Cough: An Interdisciplinary Problem, An Issue of Otolaryngologic Clinics , livre ebook

Otolaryngologic Clinics of North America , Vol. 43, No. 1, February 2010
ISSN: 0030-6665
doi: 10.1016/S0030-6665(10)00006-X

Contributors
Otolaryngologic Clinics of North America
Cough: An Interdisciplinary Problem
Kenneth W. Altman, MD, PhD
Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, Annenberg 10th Floor, One Gustave Levy Place, Box 1189, New York, NY 10029, USA
Richard S. Irwin, MD
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
ISSN  0030-6665
Volume 43 • Number 1 • February 2010

Otolaryngologic Clinics of North America , Vol. 43, No. 1, February 2010
ISSN: 0030-6665
doi: 10.1016/S0030-6665(10)00007-1

Contents
Cover
Contributors
Forthcoming Issues
Cough Specialists Collaborate for an Interdisciplinary Problem
Cough: A Worldwide Problem
Afferent Nerves Regulating the Cough Reflex: Mechanisms and Mediators of Cough in Disease
Mucus and Mucins
Cough and Swallowing Dysfunction
Vocal Cord Dysfunction, Paradoxic Vocal Fold Motion, or Laryngomalacia? Our Understanding Requires an Interdisciplinary Approach
Evidence for Sensory Neuropathy and Pharmacologic Management
The Role of Voice Therapy in the Management of Paradoxical Vocal Fold Motion, Chronic Cough, and Laryngospasm
Occupational, Environmental, and Irritant-Induced Cough
Reflux and Cough
Rhinogenic Laryngitis, Cough, and the Unified Airway
Cough Due to Asthma, Cough-Variant Asthma and Non-Asthmatic Eosinophilic Bronchitis
The Spectrum of Nonasthmatic Inflammatory Airway Diseases in Adults
Pharmacologic Management of Cough
Assessing Efficacy of Therapy for Cough
Unexplained Cough in the Adult
Cough in the Pediatric Population
Future Directions in Treating Cough
Index
Otolaryngologic Clinics of North America , Vol. 43, No. 1, February 2010
ISSN: 0030-6665
doi: 10.1016/S0030-6665(10)00008-3

Forthcoming Issues
Otolaryngologic Clinics of North America , Vol. 43, No. 1, February 2010
ISSN: 0030-6665
doi: 10.1016/j.otc.2009.12.004

Cough Specialists Collaborate for an Interdisciplinary Problem

Kenneth W. Altman, MD, PhD
Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, Annenberg 10th Floor, One Gustave Levy Place, Box 1189, New York, NY 10029, USA
E-mail address: Kenneth.Altman@mountsinai.org
E-mail address: Richard.Irwin@umassmemorial.org

Richard S. Irwin, MD ,
Division of Pulmonary Allergy and Critical Care Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
E-mail address: Kenneth.Altman@mountsinai.org
E-mail address: Richard.Irwin@umassmemorial.org


Kenneth W. Altman, MD, PhD Guest Editor

Richard S. Irwin, MD Guest Editor
Both acute and chronic cough are responsible for a significant portion of ambulatory medical visits annually (about 3%), 1 over-the-counter self-medication expenses in excess of $3.6 billion in the United States, 2 and impaired quality of life. The diagnosis of cough can be simple or profoundly challenging. This ranges from a solitary cause such as allergic rhinitis, to multifactorial and synergistic contributions, to a physiologic mystery that may ultimately impair respiratory function and hinder one’s way of life. One unique aspect of this chronic cough is that it is an indicator of underlying disease, rather than being a disease itself.
Thus, as clinicians we consider cough as a manifestation of disease; yet, as scientists, we think of cough as a product of physiologic mechanisms. These diseases and mechanisms involve the spectrum of adult medical and pediatric disciplines, including otolaryngology, pulmonology and chest physicians, allergy and immunology, gastroenterology, neurology, cardiology, infectious disease, speech and swallowing pathologists, as well as psychiatry. It is particularly timely for this discussion of cough as a true interdisciplinary problem, since we now consider both “macrophysiologic” (interplay of diseases) and “microphysiologic” perspectives (interplay of mechanisms).
The list of diseases that may induce cough is growing, along with an appreciation of the inter-relatedness of these diseases, as described in Fig. 1 . For example, emerging evidence now supports our long-held observation that the upper and lower airway diseases are closely related as an unified airway, and that allergy plays an important role in exacerbating both upper and lower airway disease. There is also a spectrum of both asthmatic and non-asthmatic lower airway inflammatory disease that often has overlapping clinical signs. Asthmatic, allergic, infectious and other irritant and inflammatory processes in the nose and lung similarly have complex and synergistic physiologic relationships.

Fig. 1 Inter-relatedness of clinical disease relating to cough. Multiple mechanisms exist at both the local and systemic levels to account for synergy in exacerbation of disease processes. Note: systemic disease includes congestive heart failure (CHF), hypertension treated with angiotensin converting enzyme inhibitors (ACEi), and cystic fibrosis (CF). Tumor may have a direct effect on nerves triggering cough, particularly all branches of the vagus. It may also result in an indirect cause of cough through a post-obstructive inflammatory/infectious process in the lung or paranasal sinuses. There are a number of mechanisms by which gastroesophageal reflux disease (GERD) may trigger cough, both directly related to gross or microspiration, as well as through neurologic reflex (see text). Aspiration may also occur independent of GERD.
The role of gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR) in inducing cough as a protective mechanism of aspiration is increasingly recognized, even if the gastric chyme extends only to the distal esophagus. The presence of vagal-mediated neural reflexes that produces cough in response to distal esophageal reflux may also produce an indirect effect on the lung through the esophageal-bronchial reflex. Silent, or “microaspiration” of food contents, saliva or refluxed contents may not initially trigger a cough, but produce a chronic inflammatory condition in the lung that does result in cough. We also know that diaphragmatic movements as a result of cough may precipitate GERD or LPR. Cough sensitivity is further modulated by the interplay of these disease states, the potential additive effects of chronic disease versus acute exacerbation, baseline neurologic disease, certain medications and the presence of microaspiration. And lack of a cough when needed, may result in the devastating effects from aspiration or impaired pulmonary toilet.
The brain and its relationship with cough is seen as a “two-sided arrow” in Fig. 1 . Clearly the cortex of the brain may initiate a cough voluntarily, as well as attempt to suppress it. From the other side of the nervous pathway, sensory afferent fibers stimulate brainstem nuclei to trigger the cough reflex. In the brainstem, there is also considerable overlap between cough and respiratory nuclei. This convergence between higher cortical influence, and primitive brainstem reflexes may result in the clinical presentation of laryngeal spasm, paradoxical vocal fold motion, and other forms of disordered breathing.
When one studies the triggers of cough, it becomes straightforward to recognize that there is an intense interplay of physiologic mechanisms. These are described in Fig. 2 , and includes the roles of:
• Sensory receptors – chemical and mechanical (temperature and pH-sensitive).
• Transient receptor potential (TRP) family of ion channels and especially over-expression of TRPV1 (the capsaicin receptor) may explain the overly sensitive cough reflex in unexplained cough.
• Peripheral nerve afferent vagal fibers - rapidly adapting stretch receptors (RAR) associated with small diameter myelinated fibers, cough receptors, and the pulmonary and bronchial C-fiber receptors. There are also likely vagal-mediated reflexes triggering cough from sources outside the lung.
• Airway mucus – viscosity and the presence of cellular and secreted inflammatory mediators. It may be postulated that reflexive vascular dilation leads to transudate of fluid that affects mucus viscosity, and also leads to increased blood flow of the submucosal seromucinous glands to increase or change the nature of seromucinous secretions.
• Neurogenic mediators – tachykinins such as substance P and other sub-epithelial chemicals that mediate the afferent neural response to sensory triggers. (While these mediators have been shown to play a role in cough in animal models, evidence to support this in humans has yet to be demonstrated).
• Systemic inflammation – both cellular and humoral, and
• Central neurologic integration – including brainstem overlap between nuclei responsible for cough and respiration.

Fig. 2 Inter-relatedness of mechanisms inducing cough. Note: “•” denotes sensory receptor. Sensory receptors may include both cough receptors, as well as c-fiber receptors in the lung. Although the latter communicates with slower conducting fibers to the brainstem, strong stimuli may result in an inhibitory effect. The transient receptor potential (TRP) family of ion channels and especia