The clinical assessment of severe asthma.

Thorough and ongoing clinical assessment is the foundation of modern asthma management. The history delineates the severity, circumstances, and time course of the present attack, placing it in the clinical context of the patient and his disease. A physical examination disclosing airflow obstruction, tissue hypoxia, respiratory muscle fatigue, and complications of therapy, in conjunction with simple objective measures of airflow obstruction and arterial gas tensions, allows the physician to make informed management decisions in the care of these severely ill patients.

Bronchoalveolar lavage in asbestosis.

The interstitial lung disease associated with asbestosis is unique in that the etiological agent and its effects on the pulmonary parenchyma can be studied on a serial basis using bronchoalveolar lavage. In this way both disease activity and structural derangements can be assessed and used in the treatment of the affected individual. In this review, attention has been drawn to the cascade of inflammatory changes induced by asbestos fibers. The activated inflammatory cells are responsible for the alveolitis characteristic of this condition. Like the other forms of diffuse interstitial lung disease, it is the alveolitis that precedes and predicts eventual fibrosis.

Neuropsychological effects of short-term discontinuation of oxygen therapy. Observations in patients with chronic hypoxemia who are receiving long-term oxygen therapy.

Twelve patients receiving long-term oxygen therapy were assessed for possible detrimental neuropsychological effects of short-term withdrawal of oxygen. Patients served as their own controls and received either their usual oxygen prescriptions or room air, through nasal prongs, over four-hour periods on two successive days. A battery of neuropsychological tests assessing memory and learning, sustained concentration, and motor and visuomotor speed were administered. In the room-air condition, the mean arterial oxygen partial pressure fell from 86.1 +/- 25.7 to 59.1 +/- 11.7 mm Hg, and the mean oxygen saturation fell from 94.7% +/- 3.2% to 89.9% +/- 5.3%, but the mean carbon dioxide partial pressure did not change significantly. No significant differences in neuropsychological test scores were found between the two conditions, suggesting that four hours of mild hypoxemia causes no significant deficits in cognition in patients receiving long-term oxygen therapy. Paradoxically, low-order inverse correlations were found between arterial oxygen partial pressures and results of visuomotor speed and memory tests, suggesting that an improvement in performance may have taken place during oxygen withdrawal.

Hemodynamic effects of an inhaled beta-2 agonist.

We examined echocardiographically in a single-blind crossover trial the circulatory effects of an inhaled selective beta 2-adrenergic bronchodilator, fenoterol. Eight healthy subjects were studied on the first and fourteenth day after randomly assigned therapy with either no drug or 400 micrograms fenoterol by metered dose inhaler four times a day. Heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure responses to fenoterol were small (means +/- SE; HR: +4 +/- 1.3 bpm; SBP: +6 +/- 1.3 mm Hg; DBP: -3 +/- 1.4 mm Hg). In contrast, mean cardiac output increased 26% (1.1 +/- 0.2 l/min), accompanied by an 18% fall in total peripheral vascular resistance (-6 +/- 1.3 U), a 16% increase in stroke volume (+12 +/- 2.5 ml), and an 18% increase in the mean velocity of circumferential shortening (+0.2 +/- 0.04 c/s). Responses varied widely among subjects; maximum observed increase in cardiac output was 117% (+5.48 l/min) in one subject. There was no evidence to suggest development of tolerance to these hemodynamic effects, as the response of measured variables did not differ after 2 wk of regular fenoterol therapy. We conclude that selective beta 2-bronchodilators are not without potential for hemodynamically significant effects when taken by metered inhalers in recommended therapeutic doses and that the magnitude of such effects is underestimated when measured by HR and blood pressure changes.

Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room.

The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy.

Ventilatory patterns during hypoxia, hypercapnia, and exercise in adolescents with mild scoliosis.

Adolescents with mild, asymptomatic scoliosis (thoracic curvature less than 35 degrees) may have little or no impairment of resting lung volumes. Progression to more severe disease may, however, be accompanied by lung restriction, impaired exercise tolerance, and respiratory failure with CO2 retention. We wished to see whether adolescents with mild scoliosis and minimally abnormal resting pulmonary mechanics had impairment of their responses to hypercapnia, hypoxia, and progressive cycle exercise. Forty-four adolescents with idiopathic scoliosis were studied. The mean forced vital capacity (FVC), expressed as a percentage of the predicted value, was 94.3 +/- 2.2 (SE). The mean ventilatory response to hypercapnia (2.57 +/- 0.24 L/min/mm Hg) was within the normal range but was achieved with a tidal volume response (1.87 +/- .17% vital capacity [VC]/mm Hg) that was significantly lower than that previously reported in healthy young adults. Ventilatory responses to exercise were also within the normal range, the mean dyspnea index (VE-max/maximal voluntary ventilation) = 0.92 +/- 0.04. However, at a ventilation of 30 L/min, the tidal volume was 0.38 +/- 0.01% FVC, which was considerably lower than predicted. The tidal volume response to hypoxia was also abnormally low, the mean response being 0.52 +/- 0.059% VC/% decrease in arterial O2 saturation. These findings indicated that, even when scoliosis is asymptomatic and associated with minimal impairment of resting pulmonary function, abnormal patterns of ventilation occur during exercise or in response to chemical stimuli.

Acute asthma: observations regarding the management of a pediatric emergency room.

Because inadequate assessment and inappropriate treatment of acute asthma have been implicated as contributing factors in morbidity and even deaths, the management of acute asthma, as practiced in an emergency room, were reviewed. The study population comprised 1,864 children (mean age 5.6 years; 65% boys) who attended the emergency room with acute asthma on 3,358 occasions during a 16-month period. Visits occurred more commonly in winter and usually in the evenings; 93% were self-referred and the mean duration of symptoms was 41 hours. Most acute episodes were associated with infection. Although chest auscultation, heart rate, and respiratory rate were recorded during the majority of visits, evidence that pulsus paradoxus had been measured could be found for only 1% of visits. Results of lung function and blood gas values were rarely recorded, but chest radiographs were obtained in 18% of visits. Drugs used in the emergency room included beta 2-agonists (93% of visits), theophylline (16%), and systemic steroids (4%), but no child received anticholinergic therapy. In 26% of patient visits, admission to hospital occurred; one patient died. The erratic fashion in which asthma severity appears to have been assessed and the failure to document whether lung function had been measured are causes for concern. The surprisingly high hospitalization rate may have been avoided if bronchodilators and corticosteroids had not been underused in the emergency room.

Pulmonary disposition of gallium-67 in humans: concise communication.

Pulmonary gallium-67 imaging for inflammatory and neoplastic diseases has become an important diagnostic tool in respiratory medicine. However, the extent to which Ga-67 is delivered to normal lungs has not been fully evaluated. Accordingly, we measured the disposition of Ga-67 using scintiscanning, bronchoalveolar lavage (BAL), and blood analysis in healthy subjects. Following an intravenous dose of 6 mCi Ga-67 citrate, the gallium scan showed no pulmonary uptake at 48 hr. In all subjects, radioactivity was detected in both blood and recovered BAL fluid at 72 hr, being predominantly in the cellular component of the BAL washings. We conclude that despite negative pulmonary imaging, Ga-67 accumulates in the cells that line the alveolar acini of normal nonsmoking individuals.

Management of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by insidiously progressive airflow limitation. The necessarily multifactorial management programme should include smoking cessation, prevention of infections, bronchodilator and steroid therapy, supplemental oxygen, physical therapy, pulmonary rehabilitation programmes, psychosocial support and treatment of concomitant disease. There have been many advances in medical therapy but some of the notorious controversies remain. New sympathomimetic agents and methylxanthines, as well as the availability of inhaled anticholinergic medications free of toxicity, have led to improvement in symptoms and complications related to COPD. There is a clear place for the judicious use of systemic steroids.

Assessment of drug disposition in the lung.

Airway disposition of drugs is assessed with either physiological changes in lung mechanics or nuclear scanning of the tagged medication. Several methods have been described for assessment of the pulmonary disposition of drugs delivered by routes other than the airways. These methods include tissue biopsy and sputum analysis of pooled secretions and tracheal washings. More recently, bronchoalveolar lavage fluid has been analysed for a variety of pharmacological agents and comparisons drawn between blood and lavage supernatant levels. Problems in correcting for dilution have been overcome by using a naturally occurring tracer substance, such as creatinine or albumin, which has a similar molecular weight to the test chemicals and which can be assayed readily in blood and lavage fluid. It has become apparent that neither naturally occurring not exogenous chemicals enter the lung in a concentration that is predictable from their levels in the blood. While the alpha 2-macroglobulin level in lavage fluid is approximately 25 times less than that in serum, a 1:1 relationship exists for alpha 1-antitrypsin. Cortisol achieves a concentration in lung fluid equal to that of blood, but lung fluid concentrations of methylprednisolone and prednisone are one-half, or at best one-third, of the blood concentration, respectively. Knowledge regarding the penetration of antibiotics into the lung is useful in determining the potential effectiveness of a given agent and its likely acinar MIC. It appears that the alveolar-capillary unit is not freely permeable to all agents, raising the possibility that a blood-lung barrier exists which is responsible for maintaining the alveolar environment. The knowledge that there is a differential permeability among drugs makes it important for clinicians to assess this characteristic of each agent before conclusions linking dose and response are drawn.

Severe asthma: prevention is better than cure.

Asthmatic patients during sympton-free periods almost invariably have abnormalities in lung mechanics and gas exchange. Tentacious secretions and mucosal thickening exaggerate maldistribution of ventilation and cause flow limitation in small airways. Hence, the maximal expiratory flow volume loop in these patients will show impaired flow rates at low lung volumes and many will show a widened alveolar-arterial O2 tension difference. Preventive treatment should be aimed at reversing these abnormalities. The regular use of inhaled sympathomimetics and oral theophylline preparations is justified in the symptom-free patient whose history suggests that he is susceptible to acute exacerbations. Such patients commonly experience an improved sense of well-being, increased exercise tolerance, and a decrease in the frequency and severity of their acute episodes.

Dysphagia as a manifestation of occult hypoxemia. The role of oximetry during meal times.

A 25-year-old woman with severe kyphoscoliosis reported a six-month history of increasing dysphagia to both liquids and solids. A barium swallow and esophageal motility studies showed no significant gastrointestinal abnormalities. Trials of antispasmodic agents were unsuccessful in relieving her symptoms. Pulmonary function tests showed a severe restrictive ventilatory defect (vital capacity = 0.67 L) with adequate oxygenation and alveolar ventilation as reflected by arterial blood gas testing during quiet wakefulness. However, continuous noninvasive oximetry demonstrated desaturation to 85 percent while eating. These transient episodes of desaturation were abolished by the administration of supplemental oxygen delivered by nasal prongs. Following the prescription of supplemental oxygen, dysphagia resolved immediately, with weight gain following over several weeks. We conclude that dysphagia may be a presenting feature of hypoxemia. This case report draws attention to the usefulness of continuous noninvasive monitoring of oxygenation and the clinical importance of at least some transient hypoxemic events.

Is the short-term response to inhaled beta-adrenergic agonist sensitive or specific for distinguishing between asthma and COPD?

In view of the ubiquitous practice of using bronchodilator responsiveness to determine suitable patients for clinical trials, we wanted to know whether changes in FEV1 or forced vital capacity (FVC) really were useful in differentiating COPD from asthma. Pulmonary function test results from 450 patients were documented by two technicians who had been asked to select consecutive studies in which flow-volume loops showed an obstructive pattern. The respirologist responsible for the care of each patient was asked to record the clinical diagnosis from the existing outpatient chart using clinical judgment based on American Thoracic Society criteria. In 395 cases, a single, unambiguous diagnosis of asthma or COPD was recorded; this diagnosis then formed the database for subsequent analysis. While the mean change in FEV1 in patients judged to have asthma was different from that found in COPD patients (16.4 vs 10.6 percent, p < 0.01), the change in FVC was similar (9.8 vs 10.3 percent, p > 0.06). However the sensitivities and specificities of postbronchodilator changes in FEV1 (dFEV1) for the diagnosis of asthma were not generally sufficient to diagnose or exclude asthma reliably. The FEV1 correlated better with residual volume (RV) in COPD (r = -0.55 vs r = -0.31), but with total lung capacity (TLC) in asthma (r = 0.51 vs r = -0.09). However, FEV1 correlated better with the RV-TLC ratio than RV or TLC alone in both groups, the correlation in each being similar (asthma, r = -0.72; COPD, r = -0.78). We conclude that acute responses of FEV1 and FVC following a standard dose of inhaled bronchodilator are neither sufficiently sensitive nor sufficiently specific to differentiate asthma from COPD purely on spirometric grounds. Furthermore, neither RV nor TLC reflected degrees of airflow limitation as well as did the RV-TLC ratio.

Response characteristics of a dual transcutaneous oxygen/carbon dioxide monitoring system.

We tested the response characteristics of a dual transcutaneous (tc) PO2/PCO2 monitoring system in healthy subjects who breathed various gas mixtures, and we compared steady-state tc readings to simultaneous arterial blood gas analysis in 20 stable respiratory outpatients. The electrodes were simple to apply, required very little skin preparation, and had trivial signal drift. In healthy subjects, tcPCO2 lag time during CO2 rebreathing was 16.8 seconds, with a 90 percent response time of 77.9 seconds after CO2 breathing was discontinued. The 90 percent response times of the O2 electrode when subjects breathed a hypoxic mixture was 257 seconds after a lag of 31 seconds. When inhaled gas mixtures were changed from hypoxia to room air, the lag time was shorter (12.5 seconds), but 90 percent response time exceeded 5 minutes. In stable patients with respiratory disease, tcPCO2 and tcPO2 were linearly related to PaCO2 (range, 19 to 53 mm Hg) and PaO2 (range, 45 to 99 mm Hg), respectively (tcPCO2 = 1.4 PaCO2-9.44, with r = 0.90 and SEE = 5.35 mm Hg; tcPO2 = 0.56 PaO2 + 20.4, with r = 0.53 and SEE = 11.7 mm Hg). We conclude that the response of the dual transcutaneous monitoring system is more rapid for the CO2 than the O2 electrode and may be rapid enough to be useful in some clinical settings; however, the O2 system fails to offer the response characteristics and accuracy that would allow it to be substituted for arterial gas tensions in unstable clinical situations.

Impaired exercise capacity in adults with moderate scoliosis.

We measured lung function and exercise tolerance in 15 adults with moderate kyphoscoliosis (thoracic curvatures between 25 degrees and 70 degrees, mean +/- SD = 46.93 degrees +/- 14.02 degrees). Forced vital capacity showed a slight reduction from values predicted from age and sex matched control subjects (3.39 +/- 1.06 vs 4.06 +/- 0.82 L, p less than 0.05). However, exercise tolerance was significantly lower than previously reported in healthy adults (VO2max = 31.60 +/- 9.12 vs 37.07 +/- 4.91 ml/kg/min, p less than 0.05). Despite the reduced exercise tolerance, the ratio of maximum tidal volume to vital capacity (VTmax/VC) was similar to that observed in healthy adults. The mean dyspnea index (VEmax/MVV) was also normal at 69.4 +/- 19.0. Hypoxic and hypercapnic ventilatory responses were within predicted normal limits at 0.67 +/- 0.37 L/min-1 fall in SaO2-1 and 1.67 +/- 0.92 L/min-1 mm Hg PCO2(-1). We conclude that the impairment of exercise performance found in adults with moderate scoliosis cannot be attributed to any important ventilatory limitation, abnormality in lung volume, or impaired chemoreceptor sensitivity. We suggest that the reduced VO2max likely arises from deconditioning and lack of regular aerobic exercise.

The accuracy and response characteristics of a simplified ear oximeter.

We evaluated the accuracy and speed of response of a newly available, lightweight, and relatively inexpensive ear oximeter (Biox II oximeter). The instrument was compared with another oximeter (Hewlett-Packard 47201A) under conditions of both steadily maintained and progressively increasing hypoxia induced in normal subjects by rebreathing. The new oximeter (Biox II), which can be operated in either a "normal" or "fast" response mode, as selected by a switch on the front panel, was evaluated in its "normal" mode during steady-state hypoxic conditions and in both "normal" and "fast" modes during progressive hypoxic conditions. The other oximeter (HP 47201A) was operated in its factory preset "normal" mode for all measurements. During steady-state hypoxia the relationship between oximetric arterial oxygen saturation (SaO2) readings (y) and spectrophotometrically measured SaO2 in samples of arterial blood (x) when SaO2 exceeded 65 percent was as follows: for the new oximeter (Biox), y = 0.95x + 3.25 (r = 0.96); and for the other oximeter (HP 47201A), y = 1.03x - 2.31 (r = 0.94). Neither of these relationships differed significantly from the line of identity. During trials of progressive isocapnic hypoxia induced acutely in ten normal subjects, SaO2 was measured continuously by both oximeters. With the new oximeter (Biox) operated in the "normal" mode, the relationship between values for SaO2 from it (y) and the other oximeter (Hewlett-Packard) (x) was y = 0.85x + 12.91 (r = 0.93). When the new oximeter (Biox) was switched to its "fast" response mode, the relationship more closely approximated the line of identity such that y = 1.05x - 5.95 (r = 0.98). The response of the new oximeter (Biox II) to an in vitro step change in saturation followed a complex nonexponential function characterized by small initial changes in output signal with the greatest changes in output occurring during the latter portion of the response period. The 50 percent response times of the new oximeter (Biox II) were 5.65 seconds and 2.86 seconds in the "normal" and "fast" modes, respectively, by contrast to the 50 percent response time of 2.87 seconds for the other oximeter (H-P 47201A). We conclude that the new oximeter (Biox II) demonstrated accuracy comparable to a more complex and expensive oximeter and had response characteristics that may be useful in clinical and laboratory settings.

Arterial PCO2 as an index of activity in fibrosing alveolitis.

Alveolar hyperventilation is a characteristic feature of the interstitial lung diseases, yet its pathogenesis remains unknown. We examined the relationship between inflammatory alveolar acinar cell counts and the steady state, resting arterial PCO2 in patients with fibrosing alveolitis. To eliminate the influence of overwhelming mechanical lung restriction or resting hypoxemia, we studied 20 patients who, despite having clinicopathologically confirmed fibrosing alveolitis, had vital capacities exceeding 50 percent of predicted, and arterial O2 saturations above 90 percent. There was a significant inverse relationship between the proportion of polymorphonuclear leukocytes (PMNs) in the recovered BAL fluid and the arterial PCO2 (r = -0.67; p less than 0.01). When PCO2 was above 35 mm Hg, the BAL PMN count was 8 percent or less (mean = 3.4; SD = 2.5), while the mean BAL PMN count among those patients whose PCO2 was less than 35 mm Hg was significantly higher (mean = 11.7; SD = 3.7; p less than 0.01). PCO2 levels were unrelated to arterial O2 saturation or PaO2. No relationship was found between the PCO2 and BAL lymphocyte counts. The findings suggest that in fibrosing alveolitis, the arterial PCO2 may be used as an indicator of the state of the inflammatory component of the alveolitis.

Maximal inspiratory and expiratory pressures in adolescents. Normal values.

The measurement of maximal inspiratory and expiratory pressures at the mouth (MIP and MEP, respectively) provides a noninvasive clinical method for evaluating the strength of respiratory muscles. In an attempt to reconcile the widely divergent normal values reported in the literature for healthy adolescents, we have measured, using simple manometry, MIP and MEP in 112 white subjects, 76 adolescents and 36 healthy adults. For female adolescents the values for MIP and MEP were 76 +/- 25 and 86 +/- 22 cm H2O, respectively, and were significantly less than those for male adolescents (p less than 0.01), whose mean values were 107 +/- 26 and 114 +/- 35 cm H2O, respectively. Mean values for adolescents were comparable to values measured in adult control subjects, and for both adolescents and adults, mean values approximated the lower end of the previously reported ranges of normal values in healthy subjects. Thus, MIP and MEP in healthy adolescents are significantly greater in male subjects than female subjects, but are comparable to those of healthy adults of the same sex. Furthermore, these studies suggest that the choice of normal values for MIP and MEP must take into account significant methodologic differences among laboratories.

Human lung transplantation.

The 38th attempt at allotransplantation of a human lung is described in a patient with injury due to smoke inhalation. The innovative features in the procedure included prolonged support with an extracorporeal membrane oxygenator during and for four days following transplantation, pharmacologic control of platelet function with sulfinpyrazone, continuous monitoring with a fiberoptic ear oximeter, and pretreatment of the transplanted lung with cytotoxic durgs. The patient survived until the 18th postoperative day, with no evidence of tissue rejection, but he died following ischemic disruption of the bronchial anastomosis. We conclude that the major determinant in the future of human lung transplantation is related to the establishment of a bronchial arterial supply to the transplanted bronchus.

Hypertrophic pulmonary osteoarthropathy in four patients with interstitial pulmonary disease.

The association between digital clubbing and idiopathic pulmonary fibrosis has been well established; however, the simultaneous occurrence of hypertrophic pulmonary osteoarthropathy and interstitial fibrosis, in the absence of neoplastic disease, has only been described in two case reports and was not mentioned in any of 336 patients described in several recent reviews. Among 70 patients referred for investigation of pulmonary infiltrates, four were found to have hypertrophic pulmonary osteoarthropathy associated with interstitial pulmonary disease, in the absence of malignant disease. We conclude that the use of bone scans and roentgenographic examination of the extremities may draw attention to an association between hypertrophic pulmonary osteoarthropathy and idiopathic pulmonary fibrosis.