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.

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.

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.

Meeting report: consensus recommendations for a research agenda in exercise in solid organ transplantation.

With improved survival rates in solid organ transplantation there has been an increased focus on long-term outcomes following transplant, including physical function, health-related quality-of-life and cardiovascular mortality. Exercise training has the potential to affect these outcomes, however, research on the optimal timing, type, dose of exercise, mode of delivery and relevant outcomes is limited. This article provides a summary of a 2-day meeting held in April 2013 (Toronto, Canada) in which a multi-disciplinary group of clinicians, researchers, administrators and patient representatives engaged in knowledge exchange and discussion of key issues in exercise in solid organ transplant (SOT). The outcomes from the meeting were the development of top research priorities and a research agenda for exercise in SOT, which included the need for larger scale, multi-center intervention studies, development of standardized outcomes for physical function and surrogate measures for clinical trials, examining novel modes of exercise delivery and novel outcomes from exercise training studies such as immunity, infection, cognition and economic outcomes. The development and dissemination of "expert consensus guidelines," synthesizing both the best available evidence and expert opinion was prioritized as a key step toward improving program delivery.

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis.

BACKGROUND: Airway inflammation, mediated in part by LTB4, contributes to lung destruction in patients with cystic fibrosis (CF). LTB(4)-receptor inhibition may reduce airway inflammation. We report the results of a randomized, double-blind, placebo-controlled study of the efficacy and safety of the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 BS in CF patients. METHODS: CF patients aged ≥6 years with mild to moderate lung disease were randomized to oral BIIL 284 BS or placebo once daily for 24 weeks. Co-primary endpoints were change in FEV(1) and incidence of pulmonary exacerbation. RESULTS: After 420 (155 children, 265 adults) of the planned 600 patients were randomized, the trial was terminated after a planned interim analysis revealed a significant increase in pulmonary related serious adverse events (SAEs) in adults receiving BIIL 284 BS. Final analysis revealed SAEs in 36.1% of adults receiving BIIL 284 BS vs. 21.2% receiving placebo (p = 0.007), and in 29.6% of children receiving BIIL 284 BS vs. 22.9% receiving placebo (p = 0.348). In adults, the incidence of protocol-defined pulmonary exacerbation was greater in those receiving BIIL 284 BS than in those receiving placebo (33.1% vs. 18.2% respectively; p = 0.005). In children, the incidence of protocol-defined pulmonary exacerbation was 19.8% in the BIIL 284 BS arm, and 25.7% in the placebo arm (p = 0.38). CONCLUSIONS: While the cause of increased SAEs and exacerbations due to BIIL 284 BS is unknown, the outcome of this trial provides a cautionary tale for the administration of potent anti-inflammatory compounds to individuals with chronic infections, as the potential to significantly suppress the inflammatory response may increase the risk of infection-related adverse events.

Cost effectiveness of newborn screening for cystic fibrosis: a simulation study.

BACKGROUND: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. OBJECTIVE: To compare the cost effectiveness of various CF NBS options. METHODS: A Markov model was built to simulate the cost effectiveness of various CF-NBS options for a hypothetical CF-NBS program over a 5-year time horizon assuming its integration into an existing universal NBS program. NBS simulated options were based on a combination of tests between the two commonly used immunoreactive trypsinogen (IRT) cutoffs (96th percentile and 99.5th percentile) as first tier tests, and, as a second tier test, either a second IRT, pancreatic-associated protein (PAP) or CFTR mutation panels. CFTR mutation panels were also considered as an eventual third tier test. Data input parameters used were retrieved from a thorough literature search. Outcomes considered were the direct costs borne by the Quebec public health care system and the number of cases of CF detected through each strategy, including the absence of screening option. RESULTS: IRT-PAP with an IRT cutoff at the 96th percentile is the most favorable option with a ratio of CAD$28,432 per CF case detected. The next most favorable alternative is the IRT1-IRT2 option with an IRT1 cutoff at the 96th percentile. The no-screening option is dominated by all NBS screening protocols considered. Results were robust in sensitivity analyses. CONCLUSION: This study suggests that NBS for cystic fibrosis is a cost-effective strategy compared to the absence of NBS. The IRT-PAP newborn screening algorithm with an IRT cutoff at the 96th percentile is the most cost effective NBS approach for Quebec.

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.

Dietary supplementation with pressurized whey in patients with cystic fibrosis.

Cystic fibrosis (CF) is characterized by malnutrition, chronic pulmonary inflammation, and oxidative stress. Whey protein is rich in sulfhydryl groups and is recognized for its ability to increase glutathione and reduce oxidative stress. Previously, we have shown that supplementation with whey increased intracellular glutathione levels in patients with CF. We have subsequently shown that hyperbaric pressure treatment of whey protein promotes the release of novel peptides for absorption, increases intracellular glutathione in healthy subjects, and reduces in vitro production of interleukin (IL)-8. We hypothesized that pressurized whey supplementation in children and adults with CF could have significant nutritional and anti-inflammatory benefits. A pilot open-label study of 1-month dietary supplementation with pressurized whey in CF patients was undertaken to assess the effects. Twenty-seven patients with CF (nine children, 18 adults) were enrolled. The dose of pressurized whey was 20 g/day in patients less than 18 years of age and 40 g/day in older patients. Anthropometric measures, pulmonary function, serum C-reactive protein (CRP), whole blood glutathione, and whole blood IL-8 and IL-6 responses to phytohemagglutinin (PHA) stimulation were measured at baseline and at 1 month. Three adults withdrew (one with gastrointestinal side effects, two with acute infection). Both children and adults showed enhancements in nutritional status, as assessed by body mass index. Children showed improvement in lung function (forced expiratory volume in 1 second). The majority of patients with an initially elevated CRP showed a decrease. PHA-stimulated IL-8 responses tended to decrease in the adults. Whole blood glutathione levels did not change. Thus, oral supplementation with pressurized whey improves nutritional status and can have additional beneficial effects on inflammation in patients with CF.

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.

Laboratory 20-km cycle time trial reproducibility.

This study evaluated the reproducibility of laboratory based 20-km time trials in well trained versus recreational cyclists. Eighteen cyclists (age = 34 +/- 8 yrs; body mass index = 23.1 +/- 2.2 kg/m (2); VO(2max) = 4.19 +/- 0.65 L/min) completed three 20-km time trials over a month on a Velotron cycle ergometer. Average power output (PO) (W), speed, and heart rate (HR) were significantly lower in the first time trial compared to the second and third time trial. The coefficients of variation (CV) between the second and third trial of the top eight performers for average PO, time to completion, and speed were 1.2 %, 0.6 %, 0.5 %, respectively, compared to 4.8 %, 2.0 %, and 2.3 % for the bottom ten. In addition, the average HR, VO(2), and percentage of VO(2max) were similar between trials. This study demonstrated that (1) a familiarization session improves the reliability of the measurements (i.e., average PO, time to completion and speed), and (2) the CV was much smaller for the best performers.

Sex differences in habitual physical activity and lung function decline in children with cystic fibrosis.

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.

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.

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.

Weaning to extubation directly from high-frequency oscillatory ventilation in an infant with cystic lung disease and persistent air leak: a strategy for lung protection.

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.

Accounting for radioactivity before and after nebulization of tobramycin to insure accuracy of quantification of lung deposition.

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.

Inhaled tobramycin and bronchial hyperactivity in cystic fibrosis.

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.

Monitoring of 25-OH vitamin D levels in children with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are at risk for malabsorption of fat-soluble vitamins, and those with low 25-OH vitamin D levels have a higher risk of low bone mineral density and long-term skeletal complications. It is currently recommended that vitamins A and E be monitored yearly; however, no recommendations exist for 25-OH vitamin D. Because all three vitamins are fat-soluble, the hypothesis in the current study was that low levels of vitamins A and E could identify patients at risk for low 25-OH vitamin D, so that 25-OH vitamin D measurements could be obtained in only selected circumstances. METHODS: Forty (21 girls) patients with CF, age 10.5 +/- 3.9 (SD) years, were assessed in a cross-sectional survey for ideal weight for height (percentage of predicted), spirometry (percentage of predicted FEV1, 33/40 patients), and serum levels of vitamins A, E, 25-OH vitamin D, and cholesterol (37/40 patients). RESULTS: Nine (22.5%) of 40 patients were malnourished (percentage of predicted ideal weight for height <85%), 7 (21.2%) of 33 had moderate to severe lung disease (FEV1 <60%), 4 (10%) of 40 had low levels of vitamin A, 3 (7.5%) of 40 had low vitamin E levels, 4 (10.8%) of 37 low vitamin E/cholesterol levels, and 4 (10%) of 40 had marginal or low levels of 25-OH vitamin D (<40 mmol/l). The patients with low 25-OH vitamin D were older, with no child < 12 years of age having a 25-OH vitamin D level less than 40 mmol/l. They also had lower vitamin E and vitamin E/cholesterol levels than those with normal 25-OH vitamin D levels. The groups did not differ in percentage of predicted ideal weight for height, lung function, or vitamin A levels. The best positive predictor for 25-OH vitamin D less than 40 mmol/l was low vitamin E (66.7%), with a negative predictive value of 94.6%. 25-OH vitamin D levels correlated with vitamin E/cholesterol levels (r = 0.41, P < 0.01) and weakly with vitamin E levels (r = 0.28, P < 0.08), but not with vitamin A levels. CONCLUSIONS: These results suggest that children aged less than 12 years and older children with normal vitamin E levels are especially unlikely to have low 25-OH vitamin D levels, and this measure can therefore be omitted. In contrast, those children with low vitamin E levels may warrant monitoring.