Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in ...the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.
Aims
We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic ...fibrosis.
Methods
A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed.
Results
Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb.
Conclusions
Nebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.
16S-based sequencing provides broader information on the respiratory microbial community than conventional culturing. However, it (often) lacks species- and strain-level information. To overcome this ...issue, we used 16S rRNA-based sequencing results from 246 nasopharyngeal samples obtained from 20 infants with cystic fibrosis (CF) and 43 healthy infants, which were all 0 to 6 months old, and compared them to both standard (blind) diagnostic culturing and a 16S-sequencing-informed "targeted" reculturing approach. Using routine culturing, we almost uniquely detected Moraxella catarrhalis, Staphylococcus aureus, and Haemophilus influenzae (42%, 38%, and 33% of samples, respectively). Using the targeted reculturing approach, we were able to reculture 47% of the top-5 operational taxonomical units (OTUs) in the sequencing profiles. In total, we identified 60 species from 30 genera with a median of 3 species per sample (range, 1 to 8). We also identified up to 10 species per identified genus. The success of reculturing the top-5 genera present from the sequencing profile depended on the genus. In the case of
being in the top 5, we recultured them in 79% of samples, whereas for Staphylococcus, this value was only 25%. The success of reculturing was also correlated with the relative abundance of those genera in the corresponding sequencing profile. In conclusion, revisiting samples using 16S-based sequencing profiles to guide a targeted culturing approach led to the detection of more potential pathogens per sample than conventional culturing and may therefore be useful in the identification and, consequently, treatment of bacteria considered relevant for the deterioration or exacerbation of disease in patients like those with CF.
Early and effective treatment of pulmonary infections in cystic fibrosis is vital to prevent chronic lung damage. Although microbial diagnostics and treatment decisions are still based on conventional culture methods, research is gradually focusing more on microbiome and metagenomic-based approaches. This study compared the results of both methods and proposed a way to combine the best of both worlds. Many species can relatively easily be recultured based on the 16S-based sequencing profile, and it provides more in-depth information about the microbial composition of a sample than that obtained through routine (blind) diagnostic culturing. Still, well-known pathogens can be missed by both routine diagnostic culture methods as well as by targeted reculture methods, sometimes even when they are highly abundant, which may be a consequence of either sample storage conditions or antibiotic treatment at the time of sampling.
Objectives To predict peak oxygen uptake (VO2peak) from the peak work rate (Wpeak) obtained during a cycle ergometry test using the Godfrey protocol in adolescents with cystic fibrosis (CF), and ...assess the accuracy of the model for prognostication clustering. Methods Out of our database of anthropometric, spirometric and maximal exercise data from adolescents with CF (N=363; 140 girls and 223 boys; age 14.77±1.73 years; mean expiratory volume in 1 s (FEV1%pred) 86.82±17.77%), a regression equation was developed to predict VO2peak (mL/min). Afterwards, this prediction model was validated with cardiopulmonary exercise data from another 60 adolescents with CF (28 girls, 32 boys; mean age 14.6±1.67 years; mean FEV1%pred 85.43±20.01%). Results We developed a regression model VO2peak (mL/min)=216.3–138.7×sex (0=male; 1=female)+11.5×Wpeak; R2=0.91; SE of the estimate (SEE) 172.57. A statistically significant difference (107 mL/min; p<0.001) was found between predicted VO2peak and measured VO2peak in the validation group. However, this difference was not clinically relevant because the difference was within the SEE of the model. Furthermore, we found high positive predictive and negative predictive values for the model for prognostication clustering (PPV 50–87% vs NPV 82–94%). Conclusions In the absence of direct VO2peak assessment it is possible to estimate VO2peak in adolescents with CF using only a cycle ergometer. Furthermore, the regression model showed to be able to discriminate patients in different prognosis clusters based on exercise capacity.
After a positive newborn screening test for cystic fibrosis (CF), a sweat test is performed to confirm the diagnosis. The success rate of the generally acknowledged methods (Macroduct/Gibson and ...Cooke) in newborns varies between 73 and 99 %. The Nanoduct sweat test system is easier to perform and less sweat is needed. The main aim of this study was to measure the success rate of the Nanoduct compared to current approved sweat test methods in a newborn population. After informed consent of the parents, newborns with a positive screening test for CF were included. The Macroduct or Gibson and Cooke and Nanoduct were performed in all infants, during the same appointment. The chloride concentration was determined by standard coulorimetry; conductivity was measured directly and converted to a NaCl molarity. One hundred eight newborns were included: 17 with CF, 7 with cystic fibrosis transmembrane regulator (CFTR)-related metabolic syndrome (CRMS), and 84 healthy children. The success rate of the Nanoduct was 93 % and for the Macroduct/Gibson and Cooke 79 % (McNemar,
p
= 0.002). The Nanoduct detected the same CF patients as the Macroduct/Gibson and Cooke; one CF patient had an equivocal result for both tests, and no patients were missed. The area under the receiver operating characteristic curve for detection of CF with the Nanoduct was 0.999, with ideal cutoff levels of 91 and 66 mmol/l, comparable to former studies.
Conclusion
: The success rate of the Nanoduct to collect sufficient sweat in infants was higher compared to the Macroduct and Gibson and Cooke.
What is known:
•
The internationally accepted methods for collecting and determining NaCl values in sweat, the Gibson and Cooke method and Macroduct, are difficult to perform and require well-trained and experienced personnel. The test often fails in newborns. As yet there is insufficient evidence to recommend the use of the Nanoduct which fails less often, requires less sweat, and is much easier to perform.
What is new:
•
This study provides further evidence that the Nanoduct fails less often in newborns than the Gibson and Cooke/Macroduct and can be used to exclude or confirm the diagnosis CF in infants with a positive newborn screening test for CF.
The oxygen uptake efficiency slope (OUES) has been proposed as an 'effort-independent' measure of cardiopulmonary exercise capacity, which could be used as an alternative measurement for peak oxygen ...uptake (VO(2peak)) in populations unable or unwilling to perform maximal exercise. The aim of the current study was to investigate the validity of the OUES in children with cystic fibrosis (CF).
Exercise data of 22 children with CF and mild to moderate airflow obstruction were analyzed and compared with exercise data of 22 healthy children. The OUES was calculated using data up to three different relative exercise intensities, namely 50%, 75%, and 100% of the total exercise duration, and normalized for body surface area (BSA).
Only the OUES/BSA using the first 50% of the total exercise duration was significantly different between the groups. OUES/BSA values determined at different exercise intensities differed significantly within patients with CF and correlated only moderately with VO(2peak) and the ventilatory threshold.
The OUES is not a valid submaximal measure of cardiopulmonary exercise capacity in children with mild to moderate CF, due to its limited distinguishing properties, its nonlinearity throughout progressive exercise, and its moderate correlation with VO(2peak) and the ventilatory threshold.
Cystic fibrosis (CF) patients are colonized with a multitude of bacteria and fungi. From respiratory samples of two CF patients in our institute, a difficult to identify yeast was isolated ...repeatedly. This yeast was eventually identified as
(
)
by internal transcribed spacer (ITS) and ribosomal large subunit (LSU) sequencing.
is a basidiomycetous yeast originally reported as environmental isolate from South African soil and has not been described before as clinical isolate from CF patients.
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