Effect of nirsevimab on hospitalisations for respiratory syncytial virus bronchiolitis in France, 2023-24: a modelling study.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalisations and deaths among infants worldwide. France was one of the first countries to implement a national programme (beginning on Sept 15, 2023) for administration of nirsevimab, a single-dose long-acting monoclonal antibody treatment, to infants born on or after Feb 6, 2023, to prevent lower respiratory tract infection caused by RSV. We aimed to estimate the effectiveness of nirsevimab and the number of hospitalisations averted in children younger than 24 months in real-world settings. METHODS: In this modelling study, we developed an age-structured deterministic model characterising RSV transmission as well as plausible scenarios for the administration of nirsevimab doses based on maternity ward and community pharmacy supply data. We retrospectively estimated nirsevimab effectiveness in infants younger than 24 months during the 2023-24 RSV season in France (excluding overseas territories) and the number of averted hospitalisations for RSV bronchiolitis occurring after emergency department visits, by calibrating the model to hospital and virological surveillance data from Aug 21, 2017, to Feb 4, 2024, alongside serological data from a previous cross-sectional study. To assess the robustness of our estimates, we conducted sensitivity analyses in which we modified our assumptions about the number of doses administered, the reconstruction of the number of RSV-associated hospitalisations for bronchiolitis, the duration of maternal and post-infection immunity to RSV, and the number of contacts in children aged 0-2 months. FINDINGS: We estimated that nirsevimab administration prevented 5800 (95% credible interval 3700-7800) RSV-associated hospitalisations for bronchiolitis after emergency department visits among children younger than 24 months, including 4200 (2900-5600) hospitalisations among those aged 0-2 months, between Sept 15, 2023 (the date nirsevimab was introduced), and Feb 4, 2024-a 23% (16-30) reduction in the total number of hospitalisations and a 35% (25-44) reduction in the 0-2 months age group, compared with the scenario without administration. In our baseline scenario, in which we estimated that 215 000 doses of nirsevimab were administered by Jan 31, 2024, the estimated effectiveness against RSV-associated hospitalisations for bronchiolitis was 73% (61-84), corresponding to one hospitalisation averted for every 39 (26-54) doses administered. In sensitivity analyses, nirsevimab remained effective against RSV-associated hospitalisations for bronchiolitis after emergency department attendance. INTERPRETATION: Our findings show that nirsevimab administration campaigns could effectively reduce the RSV-related hospital burden of bronchiolitis in children younger than 24 months. FUNDING: European Commission, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme, and INCEPTION project.

SARS-CoV-2 and RSV bronchiolitis outcomes.

BACKGROUND: Severe acute respiratory syndrome related coronavirus (SARS-CoV-2) bronchiolitis has arisen with the SARS-CoV-2 pandemic. There is a paucity of literature on SARS-CoV-2 bronchiolitis. OBJECTIVE: The purpose of our paper was to review and compare outcomes in bronchiolitis due to severe acute respiratory syndrome related coronavirus 2 (SARS- CoV-2) and Respiratory Syncytial Virus (RSV). We also performed a subgroup analysis of two disrupted RSV seasons during the pandemic. METHODS: This was a retrospective study from a US TriNetX database from March 1, 2020-January 1, 2023. Propensity matching was utilized for confounders. RESULTS: There was a total of 3,592 patients (1,796 in each group) after propensity matching. There was an increased risk of oxygen saturation ≤95 % (RR=1.50 95 % CI 1.58-1.94, p = 0.002) and ICU admission (RR=1.44 95 % CI 1.06-1.94, p = 0.02) in those with SARS- CoV-2 but not for oxygen saturation ≤90 % (RR=1.03 95 %CI 0.75-1.42, p = 0.85) or intubation (RR=0.73 95 % CI 0.35-1.47, p = 0.37). There was a decreased risk of a patient with SARS- CoV-2 bronchiolitis being hospitalized (RR=0.65 95 % CI 0.57-0.74, p < 0.0001), respiratory rate ≥60 (RR=0.64 95 % CI 0.48-0.88, p < 0.001) or ≥70 (RR=0.64 95 % CI 0.43-0.96, p = 0.03) when compared to RSV bronchiolitis. Specifically examining SARS- CoV-2 versus RSV bronchiolitis during the delayed RSV seasons, during the first season both infections were not severe, but during the second RSV bronchiolitis season, patients infected with RSV had less risk of ICU admission compared to those infected with SARS- CoV-2. CONCLUSION: SARS- CoV-2 bronchiolitis patients appeared to have more severe outcomes since the risk of ICU admission was higher for these patients. Also, during the second delayed RSV season, SARS- CoV-2 bronchiolitis was more severe than RSV bronchiolitis.

Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?

BACKGROUND: Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis. METHODS: We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O 2 supplementation and the admission at the pediatric intensive care unit. RESULTS: A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O 2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons ( P < 0.001). CONCLUSIONS: This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.

Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections.

OBJECTIVES: To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration. DESIGN: Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration. SETTING: PICUs in 12 high and low/middle-income countries. PATIENTS: Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% ( n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684-1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value. CONCLUSIONS: Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.

Epidemiological shifts in bronchiolitis patterns and impact of the COVID-19: A two-season comparative study.

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection (LRTI) affecting infants and young children. Respiratory syncytial virus (RSV) has historically been the primary causative agent, but other viruses also contribute to the LRTI epidemiology. Recent changes in epidemiology and clinical patterns due to the coronavirus disease 2019 (COVID-19) pandemic have raised concerns. This study aims to analyze the impact of the pandemic on bronchiolitis epidemiology and severity. METHODS: Two consecutive bronchiolitis seasons (October 2021 to March 2022 and October 2022 to March 2023) were compared. Data on viral agents, hospitalization duration, clinical severity, and respiratory support requirements were collected from pediatric patients at San Marco Hospital, University of Catania. RESULTS: In the 2021-2022 season, RSV was the predominant virus (40%), followed by other viruses, with mild clinical outcomes. In the 2022-2023 season, RSV remained prevalent (58.7%), but other viruses, including rhinovirus (RV) and influenza, showed a significant increase (p < .05) in bronchiolitis cases and severity. Notably, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season, contrary to the previous year. CONCLUSION: The COVID-19 pandemic appears to have shifted the epidemiological landscape of bronchiolitis, with a peak incidence in November instead of January/February. Non-RSV viruses (RV, influenza A and B, as well as metapneumovirus) have gained prominence, possibly due to viral competition and reduced pandemic-related restrictions. Traditionally, RSV has been the primary pathogen responsible for most bronchiolitis cases. Nonetheless, the findings of this study indicate a shifting landscape in bronchiolitis etiology, with RSV gradually diminishing in its role. Contrary to the previous year, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season.

Head-to-Head Comparison Between Respiratory Syncytial Virus and Human Metapneumovirus Bronchiolitis in the Setting of Increased Viral Testing.

We compared the epidemiology, severity and management of hospitalized respiratory syncytial virus (n = 305) and human metapneumovirus (n = 39) bronchiolitis in a setting with high respiratory virus testing (95% of admissions tested). Respiratory syncytial virus-positive infants were younger and tended to require more hydration support and longer hospital stays compared to human metapneumovirus-positive infants. Respiratory support requirements were similar between groups despite significant age differences.

Multilevel analysis identifying the factors associated with RSV detection in infants admitted for viral bronchiolitis in the era of the COVID-19 pandemic.

OBJECTIVES: To identify factors independently associated with respiratory syncytial virus (RSV) detection in infants admitted for viral bronchiolitis during 3 consecutive years, before and during the COVID-19 pandemic, in Bogota, Colombia, a middle-income country with a subtropical highland climate. METHODS: An analytical cross-sectional study was conducted before and during the COVID-19 pandemic, including patients with a diagnosis of viral bronchiolitis admitted to all the hospitals of the city between January 2019 and November 2021. We evaluated a set of a priori-selected predictor variables that included individual, healthcare system, meteorological, air pollutant, and COVID-19 variables. Since the variables analyzed are hierarchical in nature, multilevel modeling was used to identify factors independently associated with detection of RSV as the causative agent of viral bronchiolitis. RESULTS: A total of 13,177 patients were included in the study. After controlling for potential confounders, it was found that age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.76-0.97), a third level of medical care institution (OR 3.05; 95% CI 1.61-5.76), temperature (OR 1.60; 95% CI 1.24-2.07), rainfall (OR 1.003, 95% CI 1.001, 1.005), NO2 (OR 0.97; 95% CI 0.95-0.99), CO (OR 0.99; 95% CI 0.99-0.99), and COVID-19 pandemic period (OR 0.84, 95% CI 0.71-0.99) were independently associated with RSV detection in our sample of patients. CONCLUSIONS: The identified factors associated with RSV detection provide additional scientific evidence that may be useful in the development of specific interventions aimed at ameliorating or preventing the impact of RSV in Bogota and probably other similar low- to middle-income countries in high-risk infants.

Temporal-spatial analysis of hospitalizations for bronchiolitis in Brazil: prediction of epidemic regions and periods for immunization against the Respiratory Syncytial Virus.

OBJECTIVE: Due to the high cost and short term of passive immunization against the respiratory syncytial virus, the main virus causing acute viral bronchiolitis, predicting epidemic regions and epidemic months is extremely important. The objective of this study is to identify both the month when the seasonal peak begins and Brazilian regions and states with the highest incidence of monthly hospitalizations due acute viral bronchiolitis. METHODS: Based on data obtained from DATASUS, monthly hospitalization rates due acute viral bronchiolitis were calculated for every 10,000 live births to children under 12 months of age in all Brazilian states and the Federal District between 2000 and 2019. Seasonal autoregressive integrated moving average models were estimated to forecast monthly hospitalization rates in 2020. RESULTS: A higher incidence of hospitalizations was found for male children, especially under six months of age. As for Brazilian regions, between 2000 and 2019, the South region registered the highest incidence of hospitalizations, followed by the Southeast, Midwest, North and Northeast regions, in this order. Considering the seasonal peak, the period between March and July 2020 comprised the highest expected hospitalization rates. CONCLUSIONS: Palivizumab is suggested to be started between February/March and June/July for most Brazilian states, with the exception of Rio Grande do Sul, which, in addition to presenting the highest rates of hospitalizations for acute viral bronchiolitis per 10,000 live births, has the longest seasonal peak between May and September.

Increased RSV-A Bronchiolitis Severity in RSV-Infected Children Admitted to a Reference Center in Catalonia (Spain) Between 2014 and 2018.

Between 2014 and 2018, we evaluated the severity of 687 cases of bronchiolitis caused by respiratory syncytial virus (RSV) in Catalonia, Spain. Compared to RSV-B, RSV-A cases required intensive care (adjusted relative risk (aRR) = 1.44, p < 0.01) and respiratory support (aRR = 1.07, p < 0.01) more often; hospital stay was one day longer (p < 0.01). Subgroup identification may aid clinical evaluation and seasonal healthcare planning.

Uso de solución salina hipertónica al 3 por ciento en niños con bronquiolitis aguda / Usage of 3 percent Hypertonic Saline Solution in Children with Acute Bronchitis

Introducción: La bronquiolitis aguda es la infección del tracto respiratorio inferior más frecuente en el lactante. Tiene una incidencia anual del 10 por ciento en los lactantes y una tasa de ingreso de entre el 2 y el 5 por ciento con un incremento importante en los últimos años. Objetivo: Determinar la efectividad del uso de solución salina hipertónica al 3 por ciento nebulizada en pacientes con bronquiolitis aguda. Métodos: Se realizó un estudio analítico longitudinal prospectivo de tipo casos y controles. El universo estuvo constituido por 132 pacientes distribuidos en 66 casos y 66 controles. Resultados: La edad media fue de 3,6 ± 2,5 meses. Los sibilantes se hallaron en 129 pacientes, lo que representó el 97,7 por ciento. Se encontró una estadía hospitalaria media de 3,19 ± 1,41 días en los casos, mientras que en los controles se encontró una media de 4,97 ± 1,77 días, diferencia que resultó altamente significativa (p < 0,001). Conclusiones: Aunque los pacientes tratados con solución salina hipertónica al 3 por ciento necesitaron más días con oxigenoterapia, el tratamiento resultó ser efectivo al mostrar una menor estadía hospitalaria y un menor número de complicaciones en pacientes con bronquiolitis aguda(AU)

Introduction: Acute bronchiolitis is the most frequent lower respiratory tract infection in the infant. It has a yearly incidence of 10 percent in infants and an admission rate of 2 percent to 5 percent, with a significant increase in recent years. Objective: To determine the effectiveness of nebulized 3 percent hypertonic saline solution treatment in patients with acute bronchiolitis. Methods: A prospective, longitudinal and analytical study of case-control design was carried out. The universe consisted of 132 patients distributed into 66 cases and 66 controls. Results: The mean age was 3.6±2.5 months. Wheezing was found in 129 patients, accounting for 97.7 percent. A mean hospital stays of 3.19±1.41 days was found in cases, while a mean of 4.97±1.77 days was found in controls, a difference that was highly significant (P<0.001). Conclusions: Although patients treated with 3 percent hypertonic saline solution required more days with oxygen therapy, the treatment proved to be effective by showing a shorter hospital stay and a lower number of complications in patients with acute bronchiolitis(AU)

Lung function, allergic sensitization and asthma in school-aged children after viral-coinfection bronchiolitis.

Our main objective was to compare the lung function, the rate of allergic sensitization and the prevalence of asthma at 7-9 years in children hospitalized for bronchiolitis with viral coinfection versus single viral infection. Observational study in children with previous bronchiolitis and current age 7-9 years. Clinical data were collected. Fraction of exhaled nitric oxide (FeNO) determination, spirometry and skin prick test for common aeroallergens were performed. A total of 181 children hospitalized for bronchiolitis (40 coinfections and 141 single infections), with median age of 8.3 years (IQR:7.5-9.1) were included. Single-HRV-infections showed lower basal FEV1(%) than coinfections (p = 0.04) and lower z-score FEV1 than single-RSV-infections (p = 0.04) or coinfections (p = 0.02). Also, single-HRV-infections had lower post-bronchodilator FEV1(%) and z-score FEV1 values than coinfections (p = 0.03 and p = 0.03). Single-HRV-bronchiolitis was an independent risk factor for FEV1 < 80% (p = 0.007). FeNO value > 25 ppb was detected in 21(12.5%) cases, without differences between viral groups (p = 0.768). The prevalence of allergic sensitization was similar in coinfections (31.4%) versus single infections (38.7%), (p = 0.428). The highest frequency of allergic rhinitis was observed in single-HRV patients (p = 0.004). The respiratory morbidity at 7-9 years of coinfected patients was similar to the single-HRV ones. In contrast, the likelihood of current asthma was up to 5 times higher in RSV/HRV coinfections than in the single-RSV-infections ones (p = 0.012). The respiratory morbidity at 7-9 years of age after severe bronchiolitis is significantly higher in single-HRV or viral coinfection patients that in single-RSV ones. Single-HRV-bronchiolitis is independently associated with lower lung function at school-age.

Evaluation of reported medical services provided to pediatric viral bronchiolitis diagnoses during the COVID-19 pandemic.

BACKGROUND: Mitigation strategies were implemented during the coronavirus disease 2019 (COVID-19) pandemic that slowed the spread of this virus and other respiratory viruses. The objective of this study is to assess the impact of COVID-19 mitigation strategies on the medical services that children less than 1 year of age with acute bronchiolitis required (emergency department services, hospitalization, critical care services, and mechanical ventilation). METHODS: This was a retrospective observational cohort study utilizing TriNetX ® electronic health record (EHR) data. We included subjects less than 1 year of age with a diagnosis of acute bronchiolitis. After the query, the study population was divided into two groups [pre-COVID-19 (March 1st, 2019 until February 29th, 2020) and COVID-19 (March 1st, 2020 until February 1th, 2021)]. We analyzed the following data: age, sex, race, diagnostic codes, common terminology procedures (CPT), and antimicrobials administered. RESULTS: A total of 5063 subjects (n,%) were included [4378 (86.5%) pre-COVID-19 and 685 (13.5%) during the COVID-19 pandemic]. More subjects were diagnosed with acute bronchiolitis in the pre-COVID time frame (4378, 1.8% of all hospitalizations) when compared to the COVID-19 pandemic time frame (685, 0.5%). When diagnosed with acute bronchiolitis, the frequency of emergency department services, critical care services, hospitalization, and mechanical ventilationwere similar between the two cohorts. CONCLUSIONS: During the COVID-19 pandemic, less infants were diagnosed with acute bronchiolitis but the frequency of emergency department services, hospitalization, and mechanical ventilation, reportedly required was similar. Longer-term studies are needed to evaluate the benefits of COVID-19 mitigation strategies on common viruses that require critical care.

RSV Epidemiology in Australia Before and During COVID-19.

COVID-19 public health measures altered respiratory syncytial virus (RSV) epidemiology. We examined age-stratified trends in RSV-related disease in Australian children in 2020 compared with previous years.

Rhinoviruses as critical agents in severe bronchiolitis in infants.

OBJECTIVES: To detect RSV or other thirteen respiratory viruses as possible causer agent of bronchiolitis in infants. METHOD: This is an epidemiological analytical study, conducted using a nasopharyngeal aspirate of 173 hospitalized children younger than two years old with severe bronchiolitis in three hospitals in the Campinas Metropolitan Region (CMR) during 2013-14. The data was statically evaluated by Pearson's chi-squared test with statistical significance of 0.05 and 95% confidence level. RESULTS: As expected, the most prevalent viruses detected were RSV A and B in 47% and 16% of the samples, respectively. However, almost a third of severe bronchiolitis cases there were no detection of RSV, and the viruses more commonly detected were rhinoviruses, which were identified in almost a quarter of all positive samples for at least a viral agent. CONCLUSIONS: Although nothing could be concluded from the disease severity and clinical-epidemiological data, the present study's results indicate that severe bronchiolitis is not always related to RSV infections in children younger than two years old, and the rhinoviruses were more prevalent in these cases. These findings reinforce the need to carry out a viral diagnosis in the hospital emergency would be very appropriate for all cases of respiratory infections in children, even for diseases in which the primary etiological agent seems to be well known.

Increasing burden of viral bronchiolitis in the pediatric intensive care unit; an observational study.

PURPOSE: Viral bronchiolitis is a major cause of pediatric intensive care unit (PICU) admission. Insight in the trends of bronchiolitis-associated PICU admissions is limited, but imperative for future PICU resource and capacity planning. MATERIALS AND METHODS: We retrospectively studied trends in PICU admissions for bronchiolitis in six European sites, including three full national registries, between 2000 and 2019 and calculated population-based estimates per 100,000 children where appropriate. Information concerning risk factors for severe disease and use of invasive mechanical ventilation was also collected when available. RESULTS: In total, there were 15,606 PICU admissions for bronchiolitis. We observed an increase in the annual number, rate and estimates per 100,000 children of PICU admissions for bronchiolitis at all sites over the last two decades, while the proportion of patients at high risk for severe disease remained relatively stable. CONCLUSIONS: The international increased burden of bronchiolitis for the PICU is concerning, and warrants further international attention and investigation.

Epidemiology and prevention of respiratory syncytial virus infections in children in Italy.

Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.

High Frequency of Viral Co-Detections in Acute Bronchiolitis.

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6-week- to 12-month-old infants presenting at the emergency department with moderate to severe acute bronchiolitis. Viral testing was performed, and we found that 98% of samples were positive, including 90% for respiratory syncytial virus, 34% for human rhino virus, and 55% for viral co-detections, with a predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) exist. The role of virus detection and the burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.