Marion Gouitaa

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.

Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases.

Ara h 2 and Ara h 6 sensitization predicts peanut allergy in Mediterranean pediatric patients

Peanut allergy (PA) management was improved by the introduction of molecular allergology, but guidelines for Mediterranean patients are lacking. We aimed at evaluating peanut component‐resolved diagnosis as a diagnostic and prognostic tool in children from Southern France.

Home-based respiratory rehabilitation in adult patients with moderate or severe persistent asthma

Abstract Objective: We assessed retrospectively the feasibility of a home-based respiratory rehabilitation (RR) program for asthmatics under optimal pharmacological treatment, as this type of care can reduce costs and offer a more patient-friendly approach for subjects with persistent asthma. Methods: Fifty-two patients with persistent asthma were recruited to the RR program (20 males, 32 females, 54 ± 11 (SD) years, forced expiratory volume in one second 71 ± 33% of predicted mean value, BMI 29.9 ± 7.9 kg/m2). This two-month protocol comprised education sessions, respiratory physiotherapy and an exercise training program at home and in groups supervised by an adapted physical activity instructor. Results: Thirty-nine patients completed the whole RR program, i.e. 25% dropout. The dropout rate was significantly higher with respect to younger patients in employment. The number of exacerbations decreased significantly during the year following the program, regardless of whether the patients had dropped out (p < 0.02) or not (p < 0.001). The distance walked during a 6-min walking test increased by 33 m (p < 0.001). Several indices measured during a cycle ergometer test increased significantly after RR: peak oxygen uptake (10%), oxygen uptake at ventilatory threshold (12%) and maximum load (19%), all at a similar maximum heart rate. Concerning quality of life assessment, the Short-Form-36 Item Health Survey revealed a non-significant improvement in the “health change” item after RR (p < 0.07). Conclusions: This study demonstrates the potential of a home-based program in the treatment and rehabilitation of patients with asthma. Both functional and physiologic indices improved during the follow-up period.

Aspergillus fumigatus components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho-pulmonary aspergillosis.

Aspergillus fumigatus is the causative agent of allergic broncho‐pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho‐pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho‐pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho‐pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.

Why is the prevalence of allergic diseases increasing? A critical assessment of some classical risk factors

presence of Fc«RI-expressing LC/IDEC, bearing IgE molecules, is a prerequisite to provoking eczematous lesions, observed after application of aeroallergens to the skin of atopic patients, strongly supports this concept. Thereby, IgE receptors are the connecting link between the specificity gaining IgE molecules and the APC. However, Fc«RI seems to play the major role in these phenomena. It should be noted that Fc«RI expressed on circulating monocytes may have other functions, mainly in regulating their survival and differentiation outcome. 12 Following the presentation of allergens to T cells, allergen-specific B cells may be activated to produce high amounts of allergen-specific IgE. This IgE may then in turn bind to the Fc«RI on the APC, closing a vicious circle of facilitated antigen presentation. The intermittent or continuous supply of aeroallergens or autoantigens to the process of facilitated antigen presentation may define the pathophysiological basis of the recurrent or self-perpetuating course of AD frequently seen in untreated patients. The successful application of aeroallergens such as cat dander in the recently standardized atopy patch test 13 shows that it is possible to elicit eczematous skin lesions by solely external application of aeroallergens to the skin. Based on the facilitated antigen presentation model of AD, the need for an identification of the individual provocation factors in each patient calls for diagnostic procedures based on the allergen-specific IgE. Cat dander, house dust mite allergens and a variety of food allergens may be successfully avoided following a thoroughly undertaken prick test and in vitro IgE diagnostic evaluation.

Anaphylactic Reaction to Pemetrexed: A Case Report

Pemetrexed is approved to treat non-small cell lung cancer and has an overall favorable toxicity profile. We describe a 58-year-old man who developped an anaphylactic shock within few minutes from the beginning of pemetrexed perfusion. Pemetrexed was discontinued and the patients symptoms gradually resolved with administration of symptomatic treatment. Serum tryptase level remained normal and intra dermal skin tests were negative eventhough a nonspecific papule was noted. This case suggests that caution should be exercised when prescribing pemetrexed and clinicians must be warranted for the possibility of serious adverse events associated with pemetrexed use.

Right-to-Left Atrial Shunt without Pulmonary Artery Hypertension

A 70-year-old woman without any history of pulmonary or cardiac disease developed breathlessness with severe arterial hypoxemia. Cardiac ultrasound examination and spirometry were normal. Cardiac catheterization and intravenous microbubble injection demonstrated an interatrial right-to-left shunt. The defect was closed surgically, and the patient recovered immediately. On surgery, the aorta was elongated, inducing an angulation of the interatrial septum and leading to the atrial septal defect just above the inferior vena cava.

Mast cell tryptase changes with Aspergillus fumigatus – Host crosstalk in cystic fibrosis patients

Pulmonary and systemic antifungal immunity influences quality of life and survival of people with cystic fibrosis. Aspergillus fumigatus (Af) induces specific IgG and IgE. Mast cells respond to IgE, IgG and direct interactions with Af. Mast cells are the source of the protease tryptase. We aimed at evaluating serum baseline tryptase as a potential biomarker of the Af-host interaction in cystic fibrosis patients. Serum baseline tryptase, IgE and IgG directed to Af extract and Af molecular allergens were measured in 76 cystic fibrosis patients. The main findings were (i) lower levels of serum baseline tryptase in patients displaying specific IgE to Af (p < 0.0001) and (ii) an association between tryptase levels and IgE or IgG responses to Af and ribotoxin (Asp f 1). These findings suggest that serum baseline tryptase is influenced by Af-host interactions and thus might be a marker for mast cell regulation and pulmonary immune defenses.

Retrospective study of hypersensitivity reactions to chemotherapeutic agents in a thoracic oncology service

With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. The allergic clinical symptoms are variable and unpredictable. The aim of this study was to identify the characteristics of hypersensitivity reactions and to assess the value of skin tests for platinum salts and pemetrexed in the treatment of patients with non‐small cell lung cancers or malignant pleural mesothelioma.

Multivariate Analysis As a Support for Diagnostic Flowcharts in Allergic Bronchopulmonary Aspergillosis: A Proof-of-Concept Study

Molecular-based allergy diagnosis yields multiple biomarker datasets. The classical diagnostic score for allergic bronchopulmonary aspergillosis (ABPA), a severe disease usually occurring in asthmatic patients and people with cystic fibrosis, comprises succinct immunological criteria formulated in 1977: total IgE, anti-Aspergillus fumigatus (Af) IgE, anti-Af “precipitins,” and anti-Af IgG. Progress achieved over the last four decades led to multiple IgE and IgG(4) Af biomarkers available with quantitative, standardized, molecular-level reports. These newly available biomarkers have not been included in the current diagnostic criteria, either individually or in algorithms, despite persistent underdiagnosis of ABPA. Large numbers of individual biomarkers may hinder their use in clinical practice. Conversely, multivariate analysis using new tools may bring about a better chance of less diagnostic mistakes. We report here a proof-of-concept work consisting of a three-step multivariate analysis of Af IgE, IgG, and IgG4 biomarkers through a combination of principal component analysis, hierarchical ascendant classification, and classification and regression tree multivariate analysis. The resulting diagnostic algorithms might show the way for novel criteria and improved diagnostic efficiency in Af-sensitized patients at risk for ABPA.