Pediatric lung function testing during a pandemic: An international perspective.

The COVID pandemic has passed its first peak for now in many countries while some are still on the rise, with some facing a second wave of cases. Precautions and infection control measures for both pediatric and adult pulmonary function testing (PFT) have been a topic of debate during the pandemic. Many centers had to close their PFT laboratories during the initial periods of the pandemic and are reopening as the numbers of new cases are decreasing. This review aims to summarize different practices of PFT laboratory management in different countries, including patient appointments, personal protective equipment, testing room requirements and telemedicine during and immediately following the COVID pandemic.

Asthma and chronic sickle cell lung disease: a dynamic relationship.

Chronic lung disease is a significant source of morbidity and mortality in patients with sickle cell disease. Asthma and sickle cell lung disease share many of the same clinical features and pathophysiological mechanisms. Though there is growing evidence of an association between sickle cell disease and airway hyper-reactivity, there is still no consensus on the definition of asthma in sickle cell lung disease. This review will explore what we know about asthma and airway hyper-reactivity in sickle cell disease and whether currently available asthma therapies may be beneficial in delaying or averting the progression of sickle cell lung disease.

Exercise capacity of children with pediatric lung disease.

BACKGROUND: Pulmonary function of children with cystic fibrosis (CF) and bronchopulmonary dysplasia (BPD) is similar at rest even though the mechanisms of injury differ. We sought to compare the peak exercise responses in children with BPD versus CF while controlling for pulmonary impairment, nutritional status, gender, age, height, and predicted forced expired volume in 1 second (approximately 73% of predicted). METHODS: Nine BPD children and 9 CF children underwent spirometry and a progressive exercise test to maximum on a cycle ergometer. RESULTS: There was no difference between groups in body mass percentile (CF:97 +/- 13%, BPD: 98 +/- 11%), peak power output (Wpeak) (CF:67 +/- 19 W, BPD:73 +/- 28 W), % predicted Wpeak (CF:83 +/- 28%, BPD:88 +/- 15%), peak oxygen uptake (VO2peak, CF: 38 +/- 7 ml/kg/min, BPD: 39 +/-6 ml/kg/min), or % predicted VO2peak (CF:99 +/- 16 %, BPD:96 +/- 27%). CONCLUSIONS: Children with mild pulmonary impairments are able to achieve a near normal peak power output and a normal VO2peak. Neither the aetiology nor the developmental onset of the process appears to be important influences on VO2peak or Wpeak.

Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis.

BACKGROUND: Progressive lung damage causes the majority of deaths in cystic fibrosis (CF). Non-steroidal anti-inflammatory drugs may prevent progressive pulmonary deterioration and morbidity in CF. OBJECTIVES: To assess the effectiveness of treatment with non-steroidal anti-inflammatory agents in CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We also contacted pharmaceutical companies manufacturing non-steroidal anti-inflammatory drugs. Most recent search of the Group's Trials Register: October 2006. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials, published and unpublished, comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with CF. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for the review. MAIN RESULTS: The searches identified six trials, of which four, including 287 participants aged five to 39 years with a maximum follow up of four years, were eligible for inclusion in the review. Two trials reporting effectiveness of ibuprofen in people with mild lung disease were from the same center and included some of the same participants. A third assessed piroxicam in participants with more severe impairment of respiratory function and the Trans-Canada trial compared ibuprofen to placebo for a period of two years. Three of the trials in this review were deemed to have good or adequate methodological quality, but variation in outcomes reported and their summary measures precluded calculation of pooled treatment estimates. Authors considered objective measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival, frequency of all adverse effects and compliance with therapy. The addition of data from the Canadian trial showed evidence of a moderate absolute annual decline in per cent predicted forced expiratory volume in one second and forced vital capacity in the placebo group than in the ibuprofen group. In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low. AUTHORS' CONCLUSIONS: High-dose ibuprofen can slow the progression of lung disease in people with CF, especially in children, and this suggests that strategies to modulate lung inflammation can be beneficial for people with CF.

Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial.

INTRODUCTION: Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF). METHODS: The efficacy of inhaled mannitol in children with CF aged 6-17years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400mg every 12h or matching placebo for 8weeks, followed by an 8week washout and an 8week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1). RESULTS: A total of 92 subjects were studied, with a mean age of 12years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p=0.004) higher compared to placebo or a 4.97% (p=0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p=0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p=0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group. CONCLUSIONS: In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531).

The benefits of newborn screening for cystic fibrosis: The Canadian experience.

BACKGROUND: The impact of newborn screening (NBS) for cystic fibrosis (CF) on early indicators of long-term health was evaluated in the context of government-sponsored healthcare and access to current therapies. METHODS: Using data from the Canadian CF Registry between 2008 and 2013, we compared the rates of respiratory infections and markers of nutritional status in those diagnosed through NBS to those who were diagnosed clinically within the same time period using Mann-Whitney and Fischer's exact test as appropriate. RESULTS: The study included 303 subjects, 201 in the NBS group and 102 in the non-NBS group. NBS patients were diagnosed earlier and had their first clinic visit at a younger age. Pancreatic insufficiency was less common in NBS patients. The incidence of Pseudomonas aeruginosa and Staphylococcus aureus were lower in NBS patients. After adjusting for age at clinic visit, gender, pancreatic status, and Pseudomonas aeruginosa infection status, mean z-scores for weight-for-age and height-for-age were higher in NBS patients, with no differences in BMI-for-age. CONCLUSIONS: NBS programs for CF lead to improved long-term health outcomes for the CF population.

Sweat collection for testing in Canadian Cystic Fibrosis Centers, is it optimal?

OBJECTIVES: The goal of this study was to examine the ability of the current Canadian CF center network to conduct sweat testing, with a particular focus on testing in infants less than 3 months old. METHODS: Surveys were sent to the 37 CF centers in Canada supported by the Canadian CF Foundation, and results were interpreted with respect to their ability to obtain adequate sweat volumes in children less than 3 months and potential factors influencing these results. RESULTS: Ten centers that care for adult patients referred patients to their local pediatric CF center for sweat testing; the remaining 27 centers conducted sweat tests and 26 responded. Insufficient sweat volume results in children <3 months occurred in a median of 18.3% of tests. The corresponding proportion for the remaining population was 4.5% (P < 0.001). 15 of 19 centers had an incidence of >5% of insufficient tests in children <3 months of age, and 9 of 19 had an incidence of <20% in this age group. Six of 19 had an incidence of >5% of insufficient sweat volumes in older children and adults. CONCLUSIONS: Standardization of testing procedures is required to reduce the rates of insufficient sweat volumes in both infants less than 3 months old and children >3 months old. This will decrease the need for repeat testing and delay in diagnosis.

Sweat-testing: a review of current technical requirements.

Sweat-testing remains a key component of the diagnostic workup for cystic fibrosis. However, it is technically challenging, especially in young children. This review covers technical aspects related to the devices and protocols associated with conducting successful tests.

Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1.

BACKGROUND AND PURPOSE: There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages. EXPERIMENTAL APPROACH: CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3 ) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), or paricalcitol, synthetic analogue of 1,25(OH)2 D3 . 25OHD3 was tested at doses of 25-150 nM, whereas 1,25(OH)2 D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1. KEY RESULTS: MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3 , or >1 nM for 1,25(OH)2 D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation. CONCLUSIONS AND IMPLICATIONS: Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms.

Relationships among nutritional status and skeletal and respiratory muscle function in cystic fibrosis: does early dietary supplementation make a difference?

Relationships among nutritional status and skeletal and respiratory muscle function were examined in 16 children with cystic fibrosis (CF) and mild lung disease (FEV1 95 +/- 16% predicted). Subjects were randomly assigned to receive (or not) noninvasive nutritional supplementation at 25% of normal energy recommendations for 6 mo. Skeletal muscle strength and power were similar to those of healthy children as were respiratory muscle strength and endurance. Stepwise-regression analysis indicated that changes in skeletal muscle strength and energy intake correlated significantly with growth [weight (kg) = 1.90 - 0.60 (Tanner Stage) + 0.49 (maximum voluntary strength (Nm) + 0.03 (energy intake, % RNI), r = 0.76, P < 0.05], though body composition, protein biochemistry, muscle power, respiratory muscle strength, and use of dietary supplements did not. Thus, changes in skeletal muscle strength may be a functional index of changes in nutritional status in CF. Dietary supplementation per se was not associated with functional improvement.

Informed proxy consent: communication between pediatric surgeons and surrogates about surgery.

OBJECTIVE: Informed consent for surgical procedures requires that the procedures are explained and that the patient understands the procedures and risks and agrees to undergo them. Proxy consent occurs when an individual is provided with the legal right to make decisions on behalf of another. This study was conducted to determine how surgeons communicate information to obtain an informed proxy consent, and to investigate how that information is received and processed by surrogates responsible for providing such consent. STUDY DESIGN: Twenty English-speaking parents or legal guardians and 5 surgeons in an urban pediatric hospital were interviewed before, and 2 to 4 weeks after, the surgical procedure. In addition, the interview between the surgeon and surrogate, when consent was obtained, was audiotaped and subsequently analyzed. Semistructured interviews were used to elicit the motivations and influences on the surrogates to consent to the procedure. The same methodology was used to elicit the corresponding impressions of the surgeons. The data were analyzed using descriptive statistics and crosstabulations. RESULTS: Demographic data did not influence the results. Although there was concordance between the surrogate's understanding of the procedure and the surgeon's impression of this understanding, only 3 of 17 surrogates could recall any specifics of the explained procedure. Contrary to the stated belief of surgeons, surrogates consulted with a variety of others, including medical and paramedical professionals, family members, and spiritual leaders. CONCLUSIONS: Communication plays an important role within the surrogate-surgeon dyad. Psychologic variables such as expectations, and the perception of both the surrogates and the surgeons, influence the amount of information that is proffered and the manner in which it is received. Improved communication may be achieved by use of visual aids, discussion of anesthesia and the postoperative course, recognition of the circumstances around the discussion, such as timing and location of the discussion, and personalization of the discussion.

Estimation of mixed venous PCO2 for determination of cardiac output in children.

STUDY OBJECTIVES: Cardiac output (Q) can be estimated noninvasively during exercise by employing CO2-rebreathing techniques (equilibrium and exponential) to estimate the oxygenated mixed venous PCO2 (PvCO2). It has been found in adults and children that the equilibrium method underestimates Q as a result of overestimation of PvCO2, unless PvCO2 is "downstream corrected." In adults, it has been found that the exponential method does not require downstream correction and yields values similar to those obtained by the equilibrium method with downstream correction. The objectives of this study were as follows: to test whether the exponential method gives similar results to the equilibrium method with downstream correction in children; to verify that downstream correction is required in children; and to test whether a single equation could be used in adults and children to predict Q from oxygen consumption (VO2). DESIGN: Descriptive. SETTING: Exercise laboratory of a university hospital. PARTICIPANTS: 23 children (16 boys, 7 girls) with a mean age of 11.0 +/- 1.9 years (7.1 to 13.9 years), and 12 adults (7 men, 5 women) with a mean age of 33.6 +/- 7.2 years (24 to 48 years). INTERVENTIONS: While performing steady-state exercise on an ergometer, PvCO2 was determined in 14 children using both the equilibrium and exponential methods, and in all other subjects using the equilibrium method alone. MEASUREMENTS AND RESULTS: For the 14 children who underwent testing by both the equilibrium and exponential methods, the uncorrected equilibrium PvCO2 was significantly different from both the corrected PvCO2 and the exponential PvCO2. We found a strong relationship between Q (L/min), calculated using the downstream corrected values of PvCO2, and VO2 (L/min) (r2 = 0.95), and this relationship was similar to that obtained by dye dilution in other studies. When weight was included, it was determined that one equation could be used for children and adults: Q (L/min) = 1.42 + 5.80.VO2 (L/min) + 0.06.wt (kg), r2 = 0.97, SEY = 0.67. CONCLUSIONS: CO2-rebreathing techniques can be used to determine Q in children; the exponential method gives values that are similar to the equilibrium method with the downstream correction; and one prediction can be used for Q in adults and children.

Cardiac output determination during progressive exercise in cystic fibrosis.

Cardiac output (Q) determination using the equilibrium CO2-rebreathe indirect Fick technique (Equil) to estimate mixed venous PCO2 (Pv-CO2) has been validated during steady state (SS) exercise in subjects with lung disease. A modification of the exponential method using a low concentration of CO2 with an exponential rise in PEt-CO2 (Ex) during rebreathing to estimate Pv-CO2 has been validated during nonsteady state exercise. The purpose of the present study was to validate the Ex method in subjects with lung disease. Q was measured by Ex at every second work load during Prog. Q was measured after 5 min of SS exercise by both Ex and Equil. Arterial PCO2 was estimated from PEtCO2. There was no significant difference in the Q-VO2 relationship during Prog exercise between the combined control and mild (FEV1 > 70%) CF subjects or the moderate and severe CF subjects. Q can be determined in the nonsteady state using the exponential CO2-rebreathe indirect Fick technique in subjects with CF, allowing for noninvasive examination of cardiopulmonary interaction during exercise at a wide range of work loads.

Treatment of obstructive airway disease with a cysteine donor protein supplement: a case report.

Oxidant/antioxidant imbalance can occur in obstructive airways disease as a result of ongoing inflammation. Glutathione (GSH) plays a major role in pulmonary antioxidant protection. As an alternative or complement to anti-inflammatory therapy, augmenting antioxidant protection could diminish the effects of inflammation. We describe a case of a patient who had obstructive lung disease responsive to corticosteroids, and low whole blood GSH levels. After 1 month of supplementation with a whey-based oral supplement designed to provide GSH precursors, whole blood GSH levels and pulmonary function increased significantly and dramatically. The potential for such supplementation in pulmonary inflammatory conditions deserves further study.

Lymphocyte glutathione levels in children with cystic fibrosis.

OBJECTIVE: Lung disease in cystic fibrosis (CF) is characterized by a neutrophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. Evidence suggests that lymphocyte GSH reflects lung GSH concentrations, and so could potentially serve as a peripheral marker of lung inflammation. METHODS: We assessed peripheral blood lymphocyte GSH concentrations in 20 children (13 boys) with CF who were in stable condition at the time of evaluation. Values were compared with nutritional status and lung function parameters. RESULTS: Patients were 11.7+/-3.03 years old (mean +/- SD). Their percentage of ideal body weight was 101.8+/-17.92%; FEV1, 79.5+/-19.22% predicted; FEV1/FVC, 75.0+/-10.08%; and residual volume (RV)/total lung capacity (TLC), 31.3+/-10.47%. For the group, the GSH concentration was 1.31+/-0.52 micromol/10(6) lymphocytes, which was not different from laboratory control values. GSH values were correlated with nutritional status (percentage of ideal body weight: r = 0.49, p < 0.03) and the degree of gas trapping (RV/TLC: r = 0.50, p < 0.03), and were correlated inversely with airflow limitation (FEV1, percent predicted: r = -0.45, p < 0.05; FEV1/FVC: r = -0.48, p < 0.04), but not with age, height, or weight (p > 0.1). CONCLUSIONS: We interpret the inverse correlation between lymphocyte GSH concentration and lung function as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress. We interpret the correlation between lymphocyte GSH concentration and nutritional status as a reflection of the role of cysteine in hepatic glutamine metabolism. Peripheral blood lymphocyte GSH concentration may potentially serve as a convenient marker of lung inflammation. Furthermore, the increased demand for GSH production in the face of ongoing inflammation suggests a potential role for supplementation with cysteine donors.

A comparison of the availability of tobramycin for inhalation from vented vs unvented nebulizers.

STUDY OBJECTIVE: To compare drug output from a vented nebulizer (Pari LC Jet Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using aerosolized tobramycin, which is frequently used in the treatment of cystic fibrosis. DESIGN: Six nebulizers of each type were filled with a 4 mL tobramycin (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5, and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed through each nebulizer. Drug output was measured from changes in weight and concentration (assessed by changes in osmometry) within the nebulizer. Particle size distributions were determined by laser diffraction allowing the calculation of the amount of aerosol output in the respirable range (<5 microm). The nebulizers were first run until end-nebulization to establish total drug output and then for either 4 or 5 min to determine the rate of drug output (mg/min) before intermittent aerosol output. RESULTS: The total drug output without VI for both the unvented and the vented nebulizers was not significantly different, 55 (51, 60) mg for the Hudson 1730 vs 51 (49, 53) mg for the Pari LC Jet Plus (mean [95% confidence limits]). Inspiratory flow had no effect on the unvented Hudson 1730 nebulizer but significantly increased the rate of total drug output and the rate of drug output in the respirable range for the vented Pari LC Jet Plus nebulizer (VI=0, 3.35 [2.84, 3.85] and 1.72 [1.48, 1.96] compared with VI=20, 9.87 [9.03, 10.70] and 6.11 [5.33, 6.88] mg/min). CONCLUSIONS: These findings indicate that the increase in the rate of drug output with VI for the vented nebulizer would result in shorter nebulization times and a relative decrease in drug loss during the expiratory phase.

Effect of size and disease on estimated deposition of drugs administered using jet nebulization in children with cystic fibrosis.

STUDY OBJECTIVES: To develop a model that quantified the nebulizer output that was inhaled by subjects with cystic fibrosis (CF) in order to predict the amount of drug likely to enter the upper airway contained in particles small enough to be deposited in the lower respiratory tract of individual patients. DESIGN: Forty-three patients (age, 6 to 18 years) with CF, with FEV(1) of 26 to 124% of predicted, breathed through a nebulizer circuit with a pneumotachograph in place at the distal end. Algorithms were developed from the measured flows through the pneumotachograph, allowing partitioning of inspiration into undiluted aerosol and fresh gas. In order to validate the algorithms, argon was added to the nebulizing gas flow and then its concentration was analyzed at the mouth by mass spectrometry. RESULTS: Predictions of the concentration of argon at the mouth were concordant with that measured by mass spectrometry, thus validating the model. Combining data from the model with in vitro nebulizer performance data, predictions for estimates for lung deposition for individuals were possible. Total estimate was independent of patient size or FEV(1). The respiratory duty cycle was 0.44 +/- 0.05 (mean +/- SD) and correlated (r = 0.91, p < 0.001) with estimated deposition and minute ventilation (r = 0.60, p < 0.01). However, when expressed in milligrams per kilogram of body weight, the estimated deposition in smaller children was fourfold higher than in larger children. CONCLUSIONS: If the effect of patient size and pattern of breathing on estimated drug deposition are not considered when prescribing drugs given by nebulization, the result may be overdosing younger children, underdosing older children, or both.

Maximal exercise capacity and peripheral skeletal muscle function following lung transplantation.

BACKGROUND: There have been many suggestions that diminished exercise capacity in patients that have undergone lung transplantation is due, in part, to peripheral muscle dysfunction, brought on by either detraining or immunosuppressive therapy. There is limited data quantifying skeletal muscle function in this population, especially in those more than 18 months post-procedure. The present study sought to quantitate skeletal muscle function and cardiopulmonary responses to graded exercise in 19 lung transplant recipients, 15 of which were mostly more than 18 months post-procedure. METHODS: Ten single- (SLT) and 9 double-lung transplantation (DLT) underwent anthropometric measures and performed expiratory spirometry, whole body plethysmography to assess lung volumes, static maximal mouth pressures to assess respiratory muscle strength, progressive exercise testing on a cycle ergometer (with cardiac output measurements being performed every second workload) and isokinetic cycling to assess peripheral muscle power and work capacity. RESULTS: The DLT group was younger than the SLT group (23.0 [21.0-32.0] vs 47.5 [43.0-55.0] median [interquartile range], p < .05) with no differences in height, weight, or BMI. Despite the DLT group having significantly better spirometric values (FEV1: 86% vs 56.5% median) and less airtrapping (RV/TLC: 30% vs 53.5%), both groups were equally limited in exercise capacity (Wmax)(38.0 percent predicted [30.0-65.0] vs 37.5 percent predicted [30.0-44.0], SLT vs DLT), leg power (76.1 percent predicted [53.8-81.4] vs 69.0 percent predicted [58.3-76.0]) and leg work capacity (63.3 percent predicted [34.7-66.8] vs 38.4 percent predicted [27.5-57.3]). This lack of difference in performance persisted when the analysis was limited to those more than 18 months post-procedure. Respiratory muscle strength was also not different for the two groups, and was within normal limits. Wmax was best correlated with leg work capacity (r = .84), but also with leg power, RV/TLC, FEV1 (r = .49, -.52, .58). When normalized for age, height, and sex, percent predicted Wmax only correlated with percent predicted leg work capacity (r = .58). Cardiac output was appropriate for the work performed. CONCLUSIONS: We conclude that peripheral skeletal muscle work capacity is reduced following lung transplantation and mostly responsible for the limitation of exercise performance. While the causes of muscular dysfunction have yet to be clarified, the preservation of respiratory muscle strength with the concomitant reduction in leg power and work capacity suggests that most of the muscular dysfunction post-transplantation is attributable to detraining.

Effect of analyzer on determination of mixed venous PCO2 and cardiac output during exercise.

Cardiac output (CO) during exercise can be determined noninvasively by using the indirect Fick CO2-rebreathing technique. CO2 measurements for this technique are usually performed with an infrared analyzer (IA) or mass spectrometer (MS). However, IA CO2 measurements are susceptible to underreading in the face of high O2 concentrations because of collision broadening. We compared an IA (Ametek model CD-3A) with a MS (Marquette model MGA-1100) to see the effect this would have on mixed venous PCO2 (PVCO2) and CO measurements. After calibration with room air and a gas mixture of 5% CO2-12% O2-83% N2, both devices were tested with three different gas mixtures of CO2 in O2. For each gas mixture, IA gave lower CO2 values than did the MS (4.1% CO2: IA, 3.85 +/- 0.01% and MS, 4.13 +/- 0.01%; 9.2% CO2: IA, 8.44 +/- 0.07% and MS, 9.19 +/- 0.01%; 13.8% CO2: IA, 12.57 +/- 0.15% and MS, 13.82 +/- 0.01%). Warming and humidifying the gases did not alter the results. The IA gave lower values than did the MS for eight other medical gases in lower concentrations of O2 (40-50%). Equilibrium and exponential rebreathing procedures were performed. Values determined by the IA were > 10% higher than those determined by the MS for both rebreathing methods. We conclude that all IAs must be checked for collision broadening if they are to be used in environments where the concentration of O2 is > 21%. If collision broadening is present, then either a special high O2-CO2 calibration curve must be constructed, or the IA should not be used for both arterial PCO2 and PVCO2 estimates because it may produce erroneously low PVCO2 values, with resultant overestimation of CO.

Effect of supplementation with a cysteine donor on muscular performance.

Oxidative stress contributes to muscular fatigue. GSH is the major intracellular antioxidant, the biosynthesis of which is dependent on cysteine availability. We hypothesized that supplementation with a whey-based cysteine donor [Immunocal (HMS90)] designed to augment intracellular GSH would enhance performance. Twenty healthy young adults (10 men, 10 women) were studied presupplementation and 3 mo postsupplementation with either Immunocal (20 g/day) or casein placebo. Muscular performance was assessed by whole leg isokinetic cycle testing, measuring peak power and 30-s work capacity. Lymphocyte GSH was used as a marker of tissue GSH. There were no baseline differences (age, ht, wt, %ideal wt, peak power, 30-s work capacity). Follow-up data on 18 subjects (9 Immunocal, 9 placebo) were analyzed. Both peak power [13 +/- 3.5 (SE) %, P < 0.02] and 30-s work capacity (13 +/- 3.7%, P < 0.03) increased significantly in the Immunocal group, with no change (2 +/- 9.0 and 1 +/- 9.3%) in the placebo group. Lymphocyte GSH also increased significantly in the Immunocal group (35.5 +/- 11.04%, P < 0.02), with no change in the placebo group (-0.9 +/- 9.6%). This is the first study to demonstrate that prolonged supplementation with a product designed to augment antioxidant defenses resulted in improved volitional performance.