Resting and post bronchial challenge testing carbon dioxide partial pressure in individuals with and without asthma

Objective

There is conflicting evidence about resting carbon dioxide levels in asthmatic individuals. We wanted to determine if transcutaneously measured carbon dioxide levels prior and during bronchial provocation testing differ according to asthma status reflecting dysfunctional breathing.

Methods

We investigated active firefighters and policemen by means of a validated questionnaire on respiratory symptoms, spirometry, bronchial challenge testing with methacholine (MCT) and measurement of transcutaneous blood carbon dioxide partial pressure (PtcCO₂) at rest prior performing spirometry, one minute and five minutes after termination of MCT. A respiratory physician blinded to the PtcCO₂ results assigned a diagnosis of asthma after reviewing the available study data and the files of the workers medical screening program.

Results

The study sample consisted of 128 male and 10 female individuals. Fifteen individuals (11%) had physician-diagnosed asthma. There was no clinically important difference in median PtcCO₂ at rest, one and five minutes after recovery from MCT in asthmatics compared to non-asthmatics (35.6 vs 35.7 mmHg, p = 0.466; 34.7 vs 33.4 mmHg, p = 0.245 and 37.4 vs 36.4 mmHg, p = 0.732). The median drop in PtcCO₂ during MCT and the increase after MCT was lower in asthmatics compared to non-asthmatics (0.1 vs 3.2 mmHg, p = 0.014 and 1.9 vs 2.9 mmHg, p = 0.025).

Conclusions

PtcCO₂ levels at rest prior and during recovery after MCT do not differ in individuals with or without physician diagnosed asthma. The fall and subsequent increase in PtcCO₂ levels are higher in non-asthmatics than in asthmatics and seems to be related with increased number of respiratory maneuvers during MCT.     

Soil carbon dioxide partial pressure and dissolved inorganic carbonate chemistry under elevated carbon dioxide and ozone

Global emissions of atmospheric CO₂ and tropospheric O₃ are rising and expected to impact large areas of the Earths forests. While CO₂ stimulates net primary production, O₃ reduces photosynthesis, altering plant C allocation and reducing ecosystem C storage. The effects of multiple air pollutants can alter belowground C allocation, leading to changes in the partial pressure of CO₂ (pCO₂) in the soil , chemistry of dissolved inorganic carbonate (DIC) and the rate of mineral weathering. As this system represents a linkage between the long- and short-term C cycles and sequestration of atmospheric CO₂, changes in atmospheric chemistry that affect net primary production may alter the fate of C in these ecosystems. To date, little is known about the combined effects of elevated CO₂ and O₃ on the inorganic C cycle in forest systems. Free air CO₂ and O₃ enrichment (FACE) technology was used at the Aspen FACE project in Rhinelander, Wisconsin to understand how elevated atmospheric CO₂ and O₃ interact to alter pCO₂ and DIC concentrations in the soil. Ambient and elevated CO₂ levels were 360±16 and 542±81 l l^–1, respectively; ambient and elevated O₃ levels were 33±14 and 49±24 nl l^–1, respectively. Measured concentrations of soil CO₂ and calculated concentrations of DIC increased over the growing season by 14 and 22%, respectively, under elevated atmospheric CO₂ and were unaffected by elevated tropospheric O₃. The increased concentration of DIC altered inorganic carbonate chemistry by increasing system total alkalinity by 210%, likely due to enhanced chemical weathering. The study also demonstrated the close coupling between the seasonal ¹³C of soil pCO₂ and DIC, as a mixing model showed that new atmospheric CO₂ accounted for approximately 90% of the C leaving the system as DIC. This study illustrates the potential of using stable isotopic techniques and FACE technology to examine long- and short-term ecosystem C sequestration.     

Arterial carbon dioxide partial pressure influences CYP4A distribution in the rat brain

PaCO(2) is an important factor in the regulation of cerebral circulation, and it is often used to reduce intracranial pressure through hyperventilation during neurosurgery. Changes in concentration can cause changes in CBF (cerebral blood flow). 20-HETE is a product of CYP4A-mediated AA (arachidonic acid) metabolism and is a powerful endogenous vasoconstrictor; however, its effect on cerebral vasoconstriction in cats, dogs and rats remains to be confirmed. It is known that changes in PaCO(2) can influence the expression of CYP4A in the rat brain, demonstrating the important role of 20-HETE in the mechanism of CO(2)-mediated cerebrovascular reactivity. Thirty healthy adult male Wistar rats that weighed between 200 g and 250 g were randomly divided into three groups (A, B, and C; n=10): group A, normocapnia (PaCO(2) was maintained at approximately 40-45 mmHg); group B, hypocapnia (PaCO(2) was maintained at approximately 20-25 mmHg); and group C, hypercapnia (PaCO(2) was maintained at approximately 60-65 mmHg). Physiological parameters, including HR (heart rate), MBP(mean blood pressure), PH and PaCO(2) were recorded every 30 min, and there were no significant hemodynamic or body temperature differences. The head was removed after 3.5 h to investigate brain CYP4A by immunohistochemistry. Relative to group A, group B exhibited the following changes: an increased pH, decreased PaCO(2), and increased brain CYP4A protein expression (P<0.05). In contrast, group C exhibited decreased PH, increased PaCO(2) and decreased CYP4A protein expression (P<0.05). CO(2) can decrease the expression of brain CYP4A during hypercapnia and increase its expression during hypocapnia.     

Pseudorandom testing of ventilatory response to inspired carbon dioxide in man

A new method of testing the transient ventilatory response to inspired CO2 in humans has been developed in an attempt to improve the resolution and reproducibility of measures of peripheral chemoreceptor-mediated dynamics. The test input consisted of varying the level of inspired CO2 between 0 and 6-8% on a pseudorandom breath-by-breath basis. Cross-correlating this input with responses of end-tidal CO2, tidal volume, durations of inspiration and expiration, and respiratory rate yielded estimates of impulse responses. Computer simulation results and data collected in two subjects showed that reliable estimates of circulatory time lags and rapid dynamics are possible with this method. In one subject, the response dynamics observed were consistent with peripheral chemoreceptor rate sensitivity or adaptation. The rapid changes in inspiratory and expiratory durations also observed are probably mediated by peripheral chemoreceptors and appear to depend on the phase of the breathing cycle at which the CO2 stimulus arrives.     

Role of platelet-derived growth factor as an adjunct to surgery in the management of pressure ulcers

Management options for pressure ulcers include local wound care, surgical repair, and, more recently, topical application of platelet-derived growth factor (PDGF). PDGF is a glycoprotein that is mitogenic for mesenchymal cells and has been studied extensively for applicability in promoting the healing of chronic human wounds. Using data obtained from a multicenter clinical trial for the treatment of full-thickness pressure ulcers, a subset analysis was performed to investigate the outcome of salvage surgery for pressure ulcers, after incomplete closure occurred with the topical use of either recombinant human PDGF-BB (rhPDGF-BB) or placebo gel. At the University of Michigan Wound Care Center, subset data from a randomized, double-blind, placebo-controlled, parallel group clinical trial were reviewed to compare the effects of three concentrations of rhPDGF-BB on full-thickness pressure ulcers of the trunk with those of the placebo. Twenty-eight patients were enrolled and 27 completed the trial. An intent-to-treat analysis was used to evaluate data. If the ulcer did not heal by the end of the 16-week trial period, the surgeon, still blinded to the treatment group, offered salvage surgical repair of the pressure ulcer. Eleven patients underwent salvage surgical repair using myocutaneous flaps, primary closure, or skin grafts. Of three patients who received placebo followed by surgery, none progressed to full healing within 1 year. Of 12 patients in the treatment group who received rhPDGF-BB and salvage surgery, 11 (92 percent) ultimately healed the ulcers within 1 year after the start of the clinical trial. These findings suggest that treatment with rhPDGF-BB before surgery enhances the ability to achieve a closed wound over surgery alone. It must yet be determined to what degree rhPDGF-BB contributed to the excellent results seen in the rhPDGF-BB/surgery group. It is possible that rhPDGF-BB "primes" the local wound milieu to make it more responsive to complete closure following surgical treatment.     

Growth and maintenance components of leaf respiration of cotton grown in elevated carbon dioxide partial pressure

Elevated atmospheric carbon dioxide partial pressures have been shown to have variable direct and indirect effects on plant respiration rates. In this study, growth, leaf respiration, and leaf nitrogen and carbohydrate partitioning were measured in Gossypium hirsutum L. grown in 35 and 65 Pa CO₂ for 30d. Growth and maintenance coefficients of leaf respiration were estimated using gas exchange techniques both at night and during the day. Elevated CO₂ stimulated biomass production (107%) and net photo-synthetic rates (35–50%). Total day-time respiration (R_d) was not significantly affected by growth CO₂ partial pressure. However, night respiration (R_n) of leaves grown in 65 Pa CO₂ was significantly greater than that of plants grown in 35 Pa CO₂. Correlation of R_d and R_n with leaf expansion rates indicated that plants in both CO₂ treatments had equivalent growth respiration coefficients but maintenance respiration was significantly greater in elevated CO₂. Increased maintenance coefficients in elevated CO₂ appeared to be related to increased starch accumulation rather than to changes in leaf nitrogen.     

Intradermal tattoo as an adjunct to nipple-areola reconstruction

Improving results in breast reconstruction have encouraged more authentic restoration of the lost nipple-areola. While recreation of nipple shape can be reliably achieved, appropriate color has remained elusive, except when a composite nipple graft has been harvested from the normal breast, often at a significant aesthetic, emotional, and oncologic cost. Extensive experience with intradermal tattooing of the nipple-areola in over 100 patients over a 5-year period has shown this technique to be exceptionally safe and effective. Both medical-grade and commercial machines are available at varying prices, and medical-grade pigments may be obtained in a variety of authentic flesh tones derived from titanium or iron oxides. In nearly every case, tattooing has helped with either nipple-areola color, size, shape, or position, without any significant complications. Some degree of tattoo fading is common, requiring occasional late touch-ups and, more rarely, complete retattooing.     

Preclinical studies of porfiromycin as an adjunct to radiotherapy

The bioreductive alkylating agent porfiromycin (POR) is more toxic to EMT6 cells that are hypoxic at the time of treatment than to aerobic cells. The toxicity of POR to hypoxic EMT6 cells in vitro was similar to that of mitomycin C (MC): the aerobic toxicity of POR was considerably less than that of MC. Treatment of cells in vitro with POR before and during irradiation did not sensitize either hypoxic or aerobic cells to X rays; instead, only additive cytotoxicity was produced. In contrast, treatment of solid EMT6 tumors in vivo with POR plus radiation produced supra-additive cytotoxicity, as assessed by analyses of the complete dose-response curves for the killing of tumor cells by radiation alone or by POR alone. The supra-additivity of the combination regimens appeared to reflect the preferential killing by each agent of those tumor cells which were in an environment conferring resistance to the other agent. In contrast, combinations of POR and X rays produced only additive cytotoxicities to marrow CFU-GM. Supra-additive antineoplastic effects were obtained at doses of POR which produced little hematologic or other host toxicity. The complementary cytotoxicities of radiation and POR to cells in different microenvironments in solid tumors and the absence of a similar effect in normal tissue make optimized regimens combining radiotherapy and POR unusually promising for the treatment of solid tumors.     

Effect of treadmill exercise testing on serum enzymes and the resting electrocardiogram.

Fifty-three adult male patients with chest pain underwent treadmill exercise stress testing according to the Bruce protocol. The resting 12-lead electrocardiogram (ECG) and serum concentrations of glutamic oxaloacetic transaminase, lactic dehydrogenase creatine phosphokinase and alpha-hydroxybutyrate dehydrogenase were evaluated before, and at 1 and 20 hours after exercise. Twenty-eight subjects (53 percent) had a normal test result, 10 (19 percent) had ischemic ST -segment changes and anginal pain, and 15 (28 percent) were considered to have equivocal results because of an abnormal baseline ECG or the concurrent administration of cardioactive medication. In contrast to earlier reports, no significant changes in the serum enzyme values were seen in any of the three groups orin any individual subject, nor were ECG changes detected after recovery from exercise. The diagnostic evaluation of the exercise ECG must depend upon the demonstration of ischemic ST -segment changes and not upon changes in concentrations of serum enzymes.     

Latency of oxygen toxicity of the central nervous system in rats as a function of carbon dioxide production and partial pressure of oxygen

Oxygen toxicity of the central nervous system (CNS) can occur as convulsions and loss of consciousness, with no warning symptoms. A quantitative study of the effect of metabolic rate on sensitivity to oxygen toxicity was made in the rat. A group of 19 rats were exposed (126 exposures) to 12 combinations of four pressures (456, 507, 608 and 709 kPa) and three ambient temperatures (15, 23 and 29°C) until the appearance of the first electrical discharge (FED) preceding clinical convulsions. Carbon dioxide production (V˙CO₂) was also measured. A thermoneutral zone (mean V˙CO₂ 0.87 ml · g⁻¹ · h⁻¹) existed between the temperatures of 24 and 29°C; at temperatures lower than this, the metabolic rate increased by 1.2 to 4 times the resting level. Latency of FED decreased linearly with the increase in V˙CO₂ at all four oxygen pressures. The slopes (absolute value) and intercepts decreased with the increase in oxygen pressure. This linear relationship made possible the derivation of an equation which described latency of the FED as a function of both oxygen pressure and metabolic rate. Various environmental and other physiological factors that have been said to influence sensitivity to CNS oxygen toxicity, enhancing the effect of the partial pressure of oxygen, can be explained by their effect on metabolic rate. It is suggested that in situations where there is a risk of oxygen toxicity of the CNS, that risk would be reduced by a lower metabolic rate. Accepted: 4 May 1998     

Ventilatory responses to exercise and carbon dioxide in elderly and younger humans

The present investigation examined the relationship between CO₂ sensitivity [at rest (S _R) and during exercise (S _E)] and the ventilatory response to exercise in ten elderly (61–79 years) and ten younger (17–26 years) subjects. The gradient of the relationship between minute ventilation and CO₂ production ( _E/ CO₂) of the elderly subjects was greater than that of the younger subjects [mean (SEM); 32.8 (1.6) vs 27.3 (0.4); P<0.01]. At rest, S _R was lower for the elderly than for the younger group [10.77 (1.72) vs 16.95 (2.13) 1 · min^–1 · kPa^–1; 1.44 (0.23) vs 2.26 (0.28) 1 · min^–1 · mmHg^–1; P<0.05], but S _E was not significantly different between the two groups [17.85 (2.49) vs 19.17 (1.62) l · min^–1 · kPa^–1; 2.38 (0.33) vs 2.56 (0.21) 1 · min^–1 · mmHg^–1]. There were significant correlations between both S _R and S _E, and _E/ CO₂ (P<0.05; P<0.001) for the younger group, bot none for the elderly. The absence of a correlation for the elderly supports the suggestion that _E/ CO₂ is not an appropriate index of the ventilatory response to exercise for elderly humans.     

Costal cartilage sculpturing as an adjunct to augmentation mammaplasty

Costal cartilage irregularities are a major component of most congenital thoracic-wall deformities. A significant number of patients with these cartilage irregularities may either refuse major reconstruction or in fact have disorders of insufficient magnitude to justify such endeavors. In patients undergoing augmentation mammaplasty, recontouring or sculpturing of these abnormal costal cartilages may correct or improve the underlying chest-wall deformity and thus enhance the final aesthetic result. This method has had application in mild to moderate asymmetrical cases of both pectus excavatum and pectus carinatum, thoracic hypoplasia (Poland's syndrome), isolated cartilage deformities, and spinal scoliosis. In our hands, the combination of cartilage sculpturing with submuscular augmentation mammaplasty is performed as an outpatient local anesthetic procedure requiring not more than 90 minutes.