Prevalence and burden of chronic cough in France.

Background: Chronic cough is a common condition that is associated with lower health-related quality of life and greater healthcare resource use. There are limited data on the prevalence, population characteristics and burden of chronic cough in France. Methods: This was a cross-sectional study based on responses from French adult residents to the 2020 National Health and Wellness Survey. Respondents with chronic cough were compared to 1:3 propensity score-matched controls without chronic cough. Results: The weighted lifetime and 12-month prevalence of chronic cough were estimated as 7.5% and 4.8%, respectively. Respondents with chronic cough reported significantly worse perceived health than matched controls, with lower mean±sd scores of 46.68±9.28 versus 50.42±8.26 on the physical health component and 40.32±9.87 versus 44.32± 9.69 on the mental health component of the Medical Outcomes Study 12-item Short Form Survey Version 2 survey (p<0.001 for both comparisons). Respondents with chronic cough also had higher rates of moderate-to-severe forms of anxiety (24.4% versus 12.4%) and depression (36.4% versus 20.2%); higher rates of multiple forms of sleep disturbance; greater impairment of work productivity (38.2% versus 25.5%) and other activities (41.8% versus 28.2%; p<0.001 for all comparisons). Respondents with chronic cough also had higher rates of all-cause healthcare resource use including emergency room visits, hospitalisation, and overall and specialist healthcare provider visits compared to controls (p<0.001 for all comparisons). Conclusion: Chronic cough is a common condition in France that is associated with lower health-related quality of life and greater healthcare resource utilisation.

NOVEOS and ImmunoCAP Have Similar Performances for Diagnosing Food Allergies.

BACKGROUND: The clinical significance of newly available platforms for specific IgE measurement must be evaluated. However, data are lacking for NOVEOS (Hycor), especially for food allergens. OBJECTIVE: We compared the technical and clinical performance of two platforms (ImmunoCAP and NOVEOS) to measure specific IgE to 10 food allergens. METHODS: Sera from 289 clinically characterized patients were tested for IgE specific for six food allergen extracts (egg white, cow's milk, peanut, hazelnut, fish, and shrimp) and four molecular allergens (Gal d 1, Bos d 8, Ara h 2, and Cor a 14). Specific IgE measurements were carried out using ImmunoCAP and NOVEOS methods. Food allergy diagnoses were established according to international guidelines. RESULTS: A strong correlation (ρ > 0.9) was present between the two platforms whereas specific IgE concentrations measured with NOVEOS were consistently lower (mean, -15%) than with ImmunoCAP. NOVEOS and ImmunoCAP provided similar overall odds ratios and relative risks for food allergy diagnosis with both allergen extracts and molecular allergens. When all 10 allergens were considered, NOVEOS provided better receiver operating characteristic curves (P = .04). Finally, we found that the most discordant results were observed with hazelnut and peanut extracts and were related to cross-reactive carbohydrate determinants for these two with ImmunoCAP. CONCLUSIONS: Specific IgE determination by either ImmunoCAP or NOVEOS (odds ratios of allergy, 25.1 or 33.0, respectively) is highly informative regarding the risk of allergy in the selected population. The NOVEOS platform presents the advantage of being less affected by unwanted reactivity owing to carbohydrate determinant-specific IgE while requiring a 10-fold lower test sample volume.

The economic burden of asthma prior to death: a nationwide descriptive study.

Background: In addition to the clinical burden, asthma is responsible for a high economic burden. However, little is known about the economic burden of asthma prior to death. Objective: We performed an economic analysis to describe the costs during 12 and 24 months prior to asthma death between 2013 and 2017 in France. Methods: An observational cohort study was established using the French national health insurance database. Direct medical and non-medical costs, as well as costs related to absence from the workplace, were included in the analysis. Results: In total, 3,829 patients were included in the final analysis. Over 24 and 12 months prior to death, total medical costs per patient were €27,542 [26,545-28,641] and €16,815 [16,164-17,545], respectively. Total medical costs clearly increased over 24 months prior to death. Over 12 months prior to death, costs increased significantly according to age categories, with mean total costs of €8,592, €15,038, and €17,845, respectively, for the categories <18 years old, 18-75 years old, and 75+ years old (p < 0.0001). Over 12 months prior to death, costs were statistically higher in patients with a dispensation of six or more SABA canisters compared to those with a dispensation of five or less canisters (p < 0.0001). In multivariate analysis, comorbidities, hospital as location of death, and dispensation of 12 or more canisters of SABA per year are independent factors of the highest costs. Conclusion: To conclude, the economic burden of asthma death is high and increases with time, age, and SABA dispensation.

Articular manifestations related to anti-interleukin-5 therapies in severe asthma: a case series.

Articular manifestations should be screened before and during anti-IL-5/5R biologic treatment in severe asthma. Rigorous multidisciplinary team discussion should be carried out to assess the risk-benefit balance of withholding effective treatment. https://bit.ly/3vfPn4k.

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.

Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study.

Background: Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods: We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results: An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions: The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.

Impact of pharmacological and non-pharmacological interventions on mortality in chronic obstructive pulmonary disease (COPD) patients.

PURPOSE: This review aimed to summarise evidence about the impact of pharmacological and non-pharmacological interventions on survival in COPD patients. METHODS: We performed a narrative literature review on the effect of pharmacological and non-pharmacological interventions on survival in COPD patients. RESULTS: Inhaled therapies are central to reduce symptoms in COPD. In particular, inhaled steroids seem to have the greatest effect on mortality. Despite the anti-inflammatory effects attributed to statins, their benefit in COPD has been shown only in cases of combined cardiovascular diseases. The use of beta-blockers in COPD has not been associated with increased COPD-related mortality and a beneficial effect on all-cause mortality has even been shown in COPD patients with cardiovascular diseases. Influenza and pneumococcal vaccination reduced the occurrence of exacerbations and mortality due to COPD. In addition, long-term oxygen therapy (LTOT) (≥15h/day) in COPD patients with severe hypoxemia had a positive effect on survival. Regarding non-pharmacological interventions, it has been demonstrated that smoking cessation, treatment compliance and nutritional supplementation for underweight patients also have a positive effect on survival. Non-invasive ventilation results were dependent on patient PaCO2 levels. In patients with advanced COPD, further prospective studies are needed to know the effect of bronchoscopic lung volume reduction and lung transplant on COPD survival. Regarding lung transplant, a survival benefit in patients with a pre-transplant BODE score of ≥7 has been shown in retrospective studies. CONCLUSION: Most of the studies did not evaluate survival as the main criteria and further long-term studies on the global management of COPD are required.

Benralizumab for eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. METHODS: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. RESULTS: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004). CONCLUSIONS: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study.

INTRODUCTION: The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC). METHODS: PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention. RESULTS: Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose-response signal with eliapixant was detected for the primary endpoint (all dose-response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43-51 (57-65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1-16% (n = 1-13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant. CONCLUSION: Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020.

Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial.

BACKGROUND: A written action plan (WAP) for managing asthma exacerbations is recommended. OBJECTIVE: We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone. METHODS: This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse. RESULTS: Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI -0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app. CONCLUSIONS: The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958.

Guidelines for the management of chronic cough in adults. Endorsed by the French speaking society of respiratory diseases (Société de Pneumologie de Langue Française, SPLF), the Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou (SFORL), the Société Française de Phoniatrie et de Laryngologie (SFPL), the Société Nationale Française de Gastro-entérologie (SNFGE).

Patients with chronic cough experience a high alteration of quality of life. Moreover, chronic cough is a complex entity with numerous etiologies and treatments. In order to help clinicians involved in the management of patients with chronic cough, guidelines on chronic cough have been established by a group of French experts. These guidelines address the definitions of chronic cough and the initial management of patients with chronic cough. We present herein second-line tests that might be considered in patients with cough persistence despite initial management. Experts also propose a definition of unexplained or refractory chronic cough (URCC) in order to better identify patients whose cough persists despite optimal management. Finally, these guidelines address the pharmacological and non-pharmacological interventions useful in URCC. Thus, amitryptilline, pregabalin, gabapentin or morphine combined with speech and/or physical therapy are a mainstay of treatment strategies in URCC. Other treatment options, such as P2 × 3 antagonists, are being developed.

Sputum-Rheology-Based Strategy for Guiding Azithromycin Prescription in COPD Patients with Frequent Exacerbations: A Randomized, Controlled Study ("COPD CARhE").

(1) Background: We have previously shown that sputum rheology can discriminate between patients with COPD and other muco-obstructive lung diseases, and that it is correlated with mucin content and sputum eosinophilia. We now hypothesize that it could be a more-accurate guide than clinical evaluation for the prescription of azithromycin to prevent exacerbations of COPD and to reduce exposure to antibiotics; (2) Methods: "COPD CaRhe" is a multicentric, randomized, controlled trial comparing outcomes in two parallel arms (36 vs. 36 patients). Patients will be recruited in the university hospitals of Montpellier, Bordeaux, and Toulouse, in France, and they should have a diagnosis of COPD with frequent exacerbations (≥3/year). Enrollment will occur during a routine visit to a respiratory department, and follow-up visits will occur every 3 months for a period of 1 year. At each visit, a 3-month prescription of azithromycin will be provided to those patients who obtain a score of <70 on the Cough and Sputum Assessment Questionnaire (CASA-Q) or a critical stress score of σc > 39 on a rheological assessment of sputum, depending upon their randomization group. The primary outcome will be the number of exacerbations of COPD; (3) Discussion: By using sputum rheology, the COPD CaRhe study may provide clinicians with an objective biomarker to guide the prescription of azithromycin while reducing the cumulative exposure to macrolides.

Healthcare resource consumption prior to asthma-related death: a nationwide descriptive study.

BACKGROUND: Although asthma mortality declined sharply until the mid-2000s, a stagnation in mortality has been observed over the past decade in different countries. OBJECTIVE: The objective of this study is to describe healthcare resource consumption for patients who died from asthma in France. METHOD: This study was conducted using data from the French National Health Data System. Patients who died from asthma between 2013 and 2017 were identified by the ICD10 codes J45 and J46. Health care consumption data were collected. Patients were categorized into four categories according to age: ⩾75, (18-75), (12-18), (0-12). Daily doses of ICS were categorized according to GINA guidelines. RESULTS: A total of 3829 patients were included. No ICS or an inadequate ICS dose was observed in 43.8%, 50.6%, 48.1%, and 54.0% of patients aged ⩾75, (18-74), (12-18), and (0-12) years, respectively. Dispensation of six or more SABA canisters was observed in 37.2%, 49.0%, and 70.3% of patients aged of ⩾75, (18-75), and (12-18) years, respectively. Omalizumab dispensation rate was very low [1.1% and 2.8% in patients aged ⩾75 and (18-75) years)]. The proportion of patients with a pulmonologist office visit was 13.8% and 14.6% in patients ⩾75 and (18-75) years, respectively. A lung function test was noted in only 18.6%, 28.3%, and 25.9% of patients ⩾75, (18-75) and (12-18) years, respectively. CONCLUSION: Half of the patients who died from asthma received inadequate ICS doses and only a small proportion had access to biological therapies. Less than 15% were referred to a specialist.

Updated guidelines (2021) for management and follow-up of asthmatic patients of the French Society of Pneumology (SPLF) and the French Society of Pediatric Pneumology and Allergology (SP2A). Short version.

The therapeutic management strategy is based on the regular evaluation of the control of asthmatic disease, with an effective minimum dose research and the assessment of environmental factors, not to mention the important place of therapeutic education. These professional recommendations relate to the management and follow-up of adult and adolescent asthma patients aged 12 and over. The recommendations answer the following questions: 1. How to make the initial diagnosis of asthma? 2. What allergological check-up should be done in asthmatics 3. How to manage an asthma exacerbation? 4. How to manage difficult asthma? 5. What therapeutic strategies? 6. How to manage a woman's asthma during pregnancy? 7. Environmental factors in asthma management review.