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Study Objectives: To determine if African-American and white patients with asthma (1) differ in the words they use to describe their breathlessness, and (2) differ in their perception of breathlessness., Design: Descriptive cross-sectional design., Setting and Participants: The study setting was located in Northern California, an ethnically and economically diverse area. A total of 32 subjects, 16 per group, completed the study., Measurements: All had a provocation concentration of methacholine chloride causing a 30% fall in FEV(1) (PC(30)) of

We studied the responses to antigen in animals selected from a colony of inbred dogs sensitized to specific allergens to determine if they had characteristics similar to those of human asthmatics. They were immunized with ragweed and grass pollen extracts (10 micrograms in alum) immediately after routine vaccination with attenuated live virus (distemper and hepatitis) and killed bacteria (Leptospira) at 4, 8, and 12 wk of age. Subsequently, ragweed and grass injections were repeated every 2 months. Immunized dogs made specific IgE-antibodies in serum averaging 3 to 4 times that of control animals (no immunization with pollen or vaccine). They showed positive skin responses to the injection of ragweed pollen extract, whereas control dogs did not respond to ragweed pollen by quantitative skin test or inhalation challenge. In immunized dogs under barbiturate anesthesia, air-flow resistance of the total respiratory system increased from 0.60 +/- 0.07 (mean +/- SEM) before to 12.6 +/- 3.4 cm H2O/lps 5 min after the start of antigen aerosol; respiratory resistance remained increased for 20 min and was associated with 0 hypoxemia and increased arterial plasma histamine. In addition, airway responsiveness to both inhaled histamine and methacholine was greater in immunized dogs than in nonimmunized dogs of comparable age. Airway responses to each agonist were highly reproducible on repeated testing. These results indicate that physiologic responses to antigen by inbred, ragweed-sensitized dogs resemble human asthma closely and that these dogs appear suitable for a variety of experimental studies of asthma with respect to pathogenesis, diagnosis, prevention, and treatment.

Histamine release after antigen inhalation was studied in 12 dogs sensitive to nematode antigens. In 19 experiments, histamine was detected in arterial plasma after antigen inhalation; its concentration was correlated with changes in airflow resistance of the respiratory system (Rrs) (per cent change above control equals 132.3 plus 250 log histamine concentration). Histamine was released from the lung and was not attributable to the concomitant hypoxia. In 6 dogs given aerosols of dilute antigen and in 4 dogs given aerosols of compound 48/80, Rrs increased significantly, but no histamine was detected. Histamine may have been released close to airway receptors, inducing bronchoconstriction, but in amounts undetectable in arterial plasma. In 6 dogs, administration of 48/80 caused partial depletion of histamine stores but prevented the response to antigen inhalation in only one of 6 dogs tested. The close correlation between arterial histamine concentration and Rrs, the qualitatively similar response to antigen and 48/80 aerosols, and the inhibition of the response to antigen when histamine was depleted completely from the lung tissues suggests that chemical mediators are critically important in antigen-induced airway reactions.

In five treadmill-exercising, unsedated dogs, we studied the effect of inhaled Ascaris suum antigen aerosols on minute volume of ventilation (VE), respiratory frequency (f), tidal volume (VT), total pulmonary resistance (RL), and dynamic pulmonary compliance (CLdyn), before and during cooling of the vagus nerves. With the vagi warm, inhaled antigen increased VE (mean + 62%; P less than 0.01)by increasing f (mean + 180%; P less than 0.01), despite a decrease in VT (mean - 42%; P less than 0.01). RL increased (mean + 170%; P less than 0.001) and CLdyn decreased (mean - 43%; P less than 0.005). With the vagi cool, inhaled antigen no longer affected VE, f, or VT (P greater than 0.5), although RL still increased and CLdyn still decreased. Inhalation of a bronchodilator, terbutaline, prevented the broncho-constriction induced by antigen but did not prevent the ventilatory response. We conclude that vagal afferent pathways mediate the ventilatory response to inhaled antigen and suggest that the primary stimulus for this response is not airway narrowing.

We studied the effect of inhaled specific antigen on airflow resistance, histamine concentration, and mast cell numbers in airway tissues in allergic dogs. In each of six allergic dogs with open chests, inhalation of specific antigen aerosol (Ascaris suum) increased airflow resistance from 0.30+/-0.40 (mean+/-SE) to 2.8+/-0.41 cmH2O/1 per s (P less than 0.05); decreased mast cell number from 38.6+/-3.2 to 24.3+/-4.5 mast cells/mm2 (P less than 0.05); decreased histamine (per mg airway tissue) from 5.3+/-0.4 to 3.5+/-0.2 ng (P less than 0.05) in lobar bronchi 5-7 mm in diam; and released histamine into the blood perfusing the lung, control arterial plasma histamine; 2.8+/-0.64 ng/ml; antigen: 154+/-1.7 ng/ml (P less than 0.005). Specific antigen caused no significant changes in mast cells or histamine in bronchi 1-2 mm in diam. Control aerosols of nonspecific antigen or methacholine did not change levels of mast cells or histamine in airway tissues. These results suggest that experimental canine asthma involves local airway reactions with degranulation of mast cells and histamine release, as well as vagally mediated reflex bronchoconstriction.

The role of arachidonic acid metabolites in the pathogenesis of airway inflammation and clinical asthma is currently unknown. The addition of eicosapentaenoic acid (EPA) to the diet of humans has been shown to generate metabolites that are less potent than their arachidonic acid counterparts. The substitution of EPA for arachidonic acid metabolites in patients might cause a decrease in airway inflammation and an improvement in clinical asthma. We studied the effect of addition of EPA to the diet of twelve asthmatic patients. Standard clinical evaluations and pulmonary function tests were done on weeks 0, 3, 6, 10, 12 and 14. Patients ingested either low-dose EPA (0.1 g/day) or high-dose EPA (4.0 g/day) from weeks 6-14 (total of 8 weeks). There was no difference in clinical status or pulmonary function between groups at the start of the study. There was no change in clinical status or pulmonary function between or within groups at the end of 8 weeks of EPA ingestion.

Three allergic dogs were trained to swallow an esophageal balloon, breathe through a tracheostomy tube, and stand quietly in a wooden stall. The mechanical properties of their lungs were measured reproducibly over many months. Average values were: pulmonary resistance 1.33 cmH2O/l per s, static lung compliance 104 ml/cmH2O, and functional residual capacity 982 ml. In two dogs inhalation of histamine aerosol caused a 374% increase in resistance; inhalation of Ascaris suum aerosol caused a 307% increase in resistance. The increased resistance was associated with mild-to-moderate respiratory distress and slightly increased functional residual capacity. Aerosols of isoproterenol or atropine sulfate inhibited the increased resistance. We conclude that the conscious allergic dog is a suitable subject for the long-term study of asthma. Our present results are consistent with our earlier findings in anesthetized dogs, that a vagal reflex is involved in acute bronchomotor responses to inhalation of histamine as well as specific antigen.