David W. Cugell

Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease: A 90-day multi-center study

The short- and long-term efficacy and safety of an inhaled quaternary ammonium anticholinergic agent, ipratropium bromide, and a beta agonist aerosol, metaproterenol, were compared in 261 nonatopic patients with chronic obstructive pulmonary disease (COPD). The study was a randomized, double-blind, 90-day, parallel-group trial. On three test days-one, 45, and 90-mean peak responses for forced expiratory volume in one second and forced vital capacity and mean area under the time-response curve were higher for ipratropium than for metaproterenol. Clinical improvement was noted in both treatment groups, especially during the first treatment month, with persistence of improvement throughout the remainder of the study. Side effects were relatively infrequent and generally mild; tremor, a complication of beta agonists, was not reported by any subject receiving ipratropium. These results support the effectiveness and safety of long-term treatment with inhaled ipratropium in COPD.

The clinical course of epidemic hemorrhagic fever.

Abstract 1.1. The clinical characteristics and course of epidemic hemorrhagic fever are described on the basis of observations made on United Nations forces hospitalized at the Hemorrhagic Fever Center in Korea in 1952. 2.2. The clinical picture is characterized by sudden onset, in a person recently situated in an endemic area, of chills, fever, prostration, frontal headache, marked thirst and myalgias. There is a marked facial flush, injection of the palate and conjunctivae, and petechiae of the conjunctivae, palate, axillary folds and waist line. Proteinuria and reduction in specific gravity of the urine are present. 3.3. The clinical course may be divided into four phases, each designated for a characteristic physiologic aberration: (1) febrile, (2) hypotensive, (3) oliguric and (4) diuretic. The presenting clinical features of each phase are described. 4.4. Two representative case histories, one illustrating a mild course and the other a severe attack, are summarized. 5.5. The differential diagnosis is briefly considered .

Effect of deep inspiration on airway conductance in subjects with allergic rhinitis and allergic asthma.

We measured specific airway conductance (Gaw/Vtg) in a body plethysmograph before and after a deep inspiratory maneuver in 8 subjects with allergic rhinitis and 8 subjects with allergic asthma. In hay fever subjects deep inspiration had no effect on Gaw/Vtg if it was performed in the control state; however, when methacholine-induced bronchoconstriction was present, deep inspiration transiently increased Gaw/Vtg. In asthmatic subjects deep inspiration was followed by a transeint fall in baseline Gaw/Vtg in the control state; however, when bronchoconstriction was present, deep inspiration was followed by small and variable changes in Gaw/Vtg in 7 subjects and marked improvement in Gaw/Vtg in 1 subject. In asthmatic subjects the bronchoconstrictor response to deep inspiration performed in the control state is thought to be due to reflex changes in bronchomotor tone mediated by cholinergic (vagal) nerve pathways. Like asthmatic subjects, hay fever subjects, hay fever subjects also possess cholinergic-mediated airway hyperreactivity compared with normals. Our results indicate that, in spite of their increased airway reactivity, hay fever subjects respond more like normal subjects than like asthmatic subjects after a deep inspiratory maneuver.

Serum IgE and IgG to formaldehyde-human serum albumin: Lack of relation to gaseous formaldehyde exposure and symptoms

Fifty-five subjects were studied to determine if the presence of IgE or IgG antibodies to formaldehyde (F)-human serum albumin (HSA) was associated with exposure to gaseous F or with respiratory or conjunctival symptoms from such exposure. The study population included cohorts exposed to F in the workplace, smokers, and normal subjects. IgE antibody specific for F-HSA was detected by ELISA in three subjects; immediate-type skin testing was negative in two of these subjects, and not interpretable because of dermatographism in one subject. One of these subjects had a history of respiratory symptoms when the subject was working in a histology laboratory that contained ambient F and xylene; a respiratory challenge with F at concentrations of up to 2 ppm failed to produce respiratory symptoms or significant changes in pulmonary function. Serum from the three subjects with IgE to F-HSA by ELISA failed to passively transfer skin reactivity to F-HSA to rhesus monkey recipients. These three subjects and two other subjects had IgG to F-HSA by ELISA, although this was of generally low titer. We could not define a relationship between the presence of antibodies and (1) a history of F exposure or (2) a history of adverse respiratory or conjunctival symptoms from F. This study is a continuum of 5 years of study in our laboratory attempting to define allergy to gaseous F, and the current study does not support an immunologic basis for respiratory or conjunctival symptoms from gaseous F exposure. Based on the findings of this and our other studies, it is possible that clinical IgE-mediated allergy to gaseous F does not exist, or if it does exist, it is extremely rare.

Evaluation of a worker with possible formaldehyde-induced asthma.

BACKGROUND We describe the evaluation of a worker with clinical symptoms compatible with bronchospasm caused by formaldehyde exposure. METHODS The worker was evaluated by means of enzyme-linked immunosorbent assay, cutaneous tests, and methacholine and formaldehyde inhalation challenges. The workers serum was injected intradermally into the skin of a normal rhesus monkey to determine whether hypersensitivity could be transferred from human to primate. RESULTS An enzyme-linked immunosorbent assay showed that the worker had positive IgE and IgG titers to formaldehyde-human serum albumin. The worker had a positive cutaneous test for formaldehyde-human serum albumin, and this cutaneous reactivity was transferred to a rhesus monkey through the workers serum. The worker had a negative methacholine challenge at 25 mg/ml and negative formaldehyde inhalation challenges at 0.3, 1, 3, and 5 ppm for 20 minutes. It is possible that the worker would have had a positive result if a higher concentration of F were used for the challenge, but it is more probable that the workers symptoms were not caused by immunologically mediated asthma. We have studied individuals exposed to formaldehyde, their clinical syndromes, and serologic results for a decade. This worker is the one subject with the most compatible history and immunology, but the worker had a negative challenge. CONCLUSION Immunologically mediated asthma caused by formaldehyde is extremely rare, if it exists at all.

Clinical pharmacology and toxicology of ipratropium bromide

Anticholinergic drugs inhibit a variety of intrapulmonary events related to airflow obstruction. When administered as an inhaled aerosol, approximately 90 percent of ipratropium bromide (as with beta-adrenergic aerosols) can be assumed to be swallowed. Peak pharmacologic effects occur prior to any detectable plasma drug concentrations. Ipratropium does not exhibit the well-known toxic effects of atropine, and doses many times those required for maximum therapeutic benefit do not produce any effects on the eye, urinary bladder, heart rate, or mucociliary function. Ipratropium seems to act primarily on large- and intermediate-size airways; beta-adrenergic agents, on the other hand, appear to act primarily on the smaller airways. The drug is a promising addition to the therapeutic armamentarium, and may be especially useful in certain groups of patients whose condition is less responsive to other agents.

Measurements and Theory of Normal Tracheal Breath Sounds

We studied the mechanisms by which turbulent flow induces tracheal wall vibrations detected as tracheal breath sounds (TRBSs). The effects of flow rate at transitional Reynolds numbers (1300–10,000) and gas density on spectral patterns of TRBSs in eight normal subjects were measured. TRBSs were recorded with a contact sensor during air and heliox breathing at four flow rates (1.0, 1.5, 2.0, and 2.5 l/s). We found that normalized TRBSs were proportional to flow to the 1.89 power during inspiration and to the 1.59 power during expiration irrespective of gas density. The amplitude of TRBSs with heliox was lower than with air by a factor of 0.33 ± 0.12 and 0.44 ± 0.16 during inspiration and expiration, respectively. The spectral resonance frequencies were higher during heliox than air breathing by a factor of 1.75 ± 0.2—approximately the square root of the reciprocal of the air/heliox wave propagation speed ratio. In conclusion, the flow-induced pressure fluctuations inside the trachea, which cause tracheal wall vibrations, were detected as TRBSs consist of two components: (1) a dominant local turbulent eddy component whose amplitude is proportional to the gas density and nonlinearly related to the flow; and (2) a propagating acoustic component with resonances whose frequencies correspond to the length of the upper airway and to the free-field sound speed. Therefore, TRBSs consist primarily of direct turbulent eddy pressure fluctuations that are perceived as sound during auscultation.

RESPIRATORY AND CARDIOVASCULAR FUNCTION IN PATIENTS WITH SEVERE PULMONARY HYPERTENSION.

HEATH and Whitaker 1 applied the term hypertensive pulmonary vascular disease to patients with chronic, severe pulmonary hypertension. They emphasized that this disease is a distinct clinicopathologic entity with uniform clinical features and characteristic morphologic changes of the pulmonary arteries and arterioles irrespective of the etiology of the hypertension. The vascular changes indicate restriction of the pulmonary vascular bed, which may alter pulmonary gas exchange. This study of the respiratory physiology of such patients was undertaken to determine if the uniform clinical picture could in part result from some common, specific pathophysiologic mechanism.

Lactic Acidosis from Carboxyhemoglobinemia After Smoke Inhalation

Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.

Blood Gases: Hemoglobin, Base Excess and Maldistribution

Not apparent from the title of this soft-cover, full-page size, spiral-bound volume is the nature of its contents. It contains a scant 19 pages of explanatory text with the balance devoted to three types of nomograms: (1) parallel line blood oxygen-carbon dioxide relationships modified from the original charts of Dill et al; (2) the same oxygen-carbon dioxide information presented in a coordinate form as originally proposed by Rahn and Fenn. (this is the standard form used to study alveolar gas exchange); and (3) maldistribution charts from which the effects of nonhomogeneity of distribution of blood and gas within the lung on blood gas composition can be determined. Modern computer technology has enabled the authors to prepare an extensive set of nomograms suitable for use over the broad range of abnormal blood gas values encountered in patients with cardiopulmonary diseases. As noted in the preface, this is not a volume for