Influenza and pneumococcal vaccination in patients with COPD from 3 French cohorts: Insufficient coverage and associated factors.

BACKGROUND: Low vaccination rates against influenza and Streptococcus (S.) pneumoniae infections in COPD could impair outcomes. Understanding underlying factors could help improving implementation. OBJECTIVES: To describe vaccination rates at inclusion in COPD cohorts and analyze associated factors. METHODS: Between 2012 and 2018, 5927 patients with sufficient data available were recruited in 3 French COPD cohorts (2566 in COLIBRI-COPD, 2653 in PALOMB and 708 in Initiatives BPCO). Data at inclusion were pooled to describe vaccination rates and analyze associated factors. RESULTS: Mean age was 66 years, 34 % were women, 35 % were current smokers, mean FEV1 was 58 % predicted, 22 % reported ≥2 exacerbations in the year prior to inclusion, mMRC dyspnea grade was ≥2 in 59 %, 52 % had cardiovascular comorbidities and 9 % a history of asthma. Vaccinations rates in the year prior to study entry were 34.4 % for influenza + S. pneumoniae, 17.5 % for influenza alone and 8.9 % for S. pneumoniae alone. In multivariate analyses, influenza vaccination rate was greater in older age, smoking status, low FEV1, exacerbation history, mMRC dyspnea>2, asthma history, hypertension, diabetes mellitus, and the year of inclusion. SP vaccination was associated with type of practice of the respiratory physician, age, smoking status, FEV1, exacerbation history, dyspnea grade, asthma history and the year of inclusion. CONCLUSION: Rates of vaccination against influenza and S. pneumoniae infection at inclusion in COPD cohorts remain insufficient and vaccination appears restricted to patients with specific features especially regarding severity and comorbidities, which is not consistent with current recommendations.

Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.

Rationale: Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives: To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods: A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV1) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results: ETI was initiated in 434 pwCF with a median ppFEV1 of 30 (interquartile range, 25-35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396-728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV1 by a mean of +14.2% (95% confidence interval, 13.1-15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV1 in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index < 18.5 kg/m2 was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions: ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.

Whispers of change in preschool asthma phenotypes: Findings in the French ELFE cohort.

RATIONALE: Early life asthma phenotyping remains an unmet need in pediatric asthma. In France, severe pediatric asthma phenotyping has been done extensively; however, phenotypes in the general population remain underexplored. Based on the course and severity of respiratory/allergic symptoms, we aimed to identify and characterize early life wheeze profiles and asthma phenotypes in the general population. METHODS: ELFE is a general population based birth cohort; which recruited 18,329 newborns in 2011, from 320 maternity units nationwide. Data was collected using parental responses to modified versions of ISAAC questionnaire on eczema, rhinitis, food allergy, cough, wheezing, dyspnoea and sleep disturbance due to wheezing at 3 time points: post-natal (2 months), infancy (age 1) and pre-school (age 5). We built a supervised trajectory for wheeze profiles and an unsupervised approach was used for asthma phenotypes. Chi squared (χ2) test or fisher's exact test was used as appropriate (p < 0.05). RESULTS: Wheeze profiles and asthma phenotypes were ascertained at age 5. Supervised wheeze trajectory of 9161 children resulted in 4 wheeze profiles: Persistent (0.8%), Transient (12.1%), Incident wheezers at age 5 (13.3%) and Non wheezers (73.9%). While 9517 children in unsupervised clusters displayed 4 distinct asthma phenotypes: Mildly symptomatic (70%), Post-natal bronchiolitis with persistent rhinitis (10.2%), Severe early asthma (16.9%) and Early persistent atopy with late onset severe wheeze (2.9%). CONCLUSION: We successfully determined early life wheeze profiles and asthma phenotypes in the general population of France.

Impact of biomass fuel smoke on respiratory health of children under 15 years old in Madagascar.

BACKGROUND: Children exposed to biomass used in households are at risk to develop diseases or respiratory symptoms. In Madagascar more than 95% of households use it daily. The main objective is to study the impact of chronic exposure to biomass on respiratory health of children under 15 years old in Madagascar. METHODS: Descriptive cross-sectional study conducted with questionnaires among urban and rural population of Antananarivo and Mahajanga provinces between 2016 and 2017. Variables were collected: number of hours spent in kitchen per day, respiratory symptoms and spirometric data. Categorized symptoms score and exposure index expressing chronic exposure to biomass were analyzed with multinomial logistic regression models. RESULTS: Of the 661 children included in the analysis, 27.7% had 1 respiratory symptom and 29.3% had 2 or more respiratory symptoms. Moderate exposure index (aOR=1.57; CI95%=[1.30-1.89]; p<0.001) and high exposure index (aOR=1.76; CI95%=[1.39-2.24]; p<0.001) were significantly associated with 1 respiratory symptom, adjusted with provinces, household members and visitors smoking, perceived discomfort related to air pollution and birthweight. Exposure index was not significantly associated with an increased risk of having 2 or more respiratory symptoms (p = 0.754). CONCLUSION: Respiratory symptoms were associated with exposure to biomass, living in coastal areas, birthweight, tobacco and perceived discomfort related to air pollution. Recommendations and actions must be implemented in order to improve respiratory health related to biomass among children.

The external validation of the asthma prediction tool in the French ELFE cohort.

BACKGROUND: Existing predictive scores for early identification of children at high risk of developing asthma include invasive procedures, and hence have limited utility in a primary care setting. The Leicestershire respiratory cohort (LRC) has developed a noninvasive asthma prediction tool (APT) for children with promising results. We aimed to perform its external validation in the French general population Étude Longitudinale Française depuis l'Enfance (ELFE) cohort. METHODS: Predictive scores were determined at Age 1 and the primary outcome of asthma was defined as parental reporting of "asthma ever or "wheezing in the past 12 months" at Age 5. Logistic regression was used to calculate the odds ratio (OR) and performance measures, and discriminative performance was reported using the receiver operating curve and area under curve (AUC). Calibration was assessed using Hosmer-Lemeshow goodness-of-fit test and visualized with a calibration plot. Overall performance was determined using Brier scores. RESULTS: Of the 10,689 children analyzed: 84.9% were at low, 13.1% medium, and 2% at high risk of developing asthma at Age 5. Children in the medium-risk category were three times more likely to develop asthma (OR = 3.3, 95% confidence interval [CI] = 2.97-3.78) whereas 13 times more likely in the high-risk category (OR = 13.8, 95% CI = 10.2-18.8). The tool's AUC was comparable: LRC 0.74 versus ELFE 0.68; as were the Brier scores LRC 0.16 versus ELFE 0.14. The tool's performance was robust to changes in inclusion criteria and outcome definitions. CONCLUSIONS AND RELEVANCE: Results of the present study and previous validation studies performed in high-risk populations provide a comprehensive measure of the effectiveness of the APT, providing encouragement for its application by general practitioners.

Susceptibility to frequent exacerbation in COPD patients: Impact of the exacerbations history, vaccinations and comorbidities?

INTRODUCTION: Exacerbations are key events in the natural history of COPD, but our understanding of their longitudinal determinants remains unclear. We used data from a large observational study to test the hypothesis that vaccination status and comorbidities could be associated with the occurrence of exacerbations profile. METHODS: Diagnosed COPD patients have been included by their pulmonologists, with up to 3 years of follow-up. Data were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic curve analysis to determine the best threshold to allocate patients to identified clusters. RESULTS: 932 COPD patients were included since January 2014, 446 patients (65.68% males, 35.59% current smokers) were followed over a period of 3 years with complete data. 239(28.15%) patients reported two or more exacerbations in the year before enrolment (frequent exacerbations). Among them 142(16.68%) also had frequent exacerbations in the first year of the study, and 69(8.10%) who remained frequent exacerbators in the second year. Based on our hypothesis, we were able to determine four phenotypes: A (infrequent), B (frequent in underweight patients), C (transient), and D (frequent in obese patients). Frequent exacerbators had more airflow limitation and symptoms. Irrespective of cut-offs set to define the optimal number of clusters, a history of exacerbations OR: 3.72[2.53-5.49], presence of anxiety OR: 2.03[1.24-3.31] and absence of the annual influenza vaccination OR: 1.97[1.20-3.24] remained associated with the frequent exacerbator phenotypes. CONCLUSIONS: The most important determinants of frequent exacerbations are a history of exacerbations, anxiety and unvaccinated against influenza.

Comorbidities and COPD severity in a clinic-based cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality around the world. The aim of our study was to determine the association between specific comorbidities and COPD severity. METHODS: Pulmonologists included patients with COPD using a web-site questionnaire. Diagnosis of COPD was made using spirometry post-bronchodilator FEV1/FVC < 70%. The questionnaire included the following domains: demographic criteria, clinical symptoms, functional tests, comorbidities and therapeutic management. COPD severity was classified according to GOLD 2011. First we performed a principal component analysis and a non-hierarchical cluster analysis to describe the cluster of comorbidities. RESULTS: One thousand, five hundred and eighty-four patients were included in the cohort during the first 2 years. The distribution of COPD severity was: 27.4% in group A, 24.7% in group B, 11.2% in group C, and 36.6% in group D. The mean age was 66.5 (sd: 11), with 35% of women. Management of COPD differed according to the comorbidities, with the same level of severity. Only 28.4% of patients had no comorbidities associated with COPD. The proportion of patients with two comorbidities was significantly higher (p < 0.001) in GOLD B (50.4%) and D patients (53.1%) than in GOLD A (35.4%) and GOLD C ones (34.3%). The cluster analysis showed five phenotypes of comorbidities: cluster 1 included cardiac profile; cluster 2 included less comorbidities; cluster 3 included metabolic syndrome, apnea and anxiety-depression; cluster 4 included denutrition and osteoporosis and cluster 5 included bronchiectasis. The clusters were mostly significantly associated with symptomatic patients i.e. GOLD B and GOLD D. CONCLUSIONS: This study in a large real-life cohort shows that multimorbidity is common in patients with COPD.