Chronic oral corticosteroids use and persistent eosinophilia in severe asthmatics from the Belgian severe asthma registry.

BACKGROUND: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. METHODS: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. RESULTS: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. CONCLUSION: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

Secondary organizing pneumonia associated with sertraline: A case report.

Cryptogenic organizing pneumonia is a rare idiopathic interstitial lung disease, with a well-defined clinical-radiological and pathological entity. It may also be secondary to several causes. Rapid clinical and imaging improvement is usually obtained with corticosteroid therapy. We report here, to the best of our knowledge, a unique case of organizing pneumonia associated with Sertraline, a selective serotonin reuptake inhibitor, commonly used in antidepressant therapy.

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.

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.

Low-dose endotoxin in allergic asthmatics: effect on bronchial and inflammatory response to cat allergen.

BACKGROUND: Endotoxin was proposed to increase the severity of asthma. Endotoxin levels greatly differ according to settings. In domestic environments, airborne concentrations may be dramatically low compared with levels reported in occupational settings. OBJECTIVE: Our first objective was therefore to assess the effect of inhalation of low-level lipopolysaccharide (LPS) on the immediate and late-phase asthmatic bronchial response. Our second objective was to evaluate the effect of exposure to LPS on the local and systemic inflammatory response. METHODS: Nineteen asthmatics sensitized to cat underwent on two separate occasions a bronchial challenge test to cat allergen (cat BCT) preceded randomly by a pre-exposure to either saline or LPS (2 microg). Methacholine challenge test was performed 24 h before exposure to LPS or saline. The Borg scale for dyspnoea and lung function were recorded before and after exposure to LPS or saline, and before and after cat BCT. Induced sputum and blood samples were collected before and after cat BCT, and analysed for cell counts and eosinophil cationic protein (ECP) levels. RESULTS: Inhalation of 2 microg LPS did not induce any changes in forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), FEF 25-75 and Borg scale of dyspnoea. It neither modified Fel d 1 PD20 (45.03 ng as compared with 87.03; P=0.42). As well, there was no significant difference in late-phase reaction. Pre-exposure to LPS did not influence eosinophil counts or ECP levels in blood and sputum. CONCLUSION: Our study demonstrated that pre-exposure to LPS at low levels, which may be encountered in domestic environment, had no significant effect on the immediate and late-phase bronchial response to cat allergen. It neither modified local and systemic eosinophilic inflammation.

[Critical analysis of hypotheses explaining the increase in respiratory allergens]. / Etude critique des hypothèses explicatives de l'augmentation des allergies respiratoires.

There are three hypotheses to explain the relation between allergens and other factors and the onset of atopy: the hygiene hypothesis, the TH2 like hypothesis and the allergenic hypothesis. None of them have been confirmed. It seems necessary to wait for the results of prospective studies before giving recommendations for primary prevention of respiratory allergic diseases. In contrast, tertiary prevention appears as an essential method for treatment of allergic diseases.

Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?

The use of antibiotics in acute exacerbations of chronic bronchitis (AECBs) remains the subject of controversy despite considerable medical and socioeconomic implications. First, the contribution of bacterial infection to AECBs is difficult to assess in patients with chronic obstructive pulmonary disease (COPD) who are chronically colonized with respiratory pathogens. In addition, several studies suggest a major role of viral infections in AECBs. Secondly, it is unlikely that all COPD patients will benefit from antibiotics during AECBs. In particular, the benefit in mild COPD remains uncertain. Unfortunately, the number of studies complying with evidence-based medicine requirements is too small for definite recommendations in AECBs to be drawn up. Considering the impact of acute exacerbations of chronic bronchitis on chronic obstructive pulmonary disease patients, as well as the community, and the impact of antibiotic therapy on the development of bacterial resistance, there is an urgent need for the design of appropriate multicentric studies to define the usefulness of this type of treatment in acute exacerbations of chronic bronchitis.

Occupational asthma in symptomatic workers exposed to natural rubber latex: evaluation of diagnostic procedures.

BACKGROUND: Natural rubber latex (NRL) has been increasingly identified as a cause of occupational asthma (OA). OBJECTIVE: We sought to examine the accuracy of the clinical history, immunologic tests, and assessment of nonspecific bronchial hyperresponsiveness in diagnosing OA caused by latex compared with that of the specific inhalation challenge (SIC). METHODS: Forty-five consecutive patients referred for investigation of possible OA caused by latex underwent a diagnostic protocol, including an open medical questionnaire, skin prick testing against latex, measurement of bronchial responsiveness to histamine, and inhalation challenge with latex gloves. Recorded clinical history was judged retrospectively by 4 physicians who were blinded for the results of other objective tests. RESULTS: The clinical history, skin prick testing against NRL, and assessment of nonspecific bronchial hyperresponsiveness showed a high sensitivity (87%, 100%, and 90%, respectively) but a low specificity (14%, 21%, and 7%, respectively) when compared with the results of the SIC. Logistic regression analysis showed that combining the results of skin prick tests against latex with the clinical history enhanced the negative predictive value from 50% to 71%, whereas the positive predictive value remained virtually unchanged (75% vs 76%). CONCLUSION: The clinical history and immunologic tests were the most useful procedures in diagnosing NRL-induced asthma, although combining the 2 procedures remained less accurate than SIC. Further examination of the predictive values of available tests is warranted to recommend diagnostic strategies that are specific to the various agents causing OA.