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Publications and source records attributed to L C Lands.
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.
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.
OBJECTIVES: To evaluate the feasibility of measuring habitual physical activity (HPA) in children with cystic fibrosis (CF) and to assess the relation between HPA and the rate of decline in FEV1 over a period of 2 years. STUDY DESIGN: At regular clinic visits, 109 patients (7 to 17 years; 56 girls) performed pulmonary function testing and completed the Habitual Activity Estimation Scale (HAES). Patients were divided into quartiles, based on activity levels derived from the HAES. RESULTS: Girls in the two lowest activity quartiles had a more rapid rate of decline FEV1 (-3.40% and -3.05% predicted, respectively) than girls in the two highest activity quartiles (-0.93% and +1.17% predicted, respectively) (P = .02). In boys, the rate of decline of FEV1 was similar in all activity quartiles (-1.95% predicted). Patients reported significantly more activity in summer compared with spring, winter, and fall (P < .0001), and boys reported greater activity than girls (6.5 +/- 2.9 vs 5.4 +/- 2.5 h/d, P < .05). CONCLUSIONS: The annual rate of change of FEV1 was related to activity quartile in girls but not in boys. This research suggests that an inactive lifestyle may partially explain the poorer survival of female patients with CF. The HAES is a feasible tool for routine follow-up of HPA in our CF clinic.
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.
We report the successful weaning and extubation of an infant from a SensorMedics 3100A high-frequency oscillator without returning to conventional ventilation. A 7-week-old term infant with respiratory syncytial virus bronchiolitis complicated by cystic pulmonary lesions repeatedly failed attempts to return to conventional ventilation from high-frequency oscillatory ventilation (HFOV) for weaning, because of recurrent pneumothoraces. A computed tomography of the chest revealed multiple well defined cysts of various sizes involving both lungs. Therefore, weaning to extubation from HFOV was proposed as a way of preventing further air leak. The weaning strategy consisted of a technique we refer to as "sprinting." Using this method, the patient was successfully extubated directly from HFOV, with no complications. A follow-up computed tomography of the chest showed marked improvement in the size of the cystic lesions. The patient was discharged home with no need for home oxygen therapy.
Several studies have demonstrated ongoing oxidative stress in cystic fibrosis (CF). With the complexity of the antioxidant network, measurement of individual antioxidants does not necessarily assess how they work in combination. One measure that has been proposed as a gauge of total plasma antioxidant capacity is the Trolox-equivalent antioxidant capacity (TEAC) of plasma. We decided to look at plasma TEAC levels in children with CF, and relate this measure to their nutritional status, lung function, and blood measurements of several known antioxidants. We hypothesized that values in general would be lower than healthy control values, especially during acute pulmonary exacerbations. Twenty-nine children were evaluated, five of whom were during an acute pulmonary exacerbation. Height and weight, expiratory spirometry, and lung volumes were assessed, as were serum concentrations of vitamins A and E, uric acid, albumin, and lymphocyte glutathione (GSH) concentrations. TEAC values for nonhospitalized patients (1.40 +/- 0. 20 mmol/L) were not different from laboratory control values (1.35 +/- 0.11 mmol/L), but greater than values for hospitalized patients (1.09 +/- 0.17 mmol/L). TEAC correlated with anthropometric values (height: r = 0.39, P < 0.03; weight: r = 0.50, P < 0.01; body mass index: r = 0.47, P < 0.01), and pulmonary function (forced expiratory volume in 1 sec: r = 0.43, P < 0.02; residual volume/total lung capacity: r = -0.42, P < 0.03), but not with age. Univariate correlation with blood measurements demonstrated a significant correlation of TEAC with uric acid (r = 0.49, P < 0.02), but not with albumin, vitamins A or E, or lymphocyte GSH. Multiple regression analysis demonstrated a correlation between TEAC and uric acid, albumin, and lymphocyte GSH in the non-hospitalized group (r(2) = 0.38, P < 0.03). We conclude that TEAC appears to represent a mixed antioxidant response, rather than response to a single antioxidant. While being responsive to oxidative stress, the mechanism of the response may differ between clinical situations, such that the clinical significance of changes in plasma TEAC remains to be defined.
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The use of inhaled tobramycin for prophylaxis and treatment of respiratory symptoms in cystic fibrosis (CF) is now widespread. There have been concerns that inhaling the intravenous (I.V.) formulation of tobramycin causes bronchoconstriction. Previous studies using this formulation have either not specified the nebulizing equipment, or studied older, more severely affected patients. This study investigated the incidence of bronchoconstriction with tobramycin inhalation in children with mild to moderate CF. We studied 26 patients between the ages of 7 and 17 years, with mild to moderate CF (20 female). Prior to being placed on prolonged inhaled tobramycin therapy, they underwent a "tobramycin challenge." FEV(1) was measured pre and post challenge. For the test, standard I.V. solution (80 mg/2 mL) diluted with 2 mL of normal saline was nebulized, using the Hudson (Temecula, CA) RCI Updraft II nebulizer. The nebulization lasted 2 min. There was a 3-min "quiet period," following which FEV(1) was measured. A decrease in FEV(1) by at least 10% post-tobramycin inhalation was considered to be a positive test. Results were analyzed using the Pearson Chi-square test. Five of 26 (19%) had a positive reaction to tobramycin. Sixteen of 26 (61.5%) were using salbutamol on a daily basis at the time of testing but not for 48 hr before the challenge, and 16 of 26 (61.5%) had a pre-tobramycin FEV(1) of < or =80%. Neither an FEV(1) of <80% (P = 0.93) nor regular use of salbutamol (P = 0. 34) were associated with a positive tobramycin challenge. This study suggests that, while bronchoconstriction does occur, many patients do not exhibit bronchoconstriction in response to the standard I.V. preparation and, as prior work suggests, this may be reduced further by pretreatment with salbutamol.
The ability to predict drug deposition of inhaled drugs used in cystic fibrosis (CF) is important if there is a need to target specific doses of drug to the lungs of individual patients. The gold standard of measuring pulmonary deposition is the quantification of an aerosolized radiolabel either mixed with the drug solution or tagged directly to the compound of interest. Accuracy of the quantification could be assured if there is agreement between the amount of radioactivity before and after administration. Before administration, the radiolabel is concentrated in the well of the nebulizer, whereas after administration, it is distributed throughout the nebulizer, the expiratory filter and connectors, and the upper airway, stomach, trachea, and lung. Not only is the geometry of the distribution that is presented to the gamma camera different, but there are different attenuation factors for the various body tissues. The primary aim of this study was to evaluate the accuracy of the quantification of deposition. Secondary goals were to compare in vitro nebulizer performance with that measured in vivo during the deposition study. Eighty milligrams of tobramycin and technetium bound to human serum albumin was administered to 10 normal adults using a Pari LC Jet Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebulizer. Techniques were developed that allowed for the accounting of 99 +/- 2% of the initial radioactivity. The fraction of the rate of lung deposition to total body deposition was the in vivo respirable fraction (0.62 +/- 0.07), which closely agreed with in vitro measurements of respirable fraction (0.62 +/- 0.04). Drug output measured from the change in weight and concentration in the nebulizer systematically overestimated drug output measured by the deposition study. The results indicate that 11.8 of the initial 80 mg would be deposited in the lungs. This technique could be adapted to accurately quantify the amount of deposition on any inhaled therapeutic agent, but caution must be used when extrapolating performance of a nebulizer on the bench to expected deposition in patients.
This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO(3) and KHCO(3) ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO(3)) and, in a separate trial, potassium bicarbonate (KHCO(3)). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO(3) ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 +/- 11% of ingested volume, resulting in a 555 +/- 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na(+) excretion accounted for 24 +/- 2% of ingested Na(+). In the KHCO(3) trial, arterial plasma K(+) concentration rapidly increased from 4.25 +/- 0.10 to a peak of 7.17 +/- 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K(+) excretion at 270 min accounted for 26 +/- 5% of ingested K(+). The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO(3) and NaHCO(3) solutions.
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.
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.
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.
The amount of drug that is delivered by nebulization is a combination of the physical properties of the agent being nebulized, the performance of the nebulizer, and the pattern of breathing of the patient. To avoid biological variation, mechanical models of breathing are frequently employed during the evaluation of the performance of a device. For simplicity, many investigators use sinusoidal models of breathing to calculate the expected inhaled mass, although some use square waves and other more complex models. Most assume that the duration of inspiration (Ti) is half of the total respiratory time (Ttot). This study compared the calculated inhaled mass from which the expected pulmonary deposition was estimated from the actual pattern of breathing of 43 children with cystic fibrosis (CF) breathing from an unvented nebulizer with a low dead volume and appropriate particle size distribution with that from a sinusoidal pattern of breathing using the same tidal volume (VT) and respiratory rate. The respiratory duty cycle (Ti/Ttot) was 0.45 +/- 0.05, which meant that less time was spent during inspiration than that found in a pure sinusoidal pattern. The difference between the predicted deposition from the actual pattern of breathing and that calculated from the sinusoidal model was 12 +/- 7%, which correlated with the respiratory rate (r = 0.67, P < 0.001). The degree of lung disease did not influence the discrepancy between the two values. In general, the actual VTs and respiratory rates were less in the patients than those employed in mechanical models of pediatric breathing. Although some patients had respiratory patterns that could be represented accurately with a sinusoidal model, most did not, and there were wide variations from child to child. These results suggest that there are both systematic and random errors arising from the use of a sinusoidal waveform to mimic respiratory events in patients.
This paper examines the time course of changes in plasma electrolyte and acid-base composition in response to NaHCO3 and KHCO3 ingestion. It was hypothesized that skeletal muscle is involved in the correction of the ensuing plasma disturbance by exchanging ions, gasses, and fluids between cells and extracellular fluids. Five male subjects, with catheters in a brachial artery and antecubital vein, ingested 3.57 mmol/kg body mass NaHCO3 or KHCO3. While seated, blood samples were taken 30 min before ingestion of the solution, at 10-min intervals during the 60-min ingestion period, and periodically for 210 min after ingestion was complete. Blood was analyzed for gases, hematocrit, plasma ions, and total protein. With NaHCO3, arterial plasma Na+ concentration ([Na+]) increased from 143 +/- 1 to 147 +/- 1 (SE) meq/l, H+ concentration ([H+]) decreased by 6 +/- 1 neq/l, and PCO2 increased by 5 +/- 1 mmHg. There was no detectable net Na+ uptake by tissues. An increased plasma strong ion difference ([SID]) accounted fully for the decrease in plasma [H+]. With KHCO3, K+ concentration increased from 4.25 +/- 0.10 to 7.17 +/- 0.13 meq/l, plasma volume decreased by 15.5 +/- 2.3%, [H+] decreased by 4 +/- 1 neq/l, and there was no change in PCO2. The decrease in [H+] in the KHCO3 trial primarily arose in response to the increased [SID]. Net K+ uptake by tissues accounted for 37 +/- 5% of the ingested K+. In conclusion, ingestion of NaHCO3 and KHCO3 produced markedly different fluid and ionic disturbances and associated regulatory responses by skeletal muscle. Accordingly, the physicochemical origins of the acid-base disturbances also differed between treatments. The tissues did not play a role in regulating plasma [Na+] after ingestion of NaHCO3. In contrast, the net influx of K+ to tissues played an important role in removing K+ from the extracellular compartment after ingestion of KHCO3.
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.
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.
OBJECTIVE: To evaluate the long-term pulmonary sequelae of survivors of bronchopulmonary dysplasia (BPD) of sufficient severity to have required supplemental oxygen for at least 1 month after term. STUDY DESIGN: Fifteen patients with a mean age of 1.1 years were matched to preterm infants of similar gestational age and age at time of study. Pulmonary function testing included spirometry, plethysmographic lung volumes, carbon monoxide diffusion capacity, and in 9 of 15 subjects with BPD, measurement of lung static elastic recoil pressures. RESULTS: The subjects with BPD had a mean expiratory volume in 1 second (FEV1) of 64% +/- 21% predicted (4 had an FEV1 < 50% predicted) compared with 85% +/- 11% (P < .01) for the preterm children in the control group. Subjects with BPD had a significant degree of gas trapping with a residual volume to total lung capacity ratio of 37% +/- 13% compared with 25% +/- 4% for the control group (P < .01). An inverse relationship was seen between the FEV1 and the time on supplemental oxygen (r = -0.84, P < .0001), with 3 of the 4 children whose FEV1 was < 50% requiring oxygen for more than 900 days. Those with the greatest degree of airflow limitation and gas trapping had the greatest abnormalities in both shape and position of the pressure volume curves of the lung. CONCLUSION: Severe BPD may result in moderate to severe long-term abnormalities in pulmonary function tests.