YEAR 2001

YEAR 2001

By 2001 I had been Chair of the Cystic Fibrosis Trust’s Research and Medical Advisory Committee (RAMAC) since before I retired from the NHS in 1997. As part of my role I attended the monthly Board Meeting of the Trustees in London to report on the medical and research aspects of the Trust’s work, in particular on the work and decisions of the RAMAC which I chaired. I also dealt with any significant new developments in treatment or research elsewhere to keep the Trustees up to date on progress.

As there seemed to an increasing amount of detail to report, rather than reading from my notes at the meeting, I decided to write a diary of my activities on behalf of the CF Trust during the previous month and hand copies of these round at the meeting to supplement my verbal report to the Trustees.

These reports proved surprisingly popular with the Trustees and “Dr. Littlewood’s Diary” became a regular item on the Board Meeting agendas from 2001 to 2004!   When I accepted the invitation to become Chairman of the CF Trust in 2003, I discontinued the diaries as the new Chair of the RAMAC, Professor Stuart Elborn, would be attending the meetings to report on the activities of the Research and Medical Advisory Committee.

There follows some information from my diaries from 2001 to 2004. I have expanded the details of many entries to add explanation for the present readers (e.g. in 2022) and  also to mention outcomes that became known  after the date of the particular entry.

In addition, I have included more general events many not directly related to cystic fibrosis as work and family events were always so closely linked throughout my career both before I retired from the NHS and then until I retired as Chair of the CF Trust in 2011 in my Eigtieth year.

Ann at ECFS meeting, Crete 2005

My wife Ann, is a qualified nurse, and accompanied me on virtually all my many travels; she planned all the arrangements and helped with constructing the slides and in recent years the numerous PowerPoint presentations. Ann, in a voluntary capacity, had helped with implementing the computerisation of the mass of clinical and laboratory data which resulted from the detailed Annual Comprehensive Assessments which we had pioneered from the early Eighties and which were central to the Leeds Regional CF Unit’s success.

Jan.10th.  Meeting of the Infection Control Group

Margaret Hodson
Duncan Geddes

Drs. Duncan Geddes and Margaret Hodson, senior consultants from the Brompton, were brought onto the group as they were the most senior and informed critics of  our  provisional Pseudomonas document that received so much stick on our segregation recommendations at the Directors’ Meeting in the autumn. 

In contrast, this was a very successful meeting where the group only slightly modified a document to suit everybody including the new members. A final version was agreed more easily than I had expected. It is now a very good document and will be available for the medical CF meeting in London on March 30th.

Jan.15th. Rosalind Smyth’s Inaugural Lecture as Professor of Paediatrics at Liverpool University

   Ros Smyth

We had known Ros since she was appointed as one of the early CF Trust  Research Fellows. These were registrar grade jobs in the 80‘s funded by the CF Trust at many of the major medical centres where CF units were developing. These doctors were already paediatric registrars and usually stayed for 2 years working in the same CF centre. They made a major contribution to developing the CF care and many went on to be CF consultants or paediatricians with a special interest in CF.

 

   John Wallwork

Ros was a CF Research Fellow at Papworth Hospital, Cambridge with Mr John Wallwork who performed some of the first heart-lung transplants in the mid-Eighties. She then moved to Liverpool as consultant and subsequently was appointed first Reader then Professor there in 2001 – hence this inauguration ceremony. 

Subsequently in 2013 Ros was appointed Head of the Institute  of Child Health at Great Ormond Street in London. Her younger brother Alan is Professor of Paediatrics in Nottingham and also now a recognised authority on CF. Definitely they are a very talented family!

When she was at Liverpool Ros started the first Cystic Fibrosis Cochrane Group with some financial support from the CF Trust. This went from strength to strength to eventually become The Cochrane Cystic Fibrosis and Genetic Disorders Group (CFGD.cochrane.org). Their new office opened in 2019 with contributions from the University of Liverpool and the CF Trust and was named after the late Dr Sarah Walters OBE, an exceptional doctor with CF, who died in 2018. 

Jan. 16th – 18th. Lecture on “CF Care for cystic fibrosis – the importance of centre treatment” at a CF Conference at Amersfoort in Holland.

We seem to go to Holland quite frequently to give lectures or take part in meetings, having been twice last autumn! This talk was similar to many I was asked to give around that time and on which I based an detailed article published at that time –

Littlewood JM. Good care for people with cystic fibrosis.  Pediatr Respir Rev 2000; 1(2):179-89.

(I have included a very detailed expanded list comparing “good care” and “suboptimal care”  in the entry of this article in our Leeds CF website (cysticfibrosis.online/history/2000).                                                                                                                                              

The main message of this article was – The improvement in the health and survival of people who have cystic fibrosis (CF) has been due to better treatment developed at major CF centres. The regimens for prevention, early treatment and later stabilisation of chronic respiratory infection and for the maintenance of normal nutrition and growth are now largely established. Treatment is life-long, complex and expensive. It should be started early after a diagnosis made following neonatal screening, and before chronic respiratory infection and malnutrition are established. Regular monitoring and input from the expert staff of a CF centre is essential, either on a ‘full’ or ‘shared care’ basis; adults with CF should attend a major Adult CF unit. The details of the staff and facilities necessary to achieve good care for CF are discussed, including the details of clinic procedures and annual assessments.

During the preparation for this article I tried to document the really important aspects of care – many of which are not dealt with in text books and guidelines. I showed my table to a number of respected experienced colleagues who were treating people with cystic fibrosis and received some helpful suggestions. I realise this list is rather formidable, but it represents over 25 years’ experience treating hundreds of cystic fibrosis children and young people. I do encourage you to examine the full table available which is also available in full on http://www.cysticfibrosis.online/history/2000.

(CF Foundation “fatal flaw” indicates it is a practice regarded as a FATAL FLAW by the CF Foundation and will influence funding of the centre by the CF Foundation unless corrected.

                  BEST CARE                                             SUBOPTIMAL CARE

CF CENTRE / CLINIC
– Segregation of all patients according to their microbiological status No segregation of patients according to microbiology
– High standards of general hygiene Poor hygienic standards – common in UK
– More than 50 patients on full care Fewer than 50 patients on full care.   (CF Foundation fatal flaw)
– Adequate clinic session time identified for CF patients only Overcrowded general clinic.                 (CF Foundation fatal flaw)
– Regular follow-up (every 1 to 2 months) Infrequent, often missed, follow-up
– A few permanent CF doctors familiar with each patient’s details Changing doctors, unfamiliar with CF and the patients they are seeing
– One named senior CF doctor (consultant) ultimately responsible for long term care Unclear who in the “team” is ultimately responsible
– Experienced permanent clinic nurses who know patients, cross infection problems, weighing and measuring, spirometry and taking throat swabs and various treatment protocols Inexperienced temporary nurses who are unfamiliar with the clinic routines
– CF Nurse Specialist available if required No CF Nurse Specialist available or one who is heavily overworked
– Usually sees CF Physiotherapist or can have an early appointment as needed Rarely or never sees Physiotherapist
– Usually sees CF Dietitian or early appointment as needed Rarely or never sees Dietitian
– Clear detailed clinic records & data sheets Brief illegible medical notes
– Accurate weight and height, charted at every attendance Inaccurate, irregular or not charted weights and heights
– Computer printout of or access to previous important basic respiratory and nutritional data readily visible in notes – print out or computer Doctor searches through disorganized notes for information of previous data every time patient attends
– Accurate, bacteriologically clean, spirometer used at every attendance Infrequent, inaccurate, unclean or no spirometry
– Sputum/throat swab cultures every attendance and also when unwell.        –   Arrangements to send to lab’ by post Infrequent sputum/throat swab cultures
– Patient asked to ring if doesn’t hear culture result – rapid treatment of positive cultures No action on positive culture for weeks until next clinic
– Patients/parents should be aware of their microbiology and its significance Patients/parents unaware of their microbiology
– Annual chest X-ray & whenever needed Chest X-rays rarely done – “chest clear – doesn’t need an X-ray”
– Antibiotic treatment at first sign of even a viral respiratory tract infection (RTI). Treatment only when RTI well established and obviously progressing – has to prise antibiotic out of doctor.
– Patient/parents have prescription for an antibiotic or an antibiotic course at home to use when required Difficulty getting extra antibiotic with colds etc.
– Vigorous eradication policy for early Pseudomonas aeruginosa positive cultures. Known to all staff. No clear policy of early Pseudomonas eradication
– Early resort to IV antibiotics with option of home IV antibiotics IV antibiotics used only as a last resort
– Annual Review completed each year No or incomplete Annual Review
– Centre Director personally discusses Annual Review results with parents/patient Junior doctor discusses results with parents/patient
– Centre Director or CF Consultant writes Annual review letter to family doctor with recommendations Junior doctor rather than Director does letter with recommendations
– Copy of letter goes to patient/parents Patient/parents not informed of results
24-hour access to a member of the CF team for advice No 24-hr direct access to CF team

(CF Foundation fatal flaw)

– Regular review of eligibility for TOBI, Pulmozyme and ventilatory support Patients missing out on effective treatments which may help them
– Direct access to Director / Consultant with phone number Senior staff unavailable out of hours
-Agreed but flexible transition arrangements to adult CF unit known to parents and patients Unclear transition policy or no adult CF unit with care continuing n the paediatric unit

(CF Foundation fatal flaw)

CF WARD ROUTINES

– Segregation according to microbiological status as in clinic No segregation according to microbiological status
– Highest standards of hygiene for all including all ancillary staff and visitors, cleaners, etc Poor hygiene standards, inadequate routines & hand washing faculties
– Sufficient, knowledgeable ward nurses Temporary overworked nursing staff
– Seen regularly by senior CF doctors Inexperienced CF naive doctors
– Protocols for all routine procedures No protocols – variable procedures
– Single rooms with en suite facilities Open ward with shared facilities
– Good ward cleaning service Inadequate ward cleaning
– Daily visits from CF physiotherapist No regular physiotherapy
– Supervision by CF dietitian No regular supervision by dietitian
– Appropriate, palatable food Unattractive unpalatable hospital food
– Regular ward rounds and information to patient/parents Irregular ward rounds / inadequate information regarding progress
– Education / occupation / interests while in the ward No education occupation or interests
– Communication with other patients via internal phone, internet, etc Isolation and boredom in cubicle
Prevention, Immunization
– Fully immunized against common infectious disease Incompletely immunized
– Annual influenza injections No influenza injections
– Avoidance of people with viral ‘colds’ when possible Unnecessary exposure to ‘colds’
– Avoidance of tobacco smoke Smoking in the environment
– Avoidance of fungal spores Indoor work at horse stables
– Adequate dry housing Overcrowded damp house
– Avoids others with CF e.g. camps/holidays and social gatherings etc Attends CF camps/holidays etc
– Always avoids others with CF Mixes freely with others with CF
– Adequate personal/family finances Financial difficulties
GENERAL
– Patients should be aware of their respiratory function (FEV1 or even PEFR for young patients) and have some idea of where they lie in terms of severity May be quite unaware of how they are compared to others with CF
– All patients severe enough to be in the “transplant window” are reviewed every 6 months Some patients who reach need for transplant referral are overlooked as need not reviewed regularly
– Advice on and aware of state benefits to which they are entitled. Reviewed by the CF social worker Not receiving full entitlements as not had adequate advice
– Aware of and contact with the national CF patients’/parents’ organization (CF Trust) Unaware of and unknown to national CF organization.
– Aware of reliable and useful CF websites (www.cftrust.org.uk;www.cfmedcine.com; http://www.cff.org) Unaware of or no access to reliable CF websites
– Well informed and “adjusting” to having CF Ill-informed and not adjusting to having CF
– Regular contact with Specialist CF centre staff (if a child on ‘shared care’ who is attending the local hospital) All care at local clinic; irregular or no contact with staff at Specialist CF centre
– Registered with UK national CF Database or their national database and regular data entry to local and national database Not registered with national database and no local database

OTHER

– Close collaboration with Microbiologist and laboratory staff experienced in culturing CF sputum specimens Routine laboratory with only occasional CF specimens and little contact with clinicians
– Efficient centre secretary/coordinator who knows staff and families/patients Temporary secretarial help to only deal with letters, telephone, appointments, etc
– Other laboratories and X-ray departments in the hospital regularly perform specialist CF investigations and procedures Other departments rarely do investigations on CF patients and so unfamiliar with techniques and likely findings
– Help of other colleagues familiar with CF –surgeons, ENT, diabetologist, gastroenterologist, radiologists obstetrician, fertility expert, geneticist, medical physics, pharmacist Referral to specialists who rarely see people with CF and unfamiliar with particular problems
– Suitable funding arrangements agreed with referring health authorities Constant difficulties prescribing CF drugs and care
– Attention to user requirements/ satisfaction/ suggestions No regular discussion with patients / parents on their views on the adequacy of the CF service
– Appropriate management of terminal care and ongoing family support – letters from senior nurse and Centre Director. Possible bereavement counselling No contact with relatives after patient dies
–  Attention to the physical and mental well-being of all members of the CF team Overwork, stress, conflict and poor relationships between members leading to inefficient service and illness. Inadequate leadership.
– Mandatory weekly meetings of all members of the CF team + microbiologist and pharmacist (when possible) No regular team meetings to discuss patients, policies and problems

(CF Foundation fatal flaw)

– Clear, informed, decisive leadership from the Centre Director – coordinating the individual views into agreed decisions and communal policies. A basis for written protocols. Independent policies and practises by different team members leading to conflict and confusion for other team members and patients
– Consultants and CF team undertake clinical research and present the results at CF meetings and in publications No research, publications or attendance at CF meetings
– Efficient CF Clinic and Data Clerk to ‘guard’ the notes and organise clinics Reliance on central appointments system & secretarial pool
Clinical notes and recent X-rays held in the Cystic Fibrosis Unit Notes and X-rays in hospital main records office and frequently unavailable

The talk went well. Some of the adult physicians were not in favour of shared care which is still the case in the UK.  All the other lectures were in Dutch. I kept hearing my name mentioned relating to subjects on  which I had published. People looked at me and smiled but I had no idea what was going on. Double Dutch is a good expression!

                       Amersfoort
                 Amersfoort

 

 

 

 

 

 

We had a look round Amersfoort the following day.   Amersfoort is described as a very historic and attractive city to the west of Amsterdam. It has many fine medieval buildings that are well maintained. It is a busy place with a population of just under 150,000 people, but the town centre is easily explored on foot, with most of the main attractions being easily within walking distance. The railway station is one of the busiest in Holland with several tracks converging on the area.

We flew back to Leeds/Bradford the next day.  There was some excitement at Schipol Airport. As we were standing at the counter in the check-in there was a huge bang and smoke appeared from the end of the huge departure lounge.  Surprisingly the staff kept on working normally until the smoke became unbearable. At this stage the whole of the huge building was evacuated. Apparently, it was not a bomb but an explosion in one of the fast food outlets on the floor below. We tramped over to the adjacent terminal and managed to catch our plane.

Jan. 19th. Neonatal CF screening meeting at our home in Bardsey. 

Rodney Pollitt

Rosie Barnes, Prof Rodney Pollitt from Sheffield and Anil Mehta from Dundee meet to work out our strategy for the neonatal screening in the immediate future.  

For over 30 years Dr.Pollitt has been professionally involved in newborn screening locally and nationally. During this time he has become a true newborn screening guru locally, nationally and internationally. This is evidenced by his large number of publications (more than 150 book chapters and full papers in addition to a large number of conference abstracts) on newborn screening and metabolic disease topics, and by his many invitations to speak at meetings.Rodney Pollitt had been in charge of neonatal screening, including CF, in the  Sheffield region.

Jan 24th. Meeting of the Standards and Accreditation Group in London

We travelled down the night before this meeting and stayed at the Royal Society of Medicine (RSM). Although not a Londoner I’m now in London so frequently it was worth joining the RSM – an excellent facility with a very comfortable accommodation, a very good restaurant and a really excellent library. Over the years the RSM almost felt like home.
I made increasing use of their really excellent library for my work on the history of cystic fibrosis for Daniel Peckham’s Leeds website  (cysticfibrosis.online/history). There were numerous old original journals and I spent many hours climbing up steps retrieving ancient journals in the basement and making photocopies. 

The Standards for the Clinical Care of Children and Adults with Cystic Fibrosis”  was completed and approved at this meeting.  I must say that the progress to this final document had sometimes not been entirely smooth – but we managed to end up with an excellent document that later  formed a template for the European CF Society Guidelines.  

Tony jackson

The document would replace the CF Trust’s 1996 Clinical Guidelines for the Care of Cystic Fibrosis. We had used this document as the basis for this our 2001 Standards.  The 1996 Working Group of the CF Trust, the British Paediatric Association and the British Thoracic Society was chaired by Dr Tony Jackson, a distinguished London paediatrician who, at the time, was Chair of the CF Trust’s  Research and Medical Advisory Committee – RAMAC

Clinical Guidelines for Cystic Fibrosis care.  J Roy Coll Phys Lond 1996; 30:305-308).
The new Standards of Care document

The wider representation of interests and expertise on our present group was in line with recent NHS recommendations. In addition to paediatricians and respiratory physicians we now included an adult with CF, a parent of a CF child, a CF nurse, physiotherapist and dietitian, a district general hospital consultant paediatrician and an epidemiologist. The document was already being used by authorities planning CF services.  Copies were freely available from the CF Trust and also on their website.  I was proud of the achievement of our very knowledgeable, and pleasant group.  Details and images of the members of the group are described in the Year 2000, October 11th section of this website.

 

Jan. 24th – 27th. Lecture in Utrecht on “Fibrosing Colonopathy”

This was a subject with which I had been deeply involved since the first description of the complication in 1994/5 by Ros Smyth

Smyth RL, van Velzen D, Smyth AR, Lloyd DA, Heaf DP.  Strictures of the ascending colon in cystic fibrosis and high strength pancreatic enzymes. Lancet 1994; 343:85-86. [PubMed]
       Dick van Velzen

In this lecture I gave a detailed review of the subject. I kept off the subject of the now notorious Liverpool pathologist Dick Van Velzen – now referred to in the popular press as “the organ doctor”.  When he was working at the Alder Hey  Hospital in Liverpool he was the main pathologist involved in the initial description of fibrosing colonopathy 1994. He was the centre of the Alder Hey  “organs scandal” and responsible for the unauthorised removal, retention, and disposal of human tissue, including children’s organs, during the period 1988 to 1996. During this period organs were retained in more than 2,000 pots containing body parts from around 850 infants. These were later uncovered at Alder Hey Children’s Hospital, Liverpool, during a public inquiry into the organ retention scandal.  There was a public inquiry and van Velzen was dismissed as was the Chief Executive of the Alder Hey. The Human Tissue Act 2004 and the creation of the Human Tissue Authority followed.

Colonopathy.Thickened fibrous colon and very severe radiological stricture in one of our CF children
Early stricture of the ascending colon in one of our patients. Did not progress when high strength Pancrease HL was changed to Creon

In the early Nineties the new high strength pancreatic enzymes (Pancrease HL, Creon 25,000) became available and were welcomed by people with CF many of whom, when taking a normal fat intake, did require a large number of standard enzyme capsules. So it was not surprising that patients, and their professional advisers, welcomed the introduction of the new “high lipase enzymes” in 1992. 
However, in 1993 a new unexpected and serious complication, fibrosing colonopathy with colonic strictures, was observed in Liverpool and eventually   related to the very high doses of the new enzymes some patients were taking (Smyth et al, 1994 above). 

Subsequently further patients with colonic strictures were reported from UK and the United States. Studies in the UK (Smyth et al, 1995) and the US (FitzSimmons et al, 1997) showed a relationship with the very high doses of lipase achieved with the new enzymes

Smyth RL, Ashby D, O’Hea U, Burrows E. Lewis P. van Velzen D. Dodge JA. Fibrosing colonopathy in cystic fibrosis. Results of a case controlled study. Lancet 1995; 346:1247-1251. [PubMed]
Freiman JP, FitzSimmons SC. Colonic strictures in patients with cystic fibrosis: results of a survey of 114 cystic fibrosis care centers in the United States. J Pediatr Gastroenterol Nutr 1996; 22:153-156. [PubMed])

The authors concluded that there was a definite dose-related association between high-strength pancreatic enzyme preparations and fibrosing colonopathy. (Also Fibrosing colonopathy in children with cystic fibrosis. Proceedings of a conference in Manchester organised by the Cystic Fibrosis Trust, 5th Nov. 1995. Littlewood JM, Hind CRK (eds). Postgrad Med J 1996; 72 (Suppl 2):S1-S64).

Professors John Dodge and Chris Taylor

The studies differed on showing an association with the Eudragit copolymer covering of certain preparations – the UK study suggested this was a significant factor. There was much heated argument amongst paediatricians regarding the role of the copolymer covering.  In particular between myself (convinced of the role of Eudragit) and Professors John Dodge and Chris Taylor (did not accept Eudragit was responsible) who regarded themselves as the only creditable paediatric gastroenterologists in the UK.   We are still good friends but there were fierce exchanges between us when I (as Chair of the CF Trust Research and Medical Advisory Committee) recommended CF children should avoid enzymes contain the copolymer covering Eudragit.

In my firm opinion it is important to avoid all enzyme preparations containing the copolymer Eudragit – these are Pancrease HL, Nutrizym 22, Nutrizym GR. Preparations that do not contain the copolymer – Creon 25,000, Creon 10,000 and standard Pancrease are quite safe. The problem has since receded in the UK following advice from the Committee on the Safety of Medicines to restrict the daily dose to an equivalent of lipase to not more than 10,000 IU /kg/day (Littlewood, 1999 below).

I published a number of papers on fibrosing colonopathy and also previously chaired a national meeting on the subject published in the Postgraduate Medical Journal.

Green MR. Southern KW. Wolfe SP. Littlewood JM. Najmaldin AS. Wyatt JI. Colonic strictures in cystic fibrosis. Arch Disease Child.1995; 72(2):191, 1995 
Littlewood JM. Fibrosing colonopathy in children with cystic fibrosis. Postgrad Med J. 1996; 72:129-30.
Littlewood JM. Update on the United States epidemiology study.  Postgraduate Medical Journal. 72 Suppl 2:S6; discussion S7-10, 1996 Mar. 
Littlewood JM. Management of malabsorption in cystic fibrosis: influence of recent developments on clinical practice.   
Postgraduate Medical Journal. 72 Suppl 2:S56-62; discussion S59-62, 1996 Mar.
 Ramsden WH, Moya EF, Littlewood JM. Colonic wall thickness, pancreatic enzyme dose and type of preparation in cystic fibrosis. Arch Dis Child 1998; 79(4):339-43 
Littlewood JM. Update on intestinal strictures. J R Soc Med. 1999; 92 Suppl 37:41-9. 

To return to the lecture – it went very well and afterwards we had a very good evening out with the medical colleagues at a museum.  

Traditional old street and buildings in Utrecht, Netherlands.
The iconic domtoren, a 14th century bell tower opposite the Gothic Cathedral of St Martin on central Domplein square

 

 

 

 

 

 

 

The next day we did some sightseeing.  Utrecht is an impressive  city in the Netherlands, known for its medieval center. It has tree-lined canals, Christian monuments and a venerable university. The iconic Domtoren, a 14th-century bell tower with city views, stands opposite the Gothic Cathedral of St. Martin on central Domplein Square. The Museum Catharijne convent shows religious art and artifacts in a former monastery. (Google)

Feb. 5th. Fly from Leeds/Bradford to Glasgow for a visit to Yorkhill Children’s Hospital with Rosie Barnes

In the evening Rosie conducted a very good meeting with about 30 parents from York Hill with whom there was a very open discussion on the staffing and accommodation problems at the hospital. It was good in that the parents are able to voice their concerns about the CF service at York Hill Children’s Hospital.  Rosie managed to reassure them that the CF Trust was there to help and improve the situation both for the staff and families.

Feb. 6th. We had a lunch with Dr John McClure in Glasgow.

Dr John McClure

John is a senior paediatrician from Kilmarnock who was intent on introducing a CF regional network for South and West Scotland – a hub and spoke concept, which is essentially a system of shared care.  Obviously such a system  requires its hub to be fully staffed and a well accommodated Specialist CF Centre at Yorkhill Hospital in Glasgow, which unfortunately does not exist at present.  

After lunch we had a meeting with the CF staff at Yorkhill and about 15 to 20 assorted managers and commissioners to discuss the present proposed CF service. The meeting went well but we were left unclear as to the nextstep the local officials will be taking.    The local paediatricians were surprisingly cooperative after the meeting when Rosie listed in great detail the parents concerns that we had heard the previous evening. It is likely that Rosie will be arranging another meeting of the parents and the CF Trust in the near future. It was definitely a productive couple of days.

The refusal and inability of the Yorkhill managers to provide adequate staffing and accommodation for this CF Unit was in stark contrast to the superb accommodation and liberal staffing I’d seen in Holland a few days earlier. It is unfortunate that, as a nation, we have come to accept secondary standards in some areas of the NHS.

Dr John McClure (1943-2018) was an extremely pleasant man and distinguished paediatrician and Medical Director of the North Ayrshire and Arran Trust . I had met him on many occasions. He had a stammer which seemed to be no handicap. He was interested in cystic fibrosis and apparently would always attend his patients’ funerals.  Another major interest was cot deaths. He was very keen to see a better service for CF in his area. He was awarded an MBE in 2017. A very nice man – always a pleasure to meet.

Feb. 7th. I wrote an urgent letter to Dr Muir-Gray.

Dr Muir Gray

He  is the Director of the National Screening Committee and Rosie and I were due to have a video conference with him. The request for this meeting appears to have been prompted by the recent adjournment debate in the House of Commons in which Tess Kingham MP for Gloucester spoke on neonatal CF screening. Rosie and Tess Kingham took up the minister’s (Yvette Cooper)  suggestion of a meeting. I enclosed detailed comments on the National Screening Committee’s document outlining why they did not recommend national neonatal screening. My document runs to some 20 pages of single space text includes all the recent data including a key study from Wisconsin. We thought the meeting went well and the new evidence from Wisconsin which considerably changed things was mentioned a number of times.

2001 Farrell PM, Kosorok MR, Rock MJ, Laxova A, Zeng L, Lai HC, Hoffman G, Laessig RH, Splaingard ML. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Pediatrics 2001; 107:1-13. [PubMed]
Philip Farrell

Follow-up of the Wisconsin screened infants showing significantly better long term growth and nutritional state in the screened group.
This particular trial and publication were influential in the eventual recommendation for national neonatal CF screening by the UK Government in May 2001.  Yvette Cooper, the Health Minister at the time, agreed to the introduction of nationwide neonatal screening, wisely ignoring the advice of the National Screening Committee!

 

 Feb. 8th. Rosie (in Bromley), Dr Miur-Gray and Stephen Pugh of the DHS (in London) and myself (In Leeds) had a good video conference. 

Dr Muir-Gray seemed very impressed by the new supportive evidence from Philip Farrell’s unit in Wisconsin, also from France and some from our own UK database prepared by Anil Mehta. He indicated the matter would be reviewed in the near future and “the door was by no means closed”.
Dr Muir-Gray was knighted in 2005 for the development of the foetal, maternal and neonatal screening programmes and the creation of the National Library of Health.

Feb. 10th. Sue and Nick took me to see Texas in the Nottingham Arena.

 Texas in 2001
Motorpoint Arena Nottingham

This was a delayed Christmas present!   Very good concert in the Nottingham Arena and Ice Rink. Ann not keen so didn’t come!

 I had not been there before and was very impressed with the building. The National Ice Centre and Nottingham Arena were opened by Olympic gold medalist Jayne Torvill on 1 April 2000. Since then, the Arena has hosted over a thousand concerts, comedy acts, family shows and sporting events. Texas and their co-founder and lead singer, Sharleen Spiteri, were very good.

Feb. 12th Travel to London and meet Paul Humphrey 

Paul Humphrey

Paul Humphrey, (Product Affaires Manager – Metabolic Disease, Orphan Europe) had requested a meeting and the CF Trust asked me to see him. He is a director of the firm Orphan Drugs that is arranging a multicentre  clinical trial in mainland Europe (not UK yet) of a vaccine against Pseudomonas aeruginosa. The small preliminary study had shown the vaccinated patients had a reduced likelihood of developing chronic Pseudomonas infection; the reasons for the vaccines effect were complex. It was interesting that an annual injection would halve the chance of chronic Pseudomonas infection.

It could be of great importance. I suggested a workshop for interested parties in the UK and Paul said this was likely to be arranged. He would keep me informed of developments and I promised to keep the CF Trust fully informed.

Perhaps I should mention the downside. The injections would perhaps cost approximately £2000 each. However, if they prevented chronic Pseudomonas and if the standard treatment for chronic Pseudomonas infection (a two week course of IV antibiotics costing £2400 every three months as occurs in  some units) there would be a net saving of £7600 per year, also a great improvement to the patient’s quality of life in avoiding hospital admission and interference with normal activities. However this was obviously some time off.

Feb 14th – 16th. Ann and I visit Exeter.
We drove to Exeter where I was to give a CF Trust branch lecture for parents and any professionals who were interested.

Dr Chris Sheldon
Dr Patrick Oades

 On the 15th Dr Patrick Oades (Paediatrician at Exeter) and Dr Chris Sheldon (Chest physician at Exeter) invite me to attend the South West CF Meeting at the Postgraduate Centre at the Royal Devon and Exeter Hospital.   The hospital is a large teaching hospital and there are branches in  in Wonford and Heavitree, Exeter. It is part of the Royal Devon and Exeter NHS Foundation Trust. The hospital is used for the clinical training of medical students from the University of Plymouth and the University of Exeter.

It was a good meeting attended by about 90 professionals from the south-west region. The geographical problems make delivery of Specialist CF service difficult. Their proposed solutions, of a Peninsula Consortium, the Bristol shared-care group and the Southampton shared-care group, seemed to be a more reasonable solution than I thought on first hearing of it   The care of children with CF had always been a problem in the SW Peninsula in view of the substantial distances between the relatively small hospitals, and the distance from the nearest major CF unit in Bristol. The reluctance of the families to travel and the wish of the local paediatricians to each continue to care for a few CF children were other important factors. This made the planning and provision of specialist CF centre care virtually impossible as a CF centre needed some 50 patients to be viable.

Eventually a “SW CF consortium” of local consultant paediatricians was formed as a compromise, which I did not think was a good idea. For this reason, I was not very popular with some of the local paediatricians who wanted to look after a small number of children with cystic fibrosis. It is true that travel was a major problem for some families and the South West peninsula is really very long. Another slight problem which annoyed some of the local consultants was the fact that a number of patients from the south west had been referred to my unit at St James’s  in Leeds for a Comprehensive Assessment.

      Dr Ty Pitt

Also at this meeting, it was reassuring to hear Dr Ty Pitt’s lecture. He is the very experienced microbiologist from Colindale who works with the Brompton CF Unit, giving his clear support to the recent recommendation of the CF Trust infection Control Group on the control and prevention of Pseudomonas infection. This included the strict segregation of Pseudomonas aeruginosa positive patients from those who are negative. Also he emphasised the importance of regular microbiological surveillance of those who are already chronically infected.

 I met Karen Giles from Bath who has been appointed and is now NHS funded to run the South and West CF Database. We agreed to keep in contact to ensure they would also enter data into the UK database. I came away really encouraged.

Feb. 5th. CF Trust Branch Meeting in Glasgow

I gave a general CF lecture at the Glasgow branch which went well – there was a big attendance of parents and professionals..  I was very pleased and flattered to see one of the lecturers who had been in Prof. Monty Losowsky’s department at St James’s, Richard Brown, now a consultant gastroenterologist in Glasgow, turn up to the lecture. He had done some research with us on the use of cimetidine.  He was a very nice chap as were all Monty’s staff. We had a very good relationship with the Department of Medicine in St James’s that resulted in a considerable amount of research. I would go as far to say our liaison with Monty’s Department of Medicine was a major factor in the acknowledged success of the St James’s CF unit.

Feb. 14th CF Trust Nutrition Group Hawley Hotel Sheffield

 This group meets in Sheffield and is moving at a rather leisurely pace. The lead authority on CF nutrition is Prof. Chris Taylor from Sheffield Children’s Hospital. The Group used to meet at a nice little pub near to the Children’s Hospital that did very good burgers.  The CF Trust funded a number of these groups who produced valuable guidelines on various aspects of CF care, not only based on published work but practical experience of professionals, doctors, nurses, physiotherapists, social workers, pharmacists, laboratory workers treating many people with CF and always with a patient or parent representatives.

Feb. 16th-18th  Emily our granddaughter from Cardiff came to stay

Emily – photo around that time

She was very well-behaved and it was a pleasure to have her stay. Her parents went for a rare weekend break.

Feb. 22nd  Went through a booklet for CF adults that is being sponsored by Solvay. Following this I had a 2 hour phone call with Elaine Evans, Product  Manager of Solvay, with suggestions for some slight changes.

Millie in 2003

Feb.23rd – 24th Millie stayed with us for few days

She was also very well-behaved and it was a pleasure to have her stay. Her parents also went for a rare weekend break.

March 3rd. Attend interviews for the new Scientific Director.                   It proved to be a very interesting day. I was particularly impressed by the value of the psychologist’s assessments. I look forward very much to working with a new scientific director.

March 6th. Accompany Rosie Barnes to meet the Health Minister at the Department of Health

                Richmond House

At 2.30 pm Rosie and I met the then Minister of Health, Yvette Cooper, in her imposing office at the Department of Health to discuss the question of Neonatal CF Screening (NCFS).   Richmond House, 79 Whitehall was the headquarters of the Department of Health and Social Care until 2017. 

The introduction of national neonatal CF screening had been a top priority for the CF Trust since 1996. However, the UK National Screening Committee had recently failed to recommend the countrywide introduction of NCFS  as they considered there was insufficient evidence of long term benefit. However, already a number of progressive areas and regions in the UK, relying on experience and common sense, had started neonatal screening – some for many years e.g. our own program in East Leeds started in 1975, and Anthony Heeley’s in East Anglia from 1980.

The CF Trust was mounting a vigorous national campaign that NCFS should be introduced nationally – the need was so blatantly obvious to anyone dealing with CF children, many of whom were not diagnosed until their lungs were permanently damaged. A national UK survey that we performed at the CF Trust showed that paediatricians who were responsible for treating such infants were well aware of the situation and were unanimous in their strong support for neonatal CF screening. However, the UK National Screening Committee (NSC), who lacked such experience, required published evidence of significant long term benefit before they would recommend national NCFS. 

Fortunately, in 2001, there was an important publication from Professor Phillip Farrell’s unit in Wisconsin which showed that screened infants, diagnosed and treated from the first weeks, had significantly better growth measured  in later childhood – even though Professor Nick Wald of the NSC considered the paper to “provide no evidence of any benefits of screening”. I wrote a 16-page reply to further outline the case for NCF screening!.

Prof. Philip Farrell
Farrell PMKosorok MRRock MJLaxova A, Zeng LLai HCHoffman GLaessig RHSplaingard ML. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group. Pediatrics. 2001 Jan;107(1):1-13.
Yvette Cooper later in 2001 with her new baby and Husband Ed Balls

Yvette Cooper listened carefully to what Rosie and I had to say and agreedwith us Prof. that it was obvious that neonatal CF screening should be introduced nationally; she understood that a number of regions had already introduced it. Certainly Phil Farrell’s 2001 publication from Wisconsin was very helpful in showing definitely better growth of screened infants.  So Yvette Cooper gave us a fair hearing and soon after, and surprisingly against the advice of  the National Screening Committee, agreed that national NCFS should be introduced in the UK.

This was the end result of 5 years of heavy pressure by the CF Trust, a victory for common sense and a defeat for the really obstructive National Screening Committee – a result which incidentally the committee understandably did not like.

     David Elliman

After the UK Government’s decision, following this 2001 paper of Phil Farrell’s, the Child Health Group of the UK National Screening Committee remained unconvinced! Even in 2002, after the Government  had agreed to neonatal CF screening in 2001, Dr David Elliman, Chair of the Child Health Subgroup of the UK National Screening Committee, a London community paediatrician, wrote in the Archives of Disease in Childhood that the National Screening Committee (NSC) concluded that there was currently insufficient evidence of longer term benefit, specifically in relation to pulmonary function, to support implementation of newborn screening. Elliman then adds, without any comment, “subsequently a ministerial decision was made in July 2001 to formally introduce screening in England followed shortly by a similar decision in Scotland” (Elliman DAC, et al. Arch Dis Child 2002; 87:6-9.) This erroneous view was still held by the NSC in 2005. I have always been grateful to Yvette Cooper since then; and had grave  doubts about the judgement of the National Screening Committee!

Prof. Howard Cuckle
Dr Jenni Murray

Addendum: I am still unhappy (in 2022) about the situation regarding CF screening for although national neonatal screening was finally fully implemented by 2007, antenatal screening is still not routine in the UK. In 1999 we were asked to produce a Health Technology Assessment coordinated by Dr Jenni Murray and Prof. Howard Cuckle from the Centre for Reproduction and Growth & Development, Research School of Medicine University of Leeds.

Murray J, Cuckle H, Taylor G. Littlewood J, Hewson J. Screening for cystic fibrosis. Health Technol Assess. 1999;3(8)

Our HTA group concluded that evidence supported the following actions – 

  1. Antenatal genetic screening should be offered routinely 
  2. Preconceptional genetic screening should be made available to those who requested it
  3. Genetic screening should be available for infertile men and sperm donors
  4. Testing should be undertaken by laboratories with an annual throughput of at least 5000 tests 
  5. Health authorities could consider introducing neonatal CF screening. 

It is disappointing that even by 2022 although neonatal CF screening is finally nationwide since 2007, antenatal screening is still not routine in the UK.

 March 22-25th. Fly with Ann to Artimino in North Italy to take part in the European CF Society Consensus Group on Nutrition in CF.

La Villa Ferdinanda – Villa of a hundred chimneys

Artimino is a pretty hill village near Florence and “accompanying persons”, my wife Ann, were also invited. There were a number of these meetings at Artimino organised by Prof. Gerd Döring, the then President of the European Cystic Fibrosis Society. Some 30 or so participants from around Europe with a special interest and experience in a one particular area of cystic fibrosis care would spend the weekend at a two-day workshop putting together guidelines on a particular aspects of treatment – on this occasion it was the ECFS Consensus Group on Nutrition in CF.

Ann with our dietitian Sue Wolfe
 It was not all work!

Our accompanying guests, wives and partners would  have a great time looking round Florence and the local sights, while we participants from most European countries were    working on  the Nutrition Consensus! The evenings were very enjoyable and good for getting to know others from around Europe and their accompanying persons.

The Medici Villa “La Ferdinanda” is situated among the hills and vineyards of Montalbano, in a dominant position on a hill which had already  hosted a sacred area at the time of the Etruscans. It was built in 1596 at the behest of Grand Duke Ferdinando I de ‘Medici, according to the project by Bernardo Buontalenti . “I  was today at Artimino and believe me Your Highness that I have found for you a Spring,” the Grand Duke wrote to his wife Christine of Lorraine on January 19, 1596. The villa, built as a hunting lodge, was completed in just four years and represented a kind of link between the various land properties of the family; a place dedicated to humanistic arts and poetry.

The 2001 Artimino Nutrition Group

Some members of the group identified in the photo -1. Gerd Doring 2. Eitam Kerem  3. Carla Colombo  4. Birgitta Strandvik  5. John Dodge  6. Harry Hiejereman  7. Chris Taylor  8. Sue Wolfe  9. Stuart Elborn  10. Felix Ratjen 11. Martten Sinaasappel  12. Jim Littlewood  13. Eddie Robrecht

There were a number of future Artimino meetings which we were fortunate to attend. Sue Wolfe our expert paediatric dietitian from St James’s attended this particular meeting in 2001.

The report was subsequently published and I presented the report on behalf of the group at the Vienna ECFS meeting

Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G, Heijerman H, Robberecht E, Döring G. Nutrition in patients with cystic fibrosis: a European Consensus. J Cyst Fibros 2002; 1:51-75.

 March 28th.  Appearance on Yorkshire TV re. neonatal CF screening

I was due to appear on Yorkshire TV with Sonny Laing, a young lady with CF f who had a heart-lung transplant at 5 years old.   Sonny lived in Tadcaster, a small town between Leeds and York – just outside the Leeds boundaries where there was no neonatal CF screening. Had she lived a few miles further west nearer Leeds she would have been screened in our East Leeds program.         

Miss Sonny Laing (with permission)

Sonny was treated in another city but not diagnosed until her chest was badly damaged.  She had recently won a CF Trust Achievers Award.   

Unfortunately Sonny was not allowed to appear with me on this occasion, as she did not have the necessary clearance from the Education Authority, now very strict about these matters. However, she made a subsequent appearance on Dr. David Bull’s TV programme and displayed her really impressive gymnastic skills! 

Sadly, in her Twenties, her chest became progressively worse and she died aged just 23 years.  She was well known and very popular in her home town of Tadcaster. When severe floods washed away the old bridge across the river Wharfe, the town named the new bridge after her – The Sonny Brogan-Lang Bridge. 

It was seeing many such children referred to my CF unit during  the Eighties, whose lungs were irreparably damaged before they were diagnosed, that made those of us involved with CF care so doggedly determined to see all UK infants were screened for cystic fibrosis.

March 29th. Meeting of the Clinical Trials Advisory Group (CTAG), London                                                                                                  I had asked Ros Smyth to chair our CTAG as she had a particular interest and expertise in clinical trials. The Clinical Trials Advisory Group (CTAG) made a steady and important contribution to raising the standards of CF clinical research and investigation. 

We subsequently invited Dr. Anil Mehta, who with his wife Gita, organized the first UK CF Database to join CTAG. Many of the questions answered by clinical trials can, to a variable extent, be answered by analysing the increasing amount of reliable patient data held in the UK CF Database.

March 30th. CF Trust Medical Meeting at Imperial College, London.   

This was a new venture organised by Sandra Kennedy and her colleagues at the CF Trust.  It replaced the Hon. Medical Advisors Meeting, which had become an anachronism in recent years.  Essentially the content was a review of current best practice for all those involved in treating people with CF. This was important for the many professionals, mostly paediatricians, who treat relatively small numbers of children on a shared care basis in district general hospitals rarely attend European or North American CF meetings. 

We had really excellent speakers at this first meeting (Duncan Geddes (Brompton), Andy Bush (Brompton), Di Bilton (Cambridge), Kevin Webb (Manchester), Sue Wolfe (Leeds), Chris Taylor (Sheffield); Ammani Prasad (Greta Ormond Street), Glenda Esmond (Respiratory Nurse Specialist), David Heaf (Liverpool)and Anil Mehta (Dundee).  There was plenty of time for discussion and the meeting was judged a great success; also the feedback was almost uniformly very enthusiastic. 

             Imperial College London

For the first time at a CF Trust meeting a small charge was made to cover costs and there were very few complaints – also it did ensure that everyone who registered turned up which was not always the case with free meetings! It was suggested that the CF Trust should hold such a meeting every two years and this did occur for a number of years.

April 5th. Attended “Achievers Awards” evening in London.

Dr David Bull

These awards were presented by the CF Trust to people with CF who had shown unusual courage or achievement. Dr David Bull’s firm organised the meetings to choose the winners of the various groups. At the time David was well known television personality and he and his firm organised  the presentation of the awards on the night. David subsequently became a member of the European Parliament in 2019 and in 2121 Deputy leader of Reform UK 

Ann and Alison Morton with author Bill Bryson

We were highly impressed by the scale and professional presentation of the whole affair and by the number of well known personalities who attended such as author Bill Bryson. It was particularly good to see Sonny Lang (mentioned above on 28.3.01), receive her award and see a video of her gymnastics. 

Sadly, as the national financial situation became more difficult over the next few years the income of the CF Trust was affected. The expense of these Awards was high (about £150K) and even though there were major contributions from pharmaceutical firms, the expense to the CF Trust was a cause for concern for the Trustees and eventually the Awards were stopped.

April 2001. Visit Sarah and Richard in their house at 13 Amesbury Rd, Cardiff.

Dinner at Sarah and Richards with Dan and Chris Evans and Emily

Here we are having dinner in their dining room with Chris Evans, Dan Evans and Emily. Unfortunately, during a delicious meal of salmon Ann had a quite severe allergic reaction – we believe due to the ginger used in the cooking. Thank goodness this has never been repeated as she really looked dreadful with pale sweaty skin and very slow pulse. She now carries an adrenalin syringe at all times and fortunately has had no further serious food reactions. 

                                                                      April 30th. Gave talk on CF to the Sixth Form Science Club at Leeds Grammar School. 

       Monty Losowsky

Monty Losowsky, the retired Professor of Medicine at St James (an old friend and colleague), asked if I would do this. 

I used PowerPoint presentation for the first time after much coaching from Ann! It went very well and I subsequently always used PowerPoint for lectures instead of slides. They sixth form were an attentive and interested audience. 

 It was good to see one 16-year-old young man in the audience who had CF and who had attended my clinic at St James’s from birth; we had a nice chat afterwards. It made my day seeing him looking so well!

May 1st. Wrote to the Editor of the Archives of Disease in Childhood about neonatal CF screening.

    Harvey Marcovitch

I wrote to Harvey Marcovitch, as the ‘Archives’ published a one-page review stating there is still insufficient evidence to recommend neonatal CF screening!  We had already obtained agreement of the Health Minister, Yvette Cooper, that screening would be introduced in the UK.

David Elliman

In 2002, after the Government  had agreed to neonatal CF screening in 2001, Dr David Elliman, Chair of the Child Health Subgroup of the UK National Screening Committee, a community paediatrician, wrote in the Archives of Disease in Childhood that the National Screening Committee (NSC) concluded that there was currently insufficient evidence of longer term benefit, specifically in relation to pulmonary function, to support implementation of newborn screening!!!!

Elliman then adds, without any comment, “subsequently a ministerial decision was made in July 2001 to formally introduce screening in England followed shortly by a similar decision in Scotland” (Elliman DAC, et al. Arch Dis Child 2002; 87:6-9) This view was still held by the NSC in 2005! 

I have always been grateful to Yvette Cooper since then; and had grave doubts about the judgement of the National Screening Committee! Harvey Marcovitch assured me that the views expressed in the Archives are quite independent of the College and advised me to write officially – which I did to Sir David Hall the President.  However, by this time I was increasingly disillusioned with the College (RCPCH) and on this issue in particular.  It was time to move forward, to work out how screening will be implemented in those backward areas not already screening, not whether it should be introduced – that had all been agreed.  

I am reluctant to observe that the paediatricians’ college (BPA and now RCPCH) has never done much for CF over the years starting with the BPA Council’s rejection of the first CF Working Party report in the early 1980s in which we recommended CF Centres. At the time it was an unacceptable concept to some senior old school “walk-on-water” consultant paediatricians who considered they could treat everything; also some wanted a few “cystics” for “teaching purposes” !  Oh Dear, let’s move on.

May 3rd. Princess Alexandra, our Patron, visits the CF Trust HQ in Bromley.


                Princess Alexandra visits the CF Trust HQ in Bromley.                                                                                (L. to R). Mayoress and Mayor of Bromley, David Stickels (Finance Director), Jim Littlewood (Chair of Research and Medcial Advisory Committee), Duncan Bluck (Chairman of the CF Trust)                                                                     

It was very interesting to meet Princess Alexandra again.  I have a picture of meeting her with Ann some 15 years ago with Joe Levy (the first Chairman and a founder of the charity) and Ron Tucker (the first Director), I think at a CF function at the Savoy.

May 1st. Ann’s 60th Birthday weekend in Bardsey 

We had a really good weekend with many members of the family and some neighbours – just those staying are in the photo around the table.

 

Family and neighbours came to the cheerful party
Ann’s 60th birthday at Bingley Bank, Bardsey (apologies for picture quality). L.to R. Lewis Haines, Jim Whitehead, Ben Haines, Nick Haines, Jim, Ann, Katie, Elliot Haines, Susan and Emily Evans in the foreground.

 May 15th. Publications Committee at  Bromley.   

There are now a number of publications both for the public and professionals, which are ready, or near ready – I chair most of the meetings and the whole operation is ably coordinated by Sandra Kennedy the Publications Manager of the CF Trust. We work well together as editorial team for the CF Trust publications – always seeing who can spot the most “typos” in the drafts of the new documents!    IMy main concern was the guidelines for professionals, although these were available to anyone on request. The main guide was “Standards for the clinical care of children and adults with cystic fibrosis”   

I have described the history of this document in the January 24th 2001 entry above

This present report of the 2001 Working Group, chaired by myself (Jim Littlewood who by then had succeeded Tony Jackson as Chair of the RAMAC), was still widely used until it was replaced by an extensively revised 2nd edition in 2011 chaired by Dr Ian Balfour-Lynn and Dr. Sue Madge. (The full text of 2nd edition Dec 2011 is available on the CF Trust website (www.cysticfibrosis.org.uk).

Addendum:  It is hard to believe that now (in 2022) it is over 18 years since we first wrote and published the 2001 CF Trust Standards of Care document. The meetings, for all to agree the various recommendations in the first document, were frequent, long, hard work and often heated but the advice has stood the test of time over the decade until the second extensively revised and excellent 2nd edition was published in 2011. The major changes in management have concerned the problem of cross infection with P. aeruginosa. Also the 2011 edition was published at the start of the CFTR modulator era which was followed by dramatic changes in CF management, treatment and outlook.

May 27th. CF Foundation. Infection Control Consensus Meeting at Bethesda, Washington.

I was invited to present the CF Trust’s recent documents on Burkholderia cepacia and Pseudomonas aeruginosa as I had chaired both CF Trust committees and essentially written the documents on behalf of   the committee. They were both well received. at the meeting                      Some 30 people attended the US meeting.

There were three of us from Europe – Prof. Niels Hoiby (Denmark), Prof. Gerd Döring (Germany) and myself.

             Gerd Döring
              Niels Hoiby

Over the course of two days the group produced guidelines for infection control for people with CF in the USA. The final recommendations would be presented at the October North American CF Conference in Orlando.  We Europeans did dissent from some of the recommendations – particularly the total segregation of all patients with CF (not just according to their microbiological status) and the wearing of masks by patients at all times except in the consulting room. 

The CF Trust seemed to be at the ‘cutting edge’ in this area and we are very fortunate to have such experts as Prof. John Govan (Edinburgh), Prof. Tony Hart (Liverpool) and, more recently, Dr. Ty Pitt (London, Colindale) on the CF Trust’s Control of Infection Group. 

Prof. Tony Hart a distinguished clinical microbiologist and co-founder of the UK’s National Centre for Zoonosis Research, died in 2007 from a cerebral haemorrhage.

The European CF Society is now considering setting up a similar Consensus Group to deal with issues of cross Infection.   

June 3rd We travel home to UK from Washington

June 5th. Travel to Vienna for the Annual European CF Society Conference.

                          Hofburg Palace

This was a good meeting in the impressive buildings of the Hofburg Conference Centre – the acoustics and layout of some of the rooms are more suited to state occasions than scientific presentations!  

I discovered that I was chairing the first scientific session shortly before it started and had two rapid taxi rides to and from our hotel to put on appropriate shirt and tie!  I really must study the programmes more carefully. 

     Inside the Hofburg Palace

 The next day I presented the main findings of the European CF Society’s Consensus on Nutrition from the recent Artimino meeting on behalf of the Group. This is quite a different group to the UK CF Trust Nutrition Group but three members of our UK group were invited to attend this European Group – Sue Wolfe (Leeds), Chris Taylor (Sheffield) and myself (Leeds).

Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G, Heijerman H, Robberecht E, Döring G. Nutrition in patients with cystic fibrosis: a European Consensus. J Cyst Fibros 2002; 1:51-75.
CF Trust team Jim L, Dad Stickels, Lorna Leyward (the new Scientific Director, Ann and Rosie Barnes

In general, the Vienna meeting was very clinically orientated. The ‘heavy science’ seems to be more a feature of the North American CF Conferences.  However, when this is the case, most people appear to enjoy the meeting as most are dealing with patients rather than basic science and are keen to improve their clinical practice. Finally we had time to enjoy a concert of Viennese music.

 

June 12th – 14th Stay in Cardiff at the Llanerch Vineyard B&B

     Llanerch Vineyard & B&B

Purpose of our visit was to help Richard and Sarah with the move to their new house in Stella Maris Close, Radyr.

We had a very pleasant stay at this B&B and the wine was good, if quite expensive – if one’s used to Morrison’s supermarket special offers! 

We stayed here on a number of occasions when we visited Cardiff.

 

 

June 27th. CF Trust Control of Infection Group

We had a good meeting where the group received the new CF Trust document Pseudomonas aeruginosa infection in people with cystic fibrosis – suggestions for prevention and control”
We were all delighted to see that this document eventually agreed and printed after it’s stormy passage over the past year. The document has been sent to all CF clinical staff, microbiologists and infection control committees. Although it is not written primarily for patients and parents (Sarah Walters has written an excellent version for them) they can have a copy if they wish on request from the CF Trust.

The main discussion at the meeting concerned the type of microbiological surveillance which should be recommended in the UK centres and clinics, to identify the presence of the so-called “highly transmissible strains” of  P. aeruginosa, such as those identified in Liverpool, Manchester in Melbourne. These strains are passing between patients who already have Pseudomonas aeruginosa infection. There is a big debate as whether Pseudomonas positive and negative patients should be segregated from each other. The group, as a stated in the document, is firmly in favour of segregation according to microbiological status

June 29th. Visited Sarah Pierce, the CF Trust’s advocate at the Adult Clinic at the Northern General in Sheffield.

Northern General Hospital Sheffield

Rosie suggested I become involved in the Trent Region CF service Implementation Team and Prescribing Subgroup. I welcome this opportunity to gain practical experience of these new arrangements and help Sarah wherever possible. We discussed the progress that has been made up to the present which is quite impressive. I’m looking forward to attending my first meeting in July.

The Northern General Hospital is a large teaching hospital and Major Trauma Centre in Sheffield, England. Its departments include Accident and Emergency for adults, with children being treated at the Sheffield Children’s Hospital on Western Bank.

 June 30th. Sue’s birthday party at 12 Cliff Way Nottingham

                       Sue’s family birthday party in their conservatory

Good family party – their house and garden are very good for a family party with the conservatory from the kitchen opening out into the extensive private back garden.

July 5th. UK Pharmacists Group Meeting in  Leeds

          Helen Cunliffe

I gave a talk on the CF Trust new “Standards of clinical care of children and adults with cystic fibrosis” as mentioned above. The document has just been printed and has been generally well received. Most regional commissioning groups when planning at CF services are already using the final draft which they requested before the final printing. This certainly makes all the hassle worthwhile. The meeting was arranged by Helen Cunliffe the very helpful pharmacist who for many years was advisor to our CF unit at St James’s and was an essential member of our CF team attending  our weekly CF ward meetings   The complexity of the drug treatments made close involvement by a pharmacist essential. We were lucky having Helen’s involvement at St James’s.

July 6th. Meeting at the Royal College of Physicians, London. 

“First isolation – decisions facing the clinician on first isolation of Pseudomonas aeruginosa“.  

To most UK and many European CF clinicians there is no great decision to be made – if Pseudomonas aeruginosa grows from a respiratory culture in a person with CF, it is treated vigorously with nebulised and oral antibiotics and usually eradicated. This applies whether there are symptoms or not.  Current best practice, agreed by the CF Trust’s Antibiotic Group, for dealing with first growth of this organism is described in detail in the CF Trust’s  “Antibiotic Treatment for Cystic Fibrosis” published in 2000. Most UK clinicians now follow this advice. It is not the rule in N America.

 There is still considerable debate in North American CF Centres as to when and how to treat the first positive P. aeruginosa culture, which is difficult for us Europeans to understand. Although there are now only a minority of clinicians, usually adult chest physicians (surprisingly one such being Duncan Geddes at the Brompton), who doubt the fundamental importance of chronic Pseudomonas infection and of preventing such infection.There is still wide variation in the proportion of patients who have chronic infection in different CF clinics reflecting different treatment practices – or lack of treatment practices!  Two clinics that have practiced early treatment of Pseudomonas from the first positive culture and segregation from the 1980s are Copenhagen and Leeds.  Chronic Pseudomonas infection is now present in less than 4% of Leeds children and in Copenhagen none below 11 years are chronically infected.  Yet at this time in the USA and Canada well over 50% of children already have chronic P. aeruginosa infection by the age of 10 years.

The meeting was good even if the talks were somewhat repetitive. In the afternoon, following a debate on “This house proposes segregation of CF patients according to their microbiological status” only slightly more than half the audience were in favour of segregating Pseudomonas positive and negative patients – really difficult to understand when one supposed to be giving optimal treatment?  Surprisingly, Duncan Geddes of the Brompton, a leading authority on CF, was one of those opposed to segregation. Rosie Barnes pointed out that patients and parents were in no doubt – they all approved of segregation!

July 7th. TOPIC  Trial Investigators’ meeting. City Hospital Nottingham

This trial is designed to determine whether the daily dose of intravenous tobramycin is as effective and as safe when given as a single daily dose or when divided into three doses given eight hourly.  There have been problems with recruitment of patients and Dr Alan Smyth, who is the principal investigator, and his colleagues have learned a great deal about the difficulties of organising a multicentre trial. However, the numbers are steadily increasing and already there is a great deal of valuable data.  It is encouraging that there are a group of young clinic directors who are keen to develop and build on experience gained in this trial.

Addendum: Alan Smyth went on to complete the trial, regarded as a great success and the findings successfully altered practice to the advantage of many patients and staff.

2005 Smyth A, Tan K H-V, Hyman-Taylor P, Mulhearn M, Lewis S, Stableforth D, Knox A, for the TOPIC study group. Once versus three-time daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis – the TOPIC study: a randomised controlled trial. Lancet 2005; 365:573-578. [PubMed]

This  important trial the results of which had a definite influence on patient management. 219 patients (107 had once and 112 thrice daily tobramycin) and both regimens were of equal efficiency for treating pulmonary exacerbations. There was a suggestion that the once daily regimen might be less nephrotoxic in children.
The results of this trial allowed the once daily treatment to be confidently recommended by the CF Trust’s Antibiotic Group (2009) for both adults and children with CF.
The trial also resulted in a number of other publications on pharmacokinetics, lack of ototoxicity and nephrotoxicity as follows –

2006 Mulheran M, Hyman-Taylor P, Tan KH, Lewis S, Stableforth D, Knox A, Smyth A. Absence of cochleotoxicity measured by standard and high-frequency pure tone audiometry in a trial of once- versus three-times-daily tobramycin in cystic fibrosis patients. Antimicrob Agents Ch 2006; 50:2293-9.  [PubMed]

The authors undertook the assessment of hearing in patients with cystic fibrosis who were taking part in this large randomized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis (the TOPIC study). Complete pre- and post treatment standard audiological data were obtained for 168/219 patients. They found no significant differences in hearing thresholds when they were assessed at the baseline, at the end of treatment, and at follow-up 6 to 8 weeks later were compared. In addition, no significant differences in hearing thresholds were detected between treatment regimens. Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry.

July 20th. Visit the Birmingham International Conference Centre

Birmingham Conference centre (in 2004)

Visited with Rosie, Davidels and Sandra Kennedy to inspect the facilities for the 2004 International/European CF meeting. Also invited were Gerd Döring. President of the European CF Society and Herman Wigan, President of ICFMA. All agreed at this International Conference Centre would be an excellent venue for the meeting.

 

July 25th. Visited at home by Mr. Malcolm Murray

Malcolm Murray is a retired NHS regional finance director who has been commissioned by the National Screening Committee (NSC) to look into the cost of introducing national neonatal CF screening. The NSC is due to discuss his findings in early September. We have been reassured that the NSC decision to introduce CF screening is quite firm and all attention is now been given to implementation.  Malcolm was very clearly on our side.

Addendum: Nationwide neonatal CF screening was eventually agreed in 2001 by the Government and achieved nationwide by 2007

July 27th. Attend the Northern CF Club in Manchester

Aug. 13th.  Visit Dr. Mary Carroll’s Specialist Adult CF Unit at the Southampton General Hospital with Rosie.  

Dr Mary Carroll

Mary Carroll, a cheerful and highly regarded chest physician, requested I visit to hear of their current research and offer comments on the content and relevance. They had recently had a number of grant applications rejected by the CF Trust. I listened to presentations from 10.0 am to 5.0 pm (with a short toilet break at 1.0 pm!).  Nevertheless, although exhausted, I was very impressed by the enthusiasm and good atmosphere in  this relatively recently established adult CF centre.  

An enthusiastic Australian CF fellow, Dr. Serisier, presented three projects on synergy testing of sputum samples, the use of inhaled heparin and the value of intravenous micronutrients during courses of intravenous antibiotics.  

After the discussion I suggested they seek the opinion of our Clinical Trials Advisory Group (CTAG). CTAG considered the protocols, and Prof. Ros Smyth (Chair of the CTAG) contacted the Southampton group with their suggestions – modifying the first two and abandoning the third. None seemed worth funding to me – but that was a personal opinion!

 August. Sally, Ann’s friend from childhood visits; also Dan, Chris and Jo Evans came to see us.

Aug. 16th. Trent Regional Implementation Group

I attended my first meeting of this group which Rosie suggested I should attend to support the local CF advocate Sarah Pierce.  The meeting was at Brigg near Hull and largely involved deciding who was going to pay for CF care at the present

Aug. 30th. UK Database Steering Committee meeting. London.

The committee considered various matters the most important being the relation between the Clinic Improvement Grants and the completion of data and submitting it to the UK database. This was further discussed at the Clinic Directors meeting. 

Sept 3rd & 4th. To Bristol to visit Nabil Jarad’s developing adult CF unit with Rosie.

       Dr Nabil Jarad

We were both impressed by this developing Adult Centre which was suffering the common problems of understaffing. The CF Trust had helped upgrade a ward for CF adults. Rosie considered the unit should be further developed and agreed to consider ways in which the CF Trust could help. 

Nabil Jarad did not continue his interest in CF. I’m not sure of the reasons.

 

Sept. 9th. Travel to Sydney Australia to help with our new grand daughter

Lowri Megan Evans aged 6 days
The new Evans family in their flat in Balmoral

The main purpose of our visit being to help with our new granddaughter, Lowri Megan Evans who was born in Sydney on 5.9.01 and her 3 year old sister Emily. We arrived when Lowri was 3 days old and stayed for about 5 weeks.
Sarah, Richard and Emily were living in a modest 2nd floor flat on the front in Balmoral.  There was an excellent fish and chip shop on the corner below and wine merchants on the ground floor immediately below the flat. There was a wonderful view over the bay from their flat and we had many pleasant dinners in their lounge overlooking the bay. We rented  a car and a flat a short distance away from them.  

Sept.11th. TERRORIST ATTACKS IN THE USA

Smoke billows from World Trade Center’s north tower as the south tower explodes after it was struck by United Airlines Flight 175.
Hijacked United Airlines Flight 175, which departed from Boston en route for Los Angeles, is shown in a flight path for the south tower of the World Trade Center on Sept, 11, 2001, as the north Tower burns after American Airlines Flight 11 crashed into it at 8:45 a.m (by .Robert Clark, Associated Press)

 

 

 

 

 

 

 

 

 

 

 

I first heard of these terrorist attacks during the night while listening to the BBC Overseas Service news on a small radio in our flat in Balmoral.  Initially I thought I was having a bad dream but then went into the lounge, turned on the television and saw the dreadful scenes from New York. Although it was quite horrendous one did feel somewhat remote from it all in Sydney.

Despite these awful happenings elsewhere, we found Sydney and particularly Balmoral was a great place and the weather marvellous, food and wines very good and reasonable, there being almost 3 A$ to the £. – although perhaps the wines were not as reasonable in price as I thought they would be. What was impressive were the young men serving in the wine shops who were polite and very knowledgeable about their wines.

             South view from the flat
Looking north from their flat 
Ann and Emily on Balmoral beach
      Balmoral Promenade looking north

 

 

 

 

 

 

Sept. 20th. Invited to give a lecture at the headquarters of CF Victoria in Melbourne. 

The Melbourne CF Association heard I was in Sydney and invited me to give a talk there at their headquarters. We were lucky that Ann had booked flights from Sydney to Melbourne with Qantas as the Australian internal airline, Ansett, went “bust” and all their flights were cancelled. 

Prof. Bob Williamson

The talk in Melbourne went well.  I was delighted, and I admit flattered, to see Prof. Bob Williamson who came along to hear my talk; Bob sent his regards to all his friends in the UK.  Bob was one of the leading CF Researchers at St Mary’s, London during the 80’s and made a significant contribution to identifying the CF gene. Now he was only involved in CF in an advisory capacity and had a number of other interests including discovering the gene for heroin addiction. He moved to Australia in 1995 to be  Director of the Murdoch Childrens and Professor of Medical Genetics at the University of Melbourne. 

The Melbourne CF clinics are well aware of the potential dangers of transmissible Pseudomonas aeruginosa having had one particular strain spreading around their paediatric clinic with serious results.  Their organism has been sent to John Govan in Edinburgh for further investigation and characterisation. The dangers of certain strains of P. aeruginosa spreading round a CF clinic were now becoming more generally appreciated.

After the Melbourne meeting we had a pleasant dinner with Jenny Reece (the new CEO), the President of CF Victoria and three members of the board. The next day we flew back to Sydney without incident.

Sept. 22. Sydney Opera House to see Barber of Seville

        Off to the Sydney Opera House
Sydney Opera House concert

Sarah and Richard surprised us with 2 tickets to the Sydney Opera House to see this opera; it was absolutely superb.   

                                                         Inside Sydney Opera House

 They said this was a reward for helping in “Grandpa & Grandma mode” for most of our time there! However, we both enjoyed our stay immensely – to the extent that we later did a return trip!

Sept. 26th  Invited to give a lecture at the weekly meeting of the Respiratory Physicians at the Royal Prince Alfred Hospital, Sydney.

St Vincent’s Hospital Sydney – CF Adult Unit

This is where the main Sydney Adult CF Centre is situated (160 patients).  Dr.   Peter Bye, whose name is linked with the use of hypertonic saline, is the clinic director.  My talk was “CF in the UK in 2001 – Some current issues”.  

Australians seem to like the word ‘issues’ and I noticed on my last trip here that it was used frequently by the lady that escorted us round the various Australian CF Centres.
This lecture seemed to go well and stimulated considerable discussion. The various more recent CF Trust documents on Standards of Care, Pseudomonas cepacia, Antibiotics, etc. have been very well received in Australia. In fact, the Australian Standards of Care is based on our UK document and this is acknowledged.

Sept. 28th. Invited to spend the afternoon at the Royal Prince Alfred Adult CF Unit. 

Dr Peter Bye

Peter Bye invited me back for a smaller seminar with just the staff of the CF Unit to discuss various issues, which they raised, mostly relating to infection and research. We had a really good discussion for a couple of hours. 

 

 

 

Oct. 4th. Visit the headquarters of New South Wales CF Association (CEO Helen Griffiths) and Cystic Fibrosis Australia (CEO Terry  Stewart). 

     Terry Stewart
        With Helen Griffiths my next vist

We had a wide-ranging discussion on a variety of CF subjects including how our medical advisory system works. They are both very pleasant people and we also had an excellent lunch at a nearby hotel!  We agreed to meet again on my next visit. 

The Australian system is complicated by the fact that the state CF organisations are very strong which makes life difficult for the national CF Australia.  A significant proportion of the state funds go on their running costs and patient care leaving only very modest amounts for research.  

The national organisation is now concentrating on research, national standards and the national database. We are certainly fortunate to have the CF Trust as the only CF organisation in the UK.

Helen Griffiths was a very pleasant lady and we had lunch together on my next visit. Terry Stewart also a nice chap who eventually became CEO of CF Worldwide

Oct. 11th. Ann and I return to the UK  

The weather here in Sydney is like a really good English summer. As I look out from the balcony of our daughter and son-in-law’s second floor sea front apartment with its panoramic views of Balmoral Bay, we seem to be so distant from autumnal London. Balmoral is one of the many northern bays of Sydney Harbour and much admired by Bill Bryson in his book ‘Down Under’ – 

“Balmoral with a sheltered beach overlooking Middle Harbour and a splendid waterfront park shaded with stout Moreton figs, the loveliest tree in Australia by far. A sign by the waters edge noted that if you were eaten by sharks it wasn’t because you hadn’t been warned.” 

As yet, we have seen none of the dreadful poisonous insects and reptiles Bill Bryson describes in such lurid detail, such as the taipan snake – “the most poisonous snake on earth with a lunge so swift and venom so potent that your last mortal utterance is likely to be “I say, is that a sn–“!!  

The weather, food and wine were excellent and the Sydneysiders very pleasant. There must be something wrong with life in Sydney but it’s difficult to spot it!  In fact, I kept drifting off into a very worrying “Grandpa-on-holiday” mode. It’s a good job we’re returning to UK next week, world situation and airlines permitting, and will be getting back to a more normal routine with the now quite demanding CF Trust work.

Oct. 17th. Clinic Improvement Grants (CIGS) –

Had a discussion with Rosie, Lorna Leyward and Carol Eagles about these grants.  The Directors of Specialist CF Centres seem to have accepted the principle of linking the payment of CIGs to providing annual data of their patients to the UK CF Database.  I’ve heard one or two “rumblings” about “heavy handedness” of the CF Trust but once the large Centres realised they may be slightly better off with the new scheme, things have settled down. 

By contrast enzyme intakes of Leeds patients
Anil Mehta’s Lancet letter
     Dr Erika Sims

The UK CF Database is now really beginning to bear fruit – using the data Anil Mehta had a letter in the Lancet (figure) recently showing that many UK patients were still taking more than the recommended dose of enzymes (10,000 IU lipase/kg lipase daily). The data he produced on neonatal screening with Dr Erika  Sims when she was working at the UK Database provided significant support for various advantages of national neonatal CF screening e.g. diagnosis after 2 months leads to worse outcomes and requires more therapy (17200267), NCFS is beneficial even in the context of modern treatment (16202781), NCFS is associated   with reduced treatment intensity (6182666), economic implications newborn screening for cystic fibrosis may favourable financial implications (17416263) [these are PMID numbers to locate abstracts on PubMed]

2002 McCormick J. Green MW. Mehta G. Culross F. Mehta A. Demographics of the UK cystic fibrosis population: implications for neonatal screening. Eur J Hum Genet 2002; 10:583-590. [PubMed].
005 Sims EJ, McCormick J, Mehta G, Connett G, Mehta A. UK CF Database Steering Committee. Newborn screening for cystic fibrosis is associated with reduced treatment intensity. J Pediatr 2005; 147:306-311. [PubMed]
2005 Sims EJ. McCormick J. Mehta G. Mehta A. Steering Committee of the UK Cystic Fibrosis Database. Neonatal screening for cystic fibrosis is beneficial even in the context of modern treatment. J Pediatr 2005; 147(3 Suppl):S42-46. [PubMed]
2007 Sims EJ, Clark A, McCormick J, Mehta G, Connett G, Mehta A, on behalf of the UK Cystic Fibrosis Database Steering Committee. Cystic fibrosis diagnosed after 2 months of age leads to worse outcomes and requires more therapy. Pediatrics 2007; 119:19-28. [PubMed]

Dr Erika Sims was involved with the UK CF Database from 2001 to 2007. More  recently she is Operations Manager of the Norwich Clinical Trials Unit.

Oct. 18th.  Dr Maurice Super’s retirement party at a hotel in North Manchester.   

  Dr Maurice Super

Maurice Super (1936-2006) first encountered CF in Windhoek in South West Africa (Namibia) in 1967 where he started a CF clinic. He subsequently became a leading geneticist and paediatrician in the UK working in Manchester. 

He was a major protagonist of carrier screening in the extended families of people with cystic fibrosis – so-called “cascade screening”. 

The party was a pleasant affair – he’s a nice chap who is a real enthusiast particularly  with regard to the “cascade screening” of relatives. 

 Oct. 19th. Conference in Barristers’ Chambers in London,

The conference concerned a young girl with CF whose diagnosis had been missed at 5 months due to misinterpretation of a sweat test by a junior doctor; this delayed the diagnosis until the age of 5 years.

Dr Anne Greene

It is good that very detailed UK Guidelines for Sweat Testing are virtually completed under the guidance of Dr. Anne Greene of Birmingham.a distinguished clinical biochemist  A final meeting was held recently in Birmingham. It is to be hoped that such disastrous cases will not occur when nationwide neonatal CF screening is eventually introduced.

 

Oct. 22nd. To Orlando USA for the North American CF Conference.  

The meeting was held again in the huge Orlando World Centre Hotel.  It was good but attendance was much smaller than usual, many Europeans and Americans opting not to travel in view of the recent 9/11 terrorist activity in the USA.  Bob Beall, their CEO, said a thousand people had cancelled – however there were still over two thousand there!  But the whole place was noticeably quieter than usual and our taxi driver said business had been very poor since the September 11th terrorist attack.   

Lorna Leyward

Lorna Leyward (our new and as it turned out soon-to-leave Scientific Director!) and I attended a small dinner hosted by the CFF where representatives from various countries discussed their current research in progress and the CFF website.
Lorna described our three ongoing trials – the TOPIC (once versus thrice daily IV tobramycin), CALICO (oral high energy supplements versus more normal food) and the inhaled steroid withdrawal trial. All these were eventually published.

Dr Lisa Saiman

Dr. Lisa Saiman, a leading US microbiologist, presented the very substantial final report of the conference, to which Niels Hoiby, Gerd Döring and I had been invited in May. The report seemed to be well received by the very large audience, who attended the session. 

The essential difference between the CF Foundation’s report and UK CF Trust’s recommendations is that we suggest close microbiological surveillance and patient segregation according to microbiological status whereas the CF Foundation suggest no mixing at all. Surveillance there, for various reasons (not least great cost), is not as close and one can never be quite sure what organism a particular patient is harbouring – hence no mixing.

Oct. 28th On reflection there was really nothing very new at the meeting but  there is a great deal of steady progress.  The big plenary sessions were below their usual standard except for the final morning, which was very good. 

Prof. Andre Cantin

Professor Andre Cantin of Canada spoke on CF Clinical Research: A Journey with a Destination”.                                 This pulmonologist from Quebec reviewed the progress in the various approaches to correcting the basic defect either by gene or drug therapy and to clinical treatment.
I knew our CF Trust Board was interested in current research on treatments hence I provided the following brief summary.

[Comments in Brackets are made in 2022]: –

Gene therapy using adeno-associated virus was showing promise without major problems and with longer duration of activity and a Phase II trial was in progress. (Gene therapy not yet available in 2022)

Drug therapy – Dr. Wilschanski, Jerusalem, has further confirmed that gentamicin applied to the nasal mucosal of patients with stop mutations (those with an X of whom there are many in Israel) will return the mucosal electrics towards normal. (Never developed into therapeutic option)

Dr. Pam Zietlin, Philadelphia shows that oral phenyl butyrate improves the trafficking of abnormal CFTR within the cell (CFTR in dF508 seems to get stuck in the cell and fails to reach the surface).  Special staining showed after phenyl butyrate there was improved movement of CFTR to the surface of the cell.  Further trials are planned.(Trails did not show significant activity)

Improved activation of CFTR occurs with genistein and CPX.  It may be combining these would be more effective. However, the mass screening for active compounds, one of the CFF’s major projects, has yielded a compound 10 times more active than genistein and this is being investigated (7.8.benzoflavine?).(Did not develop into treatments)

Various ways of using alternative channels to cross the cell wall included P2Y2 channels.  Also INS (triphosphate nucleotide) was well tolerated but INS 37217 was better and being tested – it increased the water content of the cell surface fluid.  MOL 1901 Duramycin also activates alternate Cl channels and was being investigated in two centres.(No future significant value as treatments)

There has been a recurrence of interest in mucus, in particular overproduction.  The mouse gene Gob 5 was discussed which increased mucus production and reactivity.  A compound -Lomucin -was under clinical trial.(

Inhaled Dextran reduced adherence of organisms to the mucosal and prevents pneumonia in mice.  A phase I trial is in progress at Toronto.(Dextran was not introduced)

The THAIRapy vest continues to increase in popularity in the US despite its price ($15,000).  Dr Accurso in Colorado is coordinating a multicentre trial of this and various other physiotherapy mechanical devices. In Kansas inhalation therapy is being combined with the vest.(All subsequent comparative trials of physiotherapy show no great difference between methods. The vest is very widely used in the USA but not popular in the UK – physiotherapist don’t like it and it is expensive_

With regard to nutrition, the lipid imbalance between AA (Arachidonic acid) and DHA (Docosahexanoic acid) in CF mice the degree of which influenced the severity of their pancreatic abnormalities is still being studied.  The AA: DHA imbalance has been confirmed in nasal cells from patients but the proposed treatment is still under development. Lym-X-Sorb is a mixture of lipids, which is well absorbed, and its effects are being studied in Montreal.  The few patients studied had improved weight gain and growth.(Nothing of significance came of this research)

For infection, vaccines against Pseudomonas aeruginosa (PA) were under trial and the result of the Döring and Stern trial would be completed in April 2002. Ron Crystal (of gene therapy fame) using modified dendritic cells +PA protected mice.  For respiratory syncytial virus – a serious infection in young CF patients – a monoclonal antibody seems hopeful – “Synagis” is now in a Phase IV trial. (No vaccine available by 2022)

It would be a further decade before the real breakthrough came in the form of the first CFTR modulator therapies which were to revolutionise treatment 

2009 Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P.Rescue of CF airway epithelialionise treatment cell function in vitro by a CFTR potentiator, VX-770.Proc Natl Acad Sci U S A. 2009; 106(44):18825-30.2010
Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordonez CL, Campbell PW, Ashlock MA, Ramsey BW. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation.       VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro.New Engl J Med. 2010; 363:1991-2003.

Nov. 11th I visit the Swiss Serum and Vaccine Institute, Berne.

The 13C ‘Zytglogge’ clock tower is in the centre of the old town
Bern Switzerland 

I was invited by the pharmaceutical firm Orphan Europe to hear about their  new anti-Pseudomonas vaccine (Aerugen Berna) that was currently undergoing a multi-centre trial in Europe. The modern factory manufacturing the vaccine  was impressive – reminiscent of a James Bond movie! The results could be very important but would not be available for about 2 years.

 Unfortunately, as I will describe later, the large multicentre trial eventually showed absolutely no benefit from the vaccine and  its development was halted by the firm.  The same proportion of treated and control patients developed chronic Pseudomonas infection. This broke the spirit of the scientist who was in charge of the project (Dr Alois B Lang of Berne Biotech Ltd, Bern, Switzerland) . This was very sad as he was a very nice chap and full of enthusiasm for the product.  Apparently he did progress to be Chief Development Officer of GeNeuro SA in Geneva

On this particular visit it was very windy at Berne’s tiny airport, delaying our take-off. Consequently, I missed the connecting flight to UK from Schipol and had to stay in Amsterdam overnight. 

Nov. 9th Trent Cystic Fibrosis Implementation Group.                                        Managed to get to the Clumber Park Hotel north of Nottingham for this meeting in the afternoon.  I don’t feel enthusiastic about the regional commissioning groups and hear that, even as we meet, the gaol posts are to be changed!

Nov. 13th Birmingham – “Guidelines for performance of Sweat Test for Investigation of Cystic Fibrosis in the UK”.                                                                         Failed to make this meeting due to personal virus but Prof. Stuart Elborn was the official CF Trust representative.  This is an important area, for the standards of sweat testing in some areas are still poor and mistakes can be quite disastrous and are still the basis of a number of legal cases – either false positives or false negatives.

Nov. 14th  Regional Paediatric CF Unit, St James University Hospital.

        Dr Tim Lee

I visit my old unit at St James’s at the request of the present Specialist Registrar (soon appointed consultant there) Tim Lee (figure) to discuss the  really exciting paper he is writing on the steady and highly significant fall of chronic Pseudomonas aeruginosa infection in the children the the Leeds Centre.   This was due to the various avoidance and early treatment measures we had taken in Leeds since 1975.                    These included neonatal CF screening since 1975, early eradication treatment of P. aeruginosa with nebulised colomycin started in 1984, segregation of patients according to their microbiological status since 1990. 

This had resulted in, less than 4% of the Leeds children under 12 years now have chronic Pseudomonas infection compared to 50% in the USA the results really made my day!

Lee TW, Brownlee KG, Denton M, Littlewood JM, Conway SP. Reduction in prevalence of chronic Pseudomonas aeruginosa infection at a regional pediatric cystic fibrosis center. Pediatr Pulmonol 2004; 37:104-110.

Nov. 20th  Meeting at St George’s Hotel, London, to discuss cross-infection.  Rosie, Lorna Leyward, John Govan and a small group met to discuss the infection control policy as it applied to the CF advocates. 

Nov. 21st. Research & Medical Advisory Committee, Novartis, London.

Eric Alton and David Stableforth were due to retire from RAMAC and were thanked for their important contributions.  Donna Harcombe, a CF mother,  was welcomed as a parent representative; she told me afterwards how interesting she had found the meeting.  I found it reassuring that someone who helped to raise the money saw how it was distributed as far as research grants were concerned

Nov. 23rd   “How to Establish a Cystic Fibrosis Centre”.

             Hotel Schloss Weitenberg

Invited to Germany by Prof. Martin Stern, Director of the Tubingen CF Centre, to give this lecture at his annual CF meeting for professionals in southern Germany at the impressive Hotel Schloss Weitenburg (photos).
The lecture went well and (thanks to Ann – now my IT manager) the PowerPoint presentation behaved!

Many trophies in the cooridors

The hotel was a huge old chateau-type hotel in the forests near Tubingen full of stuffed animals’ heads – definite shades of Harry Potter, which, coincidentally, we had seen the previous week!   

At  the dinner after the meeting Martin presented me with a stone with a fossil which he had found that morning on his health jog. He’s a very nice guy.

The next day Ann and I had a tour round the very impressive old town of Tubingen with its ancient university founded in 1477.

Nov 27th. CF Meeting at the Royal Society of Medicine, London.   

    Prof. Tim David

These annual meetings have been organised since 1985 by Prof. Tim David of Manchester and have been a great success.  They are well attended by professionals of all disciplines involved with CF care – particularly those from the smaller CF Clinics, as distinct from the large Specialist CF Centres, for they rarely get to the international CF meetings.  The allied professional support for children by the nurse, physiotherapist, dietitian and social worker at shared care CF Clinics is not always adequate – indeed, the whole area of shared care needs reviewing to ensure it is not second-best care.

Rosie Barnes gave an excellent talk on Advocacy at this meeting speaking both for and against, due to her opponent’s absence through illness! Rosie was an excellent speaker and for many years did not rely on slides or PowerPoint but she eventually  succumbed

Dec. 3rd & 4th. Accreditation visit to the Royal Hospital for Sick Children, Glasgow.  

Now the CF Trust’s “Standards for Clinical Care of Children and Adults with Cystic Fibrosis” has been published and adopted nationally as the agreed  benchmark for CF care, we had the basis for accreditation of CF Centres.  

     Dr David Heaf

This was our first Accreditation Visit by Dr. David Heaf (Respiratory Paediatrician) and Ms. Jenny Cottrell MBE (CF Nurse Specialist) of Liverpool and myself. David Heaf took the lead role and both he and Jenny were really excellent – tactful, yet probing and direct without offending.  We had been asked to visit by the CF staff there as they were particularly short of senior medical staff but also of allied professionals to the extent that they were unable and refused to provide shared care for the children in SW Scotland nor could they see their own patients more often than once every 4 months.

(Previous) Hospital for Sick Children Glasgow

We had an excellent visit with total cooperation of the CF Team and masses of data supplied by Dr. Jane Wilkinson, the quite outstanding full time Associate CF Specialist who is essentially acting as Centre Director, CF Consultant and CF Registrar at present.  We interviewed all the members of staff concerned with CF care, the CF team members, medical and nursing ward staff, secretaries and data manager, the Paediatric Director and Hospital Medical Director and a group of parents. It was somewhat surprising (in fact definitely “pathological”) that the senior paediatric consultant, Dr Jimmy Paton usually did not attend the weekly CF clinic as he had to take another clinic for children with a different condition – really a most unsatisfactory arrangement and definite pathological behaviour.

      Dr Jimmy Paton

I prepared a very comprehensive report, which was checked first by David and Jenny and then by the local CF team to ensure it is factually correct and then passed to the CF Trust for action.  The Glasgow team were keen that the CF Trust contact the local managers with the findings to emphasise their inability in SW Scotland to follow the CF Trust’s Standards – in particular, their inability, due to inadequate staffing, to follow the basic advice that all people with CF should have some regular contact with a Specialist CF Centre.  

It was a good start to a process of Accreditation which we had been talking about for a long time and which made an increasingly significant contribution to improving CF care in the UK.
Addendum:  CF Trust Accreditation Programme became a routine in future years – this was the start of it.

Dec. 12th. Spent the morning at St James CF Unit with our two “diet divas”   

With Sue Wolfe and Alison Morton – some years later!

Sue Wolfe (children) and Alison Morton (adults) and I went over the fine details of the CF Trust’s new document “Nutritional Management of Cystic Fibrosis”.  

The document was good but has had an “elephantine” gestation period!  

It is the only one of the CF Trust clinical documents that we initially “farmed out” (to Sheffield) to arrange the meetings and do the initial writing. Perhaps a mistake.

We certainly missed the efficient CF Trust input of Carol Eagles and Clare Pendry in organising the Nutrition Group meetings and, until recently, Sandra Kennedy to polish the final version. The document was eventually printed in January 2002.

Dec. 18th.  Meet with Dr Pamaloo and the Medical Director of Roche 

The purpose of the meeting was to discuss the role of Pulmozyme and its present used in the projected treatment of people with cystic fibrosis.  There has been a recent important report of a multicentre trial on the use of Pulmozyme in mildly patients (FEV1 of 95%) showing maintenance of lung function and the reduction of exacerbations of respiratory infections over a 96 week period. It is not clear how these results will affect the use of Pulmozyme in the UK where we already use significantly less than any other country, largely due to the high cost (£7000 a year). This was the trial that I attended the on monitoring committee in San Francisco last year.

Quan JM, Tiddens HAWM, Sy JP, McKenzie SG, Montgomery MD, Robinson PJ, Wohl ME, Konstan MW. Pulmozyme Early Intervention Trial Study Group. A two-year randomised placebo controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities. J Pediatr 2001; 139:813-820. [PubMed]

This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers and 474 children. Inclusion criteria were age six to 10 years and forced vital capacity > or = 85% predicted. At 96 weeks the treated group had maintained their respiratory function levels; the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for FEV1 (P =.006), 7.9 +/- 2.3 for FEF 25-75 % (P =.0008), and 0.7 +/- 1.0 for FVC (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa. The authors concluded that treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.

–   The results of this trial influenced some paediatricians to try young CF patients on Pulmozyme before they developed chronic infection and this became routine practice in at least one large UK Paediatric CF Centre and also in Copenhagen where the treatment was found to reduce the frequency of respiratory exacerbations and new positive respiratory tract cultures.