Robert E. Hyatt

Pulmonary mechanics: A unified analysis of the relationship between pressure, volume and gasflow in the lungs of normal and diseased human subjects

Abstract A three-dimensional graphic representation of the mechanical aspects of pulmonary ventilation has been developed from experimental data obtained in man, in which transpulmonary pressure, respiratory flow and lung inflation have been uniquely related. The basic element of this representation is the isovolume pressure-flow curve. The behavior of a simple lung model is described to emphasize the general determinants of these isovolume pressure-flow curves. The broad inferences drawn from analysis of this model are applied to the pressure-flow-volume (P-F-V) relationship of the human lung. The three-dimensional surface representing the P-F-V relationship has had certain conceptual value. The concept of the α F-V curve evolved from consideration of this surface. This curve has been studied in man and found to have certain unique characteristics that suggest that it may become a valuable clinical tool. The α F-V curve is quite reproducible, is only moderately dependent upon effort, is essentially unaffected by wide variations in upper airway resistance, is determined by the physical properties and dimensions of the intrathoracic pulmonary system, is greatly altered in emphysematous subjects and is relatively easily obtained. In the light of this three-dimensional analysis it has been possible to evaluate a number of the commonly used indices of ventilatory mechanics. The interrelationship between these tests has been demonstrated and an understanding of their potential variability gained. Certain areas meriting further experimental exploration are suggested from considerations of the surface. It is not our intent to suggest that thorough study of ventilatory mechanics requires construction of such a surface for each person. Although certain limitations of the approach are stressed, it nevertheless has proved extremely useful in visualizing these three variables simultaneously.

Induction of nasal late-phase reactions by insufflation of ragweed-pollen extract

We studied changes in NAC in 17 ragweed-sensitive individuals after intranasal ragweed-challenge testing. All patients experienced immediate symptoms of sneezing, rhinorrhea, and nasal congestion that were associated with marked decreases in NAC (mean = 68%). In 10 trials patients also experienced late (greater than 0 hr) symptoms of nasal congestion with or without rhinorrhea; the mean late NAC decrease in this group was 42%. In contrast, no late symptoms were noted in nine trials, and the mean NAC decreased 5% in this group (p less than 0.003). Attempts to passively transfer immediate or late nasal sensitivity to one individual by spraying the nasal cavity with IgE antibody-containing serum, by packing the nose with cotton pledgets soaked in serum, by injecting serum directly into the inferior turbinate, and by transfusion with IgE-containing serum were not successful. We conclude that symptomatic late-phase reactions occur in the nose after intranasal challenge in about 50% of patients and that these symptomatic reactions can be confirmed objectively by rhinomanometry.

Conditions Associated With an Abnormal Nonspecific Pattern of Pulmonary Function Tests

BACKGROUND Little is known about a fairly frequent abnormal pattern of pulmonary function test results: reduced FEV(1) and FVC with a normal FEV(1)/FVC and normal total lung capacity. We term this a nonspecific pattern (NSP). We sought to identify medical conditions having this pattern and to explore mechanisms producing it. METHODS From a database of 80,929 test results, the NSP was found in 7,702 subjects from whom was drawn a random sample of 100 subjects. Medical records and all available tests were examined. RESULTS Airway hyperresponsiveness (AHR) and obesity were common. Two groups of subjects were identified. Group A consisted of 68 subjects with evidence of airway disease, including AHR and chronic lung disease. A volume derecruitment model was proposed to explain their NSP. Group B consisted of 32 subjects with no evidence of airway disease. Restricted expansion of the thorax or lung may explain the NSP in most of these subjects. Forty subjects had repeated tests, and in only 17 were the test results consistently nonspecific. CONCLUSIONS In a random sample of 100 subjects with the NSP, the probable underlying cause of the pattern in 68 subjects was airway disease. In most of the remaining 32 subjects, restricted expansion of the thorax or lung may be implicated.

Mechanical effects of obesity on airway responsiveness in otherwise healthy humans.

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-min rest period and a 30-min walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index (r2=0.32, P<0.001) and waist circumference (r2=0.25, P<0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance (r2=0.19, P<0.001) and reactance (r2=0.40, P<0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity (r2=0.56, P<0.001) and total lung capacity (r2=0.59, P<0.001) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes.

Hypersensitivity pneumonitis induced by Penicillium species.

An entomologist developed an illness with typical features of hypersensitivity pneumonitis. On-site investigations indicated that on the days of his attacks he was exposed to dust laden with several species of mold, especially Penicillium spp., as well as to mists generated by reservoir-type humidifiers. Serologic tests to more than 40 antigens prepared from organisms and sources known to cause hypersensitivity pneumonitis showed strong reactions to Penicillium and to antigens prepared from the scum of a large industrial humidifier and from his laboratory humidifier. PFTs revealed a significant reduction in DLCO, Following a 4-mo period without laboratory exposure, he experienced no further episodes, a return to his previous exercise tolerance, and a normal DLCO, BP studies with extracts of Penicillium casei and humidifier water from his laboratory (H1) resulted in objective evidence, both clinically and by hematologic and pulmonary function testing, of hypersensitivity to Penicillium spp. and possibly also to the H1 preparation.

Effect of acute exposure to CO2 on lung mechanics in normal man

Abstract The effect of CO 2 on lung mechanics was examined in 10 healthy men at rest. Measurements were begun after each breathed an inspired concentration of 6 % CO 2 in air for 5 min. Lung volumes, expiratory flow-volume curves, static pressure-volume curves of the lung, and pulmonary conductance were measured. CO 2 breathing produced a small but statistically significant increase in total lung capacity. Pulmonary conductance measured by a flow-interruption technique increased markedly in one subject but decreased in all others. The decrease in conductance was not prevented by treatment with a bronchodilator and was considered the result of an increase in laryngeal resistance. There was no consistent effect of CO 2 breathing on any other parameter.

Lung Volumes and Closing Capacity with Continuous Positive Airway Pressure

Total lung capacity, vital capacity, residual volume, and functional residual capacity were determined by body plethysmography and the single-breath oxygen (SBO2) test was performed at 0, 5, and 11 cm H2O continuous positive airway pressure in healthy, awake, seated, spontaneously breathing subjects. Mean values for the absolute lung volume at which phase IV of the SBO2 test begins (closing capacity) did not change significantly with continuous positive airway pressure at 5 or 11 cm H2O. Mean total lung capacity, functional residual capacity, and residual volume increased significantly, and the mean closing volume, the lung volume above residual volume at which phase IV begins, decreased significantly with II cm H2O continuous positive airway pressure; differences at 5 cm H2O were not significant. The slope of the alveolar nitrogen plateau (phase III) obtained during the SBO2 test did not change with continuous positive airway pressure.

Ventilation heterogeneity in obesity

Obesity is associated with important decrements in lung volumes. Despite this, ventilation remains normally or near normally distributed at least for moderate decrements in functional residual capacity (FRC). We tested the hypothesis that this is because maximum flow increases presumably as a result of an increased lung elastic recoil. Forced expiratory flows corrected for thoracic gas compression volume, lung volumes, and forced oscillation technique at 5-11-19 Hz were measured in 133 healthy subjects with a body mass index (BMI) ranging from 18 to 50 kg/m(2). Short-term temporal variability of ventilation heterogeneity was estimated from the interquartile range of the frequency distribution of the difference in inspiratory resistance between 5 and 19 Hz (R5-19_IQR). FRC % predicted negatively correlated with BMI (r = -0.72, P < 0.001) and with an increase in slope of either maximal (r = -0.34, P < 0.01) or partial flow-volume curves (r = -0.30, P < 0.01). Together with a slight decrease in residual volume, this suggests an increased lung elastic recoil. Regression analysis of R5-19_IQR against FRC % predicted and expiratory reserve volume (ERV) yielded significantly higher correlation coefficients by nonlinear than linear fitting models (r(2) = 0.40 vs. 0.30 for FRC % predicted and r(2) = 0.28 vs. 0.19 for ERV). In conclusion, temporal variability of ventilation heterogeneities increases in obesity only when FRC falls approximately below 65% of predicted or ERV below 0.6 liters. Above these thresholds distribution is quite well preserved presumably as a result of an increase in lung recoil.

Detection of chronic obstructive lung disease. An evaluation of the medical history and physical examination.

The value of a standard medical history and physical examination in the diagnosis of chronic obstructive lung disease was tested. Nine hundred and ninety-three male patients 40 years old and older were studied at the Mayo Clinic by the use of ventilatory tests and a retrospective review of the medical record for pulmonary symptoms and physical signs. Nearly 20% had abnormal results on at least one test, and about 28% were classified as clinically abnormal according to specified criteria. Ventilatory test results were abnormal in 10% of 714 patients in whom no symptoms, signs, or past history of pulmonary disease was noted. This represents the detection rate for ventilatory abnormality by the use of routine spirometry. Severe degrees of impairment of ventilation may be undetected by the history and physical examination.

Respiratory Impedance in Normal Humans: Effects of Bronchodilatation and Bronchoconstriction

Total respiratory resistance and reactance from 3 to 30 Hz were determined by the method of forced random noise oscillation in 12 normal male subjects before and after bronchodilatation and bronchoconstriction induced by deep breaths of aerosols of isoproterenol and atropine and of methacholine and histamine. Isoproterenol and atropine induced small decreases in total respiratory resistance at most frequencies, and isoproterenol decreased resonant frequency slightly (P less than 0.01). After administration of both methacholine and histamine, resonance frequency increased (P less than 0.01) and total respiratory resistance became more frequency-dependent, increasing mainly in the lower frequency range. In six of the subjects, we attempted to produce central deposition of methacholine by rapid, shallow breathing and peripheral deposition of the drug by slow, deep breathing. Only two subjects had suggestive evidence of central bronchoconstriction. No difference was noted, however, in the impedance behavior with either type of breathing. In awake humans, impedance analysis does not seem to distinguish between central and peripheral airway constriction.