Category - Part 7
Influence of p2-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults: Data Collection
The next session consisted of a cycle ergometry test similar to the first visit. However, during this second study, classical gas exchange measures were collected and subjects also were instructed to perform maximal expiratory flow volume (MEFV) maneuvers at rest and over the last 30 s of each work level (every 2 min). Since most subjects were unfamiliar with the MEFV maneuver, this session served primarily as further familiarization with the measurements to be made on the final study day.
On the last visit, subjects exercised for 9 min at 40% and 9 min at 75% of their peak workload achieved during the initial exercise studies while gas exchange measurements were made and MEFV maneuvers were performed. During this session, a catheter was placed in the radial artery for sample collection taken just prior to performing the MEFV maneuvers for subsequent determination of catecholamines. The workloads of 40% and 75% of peak work were chosen in order to assess airway changes at a work intensity at which minimal catecholamine release would occur (< 50% maximum work) vs a work intensity at which substantial catecholamine release would be expected. read only
Influence of p2-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults: Materials and Methods
These differences were not observed in children, suggesting the Arg16Gly polymorphism may influence the rate of decline in lung function with aging.
The focus of the present study was to determine if common polymorphisms of the (P2AR differentially influence airway tone during and after short-term exercise in healthy subjects without asthma. We hypothesized that subjects with homozygous Arg16 would have an attenuated bronchodilatory response at exercise intensities that induce catecholamine release (> 50% maximum workload),
The protocol was reviewed and approved by the Mayo Clinic Institutional Review Board, and all participants signed informed consent before entering the study. Age-, gender-, and activity-matched subjects were recruited from an existing pool of subjects who had previously been genotyped for the P2AR as a part of a large study of the genetic associations with BP. Forty-two individuals who were homozygous for arginine (Arg16, n = 16) or glycine (Gly16, n = 26) at codon 16, and had no exclusion criteria (cardiopulmonary abnormalities, pregnancy, inability to exercise) agreed to participate. All subjects were healthy nonsmokers, without asthma, and were not receiving any medications. http://birthcontroltab.com/
Influence of p2-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults
The respiratory system adapts to changes in metabolic demand in an attempt to maintain gas exchange homeostasis at minimal cost. Among the many respiratory adaptations that occur during exercise is exercise-induced bronchodilation, the mechanism of which remains controversial.’2 Changes in airway tone with exercise, although small, are important, as it allows for a large increase in ventilation without significant increases in airway resistance.
Previous authors2 have suggested that changes in airway tone with exercise occur mainly due to vagal withdrawal, while others’ suggest this is primarily catecholamine mediated through the (32-adrenergic receptor (P2AR). Although the reported bronchodilation during exercise in healthy subjects can be variable, the result is a beneficial reduction in the flow-resistive work and oxygen cost of breathing.2’ The P2AR is a G protein-coupled receptor found in airway smooth muscle from the trachea to the alveoli. other
Diffusing Capacity for Nitric Oxide and Carbon Monoxide in Patients With Diffuse Parenchymal Lung Disease and Pulmonary Arterial Hypertension: Recommendation
An interesting study was performed by Bonay et al, who investigated whether the Vcap (determined with the single-breath high/low oxygen method) would be lower in subjects with DPLD and associated PAH than in subjects with DPLD without PAH. This appeared not to be the case, thus excluding the Vcap measurement as a screening test for PAH in subjects with DPLD. In this study, the Dlno/Dlco ratios differ between the different diseases, but the overlap is great. canadian health & care mall
The equation of Roughton and Forster assumes that Dmco and Vcap are independent components by assuming that the 1/Dlco resistance is the sum of two resistances. The question is whether this is correct. Hypoxemia due to thickened membranes can lead to pulmonary vasoconstriction. Capillary flow is a prerequisite to measuring the Dmco. Some investigations in patients with IPF show that capillary density is significantly decreased in diseased areas, leading to a decrease in the Vcap component of the Dlco in addition to the already lowered Dmco component as a consequence of the diseased-thickened membranes, thus making the Vcap component dependent on the Dmco component.
Diffusing Capacity for Nitric Oxide and Carbon Monoxide in Patients With Diffuse Parenchymal Lung Disease and Pulmonary Arterial Hypertension: Conclusion
There have been several studies dealing with the subdivision of the Dlco in interstitial lung diseases. In 1976, Saumon et al found that in patients with sarcoidosis with radiologic stage I and II disease, the decrease in Dlco was mainly due to decreased Dmco, but that in stage III sarcoidosis the decrease was associated with a decrease in Vcap. The Vcap values in subjects with IPF or due to systemic sclerosis were lower than in the sarcoidosis stage III group. Phansalkar et al measured rebreathing Dlno and Dmco values in 25 subjects with stage II-III sarcoidosis compared to 18 healthy nonsmoker subjects. They found a resting Dlno/Dlco ratio of 4.36 in healthy subjects and 3.48 in subjects with sarcoidosis. At 80% of peak workload, the ratios were 3.70 in healthy subjects and 2.97 in subjects with sarcoidosis. Indeed, at rest and during exercise the Dlno/Dlco ratios were lower in subjects with sarcoidosis than in healthy subjects, as expected. Reading here
Diffusing Capacity for Nitric Oxide and Carbon Monoxide in Patients With Diffuse Parenchymal Lung Disease and Pulmonary Arterial Hypertension: Discussion
In this prospective study, we found a difference in the Dlno/Dlco ratio between patients with DPLD and patients with PAH. Although this difference did reach statistical significance, the large overlap between the groups makes the Dlno/Dlco ratio inapplicable as a clinical tool in discriminating between PAH and DPLD.
Although we used a lower inspiratory NO concentration compared to others, we had no reason to expect that this would influence our data as it has been shown that the Dlno is independent of inspiratory NO in rabbits. It has been taken into account that the NO concentration in the alveolar sample is well above the natural alveolar output, which is approximately 2 to 3 ppb in healthy sub-jects, 4.7 ppb in subjects with scleroderma-associated interstitial lung disease with or without pulmonary hypertension, and 4.1 ppb in subjects with hypersensitivity pneumonitis and IPF. In our study the NO concentration in the sample volume was well > 200 ppb; therefore, the neglect of natural alveolar NO output can only lead to a very slight underestimation of the Dlno. The NO production by the conducting airways can be neglected because of the very high exhalation flows used. We found Dlno/ Dlco ratios of 4.36 in healthy subjects, which are comparable to the ratio of 4.3 in 13 healthy subjects assessed by Borland and Higenbottam by the singlebreath method and of 4.52 in 8 healthy men (singlebreath technique) measured by Zavorsky et al. In addition, the Dlno strongly correlated with the Dmco. canadian family pharmacy
Diffusing Capacity for Nitric Oxide and Carbon Monoxide in Patients With Diffuse Parenchymal Lung Disease and Pulmonary Arterial Hypertension: Results
The Dlco and Dlno were corrected to BTPS conditions, and a minimum of two measurements was performed, in which a variability of < 10% for the VA and Dlco was acceptable. All Dlco measurements were corrected to the standard Hb value according to American Thoracic Society recommendations. The obtained Dlno/ Dlco ratios were compared by means of analysis of variance using a statistical software package (SPSS for Windows, version 11.0; SPSS; Chicago, IL). The relation between the Dlno/Dlco ratio and Dmco was performed with the Pearson correlation coefficient. In a period of 1 year (April 2003 to April 2004), 71 patients were screened for study inclusion, and 67 patients were included in the study based on eligibility. Four DPLD subjects were excluded due to the presence of secondary pulmonary hypertension. In one patient, this was probably due to left ventricular failure with mitral valve regurgitation, and in the other three patients the cause of the secondary hypertension was associated with the DPLD. In the control group, 71 healthy volunteers were included (36 female volunteers and 35 male volunteers).