Undetected Respiratory Depression in People with Opioid Use Disorder.

BACKGROUND: Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. METHODS: There were four groups of participants: 1) OUD plus COPD ('OUD-COPD', n = 13); 2) OUD without COPD ('OUD', n = 7); 3) opioid-naïve COPD patients ('COPD'n = 13); 4) healthy controls ('HC'n = 7). Physiological indices, including pulse oximetry (SpO2%), end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and second intercostal space parasternal muscle electromyography (EMGpara), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO2%< 90% for > 10 s, ETCO2 per breath > 6.6 kPa, TcCO2 overall mean > 6 kPa, respiratory pauses > 10 s RESULTS: At least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher's exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). CONCLUSIONS: Undetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-naïve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.

Diaphragm electromyogram in infants with abdominal wall defects and congenital diaphragmatic hernia.

Measurement of the diaphragm electromyogram (EMGdi) elicited by phrenic nerve stimulation could be useful to assess neonates suffering from respiratory distress due to diaphragm dysfunction, as observed in infants with abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH). The study aims were to assess the feasibility of recording EMGdi using a multipair oesophageal electrode catheter and examine whether diaphragm muscle and/or phrenic nerve function was compromised in AWD or CDH infants. Diaphragm compound muscle action potentials elicited by magnetic phrenic nerve stimulation were recorded from 18 infants with surgically repaired AWD (n = 13) or CDH (n = 5), median (range) gestational age 36.5 (34-40) weeks. Diaphragm strength was assessed as twitch transdiaphragmatic pressure (TwP(di)). One AWD patient had prolonged phrenic nerve latency (PNL) bilaterally (left 9.31 ms, right 9.49 ms) and two CDH patients had prolonged PNL on the affected side (10.1 ms and 10.08 ms). There was no difference in left and right TwP(di) in either group. PNL correlated significantly with TwP(di) in CDH (r = 0.8; p = 0.009). Oesophageal EMG and magnetic stimulation of the phrenic nerves can be useful to assess phrenic nerve function in infants. Reduced phrenic nerve conduction accompanies the reduced diaphragm force production observed in infants with CDH.

Three-dimensional ultrasound fetal lung volumes and infant respiratory outcome: a prospective observational study.

OBJECTIVE: To determine if fetal lung volumes (FLVs), determined by three-dimensional rotational ultrasound and virtual organ computer-aided analysis software (vocal), correlated with neonatal respiratory outcomes in surviving infants who had a high risk [fetuses with congenital diaphragmatic hernia (CDH)], lower risk [fetuses with anterior wall defects (AWDs)] and no risk (controls) of abnormal antenatal lung growth. DESIGN: Prospective observational study. SETTING: Tertiary fetal medicine and neonatal intensive care units. POPULATION: Sixty fetuses (25 with CDH, 25 with AWDs and ten controls). METHODS: FLVs were measured and expressed as the percentage of the observed compared with the expected for gestational age. MAIN OUTCOME MEASURES: Neonatal respiratory outcome was determined by the duration of supplemental oxygen, mechanical ventilation and dependencies, and assessment of lung volume using a gas dilution technique to measure functional residual capacity (FRC). RESULTS: The infants with CDH had lower FLV results than both the infants with AWDs (P=0.05) and the controls (P<0.05). The infants with CDH had longer durations of mechanical ventilation (P<0.001) and supplementary oxygen (P<0.001) dependence, compared with infants with AWDs. The infants with CDH had a lower median FRC than both the infants with AWDs (P<0.001) and the controls (P<0.001). FLV results correlated significantly with the durations of dependency on ventilation (r= -0.744, P<0.01) and oxygen (r= -0.788, P<0.001), and with FRC results (r=0.429, P=0.001). CONCLUSIONS: These results suggest that FLVs obtained using three-dimensional rotational ultrasound might be useful in predicting neonatal respiratory outcome in surviving infants who had varying risks of abnormal lung growth. Larger and more comprehensive studies are needed to clarify the role that lung volume measurements have in assessing lung function and growth.

COVID-19 infection in patients with intestinal failure: UK experience.

BACKGROUND: The direct effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with intestinal failure (IF) has not been described. METHODS: We conducted a nationwide study of UK IF centers to evaluate the infection rates, presentations, and outcomes in patients with types 2 and 3 IF. RESULTS: A total of 45 patients with IF contracted COVID-19 between March and August 2020; this included 26 of 2191 (1.2%) home parenteral nutrition (HPN)-dependent adults and 19 of 298 (6.4%) adults hospitalized with type 2 IF. The proportion of patients receiving nursing care for HPN administration was higher in those with community-acquired COVID-19 (66.7%) than the proportion in the entire HPN cohort (26.1%; P < .01). Two HPN-dependent and 1 hospitalized patient with type 2 IF died as a direct consequence of the virus (6.7% of 45 patients with types 2 or 3 infected). CONCLUSION: This is the first study to describe the outcomes of COVID-19 in a large cohort of patients requiring long-term PN. Methods to reduce hospital and community nosocomial spread would likely be beneficial.

Ultrasound measurement of rectus femoris cross-sectional area and the relationship with quadriceps strength in COPD.

BACKGROUND: Quadriceps weakness and loss of muscle mass predict mortality in chronic obstructive pulmonary disease (COPD). It was hypothesised that a reduced quadriceps cross-sectional area could be detected by ultrasound in patients with COPD compared with healthy subjects, and that measurements relate to strength and fat-free mass (FFM). METHODS: Rectus femoris muscle cross-sectional area (RF(CSA)) was measured by ultrasound and whole-body FFM estimated using electrical bioimpedance. Quadriceps strength was measured by maximum voluntary contraction and twitch tension (TwQ) following magnetic femoral nerve stimulation. RESULTS: 26 healthy volunteers of mean (SD) age 63 (9) years and 30 patients with COPD of mean (SD) age 67 (9) years and percentage predicted forced expiratory volume in 1 s (FEV(1)) 48.0 (20.8)% with a similar FFM (46.9 (9.3) kg vs 46.1 (7.3) kg, p = 0.193) participated in the study. Mean RF(CSA) was reduced in patients with COPD by 25% of the mean value in healthy subjects(-115 mm(2); 95% CI -177 to -54, p = 0.001) and was related to MRC dyspnoea scale score, independent of FFM or sex. Maximum voluntary contraction strength was linearly related to RF(CSA) in patients with COPD (r = 0.78, p<0.001). TwQ force per unit of RF(CSA) was similar in both healthy individuals and those with COPD (mean (SD) 17 (4) g/mm(2) vs 18 (3) g/mm(2), p = 0.657). Voluntary contraction strength per unit of RF(CSA) was dependent on central quadriceps activation and peripheral oxygen saturation in COPD. CONCLUSION: Ultrasound measurement of RF(CSA) is an effort-independent and radiation-free method of measuring quadriceps muscle cross-sectional area in patients with COPD that relates to strength.

Neural respiratory drive in healthy subjects and in COPD.

The aim of the present study was to use the diaphragm electromyogram (EMG(di)) to compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects and chronic obstructive pulmonary disease (COPD) patients, and to investigate the relationship between NRD and pulmonary function in COPD. EMG(di) was recorded at rest and normalised to peak EMG(di) recorded during maximum inspiratory manoeuvres (EMG(di) % max) in 100 healthy subjects and 30 patients with COPD, using a multipair oesophageal electrode. EMG(di) was normalised to the amplitude of the diaphragm compound muscle action potential (CMAP(di,MS)) in 64 healthy subjects. The mean+/-sd EMG(di) % max was 9.0+/-3.4% in healthy subjects and 27.9+/-9.9% in COPD patients, and correlated with percentage predicted forced expiratory volume in one second, vital capacity and inspiratory capacity in patients. EMG(di) % max was higher in healthy subjects aged 51-80 yrs than in those aged 18-50 yrs (11.4+/-3.4 versus 8.2+/-2.9%, respectively). Observations in the healthy group were similar when peak EMG(di) or CMAP(di,MS) were used to normalise EMG(di). Levels of neural respiratory drive were higher in chronic obstructive pulmonary disease patients than healthy subjects, and related to disease severity. Diaphragm compound muscle action potential could be used to normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not be performed, allowing translation of the technique to critically ill and ventilated patients.

What is the value of ultrasound soft tissue measurements in the prediction of abnormal fetal growth?

Abnormal fetal growth increases the complications of pregnancy not only for the baby but also for the mother. Growth abnormalities also have lifelong consequences. These babies are at increased risk of insulin resistance, diabetes and hypertension later in life. It is important to identify these babies antenatally to optimise their clinical care. Although used extensively antenatally to monitor fetal growth, ultrasound has its limitations. Despite the use of more than 50 different formulae to estimate fetal weight, their performance has been poor at the extremes of fetal weight. Over the past 20 years there has been emerging interest in studying fetal soft tissue measurements to improve detection of growth abnormalities. This review paper outlines the value of soft tissue measurements in identifying fetal growth abnormalities, in estimating fetal weight and in managing diabetes mellitus in pregnancy.

Sleep-disordered breathing in unilateral diaphragm paralysis or severe weakness.

Few data exist concerning sleep in patients with hemidiaphragm paralysis or weakness. Traditionally, such patients are considered to sustain normal ventilation in sleep. In the present study, diaphragm strength was measured in order to identify patients with unilateral paralysis or severe weakness. Patients underwent polysomnography with additional recordings of the transoesophageal electromyogram (EMG) of the diaphragm and surface EMG of extra-diaphragmatic respiratory muscles. These data were compared with 11 normal, healthy subjects matched for sex, age and body mass index (BMI). In total, 11 patients (six males, mean+/-sd age 56.5+/-10.0 yrs, BMI 28.7+/-2.8 kg x m(-2)) with hemidiaphragm paralysis or severe weakness (unilateral twitch transdiaphragmatic pressure 3.3+/-1.7 cmH(2)O (0.33+/-0.17 kPa) were studied. They had a mean+/-sd respiratory disturbance index of 8.1+/-10.1 events x h(-1) during non-rapid eye movement (NREM) sleep and 26.0+/-17.8 events x h(-1) during rapid eye movement (REM) sleep (control groups 0.4+/-0.4 and 0.7+/-0.9 events x h(-1), respectively). The diaphragm EMG, as a percentage of maximum, was double that of the control group in NREM sleep (15.3+/-5.3 versus 8.9+/-4.9% max, respectively) and increased in REM sleep (20.0+/-6.9% max), while normal subjects sustained the same level of activation (6.2+/-3.1% max). Patients with unilateral diaphragm dysfunction are at risk of developing sleep-disordered breathing during rapid eye movement sleep. The diaphragm electromyogram, reflecting neural respiratory drive, is doubled in patients compared with normal subjects, and increases further in rapid eye movement sleep.

Respiratory function of very prematurely born infants at follow up: influence of sex.

OBJECTIVE: To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up. DESIGN: Prospective follow up study. SETTING: Tertiary neonatal intensive care units PATIENTS: Seventy six infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom oscillation study. INTERVENTIONS: Lung function measurements at a corrected age of 1 year. MAIN OUTCOME MEASURES: Airways resistance (Raw) and functional residual capacity (FRC(pleth)) measured by whole body plethysmography, specific conductance (sGaw) calculated from Raw and FRC(pleth), and FRC measured by a helium gas dilution technique (FRC(He)). RESULTS: The 42 male infants differed significantly from the 34 female infants in having a lower birth weight for gestation, requiring more days of ventilation, and a greater proportion being oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean Raw and FRC(pleth) were significantly higher and mean sGaw significantly lower. After adjustment for birth and current size differences, the sex differences in FRC(pleth) and sGaw were 15% and 26% respectively and remained significant. CONCLUSION: Lung function at follow up of prematurely born infants is influenced by sex.

Plethysmograph and interrupter resistance measurements in prematurely born young children.

BACKGROUND: Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under 2 years of age. OBJECTIVE: To compare Rint results with plethysmographic measurements of airway resistance (Raw) in prematurely born, young children. DESIGN: Prospective study. SETTING: Infant and Paediatric Lung Function Laboratories. PATIENTS: Thirty children with a median gestational age of 25-29 weeks and median postnatal age of 13 months. INTERVENTIONS AND MAIN OUTCOME MEASURES: The infants were sedated, airway resistance was measured by total body plethysmography (Raw), and Rint measurements were made using a MicroRint device. Further Raw and Rint measurements were made after salbutamol administration if the children remained asleep. RESULTS: Baseline measurements of Raw and Rint were obtained from 30 and 26 respectively of the children. Mean baseline Rint values were higher than mean baseline Raw results (3.45 v 2.84 kPa/l/s, p = 0.006). Limits of agreement for the mean difference between Rint and Raw were -1.52 to 2.74 kPa/l/s. Ten infants received salbutamol, after which the mean Rint result was 3.6 kPa/l/s and mean Raw was 3.1 kPa/l/s (limits of agreement -0.28 to 1.44 kPa/l/s). CONCLUSION: The poor agreement between Rint and Raw results suggests that Rint measurements cannot substitute for plethysmographic measurements in sedated prematurely born infants.

Measurement of neural respiratory drive via parasternal intercostal electromyography in healthy adult subjects.

Neural respiratory drive, quantified by the parasternal intercostal muscle electromyogram (EMGpara), provides a sensitive measure of respiratory system load-capacity balance. Reference values for EMGpara-based measures are lacking and the influence of individual anthropometric characteristics is not known. EMGpara is conventionally expressed as a percentage of that obtained during a maximal inspiratory effort (EMGpara%max), leading to difficulty in applying the technique in subjects unable to reliably perform such manoeuvres. To measure EMGpara in a large, unselected cohort of healthy adult subjects in order to evaluate relevant technical and anthropometric factors. Surface second intercostal space EMGpara was measured during resting breathing and maximal inspiratory efforts in 63 healthy adult subjects, median (IQR) age 31.0 (25.0-47.0) years, 28 males. Detailed anthropometry, spirometry and respiratory muscle strength were also recorded. Median (IQR EMGpara was 4.95 (3.35-6.93) µV, EMGpara%max 4.95 (3.39-8.65)% and neural respiratory drive index (NRDI, the product of EMGpara%max and respiratory rate) was 73.62 (46.41-143.92) %.breath/min. EMGpara increased significantly to 6.28 (4.26-9.93) µV (p < 0.001) with a mouthpiece, noseclip and pneumotachograph in situ. Median (IQR) EMGpara was higher in female subjects (5.79 (4.42-7.98) µV versus 3.56 (2.81-5.35) µV, p = 0.003); after controlling for sex neither EMGpara, EMGpara%max or NRDI were significantly related to anthropometrics, age or respiratory muscle strength. In subjects undergoing repeat measurements within the same testing session (n = 48) or on a separate occasion (n = 19) similar repeatability was observed for both EMGpara and EMGpara%max. EMGpara is higher in female subjects than males, without influence of other anthropometric characteristics. Reference values are provided for EMGpara-derived measures. Expressing EMGpara as a percentage of maximum confers no advantage with respect to measurement repeatability, expanding the potential application of the technique. Raw EMGpara is a useful marker of respiratory system load-capacity balance.

Dampened ventilatory response to added dead space in newborns of smoking mothers.

BACKGROUND: Term newborns can compensate fully for an imposed dead space (tube breathing) by increasing their minute ventilation. OBJECTIVE: To test the hypothesis that infants of smoking mothers would have an impaired response to tube breathing. DESIGN: Prospective study. SETTING: Perinatal service. PATIENTS: Fourteen infants of smoking and 24 infants of non-smoking mothers (median postnatal age 37 (11-85) hours and 26 (10-120) hours respectively) were studied. INTERVENTIONS: Breath by breath minute volume was measured at baseline and when a dead space of 4.4 ml/kg was incorporated into the breathing circuit. MAIN OUTCOME MEASURES: The maximum minute ventilation during tube breathing was determined and the time constant of the response calculated. RESULTS: The time constant of the infants of smoking mothers was longer than that of the infants of non-smoking mothers (median (range) 37.3 (22.2-70.2) v 26.2 (13.8-51.0) seconds, p = 0.016). Regression analysis showed that maternal smoking status was related to the time constant independently of birth weight, gestational or postnatal age, or sex (p = 0.018). CONCLUSIONS: Intrauterine exposure to smoking is associated with a dampened response to tube breathing.

Control of the respiratory cycle in conscious humans.

We studied in conscious humans the relative strength of mechanisms controlling timing and drive components of the respiratory cycle around their resting set points. A system of auditory feedback with end-tidal PCO2 held constant in mild hyperoxia via an open circuit was used to induce subjects independently to change inspiratory time (TI) and tidal volume (VTI) over a wide range above and below the resting values for every breath for up to 1 h. Four protocols were studied in various levels of hypercapnia (1-5% inspired CO2). We found that TI (and expiratory time) could be changed over a wide range (1.17 - 2.86 s, P < 0.01 for TI) and VTI increased by > or = 500 ml (P < 0.01) without difficulty. However, in no protocol was it possible to decrease VTI below the free-breathing resting value in response to reduction of auditory feedback thresholds by up to 600 ml. This applied at all levels of chemical drive studied, with resting VTI values varying from 1.06 to 1.74 liters. When reduction in VTI was forced by the more "programmed" procedure of isocapnic panting, end-expiratory of volume was sacrificed to ensure that peak tidal volume reached a fixed absolute lung volume. These results suggest that the imperative for control of resting breathing is to prevent reduction of VTI below the level dictated by the prevailing chemical drive, presumably to sustain metabolic requirements of the body, whereas respiratory timing is weakly controlled consistent with the needs for speech and other nonmetabolic functions of breathing.

Control of expiratory time in conscious humans.

Combinations of 17 normal awake humans breathed mildly hyperoxic and hypercapnic gas mixtures via a pneumotachograph into an open circuit. Respiratory pattern was measured for each breath in real time by computer. Use of computer-controlled auditory feedback at a constant end-tidal PCO2 (PETCO2) allowed prolonged changes of 1) inspiratory time (TI) at constant inspired tidal volume (VTI), 2) VTI up and down in repeated steps at constant TI, and 3) expiratory time (TE) at constant VTI. The remaining variables were free to be determined by the subjects' automatic respiratory control mechanisms. We showed that TE changed in parallel with the change in TI despite constant VTI, TE did not change in response to step changes in VTI at constant TI, and large changes in TE had no influence on the subsequent TI, but VTI increased slightly as TE lengthened despite clamping. Time for expiratory flow (TE--end-expiratory pause) changed in parallel with TE in all protocols. Thus, in conscious humans, inspiratory timing has a direct influence on expiratory timing, independent of volume change and chemical drive, but expiratory timing has no influence on the inspiratory timing of the subsequent breath but has a small influence on volume.

Influence of acute lung volume change on contractile properties of human diaphragm.

The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity. The reduction in T2 Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% of vital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responses elicited by low-frequency stimulations; this effect is distinct from and additional to the known length-tension relationship.

Sniff nasal inspiratory pressure in children.

Maximal static inspiratory pressure (P(IMAX)) generated at the mouth is one of the tests of inspiratory muscle strength in children. In adults, inspiratory muscle strength has also been assessed using sniff nasal inspiratory pressure (SNIP). This test is easier to perform than P(IMAX) and might therefore be applicable to children. To test this hypothesis, we measured P(IMAX) and SNIP in 116 children aged 4 to 11 years (54 girls, 62 boys). P(IMAX) was measured using a tube mouthpiece and SNIP using a tightly fitting plug in one nostril, while a sniff was performed through the other nostril. Both tests were performed from functional residual capacity (FRC). Pressure was measured with a differential pressure transducer and displayed in real time on a computer screen. Weight, standing height, sitting height, gender, and age were recorded. There was a significant difference (P < 0.01) in group mean (SD) data between SNIP (81.3 (27.4) cmH(2)O) and P(IMAX) (67.9 (28.1) cmH(2)O). Bland/Altman analysis demonstrated a mean difference of -13.5 cmH(2)O (SD 21.4) between the techniques. Regression analysis indicated highly significant relations (P < 0.01) between SNIP and P(IMAX), and between weight, standing and sitting height, and age for SNIP, and between weight, standing height, and age for P(IMAX). SNIP and P(IMAX) were greater in boys than girls (83.2 vs. 79.2 cmH(2)O SNIP; 72.9 vs. 62.0 cmH(2)O P(IMAX)), but this difference was only significant for P(IMAX) (P < 0.05). SNIP was significantly greater than P(IMAX) (P < 0.01) in both boys and girls. These data suggest that SNIP provides a simple, noninvasive additional test to P(IMAX) for assessing inspiratory muscle strength in children.

Effect of posture on respiratory function and drive in preterm infants prior to discharge.

Our objective was to determine the effect of posture on respiratory function and drive in prematurely born infants immediately prior to discharge. Twenty infants (6 oxygen-dependent), median gestational age 29 weeks (range, 25-32), were studied at a median postconceptional age (PCA) of 36 weeks (range, 33-39). On 2 successive days, infants were studied both supine and prone; each posture was maintained for 3 hr. The order on each day in which postures were studied was randomized between infants. At the end of each 3-hr period, tidal volume (Vt), inspiratory (Ti) and expiratory (Te) time, respiratory rate, and minute ventilation were measured. In addition, respiratory drive was assessed by measuring the pressure generated in the first 100 msec of an imposed airway occlusion (P(0.1)), and respiratory muscle strength was assessed by recording the maximum inspiratory pressure (Pimax) generated against an occlusion which was maintained for at least five breaths. Overall, tidal volume was higher (P < 0.05), but respiratory rate (P < 0.05), P(0.1) (P < 0.05), and Pimax (P < 0.05) were lower in the prone compared to the supine position. There were no significant differences in Ti or Te between the two postures. In oxygen-dependent infants only, minute volume was higher in the prone position (P < 0.05). In conclusion, posture-related differences in respiratory function are present in prematurely born infants studied prior to neonatal unit discharge.

Tidal breathing parameters in young children: comparison of measurement by respiratory inductance plethysmography to a facemask pneumotachograph system.

The ratio of expiratory time at tidal peak flow to total expiratory time (t(ptef)/t(e)) correlates with conventional measures of airway obstruction. It is usually assessed using a facemask and pneumotachograph system which may be poorly tolerated in young children and hence limits the usefulness of this technique. We therefore determined in young asthmatic children the accuracy of t(ptef)/t(e), using an uncalibrated respiratory inductance plethysmograph (RIP), and compared the results with those from a facemask-pneumotachograph system. We also assessed whether age influenced the agreement between measurements using the two devices. Forty-seven children aged between 1 month and 12 years were recruited: 39 were inpatients recovering from an acute wheezy episode, and 8 were recruited from the asthma clinic. All were receiving bronchodilators. Tidal breathing parameters t(ptef)/t(e), the duty cycle (t(i)/t(tot)), and respiratory rate were initially measured using the Respitrace alone and then simultaneously with both the Respitrace and the facemask-pneumotachograph system. Eight children did not tolerate the facemask, and in two others it was impossible to analyze the Respitrace trace due to artefacts. In the remaining 37 children, the reliability coefficients and coefficients of variation of the two techniques were similar. Similar values of t(i)/t(tot) and respiratory rate were obtained using the two devices. The mean t(ptef)/t(e) obtained using the Respitrace was lower than with the facemask-pneumotachograph system (P < 0.01), although this was age group-dependent (P < 0.05), as the difference was less apparent in the 1 to 2-year-old children than in other age groups. Application of the facemask-pneumotachograph system did not significantly influence the results obtained using the Respitrace. We conclude that uncalibrated respiratory inductance plethysmography can measure tidal breathing parameters as reliably as a facemask-pneumotachograph system in young asthmatic children, and is better tolerated than the pneumotachograph system. The results obtained using the two devices are not interchangeable.

Relation of hypocapnic symptoms to rate of fall of end-tidal PCO2 in normal subjects.

Hyperventilation is of little clinical relevance unless it causes symptoms. These are often non-specific. Their threshold for onset and relation to steady level of arterial (or its equivalent, end-tidal PCO2; PETCO2) are uncertain, and it has been suggested that they may relate better to the rate of fall of PCO2 than to the absolute level. We investigated this in nine normal subjects, who breathed to and fro through a pneumotachograph into an open circuit in which the concentration of CO2 could be varied. Tidal volume, respiratory frequency and ventilation was measured on-line by a Compaq computer, and PETCO2 at the mouth was measured by capnograph. Subjects overbreathed at a fixed rate and depth until symptoms consisting of dizziness, paraesthesiae and light headedness occurred. Then, without their knowledge and while they continued to overbreathe, inspired CO2 was increased to restore PETCO2 to normal and abolish symptoms, and was then withdrawn again over either approximately 0.1, 2.5 or 5 min until symptoms were again reported. The PETCO2 at this point was noted. The three protocols were performed in each subject in a random order and the same symptoms were reported each time. When averaged across all subjects, symptoms occurred at mean PETCO2 values of 20.3, 19.2 and 18.6 mmHg (2.71, 2.56 and 2.48 kPa), respectively. These were not significantly different, and it can be concluded that there was no influence of rate of fall of PCO2 on threshold for symptoms. Chest pain only occurred in one subject and may have a different mechanism.

Reproducibility of twitch and sniff transdiaphragmatic pressures.

Twitch transdiaphragmatic pressure (Tw Pdi) measured with magnetic stimulation of the phrenic nerve is used to follow up patients and to assess the effect of clinical treatments on diaphragm function. However the reproducibility of Tw Pdi on different occasions has been little studied. We investigated 32 normal subjects, measuring Tw Pdi elicited by bilateral magnetic stimulation of the phrenic nerves on two to 14 occasions. Sniff transdiaphragmatic pressure (sniff Pdi) was also measured. The mean value of Tw Pdi and sniff Pdi were 28+/-5 and 134+/-24 cm H(2)O, respectively. The within subjects coefficient of variation was 11% for both Tw Pdi and sniff Pdi. We conclude that there is a variability of Tw Pdi and the variability of Tw Pdi is the same as that of sniff Pdi.