This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were ...sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.
The aim of this study was to assess the role of European ambulatory pediatricians in caring for asthmatic children, especially in terms of their therapeutic education. We developed a survey that was ...observational, declarative, retrospective and anonymous in nature. 436 ambulatory pediatricians in Belgium, France, Germany, Italy, Luxembourg and Slovenia were asked to participate in the survey providing information on three children over 6 years old suffering from persistent asthma, who had been followed for at least 6 months. We considered the pediatricians' profile, and their role in the therapeutic education of children. 277 pediatricians (64%) responded: 81% were primary care pediatricians; 46% participated in networks; 4% had specific training in Therapeutic Patient Education; 69% followed more than 5 asthmatic children per month, and over long periods (7 ± 4 years). The profiles of 684 children were assessed. Answers diverged concerning the provision of a Personalized Action Plan (60-88%), training the child to measure and interpret his Peak Expiratory Flow (31-99%), and the prescription of pulmonary function tests during the follow-up programme of consultations (62-97%). Answers converged on pediatricians' perception of their role in teaching children about their condition and its treatment (99%), about inhalation techniques (96%), and in improving the children's ability to take preventive measures when faced with risk situations (97%). This study highlights the role of European pediatricians in caring for asthmatic children, and their lack of training in Therapeutic Patient Education. Programmes and tools are required in order to train ambulatory pediatricians in Therapeutic Patient Education, and such resources should be integrated into primary health care, and harmonized at the European level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The global prevalence of severe asthma among adolescents ranges from 4% to 11%; and up to 7% of children with asthma display an uncontrolled and severe form that is often associated with a ...substantial burden on the quality of life of patients and their families, and increasing costs of healthcare 1, 2. “Childhood asthma” is an umbrella term describing a heterogeneous disease comprising different phenotypes and a wide range of symptoms 3–5.
A digital multidisciplinary European expert meeting took place on the 9 July 2020 to identify the unmet needs of paediatric severe asthma patients, and set the priorities for clinical and research activities ahead
https://bit.ly/3CeLBHB
(1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric ...sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (≤15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (±2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3–44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0–32), resulting in mostly mild (18; 35.3%) and rarely severe (2; 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood.
Background Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by short-limbed skeletal dysplasia. Some patients also have defects in cell-mediated immunity and ...antibody production. Granulomatous inflammation has been described in patients with various forms of primary immunodeficiencies but has not been reported in patients with CHH. Objective We sought to describe granulomatous inflammation as a novel feature in patients with CHH, assess associated immunodeficiency, and evaluate treatment options. Methods In a retrospective observational study we collected clinical data on 21 patients with CHH to identify and further characterize patients with granulomatous inflammation. Results Four unrelated patients with CHH (with variable degrees of combined immunodeficiency) had epithelioid cell granulomatous inflammation in the skin and visceral organs. Anti–TNF-α mAb therapy in 3 of these patients led to significant regression of granulomas. However, 1 treated patient had fatal progressive multifocal leukoencephalopathy caused by the JC polyomavirus. In 2 patients immune reconstitution after allogeneic hematopoietic stem cell transplantation led to the complete disappearance of granulomas. Conclusion To the best of our knowledge, this is the first report of granulomatous inflammation in patients with CHH. Although TNF-α antagonists can effectively suppress granulomas, the risk of severe infectious complications limits their use in immunodeficient patients.
Airway wall structure in preschoolers with severe recurrent wheeze is poorly described.
To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze.
Flexible ...bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr).
RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 μm; P = 0.02), was correlated with age (P < 0.01; ρ = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 μm; P < 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P < 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multiple-trigger wheezers.
In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development.
Elexacaftor-tezacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator modulator combination, developed for cystic fibrosis (CF) patients with at least one Phe508del mutation.
To ...evaluate the effects of elexacaftor-tezacaftor-ivacaftor in CF patients with advanced respiratory disease.
A prospective observational study, including all patients aged ≥12 years and with ppFEV1<40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at one and three months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries.
Elexacaftor-tezacaftor-ivacaftor was initiated in 245 patients with a median IQR ppFEV1=29 24; 34. Mean (95% confidence interval) absolute increase in ppFEV1 was +15.1 (+13.8,+16.4; P<0.0001) and in weight was +4.2 kg (+3.9, +4.6; P<0.0001). The number of patients requiring long-term oxygen, non-invasive ventilation and/or enteral tube feeding decreased by 50%, 30% and 50%, respectively (P<0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only two were transplanted and one died. By September 2020 only five patients were still on transplantation path. Compared with the previous two years, a two-fold decrease in the number of lung transplantations in CF patients was observed in 2020, while the number of death without transplantation remained stable.
In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.
Background
This real-life study aimed to assess omalizumab treatment patterns in adult and paediatric asthma patients, and to describe asthma control and healthcare resource use (HCRU) at omalizumab ...initiation and discontinuation.
Methods
The French healthcare database system (Système National des Données de Santé (SNDS)) was used to identify asthma patients aged ≥6 years who initiated omalizumab for at least 16 weeks from 2009 to 2019. We examined omalizumab treatment patterns using dispensation records.
Results
We identified 16 750 adults and 2453 children initiating omalizumab. Median treatment persistence before discontinuation (T
STOP
) was 51.2 (95% CI 49.3–53.4) months in adults and 53.7 (95% CI 50.6–56.4) months in children. At 2 years of omalizumab exposure, rate of hospitalisation for asthma decreased by 75% and use of oral corticosteroids (OCS) by 30%, in adults and children. Among adults who discontinued omalizumab while asthma was controlled, 70%, 39% and 24% remained controlled and did not resume omalizumab at 1, 2 and 3 years after discontinuation, respectively. These proportions were higher in children (76%, 44% and 33%, respectively). Over 2 years of follow-up after discontinuation, HCRU remained stable in adults and children, notably rate of hospitalisations for asthma (none before T
STOP
, 1.3% and 0.6% at 2 years) and use of OCS (in adults and children, respectively: 20.0% and 20.2% before T
STOP
, 33.3% and 24.6% at 2 years).
Conclusion
This is the first large-scale study describing omalizumab real-life exposure patterns in adult and paediatric asthma patients in France with >10 years of follow-up. We showed the long-term maintenance of low HCRU in adults and children who discontinued omalizumab while asthma was controlled, notably for OCS use and hospitalisations for asthma.
Characteristics of host-microbiota interactions in asthmatic children favor asthma attacks and may allow to define asthma endotypes.
This knowledge offers promising perspectives to treat asthmatic ...children using precision medicine.
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Exacerbations are a main characteristic of asthma. In childhood, the risk is increasing with severity. Exacerbations are a strong phenotypic marker, particularly of severe and therapy-resistant asthma. These early-life events may influence the evolution and be involved in lung function decline.
In children, asthma attacks are facilitated by exposure to allergens and pollutants, but are mainly triggered by microbial agents. Multiple studies have assessed immune responses to viruses, and to a lesser extend bacteria, during asthma exacerbation. Research has identified impairment of innate immune responses in children, related to altered pathogen recognition, interferon release, or anti-viral response. Influence of this host-microbiota dialog on the adaptive immune response may be crucial, leading to the development of biased T helper (Th)2 inflammation. These dynamic interactions may impact the presentations of asthma attacks, and have long-term consequences.
The aim of this review is to synthesize studies exploring immune mechanisms impairment against viruses and bacteria promoting asthma attacks in children. The potential influence of the nature of infectious agents and/or preexisting microbiota on the development of exacerbation is also addressed. We then discuss our understanding of how these diverse host-microbiota interactions in children may account for the heterogeneity of endotypes and clinical presentations. Finally, improving the knowledge of the pathophysiological processes induced by infections has led to offer new opportunities for the development of preventive or curative therapeutics for acute asthma. A better definition of asthma endotypes associated with precision medicine might lead to substantial progress in the management of severe childhood asthma.
How to cope with food allergy symptoms? Deschildre, Antoine; Lejeune, Stéphanie
Current opinion in allergy and clinical immunology,
06/2018, Letnik:
18, Številka:
3
Journal Article
PURPOSE OF REVIEWFood allergy symptoms may involve a wide variety of organs (skin, gastrointestinal tract, and eyes) and systems (respiratory, circulatory, and neurological). They are often ...associated. Their severity ranges from mild to potentially life-threatening reactions and the presentation from acute to chronic.
RECENT FINDINGSFood allergies have been the focus of multiple studies, position papers, and guidelines in recent years. They have defined an approach in classifying symptoms as mild to anaphylactic, distinguishing objective from subjective symptoms, and describing their heterogeneity, specific phenotypes or syndromes (e.g., lipid transfer protein syndrome or pollen food syndrome). Cofactors can also influence food allergy reactions. Symptoms of non-IgE-gastrointestinal food allergies, illustrated by eosinophilic esophagitis and food-protein-induced enterocolitis syndrome, are also now better understood and defined. Improvement in the knowledge of food allergy symptoms is crucial for correct diagnosis and a personalized treatment approach.
SUMMARYThrough a better description and understanding of symptoms, the diversity of food allergies is now better known. The next step is to harmonize symptom assessment not only for clinicians but also for patients, researchers, and public health stakeholders, to describe food allergy phenotypes and their underlying mechanisms and endotypes, to develop targeted management.
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