The History of Cystic Fibrosis by Dr James Littlewood OBE

Edited and produced by Daniel Peckham

 

There are many references to allergic reactions to drugs, in particular to antibiotics. The repeated use of intravenous antibiotics over many years ahd resulted in allergic reactions emerging as a major practical problem. There are approximately 150 references to CF and antibiotics reactions on Medline and Pubmed most are not reviewed here. Allergy to pancreatic extracts is a problem in only a minority of patients.

 

Allergic bronchopulmonary aspergillosis is dealt with under a separate Mycology Topic.

 

Articles marked * are not included in main text but contain practical information and are linked to PubMed.

 

1976 Warner JO, Taylor BW, Norman AP, Soothill JF. Association of cystic fibrosis and allergy. Arch Dis Child 1976; 51:507-11. [PubMed]
A number of previous studies had shown an increased prevalence of atopy in people with cystic fibrosis. In this study from London this association was confirmed. Immediate skin hypersensitivity was present in 59% of 123 children with CF – a much higher incidence than normal. Also atopy was more frequent in the obligate heterozygotes. Allergic children with CF tended to have a worse respiratory state. The authors suggested that the increase in allergy possibly was related to impaired handling of antigen at mucosal surfaces.


One of many studies on allergy and cystic fibrosis which never seemed to have a great influence on clinical management - other than drugs allergies and the reactions to Aspergillus fumigatus. The first article on allergies in CF was by Kulczycki LL, Mueller H, Shwachman H. Respiratory allergy in patients with cystic fibrosis. JAMA 1961; 175:358-364.

 

1977 Treatment of cystic fibrosis. Brit J Dis Chest 1977; 1:295-299. (not abstracted in "Seventies"). [PubMed]
Mother of two children with CF developed allergic respiratory symptoms and severe asthma due to powder released when capsules were opened.

 

1977 Twarog FJ. Weinstein SF. Khaw KT. Strieder DJ. Colten HR. Hypersensitivity to pancreatic extracts in parents of patients with cystic fibrosis. J Allergy & Clin Immunol 1977; 59:35-40. (not abstracted in "Seventies"). [PubMed]

 

1986 Ferguson A, Merrett TG, Littlewood JM, Bolderson I. IgE antibodies to foods are not a feature of cystic fibrosis. Human Nutrition - Clinical Nutrition 1986; 40:255-258. [PubMed]
It had been suggested that patients with cystic fibrosis have abnormal immune responses to foods. In collaboration with Dr Anne Ferguson of Edinburgh, we measured IgE antibodies to inhalants and foods (by RAST) in 105 patients with cystic fibrosis aged between eight months and 28 years. Serum IgE was elevated (greater than 180 kU/l) in 21 (20%) patients. In 43, (41%) IgE antibodies were detected in serum. The majority of positive results were with house-dust mite, grass pollen or Aspergillus. Only four of the patients had a positive RAST to a food - one to milk, one to wheat and two to egg. On the basis of high serum IgE or positive RAST results, 44.8 per cent of the patients were atopic and the frequency of atopy was age-related, being higher in patients aged four years or more. However, the presence of food antibodies was unrelated to age.


This study confirms the high prevalence of atopy in patients with cystic fibrosis but unequivocally demonstrates that the presence of IgE antibodies to foods in their serum is rare. Of course, we had previously observed that many children with quite obvious clinical food intolerance (proved by withdrawal and challenge) have neither positive skin tests nor raised IgE levels nor positive RAST to foods (Minford AMB et al. Food intolerance and food allergy in children: a review of 68 cases. Arch Dis Child 1982; 57:742-747 [PubMed]).

 

1987 Lipkin GW. Vickers DW. Allergy in cystic fibrosis nurses to pancreatic extract. Lancet. [PubMed]
Letter reporting allergic reactions in nurses giving pancreatic extracts to children with CF on our ward in Leeds.

 

1998 Chamarthy, L M. Reinstein, L J. Schnapf, B. Good, R A. Bahna, S L. Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis. Pediatrics 1998; 102:e13. [PubMed]
At 29 months of age, a girl with CF developed diarrhea with bulky stools and weight loss. A fecal fat 72-hour study revealed a coefficient of absorption of 50%. She was treated with Pancrease MT 16, but had consistent vomiting 1 to 2 hours after administration of enzymes. The vomiting occurred on switching to different pancreatic enzymes preparations i. e. Creon 10, Viokase, and Pancrease MT 16. Vomiting occurred even with small doses of enzymes disguised in food. She had no vomiting on days when enzymes were not given. She was gradually desensitized with small doses of pancrease MT 16 to tolerate one capsule per meal.

 

* 2005 Parmar JS, Nasser S. Antibiotic allergy in cystic fibrosis. [Review]. Thorax 2005; 60:517-520. [PubMed]

A review article with some useful facts regarding cross reactions etc.

 

2003 Burrows JA, Toon M, Bell SC. Antibiotic desensitization in adults with cystic fibrosis. Respirology 2003; 8:359-364.[PubMed]

Encouraging experience over 7 years from a major Australian unit. 

 

2011 Whitaker P, Shaw N, Gooi J, Etherington C, Conway S, Peckham D. Rapid desensitization for non-immediate reactions in patients with cystic fibrosis. J Cyst Fibros 2011; 10:282-285. [PubMed]
Non-immediate hypersensitivity reactions to antibiotics in patients with CF represent a real-life challenge for clinicians. Desensitization is often performed in patients who have exhausted all therapeutic options. Whilst desensitization is an established procedure for immediate reactions the authors assessed the outcomes and safety of desensitization for non-immediate reactions. They retrospectively reviewed 275 desensitization procedures in 42 patients with a range of non-immediate reactions to six commonly used antibiotics. Desensitization was performed using a 7-step rapid intravenous protocol on a normal medical ward. 250 (91%) of overall desensitization procedures were successful; however, this figure incorporates certain individuals having multiple successful procedures. Individual patient success ranged from 55% with tenuously through to 88% with tobramycin. In the 25 patients who failed desensitization the reactions were mild and the majority occurred within 48 h of starting treatment. Prophylactic anti-histamines and steroids did not reduce the risk of reaction. Whilst the mechanisms remain uncertain the authors confirm that rapid desensitization is a safe and effective way of re-introducing an antibiotic to a patient with a non-immediate reaction.

 

Allergic reactions are a very common and important problem for CF patients who are having repeated course of antibiotics over many years. The report provides useful information for those facing these problems.

 

2012 Whitaker P, Naisbitt D, Peckham D. Nonimmediate b-lactam reactions in patients with cystic fibrosis. Curr Opin Allergy Clin Immunol 2012; 12:369-375.[PubMed]

This review discusses new developments regarding b-lactam sensitivity in people with cystic fibrosis. It is a common complication and some 30% of patients have multiple b-lactam reactions.

 

 

Morrow CB. Raraigh KS. Green DM. Blackman SM. Cutting GR. Collaco JM. Cat and dog exposure and respiratory morbidities in cystic fibrosis. Pediatrics 2014; 165:830-5.[PubMed]
A total of 703 subjects with CF were recruited through the US CF Twin-Sibling Study. There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and non-cat/dog owners. Within the sample, 47% of subjects reported owning a dog, and 28% reported owning a cat.
The authors found that cat ownership was associated with a greater frequency of developing nasal polyps and combined cat-dog ownership was associated with a greater rate of wheezing.
 
Please see also Topics section -> Microbiology -> Cross infection where there is an article on sources of infection where pets are discussed.

 

 

Pabary R. Severe pulmonary exacerbation in cystic fibrosis caused by cat allergy. Paediatr Respir Rev 2014; 15 Suppl 1:29-31.[PubMed]
A preschool child who had persistent symptoms suggestive of significant cystic fibrosis lung disease over a period of eighteen months following first isolation of Pseudomonas aeruginosa. Despite vigorous anti-infective treatment and extensive investigations seeking undetected infection, improvement only occurred once severe cat allergy was diagnosed and cats were removed from the household.
 
A reminder that it is important to consider non-infective pathologies when the response to anti-infective antibiotic treatment is unexpectedly poor. Similar suboptimal response to intravenous antibiotics may be observed when Aspergillus, rather than bacterial infection, is the main cause of the patients symptoms.