Elevated Functional Residual Capacity Research Articles

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

Background: Chlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aims at quantifying and differentiating pulmonary dysfunction and acid–base imbalances induced by Cp.
 Methods: Forty-two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls shaminoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and FRC (functional residual capacity) measurement were applied to spontaneously breathing animals. Variables of acid–base status were assessed in venous blood using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach.
 Results: Both obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. Although disorders in respiratory mechanics lasted for 8–11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume (−25%) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10%. Minute ventilation increased significantly (+50%) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2–3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid–base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2–10 dpi), a negative acute-phase marker, resulted in a decrease in the sum of non-volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects of decreased strong ion difference (SID), mediated by the interplay between hypochloraemia (alkalotic effect) and hyponatraemia (acidic effect).
 Conclusions: This bovine model was found to be suitable for studying pathophysiology of respiratory Cp infection and may help elucidating functional host-pathogen interactions in the mammalian lung.

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

BackgroundChlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aims at quantifying and differentiating pulmonary dysfunction and acid–base imbalances induced by Cp.MethodsForty-two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls sham-inoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and FRC (functional residual capacity) measurement were applied to spontaneously breathing animals. Variables of acid–base status were assessed in venous blood using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach.ResultsBoth obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. Although disorders in respiratory mechanics lasted for 8–11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume (−25%) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10%. Minute ventilation increased significantly (+50%) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2–3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid–base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2–10 dpi), a negative acute-phase marker, resulted in a decrease in the sum of non-volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects of decreased strong ion difference (SID), mediated by the interplay between hypochloraemia (alkalotic effect) and hyponatraemia (acidic effect).ConclusionsThis bovine model was found to be suitable for studying pathophysiology of respiratory Cp infection and may help elucidating functional host-pathogen interactions in the mammalian lung.

Ventilatory defect in coal workers with simple pneumoconiosis: early detection of functional abnormalities.

Airway obstruction is a prominent feature in coal workers' pneumoconiosis (CWP). However, many patients with CWP have even demonstrated a normal forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1). The purpose of this study was to evaluate the ventilatory defect by spirometry and search for parameters, other than FVC and FEV1, suitable for early detection of pulmonary impairment in CWP. A sample of 227 coal miners was selected from the medical clinics of two teaching hospitals. Maximal expiratory flow volume measurement and determination of functional residual capacity (FRC) and residual volume (RV) were carried out with an automated plethysmograph. The prevalence of airway obstruction (FEV1/FVC < 70%) in this sample of miners was 52.9% (120/227). There was a progression of functional impairment with the transition from category 0 to categories 2 and 3, no matter what the miners smoking habits. All of the 107 non-obstructed miners had a normal FVC and FEV1. However, the mean values for FEF25-75% (mean forced expiratory flow during the middle half of FVC) and Vmax50 (maximal expiratory flow rate at 50% FVC) were abnormally low, and RV was already elevated, in those non-obstructed subjects with category 1 simple pneumoconiosis. A borderline abnormally elevated FRC in the miners with radiological category 3 of CWP was also noted. We conclude that the Vmax50, FEF25-75%, and RV appeared to be the discriminative indices for detecting early ventilatory defect in non-obstructed patients with simple CWP. Further studies is still needed to clarify the cause of small airway dysfunction.

Lung function in infants with sickle cell disease.

We performed pulmonary function testing in 20 infants (11 male and 9 female; ages 3-30 months) with sickle cell disease to assess whether abnormal lung function develops early in life. Respiratory system compliance (Crs) and resistance (Rrs) were measured by the passive occlusion technique, functional residual capacity (FRC) was measured by the nitrogen washout technique, and tidal flow-volume loops and partial expiratory flow-volume curves were obtained by the thoracoabdominal compression technique to detect airway obstruction. Patients with Hb SS (Group I, n = 12) had significantly lower hemoglobin levels and a higher (but not significant) incidence of acute chest syndrome (ACS), vasoocclusive crisis (VOC), splenic sequestration, transfusions, and history of intermittent bronchospasm compared to with patients with hemoglobinopathies Hb SC, Hb Sbt and Hb SF (Group II; n = 8). Both groups had elevated FRC, decreased maximum expiratory flows at FRC (V'max,FRC), and decreased time needed to reach peak expiratory flow (tme/tE), suggesting lower airway obstruction (LAO) and hyperinflation. Restrictive disease was found in only three patients of Group I. Our findings suggest that in sickle cell disease (especially among patients with Hb SS), abnormal lung function (predominantly LAO) may be present in early infancy. Airway reactivity may play a role in the pathogenesis, but the relation to VOC or ACS remains unclear.

Value of body plethysmography in preoperative assessment of thoracotomy candidates.

The usefulness of body plethysmography in the assessment of thoracotomy candidates is not well documented. Reported thresholds for operability are generally expressed in absolute values, which do not take into account a patient's size, age or gender. Spirometric and plethysmographic data of 103 patients undergoing thoracotomy were examined for their ability to predict death due to cardiopulmonary insufficiency, pneumonia, and atelectasis during the first 30 postoperative days. Neither plethysmographic nor spirometric parameters could predict atelectasis. Patients who underwent lobectomy were susceptible to the development of atelectasis. A weak correlation between elevated functional residual capacity (FRC) and occurrence of postoperative pneumonia was found. Lung function testing was not able to separate survivors from non-survivors. Patients with pneumonia were at high risk of death in their postoperative course. Because of the non-linear relationship, a correlation coefficient between spirometric and plethysmographic variables was not calculated. The prevalence of cardiac risk factors was high, so the decision for invasive hemodynamic studies should rather be based upon a patient's history than restricted to patients with impaired lung function. Because of methodological differences, and probably insuitable reference values, body plethysmography cannot substitute for spirometry. For FRC and FRC to total lung capacity (FRC/ TLC) ratio, further investigations must be undertaken to establish a correct reference value.

Abnormalities of functional residual capacity in symptomatic and asymptomatic young asthmatics.

Functional residual capacity (FRC) was measured by helium gas dilution in 186 young asthmatics, aged between 2 and 9 years. The majority were hyperinflated, as evidenced by an increase in FRC, regardless of symptom status. Symptomatic children and those hospitalized with an acute asthma attack had significantly elevated FRC when compared to asymptomatic children (p less than 0.01). Eight symptomatic children, following treatment modification, became asymptomatic. This was associated with a reduction in FRC. We suggest that an FRC result greater than one standard deviation from the mean of asymptomatic asthmatics could be used to predict inadequacy of treatment.

Effect of thoracoabdominal configuration on the diaphragmatic contribution to rib cage motion.

Owing to the diaphragm-rib cage interaction the diaphragm can reduce the load on the intercostal muscles. The extent of this load reduction was evaluated by analyzing the EMG activity of intercostal muscles as an index of the pressure generated by the intercostal muscles. Three trained subjects shifted their breathing configuration while the rib cage volume and flow were kept constant. Analysis of data thus obtained indicated that the diaphragmatic contribution to the rib cage motion improved with a thoracic shift of breathing. The significance of this effect was further evaluated by performing respiratory maneuvers at constant tidal volume and flow at normal and elevated functional residual capacity. At both lung volumes, a substantial saving of diaphragmatic activity attained by the thoracic shift of breathing was associated with a moderate increase or even a decrease in the intercostal EMG activity, suggesting an overall mechanical advantage of inspiratory muscles during thoracic breathing.

Respiratory volume-timing relationship during sustained elevation of functional residual capacity

In 7 spontaneously breathing dial-urethane anesthetized cats a negative pressure was produced arounf the thorax and abdomen to increase the functional residual capacity (FRC) by about 1 tidal volume for up to 60 min. A tracheal cannula was connected to a resistive manifold for selective loading of inspiration or expiration. Two resistive loads and tracheal occlusion were presented six times each at control FRC (FRCc), after 60 min at elevated FRC (FRCe) and 30 min after return to FRCc. Inspiratory and expiratory durations (Ti and Te) were measured from diaphragmatic EMG. We observed that Ti at FRCe (0.88 ± 0.11 sec) was not significantly shorter than Ti at FRCc (1.06 ± 0.14 sec). Tracheal occlusion at FRCe caused a shorter Ti (1.37 ± 0.15 sec) than at FRCc (1.79 ± 0.21 sec) (P < 0.05). The slope (m) of the Vi-Ti relationship generated by the resistive loads at FRCe was steeper (m = −65 ± 7 ml·sec−1) and shifted upward from the Vi-Ti curve at FRCc (−50 ± 6 ml·sec−1) (P < 0.05). The Ve-Te relationship at FRCe was not significantly changed from control. Thirty minutes following return to FRCc, Ti was still slightly shorter (0.96 ± 0.11 sec) than the initial Ti at FRCc.We conclude: (1) The slope of the Vi-Ti relationship is determined to a great extent by the total lung volume. However, under the conditions of sustained elevation of FRC, this relationship is influenced by the partial adaptation of slowly adapting pulmonary receptors SARs. (2) The increased SAR activity at end expiration during FRCe may not influence the control of Te.

Response of pulmonary stretch receptors to shifts of functional residual capacity

The response of slowly adapting pulmonary stretch receptors (PSRs) to sustained elevations of functional residual capacity (FRC) was investigated in spontaneous breathing anesthetized cats. A subatmospheric pressure was produced around the thorax and abdomen to increase FRC by approximately one tidal volume (V T) for up to 60 min. During eupneic breathing the PSR frequency (f PSR) was closely related to changes in transpulmonary pressure (P TP), bu occasionally hysteresis was observed in the f PSR - P TP relationship. Elevation of FRC caused most phasic PSRs to discharge continously for a few breaths before returning to a phasic discharge pattern. During the shift in FRC there were increases in mean f PSR, peak f PSR and PSR firing threshold which were sustained throughout the period of elevated FRC. PSRs that normally showed discharges at FRC similarly increased their mean and peak firing rates. For all PSRs the y-intercept ( f PSR at P TP = 0) of the f PSR - P TP relationship was decreased but the sensitivity of the PSRs as defined by Δf PSR/ΔP TP was not changed until the period of elevated FRC exceeded 30 min. Thereafter, PSR sensitivity tended to decline. There results suggest that PSRs undergo some modification of their discharge parameters during prolonged elevation of FRC.

EFFECTS OF COMPRESSIBILITY OF ALVEOLAR GAS ON DYNAMICS AND WORK OF BREATHING.

Alveolar gas is compressed and expanded during every breathing cycle. The volume displacement measured at the mouth Vt (tidal volume) is therefore smaller than the volume displacement of the lung V't that may be measured with a body plethysmograph. Experimental data found in normal subjects and in patients with obstructive emphysema confirm the theoretical prediction that the ratio Vt/V't decreases with increasing airway resistance, breathing frequency, and lung volume. The effect was found to be very small in normal subjects breathing at different breathing rates; however, in patients with obstructive emphysema it may be appreciable, presumably because of the high airway resistance and the elevated functional residual capacity. With increasing altitude the effect is expected to be more pronounced. The mechanical work performed in compressing and expanding alveolar gas is not included in the conventional pressure-volume diagram, when intraesophageal pressure is plotted against the volume displacement measured at the mouth. This work may be determined, however, by recording the volume displacement of the lung simultaneously with tidal volume and intraesophageal pressure. Work related to compressibility is insignificant in most circumstances. In patients with obstructive emphysema, however, it becomes appreciable during hyperpnea. The compressibility of alveolar gas was also found to increase the negative work performed by respiratory muscles. volume displacement of the lung (V't); Vt/V't in obstructive emphysema; dynamic pressure-volume diagram; mechanical model - respiratory dynamics; ventilation; negative work of inspiratory muscles; ventilation and breathing work at high altitudes; mechanics of breathing Submitted on June 21, 1963