A micro double capillary method for rheologic measurements of lower airway secretions.

We modified the double capillary method of Philipoff et al. [23] to allow rheologic measurements of lower respiratory secretions. The system consists of a precision bore stainless steel capillary (0.

Hypoxic pulmonary vasoconstriction in conscious sheep: role of mast cell degranulation.

We used pharmacologic and histologic techniques to investigate the role of mast cells in the mediation of hypoxic pulmonary vasoconstriction in conscious sheep. Breathing a hypoxic gas mixture (13%, 02, 87% nitrogen) caused hypoxic pulmonary vasoconstriction (HPV) with increases in mean pulmonary artery pressure and pulmonary vascular resistance by 97 and 90%, respectively. Intravenous pretreatment with the mast cell membrane stabilizing agent cromolyn sodium (3 mg/kg/min) completely blocked HPV, whereas the H1-histamine receptor antagonist chlorpheniramine, alone or in combination with the H2-receptor antagonist metiamide and the prostaglandin synthetase inhibitor indomethacin, failed to prevent HPV.

Characterization of H1- and H2-receptor function in pulmonary and systemic circulations of sheep.

We investigated the histamine H1- and H2-receptor function in the pulmonary and systemic circulations of sheep by in vivo and in vitro techniques. Combined H1 and H2 stimulation (by intravenous histamine) in vivo increased pulmonary vascular resistance (PVR) to 435% of base line and decreased systemic vascular resistance (SVR) to 49% of base line. Selective H2 stimulation (histamine after chlorpheniramine pretreatment) decreased PVR and SVR to 86 and 82% at base line, respectively, while selective H1 stimulation (histamine after metiamide pretreatment) increased PVR to 424% of base line and decreased SVR to 64% of base line.

Role of ciliary motility in acute allergic mucociliary dysfunction.

The purpose of this investigation was to determine if abnormal ciliary function contributes to allergic mucociliary dysfunction. In conscious sheep with Ascaris suum hypersensitivity, ciliated cells were obtained with a cytology brush and tracheal mucous velocity (TMV) was determined before and serially for 2 h following antigen inhalation. The recovered cells (also containing mast cells) were suspended in a chamber, and ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of ciliary beat frequency (CBF).

Differences in airway reactivity in normal and allergic sheep after exposure to sulfur dioxide.

The effect of breathing 5 ppm sulfur dioxide (SO2) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in which inhalation of Ascaris suum extract resulted in bronchospasm as evidenced by an increase in mean pulmonary flow resistance (RL), hyperinflation, and a fall in dynamic compliance. Airway reactivity was assessed by measuring the increase of RL after 18 breaths of 0.

Effect of pharmacologic agents on antigen-induced decreases in specific lung conductance in sheep.

The purpose of this investigation was to determine the primary mediators responsible for the decrease in specific lung conductance (SGL) after airway challenge with Ascaris suum antigen in allergic sheep. On different occasions, separated by 10 to 14 days, pulmonary resistance and thoracic gas volume were measured in 5 sheep with Ascaris suum hypersensitivity before and for 2 h after a standard inhalation challenge with this antigen. Initially and at the end of the study, inhalation challenge decreased mean SGL to 38 and 44% of baseline, respectively.

Abnormal mucociliary transport in allergic patients with antigen-induced bronchospasm: role of slow reacting substance of anaphylaxis.

We evaluated the possible role of slow reacting substance of anaphylaxis (SRS-A) in mediating mucociliary dysfunction in allergic asthma. In 6 asymptomatic nonsmokers with ragweed asthma, we measured specific airway conductance (SGaw) and tracheal mucous velocity (TMV) before and after bronchial challenge with ragweed extract, with or without pretreatment with 0.5% and 1% FPL-55712 (SRS-A antagonist).

Impaired tracheal mucus transport in allergic bronchoconstriction: effect of terbutaline pretreatment.

The transport velocity of mucus within the trachea, pulmonary resistance, and arterial blood gas composition were measured in intubated conscious sheep with Ascaris suum sensitivity before and during allergic bronchoconstriction. Inhalation of A. suum extract for 15 min increased mean pulmonary resistance significantly from 1.

Differential effects of methacholine and antigen challenge on gas exchange in allergic subjects.

In order to better characterize the differential effects of nonspecific and specific (antigen) bronchial challenge on gas exchange, seven ragweed-sensitive subjects with a history of asthma underwent progressive inhalation challenge with methacholine and ragweed extract on two different days. For comparable severity of bronchospasm (mean specific airway conductance 0.05 sec-1cm-1H2O for methacholine and 0.

Airway responses to antigen challenge in allergic rhinitis and allergic asthma.

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC), and specific airway conductance (SGaw) were determined before and during bronchial provocation with ragweed extract in 27 subjects with ragweed hypersensitivity and a history of either bronchial asthma (16 subjects) or allergic rhinitis (11 subjects). Mean baseline SGaw was significantly lower while mean volume of isoflow (Visov) and FrC were significantly higher in subjects with bronchial asthma. During antigen challenge, 10 of 16 subjects with bronchial asthma (63%) and five of 11 subjects with allergic rhinitis (45%) showed a greater than 35% decrease in SGaw ("reactors"): mean relative decreases in SGaw from baseline were 46% and 53%, respectively.

Mucociliary dysfunction in bronchial asthma.

The presence of mucociliary dysfunction in bronchial asthma is suggested by clinical observations and has been confirmed by pathologic and physiologic studies. Since mucociliary dysfunction may play a considerable role in the pathophysiology of bronchial asthma, currently available therapeutic measures which enhance mucous transport should be included in the treatment plan. It is expected that a better understanding of the underlying mechanisms will ultimately result in the development of more potent pharmacologic agents capable of improving abnormal mucociliary function.

Influence of lung inflation on the cross-sectional area of central airways in normals and in patients with lung disease.

The influence of lung inflation on the cross-sectional area of the trachea and main bronchi was investigated in 2 normal subjects, 2 patients with emphysema, and 1 patient with pulmonary fibrosis. Fiberoptic cinebronchoscopy was used to measure the cross-sectional area of the airways using calibrated small Teflon discs placed on the airway wall as reference. As an estimate of airway compliance at intermediate lung volumes, radial distensibility was defined as the change in cross-sectional area per change in airway pressure minus esophageal pressure divided by the cross-sectional area at functional residual capacity.

Tracheobronchial mucus: abnormalities related to asthma and its treatment.

The presence of mucociliary dysfunction in bronchial asthma is suggested by clinical observations and has been confirmed by pathologic and physiologic studies. Since mucociliary dysfunction may play a considerable role in the pathophysiology of bronchial asthma, currently available therapeutic measures which enhance mucous transport should be included in the treatment plan. It is expected that a better understanding of the underlying mechanisms will ultimately result in the development of more potent pharmacologic agents capable of improving abnormal mucociliary function.

Clinical indications for and effects of bland, mucolytic, and antimicrobial aerosols.

The clinical usefulness of bland, mucolytic, and antimicrobial aerosols in the management of obstructive airway disease or bronchopulmonary infections was critically reviewed at th last Conference on th Scientific Basis of Respiratory Therapy in 1974. From the information available at that time, it was cocluded that there was little scientific basis for these therapeutic modalities. It was also suggested that the value of aerosol therapy should be evaluated by objective tests.

Peripheral airway function in antigen-induced bronchoconstriction.

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC) and specific airway conductance (SGaw) were studied in 16 asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma, before and during bronchial provocation with ragweed extract (dose-response curve), and following inhalation of isoetharine. In ten of these subjects (seven "reactors" and three "non-reactors"), the baseline volume of isoflow (VisoV) was found to be greater than 20% of forced vital capacity. During antigen challenge, VisoV increased in all subjects; ten of these showed a greater than 35% decrease in SGaw (mean 45%) while the remaining six showed a decrease in SGaw of less than 20% (mean 9%), suggesting central and peripheral airway constriction in the former ("reactors") and primarily peripheral airway constriction in the latter ("non-reactors").

Role of H1- and H2-receptors in airway reactions to histamine in conscious sheep.

We investigated the role of histamine H1- and H2-receptors in the control of airway function in six conscious sheep. In five of these, inhalation of histamine (combined H1- and H2-receptor stimulation) caused an increase in pulmonary resistance (RL) and functional residual capacity and had a variable effect on distribution of ventilation as measured by N2-clearance delay. Pretreatment with the H1-antagonist, chlorpheniramine, prevented these functional effects of histamine challenge, whereas pretreatment with the H2-antagonist, metiamide, potentiated the effects of histamine on RL and caused a uniform increase in N2-clearance delay.

Sensitivity of bronchoprovocation and tracheal mucous velocity in detecting airway responses to O3.

This study was undertaken to determine whether measurements of tracheal mucous velocity or airway reactivity to inhaled carbachol more sensitively detect airway effects of inhaled ozone (O3) in conscious sheep. Dose-response curves of mean pulmonary flow resistance (RL) to carbachol were obtained by measuring RL after five breaths of carbachol aerosol with stepwise increases in drug concentration. The animals then breathed 0.

Sulfur dioxide induced airway hyperreactivity in allergic sheep.

The effects of a four-hour exposure (via a Plexiglas hood) to sulfur dioxide (SO2) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in whom inhalation of Ascaris suum extract resulted in an increase in mean pulmonary flow resistance (RL). Airway reactivity (delta RL) was assessed by measuring the increase in RL after 18 breaths of 0.

Distribution of ventilation in normal children.

Measurements of closing volume and the distribution fo ventilation by both single-breath (SBN2) and multiple-breath nitrogen washout methods were obtained in 376 healthy boys and girls, ages 6 to 18 years. A closing volume could be demonstrated in 39 percent of the subjects, and closing volume expressed as percentage of vital capacity did not change with height. Closing capacity expressed as percentage of total lung capacity showed a slight decrease with height.