85% in those whose TLCO was ≥65% (p &lt; 0.01). <h3>Conclusions</h3> Simple non-invasive testing such as TLCO and exercise capacity measured by the ISWT predict outcome in patients with PH-HF-pEF.

P100 The Feasibility Of Using Commercial Multiple Breath Nitrogen Washout Devices In School-aged Children

Background Multiple breath inert-gas washout (MBW) using sulphur hexafluoride (SF 6 ) measured by mass spectrometry (MS), is sensitive to early lung disease in children with Cystic Fibrosis (CF) 1 but is not widely available. To increase the accessibility of MBW, commercial devices have been adapted using nitrogenwashout (N 2 -MBW). Our aim was to assess the feasibility of two commercial N 2 -MBW devices as supplied by the manufacturers compared to a custom-built MS system in school-aged children. Methods Patients with CF and controls performed MBW on three devices; the Exhalyzer ® D (ECO MEDICS AG); the EasyOne Pro ® LAB (ndd Medizintechnik AG) and the MS system (AMIS 2000, Innovision ApS) on the same test occasion (order randomised). Attempts were made to obtain 3 technically acceptable runs/device (maximum 8 attempts on each). During testing children watched a DVD and were encouraged to breathe normally. Data were analysed using the ‘clinical application’ setting for both commercial devices, and customised software for the MS. Quality control was in accordance with the ATS/ERS consensus statement 1 and manufacturers’ guidelines. Results 14 control (mean[range]age: 15.0[12.5–16.7]yrs) and 18 children with CF (13.5[7.8–17.4]yrs) were assessed. The median (range) number of runs attempted were: MS 3(3–8), Exhalyzer ® D 4(3–6), EasyOne Pro ® LAB 4(3–8). Average calibration time was shorter for EasyOne Pro ® LAB (5 min) than either MS (11 mins) or Exhalyzer ® D (12 min). Total test duration was similar between devices and dependent on disease severity. 3 acceptable MBW runs were achieved in all children using the MS, 75% with the EasyOne Pro ® LAB, and 47% on the Exhalyzer ® D system (see Table). Reasons for failure with Exhalyzer ® D were usually due to technical/equipment problems, whereas for the EasyOne Pro ® LAB these were generally associated with marked changes of breathing pattern at commencement of washout, leading to exclusion of one or more runs. Discussion Despite use in an experienced MBW centre, our initial attempts to implement commercial MBW devices according to manufacturers’ guidelines resulted in a relatively low success rate in schoolchildren when compared to MS. Subsequent feedback to manufacturers has led to further adaptations which should improve feasibility in future, although this has yet to be assessed in very young children. Reference Robinson et al . Eur Resp J 2013

P233 Efficacy and safety of once-daily glycopyrronium compared with blinded tiotropium in patients with COPD: the GLOW5 study

BackgroundGlycopyrronium, a once-daily long-acting muscarinic antagonist (LAMA), has demonstrated a similar efficacy and safety profile to open-label tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).1 The GLOW5 study...

P78 Physical Inactivity is Associated with Mid-Thigh Intramuscular Fat in Patients with COPD

IntroductionQuadriceps muscle impairment is an important complication of COPD occurring in mild as well as more advanced disease1. This is driven by physical inactivity and can include muscle atrophy and/or...

Abstract B16: Histology and intervention related miRNA expression changes from baseline to follow-up paired bronchial biopsies of patient in the iloprost chemoprevention trial

Abstract The iloprost lung cancer chemoprevention trial is the first to meet a primary endpoint of improvement in endobronchial histology, which is currently considered to be the best intermediate endpoint for chemoprevention (Keith et al, Cancer Prev Res, 2011). This placebo-controlled study offers the opportunity for discovering other surrogate endpoints and predictive biomarkers to incorporate into chemoprevention trials. We compared miRNA expression in follow-up (FU) versus baseline biopsies in relation with histology change or not globally and stratified by treatment arm and smoking status. In the 152 patients randomized in the iloprost trial, the paired baseline and FU biopsies were available in 125 patients: 40/35 current/former smokers in the iloprost arm and 25/25 current/former smokers in the placebo arm, respectively. We planned to analyze 500 biopsies: four biopsies from each of the 125 patients, 2 biopsies at baseline (worst and best diagnosis) and 2 biopsies at FU at the same site after six months of treatment with iloprost or placebo. We selected and analyzed 14 miRNAs differentially expressed during squamous cell lung carcinogenesis in our previous study (Mascaux et al, Eur Resp J, 2009). In total, 496/500 biopsies with appropriate tissue were available. For every biopsy, total RNA was extracted from 8 adjacent 4 um cuts of formalin fixed paraffin embedded (FFPE) adjacent to the diagnostic section. A good reproducibility of the previously published data for the expression changes in the 14 miRNA accross lung preneoplasia stages was shown in the current study in baseline samples. This new study identifies significant changes in miR-34c expression between paired samples when histology is up- or downgraded. miR-34c is significantly down-regulated in paired biopsies when histology is up-graded and inversely. This correlation between miR-34c expression and histology changes is shown including all samples (r spearman correlation=0.23 p=0.0003), but also consistently in subgroups (iloprost.arm, current r=0.26, p=0.041 and former smokers r=0.24, p=0.066, placebo arm, current (r=0.23, p=0.046)). In contrast, miR-9 was significantly down-regulated in follow-up as compared with baseline biopsies, but was not correlated with histology changes. The down-regulation of miR-9 in follow-up versus baseline samples was found in all samples (t test, p&amp;lt;0.0001) and was consistent in all and significant in most of subgroups (iloprost arm, all patients (p=0.0007) and current smokers (p=0.0023) and placebo arm, all patients (p=0.001), current smokers (p=0.047) and former smokers (p=0.0071). In conclusion, miR-34c, a transcriptional target of p53 which is down-regulated by hypermethylation in lung cancer, is down-regulated when histology changes from the normal bronchial mucosa to high-grade bronchial lesions, and inversely, independently of treatment and smoking status. miR-34c expression is a good reflection of baseline histology and histology changes. Alternatively, miR-9 is systematically down-regulated in follow-up biopsies 6 months later at the same site independently of histology, treatment and tobacco status. This suggests that the down-regulation of miR-9 in the follow-up samples may be related to the biopsy: this miRNA could be involved in the tissue repair.

The Usefulness of Screening for Cardiopulmonary Complications in Asymptomatic Sickle Cell Patients in the United Kingdon (UK)

Background: Pulmonary hypertension (PHT) and chronic lung disease (CLD) are the chronic cardiorespiratory complications recognized in sickle cell disease (SCD). Although the incidence of these complications has been reported to be important, even in the asymptomatic patients, there is no data of the prevalence of these problems in a UK sickle population. Therefore, we established a ‘one-stop’ cardiopulmonary sickle screening clinic, which ran in conjunction with a routine review.Method: Adult patients with a diagnosis of SCD (HbSS, HbSC, HbSBthalassaemia), irrespective of symptoms were approached either during an outpatient visit, by a letter or telephone over a 4 month period. The initial screening tests consisted of an echocardiogram and pulmonary function tests (PFTs). Transthoracic Doppler echocardiography was used to measure tricuspid regurgitant jet velocity (TRV) Pulmonary hypertension was defined as a peak TRV of ≥ 2.5m/s and moderate to severe PHT was defined as a peak TRV ≥ 3m/s (Gladwin et al NEJM 2004). Spirometric tests were classified as normal, restrictive, and obstructive with a FEV1/FVC ratio of 70–80%, >80% and <70%, respectively (Eur Resp J, 1993). The patients' perspective of this approach was evaluated by a psychologist using a short semi-structured interview either in person or via telephone.Results: 62 patients agreed to take part, but only 44 (71%) attended the ‘one-stop clinic’. 29 patients had HbSS, 13 patients had HbSC, 1 patient had HbSB0 and 1 had HbSB+thalassaemia. Mean age (SD) was 36.6 years (9.5), and 20 participants were men. 30 patients had both an echocardiogram and full PFTs as planned. An additional 4 patients had an echocardiogram alone and 10 had PFTs alone. 2 patients were excluded due to an acute vasoocclusive crisis at the time of the test. Only 3/32 (9.4%) patients had abnormal echocardiograms with peak TRVs of 2.5, 2.5 and 2.6 m/s, respectively. Of the 38 patients, spirometry was normal in 6/38 (16%), restrictive in 13/38 (34%) and obstructive in 6/38 (16%). Interestingly, isolated low total lung capacity (TLC) was found in 13/38 (34%). Of the patients who a TRV≥ 2.5m/s, 2/3 had obstructive spirometry and 1/3 had an isolated low TLC. There was no association with type of SCD, use of hydroxyurea or previous chest crises. Finally, 18/44 (41%) of patients completed the interview with the majority reporting that the increased time spent in clinic was not obviously beneficial.Conclusion: The uptake of the ‘one-stop’ clinic for asymptomatic patients with SCD was reasonable. Although we found 32/38 (84%) patients had an abnormality of their PFTs, the echocardiographic data do not concur with the published data with respect to the prevalence of PHT in the asymptomatic SCD population. This needs further assessment on a large scale. Finally, the ‘one stop’ cardiopulmonary screening clinic does not appear a clinically effective use of resources in the UK with little perceived benefit by the patients.

Review of "Pharmacological strategies of self management of asthma exacerbations." Reddel H, Barnes D, on behalf of Exacerbation Advisory Panel. Eur Resp J 2006; 28: 182-199.

Review of "Pharmacological strategies of self management of asthma exacerbations." Reddel H, Barnes D, on behalf of Exacerbation Advisory Panel. Eur Resp J 2006; 28: 182-199.

How the Discrepancy between Symptoms and Peak Expiratory Flow Rate Influences Evaluation of Asthma Severity

Recent asthma guidelines recommend the assessment of severity levels based on the most severe symptoms and peak expiratory flow rate (PEFR). Discrepancies are frequently encountered in the use of these variables in determining the severity levels of asthmatics. The objective of this study was to determine the difference in asthma severity levels as assessed by either symptoms alone or by PEFR alone, as compared with the assessment by the asthma guidelines. Severity levels that were determined by recent asthma guidelines for 60 asthmatic patients were reassessed, based on symptoms alone and PEFR alone. They were compared for any significant differences to the asthma guidelines. Asthmatics were aged between 15 and 70 (mean 34) years, and 63.8% were females. Severity levels by symptoms alone were different from the guidelines in 27 cases (45%). Of these, 89% showed a tendency toward higher severity levels. Severity levels by PEFR alone were different in only three cases (5%). In both comparisons, differences of severity levels were significant (P<0.0001), but assessment by symptoms alone showed more deviation (x(2) =162.1) than PEFR alone (x(2) =73.1). The study documented significant discrepancies in asthma severity assessed by symptoms alone and PEFR alone, when compared to the recent asthma guidelines. Severity assessed by symptoms alone showed lower levels, and the use of PEFR tended to categorize some asthmatics into a more severe level.

ADDITION OF SYNTHETIC SURFACTANT PROTEIN B TO SURVANTA IMPROVES GAS EXCHANGE IN SURFACTANT-DEFICIENT RATS. † 2114

Surfactant protein B (SP-B) is critical to surfactant function. Survanta®, a modified bovine lung extract, contains less SP-B than surfactants derived from lung lavage (Seeger et al., Eur Resp J 1993;6:971). Supplementation of Survanta with native SP-B increases dynamic compliance and deflation lung volume in preterm rabbits (Mizuno et al., Pediatr Res 1995;37:271). We hypothesized that the in vivo function of Survanta can be improved by supplementation with synthetic SP-B and SP-C and tested this hypothesis in a surfactant-deficient rat model. Full length SP-B1-78 and palmitoylated SP-C1-34 were synthesized, purified, derivatized, and analyzed by mass spectrometry and amino acid analysis. Survanta was extracted, unmodified (Surv-1) or enriched with 1% SP-B (Surv-2), 2% SP-B (Surv-3), or 2% SP-B + 1% SP-C (Surv-4), and resuspended. In vitro surface activity was tested on a modified Langmuir/Wilhelmy balance and SP-B and SP-C content were measured by Fourier transform infrared spectroscopy. Adult rats were anesthetized, tracheotomized, had an arterial line placed, and were ventilated with 100% oxygen, a peak inspiratory pressure of 30 cm H2O and a rate of 40/min. The lungs were lavaged with warmed normal saline until the PaO2 dropped below 60 torr, at which time 100 mg/kg of one of the four surfactant preparations was instilled. After 15 min of ventilation, the rats were killed and pressure-volume curves performedin situ. The mean arterial/Alveolar PO2 ratio was 0.08 post-lavage and increased by 74% after treatment with Surv-1 (n=5), by 92% after treatment with Surv-2 (n=6), by 257% after treatment with Surv-3 (n=5), and by 202% after treatment with Surv-4 (n=6). Surv-4 not only improved PaO2, but also reduced PaCO2 values. These data suggest that the addition of 2% synthetic SP-B to Survanta improves its short-term positive effects on oxygenation in this surfactant-deficient rat model.