Chronic obstructive pulmonary disease (COPD) is a main cause of death due to interplaying factors, including comorbidities that interfere with symptoms and response to therapy. It is now admitted that COPD management should be based on clinical symptoms and health status and should consider the heterogeneity of patients' phenotypes and treatable traits. This precision medicine approach involves a regular assessment of the patient's status and of the expected benefits and risks of therapy. The cornerstone of COPD pharmacological therapy is inhaled long-acting bronchodilation. In patients with persistent or worsened symptoms, factors likely to interfere with treatment efficacy include the patient's non-adherence to therapy, treatment preference, inhaler misuse and/or comorbidities, which should be systematically investigated before escalation is considered. Several comorbidities are known to impact symptoms, physical and social activity and lung function. The possible long-term side-effects of inhaled corticosteroids contrasting with their over-prescription in COPD patients justify the regular assessment of their benefits and risks, and de-escalation under close monitoring after a sufficient period of stability is to be considered. While commonly used in clinical trials, the relevance of routine blood eosinophil counts to guide therapy adjustment is not fully clear. Patients' characteristics, which define phenotypes and treatable traits and thus guide therapy, often change during life, forming the basis of the concept of clinical trajectory. The application of individual trajectory-based management of COPD in clinical practice therefore implies that the benefit:risk ratio is regularly reviewed according to the evolution of the patient's traits over time to allow optimised therapy adjustments.

SARS CoV-2 is an epidemic viral infection that can cause mild to severe lung involvement. Newly apprehended knowledge on thoracic imaging abnormalities and the growing clinical experience on the evolution of this disease make the radiographic follow-up of hospitalized patients relevant. The value of consecutive bedside lung ultrasonography in the follow-up of hospitalized patients with SARS CoV-2 pneumonia and its correlation with other clinical and laboratory markers needs to be evaluated.We assessed 39 patients [age: 64 y(60.1–68.7)] with confirmed SARS CoV-2 pneumonia. A total of 24 patients were hospitalized until the follow-up test, 9 were discharged early and 6 required a transfer to critical care unit. Two ultrasound scans of the lung were performed on day 1 and 4 of patients’ hospitalization. Primary endpoint was the magnitude of association between a global lung ultrasound score (LUS) and clinical and laboratory markers. Secondary endpoint was the association between the evolution of LUS with the corresponded changes in clinical and laboratory outcomes during hospitalization period.LUS score on admission was higher among the deteriorating patients and significantly (P = 0.038–0.0001) correlated (Spearman's rho) with the levels of C-reactive protein (0.58), lymphocytes (−0.33), SpO2 (−0.48) and oxygen supplementation (0.48) upon admission. The increase in LUS score between the two scans was significantly correlated (0.544, P = 0.006) with longer hospital stay.Lung ultrasound assessment can be a useful as an imaging modality for SARS CoV-2 patients. Larger studies are needed to further investigate the predictive role of LUS in the duration and the outcome of the hospitalization of these patients.

Introduction The use of two quality-of-life questionnaires in a single clinical trial with an economic component can be challenging due to the associated workload in terms of data collection and an increased risk of missing data. The aim of our study was to determine whether the questionnaire chosen to measure health status, the St. George’s Respiratory Questionnaire (SGRQ), could be administered on its own without adding the EuroQol five dimensions questionnaire (EQ-5D) for economic evaluation in emphysema studies. Materials and Methods Data were prospectively collected during the REVOLENS trial assessing endobronchial coil treatment in severe emphysema. To quantify the association between the two questionnaires, correlations between the EQ-5D and the SGRQ were first tested and the concordance was then studied in order to know whether the two questionnaires were interchangeable. Finally, the Starkie et al algorithm predicting EQ-5D utility values from the SGRQ was used on REVOLENS’s individual patient data. The Student’s t-test, correlation and concordance between EQ-5D individual value (from the REVOLENS study) and predicted value (from the Starkie et al algorithm) were studied to test this algorithm. Results Results showed a strong correlation but no concordance between the EQ-5D and the SGRQ, demonstrating that the two questionnaires are not interchangeable. Moreover, the algorithm predicting EQ-5D utilities from the SGRQ did not provide utility values comparable to those observed in the REVOLENS study. Indeed, our study demonstrated a strong correlation between predicted and individual EQ-5D values but no concordance. Conclusion The use of both the EQ-5D and the SGRQ in a clinical study with an economic component is justified. Based on our results, the SGRQ should not be used to obtain a utility score to calculate the incremental cost-effectiveness ratio and conclude on the efficiency of an intervention in emphysema patients.

Recent studies show that relapsing polychondritis patients with tracheobronchial involvement are distinct from others in terms of clinical characteristics, therapeutic management, and disease evolution. Tracheobronchial involvement affects 20 to 50% of patients and may reveal the disease. It should be sought at the time of diagnosis and at each follow-up visit. Respiratory impairment is confirmed by computed tomography (CT) of the chest, including the cervical portion of the trachea, with end-inspiratory and dynamic expiratory scans, and pulmonary function tests. These investigations should be performed, even in asymptomatic patients, at the time of diagnosis, and repeated as necessary during follow-up. Bronchoscopy and a fortiori endoscopic intervention should be considered with caution and performed only by expert endoscopists after careful evaluation of the risks and benefits of such procedures, which can lead to damage or perforation of the airways and bronchospasm. Early detection and management of tracheobronchial involvement in relapsing polychondritis has significantly improved the prognosis of patients, especially with the development of interventional fiberoptic bronchoscopy. However, relapsing polychondritis-related morbidity and mortality are still elevated, particularly in tracheobronchial disease.

Given the high proportion of patients with asthma who remain uncontrolled despite controller treatment, there remains a need for the development of more effective treatment options with a proven safety and tolerability profile. Recently, asthma guidelines have evolved to incorporate new therapies, including long-acting muscarinic antagonists (LAMAs) and biologics. Here we focus on the safety profile of tiotropium, a LAMA, using data from the large-scale UniTinA-asthma® clinical trial program, which investigated the use of tiotropium in over 6000 patients with asthma who remained symptomatic despite receiving inhaled corticosteroids maintenance therapy, with or without other adjunct therapies. The large number of patients included allows robust analysis of safety and tolerability. Overall, a similar incidence of patients reporting any adverse event (AE) was observed in the tiotropium (5 µg and 2.5 µg) and placebo groups. Asthma worsening, decreased peak expiratory flow, and upper respiratory tract infections were the most frequently reported AEs. Serious AEs (SAEs) and investigator-defined drug-related AEs were infrequently reported across all treatment groups, including the placebo group, and there were no deaths in any study. Reports of side effects typically associated with anticholinergic drugs, such as dry mouth and urinary retention, were either infrequent or not reported in children, adolescents or adults. The similar proportions of tiotropium- versus placebo-treated patients reporting AEs and SAEs in African-American and Japanese populations, as well as in elderly patients, contribute to the accumulating evidence of the safety and tolerability of tiotropium across broad ethnic and age populations.

Chronic obstructive pulmonary disease (COPD) is a risk factor of post-operative complications after lung cancer resection. The influence of the "frequent exacerbator (FE)" phenotype (at least three exacerbations per year) is unknown. Postoperative outcomes of frequent exacerbators (POFE) was a prospective observational study of patients with COPD undergoing lung resection for cancer. The inclusion criteria were: age >40 years, FEV1/FVC <70%, non-urgent surgery for lung cancer, filled out self-questionnaires. The primary outcome was assessment of postoperative pulmonary complications (purulent tracheobronchitis, atelectasis, pneumonia, acute respiratory failure, need of mechanical ventilation). Secondary outcomes encompassed the prevalence of the FE phenotype and its impact on postoperative complications. A total of 682 patients were screened from June 2014 to October 2015. 93 patients with COPD were included, 21 (23%) were FE. Postoperative tracheobronchitis, atelectasis pneumonia or respiratory failure (isolated or associated) occurred in 47%, 48%, 26%, and 38% of patients, respectively. Non-invasive and invasive mechanical ventilation were necessary in 4 (4%) and 22 (23%) patients. Purulent tracheobronchitis, pneumonia and hypercapnia (this last requiring noninvasive mechanical ventilation) were more frequent in FE (p = 0.043, 0.042, 0.015); however the number of patients wth at least one respiratory complication was not different (76% vs. 52%, p = 0.056). In all patients, multivariate logistic regression identified two independent factors of postoperative respiratory complications: male sex (OR 10.6 [95% CI 1.97-57.6], p = 0.006) and the FE phenotype (OR 6.33 [1.04-38.39], p = 0.045). Occurrence of postoperative complications in patients with COPD is high. FE phenotype is an independent risk factor.

Rationale Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown. Objective We examined whether the treatment given for exacerbations predicted subsequent outcomes. Methods This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®). Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan–Meier plots. Results Of 8,061 patients with moderate to severe exacerbation(s), demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization. Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively), and a greater risk of having a hospitalized (severe) exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively) or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively) compared with exacerbations treated with antibiotics alone. Initial hospitalization led to the highest risk of subsequent hospitalization (all-cause or COPD related [severe exacerbation], HR: 3.35 and 4.31, P<0.0001, respectively) or death (all-cause or COPD related, HR: 3.53 and 5.54, P<0.0001, respectively) versus antibiotics alone. Conclusion These data indicate that the way exacerbations are treated initially is a useful guide to the patient’s subsequent clinical course. Factors that clinicians consider when making treatment choices require further clarification.

L’atteinte trachéo-bronchique touche 20 à 50 % des patients atteints de polychondrite atrophiante et peut représenter le mode d’entrée dans la maladie. Il convient de la rechercher lors du diagnostic et à chaque visite de suivi. La recherche d’une atteinte respiratoire doit inclure la réalisation d’un scanner thoracique avec des coupes réalisées en expiration et des épreuves fonctionnelles respiratoires. Ces examens complémentaires doivent être réalisés systématiquement au diagnostic, même chez les patients asymptomatiques, et ils doivent être répétés régulièrement au cours du suivi. L’indication de la fibroscopie doit rester très prudente et elle ne doit être réalisée que chez des patients symptomatiques par des endoscopistes experts. L’indication d’un geste local doit être posée avec grande prudence, après concertation pluridisciplinaire, en raison notamment des risques de perforation de la muqueuse trachéo-bronchique. Un dépistage précoce et la prise en charge des atteintes trachéo-bronchiques de la polychondrite atrophiante ont permis l’amélioration de leur pronostic, notamment depuis le développement de la fibroscopie interventionnelle.

3055 Background: Nivolumab is the first checkpoint immunotherapeutic agent approved for NSCLC. By enabling host immune-mediated cytotoxic activity against tumor cells, nivolumab induces a tumor response in 15% of patients (pts). However, host-related parameters to predict nivolumab activity are still missing. We evaluated the predictive and prognostic value of the presence of a systemic inflammatory response. Methods: From July 2015 to December 2016, we measured at nivolumab initiation the Glasgow Prognostic Score (GPS), a cumulative prognostic score based on C-reactive protein and albumin, the neutrophil-lymphocyte ratio (NLR), the Nutrition Risk Index (NRI) and the Prognostic Nutritional Index (PNI). Univariate and multivariate analyses tested the association between initial patient characteristics and clinical outcome. Results: The characteristics of the 57 consecutive pts analyzed are: median age of 66 years (range 41-78), 65% non-squamous cell lung cancer, 61.4% males and 52.6% Performance Status (PS) 0-1. GPS was 0 in 27 (47.4%), 1 in 21 (36.8%) and 2 in 9 (15.8%) pts. In multivariate analysis, parameters associated with disease progression (per RECIST 1.1) were GPS (1-2 vs 0; HR 1.45 [1.11-1.90], p= 0.009) and number of metastatic sites (>2 vs ≤ 2; HR: 0.75 [0.57-0.98], p = 0.04). Overall survival was significantly worse for pts with PS 2-3 vs PS 0-1 (p=0.01) and for pts with GPS 2 vs GPS 0-1 (p=0.01). The GPS was an independent predictive marker of progression and was superior to other inflammation-based prognostic scores in our cohort (Table). Conclusions: The Glasgow Prognostic Score (GPS) allows identifying patients with disease progression and long survivors among metastatic NSCLC patients treated with nivolumab. [Table: see text]

Introduction: Dyspnoea is one of the most common symptoms in chronic obstructive pulmonary disease (COPD) and has been associated with poor clinical outcomes. Aims and objectives: To investigate relationships between dyspnoea severity, baseline characteristics and outcomes in patients with COPD. Methods: Data from two 1-year, randomized trials (NCT00168844; NCT00168831) of tiotropium Respimat® 5 µg and placebo were pooled. This retrospective analysis assessed characteristics and outcomes of patients by Baseline Dyspnea Index score. Results: Of 1317 patients, 337 (26%) had mild or no dyspnoea at baseline, 743 (56%) moderate dyspnoea and 237 (18%) severe dyspnoea (Table). Baseline demographic characteristics were similar across dyspnoea categories. However, higher levels of dyspnoea correlated with more advanced COPD (GOLD Stage), and greater use of short-acting bronchodilators and inhaled corticosteroids. Patients with severe dyspnoea reported more exacerbations within the past year. Increasing dyspnoea at baseline correlated with greater risk of moderate–severe (P=0.0005) and severe (P=0.0198) exacerbations during the study. Tiotropium reduced moderate–severe exacerbation risk and significantly improved FEV1 and FVC across all dyspnoea categories. Conclusions: Patients with more severe dyspnoea had more advanced COPD, and a higher risk of exacerbation. Tiotropium improved outcomes regardless of baseline dyspnoea severity.

BACKGROUND:Exacerbation history is used to grade the risk of COPD exacerbation, but its reliability and relationship to other risk factors and prior therapy is unclear. To examine these interrelationships, we conducted a post hoc analysis of patients in the TIOSPIR trial with ≥2 years' follow-up or who died on treatment.PATIENTS AND METHODS:Patients were grouped by their annual exacerbation rate on treatment into nonexacerbators, infrequent, and frequent exacerbators (annual exacerbation rates 0, ≤1, and >1, respectively), and baseline characteristics discriminating among the groups were determined. We used univariate and multivariate analyses to explore the effect of baseline characteristics on risk of exacerbation, hospitalization (severe exacerbation), and death (all causes).RESULTS:Of 13,591 patients, 6,559 (48.3%) were nonexacerbators, 4,568 (33.6%) were infrequent exacerbators, and 2,464 (18.1%) were frequent exacerbators; 45% of patients without exacerbations in the previous year exacerbated on treatment. Multivariate analysis identified baseline pulmonary maintenance medication as a predictive factor of increased exacerbation risk, with inhaled corticosteroid treatment associated with increased exacerbation risk irrespective of exacerbation history.CONCLUSION:Our data confirm established risk factors for exacerbation, but highlight the limitations of exacerbation history when categorizing patients and the importance of prior treatment when identifying exacerbation risk.

Background: Overweight and obesity (OW/OB) are increasingly reported in pediatric and adult CF patients.Characteristics of OW/OB adult patients are not fully described.OW/OB is not clearly associated with metabolic syndrome, while it may correlate positively with lung function.Objectives: To identify and describe clinical characteristics of adult OW/OB CF patients and compare them to CF patients with optimal BMI.Methods: Retrospective study based on medical files review.OW (BMI >25) and OB (BMI >30) CF patients were compared to patients with optimal BMI (22-24.9 for males).Age at follow up, age at diagnosis, genotype (minimal vs residual function mutations), FEV 1 % predicted, pancreatic sufficiency, Pseudomonas and Staphylococcus colonization, CF related diabetes (CFRD) and liver disease (CFLD), serum lipid profile and number of hospitalizations for IV treatment (last 5 years) were recorded.Results: Out of 180 adult CF patients, 16 were OW and 5 OB (18/21 male).26 male patients had BMI 22-24.9 and were compared to OB/OW male CF patients.Main results are shown in Table 1. Conclusion:In our study population OW/OB concerned largely male patients.OW/OB CF patients had preserved lung function despite being older than patients with optimal BMI.A milder genotype could account for this effect.Serum lipid levels were higher in OB/OW patients without reaching treatment threshold.

Bronchial artery embolization is the recommended therapy for massive hemoptysis in patients with cystic fibrosis (CF). We report on two cases of multiple renal infarcts and renin-associated hypertension and hypokalemia occurring in CF adults after bronchial artery embolizations. These complications were presumably related to crossing of small calibrated microspheres through arteriovenous anastomoses. Although hypokalemia resolved rapidly, hypertension persisted at least 6 months and its control required multiple antihypertensive agents. Physicians should be aware of this potentially severe, but previously unreported, complication of bronchial artery embolization.

We read with interest the publication of Schmiedl et al. 1describing the characteristics of patients treated with tiotropium HandiHaler® or Respimat® in the Tiotropium Safety and Performance in Respimat (TIOSPIR®) study compared with their ‘real‐world’ database 2. The authors noted that patients starting either treatment had similar characteristics but suggest that we may have included a selected population with chronic obstructive pulmonary disease (COPD), who might react differently to treatment (and be at lower risk of cardiac adverse effects) than a ‘real‐world’ population.

Background: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat (R) 5 mu g add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure.Methods: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 mu g (evening dosing) or twice-daily 2.5 mu g (morning and evening dosing), as add-on to maintenance therapy with ICS (400-800 mu g budesonide or equivalent) as controller medication. There was no washout between treatment periods.Results: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 mu g (217 mL) and twice-daily 2.5 mu g (219 mL), with no difference between the two regimens (-2mL [95% confidence interval: -38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination.Conclusions: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 mu g and twice-daily 2.5 mu g as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma.

Daniel Dusser,1 Robert A Wise,2 Ronald Dahl,3 Antonio Anzueto,4,5 Kerstine Carter,6 Andy Fowler,7 Peter M Calverley8 1Service de Pneumologie, Hôpital Cochin, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 2Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Allergy Centre, Odense University Hospital, Odense C, Denmark; 4Pulmonary/Critical Care, University of Texas, 5South Texas Veterans Health Care System, San Antonio, TX, USA; 6Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA; 7Boehringer Ingelheim Pharma Ltd, Bracknell, UK; 8Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Background: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR®, the largest randomized clinical trial in COPD performed to date.Methods: A total of 17,135 patients from TIOSPIR® were pooled and grouped by GOLD grading (A–D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV) and respiratory mortality were assessed.Results: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality – hazard ratio [HR] =1.74, P=0.004; all-cause mortality – HR =1.18, P=0.11). Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%). Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A–D (0.3%, 0.8%, 1.6%, and 4.2% of patients, respectively).Conclusion: The data obtained from the TIOSPIR® trial, supporting earlier studies, suggest that proportionally more CV medication and CV deaths occur in GOLD Group B COPD patients, although deaths attributed to respiratory causes are more prevalent in Groups C and D. Keywords: TIOSPIR®, GOLD, cardiovascular comorbidity, mortality, respiratory death, cardiovascular death

Innate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency.In patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease.Small airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies.