Nonspecific provocation of target organs in allergic diseases: EAACI-GA(2)LEN consensus report.

It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli.

[Revised terminology for allergies and related conditions]. / Herziene terminologie voor allergie en verwante aandoeningen.

The European Academy of Allergology and Clinical Immunology has proposed a revised terminology for allergic and allergy-related reactions that can be used independently of target organ of patient age group. The proposed terminology is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. 'Hypersensitivity' is an umbrella term, 'allergy' involves a hypersensitivity reaction which is initiated by an immunological mechanism, and 'atopy' is an individual or familial tendency to produce IgE antibodies in response to low doses of allergens, and is accompanied by the typical symptoms or asthma, rhino-conjunctivitis or eczema/dermatitis. Each condition should be categorised als 'allergic/not allergic', and the allergic conditions should be further categorised as 'IgE-mediated/non IgE-mediated' (sometimes: 'IgE-associated'). Terms which are no longer in use include: 'idiosyncrasy' (this will now become 'hypersensitivity'); 'pseudo-allergy' ('non-allergic hypersensitivity'); 'extrinsic', 'intrinsic', 'endogenous' and 'exogenous asthma' ('allergic' (possibly 'IgE-mediated') and 'non-allergic asthma'); 'atopic eczema' ('atopic eczema/dermatitis syndrome'; 'allergic (possibly 'EgE-mediated') or 'non-allergic'); 'intrinsic' and 'cryptogenic variants of eczema' (non-allergic atopic eczema/dermatitis syndrom'); 'food intolerance' (non-allergic food hypersensitivity') and 'anaphylactoid reaction' ('non-allergic anaphylaxis').

[Revised terminology for allergies and related conditions]. / Herziene terminologie voor allergie en verwante aandoeningen.

The European Academy of Allergology and Clinical Immunology has proposed a revised terminology for allergic and allergy-related reactions that can be used independently of target organ or patient age group. The proposed terminology is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. 'Hypersensitivity' is an umbrella term, 'allergy' involves a hypersensitivity reaction which is initiated by an immunological mechanism, and 'atopy' is an individual or familial tendency to produce IgE antibodies in response to low doses of allergens, and is accompanied by the typical symptoms or asthma rhino-conjunctivitis or eczema/dermatitis. Each condition should be categorised as 'allergic/not allergic', and the allergic conditions should be further categorised as 'IgE-mediated/non IgE-mediated' (sometimes: 'IgE-associated'). Terms which are no longer in use include: 'idiosyncrasy' (this will now become 'hypersensitivity'); 'pseudo-allergy' ('non-allergic hypersensitivity'); 'extrinsic', 'intrinsic', 'endogenous' and 'exogenous asthma' ('allergic' (possibly 'IgE-mediated') and 'non-allergic asthma'); 'atopic eczema' ('atopic eczema/dermatitis syndrome': 'allergic (possibly 'IgE-mediated') or 'non-allergic'); 'intrinsic' and 'cryptogenic variants of eczema' ('non-allergic atopic eczema/dermatitis syndrome'); 'food intolerance' ('non-allergic food hypersensitivity') and 'anaphylactoid reaction' ('non-allergic anaphylaxis').

Viral rhinitis and asthma.

Upper respiratory tract infections are among the most common infectious diseases. Approximately 80% of the common colds are caused by rhinoviruses. Recently, rhinovirus colds have been linked with lower airway illnesses such as asthma exacerbations resulting in a considerable interest in the pathogenesis of lower respiratory tract pathology. The important role that allergic airway disease plays in virally induced changes in airway function has been experimentally shown in several studies. Unfortunately, the precise mechanisms by which viruses could induce lower airway symptoms have not yet been determined.

The common cold at the turn of the millennium.

Upper respiratory tract infections are one of the most common infectious diseases in man and are characterized by transient, relatively mild symptoms. Human rhinoviruses are known to be the major causative agent in adult common colds and their relative importance has further increased with the use of the sensitive RT-PCR technique. Characteristic for a common cold is the selective neutrophil recruitment and time-limited increase in mediator, cytokine, and chemokine concentrations that orchestrate chemotaxis, transmigration, and activation of inflammatory and immunocompetent cells. Common cold symptoms are found to correlate to rhinovirus-induced IL-8 elaboration and neutrophil activation. Treatment of rhinoviral upper respiratory tract infections consists of an inhibition of viral infection by antiviral agents and/or a reduction of symptoms by damping the host inflammatory response.

The common cold.

Upper respiratory tract infections are one of the most common infectious diseases in man and are mainly caused by rhinoviruses. A rhinoviral cold is characterized by a neutrophilic inflammatory reaction with relatively mild symptoms that rather result from the host inflammatory response to the virus than from a direct viral cytotoxic effect. As regulators of chemotaxis, transmigration and activators of inflammatory and immunocompetent cells, cytokines and mediators were shown to play a crucial role in the pathogenesis of a rhinovirus infection.

The immune response in adenoids and tonsils.

The adenoid and tonsils are lymphoid tissues located in the pharynx that play an important role in host defense against invading antigens of the upper respiratory tract. Histologically, these structures consist of four well-defined microcompartments which all participate in the immune response: the cryptepithelium, the follicular germinal center with the mantle zone and interfollicular area. With the uptake of antigen by M-cells present in the cryptepithelium a process is initiated which ultimately results in the generation and dissemination of antigen-specific memory and mainly dimeric IgA-producing effector B-lymphocytes. This process requires successful cognate interactions between antigen-presenting cells and lymphocytes and mutually between lymphocytes, which depend not only on antigen-specific signals but also on the expression of various complementary adhesion and costimulatory molecules.

Cineradiography of the pharyngoesophageal segment in postlaryngectomy patients.

The use of tracheoesophageal voice prostheses has gained wide acceptance in the field of vocal rehabilitation after total laryngectomy. In a randomized study with 3 arms, alaryngeal speech proficiency was assessed in 60 postlaryngectomy patients: 20 patients underwent primary unilateral pharyngeal myotomy, 21 patients underwent neurectomy of the pharyngeal plexus in addition to pharyngeal myotomy, and 19 patients did not undergo an additional surgical procedure. Pharyngoesophageal (PE) dynamics were examined during esophageal and tracheoesophageal speech. A single vibrating PE segment was seen in good alaryngeal speakers. Hypertonicity, spasm, strictures, and hypotonicity of the PE segment were correlated significantly with poor or moderate alaryngeal speech. Unilateral myotomy with or without unilateral neurectomy prevented hypertonicity or spasm of the PE segment. The acquisition of alaryngeal speech did not differ significantly between the 2 groups who had undergone an additional surgical procedure. Evaluation of anatomic and physiological factors may be helpful in subsequent clinical management to achieve effective alaryngeal speech.

Intratemporal and intracranial complications of acute suppurative otitis media in children: renewed interest.

In recent years, a rise in the incidence of intratemporal and intracranial complications of acute otitis media (AOM) has been mentioned in the literature. Lack of a well-developed immune system and difficulties in diagnosing AOM, can account for part of the rise in the incidence of complications of purulent middle ear infections in young children. Antibiotic treatment of AOM is certainly not an absolute safeguard against the development of complications. Antibiotic therapy may have a masking effect on significant signs and symptoms of complications, causing delay in diagnosis. Myringotomy, especially in young children, should not be forgotten for drainage and to provide material for culture. Increased virulence of the causative pathogens cannot be ruled out, but to date there is no evidence suggesting it. We have to maintain a high level of clinical awareness. If there is insufficient improvement of the patient with the appropriate conservative treatment, radioimaging followed by the necessary surgical procedures should be performed.

The Lacrimo-Auriculo-Dento-Digital (LADD) syndrome: temporal bone CT findings.

The temporal bone CT examination of a 16-year-old female patient with the LADD syndrome or Levy-Hollister syndrome showed multiple bilateral middle as well as inner ear malformations. Ossicular chain anomalies were seen, especially of the incus and stapes. The oval window was very narrow to absent. Both cochleas were hypoplastic and showed modiolar deficiency. A common cavity between the vestibule and lateral semicircular canal was bilaterally present.

Sensitivity of transient evoked and distortion product otoacoustic emissions to the direct effects of noise on the human cochlea.

Measurement of otoacoustic emissions (OAEs) has been proposed as a sensitive test to reliably assess the effects of noise exposure. The present study in humans was designed to evaluate the sensitivity and applicability of transient evoked OAEs (TEOAEs) and 2f1-f2 distortion product OAEs (DPOAEs) as quantitative indices of the functional integrity of the outer hair cells (OHC) during growth of and recovery from temporary threshold shift (TTS). This was examined in two different groups of volunteers by measuring the per- and post-stimulatory effects of a one hour BBN and an on-site five hour exposure to loud music from a discotheque. The results of both experiments show consistent growth and recovery patterns for both DPOAEs and TEOAEs. For TEOAEs, both the reproducibility scores and signal to noise ratio values for the 4 kHz frequency band exhibited the greatest sensitivity. The DPOAEs, on the other hand, showed the greatest sensitivity between 2 and 5.5 kHz. Thus, both the TEOAEs and DPOAEs have a great potential in the detection of TTS after noise exposure.

Multiple primary malignant tumors in patients with head and neck cancer: results of a prospective study and future perspectives.

Multiple primary tumors are a known phenomenon in head and neck cancer. They are partially responsible for the limited improvement in survival of head and neck cancer during the past 20 years. Only a few prospective data have been published about the incidence of metachronous tumors. The authors prospectively studied 127 patients with squamous cell carcinoma of the head and neck. The overall incidence of second primary tumors was 13.5% (simultaneously, 3%; synchronously, 5.5%; and metachronously, 8%). More than 90% of the recurrences of the first primary tumor occurred within the first 2 years following primary treatment, but the second primary tumors continued to occur gradually in the course of follow-up. Most of the second primary tumors were discovered because the patients developed symptoms (14/17). Survival after detection of the second primary tumor was poor. The development of a second primary tumor was of equivalent prognosis to a recurrence of the primary tumor. Future directives include the development of more adequate screening methods. Identification of potential early markers for the development of a squamous cell carcinoma at the level of the mucosa at risk and in serum could be of value for the early detection of individuals at risk.

Multi-variant analysis of otoacoustic emissions and estimation of hearing thresholds: transient evoked otoacoustic emissions.

Evaluation of cochlear hearing loss by means of transiently evoked otoacoustic emissions is already established in clinical practice. However, accurate prediction of pure-tone thresholds is still questioned and is still regarded as troublesome. Both click- and tone-burst-evoked otoacoustic emissions at several intensity levels were measured and analysed in 157 ears from normally hearing and 432 ears from patients with different degrees of pure sensory hearing loss using the ILO88/92 equipment. Results of otoacoustic emissions (OAE), elicited by clicks and tone-bursts at centre frequencies from 1 to 5 kHz, were analysed using two different statistical methods. Both multivariate discriminant analysis and forward multiple regression analysis were used to determine which OAE variables were most discriminating and best at predicting hearing thresholds. We found that a limited set of variables obtained from both tone-burst and click measurements can accurately predict and categorize hearing loss levels up to a limit of 60 dB HL. We found correct classification scores of pure-tone thresholds between 500 and 4000 Hz up to 100 per cent when using combined click and tone-burst otoacoustic measurements. Prediction of pure-tone thresholds was correct with a maximum estimation error of 10 dB for audiometric octave frequencies between 500 and 4000 Hz. Measurements of multiple tone-bursts OAEs have a significant clinical advantage over the use of clicks alone for clinical applications, and a good classification and prediction of pure-tone thresholds with otoacoustic emissions is possible.

Choice of a tone-pip envelope for frequency-specific threshold evaluations by means of the middle-latency response: normally hearing subjects and slope of sensorineural hearing loss.

The effects of stimulus rise-fall and plateau times on the middle-latency response (MLR) waveform (Na-Pa amplitude and Pa latency) were investigated in 14 normally hearing subjects and an objective MLR threshold was evaluated at low and middle frequencies in ten normally hearing subjects and ten patients with slope of sensorineural hearing loss, using a selected stimulus-envelope time. After analyzing the effects of envelope times on the MLR waveform and the spectra of tone-pips, it was found that a rise-fall time of 4 ms with a plateau of 2 ms (4-2-4) is an acceptable compromise between a synchronous discharge and frequency specificity for estimating the MLR threshold. The MLR threshold produced by 4-2-4 tone-pips approximated the psychoacoustic threshold at low and middle frequencies in the normal and hearing impaired subjects. This demonstrates the clinical usefulness of the MLR in estimating low- and middle-frequency thresholds.

Nasal sensitization.

Because humans breathe through the nose, the nasal mucosa becomes sensitized to inhalant allergens. Allergic rhinitis is, together with allergic conjunctivitis, the best example of a type I hypersensitivity reaction. It is an inflammation of the nasal mucosa induced by specific immune recognition of exogenous allergens. The production of IgE plays a major role in the pathophysiology. During the sensitization phase, an antigen is presented to an antigen-presenting cell at the epithelial level. Cells that express class II major histocompatibility complex Ia on their surface can act as an antigen-presenting cell for immunocompetent cells (dentritic cells, monocytes, macrophages, B lymphocytes and epithelial cells). Macrophages and Langerhans cells are increased in number in the nasal mucosa of patients with seasonal allergic rhinitis during the season and also after allergen challenge. Topical corticosteroid treatment reduces the number of Langerhans cells in the epithelium. The epithelium also participates in antigen presentation through its possession of antigen-binding surface proteins. The antigen is finally presented to CD4 T-helper cells and B cells; this is monitored by cytokines and leads to the development of memory cells and IgE-producing plasmocytes. In humans, IL-4 has been shown to be capable of differentiating B cells into IgE-producing plasma cells. The IL-4 production is inhibited by interferon gamma and by prostaglandin E2. The CD4+ cells also produce IL-2, which causes differentiation and proliferation of T lymphocytes, and IL-3, IL-5, IL-6 and IL-7, which stimulate the B lymphocytes. Topical administration of anti-allergic drugs or immunotherapy seems to be a logical approach in the treatment of patients with allergic rhinitis, because it has very direct activity on the main components of nasal sensitization.

Physiopathology of H3-receptors and pharmacology of betahistine.

This article reviews published research on the physiology of histamine H3-receptors. The function of this inhibitory autoreceptor, its localisation and influence on histaminergic neurones as well as histamine-controlled processes are presented together with the role of H3-receptors in the vestibular system. In addition to a summary of the properties of the main H3-agonists and -antagonists, the pharmacology of betahistine and its place in the treatment of vertigo are discussed.

Inflammatory mechanisms in chronic sinusitis.

Apart from ventilatory and bacteriologic aspects, understanding the pathomechanisms of inflammation in chronic sinusitis and nasal polyposis seems crucial for further success in disease treatment. New insights into inflammatory processes became recently possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases. The proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and especially the neutrophil-chemoattractant IL-8 play a dominant role in acute sinusitis, as was shown before for viral and allergic rhinitis. In contrast, IL-3 protein dominates the cytokine profile in chronic sinusitis, giving support to a variety of inflammatory cells. The most striking finding was the increased synthesis of IL-5 protein in bilateral nasal polyposis, whereas IL-5 was not found in controls or antrochoanal polyps. As this cytokine is known to enhance eosinophil activation and survival, our data point to IL-5 as a key protein in the pathomechanism of tissue eosinophilia in nasal polyposis. The investigation of cytokine patterns may furthermore help to differentiate between sinusitis subgroups, e.g. in the classification of sinus diseases.

Microbiology of chronic sinusitis.

Much controversy still exists about the role of viruses, bacteria and fungi in sinusitis. Until recently, it was not really known that the sinuses take part in the infectious process of a common cold (viral rhinitis). Indeed, CT scans show that in the vast majority of otherwise healthy volunteers with a common cold, and without a previous history of recurrent or chronic sinusitis, the sinuses are involved too. A viral rhinitis alone, however, does not seem to be able to elicit a "clinical" acute sinusitis. Bacteria determine the clinical picture and outcome of sinusitis. There is not much controversy about the role of bacteria in acute sinusitis, S. pneumoniae, H. influenzae and M. catarrhalis being the most frequently involved bacteria. Much more conflicting reports are published about the normal flora of the sinuses, the role of anaerobes and the microbiology of chronic sinusitis. In this chapter the defense and pathophysiologic mechanisms of viral, bacterial and fungal infection of the nasal and sinusal mucosa are described. It is postulated that, although bacteria are very important in acute sinusitis, their role in chronic sinusitis is minimal, the bacteria being opportunistic colonisers.

Distortion product otoacoustic emissions: a normative study.

Distortion product otoacoustic emissions (DPOAEs) were quite recently introduced as a new objective auditory screening technique, having a unique potential because of their ability to analyze the micromechanical functions of the cochlea in a frequency-specific way. In 1992, Kemp and Bray released the commercially available Otodynamics Analyzer ILO92, which enabled investigators and audiological centres to perform DPOAE measurements in different populations, but without any relationship to normative data. The purpose of this study was to describe the normative aspects of 2f1-f2 DPOAEs obtained with the ILO92 from 101 normal ears of 101 healthy young adults. The DPOAEs were obtained automatically by means of two data-collection protocols on the ILO92 in the form of DP-gram and DP-growth functions. These data were statistically processed to form a normative database which has the potential of serving as a basis of for further research aimed at determining the utility of DPOAE testing in evaluating ear pathology.