Gastroesophageal re¯ux disease and asthma: an intriguing dilemma Background: Gastroesophageal re¯ux disease (GORD) is characterized by typical re¯ux symptoms and multiple atypical extraesophageal symptoms. Gastric asthma is a prominent extraesophageal manifestation of GORD. There is persistent debate about the pathophysiologic mechanisms triggering asthma by GOR. Methods: We conducted a review of the literature. Results: The pathogenic mechanism could be either a vagally transmitted re¯ex or an intratracheal aspiration of re¯uxed material. In both hypotheses, the role of in¯ammatory mediators has been proposed. Conclusions: Neurogenic in¯ammation is a good theoretic basis for a pathogenic interpretation of the disorder. In atopic patients, food allergy has been recently proposed as a possible cause of GOR and associated respiratory symptoms, and it should be considered in the diagnostic work-up of all patients with GORD. C. Astarita, D. Gargano, M. Cutajar, A. Napolitano Dipartimento di Internistica Clinica e Sperimentale ``F. Magrassi'', Clinica Medica Seconda Universita Á di Napoli, Naples F. Manguso Istituto di Gastroenterologia, Facolta Á di Medicina, Universita Á di Napoli ''Federico II``, Naples G. F. Abbate Servizio di Patologia Internistica Critica, Dipartimento, ``F. Magrassi'', Seconda Universita Á di Napoli, Naples, Italy Key words: asthma; food allergy; gastroesophageal re¯ux. Dr Corrado Astarita Dipartimento di Internistica Clinica e Sperimentale ``F. Magrassi'' Clinica Medica Seconda Universita Á di Napoli via S. Pansini 5 80100 Naples Italy Tel. 081 5666725 Fax: 081 5666728 A relationship between the typical gastroesophageal re¯ux (GOR) symptoms of heartburn, regurgitation or dysphagia, and asthma was suggested by Osler more than a century ago (1). It was more than a century later that Kennedy ®rst suggested that silent GOR could be a ``little known'' cause of pulmonary symptoms, including bronchospastic conditions arising especially during the night (2). Gastroesophageal re¯ux disease (GORD) has other extraesophageal manifestations as well, particu- larly pulmonary and ear, nose, and throat conditions (3) (Table 1). However, dif®culty has always arisen in deciding either whether GOR itself will initiate or exacerbate asthma, or whether asthma itself or its treatment may cause GOR to occur in a particular patient (4). In the general population, 7±43% are estimated to suffer from GORD to some extent (3, 5, 6). The prevalence of GORD among asthmatics is high, ranging from 34% to 89% in different studies (7±11), although there have been reports of a normal prevalence of increased GOR (12) in asthmatics; moreover, an increased prevalence of GORD in asthmatics does not imply a truly causal relation in associating the two diseases. Pathophysiology of triggering asthma by GOR Three main mechanisms may be involved in producing GOR-induced or -aggravated asthma: 1) microaspiration of gastric acid into the respiratory airways after re¯ux (13) 2) a vagally mediated re¯ex inducing bronchocon- striction (14) 3) a sensitized vagal system inducing or enhancing airways hyperresponsiveness (15, 16). Microaspiration into airways has been directly investigated in animals (17), as well as in man, by scintigraphic studies (18), with simultaneous pH-metry in the esophagus and trachea (19, 20) and with associated proximal and distal pH-metry in the esophagus (11, 16, 21). In cats, intratracheal acid infusion caused an immediate but short-lasting increase Allergy 2000: 55: Suppl 61: 52±55 Printed in UK. All rights reserved Copyright # Munksgaard 2000 ALLERGY ISSN 0108-1675 52