xRead - Globus and Chronic Cough (April 2024)

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Otolaryngology–Head and Neck Surgery 144(3)

Table 1. Relationships Between Extent of Gastroesophageal Reflux Disease/Laryngopharyngeal Reflux and the Mechanism Triggering Cough Extent of Reflux Mechanism of Cough Distal esophageal reflux and reflux laryngospasm Vagal-mediated cough reflex Regurgitation of gastric contents to the laryngopharynx Mechano and cough receptors pH sensitivity of receptors Pepsin-mediated tissue change Enhanced cough receptor sensitivity to other irritants Gross and “micro” (or “silent”) aspiration

Aspiration pneumonia Chemical pneumonitis

Esophagobronchial reflex

Vagal mediated Likely cough secondary to pulmonary exacerbation

Cough-inducing reflux

Diaphragmatic/lower esophageal sphincter discoordination or relaxation allowing regurgitation

endoscopy. Finally, the relationships between allergic, infec tious, and other irritant inflammatory processes in the nose and lung have similar complex/synergistic physiology. Esophageal disease , gastroesophageal reflux disease (GERD) , and laryngopharyngeal reflux (LPR) are among the most com mon causes of chronic cough. Table 1 summarizes the many relationships between the extent of reflux and the mechanisms resulting in cough. Even distal esophageal reflux can cause cough through the same vagal-mediated evolutionary mecha nism that causes reflux laryngospasm. Diaphragmatic move ments as a result of coughing may also precipitate reflux. Gross aspiration can surely result in cough. Silent or “micro aspiration” of food, saliva, or refluxed chyme may not ini tially trigger a cough but produce a chronic inflammatory condition in the lung that secondarily results in cough. Similarly, the presence of vagal-mediated neural reflexes that produces cough in response to distal esophageal reflux may also pro duce an indirect effect on the lung through the esophageal bronchial reflex. Cough sensitivity is further modulated by the interplay of these disease states, the potential additive effects of chronic disease vs acute exacerbation, baseline neu rologic disease, certain medications, and the presence of microaspiration. Also, lack of a cough when needed may result in the devastating effects from aspiration or impaired pulmonary toilet. Neurologic etiologies of chronic cough range from sensory receptor irritability to brainstem reflexes to maladaptive behaviors. Clearly, the cortex of the brain may initiate a vol untary cough, as well as attempt to suppress it. Vocal fold paralysis and impaired motor control to the larynx predispose to aspiration and also result in an incompetent/ineffective cough. From the other side of the nervous pathway, sensory afferent fibers stimulate brainstem nuclei to trigger the cough reflex. In the brainstem, there is considerable overlap between cough nuclei and respiratory nuclei. This convergence between higher cortical control and primitive brainstem reflexes may result in laryngeal spasm, paradoxical vocal fold motion, and other forms of disordered breathing. Tumor may also be present as an instigating factor in chronic cough. Laryngeal tumors need to be considered, espe cially when hoarseness, dyspnea, or globus is present. Many

other tumors may be present even if they are not obvious on external examination or laryngoscopy. Nasal tumors may rarely be the primary cause of a cough but can understandably result in a postobstructive sinusitis. Postobstructive pneumo nia is a more common effect of pulmonary tumors such as bronchogenic carcinoma that should also be considered in the evaluation of chronic cough. Also, large gastric stromal tumors have been shown to result in gastric outlet obstruction, increasing the likelihood of GERD and LPR with secondary effects resulting in cough. Tumors in the skull base, neck, and chest may cause cough based on vagal irritability; more com monly, vagal involvement with the tumor (thyroid, nerve sheath, mediastinal, and metastatic disease) may result in vocal fold paralysis or paresis, with secondary effects result ing in microaspiration and cough. Systemic disease includes a group of disorders that may result in cough as a consequence of the disease or the treatment. Congestive heart failure results in cough through pulmonary congestion. Hypertension is another cardiovascular disease that can cause cough when treated with angiotensin-converting enzyme inhibitors through bradykinin upregulation and increased vascular permeability. Cystic fibrosis (CF) is a group of genetic disorders that results in alteration of mucus metabo lism in the respiratory as well as gastrointestinal systems. CF is not a single disease, and there is a growing list of gene muta tions that result in variable penetrance and manifestations that result in cough. Immune disorders (such as common variable immune deficiency) predispose to upper and lower respiratory infection. Also, autoimmune diseases such as sarcoidosis and antineutrophil-cytoplasmic antibody (ANCA)–associated granu lomatous vasculitis (previously referred to as Wegener’s granulo matosis) may have a direct effect in the larynx and lungs or cause secondary sinusitis or bronchitis. This set of interrelated diseases possibly causing a chronic cough makes diagnosis especially challenging. As such, there is a large spectrum of procedure-based testing and treatment that come under the purview of the otolaryngologist, as demonstrated in Figure 2 . The challenge remains how to prioritize the workup and further consider the costs of procedures vs the costs of delayed diagnosis. Evidence-based management algorithms for chronic cough should be followed, 7 and ultimately, measuring