Future Exacerbations Research Articles

PREDICTORS OF FUTURE EXACERBATIONS IN A MULTI‐ETHNIC ASIAN POPULATION WITH ASTHMA

RespirologyVolume 22, Issue S3 p. 164-164 APSR Poster Abstracts PREDICTORS OF FUTURE EXACERBATIONS IN A MULTI-ETHNIC ASIAN POPULATION WITH ASTHMA First published: 23 November 2017 https://doi.org/10.1111/resp.13207_210Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 164-164 RelatedInformation

Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort.

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40-85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755-0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.

Acute exacerbated COPD: room for improvement in key elements of care.

IntroductionHospitalizations because of acute exacerbated COPD (AECOPD) are a major burden to patients and the health care system. Interventions during acute and post-acute hospital care exist not only to improve short-term outcomes but also to prevent future exacerbations and disease progression. We aimed at measuring the implementation rates of acute and post-acute hospital care interventions for AECOPD.MethodsWe performed 24 months (January 1, 2012, to December 31, 2013) retrospective medical chart review of consecutive cases hospitalized to one of three public hospitals in the canton of Zurich due to AECOPD. Implementation rates of five acute care and seven post-acute care interventions were assessed.ResultsData from 263 hospitalizations (61% male, mean age 68.5 years, 47% active smokers) were analyzed. The median length of stay was 9 days (interquartile range [IQR] 6–12 days). In all, 32% of hospitalizations were caused by individuals with previous hospitalizations because of AECOPD. Implementation rates of four acute care interventions were >75% (lowest was appropriate antibiotic therapy with 56%). Compared to this, implementation rates of five post-acute care interventions were <25% (lowest was patient education and self-management advice with 2%).ConclusionThe results of this audit revealed room for improvement mainly in post-acute care interventions for AECOPD.

Longitudinal change of COPD assessment test (CAT) in a telehealthcare cohort is associated with exacerbation risk.

BackgroundThere are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time. Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations.Patients and methodsThe CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention. The evolution of the CAT was analyzed using linear regression. The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen–Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors.ResultsThe median CAT at inclusion was 17 (interquartile range 13–22) points. During the study, 25% of patients had a significant negative slope (median −7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy). The median slope of the CAT in the overall cohort was +1 (interquartile range −3 to +6) ppy. A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03–1.13; p<0.001). There was an 8% increase of the risk of exacerbation per unit increase in CAT. We detected a significant learning effect in filling out the CAT in 18.4% of patients with a median learning phase of five filled questionnaires.ConclusionSixty-three percent of the COPD patients monitored by THC experienced a stable or improved CAT during 1-year follow-up. We found a significant positive association between the evolution of the CAT over time and the risk of exacerbations. In about one-fifth of patients, there was a significant learning effect in filling out the CAT, before reliable results could be obtained. The evolution of the CAT could help to assess the risk for future exacerbations.

Validating the Concept of COPD Control: A Real-world Cohort Study from the United Kingdom

ABSTRACTThe concept of Chronic Obstructive Pulmonary Disease (COPD) control has been developed to inform therapeutic decision-making. We explored the validity of a definition of COPD control in a representative population of patients with COPD in the United Kingdom. Electronic medical records and linked COPD questionnaire data from the Optimum Patient Care Research Database were used to characterize control status. Patients were aged ≥40 years, with spirometry-confirmed COPD, current or ex-smokers, and continuous records throughout the study period. Control was evaluated based on COPD stability and patients' (i) clinical features or (ii) COPD Assessment Test (CAT) score over a three-month baseline period and linked to time to first exacerbation. Of 2788 eligible patients, 2511 (90%) had mild/moderate COPD and 277 (10%) had severe/very severe COPD based on Body Mass Index, Obstruction, Dyspnoea, Exacerbations (BODEx) cut-off of 4. Within the mild/moderate cohort, 4.5% of patients were controlled at baseline according to clinical features and 21.5% according to CAT threshold of 10. Within the severe/very severe cohort, no patients were controlled at baseline according to the proposed clinical features and 8.3% were controlled according to CAT threshold of 20. Compared with uncontrolled patients, time to first exacerbation was longer for controlled patients with mild/moderate COPD but not for those with severe/very severe COPD. Lowering the BODEx threshold for severity classification to 2 increased the number of patients achieving control. CAT scores were not good predictors of the risk of future exacerbation. With the proposed definition, very few patients were defined as controlled.

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting

Objective: Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.Methods: A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed.Results: An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios.Limitations: Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients.Conclusion: Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization’s cost-effectiveness threshold of up to 3-times the gross domestic product.

WS11.5 Risk factors for lung function decline and future exacerbations in children with cystic fibrosis

WS11.5 Risk factors for lung function decline and future exacerbations in children with cystic fibrosis

WS02.4 A peripheral blood transcriptional profile predicts disease severity and the risk of future exacerbations in adults with cystic fibrosis (CF)

WS02.4 A peripheral blood transcriptional profile predicts disease severity and the risk of future exacerbations in adults with cystic fibrosis (CF)

New opportunities for prevention of exacerbations of chronic obstructive pulmonary disease. Russian Respiratory Society Expert Opinion

Combination therapy with long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) can reduce symptoms of chronic obstructive pulmonary disease (COPD) and the risk of future exacerbations. To date, the only fixed combination of long-acting bronchodilators, indacaterol/glycopyrronium, has demonstrated a significant reduction in dyspnea and in the risk of moderate and severe exacerbations of COPD in clinical trials when compared with the combination of salmeterol/fluticasone. Addition of inhaled steroids (ICS) to long-acting bronchodilators is recommended for patients with recurrent COPD exacerbations, especially in those with asthma-COPD overlap syndrome or history of elevated blood or sputum eosinophil levels. It is recommended to consider phenotype-specific therapy including roflumilast, N-acetylcysteine, and macrolides, in patients who continue to exacerbate despite being treated with LABA/LAMA or LABA/LAMA/ICS combinations. Withdrawal of inhaled corticosteroids is possible in patients with the low risk of exacerbation and in those with severe adverse events during ICS treatment. ICS should be withdrawn in a single step in patients with no repeated exacerbations during 12 months and with moderate bronchial obstruction (FEV1 ≥ 50% predicted). Stepwise withdrawal of ICS during 3 month with continuous dual bronchodilator therapy is recommended in COPD patients with severe bronchial obstruction (FEV1 ˂ 50% predicted) without frequent exacerbations in the previous year.

Serum periostin in patients hospitalized for COPD exacerbations

Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory response in patients with asthma, but its predictive role in hospitalized patients with COPD has not been evaluated.The aim of the present observational prospective cohort study was to evaluate the possible role of serum periostin as predictor of outcome in COPD patients hospitalized for AECOPD.Serum periostin was measured on admission and at discharge in patients admitted to the hospital for a COPD exacerbation. Patients were followed-up for 1year for future exacerbations, hospitalizations and mortality.155 consecutive patients admitted to the hospital for AECOPD were included to the study. Periostin levels on admission were elevated compared to discharge [34.7 (25.2–52.2) vs. 25.9 (17.4–41.0) ng/mL, p=0.003], but serum periostin levels did not differ between patients with or without prolonged hospitalization, or those who required non-invasive ventilation, intubation, or died during hospitalization. Frequent exacerbators had higher serum periostin levels at the time of discharge compared to non-frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p<0.001]. Periostin levels above the median value (25ng/mL) were not related to the time of next exacerbation, time of next COPD hospitalization, (p=0.858) or time to death.The role of serum periostin levels as a predictive biomarker of future risk in hospitalized patients with COPD is of limited value.

Risk of pneumonia during long term regular treatment of stable COPD with inhaled glucocorticoids: a systematic review.

Inhaled glucocorticoids are anti-inflammatory drugs used in combination with long acting bronchodilators beta2-agonists for the treatment of stable chronic obstructive pulmonary disease (COPD), to improve lung function and symptoms and to reduce the future risk COPD exacerbations. However, has been also associated to an increased risk of pneumonia. The objective of this systematic review was therefore to analyze all randomized controlled trials to identify the risk of pneumonia during the regular treatment with long-term inhaled glucocorticosteroids compared to treatment with placebo in patients with stable COPD. From a literature search on PubMed, 19 randomized, placebo-controlled, long term (at least 52-week) studies have been identified. The inhaled glucocorticoids administered were: budesonide (6 studies), mometasone furoate (3 studies), beclomethasone dipropionate (1 study), triamcinolone acetonide (1 study), fluticasone propionate (7 studies) and fluticasone furoate (1 study). Only 7 of the 19 trials identified in our systematic review reported data on pneumonia and only one study required radiological evidence for diagnosis. The incidence of pneumonia was slightly increased in patients treated with glucocorticoid inhaled compared to placebo in most studies, regardless of the type of glucocorticoid inhalation used, suggesting a class effect. Older age, low body mass index, low FEV1, being a smoker are all factors variously associated with increased risk of pneumonia.

Bronchial thermoplasty.

Even with the use of maximum pharmacological treatment, asthma still remains uncontrolled in some cases. For such cases of uncontrolled asthma, a novel therapy--Bronchial Thermoplasty (BT)--has shown some promising results over the past few years. BT is application of controlled radiofrequency heat via catheter inserted through a flexible bronchoscope, to the bronchial walls. It reduces the smooth muscle mass in bronchial wall and thus results in decreased contractility. Three major trials of BT show that it does not cause any improvement in FEV1. However, BT causes improvement the quality of life and decreases the future exacerbations and emergency hospital visits due to asthma. But the benefit observed was too small to be clinically significant. Follow up (two to five years) results of these BT trials did not show any significant long-term adverse event related to BT. However, further independent large randomized controlled trials and results of application of BT in real hospital settings are needed to define its role in asthma management.

Association of Asthma Symptoms and Exacerbation with Inflammatory Biomarkers

Objective: To investigate a relationship of asthma symptoms and exacerbations with systemic (high-sensitivity Creactive protein (hs-CRP), eosinophilic cationic protein (ECP), leukocytes) and local (exhaled NO (FENO), pH and urates in exhaled breath condensate (EBC) and exhaled breath temperature (EBT)) inflammatory biomarkers (BMs) in asthmatic children. Methods: This cross-sectional study comprised 93 consecutive asthmatic patients (age 6-18 years, 22 girls) with mild intermittent asthma ((IA), N=44) and mild to moderate persistent asthma ((PA), N=49). Medical history (asthma symptoms and exacerbation), pulmonary function, FENO, EBT, samples of exhaled breath and peripheral blood were collected. Results: Local BMs (EBC urates and EBT) showed stronger correlation with asthma symptoms then systemic BMs (hs-CRP, blood count with differencials) (r=0.26-0.68, r=0.06-0.32, p<0.05; respectively). Single measurements of inflammatory BMs are not good predictors for future asthma exacerbation (binary logistic regression; χ²=13.9; df=11; p=0.238). Conclusion: Study of combination of various exhaled breath and exhaled breath condensate BMs should continue, especially in longitudinal studies with repeated measurements of BMs.

The Potential Role of Allergen Immunotherapy in Stepping Down Asthma Treatment

For patients whose asthma is controlled and who have a low risk for future exacerbations, current guidelines recommend gradually stepping down pharmacotherapy to identify the lowest dose needed to maintain control. This review article will discuss the benefits and risks of step down in asthma management and the different strategies of achieving step down with particular focus on allergen immunotherapy (AIT). A literature search was conducted to identify studies that assessed the effect of AIT on asthma step down and evaluated this and asthma control as one of the outcomes. Six studies were identified: 2 subcutaneous and 4 sublingual AIT studies. Five studies assessed house dust mite-induced asthma, whereas 1 study focused on birch-induced seasonal asthma. Regarding house dust mite-induced asthma, the AIT studies reviewed suggest that individuals with moderate rather than mild asthma are the patients who are more likely to benefit from the addition of AIT for their asthma condition. The potential value of AIT is likely to be in enabling successful step down of the inhaled corticosteroid dose in Global Initiative for Asthma step 3 or 4. It is important to further explore this effect so that affected individuals can benefit from this treatment.

Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis.

Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis. This was a single-center prospective cohort study using the TAYBRIDGE (Tayside Bronchiectasis Registry Integrating Datasets, Genomics, and Enrolment into Clinical Trials) registry in Dundee, UK. A total of 433 patients with high-resolution computed tomography-confirmed bronchiectasis provided blood samples for desmosine measurement, and 381 provided sputum for baseline elastase activity measurements using an activity-based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3 years. Elastase activity in sputum was associated with the bronchiectasis severity index (r = 0.49; P < 0.0001) and was also correlated with the Medical Research Council dyspnea score (r = 0.34; P < 0.0001), FEV1% predicted (r = -0.33; P < 0.0001), and the radiological extent of bronchiectasis (r = 0.29; P < 0.0001). During a 3-year follow-up, elevated sputum elastase activity was associated with a higher frequency of exacerbations (P < 0.0001) but was not independently associated with mortality. Sputum elastase activity was independently associated with FEV1 decline (β coefficient, -0.139; P = 0.001). Elastase showed good discrimination for severe exacerbations with an area under the curve of 0.75 (95% confidence interval [CI], 0.72-0.79) and all-cause mortality (area under the curve, 0.70; 95% CI, 0.67-0.73). Sputum elastase activity increased at exacerbations (P = 0.001) and was responsive to treatment with antibiotics. Desmosine was correlated with sputum elastase (r = 0.42; P < 0.0001) and was associated with risk of severe exacerbations (hazard ratio 2.7; 95% CI, 1.42-5.29; P = 0.003) but not lung function decline. Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with bronchiectasis.

Optimum treatment for chronic obstructive pulmonary disease exacerbation prevention.

An exacerbation of chronic obstructive pulmonary disease (COPD) is defined as an acute worsening of symptoms greater than the usual day to day variation that requires increased pharmacotherapy (1). Some COPD patients suffer with exacerbations regularly, and the history of previous exacerbations is the best predictor for the risk of future exacerbations (2). The Global initiative for chronic Obstructive Lung Disease (GOLD) uses a threshold of ≥ two exacerbations or one hospitalization in the last year to identify patients with an increased risk of future exacerbations (3).

Perspectives on advance care planning among patients recently requiring non-invasive ventilation for acute respiratory failure: A qualitative study using thematic analysis

Background: Patients requiring non-invasive ventilation for acute-on-chronic respiratory failure due to chronic obstructive pulmonary disease or heart failure exacerbations may have a poor prognosis underscoring the importance of advance care planning. Aim: We aimed to describe attitudes to, and experiences of, discussing the future among patients recently treated with non-invasive ventilation. Design: Qualitative research using thematic analysis. Settings and participants: Tertiary teaching hospital. Patients with acute hypercapnic respiratory failure requiring non-invasive ventilation. Results: Individuals recently treated with non-invasive ventilation describe feeling the future is beyond their control and instead controlled by their illness. Participants often recognised their poor prognosis but avoided discussing some difficult topics. The majority preferred not to undergo cardiopulmonary resuscitation but most had not discussed this with healthcare professionals. When participants voiced concerns about their future health to family members, they were met with polarised responses. Some encountered willingness for further discussion, while others met deflection, deterring further conversation. An overarching narrative of ‘Looking through my illness to an uncertain but concerning future’ unites these themes. Conclusion: This study suggests opportunities and barriers for advance care planning in individuals with chronic disease. Patients’ understanding of their prognosis and their attitudes to cardiopulmonary resuscitation suggests an opportunity for advance care planning. Structuring discussions around patients’ preferences for care during future exacerbations may foster a sense of control over the future despite illness. The diversity of familial responses to patients’ concerns about their future health has implications for advance care planning. These findings have the potential to improve care for patients with respiratory failure and suggest an important ongoing research agenda.

Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study.

Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1–4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54–6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50–9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75–5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year.

Real life data on incidence and risk factors of severe asthma exacerbations in children in primary care

Real-life data on the incidence rates (IR) and risk factors of severe asthma exacerbations in children are sparse. We aimed to assess IR and risk factors of severe asthma exacerbations in children in real life.We conducted a population-based cohort study using a Dutch GP database containing complete medical records of >1 million patients. All records of children with physician-diagnosed asthma aged 5–18 years between 2000 and 2012 were examined for exacerbations, defined as either hospitalization, emergency department visit or need of systemic steroids for asthma. IR was expressed as number of exacerbations per person year (PY).We identified 14,303 asthmatic children with 35,118 PY of follow-up and 732 exacerbations. The overall IR was 2.1/100PY (95% CI 1.9–2.2), 4.1/100PY (3.8–4.4) for children on asthma treatment. Re-exacerbation occurred in 2% (1.3–4.3) of patients within 1 month, in 25% (20.6–28.8) within 1 year. Predictors for (frequent) exacerbations were age, medication use and prior exacerbations (all p < 0.001).The overall IR of severe asthma exacerbations was 4/100PY in children on asthma treatment, highest in spring and fall. 25% of the patients with an exacerbation will experience a next exacerbation within 1 year. More severe asthma is a predictor of subsequent and future exacerbations.

Predictors of future exacerbation risk in patients with asthma

ABSTRACTObjectives: Although modern treatment of asthma improves asthma control, some patients still experience exacerbations. The aim of the present study was to detect predictors of asthmatic exacerbationsMethods: We included patients with asthma followed up in asthma clinics of 2 tertiary University hospitals. Demographic and functional characteristics, levels of exhaled NO, and inflammatory biomarkers (IL-13, ΕCP και IL-8) and cell counts in induced sputum were recorded at baseline. Measurements were performed with the patients in stability and were considered as their personal best. Patients received optimal treatment with good compliance and were followed up for 1 year for asthma exacerbations occurrence. Evaluation of the effect of recorded parameters on asthma exacerbations was performed with univariate and multivariate Poisson regression analysis.Results: 171 patients (118 female) with bronchial asthma (mean age 51.6 ± 13.2 years) were included in the study. The mean number of exacerbations in 1 year of follow up was 0.4 ± 0.8 while the majority of patients (71.9%) did not experience any exacerbation. In multivariate Poisson Regression analysis only 3 characteristics were predictors of future exacerbations: FEV1 [IRR(95% CI)], [0.970(0.954–0.987)], p = 0.001, high BMI [1.078(1.030–1.129)], p = 0.001, and the need for permanent treatment with oral corticosteroids for asthma control maintenance [2.542(1.083–5.964)], p = 0.032Conclusion: Optimal guideline-based asthma management results in minimal occurrence of exacerbations in the majority of patients. Predictors of exacerbations are low FEV1 levels in stability, high BMI and the need for permanent treatment with oral corticosteroids.