Severe asthma care trajectories: the French RAMSES cohort.

Background: The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs). Methods: Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs. Results: 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm-3; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390). Conclusions: Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care.

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

BACKGROUND: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. RESEARCH QUESTION: What are the most relevant changes in CT scan parameters over time for assessing response to treatment? STUDY DESIGN AND METHODS: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists anonymized to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated. RESULTS: Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24). INTERPRETATION: Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02273661; URL: www. CLINICALTRIALS: gov).

Dyspnea-induced Limitation (DYSLIM), a new self-administered concise questionnaire to evaluate dyspnea-related activity limitation in chronic respiratory diseases.

BACKGROUND AND AIM: Few questionnaires are available for routine assessment of dyspnea. The study aimed to design a self-administered questionnaire assessing the impact of chronic dyspnea on daily activities, named DYSLIM (Dyspnea-induced Limitation). METHODS: The development followed 4 steps: 1: selection of relevant activities and related questions (focus groups); 2: clinical study: internal and concurrent validity vs. modified Medical Research Council (mMRC), Baseline Dyspnea Index (BDI) and Saint George Respiratory Questionnaire (SGRQ); 3: item reduction; 4: responsiveness. Eighteen activities (from eating to climbing stairs) were considered with 5 modalities for each: doing the task slowly, taking breaks, seeking assistance, changing habits, and activity avoidance. Each modality was graded from 5 (never) to 1 (very often). Validation study included 194 patients: COPD (FEV1 ≥ 50% pred: n = 40; FEV1 < 50% pred: n = 65); cystic fibrosis (n = 30), interstitial lung disease (n = 30), pulmonary hypertension (n = 29). Responsiveness was evaluated by post-pulmonary rehabilitation data in 52 COPD patients. RESULTS: Acceptability was high and short term (7 days) reproducibility was satisfactory (Kappa mostly above 0.7). Concurrent validity was high vs. mMRC (Spearman correlation coefficient, r = 0.71), BDI (r = - 0.75) and SGRQ (r = - 0.79). The reduced questionnaire with 8 activities (from cleaning to climbing stairs) and 3 modalities (slowly, seeking help, changing habits) showed a comparable validity and was chosen as the final short version. Effect size of rehabilitation was good for both the full (0.57) and short (0.51) versions. A significant correlation was also found between changes of SGRQ and DYSLIM post rehabilitation: r = - 0.68 and r = - 0.60 for full and reduced questionnaires, respectively. CONCLUSION: The DYSLIM questionnaire appears promising for the evaluation of dyspnea-induced limitations in chronic respiratory diseases and seems suitable for use in various contexts.

Severity and phenotypes of dyspnea in asthma: Impact of comorbidities.

BACKGROUND: Dyspnea is a common but non-specific symptom of asthma, which in particular may be related to anxiety and hyperventilation syndrome, two frequent comorbidities of asthma. METHODS: We conducted a prospective multicentric cohort study in dyspneic asthmatic adults. Dyspnea was assessed using the Multidimensional Dyspnea Profile questionnaire. We described the sensory (QS) and affective (A2) domains of dyspnea and investigated the effect of poor asthma control, hyperventilation and anxiety on each dimension at baseline and after 6 months. RESULTS: We included 142 patients (65.5% women, age: 52 years). Dyspnea was severe and predominated on its sensory domain (median QS: 27/50; A2: 15/50). Uncontrolled asthma (ACQ≥1.5), hyperventilation symptoms (Nijmegen≥23) and anxiety (HAD-A≥10) were present in 75%, 45.7% and 39% of cases, respectively. Hyperventilation symptoms were associated with higher QS and A2 scores: QS at 28.4(10.7) vs. 21.7(12.8) (p = 0.001) and A2 at 24(14) vs. 11.3(11) (p < 0.001) in patients with vs. without hyperventilation symptoms. Anxiety was only associated with increased A2 (27(12.3) vs. 10.9(11), p < 0.001). At 6 months, QS and A2 decreased of 7 and 3 points, respectively, in relation with changes in ACQ-6 and Nijmegen scores as well as the HAD-A score for A2. CONCLUSION: In breathless asthmatics, dyspnea is severe and worsened but differentially modulated by hyperventilation symptoms and anxiety. A multidimensional phenotyping of dyspnea in asthmatics could be useful to understand its origins and personalize treatment.

Otological Manifestations in Adults with Primary Ciliary Dyskinesia: A Controlled Radio-Clinical Study.

Primary ciliary dyskinesia (PCD) is a rare genetical disease characterized by an abnormal structure or function of the cilia, causing sinusitis, otitis, and bronchiectasis. Hearing loss affects 60% of PCD patients, but data are lacking concerning hearing and temporal bone imaging in adults. Our aim was to describe clinical and radiological ear disease in adults with genetically confirmed PCD. Data were recorded from January 2018 to December 2019. PCD patients were compared with controls with bronchiectasis without PCD. Clinical examination included otomicroscopy and auditory tests. A temporal bone CT scan (TBCT) was systematically performed. Seventeen patients (34 ears) were included in each group. The eardrums were abnormal in 25 (74%) PCD ears versus 8 (24%) ears in the controls (p < 0.05). Conductive hearing loss was more frequent in the PCD group (24% vs. 12% in controls). TBCT were abnormal in 94% PCD patients vs. 32% in the controls (p < 0.05). The Main CT-scan images in PCD were middle ear inflammation (65%), mastoid condensation (62%), or ossicular anomalies (35%). With its excellent sensitivity, TBCT gives typical arguments for PCD diagnosis, adding otological signs to the usual sinus CT signs (hypoplasia, aplasia). Systematic TBCT could be useful in the initial evaluation of patients with suspicion of PCD.

Real-life impact of uncontrolled severe asthma on mortality and healthcare use in adolescents and adults: findings from the retrospective, observational RESONANCE study in France.

OBJECTIVE: To characterise uncontrolled severe asthma and compare the disease burden with the general and asthmatic populations. DESIGN: Retrospective observational study using a national sample of a French healthcare database (Echantillon Généraliste des Bénéficiaires (EGB)). SETTING: The EGB, an anonymised permanent sample of health insurance databases, representing 1/97th of the French population. PARTICIPANTS: Patients (≥12 years) were selected in year 2014 and followed 2 years. A cohort of patients with uncontrolled severe asthma was defined using an algorithm based on peer-reviewed literature and Global Initiative for Asthma recommendations. Index date was the occurrence of the first marker of uncontrolled asthma. This cohort was matched with two control cohorts, general population and asthmatic controls, on baseline characteristics. MAIN OUTCOMES MEASURES: Mortality, healthcare use and associated costs were studied in the 2 years of follow-up. RESULTS: Among 467 716 individuals in the EGB, 16 588 patients with asthma were identified, including 739 (4.5%) with uncontrolled severe disease. The survival probability at 2 years for patients with uncontrolled severe asthma (92.0%) was lower than in the general population cohort (96.6%; relative risk of death: 2.35; 95% CI: 1.70 to 3.29; p<0.0001) and tended to be lower than in the control asthmatic cohort (94.3%; p=0.07). Emergency department visits and hospitalisations were higher in patients with uncontrolled severe asthma than in the general population (64.7% vs 34.9%; p<0.0001) and asthmatic controls (64.7% vs 55.2%; p=0.0002). Other components of healthcare use (medical and paramedical visits, medications) were increased in patients with uncontrolled severe asthma compared with control populations. These increases translated into higher costs (p<0.0001 for both comparisons). CONCLUSIONS: This study demonstrates the huge burden of uncontrolled severe asthma in terms of mortality, morbidity and healthcare resource consumption compared with other patients with asthma and with the general population and emphasises the importance of appropriate management in this high-risk population.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

Hypoxemia during sleep and overnight rostral fluid shift in pulmonary arterial hypertension: a pilot study.

Sleep-related breathing disorders, including sleep apnea and hypoxemia during sleep, are common in pulmonary arterial hypertension, but the underlying mechanisms remain unknown. Overnight fluid shift from the legs to the upper airway and to the lungs promotes obstructive and central sleep apnea, respectively, in fluid-retaining states. The main objective was to evaluate if overnight rostral fluid shift from the legs to the upper part of the body is associated with sleep-related breathing disorders in pulmonary arterial hypertension. In a prospective study, a group of stable patients with idiopathic, heritable, related to drugs, toxins, or treated congenital heart disease pulmonary arterial hypertension underwent a polysomnography and overnight fluid shift measurement by bioelectrical impedance in the month preceding or following a one-day hospitalization according to regular pulmonary arterial hypertension follow-up schedule with a right heart catheterization. Results show that among 15 patients with pulmonary arterial hypertension (women: 87%; median (25-75th percentiles); age: 40 (32-61) years; mean pulmonary arterial pressure 56 (46-68) mmHg; pulmonary vascular resistance 8.8 (6.4-10.1) Wood units), two patients had sleep apnea and eight (53%) had hypoxemia during sleep without apnea. The overnight rostral fluid shift was 168 (118-263) mL per leg. Patients with hypoxemia during sleep had a greater fluid shift (221 (141- 361) mL) than those without hypoxemia (118 (44-178) mL, p = 0.045). In conclusion, this pilot study suggests that hypoxemia during sleep is associated with overnight rostral fluid shift in pulmonary arterial hypertension.

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort.

BACKGROUND: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations. OBJECTIVE: To assess changes in asthma control between baseline and 12 months of treatment. METHODS: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). RESULTS: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.

Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme.

BACKGROUND: Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU. METHODS: This retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated. FINDINGS: Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL-1 at baseline to 92 cells·µL-1 at 24 months of follow-up; lung function and asthma control followed a similar trend. INTERPRETATION: Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial.

Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases.

BACKGROUND AND OBJECTIVE: Ventilatory inefficiency (high V'E/V'CO2) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO2 suggests increased chemosensitivity or an altered PaCO2 set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO2 set-point, exercise capacity, hemodynamics and V'E/V'CO2. METHODS: Pulmonary arterial hypertension (n=34), chronic thromboembolic pulmonary hypertension (CTEPH, n=19) and pulmonary veno-occlusive disease (PVOD, n=6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO2: hypocapnic (PaCO2 ≤34mmHg) or normocapnic (PaCO2 35-45mmHg). The PaCO2 set-point was estimated by the maximal value of end-tidal PCO2 (maximal PETCO2) between the anaerobic threshold and respiratory compensation point. RESULTS: The hypocapnic group (n=39) had lower resting cardiac index (3.1±0.8 vs. 3.7±0.7L/min/m2, p<0.01), lower peak V'O2 (15.8±3.5 vs. 20.7±4.3mL/kg/min, p<0.01), and higher V'E/V'CO2 slope (60.6±17.6 vs. 38.2±8.0, p<0.01). At peak exercise, hypocapic patients had lower PaO2, higher VD/VT and higher P(a-ET)CO2. Maximal PETCO2 (r=0.59) and VD/VT (r=-0.59) were more related to cardiac index than PaO2 or PaCO2 at rest or peak exercise. Maximal PETCO2 was the strongest correlate of V'E/V'CO2 slope (r=-0.86), peak V'O2 (r=0.64) and peak work rate (r=0.49). CONCLUSIONS: Resting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO2 set-point. Maximal PETCO2 may be a useful non-invasive marker of PaCO2 setpoint and disease severity even with submaximal effort.

Patient-Reported Outcome in Two Chronic Diseases: A Comparison of Quality of Life and Response Profiles in Severe Migraine and Severe Asthma.

INTRODUCTION: Migraine and asthma are two frequent, disabling, chronic disorders with a major impact on patient well-being. The objectives of this study were to compare subjective well-being between patients with severe forms of migraine or asthma using a panel of PROs. METHODS: Adult patients were recruited during routine consultations with chest physicians or neurologists. Patients with severe migraine (reporting headaches on ≥8 days/month and having failed ≥2 prophylactic treatments) and patients with severe asthma (according to the 2017 GINA definition: requiring Step 4 or 5 treatment or presenting uncontrolled symptoms) were eligible. Each patient completed the EuroQol Questionnaire (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire (WPAI) and the Hospital Anxiety and Depression scale (HAD). Patients with severe migraine the 6-item Headache Impact Test (HIT-6) and those with severe asthma completed the Asthma Control Test (ACT). RESULTS: 249 patients with severe migraine and 96 with severe asthma were enrolled. Mean EQ-5D-5L utility scores were significantly higher in the severe migraine group than in the severe asthma group (0.75±0.25 vs 0.68±0.26; p<0.01). Low EQ-5D-5L utility scores were associated with frequent (≥15 headache days/month) or disabling (HIT-6 score ≥60) headaches and with poor asthma control. Patients with severe migraine more frequently presented a HAD depression score ≥11 (23.0% in severe migraine; 7.5% in severe asthma; p<0.01), whereas those with severe asthma more frequently reported problems with mobility, self-care and usual activities. Absenteeism (percent worktime missed) was similar in both groups (severe migraine: 9.0%±19.1%; severe asthma: 13.8%±22.9%) but work impairment was higher in the severe migraine group (44.3% vs 28.4%; p<0.01). CONCLUSION: Quality of life, work activity and psychological distress are all deteriorated in both severe migraine and severe asthma. Different aspects are affected in the two diseases: a greater impact on psychological aspects in severe migraine and a greater impact on physical aspects in severe asthma.

How can we minimise the use of regular oral corticosteroids in asthma?

Options to achieve oral corticosteroid (OCS)-sparing have been triggering increasing interest since the 1970s because of the side-effects of OCSs, and this has now become achievable with biologics. The Société de Pneumologie de Langue Française workshop on OCSs aimed to conduct a comprehensive review of the basics for OCS use in asthma and issue key research questions. Pharmacology and definition of regular use were reviewed by the first working group (WG1). WG2 examined whether regular OCS use is associated with T2 endotype. WG3 reported on the specificities of the paediatric area. Key "research statement proposals" were suggested by WG4. It was found that the benefits of regular OCS use in asthma outside episodes of exacerbations are poorly supported by the existing evidence. However, complete OCS elimination couldn't be achieved in any available studies for all patients and the panel felt that it was too early to conclude that regular OCS use could be declared criminal. Repeated or prolonged need for OCS beyond 1 g·year-1 should indicate the need for referral to secondary/tertiary care. A strategic sequential plan aiming at reducing overall exposure to OCS in severe asthma was then held as a conclusion of the workshop.

Intensity and quality of exertional dyspnoea in patients with stable pulmonary hypertension.

Dynamic hyperinflation is observed during exercise in 60% of patients with clinically stable pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), intensifying exertional dyspnoea. The impact of dynamic changes in respiratory mechanics during exercise on qualitative dimensions of dyspnoea in these patients has not been evaluated.26 patients (PAH n=17; CTEPH n=9) performed an incremental symptom-limited cycle exercise test. Minute ventilation (V'E), breathing pattern, operating lung volumes and dyspnoea intensity were assessed throughout exercise. Dyspnoea quality was serially assessed during exercise using a three-item questionnaire (dyspnoea descriptors). The inflection point of tidal volume (V T) relative to V'E was determined for each incremental test. Changes in inspiratory capacity during exercise defined two groups of patients: hyperinflators (65%) and non-hyperinflators (35%). Multidimensional characterisation of dyspnoea was performed after exercise using the Multidimensional Dyspnea Profile.In hyperinflators, inspiratory capacity decreased progressively throughout exercise by 0.36 L, while remaining stable in non-hyperinflators. The "work/effort" descriptor was most frequently selected throughout exercise in both types of patients (65% of all responses). At the V T/V'E inflection, work/effort plateaued while "unsatisfied inspiration" descriptors became selected predominantly only in hyperinflators (77% of all responses). In the affective domain, the emotion most frequently associated with dyspnoea was anxiety.In pulmonary hypertension patients who develop hyperinflation during exercise, dyspnoea descriptors referring to unsatisfied inspiration become predominant following the V T/V'E inflection. As these descriptors are generally associated with more negative emotional experiences, delaying or preventing the V T/V'E inflection may have important implications for symptom management in patients with pulmonary hypertension.

[New approaches of inhaled steroid asthma management in mild to moderate asthma]. / Nouvelles modalités de prescription des corticoïdes inhalés dans l'asthme léger à modéré.

Inhaled corticosteroids (ICS) are the cornerstone of the management of asthma. Daily use allows to reduce mortality, intensity and frequency of exacerbations, to increase the control of symptoms of asthma and the quality of life of asthmatics patients and to reduce the decline of the lung function. A daily use of a weak dose of ICS allows to control the symptoms of asthma of the vast majority of mild to moderate asthmatics patients who account for about 75-80 % of the French asthmatic patients. An add-on strategy with a combination by ICS/LABA allows to decrease by 20 % the risk of an exacerbation compared with a treatment by CSI in monotherapy. "SMART" which consists in using a fixed ICS/LABA combination as a maintenance and reliever therapy had showed better results in the prevention of exacerbations that the use of the same combination associated with a SABA as a reliever therapy. This strategy is recommended by GINA at the same level of proof as the classical treatment. An "on-demand" use of a ICS/LABA combination according to symptoms is clearly less efficacious in terms of control of the symptoms than the classical strategy by ICS/LABA; but both strategies are identical in terms of prevention of exacerbations. The daily dose of ICS is 4 to 5 times less than in the daily ICS group. The clinical effectiveness and cost-effectiveness of a standard asthma self-management plan that advises patients to temporarily quadrupling the dose of ICS in case of asthma worsening can be an alternative and allow to reduce 20 % of clinically important asthma exacerbations.

Outpatient pulmonary rehabilitation for severe asthma with fixed airway obstruction: Comparison with COPD.

Background: The benefit of exercise has been demonstrated in asthma, but the role of pulmonary rehabilitation (PR) in people with severe asthma, especially with airway obstruction, has been less investigated. The activity limitation mechanisms differ in asthma and COPD, so the effect of a PR program not specific to asthma is unclear. Methods: We retrospectively compared the effect of an ambulatory PR program in nonsmoking patients with severe asthma and airway obstruction (FEV1/FVC ratio <70% and FEV1 < 80% measured twice, not under an exacerbation) and sex-, age-, FEV1-, and BMI-matched COPD controls. Results: We included 29 patients, each with asthma and COPD. Airway obstruction was moderate (median FEV1 57% [44-64]). VO2 at peak was higher for asthma than COPD patients (19.0 [15.7-22.2] vs 16.1 [15.3-19.6] ml.min-1.kg-1, p = 0.05). After PR, asthma and COPD groups showed a significant and similar increase in constant work cycling test of 378 [114-831] s and 377 [246-702] s. Changes in Hospital Anxiety and Depression Scale (HAD) total score were similar (-2.5 [-7.0 to 0.0] vs -2.0 [-5.0 to 2.0], p > 0.05). Quality of life on the St. George's Respiratory Questionnaire (SGRQ) was significantly improved in both groups (-14.0 [-17.7 to -2.0], p < 0.005 and -8.3 [-13.0 to -3.6], p < 0.0001). Conclusion: Outpatient PR is feasible and well tolerated in patients with severe asthma with fixed airway obstruction. A nondedicated program strongly improves HAD and SGRQ scores and constant work-rate sub-maximal cycling, with similar amplitude as with COPD.

Ventilatory response to exercise in cardiopulmonary disease: the role of chemosensitivity and dead space.

The lungs and heart are irrevocably linked in their oxygen (O2) and carbon dioxide (CO2) transport functions. Functional impairment of the lungs often affects heart function and vice versa The steepness with which ventilation (V'E) rises with respect to CO2 production (V'CO2 ) (i.e. the V'E/V'CO2 slope) is a measure of ventilatory efficiency and can be used to identify an abnormal ventilatory response to exercise. The V'E/V'CO2 slope is a prognostic marker in several chronic cardiopulmonary diseases independent of other exercise-related variables such as peak O2 uptake (V'O2 ). The V'E/V'CO2 slope is determined by two factors: 1) the arterial CO2 partial pressure (PaCO2 ) during exercise and 2) the fraction of the tidal volume (VT) that goes to dead space (VD) (i.e. the physiological dead space ratio (VD/VT)). An altered PaCO2 set-point and chemosensitivity are present in many cardiopulmonary diseases, which influence V'E/V'CO2 by affecting PaCO2 Increased ventilation-perfusion heterogeneity, causing inefficient gas exchange, also contributes to the abnormal V'E/V'CO2 observed in cardiopulmonary diseases by increasing VD/VT During cardiopulmonary exercise testing, the PaCO2 during exercise is often not measured and VD/VT is only estimated by taking into account the end-tidal CO2 partial pressure (PETCO2 ); however, PaCO2 is not accurately estimated from PETCO2 in patients with cardiopulmonary disease. Measuring arterial gases (PaO2 and PaCO2 ) before and during exercise provides information on the real (and not "estimated") VD/VT coupled with a true measure of gas exchange efficiency such as the difference between alveolar and arterial O2 partial pressure and the difference between arterial and end-tidal CO2 partial pressure during exercise.