Temporal variations in the pattern of breathing

Breath-to-breath variations in the pattern of breathing can occur as uncorrelated random variations ("white noise"), correlated random changes, or as one of two types of nonrandom variations: periodic oscillations or nonrandom nonperiodic fluctuations. White noise is probably present in all physiological processes. In many cases, periodic variations are due to oscillations originating in chemoreflex feedback loops. It has long been hypothesized that correlated random variations in breathing pattern are due to central neutral "memory" mechanisms, but part of this behavior might be due to chemoreflex mechanisms. Recently it has been concluded that nonlinear interactions between pulmonary and airway afferent activities and integrative central respiratory mechanisms can produce nonrandom nonperiodic (and also periodic) variability of the respiratory pattern. These latter studies have provided new insights about the behavioral relevance of the integrative character of central respiratory mechanisms and the time-varying nature of pulmonary afferent activities and have emphasized the importance of identifying the physiological bases for these phenomena. These and other findings are interpreted assuming that respiratory rhythm generation/pattern formation occurs via a nonlinear oscillator, and novel inferences concerning temporal variations of the breathing pattern are proposed.     

Thoracoabdominal pattern of breathing in neuromuscular disorders

STUDY OBJECTIVE: To assess abnormalities in thoracoabdominal pattern of breathing (TAPB) in neuromuscular disorders during spontaneous breathing, intermittent positive pressure ventilation (IPPV) with and without abdominal (AB) binder, and immediately after IPPV. DESIGN: Repeated measures design: Pre-IPPV spontaneous breathing, IPPV, IPPV with AB binder, and post-IPPV spontaneous breathing. In protocol 1, ventilator pressure was held constant at the individual value habitually adopted in sessions of IPPV. In protocol 2, it was increased stepwise from 5 to 30 cm H2O. SETTING: University hospital, Department of Pediatrics, Intensive Care, and Neuro-Ventilatory Rehabilitation. PATIENTS: Thirty-one patients with spinal muscular atrophy (SMA) and 19 patients with myopathy, mean age (+/- SD) 9.7 +/- 3 years. MEASUREMENTS: Tidal volume (VT), percent thoracic contribution to VT (%RC), the phase angle between the thoracic and the AB volume changes and the labored breathing index, which is an index of asynchrony taking into account both the phase relationships and relative volumes of rib cage and AB compartments. RESULTS: We observed marked abnormalities in TAPB during spontaneous breathing, especially in the SMA group. %RC, labored breathing index, and phase angle displayed nearly normal values during IPPV. IPPV pressures of 25 to 30 cm H2O were necessary to increase %RC above 80%. AB binding decreased VT, but led to larger thoracic volumes, especially in patients with SMA. Thoracic contribution to VT and thoracic volume after IPPV were higher than baseline levels. CONCLUSIONS: The quantitative assessment of TAPB enhances the ability to estimate pulmonary function in neuromuscular disorders, and the efficiency of mechanical ventilation.     

The effects of CO2 on the components of breathing pattern

Experiments were performed on 12 rabbits in 4 experimental groups: A. breathing spontaneously; B. nonparalysed and ventilated by means of a pump driven by the integrated phrenic nerve activity; C. paralysed and ventilated as mentioned above; D. like in the group C, but subjected to bilateral vagotomy. The relationships were investigated between the chosen basic parameters describing the rhythm and depth of respiration in steady states during exposure to hypercapnic mixtures. A high correlation was found between the amplitude of the integrated phrenic nerve activity and the time of inspiration which is modified by the afferent activities from the lungs and thorax TI and TE seem to be controlled by different mechanisms, and the contribution of TE to the control of the cycle duration is greater than that of TI.     

Effects of mechanical ventilation on control of breathing

The presence of thermotolerant Campylobacter in rivers and lakes of Warsaw region was examined with the detectability of 1 c.f.u./ml. Samples were taken from depth of water and from the surface of different objects deposited on the bottom. The results indicate that about 70% of water samples are contaminated with Campylobacter, whereas the contamination of the underwater objects is less prevalent. The species distribution was as follows: C. jejuni-65%, C. coli-22%, C. lari-13%. In vitro experiment was also performed to test the ability of Campylobacter to create biofilms on the surface of wood, metal and plastic, however no such property was revealed. From the analysis of presented results it was established that localization of the highest contamination is connected mainly with presence of municipal sewage and in less extent with the presence of the droppings of wild animals. The samples of water give the better reflection of the examined reservoir contamination than solid samples.     

Effect of sleep on changes in breathing pattern accompanying sigh breaths

We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering-Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep.     

Dyspnea sensation and chemical control of breathing]

In order to estimate the role of peripheral chemosensitivity in dyspnea sensation, we performed BH experiment under the acute or chronic hypoxic condition. The former was simulated by a given rate (0-3.2 mg/kg/hr) of doxapram infusion. The latter experiment was carried out during sojourn in Lhasa (3700 m), China. Subjects conducted BH by inhaling 7% CO2 in O2 and assessed dyspnea sensation by visual analog scale (VAS) while repeatedly measuring PCO2 at breaking point (BP). Lowering of resting PETCO2 by augmented ventilation was derived by doxapram infusion and during acclimatization at high altitude. The effect of PCO2 on VAS was enhanced by doxapram. However, altitude acclimatization resulted in attenuated effect of PCO2 on VAS despite of further development of hypocapnia. The rate of PCO2 elevation during doxapram infusion was reduced and it might be attributed to decreased body storage of CO2. On the other hand, its rate was tended to recover to sea level value after acclimatization at high altitude and it may have cancelled the mitigated dyspnea sensation. Thus, BHT almost comparable period in both acute hypoxia and during altitude acclimatization. These results suggest that CO2 storage in the body contributes to modify dyspnea sensation as well as augmented peripheral chemosensitivity.     

Chemical control of breathing in identical twin athletes

The dosimetric characteristics of the electron beams from the Sagittaire (C.G.R. MeV) linear accelerator are presented. The variations in dose output with the distance from the source are indicated for the usual treatment distances. The measurements carried out demonstrating the deviations from the inverse square law for distances. The graphs for the variation in dose output in terms of the opening of the collimator are given for square and rectangular openings. The measurements demonstrate the preponderant influence of the short side 1 of the rectangular field of the relative variation in dose output. The variations in the graphs of the deep yield in terms of beam energy, distance from the source and field dimension were studied. For the different energies, the influence of the distance from the collimator and the dimension of the field on the dose at entry and on the depth of the maximum was shown. Measurements of the deep yields were carried out in the case of rectangular fields. In each case, the side of the equivalent square field corresponding to the same deep yield as a 1 X L rectangular field was determined; a comparison was carried out with the equivalent square field defined for colbat radiation.     

The effect of lung reflexes on the pattern of breathing in cats

Tidal volume (VT), and inspiratory (tI) AND EXPIRATORY (TE) durations have been measured in anaesthetized cats on stimulation of alveolar type J (nociceptive) and lung irritant receptors by intravenous injections of phenyl diguanide and of histamine acid phosphate respectively. The reflexes were studied during eupnoea, hypercapnic and hypoxic hyperpnoea, during rebreathing from hyperventilation apnoea and at different body temperatures. In all conditions the drugs caused rapid shallow breathing with reduction in VT, tI and tE. The VT/tI relationship for injection of the drugs was different from that caused by hypercapnic stimulation of breathing, but the tI/tE relationship was proportionally similar for all conditions. Recording single unit activity from phrenic motor fibres showed that the lung reflexes had little action on the initial frequency of discharge of the fibres, but cut short the discharge earlier than for the controls. The results are interpreted in terms of the ways in which lung reflexes can modify the pattern of breathing.     

Effects of negative pressure assisted ventilation on dyspnoeic sensation and breathing pattern

Although negative pressure assisted ventilation with an assist-control mode may have a potential therapeutic role in the treatment of severe dyspnoea, the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns have not been examined. We examined the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns produced by a combination of resistive loading and hypercapnia in nine healthy subjects breathing spontaneously. Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale. Negative pressure assisted ventilation caused a significant reduction in sensation of respiratory discomfort from a visual analogue scale score of 74 (55-91) (median (range)) before negative pressure assisted ventilation to 34 (15-53) during negative pressure assisted ventilation (p<0.01). During negative pressure assisted ventilation, there were significant changes in breathing patterns characterized by an increase in tidal volume and a decrease in respiratory frequency, while neither minute ventilation nor end-tidal carbon dioxide tension changed. Our results indicate that negative pressure assisted ventilation with the assist-control mode is effective in relief of dyspnoea and that negative pressure assisted ventilation influences the control of breathing to minimize respiratory discomfort.     

Stability of total respiratory resistance under multiple baseline conditions, isometric arm exercise and voluntary deep breathing

Little is known about total respiratory resistance (TRR) as a psychophysiological parameter in normal subjects. Therefore, we investigated TRR in 45 healthy students under multiple baseline conditions, isometric arm muscle tension and voluntary deep breathing (VDB). TRR was measured by the forced oscillation technique. In addition, heart rate (HR) as well as volume and time components of the respiratory cycle, respiratory timing and respiratory drive were monitored. Subjects repeated the protocol 14 days later. Coefficients of stability and dependability were calculated for 20 s measurement epochs within and between both sessions. Increases of HR and shortening of time components of the respiratory cycle were found during muscle tension, prolongation of time components and increases in volume were found for deep breathing. During both experimental tasks TRR increased significantly. Short-term as well as long-term stability of absolute TRR scores proved to be comparable or even better than reliability of other physiological parameters, however, difference scores from baseline revealed only low coefficients.     

Chemical control of breathing in patients with obstructive sleep apnea

The authors have studied chemical control of breathing in 37 normocapnic patients with OSA. These patients had increased apnea-hypopnea index (AHI = 51 +/- 22), obesity (BMI = 32.4 +/- 5.6 kg/m2) and normal lung function tests. Control group consisted of 20 healthy subjects with normal weight (BMI = 23.1 +/- 2.4 kg/m2). Respiratory responses (ventilatory and P0.1) to hypercapnic and hypoxic stimulation during rebreathing tests were measured with computerized methods. The obtained results in OSA patients were compared with the data of the control group. The results exceeding mean values of the control group above 1.64 SD were recognized as hyperreactive responses. The majority e.g. 26 patients (OSA-N) had normal respiratory responses during hypercapnic stimulation. delta V/delta PCO2 = 16.8 +/- 4.5 L/min/kPa, P0.1/delta PCO2 = 3.5 +/- 2.4 cm H2O/kPa/. In remaining 11 patients (OSA-H) respiratory responses were significantly increased delta V/delta PCO2 = 39.1 +/- 18.8 L/min/kPa, P0.1/delta PCO2 = 8.6 +/- 3.9 cm H20/kPa). During isocapnic hypoxic stimulation majority e.g. 25 patients (OSA-H) had significantly increased respiratory responses delta V/delta SaO2 = 3.28 +/- 1.63 L/min/%, delta P0.1/delta SaO2 = 0.54 +/- 0.43 cm H2O/%/. In remaining 12 patients (OSA-N) respiratory responses were within normal limits delta V/SaO2 = 1.2 +/- 0.28 L/min/%, delta P0.1/ delta SaO2 = 0.21 +/- 0.07 cm H2O/%/. The above results indicated, that majority OSA patients (67.5%) had increased ventilatory and P0.1 responses to hypoxic stimulation. Among them also 11 patients had increased respiratory responses to hypercapnia. It seems, that increased respiratory responses to hypoxic stimulus in OSA patients are symptoms of protective reaction to hypoxaemia occurring during repetitive sleep apnoea and reveals increased neuro-muscular output.     

Genetic control of diabetes progression

Autoimmune diabetes in both the human and the nonobese diabetic mouse has elaborate genetics; in the latter case, the disease is influenced by at least 15-20 loci. We anticipated that the genetics would be simpler in the BDC2.5 T cell receptor transgenic mouse model of diabetes, wherein many T cells express a particular diabetogenic specificity. Initiation of insulitis in this model was the same on the two genetic backgrounds analyzed, but the kinetics and penetrance of diabetes were strikingly different, permitting us to focus on genetic influences during a defined window of disease progression. The differences correlated with variations in five genomic intervals, certain ones of which have been previously implicated in susceptibility to autoimmune disease. This reductionist approach indeed simplified the analysis of diabetes susceptibility loci.     

Sister chromatid differential staining pattern in prematurely condensed chromosomes

Application of sister chromatid differential (SCD) procedure on G1, S and G2 prematurely condensed chromosomes (PCC) of cells in the second and third cycle of DNA replication in medium containing BrdU reveals differential staining patterns characteristic of their respective stages in the cell cycle. These findings also suggest a structural similarity between PCC and metaphase chromosomes.     

Effects of body temperature on ventilatory response to hypoxia and breathing pattern in man

The ventilatory response to hypoxia (PAO2 55 and 45 Torr) at each of four levels of PACO2 was studied in five healthy subjects before and after a rise in rectal temperature of 1.4 degrees C had been induced by means of a heated flying suit. At a given level of chemical drive both ventilation and mean inspiratory flow increased after heating, frequency relatively more than tidal volume. In isoventilation comparisons mean inspiratory flow was identical in normo- and hyperthermia, whereas the durations of inspiration (TI) and expiration (TE) were proportionately shortened. It is suggested that a rise in temperature shortens TI by affecting a central "clock" and that TE changes are secondary to changes in end-inspiratory volume. The euoxic CO2 response in hyperthermia was suggestive of multiplication between CO2 and temperature. Hypoxic sensitivity was significantly increased, indicating a temperature effect on the arterial chemoreceptors. The breathing pattern was in either temperature condition identical in euoxia and in hypoxia.     

Effect of step duration during incremental exercise on breathing pattern and mouth occlusion pressure

We compared the effects of two step durations on breathing pattern, mouth occlusion pressure and "effective" impedance of the respiratory system during incremental exercise. Nine normal subjects (mean age: 27.8+/-1.21 years) performed two incremental exercise tests in randomized order: one test with step increments every 1 min 30s and the other, every 4 min. After a warm-up at 25 W for the 1 min 30 s test, the power was increased by 50 W from 50 W to exhaustion. During the last minute at each power, we measured ventilation (VE), tidal volume (VT), breathing frequency (fR), inspiratory and expiratory time (TI and TE), total time of the respiratory cycle (TTOT), TI/TTOT, mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1), "effective" impedance of the respiratory system (P0.1/(VT/ TI)) and venous blood lactate concentration ([La]). Our result showed that at maximal exercise the power was significantly higher (p < 0.01) and [La] lower (p < 0.01) in the 1 min 30 s test. At 100, 150 and 200 W, the 4 min test showed significantly higher oxygen uptake (VO2), carbon dioxide output (VCO2), VE, P0.1, fR, VT/TI and HR (p <0.001) and significantly lower TI, TE and TTOT (p<0.01). [La] was significantly higher at 150 W (p<0.05) and 200 W (p<0.001). At the same VCO2, P0.1 was not significantly different between the two tests, whereas VE showed a tendency to be higher (p = 0.08) and P0.1/(VT/TI) was significantly lower during the 4 min test. In conclusion, this study allowed us to quantify the difference in inspiratory neuromuscular output and ventilatory response between 1 min 30s and 4 min tests and showed that different step durations alter the relationship between inspiratory neuromuscular output and mean inspiratory flow.     

Effects of potassium depletion on control of breathing in awake rats

Possible mechanisms for the variable ventilatory response to metabolic acid-base disturbances have been examined in normal and K-depleted rats. Ventilatory measurements are correlated with CSF acid-base data. The ratios VE/VO2 and 1/PaCO2 are utilized as indices of alveolar ventilation. The log of these indices correlates closely with CSF [H+] independent of [K+] except at very low CSF [H+] where the change in log 1/PaCO2 and log VE/VO2 per change in CSF [H+] is much diminished in low-K rats. This finding suggests the presence of an additional stimulus to breathing in the low-K rat opposing the inhibitory effect of low CSF [H+]. Otherwise the chemical control of ventilation appears to be normal. However, low-K rats always breath with a low-flight-Vt pattern and occasionally with abnormal rhythms. The similarity of the low K breathing pattern to that reported in awake animals with vagotomy and pneumotaxic center (PC) lesions suggests that the altered breathing pattern in depletion involves vagal and/or PC pathways. The similarity of the low-K breathing pattern to that observed with reserpine administration together with the known relationships of K and catecholamine metabolism lead to the speculation that K depletion alters breathing via an effect on central catecholamine metabolism. However, other mechanisms involving changes in membrane excitability and intracellular pH in K depletion might also be involved.     

Respiratory muscle function and control of breathing in patients with acromegaly

Increase in lung size has been described in acromegalic patients, but data on respiratory muscle function and control of breathing are relatively scarce. Lung volumes, arterial blood gas tensions, and respiratory muscle strength and activation during chemical stimulation were investigated in a group of 10 patients with acromegaly, and compared with age- and sex-matched normal controls. Inspiratory muscle force was evaluated by measuring pleural (Ppl,sn) and transdiaphragmatic (Pdi,sn) pressures during maximal sniffs. Dynamic pleural pressure swing (Ppl,sw) was expressed both as absolute value and as percentage of Ppl,sn. Expiratory muscle force was assessed in terms of maximal expiratory pressure (MEP). In 8 of the 10 patients, ventilatory and respiratory muscle responses to hyperoxic progressive hypercapnia and to isocapnic progressive hypoxia were also evaluated. Large lungs, defined as total lung capacity (TLC) greater than predicted (above 95% confidence limits), were found in five patients. Inspiratory or expiratory muscle force was below normal limits in all but three patients. During unstimulated tidal breathing, respiratory frequency (fR) and mean inspiratory flow (tidal volume/inspiratory time (VT/tI)) were greater, while inspiratory time (tI) was shorter than in controls. Minute ventilation (V'E) and mean inspiratory flow response slopes to hypercapnia were normal In contrast, four patients had reduced delta(VT/tI)/arterial oxygen saturation (Sa,O2) and three had reduced deltaV'E/Sa,O2. Ppl,sw(%Ppl,sn) response slopes to increasing end-tidal carbon dioxide tension (PET,CO2) and decreasing Sa,O2 did not differ from the responses of the normal subjects, suggesting normal central chemoresponsiveness. At a PET,CO2 of 8 kPa or an Sa,O2 of 80%, patients had greater fR and lower tI compared with controls. Pdi,sn and Ppl,sn related both to deltaV'E/deltaSa,O2 (r=0.729 and r=0.776, respectively) and delta(VT/tI)/deltaSa,O2 (r=0.860 and r=0.90, respectively). Pdi,sn also related both to deltaV'E/deltaPET,CO2 (r=0.8) and delta(VT/tI)/deltaPET,CO2 (r=0.76). In conclusion, the data suggest the relative independence of pneumomegaly and respiratory muscle strength. Peripheral (muscular) factors appear to modulate a normal central motor output to give a more rapid pattern of breathing.     

Breathing pattern and additional work of breathing in spontaneously breathing patients with different ventilatory demands during inspiratory pressure support and automatic tube compensation

OBJECTIVE: To identify predictors of hypoglycemic and hyperglycemic episodes in hospitalized patients with diabetes with special attention to the effectiveness of sliding scale insulin regimens. DESIGN: Prospective cohort study. SETTING: Urban university hospital. PARTICIPANTS: One hundred seventy-one adults with diabetes mellitus as a comorbid condition admitted consecutively to medical inpatient services during a 7-week period. MEASUREMENTS: Demographic, clinical, and laboratory data from inpatient medical records. MAIN OUTCOMES: Rates of hypoglycemic (capillary blood glucose, < or = 3.3 mmol/L [< or = 60 mg/dL]) and hyperglycemic (capillary blood glucose, > or = 16.5 mmol/L [> or = 300 mg/ dL]) episodes. RESULTS: Of the patients, 23% experienced hypoglycemic episodes, and 40% experienced hyperglycemic episodes. The overall rates of hypoglycemic and hyperglycemic episodes were 3.4 and 9.8 per 100 capillary blood glucose measurements, respectively. Independent predictors of hypoglycemic episodes included African American race (relative risk [RR], 2.13) and low serum albumin level (RR, 1.92 per 100-g/L decrease); corticosteroid use was associated with a reduced risk of hypoglycemic episodes (RR, 0.32; P < .05). Independent predictors of hyperglycemic episodes included female gender (RR, 1.67), severity of illness (RR, 1.22 per 10 Acute Physiology and Chronic Health Evaluation III units), severe diabetic complications (RR, 2.32), high admission glucose level (RR, 1.33 per 5.5 mmol/L), admission for infectious disease (RR, 2.14), and corticosteroid use (RR, 3.74; P < .05). Of 171 patients, 130 (76%) were placed on a sliding scale insulin regimen. When used alone, sliding scale insulin regimens were associated with a 3-fold higher risk of hyperglycemic episodes compared with individuals following no pharmacologic regimen (RRs, 2.85 and 3.25, respectively; P < .05). CONCLUSIONS: Suboptimal glycemic control is common in medical inpatients with diabetes mellitus. The risk of suboptimal control is associated with selected demographic and clinical characteristics, which can be ascertained at hospital admission. Although sliding scale insulin regimens are prescribed for the majority of inpatients with diabetes, they appear to provide no benefit; in fact, when used without a standing dose of intermediate-acting insulin, they are associated with an increased rate of hyperglycemic episodes.     

Influence of drive and timing mechanisms on breathing pattern and ventilation during mental task performance

Assessment of multiple respiratory measures may provide insight into how behavioral demands affect the breathing pattern. This is illustrated by data from a study among 44 subjects, in which tidal volume, respiration rate, minute ventilation and indices of central drive and timing mechanisms were assessed via inductive plethysmography, in addition to end-tidal PCO2. After a baseline, three conditions of a memory comparison task were presented. The first two conditions differed only with regard to the presence or absence of feedback of performance (NFB and FB). In the third 'all-or-nothing' (AON) condition, subjects only received a monetary bonus, if their performance exceeded that of the previous two conditions. Minute ventilation increased from baseline to all task conditions, and from NFB and FB to AON. Respiration rate increased in all task conditions, but there were no differences between task conditions. Tidal volume decreased during NFB, but was equal to baseline during FB and AON. Of the respiratory control indices, inspiratory flow rate covaried much more closely with minute ventilation than duty cycle. The task performance induced a minor degree of hyperventilation. The discussion focusses on how behavioral demands affect respiratory control processes to produce alterations in breathing pattern and ventilation.