Nasal and sinus disease in cystic fibrosis

Paranasal and sinus disease is present in almost every patient with cystic fibrosis. However, symptoms are rarely reported. Some aspects including polyposis and microbial flora change with patient age. Endoscopy and computerised tomography have broadened our understanding of how this disease affects the sinuses, including an increased recognition of polyposis than previously thought and identification of several disease specific entities such as abnormalities of the lateral nasal wall and uncinate process. Few randomised, controlled trials evaluating medical or surgical treatments of CF sinus disease exist. Sinus surgery may provide some benefit, though there are no established selection criteria for appropriate candidates. A link between sinus disease and lower respiratory tract function may contribute to general health and survival following lung transplantation. Complications of sinonasal disease in CF are rare and include mucoceles and periorbital abscesses.     

Complement in cystic fibrosis

Complement components C3, C4, and C3A were estimated in 30 patients with cystic fibrosis aged 1 to 21 years (MF=1614) and were compared with results in 40 healthy, age-matched subjects. The influences of the clinical score, sputum microbiology, and the patients' sex were also investigated. In contrast to most previous communications, this paper shows that, compared to the control group, a significant decrease of C3 (P<0.001) and C4 (P<0.02) was observed whereas C3A levels were not altered. There were no increases in complement. Shwachman-scores above or below 70 did not influence the complement levels, nor did exacerbations of the disease change the levels. No influence of the patients' sex could be shown. Pseudomonas aer. in the sputum was clearly associated with complement defects (14/18). Alternative-pathway involvement of complement activation could be demonstrated in 32%. The results make complement activation due to pulmonary infection most likely. The defects observed probably represent secondary changes.Presented at the VIIth Annual Meeting of the European Working Group for Cystic Fibrosis, Dresden, June 20–21, 1977Dedicated to Professor E. Zweymüller on the occasion of his 60th birtday     

Osteoporosis in cystic fibrosis

To determine if osteoporosis is prevalent among patients with cystic fibrosis, we compared the vertebral bone density measured by quantitative computed tomography in 57 such patients (29 male, 28 female, aged 3 to 21 years) with those of an age-, race-, and sex-matched control group of 57 healthy subjects. Patients with cystic fibrosis had significantly lower bone density (10% lower, p less than 0.001) than in controls. The decrease in bone density in patients with cystic fibrosis was unrelated to age. Shwachman clinical evaluation scores (based on case history, pulmonary physical findings, growth, and x-ray findings) correlated positively with age-standardized bone density values (p less than 0.01). Male patients had substantially lower bone density than did female patients (p less than 0.02), but bone density differences related to gender were not significant when effects of disease severity were controlled for. Decreased bone density was more common in patients with poor nutritional status as determined by anthropometric measurements (p less than 0.05). We conclude that osteoporosis is a frequent complication in children with cystic fibrosis regardless of their age and is more prevalent in patients with greater disease severity.     

Pneumonectomy in cystic fibrosis

We present the case of a 13-year-old boy with cystic fibrosis (CF) who developed severe right-sided lung infection with formation of abscess and localized bronchiectasis. The boy's lung disease was complicated by nephrotic syndrome and secondary amyloidosis. Unilateral pneumonectomy was performed, producing significant clinical improvement with a remarkable increase in quality of life which has lasted to the present date, 15 years later. Most patients with CF develop lung disease, which is the main cause of adult mortality in this population. Lung transplantation is currently considered the treatment of choice in severe bilateral lung disease in CF. However, in severe unilateral lung disease such as localized bronchiectasis, surgical resection of the affected lobe or lung is still a worthwhile option as a rescue therapy for patients who are at high risk of dying while waiting for lung transplantation.     

Complement in cystic fibrosis

Quantitative and functional assessments were made of both the classical and alternative pathways of complement activation in sera from 23 patients with cystic fibrosis. The classical pathway functioned similarly in patients and controls as measured by CH50 titre. Alternative pathway function, initiated in patient sera by incubation with inulin, was equal to that of controls as determined by cleavage of Factor B and C3, and by the consumption of terminal components. Factor B, however, was more readily activated in patient than in control sera. This rapid alteration of Factor B did not lead to accelerated or more extensive activation of the terminal complement components via the alternative pathway when assessed by C3 cleavage and the consumption of terminal components. Thus, a complement deficiency was not found. The importance of the easily activated Factor B is undefined.     

Encephalopathy in cystic fibrosis

Cystic fibrosis liver disease (CFLD) affects a large proportion of cystic fibrosis (CF) patients; however encephalopathy is a rare complication. While classical hepatic encephalopathy can be a feature of end-stage liver disease, “hyperammonemic encephalopathy” can be precipitated in previously stable CFLD by various triggers including systemic corticosteroids. We describe one such case and review the relevant literature.     

Mucolytics in cystic fibrosis

Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy. In addition, thinning of secretions may not always be beneficial, since it may negatively affect certain aspects of mucus transport such as cough clearance. While inhaled N-acetylcysteine has been used as a mucolytic drug in CF for decades, there is little evidence that it has any beneficial effect. Dornase alfa has been shown to reduce pulmonary exacerbations and improve lung function and is currently the only mucolytic agent with proven efficacy in CF. Newer agents targeting other components of CF mucus, such as filamentous actin, are currently in development. Ultimately, drugs that are mucokinetic, which preserve viscoelasticity, rather than mucolytic may prove to be beneficial for CF lung disease in the future.     

Immunological studies in cystic fibrosis

Evidence is presented to support the concept that much of the allergy in cystic fibrosis (CF) is IgE mediated. Total IgE levels were higher in allergic than in nonallergic CF patients. Levels were also higher in those patients who had had the greatest number of chest infections in the preceding 12 months. IgE antibody levels to Dermatophagoides pteronyssinus, Timothy grass pollen, and Aspergillus fumigatus were higher in those with positive results from skin tests to these allergens. The serum IgG, IgM, and IgA levels of allergic and nonallergic CF patients did not differ but the overall mean values for IgG and IgM were higher than those reported for healthy British children. The highest levels tended to be present in patients with the greatest number of recent major chest infections and the difference was significant for IgG. 16 patients had IgA levels 72SD below the reported means for age-matched controls and 11 of these were nonallergic. IgA levels were also higher in patients who had recently experienced major chest infections. 45 of the patients were tissue types for HLA A and B antigens but no significant clinical associations with single antigens were observed. The antigen phenotype A1 + B8 was more common in datients with multiple allergic symptoms than in those with a single allergy or merely a positive result from a skin test Nonsignificant increases of W19 in patients with frequent infections and of A2 in patients presenting with meconium ileus were also noted. The data presented do not permit a choice to be made between the alternative concepts of allergy as a primary abnormality in CF, and allergy arising secondary to infection.     

Bronchial lability in cystic fibrosis

Bronchial lability was studied in 52 children with cystic fibrosis (CF) and assessed by changes in the peak expiratory flow measured before, during, and after running. The findings are discussed in relation to the severity of pulmonary involvement assessed clinically and radiologically, and with those found in asthmatic children and those with a history of wheezy bronchitis in early childhood.In patients with CF, bronchial lability was found even in those with minimal pulmonary involvement. The lability was due not only to bronchoconstriction but to a dilatation which was greater than occurs in normal and asthmatic children; this dilatation increased with the severity of the disease.Only 14 of 52 children with CF had results within the normal range for all indices; 50% had abnormal bronchodilatation during exercise and 46% had abnormal bronchoconstriction after exercise.