Chronic bronchitis. Key points in evaluation.

Thorough history taking is essential in evaluation of chronic bronchitis. Patients often reveal key symptoms that help define the disorder and provide information about contributing factors, such as cigarette smoking, that can be eliminated. Useful baseline data can be collected through pulmonary function studies, electrocardiogram, chest radiographs, complete blood cell count, and measurement of electrolyte levels.

Chronic bronchitis. Choosing the optimal treatment.

Among the various therapies for chronic bronchitis none is more important, both for relieving symptoms and for preserving pulmonary function, than cessation of cigarette smoking. Unfortunately, even when patients are motivated and programs are aggressive, results are unspectacular. Chronic bronchitis often responds favorably to bronchodilating agents. For initial therapy, ipratropium bromide (Atrovent) is the agent of choice because of its efficacy and safety. The role of antiinflammatory drugs is not yet clear, although inhaled steroids are beneficial in some patients. Most patients improve with smoking cessation and/or judicious pharmacologic intervention.

Con: antibiotic use in exacerbations of chronic bronchitis.

An acute exacerbation of chronic bronchitis represents one of the most common illnesses treated by physicians. In spite of this, the role of infection in general, and bacterial infection in particular, is difficult to establish. Clinical signs and symptoms in patients with bacterially associated disease are not separable from those in patients without bacterial infection. Studies evaluating the efficacy of antibiotics in this setting, though suggesting that antibiotics are useful, do not provide sufficient benefit to justify routine antibiotic use. Further, these studies have not defined a subpopulation for whom antibiotics are necessary. Routine antibiotic use may delay diagnosis of other serious disease and is unequivocally very expensive, primarily because of the use of the newer and higher-cost drugs. In some situations, such as severe infection or associated with surgery, routine antibiotic use may be justified, but the use of sputum culture to guide antibiotic choice is recommended. A well designed study to finally settle the issue of antibiotic need in acute exacerbations of chronic bronchitis is badly needed.

Airflow obstruction in nonsmoking, asbestos- and mixed dust-exposed workers.

Obstructive changes in small airways have been described in patients exposed to asbestos and other mineral dusts. The physiologic significance of these small airways abnormalities and their relationship to dust burden and alveolitis remain unclear. We performed bronchoalveolar lavage (BAL) in 30 nonsmoking and 30 age-matched smoking subjects, all with mild asbestos and mixed dust exposure, to determine if parameters of lung dust burden correlated with spirometric evidence of airflow obstruction. Seventeen of 30 nonsmoking subjects and 24 of 30 smoking subjects met spirometric criteria for airflow obstruction. There were significantly more obstructed subjects in both dust exposed groups (P < 0.05) than in an age-matched nondust exposed group. There was, however, no significant difference in the number of obstructed subjects between the smoking and nonsmoking groups. There was no correlation in either group between airflow obstruction and total or differential cell counts, ferruginous bodies, total asbestos fibers, or the percent of free silica in the particulate fraction recovered by BAL. We conclude that evidence of small airways obstruction occurs commonly in occupationally dust exposed subjects and appears to be related to dust exposure per se and not to alveolar inflammation or fiber retention, important factors in the development of alveolitis and interstitial lung disease.

The usefulness of bronchoalveolar lavage in identifying past occupational exposure to asbestos: a light and electron microscopy study.

Fiberoptic bronchoscopy has permitted the development of lavage procedures for the collection of lung washes. In certain disease states this material may contain large numbers of phagocytic cells (macrophages and neutrophils). Since these phagocytes are the predominant "dust scavenger cells" in the lung, the assessment of their particulate burden as well as that of the overall lavage material has been suggested as a potentially important diagnostic tool. The studies to date have shown that the presence of ferruginous bodies is an indication of past occupational exposure. In the present study, a digestion procedure was carried out on bronchoalveolar lavage material collected from individuals who were occupationally exposed to asbestos and from samples obtained from the general population. The parameters used for distinguishing the source of these samples included both light microscopy assessment of the filters for the presence of ferruginous bodies and electron microscopic screening for the presence of uncoated fibers.

Reduced diffusing capacity as an isolated finding in asbestos- and silica-exposed workers.

From a cohort of 286 patients referred to an Occupational Medicine Clinic because of exposure to asbestos and/or silica, we identified 53 patients with a reduced diffusing capacity (Dco) (less than 75 percent predicted) as their only abnormality. Specifically, their clinical evaluation, chest roentgenograms, and remaining pulmonary function test results were all normal. These patients were divided into non-smokers (n = 13) and smokers (n = 40). The significance of the isolated reduction in diffusing capacity in these patients (n = 53) was explored with graded exercise testing (n = 19) and bronchoalveolar lavage (BAL) (n = 50). The results obtained from the patients with reduced diffusion were compared with those obtained from comparable smoking (n = 35) and nonsmoking patients (n = 37) in the original cohort who had normal chest roentgenograms and normal results of pulmonary function studies, including normal Dco values (greater than or equal to 75 percent of predicted value). Patients with low diffusion demonstrated a tendency for elevated alveolar to arterial O2 differences both at rest and during exercise, and a significant reduction in exercise capacity (VO2 max) was observed in the smoking patients with reduced diffusion when compared with their smoking counterparts with normal diffusion. All other exercise testing indexes were normal in the study groups and there was no correlation between the percent predicted Dco value and any of the exercise variables. In contrast, BAL revealed significant differences between patient groups. Both the smoking and nonsmoking patient groups with low Dco values had greater numbers of total BAL cells, alveolar macrophages, neutrophils, lymphocytes, and eosinophils in their BAL fluid than did their comparable controls with normal diffusion values. These differences were statistically significant (p less than .05) for total BAL cells and total macrophages in the nonsmoking patients and for total BAL cells, total macrophages, and total lymphocytes in the smoking patients expressed as either the total cell number per BAL or total cells per milliliter of BAL. In contrast to the observed exercise testing results, there was significant and inverse correlation between Dco values and each BAL cell type for all four groups combined as well as nonsmokers alone. The Dco values from smokers were significantly and inversely correlated with total BAL cells and total macrophages. These results suggest that the finding of a reduced Dco may be related to an active inflammatory process in the lung caused by occupational dust exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of chronic administration of codeine and promethazine on breathlessness and exercise tolerance in patients with chronic airflow obstruction.

It has been reported that short-term treatment with relatively high doses of opiates or promethazine causes improvements in dyspnoea and exercise tolerance in patients with chronic airflow obstruction (CAO). This study was designed to determine whether initial benefits were sustained during chronic administration of codeine or promethazine and to compare the two drugs in terms of their efficacy and possible mechanisms of action. Eleven patients with stable CAO were entered into a double-blind, randomized cross-over trial in which codeine (30 mg four times daily) or promethazine (25 mg four times daily) were orally administered for 1-month periods. Treatment effects were assessed by spirometry, arterial blood gases, 12-minute walk distance and subjective dyspnoea ratings. A statistically significant increase from the baseline in mean arterial PCO2 at at 24 hours (P less than 0.01) and at 1 month (P less than 0.05) occurred with codeine administration. There was no significant change from baseline for any other measurement with either drug, and no differences were detected between the two treatment arms. Four of the eleven patients did not complete the study; three of the four experienced worsening of their CAO requiring hospitalization (two while receiving codeine, one while receiving promethazine). We conclude that chronic treatment with either codeine or promethazine provides uncertain benefits to patients with CAO which may not outweigh potential risks.

Flurazepam attenuates the arousal response to CO2 during sleep in normal subjects.

Increased episodes and duration of apnea during sleep associated with arterial oxygen desaturation have been reported after administration of flurazepam. We postulated that an alteration in respiratory control during sleep might be the underlying mechanism of this observation. Accordingly, we measured isocapnic hypoxic and hyperoxic hypercapnic ventilatory and arousal responses during natural (NS) and during flurazepam-induced (FS) sleep. We found no significant difference in the ventilatory response to hypoxia during FS compared with that during NS in 8 normal subjects. Similarly, although the ventilatory response to hypercapnia was performed in only 4 of the 8 subjects during FS, no significant difference from that during NS was noted in these subjects. There was, however, a significant decrease in the number of hypercapnic response tests in which arousal occurred after flurazepam administration (85% in NS versus 54% in FS; p less than 0.005). Additionally, an increase was seen in the mean PACO2 level at which arousal occurred during FS (51 +/- 1.6, means +/- SEM) as compared with that during NS (49 +/- 0.9; p less than 0.07). A similar but not significant decrease was noted in the number of hypoxic response tests in which arousal occurred (28% during NS versus 17% during FS). We conclude that while ventilatory responses to hypoxia and hypercapnia are normal during sleep after flurazepam administration, a decrease in arousal response is seen after administration of this drug in normal subjects. This alteration in arousal response may be the pathogenic mechanism of the increased duration of apnea reported in association with flurazepam.

The value of bronchoscopy in establishing the etiology of pneumonia in renal transplant recipients.

Fifty-two episodes of fever and new pulmonary infiltrates were evaluated prospectively in 51 renal allograft recipients. Thirty-nine flexible fiberoptic bronchoscopies were performed in the diagnostic evaluation of these infiltrates. Specific etiologic diagnoses were obtained in 30 (77%) of the patients. This information was clinically useful, as defined by preset criteria, in 21 (54%) of the patients and definitive but not clinically useful in an additional 9 (23%). In the remaining 9, it was neither definitive nor clinically useful. Microbiology brush specimens were useful in establishing etiologic diagnoses in 12 (44%) of the 27 patients in whom it was performed. Transbronchial lung biopsies yielded specific etiologic diagnoses in 9 (53%) of the 17 biopsies obtained. Complications related to the bronchoscopic procedure occurred in 2 patients (5% of total bronchoscopies). No prolonged morbidity was noted. We conclude that fiberoptic bronchoscopy is a safe, useful procedure, and should be considered early in the diagnostic evaluation of pulmonary infections in renal transplant recipients.

Ventilatory and heart rate responses to hypoxia and hypercapnia during sleep in adults.

Ventilatory and heart rate responses to hypoxia and hypercapnia were measured in eight normal subjects (5 women, 3 men, ages 22-27 yr) during wakefulness (W), slow-wave sleep (SWS), and rapid-eye-movement sleep (REM). Ventilatory responses to progressive isocapnic hypoxia were measured as k, the slope of the line relating the logarithm of incremental ventilation to alveolar O2 partial pressure (PAO2) and as the incremental ventilation at PAO2 = 40 Torr delta V 40. Values for k (mean +/- SE) were 40.5 +/- 2.4 Torr during W, 42.1 +/- 2.5 during SWS, and 29.9 +/- 2.3 (5 subj) during REM (P less than 0.02 vs. W). Comparable values for delta V 40 were 5.4 +/- 0.3, 6.3 +/- 1.0, and 5.4 +/- 0.31/min. Hypoxia increased heart rate 19 +/- 1.3% during W, 18 +/- 1.8% during SWS, and 15 +/- 2.2% during REM. Ventilatory responses to rebreathing CO2 (6 subj) were 1.7 +/- 0.3 1 X min-1 X Torr-1 during W and 1.3 +/- 0.2 during SWS. Hypercapnia consistently produced arousal from sleep in all eight subjects at levels between 6 and 15 Torr (11.2 +/- 1.1) above resting alveolar CO2 partial pressure. No consistent arousal was noted during hypoxia. Arousal occurred in 87% of the CO2-rebreathing tests compared with only 28% of the progressive isocapnic hypoxia tests (P less than 0.001). We conclude that ventilatory and heart rate responses to hypoxia and ventilatory responses to hypercapnia are not significantly altered by SWS. Arousal from sleep during hypercapnia is reproducible and predictable, but there is no consistent arousal during hypoxia.

Attenuated responses to CO2 and hypoxia in parents of threatened sudden infant death syndrome infants.

Ventilatory and heart rate responses to hypercapnia and hypoxia were measured in the following three groups: group I, controls (n equals 15); group II, parents of threatened sudden infant death syndrome (SIDS) infants (n equals 10); and group III, parents of SIDS infants (n equals 17). We found significantly reduced heart rate responses to carbon dioxide and hypoxia in group II (1.4 plus or minus 1.9 percent and 16.0 plus or minus 4.0 percent; mean plus or minus SEM) compared with controls (7.1 plus or minus 1.4 percent and 26 plus or minus 2.4 percent; P less than .025). Ventilatory responses to hypoxia in groups II and III were not significantly different from controls. Two group II mothers had a greatly reduce ventilatory response to carbon dioxide. Four other parents in group II had abnormally low heart rate responses to hypoxia or carbon dioxide. We concluded that parents of threatened SIDS infants had reduced heart rate responses to carbon dioxide and hypoxia and may have reduced ventilatory responses to carbon dioxide.

Upper airway obstruction during head flexion in Morquio's disease.

Previous reports of pulmonary function in patients with Morquio's disease have emphasized the restrictive nature of their ventilatory defect. We describe a patient in whom pulmonary disability was secondary to upper airway obstruction from collapse of the trachea during head flexion. The same phenomenon was demonstrated in one of two other patients with Morquio's disease, both of whom were asymptomatic. Positionally dependent airway obstruction may be an important cause of pulmonary disability in Morquio's disease.

Altered cerebral inhibition of respiratory and cardiac responses to hypercapnia in acute stroke.

Ventilatory and heart-rate responses to hypercapnia were evaluated by a CO2 rebreathing technique in 56 patients with acute ischemic stroke and 14 normal controls. Both ventilatory and heart-rate responses were increased in patients with hemispheral lesions, but not in patients with brainstem lesions. In patients with hemispheral infarct, there was a decrease in CO2 sensitivity 1 to 3 weeks later. Acute hemisphere lesions may result in a transient decrease of cerebral inhibition of brainstem-mediated autonomic responses to a chemical stimulus.

Increased hypoxic ventilatory drive due to administration of aminophylline in normal men.

We evaluated the effects of intravenous administration and five days of oral administration of aminophylline on hypoxic and hypercapnic ventilatory drives in seven normal men. Serum levels of theophylline were 13.2 micrograms/ml +/- 1.0 micrograms/ml (mean +/- SD) after intravenous administration of aminophylline and 8.8 micrograms/ml +/- 1.7 micrograms/ml after oral administration of aminophylline. Aminophylline had no effect on the slope of the line for carbon dioxide response or on hypoxic ventilatory drive, measured at resting alveolar carbon dioxide tension (PACO2). Hypoxic ventilatory drive was significantly increased (P < 0.025) after intravenous administration of aminophylline when the PACO2 was raised to the control level before aminophylline. Intravenously administered aminophylline shifted the intercept of the line for carbon dioxide response from 40.7 +/- 2.3 to 32.9 +/- 4.6 mm Hg (P < 0.005) and lowered the resting PACO2 from 38.3 +/- 1.8 to 33.7 +/- 2.1 mm Hg (P < 0.005). Similar but smaller changes were seen after oral administration of aminophylline. There was a significant correlation between end-tidal carbon dioxide tension and the serum level of theophylline (P < 0.001), indicating that aminophylline stimulates ventilation in a dose-dependent fashion. This increase in ventilation is due in part to an increase in hypoxic ventilatory drive.