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Effects of chronic lung denervation on breathing pattern and respiratory gas exchanges during hypoxia, hypercapnia and exercise.

The influence of vagal fibres from the lung on ventilatory responses to hypercapnia, hypoxia and exercise was studied in two intact dogs (C) and two chronically lung denervated dogs (C.L.D.). In intact dogs, inspiration duration did not change as tidal volume increased in response to increased chemical drives. Chronic lung denervation did not affect the hypercapnia- or hypoxia-induced elevations in V, despite significant changes in breathing pattern. During exercise, oxygen consumption was similar for C and C.L.D. animals. V for a given oxygen uptake was the same in C and C.L.D. dogs, but VT was higher in C.L.D. animals at all levels of exercise. It is concluded that vagal fibres from the lung play a role in determining the breathing pattern, but are not required for a normal ventilatory response to hypercapnia, hypoxia and exercise. Interaction between vagal sensory input and specific structures sensitive to chemical or physical stimuli is discussed.

Animals↗

Ventilatory compensation for changes in posture after human heart-lung transplantation.

We have studied the contribution of vagal pulmonary receptors to the stability of breathing during postural changes in humans. Quiet breathing was quantified in the seated and the supine postures in 10 patients with chronic pulmonary denervation due to heart-lung transplantation and 10 age and sex matched normal controls. In the vast majority of patients and normal subjects frequency histograms for tidal volume and mean inspiratory flow rate were virtually superimposed seated and supine. There were no significant differences in the mean levels of respiratory variables between postures in either group (except for mean inspiratory flow rate in the patients which was slightly greater seated than supine). Experiments performed on a tilt table in two additional patients showed that the ventilatory response to postural changes was immediate. In addition, the response was maintained after blockade of intact tracheal stretch receptors with aerosolized lidocaine. These results indicate that adequate ventilatory compensation during postural changes does not depend on vagal afferent information arising in intrapulmonary or tracheal airway stretch receptors. The appropriate receptors may be diaphragmatic Golgi tendon organs.

Adolescent↗

Tonic activity in inspiratory muscles during continuous negative airway pressure.

We studied tonic inspiratory activity (TIA) induced by continuous negative airway pressure (CNAP) in anaesthetized, spontaneously breathing cats. TIA in the diaphragm and parasternal intercostal muscles (ICM) was quantified in response to tracheal pressure (PTR) = -0.3 to -1.2 kPa. To differentiate between reflexes from rapidly adapting receptors (RARs), slowly adapting receptors (SARs) and C-fiber endings different temperatures of the vagus nerves (TVG) were used between 4 and 37 degrees C. At PTR = -1.2 kPa mean TIA values were 41% and 62% of peak inspiratory EMG activity of control breaths for the diaphragm and ICM, respectively. After vagotomy and for TVG < 6 degrees C CNAP did not induce TIA anymore. Changes in inspiratory and expiratory time during vagal cooling down to 4 degrees C confirmed the selective block of conductance in vagal afferents of the three types of lung receptors. We conclude that CNAP-induced TIA results from stimulation of RARs. Our data strongly indicate that stimulation of SARs suppresses TIA, whereas C-fiber endings are not involved in TIA at all. The results suggest that part of the hyperinflation in bronchial asthma may be caused by TIA in response to mechanical stimulation of RARs.

Airway Resistance↗

Respiratory failure due to altered central drive during inspiratory loading in rabbits.

Mechanisms of respiratory muscle dysfunction leading to respiratory failure during incremental inspiratory threshold loading were studied in unbound spontaneously breathing rabbits during light and deeper anesthesia. Low or high frequency contractile fatigue was not found at the point of respiratory failure in any of the animals. On the other hand, alterations in central drive to the diaphragm played a dominant role in the observed respiratory failure. In animals receiving light anesthesia the intensity of central drive increased with loading, but then fell as respiratory failure approached. In all animals the intensity of central drive at peak activation and at the point of respiratory failure was submaximal, in spite of the diaphragm's ability to generate additional forces. In addition, the time tension index of the diaphragm rose in response to increasing loads to a level reported to produce contractile fatigue, at which time the index peaked and then fell in spite of increasing load demands. The fall in the time tension index as respiratory failure approached was due primarily to a fall in inspiratory time and duty cycle. Ultimately, there was an abrupt cessation in central drive resulting in apnea. These findings suggest that alterations in central drive play a major role in respiratory muscle dysfunction and respiratory failure associated with inspiratory loading in unbound spontaneously breathing rabbits.

Animals↗

The effect of inspiratory flow rate regulation on nebulizer output and on human airway response to methacholine aerosol.

Increased inspiratory flow rate has been demonstrated to decrease pulmonary deposition of inhaled aerosols. To study the effect of inspiratory flow rate regulation on the physiologic response to an active substance administered by aerosol, we compared the effect of high unregulated flow rate (66 to 212 L/min) with regulated low flow rate (20 to 35 L/min) on nebulizer output and on the pulmonary response to methacholine in patients with asthma. Four No. 646 DeVilbiss nebulizers were used in sequence with a nebulization dosimeter to deliver tenfold incremental concentrations of methacholine aerosol (mass median aerodynamic diameter = 1.52 micron; geometric standard deviation = 1.96) ranging from 0.025 to 25 mg/ml. When flow was unregulated, nebulizer output was not greater than when flow was regulated, but coefficients of variation of output were significantly greater (p less than 0.01). The PD20 on the two unregulated days was significantly different (p = 0.01), whereas the PD20 on the two flow regulated days was not significantly different (p greater than 0.05). We conclude that regulation of inspiratory flow rate at rates within the range of tidal breathing significantly decreases variability in nebulizer output and variation of pulmonary responses to methacholine challenge.

Aerosols↗

Visual attention in patients with chronic obstructive pulmonary disease.

The selective visual attention of 39 patients with chronic obstructive pulmonary disease (COPD) was measured by the Bourdon-Vos test and compared with the attention performance of 38 healthy controls of the same age range. The correlation between the attention of the COPD patients and day- and night-time parameters was determined. Furthermore, in 44 other COPD patients with daytime hypoxaemia, the effect of one night of oxygen supplementation and of a 7-day treatment with two respiratory stimulants (chlormadinone acetate) (CMA) or acetazolamide (ACET) on attention performance was studied. The results showed that the attention performance of COPD patients was lower than that of controls. Significant correlations were found between the mean line time (attention parameter) and the following parameters: age, inspiratory vital capacity (IVC), hypercapnic ventilatory response (HCVR), daytime arterial oxygen saturation (SaO2), daytime arterial oxygen pressure (PaO2), daytime arterial carbon dioxide pressure (PaCO2), mean nocturnal SaO2, lowest nocturnal SaO2 and the standard deviation of the mean nocturnal SaO2. Multiple linear regression analysis showed that, apart from age, only the nadir of the nocturnal SaO2 contributed to the prediction of the attention. No clinically important short-term effect of oxygen or respiratory stimulating therapy on the attention performance was found.

Acetazolamide↗

Increasing background inspiratory resistance changes somatosensory sensations in healthy man.

The central purpose of the study was to investigate if increasing background inspiratory resistance, a circumstance which activated afferents from the lungs and respiratory muscles, modified somatosensory and/or auditory sensations in healthy individuals. Estimation of mechanical stimulations applied on the middle finger (somatosensory sensation) and unilateral sound-pressure stimulations (auditory sensation) was based on the computation of Stevens' power function psi = k.phi n, where psi is the estimate and phi is either the somatosensory stimuli or sound-pressures. This was studied during eupnoeic unloaded ventilation then during a 10-min period of loaded breathing followed by a 10-min recovery period. Loaded breathing significantly lowered the estimate of somatosensory stimuli (decreased n coefficient). This effect persisted during the two first minutes of recovery period. By contrast, loaded breathing did not modify the perception of auditory stimulus. As somesthetic and respiratory afferents, but not auditory afferents, project on the same area in the sensory cortex we suggest the existence of central interactions which could explain observations of the difficulties to execute accurate tasks in patients suffering from obstructive lung disease independently from the alterations in their arterial blood gases.

Acoustic Stimulation↗

Volume delivery during positive pressure inflation--relationship to spontaneous tidal volume of neonates.

Volume delivery by positive pressure inflation was determined in 20 premature infants and 10 infants born at term on days 1 and 2. The spontaneous tidal volume, respiratory rate and inspiratory to expiratory (I:E) ratio were measured daily in the first week of life in an additional group of 20 infants born prematurely. Measurements were made using a pneumotachograph only when the infants were stable and had acceptable blood gases for at least 2 h. There was variability between individuals but the median delivered volume by positive pressure ventilation ranged between 4.9 and 6.1 ml/kg on days 1 and 2 and within the groups of different maturity. There was no significant difference in the results of infants born prematurely or at term or when studied on days 1 or 2. The median spontaneous tidal volume during the first week of life varied between 5.4 and 6.7 ml/kg; respiratory rate between 72 and 80 breaths/min and I:E ratio from 0.67 to 0.77. Postnatal age had no significant effect on the results. These results suggest volume delivery by positive pressure inflation during a stable period of ventilation is similar to the spontaneous tidal volume.

Forced Expiratory Flow Rates↗

Continuous oxygen insufflation in addition to IPPV causes air trapping in a mechanical lung model.

It has previously been reported that continuous insufflation of either supracarinal or subcarinal oxygen in addition to intermittent positive-pressure ventilation (IPPV) in patients under general anesthesia, and in critically ill patients in the intensive care unit, causes increased proximal airway pressure, decreased systemic blood pressure, and decreased cardiac output. The investigators hypothesized that these deleterious hemodynamic effects were due to intrapulmonary air trapping, resulting in an increased distal intrapulmonary pressure and volume. The purpose of this study was to test this hypothesis in an appropriate mechanical lung model. The study determined end-inspiratory and end-expiratory lung pressures and volumes during eight experimental sequences: (1) IPPV alone; (2) insufflation of oxygen alone at 2.5, 5.0, and 10.0 L/min (O2-2.5, 5.0, 10.0); (3, 4, and 5) IPPV plus insufflation of oxygen (IPPV + O2-0.0, 2.5, 5.0, 10.0) through a supracarinal catheter (sequence 3), subcarinal catheters (sequence 4), and through a CO2 sampling port of an endotrachael tube (sequence 5); (6 and 7) IPPV + O2-5.0 with increased expiratory time caused by an increased inspiratory flow rate (sequence 6) and a decreased respiratory rate (sequence 7); (8) IPPV + O2-5.0 with increased airway diameter. Experimental sequences 1 and 2 resulted in no increases or minimal ones in lung pressure and volume, respectively. With each insufflation catheter system (sequences 3, 4, and 5), each incremental increase in insufflation flow rate resulted in significant increases in lung pressure and volume. Increasing expiratory times (sequences 6 and 7 compared with 3, 4, and 5) decreased lung pressure and volume. Increasing the airway diameter (sequence 8) had only slight effect on lung pressure and volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗

The influence of fresh gas flow and inspiratory/expiratory ratio on tidal volume and arterial CO2 tension in mechanically ventilated surgical patients.

The relative importance of fresh gas flow and inspiratory/expiratory ratio in determining delivered tidal volume and PaCO2 was studied in anesthetized adult patients ventilated with a fixed ventilator bellows volume. The fresh gas flows studied were 2, 6, and 10 L/min, and inspiratory/expiratory ratio was either 1:2 or 1:4.5. Bellows volume and respiratory rate were held constant throughout the study. At the lowest fresh gas flow and smallest inspiratory/expiratory ratio, PaCO2 was 43 +/- 2 mm Hg. The PaCO2 decreased progressively and significantly with each increase in fresh gas flow during ventilation with either inspiratory/expiratory ratio setting. PaCO2 averaged 30 +/- 3 during ventilation with the highest fresh gas flow and largest inspiratory/expiratory ratio. As fresh gas flow increased, PaCO2 and tidal volume changed to a significantly greater degree in response to changes in inspiratory/expiratory ratio. These data demonstrate that altering either fresh gas flow or inspiratory/expiratory ratio can produce clinically significant perturbations in PaCO2 and tidal volume during anesthesia. These perturbations occur even if bellows volume is held constant. Furthermore, changes in inspiratory/expiratory ratio will affect these parameters to a greater degree as fresh gas flow is increased.

Adult↗

Chronic rejection following lung transplantation. Incidence, time pattern and consequences.

UNLABELLED: The long-term prognosis following lung transplantation (LTX) depends mainly on the development of chronic rejection which appears clinically as deterioration of the lung function while, histologically, obliterative bronchiolitis (OB) is found. However, it still remains questionable whether heart-lung (HL), double or single lung (DL/SL) transplants behave similarly with regard to incidence and time pattern. Eighty-two patients, transplanted until August 92, were analyzed. Early and late deaths within 180 days postoperatively were excluded. A total of 64 patients at risk could be evaluated. By repeated lung function tests, obstructive airway disease was defined by a drop of 25% or more of the forced expiratory volume in one second (FEV1) in percent of the inspiratory vital capacity. RESULTS: The functional optimum after transplantation was reached after a comparable time-span postoperatively in all groups. Chronic deterioration of the lung function developed earlier following DLTX compared to HLTX and SLTX. Obstructive airway disease was diagnosed in 9/20 (45%) HL, 7/19 (37%) DL, and 7/25 (28%) SL patients. Of these, 4 died and 4 had to be retransplanted for the disease while an additional 15 patients are currently under investigation. It is concluded that the development of obstructive airway disease represents a serious problem in all types of lung transplantation. There is a tendency to earlier development following DLTX--perhaps caused by the greatest immunological potential in this group of patients.

Adult↗

Prospective comparison of ventilatory equivalent versus peak oxygen consumption in predicting outcomes of patients with heart failure.

In patients with heart failure (HF), peak exercise oxygen consumption (VO2) is an important prognostic tool on which critical clinical decisions are made. However, recent retrospective data have suggested that ventilatory equivalent (VE = ventilation [liters per minute]/VO2 [liters per minute]) may be a stronger predictor of outcomes than VO2 in patients with HF on modern medical therapies. We prospectively collected baseline demographics, cardiovascular history, hemodynamics, and exercise ventilatory data from 221 consecutive patients with HF who underwent treadmill exercise VO2 testing. The composite primary end point was death or heart transplantation. Mean follow-up was 508 days, during which 27 events occurred (13 deaths and 14 transplantations). One-year event-free survival was 88% (n = 104 with 1-year follow-up). Mean age was 49 years, 68% were men, 84% were taking beta blockers, 82% were taking angiotensin-converting enzyme inhibitors, and 21% had an implantable cardioverter-defibrillator. Mean VO2 was 16 +/- 5 ml/kg/min. Mean VE was 47.4 +/- 15.2. Univariate predictors of events included lower VO2 (p <0.0001), higher heart rate at rest (p = 0.05), and presence of an implantable cardioverter-defibrillator (p = 0.024). Higher VE (p = 0.10) and lower maximum systolic blood pressure (p = 0.09) were of borderline significance. Age, gender, HF etiology or severity, and other ventilatory parameters were not significant predictors. Multivariate models that incorporated VE, VO2, or their combination confirmed VO2 as an independent predictor of event-free survival (p < or =0.0002); VE did not independently predict outcomes. Other independent predictors were higher heart rate at rest (p < or =0.02) and presence of an implantable cardioverter-defibrillator (p < or =0.04). In conclusion, peak VO2, but not VE, predicts clinical outcomes of patients with HF who are treated with contemporary medical therapies.

Disease Progression↗

Combined intercostal and diaphragm pacing to provide artificial ventilation in patients with tetraplegia.

OBJECTIVE: To evaluate the usefulness of combined intercostal and diaphragm pacing to maintain independence from mechanical ventilation. DESIGN: A prospective trial. SETTING: Clinical research center at a large tertiary hospital. PARTICIPANTS: Four ventilator-dependent subjects with spinal cord injury with only unilateral phrenic nerve function. INTERVENTION: During an initial surgical procedure, a multipolar epidural disk electrode was positioned on the ventral surface of the upper-thoracic spinal cord via a hemilaminectomy to activate the inspiratory intercostal muscles. A phrenic nerve electrode was implanted unilaterally via the thoracic approach. MAIN OUTCOME MEASURES: Inspired volume production and duration that subjects could be comfortably maintained when off mechanical ventilatory support. RESULTS: Initial maximum inspired volumes from combined intercostal and diaphragm stimulation ranged between .23 and .93L and significantly increased over the course of reconditioning period to between 0.55 and 1.31L; subjects could be maintained off mechanical ventilation between 16 and 24 hours a day. CONCLUSIONS: Combined intercostal and unilateral diaphragm pacing may be a useful therapeutic modality capable of maintaining long-term ventilatory support in patients with only unilateral phrenic nerve function.

Diaphragm↗

Respiratory muscle training in restrictive thoracic disease: a randomized controlled trial.

OBJECTIVE: To investigate the effects of respiratory muscle training (RMT) in patients with restrictive thoracic disorders and intermittent noninvasive positive-pressure ventilation (NPPV). DESIGN: Prospective randomized controlled trial. SETTING: Home-based RMT, with assessment in a primary care pulmonary center. PARTICIPANTS: Thirty patients with restrictive thoracic disorders; 28 patients completed the trial. INTERVENTION: Three months of RMT by isocapnic hyperpnea or sham training. MAIN OUTCOME MEASURES: Respiratory muscle strength and endurance, lung function, exercise performance, and health-related quality of life (HRQOL). RESULTS: After RMT, maximal inspiratory mouth pressure was increased (27.6%+/-36.5%, P=.013). In patients who could perform cycle ergometer testing (n=17), peak oxygen consumption (2.24+/-3.39mLxkg(-1).min(-1) vs -1.71+/-2.54mLxkg(-1).min(-1), P=.014) and maximal work rate (9.4+/-14.8W vs -5.1+/-10.8W, P=.043) increased relative to a control group. Similar differences occurred regarding changes of HRQOL (physical performance, 3.3+/-11.4 score vs -6.6+/-9.0 score; P=.012) and time of ventilator use (-0.6+/-1.2h/d vs 0.4+/-0.5h/d, P=.010). Lung volumes, 12-second maximum voluntary ventilation, 6-minute walking distance, and blood gases were unchanged. CONCLUSIONS: In patients with restrictive thoracic disorders and NPPV, RMT improved inspiratory muscle strength. Exercise performance and HRQOL were improved when the 2 groups were compared. RMT was practicable and safe despite severe respiratory impairment. Further evaluation, including different training intensities and modalities, seems warranted.

Breathing Exercises↗

Inspiratory muscle strength training with behavioral therapy in a case of a rower with presumed exercise-induced paradoxical vocal-fold dysfunction.

Paradoxical vocal fold dysfunction (PVFD) with high effort exercise can result in disruptions to ventilation, dyspnea, inspiratory stridor, elevated heart rate, and syncope. This single subject study experimentally tested an inspiratory muscle strength training (IMST) program with behavioral therapy on a 15-year-old male crew member. Outcome variables were maximum inspiratory pressure (MIP), and dyspnea ratings. Following 5 weeks of IMST, MIP increased by 93% from baseline function while dyspnea ratings substantially decreased. Outcome included successful competition with his high-school crew team, a task he was previously unable to complete. Discussion focuses on IMST combined with traditional approaches of voice therapy for treating PVFD.

Adolescent↗

Inspiratory muscle training in exercise-induced paradoxical vocal fold motion.

The purpose of the study was to determine if inspiratory muscle training (IMT) would result in increased inspiratory muscle strength, reduced perception of exertional dyspnea, and improved measures of maximal exercise effort in an athlete with exercise-induced paradoxical vocal fold motion (PVFM). The participant, an 18-year-old woman, had a 2-year history of acute dyspnea with exertion during soccer games. Spirometry, transnasal flexible laryngoscopy, and patient history supported a PVFM diagnosis. The ABAB within-subject withdrawal design study comprised IMT treatment and withdrawal phases, each lasting 5 weeks. The participant trained 5 days per week, completing five sets of 12 breaths at 75% maximum inspiratory pressure (MIP) per session. Data consisted of MIP, exertional dyspnea ratings, and maximal exercise measures. IMT resulted in increased MIP and decreased dyspnea ratings across both treatment phases. No change in MIP or dyspnea ratings occurred in response to treatment withdrawal. The maximal exercise test revealed minimal changes across phases. At end of the study, the participant reported experiencing no PVFM symptoms when performing the outcome measurement tasks and when playing soccer. Transnasal flexible laryngoscopy, after strenuous exercise and during rapid breathing and phonation tasks, revealed normal laryngeal findings. The findings suggest that IMT may be a promising treatment approach for athletes with exercise-induced PVFM.

Adolescent↗

Perceived inspiratory difficulty in neuromuscular patients with primary muscle disorders.

Intensity of perceived inspiratory difficulty was investigated in 17 patients with severe respiratory insufficiency due to muscle disease, compared with healthy matched controls. Subjects breathed through a threshold valve generating a constant inspiratory negative pressure proportional to their maximal inspiratory pressure. Four load levels ranging from 10 to 40% of the maximal inspiratory pressure were applied in random order. Patients had significantly less perceived inspiratory difficulty than controls at each load level expressed as a percentage of maximal inspiratory pressure P < 0.001. However, when the load was expressed as the absolute value, the slope of the Borg scale score versus mouth pressure was similar in the two groups (P = 0.11). The ventilatory pattern remained unchanged in each group as the load increased. We conclude that in patients with myopathy, loads leading to respiratory muscle fatigue (40% of maximal inspiratory pressure) may fail to produce perceived inspiratory difficulty.

Adult↗

Comparison of subjective perception with objective measurement of olfaction.

OBJECTIVE: To see if nasal peak inspiratory flow rate and subjective sense of smell had any correlation with olfactory thresholds. STUDY DESIGN AND SETTING: A cohort study of 186 normal volunteers was recruited from among staff and visitors at a university hospital. Olfactory thresholds were detected for each subject (103 with eucalyptol and 83 with phenethyl alcohol), along with nasal peak inspiratory flow (PIFR). Subjective sense of smell, along with nasal symptoms, mood, and alertness, were recorded on visual analogue scores. RESULTS: Subjective perception of smell had no correlation with olfactory thresholds detected (P = 0.4057) and the other subjective measures also had no correlation. There was a significant relationship of PIFR to thresholds in the group tested with phenethyl alcohol (P = 0.002). CONCLUSION: As with the sensation of nasal patency, the self-assessment of a subject's sense of smell has poor correlation with their actual olfactory ability. SIGNIFICANCE: A patient's history cannot be relied upon when determining their olfactory ability and formal testing should be performed. EBM RATING: A-1b.

Adolescent↗