Cystic fibrosis: future trends in care.
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Biomedical subjects
Publications and source records attributed to D M Geddes.
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The influence of supplemental oxygen on exercise performance was assessed in 17 patients with severe airflow obstruction. Exercise capacity was measured by the six minute walking distance, by an endurance walking test, and by an endurance cycling test and comparison was made with performance when the patient was breathing air. In addition, the relation between the flow rate of supplemental oxygen and cycling endurance time was studied. Portable oxygen (41 min-1) carried by the patient increased the mean endurance walking time by 59% and the six minute walking distance by 17%. The endurance time for cycling at a constant work load was increased by 51% with oxygen at a flow rate of 21 min-1, by 88% at 41 min-1, and by 80% at 61 min-1. Supplemental oxygen prolonged the length of time that the patients were able to walk at a fixed speed. It also increased the mean speed achieved during a six minute walk but this was variable and did not occur in all the subjects. The benefit from supplemental oxygen was not cancelled by the effort of carrying the portable cylinder.
The practicality of physicians performing thoracoscopy for diagnostic purposes was assessed in 30 patients with pleural effusions of unknown cause. A rigid thoracoscope was compared with a fibreoptic bronchoscope used as a flexible thoracoscope and the diagnostic adequacy of biopsy specimens obtained with the two instruments assessed. The two instruments were inserted by a physician in the bronchoscopy suite using local anaesthesia. The procedure proved safe, acceptable, and diagnostically effective. The rigid thoracoscope proved a more satisfactory instrument but the fibreoptic bronchoscope, with minor adaptations, may be used for thoracoscopy.
The aims of antimicrobial therapy extend beyond short-term bacterial killing to long-term maintenance of weight and lung function. A review of antimicrobial drug trials shows that empiricism is still ahead of science and more studies are needed both to justify current practice and to make future changes logical.
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Previous work confirmed the abnormal potential difference between the undersurface of the inferior nasal turbinate and a reference electrode in cystic fibrosis, but the technique is difficult and the results show overlap between the cystic fibrosis and the control populations. In the present study the potential difference from the floor of the nose has therefore been assessed in normal subjects, as well as in adult patients with cystic fibrosis, bronchiectasis and Young's syndrome. Voltages existing along the floor of the nasal cavity were recorded. The mean potential difference was similar in controls (-18 (SD 5) mv) and in patients with bronchiectasis (-17 (6) mv) and Young's syndrome (-20 (6) mv). The potential difference in cystic fibrosis (-45 (8) mv) was significantly different from controls (p less than 0.002) and there was no overlap between the cystic fibrosis values and values obtained in normal and diseased controls. This simple technique therefore discriminates well between patients with cystic fibrosis and other populations, raising the possibility of its use to assist in diagnosis.
Two cases of cystic fibrosis complicated by sarcoidosis are described. Possible pathogenetic interactions between the two diseases are discussed. The diagnosis of sarcoidosis in patients with chronic pulmonary inflammation is difficult, and if overlooked may lead to inappropriate treatment.
An oral intestinal lavage solution has been successfully used in the treatment of six patients with chronic distal intestinal obstruction syndrome (previously referred to as meconium ileus equivalent) complicating cystic fibrosis and a further case of recurrent small bowel obstruction. The patient with recurrent obstruction is unusual in having no evidence of pancreatic maldigestion, which previously has been considered a prerequisite for the syndrome.
Twenty-six normal volunteers were exposed to rhinovirus or influenza B virus. Measurement of nasal mucociliary clearance, ciliary beat frequency, percent of epithelium ciliated, ciliary ultrastructure and nasal transmucosal potential difference were made before exposure, during viral incubation and at the time of expected overt infection. Ten volunteers failed to become infected, six were subclinically infected and nine were infected with symptoms. There were no significant differences between the results in volunteer groups during the incubation period or between uninfected and subclinical groups at the time of expected symptoms. Six of nine symptomatic infected volunteers had prolonged nasal clearance, and six of the seven biopsied had less than 50% of their epithelium ciliated. However, there was no significant reduction in ciliary beat frequency nor increase in ultrastructural ciliary abnormalities within this group of symptomatic volunteers. Of the two symptomatic infected (influenza B) volunteers tested, both showed significantly reduced transmucosal potential difference.
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Computed tomography (CT) is more sensitive in detecting pulmonary nodules than conventional chest radiography. The incidence of pulmonary nodules on thoracic CT scans, not visible on chest radiographs, in patients with small-cell carcinoma of the bronchus (SCCB) was 27%, and in patients with non-small-cell carcinoma (non-SCCB) the incidence was 28%. Some of these nodules may be malignant. This has implications for the surgical staging of patients with lung cancer in the United Kingdom, where there is a lower incidence of benign granulomatous nodules than in the USA.
We have studied various functional and morphological characteristics of mast cells obtained in bronchoalveolar lavage from fifty-two patients with several lung diseases. The percentage of mast cells ranged from 0.04 to 0.6% (bronchial carcinoma), 0.05-0.3% (sarcoidosis), 0.06-0.25% (asthma), 0.04-1.8% (miscellaneous) and 0.02-0.04% (normals). There were no significant differences in the mast cell counts between the disease groups. Lung mast cells exhibited heterogeneity of size, shape and intensity of staining. Cells from thirty-seven subjects were further studied for total histamine content and histamine release using various secretagogues. There was a significant correlation (P less than 0.001) between the histamine content of the total lavage cell population and mast cell counts. The calculated mean histamine content per mast cell was 6.35 pg. Histamine was released in a dose-dependent fashion after stimulation with anti-IgE, calcium ionophore and phorbol myristate acetate with a time course of histamine release characteristic of the mast cell. Unlike peripheral blood basophils, no release was observed following incubation with f-met-leu-phe (10(-6)-10(-8) M) and neither cell type released histamine following incubation with 48/80 (10 micrograms/ml). Inhibition of anti-IgE-induced histamine release was obtained following pre-incubation with salbutamol (10(-4)-10(-6) M). These studies indicate that bronchoalveolar lavage is a suitable model for the study of human lung mast cells.
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Twenty-five previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide 160 to 200 mg/kg (with autologous bone marrow support) followed by radiotherapy (4000 cGy) to the primary site and mediastinum. No other treatment was given until relapse occurred. Nineteen patients were assessable at least 4 months after radiotherapy; of these, 15 (79%) developed radiologic evidence of fibrosis, which was symptomatic in 14 (74%). The time of onset of fibrosis was related to the volume of lung irradiated. A retrospective analysis was made of 20 consecutive patients treated with multiple-drug chemotherapy and an identical radiotherapy regimen as part of a randomized trial. Radiologic and symptomatic fibrosis was one half as frequent (35%) as in the high-dose cyclophosphamide group. Very high-dose cyclophosphamide appears to sensitize the lung to radiotherapy and promotes the production of fibrosis.
The time spent in hospital when cerebral metastases occur as the first site of relapse in patients with small cell carcinoma of the lung (SCCL) has been analysed and compared to the consequences of relapse in the liver. In the course of a clinical trial with 370 patients, 50 patients relapsed initially in the brain and 20 in the liver. The 2 groups were comparable with respect to performance status at diagnosis and the amount of home support available. Patients who relapsed in the brain suffered a greater deterioration in performance status, and spent a greater proportion of their remaining life in hospital than did patients whose initial relapse was in the liver. This difference was most marked in patients who died soon after relapse. Radiotherapy (20 Gy in 5 fractions over one week or 30 Gy in 10 fractions over 2 weeks) and dexamethasone were not very effective treatments for brain relapse though subjective responses were common. The substantial morbidity and lengthy hospitalisation resulting from brain relapse compared with relapse at another site is a important factor to be considered in assessing whether prophylactic cranial irradiation should routinely be offered to patients with SCCL.
Oscillation of the air within the lungs at high frequency is associated with an increased clearance of CO2. Because of the high frequency and low volume of these oscillations, spontaneous breathing is unhindered and the technique has potential value as a supplement to ventilation. High-frequency oscillations were superimposed upon tidal breathing by using a loudspeaker attached to a mouthpiece (oral high-frequency oscillation, OHFO) or by external chest wall compression (ECWC). We set out (a) to compare the changes in ventilation and breathlessness by using OHFO and ECWC in normal subjects with those in patients with chronic airflow obstruction (CAO), and (b) to relate the pattern of saving to the resonant frequencies of the respiratory system as a whole (for, 5-10 Hz in normal subjects, 16-26 Hz in CAO) and those of the ribcage (foc, 70 Hz). OHFO reduced minute ventilation (VE) by up to 46% in normal subjects (P less than 0.01) and 29% in CAO (P less than 0.01) without any rise in CO2. ECWC reduced VE by 27% in normal subjects (P less than 0.01) and 16% in CAO (P less than 0.01) without a rise in CO2. High-frequency oscillation by either method relieved breathlessness in those with CAO and was comfortable and well tolerated. In normal subjects for was discrete and varied little with respiration. Maximum savings occurred around for (5-10 Hz). In CAO, there was no obvious single resonant frequency and flow and pressure signals were intermittently in phase over a band of about 10 Hz. Thus the reductions in minute ventilation were only loosely related to for (13-26 Hz). Neither group reduced VE at foc (65-75 Hz). OHFO has considerable potential in the management of patients with CAO, where it may be of value as an assistance to breathing and in the relief of breathlessness. ECWC, although effective in principle, is impractical by our methods and awaits the development of an acceptable delivery system.