ERS statement on transition of care in childhood interstitial lung diseases.

Interstitial lung diseases (ILD) are a heterogeneous group of rare diffuse diseases affecting the lung parenchyma in children and adults. Childhood interstitial lung diseases (chILD) are often diagnosed at very young age, affect the developing lung, and can have different presentations and prognosis compared to adult forms of these diseases. Also, chILD in many cases may apparently remit, and have a better response to therapy and better prognosis than adult ILD. Many affected children will reach adulthood with minimal activity or clinical remission of the disease. They need continuing care and follow-up from childhood to adulthood if the disease persists and progresses over time but also if they are asymptomatic and in full remission. Therefore, for every chILD patient an active transition process from paediatric to adult care should be guaranteed. This ERS statement provides a review of the literature and current practice concerning transition of care in chILD. It draws on work in existing transition care programs in other chronic respiratory diseases, disease-overarching transition of care programs, evidence on the impact of these programs on clinical outcomes, current evidence regarding long-term remission of chILD as well as the lack of harmonisation between the current adult ILD and chILD classifications impacting on transition of care. While the transition system is well established in several chronic diseases, such as cystic fibrosis or diabetes mellitus, we could not find sufficient published evidence on transition systems in chILD. This statement summarises current knowledge but cannot yet provide evidence-based recommendations for clinical practice.

Baseline reticular basement membrane morphology is related to subsequent spirometry deterioration in pediatric chronic airway inflammation: a follow-up study.

Reticular basement membrane (RBM) thickening may occur in children with allergic bronchial asthma (BA), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD). Its functional consequences remain unknown. We investigated the relationship between baseline RBM thickness and subsequent spirometry. In our cohort follow-up study, patients aged 3-18 yr with BA, CF, and PCD and controls underwent baseline lung clearance index (LCI) measurement, spirometry, and endobronchial biopsy sampling. Total RBM and collagen IV-positive layer thickness were measured. Trends in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), and FEV1/FVC were analyzed during follow-up, and their relationship to baseline characteristics was studied using univariate analysis and multiple regression models. Complete baseline data were available in 19 patients with BA, 30 patients with CF, 25 patients with PCD, and 19 controls. The RBM was thicker in patients with BA (6.33 ± 1.22 µm), CF (5.60 ± 1.39 µm), and PCD (6.50 ± 1.87 µm) than in controls (3.29 ± 0.55 µm) (all P < 0.001). The LCI was higher in patients with CF (15.32 ± 4.58, P < 0.001) and PCD (10.97 ± 2.46, P = 0.002) than in controls (7.44 ± 0.43). The median follow-up times were 3.6, 4.8, 5.7, and 1.9 years in patients with BA, CF, PCD, and controls, respectively. The z-scores of FEV1 and FEV1/FVC deteriorated significantly in all groups except in controls. In patients with CF and PCD, trends in FEV1 z-scores correlated with baseline LCI and RBM; in BA, it correlated with collagen IV. In multiple regression models, RBM morphology and ventilation inhomogeneity could predict up to 84.4% of variability in spirometry trends. In conclusion, baseline LCI value and RBM morphology may predict trends in subsequent spirometry.NEW & NOTEWORTHY This paper deals with the relationship between reticular basement membrane (RBM) morphology at baseline and follow-up spirometry in children with asthma, cystic fibrosis, and primary ciliary dyskinesia. For the first time, to our knowledge, the possibility to predict subsequent lung function development using selected baseline characteristics (reticular basement membrane morphology from endobronchial biopsy and ventilation inhomogeneity from nitrogen multiple breath washout test) is proposed. Corresponding predictive models are presented.

Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK.

BACKGROUND: Inborn errors of immunity are genetic disorders characterized by various degrees of immune dysregulation that can manifest as immune deficiency, autoimmunity, or autoinflammation. The routine use of next-generation sequencing in the clinic has facilitated the identification of an ever-increasing number of inborn errors of immunity, revealing the roles of immunologically important genes in human pathologies. However, despite this progress, treatment is still extremely challenging. OBJECTIVE: We sought to report a new monogenic autoinflammatory disorder caused by a de novo activating mutation, p.Tyr515∗, in hematopoietic cell kinase (HCK). The disease is characterized by cutaneous vasculitis and chronic pulmonary inflammation that progresses to fibrosis. METHODS: Whole-exome sequencing, Sanger sequencing, mass spectrometry, and western blotting were performed to identify and characterize the pathogenic HCK mutation. Dysregulation of mutant HCK was confirmed ex vivo in primary cells and in vitro in transduced cell lines. RESULTS: Mutant HCK lacking the C-terminal inhibitory tyrosine Tyr522 exhibited increased kinase activity and enhanced myeloid cell priming, migration and effector functions, such as production of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α, and production of reactive oxygen species. These aberrant functions were reflected by inflammatory leukocyte infiltration of the lungs and skin. Moreover, an overview of the clinical course of the disease, including therapies, provides evidence for the therapeutic efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in inflammatory lung disease. CONCLUSIONS: We propose HCK-driven pulmonary and cutaneous vasculitis as a novel autoinflammatory disorder of inborn errors of immunity.

Lung function from school age to adulthood in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores), but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low body mass index was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosis.

The respiratory consequences of COVID-19 lasted for a median of 4 months in a cohort of children aged 2-18 years of age.

AIM: We focused on the clinical picture, severity and prognosis of children who experienced long-term respiratory issues after COVID-19. METHODS: This was a national Czech multicentre study of paediatric post-COVID syndrome, which used a standard protocol to evaluate structural and functional anomalies and exclude alternative diagnoses. From 6 January to 30 June 2021, 11 paediatric pulmonologists enrolled all paediatric referrals aged 2-18 years with persistent respiratory symptoms more than 12 weeks after COVID-19, namely cough, dyspnoea and chest pain. Medical histories were taken, and physical examinations, lung function testing, chest X-ray and blood tests were performed. RESULTS: The dominant symptoms in the 39 children (56.4% girls) were exertional dyspnoea (76.9%) and a chronic cough (48.7%), while dyspnoea at rest (30.8%) and chest pain (17.9%) were less prevalent. More than half (53.8%) reported more than 1 symptom, and 38.5% had abnormal results for 1 of the following tests: lung function, chest X-ray or D-dimers. The median age of the children was 13.5 years (interquartile range ±4.8 years), and the median recovery time was 4 months (range 1.5-8 months). CONCLUSION: Our initial data suggest that the long-term respiratory impact of COVID-19 was relatively mild in our cohort, with a favourable prognosis.

Bronchodilating effects of a new beclometasone dipropionate plus formoterol fumarate formulation via pressurized metered-dose inhaler in asthmatic children: a double-blind, randomized, cross-over clinical study.

A new pediatric fixed combination of beclometasone dipropionate (BDP) 50 µg and formoterol fumarate (FF) 6 µg via pressurized metered-dose inhaler (pMDI) (CHF1535, Chiesi, Italy) was investigated. In a double-blind, randomized, placebo-controlled, cross-over study, a single CHF1535 administration using AeroChamber Plus™ spacer device (2 actuations, total dose BDP 100 µg/FF 12 µg) was compared to the same pMDI free combination in 56 asthmatic children aged ≥ 5 and < 12 years. Primary efficacy variable was forced expiratory volume during the first second (FEV1) area under the curve corrected by time over 12 h following morning dose (AUC0-12h). Further CHF1535 doses (50 µg/6 µg, 100 µg/12 µg, and 200 µg/24 µg) were also explored. Adverse events, electrocardiogram, and vital signs were monitored for safety. CHF1535 was non-inferior to free combination [adjusted mean difference (95% CI) 0.004 L (- 0.050, 0.041] with lower confidence limit greater than the limit set at 0.1 L. FEV1 AUC0-12h of each CHF1535 dose vs placebo were 0.037 L (p = 0.160), 0.119 L (p < 0.001), and 0.094 (p < 0.001) for 50/6, 100/12, and 200/24, respectively. No safety signals were found.Conclusion: CHF1535 was as effective as free combination BDP/FF, with a trend towards a dose-related response. All treatments were safe.Trial registration: ClinicalTrials.gov ID: NCT01584492 What is Known: •Inhaled pressurized metered-dose solutions (pMDI) are the preferred treatment for pediatric asthma. •Combination therapy of inhaled corticosteroids and long-acting ß2- agonists is a well-established approach to control airway inflammation and airway obstruction also in pediatric patients. What is New: •A novel pediatric pMDI fixed combination of beclomethasone dipropionate 50 µg and formoterol fumarate 6 µg (CHF 1535) was non-inferior to the free combination at the same dose in pulmonary function over the 12-h post-dose period in asthmatic children, with trend towards a dose-related response.

Four seasons of Czech asthma study: asthma characteristics and management reality in the Czech Republic.

Objective: To describe the characteristics and management of asthma in clinical practice in the Czech Republic in the context of international guidelines and clinical realities.Methods: Data were collected over four seasons from summer 2016 to spring 2017 and are mostly presented using descriptive statistics.Results: We obtained valid data for 4557 adult patients with asthma, including detailed phenotyping (71% eosinophilic allergic, 10% eosinophilic non-allergic, 19% non-eosinophilic non-allergic asthma) from 58 allergologists and 56 pulmonologists. The average time to diagnosis was 3 years. In more than half of the subjects, bronchodilator testing (BDT) results were available at primary diagnosis. More than 10% of physicians did not test for mold allergy. Occupational asthma was diagnosed in 0.7% of subjects. According to the attending physician, 68% of patients had well-controlled and 10% had uncontrolled asthma. Ninety-four percent of patients were on preventive treatment, with 91% using an inhaled corticosteroids (ICS) at an average dose of 705 µg/day budesonide equivalent. Approximately 75% of patients were on an ICS/LABA, with 91% using fixed combinations. Among patients using ICS/formoterol, a maintenance and reliever therapy regime was prescribed in 67%.Conclusions: The quality of asthma management in the Czech Republic is comparable to that of other developed countries and better in some respects (frequent BDT, phenotyping, and use of preventive treatment). Nevertheless, there is unnecessary delay in diagnosis and lack of research on possible environmental causes (workplace, molds). Pharmacotherapy shows good adherence to guidelines. Although 10% of patients show poor control, there is concurrently a trend for overtreatment.

Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

ERS statement: interventional bronchoscopy in children.

Paediatric airway endoscopy is accepted as a diagnostic and therapeutic procedure, with an expanding number of indications and applications in children. The aim of this European Respiratory Society task force was to produce a statement on interventional bronchoscopy in children, describing the evidence available at present and current clinical practice, and identifying areas deserving further investigation. The multidisciplinary task force panel performed a systematic review of the literature, focusing on whole lung lavage, transbronchial and endobronchial biopsy, transbronchial needle aspiration with endobronchial ultrasound, foreign body extraction, balloon dilation and occlusion, laser-assisted procedures, usage of airway stents, microdebriders, cryotherapy, endoscopic intubation, application of drugs and other liquids, and caregiver perspectives. There is a scarcity of published evidence in this field, and in many cases the task force had to resort to the collective clinical experience of the committee to develop this statement. The highlighted gaps in knowledge underline the need for further research and serve as a call to paediatric bronchoscopists to work together in multicentre collaborations, for the benefit of children with airway disorders.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia.

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood.

BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease. CASE PRESENTATION: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient's pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient's brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient's family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

Paediatrics in Barcelona.

This update will describe the paediatric highlights from the 2013 European Respiratory Society (ERS) annual congress in Barcelona, Spain. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) have been chosen by group officers and are presented in the context of current literature.

Structural changes in the bronchial mucosa of young children at risk of developing asthma.

BACKGROUND: Bronchial asthma often starts in early childhood. Clinical manifestation of the disease is likely due to inflammatory processes in the airways initiated by various stimuli. Developed remodelling is regularly observed in the bronchial mucosa of adult asthmatics but we still lack information about its onset and latter development with the natural course of the disease. In this study, we analysed histological findings in bronchial biopsies obtained from very young children (under 4 yr of age). We hypothesized that initial undetectable changes in the airway epithelium of children predisposed to asthma may be one of the first mechanisms leading to morphological changes in the bronchial mucosa. METHODS: We measured the thickness of the basement membrane using a light microscope and analysed the presence of its three basic structural glycoproteins: laminin, tenascin and collagen IV, using immunohistochemical techniques. We compared these findings in children predisposed to asthma according to the selected clinical criteria of the Asthma Predictive Index and in a control group of children. RESULTS: We found a significant difference in the thickness of the basement membrane between the two groups. We also found a difference in the subepithelial deposition of laminin and collagen IV in the basement membrane but no difference in the deposition of tenascin. CONCLUSIONS: We conclude that initial changes leading to further remodelling may start at a very early age even before clinical manifestation of the disease.

Epithelial basement membrane thickening is related to TGF-Beta 1 expression in children with chronic respiratory diseases.

BACKGROUND: The complex structural changes of bronchial mucosa, known as remodelling, have been considered unique and typical for asthma. However, similar changes were recently found in other chronic respiratory diseases. The aim of this study was to compare basement membrane (BM) thickness and the number of transforming growth factor beta 1 (TGF-ß1) positive epithelial cells in children with asthma, cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and healthy controls. METHODS: A total of 58 children (11.1 ± 3.9 yr, 55% males) were enrolled in this cross-sectional study. Endobronchial biopsy was performed in 27 children with asthma, 12 with CF, 12 with PCD and in 7 control patients. We studied the samples using light microscopy to assess BM width, the number of TGF-ß1 positive epithelial cells and their correlation. RESULTS: We found increased BM thickness (6.65 ± 1.22 µm vs. 2.93 ± 0.75 µm, p < 0.01) and a higher number of TGF-ß1 positive epithelial cells (61.39 ± 19.03 vs. 21.57 ± 12.58, p < 0.01) in children with chronic respiratory diseases compared to controls. There was no difference in these parameters between asthma, CF and PCD. A positive correlation between BM thickness and the number of TGF-ß1 positive cells was observed in all groups including controls (r = 0.84, p < 0.01). CONCLUSIONS: Increased BM thickness and number of TGF-ß1 positive epithelial cells were found in children with asthma, CF and PCD. The number of TGF-ß1 positive cells correlated positively with the BM thickness in all groups. We suggest that this might be a common generic feature of bronchial remodelling in chronic respiratory diseases.

Complication rates in rigid vs. flexible endoscopic foreign body removal in children.

While foreign body aspiration remains a frequent and preventable cause of morbidity and mortality in children, recommendations on the appropriate removal technique do often not match the lived practice and expertise of the performing examiners. As there is a scarcity of data regarding success and complication rates of the procedure, the aim of this study was to set up a classification system for procedure-related complications, prospectively record and analyze them. Specialists in the field of foreign body removal contributed cases anonymously. Information regarding procedural details of the bronchoscopy, type, and severity of complications as well as patient characteristics were classified and recorded. Correlations were calculated using Pearson's Chi Square test. A total of 314 rigid and 178 flexible bronchoscopies were compared. Complications were categorized and their severity was defined by the anesthesiologist's assessment of whether to interrupt or terminate the procedure. The overall complication rate was similar in rigid vs. flexible bronchoscopy (19.1% vs. 24.2%, p = 0.232), while respiratory complications occurred significantly less frequent during rigid bronchoscopy (9.2% vs. 16.3%, p = 0.025). This is the largest pediatric case collection recording and comparing complications between rigid and flexible foreign body removal. The higher rate of respiratory complications in flexible bronchoscopy has been shown for the first time and validates some of the concerns about its use for foreign body removal. Flexible bronchoscopy is a safe procedure when extended respiratory monitoring and the possibility of an immediate switch to a secured airway are assured.

Management of primary ciliary dyskinesia in European children: recommendations and clinical practice.

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.

Repeatability of lung clearance index in infants with cystic fibrosis and recurrent wheeze.

OBJECTIVES: To describe the short- and medium-term repeatability of lung clearance index at 2.5% (LCI2.5 ) in infants and calculate the number of patients needed to enroll in a study (N) using LCI2.5 as a primary outcome. METHODS: An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)] and medium-term repeatability (Bland-Altman method) of LCI2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N2 -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated. RESULTS: Forty infants with CF and 21 with RW were enrolled. Initial N2 -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI2.5 value. In clinically stable patients, LCI2.5 did not significantly change during the 8-month follow-up. Mean LCI2.5 change was -0.08 (1% of baseline) in CF and -0.05 (0.6%) in RW, with 95% limits of agreement being (-1.70; 1.53) in CF and (-1.51; 1.40) in RW patients. N = 23 infants if both intragroup differences of LCI2.5 and minimal difference to be detected would be 2.0. CONCLUSION: N2 -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies.

Effectiveness and Durability of mRNA Vaccine-Induced SARS-CoV-2-Specific Humoral and Cellular Immunity in Severe Asthma Patients on Biological Therapy.

Coronavirus disease 2019 (COVID-19) vaccines effectively elicit humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthy populations. This immunity decreases several months after vaccination. However, the efficacy of vaccine-induced immunity and its durability in patients with severe asthma on biological therapy are unknown. In this study, we evaluated the effectiveness and durability of mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy. The study included 34 patients with severe asthma treated with anti-IgE (omalizumab, n=17), anti-IL5 (mepolizumab, n=13; reslizumab, n=3), or anti-IL5R (benralizumab, n=1) biological therapy. All patients were vaccinated with two doses of the BNT162b2 mRNA vaccine with a 6-week interval between the doses. We found that this COVID-19 vaccination regimen elicited SARS-CoV-2-specific humoral and cellular immunity, which had significantly declined 6 months after receipt of the second dose of the vaccine. The type of biological treatment did not affect vaccine-elicited immunity. However, patient age negatively impacted the vaccine-induced humoral response. On the other hand, no such age-related impact on vaccine-elicited cellular immunity was observed. Our findings show that treatment of patients with severe asthma with biological therapy does not compromise the effectiveness or durability of COVID-19 vaccine-induced immunity.