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PubMed1974

Circulatory effects of deep inspirations, blocked expirations and positive pressure inflations at equal transpulmonary pressures in conscious dogs.

1. Circulatory effects of deep inspirations, blocked expirations and constant endotracheal positive pressure inflations were studied in six conscious dogs under comparable geometries of the pulmonary vascular bed, i.e. at equal transpulmonary pressures (around 10.2 cm H(2)O) and similar lung volumes.2. In order to characterize these effects, we measured beat-by-beat left and right ventricular ejections, pulmonary arterial, left atrial and aortic mean transmural pressures, and concomitant intrathoracic and tracheal pressures. Changes in pulmonary-left heart blood volume were also computed.3. During inspiration when intrathoracic pressure became more negative, there was a slight increase in right ventricular output (+15%; P < 0.1) and always a net decrease in left ventricular output (-25%; P < 0.01) despite a significant increase in mean transmural left atrial pressure (+3 cm H(2)O, i.e. +40%; P < 0.005). It is concluded that the more negative intrathoracic pressure increases the left ventricular outflow impedance and that an inspiratory increase in pulmonary vascular capacity cannot explain the observed reduction in left ventricular output since this reduction occurs together with an increase in left ventricular filling pressure.4. During blocked expiration when intrathoracic pressure was positive, decreases in right ventricular output (-17%; P < 0.05) and in pulmonary-left heart blood volume (-12 ml.; P < 0.05) were observed while right ventricular outflow impedance increased. After an initial augmentation in left ventricular output (despite a concomitant progressive decrease in mean transmural left atrial pressure), left ventricular output also decreased (-17%; P < 0.05). Such circulatory changes were similar but less marked than those observed under constant positive pressure inflations. These observations suggest that the decrease in venous return (and consequently in right ventricular output) following the increase in intrathoracic pressure is the leading factor which overshadows the augmentation in left ventricular output associated with the simultaneous decrease in left ventricular outflow impedance.5. Similar experiments performed on two additional dogs in acute conditions showed the same circulatory effects before and after pharmacological blockade. These observations therefore confirm that mechanical factors play a leading part during these respiratory manoeuvres.

Animals↗
PubMed1978

Lung volumes in man immersed to the neck: dilution and plethysmographic techniques.

Previous studies of lung volumes during immersion have utilized dilution techniques for residual volume. We have compared lung volumes obtained by the use of a dual inert gas dilution technique with those determined by the Boyle's law technique in a plethysmograph designed to allow measurements in air and submersed to the neck in water. Both techniques gave similar results dry, but during immersion the dilution residual volume (RV) was 0.200 liter (16%) lower than the plethysmographic value (P greater than 0.001), which suggests that there is a significant amount of gas trapping during immersion due to breathing at low lung volumes and the central shift of blood. The unchanged RV due to hydrostatic force on the chest wall is balanced by the tendency to increase RV due to vascular congestion, which increases closing volume and stiffens the lung to compression.

Adult↗
PubMed1990

EMG study of respiratory muscles in humans immersed at different water temperatures.

The electromyograms of the rectus abdominis (EMGra) and of the diaphragm (EMGdi) have been recorded on human subjects immersed at two bath temperatures (TW), 25 and 40 degrees C. The recordings were obtained during a calibrated isometric contraction sustained for 20 s against a closed stopcock at functional residual capacity (FRC) level for EMGra (expiratory effort) and at pulmonary volume greater than 90% vital capacity for EMGdi and EMGra (inspiratory effort). After eliminating the electrocardiographic artifact, the EMG signal was processed to obtain its root-mean-square (rms) value and three parameters of its frequency spectrum, total energy (Etot), centroid frequency (fc), and high-to-low ratio (H/L). The results show that EMGdi is not modified by TW. On the other hand rms and Etot of EMGra are always increased at TW = 25 degrees C compared with TW = 40 degrees C, whereas fc and H/L decrease with temperature during the expiratory effort at FRC level but do not vary during inspiratory effort at high pulmonary volume. These results, compared with those previously published for cooled limb muscles, show that TW can elicit EMG alterations on the superficial respiratory muscles through two mechanisms, an intrinsic mechanism due to the local variation in muscle temperature and an extrinsic mechanism acting upon the control system of the muscle contraction. Linked alterations of the muscular mechanical activity probably account for the observed effects of TW on the statics and the dynamics of the pulmonary volumes.

Abdominal Muscles↗
PubMed1999

Ratio of active to passive muscle shortening in the canine diaphragm.

Active and passive shortening of muscle bundles in the canine diaphragm were measured with the objective of testing a consequence of the minimal-work hypothesis: namely, that the ratio of active to passive shortening is the same for all active muscles. Lengths of six muscle bundles in the costal diaphragm and two muscle bundles in the crural diaphragm of each of four bred-for-research beagle dogs were measured by the radiopaque marker technique during the following maneuvers: a passive deflation maneuver from total lung capacity to functional residual capacity, quiet breathing, and forceful inspiratory efforts against an occluded airway at different lung volumes. Shortening per liter increase in lung volume was, on average, 70% greater during quiet breathing than during passive inflation in the prone posture and 40% greater in the supine posture. For the prone posture, the ratio of active to passive shortening was larger in the ventral and midcostal diaphragm than at the dorsal end of the costal diaphragm. For both postures, active shortening during quiet breathing was poorly correlated with passive shortening. However, shortening during forceful inspiratory efforts was highly correlated with passive shortening. The average ratios of active to passive shortening were 1.23 +/- 0.02 and 1.32 +/- 0.03 for the prone and supine postures, respectively. These data, taken together with the data reported in the companion paper (T. A. Wilson, M. Angelillo, A. Legrand, and A. De Troyer, J. Appl. Physiol. 87: 554-560, 1999), support the hypothesis that, during forceful inspiratory efforts, the inspiratory muscles drive the chest wall along the minimal-work trajectory.

Airway Obstruction↗
PubMed1999

Medullary metastasis causing impairment of respiratory pressure output with intact respiratory rhythm.

We present an unusual case of weaning failure. A 67-yr-old man presented with confusion, hyponatremia, and hypercapnic respiratory failure that necessitated mechanical ventilation. CXR revealed a right hilar mass (non-small-cell carcinoma on biopsy). Level of consciousness improved with treatment of his hyponatremia. However, attempts at weaning were complicated by hypercapnia with no overt distress. Resistance and elastance were only slightly abnormal, excluding mechanics as a cause of respiratory failure. Maximal inspiratory pressure (MIP) and vital capacity (VC) were reduced at -15 cm H2O and 0.97 L, respectively. Limb muscle strength was well preserved, suggesting isolated respiratory muscle weakness. During a weaning trial respiratory rate increased from 7 to 40 breaths/min as PCO2 increased from 56 to 89 mm Hg, confirming an intact respiratory pacemaker and good response to CO2. However, spontaneous Pdi was only 1 to 2 cm H2O (< 20% of Pdimax) despite profound hypercapnia. The fact that the patient did not utilize a greater fraction of his pressure-generating capacity suggested preferential impairment of the automatic respiratory centers. MRI showed a large central metastatic lesion in the rostral medulla with only a thin rim of uninvolved tissue. This case illustrates the utility of relating the magnitude of spontaneous efforts to maximal voluntary efforts as a means of localizing the site of involvement in cases of respiratory muscle weakness. It also demonstrates that a large medullary mass lesion may selectively impair brainstem modulation of respiratory pressure output while sparing other medullary functions, and in particular the pacemaking function of the respiratory centers.

Aged↗
PubMed1982

The effect of aminophylline on inspiratory muscle contractility.

The effects of aminophylline on diaphragmatic muscle contractility were studied in 8 dogs. The relationships of the electromyographic signal from the diaphragm and the pressures developed by this muscle were compared before and after the administration of aminophylline in doses of 6, 20, 40, 80, and 120 mg/kg. Measurements were made during occluded inspiratory efforts at functional residual capacity. In a second group of 4 dogs the relationships were compared while the rib cage expansion was limited by a plaster cast. Finally, in a third group of 4 dogs after the diaphragm had been paralyzed by phrenicotomy, the relationship of pleural pressure to the electromyographic signal of the intercostal muscles was assessed before and after administration of aminophylline. In all cases, aminophylline progressively shifted the electromyographic pressure relationship up and to the left. This effect became significant (p less than 0.01) at a dose of 20 mg/kg, reached a peak at 80 mg/kg, and then declined at a dose of 120 mg/kg. The amount producing blood concentrations closest to the human therapeutic blood concentration was 20 mg/kg. The peak increase in pressure compared with the control values were 58% in the first group, 27% in the second group, and 52% in the third group (p less than 0.01). We conclude that aminophylline increases respiratory muscle contractility in a dose-related manner. This may have important therapeutic and pathophysiologic implications.

Aminophylline↗
PubMed2003

Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness.

Adults and children with neuromuscular disease exhibit weak cough and are susceptible to recurrent chest infections, a major cause of morbidity and mortality. Mechanical insufflation/exsufflation may improve cough efficacy by increasing peak cough flow. It was hypothesised that mechanical insufflation/exsufflation would produce a greater increase in peak cough flow than other modes of cough augmentation. The acceptability of these interventions was also compared. Twenty-two patients aged 10-56 yrs (median 21 yrs) with neuromuscular disease and 19 age-matched controls were studied. Spirometry was performed and respiratory muscle strength measured. Peak cough flow was recorded during maximal unassisted coughs, followed in random order by coughs assisted by physiotherapy, noninvasive ventilation, insufflation and exsufflation, and exsufflation alone. Subjects rated strength of cough, distress and comfort on a visual analogue scale. In the neuromuscular disease group, mean +/- SD forced expiratory volume in one second was 0.8 +/- 0.6 L x s(-1), forced vital capacity 0.9 +/- 0.8 L, maximum inspiratory pressure 25 +/- 16 cmH2O, maximum expiratory pressure 26 +/- 22 cmH2O and unassisted peak cough flow 169 +/- 90 L x min(-1). The greatest increase in peak cough flow was observed with mechanical insufflation/exsufflation at 235 +/- 111 L x min(-1) (p<0.01). All techniques showed similar patient acceptability. Mechanical insufflation/exsufflation produces a greater increase in peak cough flow than other standard cough augmentation techniques in adults and children with neuromuscular disease.

Adolescent↗
PubMed2004

Respiratory failure as a first presentation of myasthenia gravis.

BACKGROUND: Although respiratory failure commonly occurs during the course of myasthenia gravis (MG), it is rarely described at presentation in patients with previously unrecognized MG. MATERIAL/METHODS: We determined the prevalence and clinical characteristics of patients with respiratory failure associated with undiagnosed MG by review of the medical records of all patients who were diagnosed with MG related respiratory failure at four University hospitals. Respiratory failure was defined on the basis of a forced vital capacity < or =1 liter, negative inspiratory force < or =20 cm H2O, or requirement of mechanical ventilation. RESULTS: Out of 51 MG patients with respiratory failure, 7(14%) patients had no previous diagnosis of MG. Another patient was identified after the review. The mean age of these 8 patients was 56 years (range 23-76 years); six were women. Five had previous episodes of unexplained respiratory failure. On initial evaluation, ocular or bulbar signs were present in 7 patients. The diagnosis of MG was made by edrophonium test (n=3), edrophonium test with positive acetylcholine antibody levels or repetitive nerve stimulation (n=2), repetitive nerve stimulation with positive acetylcholine antibody levels (n=2), and positive acetylcholine antibody levels alone (n=1). Seven patients required mechanical ventilation. Plasma exchange (n=7) or intravenous immunoglobulins (n=1) resulted in successful extubation or resolution of symptoms in all patients. CONCLUSIONS: Respiratory failure can occur at presentation in MG. A high index of suspicion should be maintained in patients with previous history of unexplained respiratory failures.

Adult↗
PubMed1991

Prospective evaluation of epidural and intravenous administration of fentanyl for pain control and restoration of ventilatory function following multiple rib fractures.

To evaluate the efficacy of opiate administration regimens, 32 patients with multiple rib fractures were prospectively randomized to receive either continuous epidural (ED) or continuous intravenous (IV) infusions of fentanyl. Dosage was titrated to individual subjective pain relief. Ventilatory function tests (VFTs), arterial blood gases (ABGs), and visual analog scores were obtained before and after the institution of analgesia. Post-analgesia values were compared with pre-analgesia values using a two-tailed paired t-test looking for significant changes produced by the analgesic method. Both methods significantly improved analog pain scores. The ED method produced improvement in both maximum inspiratory pressure (MIP) and vital capacity (VC), whereas IV analgesia only produced improvement in VC. Intravenous fentanyl produced increases in PaCO2 and decreases in PaO2, whereas no significant changes in ABGs were observed with ED fentanyl administration. Side effects were similar between the groups, with pruritus being more pronounced with ED fentanyl administration. The data demonstrate that the continuous ED fentanyl method offers excellent relief of pain and improvement in ventilatory function and has distinct advantages over IV fentanyl administration with respect to changes in ABGs and MIP. The continuous infusion of epidural opiates should be the preferred analgesic method for patients at high risk of developing pulmonary complications following multiple rib fractures.

Adult↗
PubMed1993

[Pulsed hypoxia in the treatment of obstructive lung diseases].

A new approach to the treatment of chronic nonspecific pulmonary diseases is proposed: helium-oxygen therapy combined with repeated interrupted hypoxic stimuli. Helium inclusion into hypoxic gas mixture leads to reduced air density. Gas mixture containing 10-15% of oxygen is more effective at the level of alveolocapillary membrane. When conducted in normal atmospheric pressure, the method involved no complications and produced positive responses in coronary heart disease, hypertension, alimentary diseases. The mixture of helium with oxygen (85-90% of helium, 10-15% oxygen) in combination with impulse normobaric hypoxia has been tried in 25 chronics with obstructive bronchitis and bronchial asthma. The results were indicative of the treatment efficacy: bronchial permeability improved in 67% of the cases, forced vital capacity of the lungs increased, inspiratory reserve volume grew, dyspnea and cough diminished, sputum discharge improved, general tonicity and performance status changed positively. Six-month follow-up evidenced positive shifts too.

Adult↗
PubMed1998

Obstructive sleep apneas in relation to severity of cervical spinal cord injury.

Thirty-three subjects (28 men, five women) with complete or incomplete cervical cord injury representing a wide range of neurological impairment were investigated with regard to the prevalence of Obstructive Sleep Apnea (OSA). The relation between OSA and neurological function, respiratory capacity, body mass index and symptoms associated with OSA were studied. Overnight sleep recordings employed combined oximetry and respiratory movement monitoring. Pulmonary function tests included static and dynamic spirometry, maximal static inspiratory and expiratory pressures at the mouth. The subjects answered a questionnaire concerning sleep quality and tiredness. The prevalence of OSA was 15% (5/33) in this nonobese cervical cord injury study population. Nine percent of the subjects (3/33) fulfilled the criteria for obstructive sleep apnea syndrome, but daytime sleepiness or fatigue were also common in subjects without OSA. There was an inverse correlation between oxygen desaturation index and American Spinal Injury Association (ASIA) motor score in the subjects with complete injury, while there was no such correlation in the whole study group. There were significant correlations between maximal inspiratory and expiratory pressures and vital capacity and between ASIA motor score and vital capacity.

Adult↗
PubMed2006

[Domiciliary respiratory muscle training in myotonic dystrophy].

A 42-year-old man diagnosed with myotonic dystrophy experienced loss of respiratory muscle strength over a period of 6 months. We report the application of a domiciliary training program targeting both inspiratory and expiratory muscles. Maximal inspiratory and expiratory pressures, forced vital capacity, and forced midexpiratory flow rate were measured 6 months before start of training, just before commencement of the program, and immediately after 12 weeks of training. Adherence to the program was satisfactory. Inspiratory muscle training was efficacious in increasing respiratory muscle strength. Expiratory muscle training, which made use of the Threshold PEP bronchial hygiene device incorporating an adapted flutter valve, was not efficacious in increasing maximal expiratory pressure or halting its loss. However, decreased obstruction of medium-caliber airways was observed with use of the device.

Adult↗
PubMed1983

Functional diagnosis in surgery of the large airways.

The main indications for surgery of the airways are (1) non-tumorous airway stenosis and (2) tumors of the large airways with and without relevant stenoses. The aim of the following study was to find out which degree of stenosis is an absolute indication for resection and to what extent the functional disturbances are reversible following surgery. We investigated various groups of patients (stenosis of the trachea, lobectomy with sleeve resection, extended pneumectomy with resection of the distal trachea, pneumectomy with resection of the bifurcation, resection of the main bronchus and lobectomy, rupture of the main bronchus) from 1978 to 1982, before and up to 3 years after surgery. Body-plethysmography (one second forced expiratory volume = FEV1; one second forced inspiratory volume = FIV1; Residual volume = RV; total lung capacity = TLC; airway resistance = Raw; specific airway conductance = sGaw), flow volume relation measurements (maximal inspiratory flow = Vmax insp; maximal expiratory flow = Vmax exp; and flow at various lung volumes), blood gas analysis and an endoscopic estimation of the tracheal diameter were performed. Tracheal resection with end-to-end anastomosis in patients with non-tumerous tracheal stenosis improved the tracheal diameter from 6.0 to 11.7 mm, the sGaw from 0.04 to 0.08 (cmH2O s)-1 and the severity of dyspnea significantly. There was no measurable change in airway caliber following administration of beta 2-adrenergics. The most sensitive parameters for describing the tracheal stenosis are the resistance and flow volume values. A tracheal diameter smaller than 6.5 mm corresponding to a sGaw smaller than 0.03 (cmH2O s)-1 procedured severe dyspnea, which is incompatibly with normal life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1996

Contractility of the ventilatory pump muscles.

The ventilatory muscles are striated skeletal muscles, and their in situ function is governed by the same relationships that determine the contractile force of muscles in vitro. The ventilatory muscles, however, are functionally distinct from limb skeletal muscles in several aspects, the most notable being that the ventilatory muscles are the only skeletal muscles upon which life depends. Among the muscles that participate in ventilation, the diaphragm is closest to its optimal resting length at functional residual capacity (FRC) and has the greatest capacity for shortening and volume displacement, making it the primary muscle of inspiration. All inspiratory muscles shorten when the lung is inflated above FRC, but interactions among the various inspiratory muscles make for a wider range of high force output than could be achieved by any one muscle group acting in isolation. The velocity of inspiratory muscle shortening, especially diaphragmatic shortening, causes maximal dynamic inspiratory pressures to be substantially lower than maximal static pressures. This effect is especially pronounced during maximal voluntary ventilation, maximal exercise, and maximal inspiratory flow, volume maneuvers over the full vital capacity. During quiet breathing, the ventilatory muscles operate well below the limits of their neural activation and contractile performance. During intense activity, however, the diaphragmatic excursion approaches its limits over the entire vital capacity, and respiratory pressures may near their dynamic maximum. Because the system may operate near its available capacities during increased ventilatory demands, multiple strategies are available to compensate for deficits. For example, if the diaphragm is acutely shortened, it can still generate the required respiratory pressure if it receives more neural drive. Alternatively, other muscles can be recruited to take over for an impaired diaphragm. Thus, the whole system is highly versatile.

Animals↗
PubMed1997

Diaphragm thickness and inspiratory strength in patients with Duchenne muscular dystrophy.

BACKGROUND: There is little information on the morphometric characteristics of the diaphragm in patients with Duchenne muscular dystrophy. METHODS: The thickness of the diaphragm was measured at the zone of apposition using B mode ultrasonography in 10 boys with Duchenne muscular dystrophy of mean (SD) age 10.3 (1.3) years and 12 normal controls of mean (SD) age 11.3 (2.0) years during relaxation (DiTrelax) and during maximum effort inspiratory manoeuvres (DiTPimax) at functional residual capacity. RESULTS: DiTrelax was greater in the patients with Duchenne muscular dystrophy (1.74 (0.21) mm) than in controls (1.48 (0.20) mm), mean difference (95% CI) 0.26 (0.08 to 0.44), despite considerable impairment of maximum effort inspiratory mouth pressure (Pimax) (patients with Duchenne muscular dystrophy -37 (8) cm H2O, controls -80 (33) cm H2O), mean difference (95% CI) 43 (65 to 20). During a Pimax manoeuvre, compared with measurements taken during relaxation, the diaphragm thickened 1.6 times in patients with Duchenne muscular dystrophy and 2.3 times in controls (DiTPimax 2.62 (0.7) mm and 3.5 (0.85) mm, respectively), mean difference (95% CI) -0.88 (-1.58 to -0.18). CONCLUSIONS: Resting diaphragm thickness is increased in young patients with Duchenne muscular dystrophy with impaired respiratory muscle force. This finding could be analogous to the pseudo-hypertrophy that is observed in some limb muscle groups.

Child↗
PubMed1998

Monitoring respiratory muscles.

The respiratory system consists of two main parts, the lung and the ventilatory pump. The latter consists of the bony structure of the thorax, the central respiratory controllers, the inspiratory and expiratory muscles, and the nerves innervating these muscles. Respiratory muscle fatigue occurs when respiratory muscle endurance is exceeded. Muscle fatigue is defined as a condition in which there is a reduction in the capacity for developing force and/or velocity of a muscle, resulting from muscle activity, and which is reversible by rest. The respiratory muscles are somewhat difficult to assess and the techniques employed are still relatively primitive. The most important methods of respiratory muscles function assessment are: 1) the vital capacity manoeuvre, which depends on maximum inspiratory and expiratory effort by the muscles and may be a useful indicator of respiratory muscle function; 2) radiological screening has been proposed for the detection of diaphragm paralysis. This may be helpful if the paralysis is unilateral, but bilateral paralysis is difficult to detect; and 3) respiratory muscles strength may be assessed with either voluntary or nonvoluntary manoeuvres. The function of the inspiratory muscles is assessed with 3 voluntary dependent manoeuvres. They are the so called Müller manoeuvre (or maximal inspiratory pressure), the sniff test and the combined test. All these three manoeuvres generate a pressure that is a reflection of complex interactions between several muscle groups since the efforts produce different mechanisms of activity of inspiratory and expiratory muscles. Two techniques are presently employed to assess diaphragm function, not being dependent on the patient's motivation: electrical phrenic nerve stimulation and cervical magnetic stimulation. Since it is less painful, magnetic cervical stimulation overcomes some of the difficulties encountered during electrical stimulation. With these two techniques recordings of diaphragmatic force are possible, and at the same time useful information about the conduction time of both phrenic nerves can be obtained.

Diaphragm↗
PubMed2006

High-altitude exposure reduces inspiratory muscle strength.

It was the aim of the study to assess the maximal pressure generated by the inspiratory muscles (MIP) during exposure to different levels of altitude (i.e., hypobaric hypoxia). Eight lowlanders (2 females and 6 males), aged 27 - 46 years, participated in the study. After being evaluated at sea level, the subjects spent seven days at altitudes of more than 3000 metres. On the first day, they rode in a cable car from 1200 to 3200 metres and performed the first test after 45 - 60 minutes rest; they then walked for two hours to a mountain refuge at 3600 metres, where they spent three nights (days 2 - 3); on day 4, they walked for four hours over a glacier to reach Capanna Regina Margherita (4559 m), where they spent days 5 - 7. MIP, flow-volume curve and SpO (2) % were measured at each altitude, and acute mountain sickness (Lake Louise score) was recorded. Increasing altitude led to a significant decrease in resting SpO (2) % (from 98 % to 80 %) and MIP (from 134 to 111 cmH (2)O) (baseline to day 4: p < 0.05); there was an improvement in SpO (2) % and a slight increase in MIP during the subsequent days at the same altitude. Expiratory (but not inspiratory) flows increased, and forced vital capacity and FEF (75) decreased at higher altitudes. We conclude that exposure to high altitude hypoxia reduces the strength of the respiratory muscles, as demonstrated by the reduction in MIP and the lack of an increase in peak inspiratory flows. This reduction is more marked during the first days of exposure to the same altitude, and tends to recover during the acclimatisation process.

Adult↗
PubMed1991

Response to corticosteroids in chronic airflow obstruction: relationship to emphysema and airways collapse.

We have studied the relationship between emphysema and airways collapse, and response to corticosteroids in patients with chronic airflow obstruction. One hundred and seven patients completed a placebo-controlled trial comparing 2 wks treatment with oral prednisolone 40 mg.day-1 to inhaled beclomethasone dipropionate 500 micrograms t.d.s. Response to corticosteroids was defined on the basis of changes in forced expiratory volume in one second (FEV1), and/or forced vital capacity (FVC), and/or mean peak expiratory flow (PEF) after treatment. Patients were categorized as those with physiologically defined emphysema (carbon monoxide transfer coefficient (KCO) less than 70% predicted and total lung capacity greater than 120% predicted), and those with pressure dependent airways collapse on the flow-volume loop (ratio of inspiratory to expiratory flow at 50% vital capacity [I:E50] greater than 10). The response to placebo showed a significant order effect, probably due to a carry-over effect of active treatment of at least 3 wks. Hence, the efficacy of active treatment over placebo in the subgroups defined was assessed by analysis of data generated from the first treatment phase of the trial. The presence or absence of physiologically defined emphysema did not affect the response to oral prednisolone. Inhaled beclomethasone dipropionate, however, was less effective in the emphysema group. Pressure dependent airways collapse did not affect the response to either prednisolone or beclomethasone. However, when data from all three treatment phases were analysed there was no significant difference in the response to either drug in any of the subgroups defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗