[The role of the cardiopulmonary exercise test and pulmonary rehabilitation in long COVID-19]. / Apports de l'exploration fonctionnelle à l'exercice et de la réhabilitation respiratoire dans le COVID long.

INTRODUCTION: Long COVID refers to persistent symptoms, lasting more than 4 weeks after acute SARS-CoV-2 infection, even though the infection itself has been successfully controlled and remedied. Patient complaints are diverse, and the underlying physiopathological mechanisms are not well understood. Dyspnea and muscle fatigue are among the most commonly reported symptoms. STATE OF THE ART: Cardiopulmonary exercise test (CPET) has been recognized as a useful tool in investigation of unexplained dyspnea. In patients with chronic lung disease, pulmonary rehabilitation is a program designed to counteract dyspnea, to increase exercise capacity and to improve quality of life. PERSPECTIVES: Publications on CPET and pulmonary rehabilitation are needed in order to deepen comprehension and enhance management of long-COVID-19. CONCLUSIONS: CPET reports have shown that symptoms persisting in the aftermath of acute SARS-CoV-2 infection may be related to deconditioning, a common occurrence after ICU stay, to cardiac dysautonomia subsequent to critical infections and, finally, to dysfunctional breathing subsequent to mild infections. These findings justify pulmonary rehabilitation, which has proven to be effective regardless of the severity of the initial infection, not only immediately after hospital discharge, but also at later points in time.

[A rare and atypical form of tularemia in a context of immunodepression]. / Forme rare et atypique de tularémie dans un contexte d'immunodépression.

INTRODUCTION: We present an original severe case of tularemia with cutaneous damage, lymphadenopathy and pericarditis ; pathology of increasing incidence in Europe due to global warming. OBSERVATION: A 33-years-old women consulted emergency unit for altered general condition, anorexia, hyperthermia at 38,3°C, dyspnea and dry cough evolving for few days. Her only history was Crohn's disease with introduction of an anti-TNF alpha for 3 months. The interrogation found regular forest walks ¼. Treatment with Amoxicillin/clavulanic acid 1g 3 times daily and curative anticoagulation was started after the initial diagnosis of infectious pneumonia associated with pulmonary embolism. The patient reconsulted 2 weeks later for clinical deterioration associated with skin lesions. The chest CT scan showed increased mediastinal lymphadenopathy and a circumferential pericardial effusion ; quantified at 5mm on transthoracic ultrasound. Tularemia serology was positive in IgG at 400IU/mL. Despite an adapted antibiotic therapy with Ciprofloxacin, the patient presented a new brutal clinical deterioration. A pericardiocentesis was performed and the analysis revealed a predominantly neutrophilic exudate and a strongly positive PCR Francisella tularensis. Gentamicin 5mg/kg was associated allowing a resolution of the symptoms. CONCLUSION: Tularemia is one of the pathologies whose atypical presentation with pericarditis (favored by a certain immunodepression) worsens the prognosis. Global warming influences the epidemiology of inoculation diseases, including tularemia, making it more frequent.

[Markers of severity and predictors of response to treatment in severe asthma]. / Marqueurs de sévérité et marqueurs prédictifs de réponse au traitement dans l'asthme sévère.

Asthma is a multifactorial disease with complex pathophysiology. Knowledge of its immunopathology and inflammatory mechanisms is progressing and has led to the development over recent years of increasingly targeted therapeutic strategies. The objective of this review is to pinpoint the different predictive markers of asthma severity and therapeutic response. Obesity, nasal polyposis, gastroesophageal reflux disease and intolerance to aspirin have all been considered as clinical markers associated with asthma severity, as have functional markers such as bronchial obstruction, low FEV1, small daily variations in FEV1, and high FeNO. While sinonasal polyposis and allergic comorbidities are associated with better response to omalizumab, nasal polyposis or long-term systemic steroid use are associated with better response to antibodies targeting the IL5 pathway. Elevated total IgE concentrations and eosinophil counts are classic biological markers regularly found in severe asthma. Blood eosinophils are predictive biomarkers of response to anti-IgE, anti-IL5, anti-IL5R and anti-IL4R biotherapies. Dupilumab is particularly effective in a subgroup of patients with marked type 2 inflammation (long-term systemic corticosteroid therapy, eosinophilia≥150/µl or FENO>20 ppb). Chest imaging may help to identify severe patients by seeking out bronchial wall thickening and bronchial dilation. Study of the patient's environment is crucial insofar as exposure to tobacco, dust mites and molds, as well as outdoor and indoor air pollutants (cleaning products), can trigger asthma exacerbation. Wider and more systematic use of markers of severity or response to treatment could foster increasingly targeted and tailored approaches to severe asthma.

[Asthma and the microbiome]. / Asthme et microbiome.

INTRODUCTION: It has been demonstrated recently that the respiratory tract, considered for a long time to be sterile in the healthy subject, contains a vast community of bacteria called the respiratory microbiome. This microbiome, like the intestinal microbiome, is in constant interaction with the immune system of the human host. This relationship has allowed us to formulate some new theories on the pathophysiology of asthma. BACKGROUND: The respiratory microbiome of the asthmatic differs quantitatively and qualitatively from that of the healthy subject. Equally there seem to be differences in the microbiome according to the degree of severity of the asthma and the response to treatment with corticosteroids. It has been shown in murine models of allergic asthma that an early disturbance of the microbiome by different perinatal factors could be responsible for disorders of the development of the immune system, leading to the development of asthma in the long term. OUTLOOK: As a disorder of the microbiome might be implicated in the pathophysiology of asthma, the maintenance or restoration of a healthy microbiome is emerging as a possible new strategy in the management of the disease. CONCLUSION: The implication of the microbiome in the pathogenesis of human asthma seems to be more and more likely. This could have possible therapeutic implications, notably the restoration of a healthy microbiome.

[Omalizumab: Beyond anti-IgE properties]. / Mécanismes d'action de l'omalizumab : au-delà de l'action anti-IgE.

INTRODUCTION: Omalizumab is used as a treatment for severe allergic asthma. Its intended mechanism of action is based on its anti-IgE proprieties. However, recent studies have highlighted other mechanisms of action. STATE OF THE ART: Omalizumab treatment is associated with a decrease in the number of dendritic cells, T and B lymphocytes and eosinophils. This anti-inflammatory activity is characterized by a decrease in the levels of several cytokines involved in the recruitment, activation and survival of eosinophils and mastocytes, and in a Th2 orientation of the immune response. A modulation of bronchial remodeling by omalizumab has recently been shown. A decrease in the production of extracellular matrix components and in the proliferation of smooth muscle cells could be involved in this modulation. These mechanisms of action could explain in part the clinical efficiency of omalizumab in non-allergic conditions such as non-allergic asthma, non-allergic urticaria or nasal polyposis. CONCLUSION: A precise knowledge of the mechanisms of action of omalizumab could allow the identification of biomarkers predictive of efficacy of this treatment. These could be useful tools in the phenotyping of severe asthma.

Rivaroxaban-induced drug reaction with eosinophilia and systemic symptoms

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Component-based allergen-microarray: der p 2 and Der f 2 dust mite sensitization is more common in patients with severe asthma

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Nonallergic airway hyperresponsiveness and allergen-specific IgE levels are the main determinants of the early and late asthmatic response to allergen.

BACKGROUND: Conflicting results have been reported in studies of predictive factors for airway responsiveness to allergens during bronchial challenges. OBJECTIVE: The aim of this study was to assess determinants of airway responsiveness to 3 different allergens during standardized bronchial challenges. METHODS: Data were collected from asthmatic patients who participated in allergen challenge trials between 2000 and 2006 (cat, n = 37; house dust mite [HDM], n = 35; grass pollen, n = 27). PD20 (provocative dose causing a 20% fall in forced expiratory volume in the first second) methacholine, PD20 allergen, allergen skin test endpoint, allergen-specific immunoglobulin (Ig) E levels, and late asthmatic response were analyzed for each allergen group. RESULTS: During the early asthmatic response, a significant relationship was found between PD20 allergen and PD20 methacholine (P < .01 for cat, HDM, and grass pollen), as well as between PD20 allergen and allergen-specific IgE levels (P < .05 for cat and HDM). No relationship was observed between PD20 allergen and allergen skin test endpoint (P > .05). Late asthmatic response was significantly more frequent after HDM challenge than after cat or grass pollen challenges (57.1% vs16.2% and 33.3%, P < .01). Dual responders during HDM challenges had significantly higher allergen-specific IgE levels (P < .05) and higher nonallergic airway responsiveness (P < .05). CONCLUSION: Nonallergic airway hyperresponsiveness and allergen-specific IgE levels were the main determinants of early and late asthmatic responses. HDM challenges were the most interesting model with regard to the occurrence of late asthmatic response. In contrast to previous publications and to the official statement on standardized challenge testing with sensitizing stimuli, skin sensitivity appears to be a poor predictor of the early asthmatic response.

[Pathophysiology of multiple chemical sensitivity]. / Physiopathologie du syndrome d'hypersensibilité chimique multiple.

INTRODUCTION AND BACKGROUND: Multiple chemical sensitivity (MCS) is a complex clinical entity that includes a large number of non-specific symptoms, associated in a univocal manner in each patient and triggered by exposure to various chemicals at low concentrations, well below those known to cause toxic effects. However, no objective test exists currently to diagnose this syndrome. One of the main reasons is that the pathophysiology is poorly understood. However, many explanatory hypotheses have been proposed. VIEWPOINTS AND CONCLUSIONS: Patients with symptoms of MCS are often encountered by pulmonologists. Their suffering is undeniable but, unfortunately, the lack of understanding of the pathophysiological mechanisms makes treatment difficult and empirical.

Nonallergic Airway Hyperresponsiveness and Allergen-Specific IgE Levels Are the Main Determinants of the Early and Late Asthmatic Response to Allergen

Introducción: Hay una gran controversia sobre los posibles factores predictivos de la respuesta a la provocación bronquial con alérgenos. Objetivos: El objetivo del estudio fue analizar factores determinantes de la reactividad bronquial frente a tres diferentes alérgenos durante la provocación bronquial estandarizada. Métodos: Se estudiaron los datos de pacientes asmáticos participantes en diversos estudios de provocación con alérgenos, realizados entre los años 2000 al 2006 (gato, n=37, ácaros del polvo, n=35, polen de gramíneas, n=27). Se analizaron para cada grupo de alérgeno la PD20 metacolina, la PD20 alérgeno, la titulación a punto final de la prueba cutánea, los niveles de IgE específica y la respuesta asmática tardía. Resultados: En relación con la respuesta inmediata, se observaron correlaciones significativas entre la PD20 alérgeno y la PD20 metacolina (gato, ácaros del polvo, polen de gramíneas; p<0.01), y también entre la PD20 alérgeno y los niveles de IgE específica (gato y ácaros del polvo; p<0.05). No encontramos correlación entre la PD20 alérgeno y la titulación a punto final de la prueba cutánea. Se observaron respuestas tardías de significativamente mayor frecuencia tras la provocación bronquial con ácaros del polvo que las observadas tras la provocación con gato o polen de gramíneas (57.1% vs. 16.2% y 33.3%; p<0.01). Los pacientes que presentaron respuestas duales durante la provocación bronquial con ácaros del polvo presentaban niveles más elevados de IgE específica (p<0.05) junto con una mayor reactividad bronquial frente a metacolina (p<0.05). Conclusion: La reactividad bronquial no relacionada con alérgeno y los niveles de IgE específica frente al alérgeno fueron los principales determinantes de la respuesta asmática inmediata y tardía. La provocación bronquial con ácaros presentaba frecuencias mayores de respuestas tardías. En contra de lo referenciado en la literatura, incluyendo un protocolo oficial de estandarización de la provocación bronquial, la reactividad cutánea parece un pobre factor predictivo de la respuesta asmática inmediata (AU)

Background: Conflicting results have been reported in studies of predictive factors for airway responsiveness to allergens during bronchial challenges. Objective: The aim of this study was to assess determinants of airway responsiveness to 3 different allergens during standardized bronchial challenges. Methods: Data were collected from asthmatic patients who participated in allergen challenge trials between 2000 and 2006 (cat, n=37; house dust mite [HDM], n=35; grass pollen, n=27). PD20 (provocative dose causing a 20% fall in forced expiratory volume in the first second) methacholine, PD20 allergen, allergen skin test endpoint, allergen-specific immunoglobulin (Ig) E levels, and late asthmatic response were analyzed for each allergen group. Results: During the early asthmatic response, a signifi cant relationship was found between PD20 allergen and PD20 methacholine (P<.01 for cat, HDM, and grass pollen), as well as between PD20 allergen and allergen-specific IgE levels (P<.05 for cat and HDM). No relationship was observed between PD20 allergen and allergen skin test endpoint (P>.05). Late asthmatic response was significantly more frequent after HDM challenge than after cat or grass pollen challenges (57.1% vs16.2% and 33.3%, P<.01). Dual responders during HDM challenges had significantly higher allergen-specific IgE levels (P<.05) and higher nonallergic airway responsiveness (P<.05). Conclusion: Nonallergic airway hyperresponsiveness and allergen-specifi c IgE levels were the main determinants of early and late asthmatic responses. HDM challenges were the most interesting model with regard to the occurrence of late asthmatic response. In contrast to previous publications and to the official statement on standardized challenge testing with sensitizing stimuli, skin sensitivity appears to be a poor predictor of the early asthmatic response (AU)

Indoor dust and air concentrations of endotoxin in urban and rural environments.

SIGNIFICANCE AND IMPACT OF THE STUDY: Rural dairy farming is associated with high exposure to indoor endotoxins as compared to rural nonfarming houses and urban houses. The time spent on the mattress (7 h for an adult) and of the proximity of the contaminated source should be taken into account with the other causes of exposure. Studies in European children from a farming background have shown that these children have a reduced risk of asthma and atopic sensitization compared to their urban counterparts. It has been suggested that this might be due to exposure to high levels of endotoxin in the farming environment. The aim of this study was to compare indoor endotoxin concentrations in air and dust samples from randomly selected urban and rural dwellings. In the rural area, endotoxins were analysed in farmhouses and nonfarmhouses as well as housing characteristics, lifestyle factors and agricultural practices likely to influence air and dust endotoxin levels. Endotoxin levels were significantly higher in floor (6600 ± 6100 vs 3600 ± 5600 and 3800 ± 17,000 ng g⁻¹; P < 0·001) and mattress dust (2900 ± 4100 vs 1100 ± 2400 and 800 ± 2600 ng g⁻¹; P < 0·001) from farmhouses compared to other rural and urban homes. However, no difference was observed between endotoxin concentrations in the air of urban and rural houses, and airborne endotoxin levels did not correlate to dust levels. Lack of ventilation and direct entry into the house were correlated with an increase in dust endotoxin levels. These results confirm that dairy farming is associated with high exposure to endotoxins in indoor dust samples. No difference was observed between indoor airborne concentrations between urban and rural houses. These results suggest that measuring endotoxin in dust is the most relevant method to assess endotoxin exposure.

[Respiratory allergens and asthma exacerbation]. / Facteurs déclenchants : allergènes respiratoires (usuels et professionnels).

INTRODUCTION: Asthma exacerbations are characterized by a progressive aggravation of respiratory symptoms such as dyspnea, cough, wheezing or chest tightness. BACKGROUND: The relationship between allergy and asthma exacerbations has been evaluated by epidemiological studies based on various criteria such as oral corticosteroid requirement, emergency room visits and hospital admission for asthma. Many studies have observed that deteriorating asthma can be related to increased exposure to allergens, particularly allergens from house dust mite, cockroach, cat, rodent, mold or pollen. Several studies have demonstrated that sensitization to respiratory allergens and allergen exposure increases the risk of exacerbation of asthma. When asthma exacerbations are work-related, occupational allergens may be implicated. CONCLUSIONS AND PERSPECTIVES: Most studies provide evidence that allergen exposure contributes to the risk of asthma exacerbations, but other precipitating factors, such as viruses, can interact and increase the risk.

EAACI consensus statement for investigation of work-related asthma in non-specialized centres.

Work-related asthma (WRA) is a relevant problem in several countries, is cause of disability and socioeconomic consequences for both the patient and the society and is probably still underdiagnosed. A correct diagnosis is extremely important to reduce or limit the consequences of the disease. This consensus document was prepared by a EAACI Task Force consisting of an expert panel of allergologists, pneumologists and occupational physicians from different European countries. This document is not intended to address in detail the full diagnostic work-up of WRA, nor to be a formal evidence-based guideline. It is written to provide an operative protocol to allergologists and physicians dealing with asthma useful for identifying the subjects suspected of having WRA to address them to in-depth investigations in a specialized centre. No evidence-based system could be used because of the low grade of evidence of published studies in this area, and instead, 'key messages' or 'suggestions' are provided based on consensus of the expert panel members.

Transfer of peanut allergy following lung transplantation: a case report.

This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient.