James E. Fish

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.

Measurements of responsiveness in bronchoprovocation testing

The relative sensitivity and usefulness of FEV1 and SGaw measurements in determining airway responsiveness to stimuli causing changes in bronchomotor tone depend to a great extent on the population studied. Though neither test provides a great deal of information regarding the site of airway obstruction, when used together they provide a reliable and sensitive indicator of airway responsiveness.

Comparison of responses to pollen extract in subjects with allergic asthma and nonasthmatic subjects with allergic rhinitis

Abstract We compared pulmonary responses with inhaled pollen-antigen extract in eight subjects with allergic asthma and eight nonasthmatic subjects with allergic rhinitis. Lower respiratory tract sensitivity to antigen was determined from dose-response curves using SGaw and FEV 1 measurements to quantitate responses. We found no difference in antigen sensitivity in terms of SGaw between the two groups (p > 0.05). Hay fever subjects required almost eight times more antigen to produce a 20% fall in FEV 1 , although there was considerable overlap between the two groups. After antigen challenge there were significant increases in lung volumes in asthmatic subjects (RV, +78.6%; FRC, +33.6%; TLC, +12.6%) which were not significantly different from rhinitis subjects (RV, +98.3%; FRC, +39.1%; TLC, +10.3%). Six rhinitis and five asthmatic subjects were rechallenged after pretreatment with atropine (2.5 mg aerosol). Atropine caused an initial increase in SGaw and FEV 1 but failed to alter sensitivity or volume responses in both groups. The effects of a maximum inspiration on physiologic responses to antigen were different in the two groups. Deep inspiration transiently improved SGaw and FRC toward prechallenge values in rhinitis subjects but the same maneuver had little effect in asthma subjects. Although only asthma subjects experience lower respiratory tract symptoms during periods of environmental pollen exposure, these two groups of subjects were indistinguishable on the basis of their immediate responses to inhaled antigen. This suggests that asthmatic symptoms during the pollen season are unrelated to the immediate effects of allergic reactions to pollen. This also suggests that these bronchial challenge responses represent a localized anaphylactic reaction, whereas naturally occurring asthma during the pollen season may represent a syndrome of increased airways reactivity which is perhaps related to antigen exposure.

Effects of inhaled lidocaine on airway function in asthmatic subjects.

We measured the effect of inhaled lidocaine on pulmonary function in 8 asthmatic subjects. Plethysmographic specific airways conductance (SGaw) and the 1-sec forced expired volume (FEV1) were measured before and after the inhalation of 2cm3 of lidocaine (4%). Responses were also measured after patients were pretreated with either aerosolized isoproterenol, aerosolized atropine, or intramuscular atropine. In response to lidocaine alone, we observed a 23.4 +/- (SE) 4.8% fall in FEV1 and a 64.1 +/-(SE)3.8% fall in SGaw (p is less than 0.001). These effects were reversed with aerosolized atropine or isoproterenol. After pretreatment with aerosolized atropine or isoproterenol, the bronchoconstrictor effect of lidocaine were either prevented or markedly reduced. The protective effects of intramuscular atropine varied in different subjects, but in general, aerosolized bronchodilators afforded better protection against the bronchoconstrictor effect of lidocaine. Although lidocaine is theoretically capable of blocking neurogenic reflexes in the lung, our studies indicate that this topical anesthetic agent produces untoward reflex-mediated bronchoconstriction in patients with asthma and hyperirritable airways.

Methacholine and physostigmine airway reactivity in asthmatic and nonasthmatic subjects

Inhalation challenges using methacholine and physostigmine were performed in 3 human asthmatic and 3 nonallergic normal subjects. Plethysmographic measurements of specific airways conductance (Gaw/Vtg) were used to monitor the response. The dose required to produce a 17% fall in Gaw/Vtg was significantly lower in asthmatic subjects than in normal subjects for both physostigmine (p less than 0.0125) and methacholine (p less than 0.05). Moreover, in all subjects the relative airway sensitivity to methacholine correlated with the relative airway sensitivity to physostigmine. Both methacholine and physostigmine are cholinergic agents. Whereas methacholine acts directly at the end organ cholinergic receptor, physostigmine acts by increasing release and decreasing destruction of endogenous acetycholine at the vagal distal innervation. This suggests that the cholinergic airway hyperreactivity characteristic of asthma is a manifestation of end organ hypersensitivity.

Effect of Deep Inspiration on Maximum Expiratory Flow Rates in Asthmatic Subjects

Maximal inspiration may produce a transient fall in airway conductance in asthmatic subjects. Since most forced expiratory maneuvers are preceded by maximum inspiration, a study was undertaken to dete

Hypersensitivity lung disease: early diagnosis.

The early diagnosis of hypersensitivity lung disease (HLD) is important because of its progressive morbidity. It is often difficult to establish the diagnosis in the early stages because of the absence of defined symptoms. Case histories of 2 patients with pigeon breeders HLD are reported. Both patients presented with unusual manifestations of the disease: one patient was asymptomatic but had an abnormal chest radiograph; the other patient had a normal chest radiograph but experienced occasional symptoms of exertional dyspnea. Both patients had abnormal pulmonary function and precipitin bands against pigeon serum. Following inhalation challenge with pigeon serum both patients developed fever and leukocytosis, but no significant pulmonary function response was observed. In both patients pulmonary function tests returned to near normal levels after corticosteroid therapy. Early detection of HLD may prevent progressive irreversible pulmonary damage. This requires a high index of clinical suspicion and appropriate screening tests. Inhalation challenge procedures are useful in establishing the diagnosis.

Effect of Environmental Exposure on Bronchial Sensitivity to Antigen

Bronchial sensitivity to grass and ragweed extracts was determined in four adult asthmatic subjects at the beginning and end of the grass and ragweed pollen seasons. 4 subjects with ragweed sensitivity had increased bronchial sensitivity to ragweed antigen at the end of the ragweed season. 2 of 3 grass sensitive subjects demonstrated increased bronchial sensitivity to grass antigen after the grass pollen season. This study suggests that natural environmetnal exposure to pollen antigens may induce priming in the lung.

Experimental squamous cell lung tumors in Sprague-Dawley and murine pneumonitis-free rats.

Squamous cell bronchogenic carcinoma was produced in 34% of a group of specific pathogen‐free rats in a mean time of 139 days by the use of point‐source irradiation. In a group of Sprague‐Dawley rats, identical tumors developed in 54% of animals after an average exposure time of 147 days. This study was undertaken to clarify whether the bronchogenic squamous cell carcinomas produced by this method are due to the effects of the point source of irradiation alone or to the additive effects of irradiation and chronic murine pneumonitis. The results of this study in specific pathogen‐free rats indicate that murine pneumonitis is not a prerequisite for the development of neoplasia by this method. The electron microscopic findings presented support the histologic diagnosis of a well‐differentiated squamous cell bronchogenic carcinoma, similar in appearance to the tumor found in humans. Cancer 44:598‐603, 1979.