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AD_HTT_027_034___OCT29_04 22/10/04 2:24 PM Page 27 How to Treat pull-out section read online @ www.australiandoctor.com.au You can now earn CPD points with How to Treat by completing quizzes online (www.australiandoctor.com.au/cpd) or in every issue. See page 34 for details and this week’s quiz. INSIDE Cough Asthma Interstitial lung disease and bronchiectasis Obstructive sleep apnoea Lung transplantation Diagnosis of pulmonary GORD symptoms Managing pulmonary GORD symptoms The authors Pulmonary manifestations of gastro-oesophageal Dr David Joffe, senior staff physician, department of respiratory and sleep medicine, Royal North Shore Hospital, Sydney, NSW. reflux disease Dr Garrett Smith, department of surgery, Royal North Shore Hospital, Sydney, NSW. Background GASTRO-oesophageal reflux disease (GORD) is a common disorder. Studies from the US have estimated 20% of the population have at least weekly GORD symptoms and more than 50% have experienced GORD symptoms at some time. Among adults the prevalence of symptoms appears fairly constant between 25 and 70 years and there is little gender difference. GORD thus represents one of the most common, chronic medical conditions presenting to GPs, with the most classic symptoms being heartburn and regurgitation. With the ready availability of protonpump inhibitors and appropriate attention to lifestyle factors, these symptoms are generally well managed in general practice and do not require investigation or specialist referral. Evidence is emerging of the poor correlation between endoscopic evidence of oesophagitis and GORD severity, measured either by symptoms or complications. This has led to the concept of nonerosive reflux disease, which may account for 50% of all GORD patients. There is also increasing reporting in the literature of atypical and extra-oesophageal presentations of GORD, ranging from dental to laryngeal and respiratory symptoms. The relationship of these symptoms with GORD may be difficult to assess, and standard GORD therapies may not be as effective as in the more traditional reflux patient. This article seeks to highlight some of the putative respiratory manifestations of GORD. The main conditions believed to be either a direct end product of GORD or to have pulmonary disease manifestations exacerbated by GORD include cough, asthma, interstitial lung disease, bronchiectasis, obstructive sleep apnoea and lung transplantation. www.australiandoctor.com.au Dr Daniel Stiel, department of gastroenterology, Royal North Shore Hospital, Sydney, NSW. 29 October 2004 | Australian Doctor | 27 AD_HTT_027_034___OCT29_04 22/10/04 2:24 PM Page 29 Cough THE earliest reports of an association between reflux and cough were published by Ing, et al in the early 1990s.1,2 Twenty-four-hour ambulatory pH monitoring was performed in 13 patients with chronic persistent cough (defined as lasting more than two months) in whom all other diagnostic tests were negative. To assess the level of symptoms, cough diaries were kept for eight weeks. There was a significant difference in the number of reflux episodes and the length of the episodes between the study group and matched controls. Also, the amount of time when the pH was less than four was considerably longer in the patient group. Furthermore, gastro-oesophageal reflux occurred simultaneously with 78% of cough episodes, while cough occurred with 13% of reflux episodes, confirming an association between asymptomatic reflux and chronic persistent cough. Subsequent work by the same authors demonstrated impaired acid clearance in a group of patients with persistent cough compared with a group of matched controls. These findings not only supported the hypothesised relationship but also determined a likely pathological mechanism. To further explore the possible aetiological mechanisms, Ing, et al performed a double-blind placebo-controlled study in a small group of patients and matched controls, in which either saline or acid was instilled via a catheter to the lower oesophageal sphincter.3 Although the cough frequency and amplitude were greater in the patient group, the duration of the cough was not significantly different. The authors concluded that cough could be induced in normal subjects with acid instillation, although the characteristics of the cough in the symptomatic patient group were different. Instillation of lignocaine to the lower oesophageal sphincter impaired the cough reflex, suggesting local factors at the level of the lower oesophageal sphincter were part of the mechanism of cough genesis. More recent work by Benini, et al4 demonstrated that patients with reflux oesophagitis have a decreased cough threshold, which appears to relate to both laryngeal inflammation and acid flooding of the oesophagus. A great deal of further research has added evidence to the original hypotheses of Ing and colleagues, to support the relationship between cough and reflux. A 2001 study by Theodoropoulos, et al5 used an inverse paradigm of investigation. Seventy-four subjects referred specifically to a gastroenterology service for investigation of symptomatic reflux were concomitantly administered a questionnaire about upper respiratory symptoms. After a 24-hour probe study it was found that 75% of stressed some key points: Reflux may be asymptomatic in patients with chronic cough. ■ When aspiration predominates, gastroenterological symptoms are prominent. ■ Extra-thoracic reflux may lead to dysphonia, hoarseness, sore throat and gum disease. ■ Treatment should only be considered as failing if double the standard doses of a PPI have been used for at least eight weeks. Several recent publications have demonstrated a diminution of cough with therapy for gastroenterological symptoms, whether medical or surgical. In eight patients with GORD-related but medically resistant chronic cough, Irwin, et al described a significant decrease in the measures of cough, after anti-reflux surgery.7 The authors emphasised that, while there is a clinical profile that can predict GORD as a cause of cough (eg, cough related to meals, speech or at night), GORD cannot be excluded on clinical grounds alone. It is important to remember that if a patient has a cough but no reflux symptoms, it does not mean the cough is unrelated to reflux. Papers published by Lindstrom, et al8 and Allen, et al9 have also demonstrated a similar response of extraoesophageal manifestations of GORD after fundoplication. ■ Reflux may be asymptomatic in patients with chronic cough. patients with proven upper oesophageal reflux, and 68% of patients with demonstrated lower oesophageal reflux, complained of laryngeal symptoms for at least five days each month. In comparison, only 36% of those with normal pH studies and 9% of normal volunteers reported similar symptom scores. This study suggested a relationship between ‘symptomatic’ reflux and the likelihood of respiratory symptoms, and that those with a primarily gastroenterological presentation may have unrecognised respiratory complications. This is in contrast to Ing’s group, who had a respiratory presentation with a demonstrable gastroenterological disorder. Evidence for abnormal oesophageal motility in the genesis of cough has been proposed more recently. Kastelik, et al6 demonstrated manometric abnormalities in 32% of a group of 43 patients complaining of chronic cough, abnormal 24-hour pH monitoring in 15%, and combined abnormalities in 53%. Only one patient in the control group had manometric abnormalities. This later work provides some substance to the argument that acid is not the sole cause of cough but that dysmotility and so-called ‘volume-reflux’ (see Intraluminal oesophageal impedance testing, page 31) may also be crucial in the genesis of cough and pulmonary manifestations of reflux. Several review articles have further delineated the coughreflux hypothesis and have Asthma SEVERAL recent papers have taken up the cudgel of reflux and its possible role in pre-existing pulmonary disease, particularly asthma. We know that gastro-oesophageal reflux may trigger asthma. Data suggest about 77% of people with asthma experience reflux symptoms, although GORD may be clinically silent in some. Oesophagitis is found in 43% of patients with asthma, and 82% have abnormal oesophageal acid contact 10 times on oesophageal pH testing. In the first of many articles on this subject, Harding, et al demonstrated that the presence of “regurgitation or excessive proximal oesophageal reflux, predicted asthma response with 100% sensitivity, 100% negative predictive value, specificity of 44% and a positive predictive value of 79%” in a group of 30 non-smok11 ers with asthma. The authors concluded that suppressive therapy with omeprazole improved asthma symptoms and/or peak flows by more than 20% and improved pulmonary function in 73% of subjects with asthma and GORD. The study demonstrated persistent effects beyond three months of acidsuppressive therapy. Notably, almost 30% of subjects with asthma GORD is a prominent feature of patients with asthma despite the absence of symptoms. required more than 20mg/day of omeprazole to adequately suppress acid. A subsequent prevalence paper by Harding demonstrated abnormal 24-hour pH testing in 62% of subjects with asthma, none of who had reflux symptoms. Indeed, those with higher amounts of proximal oesophageal acid exposure had fewer symptoms of GORD than those with 12 predominantly distal disease. Thus the authors rightly assert that GORD is a prominent feature of patients with asthma despite the absence of symptoms. This has clear and practical implications for the management of asthma, particularly in difficult-to control and severe disease. One of the prominent and wellrecognised features of severe asthma www.australiandoctor.com.au is nocturnal symptoms. In a review article, Harding described evidence from one study in a paediatric population showing that oesophageal acid infusions caused more airway responses at 4am than at midnight. In addition, children with asthma and nocturnal asthma symptoms had higher reflux scores, with a positive correlation between reflux score and night-time-associated wheez13 ing. Although the evidence for a similar response in adults has been less convincing, more recent work by Liou, et al, using an analysis of patients in a specialised asthma clinic, determined that symptomatic GORD and chronic sinusitis are comorbid conditions associated with more severe 14 asthma. The work of Kiljander, et al in two separate studies has demonstrated a reduction in cough and subsequently in nocturnal asthma symp15,16 toms when GORD is treated. Both studies were performed in a randomised, double-blind, placebo crossover fashion, conferring a strong correlation between treatment and response while simultaneously defining a strong supportive evidence base (level 1) for the role of GORD in asthma. The authors again emphasise the “often silent” nature of GORD in people with asthma. 29 October 2004 | Australian Doctor | 29 AD_HTT_027_034___OCT29_04 22/10/04 2:24 PM Page 30 how to treat - pulmonary manifestations of gastro-oesophageal reflux disease Interstitial lung disease and bronchiectasis PERHAPS the most intriguing and recent advances of GORD and lung disease have been the postulate that GORD may play an aetiological role in the development of interstitial pulmonary fibrosis and other parenchymal lung disease such as bronchiectasis. Tobin, et al17 demonstrated that 16 of 17 patients with biopsyproven interstitial pulmonary fibrosis had distal and/or proximal abnormalities on pH testing. In comparison, only four of eight controls with other types of interstitial lung disease were found to have abnormal pH readings. Also, only 25% of the fibrosis patients with increased acidity actually had symptoms typical of GORD and in this group the acidity was predominantly nocturnal and occurred in the more proximal oesophagus. The authors speculated that GORD may well have a role in the pathogenesis of interstitial pulmonary fibrosis. Further to this hypothesis, Hope-Gill, et al showed that, in comparison with a control group, patients with pulmonary fibrosis had an increased cough sensitivity to capsaicin, which was sensitive to corticosteroids.18 They hypothesised that there was something intrinsic to the mechanism of disease in interstitial pulmonary fibrosis that promotes the cough reflex. In a study looking at diffusing capacity in patients with GORD, Schachter, et al demonstrated that in patients with severe GORD there was an appreciable fall in diffusing lung capacity for carbon monoxide compared with patients with mild GORD.19 This elegant study was the first to demonstrate a correlation between a physiological variable known to be associated with interstitial pulmonary fibrosis (and, indeed, with its prognosis) and the measured severity of reflux. These tantalising data hint at the possible relationship between the development of interstitial lung disease and gastrooesophageal reflux, considering all other variables were accounted for in the multiple regression analysis. In response to these findings Raghu wrote: “Compelling clinical data suggest that a high percentage of patients with idiopathic pulmonary fibrosis also experience abnormal oesophageal acid exposure, without necessarily experiencing the typical symptoms of gastro-oesophageal reflux disease (GORD). Aggressive, long-term therapeutic trials of patients with GORD and evaluation of the therapeutic effects on pulmonary disease will allow determination of the real influences of abnormal esophageal acid exposure in the development of idiopathic pulmonary fibrosis.”20 Reports of the association between GORD and bronchiectasis were described as early as 1978 when, in a case series of 1000 consecutive patients with reflux, 279 aspirated either by coughing and choking during swallowing, or as a result of night reflux. Of these, 159 had associated respiratory symptoms, GORD may well have a role in the pathogenesis of interstitial pulmonary fibrosis. which included cough, voice change, recurrent respiratory infection, bronchiectasis and asthma.21 In a retrospective study of more than 100,000 patients with erosive eosophagitis and stricture, pulmonary fibrosis (odds ratio 1.36), bronchiectasis (OR 1.26), and pulmonary collapse (OR 1.31), occurred more often in the patient group, suggesting patients with severe reflux may harbour a large variety of sino-pulmonary diseases.22 This work was confirmed in a large population study of nearly 70,000 participants.23 The relationship between hospitalisation for hiatus hernia, and reflux oesophagitis, and a subsequent hospitalisation for a respiratory condition was measured in persons free of respiratory disease at baseline and at their first hospitalisation. The relative risk of developing bronchiectasis in this group was found to be 6.2. The risk of pneumonia (RR 1.3), and asthma (RR 2.1), while more traditionally associated with reflux, were not as great as for bronchiectasis. While the causal link appears to be evident from analysis of these papers, Tsang, et al published a fascinating study in 1998 supporting a causal link between reflux and bronchiectasis.24 In 100 consecutive patients with bronchiectasis, of who 87 had active tuberculosis, 76% were found to be seropositive for Helicobacter pylori. However, only 54.3% of controls and 52.9% of matched patients with tuberculosis but no bronchiectasis were H pylori seropositive. There were significant associations between H pylori serology and sputum volume and age in the patients with bronchiectasis, but not with lung function indices or causes of bronchiectasis. The H pylori seroprevalence in bronchiectasis was significantly higher in patients who were excessively productive of sputum (>5mL sputum/24 hours). This was the first report of a high H pylori seroprevalence in bronchiectasis and suggests there may be a common link between these conditions and that H pylori may have a pathogenic role in the development of bronchiectasis once deposited in the mucosa of the airway. While a thorough investigation of all possible causes in cases of bronchiectasis has been encouraged, assessment of possible gastro-oesophageal reflux, whether acid or volume, often remains overlooked in clinical practice, especially given the implications for treatment and prognosis. Clearly reflux may cause cough, a frequent symptom of bronchiectasis. It may also play a role in recurrent pneumonia — another frequent consequence of abnormal airway structure and function. Indeed, the literature would seem to support the hypothesis that reflux plays a role in the genesis of bronchiectasis and in the level of cough, sputum and recurrent infection. Thus, the finding of bronchiectasis should alert the physician to consider the investigation and management of reflux. Obstructive sleep apnoea THE earliest indications of a possible interaction between obstructive sleep apnoea (OSA) and reflux were predominantly case studies in which small groups of patients with GORD or aperistaltic disorders of oesophageal motility were noted to improve when treated with continuous positive airways pressure, whether or not they had concomitant OSA. The explanation appeared to be that OSA predisposed to nocturnal gastro-oesophageal reflux by lowering intrathoracic pressure and that this added to the severity of sleep fragmentation by increasing arousability and movements in sleep. Whether the reflux contributed to the OSA or vice versa remained unclear. In a study to help clarify the interaction between the two conditions, 25 Ing, et al studied the effect of antireflux therapy (nizatidine [Tazac]) on OSA parameters. Patients with OSA were found to have significantly more gastrooesophageal events than controls, and the percentage of time spent at pH <4.0 was also greater in the OSA group. Furthermore, in patients with proven OSA, just over half of all 30 | Australian Doctor | 29 October 2004 Patients with obstructive sleep apnoea were found to have significantly more gastro-oesophageal events than controls. gastro-oesophageal reflux episodes were temporally related to apnoeas or hypopnoeas. Less than half (46.8%) of all apnoeas were temporally related to acid reflux, and only 43.8% of arousals were related to reflux events. Treatment reduced the frequency of arousals but had no impact on the apnoea-hypopnoea index. The researchers concluded that patients with OSA appeared to have a higher prevalence of reflux than matched controls, and that CPAP appeared to ameliorate gastro-oesophageal reflux parameters in a “non-specific” way. They were unable to conclude a causal link between GORD and the development of OSA. In the first prevalence study, 26 Valipour, et al studied patients referred for overnight sleep studies who were investigated for a breathing sleep disorder, occurrence of symptomatic gastro-oesophageal reflux, potential risk factors for both conditions, and comorbidity. Overall, nearly three-quarters of the respondents reported refluxrelated symptoms, with heartburn and/or acid regurgitation the leading symptoms. No difference was observed in the occurrence of symptomatic reflux between subjects who www.australiandoctor.com.au snored and those with OSA, and the occurrence of reflux symptoms was not influenced by the severity of OSA. The authors concluded the incidence of both conditions was high in this patient group but there was no discernable difference between snorers and those with demonstrable OSA. While this seems to suggest that the two disorders are merely associated by way of common factors such as body habitus and posture, it does not exclude a separate association, because even those with snoring only may generate significant negative intrathoracic pressures. Despite the patient group being derived from those presenting with suspected sleep-disordered breathing (selection bias) it did confirm the findings of Ing in concluding the lack of evidence for reflux as an aetiological factor in the genesis of OSA. Having determined that reflux was not causally related to OSA, but that OSA was likely to contribute to reflux, investigators returned to the possible effect of treating OSA on reflux-associated outcomes. 27 Green, et al graded patients diagnosed with OSA on their frequency of nocturnal reflux symptoms, with all patients then prescribed CPAP for their OSA and follow-up obtained in almost 90%. Those who continued to use CPAP had a statistically greater improvement in reflux symptoms than those who had abandoned therapy. An unexpected finding was the strong correlation between CPAP pressure and improvement in nocturnal reflux symptom scores. Contrary to the commonly held belief that higher pressures would be more problematic, patients with higher CPAP pressures demonstrated a greater improvement in their nocturnal reflux scores. Indeed, CPAP improved nocturnal reflux by 48% overall and higher pressures were more beneficial. This important paper puts pay to the long-held argument that higher pressures cause increased aerophagia and discomfort; indeed, the response to symptoms of GORD should lead to consideration of a CPAP pressure increase. It also confirms the role of OSA in the genesis of reflux and suggests that a thorough history of snoring and witnessed apnoeas should be sought in all patients presenting for investigation of dyspepsia and other symptoms of GORD. AD_HTT_027_034___OCT29_04 22/10/04 2:25 PM Page 31 Lung transplantation THE earliest observations of an association between lung transplantation and GORD were small, largely descriptive studies suggesting an increase in chronic cough, slower-than-normal gastric emptying and/or oesophageal dysmotility in heart-lung recipients with documented bronchiolitis obliterans, long described as the predominant feature of chronic rejection. The possibility of vagally mediated disorders of gastric emptying was suggested because vagotomy is an inevitable consequence of transplant and was long purported to be a surgical approach to hyperacidity before the age of inhibitors and H pylori. Given the increased risk of recurrent pulmonary sepsis and accelerated rejection in lung transplanta28 tion, Au, et al undertook a study using oesophageal manometry, 24-hour pH monitoring, and radioisotopic gastric emptying in 10 patients who had undergone heart-lung transplantation. They found three patients had grossly delayed liquid and solid emptying that was compatible with complete vagotomy. Six other Vagal injury during lung transplantation did not increase the risk of reflux. patients had delayed liquid but normal solid emptying, which is the opposite of what would be expected with vagal injury and could not be explained by the authors. One patient demonstrated fasterthan-normal gastric emptying for both solids and liquids, and two of the remaining nine patients had esophageal dysmotility but no demonstrated gastro-oesophageal reflux. The authors of this small study concluded that, while vagal injury commonly occurred, the gastric sequelae were not always predictable and did not appear to increase the risk of reflux. A more recent paper by Davis, 29 et al differed in its view of the role of GORD and its implications for transplantation. In this study of 400 lung transplant patients, 128 underwent ambulatory oesophageal pH monitoring. Of these, 93 (almost 75%) had abnormal results consistent with GORD, and 43 (about 33%) went on to surgical fundoplication. After fundoplication, 16 patients had improved bronchiolitis obliterans syndrome scores, 13 of these no longer meeting the criteria for the syndrome. In patients at least six months post lung transplantation and six months after fundoplication, the FEV 1 improved by an average of 24%. Overall survival was significantly better in patients who had either normal pH studies or fundoplication. On balance it is difficult to understate the importance of GORD in the rate of progression of bronchiolitis and indeed the likely longer-term success of transplanted lungs. The authors stressed the need to look for reflux early and to treat it while the bronchiolitis obliterans is in its early histological forms and may possibly be reversed with aggressive medical therapy or fun- doplication. While the exact mechanism and the possible role of vagotomy in the genesis of GORD remain unclear, there is little doubt about its consequences. Alternative theories on the cause of bronchiolitis obliterans, including the side effects of anti-rejection drugs such as prednisone and cyclosporine, and the mechanical effects of surgery on the function of the lower eosophageal sphincter, may all be relevant and the aetiology is most likely to be multifactorial. It is clear from the literature that reflux and respiratory sequelae are strongly superimposed and that unexplained respiratory symptoms and/or disease should always raise the possibility of reflux in the mind of the attending physician. Furthermore, the inverse paradigm is pertinent to those with symptoms of reflux: a thorough history of symptoms of cough, OSA, recurrent chest infection or progressive pulmonary disease should be sought in all patients with symptoms of reflux, as it may well improve outcome and dictate the need for surgical fundoplication. Diagnosis of pulmonary GORD symptoms SEVERAL investigations can be used in assessing patients with suspected extra-oesophageal manifestations of GORD. The exclusion of aetiology other than GORD in patients with ENT or pulmonary symptoms often requires specialist consultation and investigation. Therapeutic trial of proton-pump inhibition Provided there are no ‘alarm symptoms’ (dysphagia, odynophagia, haematemesis, nocturnal choking attacks, weight loss), a trial of antisecretory therapy may be carried out before any investigation. Investigation is indicated when any of these symptoms are present, if the diagnosis is unclear, if symptoms persist or are refractory to treatment, or if complications are suspected. The trial of medication usually involves 2-8 weeks of high-dose proton-pump inhibition. A good symptomatic response, especially if followed by relapse on withdrawal of treatment, is almost diagnostic of GORD. Contrast radiology studies Contrast barium radiological studies have a limited role in assessing patients with GORD because the usual physiological disturbances seen in GORD (exaggerated transient lower oesophageal sphincter relaxations) do not occur during swallowing. Although free reflux may be observed during a barium swallow in severe GORD cases, normal barium studies do not exclude GORD. Associated hiatus hernia may be demonstrated radiologically, but this is not a prerequisite for GORD. Endoscopy is more appropriate for mucosal examination of the oesophagus, and oesophageal physiological testing provides a more accurate indicator of oesophageal function. Endoscopy The endoscopic demonstration of reflux oesophagitis clinches the diagnosis of GORD. However, as with many patients with heartburn who have so-called non-erosive reflux disease, patients with pulmonary manifestations of GORD often have a normal endoscopy, that is, oesophagitis is usually absent, even if the patient has not been using antisecretory medications. As with radiology, the presence of a sliding hiatus hernia may indicate that reflux disease is more likely, but this is not diagnostic. Moreover, patients with long-term symptomatic reflux are at greater risk than the general population of developing Barrett’s oesophageal metaplasia, a condition diagnosed only by endoscopy and biopsy. Although acid reflux has been regarded as the primary pathogenic mechanism of most GORD symptoms ... a small but significant proportion of the reflux population may have pulmonary symptoms. Laryngoscopy Direct laryngoscopy enables direct visualisation of the posterior larynx, where supra-oesophageal signs due to reflux may be seen. Early changes indicating reflux include reddening of the posterior wall of the larynx, which in more severe cases may progress to fibrosis with associated vocal cord hyperaemia and nodules. Oesophageal physiological testing Ambulatory oesophageal pH monitoring Ambulatory pH monitoring www.australiandoctor.com.au enables continuous measurement of acid exposure in the distal oesophagus by placement of an intraluminal probe via a soft transnasal catheter. Additional sensors may be placed more proximally to enable measurement of acid in the upper oesophagus and, by inference, the larynx and airways. Ambulatory pH monitoring provides the current gold standard for diagnosing GORD because, unlike endoscopy, it does not require the manifestation of oesophagitis to provide a diagnosis. Moreover, its duration over several hours permits observation of the effects of postprandial, interprandial and nocturnal reflux episodes. It can also be used to correlate reflux events with symptoms, which is particularly useful in patients who complain predominantly of cough or wheeze. It can also be used as a reproducible comparative and objective measurement before and after treatment (medical or surgical). Although acid reflux has been regarded as the primary pathogenic mechanism of most GORD symptoms and complications, a small but significant proportion of the reflux population may have pulmonary symptoms due to so-called non-acid, or ‘volume’, reflux. These patients are ideally investigated by intra-oesophageal impedance testing. Intraluminal oesophageal impedance testing Oesophageal impedance testing uses a soft transnasal catheter connected to an ambulatory recording device to measure the character, quantity and direction of bolus movement within the oesophagus, independent of pH. This enables the diagnosis of volume (ie, acid and non-acid) reflux to be made. Electrical current impedance between several small electrodes along the catheter is used to characterise intraoesophageal content at any given time. In this way gas, liquid and food bolus movement may be recorded. Oesophageal impedance testing may be combined with pH and oesophageal manometry testing, but is not yet widely available in Australia. Oesophageal manometry Oesophageal manometry measures the muscular contractile activity of the oesophagus, allowing assessment of both the lower oesophageal sphincter and the musculature of the oesophageal body. Primary oesophageal motility disorders such as achalasia may need to be excluded by manometry in patients with airways-related symptoms, in whom classical symptoms such as dysphagia may not be prominent. A non-specific pattern of ineffective oesophageal motility may also be seen in patients with pulmonary manifestations of GORD. 29 October 2004 | Australian Doctor | 31 AD_HTT_027_034___OCT29_04 22/10/04 2:25 PM Page 32 how to treat - pulmonary manifestations of gastro-oesophageal reflux disease Managing pulmonary GORD symptoms DETAILED discussion of the conventional approaches to GORD therapy is beyond the scope of this article (see Gastro-oesophageal Reflux Disease in Adults: Guidelines for Clinicians published by the Digestive Health Foundation, Gastroenterological Society of Australia).30 The principles of therapy for patients with pulmonary symptoms due to GORD are relief of symptoms and prevention of complications. The important issue is to recognise that the entity of pulmonary GORD exists, even in the absence of classic GORD symptoms such as heartburn. Lifestyle modification As with standard GORD management, the first approach to treatment involves lifestyle modification when relevant, including weight reduction, cessation of smoking, moderation of alcohol and caffeine intake and, possibly, elevation of the bedhead for nocturnal symptoms. Medical management This does not differ from the standard therapy of GORD, namely, potent acid suppression, usually with a PPI, adopting a step-down approach to find the lowest effective maintenance dose. PPIs available in Australia include lansoprazole (Zoton), esomeprazole (Nexium), omeprazole (Acimax, Losec, Probitor), pantoprazole (Somac) and rabeprazole (Pariet). When volume symptoms predominate (eg, regurgitation or pulmonary symp- Authors’ case study The fundus is wrapped around the distal oesophagus. Nissen fundoplication for control of gastroesophageal reflux. toms), a prokinetic agent such as domperidone may be added, although this is a short-acting drug and the effectiveness of combined therapy is uncertain. Nizatidine (Tazac), an H2-receptor antagonist, has been reported to have prokinetic effects. Surgical management Anti-reflux surgery by fundoplication re-establishes the competence of the lower oesophageal sphincter mechanism and prevents excessive reflux of acid as well as nonacid material and digestive enzymes into the proximal oesophagus and respiratory tract. In this respect its aim is to address the principal pathophysiology of GORD rather than simply to control its consequences. It is an attractive option for those with suspected volume or pulmonary GORD symptoms. Fundoplication, nowadays almost exclusively performed laparoscopically, is indicated in patients with reflux whose symptoms are not adequately relieved by acid suppression (as stated, this is especially prevalent in those with nonacid volume-reflux symptoms such as regurgitation or respiratory manifestations) or in patients who have expressed a preference for surgery rather than lifelong medication. About 70-80% of patients undergoing surgery for GORD-related extraoesophageal symptoms such as asthma will report prolonged improvement. Of these, those more likely to be successfully treated by fundoplication include those with typical reflux symptoms of heartburn and regurgitation associated with their pulmonary symptoms, and those who have previously reported some degree of improvement in symptoms while on antisecretory medication. Unlike anti-secretory treatment of GORD, improvement of pulmonary and other extraoesophageal symptoms may not manifest for 6-12 months after surgery. Improved pulmonary symptoms with treatment of GORD MRS RG, 52, presented in June 2002 after repeated hospital admissions for infective exacerbations of bronchiectasis, requiring IV antibiotics and intensive chest physiotherapy. There was a background of four years of severe steroiddependent asthma. She had developed prednisoneinduced osteoporosis, with fractures, requiring bisphosphonates. She also gave a four-year history of heartburn and regurgitation, with endoscopy in 1998 revealing grade B reflux oesophagitis. Her heartburn had responded well initially to omeprazole 20mg daily, but regurgitation persisted and was interfering with attempts at postural drainage. Subsequent therapy with esomeprazole 40mg bd and domperidone 10mg nocte failed to control regurgitant symptoms, steroid use or infective episodes. Following yet another admission, this time with left lower-lobe pneumonia, Mrs RG underwent laparascopic Nissen fundoplication in July 2002. Since then her requirement for steroids and antibiotics has reduced dramatically and she has had only two hospitalisations for chest infections, compared with 10 in the preceding two years. References 1. Ing AJ, et al. Chronic persistent cough and gastro-oesophageal reflux. Thorax 1991; 46(7):479-83. 2. Ing AJ, et al. Chronic persistent cough and clearance of oesophageal acid. Chest 1992; 102(6):1668-71. 3. Ing AJ, et al. Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. American Journal of Respiratory and Critical Care Medicine 1994; 149(1):160-67. 4. Benini L, et al. Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage. Gut 2000; 46(6):762-67. 5. Theodoropoulos DS, et al. Prevalence of upper respiratory symptoms in patients with symptomatic gastroesophageal reflux disease. American Journal of Respiratory and Critical Care Medicine 2001; 164(1):72-76. 6. Kastelik JA, et al. 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American Journal of Respiratory and Critical Care Medicine 2000; 162(1):34-39. 32 | Australian Doctor | 29 October 2004 13. Harding SM. Nocturnal asthma: role of nocturnal gastroesophageal reflux. Chronobiology International 1999; 16(5):64162. 14. Liou A, et al. Causative and contributive factors to asthma severity and patterns of medication use in patients seeking specialized asthma care. Chest 2003; 124(5):1781-88. 15. Kiljander TO, et al. Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole. European Respiratory Journal 2000; 16(4):633-38. 16. Kiljander TO, et al. Gastroesophageal reflux in asthmatics: a double-blind, placebo-controlled crossover study with omeprazole. Chest 1999; 116(5):1257-64. [see comment — erratum appears in Chest 2001; 120(2):691]. 17. Tobin RW, et al. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 1998; 158(6):1804-08. 18. Hope-Gill, BD, et al. A study of the cough reflex in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 2003; 168(8):995-1002. 19. Schachter LM, et al. Severe gastroesophageal reflux is associated with reduced carbon monoxide diffusing capacity. Chest 2003; 123(6):1932-8. 20. Raghu G. The role of gastroesophageal reflux in idiopathic pulmonary fibrosis. American Journal of Medicine 2003; 115 [Suppl. 3A]:60S-64S. 21. Henderson RD, Woolfe CR. Aspiration and gastroesophageal reflux. Canadian Journal of Surgery 1978; 21(4):352-54. 22. el-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology 1997; 113(3):755-60. 23. Ruhl CE, et al. Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective, population-based study. Annals of Epidemiology 2001; 11(7):477-83. www.australiandoctor.com.au 24. Tsang KW, et al. High seroprevalence of Helicobacter pylori in active bronchiectasis. American Journal of Respiratory and Critical Care Medicine 1998; 158(4):1047-1051. 25. Ing AJ, et al. Obstructive sleep apnoea and gastroesophageal reflux. American Journal of Medicine 2000; 108 [Suppl. 4a]:120S-125S. 26. Valipour A, et al. Symptomatic gastroesophageal reflux in subjects with a breathing sleep disorder. Chest 2002; 121(6):1748-53. 27. Green BT, et al. Marked improvement in nocturnal gastroesophageal reflux in a large cohort of patients with obstructive sleep apnea treated with continuous positive airway pressure. Archives of Internal Medicine 2003; 163(1):41-45. 28. Au J, et al. Upper gastrointestinal dysmotility in heart-lung transplant recipients. Annals of Thoracic Surgery 1993; 55(1):9497. 29. Davis RD Jr, et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. Journal of Thoracic and Cardiovascular Surgery 2003; 125(3):533-42. 30. Digestive Health Foundation, Gastroenterological Society of Australia: Gastro-oesophageal Reflux Disease in Adults: Guidelines for Clinicians. www.medeserv.com.au/gesa/members_guidelines/goreflux Online resources The Thoracic Society of Australia and New Zealand (information about the society and its activities and links to related scientific societies and groups): www.thoracic.org.au Digestive Health Foundation, Gastroenterological Society of Australia: Gastro-oesophageal Reflux Disease in Adults: Guidelines for Clinicians. www.medeserv.com.au/gesa/ members_guidelines/goreflux AD_HTT_027_034___OCT29_04 22/10/04 2:25 PM Page 34 how to treat - pulmonary manifestations of gastro-oesophageal reflux disease GP’s contribution Case study DR DIANNE CHAMBERS Leichhardt, NSW MRS MC, 62, had what was always thought to be adultonset asthma. She had been well controlled with inhaled steroids and prn bronchodilators but recently complained of worsening cough with dyspnoea and wheeze. She was seen by a respiratory physician and a methacholine challenge test was performed, which was negative. Her puffers were withdrawn but quickly re-instituted when she had worsening of her wheeze and cough. Mrs MC’s other problems include GORD, chronic rhinorrhoea and cholecystectomy. Previous investigation included a gastroscopy, which showed minor erosion at the gastro-oesophageal junction, with normal stomach and duodenum. A urease test for H pylori was positive both for her and her husband. A high-resolution CT of the chest was negative for bronchiectasis and other chest pathology, while CT of the sinuses showed significant pathology, with mucoperiosteal thickening. Mrs MC has had H pylori eradication treatment on two occasions and earlier this year had sinus surgery. However, her debilitating cough persists. Current medications include Seretide 50/250 tds, Bricanyl tds, Losec, Beconase and Zocor. She is due to have a bladder repair and is very keen to reduce her chronic cough. there is no guarantee surgery will cure her cough, even if it resolves her GORD symptoms. With these significant caveats, laparoscopic fundoplication has a role in this clinical setting. Questions for the authors Do you have additional advice for management of chronic cough? Mrs MC should increase her inhaled corticosteroid dose perioperatively. Her gynaecologist should arrange nebulised sabutamol both pre and postoperatively as well as early postoperative chest physiotherapy (with incentive spirometry and/or flutter valve) to reduce the risk of atelectasis and worsening cough after the surgery. Could you comment on H pylori eradication protocols and their varying success rates? Is it necessary to treat other household members concurrently? What should be done about recurrent H pylori infection? Should we document eradication by posttreatment assessment? H pylori and its therapy do not play major roles in GORD or its respiratory complications. However, if the decision is made to treat H pylori infection, an initial one-week course of triple therapy should be given, comprising a PPI (double standard dose), combined with amoxicillin and clarithromycin. A success rate of 80-90% should be expected. Addition of bismuth subcitrate may increase the eradication rate slightly, but probably not sufficiently to justify its routine use. Ideally, eradication should be checked by urea breath testing four weeks or more after completion of triple therapy (and at least one week off PPIs). Routine testing and treatment of household members is controversial but not generally necessary (unless, of course, they have relevant symptoms). Is reflux surgery likely to help this woman? A trial of double-dose PPI therapy for two months should first be given. Antireflux surgery should be offered if there is no beneficial response to full medical therapy and if the cough is sufficiently disabling. However, the patient needs to be aware that it is not certain her GORD, cough and wheeze are causally related, that her symptoms do not reflect serious morbidity, and that General questions for the authors Given the study results implicating H pylori infection in bronchiectasis, do you now consider that GPs should routinely test all patients with bronchiectasis and, if so, which eradication therapy would be recommended? As there is only one study showing an association (not yet proven to be causal) it is difficult to advise routine H pylori testing in this clinical situation. More data are needed. However, a diagnosis of GORD should at least be considered if no other causes of bronchiectasis are evident. Fundoplication is now routinely done laparascopically. What should patients be told about this procedure? What is the recovery time? This is a keyhole version of an operation that has been in use for several decades and which has stood the test of time. Its great advantage over the older open operation is the shortened hospitalisation (generally 2-3 days) and recovery time (about one week). In experienced surgical hands, the need to convert to open operation is very infrequent. More than 90% of patients regard the operative results as satisfactory and are able to stop all antireflux medications. A small number may notice inability to belch, ‘gas bloat’ or mild dysphagia. These adverse effects need to be borne in mind when considering the indications for the operation — that is, they may only be acceptable when the initial GORD symptoms or complications are severe and refractory to maximal medical therapy. Australian Doctor How To Treat CPD Instructions Earn 2 CPD points by completing this quiz online or on the attached card. Mark your answers on the card and drop in the post (no stamp required) or fax to (02) 9422 2844. For immediate feedback click the ‘Earn CPD pts’ link at www.australiandoctor.com.au Note that some questions have more than one correct answer. The mark required for CPD points is 80%. Your CPD activity will be updated on your RACGP records every January, April, July and October. 1. Which ONE condition is not thought to be potentially caused or exacerbated by GORD? a) Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ b) Bronchiectasis . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Hypersensitivity pneumonitis . . . . . . . . . . . . .❏ d) Interstitial lung disease . . . . . . . . . . . . . . . . . .❏ 2. For more than two months Pam, 44, has had a cough. She never smoked and has no history of asthma, postnasal drip or symptoms suggestive of GORD. Pam is otherwise well. Examination is normal. Which ONE of the following statements is correct regarding initial management? a) In the absence of symptoms of GORD, no treatment for GORD should be considered . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ b) A trial of high doses of proton-pump inhibitor for 2-8 weeks may be diagnostic . . . . . . . . . . . .❏ c) Referral for endoscopy is required . . . . . . . . .❏ d) Regular bronchodilators should be trialled . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ HOW TO TREAT 3. Which tests would assist with the diagnosis of GORD (choose TWO)? a) Barium swallow . . . . . . . . . . . . . . . . . . . . . . .❏ b) Ambulatory oesophageal pH monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Endoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ d) CXR demonstrating a hiatus hernia . . . . . . . .❏ 4. Pam has a good response to PPIs but relapses when these are stopped. Which statements concerning fundoplication are correct (choose TWO)? a) Fundoplication re-establishes the competence of the lower oesophageal sphincter mechanism❏ b) After fundoplication the improvement of pulmonary symptoms will be immediate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Fundoplication will only benefit symptoms caused by increased acid reflux . . . . . . . . . . . .❏ d) Fundoplication can be offered as an option if Pam prefers to avoid lifelong medication . . . . .❏ 5. The diagnosis of volume reflux can be made by which ONE investigation? a) Oesophageal manometry . . . . . . . . . . . . . . . .❏ b) Direct laryngoscopy . . . . . . . . . . . . . . . . . . . .❏ c) Intraluminal oesophageal impedance testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ d) Endoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ 6. Paul, 55, presents with dyspepsia and daytime sleepiness. Questioning concerning which symptom is least likely to be helpful (choose ONE)? a) Snoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ b) Weight loss . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Abdominal bloating . . . . . . . . . . . . . . . . . . . .❏ d) Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ 7. Investigations confirm oesophagitis (without malignancy) and obstructive sleep apnoea. Which ONE treatment option is least likely to be beneficial in managing Paul’s dyspepsia? a) Regular use of antacids . . . . . . . . . . . . . . . .❏ b) CPAP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Regular use of PPIs . . . . . . . . . . . . . . . . . . . .❏ d) Lifestyle changes . . . . . . . . . . . . . . . . . . . . . .❏ 8. Joan, 55, has some mild symptoms of GORD, and extra-thoracic reflux is suspected. Which symptoms may be relevant (choose THREE)? a) Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ b) Rhinorrhoea . . . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Pharyngitis . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ d) Dysphonia . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ 9. Norma has bronchiectasis. Current literature appears to support the hypothesis that GORD is associated with bronchiectasis. Which ONE statement is incorrect? a) In the investigation of bronchiectasis, reflux should be considered . . . . . . . . . . . . . . . . . . . . .❏ b) Reflux possibly plays a role in recurrent infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ c) Helicobacter pylori seroprevalence has not been associated with bronchiectasis . . . . . . . . .❏ d) Reflux may play a role in the level of cough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ 10. Norma has symptoms of GORD and starts omeprazole 40mg/day with a plan to use the step-down approach. Which statements about the step-down approach are correct (choose THREE)? a) After six months an attempt should be made to decrease Norma’s dose of omeprazole if there has been symptomatic relief . . . . . . . . . . . . . . .❏ b) Lifestyle changes should complement the step-down approach . . . . . . . . . . . . . . . . . . . . .❏ c) The step-down approach involves gaining symptom relief quickly and then stepping down the medication . . . . . . . . . . . . . . . . . . . . . . . . . .❏ d) The aim of step-down therapy is to maintain the patient on the lowest possible dose that provides effective relief . . . . . . . . . . . . . . . . . .❏ NEXT WEEK Editor: Dr Lynn Buglar The next How to Treat presents the benefits of rehabilitation in neurodegenerative and chronic neurological disorders The author, Dr Fary Khan, is lecturer Co-ordinator: Julian McAllan in rehabilitation medicine, department of medicine, University of Melbourne; neuro-rehabilitation physician at the Melbourne Extended Care Centre and Royal Quiz compiled by Dr Marg Tait MBBS Melbourne Hospital, Melbourne Health; and head of the orthopaedic and musculoskeletal unit, Caulfield General Medical Centre, Bayside Health, Melbourne. 34 | Australian Doctor | 29 October 2004 www.australiandoctor.com.au