NEGATIVE EXPIRATORY PRESSURE TO DETECT FLOW LIMITATION 
Detection of expiratory flow limitation is useful in the assessment of
patients with obstructive lung disease. Flow limitation is
conventionally detected by comparing flow-volume curves obtained during
natural breathing with those obtained during maximal expiratory effort:
if flow at a given volume is no higher during the maximal effort than
during a natural breath, then flow limitation is present during the
natural breath. This approach is complicated by gas-compression artifacts and problems with alignment of the curves on the volume axis.
Koulouris et al. (p. 723) circumvented these difficulties by using a
negative expiratory pressure method to induce maximal expiratory flow
during a natural breath. The utility of this technique is demonstrated
in normal subjects and patients with obstructive lung disease, at rest
and during exercise. The paper is discussed in an Invited Editorial by
Rodarte (p. 721).
AIRWAY NEUROGENIC INFLAMMATION BY ESOPHAGEAL STIMULATION
Gastroesophageal reflux is commonly associated with respiratory
symptoms, including chronic cough and exacerbation of asthma. Although
microaspiration of gastric contents could underlie these pulmonary
symptoms, Hamamoto et al. (p. 738) examined the alternative possibility
that a vagally mediated reflex initiated by intraesophageal acidification causes tachykinin release in the airways, thereby causing
plasma extravasation and an inflammatory response. In guinea pigs,
intraesophageal HCl stimulation increased airway plasma leakage, as
indicated by extravasation of Evans blue. This response was potentiated
by the neutral endopeptidase inhibitor phosphoramidon and was inhibited
by the neurokinin NK1-receptor antagonist FK-888. The HCl
response was also inhibited by capsaicin treatment and by bilateral
vagotomy. The investigators conclude that tachykinin-like substances
are released by intraesophageal HCl stimulation and that this response
is mediated by a vagal reflex.
EXERCISE, FITNESS, AND NITRIC OXIDE FORMATION
Endothelial nitric oxide (NO) influences vascular resistance and growth
and antithrombotic and antiatherosclerotic processes. As an index of NO
metabolism, Jungersten and co-workers (p. 760) measured the
concentration of plasma and urine nitrate (a major stable end product
of NO metabolism in vivo) in 12 athletic subjects from a sports club
and in 12 nonathletic control subjects. Resting plasma nitrate was
higher in the athletic individuals. In other subjects, not selected for
activity level, resting plasma nitrate and urinary nitrate excretion
correlated significantly with the subjects' peak work rates, achieved
during an incremental cycle exercise test to exhaustion. An exercise
bout of 2 h elevated plasma nitrate in both athletes and nonathletes.
These results indicate that physical activity and NO formation are
positively linked. Their relationship may help explain the beneficial
effects of physical exercise on cardiovascular health.
VENTILATORY INHIBITION BY CAROTID BODY HYPOCAPNIA
The ventilatory response to hypoxia is well known to be attenuated by
concomitant hypocapnia, but the relative importance of peripheral and
central chemoreceptors in sensing the hypocapnia has not been
established. Smith et al. (p. 791) used an elegant experimental
approach with awake chronically instrumented dogs to
assess the effects of specific carotid body hypocapnia and of systemic
hypocapnia on ventilation during mild and severe carotid body hypoxia.
The results indicate that carotid body hypocapnia is a major source of
inhibitory feedback during hyperventilation elicited by carotid body
hypoxia.
BRONCHIAL VASCULAR RESPONSE TO INJECTION OF CONTRAST MEDIA
Bronchial angiography is often used to locate the site of hemorrhage in
patients with hemoptysis. However, recent evidence indicates that
injection of a contrast medium itself causes bronchial vasodilation.
Baile et al. (p. 841) examined, in Dorset-cross rams, the bronchial
blood flow response to bronchial arterial injection of conventional
ionic and nonionic contrast media, as well as dextrose, which had
intermediate osmolality. They found that there was a linear
relationship between the osmolality of the injected medium and the
increased bronchial blood flow. This blood flow response was only
partially inhibited by the nitric oxide synthase inhibitor
N
-nitro-L-arginine.
The investigators conclude that an osmolar stress triggers the contrast
medium-induced bronchial vasodilation and that this response is only
partially mediated by endothelial release of nitric oxide.
GAS MIXING IN THE LUNG DURING SHORT-TERM WEIGHTLESSNESS
When a subject inhales a deep breath that contains an insoluble inert
gas marker and then exhales slowly, the alveolar slope of the inert gas
concentration, measured at the mouth after clearance of the dead space,
is an index of ventilatory inhomogeneity. If the inspirate contains two
inert gases, He and SF6, which differ greatly in density,
the slope for the less dense gas (He) is less than that for the more
dense SF6. This difference has been attributed to a more
homogeneous distribution of He because of its greater gaseous
diffusivity, a mechanism that should not be influenced importantly by gravity. However, the difference in slopes is
abolished during sustained spaceflight, suggesting that it is
gravity dependent. Lauzon et al. (p. 859) have made similar
measurements during short-term (27-s) weightlessness in an aircraft
flying in a parabolic pattern and report that the difference between He
and SF6 slopes increased in this condition. The explanation
is unclear but may depend on short-term gravitational changes that take
more than 27 s to occur.
GENETIC REGULATION OF BREATHING PATTERN
The rate and depth of breathing are complex physiological variables
that are influenced by the inherent respiratory rhythm originating in
the brain stem, by the mechanical properties of the respiratory system,
and by several neural and chemical feedback loops. The genetic basis of
variations in the pattern of breathing has not been explored
beyond the obvious observation that small species breathe with higher
frequencies than do large ones. Tankersley et al. (p. 874)
have examined the genetic regulation of the resting breathing
pattern using two strains of inbred mice, one with rapid, shallow breathing and the other with a slow, deep pattern. The results
of their analysis of breathing in the two strains and various
combinations of their progeny suggest that the phenotypic difference in respiratory timing between the two progenitor
strains may be attributable to genetic differences in as few as two
loci.
TEMPORAL STABILITY OF SPATIAL HETEROGENEITY OF PULMONARY PERFUSION
Regional heterogeneity of pulmonary capillary blood flow is an
important determinant of the gas-exchange function of the lungs. To
investigate the temporal stability of the regional pattern of pulmonary
perfusion, Glenny et al. (p. 902) measured the spatial distribution of
flow using a fluorescent microsphere technique with dyes of different
colors on 5 successive days in healthy standing dogs. They found that
the spatial distribution pattern was almost invariant over this period,
suggesting that the pattern is determined by time-invariant geometric
factors rather than by local vasoregulation.
SPATIAL MATCHING OF PULMONARY VENTILATION AND PERFUSION IN
PRONE PIGS
Robertson et al. (p. 942) measured the regional distribution of
ventilation by inhaled aerosol (1-µm fluorescent microspheres) and
regional distribution of blood flow by intravenous injection of 15-µm radioactive microspheres in anesthetized mechanically ventilated pigs. Measurements of fluorescence and radioactivity were
made from 1.9-cm3 pieces from the
lung air dried while inflated. Ventilation and perfusion
heterogeneities were similar, with coefficients of variation of
~47%. There was a close spatial matching of ventilation and perfusion and a notable absence of radial and gravitational gradients of blood flow and ventilation. Regional perfusion was the strongest statistical predictor or regional ventilation.
MEASUREMENT OF EVAPORATIVE WATER LOSS
Evaporative water loss (EWL), including both transepidermal vapor
diffusion and sweating, is an important component of heat and water
exchange, especially in infants. Techniques for measuring EWL have been
unsatisfactory because of influence by ambient conditions. Ariagno et
al. (p. 1008) describe a ventilated capsule method that minimizes
measurement errors due to environmental variables and permits accurate
measurements of EWL to be made on time scales ranging from seconds to
hours. Performance of the new system is demonstrated in recordings made
from a healthy infant.
NEGATIVE EXPIRATORY PRESSURE TO DETECT FLOW LIMITATION
