May 1980. North American Cystic Fibrosis Conference in Toronto
The 1980 North American Cystic Fibrosis Conference was held at the Royal York Hotel in Toronto. Formerly and commonly known as the Royal York, the hotel is a large historic luxury hotel in Toronto, Ontario, Canada. Located along Front Street West, the hotel is situated at the southern end of the Financial District, in Downtown Toronto. The Royal York was designed by Ross and Macdonald, in association with Sproatt and Rolph, and built by the Canadian Pacific Railway company. In recent years the hotel is managed by Fairmont Hotels and Resorts.
Opened on 11 June 1929, the Châteauesque-styled building is 124-metre-tall (407 ft), and contains 28 floors. It is considered one of Canada’s grand railway hotels. After its completion, the building was briefly the tallest building in Toronto, as well as the tallest building in the country, and the British Empire, until the nearby Canadian Bank of Commerce Tower was built the following year. The building has undergone several extensive renovations since it first opened, with its first major renovation in 1972. An underground walkway linking the hotel with the Royal Bank Plaza and Union Station form part of the Toronto’s PATH underground city system – a necessary facility in the very cold winters.
I attended this conference and, with some trepidation, gave an oral presentation of the results of our detailed nutritional assessment on our few CF children; also I had a poster reporting our neonatal screening results form St Mary’s Hospital in Leeds. Both these studies were later published.
Congdon PJ, Bruce G, Rothburn MM, Clarke PCN, Littlewood JM, Kelleher J, Losowsky MS. Vitamin status in treated patients with cystic fibrosis. Arch Dis Child 1981; 56:708-714.[PubMed]
Evans RT, Little AJ, Steel AE, Littlewood JM. Satisfactory screening for cystic fibrosis with the BM meconium procedure. J Clin Path 1981; 34:911-913. [PubMed]
For my part, although by now a busy and increasingly experienced general consultant paediatrician for some 12 years, as far as CF was concerned, I definitely felt a relative “CF rookie”. Attendance at this excellent conference was the start a very steep learning curve for me and subsequently my immediate colleagues at St James’s.
Undoubtedly attendance at this Toronto conference had a major influence on my approach to treating children with CF and represented a definite turning point in my professional life in that over the next two decades CF would eventually become my main interest.
Also at this 1980 meeting I had the opportunity to visit the CF Centre at the Sick Children’s Hospital in Toronto and talk with the CF Centre Director, Dr Henry Levison (photo in his later years but photo from 1964 below)). I could find no recent images of Henry Levison. However, I was fortunate to find one from 1964 (below) when he was involved in successful early neonatal ventilation (photo from Science and Practice of Pediatric Critical Care Medicine. Eds. DS Wheeler, HR Womg, TP Stanley).
At the Toronto meeting it was announced that anyone wishing to visit the respiratory unit would be welcome. I recall there were only four of us took up the offer – Dr Archie Norman, Mrs Norman, myself and another doctor. Henry saw us amid a vast collection of complex machines which made the Vitalograph, a small table top machine for testing respiratory function we used in Leeds, seem rather inadequate!
On the lighter side, on this first visit I enquired if Henry checked the children with CF and asthma for allergies. Henry appeared horrified and exclaimed “Oh no! You’re not a bloody allergist are you?”. Although I denied this firmly at the time, whenever we met subsequently at meetings it was “Oh here’s the allergist from Leeds!”. I visited him again in Toronto some 6 years later (as I describe later in some detail) and was equally overwhelmed and impressed. He was also a recognised art expert.
Dr Douglas Crozier (1940-2014) started the Toronto CF clinic in 1958, the second after Dr Alan Ross had opened the first at Montreal Children’s Hospital Crozier wrote that “success of treatment will depend on a complete assessment of the patient and then continuing attempts to obtain normal bodily function and maintain it”. He described how he advised his patients to abandon the traditional low fat diet and used very high doses of pancreatic enzymes (up to 100 Cotazym pancreatic enzyme capsules per day!). Crozier believed that “to deprive a child with cystic fibrosis, who usually has very little subcutaneous fat, of this important nutrient seems ridiculous”. The superior nutritional state of the Toronto patients from this approach is believed to be the main reason for their significantly better survival compared to those in the USA. As far back as 1973, 428 people with CF were attending the Toronto clinic of whom 92 (21.4%) were 16 years or older – this was quite remarkable for that time.
I was told by a paediatrician who worked with him for a time that Crozier was very thorough always analysing how his treatment could be improved in the management of his patients throughout their lives.
Undoubtedly Douglas Crozier’s approach to the treatment of children with CF had a major influence on my subsequent approach to management of the condition. I discuss this in more detail in the section of the Development of the Leeds Regional CF Service.
1986 July. Visit to North America with Ann and our youngest daughter Katie. I visit some CF centres.
It is important to stress the account of treatments and routines in the clinics visited are very detailed as they may be of interest to those involved in treating cystic fibrosis. In this context it is stressed these are accounts of treatment in 1986 and now represent an historical record of treatment at the time.
I had a growing sense of curiosity as to how cystic fibrosis was managed in N. America. Ron Tucker, the very experienced and very supportive Director of the CF Trust, said I wouldn’t gain anything from it but I was keen to see, first hand, how some of the more well-known N. American CF Centres functioned. So Ann, Katie and myself went on a bus tour of various US and Canadian cities. I would periodically leave the tour for 24 hours or so to visit various hospitals to see their CF units. I would then catch a flight and meet up with Ann and Katie the tour’s next stop. This was rather confusing for the tour guide when he counted the passengers but it worked surprisingly well!
Visits to CF centres – St Vincent’s New York, Quebec, Montreal, Toronto, and Washington.
Some of the units were very impressive and some less so. It was clear how they were restricted by cost and administrative problems (much the same as in UK in 2018!) but which we had not experienced to any serious degree at the time of my visit in 1986. If we thought nebulised colomycin would help in eradicating pseudomonas, and it appeared safe, we tried it with no concern as to the cost. We had a rapidly expanding Regional CF Unit in Leeds at St James’s by 1986 and had reported the results of Comprehensive Assessment of 103 patients by 1984 at the International Brighton CF Meeting. At that time and it was good to see a really good US clinician, such as Dr. Carolyn Denning in action at St Vincent’s in New York, with her team. Ron Tucker had said that if I insisted on visiting US centres this was the unit I must visit and as usual he was right. I was fortunate to spend the day in New York with Carolyn Denning and her team.
St Vincent’s Hospital CF Center, New York
Dr Carolyn Denning (1927-2016) was one of the leading CF paediatricians at that time working first in New York with Dorothy Andersen (who first clearly described CF in 1938) for 20 years and later at St Vincent’s Hospital in New York. Carolyn Denning was the first woman to chair the National Cystic Fibrosis Foundation’s Medical Advisory Council and was one of the first to organise and initiate a multidisciplinary team approach to management of the disease – this was very apparent when I visited her and her team at St Vincent’s, New York. In 1956 she married Dr Peter Scaglione; they had four children.
A quote of hers from the website “A Changing Face of Medicine” typifies her general approach – “My office visits,” she says, “are conducted in a private setting with no interruptions by telephone or office personnel with a one-hour minimum allotted to each patient. I am realistic yet optimistic, stressing the importance of hope. I am current on research activities in the field as well as other important relevant events. I follow through on all matters pertaining to the patient and his office visit and I am available by telephone at all times. I put great stress on personal integrity, ethics and moral beliefs. As director of a large, multi-disciplinary group of health professionals, I have worked hard to choose people who share the same philosophy.”
I describe this visit to St Vincent’s in some detail as it undoubtedly represents one of the best clinics for people with CF in the USA in the mid-Eighties
St Vincent’s Hospital New York – Dr. Carolyn Denning and her team (11.7.86)
I spent the day at this centre which is in the main medical building separate from the general out-patients; a suite in this building is occupied by Dr Denning who is the director of the staff. The clinic undertakes medical care of approximately 200 patients and 102 of these are over the age of 18 years. There are approximately 40 aged 1-5years, 46 aged 6-10 years, and 58 aged 11-17 years. Patients attend approximately four times a year. All the outpatient care is given in the CF centre which is in the consulting building.
Dr. Denning is the medical Director. There are two attending physicians who work full time in the centre (these are the equivalent of consultants), three full-time fellows (equivalent to registrars), three paediatric pulmonary and CF fellows and one intern. There is a clinic coordinator was is also Dr Denning’s secretary. There is an administrative assistant, a full tine nurse, part time dietitian, psychologist, a physical therapist, receptionist and organiser. In addition there are two laboratory technicians who work in the main hospital and perform laboratory tests related to cystic fibrosis including a tertiary referral service for sweat tests, faecal fats, vitamin E etc. There is also a pulmonary function laboratory and all patients have regular full respiratory function tests.
There are three clinics a week; one for private patients and one for non-private patients. There will be three senior doctors in each clinic and up to 3/4 or an hour will be given to each patient. At these attendances the patients also see a selection of other members of the team. There are regular meetings; a general meeting for the whole team on Thursday afternoon and an x-ray meeting on Friday lunchtime. The patients come from considerable distances and their care seems to be mainly centred on the CF Centre and the ward although certain treatments are undertaken at local hospitals. However, there is not much contact with the smaller hospitals nor with the other cystic fibrosis centres in New York of which St Vincent’s is the largest. All team members do not all see the patients at every attendance; for example the social worker does not see all the patients but would pick up any problems such as supply of equipment, various funding programmes which become an increasing problem for patients after the age of 21. On Wednesday afternoons she holds a group meeting for the relatives of patients who are in the ward at the time. She also combines with the other paediatric social worker in the hospital. The work is divided between administrative problems and psychosocial problems. However, there is also a full time psychologist
With regard to adult care, when the children become adults they are not transferred to internists, pulmonologists or gastroenterologists. This was tried but found to be quite unsatisfactory and the patients returned to the care of the CF centre. The inpatient arrangements are that the patients are looked after on the paediatric ward in a single or double room; on the paediatric ward there is spacious room fitted out with pool, television, microwave, space invaders etc. This is not usually used by the children but apparently has been at times. There is an attempt to segregate patients and the majority are chronically infected with Pseudomonas. As much of the treatment as possible is done in the outpatients in view of cost, the hospital does rely on in patient treatments for part of their funding so there are really divided loyalties. However I gained the impression that the doctors do what they consider is in the patient’s best interest at the time!
The therapy on the ward is interesting in that there is only one physiotherapist but a team of 20 part-time trained “respiratory aides”. These are young people trained by the physiotherapist who is a qualified physical therapist. They are paid six dollars an hour to administer physiotherapy to patients in the ward. Many of them find this a very rewarding job and it is commonly undertaken by students, nursing students and has on occasion prompted them to go in for respiratory therapy. Intravenous work is performed by the intravenous team and the respiratory care specialists are also available. Intravenous drugs are given via an IV cannula and infusion pumps are used regularly to maintain patency. The drips are set up and managed by a specialised permanent IV team rather than by the junior doctors. On the ward there is also a newly opened, voluntarily donated, small exercise room with a treadmill to exercise bikes and various weightlifting apparatus which is proving very popular.
I had a long interview with Debbie a very pleasant social worker who works full time with the unit. Mrs Gluckson, an experienced geneticist, who is obviously a member of the original team and thoroughly au fait with every aspect of care in the centre; she organises the DNA studies and provides detailed genetic counselling for the majority of the patients. There have been eight pregnancies and one fertile male. All males are told of infertility and this is said to be particularly important in some Latin American races. Demand for abortion in parents who have an affected child is somewhat modified by the fact that 60% of the families are Catholics.
The physical therapist Miss Gregory sees her role as a teacher and organiser she also organises inhalation therapy mucomyst 20% is used to quite frequently also bronchodilators and all patients have their way the ability checked annually tobramycin and ticarcillin are used in some patients are at times for exacerbations of respiratory symptoms Duggleby’s nebulisers are used and cost around $150 also jet nebuliser issued with a mouthpiece. Patients get three physiotherapy treatments daily in-hospital seven days a week largely due to the 20 physiotherapy aids who are trained by Miss Gregory. This system seems to have been accepted by patients other physical therapists and the hospital. A major difference in physiotherapy technique from the UK is that mechanical percussors are used in the majority of adult patients; they have over 100 of these. They seem to be very similar to the Salford percussor. One further point is the forced expiratory technique (FET) is not used by any patient neither are Pep Masks used at all. Apparently huffing is not used much in the United States clinics but in the near future therapists from Holland are coming to start a project on the Forced Expiratory Technique. Exercise programmes are recommended though they are not formally used but the new exercise room off the ward is proving popular. Patients are advised to do jogging, cycling and swimming. Pseudomonas cepacia was not mentioned although the majority of older patients appear to be chronically infected with P. aeruginosa. No attempt is made to segregate the patients and cross infection was not regarded as a problem.
The emphasis appeared to be on pulmonary therapy although I gained the impression that the patients were all on normal diets rather than low-fat diets. There is a dietitian or works halftime in the clinic. Pancrease appears to be used as the pancreatic supplement. Certain patients are on home parenteral nutrition.
At lunchtime I attended an x-ray meeting. Members of the team were present and a large number of patients x-rays were demonstrated and their progress discussed. The main impression was the use of detailed respiratory function tests which were reported on all patients and are performed regularly. I obtained the impression that the inpatient monitoring is not as detailed as in our own unit. More notice was taken of detailed respiratory function tests, particularly the residual volume, evidence of small airways obstruction indicated by the FEV 25-75%. There was perhaps less emphasis on detailed bacteriology and the doctors knew less readily the organisms present. The routine intravenous therapy is tobramycin and ticarcillin. Piperacillin is said to have been associated with side effects, particularly rashes and temperature. However, chloramphenicol was regarded as a very useful drug which was used relatively frequently and would commonly improve the chest of patients with Pseudomonas where Pseudomonas was the only organism growing, presumably due to the treatment of other organisms obscured by the Pseudomonas? The approach to the chest infection was generally aggressive although I think our Leeds approach is equally aggressive. We had a similar use of corticosteroids and a combined multicentre trial was starting in the United States in the near future.
My overall impression was of a very well established, experienced, caring team who worked as an effective group and who had very good relationships with each other. In fact in the clinic if the nurse was away the patients would be weighed by physiotherapist and even at times by the social worker.
It was quite obvious that this team is successful in attracting and satisfying cystic fibrosis patients of all ages but they had tried the transfer of adult patients to internists with a total lack of success. Their idea of having an adult unit reasonably close to the experienced paediatric unit seemed to be working well and was accepted by the patients. I was most impressed by the friendliness of all concerned and the way that great trouble had been taken to ensure the I obtained as much information during the day as possible.
St Vincent Catholic Medical Centers was a health care system based on St Vincent’s Hospital, Manhattan. St Vincent’s was founded in 1849 and was a major teaching hospital in the Greenwich Village neighbourhood of Manhattan, New York. The hospital closed in 2010 faced with “financial troubles and mounting debts” under circumstances that triggered an investigation by the District Attorney of Manhattan.
Centre Hospitalier de l’Universite Laval, Quebec – Drs. Pierre Bijonese and George River. (15.7.86)
Next stop Quebec. This clinic is the third largest in Canada looking after 116 patients. The clinic is essentially run as part of the University Department of Paediatrics. There are some 15 paediatricians, six of whom are employed by the university and who work full time in the hospital.
In the clinic there are two paediatricians who devote about a third of their time to CF; three sessions each of a nurse/coordinator, a CF nurse and a social worker. These staff are paid by the Cystic Fibrosis Association rather than the hospital. The unit receives about $50,000 pa from this source. The dietitian is the hospital paediatric dietitian who does CF as part of her general work: she was not in the clinic. There are two clinic sessions each week and one full afternoon discussion session for all the team.There are usually one or two patients in the ward for treatment. The patients attend the clinic every two months. There are usually two senior doctors and they see no more than six patients each in the afternoon. There is also a resident doctor in the clinic who is rotating through. Each patient is given half an hour or more if necessary.
When the patients arrive at the clinic they have an interim history taken by the nurse, are weighed and measured, have a session with the physiotherapist and are then seen and examined by the doctor.Prescriptions are then written and patient leaves the clinic. The patients have regular X-rays every two months but are less likely to have other investigations performed. The adult patients attend the paediatric clinic. There is no attempt to separate Pseudomonas infected and non-infected patients – perhaps 60-70% of children aged 10 years or more are infected with Pseudomonas.
There are major problems regarding the adult patients who are still locked after by the paediatricians. Attempts have been made to involve internists but it was found the time for treatment of cystic fibrosis was too demanding for them in terms of time expended. At present an adult patient is admitted to an adult ward , put under the nominal care of an internist who then seeks the opinion of Dr. Bijonese. Thereafter follow-up is in the paediatric clinic. The patients come from quite large distances up to a few hundred miles from around Quebec and all patients in Quebec are treated at this clinic.
The hospital has 350-400 beds and a reputation for the treatment of Ca prostate. There is an increasingly large paediatric unit but no obstetric unit. It was previously a Veteran’s hospital but as there are fewer veterans, there is increasing involvement by the University Dept of Paediatrics. The hospital receives considerable funding. The patients have to pay 2 dollars an item for outpatient prescriptions. Inpatient treatment is covered either by the state or Medicare. However, there does seem to be some restrictions on drugs and thought is given to the cost e.g cloxacillin is used rather than the more expensive flucloxacillin.
With regard to general management. Physiotherapy is given but members of the clinic were unfamiliar with PEP but the patients were taught FET. Long term antibiotics were not used. Cloxacillin was given during colds. Pseudomonas was treated on symptoms and early Pseudomonas infection was commonly treated with nebulised tobramycin starting with 40mg twice daily and increasing doubling or quadrupling if necessary. Dr Bijonese was impressed by the use of tobramycin in this way. They have no significant problems with P. cepacia – it had been isolated from only one patient. Steroids were used in small wheezy infants and those with allergic pulmonary aspergillosis.
Usually pathogens isolated from the sputum received antibiotic treatment on their merits but I obtained the impression that they would not resort to IV therapy to eradicate a pathogen from the sputum and would prefer to use nebulised antibiotics these circumstances. An example was a thin girl 0f 12 years with chronic Staph. aureus in the sputum was being treated with oral cephaclor and nebulised tobramycin – her compliance was said to be poor. I noticed she had a productive cough and early finger clubbing. (I think we would have tried a course of IV antibiotic therapy even in 1986).
With regard to the nutrition, infants were treated with either Portagen or Pregestimil, the former being cheaper and more easily obtained. A mixture approaching our “CF mixture” was not used. Unfortunately I did not see the dietitian and did not discover what dietary information was given to the families but they all seemed be on normal diets eating large quantities of normal food. One 3-year old wa taking 5 Pancrease per meal and looked very well-nourished being between the 25th and 50th centile for weight and height.
Most were given general vitamin supplements. Nasogastric feeding was used in two patients who were poorly nourished; the staff were favourably impressed by the effect; the enteral feed used was Vivonex. Pancrease enzymes were given in the standard way throughout the meal.
I visited the two paediatric wards and the 30 bed ward for children in the late afternoon. The ward was supervised by an experienced university paediatrician who worked full time on the ward for stretches of six months a time. There were also three residents and a number of interns and students. The wards were considered to be busy by North American standards, some 24 admissions a week occurring on the 30-bedded ward. patients had a wide variety of disorders – children with a variety of problems being nursed next CF patients. The majority of rooms were two bedded with a few four bedded. Parents could stay with their children.
I gained the impression of a very experienced caring team at this hospital largely funded by the CF Foundation. Plenty of time was given to the patients who were seen by senior doctors although much of their “processing” was carried out by other members of the team. This seemed very satisfactory all members were involved with the process of seeing the patients and the overall opinion was brought together in the weekly discussion sessions. I thought probably the treatment was less aggressive than in some centres and the low level of inpatients and the absence of a home IV programme suggested more oral antibiotics and physiotherapy were used for milder exacerbations. For example one child with a collapsed right middle lobe was being dealt with an increase in oral antibiotic, physiotherapy and aerosols. 10% propylene glycol and salbutamol in addition to antibiotics were used as aerosols. Aerosols were not used regularly but during exacerbations. None of the clinic data was computerised but they had a nice data sheet similar to our own but with more space and using both sides. The nurse coordinator was in the clinic updating records as to when families phoned in. There were some problems with meconium ileus equivalent for which oral lactulose was used. There was perhaps a more modest use of pancrease than in our own clinic although one 5-year old was taking 5 per meal.
Hospital for Sick Children, Toronto. Dr Henry Levision
The Cystic Fibrosis Clinic at the Hospital for Sick Children Toronto had been under the
direction of Dr. Henry Levison for the past eight years. There were approximately 530 patients were attending the clinic of whom some 200 were aged over 18 years.. The clinic is organised in the Hospital for Sick Children outpatient department which is next to Toronto General Hospital. Adults are generally gradually filtered into the clinic of a pulmonologist from the Toronto General who does one clinic a week at the Sick Children’s Hospital. There are three paediatric pulmonologists, one or two gastroenterologist working in the clinic as well as two nurses, two dietitians, a physiotherapist, secretary, full-time statistical expert Dr Mary Corrie. On this visit I did not see the extensive pulmonary function laboratories. There is standard children’s cubicalised ward. The outpatients was relatively small with relatively small rooms. The patients attend the clinic every 14 weeks; they are admitted on diagnosis but the number of beds used was extremely small. Standard data is collected on arrival usually by the nurse. The patient sees the doctor, usually also the physiotherapist and has whatever investigations are considered necessary. The data is computerised. There are three clinics each week. Patients communicate with the clinic nurse who may deal with any problems herself or discuss with the relevant doctor.
The patients have individual consultations with the gastroenterologist, when necessary
but he does not see all the patients. The gastroenterologist is Dr Peter Durie and Dr. Paul Pencharz is a nutritionist; they were already distinguished members of the team with an international reputation. When the patient reach 18 years or so they are gradually filtered into the clinic of the adult pulmonologist who does this clinic in the children’s hospital. After that, if hospitalisation is required the patients are either admitted to the Toronto General Hospital, which is next door, or to a cubicle on the children’s ward. There are some ten children and young people who they refuse to admit to the children’s ward; indeed one was usually in custody. There was no home visiting and no home intravenous antibiotic treatment. I did not go into the financing of the clinic but there seems to be a satisfactory insurance scheme in Canada.
Computerisation is advanced and has been the basis of other systems , for example in San Francisco. Dr Mary Corrie runs the system and is a world expert on the subject. Survival in the clinic is good with a 50% survival to 30 years and 80% survival to 18 years. It is interesting the Dr Levison had no knowledge of survival in other clinics in Canada. The patients were also entered into the United States registry but were not told of survival at other clinics. There seemed to be little contact between clinics in Canada at that time – perhaps distance and less communication facilities than in present times.
The Brasfield Xray scoring system and Shwachman clinical scoring system were used in the clinic. However, satisfactory answers to such questions as how many patients have a normal or near normal Xray at 10 years were difficult to obtain. The majority of patients were chronically infected with Pseudomonas – over 80% by ten years ; also 40% were infected with Pseudomonas (now Burkholderia) cepacia – the latter subsequently a major problem.
Management of the chest. Management in the Toronto clinic differed in a number of respects from that accepted as optimal in other centres. For example there had been a lessening of intravenous courses of antibiotics for “tune ups” over the previous 5 years or so. Patients were only given intravenous therapy when symptomatic, loss of weight, temperature, increasing sputum etc, not given on minimal changes on the chest Xray. At the time of my visit there were 530 patients in the clinic but only four inpatients three of whom were having IV antibiotics having treatment. They did not resort early to IV antibiotic therapy. Five years ago there would have been well over 15 patients in the wards having IV antibiotic therapy. Approximately half the clinic are on no long term antibiotic treatment either oral or inhaled; a few patients were on cloxacillin. New symptoms rather than new organisms on culture appeared to be indication for treatment. Septrin seemed to be used regularly as the oral antibiotic to cover respiratory infections. Chloramphenicol was used frequently in these circumstances and in exacerbations in patients growing Pseudomonas aeruginosa. Aerosol antibiotics were not used at all and IV aminioglycosides and a synthetic penicillin only when there was symptomatic deterioration in the presence of Pseudomonas infection.
With regard to general routine, the sputum was cultured on every visit, chest X-rays every six months. The Hoiby Copenhagen approach of regular IV antibiotics every three months, for patients chronically infected with P. aeruginosa, was considered very bad practice by Henry Levison. Pseudomonas cepacia was certainly a major problem but treated in exactly the same way as P. aeruginosa. Routine respiratory function standard values were checked at every clinic. Steroids were used occasionally and they were due to take part in a trial of steroids to confirm the Boston findings. Aerosols weren’t used at all but a bronchodilators were prescribed when there was hyper reactivity. Informal exercise activities were encouraged however, routine physiotherapy (considered by most authorities to be one of the mainstays of treatment!) was not recommended and not started initially unless there was a problem with sputum production. Dr Levison and colleagues had produced evidence that there was no difference in patients receiving regular physiotherapy or no physiotherapy in the absence of significant sputum production.
All in all, from a prolonged interview I could not determine anything in the management which would provide an explanations for the much superior survival figures in Toronto! Could it be the superior nutritional state – a legacy from the intensive management of Douglas Crozier, Henry Levison’s predecessor.
Dr. Levison thought that the heavy use of antibiotics was in itself a contributory factor to poor prognosis. He suggested that in countries where controlled trials could be done between a few centres a useful study would be a prophylactic versus non-prophylactic antibiotic study. In fact there was a multicentre trial starting in North America using Keflex (this failed provide an answer) . He also felt it was important that a controlled trial be done to confirm or refute the claims of Hoiby et al that regular three monthly IV anti-pseudomonal therapy would lead to significant improvement and morbidity and mortality of patients with established chronic pseudomonal infection (no satisfactory trial was ever completed).
With regard to nutritional management I had a short interview with Dr. Paul Pencharz. Patients usually follow normal diet, the Crozier high-fat diet which has been in operation for many years in Toronto. This is really the same as we use in Leeds that is to say a lot of normal food that does include rather more than average intake of fat. The written advice was not available although teaching on that diet tended to be done by the dietitian who I did not have an opportunity to see. Infants on diagnosis receive Pregestimil only if they have a bowel resection for meconium ileus otherwise they receive large volumes of normal infant formula. Jejunostomy feeding had been used but there was generally poor acceptance of nasogastric feeding; the method preferred was a non-operative gastrostomy that was performed as described by Levy in 1986. If there was significant oesophageal reflux, a jejunostomy tube was inserted by gastrostomy. They are are generally impressed by this method of improving nutrition; either Vital or Vivonex was used. Fat soluble vitamins 50 to 100 international units of water soluble vitamin E daily. Monitoring nutrition was discussed. There was no regular chemical monitoring and more stress was placed on anthropomorphic measurements. Meconium ileus equivalent did occur but did not appear to be a major problem.
With regard to the general reasons why the survival in Toronto is better than in other centres, there is no direct difference in the practice apart from a much more aggressive approach to nutrition which has been going on for longer than in any other centre having been started by Crozier in the Seventies. My impression was that it was certainly not because of more aggressive antibiotic therapy nor was it related to intensive physical therapy either physiotherapy, the use of aerosols or mucolytics, also nebulised antibiotics were not used at all.
The aspects of therapy that did appear to be different were the clinic is bigger than most and presumably experience in management is greater. Secondly there has been an aggressive policy of nutrition in operation for many years both with the present doctors and with Dr. Douglas Crozier who started the clinic in 1958.
An important future publication from Toronto would suggest that the significant survival difference between Boston (a major US clinic) and Toronto was related to the better nutritional state of the Toronto patients (Corrie et al, 1988). Also differences in favour of Canada were still evident in 2017 (Stephenson et al, 2017) when in 2011 the median age of survival in Canada was 48.5 years compared with 36.8 years in the United States. (both these papers are discussed in cfmedicine.com/history on the Leeds CF website)
I was left with the impression that it was vital to have a better scoring system to compare the condition of the patients with regard to their nutritional status, pseudomonas status etc. so that there condition could be compared realistically between the various clinics. This would be essential before any further progress was made in determining the part of the CF centre package of treatment contributes to improved survival.
Hospital St Justine, Montreal, Dr Lasalle and Prof. Claude Roy
The cystic fibrosis units at this large children’s hospital is one of two large clinics in Montréal. There are 270 patients 35% are more than the age of 16 yrs; adults over the age of 21yrs are now transferred to another hospital in the city where they are seen by a
pulmonologist who has had considerable contact with this clinic. He is now running his own clinic. The clinic Director here is Dr. Lasalle , a general paediatrician who spends 25 to 30% of his time dealing with cystic fibrosis patients He is responsible for the organisation of the service. Others involved in the clinic are a social worker, provided by the hospital, the physiotherapist employed for 33% of her time and paid for by the CF Foundation, the secretary fully paid by the CF foundation and a guidance counsellor who works with both children and adults 50% of his time paid by the CF foundation. The dietitian attends every clinic and puts in approximately three sessions a week for cystic fibrosis. There is a weekly clinic and one week in the month two clinics.
At each clinic there are approximately 15 patients. They see one of the doctors and any other member of the team they wish. In each clinic there is always Dr. Lasalle plus another general paediatrician who attends every clinic, one of three pulmonologists. The gastroenterological input is by individual consultation with Dr. Roy and his team who do a considerable amount of research.
Medical care is paid for by the state. In addition to this patients’ families who have a child with CF automatically receive an extra allowance of $90 a month. Drugs are usually free and paid for by the hospital. Patients obtain equipment at reduced prices; other diseases covered in this way include glaucoma and TB. In Montréal where there are over 2 million people, there are 300 paediatricians who if qualified have the right to access to inpatient beds provided that their standards are maintained in the judgment of the Director of the paediatric clinic. Patients are transferred to the adult clinic at the age of 21 years. The pulmonologist running that clinic must be approved by the CF Foundation. Before funding the clinic must have certain facilities provided for the patients.
A great deal of effort was going into computerising the patient data which is available for the doctor at the next clinic.. Young patients attend every month and older children every three months.
I had further discussions with Dr Lasalle concerning the chest. The patients have a respiratory culture at every attendance. Any pathogens growing in this culture are treated by a course of antibiotics given even if symptoms do not change. Prophylactic antibiotics either cloxacillin or cephalexin are given for the first year of life. With colds a further course of cephalexin is given usually for 2-4 weeks. Routine therapy is not given if Pseudomonas is cultured and there was no enthusiasm for home intravenous antibiotic therapy; also there was no nurse to help with such therapy. The only home visiting was by the physiotherapist who was paid by the CF Foundation. No mention was made of P. cepacia infection that was so common in Toronto. The incidence of chronic Pseudomonas aeruginosa infection is high some 60-70% being chronically infected by 10 years. There are facilities for complex respiratory function test but the clinicians find FEV1 and FVC are usually adequate.
In patients with chronic Pseudomonas infection, if the Brasfield score is less than 18 and the respiratory function less than 80% predicted, the patients are admitted twice a year for intravenous antibiotics. This has been the policy over the past 5 years and it is felt has had a favourable effect on mortality. Bronchodilators are used if there is reversibility but aerosols are not routine and all patients do not have nebulisers. Nebulised tobramycin 80mg bd. is used for patients with chronic Pseudomonas who are having frequent relapses – Dr. Lasalles is convinced it is a useful adjunct to therapy. Unfortunately, I did not meet the physiotherapist but I gathered the treatment used was standard methods. There was no formal exercise programme.
In the afternoon I had an intensive (interesting but rather stressful!) 2 hour session with Dr. Claude Roy and his team on their present work and research on CF with their particular interest in liver disease. Dr Roy is an international expert on paediatric liver disease.
A study was being performed looking at liver function tests and evidence of liver disease in CF patients to determine if any risk factors could be identified also to see whether the caffeine test, a standard load of caffeine recording the 16 hour level, is of a value on detecting early liver a change in CF
Multilobular cirrhosis was present in 4% of the St Justine patients, 5% of St Anthony’s patients and 10% of the adult series reported by Harry Shwachman from Boston. An autopsy studied was done to see if there were any associated factors in the patients who had died at St Justine’s. There were 267 patients of whom 38 had autopsies 21 boys and 17 girls. Between 1970 and 1980 22% of those less than a year and 50% of those over a years had evidence of cirrhosis at autopsy. Those with evidence of cirrhosis mucus plugging was evident in 50%, this could be differentiated from bile plugging. Gall bladder disease was present in 30%. Further data was presented but no association was shown between lung disease and liver involvement. There was discussion on taurine, its various functions including improving malabsorption. (work subsequently published). There was also a discussion on essential fatty acids which I found heavy going.
With regard to routine nutritional management, large quantities of normal food were advised; Pregestimil was used for infants. nasogastric feeding was used quite frequently also the usual supplements of fat soluble vitamins. The patients did not have a detailed annual assessment. They are admitted at the time of diagnosis for teaching and starting therapy.
Children’s Hospital National Medical Centre, Washington. Dr.Han Athan Ganez and Dr. Robert Fink (away)
This is the largest children’s hospital in Washington. The CF service in within the department of pulmonology. There are 150 patients aged between 2 months and 42 years. – 25% of the patients are over 18 years. The adults are cared for on the adolescent and adult floor. There has been no attempt to involve an internist and although there is a large hospital nearby. There are three CF centres in Washington, this for a population of 4-5 million. This is the biggest centre. The George Town centre sees mainly adults.
The present hospital was built in 1978. The outpatients are of standard design and the pulmonary function laboratory is on the third floor. It is an impressive modern hospital with 280 beds; two wards take CF patients. There are four pulmonology clinics each week and the CF patients are seen in these general pulmonology clinics – approximately 10 patients per session, patients attend every 2 months and have at least half an hour appointments. They are seen by the clinic nurse of whom there are three with one full time equivalent dealing with CF. She weights measures the patients, takes an interim history and determines which investigations are required. The physiotherapist sees patients periodically but the dietitian sees only patients at a separate appointment and does not appear to be part of the general team.
The clinic is staffed by two full time physicians and the usual fellows and residents. There is a small weekly meeting but this is attended only by the two physicians, a nurse for each of the wards that take CF patients and usually the CF nurse goes but no physiotherapist or dietitian, nor junior doctors. However, the chaplain attends and also two “child life” members who are paid individuals who appear to be a cross between social worker, psychologist and occupational therapist. There is no computerisation of the patient data. The service cost and mostly covered by insurance but a third of patients are not well covered. Pulmonary function tests cost $250. Survival data is provided by the CF Foundation national registry.
Management of the chest. Patients have respiratory cultures 3-4 times a year. Usually isolated pathogens are treated but not always. All patients receive prophylactic antibiotics – usually Keflex, occasionally bacterium or cloxacillin. If not on antibiotics patients do get a course of Keflex with colds. Pseudomonas is not treated in the initial stages but when established intravenous antibiotics if there is clinical deterioration. There are usually 7 or 8 patients in the wards at any one time usually for treatment of Pseudomonas. Intravenous tobramycin and ticarcillin or piperacillin are preferred. Ceftazidime is also used and anti-staphylococal therapy is added in young children or when the organism has been grown in the past. Treatment need is determined mainly on symptoms. Rarely IV therapy is given at home. More than 50% of patients have Pseudomonas and six P. cepacia which they do not see as a serious problem. Nebulised antibiotics are used with slight increase in symptoms to prevent admission or frequent relapses.
There is regular extensive monitoring of the laboratory parameters. In some a tiny catheter via a small tracheostomy is used to insert colistin into the trachea. Bronchoscopes are used to irrigate the lungs with colistin. Pulmonary washouts are not performed. Some patients receive bronchodilators and 25% of young children receive steroids. Daily physiotherapy is recommend but PEP and FET are not used. There is no formal exercise programme. Theophylline appears to be used quite frequently as a bronchodilator and the blood levels are checked every 2 months.
Dr Ganez had previously worked at Hertford Connecticut and felt that diet was not emphasised here to the extent it was in his previous clinic; it was difficult to get patients to see a dietitian. Infants are fed Pregestimil without enzymes up to six month and Pancrease added when they start weaning foods. Nasogastric feeds are not used and few have gastrostomies. Oral supplements are used (Sustacal). Weight is monitored but there is no particular growth monitoring. Both fat soluble vitamins and a salt supplement are given. About 50% of patient are normally grown. Some 20% have meconium equivalent problems. Older children would receive 3 pancreas per meal.
In general discussion Dr Ganez regarding the impressive Canadian results, he said in his opinion the care in Canada was better, there was state provision of funding and the standard of living and home conditions were better in many cases.
I interviewed Miss Debbie Bowman RN the clinic nurse who was half time with the Apnoea Service and half time Pulmonology. The clinic nurses spend much time on the phone with relatives and patients. They have an important coordinating role in the unit just as our CF nurses have in Leeds. I was impressed by the interchangeability of the staff doing each others jobe when required. I was also shown the respiratory function laboratory and a full test was done every 6 months after the age of five years.
Dr Ganez had previous worked for 9 years in a smaller clinic at St Francis Hospital and Medical Centre Hertford Connecticut which he built up from 30 to 75 CF patients. There was more emphasis on nutrition and full attendance at weekly team meetings.
Dr Ganez was a pleasant man and was in charge as the clinic director was away at the time of my visit
It was a surprise to see a police officer on duty at the reception of the Children’s Hospital! However Dr Ganez did mention that social deprivation was a significant factor in failing to achieve results as were the rule in Toronto.
It was a great privilege to make these visits and everywhere I visited the staff were very friendly and welcoming, keen to provide me with as much information as possible during my day with them. There were obvious differences both between N. American clinics and our own practice in Leeds and I have discussed these in the text. However everywhere I went there were interested, caring and knowledgeable staff keen to do their best for their patients.
However, as I had found previously at the 1980 North American CF Conference in Toronto meeting, there were already many excellent CF centres in N. America – quite unlike the situation in the UK, even in the mid Eighties, where most children with CF were treated at their local hospital by a general paediatrician and usually died in childhood or in their teenage years. The CF centres I visited already had well established teams involved in the care of children and some, such as Toronto, in the care of adults with CF.
However, by 1986 we were catching up in the UK where, in 1982, the British Paediatric Association set up a working party on cystic fibrosis to advise on whether special CF centres for patients should be established. Data from Peter Phelan and Edmund Hey in Australia had highlighted the significantly inferior outlook for children in the UK compared with those in Australia. The authors suggested the difference in survival was related to the superior care the Australian children received their CF centres – hence the the remit of the UK CF Working party to advise on whether CF centre should be established in the UK.