Merriman v Accident Compensation Corporation

IN THE DISTRICT COURT AT WELLINGTON DECISION No. 219/2006 UNDER The Injury Prevention, Rehabilitation and Compensation Act 2001 IN THE MATTER OF an appeal pursuant to section 149 of the Act (Appeal No. Al 312/03) BETWEEN CLIFTON KERI MERRIMAN Appellant AND ACCIDENT COMPENSATION CORPORATION Respondent Hearing: 28 June 2006 Appearances: Mary Speller advocate for appellant Jessica Hodgson for respondent Judgment: 13 September 2006 RESERVED JUDGMENT OF JUDGE D A ONGLEY [1] The appeal concerns a decision of the Corporation dated 22 December 2002 which declined the appellant's medical misadventure claim for the development of eosinophilic bronchitis, said to have been caused by administration of omeprazole, a drug used to treat gastroesophageal reflux disease. [2] Eosinophils are white blood cells which are part of the body's immune mechanism and which play a role in allergic reactions including bronchial or bronchiolitic reactions. Before he ingested omeprazole prescribed to him in various forms between August 1999 and March 2000, Mr Merriman had a persistent dry cough. After a hypersensitive reaction to omeprazole in October 1999 he developed a productive cough and symptoms that were eventually diagnosed as eosinophilic bronchitis. Blood tests taken in 1996 had shown a moderate level of eosinophils. [3] Mr Merriman's cough was and remains extremely debilitating to the extent that he is subjected to fits of coughing and retching for hours at a time. His social activity is severely limited by his debilitating coughing fits. The presence of an earlier dry cough and prior blood eosinophilia were regarded as indications that the bronchial condition could have originated before he used omeprazole. An explanation for his condition is that it is gastrointestinal in origin. A further reason for the Corporation's declining cover was that it received specialist medical advice that there is no known association between omeprazole and eosinophilic bronchitis. Background [4] On 7 August 1999, Dr Trevor Parry, general practitioner, prescribed omeprazole. Mr Merriman developed a hypersensitive reaction so treatment was discontinued. On 2 October 1999, Dr Venkatesh Lakshman, locum gastroenterologist at Palmerston North Hospital prescribed Losec, being unaware of Mr Merriman's previous hypersensitive reaction to omeprazole. AstraZenica markets omeprazole in New Zealand under the brand name Losec. Mr Merriman was unaware that omeprazole was the same as Losec. [5] In March 2000, Dr Parry prescribed Heliosec when Mr Merriman developed swelling in his ankles. Mr Merriman also developed a painful arthropathy and severe pruritis. Heliosec is a triple therapy treatment in which one of the active ingredients is omeprazole. The resultant adverse effects increased in severity on each subsequent occasion. In 2005 Mr Merriman obtained cover for the arthropathy and pruritis caused by his reaction to the drug. The Corporation refused to extend cover to the bronchial condition on the ground that there was insufficient evidence to associate it with administration of omeprazole. [6] The basis for the Corporation's decision followed a report of the ACC Medical Misadventure Panel dated 9 December 2002. The report contained a useful summary as follows: "Personal injury: The claim relates to the development of an allergic response to omeprazole resulting in eosinophilic bronchitis and sensitisation to other medicines. The Panel accepts, on the evidence before it, that Mr Merriman has been prescribed omeprazole on three separate occasions. This particular drug was prescribed for him as omeprazole by his General Practitioner Dr T Parry on 7 August 1999, as Losec by the Gastroenterologist Dr Lakshman on 8 October 1999 and again as Helicosec on 23 March 2000 by his General Practitioner Dr T Party. The Panel notes the evidence that Mr Merriman's cough was present prior to his receiving omeprazole. Mr Merriman was diagnosed as having eosinophilic bronchitis following a bronchial biopsy performed by Dr Andy Veale in Auckland on 30 March 2001. However, the Panel again notes that Mr Merriman was diagnostically proven to have blood eosinophilia from 1996 and diagnostic investigations in October 1999 found he had eosinophilia in his sputum. The Panel notes the report from Clinical Pharmacologist and Professor of Medicine Carl Burgess. In his report of 10 October 2002, Professor Burgess states that Mr Merriman's eosinophilia predates the prescribing of omeprazole in August 1999. He further states there is no evidence that omeprazole is associated with eosinophilia or eosinophilic bronchitis. In his view as a specialist Physician and Clinical Pharmacologist, there is no evidence supporting the fact that omeprazole is responsible for Mr Merriman's ongoing respiratory problems." [7] The introductory paragraphs of the Panel report touched on two central questions in the appeal, first whether Mr Merriman did have eosinophilic bronchitis before the repeated prescribing of omeprazole, and secondly whether omeprazole could have been responsible for ongoing respiratory problems. Initially, the Panel was unable to decide whether medical error had occurred. It adjourned to allow new information to be sought concerning the responsibility of the dispensing pharmacist. The Corporation's decision was concerned only with causation. As the Corporation did not implicate omeprazole as a cause of the appellant's eosinophilic bronchitis, there was no need to consider whether there had been medical error on the part of the medical practitioners or the pharmacist. For the same reason, this appeal does not deal with responsibility for repeated prescribing of omeprazole after the appellant had suffered an allergic reaction. ACC Decision [8] The Corporation's decision letter of 23 December 2002 stated in part: "ACC has considered your claim for cover from ACC for medical misadventure arising from the development of an allergic response to omeprazole resulting in eosinophilic bronchitis. …. ACC has decided that your claim cannot be accepted because: • Although it is accepted that you received omeprazole on three separate occasions, the evidence indicates that your cough was present prior receiving omeprazole. Dr Veale made a diagnosis of eosinophilic bronchitis following a bronchial biopsy performed by Dr Veale, on 30 March 2001. However, it is noted that a diagnosis of blood eosinophils was proven from 1996 and diagnostic investigations in October 1999 recorded presence of eosinophils in the sputum. Thus, as stated by Professor Burgess, in his independent advice of 10 October 2002, eosinophilia predates the prescribing of omeprazole in August 1999. In this regard, Professor Burgess states: - 'The report from the chest physician Dr Watson at Mid Central health, notes that this man was known to have eosinophilic bronchitis but in his letter he mentions that the cough was present well before this man had omeprazole. He was known to have eosinophilia in his sputum in October 1999 and to have had eosinophilia in his blood since 1996 which was well before he received omeprazole.' • Professor Burgess further notes that your bronchitis did not respond to corticosteroid treatment, and was subsequently discontinued due to side effects. A repeat bronchoscopy performed in August 2001, did not show any evidence of eosinophilic bronchitis. There is no evidence of any association between omeprazole and eosinophilia and eosinophilic bronchitis. • A letter from Dr Philip Wong to Dr Hayhurst, dated 4 July 2002, clearly sets out the chronology of events. In that letter, Dr Wong states that a very distressing non-productive cough started in April 1999, following an upper respiratory tract infection. As your general practitioner considered this cough to be gastro-oesophageal in origin, a trial of omeprazole was started. The omeprazole had to be discontinued due to the development of an allergic reaction that is, swollen legs and feet. • Further, Dr Watson, with regard to lack of any casual link, states in his report of 20 May 2002, as follows:- • Repeatedly he has been noted to have abnormalities in investigations of and symptoms from, his gastrointestinal tract. It has been felt by a number of respiratory Physicians, including myself, that his problem originates form his gastrointestinal system. The cough first came on prior to the initial administration of the omeprazole, The explanation for the eosinophils noted initially in his sputum and bronchial biopsy remains unexplained as does the persisting mild eosinophilia'. • Thus, although your claim is declined with regard to the association of omeprazole and your ongoing respiratory symptoms, there is evidence to support further investigation with regard to the allergic reaction - arthropathy and pruritis - following rechallenge with omeprazole. • Hence the Medical Misadventure Unit will continue to investigate and issue a further decision with regard to the association between further prescribing of omeprazole-as part of triple therapy for H pylori – and the development of swelling in the legs and feet." The evidence [9] Blood tests in 1995 and 1996 had shown the presence of eosinophils, described as mild. A slightly raised eosinophil level returned to normal. One of three tests in 1996 showed an eosinophil level of 0.47. That has been referred to as "only marginally elevated". The appellant also had a dry non-productive cough. The cough appears to have started in about April 1999 and to have become worse when he returned from a trip to Ireland in August of that year. It was not symptomatic of bronchitis until the cough produced sputum, following the prescribing of omeprazole. The appellant also submits that the presence of eosinophils in 1996 did not indicate eosinophilic bronchitis. Dr Parry's notes of 7 August 1999 noted he did not have sputum available to test and "chest clinically clear" [10] The appellant was seen by Dr P D Swinburn of the Respiratory Services Unit of Midcentral Health on 6 October 1999, who reported that: "This man was seen at the Respiratory Services Unit today for assessment of his chronic cough, This has troubled him on and off since about April. It seemed to improve for a while and then get worse when he was overseas in Ireland. He returned to New Zealand in August with his cough still troubling him, occurring in bouts lasting up to an hour or so, often terminating in vomiting which seemed to give some relief. … I have a strong feeling that his cough may well be related to regurgitation with inhalation of acid contents from the stomach" [11] A sputum cytology test on 8 October 1999, after the appellant had experienced an allergic reaction to omeprazole, reported "No Malignant cells detected ... Numerous alveolar macrophages are present", and: "Eosinophils are present. These are commonly associated with allergic conditions such as asthma, very rarely drug induced pulmonary disease, deep aspergillosis and collagen disease (PAN. Churg-Strauss syndrome) may be considered." [12] Dr Lakshman indicated in a clinic note of 8 October 1999, that he had prescribed omeprazole "both to heal his duodenitis and also to treat what is probably silent reflux". Dr Lakshman thought it likely that reflux could account for the coughing. [13] Following a further allergic reaction, Mr Merriman was admitted to Palmerston North Hospital on 18 October 1999, and discharged on 22 October 1999. The discharge record noted diagnoses of cellulitis of the left elbow, persistent cough and longstanding gastritis. The note further records: "Persistent cough since April last year which is gradually getting worse. Currently under investigation via the gastroenterologists and Resp physician ... Blood test results during the above admission record the following eosinophil levels (reference range 0.05 – 0.45): 18/10/1999 0.23 20/10/1999 0.53 21/10/1999 0.56" [14] Dr Swinburn noted in a clinic letter dated 21 October 1999, that a sputum test showed Eosinophils "suggesting this may be an allergic type reaction". It is said that the appellant had a continuous work history without sick leave in the years before being admitted to hospital on 18 October 1999 after the second prescribing of omeprazole by Dr Lakshman. After a six week period of sick leave he resigned from his job as a school caretaker. [15] The appellant's wife kept a record of events throughout this time. From 29 October, 1999 it shows that the appellant's cough was affecting him very severely. For example, Mrs Merriman recorded: 29.10.99 9.30 pm Slept in armchair to prevent coughing 30.10.99 3.00 am Wakes up with sudden coughing - continuous Has to kneel with head on lounge chair seat 3.45 am Vomits and dry retches - complains of having no air and can't breathe, 4.00 am Coughing eases off- dozed at kitchen table 7.30 am Woke and had Breakfast 9.00 am Went to bed and slept till 10.30am Afternoon Coughed for 2 hours Night: Coughed for an hour at night till vomited then slept quite well. [16] After another bout of severe coughing on 1 December 1999, he saw Dr Parry. His prednisone dosage was increased. The GP's notes reported that the appellant was "coughing mucous +++" and also noted "asthma/allergy". Mrs Merriman noted: "Great improvement over this period. Was able to wean himself off the prednisone." The GP noted an apparently good effect from prednisone". [17] GP notes for 22 March 2000 record that the appellant was prescribed triple therapy. It is unclear exactly how it came about that Mr Merriman was given Helicosec, but he took 6 to 7 days of the medication before stopping. GP notes for 25 March 2000 show that his legs and feet became swollen. On 28 March 2000 the Helicosec was stopped. [18] In April 2000 the appellant saw Dr Edge, consultant gastroenterologist, who wrote to Dr Parry reporting that Mr Merriman was "unable to sleep unless he sits forward and he is troubled with severe coughing bouts which end in him vomiting. Unfortunately he has developed swelling of both feet ... Clearly the problem is getting worse". Dr Edge saw him again four days later, and considered hospital admission. Mrs Merriman noted that on 12 April her husband had developed an itch and that on 13 April he was coughing and had "one of the worse bouts he has had, lasting several hours " . [19] Ms Speller submitted that the connection in time between the itch (an allergic reaction) and the cough is an indication that both were produced by the same allergic reaction. While that logic may be superficially attractive, it is not a good basis for a finding by a non-medical tribunal such as this Court. Whether the contemporaneous occurrence of symptoms is to be associated with a common cause is- a medical question that can only be answered with the assistance of expert opinion. The Court will not arrive at a different conclusion from a cogent body of medical opinion unless there is persuasive countervailing evidence. [20] On 19 July 2000, the appellant underwent fundoplication surgery to remedy his gastroesophageal reflux symptoms. Following surgery he had an abnormally prolonged effect from the neuromuscular blocking agents. In an initial post-operative assessment noted that he still had a cough, though he felt at that time is was improving. However in a re-assessment on 30 August 2000, the surgeon recorded that: "[h]e still has a lot of coughing fits. I am not sure what is causing these coughing fits, except that Gastro-oesophageal reflux has now been treated" [21] On 27 September 2000, the appellant was seen in the chest clinic for assessment. Dr Jeanne Tie (Respiratory Registrar to Dr Watson) noted that "his cough started in April 1999 following a flu-like illness". Dr Tie noted that she was unable to diagnose a cause of the coughing, although did comment that "it seems likely that his chronic cough could still be secondary to his gastroesophageal reflux … ” . [22] During this time the medical investigations looked for an explanation for the coughing other than allergic reaction caused by omeprazole. Dr Wyeth, Gastroenterologist at Wellington Hospital, reported in an outpatient letter of 12 December 2000 following a barium swallow, video swallow and speech therapist assessment: "The opinion is that the oesophagus does have general lack of muscle activity and in particular in the proximal oesophagus. There appears to be pooling in the upper oesophagus which would certainly increase the likelihood of aspiration which would account for the cough. There also does appear to be some dilation of the upper oesophagus" [23] On 20 February 2001 the appellant underwent a videofluoroscopy study while swallowing. The study identified that he had some swallowing problems. Ms Siobhan Malloy, a speech therapist, reported that: "Mr Merriman is not bothered by the pharyngeal dysphagic symptoms and he has no signs of pulmonary problems but I wonder if there is a link between the persistent coughing (? Residue falling into trachea). Even if there is no link with the trigger for coughing; such abnormal physiology may work up into increased symptoms over time..." [24] On 30 March 2001, Dr Veale performed a bronchial biopsy, upon which a diagnosis of eosinophilic bronchitis was made. Mr Merriman was then assessed by Dr Watson, respiratory physician. In a letter of 15 May 2001 to Dr S Riddell, who was then Mr Merriman's GP, Dr Watson said: "It is felt that Mr Merriman has a form of eosinophil bronchiolitis pneumonia. This is not Eosinophil pneumonia, As a consequence of this he has been commenced on a combination of steroids and Roxthromycin. This is an unusual condition. With the introduction of Prednisone and Roxthromycin he clearly had a very significant improvement in his symptomatology and also a subjective lung function test." [25] The appellant refers to Dr Watson's reference to a diagnosis of eosinophil bronchiolitis pneumonia as a basis of medical support for this appeal, in conjunction with the evidence of raised eosinophil level in the blood tests of October 1999 after the first allergic reaction to omeprazole. [26] Various biopsies were taken in August, September and October 2001. A biopsy in August 2001 revealed no eosinophilic bronchitis. Histological examination of a biopsy from the oesophagus was reported as: "Barrett's oesophagus with extensive complete and incomplete intestinal metaplasia and moderate chronic inflammatory changes." [27] The medical opinions favoured a gastro-oesophageal cause for the chronic cough. In December 2001 Dr Watson referred the appellant to Dr Edge, who noted a high eosinophil count in the blood stream, but said: "I have never seen a patient develop profound hypersensitivity to omeprazole, and as it is almost three years since the last exposure it should have cleared the system by now." [28] Dr Mike Hayhurst, respiratory physician, saw Mr Merriman twice and reported in a clinic note in April 2002 a debilitating cough that had been present since October of 1999. Dr Hayhurst considered the most likely cause of the cough to be gastro- oesophageal in origin, and did not consider eosinophilic bronchitis to be a significant ongoing condition. In a report of 30 April 2002, he said: "I think the most likely cause for the cough is gastro-oesophageal in origin. There is a positional element to the cough and he is unable to lay flat. He spends most of the night sleeping in a chair. Attempts at doing investigations on him that require him to be flat have often been impossible. Difficulties in swallowing occur after oesophageal surgery (up to 12% of cases undergoing fundoplication). The abnormal swallowing leads to episodes of aspiration. Investigations on the swallowing mechanism in Mr Merriman's case are abnormal. An abnormal video fluoroscopy study showing vallecular and piriform sinus residue on swallowing leading to potential for aspiration. His barium swallow is also abnormal showing a generalised lack of muscle activity involving the proximal oesophagus. There was pooling of barium in the upper oesophagus which would increase the likelihood of aspiration. He also vomited during bronchoscopy. He also has Barrett's oesophagus though the exact importance of this I am not sure. A recent review of the causes of cough showed gastroesophageal reflux and sinus disease with post nasal drip being the most common at about 40% of cases each with asthma at about 15%. Other causes such as chronic bronchitis, bronchiectasis, carcinoma of the lung, ACE inhibitors make up the rest. Eosinophilic bronchitis is a relatively newly described entity and can be a cause of cough. This was diagnosed at bronchoscopy in March 2001 and he was treated with steroids with initially good response. However his symptoms have recurred and treatment with inhaled steroids has been discontinued due to side effects. A repeat bronchoscopy in August showed no evidence of eosinophilic bronchitis. Subsequent treatment with steroids has not helped. I therefore feel that eosinophilic bronchitis whilst it might have been important in the past is no longer a factor now. … He has had a mild chronic peripheral eosinophilia using the absolute eosinophilic count of >450 per microlitre. He has had counts between 480 and 990. Whether this is relevant I am not sure. I was interested to find an association in the literature between gastroesophageal reflux and eosinophilia. Apparently Eosinophils are present in the oesophagus in patients with gastroesophageal reflux. I was unable to find an association between omeprazole use and eosinophilia but was fortunate to receive a letter from Dr Riddell which relates to cases of pulmonary infiltrates with oesinophilia in patient taking omeprazole treatment ... " Dr Hayhurst found no evidence of eosinophilic bronchitis. The presence of eosinophils accompanied by coughing does not equate with eosinophilic bronchitis. [29] The next specialist report is from Dr Watson on 20 May 2002, in which Dr Watson said: "He was noted to have oesinophilia in his sputum in October 1999 and to have a blood eosinophilia from 1996. He was also found to have Eosinophils on a bronchial biopsy performed by Dr Andy Veal on 30 March 2001 and following this he was labelled as having `eosinophilic bronchitis'. He seemed to respond to a combination of Roxithromycin and steroids. However the symptoms relapsed when these medications were withdrawn but he did not respond again when they were re-introduced. He had a further bronchoscopy and at this time there were no Eosinophils on either transbronchial biopsies or bronchial lavage. He has been extensively screened for a number of respiratory conditions including bronchiolitis, allergic bronchopulmonary fungal disease, asthma, interstitial lung disease, vascular disease etc without any obvious cause for his cough being established. Repeatedly he has been noted to have abnormalities in investigations of, and symptoms from, his gastrointestinal tract. It has been felt by a number of Respiratory Physicians including myself, that his problem originates from his gastrointestinal system. The cough first came on prior to the initial administration of the omeprazole. The explanation for the Eosinophils noted initially in his sputum and bronchial biopsy remains unexplained as does the persisting mild eosinophilia. A syndrome of eosinophilic bronchitis has been described and a number of causes for this have been identified including asthma, allergic rhinitis, cough variant asthma and COPD. I am not certain as to the clinical significance of this 'syndrome' however. There is no evidence that Mr Merriman has had pulmonary eosinophilia. I note there has been an association made between pulmonary eosinophilia and Losec although this remains unproven." [30] Dr Watson had reached no firm diagnosis and did not adopt a diagnosis of eosinophilic bronchitis. He went only so far as to state that Mr Merriman "was labelled as having `eosinophilic bronchitis" after the bronchial biopsy in March 2001. The appellant takes issue with Dr Watson's reference to blood eosinophilia 'from 1996" because there were no tests between 1996 and 1999. I do not think it can be assumed that the reporting specialists read that shorthand expression as suggesting continuous blood eosinophilia since 1996. [31] Reports were obtained from Dr Edge on 6 June 2002 and Dr Philip Wong, gastroenterologist, on 4 July 2002, neither attempting any conclusion about the cause of the coughing or of eosinophilic bronchitis. On 7 August 2002, the appellant underwent an ambulatory oesophageal pH study. Dr Wong reported in a letter dated 12 August 2002, that: "It appears that he has significant ongoing acid reflux into the distal oesophagus, particularly in the supine position. The fractional time below a pH4 was 20.3% (normal [less than or equal to] 4.5%). Interestingly, there was not good correlation between his symptom of coughing and retching with the documented episodes of acid reflux. It seems clear to me that Mr Merriman has ongoing acid reflux despite his fundoplication procedure. Thus it seems likely that at least a component of his symptoms relate to ongoing gastro-oesophageal reflux disease." [32] Professor Carl Burgess provided an opinion of 10 October 2002, in which he concluded that the evidence did not support that Mr Merriman had suffered from eosinophilic bronchitis related to omeprazole use. He said: "The report from the chest physician Dr Watson at Mid Central Health, notes that this man was known to have eosinophilic bronchitis but in his letter he mentions that the cough was present well before this man had omeprazole. He was known to have eosinophilia in his sputum in October 1999 and to have had eosinophilia in his blood since 1996 which was well before he received omeprazole. Theoretically his bronchitis ought to have responded to corticosteroid treatment which it did, but these were discontinued due to side effects. A repeat bronchoscopy in August 2001 has not shown any evidence of eosinophilic bronchitis. There is no evidence that omeprazole is associated with eosinophilia or eosinophilic bronchitis. Therefore my opinion is that there is no evidence supporting the fact that omeprazole is responsible for any of this man's symptoms. In regard to his surgery, he had a fundoplication performed in July 2000 and he was slow to wake and developed respiratory distress following the procedure. He required ventilation and was treated in the intensive care unit with respiratory support. It is not clear what the cause of the slow response post-operatively was but it seems highly unlikely to be related to omeprazole. I can find no evidence for either medical error or medical mishap in this particular case and I can find no evidence that omeprazole has been responsible for any of this man's ailments besides one inflammatory bout of arthritis which occurred following the second prescription of this agent. This claim should be declined." [33] The Court does not have a report for the repeat bronchoscopy in August 2001, but it was referred to in Dr Hayhurst's letter of 30 April 2002. Ms Speller for the appellant submitted that the reports, and in particular Prof Burgess' report, relied on misleading information originating with Dr Watson. The misleading information was that Mr Merriman had a cough before August 1999 and had eosinophils in his blood from 1996, omitting to note that the cough was unproductive and that the eosinophils were unremarkable and known to be present only in 1996. [34] Mr Alan Fraser, a pharmacist consulted by the Medical Misadventure Panel, advised that he did not consider there was an association between the administration of omeprazole and eosinophilic bronchitis. He said "A through search of the literature and discussions with a now retired, but former senior respiratory physician from Wellington Hospital, have failed to show a link between omeprazole and eosinophilic bronchitis. Bronchospasm accompanied by cough or wheeze is noted as a hypersensitivity reaction. However it must be remembered that Mr Merriman's cough was a problem well before the start of the omeprazole treatment." [35] On 9 December, 2002 the Medical Misadventure Panel met to consider the appellant's case. The Panel members recorded that they were not satisfied that Mr. Merriman's respiratory problems are causally linked with the prescribing of omeprazole. The panel accepted that there was evidence to support the claim of allergic reaction in terms of the arthropathy and pruritis as a consequence of the prescribing of omeprazole. On 23 December, 2002 the Corporation issued its claim decision declining cover for eosinophilic bronchitis. The Corporation continued its investigation of the other claim. A letter of 24 December 2002 from the Corporation to Dr Parry suggested that the association of eosinophilic bronchitis with omeprazole was still under investigation. No reply was received and the investigation of this question was not renewed until the subsequent Review. [36] Ms Speller submitted that the reason for the Corporation's declining the claim has been taken substantially from Professor Burgess's report dated 10 October 2002, which is said to have been fatally flawed as it relied on incorrect information from the file. It had been stated in various letters that the appellant developed a cough while in Ireland. The Corporation has since been provided with information from Trafalgar Tours confirming that the appellant did not get sick while away on holiday. Professor Burgess refers to the omeprazole treatment which the appellant was apparently given in September 1999. This was incorrect. The appellant was given a treatment in August and October 1999. The claim decision letter stated "Professor Burgess further notes that your bronchitis did not respond to corticosteroid treatment". It is submitted that statement is wrong. [37] All these points have only limited weight in the appeal. As to the last point, Prof Burgess' comment may have been based on a letter from Dr Hayhurst which stated: "A repeat bronchoscopy in August showed no evidence of eosinophilic bronchitis. Subsequent treatment with steroids has not helped. I therefore feel that eosinophilic bronchitis whilst it might have been important in the past is no longer a factor now." At various times the bronchitis had responded to steroid treatment, but it did not do so in August 2001 when there was no evidence of eosinophilic bronchitis. There was some confusion about whether Mr Merriman had become ill while in Ireland, but there was also evidence that he had a troublesome cough since about April 1999, before going to Ireland, worsening on his return. It was that circumstance that influenced medical opinions. Similarly, whether the Losec treatment was in September 1999 or in October is inconsequential. Those points raise questions about the accuracy of Prof Burgess' report, but they are by no means "fatal flaws". [38] The presence of eosinophils and the development of a chronic cough have been recorded at various times before and after the omeprazole exposure. The appellant places a good deal of weight on the change in nature of the cough at the time of his reaction to omeprazole. Ms Speller submitted that the nature of the cough first noted in April 1999 by Dr Wong has been misunderstood. Dr Wong had noted that there was no wheeze, shortness of breath or sputum and that the appellant was feeling quite well. The Court cannot evaluate this argument without expert assistance. The cough was consistently reported as non-productive. It was considered possibly gastro- oesophageal in origin and that is why omeprazole was prescribed. It was continuous, becoming worse after administration of omeprazole and developing into a productive cough symptomatic of bronchitis. There is not enough evidence to support a finding that Dr Hayhurst or Dr Watson wrongly regarded the earlier dry cough as a significant point of differential diagnosis. Obviously it had to be taken into account, and the specialists considered it to be part of the relevant history. It is true that it was relied on as one of the principal diagnostic indicators, but that is a matter for medical judgment. I can find no real evidence that the nature of the cough was misunderstood in the context of the medical advice received by the Corporation. The review [39] A review was heard on 5 May 2003. A letter of 19 March 2003 had been received from Dr John Windsor, Associate Professor of Surgery at Auckland Hospital, commenting that the nature of the coughing changed from a dry unproductive cough before surgery to a very productive cough, with episodes of coughing that last up to two hours, the patient feeling that the mucous is not only coming from the chest but also from the stomach. [40] The Reviewer found that, despite the extensive medical investigations, no obvious cause was found for Mr Merriman's cough. The hearing was adjourned for ACC to consider blood test results which had apparently not been attached to Dr Watson's original report which referred to them. The Reviewer found that they indicated the presence of mild eosinophilia prior to the prescription of omeprazole in 1998. In her final decision, the Reviewer found that Mr Merriman had not discharged the onus upon him to demonstrate that his respiratory condition was caused by the prescription of omeprazole. In this appeal, Ms Speller submitted that there was no evidence that the Corporation or the Reviewer had obtained an independent evaluation of the blood test results and the Reviewer's finding echoed the Corporation's submission without supporting evidence. [41] The Reviewer relied substantially on the opinion of Professor Burgess, which is criticised by the appellant for the reasons set out earlier in this judgment. In essence, the Reviewer found that the medical reports and opinions either supported the Corporation's decision or did not express an opinion, while there was no clear medical support for Mr Merriman's claim that the cough was so substantially different following administration of omeprazole that medical conclusions associating the bronchitic cough with the earlier dry cough could not be accepted. The appeal [42] Before this appeal, some further opinions had been obtained. Dr Marianne Empson specialising in clinical immunology and allergy at Auckland Hospital said that the 1996 eosinophil count was not significant. In a letter of 27 January 2006, she wrote: "With respect to your question about the eosinophils in the blood in 1996 0.47 is a very marginal increase; this could have been as a result of laboratory variation, it could represent some mild drug reaction or it could have been because he has a background history of asthma or other allergic disease and I do not have all the information to be able to address that. I don't think that the eosinophil count was relevant to his reaction to the omeprazole. It may be relevant for the eosinophilic bronchitis if he had symptoms back in 1996, however the level is so marginally elevated above the normal that I would not normally take much notice of that." But she did not support the view that omeprazole could have caused eosinophilic bronchitis, saying: "I am not aware of omeprazole being implicated in eosinophilic bronchitis in the international literature, so I don't think it is possible to say that this was the cause. Certainly omeprazole has been well documented to cause allergic reactions but these are usually IgE mediated resulting in immediate allergic symptoms such as what this gentleman had with swelling, shortness of breath, rash etc, but this usually resolves and I know of no case where eosinophilic bronchitis has subsequently developed." [43] Dr Ruth Savage, a clinical pharmacologist of the Centre for Adverse Reactions Monitoring, wrote on 28 February 2006: "As I stated in my last letter omeprazole was intensively monitored in New Zealand through the Intensive Medicines Monitoring Programme (IMMP). Overall 22050 patients were monitored. Health events were recorded whether or not they were considered to be adverse reactions to omeprazole. Bronchitis was reported as a health event in seven patients and 47 patients developed bronchopneumonia or pneumonia but none of these were considered attributable to omeprazole use. Also none of these patients were described as having eosinophilic bronchitis or other eosinophilic lung disease. … As I also stated in my last letter we now have a total of three reports of patients with eosinophilia. One also had a severe skin reaction, arthralgia and liver involvement, one had a rash, arthralgia and blood in the urine and the third had increased urinary frequency. I think that these patient's experiences are most similar to those of your client's ie evidence of an immunologically mediated adverse reaction with arthritis, an eosinophilia and involvement of an organ, in this case the lungs." Concerning the chronic symptoms, Dr Savage said: "In the case of the ongoing breathing difficulties and cough once omeprazole was discontinued, I would only expect this to occur if there was some long term damage to the lungs. Thus I cannot comment on the role of omeprazole in the persistence of the respiratory symptoms without any knowledge of the underlying pathology and his physician would have to comment on this. … In summary from the information you have provided there is evidence that your client developed an immunological reaction to omeprazole. omeprazole may also have causes his loss of taste depending on when this commenced in relation to taking omeprazole. With regard to the persistence of his respiratory symptoms and also the itching and joint problems if they are persisting I would need more information about the underlying pathology and the hospital physicians responsible may well be able to provide this information and their opinion. [44] Dr Savage's opinion supported a possible association between omeprazole and eosinophilia. She was not able to comment on the persistence of the respiratory symptoms. The opinion is helpful to the appellant, but it stops short of supporting the case for a probable causal connection between omeprazole and eosinophilic bronchitis. It is less supportive of a connection with continuing respiratory disease after discontinuing treatment with omeprazole. [45] Dr Richard Steele, a consultant immunologist with Capital and Coast District Health Board wrote after seeing Mr Merriman on 1 March 2006. Dr Steele had been involved in Mr Merriman's care in 2004 and 2005. He agreed with Dr Empson's comment that a marginally raised eosinophil count in the context of a number of normal eosinophil counts is of marginal clinical significance. He wrote: " .. The cause of Keri's ongoing symptoms of cough have been difficult to fully discern and I agree that there may be more than one cause. In particular, he had reflux oesophagitis, eosinophilic-bronchitis and more recently he had pansinusitis with nasal polyposis. Interestingly, he underwent a functional endoscopic sinus surgery on 21.7.04 which led to significant relief from his cough. Unfortunately, subsequently his cough returned. This suggests that his sinus disease is likely to be an important contributor to his cough. With respect to the specific question regarding whether or not omeprazole can cause eosinophilic bronchitis, given that adverse reactions to omeprazole are rare and that eosinophilic bronchitis is a relatively poorly defined condition, I do not think that I can comment with any certainty that omeprazole may have caused this problem." Dr Steele's opinion did not therefore support the appellant's case for omeprazole being a probable cause of eosinophilic bronchitis. [46] Dr Steele suggested that histology from an oesophageal biopsy could usefully be reviewed. Dr Savage had also mentioned other enquiries, namely information about recovery rates, and about the underlying pathology of appellant's respiratory problems. Ms Speller submitted that the Corporation was at fault in failing to follow up those and other possible investigations. The Corporation's Clinical Advisor wrote to Ms Speller on 9 April 2006 expressing the view that the reports did not support the claim and that the Corporation's view remained unchanged. Submissions Whether the appellant had eosinophil bronchitis at all? [47] This point is mentioned only to record that Ms Hodgson for the Corporation submitted that the evidence does not support that on the balance of probabilities that the appellant has suffered from eosinophilic bronchitis. The diagnosis of eosinophilic bronchitis was proposed on the basis of the biopsy in March 2001 but more recent clinical opinion on file does not support this as an ongoing condition. [48] Because of the view that I have reached concerning proof of causation, I propose to make no finding concerning the diagnosis of eosinophilic bronchitis either as an acute or as a chronic condition. The following submissions will be considered on the assumption that the appellant did suffer eosinophilic bronchitis following his reactions to omeprazole. Whether eosinophilic bronchitis was caused by omeprazole [49] Ms Hodgson for the respondent submitted no cause has been established. There are three main areas of conflict. (a) whether there is evidence of a pre-existing cause or idiopathic condition before the administration of omeprazole in 1999. Two main factors bearing on that point are (i) whether the appellant had significant eosinophils in 1996, and (ii) whether the pre-existing cough was significant. (b) The second area of conflict is the temporal significance of development of symptoms at the time of administration of omeprazole. (c) The third area of conflict is the question whether omeprazole cart cause eosinophilic bronchitis at all Whether the condition pre-dated omeprazole [50] Ms Speller submitted that the slightly raised eosinophil level in 1996 quickly returned to normal and was not significant in considering the cause of eosinophilic bronchitis in 1999. The appellant had a dry non-productive cough which only showed changes to produce sputum following the prescribing of omeprazole. He was working as a caretaker at West End School doing 10 hours a week and had worked there for 4½ years at the time of the illness resulting in this claim. His last sick leave had been for a hernia repair in November 1997, before being off work after the second treatment of omeprazole on 8th October 1999. He was then obliged to resign. He had taken a number of overseas trips with his wife without difficulty and had resisted a flu bug which had affected people, including his wife, when travelling in Ireland in August 1999. It was submitted that the dry cough was not serious. [51] Ms Speller submitted that the specialist opinions adopted Dr Watson's misleading comment that the appellant had blood eosinophilia from 1996, while there was no evidence apart from a slightly raised blood eosinophilia on one test in 1996 and nothing known subsequently. The level had returned to .16 in the normal range on 2 October 1996 but that was not acknowledged by the advising doctors. Ms Speller pointed to the 2004 form of haematology reporting in which the normal range for eosinophils is shown as .05 to .45. The 1996 information was missing from the ACC file until the appellant provided it at the Review. [52] I do not read the medical opinions as suggesting that a blood eosinophilia in 1996 meant that eosinophilic bronchitis must have originated then. It shows that blood eosinophilia was not caused for the first time by the allergic reaction. I understand that eosinophils are to be associated with an allergic reaction, and eosinophils might well have been expected in October 1999. There was clear evidence of eosinophil bronchial inflammation from the biopsy in 30 March 2001 and that was the first time that a diagnosis of eosinophilic bronchitis was offered, but it was not regarded as the whole explanation for the bronchial cough, and did not explain the development of a chronic condition. No eosinophilia was found in another biopsy in August 2001. I do not find the evidence supports the appellant's view that opinions were skewed by Watson's reference to blood eosinophilia "from 1996". Temporal evidence of development of symptoms [53] Ms Hodgson submitted that the first mention in the clinical records of eosinophilic bronchitis, was from Dr Watson in May 2001, some two years after the development of the appellant's cough. Dr Watson's diagnosis appears to have been based on the presence of eosinophils in the sputum and an elevated blood eosionophil level, combined with the presence of eosinophils in a bronchial biopsy. Dr Watson further noted that the claimant responded to treatment for eosinophilic bronchitis, which supported that diagnosis at the time. [54] Ms Speller relies on general practitioner notes and other evidence to show that Dr Parry listened to the appellant's lungs on 7 August 1999 before prescribing omeprazole. Chest examination was normal and the cough had not become productive. Notes in April 1999 and August 1999 recorded that there was no sputum. Ms Speller submitted that there is no evidence that either the Corporation or the specialists undertook an exercise of drawing up a list of symptoms occurring for the first time when the omeprazole was taken, and placed it alongside the list of symptoms that had previously occurred. Ms Speller set out that comparison in a latter to the Medical Misadventure Unit and repeated the points in her submissions on this appeal. [55] The Court cannot reach an independent conclusion about cause and effect on the basis of reasoning from temporal coincidences. The process of diagnosis is complex and depends on weighting signs and symptoms with the benefit of professional skill and experience. Even bearing in mind the criticism that Dr Watson referred to blood eosinophilia "from" 1996, the various specialists should have been ready to make further enquiries in the case of any ambiguous or uncertain information which they considered to be of crucial significance. It is not possible to say that any of the advisors who influenced the Corporation's decision had been materially misled by Dr Watson's comment. In general terms, the chronology of events was appreciated by the specialists who advised the Corporation. The developing of a productive cough after taking omeprazole was known. I can find no evidence that the doctors were misled or did not understand the significance of the sequences of events. Alleged failures by the Corporation [56] Ms Speller submitted also that the Corporation did not effectively investigate the claim, and that important aspects were submerged in a "sheer volume of available information". The Corporation has erred in selecting from that information the briefing documents for independent advisors. The particulars of this ground of appeal refer again to Dr Watson's description of "blood eosinophilia from 1996" and Dr Watson's apparent omission of enclosures from his letter of 20 May 2002. The argument relies on the same alleged shortcomings that are advanced in relation to the argument that the medical opinions are flawed. It is further submitted that the Corporation failed to obtain more information when Dr Empson and Dr Steele referred to possible avenues of enquiry. Ms Steele also noted that the opinions given by the various specialists have not clearly shown whether they have considered whether the appellant developed eosinophilic bronchitis after taking omeprazole, instead they have simply argued that he had a cough prior to taking omeprazole. It is submitted that the Corporation had a responsibility to investigate whether the appellant developed eosinophilic bronchitis as a result of medical misadventure; this included ensuring that the opinions received did clarify that point. [57] On 16 April 2004 Ms Speller wrote to the Case Manager. She says that in spite of oral assurances to look into the matter there was no further action. [58] I am not able to find a failure by the Corporation to meet its obligations of reasonable investigation of the claim. It is a case in which there is very little conflict in the medical views. The Corporation was justified in considering that a point had been reached at which there was a persuasive body of opinion against the medical misadventure claim. No contrary medical or specialist view had been articulated at all. The further step that the Corporation could have taken would have been to ask its advisors to review their opinions in light of the questions raised by the appellant's advocate. In my view, the evidence in this case is not strong enough for the Court to find the Corporation at fault in failing to do that. Many cases come before this Court on appeal where the disputed opinions are challenged by the claimant meeting the cost of putting further material before medical advisors in order to test their previously expressed views. It is a question of fact whether or not there has been evidence of an error or omission in material considered by medical advisors obliging the Corporation to request reconsideration of an opinion. In the present case, I find that the evidence of possible ambiguity or omission in the considered material was not sufficiently cogent for the Court to find that the Corporation did not meet its obligations. Whether omeprazole can cause eosinophilic bronchitis [59] Ms Speller submitted that the appellant had a number of different symptoms indicating adverse reactions to omeprazole. These included anorexia, arthropathy, pruritis weight loss, and loss of taste. These symptoms all occur in less than 1% of patients. That means that each of these rare symptoms have had to occur for the first time in a patient who then had to prove the reaction was caused by omeprazole without the historical evidence of other patients with similar reactions. The appellant has shown a tendency to develop a number of different rare reactions. If anyone was likely to develop another rare reaction that was not clearly documented at this point it was Mr Merriman. The fact that eosinophilic bronchitis has not been clearly identified as an adverse drug reaction for omeprazole does not mean that the appellant did not developed eosinophilic bronchitis as a result of taking omeprazole. [60] That is a submission without an argument. The suggestion is that more than one of the appellant's reactions were rare or unexpected, so that it is more likely that he could have experienced a rare consequence of ingesting omeprazole. In oral argument, Ms Speller said "any rare symptom has to occur once". But to suggest that it occurred in the appellant's case is entirely speculative. The problem remains that there is no medical opinion to support the claimed cause and effect. Neither do I consider that the Corporation should have regarded this as a rare case requiring a special degree of investigation, in the face of the general measure of agreement in the available medical opinions. [61] Ms Speller referred again to the sequences of events in the appellant's case. She also referred to comments in letters from Dr Watson and Dr Edge referring to "cases of pulmonary infiltrates with eosinophilia in patients taking omeprazole treatment" and to "an association made between pulmonary eosinophilia and Losec although this remains unproved". But there has been no evidence of an association between that omeprazole or Losec and eosinophilic bronchitis. The doctors considered the question carefully and came up with nothing to support a causal connection. Decision [62] I accept Ms Hodgson's submission that for the appellant's claim to be accepted as medical misadventure, he must show on the evidence that he has sustained a personal injury causally linked to treatment, and that the criteria for either medical mishap or medical error have not been met. A possibility that the appellant suffered a rare and hitherto unrecognised consequence of administration of omeprazole is not enough. [63] The appeal is dismissed. Signed at Wellington on 13 September 2006 at Judge D A Ongley District Court Judge