Short-term associations between outdoor air pollution and mortality in London 1992-4.

OBJECTIVES: A previous study of the short term effects of air pollution in London from April 1987 to March 1992 found associations between all cause mortality and black smoke and ozone, but no clear evidence of specificity for cardiorespiratory deaths. London data from 1992 to 1994 were analysed to examine the consistency of results over time and to include particles with a mean aerodynamic diameter of 10 microns (PM10) and carbon monoxide. METHODS: Poisson regression was used of daily mortality counts grouped by age and diagnosis, adjusting for trend, seasonality, calendar effects, deaths from influenza, meteorology, and serial correlation. The pollutants examined were particles (PM10 and black smoke), nitrogen dioxide, ozone, sulphur dioxide, and carbon monoxide with single and cumulative lags up to 3 days. RESULTS: No significant associations were found between any pollutant and all cause mortality, but, with the exception of ozone, all estimates were positive. Each pollutant apart from ozone was significantly associated with respiratory mortality; PM10 showed the largest effect (4% increase in deaths of all ages for a 10th-90th percentile increment). The pollutants significantly associated with cardiovascular deaths were nitrogen dioxide, ozone, and black smoke but there was no evidence of an association with PM10. In two pollutant models of respiratory deaths, the effect of black smoke, which in London indicates fine particles of diesel origin, was independent of that of PM10, but not vice versa. CONCLUSION: These results from a new data set confirm a previous report that there are associations between various air pollutants and daily mortality in London. This new study found greater specificity for associations with respiratory and cardiovascular deaths, and this increases the plausibility of a causal explanation. However, the effects of ozone found in the earlier study were not replicated. The fraction of PM10 which comprises black smoke accounted for much of the effect of PM10.

Air pollution, pollens, and daily admissions for asthma in London 1987-92.

BACKGROUND: A study was undertaken to investigate the relationship between daily hospital admissions for asthma and air pollution in London in 1987-92 and the possible confounding and modifying effects of airborne pollen. METHODS: For all ages together and the age groups 0-14, 15-64 and 65+ years, Poisson regression was used to estimate the relative risk of daily asthma admissions associated with changes in ozone, sulphur dioxide, nitrogen dioxide and particles (black smoke), controlling for time trends, seasonal factors, calendar effects, influenza epidemics, temperature, humidity, and autocorrelation. Independent effects of individual pollutants and interactions with aeroallergens were explored using two pollutant models and models including pollen counts (grass, oak and birch). RESULTS: In all-year analyses ozone was significantly associated with admissions in the 15-64 age group (10 ppb eight hour ozone, 3.93% increase), nitrogen dioxide in the 0-14 and 65+ age groups (10 ppb 24 hour nitrogen dioxide, 1.25% and 2.96%, respectively), sulphur dioxide in the 0-14 age group (10 micrograms/m3 24 hour sulphur dioxide, 1.64%), and black smoke in the 65% age group (10 micrograms/m3 black smoke, 5.60%). Significant seasonal differences were observed for ozone in the 0-14 and 15-64 age groups, and in the 0-14 age group there were negative associations with ozone in the cool season. In general, cumulative lags of up to three days tended to show stronger and more significant effects than single day lags. In two-pollutant models these associations were most robust for ozone and least for nitrogen dioxide. There was no evidence that the associations with air pollutants were due to confounding by any of the pollens, and little evidence of an interaction between pollens and pollution except for synergism of sulphur dioxide and grass pollen in children (p < 0.01). CONCLUSIONS: Ozone, sulphur dioxide, nitrogen dioxide, and particles were all found to have significant associations with daily hospital admissions for asthma, but there was a lack of consistency across the age groups in the specific pollutant. These associations were not explained by confounding by airborne pollens nor was there convincing evidence that the effects of air pollutants and airborne pollens interact in causing hospital admissions for asthma.

Air pollution and daily mortality in London: 1987-92.

OBJECTIVE: To investigate whether outdoor air pollution levels in London influence daily mortality. DESIGN: Poisson regression analysis of daily counts of deaths, with adjustment for effects of secular trend, seasonal and other cyclical factors, day of the week, holidays, influenza epidemic, temperature, humidity, and autocorrelation, from April 1987 to March 1992. Pollution variables were particles (black smoke), sulphur dioxide, ozone, and nitrogen dioxide, lagged 0-3 days. SETTING: Greater London. OUTCOME MEASURES: Relative risk of death from all causes (excluding accidents), respiratory disease, and cardiovascular disease. RESULTS: Ozone levels (same day) were associated with a significant increase in all cause, cardiovascular, and respiratory mortality; the effects were greater in the warm seasons (April to September) and were independent of the effects of other pollutants. In the warm season an increase of the eight hour ozone concentration from the 10th to the 90th centile of the seasonal change (7-36 ppb) was associated with an increase of 3.5% (95% confidence interval 1.7 to 5.3), 3.6% (1.04 to 6.1), and 5.4% (0.4 to 10.7) in all cause, cardiovascular, and respiratory mortality respectively. Black smoke concentrations on the previous day were significantly associated with all cause mortality, and this effect was also greater in the warm season and was independent of the effects of other pollutants. For black smoke an increase from the 10th to 90th centile in the warm season (7-19 microg/m3) was associated with an increase of 2.5% (0.9 to 4.1) in all cause mortality. Significant but smaller and less consistent effects were also observed for nitrogen dioxide and sulphur dioxide. CONCLUSION: Daily variations in air pollution within the range currently occurring in London may have an adverse effect on daily mortality.

Health effects of an air pollution episode in London, December 1991.

BACKGROUND: In December 1991 London experienced a unique air pollution episode during which concentrations of nitrogen dioxide rose to record levels, associated with moderate increases in black smoke. The aim of this study was to investigate whether this episode was associated with adverse health effects and whether any such effects could be attributed to air pollution. METHODS: The numbers of deaths and hospital admissions occurring in Greater London during the week of the episode were compared with those predicted using data from the week before the episode and from equivalent periods from the previous four years. Relative risks (RR) (episode week versus predicted) for adverse health events were estimated using log linear modelling and these were compared with estimates from control areas which had similar cold weather but without increased air pollution. RESULTS: In all age groups mortality was increased for all causes (excluding accidents) (relative risk = 1.10) and cardiovascular diseases (1.14); non-significant increases were observed for all respiratory diseases (1.22), obstructive lung diseases (1.23), and respiratory infections (1.23). In the elderly (65 + years) the relative risk of hospital admission was increased for all respiratory diseases (1.19) and for obstructive lung diseases (1.43), and a non-significant increase was observed for ischaemic heart disease (1.04). In children (0-14 years) there was no increase in admissions for all respiratory diseases and only a small non-significant increase for asthma. When compared with control areas the relative risks became non-significant but remained increased. CONCLUSIONS: The air pollution episode was associated with an increase in mortality and morbidity which was unlikely to be explained by the prevailing weather, a coincidental respiratory epidemic, or psychological factors due to publicity. Air pollution is a plausible explanation but the relative roles of nitrogen dioxide and particulates cannot be distinguished.

Performance of a demand oxygen saver system during rest, exercise, and sleep in hypoxemic patients.

Demand oxygen systems have been shown to be effective in treating hypoxemia during seated rest and during exercise, but the performance of these systems during sleep has not been previously studied. We compared the efficacy of a new demand oxygen saver system with that of continuous flow nasal oxygen during the usual activities of daily life including sleep, seated rest, and exercise. Six hypoxemic patients were studied. All six had chronic obstructive pulmonary disease, though one patient had kyphoscoliosis with mixed obstructive and restrictive lung disease. Patients were studied during each activity of daily life while receiving supplemental oxygen by continuous flow nasal cannula at 2 liters per minute and during use of the demand oxygen saver system. The demand oxygen system produced arterial oxygenation equivalent to continuous flow nasal cannula under all conditions while utilizing substantially less oxygen. When compared with administration of oxygen by continuous flow nasal cannula, the demand oxygen saver cannula utilized only 45 percent as much oxygen during seated rest, 44 percent as much oxygen during exercise, and 39 percent as much oxygen during sleep. Our data support the use of demand oxygen systems for treatment of hypoxemia in patients with chronic obstructive lung disease.

Time domain analysis of diaphragmatic electromyogram during fatigue in men.

Diaphragmatic fatigue has been correlated with a change in the electromyogram recorded from the diaphragm (EMGdi), which suggests that the electromyogram is a potential clinical tool to detect respiratory muscle fatigue. Changes in the EMGdi have previously been quantified by using the power spectral parameters high-low ratio or mean frequency. In this study, we developed an autoregressive model of the EMG in an attempt to improve the analysis of the EMGdi. This model was tested on recordings of the EMGdi that were obtained from an esophageal electrode in five normal subjects breathing to fatigue through an inspiratory resistor. The data obtained from the autoregressive model were directly compared with data from the high-low ratio and mean frequency techniques. The autoregressive model showed an excellent correlation with mean frequency. Both techniques were superior to the high-low ratio measurement. Because the autoregressive model requires much less computation than mean frequency and can be easily implemented in real time on a minicomputer, we propose this as a preferable approach.

Pulmonary gas exchange during exercise in patients with chronic obliterative pulmonary hypertension.

The effect of exercise on pulmonary gas exchange was investigated in 7 patients with pulmonary hypertension resulting from primary pulmonary hypertension or recurrent pulmonary emboli. During supine bicycle exercise averaging 2.4 times baseline O2 consumption there was a significant fall in the arterial PO2 (64 +/- 1.1 to 56 +/- 5.4) and widening of the alveolar-arterial gradient for O2 (50 +/- 4.6 to 62 +/- 5.5). Measurement of the distribution of ventilation-perfusion (VA/Q) ratios by the multiple inert gas technique demonstrated no increase in VA/Q inequality. The increased hypoxemia was due to the fall in the mixed venous PO2 and its impact on the end-capillary blood of the shunt and low VA/Q units present at both rest and exercise. A concomitant shift in the mean VA/Q ratio for the normal lung units mitigated but could not eliminate the fall in the arterial PO2. We conclude that the increased hypoxemia seen during exercise in these patients is due to the widened arterial-venous O2 difference expected with exercise and its effect on the mild VA/Q inequality characteristic of this disorder.

Differentiation of patients with primary and thromboembolic pulmonary hypertension.

Twenty-five consecutive patients with obliterative pulmonary hypertension were studied. Primary pulmonary hypertension (17 patients) or chronic thromboembolic pulmonary hypertension (eight patients) was diagnosed by pulmonary angiography or autopsy. Clinical symptoms, physical findings, chest roentgenograms, electrocardiograms, and pulmonary function studies did not differentiate the patients with primary pulmonary hypertension (PPH) from those with chronic thromboembolic pulmonary hypertension (TPH). All eight patients with TPH had a lung scan interpreted as high probability for pulmonary emboli while all 17 patients with PPH had a lung scan interpreted as normal or low probability for emboli. While there was close clinical similarity between patients with PPH and TPH, the presence of a normal or low probability lung scan excluded the diagnosis of TPH.

The mechanisms of abnormal gas exchange in acute massive pulmonary embolism.

Hypoxemia usually accompanies acute pulmonary embolism in humans, but its mechanism remains poorly understood. We studied 2 patients with acute, massive pulmonary embolism (APE) documented by pulmonary angiography. Both patients had a markedly increased alveolar-arterial oxygen difference (AaPO2). The technique of multiple inert gas elimination was used to determine the distribution of ventilation-perfusion ratios (VA/Q). An increase in VA/Q inequality was found in both patients, but this increased inequality was caused entirely by an increase in the ventilation of lung units with high VA/Q ratio. No blood flow was found perfusing lung units with a VA/Q ratio of less than 1.0. Both patients, however, had a large amount of blood flow (20 and 39% of the cardiac output) perfusing unventilated lung units (shunt), and the percent of minute ventilation to unperfused lung units as well as the VD/VT determined from the Bohr equation were increased. We conclude that in these 2 patients with APE, VA/Q inequality did not play a major role in their hypoxemia and that the widened AaPO2 is explained by the large shunts that were found.

Gas exchange alterations associated with weaning from mechanical ventilation following coronary artery bypass grafting.

This study was done to clarify the effects of positive-pressure mechanical ventilation on gas exchange in the lungs of conscious patients. Nine hemodynamically stable patients were studied following coronary artery bypass grafting at the time they were weaned from mechanical ventilation. The adequacy of gas exchange was assessed by traditional measurements as well as the multiple inert gas technique used to measure the ventilation-perfusion (VA/Q) distribution. During mechanical ventilation, gas exchange was characterized by a variable degree of VA/Q inequality as well as a substantial shunt ranging from 11.9 to 27.7 percent. Following removal from mechanical ventilation, there was a decrease in the mean VA/Q subsequent to a decrease in the minute ventilation. However, there was no significant change in the level of shunt or in the amount of VA/Q inequality.

Gas exchange at rest and during exercise in adults with cystic fibrosis.

The abnormalities of gas exchange at rest and during mild exercise were characterized in 6 adults with cystic fibrosis. All patients were hypoxemic at rest with a venous admixture ranging from 9.8 to 39.9%. Using the technique of multiple inert gas elimination we demonstrated that all 6 patients had significant intrapulmonary shunt and that this accounted for most of the venous admixture in three patients. In the remaining three patients there was, in addition, significant perfusion to lung units with low ventilation-perfusion ratios (VA/Q). The abnormalities of VA/Q adequately accounted for the measured arterial blood gases and no diffusion impairment for oxygen was noted. During exercise there was an improvement in the efficiency of gas exchange, but there were only minimal changes in the arterial PO2. This resulted from a widened arteriovenous O2 difference and in 2 patients an increase in shunt. The consistent presence of shunt and variability of the pattern of the VA/Q distributions differ from previously described studies in other patients with chronic airway obstruction.

Airway hyperreactivity in patients with sarcoidosis.

Methacholine challenge testing was performed in 20 patients with pulmonary sarcoidosis and 13 normal control subjects. Increased methacholine responsiveness was demonstrated in 10 of 20 patients with sarcoidosis. Sarcoidosis patients with increased reactivity differed from those with normal reactivity in that they had more airway obstruction, smaller vital capacities, and lower single breath diffusing capacities for carbon monoxide. Responders tended to be more symptomatic with wheezing and cough and to have a longer duration of disease, although these differences did not reach statistical significance.

Reversal of progressive, life-threatening gold hypersensitivity pneumonitis by corticosteroids.

Hypersensitivity pneumonitis secondary to gold therapy has been described in only a limited number of patients. The clinical presentation is variable and optimal therapy is not well established. Two patients presenting with life-threatening respiratory insufficiency that progressed despite discontinuation of gold therapy are described. Dramatic improvement occurred following corticosteroid administration. Review of previously reported cases shows corticosteroid therapy to be efficacious. Patients with gold hypersensitivity pneumonitis may have a fulminant course and many require corticosteroids for relief.

Pulmonary vascular tone improves VA/Q matching in obliterative pulmonary hypertension.

We have studied the influence of pulmonary vascular tone on ventilation-perfusion relationships in subjects with chronic obliterative pulmonary vascular disease. We administered oxygen, isoproterenol, or nitroprusside on 15 occasions in 7 subjects and observed a fall in pulmonary vascular resistance of greater than 15% in 8 of these 15 trials. When pulmonary vascular resistance was reduced, there was an increase in the perfusion of lung units with low ventilation-perfusion ratios (VA/Q) and/or shunt as determined by the multiple inert gas technique. The pattern of increased VA/Q inequality was independent of the specific agent used. In only one instance in which pulmonary vascular resistance was not reduced did drug administration lead to a worsening of VA/Q relationships. The detrimental effect of the increased perfusion of low VA/Q units on arterial oxygenation was frequently attenuated by an increased mixed venous oxygen content due to an increase in total cardiac output. We conclude that pulmonary vascular tone contributes to the maintenance of VA/Q matching in subjects with obstruction of the pulmonary vascular bed.

Partial reversibility of chronic pulmonary hypertension caused by pulmonary thromboembolic disease.

Vasodilators including isoproterenol, nitroprusside, nitroglycerin, and oxygen were administered to 5 patients with chronic pulmonary hypertension secondary to pulmonary embolism. The patients' mean pulmonary artery pressure was 54 +/- 8 mmHg, and their average total pulmonary resistance (TRP) was 17 +/- 11 mmHg/L/min. Each patient experienced a decrease in TRP in response to at least 1 of the vasodilators, and the mean maximal decrease was to 57 +/- 10% of the baseline value. Although these decrements in TRP were accompanied by an increase in cardiac output in all but 1 patient, changes in PAP were variable. Treatment with nitroglycerin was continued in 3 of the 5 patients and all 3 have reported improvement in their exercise tolerance. We conclude that the elevated TPR seen in patients with chronic embolic pulmonary hypertension is due to increased vascular tone in addition to fixed vascular obstruction.

Major pulmonary artery stenosis causing pulmonary hypertension in sarcoidosis.

A chest bruit and evidence of pulmonary hypertension developed in a woman with sarcoidosis. A perfusion lung scan revealed decreased perfusion to the right upper lobe and to the entire left lung, while a ventilation scan was normal. Pulmonary angiography demonstrated multiple bilateral concentric pulmonary artery stenoses most consistent with extrinsic compression by mediastinal granulomatous inflammation and fibrosis. The patient was treated with systemic corticosteroids for one year without improvement. Major pulmonary artery stenosis should be considered in patients with sarcoidosis who developed pulmonary hypertension and are found to have lung scans showing segmental perfusion defects in normally ventilated areas or who develop an unexplained chest bruit.

Manifestations and treatment of laryngeal sarcoidosis.

Sarcoidosis involving the larynx presents with hoarseness, cough, dysphagia, and dyspnea secondary to upper airway obstruction. it may occur in patients with previously diagnosed sarcoidosis, or it may be the first or the only manifestation of the disease. Laryngoscopy reveals mucosal alterations including erythema and edema, punctate nodules, and mass lesions. The epiglottis is the most frequently affected area, but any portion of the larynx may be involved. The diagnosis is established by demonstrating granulomatous inflammation on laryngeal biopsy and excluding other causes of granulomatous laryngitis. Systemic corticosteroid therapy is the treatment of choice in most cases, but local steroid injection or surgical excision of affected areas may be useful in selected patients. Symptomatic laryngeal sarcoidosis can be managed successfully, but if it is left untreated, life-threatening upper airway obstruction may occur.