Advances in knowledge and medical science have resulted in an increased life span and quality of life of patients with cystic fibrosis (CF). The median age of survival for CF patients is 32.3 years of age and patients 18 years of age or older now constitute one third of the total patients with CF. Because of these advances, a new patient population has emerged: the adolescents and young adults with CF. Adolescence is normally a time of great cognitive, social and developmental changes. Adolescents with CF not only have to deal with the normal changes expected, but also have to deal with the transition of assuming responsibility for their care from the parents and transitioning their care from a pediatric to an adult care team. Moreover, many of these young adults have to deal with the impact of the progressive deterioration of their CF disease. This review discusses issues of significance to this emerging patient population, including medical care, issues of disability, and psychosocial and other medical conditions associated with an increased life expectancy.

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.

BACKGROUND:Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues.METHODS:Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum.RESULTS:Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)).CONCLUSIONS:These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.

A patient with a 27 year history of schizophrenia is described. Post-mortem revealed the presence of a right sided parietal meningioma. It is possible that this lesion caused the schizophrenic symptoms and that earlier investigation might have led to removal of the lesion.

Cystic fibrosis (CF) is an autosomal recessive condition affecting one in 2,000 live births in the UK. There are few reports of malignant tumours in this condition probably because, until recently, the majority died before the age of 30 years as a result of recurrent and chronic bronchopulmonary infection with impaired growth and development and resistance to infection due to pancreatic malabsorption. We describe an adult male with CF who died from an adenocarcinoma affecting the ileocaecal region of the bowel.

An open randomised comparison of a new intravenous cephalosporin, ceftazidime, with the established regimen of gentamicin and carbenicillin was carried out in patients with cystic fibrosis who had persisting pulmonary infection with Pseudomonas species and who developed acute exacerbations of respiratory symptoms. Fifty patients received ceftazidime and 32 gentamicin and carbenicillin. The ceftazidime and gentamicin were given every eight hours and the carbenicillin every six hours. The mean total daily doses were 151 mg/kg for ceftazidime, 6.3 mg/kg for gentamicin and 450 mg/kg for carbenicillin. The mean duration of treatment was 10 days in patients receiving gentamicin and carbenicillin and 12 days in those receiving ceftazidime. Of the patients with pseudomonas in the initial sputum specimen in whom sputum was cultured after treatment, six (26%) of 23 receiving gentamicin and carbenicillin and seven (18%) of 39 receiving ceftazidime had sputum free from pseudomonas at the end of treatment, but recolonisation occurred subsequently. In those receiving ceftazidime all 10 coexisting organisms were eliminated, whereas only four of seven coexisting organisms in patients receiving gentamicin and carbenicillin were eliminated. Overall clinical improvement occurred in 25 (78%) of 32 patients treated with gentamicin and carbenicillin and 48 (96%) of 50 patients treated with ceftazidime. Nineteen (59%) of the patients receiving gentamicin and carbenicillin but only 15 (30%) of those receiving ceftazidime required admission to hospital or intravenous antibiotics, or both, or died during the three months after treatment. Side effects in both groups were similar, mild, and infrequent. Thrombophlebitis occurred in four patients treated with gentamicin and carbenicillin but in no patients treated with ceftazidime.

A 21-year retrospective autopsy study of bronchioloalveolar cell carcinoma in the Western District of Glasgow is presented which includes a detailed review of the case notes and post-mortem pathology of 18 patients. Aspects of the histogenesis of the tumour and its prognosis are included in the discussion. It is concluded that bronchioloalveolar cell carcinoma is a valid term which describes a disease entity that is amenable to successful surgical resection when at a limited stage but that in pathological terms it represents a heterogeneous population of tumours.

Summary In a double blind cross‐over comparison of a single dose 450‐mg slow‐release aminophylline (SRA) with placebo in eleven patients with stable, reversible airways obstruction SRA produced significantly greater increase in FEV 1 and vital capacity from 2 to 9 hr after administration. A second double‐blind cross‐over comparison of 450‐mg SRA with 400 mg of choline theophyllinate (CT) in eleven similar patients showed that SRA produced a slower rise in FEV 1 and VC than CT. However, the increase in spirometric readings following SRA was sustained at 9 hr after administration where the spirometric recordings after CT were falling. Whereas CT produced a peak value in plasma theophylline at 1 hr, the highest values after SRA occurred at 4 or 8 hr after administration. The plasma theophylline level at 8 hr after SRA was significantly higher than that following CT. In this single‐dose study, plasma theophylline levels obtained were within the normal therapeutic range and this was not exceeded and no side effects were recorded.

One hundred and five patients with inoperable non-small cell lung cancer were included in a randomized trial comparing the activity of vindesine as a single agent with the combination of vindesine and cisplatin. All patients were previously untreated and the majority (70%) had squamous carcinoma. The overall partial response rates in 88 evaluable patients were 7% for vindesine alone and 33% for the combined regime. There were no complete responders in either arm. The median survival of patients treated with vindesine and cisplatin was 11 months, compared with 4 months in those treated with vindesine alone (P = 0.008). Patients showing a partial or complete response to vindesine and cisplatin survived a median duration of 13 months, compared with 7 months for non-responders (P = 0.03). This survival benefit associated with the combination was particularly apparent for patients with ECOG performance status 0 or 1 (median survival greater than 18 months and 13 months respectively), locoregional disease (median survival 14 months) and squamous cell histology (median survival 13 months). Myelo-suppression was greater with the combination but was not a major treatment problem. Neurotoxicity, which was frequently dose-limiting, was of similar severity in both treatment groups. The results indicate that the combination of vindesine and cisplatin is superior to vindesine alone for remission induction in non-small cell lung cancer and confers a significant survival advantage compared with vindesine alone in patients with favourable prognostic factors.

To determine the value of specific immunotherapy with adjuvant BCG in operable lung cancer, the immunological and clinical results of serial postoperative injections of autologous irradiated tumour cells and BCG were compared with those of a single preoperative injection of BCG in two randomly selected groups of patients undergoing resection of their tumours. There was a significant rise in tuberculin skin reactivity from seven weeks to 11 months after operation in the treated group. Actuarial curves for survival and freedom from tumour recurrence and median survival times showed an advantage for the treated patients who had stage I tumours, but these differences were significant only at the levels p = 0.07 - 0.09. Survival and duration of freedom from tumour recurrence was greater in autograft-treated patients whose skin responded to a weak test dose of dinitrochlorobenzene (DNCB) after sensitisation with 2% DNCB than in control DNCB-positive patients (p = 0.02). There were no significant differences in the actual proportion of patients from each group surviving at two years. The results show that this form of specific immunotherapy with adjuvant may have a beneficial effect in patients with stage I tumours and those who become sensitised to 2% DNCB after the first exposure.

Todetermine thevalue ofspecific immunotherapy withadjuvant BCG inoperable lung cancer,theimmunological andclinical results ofserial postoperative injections ofautolog- ousirradiated tumourcells andBCG werecompared withthose ofasingle preoperative injection ofBCGintworandomly selected groupsofpatients undergoing resection oftheir tumours. There was asignificant rise intuberculin skin reactivity fromsevenweeksto11months after operation inthetreated group.Actuarial curvesforsurvival andfreedom fromtumourrecurrence and median survival times showed anadvantage forthetreated patients whohadstageItumours,but these differences were significant onlyatthelevels p = 0-07-0-09. Survival andduration of freedom fromtumourrecurrencewas greater inautograft-treate d patients whoseskin responded toaweaktestdoseofdinitrochloroben zene (DNCB)after sensitisation with2% DNCB thanin control DNCB-positive patients (p 0.02). There were no significant differences intheactual proportion ofpatients fromeach groupsurviving attwoyears.Theresults showthat this formof specific immunotherapy withadjuvant may havea beneficiat effect inpatients withstageI tumoursandthose whobecomesensitised to2% DNCB after thefirst exposure. Manyinvestigations ofimmunotherapy inlung cancer haveshownthatithasatthemostaweak therapeutic action. Itisthuslikely tobeofvalue onlywherethetumourcell population hasbeen reduced toaminimum, asafter surgical resection.' Withtheexception oftheunconfirmed results of intrapleural BCG,2non-specific immunological stimulants haveproduced little effect insurgical cases.34 A possible reason forthis ineffectiveness maybefailure tofocus theavailable cytotoxic potential ofactivated lymphocytes andmacrophages against residual tumourcells. Possibly this lackof specific activity could beovercome byinjecting lung cancer cells into patients whoseimmunological sys- temshavepreviously beenstimulated bymycobac- teria. Weheredescribe theimmunological andclini- calresults ofinjecting irradiated autologous tumour cells into skin areas previously treated withBCGin patients whohaveundergone resection oflung cancer.

In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age- and sex-matched controls. Sensitisation to DNCB occurred in 52% of 37 patients but in 78% of controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (P=0.001), but there was no difference in lymphocyte transformation by PHA or pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in cutaneous tuberculin reactivity (P=0.08) and total leucocyte count (P=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (P less 0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort.

Five of eleven patients with bronchiectasis and/or cystic fibrosis developed a polyarthritis with positive tests for rheumatoid factor. Possible mechanisms of this complication are discussed.