Alvin Ing

Obstructive sleep apnea and gastroesophageal reflux

A number of recent studies have described the presence of significant gastroesophageal reflux (GER) in patients with obstructive sleep apnea (OSA). The aims of our studies were to determine the prevalence of this in a controlled population and to investigate the potential for a causal relationship between the two entities by determining whether therapy of OSA altered GER parameters, and vice versa. All patients presenting to our sleep laboratory for screening polysomnography underwent distal esophageal pH monitoring simultaneously with polysomnography. Control subjects were selected if the apnea-hypopnea index (AHI) was <5.0, and patients were selected if AHI was >15.0. Fourteen subjects with OSA undertook a second polysomnographic study including distal esophageal pH monitoring, with nasal continuous positive airway pressure (nCPAP) intervention. Twelve subjects with proven OSA took part in a randomized, placebo-controlled, double-blinded, parallel group study of the effect of antireflux therapy (nizatidine) on OSA parameters. In 63 patients and 41 controls, we found that patients with OSA had significantly more GER events than controls as measured by number of reflux events over 8 hours (115 vs 23; P <0.001), and percent of time spent at pH <4.0 (21.4% vs 3.7%; P <0.001). In patients with proven OSA, 53.4% of GER episodes were temporally related to apneas or hypopneas. Less than half (46.8%) of all apneas were temporally related to acid reflux, and only 43.8% of arousals were related to reflux events. In the therapeutic trials, nCPAP reduced GER parameters in both patients with OSA and without OSA, suggesting a nonspecific effect. Antireflux therapy (nizatidine) reduced arousals but not apnea-hypopnea index in patients with OSA. Patients with OSA have a higher prevalence of GER than matched control subjects. Nasal CPAP reduces GER parameters nonspecifically, and thus the role of OSA in the pathogenesis of GER remains unclear. GER, however is likely to be important in the pathogenesis of arousals, but there is no evidence that it is involved in the pathogenesis of apneas.

Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity.

Background: Laryngopharyngeal sensitivity (LPS) is important in preventing pulmonary aspiration and may be impaired by anaesthesia and stroke. It has been suggested that gastro-oesophageal reflux disease (GORD) may also impair LPS, although the underlying mechanism is unclear. The aim of this study was to compare LPS in patients with chronic cough and GORD with healthy subjects and to determine the effect of laryngopharyngeal infusions of both acid and normal saline on LPS. Methods: Fifteen patients with chronic cough and GORD and 10 healthy subjects without GORD underwent LPS testing using the fibreoptic endoscopic evaluation of swallowing with sensory testing (FEESST) technique. LPS, as measured by the lowest air pressure required to elicit the laryngeal adductor reflex (LAR), was determined both before and after laryngopharyngeal infusions of normal saline and 0.1 N hydrochloric acid performed on separate days. Results: The mean baseline LAR threshold of the patient group was significantly higher (9.5 mm Hg, range 6.0–10.0) than in normal subjects (3.68 mm Hg, range 2.5–5.0; p<0.01). Retest thresholds were not significantly different. In normal subjects LAR thresholds were significantly raised after acid but not after saline infusion (p = 0.005). There were no complications associated with the procedure. Conclusions: Patients with cough and GORD have significantly reduced LPS to air stimuli compared with healthy subjects which could potentially result in an increased risk of aspiration. Exposure to small amounts of acid significantly impaired the sensory integrity of the laryngopharynx.

Chronic persistent cough and gastro-oesophageal reflux.

Chronic cough persisting for two months or more that remains unexplained after extensive investigations is a common clinical problem. The purpose of this study was to determine whether such cough is associated with otherwise asymptomatic gastro-oesophageal reflux. Thirteen patients with chronic persistent cough that was unexplained after a standard diagnostic assessment were identified. All were non-smokers. The mean (SE) duration of cough was 17.8 (8.0) months. Ten had never had reflux symptoms and three had had mild symptoms only after the onset of the cough. All the patients completed standardised cough diary cards for eight weeks and underwent 24 hour ambulatory oesophageal pH monitoring. A reflux episode was defined as a fall in oesophageal pH to below 4.0. Nine control subjects were matched for age, lung function, and body mass index. The patients experienced significantly more episodes of reflux per 24 hours than the controls (115.8 (SE 31.7) versus 4.7 (1.4) and longer reflux episodes (15.5 (5.8) versus 1.7 (0.5) minutes), and the oesophageal pH was below 4.0 considerably longer (84.5 (20.2) versus 3.8 (1.3) minutes). Cough occurred simultaneously with 13% (2.2%) of reflux episodes and within five minutes in another 35% (5.8%) of episodes, whereas gastro-oesophageal reflux occurred simultaneously with 78% (5.5%) of cough episodes and within five minutes in another 12% (2.3%) of episodes. It is concluded that chronic persistent cough that remains unexplained after a standard diagnostic assessment is associated with otherwise asymptomatic gastro-oesophageal reflux. It is suggested that a self perpetuating mechanism may exist whereby acid reflux causes cough via a local neuronal oesophageal-tracheo-bronchial reflex, and the cough in turn amplifies reflux via increased transdiaphragmatic pressure or by inducing transient lower oesophageal sphincter relaxation. Further study of this mechanism and the role of specific antireflux treatment in chronic persistent cough is warranted.

A Locus for Hereditary Sensory Neuropathy with Cough and Gastroesophageal Reflux on Chromosome 3p22-p24

Hereditary sensory neuropathy type I (HSN I) is a group of dominantly inherited degenerative disorders of peripheral nerve in which sensory features are more prominent than motor involvement. We have described a new form of HSN I that is associated with cough and gastroesophageal reflux. To map the chromosomal location of the gene causing the disorder, a 10-cM genome screen was undertaken in a large Australian family. Two-point analysis showed linkage to chromosome 3p22-p24 (Zmax=3.51 at recombination fraction (theta) 0.0 for marker D3S2338). A second family with a similar phenotype shares a different disease haplotype but segregates at the same locus. Extended haplotype analysis has refined the region to a 3.42-cM interval, flanked by markers D3S2336 and D3S1266.

Interstitial Lung Disease and Gastroesophageal Reflux

Gastroesophageal reflux (GER) has been associated with a number of interstitial lung diseases, including systemic sclerosis and idiopathic pulmonary fibrosis. Systemic sclerosis results in both pulmonary and esophageal manifestations, and studies have shown a correlation, but no causal relation, between GER and pulmonary fibrosis in this condition. The role of GER in idiopathic pulmonary fibrosis has recently been studied using esophageal pH monitoring, and the results show high prevalence of GER compared with normal individuals and patients with other interstitial lung diseases of known cause. Aggressive, long-term therapy of GER and evaluation of its effect on pulmonary disease will allow determination of the real influence of GER on idiopathic pulmonary fibrosis. Additional outcomes-based studies and therapeutic trials are needed to clarify the association between GER and interstitial lung diseases.

Cough and Gastroesophageal Reflux

Cough is a very common clinical problem, being the most common complaint for which patients seek medical attention and the second most common reason for a medical examination in the United States. The annual cost of treatment of cough in the United States alone is u

Obstructive sleep apnoea: a cause of chronic cough

1 billion. There are many causes of both acute and chronic cough, with chronic cough being defined as the presence of cough for at least 3 weeks. The majority of the clinical scientific literature on cough addresses chronic unexplained cough, which is defined as follows; cough for at least 3 weeks, cough is the only presenting symptom, there is no associated hemoptysis, there is no prior history of chronic respiratory disease to account for the cough, and current chest xray does not contribute to the diagnosis. Utilizing a diagnostic protocol based on the anatomy of the cough reflex (Figure 1), Irwin and co-workers were able to diagnose and treat successfully the majority of patients who presented with previously unexplained chronic cough. These results have been successfully duplicated by other investigators and by Irwin’s group in subsequent series. The anatomic diagnostic protocol utilizes a complete history and physical examination; chest x-ray; lung function testing (including spirometry, lung volumes, diffusing capacity, bronchial provocation testing, and home peak flow monitoring); ear, nose, and throat examination; laryngoscopy; and paranasal sinus imaging. Studies applying this protocol to patients with previously unexplained chronic persistent cough have found that the 3 most common causes of chronic cough are bronchial asthma, postnasal drip, and gastroesophageal reflux (GER; Table I). GER has long been associated with pulmonary symptoms and diseases, many of which present with cough. These range from bronchopulmonary dysplasia in infants, bronchial asthma, chronic bronchitis, and diffuse pulmonary fibrosis, to the pulmonary aspiration syndromes, including lung abscess, bronchiectasis, pneumonitis, recurrent pneumonia and respiratory failure.

Chronic cough in patients with sleep-disordered breathing

Chronic cough is a common reason for presentation to both general practice and respiratory clinics. In up to 25% of cases, the cause remains unclear after extensive investigations. We report 4 patients presenting with an isolated chronic cough who were subsequently found to have obstructive sleep apnoea. The cough improved rapidly with nocturnal continuous positive airway pressure therapy. Further studies are required to investigate the prevalence of coexistence of these common conditions.

Left Atrial Compression and the Mechanism of Exercise Impairment in Patients With a Large Hiatal Hernia

Chronic cough can be the sole presenting symptom for patients with obstructive sleep apnoea. We investigated the prevalence, severity and factors associated with chronic cough in patients with sleep-disordered breathing (SDB). We invited 108 consecutive patients who had been referred for evaluation of SDB to complete a comprehensive questionnaire on respiratory and sleep health, which included the Leicester Cough Questionnaire (cough specific quality of life; LCQ), Epworth Sleepiness Scale (ESS) and the Mayo Clinic gastro-oesophageal questionnaire. Chronic cough was defined as cough for a duration of >2 months. 33% of patients with SDB reported a chronic cough. Patients with a chronic cough had impaired cough related-quality of life affecting all health domains (mean±sem LCQ score 17.7±0.7; normal = 21). Patients with SDB and chronic cough were predominantly females (61% versus 17%; p<0.001) and reported more nocturnal heartburn (28% versus 5%; p = 0.03) and rhinitis (44% versus 14%; p = 0.02) compared to those without SDB. There were no significant differences in ESS, respiratory disturbance index, body mass index, or symptoms of breathlessness, wheeze, snoring, dry mouth and choking between those with cough and those without. Chronic cough is prevalent in patients with SDB and is associated with female sex, symptoms of nocturnal heartburn and rhinitis. Further studies are required to investigate the impact of continuous positive airway pressure therapy on cough associated with SDB to explore the mechanism of this association.

Mucociliary function, ciliary ultrastructure, and ciliary orientation in Young's syndrome.

OBJECTIVES The purpose of this study was to determine the association between cardiac compression and exercise impairment in patients with a large hiatal hernia (HH). BACKGROUND Dyspnea and exercise impairment are common symptoms of a large HH with unknown pathophysiology. Studies evaluating the contribution of cardiac compression to the pathogenesis of these symptoms have not been performed. METHODS We collected clinical data from a consecutive series of 30 patients prospectively evaluated with resting and stress echocardiography, cardiac computed tomography, and respiratory function testing before and after laparoscopic HH repair. Left atrial (LA), inferior pulmonary vein, and coronary sinus compression was analyzed in relation to exercise capacity (metabolic equivalents [METs] achieved on Bruce treadmill protocol). RESULTS Exertional dyspnea was present in 25 of 30 patients (83%) despite normal mean baseline respiratory function. Moderate to severe LA compression was qualitatively present in 23 of 30 patients (77%) on computed tomography. Right and left inferior pulmonary vein and coronary sinus compression was present in 11 of 30 (37%), 12 of 30 (40%), and 26 of 30 (87%) patients, respectively. Post-operatively, New York Heart Association functional class and exercise capacity improved significantly (number of patients in New York Heart Association functional classes I, II, III, and IV: 6, 11, 11, and 2 vs. 26, 4, 0, and 0, respectively, p < 0.001; METs [percentage predicted]: 75 ± 24% vs. 112 ± 23%, p < 0.001) and resolution of cardiac compression was observed. Absolute change in LA diameter on the echocardiogram was the only independent cardiorespiratory predictor of exercise capacity improvement post-operatively (p = 0.006). CONCLUSIONS We demonstrate, for the first time, marked exercise impairment and cardiac compression in patients with a large HH and normal respiratory function. After HH repair, exercise capacity improves significantly and correlates with resolution of LA compression.