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Background and Objective: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV., Methods: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards., Results: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF., Conclusion: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions., (© 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium. Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB. Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ). Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV 1 , 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount ( P  < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P  = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P  = 0.0002) scores were observed, with similar observations through 12 months. Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic. Of the 217 passengers and crew on board, 128 tested positive for COVID-19 on reverse transcription-PCR (59%). Of the COVID-19-positive patients, 19% (24) were symptomatic; 6.2% (8) required medical evacuation; 3.1% (4) were intubated and ventilated; and the mortality was 0.8% (1). The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients). We conclude that the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Transbronchial lung cryobiopsy (TBCB) plays an increasing role in the evaluation of diffuse parenchymal lung disease with acceptable diagnostic yield and safety profile compared with that of video-assisted thoracoscopic surgical lung biopsy on most reports. However, published outcomes with regard to safety and complication rates vary. We aim to determine the safety profile of TBCB when performed using a standardized protocol consistent with recently published expert guidelines., Materials and Methods: We reviewed prospectively maintained databases from 5 Australian tertiary referral centers. The procedures were performed in accordance with a recent expert statement recommending standardization of TBCB procedures, in particular with fluoroscopy, a secured airway, and prophylactic bronchial blockers. Periprocedural complications were assessed along with clinical outcomes., Results: A total of 121 patients underwent TBCB between August 2013 and August 2017 following a standardized protocol using general anesthesia. Of them, 84 patients (66.7%) were discharged on the day of the procedure. Pneumothorax occurred in 18 patients (14.9%), 13 (10.7%) of whom required chest tube drainage. Moderate bleeding occurred in 15 patients (13.2%) and severe bleeding in 1 (0.83%). Histopathologic diagnosis was made in 80 patients (66.1%)., Conclusion: Pooled outcomes from Australian tertiary centers indicate that TBCB is safe when performed in a protocolized fashion. Active measures to anticipate and manage bleeding and to direct biopsy position result in low rates of major complications.

Background: We have previously reported significant improvements in ventilation and perfusion (VQ) and V/Q matching in the contralateral lung, especially the non-targeted lower zone in patients with severe COPD following upper lobe ELVR with endobronchial valves. However, V/Q changes after lower lobe ELVR have not been described., Methods: Seven patients with lower lobe heterogeneous emphysema underwent unilateral lower lobe ELVR at Macquarie University Hospital. Lung function tests, 6-minute walk tests (6MWT), St George's Respiratory Questionnaire (SGRQ) and planar differential VQ scans were performed at baseline and at 1, 3 and 12 months post-ELVR., Results: Compared to baseline, patients showed significant improvements in FEV1 (0.83 ± 0.09L-0.97 ± 0.12L, p < 0.05), 6MWD (200.33 ± 56.54 m-274.24 ± 48.03 m, p < 0.05) and SGRQ (61.13 ± 5.33-42.86 ± 6.99, p < 0.05) at 3 months after ELVR. This improvement was maintained at 12 months. There was a corresponding significant improvement in the differential ventilation (30.21 ± 3.04%-37.82 ± 3.76%, p < 0.05) and perfusion (31.77 ± 2.53%-35.60 ± 2.58%, p < 0.05) of the contralateral non-targeted upper zone., Conclusions: Within the limitations of a small sample size, we have found that in heterogeneous severe COPD patients undergoing ELVR targeting the lower lobes, there are clinical and PFT improvements similar to that reported in ELVR targeting upper lobes. Contralateral improvement in V/Q matching also occurs following lower lobe ELVR with the greatest improvement in the contralateral upper zone, suggesting the contralateral upper lobe should be the least affected lobe if the lower lobe is targeted in ELVR. These findings need to be confirmed in a study with a larger number of patients., (© 2019 John Wiley & Sons Ltd.)

Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.

Purpose: Abdominal pain is the most common reason for surgical referral. Imaging, aids early diagnosis and treatment. However unnecessary requests are associated with increased costs, radiation exposure and increased length of stay. Pathways can improve the quality of the diagnostic process. The aim of this systematic review was to identify the current evidence for diagnostic pathways and their use of imaging and effect on final outcomes., Data Sources: A systematic search of Embase, Medline and Cochrane databases was performed using keywords and MeSH terms for abdominal pain., Study Selection: All papers describing a pathway and published between January 2000 and January 2017 were included., Data Extraction: Data was obtained about the use of imaging, complications and length of stay. Quality assessment was performed using MINORS and Level of Evidence., Results: Ten articles were included, each describing a different pathway. Five studies based the pathway on literature reviews alone and five studies on the results of their prospective study. Of the latter five studies, four showed that routine imaging increased diagnostic accuracy, but without showing a reduction in length of stay, complication rate or mortality. None of the studies included evaluated use of hospital resources or costs., Conclusion: Pathways incorporating routine imaging will improve early diagnosis, but has not been proven to reduce complication rates or hospital length of stay. On the basis of this systematic review conclusions can therefore not be drawn about the pathways described and their benefit to the diagnostic process for patients presenting with abdominal pain.

Background: Endoscopic lung volume reduction (ELVR) has been shown to improve lung function, quality of life, and exercise tolerance in patients with severe heterogeneous emphysema. Our study aims to determine the effect of ELVR on gas transfer capacity corrected for alveolar volume (KCO) and investigate the relationship between KCO and ventilation and perfusion (VQ) matching. We speculate on possible mechanisms for the observed changes METHODS:: Patients with severe chronic obstructive pulmonary disease were prospectively recruited and underwent unilateral upper lobe ELVR between 2012 and 2014. Each had respiratory function test and differential VQ scans at baseline, 1-, 3-, and 12-month post-ELVR., Results: In total, 11 patients had 3 sets of respiratory function test (at baseline, 1, and 3 mo), whereas 7 had 4 sets (at baseline, 1, 3, and 12 mo). KCO improved by 10.3 (±7.5)% at 1 month (P=NS) and 39.8 (±15.4)% at 12 months (P<0.05). VQ of the nontargeted lung increased by 12.8 (±5.6)% and 7.9 (±2.3)%, respectively at 1 month, whereas those of the targeted lung both decreased (P<0.05). At 3 and 12 months, the VQ changes were similar to those at 1 month, though some were not statistically significant., Conclusions: ELVR results in improved KCO for at least 12 months. This may be explained by the VQ redistribution to the nontargeted and less emphysematous lung with improved VQ matching.

Background: The aim of this study was to assess the safety and efficacy of large balloon sphincteroplasty when used in conjunction with endoscopic biliary sphincterotomy during endoscopic retrograde cholangiopancreatography (ERCP) for therapy of choledocholithiasis., Methods: A retrospective audit of all ERCP's performed for choledocholithiasis between January 2012 and October 2013 at one institution was performed. Procedures that utilized large balloon sphincteroplasty were compared with those underwent standard endoscopic stone extraction. Outcomes including stone clearance rate for the individual procedure type, post-ERCP complications and need for surgical exploration of the bile duct were documented., Results: A total of 346 procedures on 306 patients that met the inclusion criteria were identified. Fifty-four (15.6%) procedures included large balloon sphincteroplasty and were compared with 292 (84.4%) procedures that used standard balloon extraction techniques. Despite those patients in the large balloon sphincteroplasty group having a higher rate of previous ERCP (33.3% versus 19.5%, P = 0.031) and a larger proportion of patients with stones greater than 10 mm (40.3% versus 11.3%, P < 0.001), the overall initial clearance rate was similar at 83%. Ultimately, only 14 out of 306 (4.6%) of all patients required surgical intervention. There was no significant difference in the rate of post-ERCP pancreatitis between the two groups (5.6% versus 3.8%, P = 0.466)., Conclusion: Large balloon sphincteroplasty of the sphincter of Oddi is a safe and effective adjunct to endoscopic biliary sphincterotomy in difficult to treat choledocholithiasis. The current study demonstrated large balloon sphincteroplasty did not result in more complications despite a tendency to being used for larger stones., (© 2014 Royal Australasian College of Surgeons.)

Research indicates that patients with Chronic Obstructive Pulmonary Disease (COPD) have increased aspiration risk. Several factors may pre-dispose a patient to aspiration including a reduction in laryngopharyngeal sensitivity (LPS). Reduced LPS has been associated with increased aspiration risk in pathologies including stroke; however, this has not been examined in COPD. This study aims to explore possible associations between LPS and swallowing function in COPD patients, and determine whether a LPS predictive value may be used as a method of evaluating dysphagia risk in this patient population. Twenty participants with COPD underwent LPS discrimination testing, respiratory function testing, self-reporting swallowing questionnaire, clinical swallowing examination, and fibre-optic endoscopic evaluation of swallowing (FEES). Participants with COPD demonstrated impaired LPS defined by elevated laryngeal adductor reflex thresholds and high incidence of pharyngeal residue on FEES. Positive correlations were identified between their clinical swallowing examination and FEES results for the presence of laryngeal penetration/aspiration (p < 0.04), vallecular residue (p < 0.01), and piriform residue (p < 0.01). In conclusion, COPD patients have reduced laryngopharyngeal mechanosensitivity and impaired swallowing function characterized primarily by pharyngeal stasis. The combination of these deficits may place patients with COPD at increased aspiration risk due to lack of detection of pharyngeal residue and subsequent inhalation of pharyngeal contents.

Patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of aspiration secondary to impaired swallow function. One possible cause of this impairment is a reduction in laryngopharyngeal sensitivity. The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. We conducted a study to investigate the effect of COPD on laryngopharyngeal sensitivity by using laryngopharyngeal sensory discrimination testing (LPSDT). Our study population was made up of 20 adults (mean age: 71.7 yr) with clinically proven COPD and 11 healthy, age-matched controls. All 31 subjects underwent LPSDT with the use of an air-pulse stimulator via a nasendoscope. The threshold of laryngopharyngeal sensation was evaluated by measuring the amount of air pressure required to elicit the laryngeal adductor reflex (LAR). We found that the patients with COPD had a significantly higher LAR threshold than did the controls (p< 0.001). We conclude that patients with COPD have significantly less mechanosensitivity in the laryngopharynx. This sensory change may place patients with COPD at increased risk for aspiration.

Introduction: This study aims to examine the impact of laparoscopic repair of large hiatal hernia on dyspnoea severity, respiratory function and quality of life., Methods: From 2004 to 2008, 30 consecutive patients with large para-oesophageal hernia defined as >50% of stomach in the intra-thoracic cavity and minimum follow-up of 2 years were included in this study. All patients had a formal respiratory function test 1 week prior and 3 months after their laparoscopic hiatal hernia repair. Patients rated symptom severity and completed a quality-of-life questionnaire [Gastrointestinal Quality of Life Index (GIQLI)] pre-operatively, and post-operatively at 3 months, 6 months and yearly thereafter., Results: There was no hospital mortality, and the morbidity rate was 10%. In 26 patients with pre-operative dyspnoea, 22 had complete resolution while the remaining 4 had improvement of dyspnoea severity post-operatively. The mean dyspnoea severity index reduced from 2.4 to 1.3 (P < 0.001). Overall, there was 1%, 3% and 3% post-operative increase in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) values for the whole group, none of which reached statistical significance. For patients with resolution or improvement of dyspnoea after laparoscopic repair, no significant change of respiratory function parameters was demonstrated. GIQLI score improved from a pre-operative value of 85.7 to 107.9 post-operatively (P < 0.001)., Conclusions: We failed to show a significant change in post-operative respiratory function despite clearly demonstrated improvement of respiratory symptoms. Alternative explanations for reduction of dyspnoea severity should be sought.

Background and Objective: The effects of bronchoscopic lung volume reduction (BLVR) on pulmonary ventilation and perfusion are incompletely understood. In this pilot trial, we investigated serial changes in regional ventilation and perfusion following unilateral endobronchial valve placement in COPD patients with heterogeneous emphysema., Methods: At baseline and at days 30 and 90 following BLVR, subjects underwent lung function, 6MWD and St George's Respiratory Questionnaire. Ventilation and perfusion scintigraphy were performed to quantitate and serially compare regional differences., Results: Six out of eight subjects completed the study; all had endobronchial valves targeting their left upper lobe. At day 90 post-BLVR, there was a trend towards an increase in FEV(1) and a mean reduction in St George's Respiratory Questionnaire score of nine units. In the targeted left upper zone there was reduced ventilation and perfusion. Ventilation and perfusion to the right lung; and specifically the right lower zone, significantly increased., Conclusions: There appears to be redistribution of ventilation and perfusion to the contralateral lung following endobronchial valve placement. This may be of importance when assessing patients for unilateral BLVR. Selecting patients with heterogeneous disease is emphasized, taking into consideration not just comparison between upper and lower lobes, but between left and right lungs. A larger trial is currently underway, guided by these findings., (© 2010 The Authors. Respirology © 2010 Asian Pacific Society of Respirology.)

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.

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.

Autosomal dominant hereditary sensory neuropathy (HSN I) is a clinically and genetically heterogeneous group of disorders, and in some families it is due to mutations in the serine palmitoyltransferase (SPTLC1) gene. We have characterized two families with HSN I associated with cough and gastro-oesophageal reflux (GOR). From a large Australian family, 27 individuals and from a smaller family, 11 individuals provided clinical information and blood for genetic analysis. Affected individuals had an adult onset of paroxysmal cough, GOR and distal sensory loss. Cough could be triggered by noxious odours or by pressure in the external auditory canal (Arnold's ear-cough reflex). Other features included throat clearing, hoarse voice, cough syncope and sensorineural hearing loss. Neurophysiological and pathological studies demonstrated a sensory axonal neuropathy. Gastric emptying studies were normal, and autonomic function and sweat tests were either normal or showed distal hypohidrosis. Cough was likely to be due to a combination of denervation hypersensitivity of the upper airways and oesophagus, and prominent GOR. Most affected individuals were shown on 24 h ambulatory oesophageal pH monitoring to have multiple episodes of GOR, closely temporally associated with coughing. Hoarse voice was probably attributable to acid-induced laryngeal damage, and there was no evidence of vocal cord palsy. No other cause for cough was found on most respiratory or otorhinological studies. Linkage to chromosome 3p22-p24 has been found in both families, with no evidence of linkage to loci for known HSN I, autosomal dominant hereditary motor and sensory neuropathy, hereditary GOR or triple A syndrome. These families represent a genetically novel variant of HSN I, with a distinctive cough owing to involvement of the upper aerodigestive tract.

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.

A number of authors have reported a significant percentage of patients whose cause of cough remains undetermined despite a systematic evaluation as recommended in a number of International Guidelines. This subset of patients, which may be regarded as having an idiopathic cough, are often female and of peri or postmenopausal age. Sex hormones may influence the cough reflex in disease or contribute to the chronic lymphocytic airway inflammation seen in some cases and to the association with organ specific autoimmune disease reported. This paper seeks to investigate some of the possible causes of idiopathic cough.

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.

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.

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.

The most effective management of cough is specific therapy, which results in a greater than 90% response rate, so the cause should be thoroughly investigated. A chest x-ray should be taken early in the clinical investigation of chronic cough. The three most common causes of chronic cough when chest x-rays are normal are postnasal drip, bronchial asthma and gastro-oesophageal reflux. Chronic cough has more than one cause in 20% of patients, so therapy may need to be directed at multiple causes. Gastro-oesophageal reflux may complicate cough from any cause because a cough-reflux feedback cycle can develop. Hence, a four-week trial of an H2-receptor antagonist is indicated in patients with unexplained chronic cough where the history, physical examination, chest x-ray, lung function tests, ear/nose/throat examination and home peak flow monitoring all fail to elucidate a cause. Non-specific therapy should be reserved for when no diagnosis can be made, or when therapy is likely to be ineffective (e.g., lung malignancy).

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.

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.