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[Idiopathic fibrosing alveolitis].

The prognostic features of the disease are summed up. The leading symptom of the disease is the dyspnoe followed by a dry hacking cough, loss of weight and fever. Clinically we find rales, cyanosis clubbing and signs of right heart insufficiency. Lung function data point to a decreased vital capacity and diffusing capacity; residual volume and functional residual capacity are about normal. Corticosteroid monotherapy is not an efficient treatment. The combination of prednisolon + azathioprine improves vital capacity but not working capacity. Prednisolone and d-penicillamine improve all parameters including working capacity. This can be enhanced by still adding azathioprine or cyclophosphamide to prednisolone and d-penicillamine.

Azathioprine↗

Altered respiratory physiology in obesity.

The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.

Adiposity↗

[Ventilatory support after open heart surgery: effects of PEEP and CPAP on gas exchange and lung function (author's transl)].

In 11 patients requiring coronary bypass surgery during extracorporeal circulation we measured pulmonary function and hemodynamic variables before surgery and during the postoperative period. None of the patients presented with pulmonary hypertension or cardiac failure. Cardiac surgery with extracorporeal circulation caused an important decrease in functional residual capacity (-60%) and in arterial oxygenation (-44%). In the immediate postoperative period, the addition of a positive end-expiratory pressure (PEEP) to mechanical ventilation produced an increase in functional residual capacity and in arterial oxygen tension, and a slight decrease in cardiac output. In contrast to the results obtained in children after cardiac surgery and in adults presenting with viral pneumonia or respiratory distress after polytrauma or surgery, continuous positive airway pressure during spontaneous breathing (CPAP) did not improve pulmonary gas exchange in our patients, despite the significant increase in functional residual capacity produced. This suggests that CPAP did not cause recruitement of atelectatic areas or that this effect was offset by a parallel overdistension of gas exchange units.

Adult↗

Respiratory function and ribcage contribution to ventilation in body positions commonly used during anesthesia.

Lung function tests are normally performed in the upright position, whereas anesthesia is usually administered with the patient in the supine position, and occasionally in other postures. We therefore compared forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), and ribcage contribution to ventilation by respiratory inductive plethysmography in 13 conscious healthy male volunteers, sitting and in four horizontal positions used during anesthesia. Forced vital capacity and FEV1 were similar in all positions, except for a significant mean increase in FVC of 300 mL (SD 213) when sitting compared with when supine (P less than 0.001). The mean decrease in FRC was 806 mL (SD 293) between the sitting and supine positions (P less than 0.001). A significant increase in FRC occurred (252 mL, SD 329, P less than 0.01) when supine subjects raised their arms above their heads as required for computed tomography. Functional residual capacity in the prone and lateral positions was significantly larger than in the supine position (mean change 350 mL, P less than 0.001), but was still some 450 mL less than in the sitting position. Mean ribcage contribution was similar in all horizontal positions (32%-36%), whereas supine values were significantly different from those of the sitting position (mean 70%, SD 11, P less than 0.001). In conclusion, the various horizontal postures studied have no effect on FVC, FEV1, or ribcage contribution to ventilation. However, FRC in the prone, lateral, and arms-up positions is on average 250 mL larger than in the supine position, an observation that may affect gas exchange during anesthesia in these positions.

Adult↗

Effect of salbutamol on respiratory mechanics in bronchiolitis.

The effect of inhaled bronchodilators in bronchiolitis has been difficult to evaluate due to problems with techniques for assessing respiratory function in infants. Two new techniques were used to assess the response to inhaled salbutamol in 17 infants with bronchiolitis. With one technique, expiratory flow, volume, and airway occlusion pressure were measured and used to derive compliance (Crs) and conductance (Grs) of the respiratory system from a passive expiration induced by a brief end-inspiratory airway occlusion. With the other technique, the maximum flow at functional residual capacity (VmaxFRC) was measured from a partial maximum expiratory flow-volume curve generated by external chest compression. For the group, there was no change in compliance or conductance after salbutamol, but salbutamol caused a fall in maximum flow at functional residual capacity (p less than 0.01) and in the time constant of tidal expiration (p less than 0.01). The decrease in maximum flow at functional residual capacity with salbutamol is consistent with increased airway collapse on forced expiration. The decrease in tidal time constant suggests that the drug decreases expiratory braking. Presence of such braking activity may be an important strategy for maintaining lung volume. In summary, salbutamol failed to produce a beneficial effect on airways in bronchiolitis, but did produce changes in expiration which may be harmful in some infants.

Administration, Inhalation↗

Pulmonary function tests in preschool children with cystic fibrosis.

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90-130 cm; 16 homozygous Delta F508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rint(exp)) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rint(exp), expressed as absolute values and as Z-scores (1.05 +/- 0.36 versus 0.80 +/- 0.20 kPa.L(-1). second, p < 0.0001; and 1.31 +/- 1.72 versus 0.19 +/- 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 +/- 0.34 versus 1.63 +/- 0.43 kPa(-1). second, p < 0.0001). The effect of the bronchodilator salbutamol on Rint(exp) was not significantly different between children with CF and control children. Rint(exp) Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rint(exp) and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.

Airway Resistance↗

Correlation between standing height, sitting height, and arm span as an index of pulmonary function in 6-10-year-old children.

The present study evaluates the relationships of pulmonary volumes and flows and the anthropometric variables of standing height, sitting height, and arm span in 100 6-10-year-old children. To be included in the study, all children were required to be healthy and above the 3rd percentile of the curve of Tanner et al. (Arch Dis Child 1966;41:454-471; Arch Dis Child 1966;41:613-635) for height and weight. Standing height, sitting height, and arm span were measured according to standard protocol. The pulmonary function measurements were: tidal volume, minute respiratory volume, respiratory rate, expiratory reserve volume, inspiratory capacity, vital capacity, residual volume (RV), functional residual capacity, total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 sec of FVC (FEV(1)), forced expiratory flow measured between 25-75% of FVC, and FEV(1)/FVC and RV/TLC ratios. Simple linear regression best expressed the correlation between pulmonary function and the anthropometric variables. Significant correlations between anthropometric and pulmonary function measurements were observed, with FVC and FEV(1) showing the highest and RV the lowest r(2) values. There was a significant positive correlation between standing height and arm span according to linear regression and Bland-Altman comparison (Bland and Altman, Lancet 1968;8:307-310). Our results suggest that when an accurate determination of standing height cannot be obtained, arm span could be used interchangeably, using the same regression equation. However, for patients with limb deformities, regression equations of pulmonary function measurements in relation to sitting height may be a better choice for estimating pulmonary function.

Anthropometry↗

Inhaled bronchodilator treatment via the nebuhaler in young asthmatic patients.

Changes in functional residual capacity and peak flow rate were measured to assess bronchodilator response to terbutaline inhaled via a nebuhaler. In 10 children with asthma, aged 5-7 years, five breaths sufficient to operate the nebuhaler valve resulted in clinically important improvement in both the functional residual capacity and the peak flow rate. In 18 of 22 children, aged 2-5 years, who were too young to have their peak flow rate measured reliably, terbutaline administered via this modified nebuhaler technique was also associated with a clinically important change in functional residual capacity. The results suggest that effective bronchodilation using a nebuhaler can be achieved even in very young children.

Aerosols↗

Use of external expiratory resistance in intubated neonates to increase lung volume.

Ten intubated neonates (weights 0.90 to 2.58 kg) recovering from respiratory disease had lung mechanics, respiratory patterns, and functional residual capacity measured at 0 cmH2O continuous positive airways pressure and then after application of serially increasing levels of external expiratory resistance. At an external expiratory resistance greater than 40 cmH2O/1 per second, there was a significant increase in mean functional residual capacity compared with control levels. Immediately after the application of external expiratory resistance, there was a significant decrease in flow which returned to control values after a few breaths. Tidal volume and respiratory rate decreased for a few breaths after the application of the external expiratory resistance, but returned to control values after several seconds. Study age, gestational age, or study weight had no appreciable effect on the relationship between functional residual capacity and external expiratory resistance. Application of external expiratory resistance may be useful for stabilising lung volume in neonates recovering from respiratory disease.

Humans↗

Effect of removal of bullae on airway conductance and conductance volume ratios.

Airway conductance is known to increase with an increase in the lung volume at which it is measured, owing to a change in transpulmonary pressure and lung tissue tension. We investigated the effect of surgical resection of lung tissue on functional residual capacity and airway conductance in patients with localized lung disease (i.e., carcinoma or tuberculosis) and in patients with lung cysts or bullous emphysema. In four out of five of the patients who had resection of one or more lobes of the lung to remove localized disease there was a reduction both in the airway conductance and in the functional residual capacity with relatively little change in the conductance volume ratio. By contrast, in all patients who underwent bullectomy, there was a decrease in functional residual capacity but an increase in airway conductance, and an increase in the conductance/volume ratio. This change was sustained in patients who had had localized cysts removed. However, the measurements gradually reverted toward preoperative values in those patients who had generalized emphysema. The increase in airway conductance after resection of blebs and bullae presumably was due to improved lung elastic pressure causing the airways to increase in diameter and conductance. In addition, some patients may have experienced relief of compression of neighboring airways.

Adult↗

Lung function and bronchial challenges in infants: repeatability of histamine and comparison with methacholine challenges.

UNLABELLED: Limited information exists regarding the repeatability of lung function and bronchial challenge tests using the rapid thoracic compression technique (RTC) in infants. AIMS: To determine the repeatability of lung function and histamine challenge test results using the RTC technique and to compare the results obtained for bronchial challenges using histamine (H) and methacholine (M). METHODS: Twelve infants [7 healthy, 5 with cystic fibrosis (CF) had pairs of H challenges 1 week apart. Eleven infants (7 healthy, 4 CF) had one H and one M challenge a week apart. The provocative concentration of H or M to cause a 40% fall in maximum flow at functional residual capacity (PC40) was determined using the RTC technique. Twenty-three comparisons were possible between maximal expiratory flow at functional residual capacity (VmaxFRC) measurements made 1 week apart. RESULTS: The mean difference between pairs of VmaxFRC measurements was 6.4% of baseline, and the coefficient of repeatability was 31.1% of baseline. The mean difference between PC40(H) measurements was 0.163 doubling concentrations, with a coefficient of repeatability of 1.66 doubling concentrations. The mean difference between PC40(H) and PC40(M) was 0.75 doubling concentrations, with 95% of PC40(H) between -0.18 to 1.69 doubling concentrations of the PC40(M). CONCLUSIONS: Although the repeatability of VmaxFRC using the RTC technique is less than for voluntary forced expiratory flow parameters in older children, similar results were obtained for infants as observed in older subjects for repeatability of H challenges and agreement between measures of bronchial responsiveness using H or M.

Bronchial Provocation Tests↗

Transmission of pressure across the chest wall during the rapid thoracic compression technique in infants.

During the rapid thoracic compression maneuver in infants, the transmission of pressure from compression jacket to pleural space and airway is less at functional residual capacity than at end inspiration. To examine whether reduced pressure transmission at functional residual capacity vs. higher lung volumes is explained by passive characteristics of the chest wall rather than by respiratory muscle activity, we assessed the pressure transmitted across the chest wall in nine anesthetized infants and young children after muscle relaxation. We measured esophageal and airway occlusion pressure during chest compressions at different lung volumes determined by varying distending pressure. In six subjects studied under static conditions, there was an approximately linear relationship between distending pressure and the proportion of pressure transmitted to the airway and esophagus from the compression jacket. The mean r2 value (95% confidence interval) was 0.80 (0.09) for pressure transmission to the airway and 0.85 (0.04) for pressure transmission to the esophagus. This relationship between lung volume and pressure transmission observed under static conditions was also demonstrated dynamically. Thus the reduced transmission of pressure from compression jacket to airway and pleural space at low lung volumes occurs independently of respiratory muscle activity.

Anesthesia↗

The Hayek oscillator. Nomograms for tidal volume and minute ventilation using external high frequency oscillation.

The Hayek Oscillator is a recent development in external high frequency ventilation and is a useful mode of ventilatory support during anaesthesia, in chronic respiratory failure and weaning in intensive care. The Hayek Oscillator is new and its application is growing, as are the number of patients who have benefited from its use. However, there are no clear guidelines on how best to adjust the oscillator to achieve optimum ventilation. A simple method of predicting changes in tidal volume and minute ventilation following adjustment would make the oscillator more useful. We present nomograms for tidal volume, minute ventilation and effective alveolar ventilation when the three variables, oscillator frequency, mean chamber pressure and peak-to-trough pressure span were adjusted. The frequency-tidal volume relationship was unaffected by a mean chamber pressure of 0, -5, -10 cmH2O, but altered with changes in peak-to-trough pressure span. We have also determined the effect of increasing negative extrathoracic pressure on functional residual capacity. The relationship between tidal volume and frequency was non-linear and related to the peak-to-trough pressure span. Mean functional residual capacity significantly increased from 2.25 l (SEM 0.10) without the cuirass at rest to 2.61 l (SEM 0.14) at -10 cmH2O (p < 0.05; n = 5) and 2.47 (SEM 0.12) at -20 cmH2O of mean chamber pressure. Vital capacity was unchanged by increasing extrathoracic pressure as was total lung capacity.

Adult↗

Perflubron dosing affects ventilator-induced lung injury in rats with previous lung injury.

OBJECTIVES: Randomized controlled trials of partial liquid ventilation in acute respiratory distress syndrome have been negative. Reasons for this failure may reside in the use of too large doses of perfluorocarbon. The objective was to evaluate whether various doses of perflubron affect ventilation-induced injury in edematous lungs in different ways. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of a university. SUBJECTS: Male Wistar rats weighing 300+/-20 g. INTERVENTIONS: Separate groups of rats were injected with alpha-naphtylthiourea to produce mild permeability pulmonary edema. They were then given 0, 7 (low), 13 (moderate), or 20 mL/kg (near functional residual capacity) perflubron doses and mechanically ventilated with a large (33 mL/kg) tidal volume for 15 mins. MEASUREMENTS AND MAIN RESULTS: 125I-albumin distribution space was used to assess lung microvascular permeability. Quasi-static respiratory system pressure-volume curves were analyzed. Administration of low and moderate perflubron doses significantly improved respiratory mechanics and reduced the ventilator-induced permeability alterations to the level observed in rats that were not ventilated. By contrast, a perflubron dose that was near functional residual capacity increased end-inspiratory plateau pressure and aggravated the permeability alterations due to high tidal volume ventilation. CONCLUSIONS: Near functional residual capacity but not low perflubron dose worsens ventilation-induced lung injury of preinjured lungs. This may provide some explanation for the negative results of the recent clinical trials, and it stresses the importance of the amount of perflubron used for partial liquid ventilation.

Animals↗

A reevaluation of the validity of unrestrained plethysmography in mice.

Presently, unrestrained plethysmography is widely used to assess bronchial responsiveness in mice. An empirical quantity known as enhanced pause is derived from the plethysmographic box pressure [P(b)(t), where t is time] and assumed to be an index of bronchoconstriction. We show that P(b)(t) is determined largely by gas conditioning when normal mice breathe spontaneously inside a closed chamber in which the air is at ambient conditions. When the air in the chamber is heated and humidified to body conditions, the changes in P(b)(t) are reduced by about two-thirds. The remaining changes are thus due to gas compression and expansion within the lung and are amplified when the animals breathe through increased resistances. We show that the time integral of P(b)(t) over inspiration is accurately predicted by a term containing airway resistance, functional residual capacity, and tidal volume. We conclude that unrestrained plethysmography can be used to accurately characterize changes in airway resistance only if functional residual capacity and tidal volume are measured independently and the chamber gas is preconditioned to body temperature and humidity.

Airway Resistance↗

The effect of H2-blocking agents on systemic anaphylaxis in guinea pigs.

Theoretically, histamine H2 antagonists could aggravate allergic bronchoconstriction (1) by increasing mediator release, and (2) by blocking histamine-induced bronchodilatation. We measured dynamic compliance, subdivisions of lung volume, and mortality in immunized guinea pigs after parenteral administration of antigen, with and without pretreatment with the H2-blocking agents cimetidine and metiamide. Administration of antigen caused significant mortality as well as decreases in dynamic compliance, total lung capacity, and vital capacity and increases in functional residual capacity. The prior administration of cimetidine or metiamide did not protect against or enhance these effects of antigen challenge.

Anaphylaxis↗

Pulmonary function at follow-up of very preterm infants from the United Kingdom oscillation study.

Prematurely born infants supported by conventional ventilation (CV) frequently have abnormal pulmonary function when assessed in childhood. The aim of this study was to test the hypothesis that infants who were randomly assigned to high-frequency oscillatory ventilation would have superior pulmonary function at follow-up compared with those who received CV (UK Oscillation Study). Infants from 12 trial centers were recruited for pulmonary function testing at a single center. Seventy-six infants, of a mean gestational age 26.4 weeks, were studied after sedation with chloral hydrate at between 11 and 14 months of age, corrected for prematurity. Infants assigned to CV had similar pulmonary function compared with those assigned to high-frequency oscillatory ventilation, with mean (SD) results as follows: functional residual capacity measured by whole-body plethysmography, 26.9 (6.3) versus 26.5 (6.4) ml/kg; functional residual capacity measured by helium dilution, 24.1 (5.4) versus 23.5 (5.7) ml/kg; inspiratory airway resistance, 3.3 (1.3) versus 3.4 (1.6) kPa. second. L; expiratory airway resistance, 4.4 (2.8) versus 4.1 (2.5) kPa. second. L; respiratory rate, 31.2 (6.0) versus 33.9 (8.0) breaths/minute. We conclude that early use of high-frequency oscillatory ventilation in very preterm infants appears to offer no advantage over CV in terms of pulmonary function at follow-up.

Bronchopulmonary Dysplasia↗