Continuous positive airway pressure compliance in patients with mild cognitive impairment.

PURPOSE: Sleep apnoea (SA) is associated with accelerated cognitive decline in patients with mild cognitive impairment (MCI). Treatment of SA by continuous positive airway pressure (CPAP) may slow this decline if patients comply with the treatment. The aim of this study was to assess the rate of CPAP compliance in this population. METHODS: In this single-centre retrospective study conducted in a tertiary care institution, patients with a diagnosis of MCI and SA initiating CPAP between January 2015 and August 2021 were included. Data from the initial sleep recording, the 3-month follow-up and compliance with at least 12 months of CPAP were analysed. Compliance was defined as an average CPAP use of at least 4 h per night. RESULTS: 55 patients were included (49% women, age 70.7 ± 8.9 years, body mass index 28.9 ± 6.5 kg/m2). Aetiology of MCI was vascular (45.5%), psychiatric (12.7%) and related to Alzheimer's disease (7.3%), with 47.3% of amnesic disorders and 45.5% of dysexecutive disorders. The MiniMentalState score was 26.7 ± 3.1. SA was mostly obstructive (81.8%) with a mean apnoea-hypopnoea index of 41.1 ± 16.4/h. At 3 months, 38 patients were compliant (69%) with a CPAP median use of 5.9 h per night and 83% of nights. Self-reported tolerance was better in compliant patients (75.7% vs 38.5% p = 0.017). Thirty-four patients remained compliant at 12 months (62%). CONCLUSION: Our results suggest a high rate of CPAP compliance in patients suffering from MCI. Compliance was related to the device tolerance, emphasizing the need to closely monitor and improve this factor.

Risk factors for malignancy and serious infection in patients with inflammatory bowel disease: a retrospective analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population. AIMS: We aim to identify risk factors for malignancy or serious infection in our IBD cohort. METHODS: Patients with IBD from a single tertiary referral centre were included. Demographic and clinical details, including immunosuppressant exposure, were collected and medical records retrospectively screened for adverse events, including malignancy or infection requiring hospitalisation. Logistic regression was used to evaluate risk factors for adverse events. RESULTS: Five hundred and forty-nine patients with IBD (340 Crohn disease (CD) and 209 ulcerative colitis (UC)) were studied. Forty-eight malignancies, including 39 (81.3%) non-melanoma skin cancers, 3 (6.3%) haematologic malignancies and 6 (15.4%) solid-organ malignancies, were identified, and 92 cases of serious infection were detected. IBD duration (odds ratio (OR) = 1.08; 95% confidence interval (CI) = 1.03-1.13) and ileocolonic CD (OR = 4.96; 95% CI = 1.13-21.71) were associated with increased odds of overall cancer. Compared with patients not previously exposed to the given class of immunosuppression assessed, the development of overall malignancy was not higher with thiopurine exposure (OR = 1.00; 95% CI = 0.50-2.24) or anti-tumour necrosis factor-alpha (TNF-α) exposure (OR = 0.78; 95% CI = 0.37-1.64). Similarly, compared with patients not exposed, infection risk was not affected by thiopurine (OR = 0.74; 95% CI = 0.46-1.20) or anti-TNF exposure (OR = 0.60; 95% CI = 0.38-0.95). CONCLUSIONS: Factors including ileocolonic CD and increasing IBD duration were associated with higher malignancy risk in this cohort. Compared with non-exposure, patients exposed to thiopurines were not at increased risk of malignancy or serious infection. Similarly, patients exposed to anti-TNF treatment did not experience increased rates of malignancy or serious infection compared to patients not exposed to this treatment.

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study.

BACKGROUND: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. PURPOSE: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. DESIGN: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. METHODS: Adults with a confirmed diagnosis of severe asthma for at least 12 months' duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. RESULTS: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. CONCLUSION: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Outcomes of a Comprehensive Specialist Inflammatory Bowel Disease Nursing Service.

BACKGROUND: Inflammatory bowel disease (IBD) is best managed by a multidisciplinary team within a dedicated IBD service. IBD nurses play an important role within this team. We aimed to evaluate the contribution of our comprehensive outpatient IBD nursing service on patient outcomes, quality of care, and healthcare costs. METHODS: We performed a retrospective review of all IBD nurse encounters with patients over a 12-month period from October 2020 to September 2021 at a tertiary IBD referral center. Each nurse encounter was classified with respect to its clinical context, activities, and outcomes. Descriptive statistics were used to characterize these encounters and an economic analysis was performed to estimate the cost savings to the hospital. RESULTS: A total of 2537 nurse encounters occurred with 682 patients; 41% of encounters were nurse-initiated contacts with patients and 34% were patient-initiated contacts with the nurse helpline (26% via email, 8% via telephone). Most encounters involved clinical assessments (66%), providing education, counseling or updates (47%), and reviewing investigation results (38%). A gastroenterologist was consulted for advice in 35% of contacts. An estimated 29 emergency department visits, 1925 outpatient clinic visits, and 137 general practitioner visits were avoided. After deducting costs incurred, a net estimated annual saving of up to AUD $570 838 was achieved. Nurses commonly facilitated faster access to investigations (29%), education provision (28%), delivery of biologic services (25%), and medication changes (19%). CONCLUSIONS: A comprehensive IBD nursing service is associated with improved patient outcomes and quality of care, and reduced healthcare costs. This study supports the expanding role of IBD nurses in a modern multidisciplinary IBD service and the need for greater funding and integration of IBD nurses into IBD services.

Home-based pulmonary rehabilitation for adults with severe asthma exposed to psychosocial chronic stressors.

OBJECTIVE: To evaluate the effects of a home-based pulmonary rehabilitation (PR) programme on hyperventilation symptoms, anxiety and depressive symptoms, general fatigue, health-related quality of life (HRQoL) and exercise capacity in adults with severe asthma who have been exposed to psychosocial chronic stressors. METHODS: Data on 111 non-selected consecutive adults with severe asthma who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) was retrospectively analysed. Chronic stressors included physical, sexual and psychological violence and/or a traumatic experience related to an intensive care unit stay. Hyperventilation symptoms (Nijmegen questionnaire), Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, COPD Assessment Test, Six-Minute Stepper Test and Timed-Up and Go test were assessed at baseline and after PR. RESULTS: At baseline, participants who have been exposed to chronic stressors (n = 48, 43.2%) were younger, more often female, more often treated for anxiety and depressive disorders, and had a higher score for anxiety symptoms, hyperventilation symptoms and a poorer HRQoL, compared to those who had not been exposed to chronic stressors (p < 0.05). All the study assessments were statistically improved after PR for both groups (p < 0.001). Anxiety and depressive symptoms, fatigue and health-related quality of life questionnaires were also clinically improved based on the minimal clinically important difference. CONCLUSION: A large proportion of adults with severe asthma, mainly women, have been exposed to chronic stressors at the time of starting a PR programme, resulting in higher anxiety symptoms and hyperventilation symptoms. However, it did not prevent these individuals from benefiting from PR.

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.

Clinical outcomes amongst elderly patients with inflammatory bowel disease.

BACKGROUNDS AND AIMS: Inflammatory bowel disease (IBD) affects a growing cohort of elderly patients. Our aim was to compare the quality of care received by elderly patients with IBD with a nonelderly adult IBD population using clinical markers including steroid-free clinical remission. METHOD: Retrospective audit of all consecutive patients attending a specialist IBD centre over a 1-year period aged >60 (elderly cohort [EC]) and 50 consecutive patients aged 30-45 years (control cohort [CC]). A follow-up survey was completed assessing current symptoms and perceptions of care. RESULTS: One hundred thirty-nine patients were evaluated (89 EC, 50 CC). Steroid-free clinical remission was observed less commonly in the EC (58, 64%) compared with the CC (40, 80%) (P < 0.05). Biologics such as infliximab (15% EC vs 36% CC; P < 0.01) and adalimumab (14% EC vs 30% CC; P = 0.02) were used less frequently in the EC, whilst vedolizumab (6% EC vs 6% CC; P = 1) and ustekinumab (3% EC vs 2% CC; P = 1) were used at a similar frequency. Patients in the EC were less likely to have specialist IBD nursing contact (P < 0.01), smoking screening (P < 0.011) or influenza vaccinations (P < 0.006). IBD nurse contact was associated with significantly greater provision of the preventative care measures. CONCLUSION: Elderly patients with IBD were less likely to experience steroid-free clinical remission or be prescribed biologics. Elderly patients were less likely to receive education with respect to preventative medicine. The models of care for the elderly need re-evaluation and greater incorporation with the multidisciplinary IBD team.

Factors impacting performance on the 6-minute walk test by people with late-onset Pompe disease.

INTRODUCTION/AIMS: Pompe disease is a progressive myopathy that combines motor, respiratory, and cardiac impairments. The 6-min walk test is the gold standard for assessing disease severity at the motor level. The objective of this study was to better determine the parameters that influence the total distance covered in patients with Pompe disease. METHODS: We performed a retrospective review of 15 patients with late-onset Pompe disease who were followed regularly at a single referral center. Logistic regression was used to investigate the links between motor, respiratory and cardiac variables and 6-min walk test performance. RESULTS: When considering baseline clinical and demographic variables, a seven-step backward elimination regression analysis yielded a model with two predictors (age and the use of an assistive device) that explained 85.5% of the variance. When considering the cardiorespiratory variables monitored during gait, a three-step backward elimination regression analysis showed that two predictors (heart rate recovery and the baseline partial pressure of carbon dioxide) explained 42.2% of the variance. DISCUSSION: Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability) during the 6-min walk test in patients with Pompe disease. Further studies of larger cohorts are necessary to validate the model, which might enable investigators to determine whether intra-individual fluctuations in 6-min walk test performance are related to physiological parameters and/or to other variables such as the patient's level of motivation during the test.

Interventions to Improve Adherence to Preventive Care in Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: Preventive health measures reduce treatment and disease-related complications including infections, osteoporosis, and malignancies in patients with inflammatory bowel disease (IBD). Although guidelines and quality measures for IBD care highlight the importance of preventive care, their uptake remains variable. This systematic review evaluates interventions aimed at improving the rates of provision and uptake of preventive health measures, including vaccinations, bone density assessment, skin cancer screening, cervical cancer screening, and smoking cessation counseling. METHODS: We searched PubMed, MEDLINE, EMBASE, and CENTRAL for full text articles published until March 2021. Studies were included if they evaluated interventions to improve the provision or uptake of 1 or more preventive health measures in adult IBD patients and if they reported pre- and postintervention outcomes. RESULTS: In all, 4655 studies were screened, and a total of 17 studies were included, including 1 randomized controlled trial, 1 cluster-controlled trial, and 15 prospective interventional studies. A variety of interventions were effective in improving the rates of adherence to preventive health measures. The most common interventions targeted gastroenterologists, including education, electronic medical records tools, and audit feedback. Other interventions targeted patients, such as education, questionnaires, and offering vaccine administration at clinic visits. Few interventions involved IBD nurses or primary care physicians. CONCLUSIONS: A range of interventions-targeted at gastroenterologists, patients, or both-were effective in improving the provision and uptake of preventive care. Future studies should involve randomized controlled trials evaluating multifaceted interventions that target barriers to adherence and involve IBD nurses and primary care physicians.

Analysis of clinical pharmacist interventions in the COVID-19 units of a French university hospital.

OBJECTIVES: The objectives were to compare clinical pharmacist interventions between two care groups: COVID-19-positive and COVID-19-negative patients, and to identify drugs that require particular attention, especially those involved in COVID-19 management. METHODS: A prospective cohort study was conducted on patients with positive and negative COVID-19 statuses admitted to Lille University Hospital over 1 month. Pharmaceutical analysis instigated interventions to rectify drug-related errors. For each pharmaceutical intervention (PI), the anatomical therapeutic chemical classification of the drug and the outcome of such an intervention were specified. RESULTS: The study included 438 patients. Prescription analysis led to 188 PIs performed on 118 patients (64 COVID-19-positive patients and 54 COVID-19-negative patients). Most drug-related problems were incorrect dosage representing 36.7% (69/188) of all interventions: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The most frequent PI in 34% (64/188) of cases was terminating a drug: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The main drug classes involved were antithrombotic agents (20.7%, 39/188), antibacterials for systemic use (13.8%, 26/188) and drugs for gastric acid-related disorders (6.4%, 12/188). Study population was limited to a single centre over 1 month. CONCLUSION: No difference in PI was noted between the two groups. The presence of pharmacists led to a reduction in drug-related prescription problems, especially for antithrombotic and antibacterial drugs for both groups. Clinical pharmacy commitment in such a pandemic is therefore important.

Is CCL18 a potential biomarker of type-2 asthma endotypes?

Objective: This exploratory cross-sectional study aimed to evaluate the associations between the chemokine ligand 18 (CCL18) blood level and phenotypic characteristics of asthma.Methods: We evaluated in a sample of 173 asthmatic adult patients from the Cohort of Bronchial obstruction and Asthma (63.4% women; median age 50 ± interquartile range 27.5 years; median level of CCL18 was 44.1 ± interquartile range 27.5 ng/mL) the association between CCL18 blood level and allergic features of asthma using a multivariate analysis.Results: We found an association between the log-transformed value of blood CCL18 and age (+0.7% [0.1; 1.3] per 1-year increase, p = 0.033), gender (-25.1% [-42; -3.2] in women, p = 0.029), and nasal polyposis (+38.1% [11.6; 70.9], p = 0.004). No association was observed between CCL18 level and the other main phenotypic characteristics of asthma.Conclusions: Our exploratory study suggests that CCL18 is not an effective biomarker of allergic asthma endotype but may rather be a biomarker of tissue eosinophilia as supported by its association with nasal polyposis.

Influence of nocturnal hypoxemia on follow-up course after type B acute aortic syndrome.

INTRODUCTION: Association between sleep nocturnal breathing disorders and acute aortic syndrome (AAS) has been described but mid-term data are scarce. OBJECTIVES: We assessed the prognostic value of sleep apnea parameters and their relationship with aortic morphology after the onset of a type B AAS. METHODS: Between January 2010 and January 2018, sleep apnea screening in post type B AAS was prospectively performed. The association of sleep apnea parameters with aortic morphology and aortic expansion during follow-up was studied. RESULTS: Over the 8-year-study period, 103 patients were included, with a mean age of 57.8 ± 12.1 years old. Median follow-up was 25.0 months (11.0-51.0). Thirty-two patients (31%) required aortic stenting during the acute phase. In patients treated by aortic stenting, the descending thoracic aortic diameter was positively associated with a higher percentage of nocturnal time of saturation ≤ 90% after adjustment (p = 0.016). During follow-up, the nocturnal time of saturation ≤ 90% in patients treated by medical therapy was the only parameter associated with significant aortic expansion rate (r = 0.26, p = 0.04). Thirty-eight patients started and sustained nocturnal ventilation during follow-up. The association between aortic expansion rate and nocturnal time of saturation ≤ 90% did not persist during follow-up after adjustment on nocturnal ventilation initiation (r = 0.25, p = 0.056). CONCLUSIONS: Nocturnal hypoxemia parameters are positively associated with the max onset aortic diameter and significant aortic growth after type B AAS. Nocturnal ventilation seems to mitigate aortic expansion during follow-up.

Factors associated with Pneumocystis colonization and circulating genotypes in chronic obstructive pulmonary disease patients with acute exacerbation or at stable state and their homes.

Pneumocystis jirovecii colonization is frequent during chronic obstructive pulmonary disease (COPD) and patients constitute potential contributors to its interhuman circulation. However, the existence of an environmental reservoir cannot be excluded. We assessed the prevalence and factors associated with Pneumocystis colonization during COPD, and studied circulation between patients and their domestic environment. Pneumocystis molecular detection and mtLSU genotyping were performed in oro-pharyngeal washes (OPW) sampled in 58 patients with COPD acute exacerbation, and in indoor dust, sampled in patients' homes using electrostatic dust collectors (EDCs). Lung and systemic inflammation was assessed. Pneumocystis carriage was evaluated in 28 patients after 18 months at stable state. Pneumocystis was detected in 11/58 OPWs during exacerbation (19.0%). Colonized patients presented a significantly lower body mass index, and higher serum IL-17 and CD62P. One patient presented positive detection of typable isolates in both OPW and EDC, with both isolates harboring mtLSU genotype 3. Pneumocystis genotype 1 was further detected in EDCs from three non-colonized patients and one colonized patient with non-typable isolate. Genotypes 1 and 2 were predominant in clinical isolates (both 42%), with genotype 3 representing 16% of isolates. Pneumocystis was detected in 3/28 patients at stable state (10.7%). These data suggest that Pneumocystis colonization could be facilitated by a lower BMI and be related to acute alteration of lung function during COPD exacerbation. It also suggests Th17 pathway and platelet activation could be involved in the anti-Pneumocystis response during colonization. Last, Pneumocystis detection in EDCs supports its potential persistence in indoor dust. LAY SUMMARY: Chronic obstructive pulmonary disease patients tend to be more frequently colonized by Pneumocystis during exacerbation (19.0%) than at stable state (10.7%). Factors associated with colonization include lower BMI, higher IL-17, and CD62P. Pneumocystis detection in patients' dwellings suggests potential persistence in indoor dust.

Anti-interleukin 5 therapies failure criteria in severe asthma: a Delphi-consensus study.

BACKGROUND: Current practices for assessing response to anti-interleukin 5/R treatment in severe asthma patients are heterogeneous. The objective of this study was to achieve an expert consensus defining failure criteria for anti-interleukin 5/R treatment in severe asthma patients. METHODS: Experts were invited to a 5-round Delphi exercise if they were pulmonologists managing ⩾30 patients at a nationally recognized severe asthma expert centre. Following two rounds of statement-generating brainstorming, the expert panel ranked each statement according to a 5-point Likert-type scale during three additional rounds. Positive consensus was considered achieved when ⩾80% of experts agreed with a statement with >50% strong agreement and <15% disagreement. RESULTS: Twenty experts participated in the study. All experts agreed that predefined treatment goals defining effectiveness should be personalized during shared decision making via a patient contract. Treatment failure was defined as (1) absence of a reduction in exacerbation rates by ⩾25% or (2) absence of a reduction in oral corticosteroid therapy by ⩾25% of the initial dosage or (3) occurrence of emergency room visits or hospitalizations after 6 months of treatment. Treatment failure should result in discontinuation. For partial responders, treatment discontinuation was not recommended unless an alternative from another therapeutic class exists and should be discussed in a multidisciplinary consultation. CONCLUSION: The present study provides objective criteria for anti IL5 or IL5R failure in severe asthma and suggests consensus based guidelines for prescription, evaluation and discontinuation decision-making.

Assessment of pulmonary arterial circulation 3 months after hospitalization for SARS-CoV-2 pneumonia: Dual-energy CT (DECT) angiographic study in 55 patients.

BACKGROUND: During COVID-19, the main manifestations of the disease are not only pneumonia but also coagulation disorders. The purpose of this study was to evaluate pulmonary vascular abnormalities 3 months after hospitalization for SARS-CoV-2 pneumonia in patients with persistent respiratory symptoms. METHODS: Among the 320 patients who participated in a systematic follow-up 3 months after hospitalization, 76 patients had residual symptoms justifying a specialized follow-up in the department of pulmonology. Among them, dual-energy CT angiography (DECTA) was obtained in 55 patients. FINDINGS: The 55 patients had partial (n = 40; 72.7%) or complete (n = 15; 27.3%) resolution of COVID-19 lung infiltration. DECTA was normal in 52 patients (52/55; 94.6%) and showed endoluminal filling defects in 3 patients (3/55; 5.4%) at the level of one (n = 1) and two (n = 1) segmental arteries of a single lobe and within central and peripheral arteries (n = 1). DECT lung perfusion was rated as non-interpretable (n = 2;3.6%), normal (n = 17; 30.9%) and abnormal (n = 36; 65.5%), the latter group comprising 32 patients with residual COVID-19 opacities (32/36; 89%) and 4 patients with normal lung parenchyma (4/36; 11%). Perfusion abnormalities consisted of (a) patchy defects (30/36; 83%), (b) PE-type defects (6/36; 16.6%) with (n = 1) or without proximal thrombosis (n = 5); and (c) focal areas of hypoperfusion (2/36; 5.5%). Increased perfusion was seen in 15 patients, always matching GGOs, bands and/or vascular tree-in- bud patterns. INTERPRETATION: DECT depicted proximal arterial thrombosis in 5.4% of patients and perfusion abnormalities suggestive of widespread microangiopathy in 65.5% of patients. Lung microcirculation was abnormal in 4 patients with normal lung parenchyma.

Impact of domestic mould exposure on Aspergillus biomarkers and lung function in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are frequently colonised or sensitised by Aspergillus, but clinical significance remains unclear. Furthermore, little is known on the impact of indoor mould exposure during COPD. In this study, we assessed the relationship between domestic mould exposure, Aspergillus biomarkers and COPD severity during acute exacerbation and at stable state. Aspergillus section Fumigati culture in sputum and anti-Aspergillus antibodies detection (IgG and precipitins) were followed up in COPD patients that were prospectively recruited during exacerbation (n = 62), and underwent a visit at stable state after 18 months (n = 33). Clinical characteristics were collected at inclusion. Electrostatic dust collectors (EDCs) were used to measure domestic mould contamination. Aspergillus section Fumigati was more frequently detected during exacerbation (16.9%) than at stable state (4.0%), but the frequency of patients presenting with anti-Aspergillus antibodies was similar (32.2% and 33.3%, respectively). Aspergillus section Fumigati detection was associated with a higher body-mass index (BMI) during exacerbation, whereas patients with anti-Aspergillus antibodies presented a lower BMI and forced expiratory volume in 1 s, as well as a higher frequency of inhaled corticoids and higher total mould and Penicillium exposure at final visit (P < 0.05). The frequency of patients with anti-Aspergillus antibodies was higher for total mould counts >30 CFU/cm2 (P = 0.03). Aspergillosis was diagnosed in 2 patients (6.1%) who presented increased levels of antibodies. Our data suggest that anti-Aspergillus antibodies are associated with chronic lung function alteration and/or domestic mould exposure, thereby supporting the consideration of indoor mould contamination and anti-Aspergillus antibodies kinetics in COPD management.

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.