Ephraim Bar-Yishay

Bronchial provocation determined by breath sounds compared with lung function.

Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each others results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children.

Home recording of PEF in young asthmatics: does it contribute to management?

The value of home monitoring of peak expiratory flow (PEF) as part of an action plan for asthma management in children and young adults is uncertain. We sought to determine whether home recording of PEF benefited asthma management and whether any contribution was affected by the severity of the asthma. Twenty-eight children and young adults with asthma of different severity (mean age 14 yrs; 95% confidence interval (95% CI) 12-16 yrs) recorded their symptoms, drug consumption and PEF twice daily for a mean of 82 days over a 12 week period, and attended the laboratory every 2 weeks for measurement of lung function. The number of individual patients with significant correlations for laboratory lung function tests compared with ambulatory PEF and diary scores averaged over the preceeding 2 weeks was low in all severity groups. When measured in the laboratory, PEF meter readings correlated poorly with PEF measured by spirometry. The proportion of patients with significant correlations for PEF, symptoms and rescue bronchodilator use on a day-to-day basis was 70-80% in the group of severe asthmatics and significantly less in the mild asthmatics. In a subgroup of 14 patients who were sick on a mean of 19 days, the mean difference in PEF between well and sick days was 14% of predicted. Diurnal PEF variation correlated poorly with other parameters in all groups. It is concluded that PEF monitoring adds little to daily recording of symptoms and bronchodilator use in the management of young patients with severe asthma, and it is too insensitive to register meaningful clinical changes in those with milder asthma.

Computerized respiratory muscle training in children with Duchenne muscular dystrophy

The present study describes the use of simple video games for a 5-week regimen of respiratory muscle training in 15 patients with Duchenne muscular dystrophy (DMD) at various stages of the disease. The games were re-arranged to be operated and driven by the respiratory efforts of the patient and to incorporate accurate ventilation and time measurements. Improvement in respiratory performance was determined by maximum voluntary ventilation (MVV), maximal achieved ventilation (VEmax) during a progressive isocapnic hyperventilation manoeuvre (PIHV) and the PIHV duration. The actual training period was 23 +/- 4 days (mean +/- S.D.) at ventilatory effort of 46 +/- 6% MVV, for 10 +/- 3 min day-1. Patients with moderate impairment of lung function tests (LFT) showed an improvement in MVV, VEmax, and duration of PIHV of 12 +/- 7% (p < 0.02), 53 +/- 25% (p < 0.001) 57 +/- 21% (p < 0.01), respectively. Improvements correlated with actual training time and ventilation level, %MVV, but negatively correlated with years of immobilization and with the initial MVV. We conclude that computerized respiratory games may be applied for breathing exercises and may improve respiratory performance in recently immobilized children with DMD who have moderate impairment of LFT.

Lung function in infants with cystic fibrosis.

Lung function was measured in 28 infants with cystic fibrosis and repeated in 17 of the infants during the first year of life. Thoracic gas volume (TGV) and specific airway conductance (sGaw) were measured plethysmographically and maximum forced expiratory flow at functional residual capacity (VmaxFRC) was derived from the partial expiratory flow-volume curve. At the time of the initial evaluation respiratory function was correlated with the clinical condition of the infants but not with age. There was a good correlation between sGaw and VmaxFRC when both were expressed as percentages of the predicted normal values. On the basis of the normal range for sGaw the infants were divided into two groups. Group A (n = 9), who had normal sGaw, were younger and had a lower clinical score and normal VmaxFRC and TGV values. Group B (n = 19), who had low sGaw, had increased TGV and decreased VmaxFRC. There was no correlation with age for any measure of lung function for the population as a whole. Repeat testing was undertaken at intervals in 17 representative infants. In most of these infants the relation between sGaw and VmaxFRC was maintained; there was no evidence that VmaxFRC was affected before sGaw. There was no functional evidence that the earliest changes in cystic fibrosis occur in small airways, as reflected by changes in VmaxFRC in infancy.

Differences between swimming and running as stimuli for exercise-induced asthma

SummaryThirteen children each exercised for 6 min by running on a treadmill and by tethered swimming, breathing air at room temperature and either 8% or 99% relative humidity continuously. Ventilation, gas exchange and heart rate were closely matched in all four tests in each child, with a mean oxygen consumption of 32.3±1.7ml·min−1·kg−1. The post-exercise fall in FEV1 expressed as a percentage of the baseline FEV1 (δFEV1) was significantly greater after running compared with swimming breathing either humid or dry air. The δFEV1 was also related to respiratory heat loss (RHL) calculated from measurements of inspired and expired gas temperature and humidity. At a standardised RHL, the difference between running and swimming was highly significant [δFEV1 (%) ± SE=39±5 and 28±4 respectively, p<0.01]. These experiments suggest that the type of exercise influences the severity of exercise-induced asthma even under conditions of the same metabolic stress and respiratory heat loss.

Encouraging Pulmonary Outcome for Surviving, Neurologically Intact, Extremely Premature Infants in the Postsurfactant Era

OBJECTIVE The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era. METHODS We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV₁ by 20% [PC(20)]), lung volumes, diffusion, and cardiopulmonary exercise tolerance. RESULTS Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV₁ % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC(20) was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC(20) was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01). CONCLUSIONS Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.

Refractory period following induced asthma: contributions of exercise and isocapnic hyperventilation.

To compare the refractory period that follows exercise and isocapnic hyperventilation, 10 asthmatic children performed two pairs of challenge tests in random order at least six hours apart. In pair A a hyperventilation challenge was followed by an exercise challenge and in pair B the order was reversed. Both pairs of tests were done while the children were breathing cold dry air. Tests were matched in terms of work load, ventilation, and end tidal carbon dioxide tension (PCO2). The mean percentage fall in FEV1 (delta FEV1) after the first challenge (hyperventilation) of pair A and the first challenge (exercise) of pair B were the same (30% (SEM 2%)) and 30% (4%) respectively). The mean delta FEV1 of the exercise test following hyperventilation in pair A and of hyperventilation following exercise in pair B was 22% (4%) and 18% (4%) respectively. Both these latter results were significantly lower than the respective delta FEV1 when the challenge was the first test of the pair. Although the mean refractoriness index (reduction in induced asthma in the second test of each pair compared with the first test) was greater when exercise was the first challenge, the difference was not significant.

Airway resistance measurements throughout the respiratory cycle in infants

Using a constant-volume infant whole-body plethysmograph containing a heated rebreathing bag, we have been able to measure airway resistance (Raw) throughout the respiratory cycle using a computer-based technique. Data from the plethysmograph transducers are sampled at 60 Hz for the calculations and Raw is calculated at each point sampled during the breath, with appropriate corrections for absolute lung volume. It was found that in most cases Raw varied less with respect to tidal volume than to tidal flow. Various patterns of Raw change in relation to tidal volume were found. These included an elevated but relatively constant resistance, a progressively rising expiratory resistance, and in 3 infants with laryngomalacia, a progressively rising inspiratory resistance. It was also found that the dynamic performance of the rebreathing bag was such that considerable errors would occur if apparatus resistance was assumed to be constant and so the actual apparatus resistance at each point was subtracted from the total resistance to give Raw. In conclusion, Raw is not constant throughout the respiratory cycle in infants and the pattern of change conveys additional information.

Effect of Natural Oxygen Enrichment at Low Altitude on Oxygen-Dependent Patients with End-Stage Lung Disease

Long-term home oxygen therapy is the standard of care for patients with chronic obstructive pulmonary disease and end-stage lung disease with chronic hypoxemia [1-6]. Oxygen therapy improves functional and exercise capacity [4-7], reduces pulmonary hypertension, and improves right ventricular function [8, 9] and survival [10, 11]. This important tool in pulmonary medicine involves substantial cost and requires continuous maintenance of equipment and patient cooperation. Further, despite the major advances in portable oxygen devices, quality of life for patients receiving long-term oxygen therapy is substantially impaired because of the constant dependence on an oxygen source and equipment. An alternative to portable oxygen therapy is the natural oxygen enrichment resulting from high barometric pressure at altitudes below sea level, but this has not been investigated and is not routinely recommended by pulmonary physicians or in any major textbook in pulmonary medicine. To assess this therapeutic option, we took advantage of the natural topography of the Dead Sea and its holiday resorts that lie at the lowest natural altitude on earth (402 m below sea level), a short distance (40 km) from Jerusalem, which lies 800 m above sea level. This yields a 1200-m difference in altitude between the two locations. The alveolar oxygen concentration can be calculated using the following equations: PAO2 = (barometric pressure 47) x Fio 2 Pa CO2/0.8 PAO2 Dead Sea = (800 47) 0.21 Paco 2/0.8 = 158.1 - Paco 2/0.8 PAO2 Jerusalem = (696 47) 0.21 Paco 2/0.8 = 136.3 - Paco 2/0.8 Additional inspired Po 2 = 21.8 mm Hg Delta Paco 2/0.8, where PAO2 is the partial pressure of alveolar oxygen; Fio 2 is the fractional concentration of oxygen in inspired gas; Paco 2 is the partial pressure of arterial carbon dioxide; and Po 2 is the oxygen pressure. We investigated the short-term effect of lowering altitude in 10 patients with various lung diseases who used oxygen on a long-term basis and compared arterial oxygenation, spirometry, exercise tolerance, and oxygen saturation values during sleep at high and low altitudes. Methods We studied 10 oxygen-dependent patients attending the pulmonary clinic at Hadassah University Hospital in Jerusalem, Israel. Table 1 summarizes demographic data and diagnoses. The five males and five females, 12 to 77 years of age, had severe obstructive or restrictive lung disease, as indicated by their lung function results (Table 2). Table 1. Demographic Data of Patients with End-Stage Lung Disease* Table 2. Pulmonary Function of Patients* Barometric pressure was measured daily during the study. In Jerusalem it was between 696 and 697 mm Hg and at the Dead Sea it was between 797 and 800 mm Hg. We studied patients in Jerusalem 7 to 10 days before their descent to the Dead Sea resort area, on day 6 of their stay at the Dead Sea, and 7 to 14 days after returning to Jerusalem. The equipment and staff were the same at both locations. Each patient had the following studies on each examining day. Blood Gas Analysis Using radial arterial puncture and topical anesthesia, we obtained arterial blood while patients breathed room air. We used a Corning 175 gas analyzer (Corning, New York) to do blood gas analyses. Spirometry We measured spirometry and maximal voluntary ventilation for 12 seconds using an electronic spirometer (Vitalograph, Ltd., Buckingham, United Kingdom). The predicted values we used were European Coal Conference Standard 1983. In Jerusalem, we also measured lung volumes by whole-body plethysmography and carbon monoxide diffusion capacity by the single-breath method using MedGraphics equipment (Medical Graphics Corp., St. Paul, Minnesota). Data were corrected for body temperature and ambient pressure, saturated with water vapor (BTPS). Exercise Testing Patients performed incremental exercise tests using an electronically braked cycle ergometer (MedGraphics CPE 2000, Medical Graphics Corp.) and a breath-by-breath analyzing system (MedGraphics CPX, Medical Graphics Corp.). After a rest period of 2 minutes, the patients peddled at 60 rpm without added load for 2 minutes. The work load was then increased gradually in a ramp pattern at a rate calculated so each patient would complete the exercise in 6 to 10 minutes. The patients continued the test to their symptom-limited maximum capacity [12]. Data were corrected for BTPS or STPD (the gas volume at standard temperature and pressure, free of water vapor) at both locations. Sleep Oximetric Study Continuous nocturnal sleep oximetry was studied in Jerusalem and at the Dead Sea in six patients (patients 1, 2, 3, 4, 5, and 8). We used a Nonin 8600 finger oximeter and 8586 printer interface module (Nonin Medical, Plymouth, Minnesota). Minute-by-minute data and histograms were printed each morning after the night study was completed. Statistical Analysis Data are expressed as medians and observed paired differences with corresponding 95% confidence intervals of the median paired differences. We used the Wilcoxon matched-pairs signed-rank test to determine the significance of differences. Probability values less than 0.05 were considered significant. We obtained informed consent from all patients, and the study was approved by the Helsinki Committee of Hadassah University Hospital. Patients were interviewed before each study and were asked about their general well-being, use of oxygen, daily activities, and exercise capacity. Results Spirometry There were no significant differences in spirometry values at the two locations. Arterial Blood Gases Results of analyses are shown in Figure 1 and Table 3. Arterial Po 2 increased from a median of 51.6 mm Hg in Jerusalem to 67.0 mm Hg at the Dead Sea, an increase of 15.2 mm Hg (CI, 4.1 to 20.4 mm Hg). The Paco 2 values also increased but to a lesser degree. The alveolar-arterial gradient did not change substantially, and pH remained unchanged. After the return to Jerusalem, the values returned to those found before descent to the Dead Sea. Table 3. Blood Gas Analysis in Jerusalem and at the Dead Sea* Figure 1. Blood gas analysis of 10 patients in Jerusalem (before traveling to the Dead Sea resort) and at the Dead Sea. Top left. o Top right. co Bottom left. o Bottom right. Exercise Performance Results of exercise testing are given in Table 4. Maximal oxygen uptake (VO2max) increased with the descent to the Dead Sea compared with the results obtained in Jerusalem. After the return to Jerusalem, VO2max returned to the previous level. The anaerobic threshold did not change significantly (median of 650 mL/min in Jerusalem and 710 mL/min at the Dead Sea; P = 0.5). We also found no significant differences in minute ventilation during rest and maximal exercise, although heart rate increased slightly. End tidal carbon dioxide and oxygen pulse (Vo 2/heart rate) increased during rest and maximal exercise at the Dead Sea compared with the values measured in Jerusalem. At peak exercise, oxygen saturation decreased at both locations to the same degree. Table 4. Progressive Exercise Testing in Jerusalem and at the Dead Sea* Nocturnal Oximetry Results of nocturnal oximetry are shown in Figure 2. Six patients had oximetric monitoring during the night. All reported usual sleep with a median duration of 5.5 hours in Jerusalem and 5.2 hours at the Dead Sea. Median oxygen saturation increased from 85% in Jerusalem to 90% at the Dead Sea, a change of 5% (CI, 2% to 7%; P = 0.005). The percentage of total sleep time with oxygen saturation greater than 90% increased from a median of 24% in Jerusalem to 73% at the Dead Sea, an increase of 49% (CI, 20% to 87%; P = 0.02). Median heart rate during sleep was 82 beats/min in Jerusalem and 76 beats/min at the Dead Sea (P = 0.25). When questioned, all patients reported an improvement in their general well-being, with less need for oxygen during simple daily activities compared with their usual activities in Jerusalem. Figure 2. Sleep oximetry in six patients in Jerusalem and at the Dead Sea. Left. Right. Discussion Our study clearly shows the increase in arterial oxygen tension with the relatively mild change in altitude of 1200 m. The increase of 10 to 12 mm Hg in Pao 2 is a substantial improvement for patients with hypoxemia, which can shift their percentage saturation on the oxygen dissociation curve from the low to mid-80s to the low 90s. This may reduce pulmonary vascular resistance and pulmonary hypertension. The improvement in oxygenation caused a mild increase in arterial carbon dioxide tension, as is commonly found with the application of external oxygen in patients with chronic obstructive pulmonary disease. The addition of approximately 21 mm Hg inspired Po 2 is equivalent to about a 4% increase in Fio 2 in the Jerusalem area or to a nasal cannula with continuous oxygen flow of about 1 L per/min. The major advantage, however, is elimination of the need for external devices and tubing and assurance that the patient receives oxygen 24 hours a day, thus improving quality of life and psychological well-being and increasing independence. Since early studies by Abraham and colleagues [13] and Petty and Finigan [14], oxygen therapy has been considered one of the basic modes of therapy in patients with chronic obstructive pulmonary disease and other end-stage lung diseases. Oxygen therapy reduced the mortality rate and increased survival in patients in several large-scale studies [2, 3]. Researchers think the mechanism by which oxygen improves survival is reduced pulmonary vascular resistance and pulmonary artery pressure [10, 13]. Exercise capacity improves after administration of oxygen in other studies [15, 16], probably by a similar mechanism. A study in Colorado [17] showed that survival of patients with emphysema was better at low altitudes compared with survival at high altitudes (the Denver area). Renzetti and coworkers [18] previously made a similar observation. Veterans with chronic obstructive pulmon

Mechanisms of exercise-induced asthma

In a previous review in this journal McFadden eloquently presented the findings which led him and his colleagues to propose that respiratory heat loss and the subsequent cooling of the airways are the initial reaction sequence leading to airway obstruction in hyperventilation and exercise-induced asthma [62]. He further concluded that: “Exercise per se is not essential and serves only as means to increase ventilation”. Our interpretation of currently available data has led us to conclude that while respiratory heat loss may play an important permissive role in initiating the bronchoconstriction which follows exercise, the weight of evidence indicates that exercise per se serves as the trigger mechanism and is not just a tool to increase ventilation. Moreover, we believe that the role of exercise in releasing chemical mediators has been established, although pathways by which the airway smooth muscle is affected are still uncertain.