Biomedical subjects
Publications and source records attributed to M G Pearson.
This paper reviews published audit activity for a single common condition (asthma). Has this effort brought about better care for the patient? The result of this audit of audits reveals that specialists do follow the guidelines on the management of acute asthma with good results, but that general physicians, in whose care perforce many acute episodes are managed, do not seem to be aware of the published good practice guidelines.
BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.
Although inspiratory resistive loading (IRL) reduces the ventilatory response to CO2 (VE/PCO2) and increases the sensation of inspiratory effort (IES), there are few data about the converse situation: whether CO2 responsiveness influences sustained load compensation and whether awareness of respiratory effort modifies this behavior. We studied 12 normal men during CO2 rebreathing while free breathing and with a 10-cmH2O.l-1.s IRL and compared these data with 5 min of resting breathing with and without the IRL. Breathing pattern, end-tidal PCO2, IES, and mouth occlusion pressure (P0.1) were recorded. Free-breathing VE/PCO2 was inversely related to an index of effort perception (IES/VE; r = -0.63, P less than 0.05), and the reduction in VE/PCO2 produced by IRL was related to the initial free-breathing VE/PCO2 (r = 0.87, P less than 0.01). IRL produced variable increases in inspiratory duration (TI), IES, and P0.1 at rest, and the change in tidal volume correlated with both VE/PCO2 (r = 0.63, P less than 0.05) and IES/VE (r = -0.69, P less than 0.05), this latter index also predicting the changes in TI with loading (r = -0.83, P less than 0.01). These data suggest that in normal subjects perception of inspiratory effort can modify free-breathing CO2 responsiveness and is as important as CO2 sensitivity in determining the response to short-term resistive loading. Individuals with good perception choose a small-tidal volume and short-TI breathing pattern during loading, possibly to minimize the discomfort of breathing.
Short-term trials of bronchodilator drugs are widely used to assess patients with stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty about the equivalence of the FEV1 response to beta-agonists and anticholinergic drugs, their relative ability to identify patients likely to improve with corticosteroids, the most appropriate way to express the results of these tests, and whether age or allergic status affects the beta-agonist and anticholinergic response differently. We studied 100 consecutive patients with stable COPD (mean FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily. Total IgE, specific RAST, and skin prick testing values were recorded. Using modified American Thoracic Society response criteria, 33 patients failed to bronchodilate after the acute trials, 16 responded only to nebulized salbutamol, 17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved after corticosteroids. This was usually detected by a positive acute trial response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1 differed between days, and in those who responded on only 1 day, this variation correlating with the response to ipratropium (r = 0.66). Expressing the response criterion as a percentage change in the available bronchodilatation increased the numbers responding with a high baseline FEV1, and vice versa. Neither age nor allergic status was related to the change in FEV1 after either drug in these patients. In COPD patients, testing with high-dose nebulized bronchodilators identifies a substantial number of partially reversible patients whatever age it is employed.(ABSTRACT TRUNCATED AT 250 WORDS)
Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double-blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients.
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A 21 year old man presented with diarrhoea and flushing after meals and later developed miliary shadowing on his chest radiograph. Multifocal bronchial carcinoid tumour was diagnosed initially, but at necropsy metastatic medullary carcinoma of the thyroid was found. Multifocal bronchial carcinoid tumour should not be accepted as a primary diagnosis without first excluding medullary carcinoma of the thyroid because of the need to screen relatives of affected patients.
Five patients over the age of 40 with malignant mesothelioma of the pleura presented with a spontaneous pneumothorax in the course of five years. The diagnosis of malignant mesothelioma was not suspected at surgery but was made by histological examination of the pleurectomy specimens. During this time 91 pleurectomies for recurrent pneumothorax were performed, 45 in patients over the age of 40; malignant mesothelioma therefore accounted for 11% of spontaneous pneumothorax requiring pleurectomy in this age group. The association of spontaneous pneumothorax and malignant mesothelioma is not emphasised in current publications. These five cases highlight the need for all pleurectomy specimens in cases of spontaneous pneumothorax to be sent for histological examination and for a full occupational history to be taken, especially in older patients.
1. To examine the relationship between the inspiratory effort sensation (IES) and respiratory drive as reflected by mouth occlusion pressure (P0.1) we have studied loaded and unloaded ventilatory responses to CO2 in 12 normal subjects. 2. The individual coefficient of variation of the effort sensation response to CO2 (IES/PCO2) between replicate studies was 21% and was similar to the variability of the ventilatory response (VE/PCO2) (18%) and the occlusion pressure response (P0.1/PCO2) (22%). 3. IES was well correlated with P0.1 (r greater than 0.9) for both free-breathing and loaded runs. 4. Resistive loading reduced the ventilatory response to hypercapnia from 19.3 l min-1 kPa-1 (SD 7.5) to 12.6 l min-1 kPa-1 (SD 3.9) (P less than 0.01). IES and P0.1 responses increased with resistive loading from 2.28 (SD 0.9) to 3.15 (SD 1.1) units/kPa and 2.8 (SD 1.2) to 3.73 (SD 1.5) cmH2O/kPa, respectively (P less than 0.01). 5. Experimentally induced changes in PCO2 and respiratory impedance were accompanied by increases in IES and P0.1. We found no evidence that CO2 increased IES independently of its effect on respiratory drive.
Spirometry before and after an inhaled beta agonist or a course of oral prednisolone is widely used to detect reversible airflow limitation in patients with chronic obstructive lung disease. How many of these patients have a response and how the response to beta agonists relates to the response to corticosteroids is not clear. In 127 outpatients (mean (SD) FEV1 0.92 (0.38) 1) who had a clinical diagnosis of chronic obstructive lung disease (continuous breathlessness for more than six months and an FEV1/forced vital capacity (FVC) ratio less than 60%) and who appeared to be stable, the change in FEV1 was measured after salbutamol 200 micrograms from a metered dose inhaler and 5 mg from a nebuliser. Symptoms and spirometric values were recorded before and after two weeks of oral prednisolone 30 mg. Reversibility was defined as a response in FEV1 of 15% or more from baseline alone and as a 15% change and a minimum increase of at least 200 ml. The latter gave results that showed greater internal consistency between the drug regimens. On the basis of this criterion 56 patients (44%) had no response to salbutamol or prednisolone, 71 responded to salbutamol (including all 27 steroid responders), and 25 patients had a response to salbutamol 5 mg but not to 200 micrograms. In general, the largest increase in FEV1 after salbutamol occurred in the subjects with greatest improvement after prednisolone. Subjects showing a response in FEV1 after two weeks' prednisolone had a fall in total symptom score, unlike those who had no response to any treatment or a response to salbutamol only. These data show that reversibility in response to beta agonists is common in patients diagnosed on clinical grounds as having stable chronic obstructive lung disease, that it can be substantial, and that it is best detected by using a larger dose of salbutamol. Salbutamol responders were those most likely to improve after a trial of oral prednisolone. Allowance should be made for the variability of FEV1 in the calculation of the percentage response at low baseline values (less than 1 litre).
Inspiratory lung crackles are a diagnostic feature of interstitial pulmonary fibrosis, but expiratory crackles are not well documented. In a phonopneumographic study of 13 patients with fibrosing alveolitis, expiratory crackles were audible with the stethoscope in 12. Phonopneumographic analysis of these 12 patients showed the crackles to be fine with the initial wave deflection of the expiratory and inspiratory crackles in opposite directions. They were few in number, occurred predominantly in mid- and late expiration, and were not affected by varying the volume history or by breath holding maneuvers. These observations support the theory that some crackles are produced by vibration of the walls of peripheral airways. In addition, this group of patients showed a significant correlation between the number of expiratory crackles and the reduction in predicted transfer factor, suggesting that expiratory crackles may be a clinical indicator of the severity of disease in fibrosing alveolitis.
We studied the prevalence of ventilatory impairment, chest symptoms, and radiographic abnormality in a selected sample of more than 2,000 kaolin workers from east central Georgia. The presence of ventilatory impairment was related to the presence of complicated pneumoconiosis, employment in clay calcining, and cigarette smoking. In those working with calcined clay, there was an increased prevalence of abnormality of the FEV1, but not the FVC, when compared to both wet and dry processors and which could not be explained by either cigarette smoking or the presence of pneumoconiosis. The magnitude of abnormality in the calcined clay workers was, however, unlikely to lead to disabling impairment. In workers with more than 3-yr tenure, there were 90 subjects with simple pneumoconiosis and 18 with complicated pneumoconiosis, yielding an adjusted prevalence of 3.2% and 0.63%, respectively, in the sample examined. Dry processing was associated with a greater risk of developing pneumoconiosis than wet processing.
We investigated in vitro NMR properties of bleomycin-induced alveolitis and pulmonary fibrosis in 18 Lewis rats (6 controls). When alveolitis or fibrosis had developed, animal lungs were excised and examined histologically and gravimetrically and their T1 and T2 were determined by a NMR spectrometer at 10.7 MHz and 37 degrees C. Clinical diagnosis was confirmed histologically in each case. The NMR signal intensities were significantly elevated in both disease states (P less than 0.001). Both T1 and T2 values of alveolitic lungs were about the same as in controls, but were significantly decreased in fibrotic lungs (P less than 0.01). Changes in T1 and T2 correlated well (P less than 0.001) with changes in water content of diseased lungs.
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We have characterized another subset of acute nonlymphocytic leukemia (ANLL) based on the cytogenetic and morphologic findings in a group of nine patients. Five patients had chromosomal analyses performed at the University of Chicago, two patients were studied at the All-Union Cancer Research Center in Moscow, and one patient each was studied at the University of Maryland and at Fairfax Hospital in Fairfax, Virginia. All nine patients had a reciprocal translocation involving the short arm of chromosome 6 and the long arm of chromosome 9 [t(6;9)(p23;q34)]. The patients, four males and five females, ranged in age from 5 to 51 years; the median age of 38 years is lower than that typically seen in ANLL. Only two of eight treated patients entered a complete remission. Classification of bone marrow morphology according to FAB Cooperative Group criteria revealed AML-M1 in one patient, AML-M2 in four, and AMMoL-M4 in three. One patient had refractory anemia with excess blasts (RAEB) which evolved to AML-M2. All bone marrow specimens showed severe myelodysplasia, with Auer rods present in seven of the nine cases. Of note was the particular prominence of bone marrow basophils (greater than 1%) in eight of the nine (89%) patients. Among 160 evaluable patients with ANLL de novo seen at the University of Chicago whose cells lacked a t(6;9), only five (3%) had greater than 1% basophils in the marrow aspirates. It is of interest that the breakpoint in 9q involves the same chromosomal band as that in the t(9;22) observed in chronic myelogenous leukemia (CML), in which increased basophils are a prominent feature. Thus, the association of the t(6;9) with increased bone marrow basophils in ANLL may provide additional insight into the chromosomal location of genes regulating the production and/or maturation of basophils.
Were aminophylline to improve mucociliary function, it might prove useful in the management of irreversible airflow limitation. Eight subjects with irreversible airflow limitation due to emphysema inhaled an aerosol of 99mTc sulphur-colloid particles on each of 2 days. On day 1 aminophylline was administered intravenously, while on the other nothing was given. Particle clearance was measured by recording posterior gamma-camera images sequentially over a 24 h period. No significant differences were recorded between aminophylline and control studies, but there were marked variations in clearance between study days and between individuals. These differences were compatible with the known effects of airways obstruction and breathing pattern on the sites of particle deposition within the bronchial tree. The latter factors appeared to exert a far greater influence on the observed mucociliary clearance than did aminophylline.
Studies were carried out on 11 habitual cigarette smokers to ascertain whether there was a difference in the regional deposition of particles during cigarette smoking compared with tidal breathing and also to investigate whether the ventilatory maneuvers associated with smoking influence the deposition site. A cigarette holder was constructed that permitted cigarette smoke to mix with a radioaerosol. An added resistance simulated the airflow resistance present in a filter-tipped cigarette. Respiratory patterns for the control period of tidal breathing and during smoking were monitored with a respiratory inductance plethysmograph. Smoking resulted in greater apical and central deposition than expected from the distribution of resting ventilation. The changes in the site of deposition during smoking are probably influenced mainly by the properties of the particles concerned, namely, its size, reactivity, and hygroscopicity. Changes in respiratory patterns that occur during inhalation of cigarette smoke may also have an effect but are difficult to quantify and show marked intersubject variation. In selected subjects smoking caused apical deposition to exceed that of the lower zones.
We describe a subject with lymphangioleiomyomatosis who presented with chylothorax but who had an otherwise normal chest radiograph. The diagnosis was established by means of whole-body computerized tomographic scanning, which demonstrated asymptomatic involvement of the lungs, lymphatics, and kidneys. This diagnostic modality offers the potential for noninvasive serial monitoring of this rare condition, and in doing so provides an opportunity to obtain a better understanding of the disease process.