Advances in the diagnosis of exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) describes the post exercise phenomenon of acute airway narrowing in association with physical activity. A high prevalence of EIB is reported in both athletic and recreationally active populations. Without treatment, EIB has the potential to impact upon both health and performance. It is now acknowledged that clinical assessment alone is insufficient as a sole means of diagnosing airway dysfunction due to the poor predictive value of symptoms. Furthermore, a broad differential diagnosis has been established for EIB, prompting the requirement of objective evidence of airway narrowing to secure an accurate diagnosis. This article provides an appraisal of recent advances in available methodologies, with the principle aim of optimising diagnostic assessment, treatment and overall clinical care.

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)

Neumonitis por hipersensibilidad a isocianatos. Características clínico-radiológicas y de función pulmonar / Hypersensitivity Pneumonitis Due to Isocyanates: Lung Function, Clinical and Radiological Characteristics

El objetivo del presente trabajo fue describir las características clínico-radiológicas y de función pulmonar de la neumonitis por hipersensibilidad por exposición a isocianatos (NHI). Se estudiaron todos los pacientes con diagnóstico de NHI (n=5) durante los años 1995-2010. En todos ellos se realizó TC torácica y estudio de función pulmonar completo. El diagnóstico se realizó mediante prueba de provocación bronquial específica (PPBE) positiva. Se observó un predominio de varones y una variabilidad de patrones en las alteraciones radiológicas. La PPBE fue positiva por descenso de la FVC o de la DLCO en todos los casos excepto en un paciente, en que se estableció por criterios clínicos. Tan solo en un paciente se constató una IgG positiva a isocianatos. La presentación radiológica de la NHI puede ser distinta de las NH más frecuentes en nuestro medio y cursan con menor afectación clínica en la PPBE(AU)

The objective of this present study was to describe the clinical-radiological and lung function characteristics of hypersensitivity pneumonitis due to exposure to isocyanates (HPI). Included for study were all those patients diagnosed with HPI (n=5) from 1995 to 2010. In all cases, chest CT and complete lung function studies were done. The diagnosis was made with positive specific bronchial provocation tests (BPT). A predominance of males and pattern variability in the radiological alterations were observed. The BPT was positive due to a decline in FVC or DLCO in all cases except in one patient in whom the diagnosis was established with clinical criteria. Positive IgG to isocyanates was confirmed in only one patient. The radiological presentation of HPI may be different from the more common HP in our setting and run their course with less clinical affectation on the BPT(AU)

[Inhalation therapy: provocation tests, infectious risks, acute bronchiolitis and ENT diseases. GAT aerosolstorming, Paris 2011]. / Aérosolthérapie: tests de provocation, risques infectieux, bronchiolites et pathologie ORL. Aérosolstorming du GAT, Paris 2011.

Communications from the 2011 meeting of the GAT are reported in this second article on the practical management of bronchial provocation tests and infectious risks associated with the use of nebulization. Recent advances on the role of nebulized hypertonic saline in the treatment of acute bronchiolitis in infants and of the nebulization in sinusal diseases are also reported.

Past, present and future uses of methacholine testing.

Methacholine challenge testing is a valuable diagnostic and research tool used by clinicians to assist in the diagnosis of asthma, and by researchers to understand disease pathophysiology and assess novel therapeutic efficacy. The use of methacholine challenge in asthma relates to its direct effect on airway smooth muscle (i.e., bronchoconstriction) as a measure of airway hyperresponsiveness, a cardinal feature of asthma. Airway hyperresponsiveness has been documented in other airway disorders, including chronic obstructive pulmonary disease, cystic fibrosis and allergic rhinitis; however, there is little clinical application of methacholine challenge in these conditions as a diagnostic or disease management tool. The authors will review the aspects of methacholine challenge testing, as they relate to asthma, and point out its usefulness in clinical research. A brief review of past (historical) uses and speculation as to the future uses of methacholine challenge will also be discussed.

Bronchial provocation testing: the future.

PURPOSE OF REVIEW: Performing a bronchial provocation test (BPT) using a direct or indirect stimulus to identify bronchial hyper-responsiveness (BHR) reduces the possibility of over and under-diagnosis of asthma based on history and symptoms. This review discusses some long-held beliefs of BPTs to include or exclude a diagnosis of asthma or exercise-induced bronchoconstriction (EIB). RECENT FINDINGS: A high frequency of negative methacholine tests has been reported in 240 patients given a diagnosis of asthma at the end of the study, many of whom had documented EIB. This suggests that a negative methacholine test should not be relied upon to rule out asthma. Further, a positive methacholine test alone should be interpreted with caution as it may reflect airway injury rather than asthma or EIB. Mannitol, an indirect stimulus, identified a similar prevalence of BHR to methacholine and identified more patients than a single exercise test in three studies. However, neither mannitol nor methacholine identified all patients with EIB. Mannitol has a higher specificity for a physician diagnosis of asthma than methacholine. SUMMARY: It is likely that both a direct test and an indirect test result may be required in some patients in order to confirm or exclude a diagnosis of asthma with certainty.

Provocation tests in diagnosing drug hypersensitivity.

A position paper by the European Network for Drug Allergy (ENDA), the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity, defines drug provocation tests (DPTs) as "the controlled administration of a drug in order to diagnose drug hypersensitivity reactions". The DPT is widely considered to be the "gold standard" to establish or exclude the diagnosis of hypersensitivity to a certain substance, as it not only reproduces hypersensitivity symptoms, but also any other adverse clinical manifestation, irrespective of the mechanism. The DPT can be harmful and thus should only be considered after balancing the risk-benefit ratio in the individual patient. The ENDA position paper specifies two main indications for DPTs with the suspected compounds: 1. to exclude hypersensitivity in non-suggestive histories of drug hypersensitivity and in patients with non-specific symptoms, such as vagal symptoms under local anesthesia; 2. to establish a firm diagnosis in suggestive histories of drug hypersensitivity with negative, non-conclusive, or non-available allergologic tests. A positive DPT result optimizes allergen avoidance, while a negative one allows a false label of drug hypersensitivity to be removed. For these reasons, DPTs are often carried out to exclude a diagnosis of hypersensitivity to beta-lactams when other allergologic tests are negative. DPTs are also performed when the sensitivity of allergologic tests for evaluating allergic reactions to certain drugs, such as non-beta-lactam antibiotics, heparins, and glucocorticoids, is limited. On the other hand, DPTs are also performed to diagnose hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in subjects with the cross-reactive pattern, because both skin tests and in vitro diagnostic methods are ineffective in such patients.

Indirect airway challenges.

Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving. Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.

Inhalation challenges with agents causing occupational asthma.

Occupational asthma (OA) is steadily emerging as the principal cause of respiratory disease due to the workplace environment. One of the key means to ascertain diagnosis of OA is specific inhalation challenge (SIC) with occupational agents. This review: 1) describes the methodology of SIC, with a special emphasis on procedures aimed at increasing the safety and validity of these tests; and 2) outlines the roles of SIC in the diagnosis of OA in clinical and medicolegal assessment, epidemiological studies, surveillance programmes and the investigation of the pathophysiological mechanisms of asthma and OA. We discuss areas of future development, including the development of apparatus which allows exposure of subjects to low and stable concentrations of the occupational agent and the assessment of preventive procedures.