Advice on long-term corticosteroid treatment may be misleading.
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Clinical Protocols↗
Biomedical subjects
G J Gibson
Publications and source records attributed to G J Gibson.
Respiratory mechanics after heart-lung and bilateral lung transplantation.
BACKGROUND: The factors determining respiratory mechanics following heart-lung transplantation (HLT) and bilateral lung transplantation (BLT) are incompletely understood. METHODS: The dynamic and static lung volumes of 15 patients after HLT (n = 6) and BLT (n = 9) with no evidence of obliterative bronchiolitis were analysed to assess the factors which determine lung volumes following transplantation. Post-transplantation total lung capacity (TLCpost) was compared with the size of the recipient's lungs (TLCpre), the predicted capacity of the thorax of the recipient (TLCpred), and the predicted size of the donor's lungs (TLCdon). In addition, the post-transplantation respiratory mechanics were investigated by measuring the static pressure-volume (PV) curve of the lungs and the maximum respiratory pressures in a subgroup of nine patients (four HLT, five BLT). RESULTS: TLCpost was closely related to TLCpred in both groups and showed no correlation with TLCpre. The mean (95% CI) TLCpost was 102.5 (90.2 to 115)% predicted for the recipient in the HLT group and 109 (97.6 to 120)% predicted for the recipient in the BLT group. Despite the near normal TLC, residual volume (RV) and functional residual capacity (FRC) remained increased after transplantation in both groups. These abnormalities were not attributable to either airflow obstruction or expiratory muscle weakness. On average, lung compliance expressed in terms of the shape constant of the static pressure-volume curve of the lungs was mildly reduced in both groups compared with values predicted for the recipient. CONCLUSIONS: These results suggest that at high lung volumes the chest wall adapts to the size of transplanted lungs, while at lower volumes the increase in FRC and RV might be due to a persistent change in the static pressure-volume curve of the chest wall.
Adult↗
A simple radiographic scoring method for monitoring pulmonary sarcoidosis: relations between radiographic scores, dyspnoea grade and respiratory function in the British Thoracic Society Study of Long-Term Corticosteroid Treatment.
BACKGROUND: We used a simple semi-quantitative radiographic scoring system for a controlled prospective study of long term corticosteroids in pulmonary sarcoidosis, conducted by the British Thoracic Society. METHODS: Radiographic opacities were described in 4 categories: reticulo-nodular shadows [R], mass opacities [M], confluence [C], and shadows associated with possible pulmonary fibrosis [F]. The extent of each type was scored on a 0-4 scale by quartiles, and profusion by a 0-4 scale as absent, minimal (just perceptible), mild moderate or gross. Combined scores for each film were derived by multiplying the extent and profusion for each type of opacity. In the study 149 patients were examined at entry and periodically over a 5-year period. Using the whole study population we examined the relationship between the radiographic scores for extent and profusion, how predominant types change with time and how the scores correlated with other indices of disease severity. RESULTS: R was the predominant abnormality throughout the study with a strong correlation between extent and profusion. Significant correlations in the expected directions were demonstrated between the R and F scores and a dyspnoea score, spirometry and TLCO, both at study entry, after 6 months and after 5 years. Similarly, there were significant relations between changes in spirometry and TLCO over five years and changes in R and F Scores. CONCLUSION: This scoring system would seem to be suitable, perhaps after further validation work, for other prospective clinical studies.
Adolescent↗
Evaluation of activity-based techniques to identify transient arousal in respiratory sleep disorders.
Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep. Arousal is often associated with abrupt changes in the electroencephalogram (EEG), and such changes can be used as an index of sleep disturbance, but EEG analysis is laborious and requires trained observers. Possible alternative indices of arousal not reliant on EEG analysis were investigated. Recordings were made from 36 sleeping subjects who were being investigated for sleep-related breathing disorders. In each study awakenings and transient arousals according to EEG criteria were compared with activity in five potential indirect indicators of arousal: wrist movement, ankle movement, left and right tibial electromyogram, and phase change in ribcage-abdominal movement. The mean values of sensitivity to arousal ranged from only 25 to 45%. However, their high positive predictive accuracies (PPAs, 68 to 92%) indicated that activity, when present, was usually associated with arousal. Sensitivity to awakenings was higher (71-87%), though PPAs were lower (42 to 63%). For the indicator based on ribcage-abdominal phase, the number of periods of activity showed a significant relation to the number of arousals (r = 0.70, P < 0.001). It can be concluded that phase changes in chest/abdomen movement are a useful indicator of arousal associated with obstructive apnoea and related conditions. Limb activity has much lower sensitivity for transient arousal, but may be of value in indicating periods of wakefulness.
Adult↗
Automated recognition of EEG changes accompanying arousal in respiratory sleep disorders.
Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep, associated with abrupt changes in the electroencephalogram (EEG). EEG is normally assessed by trained observers from paper records, but automation offers the advantages of speed and objectivity. We assessed 10 automated indices of EEG activity as potential indicators of arousal. Arousals from light, slow wave and rapid eye movement sleep were studied in 30 subjects. Segments of EEG recorded immediately before and after each arousal were analyzed by automated measurement of 10 EEG indices using a personal computer. We investigated the ability of each index to recognize arousal while rejecting change due to variability during sleep. Nine of the 10 indices showed significant changes with arousal (p < 0.001); the better indices were related to EEG frequency, and 3 were chosen for further study. In these indices, the mean changes with arousal were 3.8 Hz (ZeroCross), 1.7 Hz (Hjorth's Mobility) and 1.2 Hz (FrqMean, an index of central EEG frequency). With none of these three indices were significant differences in performance due to base sleep stage or subject group found. We conclude that detection of arousal is feasible using automated methods that measure simple indices related to the frequency of the EEG waveform.
Adult↗
British Thoracic Society Sarcoidosis study: effects of long term corticosteroid treatment.
BACKGROUND: Corticosteroids suppress disease activity in pulmonary sarcoidosis and their use produces symptomatic, radiographic, and functional improvement. There is, however, uncertainty regarding their effects on the overall natural history of the condition and long term benefit is unproven. METHODS: Patients with pulmonary radiographic shadowing due to sarcoidosis were recruited in a multicentre study. Those who, in the first six months after entry to the study, neither required prednisolone for symptoms nor showed radiographic improvement were allocated at six months to receive either long term steroid treatment (group L) or selective treatment (group S), with regular assessment over the subsequent five years. Patients in group L were scheduled to receive steroid treatment for at least 18 months with the policy of achieving and maintaining maximal radiographic clearing, while in group S treatment was reserved for use only if warranted by later development of symptoms or deteriorating lung function. Symptoms, radiographic appearances, and respiratory function were assessed periodically during the study. RESULTS: One hundred and forty nine patients were followed: 33 required prednisolone for troublesome symptoms within six months of entry and 58 showed radiographic improvement over this period. The remaining 58 patients were allocated to groups L (n = 27) and S (n = 31). Patients in group L showed greater improvements in symptoms, respiratory function, and radiographic appearances than those in group S, although the differences were not large. After adjusting for differences at the time of allocation, the average difference in vital capacity between groups L and S at final assessment was 9% of the predicted value. Side effects of treatment were frequent but usually mild, necessitating withdrawal in only two individuals. CONCLUSIONS: After excluding those individuals who required steroids for control of symptoms, approximately half of the remaining patients with sarcoidosis and pulmonary shadowing showed spontaneous radiographic improvement during six months of observation. In those in whom the radiograph failed to improve, prolonged steroid treatment with the aim of optimising radiographic appearances resulted in a significantly better long term functional outcome.
Adult↗
Pulmonary hyperinflation a clinical overview.
Pulmonary hyperinflation is usually defined as an abnormal increase in functional residual capacity, i.e. lung volume at the end of tidal expiration. As such, it is virtually universal in patients with symptomatic diffuse airway obstruction. Hyperinflation inferred from a standard chest radiograph implies an increase in total lung capacity. The relaxation volume of the respiratory system (Vr) increases in patients with chronic airway disease as a result of changes in the elastic properties of the lungs and chest wall. In addition, a variable degree of dynamic hyperinflation may be present. This results from the onset of inspiration before lung volume has fallen to Vr. Dynamic hyperinflation is frequently present at rest in patients with moderate-to-severe airway obstruction, and it increases further on exercise, thereby increasing the mechanical load on the inspiratory muscles and at the same time reducing their mechanical advantage. Important clinical consequences and associations of hyperinflation include: distortions of chest wall motion; impaired inspiratory muscle function; increased oxygen cost of breathing; greater likelihood of hypercapnia; impaired exercise performance; and greater severity of breathlessness. The symptomatic improvement after treatment with a bronchodilator may be due, in part, to lessening of hyperinflation.
Exercise Tolerance↗
Identification, expression, and biochemical characterization of N-acetylgalactosamine-4-sulfatase mutations and relationship with clinical phenotype in MPS-VI patients.
Maroteaux-Lamy syndrome, or mucopolysaccharidosis type VI (MPS-VI), is a lysosomal storage disorder characterized by the defective degradation of dermatan sulfate due to the deficiency of N-acetylgalactosamine-4-sulfatase (4S). The clinical severity of MPS-VI ranges in a continuum from mildly affected to severely affected patients. Mutations in MPS-VI patient samples were identified by chemical cleavage and direct DNA sequencing of PCR products derived from patient cDNA. Five amino acid substitutions were identified (T92M, R95Q, Y210C, H393P, and L498P), individually introduced into the wild-type 4S cDNA by site-directed in vitro mutagenesis, and transfected into Chinese hamster ovary cells. Three of the five mutations (R95Q, Y210C, and H393P) were observed in >1 of 25 unrelated MPS-VI patients; however, the mutations were not found in 20 control individuals. The residual 4S activity and protein (biochemical phenotype) were determined for each mutant in order to confirm their identity as mutations and to dissect the contribution of each mutant allele to the overall clinical phenotype of the patient. For each patient, the combined biochemical phenotypes of the two 4S mutant alleles demonstrated a good correspondence with the observed clinical phenotype (with the possible exception of a patient who was a compound heterozygote for T92M and L498P). This preliminary correspondence between genotype and the phenotype in MPS-VI may, with further refinement, contribute to the assessment of therapeutic approaches for MPS-VI patients.
Adolescent↗
Respiratory muscles: clinical relevance.
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Cardiovascular Diseases↗
Chondrocyte apoptosis in endochondral ossification of chick sterna.
In the process of endochondral ossification, chondrocytes progress through a series of maturational changes, including division and hypertrophy, that culminate in chondrocyte loss and cartilage resorption. From an investigation of morphology, DNA fragmentation and collagen synthesis in the developing chick sterna we have characterized chondrocytes death in this process. Light microscopy of resorbing sterna demonstrated chondrocyte condensation at the interface with the invading vasculature and electron microscopy demonstrated a range of chondrocyte morphologies, including retraction from the pericellular matrix, cytoplasmic and nuclear condensation, and vesiculation suggestive of sequential changes characteristic of apoptosis. Isolation and end-labeling of DNA from chick primary ossification centers demonstrated fragmentation to nucleosome sized units, only in primary ossification centers exhibiting active resorption, and in situ detection of DNA fragmentation showed a restriction to chondrocytes at the interface with invading blood. We conclude that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels. The extent of DNA fragmentation correlated closely with the proportion of cells displaying a condensed phenotype in contralateral primary ossification centers and peaked at an early stage of resorption, suggesting that chondrocyte apoptosis may be an initiating event in tissue resorption and vascular invasion. Comparison of DNA fragmentation with expression of the hypertrophic chondrocyte phenotype, as indicated by type X collagen synthesis, suggested that DNA fragmentation was a late event in the process of chondrocyte hypertrophy and probably corresponded with chondrocyte condensation
Animals↗
Endochondral resorption of chick sterna in culture.
Endochondral resorption is most clearly recognized at the metaphyseal interface of the growth plate with the adjacent vasculature; however, apparently identical processes of endochondral resorption are seen in sites of primary and secondary ossification of the cartilaginous anlage of bones and in ossifying fracture callus. Recent evidence of the expression of the hypertrophic phenotype in osteoarthrotic articular cartilage suggests that endochondral resorption also may be a factor in the loss of articular cartilage in this condition. To investigate the mechanism of endochondral resorption, a model culture system was developed and characterized. The two primary centers of ossification with surrounding cartilage were dissected from embryonic chick sterna prior to (18-day-old embryos) or after (20-day-old embryos) the initiation of resorption. They were cultured either in plastic culture dishes or on chorioallantoic membranes, and resorption was detected by analysis of the loss of types II and X collagen and by histological characterization. Only sterna showing active resorption in vivo were resorbed when cultured on chorioallantoic membrane. The histological appearance of the resorption site and the specificity of resorption to the primary ossification center, seen from both the analysis of loss of collagen and histological observation, suggested that the resorption of sterna cultured on chorioallantoic membrane was similar to that observed in vivo. These studies further indicated that both vascular cells and viable chondrocytes were required for resorption. Susceptibility to resorption could be induced in resistant primary ossification centers by prior culture in the absence of vascular cells, and it is suggested that it results from the accumulation of resorption-susceptible cells and matrix as a result of continued chondrocyte development.
Allantois↗
Platypnoea-orthodeoxia in cryptogenic fibrosing alveolitis.
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Diagnosis, Differential↗
Measurement of respiratory muscle strength.
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Adult↗
Comparison of methods for assessing snoring.
Objective measurements of several sound level indices were made on 32 subjects referred because of snoring and who subsequently underwent uvulopalatopharyngoplasty (UPPP). The measurements were repeated approximately 6 months post-UPPP. The indices were compared with the subjective assessment of snoring by both the subject and his/her bed partner. Correlations between objective and subjective assessments were generally weak and were strongest when the supine posture only was considered. The index which correlated best with subjective assessment was the level which 1% of the sound level samples exceeded.
Abdomen↗
Objective measurement of the results of uvulopalatopharyngoplasty.
Thirty-two patients undergoing uvulopalatopharyngoplasty (UPPP) for snoring have been studied prospectively using objective measurement of snoring levels. A significant reduction was found, especially in the supine posture. The quantitative reduction was small and correlations between subjective and objective changes in snoring volume were weak.
Adult↗
Respiratory muscle activity during rapid eye movement (REM) sleep in patients with chronic obstructive pulmonary disease.
BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) periods of hypopnoea occur during rapid eye movement (REM) sleep, but the mechanisms involved are not clear. METHODS: Ten patients with stable COPD were studied during nocturnal sleep. Detailed measurements were made of surface electromyographic (EMG) activity of several respiratory muscle groups and the accompanying chest wall motion using magnetometers. RESULTS: Hypopnoea occurred in association with eye movements during phasic rapid eye movement (pREM) sleep. During pREM sleep there were reductions in EMG activity of the intercostal, diaphragm, and upper airway muscles compared with non-REM sleep. Episodic hypopnoea due to partial upper airway occlusion ("obstructive" hypopnoea) was seen consistently in four subjects while the others showed the pattern of "central" hypopnoea accompanied by an overall reduction in inspiratory muscle activity. Although activity of the intercostal muscles was reduced relatively more than that of the diaphragm, lateral rib cage paradox (Hoover's sign) was less obvious during pREM-related hypopnoea than during wakefulness or non-REM sleep. CONCLUSIONS: Hypopnoea during REM sleep in patients with COPD is associated with reduced inspiratory muscle activity. The pattern of hypopnoea may be either "obstructive" or "central" and is generally consistent within an individual. Relatively unopposed action of the diaphragm on the rib cage during REM sleep is not accompanied by greater lateral inspiratory paradox.
Aged↗
Perception, personality, and respiratory control in life-threatening asthma.
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Asthma↗
Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment.
Nocturnal secretion of growth hormone is impaired in patients with obstructive sleep apnea (OSA), but the metabolic consequences have not been reported. We measured blood levels of the hormones insulin, C-peptide, growth hormone, cortisol and glucagon together with the intermediary metabolites of carbohydrate (glucose, pyruvate, lactate, alanine) and lipid metabolism [glycerol, nonesterified fatty acids (NEFA), 3-hydroxybutyrate] in six obese nondiabetic men with OSA on two nights. In the first study, the untreated subjects showed frequent apneas and consequent hypoxemia. The hormone and metabolite concentrations were compared with those obtained on the following night when the subjects were treated effectively with nasal continuous positive airway pressure (CPAP). There were no significant differences in the concentrations of insulin, C-peptide, cortisol or glucagon. We confirmed a marked reduction in growth hormone concentrations in OSA, with a significant increase on the CPAP night. The nocturnal profiles of glucose, pyruvate, lactate, alanine and glycerol showed no differences between the two nights, but concentrations of NEFA and 3-hydroxybutyrate, both products of lipolysis, were significantly greater on the treatment night. Because growth hormone has a lipolytic action, the results suggest that suppression of secretion of growth hormone in untreated OSA results in impaired lipolysis, which is rapidly reversed by nasal CPAP.
Adult↗